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Sample records for akr1b1 rage gfpt2

  1. The prostaglandin F synthase activity of the human aldose reductase AKR1B1 brings new lenses to look at pathologic conditions.

    Directory of Open Access Journals (Sweden)

    Eva eBresson

    2012-05-01

    Full Text Available Prostaglandins are important regulators of female reproductive functions to which aldose reductases exhibiting hydroxysteroid dehydrogenase activity also contribute. Our work on the regulation of reproductive function by prostaglandins (PGs, lead us to the discovery that AKR1B5 and later AKR1B1 were highly efficient and physiologically relevant PGF synthases. PGE2 and PGF2α are the main prostanoids produced in the human endometrium and proper balance in their relative production is important for normal menstruation and optimal fertility. Recent evidence suggests that PGE2 and PGF2α may constitute a functional dyad with physiological relevance at least as important as the prostacyclin-thromboxane dyad in the vascular system. We have recently reported that AKR1B1 was expressed and modulated in association with PGF2α production in response to IL-1β in the human endometrium. In the present study, we show that the human AKR1B1 (gene ID: 231 also known as ALDR1 or ALR2 is a functional PGF2α synthase in different models of living cells and tissues. Using human endometrial cells, prostate and vascular smooth muscle cells, cardiomyocytes and endothelial cells we demonstrate that IL-1β is able to up regulate COX-2 and AKR1B1 proteins as well as PGF2α production under normal glucose concentrations. We show that the promoter activity of AKR1B1 gene is increased by IL-1β particularly around the multiple stress response region (MSRR containing two putative antioxidant response elements (ARE adjacent to TonE and AP1.We also show that AKR1B1 is able to regulate PGE2 production through PGF2α acting on its FP receptor and that aldose reductase inhibitors (ARIs like alrestatin, statil (ponalrestat and EBPC exhibit distinct and characteristic inhibition of PGF2α production in different cell models. The PGF synthase activity of AKR1B1 represents a new and important target to regulate ischemic and inflammatory responses associated with several human

  2. Expression of the prostaglandin F synthase AKR1B1 and the prostaglandin transporter SLCO2A1 in human fetal membranes in relation to spontaneous term and preterm labour

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    Hana A Alzamil

    2014-07-01

    Full Text Available Background: Human labour is a complex series of cellular and molecular events that occur at the materno-fetal and uterine levels. Many hypotheses have been proposed for the initiation of human labour, one hypothesis suggests that maturation of the fetus releases a signal in the amniotic fluid that will be transmitted to myometrium via the fetal membranes and initiate uterine contractions. There is strong evidence that prostaglandins (PGs play a central role in initiation and progression of human labour. Objectives: In this study we intended to investigate the expression of prostaglandin F synthase and the prostaglandin transporter in the human fetal membranes and to explore the relationship between cytokines and PGs in the mechanism of human labour. Methods: We used fetal membranes obtained before labour at term and after spontaneous labour at term or preterm to identify the changes in prostaglandin F synthase (AKR1B1 and human prostaglandin transporter (SLCO2A1 proteins in relation to parturition. Using fetal membranes explants we tested the effect of cytokines (interleukin-1 and tumour necrosis factor alpha on PG production and the concomitant changes in cyclooxygenase-2 (PTGS2, AKR1B1 and SLCO2A1 expression. Results: Expression of PTGS2 and AKR1B1 was upregulated in the fetal membranes in association with term labour while SLCO2A1 was downregulated with advancing gestation and during term labour. Before labour, IL-1 increased the expression of PTGS2, however during labour TNF upregulated PTGS2 and AKR1B1 proteins. Conclusions: The prostaglandin F synthase AKR1B1 is upregulated while prostaglandin transporter is downregulated during term labour. The amnion is more responsive than choriodecidua to stimulation with pro-inflammatory cytokines. The mechanisms of term and preterm labour are different.

  3. High-throughput functional genomics identifies genes that ameliorate toxicity due to oxidative stress in neuronal HT-22 cells: GFPT2 protects cells against peroxide.

    Science.gov (United States)

    Zitzler, Jürgen; Link, Dieter; Schäfer, Rolf; Liebetrau, Wolfgang; Kazinski, Michael; Bonin-Debs, Angelika; Behl, Christian; Buckel, Peter; Brinkmann, Ulrich

    2004-08-01

    We describe a novel genetic screen that is performed by transfecting every individual clone of an expression clone collection into a separate population of cells in a high-throughput mode. We combined high-throughput functional genomics with experimental validation to discover human genes that ameliorate cytotoxic responses of neuronal HT-22 cells upon exposure to oxidative stress. A collection of 5,000 human cDNAs in mammalian expression vectors were individually transfected into HT-22 cells, which were then exposed to H(2)O(2). Five genes were found that are known to be involved in pathways of detoxification of peroxide (catalase, glutathione peroxidase-1, peroxiredoxin-1, peroxiredoxin-5, and nuclear factor erythroid-derived 2-like 2). The presence of those genes in our "hit list" validates our screening platform. In addition, a set of candidate genes was found that has not been previously described as involved in detoxification of peroxide. One of these genes, which was consistently found to reduce H(2)O(2) -induced toxicity in HT-22, was GFPT2. This gene is expressed at significant levels in the central nervous system (CNS) and encodes glutamine-fructose-6-phosphate transaminase (GFPT) 2, a rate-limiting enzyme in hexosamine biosynthesis. GFPT has recently also been shown to ameliorate the toxicity of methylmercury in Saccharomyces cerevisiae. Methylmercury causes neuronal cell death in part by protein modification as well as enhancing the production of reactive oxygen species (ROS). The protective effect of GFPT2 against H(2)O(2) toxicity in neuronal HT-22 cells may be similar to its protection against methylmercury in yeast. Thus, GFPT appears to be conserved among yeast and men as a critical target of methylmercury and ROS-induced cytotoxicity.

  4. Road Rage Rampant in America

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159883.html Road Rage Rampant in America 8 of 10 drivers ... of 10 drivers demonstrated significant anger, aggression or road rage in the past year, the study found. ...

  5. A race for RAGE ligands.

    Science.gov (United States)

    Schleicher, Erwin D

    2010-08-01

    In experimental animals a causal involvement of the multiligand receptor for advanced glycation end products (RAGE) in the development of diabetic vascular complications has been demonstrated. However, the nature of RAGE ligands present in patients with diabetic nephropathy has not yet been defined; this leaves open the relevance of the RAGE system to the human disease.

  6. RAGE on the Toll Road?

    Institute of Scientific and Technical Information of China (English)

    Li Lin

    2006-01-01

    Mammalian Toll-like receptors (TLRs) are cellular pattern-recognizing receptors (PRRs) that recognize the molecular patterns of pathogens. After engaging the pathogenic patterned ligands, the cytosolic portion of the TLRs in monocytes and macrophages, recruits adaptor proteins, via a receptor-driven signaling cascade, activates the transcription factor NF-κB, leading to the expression of proinflammatory cytokines, which trigger inflammation. Such rapid, innate cellular responses serve as the first line of host defense against infection by pathogens, and also stimulate the adaptive immune system to clear the invading microbes. Increasing evidence suggests that TLRs also recognize host-derived ligands, linking this group of PRRs to diseases that may not have an etiology that is associated directly with infections. Advanced glycation end products (AGEs) are nonenzymatically glycated or oxidated proteins, lipids and nucleic acids that are formed in the environment of oxidant stress and hyperglycemia. Binding of AGEs to their receptor RAGE initiates cellular signals that activate NF-κB, which results in transcription of proinflammatory factors. RAGE can also interact with other endogenous ligands generated by cell death and tissue injuries. RAGE has been implicated in chronic diseases such as diabetes,atherosclerosis, neurodisorders, cancers, as well as aging. This review discusses the possible role of RAGE as a PRR that may use signaling mechanisms parallel to TLRs', to solicit inflammatory reactions. Thus, in this scenario,RAGE may play a prominent role in the regulation of cellular homeostasis in the context of complex disease progression.

  7. Effects of atorvastatin on progression of diabetic nephropathy and local RAGE and soluble RAGE expressions in rats

    Institute of Scientific and Technical Information of China (English)

    Lin LU; Wen-hui PENG; Wei WANG; Ling-jie WANG; Qiu-jing CHEN; Wei-feng SHEN

    2011-01-01

    Objective:Advanced glycation end-products (AGEs) exert inflammatory and oxidative stress insults to produce diabetic nephropathy mainly through the receptor for AGEs (RAGE).This study aimed to assess the effect of atorvastatin on diabetic nephropathy via soluble RAGE (sRAGE) and RAGE expressions in the rat kidney.Methods:Thirty-two male Sprague-Dawley rats were divided into four groups based on the presence or absence of streptozotocin-induced diabetes with or without atorvastatin treatment (10 mg/kg for 24 weeks).Serum sRAGE and glycated albumin (GA) levels were measured with enzyme-linked immunosorbent assay (ELISA) and improved bromocresol purple methods.Renal AGEs,RAGE,endogenous secretory RAGE (esRAGE),and sRAGE were determined with reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.Results:Mesangial expansion and microalbuminuria were aggravated in diabetic rats,and improved with atorvastatin treatment.Serum sRAGE levels were lower in diabetic than in normal rats.After atorvastatin treatment,serum and renal sRAGE levels were up-regulated,while renal RAGE expression was decreased in diabetic rats,associated with a reduction in accumulation of AGEs,though renal esRAGE mRNA expression was not significantly increased.Conclusions:Atorvastatin exerted a beneficial effect on diabetic nephropathy with reduced AGE accumulation,down-regulating RAGE expression and up-regulating sRAGE in the kidney.

  8. RAGE, receptor of advanced glycation endoproducts, negatively regulates chondrocytes differentiation.

    Directory of Open Access Journals (Sweden)

    Tatsuya Kosaka

    Full Text Available RAGE, receptor for advanced glycation endoproducts (AGE, has been characterized as an activator of osteoclastgenesis. However, whether RAGE directly regulates chondrocyte proliferation and differentiation is unclear. Here, we show that RAGE has an inhibitory role in chondrocyte differentiation. RAGE expression was observed in chondrocytes from the prehypertrophic to hypertrophic regions. In cultured cells, overexpression of RAGE or dominant-negative-RAGE (DN-RAGE demonstrated that RAGE inhibited cartilaginous matrix production, while DN-RAGE promoted production. Additionally, RAGE regulated Ihh and Col10a1 negatively but upregulated PTHrP receptor. Ihh promoter analysis and real-time PCR analysis suggested that downregulation of Cdxs was the key for RAGE-induced inhibition of chondrocyte differentiation. Overexpression of the NF-κB inhibitor I-κB-SR inhibited RAGE-induced NF-κB activation, but did not influence inhibition of cartilaginous matrix production by RAGE. The inhibitory action of RAGE was restored by the Rho family GTPases inhibitor Toxin B. Furthermore, inhibitory action on Ihh, Col10a1 and Cdxs was reproduced by constitutively active forms, L63RhoA, L61Rac, and L61Cdc42, but not by I-κB-SR. Cdx1 induced Ihh and Col10a1 expressions and directly interacted with Ihh promoter. Retinoic acid (RA partially rescued the inhibitory action of RAGE. These data combined suggests that RAGE negatively regulates chondrocyte differentiation at the prehypertrophic stage by modulating NF-κB-independent and Rho family GTPases-dependent mechanisms.

  9. "Uproar, bulk, rage, suffocation, effort unceasing, frenzied and vain": Beckett's Transports of Rage.

    Science.gov (United States)

    Smith, Russell

    2016-06-01

    In a 1961 interview, Beckett warded off philosophical interpretations of his work: 'I'm no intellectual. All I am is feeling'. Despite the emotional intensity of Beckett's post-war writing, Beckett criticism has tended to ignore this claim, preferring the kinds of philosophical readings that Beckett here rejects. In particular, Beckett criticism underestimates the element of rage in his work. This paper argues that Beckett's post-war breakthrough is enabled by a radical reconsideration of the nature of feeling and of rage in particular. It involves the rejection of the idea of rage as pathological and the embrace of a positive conception of rage as drive or compulsion, a locus of energy and even pleasure.This paper reads the 'Moran' section of Molloy as a kind of 'rage fable', drawing on the ancient Greek concept of thymos, of anger as a virtue. It draws on Alfred Adler's theory of the 'masculine protest', with which Beckett was familiar from his extensive note-taking on Adler in 1934-5, and Sianne Ngai's discussion of the distinction between irritation and rage. According to this reading, Moran's report charts a narrative of thymotic liberation from the irritations of servitude, prefiguring the Unnamable's abandonment to impersonal affective intensities. It ends by suggesting that the prose of the Trilogy might be better understood, not as a 'syntax of weakness' but as a 'syntax of rage', a stylistic correlative of the imperious drive of thymos. We might then begin to understand the Trilogy as the epic of a heroic, impersonal, implacable and liberated rage.

  10. "Uproar, bulk, rage, suffocation, effort unceasing, frenzied and vain": Beckett's Transports of Rage.

    Science.gov (United States)

    Smith, Russell

    2016-06-01

    In a 1961 interview, Beckett warded off philosophical interpretations of his work: 'I'm no intellectual. All I am is feeling'. Despite the emotional intensity of Beckett's post-war writing, Beckett criticism has tended to ignore this claim, preferring the kinds of philosophical readings that Beckett here rejects. In particular, Beckett criticism underestimates the element of rage in his work. This paper argues that Beckett's post-war breakthrough is enabled by a radical reconsideration of the nature of feeling and of rage in particular. It involves the rejection of the idea of rage as pathological and the embrace of a positive conception of rage as drive or compulsion, a locus of energy and even pleasure.This paper reads the 'Moran' section of Molloy as a kind of 'rage fable', drawing on the ancient Greek concept of thymos, of anger as a virtue. It draws on Alfred Adler's theory of the 'masculine protest', with which Beckett was familiar from his extensive note-taking on Adler in 1934-5, and Sianne Ngai's discussion of the distinction between irritation and rage. According to this reading, Moran's report charts a narrative of thymotic liberation from the irritations of servitude, prefiguring the Unnamable's abandonment to impersonal affective intensities. It ends by suggesting that the prose of the Trilogy might be better understood, not as a 'syntax of weakness' but as a 'syntax of rage', a stylistic correlative of the imperious drive of thymos. We might then begin to understand the Trilogy as the epic of a heroic, impersonal, implacable and liberated rage. PMID:26696308

  11. xRage Equation of State

    Energy Technology Data Exchange (ETDEWEB)

    Grove, John W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-16

    The xRage code supports a variety of hydrodynamic equation of state (EOS) models. In practice these are generally accessed in the executing code via a pressure-temperature based table look up. This document will describe the various models supported by these codes and provide details on the algorithms used to evaluate the equation of state.

  12. RAGE Expression and ROS Generation in Neurons: Differentiation versus Damage.

    Science.gov (United States)

    Piras, S; Furfaro, A L; Domenicotti, C; Traverso, N; Marinari, U M; Pronzato, M A; Nitti, M

    2016-01-01

    RAGE is a multiligand receptor able to bind advanced glycation end-products (AGEs), amphoterin, calgranulins, and amyloid-beta peptides, identified in many tissues and cells, including neurons. RAGE stimulation induces the generation of reactive oxygen species (ROS) mainly through the activity of NADPH oxidases. In neuronal cells, RAGE-induced ROS generation is able to favor cell survival and differentiation or to induce death through the imbalance of redox state. The dual nature of RAGE signaling in neurons depends not only on the intensity of RAGE activation but also on the ability of RAGE-bearing cells to adapt to ROS generation. In this review we highlight these aspects of RAGE signaling regulation in neuronal cells.

  13. RAGE regulates immune cell infiltration and angiogenesis in choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Mei Chen

    Full Text Available PURPOSE: RAGE regulates pro-inflammatory responses in diverse cells and tissues. This study has investigated if RAGE plays a role in immune cell mobilization and choroidal neovascular pathology that is associated with the neovascular form of age-related macular degeneration (nvAMD. METHODS: RAGE null (RAGE-/- mice and age-matched wild type (WT control mice underwent laser photocoagulation to generate choroidal neovascularization (CNV lesions which were then analyzed for morphology, S100B immunoreactivity and inflammatory cell infiltration. The chemotactic ability of bone marrow derived macrophages (BMDMs towards S100B was investigated. RESULTS: RAGE expression was significantly increased in the retina during CNV of WT mice (p<0.001. RAGE-/- mice exhibited significantly reduced CNV lesion size when compared to WT controls (p<0.05. S100B mRNA was upregulated in the lasered WT retina but not RAGE-/- retina and S100B immunoreactivity was present within CNV lesions although levels were less when RAGE-/- mice were compared to WT controls. Activated microglia in lesions were considerably less abundant in RAGE-/- mice when compared to WT counterparts (p<0.001. A dose dependent chemotactic migration was observed in BMDMs from WT mice (p<0.05-0.01 but this was not apparent in cells isolated from RAGE-/- mice. CONCLUSIONS: RAGE-S100B interactions appear to play an important role in CNV lesion formation by regulating pro-inflammatory and angiogenic responses. This study highlights the role of RAGE in inflammation-mediated outer retinal pathology.

  14. Cultural Causes of Rage and Violence in Children and Youth.

    Science.gov (United States)

    Manno, Carla J.; Bantz, Jeanmarie; Kauffman, James M.

    2000-01-01

    Examines differences between rage and violence. States that attitudes towards violence are influenced by: family, peer group, the media, weapons, school structure, and community. Strategies for preventing rage and aggression include: (1) communicating clear behavioral expectations; (2) giving frequent praise and other forms of recognition; and (3)…

  15. The Rejection-Rage Contingency in Borderline Personality Disorder

    Science.gov (United States)

    Berenson, Kathy R.; Downey, Geraldine; Rafaeli, Eshkol; Coifman, Karin; Leventhal, Nina

    2011-01-01

    Though longstanding clinical observation reflected in the DSM-IV suggests that the rage characteristic of borderline personality disorder (BPD) often appears in response to perceived rejection, the role of perceived rejection in triggering rage in BPD has never been empirically tested. Extending basic personality research on rejection sensitivity to a clinical sample, a priming-pronunciation experiment and a 21-day experience-sampling diary examined the contingent relationship between perceived rejection and rage in participants diagnosed with BPD compared to healthy controls. Despite the differences in these two assessment methods, the indices of rejection-contingent rage that they produced were both elevated in the BPD group, and were strongly interrelated. They provide corroborating evidence that reactions to perceived rejection significantly explain the rage seen in BPD. PMID:21500875

  16. xRage: HE initiation models

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Laboratory; Scovel, Christina A. [Los Alamos National Laboratory

    2012-06-01

    The xRage code contains three HE ignition models: Forest Fire, Cerro Grande and Ignition and Growth. After describing these models we present results of verification and validation (V and V) tests. These include simulations to determine the Pop-plot for each model and comparision with embedded velocity gauge data for shock-to-detonation transition (SDT) experiments. The data for the SDT experiments on PBX 9502 is taken from the recently developed high explosive database (HED). The HED data files contains additional meta-data with the key experimental parameters. This enables the use of scripts to automate testing: generating xRage input file, running simulation and generating comparison plots with experimental and simulated data. The simulations show that the models are robust. But there is a mesh dependence with the time for transition-to-detonation varying by several tenths of microseconds. After the transition to a detonation wave, the detonation speed and pressure may vary by a few per cent.

  17. RNAi-Assisted Genome Evolution (RAGE) in Saccharomyces cerevisiae.

    Science.gov (United States)

    Si, Tong; Zhao, Huimin

    2016-01-01

    RNA interference (RNAi)-assisted genome evolution (RAGE) applies directed evolution principles to engineer Saccharomyces cerevisiae genomes. Here, we use acetic acid tolerance as a target trait to describe the key steps of RAGE. Briefly, iterative cycles of RNAi screening are performed to accumulate multiplex knockdown modifications, enabling directed evolution of the yeast genome and continuous improvement of a target phenotype. Detailed protocols are provided on the reconstitution of RNAi machinery, creation of genome-wide RNAi libraries, identification and integration of beneficial knockdown cassettes, and repeated RAGE cycles. PMID:27581294

  18. The S100B/RAGE Axis in Alzheimer's Disease

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    Estelle Leclerc

    2010-01-01

    Full Text Available Increasing evidence suggests that the small EF-hand calcium-binding protein S100B plays an important role in Alzheimer's disease. Among other evidences are the increased levels of both S100B and its receptor, the Receptor for Advanced Glycation Endproducts (RAGEs in the AD diseased brain. The regulation of RAGE signaling by S100B is complex and probably involves other ligands including the amyloid beta peptide (A, the Advanced Glycation Endproducts (AGEs, or transtheyretin. In this paper we discuss the current literature regarding the role of S100B/RAGE activation in Alzheimer's disease.

  19. Pentamidine blocks the interaction between mutant S100A5 and RAGE V domain and inhibits the RAGE signaling pathway.

    Science.gov (United States)

    Cho, Ching Chang; Chou, Ruey Hwang; Yu, Chin

    2016-08-19

    The human S100 protein family contains small, dimeric and acidic proteins that contain two EF-hand motifs and bind calcium. When S100A5 binds calcium, its conformation changes and promotes interaction with the target protein. The extracellular domain of RAGE (Receptor of Advanced Glycation End products) contain three domains: C1, C2 and V. The RAGE V domain is the target protein of S100A5 that promotes cell survival, growth and differentiation by activating several signaling pathways. Pentamidine is an apoptotic and antiparasitic drug that is used to treat or prevent pneumonia. Here, we found that pentamidine interacts with S100A5 using HSQC titration. We elucidated the interactions of S100A5 with RAGE V domain and pentamidine using fluorescence and NMR spectroscopy. We generated two binary models-the S100A5-RAGE V domain and S100A5-Pentamidine complex-and then observed that the pentamidine and RAGE V domain share a similar binding region in mS100A5. We also used the WST-1 assay to investigate the bioactivity of S100A5, RAGE V domain and pentamidine. These results indicated that pentamidine blocks the binding between S100A5 and RAGE V domain. This finding is useful for the development of new anti-proliferation drugs. PMID:27297108

  20. Thalamus segmentation from MP2RAGE: a comparative study

    DEFF Research Database (Denmark)

    Eskildsen, Simon Fristed; Næss-Schmidt, Erhard; Blicher, Jakob;

    MPRAGE images with different inversion times to construct an MP2RAGE image, free of B1 bias problems [1]. Since this so-called MP2RAGE sequence is independent of B1 as well as M0 and T2*, the T1 image contrast is improved but also different from conventional MPRAGE images. Thus, existing segmentation...... methods may not work well with this new sequence. In this study we tested three different automatic methods for the important task of segmenting the thalamus from human brain MP2RAGE images. Methods: Twelve healthy control subjects (age range 19 – 38 years, two females) were scanned with a whole brain MP2...... the thalami of all subjects using in-house software. Images were separately processed with Freesurfer (version 5.3) [2] and a recent processing pipeline [3], where anatomical structures are segmented with ANIMAL [4]. Finally, a non-local means patch based segmentation method (SNIPE) was applied using...

  1. Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

    OpenAIRE

    Radha Ananthakrishnan; Ravichandran Ramasamy; Karen M O'Shea; Carmen Hurtado del Pozo; Gurdip Daffu; Ann Marie Schmidt

    2013-01-01

    Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE) mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS) and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplificatio...

  2. RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro

    NARCIS (Netherlands)

    Steenvoorden, M.M.C.; Toes, R.E.M.; Ronday, H.K.; Huizinga, T.W.J.; Groot, J. de

    2007-01-01

    Ligands for the receptor for advanced glycation endproducts (RAGE) are increased in RA synovial fluid (SF), serum and synovium. Since RAGE is present on fibroblast-like synoviocytes (FLS), the present study investigates whether the RAGE ligands HMGB-1 and AGEs are able to stimulate the characteristi

  3. RAGE Architecture for Reusable Serious Gaming Technology Components

    Directory of Open Access Journals (Sweden)

    Wim van der Vegt

    2016-01-01

    Full Text Available For seizing the potential of serious games, the RAGE project—funded by the Horizon-2020 Programme of the European Commission—will make available an interoperable set of advanced technology components (software assets that support game studios at serious game development. This paper describes the overall software architecture and design conditions that are needed for the easy integration and reuse of such software assets in existing game platforms. Based on the component-based software engineering paradigm the RAGE architecture takes into account the portability of assets to different operating systems, different programming languages, and different game engines. It avoids dependencies on external software frameworks and minimises code that may hinder integration with game engine code. Furthermore it relies on a limited set of standard software patterns and well-established coding practices. The RAGE architecture has been successfully validated by implementing and testing basic software assets in four major programming languages (C#, C++, Java, and TypeScript/JavaScript, resp.. Demonstrator implementation of asset integration with an existing game engine was created and validated. The presented RAGE architecture paves the way for large scale development and application of cross-engine reusable software assets for enhancing the quality and diversity of serious gaming.

  4. RAGE Architecture for Reusable Serious Gaming Technology Components

    NARCIS (Netherlands)

    Van der Vegt, Wim; Westera, Wim; Nyamsuren, Enkhbold; Georgiev, Atanas; Martinez Ortiz, Ivan

    2016-01-01

    For seizing the potential of serious games, the RAGE project - funded by the Horizon-2020 Programme of the European Commission - will make available an interoperable set of advanced technology components (software assets) that support game studios at serious game development. This paper describes th

  5. Physical and situational inequality on airplanes predicts air rage.

    Science.gov (United States)

    DeCelles, Katherine A; Norton, Michael I

    2016-05-17

    We posit that the modern airplane is a social microcosm of class-based society, and that the increasing incidence of "air rage" can be understood through the lens of inequality. Research on inequality typically examines the effects of relatively fixed, macrostructural forms of inequality, such as socioeconomic status; we examine how temporary exposure to both physical and situational inequality, induced by the design of environments, can foster antisocial behavior. We use a complete set of all onboard air rage incidents over several years from a large, international airline to test our predictions. Physical inequality on airplanes-that is, the presence of a first class cabin-is associated with more frequent air rage incidents in economy class. Situational inequality-boarding from the front (requiring walking through the first class cabin) versus the middle of the plane-also significantly increases the odds of air rage in both economy and first class. We show that physical design that highlights inequality can trigger antisocial behavior on airplanes. More broadly, these results point to the importance of considering the design of environments-from airplanes to office layouts to stadium seating-in understanding both the form and emergence of antisocial behavior. PMID:27140642

  6. Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

    Directory of Open Access Journals (Sweden)

    Radha Ananthakrishnan

    2013-10-01

    Full Text Available Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease.

  7. Receptor for Advanced Glycation End Products (RAGE) Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia.

    Science.gov (United States)

    Achouiti, Ahmed; de Vos, Alex F; van 't Veer, Cornelis; Florquin, Sandrine; Tanck, Michael W; Nawroth, Peter P; Bierhaus, Angelika; van der Poll, Tom; van Zoelen, Marieke A D

    2016-01-01

    Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE) is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K.) pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/-) and normal wild-type (Wt) mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated-if any-cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS) with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous) RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS. PMID:26824892

  8. Receptor for Advanced Glycation End Products (RAGE Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia.

    Directory of Open Access Journals (Sweden)

    Ahmed Achouiti

    Full Text Available Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K. pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/- and normal wild-type (Wt mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated-if any-cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS.

  9. The effects of Advanced Glycation End Products (RAGE)-374T/A and Gly82Ser variants and soluble-RAGE levels to obesity in children.

    Science.gov (United States)

    Kucukhuseyin, O; Ozgen, T; Karagedik, E H; Cesur, Y; Yilmaz Aydogan, H; Yaylim, I; Ergen, H A

    2016-04-30

    In recent years, studies related to advanced glycation end products (AGE) and their interaction with their receptors (RAGE) have advanced our knowledge of the roles of these molecules in different diseases. However, studies concerning AGE-RAGE interaction in obesity are limited and the results are conflicting. RAGE gene is located on 6p21.3, has several polymorphic sites including -374T/A, a functional polymorphism in the promoter region, and Gly82Ser, present within the ligand-binding domain. In the present study, the determination of possible risks in the development of obesity according to RAGE polymorhisms and plasma levels of RAGE (sRAGE) was aimed. 87 obese and 78 healthy children were included in this study. Genomic DNA was isolated with salting-out procedure. RAGE polymorphisms were analyzed by PCR based techniques. In contrast to Gly82Ser, -374T/A allelic and genotypic frequencies were not different between study groups. Ser(SerSer+GlySer genotype) allele frequency was higher in obese cases than controls (74.20%→25.80%,OR:2.573,95%CI:1.789-3.699;pGlySer>GlyGly for HDL-C, and opposite for FT4. Besides, Ser carriers had lower insulin (p=0.038) and homa-IR (p=0.081) levels than GG genotype. sRAGE levels were different between obese and control seperately or in combination with RAGE polymorphisms (pTA>AA for -374T/A and SerSer>GlyGly>GlySer for Gly82Ser. According to our results SerSer genotype could have significant effects on sRAGE levels, and increased sRAGE levels and Gly82Ser polymorphism either combinatorially or seperately increased the propensity towards obesity.

  10. Regulation of Receptor for Advanced Glycation End Products (RAGE) Ectodomain Shedding and Its Role in Cell Function.

    Science.gov (United States)

    Braley, Alex; Kwak, Taekyoung; Jules, Joel; Harja, Evis; Landgraf, Ralf; Hudson, Barry I

    2016-06-01

    The receptor for advanced glycation end products (RAGE) is a multiligand transmembrane receptor that can undergo proteolysis at the cell surface to release a soluble ectodomain. Here we observed that ectodomain shedding of RAGE is critical for its role in regulating signaling and cellular function. Ectodomain shedding of both human and mouse RAGE was dependent on ADAM10 activity and induced with chemical activators of shedding (ionomycin, phorbol 12-myristate 13-acetate, and 4-aminophenylmercuric acetate) and endogenous stimuli (serum and RAGE ligands). Ectopic expression of the splice variant of RAGE (RAGE splice variant 4), which is resistant to ectodomain shedding, inhibited RAGE ligand dependent cell signaling, actin cytoskeleton reorganization, cell spreading, and cell migration. We found that blockade of RAGE ligand signaling with soluble RAGE or inhibitors of MAPK or PI3K blocked RAGE-dependent cell migration but did not affect RAGE splice variant 4 cell migration. We finally demonstrated that RAGE function is dependent on secretase activity as ADAM10 and γ-secretase inhibitors blocked RAGE ligand-mediated cell migration. Together, our data suggest that proteolysis of RAGE is critical to mediate signaling and cell function and may therefore emerge as a novel therapeutic target for RAGE-dependent disease states. PMID:27022018

  11. Small Molecule Inhibition of Ligand-Stimulated RAGE-DIAPH1 Signal Transduction

    Science.gov (United States)

    Manigrasso, Michaele B.; Pan, Jinhong; Rai, Vivek; Zhang, Jinghua; Reverdatto, Sergey; Quadri, Nosirudeen; DeVita, Robert J.; Ramasamy, Ravichandran; Shekhtman, Alexander; Schmidt, Ann Marie

    2016-01-01

    The receptor for advanced glycation endproducts (RAGE) binds diverse ligands linked to chronic inflammation and disease. NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms. The cytoplasmic tail (ct) of RAGE is essential for RAGE ligand-mediated signal transduction and consequent modulation of gene expression and cellular properties. RAGE signaling requires interaction of ctRAGE with the intracellular effector, mammalian diaphanous 1 or DIAPH1. We screened a library of 58,000 small molecules and identified 13 small molecule competitive inhibitors of ctRAGE interaction with DIAPH1. These compounds, which exhibit in vitro and in vivo inhibition of RAGE-dependent molecular processes, present attractive molecular scaffolds for the development of therapeutics against RAGE-mediated diseases, such as those linked to diabetic complications, Alzheimer’s disease, and chronic inflammation, and provide support for the feasibility of inhibition of protein-protein interaction (PPI). PMID:26936329

  12. The receptor for advanced glycation end products (RAGE) affects T cell differentiation in OVA induced asthma.

    Science.gov (United States)

    Akirav, Eitan M; Henegariu, Octavian; Preston-Hurlburt, Paula; Schmidt, Ann Marie; Clynes, Raphael; Herold, Kevan C

    2014-01-01

    The receptor for glycation end products (RAGE) has been previously implicated in shaping the adaptive immune response. RAGE is expressed in T cells after activation and constitutively in T cells from patients with diabetes. The effects of RAGE on adaptive immune responses are not clear: Previous reports show that RAGE blockade affects Th1 responses. To clarify the role of RAGE in adaptive immune responses and the mechanisms of its effects, we examined whether RAGE plays a role in T cell activation in a Th2 response involving ovalbumin (OVA)-induced asthma in mice. WT and RAGE deficient wild-type and OT-II mice, expressing a T cell receptor specific for OVA, were immunized intranasally with OVA. Lung cellular infiltration and T cell responses were analyzed by immunostaining, FACS, and multiplex bead analyses for cytokines. RAGE deficient mice showed reduced cellular infiltration in the bronchial alveolar lavage fluid and impaired T cell activation in the mediastinal lymph nodes when compared with WT mice. In addition, RAGE deficiency resulted in reduced OT-II T cell infiltration of the lung and impaired IFNγ and IL-5 production when compared with WT mice and reduced infiltration when transferred into WT hosts. When cultured under conditions favoring the differentiation of T cells subsets, RAGE deficient T cells showed reduced production of IFNγ but increased production of IL-17. Our data show a stimulatory role for RAGE in T activation in OVA-induced asthma. This role is largely mediated by the effects of RAGE on T cell proliferation and differentiation. These findings suggest that RAGE may play a regulatory role in T cell responses following immune activation.

  13. RAGE Architecture for Reusable Serious Gaming Technology Components

    OpenAIRE

    Wim van der Vegt; Wim Westera; Enkhbold Nyamsuren; Atanas Georgiev; Iván Martínez Ortiz

    2016-01-01

    For seizing the potential of serious games, the RAGE project - funded by the Horizon-2020 Programme of the European Commission - will make available an interoperable set of advanced technology components (software assets) that support game studios at serious game development. This paper describes the overall software architecture and design conditions that are needed for the easy integration and reuse of such software assets in existing game platforms. Based on the component-based software en...

  14. Women's Experiences of Rage towards their Intimate Partners: Diverse Voices within the Criminal Justice System

    OpenAIRE

    Flemke, Kimberly Renee

    2003-01-01

    "Women's Experiences of Rage towards their Intimate Partners: Diverse Voices within the Criminal Justice System" By: Kimberly R. Flemke Abstract A multi-method study investigating incarcerated womenâ s experiences of rage towards their intimate partners was conducted. The sample was drawn from a Philadelphia prisonâ s recovery unit for women. Phenomenological and feminist critical theory perspectives guided the study; these combined approaches captured the essence of rage, while a...

  15. Dynamic changes in sRAGE levels and relationship with cardiac function in STEMI patients

    DEFF Research Database (Denmark)

    Jensen, Louise J N; Lindberg, Søren; Hoffmann, Søren;

    2015-01-01

    OBJECTIVES: Soluble receptor of advanced glycation end-products (sRAGE) may be a predictive biomarker in coronary artery disease (CAD). Patients with acute myocardial infarction (AMI) have higher sRAGE levels compared to healthy subjects. Accordingly, the aim of this study was to investigate......estimated by LVEF (P=0.008). Furthermore, sRAGE measured after pPCI associated with infarct size (P=0.038). CONCLUSIONS: sRAGE levels were high in the early phase rather than in the days after AMI and pPCI. The increase...

  16. Driving frequency and Its impact on road rage offending and victimization: a view from opportunity theory.

    Science.gov (United States)

    Asbridge, Mark; Butters, Jennifer

    2013-01-01

    Road rage has been described as a key criminal justice and public health concern. Although research attention to this issue has expanded dramatically, most of this work has focused on the identification of predisposing individual factors. It is equally important to begin to assess those factors that may modify the likelihood of road rage including the broader structural opportunities that are connected with the propensity to be involved in a road rage incident. Drawing on opportunity theory, this article examines whether there is a relationship between increased opportunities to be involved in road rage and an increased likelihood of being a road rage victim or offender. The analysis is further extended to specifically test whether this relationship is linear, thereby examining the applicability of the opportunity saturation hypothesis. Using data from the Centre for Addiction and Mental Health (CAMH) Monitor, our findings support both the application of opportunity theory to understanding road rage and the presence of opportunity saturation. Although a clear relationship exists between kilometers driven and experiences of road rage, evidence emerged suggesting there may be a threshold whereby increased opportunities for road rage do not lead to road rage behavior.

  17. Soluble RAGE Treatment Delays Progression of Amyotrophic Lateral Sclerosis in SOD1 Mice

    Directory of Open Access Journals (Sweden)

    Judyta K Juranek

    2016-05-01

    Full Text Available The etiology of amyotrophic lateral sclerosis (ALS, a fatal motor neuron disorder characterized by progressive muscle weakness and spasticity, remains largely unknown. Approximately 5-10% of cases are familial, and of those, 15-20% are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1. Mutations of the SOD1 gene interrupt cellular homeostasis and contribute to cellular toxicity evoked by the presence of altered SOD1, along with other toxic species, such as advanced glycation end products (AGEs. AGEs trigger activation of their chief cell surface receptor, RAGE (receptor for advanced glycation end products, and induce RAGE-dependent cellular stress and inflammation in neurons, thereby affecting their function and leading to apoptosis. Here, we show for the first time that the expression of RAGE is higher in the SOD1 transgenic mouse model of ALS versus wild-type mouse spinal cord. We tested whether pharmacological blockade of RAGE may delay the onset and progression of disease in this mouse model. Our findings reveal that treatment of SOD1 transgenic mice with soluble RAGE (sRAGE, a natural competitor of RAGE that sequesters RAGE ligands and blocks their interaction with cell surface RAGE, significantly delays the progression of ALS and prolongs life span compared to vehicle treatment. We demonstrate that in sRAGE-treated SOD1 transgenic animals at the final stage of the disease, a significantly higher number of neurons and lower number of astrocytes is detectable in the spinal cord. We conclude that RAGE antagonism may provide a novel therapeutic strategy for ALS intervention.

  18. Images en mouvement stockage, repérage, indexation

    CERN Document Server

    Turner, James

    1998-01-01

    L'avènement puis la fusion des nouveaux modes de communication que sont l'informatique, les télécommunications et l'audiovisuel ont mis à la portée de tous une grande quantité d'images fixes et en mouvement dont la conservation et le repérage risquent de prendre des proportions démesurées. Le présent ouvrage veut offrir aux responsables de collection des repères pour aborder la problématique de l'indexation des images et faciliter l'accès des usagers à ces images.

  19. Role of the RAGE Axis during the Immune Response after Severe Trauma: A Prospective Pilot Study

    Directory of Open Access Journals (Sweden)

    Florian Uhle

    2015-01-01

    Full Text Available Background. Severe traumatization induces a complex pathophysiology, driven by the patient’s own immune system. The initial activation is a result of damage-associated molecular patterns, which are released from disrupted and dying cells and recognized by immune receptors, for example, RAGE. In this study we aimed to evaluate the contribution of the RAGE axis to early and late immune responses. Methods. We enrolled 16 patients with severe trauma together with 10 patients after major abdominal surgery and 10 healthy volunteers. Blood samples were taken on admission and every 48 h for a total of 8 days. Plasma concentrations of various RAGE ligands as well as RAGE isoforms and IL-6 were measured by ELISA. Monocyte surface expression of RAGE and HLA-DR was assessed by flow cytometry. Results. High and transient levels of IL-6 and methylglyoxal characterize the early immune response after trauma, whereas samples from later time points provide evidence for a secondary release of RAGE ligands. Conclusion. Our results provide evidence for a persisting activation of the RAGE axis while classical mediators like IL-6 disappear early. Considering the immunocompromised phenotype of the monocytes, the RAGE ligands might be substantial contributors to the well-known secondary stage of impaired immune responsiveness in trauma patients.

  20. Rage Attacks in Pediatric Obsessive-Compulsive Disorder: Phenomenology and Clinical Correlates

    Science.gov (United States)

    Storch, Eric A.; Jones, Anna M.; Lack, Caleb W.; Ale, Chelsea M.; Sulkowski, Michael L.; Lewin, Adam B.; De Nadai, Alessandro S.; Murphy, Tanya K.

    2012-01-01

    Objective: Rage attacks have been documented in youth with varied psychiatric disorders, but few data have been reported on the clinical characteristics and correlates of rage attacks among children with obsessive-compulsive disorder (OCD). Method: Participants were 86 children (ages 6-16 years) with a primary diagnosis of OCD. Patients and their…

  1. The receptor for advanced glycation end products (RAGE) and the lung.

    LENUS (Irish Health Repository)

    Buckley, Stephen T

    2010-01-01

    The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. As a pattern-recognition receptor capable of binding a diverse range of ligands, it is typically expressed at low levels under normal physiological conditions in the majority of tissues. In contrast, the lung exhibits high basal level expression of RAGE localised primarily in alveolar type I (ATI) cells, suggesting a potentially important role for the receptor in maintaining lung homeostasis. Indeed, disruption of RAGE levels has been implicated in the pathogenesis of a variety of pulmonary disorders including cancer and fibrosis. Furthermore, its soluble isoforms, sRAGE, which act as decoy receptors, have been shown to be a useful marker of ATI cell injury. Whilst RAGE undoubtedly plays an important role in the biology of the lung, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.

  2. Cell migration is regulated by AGE-RAGE interaction in human oral cancer cells in vitro.

    Directory of Open Access Journals (Sweden)

    Shun-Yao Ko

    Full Text Available Advanced glycation end products (AGEs are produced in an irreversible non-enzymatic reaction of carbohydrates and proteins. Patients with diabetes mellitus (DM are known to have elevated AGE levels, which is viewed as a risk factor of diabetes-related complications. In a clinical setting, it has been shown that patients with oral cancer in conjunction with DM have a higher likelihood of cancer metastasis and lower cancer survival rates. AGE-RAGE (a receptor of AGEs is also correlated with metastasis and angiogenesis. Recent studies have suggested that the malignancy of cancer may be enhanced by glyceraldehyde-derived AGEs; however, the underlying mechanism remains unclear. This study examined the apparently close correlation between AGE-RAGE and the malignancy of SAS oral cancer cell line. In this study, AGEs increased ERK phosphorylation, enhanced cell migration, and promoted the expression of RAGE, MMP2, and MMP9. Using PD98059, RAGE antibody, and RAGE RNAi to block RAGE pathway resulted in the inhibition of ERK phosphorylation. Cell migration, MMP2 and MMP9 expression were also reduced by this treatment. Our findings demonstrate the importance of AGE-RAGE with regard to the malignancy of oral cancer, and help to explain the poor prognosis of DM subjects with oral cancer.

  3. sRAGE与糖尿病及其并发症%sRAGE, diabetes and its complications

    Institute of Scientific and Technical Information of China (English)

    苏旭东; 田亚强; 张光珍

    2011-01-01

    Interaction of advanced glycation end products (AGEs) with their receptor (RAGE)plays an important role in the occurance and development of diabetes and its complications. RAGE has an endogenous secretory receptor form, termed soluble RAGE( sRAGE), which might act as an endogenous competitive inhibitor of RAGE. The level of sRAGE decreases in patients with diabetes, while some drugs, such as statins, thiazolidinediones, inhibitors of angiotensin-converting enzyme also increase plasma sRAGE level.Further studies of sRAGE may provide a new drug for the treatment of diabetes and its complications.%晚期糖基化终末产物(AGEs)与其受体(RAGE)在糖尿病及其并发症的发生、发展中起重要作用.缺少胞内区的RAGE称为可溶性RAGE(sRAGE).其可阻断配体与RAGE的结合.糖尿病患者sRAGE水平明显降低,而他汀类、噻唑烷二酮类、血管紧张素转换酶抑制剂等药物可以提高血清sRAGE水平.对sRAGE的进一步研究有可能为糖尿病及其并发症的治疗提供新的药物.

  4. Decreased Neointimal Extracellular Matrix Formation in RAGE-Knockout Mice After Microvascular Denudation

    Energy Technology Data Exchange (ETDEWEB)

    Groezinger, Gerd, E-mail: gerd.groezinger@med.uni-tuebingen.de; Schmehl, Joerg, E-mail: joerg.schmehl@med.uni-tuebingen.de; Bantleon, Ruediger, E-mail: ruediger.bantleon@med.uni-tuebingen.de; Kehlbach, Rainer, E-mail: rainer.kehlbach@uni-tuebingen.de [University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany); Mehra, Tarun, E-mail: tarun.mehra@med.uni-tuebingen.de [University of Tuebingen, Department of Dermatology (Germany); Claussen, Claus, E-mail: gerd.groezinger@med.uni-tuebingen.de; Wiesinger, Benjamin, E-mail: benjamin.wiesinger@med.uni-tuebingen.de [University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany)

    2012-12-15

    Purpose: To evaluate in vivo the role of RAGE (receptor for advanced glycated end products) in the development of restenosis and neointimal proliferation in RAGE-deficient knockout (KO) mice compared with wild-type (WT) mice in an animal model. Materials and Methods: Sixteen WT and 15 RAGE-deficient mice underwent microvascular denudation of the common femoral artery under general anaesthesia. Contralateral arteries underwent a sham operation and served as controls. Four weeks after the intervention, all animals were killed, and paraformaldehyde-fixed specimens of the femoral artery were analysed with different stains (hematoxylin and eosin and Elastica van Gieson) and several different types of immunostaining (proliferating cell nuclear antigen, {alpha}-actin, collagen, von Willebrand factor, RAGE). Luminal area, area of the neointima, and area of the media were measured in all specimens. In addition, colony-formation assays were performed, and collagen production by WT smooth muscle cells (SMCs) and RAGE-KO SMCs was determined. For statistical analysis, P < 0.05 was considered statistically significant. Results: Four weeks after denudation, WT mice showed a 49.6% loss of luminal area compared with 14.9% loss of luminal area in RAGE-deficient mice (sham = 0% loss) (P < 0.001). The neointima was 18.2 (*1000 {mu}m{sup 2} [n = 15) in the WT group compared with only 8.4 (*1000 {mu}m{sup 2} [n = 16]) in the RAGE-KO group. RAGE-KO SMCs showed significantly decreased proliferation activity and production of extracellular matrix protein. Conclusion: RAGE may be shown to play a considerable role in the formation of neointima leading to restenosis after vascular injury.

  5. MR imaging in epilepsy with use of 3D MP-RAGE

    International Nuclear Information System (INIS)

    The patients were 40 males and 33 females; their ages ranged from 1 month to 39 years (mean: 15.7 years). The patients underwent MR imaging, including spin-echo T1-weighted, turbo spin-echo proton density/T2-weighted, and 3D magnetization-prepared rapid gradient-echo (3D MP-RAGE) images. These examinations disclosed 39 focal abnormalities. On visual evaluation, the boundary of abnormal gray matter in the neuronal migration disorder (NMD) cases was most clealy shown on 3D MP-RAGE images as compared to the other images. This is considered to be due to the higher spatial resolution and the better contrast of the 3D MP-RAGE images than those of the other techniques. The relative contrast difference between abnormal gray matter and the adjacent white matter was also assessed. The results revealed that the contrast differences on the 3D MP-RAGE images were larger than those on the other images; this was statistically significant. Although the sensitivity of 3D MP-RAGE for NMD was not specifically evaluated in this study, the possibility of this disorder, in cases suspected on other images, could be ruled out. Thus, it appears that the specificity with respect to NMD was at least increased with us of 3D MP-RAGE. 3D MP-RAGE also enabled us to build three-dimensional surface models that were helpful in understanding the three-dimensional anatomy. Furthermore. 3D MP-RAGE was considered to be the best technique for evaluating hippocampus atrophy in patients with MTS. On the other hand, the sensitivity in the signal change of the hippocampus was higher on T2-weighted images. In addition, demonstration of cortical tubers of tuberous sclerosis in neurocutaneous syndrome was superior on T2-weighted images than on 3D MP-RAGE images. (K.H.)

  6. Blockade of RAGE in Zucker obese rats with experimental periodontitis

    DEFF Research Database (Denmark)

    Grauballe, M B; Østergaard, J A; Schou, S;

    2016-01-01

    BACKGROUND AND OBJECTIVE: Periodontitis and type 2 diabetes mellitus (T2D) are two interrelated chronic diseases. Periodontitis is more prevalent in patients with T2D than in healthy subjects, and studies indicate that periodontitis impacts the metabolic control of patients with T2D. Hyperglycemia...... on the interrelationship between periodontitis and T2D in a rat model of both diseases. MATERIAL AND METHODS: Zucker obese rats (HsdHlr:ZUCKER-Lepr (fa/fa) ) and their lean littermates were divided into five treatment groups, with and without periodontitis. Monoclonal anti-RAGE IgG3 were injected into the rats three times...... evaluated in plasma. Kidney complications were evaluated by quantitative real-time PCR, the creatinine clearance rate, the albumin excretion rate and kidney hypertrophy. Periodontitis was evaluated by morphometric registration of alveolar bone loss and radiographic recording of bone support. RESULTS...

  7. MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Yuhki; Sakuraoka; Tokihiko; Sawada; Toshie; Okada; Takayuki; Shiraki; Yoshikazu; Miura; Katsuya; Hiraishi; Tatsushi; Ohsawa; Masakazu; Adachi; Jun-ichi; Takino; Masayoshi; Takeuchi; Keiichi; Kubota

    2010-01-01

    AIM:To investigate the proliferative effect of advanced glycation end-products(AGEs) and the role of their cellular receptor(RAGE) on hepatocellular carcinoma(HCC) cells,and the inhibitory effects of MK615,an extract from Japanese apricot,against AGEs were also evaluated.METHODS:Two HCC cell lines,HuH7 and HepG2,were used.Expression of RAGE was investigated by poly-merase chain reaction,Western blotting,and flow cytemetry(FACS).The effect of MK615 on RAGE expression was also evaluated by FACS.The proliferat...

  8. Pyrazole-5-carboxamides, novel inhibitors of receptor for advanced glycation end products (RAGE).

    Science.gov (United States)

    Han, Young Taek; Kim, Kyeojin; Choi, Gyeong-In; An, Hongchan; Son, Dohyun; Kim, Hee; Ha, Hee-Jin; Son, Jun-Hyeng; Chung, Suk-Jae; Park, Hyun-Ju; Lee, Jeewoo; Suh, Young-Ger

    2014-05-22

    In an effort to develop novel inhibitors of receptor for advanced glycation end products (RAGE) for the treatment of Alzheimer's disease, a series of pyrazole-5-carboxamides were designed, synthesized and biologically evaluated. Analyses of the extensive structure-activity relationship (SAR) led us to identify a 4-fluorophenoxy analog (40) that exhibited improved in vitro RAGE inhibitory activity and more favorable aqueous solubility than the parent 2-aminopyrimidine, 1. Surface plasmon resonance (SPR) and molecular docking study strongly supported the RAGE inhibitory activity of pyrazole-5-carboxamides. The brain Aβ-lowering effect of 40 is also described. PMID:24727489

  9. The role of S100 proteins and their receptor RAGE in pancreatic cancer.

    Science.gov (United States)

    Leclerc, Estelle; Vetter, Stefan W

    2015-12-01

    Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with low survival rates. Current therapeutic treatments have very poor response rates due to the high inherent chemoresistance of the pancreatic-cancer cells. Recent studies have suggested that the receptor for advanced glycation end products (RAGE) and its S100 protein ligands play important roles in the progression of PDAC. We will discuss the potential role of S100 proteins and their receptor, RAGE, in the development and progression of pancreatic cancer. PMID:26435083

  10. Expression and Clinical Significance of HMGB1 and RAGE in Cervical Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To study the expression level and clinical significance of HMGB1 and RAGE in cervical squamous epithelial carcinoma.METHODS Real time quantitative polymerase chain reaction (qRT-PCR)was employed to examine the expression of HMGB1 (high mobility group box protein1), and RAGE (receptor for advanced glycation endproducts)in 60 cervical squamous epithelial carcinomas (CSEC), their paraneoplastic tissues (PS) and 30 normal cervix tissues (NCS).RESULTS The expression of HMGB1 in the CSEC samples and PS was similar (P>0.05), but higher compared to NCS (P<0.05). Overexpression of HMGB1 in the CESC tissues was significantly correlated with the tumor (P<0.05), and the presence of metastasis (P<0.01), but not correlated with the tumor diameter or tumor grade. RAGE expression was not significantly different among these tissue types, and showed no significant correlation with the the tumor stage, diameter or grade. But there was a significant positive correlation between RAGE expression and CSEC metastasis.CONCLUSION The results suggest that HMGB1 may be related to the proliferation, progression and metastasis of CSEC. The relationship of HMGB1/RAGE may be of importance for CSEC metastasis. HMGB1 presents a new potential gene target for prevention and treatment of CSEC.Study of HMGB1/RAGE expression will offer an experimental foundation for understanding the pathogenesis of CSES.

  11. Soluble Levels of Receptor for Advanced Glycation Endproducts (RAGE) and Progression of Atherosclerosis in Individuals Infected with Human Immunodeficiency Virus: ACTG NWCS 332.

    Science.gov (United States)

    Danoff, Ann; Kendall, Michelle A; Currier, Judith S; Kelesidis, Theodoros; Schmidt, Ann Marie; Aberg, Judith A

    2016-08-01

    Identification of biomarkers and/or mediators of cardiovascular disease (CVD) associated with HIV infection would be of diagnostic and therapeutic value. As soluble receptor for advanced glycation endproducts (sRAGE) and endogenous secretory (esRAGE) have been implicated in vascular complications in other settings, we investigated whether either soluble form of RAGE was associated with changes in carotid intima-media thickness (CIMT) in HIV-infected patients and HIV-uninfected controls. We found no differences in sRAGE, esRAGE, or CIMT among groups at study entry, or in yearly rates of change in sRAGE, esRAGE, or CIMT by HIV-serostatus (all p > 0.10). However, yearly rates of change in sRAGE (p = 0.07) and esRAGE (p mediator of CVD in HIV-infected persons. PMID:27216802

  12. Road Rage: Prevalence Pattern and Web Based Survey Feasibility

    Directory of Open Access Journals (Sweden)

    Shaily Mina

    2014-01-01

    Full Text Available Introduction. Incidents of road rage are on a rise in India, but the literature is lacking in the aspect. There is an increasing realization of possibility of effective web based interventions to deliver public health related messages. Objective. The aim was to quantitatively evaluate risk factors among motor vehicle drivers using an internet based survey. Methods. Facebook users were evaluated using Life Orientation Test-Revised (LOT-R and Driving Anger Scale (DAS. Results. An adequate response rate of 65.9% and satisfactory reliability with sizable correlation were obtained for both scales. Age was found to be positively correlated to LOT-R scores (r=0.21; P=0.02 and negatively correlated to DAS scores (r=-0.19; P=0.03. Years of education were correlated to LOT-R scores (r=0.26; P=0.005 but not DAS scores (r=-0.14; P=0.11. LOT-R scores did not correlate to DAS scores. Conclusion. There is high prevalence of anger amongst drivers in India particularly among younger males. A short web survey formatted in easy to use question language can result in a feasible conduction of an online survey.

  13. HMGB1 and RAGE in skeletal muscle inflammation: Implications for protein accumulation in inclusion body myositis.

    Science.gov (United States)

    Muth, Ingrid E; Zschüntzsch, Jana; Kleinschnitz, Konstanze; Wrede, Arne; Gerhardt, Ellen; Balcarek, Peter; Schreiber-Katz, Olivia; Zierz, Stephan; Dalakas, Marinos C; Voll, Reinhard E; Schmidt, Jens

    2015-09-01

    Inflammation is associated with protein accumulation in IBM, but precise mechanisms are elusive. The "alarmin" HMGB1 is upregulated in muscle inflammation. Its receptor RAGE is crucial for β-amyloid-associated neurodegeneration. Relevant signaling via HMGB1/RAGE is expected in IBM pathology. By real-time-PCR, mRNA-expression levels of HMGB1 and RAGE were upregulated in muscle biopsies of patients with IBM and PM, but not in muscular dystrophy or non-myopathic controls. By immunohistochemistry, both molecules displayed the highest signal in IBM, where they distinctly co-localized to intra-fiber accumulations of β-amyloid and neurofilament/tau. In these fibers, identification of phosphorylated Erk suggested that relevant downstream activation is present upon HMGB1 signaling via RAGE. Protein expressions of HMGB1, RAGE, Erk and phosphorylated Erk were confirmed by Western blot. In a well established cell-culture model for pro-inflammatory cell-stress, exposure of human muscle-cells to IL-1β+IFN-γ induced cytoplasmic translocation of HMGB1 and subsequent release as evidenced by ELISA. Upregulation of RAGE on the cell surface was demonstrated by immunocytochemistry and flow-cytometry. Recombinant HMGB1 was equally potent as IL-1β+IFN-γ in causing amyloid-accumulation and cell-death, and both were abrogated by the HMGB1-blocker BoxA. The findings strengthen the concept of unique interactions between degenerative and inflammatory mechanisms and suggest that HMGB1/RAGE signaling is a critical pathway in IBM pathology.

  14. Receptor for Advanced Glycation End Products (RAGE) Deficiency Attenuates the Development of Atherosclerosis in Diabetes

    Science.gov (United States)

    Soro-Paavonen, Aino; Watson, Anna M.D.; Li, Jiaze; Paavonen, Karri; Koitka, Audrey; Calkin, Anna C.; Barit, David; Coughlan, Melinda T.; Drew, Brian G.; Lancaster, Graeme I.; Thomas, Merlin; Forbes, Josephine M.; Nawroth, Peter P.; Bierhaus, Angelika; Cooper, Mark E.; Jandeleit-Dahm, Karin A.

    2008-01-01

    OBJECTIVE—Activation of the receptor for advanced glycation end products (RAGE) in diabetic vasculature is considered to be a key mediator of atherogenesis. This study examines the effects of deletion of RAGE on the development of atherosclerosis in the diabetic apoE−/− model of accelerated atherosclerosis. RESEARCH DESIGN AND METHODS—ApoE−/− and RAGE−/−/apoE−/− double knockout mice were rendered diabetic with streptozotocin and followed for 20 weeks, at which time plaque accumulation was assessed by en face analysis. RESULTS—Although diabetic apoE−/− mice showed increased plaque accumulation (14.9 ± 1.7%), diabetic RAGE−/−/apoE−/− mice had significantly reduced atherosclerotic plaque area (4.9 ± 0.4%) to levels not significantly different from control apoE−/− mice (4.3 ± 0.4%). These beneficial effects on the vasculature were associated with attenuation of leukocyte recruitment; decreased expression of proinflammatory mediators, including the nuclear factor-κB subunit p65, VCAM-1, and MCP-1; and reduced oxidative stress, as reflected by staining for nitrotyrosine and reduced expression of various NADPH oxidase subunits, gp91phox, p47phox, and rac-1. Both RAGE and RAGE ligands, including S100A8/A9, high mobility group box 1 (HMGB1), and the advanced glycation end product (AGE) carboxymethyllysine were increased in plaques from diabetic apoE−/− mice. Furthermore, the accumulation of AGEs and other ligands to RAGE was reduced in diabetic RAGE−/−/apoE−/− mice. CONCLUSIONS—This study provides evidence for RAGE playing a central role in the development of accelerated atherosclerosis associated with diabetes. These findings emphasize the potential utility of strategies targeting RAGE activation in the prevention and treatment of diabetic macrovascular complications. PMID:18511846

  15. Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liang, E-mail: countryspring@sina.com; Ji, Yunxia, E-mail: 413499057@qq.com; Kang, Zechun, E-mail: davidjiangwl@163.com; Lv, Changjun, E-mail: Lucky_lcj@sina.com; Jiang, Wanglin, E-mail: jwl518@163.com

    2015-02-15

    An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  16. Donnees Serologiques sur la rage Vulpine Etudiee en Iran

    Directory of Open Access Journals (Sweden)

    Y. KARIMI

    1975-01-01

    Full Text Available During the epidemiological research of zoonoses, the authors have studied the rabies of wild animals : fox. For the scro lo-uical tests. the blood . was taken by heart puncture of foxes. 193 specimens were tested and 26 (13. 5% o r the foxes had neut ralizing antibody in their blood. This study confirms that during the rabies epizooty. the Vulpin population, may contract a non-fatal disease and produce the neutralizing antibody. Thus, the fox has a real place in the epidemiology of rabies in Iran."n* * *"nA la sui te des etudes effectuees par nous-merne (8, nous rapportons ici, les resultats scrologiques, des travaux acheves dans Ie but d'enrichir et  de completer les donnees precedentcs, Le present travail, ainsi que notre etude prcliminairc, ont etc realises dans la meme region, ccntree par le village d'AGH BOULAGH MORCHED, dans Ie Kurdistan, i186 Km au Nord-Ouest de HAMADAN (Ca rte N° I . Le role primordial du Renard, dans Ie processus de la Rage naturelle a deja fait l'objet de plusieurs articles (4, (5, (7, (17, (14, Cependant l'existence chez les animaux sauvages danticorps antirabiques n'est que rarement mentionnee dans ccs travaux. Les donnees experimentales ne peuvent pas toujours expliquer ce qui se passe dans les conditions naturelles de l'enzootie rabique, au point de vue de la reponse serologique chez Ie renard. C'est pourquoi nous nous sommes attaches a completer la recherche d'anticorps neutralisants antirabiques, chez Ie renard, dans son milieu nature!

  17. Ursodeoxycholic Acid (UDCA) Exerts Anti-Atherogenic Effects by Inhibiting RAGE Signaling in Diabetic Atherosclerosis.

    Science.gov (United States)

    Chung, Jihwa; An, Shung Hyun; Kang, Sang Won; Kwon, Kihwan

    2016-01-01

    A naturally occurring bile acid, ursodeoxycholic acid (UDCA), is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, the detailed action mechanisms of UDCA in atherosclerosis are not fully understood. In this study, we demonstrated whether UDCA exerts anti-atherogenic activity in diabetic atherosclerosis by targeting ER stress and "receptor for advanced glycation endproduct" (RAGE) signaling. UDCA markedly reduced ER stress, RAGE expression, and pro-inflammatory responses [including NF-κB activation and reactive oxygen species (ROS) production] induced in endothelial cells (ECs) by high glucose (HG). In particular, UDCA inhibited HG-induced ROS production by increasing the Nrf2 level. In macrophages, UDCA also blocked HG-induced RAGE and pro-inflammatory cytokine expression and inhibited foam cell formation via upregulation of the ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1. In the diabetic mouse model, UDCA inhibited atheromatous plaque formation by decreasing ER stress, and the levels of RAGE and adhesion molecules. In conclusion, UDCA exerts an anti-atherogenic activity in diabetic atherosclerosis by targeting both ER stress and RAGE signaling. Our work implicates UDCA as a potential therapeutic agent for prevention or treatment of diabetic atherosclerosis. PMID:26807573

  18. Periodontal disease and the oral-systemic connection: "is it all the RAGE?".

    Science.gov (United States)

    Katz, Joseph; Wallet, Shannon; Cha, Seunghee

    2010-03-01

    Ample studies have reported on the association between periodontal diseases, a persistent inflammatory process, and other chronic ailments such as cardiovascular diseases, diabetes mellitus, Alzheimer disease, and cancer. Other conditions such as low birth weight and premature delivery due to chorioamnionitis are also known to be linked to poor periodontal health. Although much epidemiologic data support these associations, a cause-and-effect relationship has not been established. The receptor for advanced glycation end products (RAGE) is a multiligand receptor expressed on various cell membranes, including immune, endothelial, and epithelial, and cells of the central nervous system. This receptor, which is frequently associated with proinflammatory responses, has been shown to be activated by various ligands such as high mobility group box-1 (HMGB1/amphoterin), amyloid fibrils, transthyrein, Mac-1 (Integrin Mac-1), as well as advanced glycation end products (AGEs). Recent studies indicate that signaling through RAGE has been implicated as an underlying condition in diverse pathologies including periodontal disease, cardiovascular diseases, diabetes mellitus, Alzheimer disease, cancer, and neurologic conditions. Review of the literature supports the hypothesis that activation of RAGE by ligands in a variety of cell types and tissues may play a role in oral systemic associations. In addition, the ligand cell source and timing of RAGE stimulation may determine the disease produced by this axis. Understanding the distribution and functions of RAGE and its ligands would enhance clinicians' knowledge on pathogenesis of the oral-systemic connection. PMID:20213024

  19. AGE-RAGE interaction in the TGFβ2-mediated epithelial to mesenchymal transition of human lens epithelial cells.

    Science.gov (United States)

    Raghavan, Cibin T; Nagaraj, Ram H

    2016-08-01

    Basement membrane (BM) proteins accumulate chemical modifications with age. One such modification is glycation, which results in the formation of advanced glycation endproducts (AGEs). In a previous study, we reported that AGEs in the human lens capsule (BM) promote the TGFβ2-mediated epithelial-to-mesenchymal transition (EMT) of lens epithelial cells, which we proposed as a mechanism for posterior capsule opacification (PCO) or secondary cataract formation. In this study, we investigated the role of a receptor for AGEs (RAGE) in the TGFβ2-mediated EMT in a human lens epithelial cell line (FHL124). RAGE was present in FHL124 cells, and its levels were unaltered in cells cultured on either native or AGE-modified BM or upon treatment with TGFβ2. RAGE overexpression significantly enhanced the TGFβ2-mediated EMT responses in cells cultured on AGE-modified BM compared with the unmodified matrix. In contrast, treatment of cells with a RAGE antibody or EN-RAGE (an endogenous ligand for RAGE) resulted in a significant reduction in the TGFβ2-mediated EMT response. This was accompanied by a reduction in TGFβ2-mediated Smad signaling and ROS generation. These results imply that the interaction of matrix AGEs with RAGE plays a role in the TGFβ2-mediated EMT of lens epithelial cells and suggest that the blockade of RAGE could be a strategy to prevent PCO and other age-associated fibrosis. PMID:27263094

  20. Structural insights into calcium-bound S100P and the V domain of the RAGE complex.

    Directory of Open Access Journals (Sweden)

    Srinivasa R Penumutchu

    Full Text Available The S100P protein is a member of the S100 family of calcium-binding proteins and possesses both intracellular and extracellular functions. Extracellular S100P binds to the cell surface receptor for advanced glycation end products (RAGE and activates its downstream signaling cascade to meditate tumor growth, drug resistance and metastasis. Preventing the formation of this S100P-RAGE complex is an effective strategy to treat various disease conditions. Despite its importance, the detailed structural characterization of the S100P-RAGE complex has not yet been reported. In this study, we report that S100P preferentially binds to the V domain of RAGE. Furthermore, we characterized the interactions between the RAGE V domain and Ca(2+-bound S100P using various biophysical techniques, including isothermal titration calorimetry (ITC, fluorescence spectroscopy, multidimensional NMR spectroscopy, functional assays and site-directed mutagenesis. The entropy-driven binding between the V domain of RAGE and Ca(+2-bound S100P was found to lie in the micromolar range (Kd of ∼ 6 µM. NMR data-driven HADDOCK modeling revealed the putative sites that interact to yield a proposed heterotetrameric model of the S100P-RAGE V domain complex. Our study on the spatial structural information of the proposed protein-protein complex has pharmaceutical relevance and will significantly contribute toward drug development for the prevention of RAGE-related multifarious diseases.

  1. Can Targeting the Incretin Pathway Dampen RAGE-Mediated Events in Diabetic Nephropathy?

    Science.gov (United States)

    Sourris, Karly C; Yao, Henry; Jerums, George; Cooper, Mark E; Ekinci, Elif I; Coughlan, Melinda T

    2016-01-01

    Diabetic nephropathy is the major cause of end-stage renal disease in Western societies. To date, interruption of the Renin-Angiotensin System is the most effective intervention for diabetic nephropathy, however these agents only slow progression of the disease. Thus, there is a major unmet need for new therapeutic targets. Aberrant activation of the receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic nephropathy via binding to a variety of ligands and inciting reactive oxygen species (ROS) production, inflammation and fibrosis. In recent years there have been considerable efforts in the development of effective RAGE antagonists, however, direct RAGE targeting may be problematic. Glucagon like peptide-1 (GLP-1) is an incretin hormone released by the L-cells of the small intestine to mediate glucose-dependent insulin release from pancreatic islets. The incretin-based therapies, GLP-1 receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors, are novel glucose-lowering agents used in type 2 diabetes. However, the extra pancreatic functions of GLP-1 have gained attention, including putative anti-apoptotic and anti-inflammatory properties. In rodent models of diabetes, incretin-based therapies are renoprotective. Interestingly, GLP-1 has been shown to interfere with the signalling and expression of RAGE. The current review aims to give an overview of the interactions between the RAGE and incretin pathways and to discuss the utility of targeting the GLP-1/incretin pathway in DN. It is possible that indirect targeting of RAGE through GLP-1 agonism will be of clinical benefit to patients with diabetic nephropathy. PMID:26201485

  2. Experiments at Scale with In-Situ Visualization Using ParaView/Catalyst in RAGE

    Energy Technology Data Exchange (ETDEWEB)

    Kares, Robert John [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-10-31

    In this paper I describe some numerical experiments performed using the ParaView/Catalyst in-situ visualization infrastructure deployed in the Los Alamos RAGE radiation-hydrodynamics code to produce images from a running large scale 3D ICF simulation on the Cielo supercomputer at Los Alamos. The detailed procedures for the creation of the visualizations using ParaView/Catalyst are discussed and several images sequences from the ICF simulation problem produced with the in-situ method are presented. My impressions and conclusions concerning the use of the in-situ visualization method in RAGE are discussed.

  3. "Love and Rage" in the Classroom: Planting the Seeds of Community Empowerment

    Science.gov (United States)

    Love, Kurt

    2012-01-01

    Although no one unified anarchist theory exists, educational approaches can be taken to support the full liberation of the self and the construction of an interconnected community that strives to rid itself of eco-sociocultural oppressions. An anarchist pedagogical approach could be one that is rooted in a love/rage unit of analysis occurring…

  4. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

    International Nuclear Information System (INIS)

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction

  5. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts.

    Science.gov (United States)

    Li, D X; Deng, T Z; Lv, J; Ke, J

    2014-12-01

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80 ± 5.50%, PBSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  6. Advanced glycation end products (AGEs and their receptor (RAGE induce apoptosis of periodontal ligament fibroblasts

    Directory of Open Access Journals (Sweden)

    D.X. Li

    2014-12-01

    Full Text Available Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL fibroblasts induced by advanced glycation end products (AGEs and their receptor (RAGE. We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA, bovine serum albumin (BSA alone, or given no treatment (control. Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01 and increased apoptosis (11.31±1.73%, P<0.05. Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  7. RAGE Reusable Game Software Components and Their Integration into Serious Game Engines

    NARCIS (Netherlands)

    VanderVegt, Wim; Nyamsuren, Enkhbold; Westera, Wim

    2016-01-01

    This paper presents and validates a methodology for integrating reusable software components in diverse game engines. While conforming to the RAGE com-ponent-based architecture described elsewhere, the paper explains how the interac-tions and data exchange processes between a reusable software compo

  8. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Li, D.X.; Deng, T.Z.; Lv, J.; Ke, J. [Department of Stomatology, Air Force General Hospital PLA, Haidian District, Beijing (China)

    2014-09-19

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  9. Thinking through Moments of Sexual Refusal in "Looking for Alibrandi" and "The Rage in Placid Lake"

    Science.gov (United States)

    Clarke, Kyra

    2016-01-01

    This paper explores two scenarios in which young women refuse the sexual advances of young men in the films "Looking for Alibrandi" and "The Rage in Placid Lake." The paper highlights the heteronormative nature of education around refusing sex, which reinstates gendered stereotypes of masculine as active and feminine as…

  10. RAGE genetic polymorphisms are associated with risk, chemotherapy response and prognosis in patients with advanced NSCLC.

    Directory of Open Access Journals (Sweden)

    Xiang Wang

    Full Text Available AIM: To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC. METHOD: This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, -429T/C, -374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. RESULTS: All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. CONCLUSION: The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC.

  11. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells

    Science.gov (United States)

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Chen, Yi-Ywan M.; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases. PMID:27667993

  12. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells.

    Science.gov (United States)

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Chen, Yi-Ywan M; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases. PMID:27667993

  13. Explaining seemingly paradoxical consumer experiences: conjoining weekly road rage and church attendance.

    Science.gov (United States)

    Gau, Li-Shiue; Woodside, Arch G; Martin, Drew

    2015-02-01

    The purposes of the current study are threefold: Provide evidence that an extreme paradoxical group exists-people frequently attending church and exhibiting road rage, profile this group, and frame possible explanations for the seemingly paradoxical behaviors. This study employs data from a national (USA) lifestyle survey conducted by Market Facts with 3,350 American respondents. The major questions asked about church participation and road-rage behavior ("giving a finger" and "flashing headlights"). Nomologically, relevant activities include 3 items for church goers and 3 items for road-rage givers. Additionally, 14 items profiled the lifestyles of the unique paradoxical behavior segment. Utilizing cross-tabulation tables, property space analyses identify the double extreme (XX) group (18 people) and other 6 groups with a significant chi-square test, confirming the extreme group exists. Analyses of variance test results show that comparing nomologically relevant activities among the seven groups is all statistically significant, indicating the nomological validity is met. Overall, the XX group tends to have more males, be younger, and have a higher proportion of people working in sales. The profile of lifestyle analyses shows the XX group members have both high ambitions and expectations, might be very frustrated individuals, and equip with the adventurous and masculine traits related to aggression. The XX behavior group's demographic and psychographic characteristics portray similar lifestyles that differ from other groups. Case-based analyses provide further contextual information of nuances to XX segment individuals. The limited energy theory, the Eagleman's theory of unconscious mind, and justification theory help to explain why people conjointly go to church and commit road rage. Addressing chronic paradoxical behaviors provides implications for social de-marketing to reduce aggressive anti-social behavior such as road rage. Frequent church attendance may

  14. GeneOptimizer program-assisted cDNA reengineering enhances sRAGE autologous expression in Chinese hamster ovary cells.

    Science.gov (United States)

    Wei, Wen; Kim, Ji Min; Medina, Danny; Lakatta, Edward G; Lin, Li

    2014-03-01

    Soluble receptor for advanced glycation end products (sRAGE) is a secreted mammalian protein that functions as a decoy to counter-react RAGE signaling-resultant pathological conditions, and has high therapeutic potentials. Our prior studies showed that recombinant human sRAGE expressed in Chinese hamster, Ceanothus griseus, ovary (CHO) cells is modified by specific N-glycosylation, and exhibits higher bioactivity than that expressed in other host systems including insect Spodoptera frugiperda cells. Here, we show that GeneOptimizer software program-assisted, reengineered sRAGE cDNA enhances the recombinant protein expression in CHO cells. The cDNA sequence encoding human sRAGE was optimized for RNA structure, stability, and codon usages in CHO cells. We found that such optimization augmented sRAGE expression over 2 folds of its wild-type counterpart. We also studied how individual parameter impacted sRAGE autologous expression in CHO cells, and whether sRAGE bioactivity was compromised. We found that the enhanced expression appeared not to affect sRAGE N-glycosylation and bioactivity. Optimization of sRAGE expression provides a basis for future large-scale production of this protein to meet medical needs. PMID:24373844

  15. Study on the serum level of esRAGE and other related factors in patients with type 2 diabetes

    International Nuclear Information System (INIS)

    Objective: To study the serum level of endogenous secretory receptor for advanced glycation end products (esRAGE) in type 2 diabetes (T2DM) and its relationship with other related factors. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum esRAGE level in 60 T2DM 30 of which bad carotid atherosclerosis and 28 normal controls, other clinical index was also tested. Results: Serum esRAGE level was significantly lower in T2DM with carotid atherosclerosis than in T2DM without carotid atherosclerosis and in the normal controls(P<0.01). T2DM without carotid atherosclerosis was also significantly lower than that in the normal controls (P<0.05). Pearson correlation analysis showed serum esRAGE was inversely correlated with age and components of the metabolic syndrome including glycosylated hemoglobin Alc, total cholesterol, low density lipoprotein, systolic blood pressure and body mass index (P<0.01). Multiple linear regression analyses showed that age, total cholesterol, glycosylated hemoglobin Alc and body index were independently associated with esRAGE (P<0.05). Conclusion: esRAGE is probably a potential protective factor for diabetes with atherosclerosis and metabolic syndrome. (authors)

  16. Effects of methanolic extracts of edible plants on RAGE in high-glucose-induced human endothelial cells.

    Science.gov (United States)

    Okada, Mizue; Okada, Yoshinori

    2015-01-01

    Advanced glycation end products' (AGEs) engagement of a cell-surface receptor for AGEs (RAGE) has been causally implicated in the pathogenesis of vascular complications in diabetic patients. Methanolic extracts from edible plants (MEEP) are naturally occurring phenolic compounds. The phenolic compounds have been reported to possess potent radical-scavenging properties. We investigated whether MEEP could inhibit high glucose-induced RAGE production through interference with reactive oxygen species generation in endothelial cells (ECs). ECs were incubated with 4.5 g/l of glucose in culture medium treated with 21 MEEP. Determination of RAGE production in the culture supernatants was performed by colorimetric ELISA. DNA damage was determined by using the 8-hydroxydeoxyguanosine ELISA kit. Because peroxynitrite radicals with stronger toxicity were produced by nitric oxide radical (NO), the NO scavenging activity of MEEP was assessed as nitrite generation. Peroxynitrite radical-dependent oxidation inhibition by MEEP was estimated by the Crow method. The results showed that four extracts reduced RAGE production. The extract from onion peel showed the highest RAGE production inhibition activity, followed by that of onion rhizome, cow pea and burdock. The results showed that RAGE production is correlated with the above-mentioned indicators. This study supports the utilization of four extracts for improved treatment of diabetic complications. PMID:26407112

  17. Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies

    Institute of Scientific and Technical Information of China (English)

    Masayoshi; Takeuchi; Jun-ichi; Takino; Akiko; Sakasai-Sakai; Takanobu; Takata; Tadashi; Ueda; Mikihiro; Tsutsumi; Hideyuki; Hyogo; Sho-ichi; Yamagishi

    2014-01-01

    Non-alcoholic fatty liver disease(NAFLD)is a major cause of liver disease around the world.It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis(NASH)and can lead to fibrosis,cirrhosis,liver failure,and/or hepatocellular carcinoma.NAFLD is also associated with other medical conditions such as obesity,diabetes mellitus(DM),metabolic syn-drome,hypertension,insulin resistance,hyperlipidemia,and cardiovascular disease(CVD).In diabetes,chronic hyperglycemia contributes to the development of both macro-and microvascular conditions through a variety of metabolic pathways.Thus,it can cause a variety of metabolic and hemodynamic conditions,including upregulated advanced glycation end-products(AGEs)synthesis.In our previous study,the most abundant type of toxic AGEs(TAGE);i.e.,glyceraldehyde-derived AGEs,were found to make a significant contribution to the pathogenesis of DM-induced angiopathy.Furthermore,accumulating evidence suggests that the binding of TAGE with their receptor(RAGE)induces oxidative damage,promotes inflammation,and causes changes in intracellular signaling and the expression levels of certain genes in various cell populations including hepatocytes and hepatic stellate cells.All of these effects could facilitate the pathogenesis of hypertension,cancer,diabetic vascular complications,CVD,dementia,and NASH.Thus,inhibiting TAGE synthesis,preventing TAGE from binding to RAGE,and downregulating RAGE expression and/or the expression of associated effector molecules all have potential as therapeutic strategies against NASH.Here,we examine the contributions of RAGE and TAGE to various conditions and novel treatments that target them in order to prevent the development and/or progression of NASH.

  18. Nuclear DAMP complex-mediated RAGE-dependent macrophage cell death

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ruochan [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Fu, Sha; Fan, Xue-Gong [Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Lotze, Michael T.; Zeh, Herbert J. [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Tang, Daolin, E-mail: tangd2@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Kang, Rui, E-mail: kangr@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States)

    2015-03-13

    High mobility group box 1 (HMGB1), histone, and DNA are essential nuclear components involved in the regulation of chromosome structure and function. In addition to their nuclear function, these molecules act as damage-associated molecular patterns (DAMPs) alone or together when released extracellularly. The synergistic effect of these nuclear DNA-HMGB1-histone complexes as DAMP complexes (nDCs) on immune cells remains largely unexplored. Here, we demonstrate that nDCs limit survival of macrophages (e.g., RAW264.7 and peritoneal macrophages) but not cancer cells (e.g., HCT116, HepG2 and Hepa1-6). nDCs promote production of inflammatory tumor necrosis factor α (TNFα) release, triggering reactive oxygen species-dependent apoptosis and necrosis. Moreover, the receptor for advanced glycation end products (RAGE), but not toll-like receptor (TLR)-4 and TLR-2, was required for Akt-dependent TNFα release and subsequent cell death following treatment with nDCs. Genetic depletion of RAGE by RNAi, antioxidant N-Acetyl-L-cysteine, and TNFα neutralizing antibody significantly attenuated nDC-induced cell death. These findings provide evidence supporting novel signaling mechanisms linking nDCs and inflammation in macrophage cell death. - Highlights: • Nuclear DAMP complexes (nDCs) selectively induce cell death in macrophages, but not cancer cells. • TNFα-mediated oxidative stress is required for nDC-induced death. • RAGE-mediated Akt activation is required for nDC-induced TNFα release. • Blocking RAGE and TNFα inhibits nDC-induced macrophage cell death.

  19. Abnormal Expressions of Age, RAGE, TGF- b1 and TGF- b1 Receptor in Colonic Wall Contributed to STZ-Induced Diabetic Colon Remodeling

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Gregersen, Hans

    2016-01-01

    glycation end product (AGE) and AGE receptor (RAGE) were up-regulated in the diabetic colon wall (2). However, it lacks data in relation to the association between AGE, RAGE, transforming growth factor- b1 (TGF-b1) and TGFb1 receptor expressions with colon morphological and biomechanical remodeling...... glucose level was measured. The parameters of morphometric and biomechanical properties of colonic segments were obtained from diabetic (DM) and normal (Con) rats. The expressions of AGE, RAGE, TGF- b1 and TGF- b1 receptor were detected in different layers of the colon by immunohistochemistry. In order...... to determine the expressions of AGE, RAGE, TGF- b1 and TGF- b1 receptor in association with other parameters, and to see interrelation among AGE, RAGE, TGF- b1 and TGF- b1 receptor expressions, the multiple linear regression analysis was done. Results: The expressions of AGE, RAGE, TGF-b1 and TGF- b1 receptor...

  20. HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis

    Science.gov (United States)

    Ip, Margaret; Chu, Yi Jun; Yung, Irene M. H.; Cheung, Catherine S. K.; Zheng, Lin; Lam, Judy S. Y.; Wong, Ka Tak; Sin, Winnie W. Y.; Choi, Kin Wing; Lee, Nelson

    2016-01-01

    Background We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB). Methods A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients’ PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction ex vivo. Results In active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6–15.1) vs 3.6(3.6–3.6) pg/ml, PCXCL8 (adjusted OR 1.12, 95%CI 1.02–1.23 per unit increase, P = 0.021) and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08–1.87, P = 0.012) concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2−2.8 fold). Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1) and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034). Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α) when combined with lipoarabinomannan. Conclusion In patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important roles in pathogenesis and disease manifestations. Our clinico-immunological data can provide basis for the development of new strategies for disease monitoring, management and control. PMID:27434276

  1. Sleep Now in the Fire: An Analysis of A Song By Rage Against the Machine using Marxism

    Directory of Open Access Journals (Sweden)

    Abdul Aziz Turhan Kariko

    2011-09-01

    Full Text Available Rage against the Machine is known for their politics as well as their music, which the later helped creating an aggressive-heavy rock-rap genre. Article presents a song by Rage against the Machine band related to ideological movement in America, titled Sleep Now in the Fire. This effort brings an understanding of ideology that is embraced by the band. The method is through literature study. Presentation begins with a short biography of the band, theoretical concepts, and analysis of the song as well its music video. It is concluded that the song represents ideological criticism toward capitalism using Marxism. Both of these lyric and music video represents Marxism as it shares the same movement to fight capitalism which in this case, Rage against the Machine is using their music, lyric, and video to fight the crime against humanity and cultural imperialism.

  2. Expression and purification of the soluble isoform of human receptor for advanced glycation end products (sRAGE) from Pichia pastoris.

    Science.gov (United States)

    Ostendorp, Thorsten; Weibel, Mirjam; Leclerc, Estelle; Kleinert, Peter; Kroneck, Peter M H; Heizmann, Claus W; Fritz, Günter

    2006-08-18

    RAGE is a multi-ligand receptor involved in various human diseases including diabetes, cancer or Alzheimer's disease. Engagement of RAGE by its ligands triggers activation of key cellular signalling pathways such as the MAP kinase and NF-kappaB pathways. Whereas the main isoform of RAGE is a transmembrane receptor with both extra- and intracellular domains, a secreted soluble isoform (sRAGE), corresponding to the extracellular part only, has the ability to block RAGE signalling and suppress cellular activation. Administration of sRAGE to animal models of cancer or multiple sclerosis blocked successfully tumour growth and the course of the autoimmune disease. These findings demonstrate that sRAGE may have a potential as therapeutic. We present here a fast and simple purification protocol of sRAGE from the yeast Pichia pastoris. The identity of the protein was confirmed by mass spectrometry and Western blot. The protein was N-glycosylated and 95-98% pure as judged by SDS-PAGE. PMID:16806067

  3. Perindopril Attenuates Lipopolysaccharide-Induced Amyloidogenesis and Memory Impairment by Suppression of Oxidative Stress and RAGE Activation.

    Science.gov (United States)

    Goel, Ruby; Bhat, Shahnawaz Ali; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2016-02-17

    Clinical and preclinical studies account hypertension as a risk factor for dementia. We reported earlier that angiotensin-converting enzyme (ACE) inhibition attenuated the increased vulnerability to neurodegeneration in hypertension and prevented lipopolysaccharide (LPS)-induced memory impairment in normotensive wistar rats (NWRs) and spontaneously hypertensive rats (SHRs). Recently, a receptor for advanced glycation end products (RAGE) has been reported to induce amyloid beta (Aβ1-42) deposition and memory impairment in hypertensive animals. However, the involvement of ACE in RAGE activation and amyloidogenesis in the hypertensive state is still unexplored. Therefore, in this study, we investigated the role of ACE on RAGE activation and amyloidogenesis in memory-impaired NWRs and SHRs. Memory impairment was induced by repeated (on days 1, 4, 7, and 10) intracerebroventricular (ICV) injections of LPS in SHRs (25 μg) and NWRs (50 μg). Our data showed that SHRs exhibited increased oxidative stress (increased gp91-phox/NOX-2 expression and ROS generation), RAGE, and β-secretase (BACE) expression without Aβ1-42 deposition. LPS (25 μg, ICV) further amplified oxidative stress, RAGE, and BACE activation, culminating in Aβ1-42 deposition and memory impairment in SHRs. Similar changes were observed at the higher dose of LPS (50 μg, ICV) in NWRs. Further, LPS-induced oxidative stress was associated with endothelial dysfunction and reduction in cerebral blood flow (CBF), more prominently in SHRs than in NWRs. Finally, we showed that perindopril (0.1 mg/kg, 15 days) prevented memory impairment by reducing oxidative stress, RAGE activation, amyloidogenesis, and improved CBF in both SHRs and NWRs. These findings suggest that perindopril might be used as a therapeutic strategy for the early stage of dementia. PMID:26689453

  4. RAGE mediates accelerated diabetic vein graft atherosclerosis induced by combined mechanical stress and AGEs via synergistic ERK activation.

    Directory of Open Access Journals (Sweden)

    Yuhuang Li

    Full Text Available AIMS/HYPOTHESIS: Diabetes with hypertension rapidly accelerates vascular disease, but the underlying mechanism remains unclear. We evaluated the hypothesis that the receptor of advanced glycation end products (RAGE might mediate combined signals initiated by diabetes-related AGEs and hypertension-induced mechanical stress as a common molecular sensor. METHODS: In vivo surgical vein grafts created by grafting vena cava segments from C57BL/6J mice into the common carotid arteries of streptozotocin (STZ-treated and untreated isogenic mice for 4 and 8 weeks were analyzed using morphometric and immunohistochemical techniques. In vitro quiescent mouse vascular smooth muscle cells (VSMCs with either knockdown or overexpression of RAGE were subjected to cyclic stretching with or without AGEs. Extracellular signal-regulated kinase (ERK phosphorylation and Ki-67 expression were investigated. RESULTS: Significant increases in neointimal formation, AGE deposition, Ki-67 expression, and RAGE were observed in the vein grafts of STZ-induced diabetic mice. The highest levels of ERK phosphorylation and Ki-67 expression in VSMCs were induced by simultaneous stretch stress and AGE exposure. The synergistic activation of ERKs and Ki-67 in VSMCs was significantly inhibited by siRNA-RAGE treatment and enhanced by over-expression of RAGE. CONCLUSION: RAGE may mediate synergistically increased ERK activation and VSMC proliferation induced by mechanical stretching with and without AGEs. It may serve as a common molecular bridge between the two, accelerating vascular remodeling. This study provides potential drug targets and novel therapeutic strategies for the treatment of vascular diseases resulting from diabetes with hypertension.

  5. Serum Amyloid A Stimulates PKR Expression and HMGB1 Release Possibly through TLR4/RAGE Receptors.

    Science.gov (United States)

    Li, Wei; Zhu, Shu; Li, Jianhua; D'Amore, Jason; D'Angelo, John; Yang, Huan; Wang, Ping; Tracey, Kevin J; Wang, Haichao

    2015-06-02

    Serum amyloid A (SAA) proteins are known to be surrogate markers of sepsis, but their pathogenic roles remain poorly elucidated. Here we provide evidence to support a possible role of SAA as a pathogenic mediator of lethal sepsis. In a subset of septic patients for which serum high mobility group box 1 (HMGB1) levels paralleled the clinical scores, some anti-HMGB1 antibodies detected a 12-kDa protein belonging to the SAA family. In contrast to the most abundant SAA1, human SAA induced double-stranded RNA-activated protein kinase R (PKR) expression and HMGB1 release in the wild-type, but not toll-like receptor 4/receptor for advanced glycation end products (TLR4/RAGE)-deficient, macrophages. Pharmacological inhibition of PKR phosphorylation blocked SAA-induced HMGB1 release, suggesting an important role of PKR in SAA-induced HMGB1 release. In animal models of lethal endotoxemia and sepsis, recombinant SAA exacerbated endotoxemic lethality, whereas SAA-neutralizing immunoglobulins G (IgGs) significantly improved animal survival. Collectively, these findings have suggested SAA as an important mediator of inflammatory diseases. Highlights of this study include: human SAA is possibly only expressed in a subset of septic patients; SAA induces HMGB1 release via TLR4 and RAGE receptors; SAA supplementation worsens the outcome of lethal endotoxemia; whereas SAA-neutralizing antibodies confer protection against lethal endotoxemia and sepsis.

  6. RAGE and TGF-β1 Cross-Talk Regulate Extracellular Matrix Turnover and Cytokine Synthesis in AGEs Exposed Fibroblast Cells.

    Directory of Open Access Journals (Sweden)

    Andreea Iren Serban

    Full Text Available AGEs accumulation in the skin affects extracellular matrix (ECM turnover and triggers diabetes associated skin conditions and accelerated skin aging. The receptor of AGEs (RAGE has an essential contribution to cellular dysfunction driven by chronic inflammatory responses while TGF-β1 is critical in both dermal homeostasis and inflammation. We investigated the contribution of RAGE and TGF-β1 to the modulation of inflammatory response and ECM turnover in AGEs milieu, using a normal fibroblast cell line. RAGE, TGF-β1, collagen I and III gene and protein expression were upregulated after exposure to AGEs-BSA, and MMP-2 was activated. AGEs-RAGE was pivotal in NF-κB dependent collagen I expression and joined with TGF-β1 to stimulate collagen III expression, probably via ERK1/2 signaling. AGEs-RAGE axis induced upregulation of TGF-β1, TNF-α and IL-8 cytokines. TNF-α and IL-8 were subjected to TGF-β1 negative regulation. RAGE's proinflammatory signaling also antagonized AGEs-TGF-β1 induced fibroblast contraction, suggesting the existence of an inhibitory cross-talk mechanism between TGF-β1 and RAGE signaling. RAGE and TGF-β1 stimulated anti-inflammatory cytokines IL-2 and IL-4 expression. GM-CSF and IL-6 expression appeared to be dependent only on TGF-β1 signaling. Our data also indicated that IFN-γ upregulated in AGEs-BSA milieu in a RAGE and TGF-β1 independent mechanism. Our findings raise the possibility that RAGE and TGF-β1 are both involved in fibrosis development in a complex cross-talk mechanism, while also acting on their own individual targets. This study contributes to the understanding of impaired wound healing associated with diabetes complications.

  7. Agresividad vial en la población general Road-rage in the general population

    Directory of Open Access Journals (Sweden)

    Inmaculada Fierro

    2010-10-01

    Full Text Available Objetivos: Analizar la prevalencia y los factores sociodemográficos asociados con la agresividad vial en la población. Métodos: Se han realizado 2.500 entrevistas a la población de Castilla y León de entre 14 y 70 años de edad. Se evaluó la agresividad vial en el año previo a la realización de la encuesta utilizando un test de ocho preguntas. Resultados: El 31,1% refirió haber vivido alguna situación de agresividad vial en el último año, y el 26,8% en más de una ocasión. El 2,6% fueron agresores viales «graves». Entre los conductores, la probabilidad de experimentar agresividad vial aumenta a medida que aumentan los miles de kilómetros conducidos a la semana (odds ratio [OR]=1,52, es menor cuanto mayor es la edad del entrevistado (OR=0,975 y es mayor en los hombres (OR=1,287, en los que tienen estudios universitarios (OR=1,408 y en los que viven en localidades de más de 10.000 habitantes (OR=1,25. Conclusiones: Los datos del presente estudio muestran que la agresividad vial afecta a casi un tercio de la población general de Castilla y León, lo que justificaría la adopción de medidas para su prevención y reducción.Objective: To analyze the prevalence of road rage in the general population and the sociodemographic factors associated with this phenomenon. Methods: A total of 2,500 interviews were carried out in the population of Castile and Leon aged 14-70 years. Road rage was evaluated in the year prior to the survey using a test with eight questions. Results: One-third (31.1% of the interviewees reported they had experienced a situation involving road rage during the previous 12 months (26.8% on more than one occasion. Among these episodes, 2.6% involved "serious" aggressors. In drivers, the probability of experiencing road rage increased in line with the number of kilometers driven per week (odds ratio [OR]=1.52, decreased as the age of the driver increased (OR=0.975, and was highest in men (OR=1.287, university

  8. Reviving Rage

    Science.gov (United States)

    West, Isaac

    2012-01-01

    As people commemorate ACT UP and examine its memory in public cultures, the 2011 revival of "The Normal Heart" (TNH) and the rhetorical labor undertaken to evoke political emotionalities inside and outside of the theater provides one site for analyzing how direct action politics, both past and present, are imagined as a kairotic response to…

  9. Raging water

    NARCIS (Netherlands)

    Wassink, J.

    2014-01-01

    At TU Delft neighbour Deltares, the Ballast construction company is putting the finishing touches on the world’s largest wave channel. Last month, a group of science journalists were invited to take a peek.

  10. AGEs-RAGE Signaling Pathway in Diabetic Refractory Wounds%AGEs-RAGE 信号通路与糖尿病难愈合创面

    Institute of Scientific and Technical Information of China (English)

    王丽; 李杰辉

    2015-01-01

    糖尿病难愈合创面是糖尿病比较严重的并发症和致残原因,故国内外学者对它的研究越来越多。创面愈合是炎性细胞、修复细胞及细胞因子等多种因素共同调控的复杂过程,其中晚期糖基化终末产物( Advanced Glycationend Products, AGEs)及其受体协同的AGEs-RAGE信号通路是目前研究的热点,本文就其进行概述。%Diabetic refractory wound is a serious complication of diabetes and also a cause of disability and thus studies on it are increasing both at home and abroad.Would healing is a complicated process regulated jointly by multiple factors such as inflammatory cells, repairing cells, cytokines and etc.Of the factors, advanced glycation end products ( AGEs) and its synergetic receptor-AGEs-RAGE signaling pathway are the focus of current studies, on which we carried out the review.

  11. Paeoniflorin protects HUVECs from AGE-BSA-induced injury via an autophagic pathway by acting on the RAGE.

    Science.gov (United States)

    Chen, Yufang; Du, Xing; Zhou, Yande; Zhang, Yanlin; Yang, Yaping; Liu, Zhihua; Liu, Chunfeng; Xie, Ying

    2015-01-01

    The aim of our study was to investigate the protective effects of Paeoniflorin (PF) against injury induced by AGE-modified bovine serum albumin (AGE-BSA) in human umbilical vein endothelial cells (HUVECs), and to examine the underlying mechanisms of these effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine cell viability. Protein expression levels were determined by western blotting. For function-blocking experiments, we used small interfering RNA molecules (siRNA) for function-blocking experiments. At 6 h, we found that 100 μg/mL AGE-BSA reduced the viability of HUVECs. However, pretreatment with PF restored cell viability in a dose-dependent manner. AGE-BSA increased the levels of microtubule-associated protein light chain 3-II (LC3-II) and the receptor for advanced glycation end products (RAGE). Expression of p62 protein was also increased, but not at a statistically significant level. Pretreatment with PF further increased levels of LC3-II and RAGE, but reduced the expression of p62. In cells transfected with Atg5 and RAGE siRNA, cell viability and expression of LC3-II decreased in both the AGE-BSA and PF + AGE-BSA treatments. PF can protect HUVECs from AGE-BSA-induced injury by upregulating autophagy and promoting the completion of autophagy flux. RAGE plays an important role in this autophagic protection effect.

  12. High Mobility Group Box Protein 1 Boosts Endothelial Albumin Transcytosis through the RAGE/Src/Caveolin-1 Pathway

    Science.gov (United States)

    Shang, Dan; Peng, Tao; Gou, Shanmiao; Li, Yiqing; Wu, Heshui; Wang, Chunyou; Yang, Zhiyong

    2016-01-01

    High-mobility group box protein 1 (HMGB1), an inflammatory mediator, has been reported to destroy cell-cell junctions, resulting in vascular endothelial hyperpermeability. Here, we report that HMGB1 increases the endothelial transcytosis of albumin. In mouse lung vascular endothelial cells (MLVECs), HMGB1 at a concentration of 500 ng/ml or less did not harm cell-cell junctions but rapidly induced endothelial hyperpermeability to 125I-albumin. HMGB1 induced an increase in 125I-albumin and AlexaFluor 488-labeled albumin internalization in endocytosis assays. Depletion of receptor for advanced glycation end products (RAGE), but not TLR2 or TLR4, suppressed HMGB1-induced albumin transcytosis and endocytosis. Genetic and pharmacological destruction of lipid rafts significantly inhibited HMGB1-induced albumin endocytosis and transcytosis. HMGB1 induced the rapid phosphorylation of caveolin (Cav)-1 and Src. Either RAGE gene silencing or soluble RAGE suppressed Cav-1 Tyr14 phosphorylation and Src Tyr418 phosphorylation. The Src inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2) blocked HMGB1-induced Cav-1 Tyr14 phosphorylation. PP2 and overexpression of Cav-1 with a T14F mutation significantly inhibited HMGB1-induced transcytosis and albumin endocytosis. Our findings suggest that HMGB1 induces the transcytosis of albumin via RAGE-dependent Src phosphorylation and Cav-1 phosphorylation. These studies revealed a new mechanism of HMGB1-induced endothelial hyperpermeability. PMID:27572515

  13. Using SMS as a Harm Reduction Strategy: An Evaluation of the RAGE (Register and Get Educated) Project

    Science.gov (United States)

    Crockett, Belinda; Keleher, Helen; Rudd, Annette; Klein, Ruth; Locke, Beth; Roussy, Véronique

    2013-01-01

    The RAGE (Register And Get Educated) project explored the feasibility of SMS (Short Messaging Service) as a means for communicating harm reduction messages in relation to alcohol and other drugs to young people residing in the City of Knox, Victoria. Almost 700 young people aged 12-26 years registered their mobile phone numbers to receive a series…

  14. Puerarin enhances superoxide dismutase activity and inhibits RAGE and VEGF expression in retinas of STZ-induced early diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Fang Chen; Hong-Quan Zhang; Jun Zhu; Kai-Yang Liu; Hong Cheng; Guo-Li Li; Shan Xu; Wei-Hong Lv; Zheng-Gao Xie

    2012-01-01

    Objective:To investigate the effects of puerarin on the activity of superoxide dismutase (SOD), and expressions of advanced glycation end-product (AGE) receptor (RAGE) and vascular endothelial growth factor (VEGF) in retinas of streptozotocin (STZ)-induced early diabetic rats. Methods: Diabetic rat models were established by inducing diabetes via intra-peritoneal injection of STZ. Rats were randomly divided into normal (control), diabetic (DM), and DM+puerarin groups. After intra-gastric administration of puerarin (500 mg/kg/day for 4 weeks), levels of SOD and malondialdehyde (MDA) were determined in serum and retina. mRNA and protein expression levels of RAGE and VEGF in retinas were determined by real-time polymerase chain reaction (RT-PCR) (mRNA) and Western blot analysis (protein levels). Results:There was significantly lower SOD activity and significantly higher MDA in serum and retinas of the DM group compared with the two other groups (P<0.05). After treatment with puerarin, SOD activity increased and MDA content decreased in this group (P<0.05). mRNA and protein expression levels of RAGE and VEGF in the DM group were significantly higher than those of the other groups (P<0.05), and decreased after puerarin treatment (P<0.05). Conclusions: Puerarin is able to enhance SOD activity, and inhibit RAGE and VEGF expressions in retinas of STZ-induced early diabetic rats.

  15. AGE-RAGE signal generates a specific NF-κB RelA "barcode" that directs collagen I expression.

    Science.gov (United States)

    Peng, Yunqian; Kim, Ji-Min; Park, Hal-Sol; Yang, Annie; Islam, Celia; Lakatta, Edward G; Lin, Li

    2016-01-01

    Advanced glycation end products (AGEs) are sugar-modified biomolecules that accumulate in the body with advancing age, and are implicated in the development of multiple age-associated structural and functional abnormities and diseases. It has been well documented that AGEs signal via their receptor RAGE to activate several cellular programs including NF-κB, leading to inflammation. A large number of stimuli can activate NF-κB; yet different stimuli, or the same stimulus for NF-κB in different cellular settings, produce a very different transcriptional landscape and physiological outcome. The NF-κB barcode hypothesis posits that cellular network dynamics generate signal-specific post-translational modifications, or a "barcode" to NF-κB, and that a signature "barcode" mediates a specific gene expression pattern. In the current study, we established that AGE-RAGE signaling results in NF-κB activation that directs collagen Ia1 and Ia2 expression. We further demonstrated that AGE-RAGE signal induces phosphorylation of RelA at three specific residues, T254, S311, and S536. These modifications are required for transcription of collagen I genes and are a consequence of cellular network dynamics. The increase of collagen content is a hallmark of arterial aging, and our work provides a potential mechanistic link between RAGE signaling, NF-κB activation, and aging-associated arterial alterations in structure and function. PMID:26729520

  16. The receptor for advanced glycation end-products (RAGE) plays a key role in the formation of nanotubes (NTs) between peritoneal mesothelial cells and in murine kidneys.

    Science.gov (United States)

    Ranzinger, Julia; Rustom, Amin; Heide, Danijela; Morath, Christian; Schemmer, Peter; Nawroth, Peter P; Zeier, Martin; Schwenger, Vedat

    2014-09-01

    The receptor for advanced glycation end-products (RAGE), a multiligand receptor of the immunoglobulin superfamily, takes part in various inflammatory processes. The role of this receptor in the context of intercellular communication, like nanotube (NT)-mediated interaction, is largely unknown. Here, we use cell cultures of human and murine peritoneal mesothelial cells as well as murine kidneys from wild-type and RAGE knockout mouse models to assess the role of RAGE in NT formation and function. We show that loss of RAGE function results in reduced NT numbers under physiological conditions and demonstrate the involvement of MAP kinase signaling in NT formation. Additionally, we show for the first time the existence of NTs in murine kidney tissue and confirm the correlation of RAGE expression and NT numbers. Under elevated oxidative stress conditions like renal ischemia or peritoneal dialysis, we demonstrate that RAGE absence does not prevent NT formation. Rather, increased NT numbers and attenuated kidney tissue damage could be observed, indicating that, depending on the predominant conditions, RAGE affects NT formation with implications for cellular communication.

  17. HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Ying [Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Li, Shu-Jun [Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Yang, Jian [Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Qiu, Yuan-Zhen [Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha 410078 (China); Chen, Fang-Ping, E-mail: xychenfp@163.com [Department of Hematology, Xiangya Hospital, Central South University, Changsha 410078 (China)

    2013-09-06

    Highlights: •Mechanisms of inflammatory response induced by HMGB1 are incompletely understood. •We found that endoplasmic reticulum stress mediate the inflammatory response induced by HMGB1. •RAGE-mediated ERS pathways are involved in those processes. •We reported a new mechanism for HMGB1 induced inflammatory response. -- Abstract: The high mobility group 1B protein (HMGB1) mediates chronic inflammatory responses in endothelial cells, which play a critical role in atherosclerosis. However, the underlying mechanism is unknown. The goal of our study was to identify the effects of HMGB1 on the RAGE-induced inflammatory response in endothelial cells and test the possible involvement of the endoplasmic reticulum stress pathway. Our results showed that incubation of endothelial cells with HMGB1 (0.01–1 μg/ml) for 24 h induced a dose-dependent activation of endoplasmic reticulum stress transducers, as assessed by PERK and IRE1 protein expression. Moreover, HMGB1 also promoted nuclear translocation of ATF6. HMGB1-mediated ICAM-1 and P-selectin production was dramatically suppressed by PERK siRNA or IRE1 siRNA. However, non-targeting siRNA had no such effects. HMGB1-induced increases in ICAM-1 and P-selectin expression were also inhibited by a specific eIF2α inhibitor (salubrinal) and a specific JNK inhibitor (SP600125). Importantly, a blocking antibody specifically targeted against RAGE (anti-RAGE antibody) decreased ICAM-1, P-selectin and endoplasmic reticulum stress molecule (PERK, eIF2α, IRE1 and JNK) protein expression levels. Collectively, these novel findings suggest that HMGB1 promotes an inflammatory response by inducing the expression of ICAM-1 and P-selectin via RAGE-mediated stimulation of the endoplasmic reticulum stress pathway.

  18. ANGER IS A GIFT: propaganda, performance e documentário nos Rage Against The Machine

    Directory of Open Access Journals (Sweden)

    Luís Nogueira

    2012-08-01

    Full Text Available About 20 years ago, and during the 1990s, Rage Against the Machinedid not change the world, but endeavored to cause small aesthetic (at the level of musicmakingand ethical quakes (at the level of civic intervention. The visual production that accompanied their music had become equally bold and unusual: videoclips based on foundfootage and live performances, concert films that sought to capture the visceral energy of live performance and a strong propaganda permeating both music and the images that accompany, seem to us aspects of note and worthy of reflection. This article is concernedwith the intersection between documentary and music never seen before in the entertainment industry and culture in contemporary music.

  19. Analysis of xRAGE and flag high explosive burn models with PBX 9404 cylinder tests

    Energy Technology Data Exchange (ETDEWEB)

    Harrier, Danielle [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Andersen, Kyle Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-05

    High explosives are energetic materials that release their chemical energy in a short interval of time. They are able to generate extreme heat and pressure by a shock driven chemical decomposition reaction, which makes them valuable tools that must be understood. This study investigated the accuracy and performance of two Los Alamos National Laboratory hydrodynamic codes, which are used to determine the behavior of explosives within a variety of systems: xRAGE which utilizes an Eulerian mesh, and FLAG with utilizes a Lagrangian mesh. Various programmed and reactive burn models within both codes were tested using a copper cylinder expansion test. The test was based on a recent experimental setup which contained the plastic bonded explosive PBX 9404. Detonation velocity versus time curves for this explosive were obtained using Photon Doppler Velocimetry (PDV). The modeled results from each of the burn models tested were then compared to one another and to the experimental results. This study validate

  20. Inhibitory effect of receptor for advanced glycation end products (RAGE) on the TGF-β-induced alveolar epithelial to mesenchymal transition

    OpenAIRE

    Song, Jeong Sup; Kang, Chun Mi; Park, Chan Kwon; Yoon, Hyung Kyu; Lee, Sook Young; Ahn, Joong Hyun; Moon, Hwa-Sik

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a lethal parenchymal lung disease characterized by myofibroblast proliferation. Alveolar epithelial cells (AECs) are thought to produce myofibroblasts through the epithelial to mesenchymal transition (EMT). Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation is associated with renal fibrosis during diabetes and liver fibrosis. RAGE is expressed at low basal levels in...

  1. Genetically-Determined Hyperfunction of the S100B/RAGE Axis Is a Risk Factor for Aspergillosis in Stem Cell Transplant Recipients

    OpenAIRE

    Cunha, Cristina; Giovannini, Gloria; Pierini, Antonio; Alain S Bell; Sorci, Guglielmo; Riuzzi, Francesca; Donato, Rosario; Rodrigues, Fernando; Velardi, Andrea; Aversa, Franco; Romani, Luigina; Carvalho, Agostinho

    2011-01-01

    Invasive aspergillosis (IA) is a major threat to the successful outcome of hematopoietic stem cell transplantation (HSCT), although individual risk varies considerably. Recent evidence has established a pivotal role for a danger sensing mechanism implicating the S100B/receptor for advanced glycation end products (RAGE) axis in antifungal immunity. The association of selected genetic variants in the S100B/RAGE axis with susceptibility to IA was investigated in 223 consecutive patients undergoi...

  2. The Association of -429T>C and -374T>A Polymorphisms in the RAGE Gene with Polycystic Ovary Syndrome

    Science.gov (United States)

    Park, Jung-Hyun; Li, Lan; Choi, Jin-Woo; Baek, Kwang-Hyun

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a complex disorder characterized by hyperandrogenism and insulin resistance. In addition, a number of females with PCOS have ovaries with multiple cysts, an irregular or no menstrual cycle, and an imbalance of female hormones compared to those of normal controls. A variety of genetic factors have been involved in the pathogenesis of PCOS. Among these genetic factors, the receptor for advanced glycation end products (RAGE) that is associated with diabetes and involved in the complications of PCOS, was selected. We aimed to assess the relationship between -429T>C and -374T>A single nucleotide polymorphisms (SNPs) of RAGE gene with the susceptibility to PCOS.128 controls and 265 PCOS patients were used for -374T>A polymorphism and 141 controls and 290 PCOS patients were used for -429T>C polymorphism, respectively. Genotyping of two polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and statistical analysis was performed. P values for both alleles were higher than 0.05. Frequencies of genotype and allele of two polymorphisms in RAGE gene showed no significant differences between controls and PCOS patients. The initial study on the correlation between RAGE gene and PCOS indicates that the two polymorphisms of RAGE are not associated with the pathogenesis of PCOS. However, further studies regarding the association between RAGE gene and PCOS patients in different ethnic groups are required. PMID:27279795

  3. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells

    OpenAIRE

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Yi-Ywan M Chen; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However...

  4. Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression

    Institute of Scientific and Technical Information of China (English)

    Junichi Takino; Shoichi Yamagishi; Masayoshi Takeuchi

    2012-01-01

    AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products (Glycer-AGEs)on hepatocellular carcinoma (HCC) cells.METHODS:Two HCC cell lines (Hep3B and HepG2cells) and human umbilical vein endothelial cells (HUVEC) were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs (RAGE) protein was detected in Hep3B and HepG2 cells.HepG2 cells were not affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor (VEGF) mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin (BSA)treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00 ± 0.10 vs 1.92± 0.09 (P < 0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63 ± 0.04ng/mL vs 2.28 ± 0.17 ng/mL for the 24 h treatment and 3.36 ± 0.10 ng/mL vs 4.79 ± 0.31 ng/mL for the 48 h treatment,respectively (P < 0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4% ± 9.0% vs 144.5% ± 11.3% for cell viability,4.29 ± 1.53 vs 6.78 ± 1.84 for migration indices,and 71.0 ± 7.5 vs 112.4 ± 8.0 for the number of branching points,respectively (P < 0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.

  5. AGEs-Induced IL-6 Synthesis Precedes RAGE Up-Regulation in HEK 293 Cells: An Alternative Inflammatory Mechanism?

    Directory of Open Access Journals (Sweden)

    Andreea Iren Serban

    2015-08-01

    Full Text Available Advanced glycation end products (AGEs can activate the inflammatory pathways involved in diabetic nephropathy. Understanding these molecular pathways could contribute to therapeutic strategies for diabetes complications. We evaluated the modulation of inflammatory and oxidative markers, as well as the protective mechanisms employed by human embryonic kidney cells (HEK 293 upon exposure to 200 μg/mL bovine serum albumine (BSA or AGEs–BSA for 12, 24 and 48 h. The mRNA and protein expression levels of AGEs receptor (RAGE and heat shock proteins (HSPs 27, 60 and 70, the activity of antioxidant enzymes and the expression levels of eight cytokines were analysed. Cell damage via oxidative mechanisms was evaluated by glutathione and malondialdehyde levels. The data revealed two different time scale responses. First, the up-regulation of interleukin-6 (IL-6, HSP 27 and high catalase activity were detected as early as 12 h after exposure to AGEs–BSA, while the second response, after 24 h, consisted of NF-κB p65, RAGE, HSP 70 and inflammatory cytokine up-regulation, glutathione depletion, malondialdehyde increase and the activation of antioxidant enzymes. IL-6 might be important in the early ignition of inflammatory responses, while the cellular redox imbalance, RAGE activation and NF-κB p65 increased expression further enhance inflammatory signals in HEK 293 cells.

  6. Involvement of formyl peptide receptors in receptor for advanced glycation end products (RAGE - and amyloid beta 1-42-induced signal transduction in glial cells

    Directory of Open Access Journals (Sweden)

    Slowik Alexander

    2012-11-01

    Full Text Available Abstract Background Recent studies suggest that the chemotactic G-protein-coupled-receptor (GPCR formyl-peptide-receptor-like-1 (FPRL1 and the receptor-for-advanced-glycation-end-products (RAGE play an important role in the inflammatory response involved in neurodegenerative disorders such as Alzheimer’s disease (AD. Therefore, the expression and co-localisation of mouse formyl peptide receptor (mFPR 1 and 2 as well as RAGE in an APP/PS1 transgenic mouse model using immunofluorescence and real-time RT-PCR were analysed. The involvement of rat or human FPR1/FPRL1 (corresponds to mFPR1/2 and RAGE in amyloid-β 1–42 (Aβ1-42-induced signalling were investigated by extracellular signal regulated kinase 1/2 (ERK1/2 phosphorylation. Furthermore, the cAMP level in primary rat glial cells (microglia and astrocytes and transfected HEK 293 cells was measured. Formyl peptide receptors and RAGE were inhibited by a small synthetic antagonist WRW4 and an inactive receptor variant delta-RAGE, lacking the intracytoplasmatic domains. Results We demonstrated a strong increase of mFPR1/2 and RAGE expression in the cortex and hippocampus of APP/PS1 transgenic mice co-localised to the glial cells. In addition, the Aβ1-42-induced signal transduction is dependant on FPRL1, but also on FPR1. For the first time, we have shown a functional interaction between FPRL1/FPR1 and RAGE in RAGE ligands S100B- or AGE-mediated signalling by ERK1/2 phosphorylation and cAMP level measurement. In addition a possible physical interaction between FPRL1 as well as FPR1 and RAGE was shown with co-immunoprecipitation and fluorescence microscopy. Conclusions The results suggest that both formyl peptide receptors play an essential role in Aβ1-42-induced signal transduction in glial cells. The interaction with RAGE could explain the broad ligand spectrum of formyl peptide receptors and their important role for inflammation and the host defence against infections.

  7. Plasma miR-185 is decreased in patients with esophageal squamous cell carcinoma and might suppress tumor migration and invasion by targeting RAGE.

    Science.gov (United States)

    Jing, Rongrong; Chen, Wen; Wang, Huimin; Ju, Shaoqing; Cong, Hui; Sun, Baolan; Jin, Qin; Chu, Shaopeng; Xu, Lili; Cui, Ming

    2015-11-01

    The receptor for advanced-glycation end products (RAGE) is upregulated in various cancers and has been associated with tumor progression, but little is known about its expression and regulation by microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). Here, we describe miR-185, which represses RAGE expression, and investigate the biological role of miR-185 in ESCC. In this study, we found that the high level of RAGE expression in 29 pairs of paraffin-embedded ESCC tissues was correlated positively with the depth of invasion by immunohistochemistry, suggesting that RAGE was involved in ESCC. We used bioinformatics searches and luciferase reporter assays to investigate the prediction that RAGE was regulated directly by miR-185. Besides, overexpression of miR-185 in ESCC cells was accompanied by 27% (TE-11) and 49% (Eca-109) reduced RAGE expression. The effect was further confirmed in RAGE protein by immunofluorescence in both cell lines. The effects were reversed following cotransfection with miR-185 and high-level expression of the RAGE vector. Furthermore, the biological role of miR-185 in ESCC cell lines was investigated using assays of cell viability, Ki-67 staining, and cell migration and invasion, as well as in a xenograft model. We found that overexpression of miR-185 inhibited migration and invasion by ESCC cells in vitro and reduced their capacity to develop distal pulmonary metastases in vivo partly through the RAGE/heat shock protein 27 pathway. Interestingly, in clinical specimens, the level of plasma miR-185 expression was decreased significantly (P = 0.002) in patients with ESCC [0.500; 95% confidence interval (CI) 0.248-1.676] compared with healthy controls (2.410; 95% CI 0.612-5.671). The value of the area under the receiver-operating characteristic curve was 0.73 (95% CI 0.604-0.855). In conclusion, our findings shed novel light on the role of miR-185/RAGE in ESCC metastasis, and plasma miR-185 has potential as a novel diagnostic biomarker

  8. In-Situ Visualization Experiments with ParaView Cinema in RAGE

    Energy Technology Data Exchange (ETDEWEB)

    Kares, Robert John [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-15

    A previous paper described some numerical experiments performed using the ParaView/Catalyst in-situ visualization infrastructure deployed in the Los Alamos RAGE radiation-hydrodynamics code to produce images from a running large scale 3D ICF simulation. One challenge of the in-situ approach apparent in these experiments was the difficulty of choosing parameters likes isosurface values for the visualizations to be produced from the running simulation without the benefit of prior knowledge of the simulation results and the resultant cost of recomputing in-situ generated images when parameters are chosen suboptimally. A proposed method of addressing this difficulty is to simply render multiple images at runtime with a range of possible parameter values to produce a large database of images and to provide the user with a tool for managing the resulting database of imagery. Recently, ParaView/Catalyst has been extended to include such a capability via the so-called Cinema framework. Here I describe some initial experiments with the first delivery of Cinema and make some recommendations for future extensions of Cinema’s capabilities.

  9. Verification Test of the SURF and SURFplus Models in xRage: Part II

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-06-20

    The previous study used an underdriven detonation wave (steady ZND reaction zone profile followed by a scale invariant rarefaction wave) for PBX 9502 as a validation test of the implementation of the SURF and SURFplus models in the xRage code. Even with a fairly fine uniform mesh (12,800 cells for 100mm) the detonation wave profile had limited resolution due to the thin reaction zone width (0.18mm) for the fast SURF burn rate. Here we study the effect of finer resolution by comparing results of simulations with cell sizes of 8, 2 and 1 μm, which corresponds to 25, 100 and 200 points within the reaction zone. With finer resolution the lead shock pressure is closer to the von Neumann spike pressure, and there is less noise in the rarefaction wave due to fluctuations within the reaction zone. As a result the average error decreases. The pointwise error is still dominated by the smearing the pressure kink in the vicinity of the sonic point which occurs at the end of the reaction zone.

  10. Verification test of the SURF and SURFplus models in xRage

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-18

    As a verification test of the SURF and SURFplus models in the xRage code we use a propagating underdriven detonation wave in 1-D. This is about the only test cases for which an accurate solution can be determined based on the theoretical structure of the solution. The solution consists of a steady ZND reaction zone profile joined with a scale invariant rarefaction or Taylor wave and followed by a constant state. The end of the reaction profile and the head of the rarefaction coincide with the sonic CJ state of the detonation wave. The constant state is required to match a rigid wall boundary condition. For a test case, we use PBX 9502 with the same EOS and burn rate as previously used to test the shock detector algorithm utilized by the SURF model. The detonation wave is propagated for 10 μs (slightly under 80mm). As expected, the pointwise errors are largest in the neighborhood of discontinuities; pressure discontinuity at the lead shock front and pressure derivative discontinuities at the head and tail of the rarefaction. As a quantitative measure of the overall accuracy, the L2 norm of the difference of the numerical pressure and the exact solution is used. Results are presented for simulations using both a uniform grid and an adaptive grid that refines the reaction zone.

  11. Using xRage to Model Heat Flow for Experiments to Measure Opacities in HED Plasmas

    Science.gov (United States)

    Elgin, L.; Vandervort, R.; Keiter, P.; Drake, R. P.; Mussack, K.; Orban, C.

    2015-11-01

    We are developing a NIF proposal to measure opacities of C, N and O at temperatures and densities relevant to the base of the solar convection zone. Our proposed experiments would provide the first opacity measurements for these elements within this HED regime. A critical feature of our experimental platform is a super-sonic radiation front propagating within the targets. Under these conditions, density remains constant across the radiation front for a couple nanoseconds, enabling a window during which the opacities of the hot and cold target may be measured simultaneously. Afterwards, hydrodynamic effects create temperature and density gradients, which would obfuscate analysis of opacity data. We are using xRage to simulate heat flow within our targets in order to estimate the time scale over which temperature and density gradients evolve. These simulations will better inform our target design and diagnostic requirements. If successful, our experiments could yield the data necessary to validate existing opacity models or provide physical insights to inform the development of new opacity models. Accurate opacity models are essential to the understanding of radiation transport within HED systems, with applications ranging from astrophysics to ICF. U.S. Department of Energy, through the NNSA-DS and SC-OFES Joint Program in High-Energy-Density Laboratory Plasmas, grant #DE-NA0001840. Los Alamos National Laboratory, LA-UR-15-25490.

  12. Association of advanced glycation end products with A549 cells, a human pulmonary epithelial cell line, is mediated by a receptor distinct from the scavenger receptor family and RAGE.

    Science.gov (United States)

    Nakano, Nahoko; Fukuhara-Takaki, Kaori; Jono, Tadashi; Nakajou, Keisuke; Eto, Nobuaki; Horiuchi, Seikoh; Takeya, Motohiro; Nagai, Ryoji

    2006-05-01

    Cellular interactions with advanced glycation end products (AGE)-modified proteins are known to induce several biological responses, not only endocytic uptake and degradation, but also the induction of cytokines and growth factors, combined responses that may be linked to the development of diabetic vascular complications. In this study we demonstrate that A549 cells, a human pulmonary epithelial cell line, possess a specific binding site for AGE-modified bovine serum albumin (AGE-BSA) (K(d) = 27.8 nM), and additionally for EN-RAGE (extracellular newly identified RAGE binding protein) (K(d) = 118 nM). Western blot and RT-PCR analysis showed that RAGE (receptor for AGE) is highly expressed on A549 cells, while the expression of other known AGE-receptors such as galectin-3 and SR-A (class A scavenger receptor), are below the level of detection. The binding of (125)I-AGE-BSA to these cells is inhibited by unlabeled AGE-BSA, but not by EN-RAGE. In contrast, the binding of (125)I-EN-RAGE is significantly inhibited by unlabeled EN-RAGE and soluble RAGE, but not by AGE-BSA. Our results indicate that A549 cells possess at least two binding sites, one specific for EN-RAGE and the other specific for AGE-BSA. The latter receptor on A549 cells is distinct from the scavenger receptor family and RAGE.

  13. Genetically-determined hyperfunction of the S100B/RAGE axis is a risk factor for aspergillosis in stem cell transplant recipients.

    Directory of Open Access Journals (Sweden)

    Cristina Cunha

    Full Text Available Invasive aspergillosis (IA is a major threat to the successful outcome of hematopoietic stem cell transplantation (HSCT, although individual risk varies considerably. Recent evidence has established a pivotal role for a danger sensing mechanism implicating the S100B/receptor for advanced glycation end products (RAGE axis in antifungal immunity. The association of selected genetic variants in the S100B/RAGE axis with susceptibility to IA was investigated in 223 consecutive patients undergoing HSCT. Furthermore, studies addressing the functional consequences of these variants were performed. Susceptibility to IA was significantly associated with two distinct polymorphisms in RAGE (-374T/A and S100B (+427C/T genes, the relative contribution of each depended on their presence in both transplantation counterparts [patient SNP(RAGE, adjusted hazard ratio (HR, 1.97; P = 0.042 and donor SNP(RAGE, HR, 2.03; P = 0.047] or in donors (SNP(S100B, HR, 3.15; P = 7.8e-(4 only, respectively. Functional assays demonstrated a gain-of-function phenotype of both variants, as shown by the enhanced expression of inflammatory cytokines in RAGE polymorphic cells and increased S100B secretion in vitro and in vivo in the presence of the S100B polymorphism. These findings point to a relevant role of the danger sensing signaling in human antifungal immunity and highlight a possible contribution of a genetically-determined hyperfunction of the S100B/RAGE axis to susceptibility to IA in the HSCT setting.

  14. Genetically-determined hyperfunction of the S100B/RAGE axis is a risk factor for aspergillosis in stem cell transplant recipients.

    Science.gov (United States)

    Cunha, Cristina; Giovannini, Gloria; Pierini, Antonio; Bell, Alain S; Sorci, Guglielmo; Riuzzi, Francesca; Donato, Rosario; Rodrigues, Fernando; Velardi, Andrea; Aversa, Franco; Romani, Luigina; Carvalho, Agostinho

    2011-01-01

    Invasive aspergillosis (IA) is a major threat to the successful outcome of hematopoietic stem cell transplantation (HSCT), although individual risk varies considerably. Recent evidence has established a pivotal role for a danger sensing mechanism implicating the S100B/receptor for advanced glycation end products (RAGE) axis in antifungal immunity. The association of selected genetic variants in the S100B/RAGE axis with susceptibility to IA was investigated in 223 consecutive patients undergoing HSCT. Furthermore, studies addressing the functional consequences of these variants were performed. Susceptibility to IA was significantly associated with two distinct polymorphisms in RAGE (-374T/A) and S100B (+427C/T) genes, the relative contribution of each depended on their presence in both transplantation counterparts [patient SNP(RAGE), adjusted hazard ratio (HR), 1.97; P = 0.042 and donor SNP(RAGE), HR, 2.03; P = 0.047] or in donors (SNP(S100B), HR, 3.15; P = 7.8e-(4)) only, respectively. Functional assays demonstrated a gain-of-function phenotype of both variants, as shown by the enhanced expression of inflammatory cytokines in RAGE polymorphic cells and increased S100B secretion in vitro and in vivo in the presence of the S100B polymorphism. These findings point to a relevant role of the danger sensing signaling in human antifungal immunity and highlight a possible contribution of a genetically-determined hyperfunction of the S100B/RAGE axis to susceptibility to IA in the HSCT setting. PMID:22114731

  15. Microalbuminuria and sRAGE in High-Risk Hypertensive Patients Treated with Nifedipine/Telmisartan Combination Treatment: A Substudy of TALENT

    Directory of Open Access Journals (Sweden)

    Colomba Falcone

    2012-01-01

    Full Text Available Some antihypertensive drugs have also renoprotective and anti-inflammatory properties that go beyond their effect on blood pressure. It has been suggested that microalbuminuria and glomerular filtration rate (GFR are associated with circulating levels of the soluble form of the receptor, sRAGE (soluble receptor for advanced glycation ends-products. In the present analysis, we used data from the TALENT study to evaluate soluble receptor for advanced glycation end-products (sRAGE plasma levels in patients with hypertension and high-cardiovascular risk-treated nifedipine and telmisartan in combination. Treatment with nifedipine-telmisartan significantly decreased mean systolic and diastolic ambulatory blood pressure and resulted in a significant increase in sRAGE plasma concentrations after 24 weeks of therapy. We concluded that in hypertensive patients with early-stage renal disease, sRAGE concentrations are not influenced by either microalbuminuria or GFR. Long-term treatment with a combination of nifedipine-telmisartan may have a beneficial effect increasing sRAGE plasma levels, thus exerting an atheroprotective and anti-inflammatory activity.

  16. Microalbuminuria and sRAGE in High-Risk Hypertensive Patients Treated with Nifedipine/Telmisartan Combination Treatment: A Substudy of TALENT

    Science.gov (United States)

    Falcone, Colomba; Buzzi, Maria Paola; Bozzini, Sara; Boiocchi, Chiara; D'Angelo, Angela; Schirinzi, Sandra; Esposito, Ciro; Torreggiani, Massimo; Choi, Jasmine; Ochan Kilama, Michael; Mancia, Giuseppe

    2012-01-01

    Some antihypertensive drugs have also renoprotective and anti-inflammatory properties that go beyond their effect on blood pressure. It has been suggested that microalbuminuria and glomerular filtration rate (GFR) are associated with circulating levels of the soluble form of the receptor, sRAGE (soluble receptor for advanced glycation ends-products). In the present analysis, we used data from the TALENT study to evaluate soluble receptor for advanced glycation end-products (sRAGE) plasma levels in patients with hypertension and high-cardiovascular risk-treated nifedipine and telmisartan in combination. Treatment with nifedipine-telmisartan significantly decreased mean systolic and diastolic ambulatory blood pressure and resulted in a significant increase in sRAGE plasma concentrations after 24 weeks of therapy. We concluded that in hypertensive patients with early-stage renal disease, sRAGE concentrations are not influenced by either microalbuminuria or GFR. Long-term treatment with a combination of nifedipine-telmisartan may have a beneficial effect increasing sRAGE plasma levels, thus exerting an atheroprotective and anti-inflammatory activity. PMID:22474401

  17. Voltammetric Detection of S100B Protein Using His-Tagged Receptor Domains for Advanced Glycation End Products (RAGE Immobilized onto a Gold Electrode Surface

    Directory of Open Access Journals (Sweden)

    Edyta Mikuła

    2014-06-01

    Full Text Available In this work we report on an electrochemical biosensor for the determination of the S100B protein. The His-tagged VC1 domains of Receptors for Advanced Glycation End (RAGE products used as analytically active molecules were covalently immobilized on a monolayer of a thiol derivative of pentetic acid (DPTA complex with Cu(II deposited on a gold electrode surface. The recognition processes between the RAGE VC1 domain and the S100B protein results in changes in the redox activity of the DPTA-Cu(II centres which were measured by Osteryoung square-wave voltammetry (OSWV. In order to verify whether the observed analytical signal originates from the recognition process between the His6–RAGE VC1 domains and the S100B protein, the electrode modified with the His6–RAGE C2 and His6–RAGE VC1 deleted domains which have no ability to bind S100B peptides were applied. The proposed biosensor was quite sensitive, with a detection limit of 0.52 pM recorded in the buffer solution. The presence of diluted human plasma and 10 nM Aβ1-40 have no influence on the biosensor performance.

  18. Tranilast Blocks the Interaction between the Protein S100A11 and Receptor for Advanced Glycation End Products (RAGE) V Domain and Inhibits Cell Proliferation.

    Science.gov (United States)

    Huang, Yen-Kai; Chou, Ruey-Hwang; Yu, Chin

    2016-07-01

    The human S100 calcium-binding protein A11 (S100A11) is a member of the S100 protein family. Once S100A11 proteins bind to calcium ions at EF-hand motifs, S100A11 changes its conformation, promoting interaction with target proteins. The receptor for advanced glycation end products (RAGE) consists of three extracellular domains, including the V domain, C1 domain, and C2 domain. In this case, the V domain is the target for mutant S100A11 (mS100A11) binding. RAGE binds to the ligands, resulting in cell proliferation, cell growth, and several signal transduction cascades. We used NMR and fluorescence spectroscopy to demonstrate the interactions between mS100A11and RAGE V domain. The tranilast molecule is a drug used for treating allergic disorders. We discovered that the RAGE V domain and tranilast would interact with mS100A11 by using (1)H-(15)N HSQC NMR titrations. According to the results, we obtained two binary complex models from the HADDOCK program, S100A11-RAGE V domain and S100A11-tranilast, respectively. We overlapped two binary complex models with the same orientation of S100A11 homodimer and demonstrated that tranilast would block the binding site between S100A11 and the RAGE V domain. We further utilized a water-soluble tetrazolium-1 assay to confirm this result. We think that the results will be potentially useful in the development of new anti-cancer drugs. PMID:27226584

  19. Higher plasma soluble Receptor for Advanced Glycation End Products (sRAGE) levels are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes

    DEFF Research Database (Denmark)

    Nin, Johanna W M; Jorsal, Anders; Ferreira, Isabel;

    2010-01-01

    To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunct......To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal...

  20. Novel sulfated polysaccharides disrupt cathelicidins, inhibit RAGE and reduce cutaneous inflammation in a mouse model of rosacea.

    Directory of Open Access Journals (Sweden)

    Jianxing Zhang

    Full Text Available BACKGROUND: Rosacea is a common disfiguring skin disease of primarily Caucasians characterized by central erythema of the face, with telangiectatic blood vessels, papules and pustules, and can produce skin thickening, especially on the nose of men, creating rhinophyma. Rosacea can also produce dry, itchy eyes with irritation of the lids, keratitis and corneal scarring. The cause of rosacea has been proposed as over-production of the cationic cathelicidin peptide LL-37. METHODOLOGY/PRINCIPAL FINDINGS: We tested a new class of non-anticoagulant sulfated anionic polysaccharides, semi-synthetic glycosaminoglycan ethers (SAGEs on key elements of the pathogenic pathway leading to rosacea. SAGEs were anti-inflammatory at ng/ml, including inhibition of polymorphonuclear leukocyte (PMN proteases, P-selectin, and interaction of the receptor for advanced glycation end-products (RAGE with four representative ligands. SAGEs bound LL-37 and inhibited interleukin-8 production induced by LL-37 in cultured human keratinocytes. When mixed with LL-37 before injection, SAGEs prevented the erythema and PMN infiltration produced by direct intradermal injection of LL-37 into mouse skin. Topical application of a 1% (w/w SAGE emollient to overlying injected skin also reduced erythema and PMN infiltration from intradermal LL-37. CONCLUSIONS: Anionic polysaccharides, exemplified by SAGEs, offer potential as novel mechanism-based therapies for rosacea and by extension other LL-37-mediated and RAGE-ligand driven skin diseases.

  1. Water temperature profiles for reaches of the Raging River during summer baseflow, King County, western Washington, July 2015

    Science.gov (United States)

    Gendaszek, Andrew S.; Opatz, Chad C.

    2016-03-22

    Re-introducing wood into rivers where it was historically removed is one approach to improving habitat conditions in rivers of the Pacific Northwest. The Raging River drainage basin, which flows into the Snoqualmie River at Fall City, western Washington, was largely logged during the 20th century and wood was removed from its channel. To improve habitat conditions for several species of anadromous salmonids that spawn and rear in the Raging River, King County Department of Transportation placed untethered log jams in a 250-meter reach where wood was historically removed. The U.S. Geological Survey measured longitudinal profiles of near-streambed temperature during summer baseflow along 1,026 meters of channel upstream, downstream, and within the area of wood placements. These measurements were part of an effort by King County to monitor the geomorphic and biological responses to these wood placements. Near-streambed temperatures averaged over about 1-meter intervals were measured with a fiber‑optic distributed temperature sensor every 30 minutes for 7 days between July 7 and 13, 2015. Vertical temperature profiles were measured coincident with the longitudinal temperature profile at four locations at 0 centimeters (cm) (at the streambed), and 35 and 70 cm beneath the streambed to document thermal dynamics of the hyporheic zone and surface water in the study reach.

  2. Rages or Temper Tantrums? The Behavioral Organization, Temporal Characteristics, and Clinical Significance of Angry-Agitated Outbursts in Child Psychiatry Inpatients

    Science.gov (United States)

    Potegal, Michael; Carlson, Gabrielle; Margulies, David; Gutkovitch, Zinoviy; Wall, Melanie

    2009-01-01

    Angry, agitated outbursts (AAOs) are a common precipitant of children's psychiatric hospitalization. In the hospital, AAOs present both management and diagnostic challenges, e.g., while they have recently been described as manic "rages", older studies suggest that they may be exacerbated temper tantrums. Factor analyses of 109 AAOs had by 46…

  3. AGE-RAGE signal generates a specific NF-κB RelA “barcode” that directs collagen I expression

    Science.gov (United States)

    Peng, Yunqian; Kim, Ji-Min; Park, Hal-Sol; Yang, Annie; Islam, Celia; Lakatta, Edward G.; Lin, Li

    2016-01-01

    Advanced glycation end products (AGEs) are sugar-modified biomolecules that accumulate in the body with advancing age, and are implicated in the development of multiple age-associated structural and functional abnormities and diseases. It has been well documented that AGEs signal via their receptor RAGE to activate several cellular programs including NF-κB, leading to inflammation. A large number of stimuli can activate NF-κB; yet different stimuli, or the same stimulus for NF-κB in different cellular settings, produce a very different transcriptional landscape and physiological outcome. The NF-κB barcode hypothesis posits that cellular network dynamics generate signal-specific post-translational modifications, or a “barcode” to NF-κB, and that a signature “barcode” mediates a specific gene expression pattern. In the current study, we established that AGE-RAGE signaling results in NF-κB activation that directs collagen Ia1 and Ia2 expression. We further demonstrated that AGE-RAGE signal induces phosphorylation of RelA at three specific residues, T254, S311, and S536. These modifications are required for transcription of collagen I genes and are a consequence of cellular network dynamics. The increase of collagen content is a hallmark of arterial aging, and our work provides a potential mechanistic link between RAGE signaling, NF-κB activation, and aging-associated arterial alterations in structure and function. PMID:26729520

  4. Verification Test of the SURF and SURFplus Models in xRage: Part III Affect of Mesh Alignment

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-15

    The previous studies used an underdriven detonation wave in 1-dimension (steady ZND reaction zone profile followed by a scale-invariant rarefaction wave) for PBX 9502 as a verification test of the implementation of the SURF and SURFplus models in the xRage code. Since the SURF rate is a function of the lead shock pressure, the question arises as to the effect on accuracy of variations in the detected shock pressure due to the alignment of the shock front with the mesh. To study the effect of mesh alignment we simulate a cylindrically diverging detonation wave using a planar 2-D mesh. The leading issue is the magnitude of azimuthal asymmetries in the numerical solution. The 2-D test case does not have an exact analytic solution. To quantify the accuracy, the 2-D solution along rays through the origin are compared to a highly resolved 1-D simulation in cylindrical geometry.

  5. A Correlational Study of How Airline Customer Service and Consumer Perception of Airline Customer Service Affect the Air Rage Phenomenon

    Science.gov (United States)

    Hunter, Joyce A.

    2007-01-01

    Between 1995 and 2000, customer service declined throughout the airline industry, as reported in February 2001 by the U.S. Department of Transportation (2001). One of the biggest problems today within the airline industry is the constant complaining from customers regarding the deterioraton of service (McCollough, Berry, & Yadav, 2000). Since 1995, unfortunately no airline has been immune from service deterioration, as reported by the Airline Quality Rating, an annual report by two airline industry experts who analyzed Department of Transportation statistics (Harrison & Kleinsasser, 1999). The airline' refusal to recognize the issue of customer service has perpetuated an environment that has become dangerous and detrimental to the traveling public as well as to airline employees, which in turn has fueled a new phenomenon, now referred to as "air rage".

  6. Repérage d’Images Ordinaires : Analyse des Requêtes des Chercheurs d’Images

    Directory of Open Access Journals (Sweden)

    Elaine Ménard

    2009-06-01

    also emphasizes the pressing necessity to optimize the methods used for image processing, in order to facilitate image retrieval and dissemination in multilingual environments. Résumé Depuis quelques années, le web est devenu un média incontournable pour la diffusion de ressources multilingues. Cependant, les différences linguistiques constituent souvent un obstacle majeur aux échanges de documents scientifiques, culturels, pédagogiques et commerciaux. En plus de cette diversité linguistique, on constate le développement croissant de bases de données et de collections composées de différents types de documents textuels ou multimédias, ce qui complexifie également le processus de repérage documentaire. Par exemple, les collections d’images numériques sont aussi nombreuses que diversifiées. Le besoin de repérer une image spécifique dans diverses collections est devenu une préoccupation partagée par plusieurs communautés. La croissance du web a mis en relief le besoin pressant de se doter d’outils propres à la description des images dans le but de faciliter leur repérage, puisque l’on retrouve celles-ci dans la plupart des ressources disponibles. Cette recherche compare le repérage d’images dans deux contextes linguistiques différents : un contexte monolingue, c’est-à-dire que la langue de la requête (français est la même que la langue d’indexation (français; et un contexte multilingue où la langue de la requête (français est différente de la langue d’indexation (anglais. Cet article présente les résultats de l’analyse des requêtes formulées par les participants pour repérer un ensemble d’images ordinaires représentant des objets de la vie quotidienne, en contexte de repérage multilingue. L’examen des termes contenus dans les requêtes des chercheurs d’images révèle les tendances observées sur le plan terminologique, perceptuel et structurel. Les participants emploient généralement des requêtes simples

  7. Morphological adaptation of muscle collagen and receptor of advanced glycation end product (RAGE) in osteoarthritis patients with 12 weeks of resistance training

    DEFF Research Database (Denmark)

    Mattiello-Sverzut, Ana Claudia; Petersen, Susanne G; Kjaer, Michael;

    2013-01-01

    The aim of this study was to investigate the effect of 12-week resistance training on morphological presence of collagen and RAGE (receptor for advanced glycation end products) in skeletal muscle of patients with knee osteoarthritis (OA). Little is known about the influence of exercise...... on the skeletal muscle matrix that supports joints affected by OA mainly when it is associated with medication taken by OA patients (non-steroid anti-inflammatory drugs (NSAID) and glucosamine). A biopsy was collected from the vastus lateralis muscle in all patients before and after 12-week period of training....... The patients (age 55-69 years) were divided into three groups, treated with NSAID, glucosamine or placebo. In addition, the muscle samples were analysed by immunohistochemistry for collagen types, RAGE and capillaries ratio. An increment in immunoreactivity for type IV collagen after the training period...

  8. The Association of -429T>C and -374T>A Polymorphisms in the RAGE Gene with Polycystic Ovary Syndrome

    OpenAIRE

    Park, Jung-Hyun; Li, Lan; Choi, Jin-Woo; Baek, Kwang-Hyun

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a complex disorder characterized by hyperandrogenism and insulin resistance. In addition, a number of females with PCOS have ovaries with multiple cysts, an irregular or no menstrual cycle, and an imbalance of female hormones compared to those of normal controls. A variety of genetic factors have been involved in the pathogenesis of PCOS. Among these genetic factors, the receptor for advanced glycation end products (RAGE) that is associated with diabetes an...

  9. The “2T” ion-electron semi-analytic shock solution for code-comparison with xRAGE: A report for FY16

    Energy Technology Data Exchange (ETDEWEB)

    Ferguson, Jim Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-10-05

    This report documents an effort to generate the semi-analytic "2T" ion-electron shock solution developed in the paper by Masser, Wohlbier, and Lowrie [1], and the initial attempts to understand how to use this solution as a code-verification tool for one of LANL's ASC codes, xRAGE. Most of the work so far has gone into generating the semi-analytic solution. Considerable effort will go into understanding how to write the xRAGE input deck that both matches the boundary conditions imposed by the solution, and also what physics models must be implemented within the semi-analytic solution itself to match the model assumptions inherit within xRAGE. Therefore, most of this report focuses on deriving the equations for the semi-analytic 1D-planar time-independent "2T" ion-electron shock solution, and is written in a style that is intended to provide clear guidance for anyone writing their own solver.

  10. Ethyl pyruvate inhibits proliferation and induces apoptosis of hepatocellular carcinoma via regulation of the HMGB1–RAGE and AKT pathways

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Ping; Dai, Weiqi; Wang, Fan; Lu, Jie; Shen, Miao; Chen, Kan; Li, Jingjing; Zhang, Yan; Wang, Chengfen; Yang, Jing; Zhu, Rong; Zhang, Huawei; Zheng, Yuanyuan; Guo, Chuan-Yong, E-mail: guochuanyong@hotmail.com; Xu, Ling, E-mail: xuling606@sina.com

    2014-01-24

    Highlights: • Ethyl pyruvate inhibits liver cancer. • Promotes apoptosis. • Decreased the expression of HMGB1, p-Akt. - Abstract: Ethyl pyruvate (EP) was recently identified as a stable lipophilic derivative of pyruvic acid with significant antineoplastic activities. The high mobility group box-B1 (HMGB1)–receptor for advanced glycation end-products (RAGE) and the protein kinase B (Akt) pathways play a crucial role in tumorigenesis and development of many malignant tumors. We tried to observe the effects of ethyl pyruvate on liver cancer growth and explored its effects in hepatocellular carcinoma model. In this study, three hepatocellular carcinoma cell lines were treated with ethyl pyruvate. An MTT colorimetric assay was used to assess the effects of EP on cell proliferation. Flow cytometry and TUNEL assays were used to analyze apoptosis. Real-time PCR, Western blotting and immunofluorescence demonstrated ethyl pyruvate reduced the HMGB1–RAGE and AKT pathways. The results of hepatoma orthotopic tumor model verified the antitumor effects of ethyl pyruvate in vivo. EP could induce apoptosis and slow the growth of liver cancer. Moreover, EP decreased the expression of HMGB1, RAGE, p-AKT and matrix metallopeptidase-9 (MMP9) and increased the Bax/Bcl-2 ratio. In conclusion, this study demonstrates that ethyl pyruvate induces apoptosis and cell-cycle arrest in G phase in hepatocellular carcinoma cells, plays a critical role in the treatment of cancer.

  11. De la rage à l'enthousiasme : le parcours d'un jeune électeur saoudien

    Directory of Open Access Journals (Sweden)

    Pascal Ménoret

    2004-12-01

    Full Text Available Comment apprend-on le métier d'électeur dans une société autoritairement dépolitisée ? Cet entretien approfondi, réalisé avec un jeune électeur saoudien au lendemain de la victoire du courant religieux modéré aux élections municipale de février 2005 à Riyad, permet d'avancer quelques éléments de réponse. On verra ainsi que des dispositions politiques susceptibles d'être réinvesties dans l'activisme électoral ont pu être puisées par les plus fervents partisans du processus électoral dans les schèmes de pensée et d'acion propres aux groupes islamiques des écoles, aux cercles coraniques des mosquées et aux centres d'été du ministère des Affaires islamiques. L'activisme islamique n'est pas foncièrement incompatible avec un processus de démocratisation ; encore faut-il que la « rage » contractée au spectacle de la dictature et des injustices occidentales puisse se transformer en « enthousiasme » politique et électoral.

  12. Effects of psychotropic drugs on the rage responses induced by electrical stimulation of the medial hypothalamus in cats.

    Science.gov (United States)

    Fukuda, T; Tsumagari, T

    1983-08-01

    Effects of psychotropic drugs on the rage responses induced by electrical stimulation were investigated in cats with electrodes chronically implanted in the medial hypothalamus. Diazepam produced marked elevation in the threshold for directed attack and slight elevation in that for hissing. The inhibitory effect of etizolam on hissing was about 6 times as potent as that of diazepam. Anti-anxiety drugs such as diazepam, nitrazepam, lorazepam, clotiazepam and etizolam produced marked elevation in the directed attack threshold dose-dependently. The effect of chlorpromazine on directed attack was far less potent than that of anti-anxiety drugs. The anti-anxiety drugs used in this experiment had anti-pentetrazol activity in mice as well as muscle relaxant activity in cats. There were close correlations between the directed attack inhibition produced by the anti-anxiety drugs and both anti-pentetrazol activity and muscle relaxant activity. These results indicate that the above anti-anxiety drugs have a more potent inhibitory effect on the function of the medial hypothalamus than neuroleptic drugs. The inhibitory effect of anti-anxiety drugs on directed attack may be considered to correlate with clinical anti-anxiety effects. PMID:6632385

  13. Relationship between RAGE and hepatic ischemia/reperfusion injury%RAGE与肝缺血再灌注损伤间的关系

    Institute of Scientific and Technical Information of China (English)

    何超; 支军

    2011-01-01

    晚期糖化终末产物受体(reptor for advanccd glycation end product,RAGE)是一种单穿膜受体,同时也是一种多配体受体,属于免疫球蛋白超家族的成员.其配体包括高速泳动族框1蛋白质(high mobilily group box1,HMGB1)、晚期糖化终末产物(advanced glycalion end product,AGE),S100/钙粒蛋白(calgranulin)及β淀粉样肽等.在肝脏中,RAGE主要表达于巨噬细胞与树突状细胞.RAGE一旦被激活,就会通过一系列的信号传导,诱导这些细胞释放出多种促炎症的物质,并引起中性粒细胞沉积,产生瀑布式的炎症反应链.肝脏的缺血再灌注(ischemia/reperfusion,I/R)损伤作用机制繁多.其中RAGE作为一个关键的调节点,各种外来和内在的因素都可以通过作用于RAGE从而影响炎症反应.现就肝脏I/R损伤与RAGE之间关系做一综述.%Receptor for advanced glycation end products (SAGE), as one kind of single transmembrane receptor as well as multi-ligand receptor, belongs to the immunoglobulin super family. Its ligands include high mobility group boxl (HMGB1), advanced glycation end products (AGEs), S100/calgranulins, and amyloid-β peptides, etc. In the liver, RAGE is mainly expressed on macrophages and dendritic cells. These cells induced by activated RAGE can release a great variety of pro-inflammatory substances by a series of signal transduction, leading to neutrophil deposition and causing inflammatory cascade chain. There are diverse mechanisms in the process of hepatic ischemia/reperfusion (I/R) injury. RAGE, as a key regulator of this process, can be affected by various external and internal factors. This paper reviews the research progress of the relationship between RAGE and hepatic I/R injury.

  14. Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation.

    Science.gov (United States)

    Rani, Neha; Bharti, Saurabh; Bhatia, Jagriti; Nag, T C; Ray, Ruma; Arya, Dharamvir Singh

    2016-04-25

    AGE-RAGE interaction mediated oxidative stress and inflammation is the key mechanism involved in the pathogenesis of cardiovascular disease in diabetes. Inhibition of AGE-RAGE axis by several PPAR-γ agonists has shown positive results in ameliorating cardio-metabolic disease conditions. Chrysin, a natural flavonoid has shown to possess PPAR-γ agonist activity along with antioxidant and anti-inflammatory effect. Therefore, the present study was designed to evaluate the effect of chrysin in isoproterenol-induced myocardial injury in diabetic rats. In male albino Wistar rats, diabetes was induced by single injection of streptozotocin (70 mg/kg, i.p.). After confirmation of the diabetes, rats were treated with vehicle (1.5 mL/kg, p.o.), chrysin (60 mg/kg, p.o.) or PPAR-γ antagonist GW9662 (1 mg/kg, i.p.) for 28 days. Simultaneously, on 27th and 28th day myocardial injury was induced by isoproterenol (85 mg/kg, s.c.). Chrysin significantly ameliorated cardiac dysfunction as reflected by improved MAP, ±LVdP/dtmax and LVEDP in diabetic rats. This improvement was associated with increased PPAR-γ expression and reduced RAGE expression in diabetic rats. Chrysin significantly decreased inflammation through inhibiting NF-κBp65/IKK-β expression and TNF-α level. Additionally, chrysin significantly reduced apoptosis as indicated by augmented Bcl-2 expression and decreased Bax and caspase-3 expressions. Furthermore, chrysin inhibited nitro-oxidative stress by normalizing the alteration in 8-OHdG, GSH, TBARS, NO and CAT levels and Nox4, MnSOD, eNOS and NT expressions. Co-administration of GW9662 significantly blunted the chrysin mediated cardioprotective effect as there was increase in oxidative stress, inflammation and apoptosis markers. Chrysin significantly ameliorated isoproterenol-induced myocardial injury in diabetic rats via PPAR-γ activation and inhibition of AGE-RAGE mediated oxidative stress and inflammation. PMID:26972669

  15. Hyperoside Downregulates the Receptor for Advanced Glycation End Products (RAGE and Promotes Proliferation in ECV304 Cells via the c-Jun N-Terminal Kinases (JNK Pathway Following Stimulation by Advanced Glycation End-Products In Vitro

    Directory of Open Access Journals (Sweden)

    Zhengyu Zhang

    2013-11-01

    Full Text Available Hyperoside is a major active constituent in many medicinal plants which are traditionally used in Chinese medicines for their neuroprotective, anti-inflammatory and antioxidative effects. The molecular mechanisms underlying these effects are unknown. In this study, quiescent ECV304 cells were treated in vitro with advanced glycation end products (AGEs in the presence or absence of hyperoside. The results demonstrated that AGEs induced c-Jun N-terminal kinases (JNK activation and apoptosis in ECV304 cells. Hyperoside inhibited these effects and promoted ECV304 cell proliferation. Furthermore, hyperoside significantly inhibited RAGE expression in AGE-stimulated ECV304 cells, whereas knockdown of RAGE inhibited AGE-induced JNK activation. These results suggested that AGEs may promote JNK activation, leading to viability inhibition of ECV304 cells via the RAGE signaling pathway. These effects could be inhibited by hyperoside. Our findings suggest a novel role for hyperoside in the treatment and prevention of diabetes.

  16. Generation of Soluble Advanced Glycation End Products Receptor (sRAGE)-Binding Ligands during Extensive Heat Treatment of Whey Protein/Lactose Mixtures Is Dependent on Glycation and Aggregation.

    Science.gov (United States)

    Liu, Fahui; Teodorowicz, Małgorzata; Wichers, Harry J; van Boekel, Martinus A J S; Hettinga, Kasper A

    2016-08-24

    Heating of protein- and sugar-containing materials is considered the primary factor affecting the formation of advanced glycation end products (AGEs). This study aimed to investigate the influence of heating conditions, digestion, and aggregation on the binding capacity of AGEs to the soluble AGE receptor (sRAGE). Samples consisting of mixtures of whey protein and lactose were heated at 130 °C. An in vitro infant digestion model was used to study the influence of heat treatment on the digestibility of whey proteins. The amount of sRAGE-binding ligands before and after digestion was measured by an ELISA-based sRAGE-binding assay. Water activity did not significantly affect the extent of digestibility of whey proteins dry heated at pH 5 (ranging from 3.3 ± 0.2 to 3.6 ± 0.1% for gastric digestion and from 53.5 ± 1.5 to 64.7 ± 1.1% for duodenal digestion), but there were differences in cleavage patterns of peptides among the samples heated at different pH values. Formation of sRAGE-binding ligands depended on the formation of aggregates and was limited in the samples heated at pH 5. Moreover, the sRAGE-binding activity of digested sample was changed by protease degradation and correlated with the digestibility of samples. In conclusion, generation of sRAGE-binding ligands during extensive heat treatment of whey protein/lactose mixtures is limited in acidic heating condition and dependent on glycation and aggregation. PMID:27460534

  17. Neuroprotective effect of Amaranthus lividus and Amaranthus tricolor and their effects on gene expression of RAGE during oxidative stress in SH-SY5Y cells.

    Science.gov (United States)

    Amornrit, W; Santiyanont, R

    2016-01-01

    Amaranthus plants, or spinach, are used as food sources worldwide. Amaranthus leaves are rich in antioxidant compounds, which act as free radical scavengers. Oxidative stress caused by the aberrant production of reactive oxygen species (ROS) represents an important mechanism for neuronal dysfunction and cell loss in different neurodegenerative disorders. The neuroprotective effects of antioxidant-containing plants have been extensively demonstrated in different models of neurotoxicity. However, few studies have investigated the antioxidant properties of Amaranthus extracts and their effect on the nervous system. In the present study, the leaves of Amaranthus lividus and Amaranthus tricolor were extracted using petroleum ether, dichloromethane, and methanol. Results indicated that antioxidant activities were the highest in methanol extracts from both kinds of Amaranthus leaves. In addition, oxidative stress was induced in human neuroblastoma cell lines (SH-SY5Y) by using H2O2. Intracellular oxidative stress, cytotoxicity, and gene expression of RAGE were then determined. In vitro results demonstrated that pretreatment with A. lividus and A. tricolor extracts can significantly decrease cell toxicity and intracellular ROS production in SH-SY5Y cells. Interestingly, the extracts also significantly downregulated the expression of oxidative stress genes such as HMOX-1, RAGE, and RelA/ NF-κB. Our results suggested that Amaranthus leaves may be useful for reducing oxidative stress and may be beneficial for age-related diseases and neurodegenerative disorders. PMID:27173239

  18. Choline and Cystine Deficient Diets in Animal Models with Hepatocellular Injury: Evaluation of Oxidative Stress and Expression of RAGE, TNF-α, and IL-1β

    Directory of Open Access Journals (Sweden)

    Juliana Célia F. Santos

    2015-01-01

    Full Text Available This study aims to evaluate the effects of diets deficient in choline and/or cystine on hepatocellular injury in animal models (young male Wistar rats, aged 21 days, by monitoring some of the oxidative stress biomarkers and the expression of RAGE, TNF-α, and IL-1β. The animals were divided into 6 groups (n=10 and submitted to different diets over 30 days: AIN-93 diet (standard, St, AIN-93 choline deficient (CD diet and AIN-93 choline and cystine deficient (CCD diet, in the pellet (pl and powder (pw diet forms. Independently of the diet form, AIN-93 diet already led to hepatic steatosis and CD/CCD diets provoked hepatic damage. The increase of lipid peroxidation, represented by the evaluation of thiobarbituric acid reactive species, associated with the decrease of levels of antioxidant enzymes, were the parameters with higher significance toward redox profile in this model of hepatic injury. Regarding inflammation, in relation to TNF-α, higher levels were evidenced in CD(pl, while, for IL-1β, no significant alteration was detected. RAGE expression was practically the same in all groups, with exception of CCD(pw versus CCD(pl. These results together confirm that AIN-93 causes hepatic steatosis and choline and/or cysteine deficiencies produce important hepatic injury associated with oxidative stress and inflammatory profiles.

  19. Mild exposure of RIN-5F β-cells to human islet amyloid polypeptide aggregates upregulates antioxidant enzymes via NADPH oxidase-RAGE: An hormetic stimulus

    Directory of Open Access Journals (Sweden)

    Elisabetta Borchi

    2014-01-01

    Full Text Available The presence of amyloid aggregates of human islet amyloid polypeptide (hIAPP, a hallmark of type 2 diabetes, contributes to pancreatic β-cell impairment, where oxidative stress plays a key role. A contribution of NADPH oxidase to reactive oxygen species (ROS generation after cell exposure to micromolar concentrations of hIAPP aggregates has been suggested. However, little is known about β-cells exposure to lower amounts of hIAPP aggregates, similar to those found in human pancreas. Thus, we aimed to investigate the events resulting from RIN-5F cells exposure to nanomolar concentrations of toxic hIAPP aggregates. We found an early and transient rise of NADPH oxidase activity resulting from increased Nox1 expression following the engagement of receptor for advanced glycation end-products (RAGE by hIAPP aggregates. Unexpectedly, NADPH oxidase activation was not accompanied by a significant ROS increase and the lipoperoxidation level was significantly reduced. Indeed, cell exposure to hIAPP aggregates affected the antioxidant defences, inducing a significant increase of the expression and activity of catalase and glutathione peroxidase. We conclude that exposure of pancreatic β-cells to nanomolar concentrations of hIAPP aggregates for a short time induces an hormetic response via the RAGE-Nox1 axis; the latter stimulates the enzymatic antioxidant defences that preserve the cells against oxidative stress damage.

  20. Soluble HMGB1 is a novel adipokine stimulating IL-6 secretion through RAGE receptor in SW872 preadipocyte cell line: contribution to chronic inflammation in fat tissue.

    Directory of Open Access Journals (Sweden)

    Brice Nativel

    Full Text Available Low-grade inflammation (LGI is a central phenomenon in the genesis of obesity and insulin-resistance characterized by IL-6 in human serum. Whereas this LGI was initially thought to be mainly attributed to macrophage activation, it is now known that pre-adipocytes and adipocytes secrete several adipokines including IL-6 and participate to LGI and associated pathologies. In macrophages, HMGB1 is a nuclear yet secreted protein and acts as a cytokine to drive the production of inflammatory molecules through RAGE and TLR2/4. In this paper we tested the secretion of HMGB1 and the auto- and paracrine contribution to fat inflammation using the human preadipocyte cell line SW872 as a model. We showed that 1 human SW872 secreted actively HMGB1, 2 IL-6 production was positively linked to high levels of secreted HMGB1, 3 recombinant HMGB1 boosted IL-6 expression and this effect was mediated by the receptor RAGE and did not involve TLR2 or TLR4. These results suggest that HMGB1 is a major adipokine contributing to LGI implementation and maintenance, and can be considered as a target to develop news therapeutics in LGI associated pathologies such as obesity and type II diabetes.

  1. Neuroprotective effect of Amaranthus lividus and Amaranthus tricolor and their effects on gene expression of RAGE during oxidative stress in SH-SY5Y cells.

    Science.gov (United States)

    Amornrit, W; Santiyanont, R

    2016-04-26

    Amaranthus plants, or spinach, are used as food sources worldwide. Amaranthus leaves are rich in antioxidant compounds, which act as free radical scavengers. Oxidative stress caused by the aberrant production of reactive oxygen species (ROS) represents an important mechanism for neuronal dysfunction and cell loss in different neurodegenerative disorders. The neuroprotective effects of antioxidant-containing plants have been extensively demonstrated in different models of neurotoxicity. However, few studies have investigated the antioxidant properties of Amaranthus extracts and their effect on the nervous system. In the present study, the leaves of Amaranthus lividus and Amaranthus tricolor were extracted using petroleum ether, dichloromethane, and methanol. Results indicated that antioxidant activities were the highest in methanol extracts from both kinds of Amaranthus leaves. In addition, oxidative stress was induced in human neuroblastoma cell lines (SH-SY5Y) by using H2O2. Intracellular oxidative stress, cytotoxicity, and gene expression of RAGE were then determined. In vitro results demonstrated that pretreatment with A. lividus and A. tricolor extracts can significantly decrease cell toxicity and intracellular ROS production in SH-SY5Y cells. Interestingly, the extracts also significantly downregulated the expression of oxidative stress genes such as HMOX-1, RAGE, and RelA/ NF-κB. Our results suggested that Amaranthus leaves may be useful for reducing oxidative stress and may be beneficial for age-related diseases and neurodegenerative disorders.

  2. Extracellularly secreted APE1/Ref-1 triggers apoptosis in triple-negative breast cancer cells via RAGE binding, which is mediated through acetylation.

    Science.gov (United States)

    Lee, Yu Ran; Kim, Ki Mo; Jeon, Byeong Hwa; Choi, Sunga

    2015-09-15

    The present study evaluated the mechanism of apoptosis caused by post-translational modification, hyperacetylation in triple-negative breast cancer (TNBC) cells. We previously showed that trichostatin A (TSA) induced secretion of acetylated apurinic apyrimidinic endonuclease 1/redox factor-1 (Ac-APE1/Ref-1). This is the first report showing that Ac-APE1/Ref-1 initiates apoptosis in TNBC cells by binding to the receptor for advanced glycation end products (RAGE). The functional significance of secreted Ac-APE1/Ref-1 was studied by induction of intracellular hyperacetylation through co-treatment with acetylsalicylic acid and TSA in MDA-MB-231 cells. In response to hyperacetylation, secretion of Ac-APE1/Ref-1 in vesicles was observed, resulting in significantly decreased cell viability and induction of apoptosis with increased expression of RAGE. The hyperacetylation-induced apoptosis was similar in two other TNBC cell lines: BT-459 and MDA-MB-468. Therefore, hyperacetylation may be a therapeutic target for treatment of TNBCs. This study introduces a novel paradigm whereby post-translational modification induces apoptotic cell death in breast cancer cells resistant to standard chemotherapeutic agents through secretion of auto- or paracrine molecules such as Ac-APE1/Ref-1.

  3. Curbing Relocation Rage

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    once dubbed "the most defiant house" in Beijing, a 283-square- meter house on Lincui Road outside the North Fifth Ring Road in Haidian District was finally demol- ished on December 18, 2010, nearly five years after demolition of the area’s houses began.

  4. Where is your rage?

    Science.gov (United States)

    Sawyer, E

    1998-12-01

    A new round of activism is needed to address both new and old problems related to HIV/AIDS, problems such as access to treatment, confidential reporting, testing, funding, drug pricing, and government aid. Despite the media message that a cure is on the horizon, a cure is actually a long way off, and not accessible to all. Questions are raised about the future direction of the Centers for Disease Control's (CDC) effort to require names reporting and about the lack of HIV educational material and needle exchange programs. Concern is expressed about welfare reform, the political leadership of New York City and New York State, and the plight of poor people suffering from AIDS. AIDS activism is a useful tool in lowering drug prices for the poor and in pilot programs in developing countries that provide free AIDS drugs through UNAIDS. Government funding, HIV prevention programs, and attention to human rights are needed to bring about changes. Activism can take many forms, and people with AIDS need to get involved to make a difference.

  5. Morphological adaptation of muscle collagen and receptor of advanced glycation end product (RAGE) in osteoarthritis patients with 12 weeks of resistance training: influence of anti-inflammatory or glucosamine treatment.

    Science.gov (United States)

    Mattiello-Sverzut, Ana Claudia; Petersen, Susanne G; Kjaer, Michael; Mackey, Abigail L

    2013-09-01

    The aim of this study was to investigate the effect of 12-week resistance training on morphological presence of collagen and RAGE (receptor for advanced glycation end products) in skeletal muscle of patients with knee osteoarthritis (OA). Little is known about the influence of exercise on the skeletal muscle matrix that supports joints affected by OA mainly when it is associated with medication taken by OA patients (non-steroid anti-inflammatory drugs (NSAID) and glucosamine). A biopsy was collected from the vastus lateralis muscle in all patients before and after 12-week period of training. The patients (age 55-69 years) were divided into three groups, treated with NSAID, glucosamine or placebo. In addition, the muscle samples were analysed by immunohistochemistry for collagen types, RAGE and capillaries ratio. An increment in immunoreactivity for type IV collagen after the training period was observed in 72 % of all biopsies when compared with their respective baseline samples. Reduced immunoreactivity of collagen type I was observed in all patients treated with glucosamine. A significant increase with training in the amount of RAGE was detected in the placebo group only (p muscle fibres after 12 weeks of resistance training. Glucosamine with training appeared to attenuate RAGE accumulation more than was seen with NSAID or placebo in skeletal muscle of OA patients.

  6. Predictive value of AGEs and their receptor RAGE and sRAGE for perinatal outcome of gestational diabetes%血清中晚期糖基化终产物及其受体对妊娠期糖尿病围产儿结局的预测价值

    Institute of Scientific and Technical Information of China (English)

    汤栩文; 林斯; 谢晓斌

    2012-01-01

    目的 探讨妊娠期糖尿病孕妇(GDM)血清中晚期糖基化终产物(AGEs) -晚期糖基化终产物受体(RAGE)轴所介导的氧化应激反应与国产儿结局间的关系.方法 选择2011年1月至12月在广州市妇女儿童医疗中心产科检查,孕24~28周产前检查被诊断患有GDM的孕妇100例为研究对象(GDM组),另选择同期、相应年龄的正常妊娠妇女50例作为正常对照组.抽取两组孕妇的血样,测量空腹血糖、糖化血红蛋白(HbA1c)和AGEs、可溶性RAGE(sRAGE)水平.分娩后收集胎盘,分析组织中RAGE蛋白的表达.并收集母婴临床信息,根据围产儿结局异常与否分为GDM正常围产儿结局组和GDM不良围产儿结局组.结果 GDM组治疗前孕妇血清AGEs 水平(50.44±16.21) ng/L,明显高于正常对照组(32.69±10.13)ng/L (P<0.01).GDM组经干预治疗后其空腹血糖和HbA1c水平与正常对照组比较,差异无统计学意义(P>0.05);但血清AGEs水平仍然高于正常对照组(P<0.01).GDM组孕母血清AGEs与sRAGE水平呈负相关(r=-0.582,P< 0.01).GDM不良围产儿结局组孕妇血清AGEs水平(67.39 ±14.75) ng/L明显高于GDM正常围产儿结局组(41.59±12.26)ng/L (P <0.05).Logistic回归分析显示高AGEs水平是GDM不良围产儿结局的危险因子(OR =6.197,P<0.01,95% CI 2.514 ~15.453);低sRAGE水平也是GDM不良围产儿结局的危险因子(OR =0.498,P<0.05,95% CI 0.217~0.925).GDM不良围产儿结局组(0.993±0.085)高于GDM正常围产儿结局组(0.611±0.047)和正常对照组(0.247±0.018)(P均<0.01).结论 血清高AGEs水平是GDM围产儿结局的一个不利因素,高AGEs水平可作为GDM 不良围产儿结局的预测指标.血循环中sRAGE可通过竞争结合方式中和AGEs,抑制其下游信号的传递,血清低sRAGE水平可作为GDM病变中AGEs-RAGE轴过度活跃的生物标记.%Objective Explore the relationship between gestational diabetes during pregnancy (GDM) in serum advanced glycation

  7. In vivo isotropic 3D diffusion tensor mapping of the rat brain using diffusion-weighted 3D MP-RAGE MRI.

    Science.gov (United States)

    Numano, Tomokazu; Homma, Kazuhiro; Iwasaki, Nobuaki; Hyodo, Koji; Nitta, Naotaka; Hirose, Takeshi

    2006-04-01

    The purpose of this study was to examine the potential of diffusion-weighted (DW) three-dimensional (3D) MP-RAGE MRI for diffusion-tensor mapping of the rat brain in vivo. A DW-3D-MP-RAGE (3D-DWI) sequence was implemented at 2.0 T using six gradient orientations and a b value of 1000 s/mm2. In this sequence, the preparation sequence with a "90 degrees RF-motion proving gradient (MPG): MPG-180 degrees RF-MPG-90 degrees RF" pulse train (DW driven equilibrium Fourier transform) was used to sensitize the magnetization to diffusion. A centric k-space acquisition order was necessary to minimize saturation effects (T1 contamination) from tissues with short relaxation time. The image matrix was 128x128x128 (interpolated from 64x64x64 acquisitions), which resulted in small isotropic DW image data (voxel size: 0.273x0.273x0.273 mm3). Moreover, 3D-DWI-derived maps of the fractional anisotropy (FA), relative anisotropy (RA) and main-diffusion direction were completely free of susceptibility-induced signal losses and geometric distortions. Two well-known commissural fibers, the corpus callosum and anterior commissure, were indicated and shown to be in agreement with the locations of these known stereotaxic atlases. The experiment took 45 min, and shorter times should be possible in clinical application. The 3D-DWI sequence allows for in vivo 3D diffusion-tensor mapping of the rat brain without motion artifacts and susceptibility to distortion. PMID:16563958

  8. Pinocembrin protects against β-amyloid-induced toxicity in neurons through inhibiting receptor for advanced glycation end products (RAGE-independent signaling pathways and regulating mitochondrion-mediated apoptosis

    Directory of Open Access Journals (Sweden)

    Liu Rui

    2012-09-01

    Full Text Available Abstract Background It is known that amyloid-β peptide (Aβ plays a pivotal role in the pathogenesis of Alzheimer's disease (AD. Interaction between Aβ and the receptor for advanced glycation end products (RAGE has been implicated in neuronal degeneration associated with this disease. Pinocembrin, a flavonoid abundant in propolis, has been reported to possess numerous biological activities beneficial to health. Our previous studies have demonstrated that pinocembrin has neuroprotective effects on ischemic and vascular dementia in animal models. It has been approved by the State Food and Drug Administration of China for clinical use in stroke patients. Against this background, we investigated the effects of pinocembrin on cognitive function and neuronal protection against Aβ-induced toxicity and explored its potential mechanism. Methods Mice received an intracerebroventricular fusion of Aβ25-35. Pinocembrin was administrated orally at 20 mg/kg/day and 40 mg/kg/day for 8 days. Behavioral performance, cerebral cortex neuropil ultrastructure, neuronal degeneration and RAGE expression were assessed. Further, a RAGE-overexpressing cell model and an AD cell model were used for investigating the mechanisms of pinocembrin. The mechanisms underlying the efficacy of pinocembrin were conducted on target action, mitochondrial function and potential signal transduction using fluorescence-based multiparametric technologies on a high-content analysis platform. Results Our results showed that oral administration of pinocembrin improved cognitive function, preserved the ultrastructural neuropil and decreased neurodegeneration of the cerebral cortex in Aβ25-35-treated mice. Pinocembrin did not have a significant effect on inhibiting Aβ1-42 production and scavenging intracellular reactive oxygen species (ROS. However, pinocembrin significantly inhibited the upregulation of RAGE transcripts and protein expression both in vivo and in vitro, and also markedly

  9. Comparison of contrast-enhanced modified T1-weighted 3D TSE black-blood and 3D MP-RAGE sequences for the detection of cerebral metastases and brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kammer, N.N.; Coppenrath, E.; Treitl, K.M.; Saam, T. [Ludwig-Maximilians-University Hospital Munich, Institute for Clinical Radiology, Munich (Germany); Kooijman, H. [Philips Healthcare, Hamburg (Germany); Dietrich, O. [Ludwig-Maximilians-University Hospital Munich, Josef Lissner Laboratory for Biomedical Imaging, Institute for Clinical Radiology, Munich (Germany)

    2016-06-15

    To compare a modified T1-weighted 3D TSE black-blood sequence with sub-millimetre resolution (T1-mVISTA) with a magnetization-prepared rapid gradient echo (MP-RAGE) sequence for the diagnosis of cerebral malignomas. Forty-six patients with known or suspected intracranial tumours and 15 control patients were included in this retrospective study. All patients underwent T1-mVISTA (0.75-mm isotropic resolution, 4:43 min) and MP-RAGE (0.8-mm isotropic resolution, 4:46 minutes) at 3-Tesla in random order after application of contrast agent. Two experienced radiologists determined the number of lesions. Maximum diameter, diagnostic confidence (DC), visual assessment of contrast enhancement (VCE) and CNR{sub lesion/parenchyma} were assessed for each lesion. Significantly more lesions were detected with T1-mVISTA compared to the MP-RAGE (61 vs. 36; p < 0.05). Further, DC and VCE was rated significantly higher in the T1-mVISTA (p < 0.05 and p < 0.001). Mean CNR{sub lesion/parenchyma} was twofold higher for T1-mVISTA (24.2 ± 17.5 vs. 12.7 ± 11.5, p < 0.001). The 25 lesions detected only in T1-mVISTA were significantly smaller than those detected in both sequences (4.3 ± 3.7 mm vs. 11.3 ± 10.7 mm; p < 0.01). T1-mVISTA increases the contrast of lesions significantly compared to MP-RAGE and might therefore improve detection rates of small lesions in early stages of disease. (orig.)

  10. Comparison of contrast-enhanced modified T1-weighted 3D TSE black-blood and 3D MP-RAGE sequences for the detection of cerebral metastases and brain tumours

    International Nuclear Information System (INIS)

    To compare a modified T1-weighted 3D TSE black-blood sequence with sub-millimetre resolution (T1-mVISTA) with a magnetization-prepared rapid gradient echo (MP-RAGE) sequence for the diagnosis of cerebral malignomas. Forty-six patients with known or suspected intracranial tumours and 15 control patients were included in this retrospective study. All patients underwent T1-mVISTA (0.75-mm isotropic resolution, 4:43 min) and MP-RAGE (0.8-mm isotropic resolution, 4:46 minutes) at 3-Tesla in random order after application of contrast agent. Two experienced radiologists determined the number of lesions. Maximum diameter, diagnostic confidence (DC), visual assessment of contrast enhancement (VCE) and CNRlesion/parenchyma were assessed for each lesion. Significantly more lesions were detected with T1-mVISTA compared to the MP-RAGE (61 vs. 36; p < 0.05). Further, DC and VCE was rated significantly higher in the T1-mVISTA (p < 0.05 and p < 0.001). Mean CNRlesion/parenchyma was twofold higher for T1-mVISTA (24.2 ± 17.5 vs. 12.7 ± 11.5, p < 0.001). The 25 lesions detected only in T1-mVISTA were significantly smaller than those detected in both sequences (4.3 ± 3.7 mm vs. 11.3 ± 10.7 mm; p < 0.01). T1-mVISTA increases the contrast of lesions significantly compared to MP-RAGE and might therefore improve detection rates of small lesions in early stages of disease. (orig.)

  11. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    International Nuclear Information System (INIS)

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ (PPAR-γ). Although nifedipine did not affect expression levels of PPAR-γ, it increased the PPAR-γ transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-γ activation.

  12. The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction

    Directory of Open Access Journals (Sweden)

    Junghyun Kim

    2016-09-01

    Full Text Available Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE against damage to retinal vascular cells were investigated in streptozotocin (STZ-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-κB and inducible nitric oxide synthase (iNOS were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-κB and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-κB activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells.

  13. A diffusive radiation hydrodynamics code, xRage, is implemented to compare radiation flow with experimental data from the Omega laser facility

    Science.gov (United States)

    Vandervort, Robert; Elgin, Laura; Farag, Ebraheem; Mussack, Katie; Baumgaertel, Jessica Ann; Keiter, Paul; Klein, Sallee; Orban, Christopher; Drake, R. Paul

    2015-11-01

    A sound speed discrepancy between solar models and data collected using helioseismology exists. The sound speed discrepancy is the most pronounced at the base of the convective zone (CZ) for otherwise consistent solar models. One potential solution is that the opacity models for important elements such as carbon, nitrogen and oxygen are incomplete. At these high energy-density conditions few relevant opacity measurements exist to compare to the models. Only relatively recently have user facilities been able to reach the temperatures and densities that resemble the convective zone base. It is our long term goal to determine the opacities of carbon, nitrogen and oxygen at the relevant conditions. Preliminary testing has occurred at the Omega Laser Facility in Rochester, New York. Presented are the results of the shots taken on April 22, 2015. A half hohlraum was used to drive a supersonic radiation front through a dominantly carbon, CRF, foam. These results are compared to diffusive xRage simulations. (LA-UR-15-25495)

  14. Non-professional marathon running: RAGE axis and ST2 family changes in relation to open-window effect, inflammation and renal function

    Science.gov (United States)

    Bekos, Christine; Zimmermann, Matthias; Unger, Lukas; Janik, Stefan; Hacker, Philipp; Mitterbauer, Andreas; Koller, Michael; Fritz, Robert; Gäbler, Christian; Kessler, Mario; Nickl, Stefanie; Didcock, Jessica; Altmann, Patrick; Haider, Thomas; Roth, Georg; Klepetko, Walter; Ankersmit, Hendrik Jan; Moser, Bernhard

    2016-01-01

    Conflicting data exist on the relevance of marathon (M) and half marathon (HM) running for health. The number of non-professional athletes finishing M and HM events is steadily growing. In order to investigate molecular changes occurring in amateur athletes, we enrolled 70 non-professional runners finishing a single M (34) or HM (36) event at baseline, the finish line and during recovery, and 30 controls. The measurement of the Receptor for Advanced Glycation Endproducts, Interleukin 1 receptor antagonist, ST2 and cytokeratin 18 was combined with molecules measured during clinical routine. Results were analyzed in the light of blood cell analysis, lactate measurements, correction for changes in plasma volume and body composition assessments. There were intrinsic differences in body mass index, abdominal body fat percentage and training time between M and HM runners. C-reactive protein changes in M and HM runners. While soluble RAGE, AGEs and ST2 increased immediately after the race in HM runners, HMGB1 increased in HM and M after the race and declined to baseline after a recovery period. We give insights into the regulation of various molecules involved in physical stress reactions and their possible implications for the cardiovascular system or renal function. PMID:27653273

  15. Epigallocatechin-3-gallate combined with alpha lipoic acid attenuates high glucose-induced receptor for advanced glycation end products (RAGE expression in human embryonic kidney cells

    Directory of Open Access Journals (Sweden)

    Jyh-Gang Leu

    Full Text Available The anti-oxidant effects of epigallocatechin gallate (EGCG and alpha lipoic acid (ALA have been demonstrated in previous studies. The kidney protection effects of EGCG and ALA in patients with kidney injury are still under investigation. The purpose of this study is to investigate the anti-inflammatory and anti-oxidant effects of EGCG and ALA on high glucose-induced human kidney cell damage. EGCG inhibited high glucose(HG-induced TNF-α and IL-6 production in human embryonic kidney (HEK cells. Both EGCG and ALA decreased HG-induced receptor of advanced glycation end products (RAGE mRNA and protein expressions in HEK cells. EGCG and ALA also recovered HG-inhibited superoxide dismutase production and decreased ROS expressions in HEK cells. The synergism of EGCG and ALA was also studied. The effect of EGCG combined with ALA is greater than the effect of EGCG alone in all anti-inflammation and anti-oxidant experiments. Our studies provide a potential therapeutic application of EGCG and ALA in preventing progression of diabetic nephropathy.Os efeitos antioxidantes de galato de epigalocatequina (EGCG e ácido alfa lipóico (ALA foram demonstrados em estudos anteriores. Os efeitos renais da proteção de EGCG e ALA em pacientes com lesão renal ainda estão sob investigação. A finalidade deste estudo é investigar os efeitos anti-inflamatórios e antioxidantes de EGCG e ALA em lesão de células de rim humano induzida pela alta glicose. EGCG inibiu a produção de TNF-α e IL-6 induzida por HG em células de rim embrionário humano (HEK. Ambos EGCG e ALA diminuíram o mRNA do receptor de produtos finais de glicação avançada (RAGE induzida por HG e a expressão de proteínas em células HEK. EGCG e ALA também recuperaram a produção de superóxido dismutase inibida por HG e diminuíram a expressão de ROS em células HEK. O sinergismo de EGCG e ALA também foi estudado. O efeito de EGCG combinado com ALA é maior do que o efeito de EGCG sozinho

  16. Méthodes et défis du repérage d’images sur le Web : Jean et John cherchent-ils de la même manière ?

    Directory of Open Access Journals (Sweden)

    Elaine Ménard

    2012-06-01

    Full Text Available Nous faisons ici le point sur les principales méthodes employées pour le repérage d’images numériques que l’on trouve dans la majorité des sites et pages Web. Les méthodes d’indexation manuelles et automatiques facilitant le repérage d’images sont également décrites. Nous nous attardons plus particulièrement sur les problèmes rencontrés par les chercheurs d’images lors du repérage en contexte multilingue, c’est-à-dire lorsque la langue de la requête diffère de la langue d’indexation. Le principal objectif de cette étude était d’identifier les similarités et les différences dans la manière de formuler les requêtes de quatre groupes de participants de langue maternelle différente au moment du repérage d’images sur le Web. Nous avons demandé à quatre groupes de dix participants de quatre communautés linguistiques différentes (française, anglaise, russe et chinoise de préciser quelles catégories de termes ils utilisent en général dans leurs requêtes lors de la recherche d’images sur le Web. Les résultats de notre étude sur les comportements de recherche des chercheurs d’images de quatre communautés linguistiques différentes ont révélé des différences significatives dans la manière de chercher (nombre de requêtes utilisées, longueur des requêtes, attributs conceptuels et terminologiques contenus dans les requêtes. Ces différences doivent être prises en considération au moment de l’élaboration des fonctionnalités de recherche proposées par les moteurs permettant la recherche d’images. En outre, la manière de chercher des images varie en fonction de la langue maternelle du chercheur d’images. Le défi de l’accès aux images, peu importe leur mode d’indexation, reste entier.

  17. 生物心理社会医学模式视角下的"路怒症"剖析%Analysis of Road Rage from the Perspective of Bio-psycho-social Medical Model

    Institute of Scientific and Technical Information of China (English)

    骞宪忠; 郑建中

    2011-01-01

    Road rage has become a serious concern in many countries, and some of scholars have conducted the studies about the relationships between driving safety, stress reacting and psychiatric diseases. We thought that it's necessary to study this phenomenon as a kind of health problems from the perspective of Bio-psycho-social medical model; integrate efforts were made to position it scientifically, to find the reasons and to give some advices to help the drivers who intend to perform road rage recover and maintain good physical and mental well-being.%随着汽车作为代步工具逐渐走人家庭,"路怒症"成了一种新的常见汽车综合征.国内外学者从交通安全、应激反应、精神疾患等方面对其作了一定研究,随着研究的深入,这一现象应置于生物心理社会医学模式视角下进行多方位剖析,对其进行科学定位、综合研究,并找出相应的对策,帮助有"路怒症"倾向的驾驶人恢复良好的身心健康状态.

  18. Schisandrin B Ameliorates ICV-Infused Amyloid β Induced Oxidative Stress and Neuronal Dysfunction through Inhibiting RAGE/NF-κB/MAPK and Up-Regulating HSP/Beclin Expression.

    Directory of Open Access Journals (Sweden)

    Vijayasree V Giridharan

    Full Text Available Amyloid β (Aβ-induced neurotoxicity is a major pathological mechanism of Alzheimer's disease (AD. Our previous studies have demonstrated that schisandrin B (Sch B, an antioxidant lignan from Schisandra chinensis, could protect mouse brain against scopolamine- and cisplatin-induced neuronal dysfunction. In the present study, we examined the protective effect of Sch B against intracerebroventricular (ICV-infused Aβ-induced neuronal dysfunction in rat cortex and explored the potential mechanism of its action. Our results showed that 26 days co-administration of Sch B significantly improved the behavioral performance of Aβ (1-40-infused rats in step-through test. At the same time, Sch B attenuated Aβ-induced increases in oxidative and nitrosative stresses, inflammatory markers such as inducible nitric oxide syntheses, cyclooxygenase-2, interleukin-1β (IL-1β, IL-6, and tumor necrosis factor-α, and DNA damage. Several proteins such as receptor for advanced glycation end products (RAGE, nuclear factor-κB, mitogen-activated protein kinases, and apoptosis markers were over expressed in Aβ-infused rats but were significantly inhibited by Sch B treatment. Furthermore, Sch B negatively modulated the Aβ level with simultaneous up-regulation of HSP70 and beclin, autophagy markers in Aβ-infused rats. The aforementioned effects of Sch B suggest its protective role against Aβ-induced neurotoxicity through intervention in the negative cycle of RAGE-mediated Aβ accumulation during AD patho-physiology.

  19. Repérages bibliographiques

    Directory of Open Access Journals (Sweden)

    Sabrina Mommolin

    2013-05-01

    Full Text Available Gouvernance – Governance AL AJEELI A., AL-BASTAKI Y. A. L. (2011, Handbook of research on e-services in the public sector: e-government strategies and advancements. Hershey, PA : Information Science Reference, 523 p. CHEN Y.-C., CHU P.-Y. (2011, Electronic governance and cross-boundary collaboration : innovations and advancing tools. Hershey, PA : IGI Global, 421 p. CROPF R. A., KRUMMENACHER W. S. (2011, Information Communication Technologies and the virtual public sphere: impacts of netwo...

  20. Repérages bibliographiques

    Directory of Open Access Journals (Sweden)

    Sabrina Mommolin

    2016-05-01

    Full Text Available Développement durable – Sustainable development APAK S., ATAY E. (2015, “Global Competitiveness in the EU through Green Innovation Technologies and Knowledge Production”, Procedia - Social and Behavioral Sciences, vol. 181, pp. 207-217. BORSDORF A., BENDER O., BRAUN F., HALLER A. (2015, Web-based instruments for strengthening sustainable regional development in the Alps, Geografski Zbornik / Acta Geographica Slovenica, vol. 55, N° 1, pp. 174-182. SIRSIKAR S.V., KAREMORE P. (2015, Design an...

  1. Repérages bibliographiques

    Directory of Open Access Journals (Sweden)

    Sabrina Mommolin

    2015-10-01

    Full Text Available Commerce électronique - E-commerce AYDIN, E., SAVRUL, B. K. (2014, "The Relationship between Globalization and E-commerce: Turkish Case", Procedia - Social and Behavioral Sciences, vol. 150, pp. 1267-1276. BASTARD, I., BOURREAU, M., MOREAU, F. (2014, "L’impact du piratage sur l’achat et le téléchargement légal: Une comparaison de quatre filières culturelles", Revue économique, vol. 65, n°3, pp. 573-599. FEIZOLLAHI, S., SHIRMOHAMMADI, A., KAHREH, Z. S., et al. (2014, "Investigation the Effe...

  2. Repérages bibliographiques

    Directory of Open Access Journals (Sweden)

    Sabrina Mommolin

    2015-12-01

    Full Text Available Commerce électronique - E-commerce BURKHALTER J. N., WOOD N. T., (Eds. (2015, Maximizing Commerce and Marketing Strategies through Micro-Blogging, Hershey, PA, USA: IGI Global. 354 p. ISBN: 978-1-4666-8408-9 KHOSROW-POUR M. (Ed. (2015, Strategic E-Commerce Systems and Tools for Competing in the Digital Marketplace, Hershey, PA, USA: IGI Global, 263 p. ISBN: 978-1-4666-8133-0 LTIFI M., GHARBI J. (2015, « Impact de la qualité perçue du site web marchand sur le bonheur du cyberconsommateur ...

  3. Repérages bibliographiques

    Directory of Open Access Journals (Sweden)

    Sabrina Mommolin

    2013-04-01

    Full Text Available Gouvernance – Governance AYANSO A., CHATTERJEE D., CHO D. I. (2011, “E-Government readiness index: A methodology and analysis”, Government Information Quarterly, vol. 28, n° 4, pp. 522-532. CHEN Y.-C., CHU P.-Y. (2011, Electronic Governance and Cross-Boundary Collaboration: Innovations and Advancing Tools, Hershey, PA: IGI Global, 422 p. ISBN: 9781609607548 CONCHA G., ASTUDILLO H., PORRÚA M. (et al. (2011, “E-Government procurement observatory, maturity model and early measurements”, Gove...

  4. Repérages bibliographiques

    OpenAIRE

    Mommolin, Sabrina

    2015-01-01

    Commerce électronique - E-commerce AYDIN, E., SAVRUL, B. K. (2014), "The Relationship between Globalization and E-commerce: Turkish Case", Procedia - Social and Behavioral Sciences, vol. 150, pp. 1267-1276. BASTARD, I., BOURREAU, M., MOREAU, F. (2014), "L’impact du piratage sur l’achat et le téléchargement légal: Une comparaison de quatre filières culturelles", Revue économique, vol. 65, n°3, pp. 573-599. FEIZOLLAHI, S., SHIRMOHAMMADI, A., KAHREH, Z. S., et al. (2014), "Investigation the Effe...

  5. Repérages bibliographiques

    OpenAIRE

    Mommolin, Sabrina

    2015-01-01

    Commerce électronique - E-commerce BURKHALTER J. N., WOOD N. T., (Eds.) (2015), Maximizing Commerce and Marketing Strategies through Micro-Blogging, Hershey, PA, USA: IGI Global. 354 p. ISBN: 978-1-4666-8408-9 KHOSROW-POUR M. (Ed.) (2015), Strategic E-Commerce Systems and Tools for Competing in the Digital Marketplace, Hershey, PA, USA: IGI Global, 263 p. ISBN: 978-1-4666-8133-0 LTIFI M., GHARBI J. (2015), « Impact de la qualité perçue du site web marchand sur le bonheur du cyberconsommateur ...

  6. Effect of penequinine hydrochloride on the expression of RAGE in rat hippocampal neurons after status epilepticus%盐酸戊乙奎醚对癫疒间持续状态大鼠海马神经元RAGE表达的影响

    Institute of Scientific and Technical Information of China (English)

    程伟; 朱建南; 孙秀媛; 齐敦益; 戴体俊; 刘功俭

    2012-01-01

    Objective To investigate the effect of penequinine hydrochloride on the expression of RAGE and NF -κB in rat hippocampal neurons after status epilepticus . Methods Male SD rats were randomly divided into three groups , ie. A control group, a status epilepticus group and a penequinine hydrochloride group (re = 8 each). The rats abdominal cavity of status epilepticus group were injected lithium - pilecarpine to establish status epilepticus model. The expression of RAGE and nuclear factor kappa B ( NF - κB) p65 in hippocampal was measured by Western blot. TUNEL assay was used merely to identify apoptotic cells. Results Compared with the control group , the expression of RAGE and NF - κB p65 was significantly higher in status epilepticus group and apoptotic cells were significant increased (P <0.01). Compared with the status epilepticus group , the expression of RAGE and NF - κB p65 was significantly lower and apoptotic cells were decreased in penequinine hydrochloride group ( P < 0. 01). Conclusion Penequinine hydrochloride shows a protective effects on rat hippocampal neurons after status epilepticus through inhibiting the expression of RAGE and NF -κB.%目的 探讨盐酸戊乙奎醚(长托宁)对癫(癎)持续状态(SE)后大鼠海马晚期糖基化终末产物受体(RAGE)和核因子κB(NF-κB)的影响.方法 SD大鼠随机分为A组(对照组)、B组(模型组)和C组(盐酸戊乙奎醚组),每组8只.应用氯化锂-匹罗卡品制备SE模型.TUNEL法检测大鼠海马细胞凋亡,Western blot法检测大鼠海马RAGE及NF-κB p65的表达改变情况.结果 与A组比较,B组大鼠海马RAGE、NF-κB p65水平明显增高,神经元凋亡增加(P<0.01);与B组比较,C组大鼠海马RAGE、NF-κB p65水平降低,神经元凋亡减少(P<0.01).结论 盐酸戊乙奎醚可抑制RAGE-NF-κB通路和减少神经元凋亡,对SE后大鼠海马神经元发挥保护作用.

  7. AGE-RAGE系统与糖尿病足综合征的发病机制及治疗进展%The relationship between AGE-RAGE system and pathogenesis of diabetic foot syndrome, and advance on treatment

    Institute of Scientific and Technical Information of China (English)

    孟庆元; 林炜栋; 陈向芳

    2009-01-01

    糖尿病足综合征(DFS)是糖尿病严重慢性并发症之一,其发病机制至今尚未完全阐明.晚期糖基化终末产物(AGEs)的形成参与DFS的发生、发展,AGEs与AGEs受体(RAGE)相互作用,并通过一系列分子机制导致糖尿病神经病变和外周血管病变.因此,抑制AGEs形成或阻断AGEs与其受体相互作用可以延缓糖尿病足的发生、发展.本文就AGEs形成、AGE-RAGE系统在DFS中的作用和DFS的治疗进展等作一综述.

  8. 白藜芦醇改善糖尿病血管炎症反应及其与RAGE信号的相关性%Resveratrol protecting the aorta against inflammation reaction associated with RAGE signal in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    刘涛; 巩增锋; 尹洁; 景玉宏

    2012-01-01

    Objective To study the protective effect and underlying mechanism of resveratrol treatment on vasculature injury in diabetic rats. Methods Diabetic animal models were established by single injection of STZ(40 mg/kg) through femoral vein together with high fat diet. Blood fructosamine was measured by using reaction of enzyme-substrate for four months. Lipid plaques were tested by using Oil red staining in intact aorta. Levels of TNF-α and 1L-6 in aorta tissue were analyzed by using semi-quantitative RT-PCR technique. Also, expression of RAGE in aorta was tested by Western blot method. Results Resveratrol treatment attenuated the amount of blood fructosamine, suppressed the expression of TNF-α and IL-6, and decreased the expression of RAGE in aorta as well as ameliorated the deposition of lipid plaques in inner wall of aorta in diabetic rats. Conclusion Resveratrol treatment can protect the vasculature injured by diabetes. This protective effect may relate with its functions in attenuation of accumulation of advanced glycation end product, inhibition of the RAGE signal, amelioration of the vasculature inflammatory reaction, and reduction of deposition of lipid plaques in diabetic rats.%目的 在糖尿病动物模型上研究白藜芦醇(RSV)对糖尿病血管损伤的保护效应及可能机制. 方法 STZ单次低剂量(40 mg/kg)经股静脉注射,联合高脂饮食,建立糖尿病模型.利用酶底物分析技术检测血液中糖化血清蛋白的含量,在整体主动脉组织上利用Oil Red检测血管内壁脂肪斑块沉积.利用半定量RT-PCR技术检测主动脉组织中TNF-α及IL-6的水平.利用Western blotting技术检测主动脉组织中RAGE表达水平. 结果 RSV持续给药可以减轻糖尿病大鼠血液中糖化血清蛋白的含量,抑制主动脉组织中TNF-α及IL-6的水平,同时抑制RAGE的高表达.RSV也显著减少了糖尿病所致的主动脉内壁脂肪斑块沉积. 结论 RSV可以保护糖尿病导致的血管损伤,这

  9. Advanced Glycation End Products Affect Osteoblast Proliferation and Function by Modulating Autophagy Via the Receptor of Advanced Glycation End Products/Raf Protein/Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase/Extracellular Signal-regulated Kinase (RAGE/Raf/MEK/ERK) Pathway.

    Science.gov (United States)

    Meng, Hong-Zheng; Zhang, Wei-Lin; Liu, Fei; Yang, Mao-Wei

    2015-11-20

    The interaction between advanced glycation end products (AGEs) and receptor of AGEs (RAGE) is associated with the development and progression of diabetes-associated osteoporosis, but the mechanisms involved are still poorly understood. In this study, we found that AGE-modified bovine serum albumin (AGE-BSA) induced a biphasic effect on the viability of hFOB1.19 cells; cell proliferation was stimulated after exposure to low dose AGE-BSA, but cell apoptosis was stimulated after exposure to high dose AGE-BSA. The low dose AGE-BSA facilitates proliferation of hFOB1.19 cells by concomitantly promoting autophagy, RAGE production, and the Raf/MEK/ERK signaling pathway activation. Furthermore, we investigated the effects of AGE-BSA on the function of hFOB1.19 cells. Interestingly, the results suggest that the short term effects of low dose AGE-BSA increase osteogenic function and decrease osteoclastogenic function, which are likely mediated by autophagy and the RAGE/Raf/MEK/ERK signal pathway. In contrast, with increased treatment time, the opposite effects were observed. Collectively, AGE-BSA had a biphasic effect on the viability of hFOB1.19 cells in vitro, which was determined by the concentration of AGE-BSA and treatment time. A low concentration of AGE-BSA activated the Raf/MEK/ERK signal pathway through the interaction with RAGE, induced autophagy, and regulated the proliferation and function of hFOB1.19 cells.

  10. Relationship between the advanced glycation end products content and expressions of RAGE,ICAM-1 in vascular tissue of diabetic rats%糖尿病大鼠血管糖基化终产物含量与其受体和ICAM-1表达的关系

    Institute of Scientific and Technical Information of China (English)

    张建伟; 孙仁宇

    2001-01-01

    In this study,the relationship between the advanced glycation end products(AGEs) and the expressions of receptor for AGEs(RAGE),intercellular cell adhesion molecule-1(ICAM-1) was investigated.The diabetic rat model was reconstructed and the fluorescence method,RT-PCR and in-situ hybridization techniques were used to detect AGEs content and the expressions of RAGE and ICAM-1 gene in the aorta and cardiac tissues.The results showed that AGEs content in aortic and cardiac tissues increased(P<0.01) in diabetic rats; The expressions of RAGE and ICAM-1 enhanced (P<0.05~0.01) and were positively correlated with the quantity of AGEs accumulation(P<0.01) in the aorta and cardiac tissue.These parameters change in the diabetic rats can be improved with aminoglumine(AG) treatment.Suggesting that AGEs might induce RAGE and ICAM-1 expression.It's postulated that AGEs binding to RAGE play an important role to result in diabetic endothelial cells dysfunction and lesion.%探讨糖尿病大鼠血管组织糖基化终产物(AGEs)含量与其受体(RAGE)和细胞间粘附因子-1(ICAM-1)表达的关系。复制糖尿病大鼠模型,采用荧光法、RT-PCR及原位杂交方法检测主动脉及心肌组织的AGEs含量以及RAGE和ICAM-1基因的表达。发现糖尿病大鼠主动脉和心肌组织AGEs含量升高(P<0.01);RAGE和ICAM-1基因表达增强(P<0.05~0.01);AGEs含量与RAGE及ICAM-1呈明显正相关(P<0.01);氨基胍治疗可缓解上述指标的变化。提示AGEs可诱导RAGE和ICAM-1的表达。推测AGEs -RAGE相互作用是引起糖尿病血管内皮细胞功能紊乱和损伤的关键环节。

  11. EGCG抑制四氧嘧啶致糖尿病小鼠RCCs-RAGE信号轴表达的研究%Study on the Inhibition Effects of EGCG on the Expression of RCCs-RAGE Axis in Diabetic Mouse Induced by Alloxan Monohydrate

    Institute of Scientific and Technical Information of China (English)

    钟源; 张静; 刘仲华; 蔡淑娴; 罗国安; 黄建安; 吴香兰; 瞿绍明; 金丽莎

    2014-01-01

    The RCCs-RAGE signal axis induced by RCCs, including AGEs and 4-HNE, plays a key role in degenerative diseases, such as diabetes and cancer. To study on inhibiting activity effects of EGCG on RCCs-RAGE, diabetic mouse induced by intraperitoneal injection Alloxan monohydrate were divided into model group, EGCG-L (10 mg·kg-1·d-1) group, EGCG-M (20 mg·kg-1·d-1) group, and EGCG-H (30 mg·kg-1·d-1) group according to body weight and blood glucose. After 12 days’ administration respectively to three groups of diabetic mouse by gavage, blood glucose value, insulin, sRAGE concentration, carbonyl content and fluorescence value of AGEs in serum were determinde, while the expressions of RAGE gene in kidney were detected by QPCR, RAGE protein and 4-HNE experiment by western bolt. Result showed, compared to model group, EGCG could improve diabetes symptom of mouse by significantly decreasing the formation of RCCs, including carbonyl, 4-HNE and AGEs, increasing the concentration of sRAGE in serum, inhibiting the inflammation reaction induced by RCCs-RAGE, and alleviating the oxidation stress effectively. The study revealed that EGCG inhibited the RCCs-RAGE signal axis may be one of the potential mechanisms in the treatment of degenerative diseases.%糖基化终末端产物(AGEs)和4-羟基任烯醛(4-HNE)等活性羰基化合物(Reactive carbonyl compounds, RCCs)激活的RCCs-RAGE(Receptor for AGEs,RAGE)信号轴在糖尿病、神经退行性疾病、癌症等衰退性疾病的发生发展中起了关键性的作用。本研究采用四氧嘧啶腹腔注射的方法建立糖尿病小鼠模型,探讨表没食子儿茶素没食子酸酯(Epigallocatechin Gallate,EGCG)阻抑四氧嘧啶致糖尿病小鼠RCCs-RAGE轴表达的活性。糖尿病小鼠按其体质量与血糖值随机均匀分为模型组、EGCG低剂量组(10 mg·kg-1·d-1)、EGCG中剂量组(20 mg·kg-1·d-1)和 EGCG高剂量组(30 mg·kg-1·d-1)。小鼠连续灌胃 EGCG

  12. 2型糖尿病患者糖耐量正常的一级亲属血浆sRAGE水平及相关因素的分析%Study of the plasma level of sRAGE and other related factors in first-degree relatives with normal glucose tolerance of Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    康乐; 王静; 王霞; 张娜; 任建民

    2012-01-01

    目的 探讨2型糖尿病患者糖耐量正常的一级亲属血浆sRAGE水平及其与各代谢性疾病危险因素之间的相关性.方法 应用酶联免疫法测定51例2型糖尿病糖耐量正常一级亲属及48例正常对照者血浆sRAGE水平,测量腰围(WC)、臀围(WC)、体质量、收缩压(SBP)、舒张压(DBP),并检测甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹胰岛素(FINS),计算腰臀比(WHR)、体质量指数[ BMI=体质量(kg)/身高(m2)]和胰岛素抵抗指数[HOMA-IR=(FBG×FINS)/22.5]等相关指标,运用两样本t检验比较两组人群上述指标间的差异,运用Pearson相关分析和多元线性逐步回归分析观察组血浆sRAGE水平同SBP、DBP、WC、HC、BMI、TG、TC、HDL-C、LDL-C、HOMA-IR之间的关系,探索观察组人群特点.以BMI=25为切点,将观察组分为体质量指数正常组和超重肥胖组,并对血浆sRAGE水平进行比较,进一步验证BMI与sRAGE的关系.结果 与对照组相比,观察组TG、FINS、HOMA-IR水平显著升高(P<0.05),HDL-C、sRAGE水平明显降低(P<0.05);血浆sRAGE水平与BMI、WC、HC、WHR、FBG呈明显负相关(P<0.05);BMI是血浆sRAGE的独立相关因素(复相关系数R2=0.145).超重肥胖组的sRAGE水平明显低于体质量指数正常组(P<0.05).结论 2型糖尿病患者糖耐量正常一级亲属血浆sRAGE水平较正常人群降低,BMI的升高是其下降的独立危险因素.%objective To investigate the association between plasma levels of the soluble form of RAGE ( sRAGE) and cardiometabolic risk factors in first-degree relatives of Type 2 Diabetes with normal glucose tolerance. Methods Plasma levels of sRAGE were detected by ELISA in 51 first-degree relatives of type 2 diabetes patients with normal glucose tolerance and 48 normal controls. The WC, HC, body mass, SBP and DBP were measured. In addition, other clinical indexes,including TG, TC, HDL-C, LDL-C, and FINS

  13. 银杏叶提取物、α-硫辛酸对糖尿病大鼠肾组织中糖基化终产物及其受体RAGE表达的影响%Extract of Ginkgo biloba and α-lipoic Acid Attenuate Advanced Glycation End Products Accumulation and RAGE Expression in Diabetic Nephropathy Rats

    Institute of Scientific and Technical Information of China (English)

    李雪竹; 严海东; 王俊; 江薇

    2011-01-01

    Objective To investigate the accumulation of advanced glycation end products (AGEs) and expression of receptor for AGEs (RAGE) in streptozocin (STZ)-induced diabetic nephropathy in rats, and the role of antioxidants on the AGEs-RAGE signaling.Methods Diabetic rats were induced by once intraperitoneal injection of STZ at the dose of 60 mg/kg, and randomly divided into the DN group (n=12, treated with normal saline by intraperitoneal injection, once daily), the extract of Ginkgo biloba (EGb) group ( n =14, treated with EGb 300 mg/kg by oral administration, once every other day), and the α-lipoic add (ALA) group ( n =12, treated with ALA at the dose of 35 mg/kg by intraperitoneal injection, once every other day).Rats of the normal control group (n=10) were given vehicle dtrate buffer at the dose of 60 mg/kg.Rats were sacrificed at the 12th week and the 20th week of this study.The four groups were compared in terms of body weight, blood glucose, renal function, 24-h urine protein.Renal pathological changes were observed by PAS staining.Oxidative stress indices were detected using spectrophotometry.The concentrations of AGEs were measured using fluorospectrophotometry, and the expressions of RAGE were detected by Real-time PCR and Western blot.Results Compared with the normal control group, the 24-h urine protein quantitation was higher and the glomerular filtration rate increased in rats at the 12th week and the 20th week.The pathological tissue staining showed dilated glomerular mesangium, proliferated glomerular matrix, vacuolar degeneration of the renal tubular epithelium.Malonaldehyde (MDA) levels and 8-hydroxide radical guanine deoxyriboside (8-OHdG) levels increased, and catalase (CAT) and reduced glutathione hormone (GSH) levels decreased.The AGEs contents in serum and renal tissue homogenate increased.The expressions of RAGE mRNA and protein increased in the DN group at the 12th and the 20th week.The 24-h udne protein quantitation was reduced in the EGb group

  14. GHB acid: A rage or reprive

    Directory of Open Access Journals (Sweden)

    Prakhar Kapoor

    2013-01-01

    Full Text Available Gamma-hydroxybutyric acid (GHB is a naturally occurring analog of gamma-aminobutyric acid (GABA that has been used in research and clinical medicine for many years. GHB was used clinically as an anesthetic in the 1960s but was withdrawn due to side effects that included seizures and coma. GHB has been implicated in a number of crime types; most notably in drug-facilitated sexual assault. GHB is abused by three main groups of users: Body builders who use the substance believing that it stimulated the release of growth hormone; sexual predators who covertly administer the drug for its sedative and amnesic effects and club-goers (rave parties who take the drug for its euphoric effects. The short-lived hypnotic effects, relative safety and widespread availability of the drug have made it particularly well suited to this role. The drug has an addictive potential if used for long term. The primary effects of GHB use are those of a CNS depressant and therefore range from relaxation, to euphoria, confusion, amnesia, hallucinations, and coma. Despite the increased regulation, GHB remains widely available through the Internet where one can easily purchase the necessary reagents as well as recipes for home production. There are reports of patients being unresponsive to painful stimuli and cases of oral self-mutilations linked to the abuse of GHB, though quiet rare. Such cases should remind odontologists that intra-oral lesions may be the result of self-mutilation either due to mental illness or altered states caused by the use of prescription or non-prescription drugs.

  15. GHB acid: A rage or reprive.

    Science.gov (United States)

    Kapoor, Prakhar; Deshmukh, Revati; Kukreja, Ipsita

    2013-10-01

    Gamma-hydroxybutyric acid (GHB) is a naturally occurring analog of gamma-aminobutyric acid (GABA) that has been used in research and clinical medicine for many years. GHB was used clinically as an anesthetic in the 1960s but was withdrawn due to side effects that included seizures and coma. GHB has been implicated in a number of crime types; most notably in drug-facilitated sexual assault. GHB is abused by three main groups of users: Body builders who use the substance believing that it stimulated the release of growth hormone; sexual predators who covertly administer the drug for its sedative and amnesic effects and club-goers (rave parties) who take the drug for its euphoric effects. The short-lived hypnotic effects, relative safety and widespread availability of the drug have made it particularly well suited to this role. The drug has an addictive potential if used for long term. The primary effects of GHB use are those of a CNS depressant and therefore range from relaxation, to euphoria, confusion, amnesia, hallucinations, and coma. Despite the increased regulation, GHB remains widely available through the Internet where one can easily purchase the necessary reagents as well as recipes for home production. There are reports of patients being unresponsive to painful stimuli and cases of oral self-mutilations linked to the abuse of GHB, though quiet rare. Such cases should remind odontologists that intra-oral lesions may be the result of self-mutilation either due to mental illness or altered states caused by the use of prescription or non-prescription drugs.

  16. PTW modeling in xRage

    Energy Technology Data Exchange (ETDEWEB)

    Long, Christopher Curtis [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rauenzahn, Rick M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-05-01

    Preston-Tonks-Wallace Model (PTW), is a viscoplastic material model for very high strain rates (~1011/s) and uses a Voce work hardening model. Strain rates above 109/s uses Wallace’s model of overdriven shocks in metals. PTW is applicable for broad range of strain rates (10-3) -1012).

  17. Effect of Tanshinone ⅡA on RAGE Expression and Oxidative Stress Status in Human Mesangial Cells Induced by AGE%丹参酮ⅡA对人肾小球系膜细胞晚期糖化终产物受体表达及氧化应激水平的影响研究

    Institute of Scientific and Technical Information of China (English)

    蔡伟; 徐积兄; 朱凌燕; 肖钧仁; 李刚

    2014-01-01

    Objective To investigate the effect of Tanshinone ⅡA( TanⅡA)on the expression of receptor for ad-vanced glycated endproducts( RAGE)and the oxidative stress status of human mesangial cells induced by AGE. Methods Hu-man mesangial cells(HMCs)were cultured with various concentration of AGE-BSA(1. 0 μg/ml,10. 0 μg/ml,50. 0 μg/ml and 100. 0 μg/ml),and then were treated with Tan ⅡA(0. 1 μg/ml,1. 0 μg/ml,5. 0 μg/ml and 10. 0 μg/ml). The cul-tured HMCs were divided into AGE group,AGE+TanⅡA group and control group. By using GAPDH as reference,the protein and mRNA expression of RAGE were evaluated by Western blotting analysis and real-time PCR respectively. The activity of su-peroxide dismutase( SOD),glutathione peroxidase( GSH-Px)and malonaldehyde( MDA)levels in the supernatant of HMCs were measured. Results The expressions of RAGE and mRNA in HMCs between control group and different concentration of AGE groups all showed statistically significant differences(F=4. 428 and 5. 031,P<0. 05). Compared with the control group,the expressions of RAGE and mRNA in HMCs of 10. 0 μg/ml,50. 0 μg/ml and 100. 0 μg/ml AGE groups were significantly higher (P<0. 05). The expressions of RAGE and mRNA in HMCs between control group and AGE+different concentrations of TanⅡA groups all showed statistically significant differences(F=5. 002 and 5. 312,P<0. 05). Compared with AGE+0 μg/ml Tan ⅡA group,the expressions of RAGE and mRNA in HMCs of the control group,AGE+0. 1 μg/ml TanⅡA group,AGE+1. 0μg/ml TanⅡA group,AGE+5. 0 μg/ml TanⅡA group and AGE+10. 0 μg/ml TanⅡA group were significantly lower( P<0. 05). The SOD,GSH-Px and MDA levels in the supernantant of HMCs showed statistically significant differences between the control group,different concentrations of AGE group and AGE+TanⅡA group(P<0. 05). Conclusion TanⅡA could sig-nificantly reduce the RAGE and mRNA expression in HMCs induced by AGE,and the oxidative stress levels are also improved.%

  18. 西红花酸对晚期糖化终产物诱导内皮细胞晚期糖基化终产物受体表达的抑制作用%Crocetin reduces expression of receptor for advanced glycation end products (RAGE) on endothelial cells induced by AGE

    Institute of Scientific and Technical Information of China (English)

    向敏; 钱之玉; 周成华

    2008-01-01

    AIM:To investigate the effects of crocetin on receptor for advanced glycation end products(RAGE) mRNA expression in bovine endothelial cells(BEC) induced by advanced glycation end products(AGE) and the possible mechanisms involved. METHODS:The BEC were preincubated with crocetin(1,0.1 and 0.01 μmol/L) for 12 h,then exposed to AGE (100 mg/L). The RAGE mRNA expression was detected by RT-PCR analysis, the intercellular adhesion molecule-1(ICAM-1) was measured by ELISA. The extracellular superoxide ion and thiobarbituric acid reactive substances (TBARS) were assessed with superoxide ion kit and colorimetric assay, respectively. The intracellular H2O2 was also detected using the probe 2,7-dichlorofluorescein (DCFH). The mitochondrial membrane potential(MMP) and mitochodrial Succinate dehydrogenase(MSDH) were analyzed by the retention of rhodamine123 (Rh123) and MTT. RESULTS:Compared with AGE Group, crocetin was able to significantly reduce RAGE mRNA expression (P<0.05), decrease the content of super anion and TBARS in supernatant media (P<0.01 or P<0.05) and H2O2 in cells (P<0.05). Spontaneously, the MMP and the activity of MSDH were improved. Furthermore, the expression of ICAM-1 protein was suppressed by crocetin in a time-and dose-dependant manner. CONCLUSION:These results demonstrated that crocetin could inhibit RAGE over-expression in AGE-exposed BEC by suppressing the generation of reactive oxygen species active oxygen(ROS). This study suggested that crocetin might have beneficial effects in the treatment of diabetic vascular complications.%目的:研究西红花酸对晚期糖基化终产物(AGE)诱导牛内皮细胞(BEC)中晚期糖基化终产物受体(RAGE)mRNA表达的抑制作用,并探讨其可能机制.方法:不同浓度的西红花酸(1、0.1、0.01 μmol/L)预孵BEC细胞 12 h 后,用AGE(100 mg/L)刺激细胞 12 h, RT-PCR法测定RAGE mRNA的表达水平;ELISA法测定细胞间黏附分子-1(ICAM-1)的表达;试剂盒分别检测胞外超氧阴离子

  19. Establishment of Screening Platform for Medicines Resistant to Vascular Diseases Caused by Diabetes with RAGE as Their Target%建立以RAGE为药靶的抗糖尿病血管病变药物的筛选平台

    Institute of Scientific and Technical Information of China (English)

    孟政杰; 陆茵

    2004-01-01

    晚期糖基化终产物(advanced glycation end-products,AGEs)受体(receptor for advanced glycation end-products,RAGE)在糖尿病血管病变的发生发展过程中具有相当重要的作用,可作为防治糖尿病血管病变的药物靶点.建立以RAGE为药靶的体内外筛药系统,用于中药提取物的筛选,将显著提高中药抗糖尿病血管病变有效成分的筛选效率及准确性,对于阐明中药治疗糖尿病血管病变的机制,加快中药现代化进程有重大意义.

  20. RAGE阻断剂FPS-ZM1对糖基化终末产物所致大鼠脑部炎症反应的影响及机制%Effects of RAGE inhibitor FPS-ZM1 on inflammatory reaction in the brain of rats induced by advanced glycation end products

    Institute of Scientific and Technical Information of China (English)

    孙梦晗; 洪艳; 候训尧; 马莹娟; 申超; 罗鼎真; 刘雪平

    2014-01-01

    目的:探讨RAGE受体特异性阻断剂FPS-ZM1对糖基化终末产物( AGEs)所致大鼠脑部炎症反应及认知功能的影响。方法将40只大鼠随机分为四组:生理盐水组( NC组) FPS-ZM1对照组、AGEs组和FPS-ZM1组,采用脑立体定位技术,向AGEs组及FPS-ZM1组大鼠两侧海马注射AGEs 5μl,以制造动物损伤模型,用同样方法向 NC组及 FPS-ZM1对照组注射等量生理盐水,以制造模型对照;造模前1 w以1 mg · kg-1· d-1 FPS-ZM1向FPS-ZM1组和FPS-ZM1对照组大鼠进行腹腔注射,并连续4 w给药,AGEs组、NC组则同时注射相同体积生理盐水,造模3 w后对各组大鼠进行Morris水迷宫实验,检测各组大鼠逃逸潜伏期( EL);用 Elisa 检测各组大鼠海马区 Aβ1~40, Aβ1~42的水平;用 Western 印迹检测各组大鼠RAGE,p-NF-κB和肿瘤坏死因子( TNF)-α蛋白的表达;用免疫组织化学法检测各组大鼠海马区TNF-α蛋白的表达强度。结果 AGEs组与其他各组相比,EL显著延长(P<0.01),且 Aβ1~40、Aβ1~42浓度均显著升高(P<0.01);同时 AGEs 组 RAGE、p-NF-κB 和 TNF-α的蛋白表达明显增强(P<0.01);FPS-ZM1干预后上述各指标均明显低于AGEs组。结论 FPS-ZM1作为RAGE受体特异性阻断剂,能作用中枢系统减少Aβ1~40,生成从而提高AGEs脑损伤大鼠的智能,并通过抑制脑组织 p-NF-κB上调,减轻脑AGEs损伤引起的炎性反应。该药因能透过血脑屏障有望成为抑制阿尔茨海默样病变的有效措施。%Objective To explore the effects of RAGE inhibitor FPS-ZM1 on inhibiting inflammatory reaction in the brain of rats and cognition induced by advanced glycation end products.Methods Fourty Wistar rats were randomly divided into normal control ( NC) , FPS-ZM1 control , AGEs and FPS-ZM1 groups.By brain stereotactic techniques , the bilateral hippocampus of rats in AGEs group and FPS-ZM1 group were injected

  1. 糖基化终产物通过其受体诱导小鼠足细胞表达单核细胞趋化因子1%Advanced glycation end products-induced MCP-1 expression via its receptor RAGE in mouse podocytes

    Institute of Scientific and Technical Information of China (English)

    顾乐怡; 倪兆慧; 钱家麒; Yasuhiko Tomino

    2006-01-01

    目的了解糖基化终产物(AGE)能否在体外诱导小鼠足细胞表达单核细胞趋化蛋白1(MCP-1)以及其受体RAGE在其中的作用.方法以RT-PCR和ELISA的方法检测AGE、羰甲基化白蛋白(CML)、S100蛋白和RAGE中和抗体对小鼠足细胞的MCP-1的基因和蛋白质表达的影响.结果 (1)未分化和已分化的足细胞都能表达RAGE.(2)AGE和CML以剂量依赖的方式诱导足细胞表达MCP-1mRNA.AGE和CML孵育8 h诱导足细胞产生MCP-1蛋白[分别为(7.44±1.01,8.06±0.96)ng/L],明显高于牛血清白蛋白(BSA)孵育的足细胞[(3.77±0.39)ng/L,均P<0.05],而孵育24 h MCP-1的浓度分别为(87.78±9.32,85.35±9.83和17.95±0.76)ng/L(均P<0.01).(3)RAGE的另外一个配体,S100蛋白,也能以剂量依赖的方式诱导足细胞表达MCP-1 mRNA.RAGE中和抗体完全阻断了AGE、CML和S100的作用.结论 AGE和CML通过RAGE使诱导分化的足细胞表达MCP-1.

  2. Engineering of blood vessel patterns by angio-morphogens [angiotropins]: non-mitogenic copper-ribonucleoprotein cytokins [CuRNP ribokines] with their metalloregulated constituents of RAGE-binding S100-EF-hand proteins and extracellular RNA bioaptamers in vascular remodeling of tissue and angiogenesis in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wissler, J.H. [ARCONS Applied Research, Bad Nauheim (Germany)

    2001-12-01

    Tissue vascularization is requisite to successful cell-based therapies, biomaterial design and implant integration. Thus, known problems in ossointegration of avascular implants in connection with the generation of bone tissue reflect arrays of general problems of socio-economic relevance existing in reparative medicine still waiting for to be solved. For this purpose, morphogenesis and remodeling of endothelial angio-architectures in tissue and in vitro by isolated non-mitogenic angio-morphogens [angiotropins] are considered in terms of their structure, function and action mechanisms. Extracellular angiotropins are secreted by activated leukocytes/monocytes/macrophages. They are a family of cytokines with morphogen bioactivity selectively directed to endothelial cells. Their structure was deciphered as metalloregulated copper-ribonucleoproteins [CuRNP ribokines]. They are built up of angiotropin-related S100-EF-hand protein [ARP] and highly modified and edited 5'end-phosphorylated RNA [ARNA], complexed together by copper ions. Oxidant-sensitive ARNA and their precursors represent novel types in a RNA world: They are the first isolated and sequenced forms of extracellular RNA [eRNA], may act as cytokine and bioaptamer, contain isoguanosine [crotonoside] as modified nucleoside and show up copper as RNA-structuring transition metal ion. By metalloregulated bioaptamer functions, ARNA impart novel biofunctions to RAGE-binding S100-EF-hand proteins. Angiotropin morphogens were shown suitable for neointiation and remodeling of blood vessel patterns in different, adult, embryonal and artificial tissues. These neovascular patterns manifest regulated hemodynamics for preventing tissue necrosis, supporting tissue functions and promoting wound healing. As evaluated in skin and muscle vascularization, the neovascular patterns are integrated into homeostatic control mechanisms of tissue. Thus, the morphogens show up beneficial perspectives and are suggested useful tools

  3. Advanced glycosylation end products induce CTGF and FN expression via their receptor RAGE in human renal mesangial cells%糖基化终产物通过其受体诱导人肾小球系膜细胞表达CTGF和FN

    Institute of Scientific and Technical Information of China (English)

    冯敏; 黄国良; 李健榕; 钟林娜

    2010-01-01

    目的:探讨体外培养条件下糖基化终产物(AGEs)对人肾小球系膜细胞(HRMCs)中结缔组织生长因子(CTGF)及纤维连接蛋白(FN)基因表达的影响及其可能的作用机制.方法: 将HRMCs与不同浓度的糖化牛血清白蛋白(AGE-BSA)和牛血清白蛋白(BSA)共同培养,或与同一质量浓度的AGE-BSA和BSA共同培养不同时间,以中和性抗RAGE抗体封闭细胞膜上糖基化终末产物受体(RAGE);采用免疫印迹法(Western blotting)观察AGEs对HRMCs中RAGE表达的影响,半定量逆转录-聚合酶链反应(RT-PCR)法检测CTGF、FN mRNA的表达.结果: 在HRMCs中存在少量RAGE的表达,AGE-BSA能够诱导HRMCs中RAGE的表达增加,并以时间和剂量依赖方式促进HRMCs中CTGF和FN的表达上调;CTGF、FN的表达水平在加入不同浓度(50、100、200、400 mg/L)的AGE-BSA 作用48 h后以及加入质量浓度为200 mg/L的 AGE-BSA 作用不同时间(12、24、48、72h)后,较相应质量浓度或时间的BSA组和空白对照组均明显升高(P<0.05);抗RAGE抗体干预后能够部分抑制AGE-BSA诱导CTGF及FN的表达,而人IgG没有这种作用.结论: AGEs可能通过RAGE诱导CTGF及FN的表达上调,是糖尿病肾病肾脏纤维化的可能机制.

  4. AGE-RAGE interaction promotes the proliferation of human colon carcinoma SW-480 cells%晚期糖基化终产物与其受体相互作用对人结肠癌细胞SW-480增殖的影响

    Institute of Scientific and Technical Information of China (English)

    张圭; 薛耀明; 高方; 朱波

    2010-01-01

    目的 糖尿病患者结肠癌的发病率显著高于非糖尿病人群,晚期糖基化终产物(advanced glycation end products, AGEs)在糖尿病患者体内生成明显增多.文中观察AGEs对人结肠癌细胞SW-480增殖的影响及其机制.方法 体外培养人结肠癌细胞SW-480,以终浓度分别为100μg/ml、200μg/ml、500μg/ml的AGE-BSA处理细胞24h,并设正常对照组和BSA对照组进行比较.采用四甲基偶氮唑盐(MTT)法检测SW-480细胞活力,利用流式细胞术检测细胞周期的改变,实时荧光定量PCR测定晚期糖基化终产物受体(receptor for advanced glycation end products, RAGE)mRNA、细胞周期素D1(cyclin D1)mRNA的表达.结果 ①MTT结果示100μg/ml、200μg/ml、500μg/mlAGE-BSA作用SW-480细胞24h后可以显著促进细胞增殖(P<0.05),并呈浓度依赖性.②流式细胞术结果示200μg/mlAGE-BSA干预组24h后可以减少SW-480细胞G1期百分率,同时增加S期百分率,与正常对照组比较具有统计学差异(P<0.05).③实时荧光定量PCR结果示与正常对照组相比,200μg/mlAGE-BSA干预后可以上调RAGEmRNA和cyclin D1mRNA的表达(P<0.05).结论 AGEs能促进SW-480细胞的增殖,其机制可能与上调RAGEmRNA和cyclin D1mRNA的表达,加速细胞G1期向S期转换相关.

  5. New Rage on Campus: E-Commerce Degrees.

    Science.gov (United States)

    Dobbs, Kevin

    1999-01-01

    As electronic commerce expands, higher education attempts to keep up with the demand for instruction. Some universities have added a concentration in e-commerce to their master of business administration program and others are adding majors, certifications, or degrees. (JOW)

  6. From Rage to Rap and Prison to Print:

    Directory of Open Access Journals (Sweden)

    Josephine Metcalf

    2009-11-01

    Full Text Available 1. IntroductionBy the late 1980s, while thousands of former gang members were either dead or incarcerated, their legacy and the gang subculture was being celebrated and commodified through gangsta rap music and videos, film and fashion. In the early 1990s this lucrative cultural trend sparked interest from potential authors and publishers. Such literary attention was partially fuelled by a public fascination with life in the ghettos following the 1992 Los Angeles (LA riots, resulting in a ne...

  7. Peru v. Yale: A Battle Rages over Machu Picchu

    Science.gov (United States)

    Glenn, David

    2009-01-01

    In early 1916, the legendary Yale University archaeologist Hiram Bingham III completed his third and final expedition in southern Peru. He shipped home 74 boxes of artifacts from Machu Picchu, a spectacular site in the Andes that is believed to have been the last major settlement of the Inca empire. Those boxes were supposed to be on temporary…

  8. Rages and refusals. Managing the many faces of adolescent anxiety.

    OpenAIRE

    2001-01-01

    OBJECTIVE: To provide family physicians with a practical approach to recognition, assessment, and treatment of adolescent anxiety disorders complicated by avoidance or oppositional behaviour. QUALITY OF EVIDENCE: Current literature was searched via MEDLINE using the MeSH headings Anxiety and Anxiety Disorders, focusing on epidemiology, clinical presentations in adolescence, and both pharmacologic and nonpharmacologic treatment. In addition, internationally accepted diagnostic criteria, curren...

  9. From Rage to Rap and Prison to Print:

    OpenAIRE

    Josephine Metcalf

    2009-01-01

    1. IntroductionBy the late 1980s, while thousands of former gang members were either dead or incarcerated, their legacy and the gang subculture was being celebrated and commodified through gangsta rap music and videos, film and fashion. In the early 1990s this lucrative cultural trend sparked interest from potential authors and publishers. Such literary attention was partially fuelled by a public fascination with life in the ghettos following the 1992 Los Angeles (LA) riots, resulting in a ne...

  10. Between anger and resignation; Zwischen Rage und Resignation

    Energy Technology Data Exchange (ETDEWEB)

    Roepcke, I.

    2008-07-21

    Wind power in Bavaria and Baden-Wuerttemberg is overshadowed by hydroelectric power, biomass, and solar energy. Regional development plans are obstacles to the construction of new wind power systems. (orig.)

  11. Generation of human endometrial knockout cell lines with the CRISPR/Cas9 system confirms the prostaglandin F2α synthase activity of aldo-ketoreductase 1B1.

    Science.gov (United States)

    Lacroix Pépin, Nicolas; Chapdelaine, Pierre; Rodriguez, Yoima; Tremblay, Jacques-P; Fortier, Michel A

    2014-07-01

    Prostaglandins (PGs) are important regulators of female reproductive function. The primary PGs produced in the endometrium are PGE2 and PGF2α. Relatively little is known about the biosynthetic pathways leading to the formation of PGF2α. We have described the role of aldo-ketoreductase (AKR)1B1 in increased PGF2α production by human endometrial cells following stimulation with interleukin-1β (IL-1β). However, alternate PGF synthases are expressed concurrently in endometrial cells. A definite proof of the role of AKR1B1 would require gene knockout; unfortunately, this gene has no direct equivalent in the mouse. Recently, an efficient genome-editing technology using RNA-guided DNase Cas9 and the clustered regularly interspaced short palindromic repeats (CRISPR) system has been developed. We have adapted this approach to knockout AKR1B1 gene expression in human endometrial cell lines. One clone (16-2) of stromal origin generated by the CRISPR/Cas9 system exhibited a complete loss of AKR1B1 protein and mRNA expression, whereas other clones presented with partial edition. The present report focuses on the characterization of clone 16-2 exhibiting deletion of 68 and 2 nucleotides, respectively, on each of the alleles. Cells from this clone lost their ability to produce PGF2α but maintained their original stromal cell (human endometrial stromal cells-2) phenotype including the capacity to decidualize in the presence of progesterone (medroxyprogesterone acetate) and 8-bromo-cAMP. Knockout cells also maintained their ability to increase PGE2 production in response to IL-1β. In summary, we demonstrate that the new genome editing CRISPR/Cas9 system can be used in human cells to generate stable knockout cell line models. Our results suggest that genome editing of human cell lines can be used to complement mouse KO models to validate the function of genes in differentiated tissues and cells. Our results also confirm that AKR1B1 is involved in the synthesis of PGF2α.

  12. Induction of IFNT-Stimulated Genes by Conceptus-Derived Exosomes during the Attachment Period.

    Science.gov (United States)

    Nakamura, Keigo; Kusama, Kazuya; Bai, Rulan; Sakurai, Toshihiro; Isuzugawa, Kazuto; Godkin, James D; Suda, Yoshihito; Imakawa, Kazuhiko

    2016-01-01

    Biochemical and/or physical communication between the conceptus and the uterine endometrium is required for conceptus implantation to the maternal endometrium, leading to placentation and the establishment of pregnancy. We previously reported that in vitro co-culture system with bovine trophoblast CT-1 cells, primary uterine endometrial epithelial cells (EECs), and uterine flushings (UFs) mimics in vivo conceptus attachment process. To identify molecules in UFs responsible for this change, we first characterized protein contents of UFs from day 17 cyclic (C17) and pregnant (P17) ewes through the use of two dimensional-Polyacrylamide Gel Electrophoresis (2D-PAGE), followed by Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) analysis. These analyses identified 266 proteins specific for P17 UFs, from which 172 proteins were identified as exosomal proteins. Among 172 exosomal proteins, 8 proteins that had been identified as exosomal proteins were chosen for further analysis, including macrophage-capping protein (CAPG), aldo-keto reductase family 1, member B1 protein (AKR1B1), bcl-2-like protein 15 (BCL2L15), carbonic anhydrase 2 (CA2), isocitrate dehydrogenase 2 (IDH2), eukaryotic translation elongation factor 2 (EEF2), moesin (MSN), and ezrin (EZR). CAPG and AKR1B1 were again confirmed in P15 and P17 UFs, and more importantly CAPG and AKR1B1, mRNA and protein, were found only in P15 and P17 conceptuses. Moreover, exosomes were isolated from C15, C17, P15, or P17 UFs. Only P15 and P17 exosomes, originated from the conceptus, contained interferon tau (IFNT) as well as CAPG and AKR1B1, and up-regulated STAT1, STAT2, MX1, MX2, BST2, and ISG15 transcripts in EECs. These observations indicate that in addition to endometrial derived exosomes previously described, conceptus-derived exosomes are present in UFs and could function to modify endometrial response. These results suggest that exosomes secreted from conceptuses as well as endometria are involved in cell to

  13. Induction of IFNT-Stimulated Genes by Conceptus-Derived Exosomes during the Attachment Period

    Science.gov (United States)

    Nakamura, Keigo; Kusama, Kazuya; Bai, Rulan; Sakurai, Toshihiro; Isuzugawa, Kazuto; Godkin, James D.; Suda, Yoshihito; Imakawa, Kazuhiko

    2016-01-01

    Biochemical and/or physical communication between the conceptus and the uterine endometrium is required for conceptus implantation to the maternal endometrium, leading to placentation and the establishment of pregnancy. We previously reported that in vitro co-culture system with bovine trophoblast CT-1 cells, primary uterine endometrial epithelial cells (EECs), and uterine flushings (UFs) mimics in vivo conceptus attachment process. To identify molecules in UFs responsible for this change, we first characterized protein contents of UFs from day 17 cyclic (C17) and pregnant (P17) ewes through the use of two dimensional-Polyacrylamide Gel Electrophoresis (2D-PAGE), followed by Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) analysis. These analyses identified 266 proteins specific for P17 UFs, from which 172 proteins were identified as exosomal proteins. Among 172 exosomal proteins, 8 proteins that had been identified as exosomal proteins were chosen for further analysis, including macrophage-capping protein (CAPG), aldo-keto reductase family 1, member B1 protein (AKR1B1), bcl-2-like protein 15 (BCL2L15), carbonic anhydrase 2 (CA2), isocitrate dehydrogenase 2 (IDH2), eukaryotic translation elongation factor 2 (EEF2), moesin (MSN), and ezrin (EZR). CAPG and AKR1B1 were again confirmed in P15 and P17 UFs, and more importantly CAPG and AKR1B1, mRNA and protein, were found only in P15 and P17 conceptuses. Moreover, exosomes were isolated from C15, C17, P15, or P17 UFs. Only P15 and P17 exosomes, originated from the conceptus, contained interferon tau (IFNT) as well as CAPG and AKR1B1, and up-regulated STAT1, STAT2, MX1, MX2, BST2, and ISG15 transcripts in EECs. These observations indicate that in addition to endometrial derived exosomes previously described, conceptus-derived exosomes are present in UFs and could function to modify endometrial response. These results suggest that exosomes secreted from conceptuses as well as endometria are involved in cell to

  14. Tendency to Aggressive Driving and Road Rage : Identifying Drivers Prone to Aggressive Driving and Road Rage in Motor Vehicle Traffic in Sweden

    OpenAIRE

    Teräsvirta, Jukka

    2011-01-01

    In the present study possible associations between driver characteristics and aggressive driving were examined. 210 participants responded to a questionnaire consisting of self-report measures of emotion regulation ability, personality traits, and attitudes towards traffic behaviours in a Swedish translation of the Propensity for Angry Driving Scale (PADS). The main results showed that females, older age, agreeableness, openness, and social desirability were negatively correlated with angry d...

  15. RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA

    OpenAIRE

    Sirois, Cherilyn M.; Jin, Tengchuan; Miller, Allison L.; Bertheloot, Damien; Nakamura, Hirotaka; Horvath, Gabor L.; Mian, Abubakar; Jiang, Jiansheng; Schrum, Jacob; Bossaller, Lukas; Pelka, Karin; Garbi, Natalio; Brewah, Yambasu; Tian, Jane; Chang, ChewShun

    2013-01-01

    Recognition of DNA and RNA molecules derived from pathogens or self-antigen is one way the mammalian immune system senses infection and tissue damage. Activation of immune signaling receptors by nucleic acids is controlled by limiting the access of DNA and RNA to intracellular receptors, but the mechanisms by which endosome-resident receptors encounter nucleic acids from the extracellular space are largely undefined. In this study, we show that the receptor for advanced glycation end-products...

  16. The Wellcome Prize Lecture. Genetic imprinting: the battle of the sexes rages on.

    Science.gov (United States)

    Reik, W

    1996-03-01

    Genomic imprinting in mammals is an important genetic mechanism by which genes are expressed or repressed depending on which parent they have been inherited from. Some properties of the imprinting mechanism are already established; notably, some of the effects of imprinting on mammalian development can be explained by the phenotypic effects of a number of specific imprinted genes, which include major fetal growth factors. An evolutionary explanation of imprinting has also been suggested. Some of the molecular mechanisms of imprinting are known, and these include the modification of DNA and chromosomes in the form of DNA methylation and possibly heritable chromatin structures. Loss of imprinting or altered imprinting is implicated in a large number of genetic diseases and cancers. Many important issues remain to be resolved; these include the precise molecular mechanisms and, in particular, the nature of the primary imprints that are inherited from the parental gametes, and the genes that control the imprinting process. Isolation of the majority of imprinted genes and the elucidation of their phenotypic effects and physiology are major goals for the future. These studies will provide important insights into human genetics, and will connect evolutionary understanding with physiology, genetic disease and human behaviour. PMID:8845132

  17. The Wellcome Prize Lecture. Genetic imprinting: the battle of the sexes rages on.

    Science.gov (United States)

    Reik, W

    1996-03-01

    Genomic imprinting in mammals is an important genetic mechanism by which genes are expressed or repressed depending on which parent they have been inherited from. Some properties of the imprinting mechanism are already established; notably, some of the effects of imprinting on mammalian development can be explained by the phenotypic effects of a number of specific imprinted genes, which include major fetal growth factors. An evolutionary explanation of imprinting has also been suggested. Some of the molecular mechanisms of imprinting are known, and these include the modification of DNA and chromosomes in the form of DNA methylation and possibly heritable chromatin structures. Loss of imprinting or altered imprinting is implicated in a large number of genetic diseases and cancers. Many important issues remain to be resolved; these include the precise molecular mechanisms and, in particular, the nature of the primary imprints that are inherited from the parental gametes, and the genes that control the imprinting process. Isolation of the majority of imprinted genes and the elucidation of their phenotypic effects and physiology are major goals for the future. These studies will provide important insights into human genetics, and will connect evolutionary understanding with physiology, genetic disease and human behaviour.

  18. Central Asia's raging waters the prospects of water conflict in Central Asia

    OpenAIRE

    Hartman, William B.

    2007-01-01

    This thesis examines the prospects of conflict caused by water scarcity in Central Asia. The thesis analyzes the three most recent political eras of Central Asia, Tsarist Russia, the Soviet Union and independence, utilizing indicators of water tensions including: water quality, water quantity, the management of water for multiple uses, the political divisions and geopolitical setting, state institutions and national water ethos. Although water is not likely to be the sole cause of a majo...

  19. Ruminations on the dark side: history of art as rage and denials

    Directory of Open Access Journals (Sweden)

    Branko Mitrović

    2009-12-01

    Full Text Available The holist view is that the creativity of an author is the manifestation of the creativity of the group he or she belongs to; the individualist view is that the creativity of the group is merely the sum of the creativities of the individuals who constitute that group. The holist understanding of human creativity was particularly widespread among Weimar-era historians and their almost unanimous tendency to adopt holist historical explanations constitutes a collective phenomenon in its own right. The paper explores the problems of providing an individualist explanation of this phenomenon.

  20. Rage from within the Machine: Protest Music, Social Justice, and Educational Reform, a Collective Case Study

    Science.gov (United States)

    Giancola, John A., Jr.

    2009-01-01

    School reform initiatives in the United States have been occurring since the launching of Sputnik by the U.S.S.R. in 1957. These efforts have largely been internal, within school reforms, with little consideration given to external variables such as poverty that affect student achievement. Given the pervasive link between poverty and student…

  1. RAGE and activation of chondrocytes and fibroblast-like synoviocytes in joint diseases

    NARCIS (Netherlands)

    Steenvoorden, Marjan Maria Claziena

    2007-01-01

    This dissertation describes a new model in which cartilage degradation can be studied. New cartilage is formed by bovine chondrocytes obtained from the slaughterhouse and cocultured with synovial cells from rheumatoid arthritis (RA) patients to study the interaction between the chondrocytes and syno

  2. 'Go! Sterilise the fertile with thy rage' envy as embittered desire.

    Science.gov (United States)

    Meredith-Owen, William

    2008-09-01

    This paper is concerned with the operation of envy: it considers its origins and their repercussions, in particular its compulsion to sterilize the evidence of fertility, exemplified by Roger Money-Kyrle's evocation of 'the parental intercourse as the supremely creative act'. The inevitable impact on the analytic relationship is considered in the context of two clinical examples of impasse. It is argued that such fundamentally negative transferences, one full of overt aggression and enactment, the other more covertly sabotaging, derive from envious retaliatory impulses originating in experiences--whether phantasied or factual--of exclusion from the anticipated 'good'. Significant recent Jungian contributions to this area are considered and the absence of references to 'envy'--so characteristic of Kleinian discourse--is noted. The ongoing value of integrating Jungian and Kleinian approaches is affirmed. PMID:18844733

  3. Misplaced Populist Rage: Congressional Missteps With Executive Compensation Limitations In The Bailout Legislation

    Directory of Open Access Journals (Sweden)

    Joseph Filloy

    2009-04-01

    Full Text Available Starting in the summer of 2008, the United States and most other economies of the world began to feel the effects of the subprime mortgage crisis. In response, the federal government enacted The Emergency Economic Stabilization Act of 2008 (EESA and The American Recovery and Reinvestment Act of 2009 (ARRA to help restore stability to the U.S. economy. Ultimately this legislation, commonly referred to as “the bailout bill(s,” would result in substantial outlays of taxpayer money to financial institutions deemed systemically significant, or “too big to fail.”

  4. Rage against the Machine: Vincenzo Agnetti’s Critique of Industrial Alienation

    Directory of Open Access Journals (Sweden)

    Laura Moure Cecchini

    2012-12-01

    Full Text Available This essay analyzes the work of the Milanese artist Vincenzo Agnetti (1926-1981, in particular his pieces La macchina drogata (1968 and NEG (1970. Like other Italian artists and intellectuals of the 1960s and 1970s, Agnetti was concerned about the alienation caused by industrial development and consumer society, manifested in carefully designed objects of everyday use. To counteract the automatism of perception and thought that he considered the sign of alienated experience, Agnetti’s artworks employed several strategies that obliged the public to attend to its thinking processes. Thus, Agnetti put in practice forms of aesthetic estrangement similar to those evoked in the same period by Gillo Dorfles and Umberto Eco to counteract the widespread loss of awareness.

  5. Rage Against The Machines: die "International Campaign to Stop Killer Robots"

    OpenAIRE

    Weidlich, Christian

    2013-01-01

    Bereits heute werden bewaffnete Drohnen von vielen Armeen eingesetzt, um Gegner über tausende Kilometer hinweg per Joystick zu töten. Auch die Bundesregierung hat Anfang dieses Jahres vorgeschlagen, diese Systeme für die Bundeswehr anzuschaffen und ist sich offenbar auch schon mit den Amerikanern einig. Doch die Pläne stießen auf große öffentliche Kritik und offensichtlich sah man sich gezwungen, die Entscheidung über den Kauf bewaffneter unbemannter Kampfsysteme zumindest offiziell in die nä...

  6. MicroRNAs in chronic lymphocytic leukemia: miRacle or miRage for prognosis and targeted therapies?

    Science.gov (United States)

    Van Roosbroeck, Katrien; Calin, George A

    2016-04-01

    Chronic lymphocytic leukemia (CLL) is a heterogeneous disease and has a highly variable clinical course with survival ranging from a couple of months to several decades. MicroRNAs (miRNAs), small non-coding RNAs that regulate transcription and translation of genes, have been found to be involved in CLL initiation, progression, and resistance to therapy. In addition, they can be used as prognostic biomarkers and as targets for novel therapies. In this review, we describe the association between miRNAs and the cytogenetic aberrations commonly found in CLL, as well as with other prognostic factors. We describe the presence of miRNAs as extracellular entities in the plasma and serum of CLL patients and discuss their role in resistance to therapy. Finally, we will explore the potential of targeted miRNA therapy for the treatment of CLL, with a special emphasis on MRX34, the first miRNA mimic that is currently being evaluated for clinical use. PMID:27040698

  7. Automatic thalamus and hippocampus segmentation from MP2RAGE - comparison of publicly available methods and implications for DTI quantification

    DEFF Research Database (Denmark)

    Næss-Schmidt, Erhard; Tietze, Anna; Blicher, Jakob Udby;

    2016-01-01

    PURPOSE: In both structural and functional MRI, there is a need for accurate and reliable automatic segmentation of brain regions. Inconsistent segmentation reduces sensitivity and may bias results in clinical studies. The current study compares the performance of publicly available segmentation ...

  8. Railways, Rebellions and Rage Against The Machine: Adolescents' Interests and Meaning-Making in the Creation of Multimodal Identity Texts

    Science.gov (United States)

    Nagle, Joelle; Stooke, Rosamund

    2016-01-01

    This paper draws on a Canadian qualitative case study grounded in multiliteracies theory to describe the meaning-making processes of four students aged 13-14 years as they created history projects. Students were invited to explore curriculum content in self-chosen ways and to produce presentations in a range of formats. The data we present and…

  9. Toward a Conceptual Model of Motive and Self-Control in Cyber-Aggression: Rage, Revenge, Reward, and Recreation

    Science.gov (United States)

    Runions, Kevin C.

    2013-01-01

    Despite widespread public attention to cyberbullying, online aggression and victimization have received scant conceptual development. This article focuses on how opportunities for aggression are distinct online from those of offline social contexts. The model developed here is informed by a recent aggression typology, which extends the…

  10. Raging Hormones and Powerful Cars: The Construction of Men's Sexuality in School Sex Education and Popular Adolescent Films.

    Science.gov (United States)

    Whatley, Mariamne H.

    1988-01-01

    Discusses issues of men's sexuality in the context of school sex education, and analyzes units on human reproduction in secondary biology textbooks. Compares official school knowledge about men's sexuality with alternative sources, including progressive books and the films of John Hughes, to explore the overlapping and contradictory discourses…

  11. "While a Storm is Raging on the Open Sea": Regional Development in a Knowledge-based Economy

    OpenAIRE

    Leydesdorff, Loet

    2009-01-01

    The Triple Helix of university-industry-government relations is elaborated into a systemic model that accounts for interactions among three dimensions. By distinguishing between the respective micro-operations, this model enables us to recombine the "Mode 2" thesis of a new production of scientific knowledge and the study of systems of innovation with the neo-classical perspective on the dynamics of the market. The mutual information in three dimensions provides us with an indicator for the s...

  12. Enzymes of the AKR1B and AKR1C subfamilies and uterine diseases

    Directory of Open Access Journals (Sweden)

    Tea eLanisnik Rizner

    2012-03-01

    Full Text Available Endometrial and cervical cancers, uterine myoma, and endometriosis are very common uterine diseases. Worldwide, more than 800,000 women are affected annually by gynecological cancers, as a result of which, more than 360,000 die. During their reproductive age, about 70% of women develop uterine myomas, 10% to 15% suffer from endometriosis, and 35% to 50% from infertility associated with endometriosis. Uterine diseases are associated with aberrant inflammatory responses and concomitant increased production of prostaglandins (PG. They are also related to decreased differentiation, due to low levels of protective progesterone and retinoic acid, and to enhanced proliferation, due to high local concentrations of estrogens. The pathogenesis of these diseases can thus be attributed to disturbed PG, estrogen and retinoid metabolism and actions. Five human members of the aldo-keto reductase 1B (AKR1B and 1C (AKR1C superfamilies, i.e., AKR1B1, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, have roles in these processes and can thus be implicated in uterine diseases. AKR1B1 and AKR1C3 catalyze the formation of PGF2alpha which stimulates cell proliferation. AKR1C3 converts PGD2 to 9alpha,11beta-PGF2, and thus counteracts the formation of 15deoxy-PGJ2, which can activate pro-apoptotic peroxisome-proliferator-activated receptor beta. AKR1B10 catalyzes the reduction of retinal to retinol, and in thus lessens the formation of retinoic acid, with potential pro-differentiating actions. The AKR1C1-AKR1C3 enzymes also act as 17-keto- and 20-ketosteroid reductases to varying extents, and are implicated in increased estradiol and decreased progesterone levels. This review comprises a short introduction to uterine diseases, followed by an overview of the current literature on the AKR1B and AKR1C expression in the uterus and in uterine diseases. The potential implications of the AKR1B and AKR1C enzymes and their pathophysiologies are then discussed, followed by conclusions and

  13. Screening system of blocking agents of the receptor for advanced glycation endproducts in cells using fluorescence.

    Science.gov (United States)

    Jung, Dong Ho; Kim, Young Sook; Kim, Jin Sook

    2012-01-01

    Activation of the receptor for advanced glycation endproducts (RAGE) triggers cellular responses implicated in the pathogenesis of diabetic complications; blockade of RAGE has been shown to inhibit the development of diabetic complications. To develop a screening system to identify novel disruptors of advanced glycation endproducts (AGE)-RAGE binding, we used an AGE-RAGE binding system in RAGE-overexpressing cells; test compounds were screened using this system. To construct human RAGE-overexpressing cells, mouse mesangial cells (MMCs) were stably transfected with the pcDNA-human RAGE (hRAGE) vector and selected under 1 mg/mL gentamicin (G418). RAGE expression in hRAGE-overexpressing MMCs was analyzed by Western blotting with specific RAGE antibody. To identify novel disruptors of AGE-RAGE binding, 50 single compounds and AGE-bovine serum albumin (BSA)-Alexa 488 (AGE-BSA labeled with Alexa 488) were treated to the hRAGE-overexpressing MMCs. Nonbinding AGE-BSA-Alexa 488 was washed and fluorescence measured by microtiter plate reader (excitation wavelength, 485 nm; emission wavelength, 528 nm). In hRAGE-overexpressing cells, only treatment with AGE-BSA-Alexa 488 significantly increased fluorescence intensity in a dose-dependent manner. Of 50 compounds tested, genistein disrupted AGE-RAGE binding in a dose-dependent manner. This AGE-RAGE binding system using AGE-BSA-Alexa 488 in hRAGE-overexpressing cells was suitable for screening of agents that disrupt AGE-hRAGE binding.

  14. 国内第一片ATI授权的ODM ATI显示卡联维尔ATI RAGE 128 PRO显卡

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ 显示卡市场的竞争日益激烈,nVIDIA自从推出TNT、GeForce系列显示芯片、兼并3Dfx以后,在显示卡市场的垄断地位日见巩固,这当然是多数用户特别是厂商都不愿看到的局面.目前够得上nVIDIA的对手只剩下两个--ATI与MGA.而ATI与MGA一直保持独家研发、独家生产、独家销售的模式,产量上不去,成本高昂,市场占有率也不高,在价格上根本无法同nVIDIA竞争.

  15. Detoxifying Enzymes at the Cross-Roads of Inflammation, Oxidative Stress, and Drug Hypersensitivity: Role of Glutathione Transferase P1-1 and Aldose Reductase.

    Science.gov (United States)

    Sánchez-Gómez, Francisco J; Díez-Dacal, Beatriz; García-Martín, Elena; Agúndez, José A G; Pajares, María A; Pérez-Sala, Dolores

    2016-01-01

    Phase I and II enzymes are involved in the metabolism of endogenous reactive compounds as well as xenobiotics, including toxicants and drugs. Genotyping studies have established several drug metabolizing enzymes as markers for risk of drug hypersensitivity. However, other candidates are emerging that are involved in drug metabolism but also in the generation of danger or costimulatory signals. Enzymes such as aldo-keto reductases (AKR) and glutathione transferases (GST) metabolize prostaglandins and reactive aldehydes with proinflammatory activity, as well as drugs and/or their reactive metabolites. In addition, their metabolic activity can have important consequences for the cellular redox status, and impacts the inflammatory response as well as the balance of inflammatory mediators, which can modulate epigenetic factors and cooperate or interfere with drug-adduct formation. These enzymes are, in turn, targets for covalent modification and regulation by oxidative stress, inflammatory mediators, and drugs. Therefore, they constitute a platform for a complex set of interactions involving drug metabolism, protein haptenation, modulation of the inflammatory response, and/or generation of danger signals with implications in drug hypersensitivity reactions. Moreover, increasing evidence supports their involvement in allergic processes. Here, we will focus on GSTP1-1 and aldose reductase (AKR1B1) and provide a perspective for their involvement in drug hypersensitivity. PMID:27540362

  16. Whole blood transcriptional profiling reveals deregulation of oxidative and antioxidative defence genes in myelofibrosis and related neoplasms. Potential implications of downregulation of Nrf2 for genomic instability and disease progression.

    Directory of Open Access Journals (Sweden)

    Hans Carl Hasselbalch

    Full Text Available The Philadelphia-negative chronic myeloproliferative neoplasms - essential thrombocythemia (ET, polycythemia vera (PV, and myelofibrosis (MF (MPNs - have recently been shown to be associated with chronic inflammation, oxidative stress and accumulation of reactive oxygen species (ROS. Using whole blood transcriptional profiling, we report that several oxidative stress and anti-oxidative stress genes are significantly deregulated in MPNs. Among the twenty most up- and downregulated genes, ATOX1, DEFB122, GPX8, PRDX2, PRDX6, PTGS1, and SEPP1 were progressively upregulated from ET over PV to PMF, whereas AKR1B1, CYBA, SIRT2, TTN, and UCP2 were progressively downregulated in ET, PV and PMF (all FDR <0.05. The gene Nrf2, encoding the transcription factor nuclear factor erythroid 2-related factor 2 (NFE2L2 or Nrf2 was significantly downregulated in all MPNs. Nrf2 has a key role in the regulation of the oxidative stress response and modulates both migration and retention of hematopoietic stem cells (HSCs in their niche. The patogenetic importance of Nrf2 depletion in the context of expansion of the hematopoietic progenitor pool in MPNs is discussed with particular focus upon the implications of concomitant downregulation of Nrf2 and CXCR4 for stem cell mobilization.

  17. Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Xu Wu

    2016-01-01

    Full Text Available Obstructive sleep apnea (OSA associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH triggered tissue damage. Receptor for advanced glycation end product (RAGE and its ligand high mobility group box 1 (HMGB1 are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE, the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1 normal air (NA, (2 CIH, (3 CIH+sRAGE, and (4 NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6, apoptotic (Bcl-2/Bax, and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.

  18. Screening of potential pseudo att sites of Streptomyces phage ΦC31 integrase in the human genome

    Institute of Scientific and Technical Information of China (English)

    Zhi-peng HU; Lu-sheng CHEN; Cai-yan JIA; Huan-zhang ZHU; Wei WANG; Jiang ZHONG

    2013-01-01

    Aim:ΦC31 integrase mediates site-specific recombination between two short sequences,attP and attB,in phage and bacterial genomes,which is a promising tool in gene regulation-based therapy since the zinc finger structure is probably the DNA recognizing domain that can further be engineered.The aim of this study was to screen potential pseudo att sites of ΦC31 integrase in the human genome,and evaluate the risks of its application in human gene therapy.Methods:TFBS (transcription factor binding sites) were found on the basis of reported pseudo att sites using multiple motif-finding tools,including AlignACE,BioProspector,Consensus,MEME,and Weeder.The human genome with the proposed motif was scanned tc find the potential pseudo att sites of ΦC31 integrase.Results:The possible recognition motif of ΦC31 integrase was identified,which was composed of two co-occurrence conserved elements that were reverse complement to each other flanking the core sequence TTG.In the human genome,a total of 27924 potential pseudo att sites of ΦC31 integrase were found,which were distributed in each human chromosome with high-risk specificity values in the chromosomes 16,17,and 19.When the risks of the sites were evaluate more rigorously,53 hits were discovered,and some of them were just the vital functional genes or regulatory regions,such as ACYP2,AKR1B1,DUSP4,etc.Conclusion:The results provide clues for more comprehensive evaluation of the risks of using ΦC31 integrase in human gene therapy and for drug discovery.

  19. The isolation and characterization of β-glucogallin as a novel aldose reductase inhibitor from Emblica officinalis.

    Directory of Open Access Journals (Sweden)

    Muthenna Puppala

    Full Text Available Diabetes mellitus is recognized as a leading cause of new cases of blindness. The prevalence of diabetic eye disease is expected to continue to increase worldwide as a result of the dramatic increase in the number of people with diabetes. At present, there is no medical treatment to delay or prevent the onset and progression of cataract or retinopathy, the most common causes of vision loss in diabetics. The plant Emblica officinalis (gooseberry has been used for thousands of years as a traditional Indian Ayurvedic preparation for the treatment of diabetes in humans. Extracts from this plant have been shown to be efficacious against the progression of cataract in a diabetic rat model. Aldose reductase (ALR2 is implicated in the development of secondary complications of diabetes including cataract and, therefore, has been a major drug target for the development of therapies to treat diabetic disease. Herein, we present the bioassay-guided isolation and structure elucidation of 1-O-galloyl-β-D-glucose (β-glucogallin, a major component from the fruit of the gooseberry that displays selective as well as relatively potent inhibition (IC(50 = 17 µM of AKR1B1 in vitro. Molecular modeling demonstrates that this inhibitor is able to favorably bind in the active site. Further, we show that β-glucogallin effectively inhibits sorbitol accumulation by 73% at 30 µM under hyperglycemic conditions in an ex-vivo organ culture model of lenses excised from transgenic mice overexpressing human ALR2 in the lens. This study supports the continued development of natural products such as β-glucogallin as therapeutic leads in the development of novel therapies to treat diabetic complications such as cataract.

  20. Effect of the bovine oviductal fluid on in vitro fertilization, development and gene expression of in vitro-produced bovine blastocysts.

    Science.gov (United States)

    Cebrian-Serrano, A; Salvador, I; García-Roselló, E; Pericuesta, E; Pérez-Cerezales, S; Gutierrez-Adán, A; Coy, P; Silvestre, M A

    2013-04-01

    Oviductal microenvironment generally provides better conditions for early embryo development than the conventional in vitro system. In an attempt to simulate the oviduct conditions or the main potentially influencing factors, the effect was studied of a bovine oviductal fluid (bOF) treatment applied prior to IVF on (i) IVF parameters, (ii) cleavage rate, (iii) blastocyst yield and (iv) blastocyst quality. Embryo quality was assessed by morphological embryo quality and relative transcript abundance of several developmental genes in bovine blastocysts. Furthermore, to study the effect of bOF without the male effect and zona-sperm interaction, artificially activated metaphase II oocytes were also treated with bOF. In vitro-matured bovine oocytes from abattoir ovaries were treated or untreated with bOF for 30 min and then washed prior to IVF or activation. Subsequently, in vitro-fertilized and parthenogenetic embryos were in vitro cultured for 7 to 8 days. The bOF treatment had no effect on fertilization parameters, cleavage, blastocyst rates both on parthenogenetic and IVF bovine embryos and neither on morphological quality of IVF blastocysts. G6PD and SOD2 genes from IVF blastocysts showed significant changes in their expression after a bOF treatment. Significant differences were found for the expression of SCL2A1, GPX1, BAX, AKR1B1 and PLAC8 genes between excellent or good blastocysts (Grade 1) and fair blastocysts (Grade 2). To our knowledge, this is the first study that evaluates the effect of bOF oocyte treatment on fertilization parameters, development and quality of bovine embryos. PMID:22908847

  1. Aldo-Keto Reductases 1B in Endocrinology and Metabolism.

    Science.gov (United States)

    Pastel, Emilie; Pointud, Jean-Christophe; Volat, Fanny; Martinez, Antoine; Lefrançois-Martinez, Anne-Marie

    2012-01-01

    The aldose reductase (AR; human AKR1B1/mouse Akr1b3) has been the focus of many research because of its role in diabetic complications. The starting point of these alterations is the massive entry of glucose in polyol pathway where it is converted into sorbitol by this enzyme. However, the issue of AR function in non-diabetic condition remains unresolved. AR-like enzymes (AKR1B10, Akr1b7, and Akr1b8) are highly related isoforms often co-expressed with bona fide AR, making functional analysis of one or the other isoform a challenging task. AKR1B/Akr1b members share at least 65% protein identity and the general ability to reduce many redundant substrates such as aldehydes provided from lipid peroxidation, steroids and their by-products, and xenobiotics in vitro. Based on these properties, AKR1B/Akr1b are generally considered as detoxifying enzymes. Considering that divergences should be more informative than similarities to help understanding their physiological functions, we chose to review specific hallmarks of each human/mouse isoforms by focusing on tissue distribution and specific mechanisms of gene regulation. Indeed, although the AR shows ubiquitous expression, AR-like proteins exhibit tissue-specific patterns of expression. We focused on three organs where certain isoforms are enriched, the adrenal gland, enterohepatic, and adipose tissues and tried to connect recent enzymatic and regulation data with endocrine and metabolic functions of these organs. We presented recent mouse models showing unsuspected physiological functions in the regulation of glucido-lipidic metabolism and adipose tissue homeostasis. Beyond the widely accepted idea that AKR1B/Akr1b are detoxification enzymes, these recent reports provide growing evidences that they are able to modify or generate signal molecules. This conceptually shifts this class of enzymes from unenviable status of scavenger to upper class of messengers.

  2. Aldose reductases influence prostaglandin F2α levels and adipocyte differentiation in male mouse and human species.

    Science.gov (United States)

    Pastel, Emilie; Pointud, Jean-Christophe; Loubeau, Gaëlle; Dani, Christian; Slim, Karem; Martin, Gwenaëlle; Volat, Fanny; Sahut-Barnola, Isabelle; Val, Pierre; Martinez, Antoine; Lefrançois-Martinez, Anne-Marie

    2015-05-01

    Aldose reductases (AKR1B) are widely expressed oxidoreductases whose physiological function remains elusive. Some isoforms are genuine prostaglandin F2α (PGF2α) synthases, suggesting they might influence adipose homeostasis because PGF2α inhibits adipogenesis. This was shown by Akr1b7 gene ablation in the mouse, which resulted in increased adiposity related to a lower PGF2α content in fat. Yet humans have no ortholog gene for Akr1b7, so the role of aldose reductases in human adipose homeostasis remains to be explored. We analyzed expression of genes encoding human and mouse aldose reductase isoforms in adipose tissues and differentiating adipocytes to assess conserved mechanisms regulating PGF2α synthesis and adipogenesis. The Akr1b3 gene encoded the most abundant isoform in mouse adipose tissue, whereas Akr1b7 encoded the only isoform enriched in the stromal vascular fraction. Most mouse aldose reductase gene expression peaked in early adipogenesis of 3T3-L1 cells and diminished with differentiation. In contrast with its mouse ortholog Akr1b3, AKR1B1 expression increased throughout differentiation of human multipotent adipose-derived stem cells, paralleling PGF2α release, whereas PGF2α receptor (FP) levels collapsed in early differentiation. Pharmacological inhibition of aldose reductase using Statil altered PGF2α production and enhanced human multipotent adipose-derived stem adipocyte differentiation. As expected, the adipogenic effects of Statil were counteracted by an FP agonist (cloprostenol). Thus, in both species aldose reductase-dependent PGF2α production could be important in early differentiation to restrict adipogenesis. PGF2α antiadipogenic signaling could then be toned down through the FP receptor or aldose reductases down-regulation in human and mouse cells, respectively. Our data suggest that aldose reductase inhibitors could have obesogenic potential.

  3. Aldo-keto reductases 1B in adrenal cortex physiology

    Directory of Open Access Journals (Sweden)

    Emilie PASTEL

    2016-07-01

    Full Text Available Aldose reductase proteins are cytosolic monomeric enzymes, belonging to the aldo-keto reductase (AKR superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates such as aliphatic and aromatic aldehydes or ketones. The Aldose reductase subgroup (AKR1B is one of the most characterized because of its involvement in human diseases such as diabetic complications resulting from the ability of its human archetype AKR1B1 to reduce glucose into sorbitol. However the issue of AKR1B function in non pathologic condition remains poorly resolved. Adrenal steroidogenesis is strongly associated with high production of endogenous harmful lipid aldehyde by-products including isocaproaldehyde (4-methylpentanal derived from cholesterol side chain cleavage (the first step of steroid synthesis and 4-hydroxynonenal (4- HNE that can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase activity, suggesting that in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, previous studies have established that the adrenal gland is one of the major site for human and murine AKR1B expression suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms.This review presents the molecular mechanisms accounting for the adrenal specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions.

  4. Transient and Prolonged Response of Chicken Cecum Mucosa to Colonization with Different Gut Microbiota

    Science.gov (United States)

    Volf, Jiri; Polansky, Ondrej; Varmuzova, Karolina; Gerzova, Lenka; Sekelova, Zuzana; Faldynova, Marcela; Babak, Vladimir; Medvecky, Matej; Smith, Adrian L.; Kaspers, Bernd; Velge, Philippe; Rychlik, Ivan

    2016-01-01

    In this study we determined protein and gene expression in the caeca of newly hatched chickens inoculated with cecal contents sourced from hens of different ages. Over 250 proteins exhibited modified expression levels in response to microbiota inoculation. The most significant inductions were observed for ISG12-2, OASL, ES1, LYG2, DMBT1-L, CDD, ANGPTL6, B2M, CUZD1, IgM and Ig lambda chain. Of these, ISG12-2, ES1 and both immunoglobulins were expressed at lower levels in germ-free chickens compared to conventional chickens. In contrast, CELA2A, BRT-2, ALDH1A1, ADH1C, AKR1B1L, HEXB, ALDH2, ALDOB, CALB1 and TTR were expressed at lower levels following inoculation of microbiota. When chicks were given microbiota preparations from different age donors, the recipients mounted differential responses to the inoculation which also differed from the response profile in naturally colonised birds. For example, B2M, CUZD1 and CELA2A responded differently to the inoculation with microbiota of 4- or 40-week-old hens. The increased or decreased gene expression could be recorded 6 weeks after the inoculation of newly hatched chickens. To characterise the proteins that may directly interact with the microbiota we characterised chicken proteins that co-purified with the microbiota and identified a range of host proteins including CDD, ANGPTL6, DMBT1-L, MEP1A and Ig lambda. We propose that induction of ISG12-2 results in reduced apoptosis of host cells exposed to the colonizing commensal microbiota and that CDD, ANGPTL6, DMBT1-L, MEP1A and Ig lambda reduce contact of luminal microbiota with the gut epithelium thereby reducing the inflammatory response. PMID:27685470

  5. Vessel Ultrasound Sonographic Assessment of Soluble Receptor for Advanced Glycation End Products Efficacy in a Rat Balloon Injury Model

    Directory of Open Access Journals (Sweden)

    Hyun-Jin Tae, DVM, PhD

    2014-12-01

    Conclusions: Sonograph results are consistent with those obtained from histology; that is, sRAGE produced in Chinese hamster ovary cells has significantly higher efficacy than insect cell-originated sRAGE cells.

  6. Soluble Receptor for Advanced Glycation End Product: A Biomarker for Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Louise J. N. Jensen

    2015-01-01

    Full Text Available The receptor of advanced glycation end products (RAGE and its ligands are linked to the pathogenesis of coronary artery disease (CAD, and circulating soluble receptor of advanced glycation end products (sRAGE, reflecting the RAGE activity, is suggested as a potential biomarker. Elevated sRAGE levels are reported in relation to acute ischemia and this review focuses on the role of sRAGE as a biomarker for the acute coronary syndrome (ACS. The current studies demonstrated that sRAGE levels are elevated in relation to ACS, however during a very narrow time period, indicating that the time of sampling needs attention. Interestingly, activation of RAGE may influence the pathogenesis and reflection in sRAGE levels in acute and stable CAD differently.

  7. Receptor for Advanced Glycation End Products Regulates Adipocyte Hypertrophy and Insulin Sensitivity in Mice

    OpenAIRE

    Monden, Masayo; Koyama, Hidenori; Otsuka, Yoshiko; Morioka, Tomoaki; Mori, Katsuhito; Shoji, Takuhito; Mima, Yohei; Motoyama, Koka; Fukumoto, Shinya; Shioi, Atsushi; Emoto, Masanori; Yamamoto, Yasuhiko; Yamamoto, Hiroshi; Nishizawa, Yoshiki; Kurajoh, Masafumi

    2013-01-01

    Receptor for advanced glycation end products (RAGE) has been shown to be involved in adiposity as well as atherosclerosis even in nondiabetic conditions. In this study, we examined mechanisms underlying how RAGE regulates adiposity and insulin sensitivity. RAGE overexpression in 3T3-L1 preadipocytes using adenoviral gene transfer accelerated adipocyte hypertrophy, whereas inhibitions of RAGE by small interfering RNA significantly decrease adipocyte hypertrophy. Furthermore, double knockdown o...

  8. Soluble Forms and Ligands of the Receptor for Advanced Glycation End-Products in Patients with Acute Respiratory Distress Syndrome: An Observational Prospective Study.

    Directory of Open Access Journals (Sweden)

    Matthieu Jabaudon

    Full Text Available The main soluble form of the receptor for advanced glycation end-products (sRAGE is elevated during acute respiratory distress syndrome (ARDS. However other RAGE isoforms and multiple ligands have been poorly reported in the clinical setting, and their respective contribution to RAGE activation during ARDS remains unclear. Our goal was therefore to describe main RAGE isoforms and ligands levels during ARDS.30 ARDS patients and 30 mechanically ventilated controls were prospectively included in this monocenter observational study. Arterial, superior vena cava and alveolar fluid levels of sRAGE, endogenous-secretory RAGE (esRAGE, high mobility group box-1 protein (HMGB1, S100A12 and advanced glycation end-products (AGEs were measured in duplicate ELISA on day 0, day 3 and day 6. In patients with ARDS, baseline lung morphology was assessed with computed tomography.ARDS patients had higher arterial, central venous and alveolar levels of sRAGE, HMGB1 and S100A12, but lower levels of esRAGE and AGEs, than controls. Baseline arterial sRAGE, HMGB1 and S100A12 were correlated with nonfocal ARDS (AUC 0.79, 0.65 and 0.63, respectively. Baseline arterial sRAGE, esRAGE, S100A12 and AGEs were associated with severity as assessed by PaO2/FiO2.This is the first kinetics study of levels of RAGE main isoforms and ligands during ARDS. Elevated sRAGE, HMGB1 and S100A12, with decreased esRAGE and AGEs, were found to distinguish patients with ARDS from those without. Our findings should prompt future studies aimed at elucidating RAGE/HMGB1/S100A12 axis involvement in ARDS.clinicaltrials.gov Identifier: NCT01270295.

  9. Influence of Physical Activity Intervention on Circulating Soluble Receptor for Advanced Glycation end Products in Elderly Subjects

    OpenAIRE

    Kotani, Kazuhiko; Caccavello, Russell; Sakane, Naoki; Yamada, Toshiyuki; Taniguchi, Nobuyuki; Gugliucci, Alejandro

    2011-01-01

    Background Inflammation, often accompanied by oxidation, caused by advanced glycation end products (AGEs) may be quenched by the soluble receptor for AGEs (sRAGE). The present study aimed to investigate the influence of physical activity on circulating sRAGE, and the association between changes of circulating sRAGE and paraoxonase1 (PON1) activity (as an antioxidative enzyme) in a physical activity intervention study on an elderly subject cohort. Methods Serum sRAGE, PON1 activity and cardiom...

  10. The decrease in the IgG-binding capacity of intensively dry heated whey proteins is associatead with intense Maillard reaction, structural changes of the proteins and formation of RAGE-ligands

    NARCIS (Netherlands)

    Liu, F.; Teodorowicz, M.; Boekel, van M.A.J.S.; Wichers, H.J.; Hettinga, K.A.

    2016-01-01

    Heat treatment is the most common way of milk processing, inducing structural changes as well as chemical modifications in milk proteins. These modifications influence the immune-reactivity and allergenicity of milk proteins. This study shows the influence of dry heating on the solubility, particle

  11. bFGF and TGFβ1 growth factors, inflammatory markers (IL-6, TNF-α, CRP and advanced glycation end-products (AGE, RAGE in patients with ischemic heart disease and type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ekaterina Vladimirovna Ivannikova

    2013-11-01

    Full Text Available Aims. To evaluate plasma levels of transforming growth factor beta (TGFβ1, basic fibroblast growth factor (bFGF, markers for nonspecific inflammatory process (interleukin-6 (IL-6, tumor necrosis factor alpha (TNF-α, C-reactive protein (CRP and their putative correlation with advanced glycation end-products relative to diabetes compensation in patients with ischemic heart disease (IHD.Materials and Methods. 87 patients with IHD were enrolled in this study. All subjects underwent standard clinical examination, including laboratory assessment of glycemic parameters, lipid panel and renal function, with echocardiography, supplemented with coronary angiography. Analyses for study parameters were performed on samples obtained from aorta and, separately, from cubital vein during coronary angiography.Results. Diabetes mellitus in patients with IHD is firmly associated with TGFβ1, IL-6 and CRP elevation in both arterial and venous plasma. TGFβ1 positively correlates with lipid profile parameters. Plasma concentration of inflammatory markers and advanced glycation end-products positively correlates with the extent of coronary lesions in relation to the presence of diabetes mellitus.Conclusion. Our data suggests the interplay between connective tissue growth factors and lipid metabolism in the atherosclerotic process.

  12. bFGF and TGFβ1 growth factors, inflammatory markers (IL-6, TNF-α, CRP) and advanced glycation end-products (AGE, RAGE) in patients with ischemic heart disease and type 2 diabetes mellitus

    OpenAIRE

    Ekaterina Vladimirovna Ivannikova; Konstantin Vladimirovich Melkozerov; Viktor Yur'evich Kalashnikov; Sergey Anatol'evich Terekhin; Irina Vladimirovna Kononenko; Olga Mikhailovna Smirnova

    2013-01-01

    Aims. To evaluate plasma levels of transforming growth factor beta (TGFβ1), basic fibroblast growth factor (bFGF), markers for nonspecific inflammatory process (interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP)) and their putative correlation with advanced glycation end-products relative to diabetes compensation in patients with ischemic heart disease (IHD).Materials and Methods. 87 patients with IHD were enrolled in this study. All subjects underwent standar...

  13. L'écosystème d'innovation universitaire de Aalto : une contribution au repérage des acteurs impliqués lors de la phase d'émergence

    OpenAIRE

    Froehlicher, Thomas; Barès, Franck

    2014-01-01

    The aim of this article is to better under- stand how the innovation ecosystem of Aalto University, in Helsinki, Finland, was structured in the early 2000s. Relying on an analysis of secondary data as well as on the principles of a structural analy- sis of the network, we located the actors and their connections over the emergence period of this ecosystem. The results show the coexistence of two spaces organized as socio-cognitive networks able to interact and reinforce each other. A territor...

  14. 流感流行期大气环境特征及流感分级预报%Analysis of Atmospheric Environment Change During Flu Rage and Flu Occurrence Forecast

    Institute of Scientific and Technical Information of China (English)

    山义昌; 徐太安; 鲁丹; 郑学山; 杜恒欣

    2003-01-01

    分析了1998和2001年冬季我国北方地区流感大流行期的大气环境特征,得出冬季气温偏高,冷空气活动次数偏少且降温幅度增大;降水比上一年明显偏少且年际变化大、时间分布不均以及大气中烟尘含量高等大气环境特征与流感流行有密切关系.用1991~2001年的流感住院人数,气温、降水和能见度为因子,建立流感发生的预报方程.

  15. Role of the receptor for advanced glycation end products in hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Christina Lohwasser; Daniel Neureiter; Yury Popov; Michael Bauer; Detlef Schuppan

    2009-01-01

    AIM: To study the role of advanced glycation end products (AGE) and their specific receptor (RAGE) in the pathogenesis of liver fibrogenesis. METHODS: In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells (HSC) were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin (AGEBSA) and Nε-(carboxymethyl) lysine (CML)-BSA, or with tumor necrosis factor-α (TNF-α). In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS: In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-α. RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen α1(Ⅰ) mRNA by AGE-BSA. CONCLUSION: Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.

  16. Clearance kinetics and matrix binding partners of the receptor for advanced glycation end products.

    Directory of Open Access Journals (Sweden)

    Pavle S Milutinovic

    Full Text Available Elucidating the sites and mechanisms of sRAGE action in the healthy state is vital to better understand the biological importance of the receptor for advanced glycation end products (RAGE. Previous studies in animal models of disease have demonstrated that exogenous sRAGE has an anti-inflammatory effect, which has been reasoned to arise from sequestration of pro-inflammatory ligands away from membrane-bound RAGE isoforms. We show here that sRAGE exhibits in vitro binding with high affinity and reversibly to extracellular matrix components collagen I, collagen IV, and laminin. Soluble RAGE administered intratracheally, intravenously, or intraperitoneally, does not distribute in a specific fashion to any healthy mouse tissue, suggesting against the existence of accessible sRAGE sinks and receptors in the healthy mouse. Intratracheal administration is the only effective means of delivering exogenous sRAGE to the lung, the organ in which RAGE is most highly expressed; clearance of sRAGE from lung does not differ appreciably from that of albumin.

  17. The distribution of advanced glycation end products and their receptor in the gastrointestinal tract in the rats

    DEFF Research Database (Denmark)

    Chen, Pengmin; Zhao, Jingbo; Gregersen, Hans

    2012-01-01

    To investigate the distribution of advanced glycation end products (AGEs) and their receptor (RAGE) in the gastrointestinal (GI) tract to provide a basis for further study of the association between AGE/RAGE and diabetic GI dysfunction. METHODS: The distribution of AGEs [N epsilon......-(carboxymethyl) lysine and N epsilon-(carboxyethyl) lysine] and RAGE were detected in the esopha-geal, gastric, duodenal, jejunal, ileal, colonic and rectal tissues of normal adult Wistar rats using immunohistochemistry. RESULTS: In the esophagus, AGEs and RAGE were mainly distributed in striated muscle cells...... and squamous epithelial cells. In the stomach, AGEs were mainly distributed in parietal cells, and RAGE was strongly expressed in chief cells, mast cells and neurons in ganglia, moderately in parietal cells, and mildly in surface mucous cells. In the intestine, colon and rectum, AGEs and RAGE were distributed...

  18. Pop / Tõnis Kahu

    Index Scriptorium Estoniae

    Kahu, Tõnis, 1962-

    2008-01-01

    Heliplaatidest: Chemical Brothers "Brotherhood", Plutonium 74 "Peittoalueen ulkopuolella", Disturbed "Indestructible", Thomas Feiner & Anywhen "The Opiates Revised", DefRage "Save Us from Religion", Kago "Mopskassi maja"

  19. Soluble receptor for advanced glycation end products mitigates vascular dysfunction in spontaneously hypertensive rats.

    Science.gov (United States)

    Liu, Yu; Yu, Manli; Zhang, Le; Cao, Qingxin; Song, Ying; Liu, Yuxiu; Gong, Jianbin

    2016-08-01

    Vascular dysfunction including vascular remodeling and endothelial dysfunction in hypertension often results in poor clinical outcomes and increased risk of vascular accidents. We investigate the effect of treatment with soluble receptor for advanced glycation end products (sRAGE) on vascular dysfunction in spontaneously hypertensive rats (SHR). Firstly, the aortic AGE/RAGE pathway was investigated in SHR. Secondly, SHR received intraperitoneal injections of sRAGE daily for 4 weeks. Effect of sRAGE against vascular dysfunction in SHR and underlying mechanism was investigated. SHR aortas exhibited enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE. Treatment of SHR with sRAGE had no significant effect on blood pressure, but alleviated aortic hypertrophy and endothelial dysfunction. In vitro, treatment with sRAGE reversed the effect of incubation with AGE on proliferation of smooth muscle cells and endothelial function. Treatment of SHR with sRAGE abated oxidative stress, suppressed inflammation and NF-κB activation, improved the balance between Ang II and Ang-(1-7) through reducing angiotensin-converting enzyme (ACE) activity and enhancing ACE2 expression, and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in aortas. In conclusion, treatment with sRAGE alleviated vascular adverse remodeling in SHR, possibly via suppression of oxidative stress and inflammation, improvement in RAS balance, and activation of PPAR-γ pathway. PMID:27426491

  20. Status of LANL Efforts to Effectively Use Sequoia

    Energy Technology Data Exchange (ETDEWEB)

    Nystrom, William David [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-05-14

    Los Alamos National Laboratory (LANL) is currently working on 3 new production applications, VPC, xRage, and Pagosa. VPIC was designed to be a 3D relativist, electromagnetic Particle-In-Cell code for plasma simulation. xRage, a 3D AMR mesh amd multi physics hydro code. Pagosa, is a 3D structured mesh and multi physics hydro code.

  1. Advanced glycation end product ligands for the receptor for advanced glycation end products: Biochemical characterization and formation kinetics

    NARCIS (Netherlands)

    Valencia, J.V.; Weldon, S.C.; Quinn, D.; Kiers, G.H.; Groot, J. de; TeKoppele, J.M.; Hughes, T.E.

    2004-01-01

    Advanced glycation end products (AGEs) accumulate with age and at an accelerated rate in diabetes. AGEs bind cell-surface receptors including the receptor for advanced glycation end products (RAGE). The dependence of RAGE binding on specific biochemical characteristics of AGEs is currently unknown.

  2. Decreased level of endogenous secretory receptor for advanced glycation end-products in diabetes with concomitant hyperlipidemia.

    Science.gov (United States)

    Turk, Z; Ljubić, S; Boras, J

    2014-01-01

    Endogenous secretory receptor (esRAGE) for advanced glycation end-product (AGE) acts as decoy for AGEs. The AGE-to-esRAGE ratio was hypothesized to be implicated in diabetic vasculopathy. We investigated an association of esRAGE and methylglyoxal-adducts serum level, as well as AGE-to-esRAGE ratio in subpopulation of diabetic patients with or without concomitant hyperlipidemia and macrovascular disease in history. In diabetes with concomitant hyperlipidemia esRAGE was significantly decreased compared to hyperlipidemia with normal glucose metabolism (0.306+/-0.2 vs. 0.367+/-0.1; p=0.019) or diabetes alone (0.306+/-0.2 vs. 0.404+/-0.1; p=0.004). High AGE/esRAGE ratio, found in diabetic patients with hyperlipidemia, pointed to increased production of AGEs and low expression of esRAGE. In multivariable analysis adjusted for several confounding factors, increased AGE/esRAGE ratio was recognized as a high risk for vascular disease outcomes.

  3. Do Not Go Gentle into That Good Night

    Institute of Scientific and Technical Information of China (English)

    Dylan; Thomas

    2008-01-01

    Do not go gentle into that good night,Old age should burn and rave at close of day;Rage, rage against the dying of the light.Though wise men at their end know dark is right,Because their words had forked no lightning theyDo not go gentle into that good night.

  4. Receptor for advanced glycation end products plays a more important role in cellular survival than in neurite outgrowth during retinoic acid-induced differentiation of neuroblastoma cells.

    Science.gov (United States)

    Sajithlal, Gangadharan; Huttunen, Henri; Rauvala, Heikki; Munch, Gerald

    2002-03-01

    The receptor for advanced glycation end products (RAGE), a member of the immunoglobulin superfamily, is known to interact with amphoterin. This interaction has been proposed to play a role in neurite outgrowth and process elongation during neurodifferentiation. However, there is as yet no direct evidence of the relevance of this pathway to neurodifferentiation under physiological conditions. In this study we have investigated a possible role of RAGE and amphoterin in the retinoic acid-induced differentiation of neuroblastoma cells. The functional inactivation of RAGE by dominant negative and antisense strategies showed that RAGE is not required for process outgrowth or differentiation, although overexpression of RAGE accelerates the elongation of neuritic processes. Using the antisense strategy, amphoterin was shown to be essential for process outgrowth and differentiation, suggesting that amphoterin may interact with other molecules to exert its effect in this context. Interestingly, the survival of the neuroblastoma cells treated with retinoic acid was partly dependent on the expression of RAGE, and inhibition of RAGE function partially blocked the increase in anti-apoptotic protein Bcl-2 following retinoic acid treatment. Based on these results we propose that a combination therapy using RAGE blockers and retinoic acid may prove as a useful approach for chemotherapy for the treatment of neuroblastoma.

  5. Receptor for advanced glycation end product expression in experimental diabetic retinopathy

    NARCIS (Netherlands)

    Wang, Yumei; Hagen, Filanziska Vom; Pfister, Frederick; Bierhaus, Angelika; Feng, Yuxi; Gans, Reinhold; Hammes, Hans-Peter; Schleicher, E; Somoza,; Shieberle, P

    2008-01-01

    The advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway is involved in the pathogenesis of diabetic microvascular damage. The special distribution of RAGE and its engagement has an impact on the development of diabetic retinopathy. In the present study, we used immunofluorescence an

  6. Determinants of concentrations of N(ε)-carboxymethyl-lysine and soluble receptor for advanced glycation end products and their associations with risk of pancreatic cancer.

    Science.gov (United States)

    Duan, Zhigang; Chen, Guoqing; Chen, Liang; Stolzenberg-Solomon, Rachael; Weinstein, Stephanie J; Mannisto, Satu; White, Donna L; Albanes, Demetrius; Jiao, Li

    2014-01-01

    The soluble receptor for advanced glycation end-products (sRAGE) is shown to mitigate pro-inflammatory effects triggered by ligation of RAGE with N(ε)-carboxymethyl-lysine (CML)-AGE or other ligands. We examined the associations among host, lifestyle, and genetic determinants of CML-AGE or sRAGE and risk of pancreatic cancer in the prospective ATBC Study. We obtained baseline exposure information, data on serological and genetic biomarkers from 141 patients with pancreatic cancer and 141 subcohort controls. Stepwise linear and logistic regression models were used for data analysis. Multiple linear regression analyses showed that CML-AGE concentrations were independently inversely correlated with the minor allele of rs640742 of DDOST, physical activity, alcohol consumption, diastolic blood pressure (BP), and positively correlated with heart rate, serum sRAGE and HDL concentrations (P RAGE, age, body mass index, heart rate, and serum HDL; and positively correlated with serum CML-AGE, sucrose consumption, and diastolic BP (P RAGE was associated with reduced risk of pancreatic cancer (any T compared with CC: multivariate OR = 0.61, 95% CI: 0.38-0.98). We identified host metabolic profile, lifestyle and genetic factors that explained approximately 50% of variability of CML-AGE or sRAGE in Finnish men smokers. The association between RAGE SNPs and pancreatic cancer risk warrants further investigation. PMID:25379135

  7. Comment choisir ce qui aura été?

    DEFF Research Database (Denmark)

    Wilson, Alexander

    2015-01-01

    are faced with a world lacking a future, a world dying under the stresses caused by the human’s exploitation of nature. Here, instead of the mantra ‘Enjoy it while it lasts’, an opposing moral is repeated: ‘Don’t go gentle into that good night, Rage, rage against the dying of the light.’ In the film, Thomas...

  8. Beech Lodge Care Facility, Bruree, Limerick.

    LENUS (Irish Health Repository)

    Buckley, Stephen T

    2010-01-01

    The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. As a pattern-recognition receptor capable of binding a diverse range of ligands, it is typically expressed at low levels under normal physiological conditions in the majority of tissues. In contrast, the lung exhibits high basal level expression of RAGE localised primarily in alveolar type I (ATI) cells, suggesting a potentially important role for the receptor in maintaining lung homeostasis. Indeed, disruption of RAGE levels has been implicated in the pathogenesis of a variety of pulmonary disorders including cancer and fibrosis. Furthermore, its soluble isoforms, sRAGE, which act as decoy receptors, have been shown to be a useful marker of ATI cell injury. Whilst RAGE undoubtedly plays an important role in the biology of the lung, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.

  9. Garlic decreases liver and kidney receptor for advanced glycation end products expression in experimental diabetes.

    Science.gov (United States)

    Al-Qattan, Khaled K; Mansour, Mohamed H; Thomson, Martha; Ali, Muslim

    2016-06-01

    The up-regulation of the receptor for advanced glycation end products (RAGE) has been implicated as a major mediator in the development and progression of diabetic nephropathy and hepatic fibrogenesis. The present study was designed to investigate the potential of garlic (Allium sativum L.) to modulate the level of expression of RAGE in renal and hepatic tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven specificity to RAGE indicated in immunohistochemical assays that RAGE labeling was significantly increased in renal and hepatic tissues of control diabetic rats compared to the normal group. The increased RAGE labeling involved mesangial cells in glomeruli exhibiting signs of mesangial expansion, mesangial nodule formation and glomerulosclerosis. In the liver, a significant up-regulation of RAGE was observed in hepatocytes and bile ducts and vessels in portal tracts. In 2-dimensional Western blots, RAGE expression in both tissues was dominated by heterogeneous charge variants, represented by 46-50kDa isoforms with more basic pIs compared to their counterparts in normal rats. Compared to control diabetic rats, RAGE labeling in the garlic-treated diabetic group was significantly reduced throughout renal and hepatic regions and was marked by the expression of 43-50kDa acidic charge variants comparable to those observed in normal rats. The capacity of garlic to modulate diabetes-induced up-regulation of selective RAGE polymorphic variants may be implicated in attenuating the detrimental consequences of excessive RAGE signaling manifested by diabetes-associated disorders. PMID:26968224

  10. Soluble and Endogenous Secretory Receptors for Advanced Glycation End Products in Threatened Preterm Labor and Preterm Premature Rupture of Fetal Membranes

    Directory of Open Access Journals (Sweden)

    Rafał Rzepka

    2015-01-01

    Full Text Available The aim of the study was to compare sRAGE and esRAGE plasma levels in pregnant women with (A threatened premature labor (n=41, (B preterm premature rupture of membranes (n=49, and (C preterm rupture of membranes at term (n=48. The relationship between these and classic intrauterine infection markers and the latent time from symptoms up to delivery depending on RAGE’s concentration were investigated. In groups A and B, a positive correlation was found between plasma sRAGE and latent time (r = 0,422; p = 0,001; r = 0,413, p = 0,004, resp.. High prognostic values were found in both groups for plasma sRAGE concentration and the latent time from symptoms up to delivery. Groups B and C presented higher levels of esRAGE than group A (526,315 ± 129,453 pg/mL and 576,212 ± 136,237 pg/mL versus 485,918 ± 133,127 pg/mL, p< 0,05. The conclusion is that sRAGE concentration can be a favorable prognostic factor in the presence of symptoms of threatened premature labor. Higher esRAGE plasma level in case of the rupture of membranes in mature and premature pregnancy suggests its participation in fetal membranes destruction.

  11. Receptor for Advanced Glycation End-Products Signaling Interferes with the Vascular Smooth Muscle Cell Contractile Phenotype and Function.

    Directory of Open Access Journals (Sweden)

    Elie Simard

    Full Text Available Increased blood glucose concentrations promote reactions between glucose and proteins to form advanced glycation end-products (AGE. Circulating AGE in the blood plasma can activate the receptor for advanced end-products (RAGE, which is present on both endothelial and vascular smooth muscle cells (VSMC. RAGE exhibits a complex signaling that involves small G-proteins and mitogen activated protein kinases (MAPK, which lead to increased nuclear factor kappa B (NF-κB activity. While RAGE signaling has been previously addressed in endothelial cells, little is known regarding its impact on the function of VSMC. Therefore, we hypothesized that RAGE signaling leads to alterations in the mechanical and functional properties of VSMC, which could contribute to complications associated with diabetes. We demonstrated that RAGE is expressed and functional in the A7r5 VSMC model, and its activation by AGE significantly increased NF-κB activity, which is known to interfere with the contractile phenotype of VSMC. The protein levels of the contraction-related transcription factor myocardin were also decreased by RAGE activation with a concomitant decrease in the mRNA and protein levels of transgelin (SM-22α, a regulator of VSMC contraction. Interestingly, we demonstrated that RAGE activation increased the overall cell rigidity, an effect that can be related to an increase in myosin activity. Finally, although RAGE stimulation amplified calcium signaling and slightly myosin activity in VSMC challenged with vasopressin, their contractile capacity was negatively affected. Overall, RAGE activation in VSMC could represent a keystone in the development of vascular diseases associated with diabetes by interfering with the contractile phenotype of VSMC through the modification of their mechanical and functional properties.

  12. Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-β1 expression and fibrosis in minipigs with ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    LU Lin; SHEN Wei-feng; ZHANG Qi; XU Yan; ZHU Zheng-bin; GENG Liang; WANG Ling-jie; JIN Cao; CHEN Qiu-jing; Ann Marie Schmidt

    2010-01-01

    Background The cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n=5) or saline (control group, n=5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-β1was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5 5.1) to (32.3 5.6) ml, P <0.05) and end-systolic volume (from (8.3 3.2) to (15.2 4.1) ml, P <0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6 13.3)% to (50.2 11.9)%, P<0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P<0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P<0.05). Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.

  13. 糖基化终末产物及其受体在糖尿病大鼠胃组织中的分布 (Distribution of advanced glycation end products and their receptor in the stomach of diabetic rats)

    DEFF Research Database (Denmark)

    Tian, Jia Xing; Zhao, Jingbo; Li, Min;

    2015-01-01

    AIM: To observe the distribution of advanced glycation end products (AGEs) and their receptor (RAGE) in the stomach of diabetic rats. METHODS: Diabetes mellitus (DM) and control (CON) rats were reared for eight weeks. Fasting plasma glucose (FPG), glycated serum protein (GSP) and gastric layer...... with the CON group (P stomach was significantly higher in the DM group than in the CON group (P ...: The expression of AGEs and RAGE is up-regulated in the stomach of diabetic rats. The increased levels of AGE and RAGE in gastric tissue may contribute to diabetic gastrointestinal dysfunction. © 2015 Baishideng Publishing Group Inc. All rights reserved. Key Words: Diabetes mellitus; Stomach; Advanced glycation...

  14. Subcontracting in electronics : from contract manufacturers to providers of electronic manufacturing services (EMS)

    OpenAIRE

    Liemt, Gijsbert van

    2007-01-01

    Discusses how the top contract manufacturers in the electronics industry try to become providers of electronic manufacturing services by deepening and broadening the rage of services that they offer and by diversifying into markets other than computing and telecommunications.

  15. A very brief history of relativity

    Science.gov (United States)

    O'Raifeartaigh, Cormac

    2015-08-01

    On 25 November 1915, as devastating war raged throughout Europe, Albert Einstein presented the paper Die Feldgleichungen der Gravitation (“The field equations of gravitation”) to the Prussian Academy of Sciences.

  16. Ghana's Decentralization: Two decades and still crawling?

    OpenAIRE

    Daniel Kweku Baah Inkoom

    2011-01-01

    After more than two decades of implementation, there are still debates raging on the nature, processes, financing and operationalization of the decentralization system in Ghana. Daniel Kweku Baah Inkoom looks at the legal, administrative, financial and human resource constraints.

  17. Uusi plaate / Marko T. Lepp

    Index Scriptorium Estoniae

    Lepp, Marko T.

    1999-01-01

    Uutest plaatidest Enrique Iglesias "Enrique", Will Smith "Willennium", Celine Dion "All The Way... A Decade Of Song". Korn "Issues", Rage Agains The Machine "The Battle Of Los Angeles", Sevendust "Home"

  18. Narcissistic personality disorder

    Science.gov (United States)

    Personality disorder - borderline; Narcissism ... A person with narcissistic personality disorder may: React to criticism with rage, shame, or humiliation Take advantage of other people to achieve his or her own ...

  19. Development of a Single-Frequency Narrow Linewidth 1.5mm Semiconductor Laser Suitable for Spaceflight Operation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Many space applications rely on the utilization of Light Detection and Raging (LIDAR) techniques. A key component of any LIDAR system is the laser source. Single...

  20. 英文摘要

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    COVER STORY EXHAUSTED WITH SMOG The cottony smog of toxic pollution that has covered some of China's largest cities has spurred a raging debate over the most effective methods to reduce the bad air quality.

  1. [Analysis of the impact of heparin on the affinity of high mobility group box-1 protein and the receptor of advanced glycation end products by surface plasmon resonance technology].

    Science.gov (United States)

    Ling, Yan; Wang, Chun-You; Yang, Zhi-Yong

    2009-11-01

    To investigate the affinity constants of heparin with high mobility group protein 1(HMGB1) and HMGB1 with the receptor of advanced glycation end products (RAGE) and to analyze the impact of heparin on the affinity of HMGB1 and RAGE, the standard BIAcore amine coupling chemistry protocol using EDC and NHS was employed for immobilizing. Surface plasmon resonance biosensor technology was used to detect the affinity constants of heparin/HMGB1, HMGB1/RAGE and heparin/ RAGE. Binding analysis was used to investigate the impact of heparin on the affinity of HMGB1 and RAGE. After the immobilization, 9 000 and 5 000 RU rise of HMGB1 and RAGE respectively were obtained. These meant that the immobilized values of HMGB1 and RAGE were about 9 and 5 ng x mm(-2) respectively. The kinetic constants were k(a) = 1.78 x 10(5) L x mol(-1) x s(-1), kd = 8.02 x 10(-4) s(-1), and the affinity constants were KA = 2.22 x 10(8) L x mol(-1), the equilibrium dissociation constant K(D) = 4.5 x 10(-9) mol x L(-1) for heparin and HMGB1; while the kinetic constants were k(a) = 1.85 x 10(3) L x mol(-1) x s(-1), k(d) = 1.81 x 10(-4) s(-1), K(A) = 1.02 x 10(7) L x mol(-1), K(D) = 9.77 x 10(-8) mol x L(-1) for HMGB1 and RAGE; there was very low affinity of heparin with RAGE. The highest concentration of 10 000 u x L(-1) of heparin in this experiment did not reach the saturation with HMGB1. After 50 mg x L(-1) of HMGB1 was mixed with heparin of 50, 100, 1 000, 10 000 u x L(-1), the combining amount of HMGB1 and RAGE declined from 100 to 50 RU. But there were no significant differences between different concentrations of heparin. It was concluded that heparin can combine with HMGB1 and affect the affinity of HMGB1/RAGE. In addition, this impact was not in a dose-dependent manner. PMID:20101991

  2. The Receptor for Advanced Glycation End Products Is a Central Mediator of Asthma Pathogenesis

    OpenAIRE

    Pavle S Milutinovic; Alcorn, John F.; Englert, Judson M; Crum, Lauren T.; Oury, Tim D.

    2012-01-01

    The receptor for advanced glycation end products (RAGE) is a multiligand receptor that has been shown to contribute to the pathogenesis of diabetes, atherosclerosis, and neurodegeneration. However, its role in asthma and allergic airway disease is largely unknown. These studies use a house dust mite (HDM) mouse model of asthma/allergic airway disease. Respiratory mechanics were assessed and compared between wild-type and RAGE knockout mice. Bronchovascular architecture was assessed with quant...

  3. Paradoxical function for the receptor for advanced glycation end products in mouse models of pulmonary fibrosis

    OpenAIRE

    Englert, Judson M; Kliment, Corrine R.; Ramsgaard, Lasse; Pavle S Milutinovic; Crum, Lauren; Tobolewski, Jacob M.; Oury, Tim D.

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor survival. The identification of therapeutic targets is essential to improving outcomes. Previous studies found that expression of the receptor for advanced glycation end products (RAGE) in the lung is significantly decreased in human IPF lungs and in two animal models of pulmonary fibrosis. In addition, RAGE-null mice spontaneously develop pulmonary fibrosis with age and more severe fibrosis when challenged with asbestos. ...

  4. Brain injury requires lung protection

    OpenAIRE

    Lopez-Aguilar, Josefina; Blanch, Lluis

    2015-01-01

    The paper entitled “The high-mobility group protein B1-Receptor for advanced glycation endproducts (HMGB1-RAGE) axis mediates traumatic brain injury (TBI)-induced pulmonary dysfunction in lung transplantation” published recently in Science Translational Medicine links lung failure after transplantation with alterations in the axis HMGB1-RAGE after TBI, opening a new field for exploring indicators for the early detection of patients at risk of developing acute lung injury (ALI). The lung is on...

  5. The Associations of Advanced Glycation End Products and Its Soluble Receptor with Pancreatic Cancer Risk: A Case-Control Study within the Prospective EPIC Cohort

    OpenAIRE

    Grote, Verena A; Nieters, Alexandra; Kaaks, Rudolf; Tjønneland, Anne; Roswall, Nina; Overvad, Kim; Nielsen, Michael R Skjelbo; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie Christine; Racine, Antoine; Teucher, Birgit; Lukanova, Annekatrin; Boeing, Heiner; Drogan, Dagmar; Trichopoulou, Antonia

    2012-01-01

    BACKGROUND: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. METHODS: Prediagnostic blood levels of the AGE product Nε-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic ca...

  6. Novel Inhibitory Effects of Glycyrrhizic Acid on the Accumulation of Advanced Glycation End Product and Its Receptor Expression

    OpenAIRE

    Cheng, Hong Sheng; Kong, Joana Magdelene Xiao Fang; Ng, Athena Xin Hui; Chan, Weng Keong; Ton, So Ha; Abdul Kadir, Khalid

    2014-01-01

    Abstract Beneficial effects of glycyrrhizic acid (GA), a bioactive extract of licorice root, in the prevention of metabolic syndrome have been consistently reported while advanced glycation end products (AGE) and receptor for advanced glycation end product (RAGE) are the leading factors in the development of diabetes mellitus. The aim of this study was to investigate the effects of GA on the AGE-RAGE axis using high-fat/high-sucrose (HF/HS) diet-induced metabolic syndrome rat models. Twenty f...

  7. Mechanisms of disease: advanced glycation end-products and their receptor in inflammation and diabetes complications.

    Science.gov (United States)

    Yan, Shi Fang; Ramasamy, Ravichandran; Schmidt, Ann Marie

    2008-05-01

    Many important biochemical mechanisms are activated in the presence of high levels of glucose, which occur in diabetes. Elevated levels of glucose accelerate the formation of advanced glycation end-products (AGEs). Via their chief signaling receptor-the AGE-specific receptor (commonly abbreviated as RAGE)-AGEs generate reactive oxygen species and activate inflammatory signaling cascades. Consequently, AGEs have key roles in the pathogenesis of diabetic complications. Two discoveries have advanced our knowledge of the roles of RAGE in inflammation. First, this receptor has multiple ligands and binds not only AGEs but also proinflammatory, calcium-binding S100 proteins (also known as calgranulins) and nuclear high mobility group protein box-1. Second, RAGE is expressed on T lymphocytes, monocytes and macrophages; RAGE expression on T lymphocytes is essential for effective priming of immune responses in vivo. In this Review, we chronicle roles for RAGE in the pathogenesis of diabetic complications and develop the hypothesis that, in addition to RAGE's central role in the inflammatory response, it is critically linked to the pathogenesis of types 1 and 2 diabetes. PMID:18332897

  8. Evidence for Activation of Toll-Like Receptor and Receptor for Advanced Glycation End Products in Preterm Birth

    Directory of Open Access Journals (Sweden)

    Taketoshi Noguchi

    2010-01-01

    Full Text Available Objective. Individuals with inflammation have a myriad of pregnancy aberrations including increasing their preterm birth risk. Toll-like receptors (TLRs and receptor for advanced glycation end products (RAGE and their ligands were all found to play a key role in inflammation. In the present study, we reviewed TLR and RAGE expression, their ligands, and signaling in preterm birth. Research Design and Methods. A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2010, combining the keywords “preterm birth,” “TLR”, “RAGE”, “danger signal”, “alarmin”, “genomewide,” “microarray,” and “proteomics” with specific expression profiles of genes and proteins. Results. This paper provides data on TLR and RAGE levels and critical downstream signaling events including NF-kappaB-dependent proinflammatory cytokine expression in preterm birth. About half of the genes and proteins specifically present in preterm birth have the properties of endogenous ligands “alarmin” for receptor activation. The interactions between the TLR-mediated acute inflammation and RAGE-mediated chronic inflammation have clear implications for preterm birth via the TLR and RAGE system, which may be acting collectively. Conclusions. TLR and RAGE expression and their ligands, signaling, and functional activation are increased in preterm birth and may contribute to the proinflammatory state.

  9. Receptor for Advanced Glycation End Products and Its Involvement in Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Yaw Kuang Chuah

    2013-01-01

    Full Text Available The receptor for advanced glycation end products (RAGE is a transmembrane receptor of the immunoglobulin superfamily, capable of binding a broad repertoire of ligands. RAGE-ligands interaction induces a series of signal transduction cascades and lead to the activation of transcription factor NF-κB as well as increased expression of cytokines, chemokines, and adhesion molecules. These effects endow RAGE with the role in the signal transduction from pathogen substrates to cell activation during the onset and perpetuation of inflammation. RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's disease, arthritis, acute respiratory failure, and sepsis. Despite the significant progress in other RAGE studies, the functional importance of the receptor in clinical situations and inflammatory diseases still remains to be fully realized. In this review, we will summarize current understandings and lines of evidence on the molecular mechanisms through which RAGE signaling contributes to the pathogenesis of the aforementioned inflammation-associated conditions.

  10. Effects of candesartan cilexetil and amlodipine orotate on receptor for advanced glycation end products expression in the aortic wall of Otsuka Long-Evans Tokushima Fatty (OETFF) type 2 diabetic rats.

    Science.gov (United States)

    Kang, Min-Kyu; Chung, Woo-Baek; Hong, Seul-Ki; Kim, Ok-Ran; Ihm, Sang-Hyun; Chang, Kiyuk; Seung, Ki-Bae

    2016-04-01

    The receptor for advanced glycation end products (RAGE) plays a key role in the development of vascular inflammation and acceleration of atherosclerosis in type 2 diabetes. We investigated the effect of candesartan cilexetil (CDRT) and amlodipine orotate (AMDP) on the expression of RAGE in the aortic walls of Otsuka Long-Evans Tokushima Fatty (OLETF) rats and AGE-treated endothelial cells. Twenty five-week-old OLETF rats were randomized to 8 week treatments consisting of CDRT (n = 8), AMDP (n = 8) or saline (control, n = 8). Immunohistochemical and dihydroethidine staining revealed reduced RAGE and reactive oxygen species (ROS) signals in rats treated with CDRT or AMDP compared with control rats. Both CDRT and AMDP suppressed the expression of p22phox and p47phox NADPH oxidase subunits. However, only CDRT significantly reduced expression of phosphorylated extracellular signal regulated kinase (pERK)1/2 in the aortic wall of OLETF rats. In addition, both drugs reduced RAGE expression and total and mitochondrial ROS production in the AGE-treated endothelial cells. Both ARBs and CCBs reduced RAGE expression in the aortic walls of OLETF rats, which was attributed to decreased ROS production through inhibition of NADPH oxidase. In addition, only CDRT reduced aortic expression of RAGE via suppression of the ERK1/2 pathway unlike AMDP. PMID:26960737

  11. Extract of Polygonum cuspidatum Attenuates Diabetic Retinopathy by Inhibiting the High-Mobility Group Box-1 (HMGB1 Signaling Pathway in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Eunjin Sohn

    2016-03-01

    Full Text Available High-mobility group box-1 (HMGB1 is a well-known pro-inflammatory cytokine. We aimed to investigate the effect of the ethanol extract of the root of P. cuspidatum (PCE on retinal inflammation in diabetic retinopathy. PCE (100 or 350 mg/kg/day was administered to diabetic rats for 16 weeks, and hyperglycemia and body weight loss developed in the diabetic rats. The retinal expression levels of HMGB1 and receptor for advanced glycation end products (RAGE and the activity of nuclear factor-kappa B (NF-κB in the retina were examined. Additionally, a chromatin immunoprecipitation assay was performed to analyze the binding of NF-κB binding to the RAGE promoter in the diabetic retinas. The levels of HMGB1 and RAGE expression, NF-κB activity, and NF-κB binding to the RAGE promoter were increased in the diabetic retinas. However, treatment with PCE ameliorated the increases in HMGB1 and RAGE expression, and NF-κB activity in the retina. In addition, in diabetic rats, retinal vascular permeability and the loosening of the tight junctions were inhibited by PCE. These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting HMGB1-RAGE-NF-κB activation in diabetic retinas. The oral administration of PCE may significantly help to suppress the development of diabetic retinopathy in patients with diabetes.

  12. Concentration of Endogenous Secretory Receptor for Advanced Glycation End Products and Matrix Gla Protein in Controlled and Uncontrolled Type 2 Diabetes Mellitus Patients

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    Dwi Yuniati Daulay

    2013-04-01

    Full Text Available BACKGROUND: Advanced glycation end products (AGE and their receptor (RAGE system play an important role in the development of diabetic vascular complications. Recently, an endogenous secretory RAGE (esRAGE has been identified as a novel splice variant, which lacks the transmembrane domain and is secreted in human sera. Interestingly, it was reported that esRAGE binds AGE ligands and neutralizes AGE actions. Many studies have reported that diabetes mellitus correlates with vascular calcification event and increases progressively in uncontrolled diabetes. Matrix Gla Protein (MGP is known to act as an inhibitor in vascular calcification. The aim of this study was to observe progress of vascular calcification in uncontrolled diabetes patient by biochemical markers MGP as inhibitor in vascular calcification, via mechanism of AGEs. METHODS: This study was an observational study with cross sectional design on adult type 2 diabetic male patients who were defined by the 2011 Indonesian diabetes mellitus consensus criteria. RESULTS: The results of this study showed that there was a positive significant correlation between esRAGE and HbA1C (r=0.651, p=0.009, and negative correlation between MGP and HbA1C (r=-0.465, p=0.081 in controlled diabetes group. In uncontrolled diabetes group there was a positive significant correlation between MGP and HbA1C (r=0.350, p=0.023, despite the fact esRAGE showed no significant correlation with HbA1C. There was no significant difference in level of esRAGE and MGP in controlled and uncontrolled diabetes group, but MGP showed lower level in uncontrolled diabetes group, contrary to esRAGE that had higher concentration. CONCLUSIONS: In diabetes condition, complications of vascular calcification are caused by the mechanism of increased AGE formation represented by esRAGE. In diabetes control it is very important to keep the blood vessels from complications caused by vascular calcification. KEYWORDS: type 2 diabetes mellitus

  13. Cilostazol attenuates the severity of peripheral arterial occlusive disease in patients with type 2 diabetes: the role of plasma soluble receptor for advanced glycation end-products.

    Science.gov (United States)

    Liu, Jhih-Syuan; Chuang, Tsung-Ju; Chen, Jui-Hung; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Lin, Tsung-Kun; Hsiao, Fone-Ching; Hung, Yi-Jen

    2015-08-01

    Recent studies have demonstrated that the plasma soluble receptor for advanced glycation end-products (sRAGE) play a major role in developing macrovascular complications of type 2 diabetes, including peripheral arterial occlusion disease (PAOD). Cilostazol is an antiplatelet, antithrombotic agent, which has been used for the treatment of PAOD. We hypothesized that cilostazol attenuates the severity of PAOD in patients with type 2 diabetes through the augmentation of plasma sRAGE. Ninety type 2 diabetic patients with PAOD defined as intermittent claudication with ankle-brachial index (ABI) ≦0.9 were recruited for an open-labeled, placebo-controlled study for 52 weeks with oral cilostazol 100 mg twice daily (n = 45) or placebo (n = 45). Fasting plasma sRAGE, endothelial variables of E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), and inflammatory markers of high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF-α) were determined. After completely the 52-week treatment program, the ABI values were elevated in cilostazol group (P < 0.001). The plasma sRAGE was significantly increased (P = 0.007), and hsCRP, sVCAM, and E-selectin concentrations were significantly decreased (P = 0.028, <0.001 and <0.001, respectively) with cilostazol treatment. In a partial correlation analysis with adjustments for sex and age, the net change of sRAGE significantly correlated with the change of ABI in the cilostazol group (P = 0.043). In a stepwise multiple regression model, only the change with regards to sRAGE was significantly associated with the change of ABI (P = 0.046). Our results suggest that cilostazol may effectively attenuate the severity of PAOD in patients with type 2 diabetes. Plasma sRAGE plays a role as an independent predictor for improving the index of PAOD. PMID:25666934

  14. Gene expression pattern of functional neuronal cells derived from human bone marrow mesenchymal stromal cells

    Directory of Open Access Journals (Sweden)

    Bron Dominique

    2008-04-01

    Full Text Available Abstract Background Neuronal tissue has limited potential to self-renew or repair after neurological diseases. Cellular therapies using stem cells are promising approaches for the treatment of neurological diseases. However, the clinical use of embryonic stem cells or foetal tissues is limited by ethical considerations and other scientific problems. Thus, bone marrow mesenchymal stomal cells (BM-MSC could represent an alternative source of stem cells for cell replacement therapies. Indeed, many studies have demonstrated that MSC can give rise to neuronal cells as well as many tissue-specific cell phenotypes. Methods BM-MSC were differentiated in neuron-like cells under specific induction (NPBM + cAMP + IBMX + NGF + Insulin. By day ten, differentiated cells presented an expression profile of real neurons. Functionality of these differentiated cells was evaluated by calcium influx through glutamate receptor AMPA3. Results Using microarray analysis, we compared gene expression profile of these different samples, before and after neurogenic differentiation. Among the 1943 genes differentially expressed, genes down-regulated are involved in osteogenesis, chondrogenesis, adipogenesis, myogenesis and extracellular matrix component (tuftelin, AGC1, FADS3, tropomyosin, fibronectin, ECM2, HAPLN1, vimentin. Interestingly, genes implicated in neurogenesis are increased. Most of them are involved in the synaptic transmission and long term potentialisation as cortactin, CASK, SYNCRIP, SYNTL4 and STX1. Other genes are involved in neurite outgrowth, early neuronal cell development, neuropeptide signaling/synthesis and neuronal receptor (FK506, ARHGAP6, CDKRAP2, PMCH, GFPT2, GRIA3, MCT6, BDNF, PENK, amphiregulin, neurofilament 3, Epha4, synaptotagmin. Using real time RT-PCR, we confirmed the expression of selected neuronal genes: NEGR1, GRIA3 (AMPA3, NEF3, PENK and Epha4. Functionality of these neuron-like cells was demonstrated by Ca2+ influx through glutamate

  15. The Receptor for Advanced Glycation End Products Activates the AIM2 Inflammasome in Acute Pancreatitis.

    Science.gov (United States)

    Kang, Rui; Chen, Ruochan; Xie, Min; Cao, Lizhi; Lotze, Michael T; Tang, Daolin; Zeh, Herbert J

    2016-05-15

    Severe acute pancreatitis (AP) is responsible for significant human morbidity and mortality worldwide. Currently, no specific treatments for AP exist, primarily due to the lack of a mechanistic understanding of sterile inflammation and the resultant multisystem organ dysfunction, the pathologic response of AP linked to early death. In this study, we demonstrate that the class III major histocompatibility region III receptor for advanced glycation end products (RAGE) contributes to AP by modulating inflammasome activation in macrophages. RAGE mediated nucleosome-induced absent in melanoma 2 (but not NLRP3) inflammasome activation by modulating dsRNA-dependent protein kinase phosphorylation in macrophages. Pharmacological and genetic inhibition of the RAGE-dsRNA-dependent protein kinase pathway attenuated the release of inflammasome-dependent exosomal leaderless cytokines (e.g., IL-1β and high-mobility group box 1) in vitro. RAGE or absent in melanoma 2 depletion in mice limited tissue injury, reduced systemic inflammation, and protected against AP induced by l-arginine or cerulein in experimental animal models. These findings define a novel role for RAGE in the propagation of the innate immune response with activation of the nucleosome-mediated inflammasome and will help guide future development of therapeutic strategies to treat AP. PMID:27045109

  16. Metformin protects against hyperglycemia-induced cardiomyocytes injury by inhibiting the expressions of receptor for advanced glycation end products and high mobility group box 1 protein.

    Science.gov (United States)

    Zhang, Ting; Hu, Xiaorong; Cai, Yuli; Yi, Bo; Wen, Zhongyuan

    2014-03-01

    Metformin (MET), an anti-diabetic oral drug with antioxidant properties, has been proved to provide cardioprotective effects in patients with diabetic disease. However, the mechanism is unclear. This study aimd to investigate the effects of MET on the expressions of receptor for advanced glycation end products (RAGE) and high mobility group box 1 protein (HMGB1) in hyperglycemia-treated neonatal rat ventricular myocytes. Cardiocytes were prepared and cultured with high glucose and different concentrations of MET. The expressions of RAGE and HMGB1 were evaluated by Western blot analysis. The superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), lactate dehydrogenase (LDH) and creatine kinase (CK) were measured. After 12 h-incubation, MET significantly inhibited the increase of MDA, TNF-α, LDH and CK levels induced by high glucose, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations while inhibiting the decrease of SOD level. Meanwhile, RAGE and HMGB1 expression were significantly increased induced by hyperglycaemia for 24 h (P < 0.05). MET inhibited the expressions of RAGE and HMGB1 in a dose-dependent manner, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations (P < 0.05). In conclusion, our study suggested that MET could reduce hyperglycemia-induced cardiocytes injury by inhibiting the expressions of RAGE and HMGB1. PMID:24420848

  17. Factors Influencing Oxidative Imbalance in Pulmonary Fibrosis: An Immunohistochemical Study

    Directory of Open Access Journals (Sweden)

    Simona Inghilleri

    2011-01-01

    Full Text Available Background. Idiopathic Pulmonary Fibrosis (IPF is a fatal lung disease of unknown etiology characterized by interstitial fibrosis determining irreversible distortion of pulmonary architecture. Reactive oxygen species (ROS and markers of oxidative stress play a pivotal role in human IPF pathology, possibly through induction of epithelial-mesenchymal transition (EMT. Methods. We investigated by immunohistochemistry, in UIP and COP tissue samples, the expression of most relevant markers of the molecular interplay involving RAGE, oxidant/antioxidant balance regulation, tissue nitrosylation, and mediators of EMT. Results. In both UIP and COP, the degree of RAGE expression was similarly high, while SODs and i-NOS, diffusely present in COP endoalveolar plugs, were almost absent in UIP fibroblast foci. A lower degree of tissue nitrosilation was observed in UIP than in COP. Conclusions. Fibroblast lesions of UIP and of COP share a similar degree of activation of RAGE, while antioxidant enzyme expression markedly reduced in UIP.

  18. Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat.

    Science.gov (United States)

    Son, Kuk Hui; Son, Myeongjoo; Ahn, Hyosang; Oh, Seyeon; Yum, Yoonji; Choi, Chang Hu; Park, Kook Yang; Byun, Kyunghee

    2016-08-19

    Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly. PMID:27301641

  19. Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat.

    Science.gov (United States)

    Son, Kuk Hui; Son, Myeongjoo; Ahn, Hyosang; Oh, Seyeon; Yum, Yoonji; Choi, Chang Hu; Park, Kook Yang; Byun, Kyunghee

    2016-08-19

    Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly.

  20. Skin Autofluorescence Relates to Soluble Receptor for Advanced Glycation End-Products and Albuminuria in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    J. Škrha

    2013-01-01

    Full Text Available The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE in patients with diabetes. Skin autofluorescence (AF assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/ and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P<0.0001. Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r=0.37, P<0.02 and r=0.60, P<0.0001, but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R2=0.38. Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established.

  1. Skin autofluorescence relates to soluble receptor for advanced glycation end-products and albuminuria in diabetes mellitus.

    Science.gov (United States)

    Skrha, J; Soupal, J; Loni Ekali, G; Prázný, M; Kalousová, M; Kvasnička, J; Landová, L; Zima, T; Skrha, J

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P < 0.0001). Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r = 0.37, P < 0.02 and r = 0.60, P < 0.0001), but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R (2) = 0.38). Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established.

  2. Skin autofluorescence relates to soluble receptor for advanced glycation end-products and albuminuria in diabetes mellitus.

    Science.gov (United States)

    Skrha, J; Soupal, J; Loni Ekali, G; Prázný, M; Kalousová, M; Kvasnička, J; Landová, L; Zima, T; Skrha, J

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P < 0.0001). Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r = 0.37, P < 0.02 and r = 0.60, P < 0.0001), but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R (2) = 0.38). Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established. PMID:23671885

  3. Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

    Science.gov (United States)

    Leung, Christopher; Herath, Chandana B; Jia, Zhiyuan; Andrikopoulos, Sof; Brown, Bronwyn E; Davies, Michael J; Rivera, Leni R; Furness, John B; Forbes, Josephine M; Angus, Peter W

    2016-01-01

    AIM To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. PMID:27672297

  4. Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

    Science.gov (United States)

    Leung, Christopher; Herath, Chandana B; Jia, Zhiyuan; Andrikopoulos, Sof; Brown, Bronwyn E; Davies, Michael J; Rivera, Leni R; Furness, John B; Forbes, Josephine M; Angus, Peter W

    2016-01-01

    AIM To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.

  5. Skin Autofluorescence Relates to Soluble Receptor for Advanced Glycation End-Products and Albuminuria in Diabetes Mellitus

    OpenAIRE

    Šoupal, J.; G. Loni Ekali; Prázný, M.; Kalousová, M; Kvasnička, J.; L. Landová; Zima, T.; Škrha, J.

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.3...

  6. Targeted reduction of advanced glycation improves renal function in obesity

    DEFF Research Database (Denmark)

    Harcourt, Brooke E; Sourris, Karly C; Coughlan, Melinda T;

    2011-01-01

    if treatments that lower tissue AGE burden in patients and mice would improve obesity-related renal dysfunction. Overweight and obese individuals (body mass index (BMI) 26-39¿kg/m(2)) were recruited to a randomized, crossover clinical trial involving 2 weeks each on a low- and a high-AGE-containing diet. Renal......-lowering pharmaceutical, alagebrium, and mice in which the receptor for AGE (RAGE) was deleted. Obesity, resulting from a diet high in both fat and AGE, caused renal impairment; however, treatment of the RAGE knockout mice with alagebrium improved urinary albumin excretion, creatinine clearance, the inflammatory profile...

  7. Modélisation de la morphodynamique fluviale pour la recherche des relations habitat/faune aquatique

    Directory of Open Access Journals (Sweden)

    LE COARER Y.

    1995-04-01

    Full Text Available Un matériel de topographie électronique et des méthodes adaptées nous procurent rapidité, précision et souplesse dans le repérage spatial des éléments morphodynamiques et biologiques. Le traitement informatique des données fait appel à des techniques de repérage curviligne d'interpolation et de maillage. La structure numérique et topologique de cet outil de recherche offre de nombreuses possibilités de calculs et permet des visualisations conviviales des résultats.

  8. “Entre a cólera e o ódio”: justiça popular e assassinatos no Sudoeste do Paraná (1920-1930 - 10.4025/dialogos.v13i2.414 “Between rage and hatred”: street justice and murders in southwestern Paraná (1920-1930 - doi: 10.4025/dialogos.v13i2.414 “Entre la cólera y el odio”: justicia popular y asesinatos en el sureste del estado de Paraná (1920-1930

    Directory of Open Access Journals (Sweden)

    Aruanã Antônio dos Passos

    2010-08-01

    Full Text Available O artigo discute a relação entre a justiça e a violência na Região Sudoeste do Paraná nos anos anteriores à “efetiva” colonização da região (1920-1930. Buscamos compreender as relações estabelecidas em um sistema punitivo-repressivo (aparelho judiciário que conviveu com a violência popular, bem como a forma e as condições dessas relações. Para tanto, a análise do processo contra um habitante da região e seu filho transcorrido em 1920 na Comarca de Clevelândia é capaz de demonstrar as dificuldades que o aparelho judiciário encontrou diante da violência no Interior do Paraná, onde a justiça e a violência mantinham uma relação ambivalente.The article discusses the relationship between justice and violence in the southwestern region of Paraná in the years prior to the “effective” colonization of the region (1920-1930. We sought to comprehend how, under what conditions and which relationships were established by a punitive-repressive system (the judiciary apparatus that dealt with street justice. To that end, an analysis of the 1920 case against an inhabitant of the region and his son in Clevelândia County demonstrates the difficulties the judiciary apparatus faced against violence in the Paraná countryside, where justice and violence had an ambiguous relationship.El artículo discute la relación entre la justicia y la violencia en el sureste del Estado de Paraná (Brasil durante los años anteriores a la “efectiva” colonización de la región (1920-1930. Buscamos comprender de qué forma y cuáles fueron las condiciones y relaciones que se establecieron entre un sistema punitivo/represivo (aparato judicial y la violencia popular. Para ello, el análisis del proceso judicial contra un habitante y su hijo, ocurrido en la comarca de Clevelândia en 1920, permite demostrar las dificultades con las que tropezó el aparato judicial frente a la violencia en el interior del Estado de Paraná, donde justicia y violencia mantenían una relación ambivalente.

  9. A Delinquent Discipline: The Rise and Fall of Criminology

    Science.gov (United States)

    Adams, Mike S.

    2009-01-01

    What is the cause of crime? One can find answers in many places: in Genesis, in the plays of Sophocles and Shakespeare, in Dostoyevsky's "Crime and Punishment" and "Brothers Karamazov." The many answers include impiety, appetite, rage, and even the lure of transgression itself. For many, religious and poetic insights still offer the most…

  10. Intrapsychic dynamics, behavioral manifestations, and related interventions with youthful fire setters.

    Science.gov (United States)

    Williams, Dian L; Clements, Paul T

    2007-01-01

    Fire setting in youth has often been overlooked and misunderstood as a coping skill for expressing rage. The act of deliberate fire setting, if uninterrupted, may continue throughout an individual's lifetime. Forensic examiners, mental health care providers, and criminal justice professionals can help guide referral and treatment through better understanding of behaviors and intrapsychic dynamics.

  11. The First Amendment and the Web: The Internet Porn Panic and Restricting Indecency in Cyberspace.

    Science.gov (United States)

    Mullin, Dorothy Imrich

    In the wake of the Communications Decency Act of 1996, discussions have raged both online and in the press about free speech, online pornography, and the protection of children. This paper discusses the legal and social science issues surrounding content regulation of the World Wide Web and the Internet as a whole, with an emphasis on the…

  12. An overview of the Los Alamos Crestone Project : uses for astrophysical problems

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, R. P. (Robert P.); Gittings, M. L. (Michael L.); Gisler, Galen R.; Coker, R. F. (Robert F.); New, K. C. (Kimberly C.); Hueckstaedt, R. M. (Robert M.)

    2004-01-01

    The Los Alamos Crestone Project is part of the Department of Energy's (DoE) Advanced Simulation and Computing (ASC) program. The main goal of this project is to investigate the use of continuous adaptive mesh refinement (CAMR) techniques for application to problems of interest to the Laboratory. An overview of the astrophysical simulations performed with the SAGE/RAGE codes will be shown here, including asteroid impacts in the deep-ocean, asteroid impacts on the continental shelf (e.g. - Chicxulub - the dinosaur killer), calculations of massive black holes at the galactic center, and calculations of supernova explosions. Examples of these simulations will be shown. We have shown that the SAGE and RAGE codes of the Crestone Project have been very successful products of the DoE's Advanced Simulation and Computing program. It is clear to those performing massively-parallel computations, that the use of thousands of processors in parallel is fundamentally changing the way we think about computer simulations. The Crestone Project codes are fully utilizing each new ASC supercomputer as they become available. The SAGE and RAGE codes are sophisticated Continuous Adaptive Mesh Refinement hydrodynamics codes for large parallel simulations. SAGE and RAGE are becoming useful tools for astrophysical applications. Further research is starting in a wider variety of areas, including cosmological studies with Mike Norman's group at UCSD.

  13. How Should the Financial Crisis Change How We Teach Economics?

    Science.gov (United States)

    Shiller, Robert J.

    2010-01-01

    Student dissatisfaction with teaching of economics--particularly with macroeconomics--during the current financial crisis mirrors dissatisfaction that was expressed during the last big crisis, the Great Depression. Then and now, a good number of students have felt that their lectures bear little relation to the economic crisis raging outside the…

  14. Between green and grey

    NARCIS (Netherlands)

    Jeanet Kullberg

    2016-01-01

    Taking cuttings is cool. Growing vegetables is all the rage. Green oases can now be found scattered throughout Dutch towns and cities: community gardens and roof gardens where residents can go to relax and enjoy themselves, improve the appearance of their neighbourhood and meet their fellow resident

  15. Racist-Sexist-Hate Speech on College Campuses: Free Speech v. Equal Protection.

    Science.gov (United States)

    Jahn, Karon L.

    On college campuses today, the debate rages over whether self-restraint and tolerance for nonconformity is overriding a need to protect certain individuals and groups from objectionable speech. Some administrators, students, and alumni wish to prevent "bad speech" in the form of expressions of racism, sexism, and the like. Advocates for limiting…

  16. The influence of extreme traumatization on body, mind and social relations

    DEFF Research Database (Denmark)

    Rosenbaum, Bent; Varvin, Sverre

    2007-01-01

    be given to the destruction of the ability to regulate negative emotions (extreme fear, distress, anguish, anger, rage, shame) in relation to others and activate internal good and empathic object relations. Destruction of the capacity for symbolization of traumatic experience may threaten the mind...

  17. The Effects of Disturbed Adolescents on Their Teachers.

    Science.gov (United States)

    Bloom, Robert B.

    1983-01-01

    The author first reviews emotional hazards and conflicts of teachers of the emotionally disturbed, then describes, with frequent anecdotes, nine examples of the "interpersonal underworld of special education" such as helplessness rage, anger at teammates, and implementation despair. Suggests recognizing feelings to disengage from unproductive…

  18. Follow the Leaders? An Analysis of Convergence and Innovation of Faculty Recruiting Practices in US Business Schools

    Science.gov (United States)

    Finch, David; Deephouse, David L.; O'Reilly, Norm; Massie, Tyler; Hillenbrand, Carola

    2016-01-01

    The debate associated with the qualifications of business school faculty has raged since the 1959 release of the Gordon-Howell and Pierson reports, which encouraged business schools in the USA to enhance their legitimacy by increasing their faculties' doctoral qualifications and scholarly rigor. Today, the legitimacy of specific faculty…

  19. Putting Big Data to Work: Community Colleges Use Detailed Reports to Design Smarter Workforce Training and Education Programs

    Science.gov (United States)

    Woods, Bob

    2013-01-01

    In this article, Bob Woods reports that "Big data" is all the rage on college campuses, and it makes sense that administrators would use what they know to boost student outcomes. Woods points out that community colleges around the country are using the data: (1) to guide the systematic expansion of its curriculum, providing targeted…

  20. Freedom, Revolt and "Citizenship": Three Pillars of Identity for Youngsters Living on the Streets of Rio de Janeiro

    Science.gov (United States)

    Butler, Udi Mandel

    2009-01-01

    This article investigates the experiences, identities and aspirations of children and adolescents living on the streets of Rio de Janeiro, formed as they are around the conditions of exclusion, violence and discrimination. Significant here are experiences of "revolta"--revolt or rage--the aspiration for freedom through life on the street and the…

  1. EST Table: CK511111 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available CK511111 rswdd0_007120.y1 10/09/29 99 %/222 aa ref|NP_001106747.2| sex-specific sto...rage-protein 1 precursor [Bombyx mori] 10/08/30 37 %/178 aa FBpp0240255|DwilGK11112-PA 10/08/28 n.h 10/09/10

  2. Green Science: Wildfires

    Science.gov (United States)

    Palliser, Janna

    2012-01-01

    Every summer, fires rage in different areas of the western United States. They are often massive, out of control, and extremely destructive. How do these fires begin and how are they controlled? What are the overall impacts of a wildfire? Are there any benefits of a wildfire? These questions will be addressed in this article. (Contains 3 online…

  3. Neurofeedback, Affect Regulation and Attachment: A Case Study and Analysis of Anti-Social Personality

    Science.gov (United States)

    Fisher, Sebern F.

    2007-01-01

    This case study examines the effects of neurofeedback (EEG biofeedback) training on affect regulation in a fifty-five year-old man with a history marked by fear, rage, alcoholism, chronic unemployment and multiple failed treatments. He had been diagnosed with ADHD and attachment disorder and met criteria for anti-social personality disorder. The…

  4. Access and Quality in Education in Resettlement Schools: The Case Study of Zvivingwi Secondary School in Gutu District, Masvingo Province in Zimbabwe

    Science.gov (United States)

    Jenjekwa, Vincent

    2013-01-01

    In Zimbabwe, the discourse on access and quality in education has been a raging one since the colonial days of bottlenecks and outright discrimination against black Zimbabweans in education. The doors to education were declared open to all at independence in 1980 with the new Zimbabwe government's enunciated policy of education for all. It is an…

  5. Hard Facts and Soft Skills

    Science.gov (United States)

    Terego, Alex

    2009-01-01

    The argument now raging in academic circles pits those who espouse teaching 21st century skills against those who believe that schools should be teaching explicit and well-sequenced content. This debate has largely been framed as an either-or proposition. In this author's view, portraying this debate as one between two mutually exclusive sides…

  6. A Dynamic Cascade Model of the Development of Substance-Use Onset

    Science.gov (United States)

    Dodge, Kenneth A.; Malone, Patrick S.; Lansford, Jennifer E.; Miller, Shari; Pettit, Gregory S.; Bates, John E.

    2009-01-01

    Although the onset of illicit substance use during adolescence can hit parents abruptly like a raging flood, its origins likely start as a trickle in early childhood. Understanding antecedent factors and how they grow into a stream that leads to adolescent drug use is important for theories of social development as well as policy formulations to…

  7. Dairy Sector Profit Squeeze

    Institute of Scientific and Technical Information of China (English)

    WANG PEI

    2006-01-01

    @@ Like any other industries in China,the potential in the dairy industry is huge but competition is tough,The big players such as Mengniu and Yili are happy to stay engaged in a price war that has raged for the last year,seemingly not affected by rising raw material prices.

  8. Exploring Dreamspace through Video Art with At-Risk Youth

    Science.gov (United States)

    Ehinger, Jon

    2009-01-01

    This thesis is an art-based research video demonstration of an alternate medium for art therapy. It postulates the value and validity of media arts as a therapeutic modality by way of adopting the major motion picture green screening technique for therapy with an at-risk youth population. Four male participants, raging from 16 to 19 years of age,…

  9. Teaching the Arts of Public Theology

    Science.gov (United States)

    Casey, Shaun

    2006-01-01

    While intense discussions are raging over the definition and status of public theology, within graduate theological education relatively little attention is being paid to the teaching of the practices of public theology. This article explores one venue in graduate theological education that attempts to equip seminary and divinity school students…

  10. United Nations Day (联合国成立纪念日)

    Institute of Scientific and Technical Information of China (English)

    胡亚萍

    2002-01-01

    As World War Ⅱ raged on with no end in sight, the United Nations was conceived as a way to help prevent future world wars. As early as 1943, government officials from the United States, Great Britain, and the Soviet Union agreed to meet to discuss plans for an international peacekeeping organization.

  11. "If I Knew Where the Enemy, or Even Germany Was, We Could Have Fired in that Direction": Bion's Experience of War

    Science.gov (United States)

    Likierman, Meira

    2012-01-01

    During the First World War, Bion fought in three major battles over a period of two years. He left ample writings both honest and soul searching. Travelling to The Front under raging pressure from his father, he enlisted in a state of mind, which fluctuated wildly between wanting to be a "hero" and sudden fears that made him join the Tank Corps…

  12. Massive and Open

    Science.gov (United States)

    Fasimpaur, Karen

    2013-01-01

    MOOCs--massive open online courses--are all the rage these days, with hundreds of thousands of participants signing up and investors plunking down millions to get a piece of the pie. Why is there so much excitement about this new disruptive form of online learning, and how does this model apply to professional learning for teachers? Traditional…

  13. "Their Experience Is the Immigrant Experience": Ellis Island, Documentary Film, and Rhetorically Reversible Whiteness

    Science.gov (United States)

    Irwin, Meryl J.

    2013-01-01

    Political advocates on the ideological right have long taken seriously what their counterparts on the left have not: white racialized affect. As left activists and scholars have alternately lamented and raged over the steady creep of the "middle" to the "right," they have documented in detail the outcomes of whites' refusal to engage in "genuine"…

  14. Advocacy in Action: Annual 2006 DPI/NGO Conference at the United Nations

    Science.gov (United States)

    Brown, Nancy

    2007-01-01

    The Association for Childhood Education International (ACEI) was again represented at the annual 2006 DPI/NGO conference, along with 1,600 participants from around the world. The mood this year was somber and quite serious, possibly in response to the uncertainty created by the Middle East crisis that was raging while the conference was taking…

  15. Spatial atmospheric ALD of functional layers for CIGS Solar Cells

    NARCIS (Netherlands)

    Illiberi, A.; Frijters, C.; Balder, J.E.; Poodt, P.W.G.; Roozeboom, F.

    2015-01-01

    Spatial Atmosperic Atomic Layer Depositon combines the advantages of temporal ALD, i.e. excellent control of film composition and uniformity over large area substrates, with high growth rages (up tot nm/s). In this paper we present a short overview of our research acctivity carried out on S-ALD of f

  16. Academic Superheroes? A Critical Analysis of Academic Job Descriptions

    Science.gov (United States)

    Pitt, Rachael; Mewburn, Inger

    2016-01-01

    For over a decade, debate has raged about the nature and purpose of the PhD, including its role as preparation for working in academia. Academic work has changed a great deal in the last 60 years, yet our doctoral curriculum has remained relatively static. While there is increasing interest in matching PhD programmes to "real world"…

  17. Misophonia: physiological investigations and case descriptions

    NARCIS (Netherlands)

    M. Edelstein; D. Brang; R. Rouw; V.S. Ramachandran

    2013-01-01

    Misophonia is a relatively unexplored chronic condition in which a person experiences autonomic arousal (analogous to an involuntary "fight-or-flight" response) to certain innocuous or repetitive sounds such as chewing, pen clicking, and lip smacking. Misophonics report anxiety, panic, and rage when

  18. Girl's Schooling in War-Torn Somalia

    Science.gov (United States)

    Moyi, Peter

    2012-01-01

    A civil war has raged in Somalia since 1991. The civil war was the final blow to an already collapsed education system. Somalia has received little research and policy attention yet children, especially girls, are very vulnerable during times of conflict. The different gender roles, activities, and status in society create gender differentiated…

  19. Fiddling while the ice melts? How organizational scholars can take a more active role in the climate change debate

    NARCIS (Netherlands)

    S.M. Ansari (Shahzad); B. Gray (Barbara); F.H. Wijen (Frank)

    2011-01-01

    textabstractThe debate over anthropogenic climate change or the idea that human activities are altering the physical climate of the planet continues to rage amid seemingly irreconcilable differences, both within the developed world and between developed and less developed countries. With high uncert

  20. Draadloze ondergang van een bedrijf

    NARCIS (Netherlands)

    Degen, A.J.G.

    2003-01-01

    Draadloze netwerken zijn meer dan een rage. Ze bieden netwerktoegang onafhankelijk van kabelaansluitingen, wat bijvoorbeeld zorgt voor flexibiliteit qua werkplekken. Bedrijven kunnen zodoende heel wat besparen op de aanlegkosten voor hun intranet en interne verhuiskosten. Maar hoe zit het met de bev

  1. Advanced glycation end products (AGEs) promote melanogenesis through receptor for AGEs.

    Science.gov (United States)

    Lee, Eun Jung; Kim, Ji Young; Oh, Sang Ho

    2016-01-01

    Accumulation of advanced glycation end products (AGEs) is linked with development or aggravation of many degenerative processes or disorders, including aging and atherosclerosis. AGEs production in skin cells is known to promote stiffness and loss of elasticity through their buildup in connective tissue. However, the impact of AGEs has yet to be fully explored in melanocytes. In this study, we confirmed the existence of receptor for AGE (RAGE) in melanocytes in western blot and immunofluorescence along with increased melanin production in ex vivo skin organ culture and in vitro melanocyte culture following AGEs treatment. Cyclic AMP response element-binding protein (CREB) and extracellular signal-regulated kinases (ERK) 1/2 are considered as key regulatory proteins in AGEs-induced melanogenesis. In addition, blockage experiment using anti-RAGE blocking antibody has indicated that RAGE plays a pivotal role in AGE-mediated melanogenesis. Therefore, it is apparent that AGEs, known markers of aging, promote melanogenesis via RAGE. In addition, AGEs could be implicated in pigmentation associated with photoaging according to the results of increased secretion of AGEs from keratinocytes following UV irradiation. AGE-mediated melanogenesis may thus hold promise as a novel mean of altering skin pigmentation. PMID:27293210

  2. Multiculturalism Swedish Style: Shifts and Sediments in Educational Policies and Textbooks

    Science.gov (United States)

    Gruber, Sabine; Rabo, Annika

    2014-01-01

    In the almost two decades that have passed since the Swedish parliament declared that Sweden is a multicultural society, debates about immigrants, about multiculturalism and about different ways of being a citizen have raged. So far there has been no stepping away from the declaration. In the rhetorical arena multiculturalism is still a word with…

  3. Negative Experiences as Learning Trigger: A Play Experience Empirical Research on a Game for Social Change Case Study

    Science.gov (United States)

    Mariani, Ilaria; Gandolfi, Enrico

    2016-01-01

    This study shows the results gathered from 141 subjects playing the persuasive urban game "A Hostile World" via a post-game-experience quantitative questionnaire. The aim is to problematize and deepen the role of negative emotions (e.g., frustration, rage)--explicitly fostered by "A Hostile World" to increase empathy toward…

  4. 阿里斯蒂德黯然离去

    Institute of Scientific and Technical Information of China (English)

    朱晓超; sipa

    2005-01-01

    February 28 2004, dead bodies have been left in front of the General Hospital all over Haiti as chaos,looting and violence rage in Port Au Prince, Haiti. The next day, President Jean-Bertrand Aristide left Haiti and exiled to Dominica seeking political asylum.

  5. Build Your Own Board: Brightboards Offer a Cost-Effective Alternative to Interactive Whiteboards

    Science.gov (United States)

    Vallis, Keith; Williamson, Peter

    2009-01-01

    Interactive whiteboards are all the rage in classrooms across the world these days, and for good reason. Like most technology, they hold students' attention much better than a traditional lecture-and-blackboard lesson ever could. They also solve the problem of having only one classroom computer for 30 students by projecting the screen at the front…

  6. HIV-1 Tat Regulates Occludin and Aβ Transfer Receptor Expression in Brain Endothelial Cells via Rho/ROCK Signaling Pathway

    Science.gov (United States)

    Chen, Yanlan; Jiang, Wenlin; Wu, Xianghong; Ye, Biao; Zhou, Xiaoting

    2016-01-01

    HIV-1 transactivator protein (Tat) has been shown to play an important role in HIV-associated neurocognitive disorders. The aim of the present study was to evaluate the relationship between occludin and amyloid-beta (Aβ) transfer receptors in human cerebral microvascular endothelial cells (hCMEC/D3) in the context of HIV-1-related pathology. The protein expressions of occludin, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP1) in hCMEC/D3 cells were examined using western blotting and immunofluorescent staining. The mRNA levels of occludin, RAGE, and LRP1 were measured using quantitative real-time polymerase chain reaction. HIV-1 Tat at 1 µg/mL and the Rho inhibitor hydroxyfasudil (HF) at 30 µmol/L, with 24 h exposure, had no significant effect on hCMEC/D3 cell viability. Treatment with HIV-1 Tat protein decreased mRNA and protein levels of occludin and LRP1 and upregulated the expression of RAGE; however, these effects were attenuated by HF. These data suggest that the Rho/ROCK signaling pathway is involved in HIV-1 Tat-mediated changes in occludin, RAGE, and LRP1 in hCMEC/D3 cells. HF may have a beneficial influence by protecting the integrity of the blood-brain barrier and the expression of Aβ transfer receptors.

  7. Peace Education in Societies Involved in Intractable Conflicts: Direct and Indirect Models

    Science.gov (United States)

    Bar-Tal, Daniel; Rosen, Yigal

    2009-01-01

    The present article deals with the crucial question: Can peace education facilitate change in the sociopsychological infrastructure that feeds continued intractable conflict and then how the change can be carried? Intractable conflicts still rage in various parts of the globe, and they not only cause local misery and suffering but also threaten…

  8. USA Stratified Monopoly: A Simulation Game about Social Class Stratification

    Science.gov (United States)

    Fisher, Edith M.

    2008-01-01

    Effectively teaching college students about social class stratification is a difficult challenge. Explanations for this difficulty tend to focus on the students who often react with resistance, paralysis, or rage. Sociologists have been using games and simulations as alternative methods for several decades to teach about these sensitive subjects.…

  9. Dublini festival II : Külalised. Muust / Jaak Rähesoo

    Index Scriptorium Estoniae

    Rähesoo, Jaak, 1941-

    2002-01-01

    Ka Kopenhaageni Betty Nanseni Teatri näidatud Robert Wilsoni tehtud Georg Büchneri "Woyzecki" tõlgenduse ning noore inglise trupi näidatud Edward Halli lavastatud William Shakespeare "Rose Rage" ("Henry VI") etenduse lavakujundusest ja -kostüümidest.

  10. Advanced glycation end-product expression is upregulated in the gastrointestinal tract of type 2 diabetic rats

    DEFF Research Database (Denmark)

    Chen, Peng-Min; Gregersen, Hans; Zhao, Jingbo

    2015-01-01

    and five micron sections were cut. The layer thickness was measured in Hematoxylin and Eosin-stained slides. AGE [N epsilon-(carboxymethyl) lysine and N epsilon-(carboxyethyl)lysine] and RAGE were detected by immunohistochemistry staining and image analysis was done using Sigmascan Pro 4.0 image analysis...

  11. Complete Genome Sequence of a Rabies Virus Strain Isolated from a Brown Bear (Ursus arctos) in Primorsky Krai, Russia (November 2014)

    Science.gov (United States)

    Deviatkin, Andrei A.; Ananiev, Vasily Y.; Dedkov, Vladimir G.; Shipulin, German A.; Sokol, Nataliya N.; Dombrovskaya, Irina E.; Galkina, Irina V.; Shmelev, Mikhail E.; Gorelikov, Vladimir N.; Kozhan, Valentina N.; Prosyannikova, Marina N.; Aramilev, Sergei V.; Fomenko, Pavel V.

    2016-01-01

    We report here the complete genome sequence (GenBank KP997032) of rabies virus strain RABV/Ursus arctos/Russia/Primorye/PO-01/2014, isolated in November 2014 from a brown bear (Ursus arctos) that attacked a person in Primorsky Krai (Russian Federation). This strain was clustered into the Eurasian genetic subgroup of genotype 1 (street rage). PMID:27389270

  12. A Case Study of a "Collaborative Organizational Innovation" Intervention, Combining Action Research and Design-Thinking Methodologies

    Science.gov (United States)

    Wetzler, Jeffrey Richard

    2013-01-01

    For decades, debates have raged about performance management in education. While it is essential to understand the degree of student learning and the nature of teacher impact in education systems, when attempts at managing outcomes go wrong, the consequences can be problematic. National Education Organization (a pseudonym for the organization…

  13. Landau-Zener transition in quadratic-nonlinear two-state systems

    OpenAIRE

    Ishkhanyan, A. M.

    2009-01-01

    A comprehensive theory of the Landau-Zener transition in quadratic nonlinear two-state systems is developed. A compact analytic formula involving elementary functions only is derived for the final transition probability. The formula provides a highly accurate approximation for the whole rage of the variation of the Landau-Zener parameter.

  14. Nuclear Power on Energy Agenda

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The big debate on whether or not to use nuclear power as an energy option has raged among countries like the U.S., Britain, and Germany for decades, with not even the advent and threat of global warming forcing a conclusion. China, however, has always stressed energy diversity and been determined to develop and use this alternative energy source.

  15. Oriana Fallaci viha ja raev / Urmas Kiil

    Index Scriptorium Estoniae

    Kiil, Urmas

    2006-01-01

    Ajakirjanik ja kirjanik Oriana Fallaci, kelle artikkel New Yorgis toimunud terrorirünnaku muljetest avaldati 29. sept. 2001. a. Itaalia juhtivas ajalehes Corriere della sera, avaldas peagi raamatu "Raev ja uhkus" (The Rage and Pride). Raamatus mõistab ta islamimaailma mööndusteta tervikuna hukka

  16. Religious Dialogue, World Peace and Social Harmony

    Institute of Scientific and Technical Information of China (English)

    YE XIAOWEN

    2007-01-01

    @@ Ⅰ. The World Peace Requires Religious Dialogues Peace, development and cooperation are the mainstay of the times in the present world, but there are unseen tricky and atrocious flows. The increasing opposition and conflicts are raging between different countries, nations and religions, which are challenging the wisdom and civilization of mankind.

  17. Experimental and clinical studies of fast three-dimensional MR imaging of the heart

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Shuhei [Okayama Univ. (Japan). School of Medicine

    1999-07-01

    MRI has been utilized since its inception to study the anatomy and physiology of the heart. However, the sensitivity of MRI to motion has always posed a major challenge in imaging this organ. The purpose of this study was to develop a 3D MP-RAGE technique for the heart, and to apply it clinically. In the experimental study, data acquisition timing was discussed by normal volunteers. Changes in magnetization recovery time affected imaging contrast very little in the phantom study. Fourteen adults and 21 children were examined. In the adults, MP-RAGE images were rated as high in quality in the visual estimation. In the quantitative estimation, the images provided almost the same anatomical information as those of cine MRI. In the children, MP-RAGE was useful for cases of partial anomalous pulmonary venous drainage, particularly in the evaluation of abnormal pulmonary veins. The 3D MP-RAGE technique was useful in imaging the heart because it was possible to obtain continuous views in the same cardiac cycle and to reconstruct views from any direction after the examination. (author)

  18. Facing Our Future: Children in the Aftermath of Immigration Enforcement

    Science.gov (United States)

    Chaudry, Ajay; Capps, Randy; Pedroza, Juan Manuel; Castaneda, Rosa Maria; Santos, Robert; Scott, Molly M.

    2010-01-01

    The United States is engaged in an intense debate about immigration policy, particularly with regard to unauthorized immigrants. Debates rage about the economic contributions of immigrants to the U.S. economy, job competition, tax payments and fiscal costs, and the integration of immigrants in communities and the larger society. Largely absent…

  19. "I Asked My Parents Why a Wall Was so Important": Teaching about the GDR and Post-Reunification Germany

    Science.gov (United States)

    Streitwieser, Bernhard; Lys, Franziska

    2008-01-01

    Fifteen years after the "peaceful revolutions" brought about the collapse of communism and the reunification of East and West Germany, a heated debate rages over the legacy of communism and the continuing impact of 1989. This paper describes a new course that explores the contentious issues in this debate through the innovative use of the course…

  20. Massive Open Online Librarianship: Emerging Practices in Response to MOOCs

    Science.gov (United States)

    Mune, Christina

    2015-01-01

    Massive Open Online Courses, or MOOCs, have recently emerged as a disruptive pedagogy gaining rapid momentum in higher education. In some states, proposed legislations would accredit MOOCs to provide college-credit courses in the name of cost saving, efficiency and access. While debates rage regarding the place of MOOCs in higher education, some…

  1. Disabling Emotion in Young Children with Particular Reference to Depression and Suicide: An Overview of Current Research. Unit for Child Studies Selected Papers Number 12.

    Science.gov (United States)

    Phillips, Shelley

    A review of the literature and a survey of texts show a remarkable absence of concern and reference to depression and suicidal behavior in young children. The meaning of death, the depressive and suicidal consequences of the agony of aloneness, and the fear of parental hostility, rage and abandonment are elements of early and middle childhood…

  2. A Tale of Two Continents

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Eurasian countries unite to seek a way out of the global financial crisis How should the world cope with the raging financial storm? That question topped the agenda of the Seventh Asia-Europe Meeting(ASEM), held on October 24-25 in Beijing.At the biennial summit, leaders from 45

  3. The effect of valsartan on the expression of the receptor for advanced glycation end products in human glomerular mesangial cells%缬沙坦对人肾小球系膜细胞糖基化终产物受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    钟林娜; 黄国良; 冯敏; 张莹

    2011-01-01

    目的:本实验探讨缬沙坦对糖基化终产物诱导的人肾小球系膜细胞氧化应激水平及糖基化终产物受体(RAGE)表达的影响.方法:体外常规培养人肾小球系膜细胞,运用糖基化修饰的牛血清白蛋白(AGE-BSA)和缬沙坦进行干预,流式细胞术检测细胞内活性氧(ROS),RT-PCR法检测NADPH氧化酶的亚基p47phox的mRNA表达,RT-PCR和细胞免疫化学法检测RAGE的表达量.结果:缬沙坦干预组人肾小球系膜细胞的ROS产生量、NADPH氧化酶的亚基p47phox mRNA表达量、RAGE表达量均低于AGE-BSA组(P<0.05),且缬沙坦的抑制作用呈浓度和时间依赖性.结论:缬沙坦可能通过降低氧化应激水平来抑制RAGE的表达.%Objective: To elucidate the effect of valsartan on human glomerular mesangial cells oxidative stress and the expression of the receptor for advanced glycation end products (RAGE) induced by the advanced glycation end-products (AGEs). Methods: Human glomerular mesangial cells were treated with advanced glycation end-product-bovine serum albumin (AGE-BSA) in the presence of valsartan. The reactive oxygen species( ROS) in cells were measured by Flow cytomeuy, and the mRNA of p47 phox, which was the primary subunits of NADPH oxi-dase, was detected by semi-quantitative reberse transcription polymerase chain reaction (RT-PCR). The mRNA of RAGE was detected by RT-PCR and the RAGE protein was assayed by immunocytochemistry. Results: The product of ROS, and the expression of p47 phox and RAGE in mesangial cells , which were treated with AGE-BSA in the presence of valsartan, were down-regulated compared with the groups treated with AGE-BSA(P < 0.05). Valsartan dose-dependently and ume-dependently inhibited the AGE-elicited overexpression of RAGE, ROS and p47phox in mesangial cells. Conclusion: Valsartan could inhibit RAGE expression through downregularion of oxidative stress.

  4. 糖基化终末产物及其受体在胃肠道中的分布%Distribution of advanced glycation end products and their receptor in the gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    陈朋民; 赵静波; Hans Gregersen

    2012-01-01

    目的:研究糖基化终末产物(advanced glycation end products,AGE)及其受体(receptor for advanced glycation end products,RAGE)在胃肠道中的分布,为进一步探索其在慢性糖尿病胃肠功能紊乱中的作用奠定基础.方法:分别对成年Wistar大鼠食管、胃、十二指肠、空肠、回肠、结肠及直肠组织进行AGE及RAGE免疫组织化学染色.结果:(1)食管:AGE及RAGE主要分布在横纹肌的肌细胞及黏膜的鳞状上皮细胞;(2)胃:AGE在壁细胞为强阳性.RAGE在主细胞、肥大细胞、神经细胞为强阳性,在壁细胞为中等强度阳性,在表面黏液细胞为弱阳性;(3)小肠:AGE及RAGE在绒毛及固有层上皮细胞为阳性或强阳性.RAGE在肠道的神经细胞亦为强阳性;(4)结肠及直肠:AGE及RAGE在黏膜上皮细胞为弱阳性,RAGE在神经细胞为强阳性.结论:AGE及RAGE广泛分布于肠道上皮细胞及食管的横纹肌细胞,AGE亦分布于胃的壁细胞,RAGE亦分布于胃的壁细胞、主细胞、表面黏液细胞、肥大细胞及胃肠道的神经细胞.%AIM: To investigate the distribution of advanced glycation end products (AGEs) and their receptor (RAGE) in the gastrointestinal (GI) tract to provide a basis for further study of the association between AGE/RAGE and diabetic GI dysfunction. METHODS: The distribution of AGEs [N epsilon-(c arboxymethyl) lysine and N epsilon-(carboxyethyl) lysine] and RAGE were detected in the esopha-geal, gastric, duodenal, jejunal, ileal, colonic and rectal tissues of normal adult Wistar rats using immunohistochemistry. RESULTS: In the esophagus, AGEs and RAGE were mainly distributed in striated muscle cells and squamous epithelial cells. In the stomach, AGEs were mainly distributed in parietal cells, and RAGE was strongly expressed in chief cells, mast cells and neurons in ganglia, moderately in parietal cells, and mildly in surface mucous cells. In the intestine, colon and rectum, AGEs and RAGE were distributed in mucosal

  5. Surfactant-derived proteins as markers of alveolar membrane damage in heart failure.

    Directory of Open Access Journals (Sweden)

    Paola Gargiulo

    Full Text Available In heart failure (HF alveolar-capillary membrane is abnormal. Surfactant-derived proteins (SPs and plasma receptor for advanced-glycation-end-products (RAGE have been proposed as lung damage markers.Eighty-nine chronic HF and 17 healthy subjects were evaluated by echocardiography, blood parameters, carbon monoxide lung diffusion (DLCO and cardiopulmonary exercise test. We measured immature SP-B, mature SP-B, SP-A, SP-D and RAGE plasma levels.Immature SP-B (arbitrary units, mature SP-A (ng/ml and SP-D (ng/ml, but not mature SP-B (ng/ml and RAGE (pg/ml levels, were higher in HF than in controls [immature SP-B: 15.6 (13.1, 75th-25th interquartile range Vs. 11.1 (6.4, p<0.01; SP-A, 29.6 (20.1 Vs. 18.3 (13.5, p = 0.01; SP-D: 125 (90 Vs. 78 (58, p<0.01]. Immature SP-B, SP-A, SP-D and RAGE values were related to DLCO, peak oxygen consumption, ventilatory efficiency, and brain natriuretic peptide (BNP, whereas plasma mature SP-B was not. The DLCO Vs. immature SP-B correlation was the strongest one. At multivariate analysis, RAGE was associated to age and creatinine, SP-A to DLCO and BNP, SP-D to BNP, mature SP-B to DLCO and creatinine, and immature SP-B only but strongly to DLCO.Immature SP-B is the most reliable biological marker of alveolar-capillary membrane function in HF.

  6. High-mobility group box 1 inhibits gastric ulcer healing through Toll-like receptor 4 and receptor for advanced glycation end products.

    Science.gov (United States)

    Nadatani, Yuji; Watanabe, Toshio; Tanigawa, Tetsuya; Ohkawa, Fumikazu; Takeda, Shogo; Higashimori, Akira; Sogawa, Mitsue; Yamagami, Hirokazu; Shiba, Masatsugu; Watanabe, Kenji; Tominaga, Kazunari; Fujiwara, Yasuhiro; Takeuchi, Koji; Arakawa, Tetsuo

    2013-01-01

    High-mobility group box 1 (HMGB1) was initially discovered as a nuclear protein that interacts with DNA as a chromatin-associated non-histone protein to stabilize nucleosomes and to regulate the transcription of many genes in the nucleus. Once leaked or actively secreted into the extracellular environment, HMGB1 activates inflammatory pathways by stimulating multiple receptors, including Toll-like receptor (TLR) 2, TLR4, and receptor for advanced glycation end products (RAGE), leading to tissue injury. Although HMGB1's ability to induce inflammation has been well documented, no studies have examined the role of HMGB1 in wound healing in the gastrointestinal field. The aim of this study was to evaluate the role of HMGB1 and its receptors in the healing of gastric ulcers. We also investigated which receptor among TLR2, TLR4, or RAGE mediates HMGB1's effects on ulcer healing. Gastric ulcers were induced by serosal application of acetic acid in mice, and gastric tissues were processed for further evaluation. The induction of ulcer increased the immunohistochemical staining of cytoplasmic HMGB1 and elevated serum HMGB1 levels. Ulcer size, myeloperoxidase (MPO) activity, and the expression of tumor necrosis factor α (TNFα) mRNA peaked on day 4. Intraperitoneal administration of HMGB1 delayed ulcer healing and elevated MPO activity and TNFα expression. In contrast, administration of anti-HMGB1 antibody promoted ulcer healing and reduced MPO activity and TNFα expression. TLR4 and RAGE deficiency enhanced ulcer healing and reduced the level of TNFα, whereas ulcer healing in TLR2 knockout (KO) mice was similar to that in wild-type mice. In TLR4 KO and RAGE KO mice, exogenous HMGB1 did not affect ulcer healing and TNFα expression. Thus, we showed that HMGB1 is a complicating factor in the gastric ulcer healing process, which acts through TLR4 and RAGE to induce excessive inflammatory responses.

  7. Impact of Cyanidin-3-Glucoside on Glycated LDL-Induced NADPH Oxidase Activation, Mitochondrial Dysfunction and Cell Viability in Cultured Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Xueping Xie

    2012-11-01

    Full Text Available Elevated levels of glycated low density lipoprotein (glyLDL are frequently detected in diabetic patients. Previous studies demonstrated that glyLDL increased the production of reactive oxygen species (ROS, activated NADPH oxidase (NOX and suppressed mitochondrial electron transport chain (mETC enzyme activities in vascular endothelial cells (EC. The present study examined the effects of cyanidin-3-glucoside (C3G, a type of anthocyanin abundant in dark-skinned berries, on glyLDL-induced ROS production, NOX activation and mETC enzyme activity in porcine aortic EC (PAEC. Co-treatment of C3G prevented glyLDL-induced upregulation of NOX4 and intracellular superoxide production in EC. C3G normalized glyLDL-induced inhibition on the enzyme activities of mETC Complex I and III, as well as the abundances of NADH dehydrogenase 1 in Complex I and cytochrome b in Complex III in EC. Blocking antibody for the receptor of advanced glycation end products (RAGE prevented glyLDL-induced changes in NOX and mETC enzymes. Combination of C3G and RAGE antibody did not significantly enhance glyLDL-induced inhibition of NOX or mETC enzymes. C3G reduced glyLDL-induced RAGE expression with the presence of RAGE antibody. C3G prevented prolonged incubation with the glyLDL-induced decrease in cell viability and the imbalance between key regulators for cell viability (cleaved caspase 3 and B cell Lyphoma-2 in EC. The findings suggest that RAGE plays an important role in glyLDL-induced oxidative stress in vascular EC. C3G may prevent glyLDL-induced NOX activation, the impairment of mETC enzymes and cell viability in cultured vascular EC.

  8. High-mobility group box 1 inhibits gastric ulcer healing through Toll-like receptor 4 and receptor for advanced glycation end products.

    Directory of Open Access Journals (Sweden)

    Yuji Nadatani

    Full Text Available High-mobility group box 1 (HMGB1 was initially discovered as a nuclear protein that interacts with DNA as a chromatin-associated non-histone protein to stabilize nucleosomes and to regulate the transcription of many genes in the nucleus. Once leaked or actively secreted into the extracellular environment, HMGB1 activates inflammatory pathways by stimulating multiple receptors, including Toll-like receptor (TLR 2, TLR4, and receptor for advanced glycation end products (RAGE, leading to tissue injury. Although HMGB1's ability to induce inflammation has been well documented, no studies have examined the role of HMGB1 in wound healing in the gastrointestinal field. The aim of this study was to evaluate the role of HMGB1 and its receptors in the healing of gastric ulcers. We also investigated which receptor among TLR2, TLR4, or RAGE mediates HMGB1's effects on ulcer healing. Gastric ulcers were induced by serosal application of acetic acid in mice, and gastric tissues were processed for further evaluation. The induction of ulcer increased the immunohistochemical staining of cytoplasmic HMGB1 and elevated serum HMGB1 levels. Ulcer size, myeloperoxidase (MPO activity, and the expression of tumor necrosis factor α (TNFα mRNA peaked on day 4. Intraperitoneal administration of HMGB1 delayed ulcer healing and elevated MPO activity and TNFα expression. In contrast, administration of anti-HMGB1 antibody promoted ulcer healing and reduced MPO activity and TNFα expression. TLR4 and RAGE deficiency enhanced ulcer healing and reduced the level of TNFα, whereas ulcer healing in TLR2 knockout (KO mice was similar to that in wild-type mice. In TLR4 KO and RAGE KO mice, exogenous HMGB1 did not affect ulcer healing and TNFα expression. Thus, we showed that HMGB1 is a complicating factor in the gastric ulcer healing process, which acts through TLR4 and RAGE to induce excessive inflammatory responses.

  9. HMGB1 binds to activated platelets via the receptor for advanced glycation end products and is present in platelet rich human coronary artery thrombi.

    Science.gov (United States)

    Ahrens, Ingo; Chen, Yung-Chih; Topcic, Danijal; Bode, Michael; Haenel, David; Hagemeyer, Christoph E; Seeba, Hannah; Duerschmied, Daniel; Bassler, Nicole; Jandeleit-Dahm, Karin A; Sweet, Matthew J; Agrotis, Alex; Bobik, Alex; Peter, Karlheinz

    2015-11-01

    High mobility group box 1 (HMGB1) acts as both a nuclear protein that regulates gene expression, as well as a pro-inflammatory alarmin that is released from necrotic or activated cells. Recently, HMGB1-expression in human atherosclerotic plaques was identified. Therapeutic blockade of HMGB1 reduced the development of diet-induced atherosclerosis in ApoE knockout mice. Thus, we hypothesised an interaction between HMGB1 and activated platelets. Binding of recombinant HMGB1 to platelets was assessed by flow cytometry. HMGB1 bound to thrombin-activated human platelets (MFI 2.49 vs 25.01, p=0.0079). Blood from wild-type, TLR4 and RAGE knockout mice was used to determine potential HMGB1 receptors on platelets. HMGB1 bound to platelets from wild type C57Bl6 (MFI 2.64 vs 20.3, p 0.05). RAGE expression on human platelets was detected by RT-PCR with mRNA extracted from highly purified platelets and confirmed by Western blot and immunofluorescence microscopy. Platelet activation increased RAGE surface expression (MFI 4.85 vs 6.74, p< 0.05). Expression of HMGB1 in human coronary artery thrombi was demonstrated by immunohistochemistry and revealed high expression levels. Platelets bind HMGB1 upon thrombin-induced activation. Platelet specific expression of RAGE could be detected at the mRNA and protein level and is involved in the binding of HMGB1. Furthermore, platelet activation up-regulates platelet surface expression of RAGE. HMGB1 is highly expressed in platelet-rich human coronary artery thrombi pointing towards a central role for HMGB1 in atherothrombosis, thereby suggesting the possibility of platelet targeted anti-inflammatory therapies for atherothrombosis.

  10. 可溶性晚期糖基化终末产物受体在急性呼吸窘迫综合征患者诊断及预后评估中的应用价值%Application Value of Soluble Receptor of Advanced Glycation End products in the Diagnostic and prognostic Assessment of patients With Acute Respiratory Distress Syndrome

    Institute of Scientific and Technical Information of China (English)

    胡占升

    2014-01-01

    目的:探讨可溶性晚期糖基化终末产物受体(sRAGE)在急性呼吸窘迫综合征(ARDS)患者诊断及预后预测中的价值。方法选取2012年3月-2013年3月入住辽宁医学院附属第一医院重症监护病房的 ARDS 患者60例为 ARDS 组,根据氧合指数(PaO2/ FiO2)将 ARDS 组分为轻度 ARDS 组(23例)、中度 ARDS 组(23例)及重度ARDS 组(14例),根据预后分为死亡组(18例)及存活组(42例);另选择同时期入住重症监护病房的非 ARDS 患者60例为非 ARDS 组。采用酶联免疫吸附试验(ELISA)法检测患者血浆 sRAGE 水平,记录患者PaO2/ FiO2。结果ARDS 组较非 ARDS 组患者 sRAGE 水平升高,PaO2/ FiO2降低,差异有统计学意义(P é0.05)。不同严重程度 ARDS 组患者 sRAGE 水平及PaO2/ FiO2比较,差异均有统计学意义(P é0.05);其中中度 ARDS 组、重度 ARDS 组较轻度 ARDS组,重度 ARDS 组较中度 ARDS 组患者 sRAGE 水平升高,PaO2/ FiO2降低,差异有统计学意义(P é0.05)。死亡组较存活组 ARDS 患者 sRAGE 水平升高,PaO2/ FiO2降低,差异有统计学意义( P é0.05)。直线相关性分析显示,ARDS组患者 sRAGE 水平与PaO2/ FiO2呈负相关(r =-0.949,P =0.0002)。结论 sRAGE 在 ARDS 患者预后预测方面存在价值,可作为评价 ARDS 预后的一个生化标记物;在诊断方面可能存在一定价值,有待于进一步研究验证。%Objective To discuss the application value about soluble receptor for advanced glycation end products (sRAGE)in the diagnostic and prognostic assessment of patients with acute respiratory distress syndrome(ARDS)in the inten-sive care unit(ICU). Methods 60 ARDS patients admitted to the First Affiliated Hospital of Liaoning Medical University from March 2012 to March 2013 were selected. The patients were divided into mild group(23 cases),moderate group(23 cases)and severe group(14 cases)based on o

  11. Expression of Receptor for Advanced Glycation Endproduct on Peripheral Blood Mononuclear Cells in Patients with Coronary Heart Disease%冠心病患者外周血单核细胞表面晚期糖基化终末产物受体水平的表达

    Institute of Scientific and Technical Information of China (English)

    周鹤; 牛楠; 曲鹏; 解丽颖; 杨丽

    2013-01-01

    目的探讨外周血单核细胞表面晚期糖基化终末产物受体(RAGE)的表达水平与冠心病患者临床表现及冠状动脉病变严重程度的关系,并评估其对冠心病患者风险的预测价值.方法 选择因胸痛住院并行冠状动脉造影的患者80例,据其不同临床表现、冠状动脉病变的Gensini积分、病变血管支数进行相应分组,采用流式细胞学方法测定外周血单核细胞表面RAGE水平.结果 急性心肌梗死组、不稳定型心绞痛组外周血单核细胞表面RAGE表达水平均高于稳定型心绞痛组和对照组(P<0.01).RAGE水平与高敏C反应蛋白水平呈正相关(r=0.476,P=0.01);多支病变组和两支病变组外周血单核细胞表面RAGE表达水平高于单支病变组(P<0.05);多支病变组RAGE水平高于两支病变组(P<0.05);根据冠状动脉造影Gensini评分分为三组,三组间外周血单核细胞表面RAGE水平逐渐升高,且各组间差异均具有统计学差异.外周血单核细胞表面RAGE水平与冠状动脉造影评分之间呈正相关(r=0.376,P=0.007);采用Logistic回归法分析高水平的外周血单核细胞表面RAGE水平是冠心痛患者发生急性冠状动脉综合征的独立危险因素(OR=1.180,P=0.02).结论 冠心病患者外周血单核细胞表面RAGE表达水平明显增加,且随着临床表现严重程度的增加呈逐渐升高趋势,对冠心病患者的临床表现有预测价值.外周血单核细胞RAGE水平与冠状动脉病变狭窄程度相关,对冠状动脉病变严重程度有一定的预测价值.高水平外周血单核细胞RAGE的表达是冠心痛患者临床表现严重程度的独立危险因素.%Aim To analyze the relationship between the level of receptor for advanced glycation endproducts (RAGE) on peripheral blood mononuclear cells (PBMC) and the clinical manifestations of coronary heart disease and the severity of angiographic lesion. Further investigation should be made to discuss

  12. 糖基化终产物受体在大鼠牙周膜成纤维细胞中的表达%Expression of receptor for advanced glycation end-product in rat periodontal ligament fibroblasts

    Institute of Scientific and Technical Information of China (English)

    邓天政; 吕晶; 冯岩; 李冬霞; 刘冰; 逄键梁; 柯杰

    2012-01-01

    Objective To detect expression of receptor for advanced glycation end products (RAGE) produced by human periodontal ligament fibroblasts ( PDL) cultured in vitro. Methods To collect rat periodontal ligament firbroblast induced by 50, 100, 200 mg/L advanced glycation end products-bovine serum albumin ( AGE-BSA) 200 mg/L BSA and blank control in DMEM in vitro, which were group A, B, C, D, E respectively. Detect mRNA of RAGE using RT-PCR and protein expression using immunohistochemistry. Results Immunohistochemistry showed the protein expression ofRAGE in group A, B, C, and the expression level elevated with the increase of AGE-BSA concentration. Group D and E did not express RAGE protein. RT-PCR proved the gene of RAGE expresses in group A, B, C. Group D expressed a little, group E did not express. Conclusion RAGE can be produced by PDL cultured in vitro induced by AGE-BSA.%目的 研究体外培养大鼠牙周膜成纤维细胞在糖基化终产物诱导下糖基化终产物受体( receptor for advanced glycation end-product,RAGE)的表达情况.方法 收集第三代体外培养的大鼠牙周膜成纤维细胞,在含有终浓度为50、100、200 mg/L的糖基化牛血清白蛋白、200 ms/L的牛血清白蛋白以及不含上述蛋白成分培养基内孵育48h,分别设为A组、B组、C组、D组、E组.免疫组织化学法、反转录-聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)检测细胞内RAGE蛋白及mRNA表达.结果 免疫组织化学结果显示A、B、C组中牙周膜成纤维细胞内RAGE蛋白表达均为阳性,且随浓度增高,表达强度略有增强,而D及E组无表达;RT-PCR检测发现A、B、C组RAGE mRNA均表达且表达强度随浓度增高而增强,D组有少量表达,E组不表达.结论 体外培养的牙周膜成纤维细胞在糖基化终产物诱导下能够表达RAGE.

  13. Anti-atherosclerotic effects of sitagliptin in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Omoto S

    2015-07-01

    Full Text Available Seitaro Omoto,1 Takehito Taniura,2 Tohru Nishizawa,3 Takeshi Tamaki,3 Akira Shouzu,4 Shosaku Nomura3 1Division of Internal Medicine, Korigaoka Yukeikai Hospital, 2Division of Internal Medicine, Daiwa Hospital, 3First Department of Internal Medicine, Kansai Medical University, 4Division of Internal Medicine, Saiseikai Izuo Hospital, Osaka, Japan Background: Advanced glycation end products, selectins, and adiponectin play important roles in the development of atherosclerosis in individuals with diabetes. Sitagliptin has been shown to reduce the concentration of glycated hemoglobin in diabetic patients. However, its effects on soluble receptor for advanced glycation end products (sRAGEs, selectins, and adiponectin in these patients are poorly understood. This study was conducted to assess the effects of sitagliptin on the circulating levels of sRAGEs, monocyte chemoattractant protein-1 (MCP-1, selectins, and adiponectin in patients with type 2 diabetes. Methods: Diabetic patients eligible for sitagliptin monotherapy or combination therapy (eg, sitagliptin plus a sulfonylurea were administered sitagliptin (50 mg/day for 6 months. Levels of soluble P-selectin (sP-selectin, soluble E-selectin (sE-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1, MCP-1, sRAGEs, and adiponectin were measured by ELISA at baseline and after 3 and 6 months of treatment. Results: At baseline, the levels of MCP-1, sP-selectin, sE-selectin, and sVCAM-1 were higher and the level of adiponectin was lower in diabetic patients than in nondiabetic patients. Sitagliptin therapy for 3 and 6 months significantly reduced plasma levels of sP-selectin, sE-selectin, sVCAM-1, and MCP-1 relative to baseline, while significantly increasing adiponectin levels. sRAGEs did not exhibit a statistical significance, although there was an increasing tendency. Furthermore, the reductions in sP-selectin, sE-selectin, sVCAM-1, and MCP-1 during sitagliptin therapy were significantly greater

  14. High-mobility group box 1 inhibits HCO(3)(-) absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway.

    Science.gov (United States)

    Good, David W; George, Thampi; Watts, Bruns A

    2015-10-15

    High-mobility group box 1 (HMGB1) is a damage-associated molecule implicated in mediating kidney dysfunction in sepsis and sterile inflammatory disorders. HMGB1 is a nuclear protein released extracellularly in response to infection or injury, where it interacts with Toll-like receptor 4 (TLR4) and other receptors to mediate inflammation. Previously, we demonstrated that LPS inhibits HCO(3)(-) absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-ERK pathway (Watts BA III, George T, Sherwood ER, Good DW. Am J Physiol Cell Physiol 301: C1296-C1306, 2011). Here, we examined whether HMGB1 could inhibit HCO(3)(-) absorption through the same pathway. Adding HMGB1 to the bath decreased HCO(3)(-) absorption by 24% in isolated, perfused rat and mouse MTALs. In contrast to LPS, inhibition by HMGB1 was preserved in MTALs from TLR4(-/-) mice and was unaffected by ERK inhibitors. Inhibition by HMGB1 was eliminated by the receptor for advanced glycation end products (RAGE) antagonist FPS-ZM1 and by neutralizing anti-RAGE antibody. Confocal immunofluorescence showed expression of RAGE in the basolateral membrane domain. Inhibition of HCO(3)(-) absorption by HMGB1 through RAGE was additive to inhibition by LPS through TLR4 and to inhibition by Gram-positive bacterial molecules through TLR2. Bath amiloride, which selectively prevents inhibition of MTAL HCO(3)(-) absorption mediated through Na⁺/H⁺ exchanger 1 (NHE1), eliminated inhibition by HMGB1. We conclude that HMGB1 inhibits MTAL HCO(3)(-) absorption through a RAGE-dependent pathway distinct from TLR4-mediated inhibition by LPS. These studies provide new evidence that HMGB1-RAGE signaling acts directly to impair the transport function of renal tubules. They reveal a novel paradigm for sepsis-induced renal tubule dysfunction, whereby exogenous pathogen-associated molecules and endogenous damage-associated molecules act directly and independently to inhibit MTAL HCO(3)(-) absorption through

  15. The danger signal S100B integrates pathogen- and danger-sensing pathways to restrain inflammation.

    Science.gov (United States)

    Sorci, Guglielmo; Giovannini, Gloria; Riuzzi, Francesca; Bonifazi, Pierluigi; Zelante, Teresa; Zagarella, Silvia; Bistoni, Francesco; Donato, Rosario; Romani, Luigina

    2011-03-01

    Humans inhale hundreds of Aspergillus conidia without adverse consequences. Powerful protective mechanisms may ensure prompt control of the pathogen and inflammation. Here we reveal a previously unknown mechanism by which the danger molecule S100B integrates pathogen- and danger-sensing pathways to restrain inflammation. Upon forming complexes with TLR2 ligands, S100B inhibited TLR2 via RAGE, through a paracrine epithelial cells/neutrophil circuit that restrained pathogen-induced inflammation. However, upon binding to nucleic acids, S100B activated intracellular TLRs eventually resolve danger-induced inflammation via transcriptional inhibition of S100B. Thus, the spatiotemporal regulation of TLRs and RAGE by S100B provides evidence for an evolving braking circuit in infection whereby an endogenous danger protects against pathogen-induced inflammation and a pathogen-sensing mechanism resolves danger-induced inflammation.

  16. A Psychoanalytic Study of Sylvia Plath.

    Science.gov (United States)

    Feirstein, Frederick

    2016-02-01

    Sylvia Plath's rage at her abandoning husband and at her late beloved father was partly a displacement of anger toward her loving but smothering mother. Her schizoid pathology resulting from the symbiosis (along with her bipolarity) helped prompt her suicide. At the same time her rage at the men represented a struggle to prevent it. The focus of this paper is to explore in the context of her life how the style as well as the content of her last book, Ariel, made for one long suicide note-albeit a beautifully written work of art. In the most accessible of her poems, such as "Daddy," "Lady Lazarus," and "Edge," her health overcomes her pathology. In others her pathology dominates. In Ariel Plath attempted and succeeded in turning herself into a tragic, mythic heroine, eventually drowning herself in a gas oven as she would have in the ocean-a key metaphor for her mother.

  17. 阿托伐他汀对2型糖尿病鼠主动脉糖基化终末产物受体基因表达的影响%Effects of atorvastatin on expression of receptor for advanced glycation end products in aorta of type 2 diabetic rats

    Institute of Scientific and Technical Information of China (English)

    冯波; 李栩; 徐雷; 王华; 颜新凤; 薛俊丽

    2011-01-01

    目的 观察阿托伐他汀对2型糖尿病(GK)大鼠动脉壁糖基化终末产物受体(RAGE)基因表达的影响,探讨阿托伐他汀抗糖尿病动脉粥样硬化作用的潜在机制.方法 健康雄性Wistar大鼠5只作为正常对照组,GK大鼠随机分为糖尿病对照组(5只)和糖尿病阿托伐他汀治疗组(4只,每日1次阿托伐他汀20 mg/kg灌胃).各组均采用高脂饮食喂养.12周后,采用透射电镜观察主动脉壁超微结构,定量RT-PCR测定主动脉RAGE和单核细胞趋化蛋白-1(MCP-1)的表达.结果 与正常对照组比较,糖尿病对照组主动脉RAGE和MCP-1表达明显升高,而阿托伐他汀治疗能够降低RAGE和MCP-1的表达.主动脉RAGE表达水平与MCP-1表达水平呈显著正相关(r=0.482,P=0.031).透射电镜下糖尿病大鼠动脉可见超微结构的改变.结论 RAGE表达在2型糖尿病早期动脉粥样硬化形成过程中明显上调,阿托伐他汀可通过下调RAGE的表达抗动脉粥样硬化的形成.%Objective To investigate the effect of atorvastatin on expression of receptor for advanced glycation end products (RAGE) in the aorta of type 2 diabetic Goto-Kakisaki (GK) rats and to discuss the potential anti-atherosclerosis mechanisms of atorvastatin. Methods 5 healthy Wistar rats (normal control group) and 9 GK rats were randomly divided into two groups : diabetic control group and atorvastatin-treated diabetic group (20 mg/kg,qd) were fed with the high fat diet for 12 weeks. The expressions of RAGE mRNA and MCP-1 mRNA of aorta were detected using RT-PCR. Ultramicrostructure of aorta was observed using electron microscope. Results Compared with normal control group , the expressions of RAGE mRNA and MCP-1 mRNA in diabetic control group were significant increased . Decreases in the expressions of RAGE mRNA and MCP-1 mRNA were observed in atorvastatin -treated diabetic group compared with diabetic control group. There was significant correlation between the expression levels of RAGE m

  18. Psychohistory and Family Among Antebellum Slaveholders.

    Science.gov (United States)

    Adams, Kenneth Alan

    2016-01-01

    This article examines the macroscopic reasons for maternal rage and its injection into slaveholder children in the antebellum South. It is argued that the misogyny that infected antebellum life metastasized in southern mistresses and affected the way they felt about themselves and their children. As mothers, they were casual parents, concerned with molding the character of their charges, rearing warriors and proper ladies, but uninterested in caring for them and helping them realize their own aspirations. It is argued that the misanthropic rage that they injected into their children constituted the poison that each generation of slaveholders had to ventilate into poison containers, slaves, as a homeostatic means of psycho-emotional survival. This intergenerational process of poison injection--from father to mother, from mother to child, from child to slave, constituted the process that insured the perpetuation of the psychic structure necessary for the continuation of slavery from generation to generation. PMID:26856182

  19. Simulation and Analysis of Converging Shock Wave Test Problems

    Energy Technology Data Exchange (ETDEWEB)

    Ramsey, Scott D. [Los Alamos National Laboratory; Shashkov, Mikhail J. [Los Alamos National Laboratory

    2012-06-21

    Results and analysis pertaining to the simulation of the Guderley converging shock wave test problem (and associated code verification hydrodynamics test problems involving converging shock waves) in the LANL ASC radiation-hydrodynamics code xRAGE are presented. One-dimensional (1D) spherical and two-dimensional (2D) axi-symmetric geometric setups are utilized and evaluated in this study, as is an instantiation of the xRAGE adaptive mesh refinement capability. For the 2D simulations, a 'Surrogate Guderley' test problem is developed and used to obviate subtleties inherent to the true Guderley solution's initialization on a square grid, while still maintaining a high degree of fidelity to the original problem, and minimally straining the general credibility of associated analysis and conclusions.

  20. Preliminary results investigating mix in colliding-shock experiments

    Science.gov (United States)

    Offermann, Dustin; Keiter, Paul; Loomis, Eric; Welser-Sherrill, Leslie; Fincke, Jim; Lanier, Nick

    2011-10-01

    Experiments have been performed at the Omega laser facility to investigate turbulence-driven mix from two colliding shocks, such as expected in ICF ignition capsules. Two shocks were generated at either end of a cylindrical, CH foam. The evolution of an Al tracer layer at one end of the foam was measured using point-projection radiography. Comparison of this data with simulations from the code, RAGE has been done to improve its predictive capability for ICF experiments. RAGE implements the Besnard-Harlow-Rauenzahn (BHR) model, which is intended for turbulent transport in fluids with large density variations. Los Alamos National Laboratory, an affirmative action/equal opportunity employer, is operated by the Los Alamos National Security, LLC for the National Nuclear Security Administration of the U.S. Department of Energy under contract DE-AC52-06NA25396.

  1. On the Significance of New Biochemical Markers for the Diagnosis of Premature Labour

    Directory of Open Access Journals (Sweden)

    Rafał Rzepka

    2014-01-01

    Full Text Available Preterm labour is defined as a birth taking place between 22nd and 37th weeks of gestation. Despite numerous studies on the aetiology and pathogenesis of preterm labour, its very cause still remains unclear. The importance of the cytokines and acute inflammation in preterm labour aetiology is nowadays well-proven. However, chronic inflammation as an element of the pathogenesis of premature labour is still unclear. This paper presents a literature review on the damage-associated molecular patterns (DAMPs, receptors for advanced glycation end products (RAGE, negative soluble isoforms of RAGE, chemokine-stromal cell-derived factor-1 (SDF-1 and one of the adipokines, resistin, in the pathogenesis of preterm labour. We conclude that the chronic inflammatory response can play a much more important role in the pathogenesis of preterm delivery than the acute one.

  2. 子痫前期患者胎盘组织中晚期糖基化终产物受体和P-选择素的表达%Expression of receptor of advanced glycation end products and P-selectin in placenta of preeclampsia patients

    Institute of Scientific and Technical Information of China (English)

    杨玲竹; 李亚敏

    2011-01-01

    Aim :To explore the role of receptor of advanced glycation end products (RAGE) and P-selectin in the development of preeclampsia (PE). Methods:SP method and RT-PCR analysis were used to detect the expression of RAGE and P-selectin protein and mRNA in placenta tissue from 40 cases of PE (20 cases of mild PE, 20 cases of severe PE) and 30 cases of normal term pregnant. Results: All groups showed RAGE and P-selectin positive pigmentation in the placenta.RAGE protein was mainly expressed in trophoblast cells, but there was a small amount in the vascular endothelial cells.P-selectin was mainly expressed in syncytiotrophoblast cells, vascular endothelial cells,and interstitial cells. There were significant differences among three groups on the expression of RAGE and P-selectin protein( F = 250.152 and 274. 044,P <0. 001 ) and mRNA( F =624. 550 and 708. 351 ,P <0. 001 ). Expression of RAGE and P-selectin mRNA was significantly higher in placenta tissue of PE group compared with that of control group ( P < 0.05 ), the levels of severe PE group were higher than those of mild PE group ( P < 0.05) , and there was a positive correlation between them of protein and mRNA expression ( r =0. 814 and 0. 796 ,P <0. 001 ). Conclusion:The high levels of RAGE and P-selectin in placenta tiusse in PE may be associated with the occurrence and development of PE, and both of them have synergies in the development of PE.%目的:探讨晚期糖基化终产物受体(RAGE)和P-选择素(P-selectin)在子痫前期(PE)发生发展中的作用.方法:采用免疫组织化学SP法和RT-PCR法检测30例正常孕妇(对照组)和40例PE患者(轻度20例、重度20例)胎盘组织中RAGE和P-selectin蛋白及mRNA的表达情况.结果:对照组与PE组胎盘组织内均有RAGE和P-selectin阳性表达,RAGE主要表达于滋养细胞.血管内皮细胞巾也有少量表达;P-seleetin主要表达于合体滋养细胞、血管内皮细胞及间质细胞.3组RAGE和P-seleetin蛋白(F=250.152

  3. Aggressive Behaviour in Huntington’s Disease: A Cross-Sectional Study in a Nursing Home Population

    Directory of Open Access Journals (Sweden)

    R. S. Shiwach

    1993-01-01

    Full Text Available We describe a cross-sectional study of aggressive behaviour in a sample of patients suffering from Huntington's disease in a residential nursing home. Data were obtained using the RAGE, a behaviourally oriented rating scale for measuring aggressive behaviour in cognitively impaired patients. Nursing staff rated 27 patients after a 3 day observation period. A third of the sample were rated to be at least mildly aggressive; the frequencies of some specific types of aggressive behaviour were high. In contrast, the frequency of injuries sustained and the use of restraints and medication for aggressive behaviour were low. Aggressive behaviour was found to be significantly related to the degree of functional impairment. These data are compared with those reported in a study using the RAGE to assess aggressive behaviour in a sample of elderly patients with dementia.

  4. A Psychoanalytic Study of Sylvia Plath.

    Science.gov (United States)

    Feirstein, Frederick

    2016-02-01

    Sylvia Plath's rage at her abandoning husband and at her late beloved father was partly a displacement of anger toward her loving but smothering mother. Her schizoid pathology resulting from the symbiosis (along with her bipolarity) helped prompt her suicide. At the same time her rage at the men represented a struggle to prevent it. The focus of this paper is to explore in the context of her life how the style as well as the content of her last book, Ariel, made for one long suicide note-albeit a beautifully written work of art. In the most accessible of her poems, such as "Daddy," "Lady Lazarus," and "Edge," her health overcomes her pathology. In others her pathology dominates. In Ariel Plath attempted and succeeded in turning herself into a tragic, mythic heroine, eventually drowning herself in a gas oven as she would have in the ocean-a key metaphor for her mother. PMID:26859176

  5. Paedophilia; Diagnosis, Treatment & Moral Panic

    OpenAIRE

    Sadat, Sama; Ashraf, Kashifah; Nilsson Smith, Heidi; Chemlali, Hanan; Bosboom, Chiara; Hoff, Rasmus

    2012-01-01

    Paedophilia, briefly explained, is an adult’s sexual and emotional fascination for children. This phenomenon tends to raise a lot of strong feelings of horror, disgust and rage in the general population. The mere description is seen as horrible and directly unacceptable by normative morals and values. The collection of empirical data was done through authors and researchers, who have written reports and made research in this particular field. Additionally we interviewed persons from the ...

  6. Design and Calibration of a Flowfield Survey Rake for Inlet Flight Research

    Science.gov (United States)

    Flynn, Darin C.; Ratnayake, Nalin A.; Frederick, Michael

    2009-01-01

    Flowfield rake was designed to quantify the flowfield for inlet research underneath NASA DFRC s F-15B airplane. Detailed loads and stress analysis performed using CFD and empirical methods to assure structural integrity. Calibration data were generated through wind tunnel testing of the rake. Calibration algorithm was developed to determine the local Mach and flow angularity at each probe. RAGE was flown November, 2008. Data is currently being analyzed.

  7. The UCSC Ebola Genome Portal

    OpenAIRE

    Haeussler, Maximilian; Karolchik, Donna; Clawson, Hiram; Raney, Brian J.; Rosenbloom, Kate R.; Fujita, Pauline A.; Hinrichs, Angie S.; Speir, Matthew L; Eisenhart, Chris; Zweig, Ann S.; Haussler, David; Kent, W. James

    2014-01-01

    Background: With the Ebola epidemic raging out of control in West Africa, there has been a flurry of research into the Ebola virus, resulting in the generation of much genomic data. Methods: In response to the clear need for tools that integrate multiple strands of research around molecular sequences, we have created the University of California Santa Cruz (UCSC) Ebola Genome Browser, an adaptation of our popular UCSC Genome Browser web tool, which can be used to view the Ebola virus genome s...

  8. Multistakeholder Initiatives in Corporate Social Responsibility: The OECD Guidance and Conflict Minerals

    OpenAIRE

    Johns, Matthew

    2010-01-01

    In recent years, war has raged in the Democratic Republic of Congo between various military bodies, bringing death and devastation to millions of innocent civilians. The conflict has been fuelled by the country‟s abundant mineral wealth, with factions exploiting state weakness and taking control of a large proportion of the mining sector. One of the largest purchasers of the Congo‟s minerals is the global electronics industry. NGOs and civil society have subsequently accused electronics compa...

  9. SUBJECT INDEX

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    2, 4, 6-trinitrobenzenesulphonic acid, zinc sulfate, experimental colitis, 2003328AC133 antigen, hematopoietic stem cells, fetal blood, immunophe-notyping, 2003138ALR2 gene, eNOS gene, PON1 gene, RAGE gene, 2003179 ATN-ISI, prognosis, acute renal failure, acute tubular necrosis-individual severity index, acute physiology and chronic health evaluation, 2003118 Alzheimer disease, interleukin-1 beta, tumor necrosis factor alpha,

  10. Gravitomagnetism and the significance of the curvature scalar invariants

    OpenAIRE

    Costa, L. Filipe O.; Wylleman, Lode; Natário, José

    2016-01-01

    The curvature invariants have been subject of recent interest due to the debate concerning the notions of intrinsic/extrinsic frame-dragging, the use of the electromagnetic analogy in such classification, and the question of whether there is a fundamental difference between the gravitomagnetic field arising from the translational motion of the sources, detected with Lunar Laser Raging and in the observations of binary pulsars, and the gravitomagnetic field produced by the rotation of the Eart...

  11. Tempest in a Tea Pot: How did the Public Conversation on Genetically Modified Crops Drift so far from the Facts?

    OpenAIRE

    Goldstein, Daniel A.

    2014-01-01

    The debate over genetically modified (GM) crops has raged in Europe since 1996, but had barely risen above a whisper in the USA until recent labeling debates raised public attention. This article will explain GM crops and traits discuss safety assessment provide a view on safety from authoritative organizations discuss selected issues of current debate, and provide the author’s perspective as to why the public debate has drifted so far from scientific reality. The economic and environmental b...

  12. Displaced murder.

    Science.gov (United States)

    Brand, Stewart

    1981-10-01

    Most suicide attempts appear to be impulsive and motivated by rage against another person. The author believes that publications of pro-suicide groups like EXIT or Hemlock serve a useful purpose for some terminally ill persons, although hospice care is a better approach for most dying patients. Potential suicides who are suffering from emotional stresses rather than terminal illnesses are best deterred by a personalized approach.

  13. TRADE PROTECTIONISM, Better Cooperate than Fight?

    Institute of Scientific and Technical Information of China (English)

    Guo Liqin

    2009-01-01

    @@ In 2009,China witnesses a rage of trade protectionism wave.According to the Ministry of Commerce,currently,35% of anti-dumping and71% of anti-subsidy cases are against Chinese products.In the first three quarters this year,there are 19 countries launching a total of 88 anti-dumping ("AD")and countervailing("CVD")investigations against China.

  14. A New Approach of Personality and Psychiatric Disorders: A Short Version of the Affective Neuroscience Personality Scales

    OpenAIRE

    Jean-Baptiste Pingault; Bruno Falissard; Sylvana Côté; Sylvie Berthoz

    2012-01-01

    BACKGROUND: The Affective Neuroscience Personality Scales (ANPS) is an instrument designed to assess endophenotypes related to activity in the core emotional systems that have emerged from affective neuroscience research. It operationalizes six emotional endophenotypes with empirical evidence derived from ethology, neural analyses and pharmacology: PLAYFULNESS/joy, SEEKING/interest, CARING/nurturance, ANGER/rage, FEAR/anxiety, and SADNESS/separation distress. We aimed to provide a short versi...

  15. Ethical and legal issues in aesthetic surgery

    OpenAIRE

    Suresh Gupta

    2012-01-01

    Rapid growth and expansion of plastic surgery in general and aesthetic surgery in particular in the past decade has brought in its wake some confusions particularly raising questions for the surgeons conduct towards his colleagues and the patients in the light of ethical requirements. Some thoughts from eminent thinkers form a backdrop to consideration of theories of medical ethics. In this article raging and continuous debates on these subjects have been avoided to maintain the momentum. Apa...

  16. Living it Up Mid-Air

    Institute of Scientific and Technical Information of China (English)

    GREGGWYCHERLEY

    2004-01-01

    There's something surreal about boarding a plane. Apart from the fact that you are defying gravity, the feeling of being enclosed in a large flying tube for up to 12 hours, far removed from earth and surrounded by strangers in. a strange environment can induce all kinds of behavioural changes, from air-rage to irrational fear, through to out of character flirting with aircrew or other passengers.

  17. China Relief to Pakistan

    Institute of Scientific and Technical Information of China (English)

    Audrey GUO

    2010-01-01

    @@ In Pakistan the rains and floods that started around July 22 have raged through Khyber Pakhtunkhwa,Balochistan,Punjab,Azad Kashmir and Gilgit Baltistan.The rain and floods are now headed towards the Southern Province of Sindh.The provincial governments are bracing for huge flood waters."These are the most massive and heaviest floods in Pakistan territory since 1929,"said the ambassador of Pakistan Masood Khan at a press conference on August 6 in Beijing.

  18. Feruidus Ille Canis: the Lore and Poetry of the Dog Star in Antiquity

    Science.gov (United States)

    Ceragioli, Roger Charles

    1992-01-01

    The Dog Star, Sirius, appears in many important works of classical poetry. It also appears in numerous myths and several religious rituals. A complex body of folklore surrounds it and it had a paramount importance in agriculture. Yet no one has attempted a systematic analysis of Sirius' place in Greco-Roman art and thought. This thesis begins that analysis. The introductory chapter discusses the methodology and approach that the thesis takes to the evidence, and supplies essential background information on Sirius' place among the constellations and its relation to the physical environment of the Mediterranean. Chapter one explores Sirius' role in ancient warrior traditions. Sirius embodied the principle of cosmic heat, and through heat it was thought to cause rabies in dogs. The Greek word for rabies is lussa. But lussa also named the madness of warriors such as Achilles in the Iliad. Etymologically, lussa meant "wolfishness." Rabid dogs, wolves, and raging warriors all exhibit fiery heat as an integral part of their natures. It is argued that raging warriors, wolves, and rabid dogs were largely interchangeable entities for the Greeks. Thus when Hector and Achilles in their raging are compared to Sirius, the comparison reflects more than the likeness of their surface brilliance. Chapter two explores Sirius' connection to erotic themes in ancient poetry. Because erotic experience could be represented as a conflagration that might burn the lover into a frenzy, the fiery raging Dog Star was an appropriate symbolic accompaniment. Sirius itself experienced erotic frenzy when it became passionate for Opora (the ripe fruits of summer). Chapter three turns to Sirius' involvement in viticulture. Sirius was said to ripen the grapes, but was also conceived to have once been the faithful dog of Icarius, who first introduced wine-drinking among humans. The chapter explores Sirius' role in the myth of Icarius, and the relation of that myth to the erotic and martial sides of

  19. The effect of fibroblast growth factors and advanced glycation end-products on the intima-media complex thickness in patients with coronary heart disease and type 2 diabetes

    OpenAIRE

    Ekaterina Vladimirovna Ivannikova; Victor Yurievich Kalashnikov; Olga Mikhaylovna Smirnova; Alexander Borisovich Kuznetsov; Sergei Anatolievich Terekhin; Alexander Viktorovich Il'in

    2014-01-01

    ObjectiveTo determine the levels of fibroblast transforming growth factor (TGFβ1), basic fibroblast growth factor (β-FGF), markers of nonspecific inflammatory response (interleukin-6 (IL-6)), C-reactive protein (CRP), advanced glycation end-products (AGEs) and their receptors (RAGEs) and to study their effect on the intima-media complex (IMC) thickness in patients with coronary heart disease (CHD) and type 2 diabetes, depending on carbohydrate metabolism compensation.Materials and Methods37 p...

  20. Accountants and economic governance in a dependent country, : Conflicting legacies and new professional issues in Lebanon

    OpenAIRE

    Longuenesse, Elisabeth

    2006-01-01

    Purpose: The purpose of this study was to sort out what was at stake in the fierce debates that raged after 1995 among Lebanese accountants about the conditions of membership to their new association.Approach and methodology: It fits within the recent development of the sociology of professions. But because of the specific nature of accountants expertise, it is also concerned with broader societal issues and socio-political negotiation of interests, which underlie professional battles. Lastly...

  1. Sadism linked to loneliness: psychodynamic dimensions of the sadistic serial killer Jeffrey Dahmer.

    Science.gov (United States)

    Martens, Willem H J

    2011-08-01

    In this article the psychodynamic link between loneliness and sadism is examined on basis of a case report of the sadistic and cannibalistic serial killer Jeffery Dahmer. Envy, shame/rage mechanism, a disturbed oral-sadistic development, castration fear and severe feelings of inferiority, the conviction of being unlovable and unacceptable, need to diminish tension, powerful and sadistic fantasies as a consequence of inadequate and frustrated parenting, and reality distortion appear to be involved in sadistic etiology.

  2. Intracerebroventricular application of S100B selectively impairs pial arteriolar dilating function in rats.

    Science.gov (United States)

    Changyaleket, Benjarat; Xu, Haoliang; Vetri, Francesco; Valyi-Nagy, Tibor; Paisansathan, Chanannait; Chong, Zhao Zhong; Pelligrino, Dale A; Testai, Fernando D

    2016-03-01

    S100B is an astrocyte-derived protein that can act through the receptor for advanced glycation endproducts (RAGE) to mediate either "trophic" or "toxic" responses. Its levels increase in many neurological conditions with associated microvascular dysregulation, such as subarachnoid hemorrhage (SAH) and traumatic brain injury. The role of S100B in the pathogenesis of microvasculopathy has not been addressed. This study was designed to examine whether S100B alters pial arteriolar vasodilating function. Rats were randomized to receive (1) artificial cerebrospinal fluid (aCSF), (2) exogenous S100B, and (3) exogenous S100B+the decoy soluble RAGE (sRAGE). S100B was infused intracerebroventricularly (icv) using an osmotic pump and its levels in the CSF were adjusted to achieve a concentration similar to what we observed in SAH. After 48 h of continuous icv infusion, a cranial window/intravital microscopy was applied to animals for evaluation of pial arteriolar dilating responses to sciatic nerve stimulation (SNS), hypercapnia, and topical suffusion of vasodilators including acetylcholine (ACh), s-nitroso-N-acetyl penicillamine (SNAP), or adenosine (ADO). Pial arteriolar dilating responses were calculated as the percentage change of arteriolar diameter in relation to baseline. The continuous S100B infusion for 48 h was associated with reduced responses to the neuronal-dependent vasodilator SNS (pmuscle cell-dependent vasodilators, namely hypercapnia, SNAP, or ADO. These findings indicate that S100B regulates neuronal and endothelial dependent cerebral arteriolar dilation and suggest that this phenomenon is mediated through RAGE-associated pathways. PMID:26773687

  3. Nye patologier i selvdannelsens tidsalder

    DEFF Research Database (Denmark)

    Hammershøj, Lars Geer

    2004-01-01

    The aim of this article is to inquire into today's social pathologies, i.e. the negative consequences of the developmental processes of society. In a dialogue with Axel Honneth, the article asserts that a shift has occurred in individualization, a shift that implies a fundamental change in social...... in self-Bildung', which is conceived as a ‘refusal to transcend oneself into sociality', and offers interpretations of present pathologies such as depression, anorexia, populist freedom of speech, and demonic rage....

  4. Konst Kräver Offer : En analys av Nathalia Edenmonts konstnärskap i ljuset av Pierre Bourdieus kulturteori

    OpenAIRE

    Ericsson, Kristin

    2015-01-01

    Nathalia Edenmont is a controversial and uncompromising photo artist who has caused the whole world to rage over her obscene photographs. In this thesis I have researched Edenmonts artistry with help of the sociologist Pierre Bourdieus field analysis. By using Bourdieus's different field concepts I have researched Edenmonts artistic career by concepts such as habitus, consecration and different principles. The starting point of this research has been that Nathalia Edenmont is in the autonomou...

  5. Pathways to a universal basic pension in Greece

    OpenAIRE

    Chrysa Leventi; Manos Matsaganis

    2011-01-01

    Although basic pension had for years failed to catch the imagination of policy makers in Greece, it was suddenly brought to the agenda in the context of the severe crisis raging since November 2009. In May 2010 the government committed to a harsh austerity programme, aiming at fiscal consolidation, in return for a rescue package easing the sovereign debt crisis. The July 2010 pension reform, a key provision of the austerity programme, provided for the introduction of a near-universal basic pe...

  6. Aggressive Behaviour in Huntington’s Disease: A Cross-Sectional Study in a Nursing Home Population

    OpenAIRE

    R. S. Shiwach; Patel, V.

    1993-01-01

    We describe a cross-sectional study of aggressive behaviour in a sample of patients suffering from Huntington's disease in a residential nursing home. Data were obtained using the RAGE, a behaviourally oriented rating scale for measuring aggressive behaviour in cognitively impaired patients. Nursing staff rated 27 patients after a 3 day observation period. A third of the sample were rated to be at least mildly aggressive; the frequencies of some specific types of aggressive behaviour were hig...

  7. Satirising the Norwegian language conflict: Gabriel Scott's Babels taarn contextually reconsidered

    OpenAIRE

    Hale, Frederick

    2013-01-01

    Gabriel Scott’s comedy Babels taarn (Babel Tower), first performed at the National Theatre in Kristiania in 1911, satirises the language controversy that was raging in Norway at the time. The play is regarded as important in linguistic and literary terms, but has been largely forgotten. This article argues that Scott was disillusioned by the politicisation of the language controversy and regarded the advance of landsmål as an artificial and unwelcome phenomenon in the unfolding of Norwegian c...

  8. A Simple Model of Endogenous Agricultural Commodity Price Fluctuations with Storage

    OpenAIRE

    Sophie Mitra; Jean-Marc Boussard

    2011-01-01

    A debate has been raging for centuries regarding the effects of inter-annual storage on commodity prices. Most analysts consider storage to function as a price stabilizer, while others place it at the core of an explanation of intriguing features of commodity price series, such as skewed distributions. Most studies have been developed in the context of the theory of competitive storage where random shocks affect supply or demand. Recently, the endogenous chaotic behavior of markets has become...

  9. Tragedies by Life--A slight analysis of the main characters in Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    孙灵

    2003-01-01

    @@ Ⅰ.Introduction Traditionally, tragedies refer to those calamitous events with unhappy endings, which occur on a violent and vigorous scale. However, D. H. Lawrence expresses his own understanding of tragedy from a new angle, which adds a fresh color to its original definition. Frederick J. Hoffman notes in his Freudianism and the Literary Mind: ...Tragedy for him (Lawrence)consists not in sentimental or significant dying, but in ‘ the inner war which is raged between people who love each other...'.

  10. 仙贞片对糖尿病大鼠肾皮质终末期糖化终产物及其受体mRNA表达的影响%Effect of Xianzhen Tablet on Content of Advanced Glycosylation End Products (AGEs) and mRNA Expression of AGE-specific Cellular Receptor in Renal Cortex of Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    唐代屹; 郭赛珊; 孙仁宇

    2005-01-01

    目的观察仙贞片对糖尿病大鼠肾皮质终末期糖化终产物(advanced glycation end products,AGEs)含量及其糖化终产物特异性受体(AGE-specific cellular receptor,RAGE)信使核糖核酸(messenger ribonucleic acid,mRNA)表达的影响,探讨其对糖尿病大鼠肾保护的作用机制.方法采用链脲佐菌素(streptozotocin,STZ)复制糖尿病持续性高血糖肾损害大鼠模型,用荧光测定法和逆转录-多聚酶链式反应(reverse transcription polymerase chain reaction,RT-PCR)技术检测模型大鼠肾皮质AGEs含量及RAGEmRNA的表达,与氨基胍作对照.结果实验12周模型大鼠肾皮质AGEs相对含量及RAGE mRNA表达明显高于正常对照组(P<0.05),仙贞片及氨基胍治疗组肾皮质AGEs相对含量及RAGE mRNA表达明显低于模型组(P<0.05),仙贞片与氨基胍组比较差异无显著性(P>0.05).结论仙贞片能减轻糖尿病大鼠肾皮质内AGEs的积聚,下调RAGE mRNA的过度表达,与氨基胍相近似,具有抑制蛋白非酶糖基化的作用,可能是其肾保护作用的机制之一.

  11. To standardize or not standardize international marketing : is it still a question?

    OpenAIRE

    Soares, Ana Maria; Farhangmehr, Minoo; Shoham, Aviv

    2003-01-01

    The standardization versus adaptation argument has been raging for years and international marketing research about it has spanned some four decades, attesting to its far reaching theoretical and practical relevance. The purpose of this paper is to review the literature on this debate. Major theoretical and empirical contributions from companies’ and consumers’ points of view are presented. The importance of resolving this issue cannot be underestimated as it as an impact on segmentation i...

  12. Influence of glycated low density lipoprotein on the proliferation,expression of intercellular adhesion molecule-1,von Willebrand factor of human umbilical endothelial cells

    Institute of Scientific and Technical Information of China (English)

    LU Jun; LIU Hui-ying; ZHANG Xiu-zhen; LEI Tao

    2009-01-01

    @@ Diabetes mellitus known as its macro-and microangiopathy has caused thousands of mortality per year.Recent researches showed that hyperglycemia,advanced glycation end products(AGEs)and some other factors acted on the process of atherogenesis.AGEs can combine with receptors of AGEs(RAGEs),which exist on the vascular endothelium,smooth muscle cells,macrophage,lymphocyte and so on.

  13. Devo-max could complicate David Cameron’s plans to repeal the Human Rights Act

    OpenAIRE

    McHargh, Aileen

    2014-01-01

    The Conservative Party have recently re-committed to repealing the Human Rights Act (HRA) and replacing it with a ‘home grown’ British Bill of Rights. Meanwhile, discussion of what level of devolution will be afforded to Scotland in the wake of the ‘No’ vote in their independence referendum has been raging on. Here, Aileen McHargh argues that further devolution complicates the Conservatives withdrawal pledge.

  14. Keeping E-Mail in Top Form

    Science.gov (United States)

    Goldsborough, Reid

    2005-01-01

    Despite the fact that e-mail has been firmly entrenched in offices and homes for some time, debate still rages online about e-mail usage and style. How should and e-mail message begin and end? If replying to a message, should the message be quoted before or after? What tone should be taken with a business e-mail? The author talked with some heavy…

  15. An improved expression system for the VC1 ligand binding domain of the receptor for advanced glycation end products in Pichia pastoris.

    Science.gov (United States)

    Degani, Genny; Colzani, Mara; Tettamanzi, Alberto; Sorrentino, Luca; Aliverti, Alessandro; Fritz, Guenter; Aldini, Giancarlo; Popolo, Laura

    2015-10-01

    The receptor for the advanced glycation end products (RAGE) is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily and binds a variety of unrelated ligands sharing a negative charge. Most ligands bind to the extracellular V or VC1 domains of the receptor. In this work, V and VC1 of human RAGE were produced in the methylotrophic yeast Pichia pastoris and directed to the secretory pathway. Fusions to a removable C-terminal His-tag evidenced proteolytic processing of the tag by extracellular proteases and also intracellular degradation of the N-terminal portion of V-His. Expression of untagged forms was attempted. While the V domain was retained intracellularly, VC1 was secreted into the medium and was functionally active in binding AGEs. The glycosylation state of VC1 was analyzed by mass spectrometry and peptide-N-glycosidase F digestion. Like RAGE isolated from mammalian sources, the degree of occupancy of the N-glycosylation sites was full at Asn25 and partial at Asn81 which was also subjected to non-enzymatic deamidation. A simple procedure for the purification to homogeneity of VC1 from the medium was developed. The folded state of the purified protein was assessed by thermal shift assays. Recombinant VC1 from P. pastoris showed a remarkably high thermal stability as compared to the protein expressed in bacteria. Our in vivo approach indicates that the V and C1 domains constitute a single folding unit. The stability and solubility of the yeast-secreted VC1 may be beneficial for future in vitro studies aimed to identify new ligands or inhibitors of RAGE. PMID:26118699

  16. Turkey and Copyleft Music Production : Reflectionson Bandista

    OpenAIRE

    Mehrabov, Ilkin

    2013-01-01

    This article focuses on copyleft music production in Turkey through a case study on Bandista, amusic collective with strong oppositional stance formed in 2006 in Istanbul. Describing itsmusical performances as "situationist experiment of rage and rapture" Bandista becameimmensely popular in the Turkish political music scenery after releasing its debut album De tefabula narratur in 2009 under the copyleft scheme. The article tries to look at the copyleft withthe notion of 'music as performance...

  17. Current studies of biological materials using instrumental and radiochemical neutron activation analysis

    International Nuclear Information System (INIS)

    Instrumental neutron activation analysis still remains the preferred option when analysing the trace element distribution in a wide rage of materials by neutron activation analysis. However, when lower limits of detection are required or major interferences reduce the effectiveness of this technique, radiochemical neutron activation analysis is applied. This paper examines the current use of both methods and the development of rapid radiochemical techniques for analysis of the biological materials, hair, cow's milk, human's milk, milk powder, blood and blood serum

  18. Intensified CCD Image Sensor①

    Institute of Scientific and Technical Information of China (English)

    LIUJikun; ZHAOBaoyun

    1997-01-01

    Work has been done with extending the useful imaging and detection rage of CCD.This was accomplished through direct optical coupling and bonding of image intensifiers to the CCD.It has been shown that the useful range of a CCD may be extended two orders of magnitude using these techniques in coupling a microchannel plate image intensifier to the CCD array.All of these works were done with presently available CCD made by China

  19. The impact of education, rights, obligations and protection of workers against employment

    OpenAIRE

    Vujovic, Efimija

    2012-01-01

    How in the world, and here, in the last decade of last century and the beginning of this century, the educational system meet a multitude of innovations that are caused by changes in the environment. From one side comes to deep changes in humanity and social arrangements, and the other technical and technological development experienced expansion to rage boundaries. These trends dictate economic entities, that their entrepreneurs and their management. From science to seek new solutions. Usabl...

  20. Between green and grey

    OpenAIRE

    Jeanet Kullberg

    2016-01-01

    Taking cuttings is cool. Growing vegetables is all the rage. Green oases can now be found scattered throughout Dutch towns and cities: community gardens and roof gardens where residents can go to relax and enjoy themselves, improve the appearance of their neighbourhood and meet their fellow residents. At the same time, private gardens in the Netherlands are increasingly losing their green appearance in favour of bricks, paving slabs and gravel, making the environment harder both literally and...

  1. Online úskalia folkloristického výskumu

    OpenAIRE

    Šipöczová, Eva; Ústav evropské etnologie, Filozofická fakulta, Masarykova univerzita v Brně

    2012-01-01

    The problematic aspects of internet research are slowly becoming manifest in all the Humanities. The primary concern of ethnology and folkloristics is contemporary folklore – anecdotes, urban legends, rumours, conspiracy theories, all of which are abundant on the internet. Neverteless, the nature of virtual reality has given rise to new methodological problems and uncertainties. How should we collect folklore material on the internet? A conflict rages between classic face-to-face research, an...

  2. Proprietary software versus Open Source Software for Education

    OpenAIRE

    N. Pankaja

    2013-01-01

    The Internet has brought learning "online" and offers many advantages. It is convenient, available at any time of the day, and can be accessed nearly anywhere in the world. Recently, Cloud computing is all the rage. E-Learning offers tremendous potential to increase the availability and convenience of education. Today, online content is varied and can include: text on a website, digital audio, digital video, animated images, and virtual reality environments. This content can be created in a v...

  3. Recognizing borderline personality disorder in the family practice setting.

    Science.gov (United States)

    Hubbard, J R; Saathoff, G B; Bernardo, M J; Barnett, B L

    1995-09-01

    The first step in the management of borderline personality disorder is making the correct diagnosis. A clinical example illustrates symptoms of a patient with borderline personality disorder in a family practice setting. Major characteristics of borderline personality disorder include severe mood instability, fear of abandonment, chronic boredom, self-injury, unstable interpersonal relationships, "splitting," identity instability and borderline rage. Early diagnosis may help prevent potential management problems and possible doctor-patient conflicts. PMID:7653428

  4. Genome-wide RNAi screen reveals the E3 SUMO-protein ligase gene SIZ1 as a novel determinant of furfural tolerance in Saccharomyces cerevisiae

    OpenAIRE

    Xiao, Han; Zhao, Huimin

    2014-01-01

    Background Furfural is a major growth inhibitor in lignocellulosic hydrolysates and improving furfural tolerance of microorganisms is critical for rapid and efficient fermentation of lignocellulosic biomass. In this study, we used the RNAi-Assisted Genome Evolution (RAGE) method to select for furfural resistant mutants of Saccharomyces cerevisiae, and identified a new determinant of furfural tolerance. Results By using a genome-wide RNAi (RNA-interference) screen in S. cerevisiae for genes in...

  5. 自己愛と対人距離との関連

    OpenAIRE

    内田,利広; 堀内,詩子

    2011-01-01

    To clarify how people beset with maladapted narcissism maintain distance from others, a questionnaire targeting university students and a projective method were investigated. Sub-elements of narcissism are "narcissistic rage", "fear of others", and "avoidance tendencies". The projective method was modeled after MAPS personality projection. Two illustration boards were presented―one designated as "base-life", and another as "school-life", and participants pasting clippings of their supposed se...

  6. Is behavioral economics doomed? : The ordinary versus the extraordinary

    OpenAIRE

    David K. Levine

    2012-01-01

    It is fashionable to criticize economic theory for focusing too much on rationality and ignoring the imperfect and emotional way in which real economic decisions are reached. All of us facing the global economic crisis wonder just how rational economic men and women can be. Behavioral economics - an effort to incorporate psychological ideas into economics - has become all the rage. In this book, David K. Levine questions the idea that behavioral economics is the answer to economic problems. H...

  7. Is Behavioral Economics Doomed?

    OpenAIRE

    David K. Levine

    2013-01-01

    It is fashionable to criticize economic theory for focusing too much on rationality and ignoring the imperfect and emotional way in which real economic decisions are reached. All of us facing the global economic crisis wonder just how rational economic men and women can be. Behavioral economics — an effort to incorporate psychological ideas into economics — has become all the rage. In this book, David K. Levine questions the idea that behavioral economics is the answer to economic problems. H...

  8. Aspectos de infraestrutura e serviços como indicadores da turistificação na Vila de Encantadas, Ilha do Mel (Brasil)

    OpenAIRE

    Daniel Hauer Queiroz Telles; José Manoel Gonçalves Gandara

    2011-01-01

    The isle of Mel represents the reality of some insular touristic destinations in the Brazilian coasts, with very special peculiarities raging from the image of an alternative destination to the fragility of social and environmental issues. It has different characteristics, (lack of automobiles and the predominance of small inns), that began since the touristic exploration almost four decades ago. The purpose of the present article is to analyze the conditions of the infrastructure and the ser...

  9. Simultaneous involvement of third and sixth cranial nerve in a patient with Lyme disease

    Energy Technology Data Exchange (ETDEWEB)

    Lell, M.; Schmid, A.; Tomandl, B.F. [Division of Neuroradiology, Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen (Germany); Stemper, B.; Maihoefner, C.; Heckmann, J.G. [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen (Germany)

    2003-02-01

    We report a 57-year-old woman with neuroborreliosis presenting with headache, shoulder muscle pain and double vision. MRI demonstrated enhancement of the right third and sixth cranial nerves. A 3D MP-RAGE sequence was used to perform multiplanar reformations to show this more graphically. The patient was free of symptoms 1 month after completion of therapy, when thickening and contrast enhancement of the nerves were less pronounced. (orig.)

  10. Gambaran Tingkat Kecemasan Orang Tua Dalam Menghadapi Masalah Perilaku Sosial Anak Retardasi Mental di YPAC Medan

    OpenAIRE

    Ndraha, Fourlina Noviyani

    2015-01-01

    Mental retardation children have limited capability of cognitive and adaptive so that it can affect their ability in socializing and behave. Parents who has children with mental retardation have anxiety in dealing with their children’s social behavior such as hyperactivity, rages and loves to fight. This research aims to identify the level of anxiety of parents in dealing with problems of mental retardation children’s social behavior in Yayasan Pembinaan Anak Cacat (YPAC) Medan. The design us...

  11. Simultaneous involvement of third and sixth cranial nerve in a patient with Lyme disease

    International Nuclear Information System (INIS)

    We report a 57-year-old woman with neuroborreliosis presenting with headache, shoulder muscle pain and double vision. MRI demonstrated enhancement of the right third and sixth cranial nerves. A 3D MP-RAGE sequence was used to perform multiplanar reformations to show this more graphically. The patient was free of symptoms 1 month after completion of therapy, when thickening and contrast enhancement of the nerves were less pronounced. (orig.)

  12. Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, L.; Ji, Y.X.; Jiang, W.L.; Lv, C.J. [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai (China)

    2015-05-08

    Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC{sub 50} of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  13. Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo.

    Science.gov (United States)

    Zhang, L; Ji, Y X; Jiang, W L; Lv, C J

    2015-06-01

    Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC50 of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  14. Advanced glycation end-products induce apoptosis in pancreatic islet endothelial cells via NF-κB-activated cyclooxygenase-2/prostaglandin E2 up-regulation.

    Directory of Open Access Journals (Sweden)

    Kuo-Cheng Lan

    Full Text Available Microvascular complications eventually affect nearly all patients with diabetes. Advanced glycation end-products (AGEs resulting from hyperglycemia are a complex and heterogeneous group of compounds that accumulate in the plasma and tissues in diabetic patients. They are responsible for both endothelial dysfunction and diabetic vasculopathy. The aim of this study was to investigate the cytotoxicity of AGEs on pancreatic islet microvascular endothelial cells. The mechanism underlying the apoptotic effect of AGEs in pancreatic islet endothelial cell line MS1 was explored. The results showed that AGEs significantly decreased MS1 cell viability and induced MS1 cell apoptosis in a dose-dependent manner. AGEs dose-dependently increased the expressions of cleaved caspase-3, and cleaved poly (ADP-ribose polymerase in MS1 cells. Treatment of MS1 cells with AGEs also resulted in increased nuclear factor (NF-κB-p65 phosphorylation and cyclooxygenase (COX-2 expression. However, AGEs did not affect the expressions of endoplasmic reticulum (ER stress-related molecules in MS1 cells. Pretreatment with NS398 (a COX-2 inhibitor to inhibit prostaglandin E2 (PGE2 production reversed the induction of cleaved caspase-3, cleaved PARP, and MS1 cell viability. Moreover, AGEs significantly increased the receptor for AGEs (RAGE protein expression in MS1 cells, which could be reversed by RAGE neutralizing antibody. RAGE Neutralizing antibody could also reverse the induction of cleaved caspase-3 and cleaved PARP and decreased cell viability induced by AGEs. These results implicate the involvement of NF-κB-activated COX-2/PGE2 up-regulation in AGEs/RAGE-induced islet endothelial cell apoptosis and cytotoxicity. These findings may provide insight into the pathological processes within the pancreatic islet microvasculature induced by AGEs accumulation.

  15. The Association between Fibroblast Growth Factor-23 and Vascular Calcification Is Mitigated by Inflammation Markers

    Directory of Open Access Journals (Sweden)

    Mohamed M. NasrAllah

    2013-11-01

    Full Text Available Background: Fibroblast growth factor-23 (FGF-23 has been linked to vascular calcification, ventricular hypertrophy and mortality in chronic kidney disease (CKD, although these links may not be direct and independent. Similar grave outcomes are associated with inflammation and oxidative stress in CKD. Recently, accumulating evidence has linked components of phosphate homeostasis to inflammation and oxidative stress. The interaction between the triad of inflammation, FGF-23 and cardiovascular outcomes is underinvestigated. Methods: We studied 65 patients with stage 5 CKD on hemodialysis. Serum levels of FGF-23, high-sensitivity C-reactive protein (hsCRP, endogenous soluble receptor of advanced glycation end products (esRAGE, advanced oxidation protein products (AOPP, parathormone, lipids, calcium and phosphorous were measured. The aortic calcification index (ACI was determined using non-contrast CT scans of the abdominal aorta. Results: FGF-23 was elevated (mean: 4,681 pg/ml, SD: 3,906 and correlated with hsCRP, esRAGE, AOPP, dialysis vintage and phosphorus in univariate analysis. In multiple regression analysis, hsCRP, AOPP and phosphorus but not esRAGE were all significantly correlated to FGF-23 (R2 = 0.7, p 2 = 0.65, p Conclusion: FGF-23 is strongly correlated to various markers of inflammation and oxidative stress in hemodialysis patients. The association between FGF-23 and vascular calcification was mitigated when corrected for inflammation markers.

  16. Advanced glycation end products induce human corneal epithelial cells apoptosis through generation of reactive oxygen species and activation of JNK and p38 MAPK pathways.

    Directory of Open Access Journals (Sweden)

    Long Shi

    Full Text Available Advanced Glycation End Products (AGEs has been implicated in the progression of diabetic keratopathy. However, details regarding their function are not well understood. In the present study, we investigated the effects of intracellular reactive oxygen species (ROS and JNK, p38 MAPK on AGE-modified bovine serum albumin (BSA induced Human telomerase-immortalized corneal epithelial cells (HUCLs apoptosis. We found that AGE-BSA induced HUCLs apoptosis and increased Bax protein expression, decreased Bcl-2 protein expression. AGE-BSA also induced the expression of receptor for advanced glycation end product (RAGE. AGE-BSA-RAGE interaction induced intracellular ROS generation through activated NADPH oxidase and increased the phosphorylation of p47phox. AGE-BSA induced HUCLs apoptosis was inhibited by pretreatment with NADPH oxidase inhibitors, ROS quencher N-acetylcysteine (NAC or neutralizing anti-RAGE antibodies. We also found that AGE-BSA induced JNK and p38 MAPK phosphorylation. JNK and p38 MAPK inhibitor effectively blocked AGE-BSA-induced HUCLs apoptosis. In addition, NAC completely blocked phosphorylation of JNK and p38 MAPK induced by AGE-BSA. Our results indicate that AGE-BSA induced HUCLs apoptosis through generation of intracellular ROS and activation of JNK and p38 MAPK pathways.

  17. Contribution of the toxic advanced glycation end-productsreceptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun-ichi; Takino; Kentaro; Nagamine; Takamitsu; Hori; Akiko; Sakasai-Sakai; Masayoshi; Takeuchi

    2015-01-01

    Hepatocellular carcinoma(HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus(HCV), and non-hepatitis B/non-hepatitis C HCC(NBNCHCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis(NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products(AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs(TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs(RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC.

  18. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats

    Directory of Open Access Journals (Sweden)

    Mohamed Naguib Zakaria

    2015-01-01

    Full Text Available Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE, AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS complications in STZ-induced (50 mg/kg, IP diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze, neuronal degeneration (Fluoro-Jade staining, AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde. These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications.

  19. Ischemic preconditioning and inflammatory response syndrome after reperfusion injury: an experimental model in diabetic rats.

    Science.gov (United States)

    Grigorescu, Bianca Liana; Georgescu, Anca Meda; Cioc, Adrian-Dan; Fodor, Raluca-Ştefania; Cotoi, Ovidiu Simion; Fodor, Pal; Copotoiu, Sanda Maria; Azamfirei, Leonard

    2015-01-01

    Quantification of local ischemia and inflammatory response syndrome correlated with histological changes associated with ischemia-reperfusion injury (IRI) after revascularization techniques. We included 12 adult male Wistar rats, aged eight weeks that were randomly divided into two groups. The first group acted as the control and at the second group, we induced diabetes by intraperitoneal streptozotocin administration (60 mg/kg). After eight weeks, the rats were subject to ischemic preconditioning for 10 minutes at three regular intervals. Twenty-four hours post-preconditioning, both groups were subject to ischemia for 20 minutes, followed by 30 minutes of reperfusion. Oxygen extraction was higher in Group 1, the arterio-venous CO2 gradient was higher in the control group, but not significant. The lactate production was higher in Group 1. The second group had a higher Na+ and also a significant difference in K+ values. Receptor for Advanced Glycation End (RAGE) values were higher in the second group but with no significant difference (RAGE1=0.32 ng/mL versus RAGE2=0.40 ng/mL). The muscle samples from the control group displayed significant rhabdomyolysis, damage to the nucleus, while the preconditioned group showed almost normal morphological characteristics. The lungs and kidneys were most damaged in the control group, with damage expressed as thickened alveolar septa, neutrophil infiltrates, eosinophilic precipitates in the proximal convolute tubule. Ischemic preconditioning significantly attenuates the ischemic reperfusion injury. PMID:26743274

  20. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats.

    Science.gov (United States)

    Zakaria, Mohamed Naguib; El-Bassossy, Hany M; Barakat, Waleed

    2015-01-01

    Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs) is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE), AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE) and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS) complications in STZ-induced (50 mg/kg, IP) diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze), neuronal degeneration (Fluoro-Jade staining), AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde). These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications. PMID:26491434

  1. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    International Nuclear Information System (INIS)

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration

  2. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xufang, E-mail: xufang.zhang@student.qut.edu.au [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Jiang, Hongwei, E-mail: jianghw@163.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Gong, Qimei, E-mail: gongqmei@gmail.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Fan, Chen, E-mail: c3.fan@student.qut.edu.au [Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Huang, Yihua, E-mail: enu0701@163.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Ling, Junqi, E-mail: lingjq@mail.sysu.edu.cn [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China)

    2014-08-08

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration.

  3. 血清可溶性晚期糖基化终产物受体水平与系统性红斑狼疮疾病活动度的相关性%Association between Serum Levels of Soluble Receptor for Advanced Glycation End-products and Disease Activity of Systemic Lupus Erythematosus

    Institute of Scientific and Technical Information of China (English)

    菅夏楠; 郑朝晖; 于若寒; 刘升云; 刘章锁

    2015-01-01

    Objective The aim of our study was to investigate the value of serum soluble receptor for advanced glycation (sRAGE)levels in the estimation of disease activity of systemic lupus erythematosus (SLE). Methods 104 patients who suffered from SLE and who had been treated in our hospital from June 2013 to June 2014 were included into our study.Clinical and epidemiological data were collected.Results The concentration of sRAGE in the SLE group,the non-active SLE group,active SLE group,and the control group were (1 060.16 ±762.59),(912.06 ±759.98),(1 232.96 ±736.16),and(1 300.42 ±466.01) pg/ml respectively,so the difference was statistically significant (Z = -2.891,P =0.004 ).The difference was statistically significant among the non-active SLE group,active SLE group,and the control group (χ2 =17.999,P =0.000).There was higher serum sRAGE levels in patients whose SLE disease activity index(SLEDAI)≥10 (Z =-3.052,P =0.002)and whose titer of anti-dsDNA antibody≥100 (Z =-2.276,P =0.023),and there was positive correlation between serum sRAGE levels and SLEDAI≥10(r =0.373,P =0.000),the difference was statistically significant.Conclusion We can evaluate disease activity of SLE by detecting the serum sRAGE levels,which may provide information to guide the treatment.%目的:探讨可溶性晚期糖基化终产物受体(soluble receptor for advanced glycation end-products,sRAGE)在系统性红斑狼疮(systemic lupus erythematosus,SLE)疾病活动度评价中的价值。方法收集2013年6月至2014年6月郑州大学第一附属医院 SLE 患者的临床及流行病学资料,观察血清 sRAGE 浓度与 SLE 疾病活动度的相关性。结果 SLE 组、非活动SLE 组、活动 SLE 组和健康对照组 sRAGE 浓度分别为(1060.16±762.59)、(912.06±759.98)、(1232.96±736.16)、(1300.42±466.01)pg/ml;SLE 组与健康对照组 sRAGE 浓度差异有统计学意义(Z =-2.891,P =0.004),非活动 SLE

  4. [Glycotoxins and cellular dysfunction. A new mechanism for understanding the preventive effects of lifestyle modifications].

    Science.gov (United States)

    Michalsen, A; Bierhaus, A; Nawroth, P P; Dobos, G J

    2006-08-01

    Recently the AGE-RAGE interaction was identified as a potential mechanism underlying chronic and inflammatory diseases like atherosclerosis, diabetes mellitus and kidney disease. Advanced glycation end products (AGEs) are the derivatives of glucose-protein or glucose-lipid reactions and are mainly generated from the diet (depending on intensity of heating, cooking time and oxygenation). Binding of AGEs or other ligands to the AGE receptor (RAGE) results in cellular activation, i.e. increased expression of inflammatory mediators and oxidative stress. Diet-derived AGEs thus induce deleterious effects on tissues and the cardiovascular system. Recent research also found that other lifestyle factors are associated with pronounced inflammatory activation, e.g. psychosocial stress and smoking. In addition, each intake of meals is associated with proinflammatory cellular changes. The AGE-RAGE model and investigations of the underlying cellular mechanisms thus may lead to a better understanding of the health benefits of diets (Mediterranean diet, uncooked vegetarian diets), caloric restriction and intermittent fasting. The clinical impact of low-AGE diets and fasting and the interaction between stress and food intake should be further investigated in controlled trials.

  5. [Glycotoxins and cellular dysfunction. A new mechanism for understanding the preventive effects of lifestyle modifications].

    Science.gov (United States)

    Michalsen, A; Bierhaus, A; Nawroth, P P; Dobos, G J

    2006-08-01

    Recently the AGE-RAGE interaction was identified as a potential mechanism underlying chronic and inflammatory diseases like atherosclerosis, diabetes mellitus and kidney disease. Advanced glycation end products (AGEs) are the derivatives of glucose-protein or glucose-lipid reactions and are mainly generated from the diet (depending on intensity of heating, cooking time and oxygenation). Binding of AGEs or other ligands to the AGE receptor (RAGE) results in cellular activation, i.e. increased expression of inflammatory mediators and oxidative stress. Diet-derived AGEs thus induce deleterious effects on tissues and the cardiovascular system. Recent research also found that other lifestyle factors are associated with pronounced inflammatory activation, e.g. psychosocial stress and smoking. In addition, each intake of meals is associated with proinflammatory cellular changes. The AGE-RAGE model and investigations of the underlying cellular mechanisms thus may lead to a better understanding of the health benefits of diets (Mediterranean diet, uncooked vegetarian diets), caloric restriction and intermittent fasting. The clinical impact of low-AGE diets and fasting and the interaction between stress and food intake should be further investigated in controlled trials. PMID:16897151

  6. Effect of KIOM-79 on Diabetes-Induced Myocardial Fibrosis in Zucker Diabetic Fatty Rats

    Directory of Open Access Journals (Sweden)

    Junghyun Kim

    2013-01-01

    Full Text Available KIOM-79, a herbal mixture of parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix, and Euphorbiae radix, has a strong inhibitory effect on advanced glycation end products (AGEs formation. We investigated the beneficial effects of KIOM-79 on cardiac fibrosis in Zucker diabetic fatty (ZDF rats. KIOM-79 (50 or 500 mg/kg/day was orally administered for 13 weeks. AGEs formation and collagen expression in the myocardium were assessed by immunohistochemistry. The expression levels of the receptor for AGEs (RAGE, transforming growth factor-β1 (TGF-β1, collagen IV, fibronectin, urotensin II, and urotensin II receptor were examined in the myocardial tissue of ZDF rats. KIOM-79 treatment at 500 mg/kg inhibited the accumulation of AGEs, reduced RAGE mRNA and protein expression, and reduced the upregulation of cardiac fibrogenic factors, such as fibronectin and collagen IV, in heart of ZDF rats. Additionally, KIOM-79 ameliorated urotensin II/receptor gene expression in the cardiac tissue of ZDF rats. Our findings indicate that KIOM-79 diminishes cardiac fibrosis in ZDF rats by preventing AGEs accumulation and RAGE overexpression and by modulating the cardiac urotensin II/receptor pathway, which decreases the amount of profibrotic factors, such as TGF-β1, fibronectin, and collagen in cardiac tissue.

  7. Low levels of amyloid-beta and its transporters in neonatal rats with and without hydrocephalus

    Directory of Open Access Journals (Sweden)

    Silverberg Gerald D

    2009-05-01

    Full Text Available Abstract Background Previous studies in aging animals have shown that amyloid-beta protein (Aβ accumulates and its transporters, low-density lipoprotein receptor-related protein-1 (LRP-1 and the receptor for advanced glycation end products (RAGE are impaired during hydrocephalus. Furthermore, correlations between astrocytes and Aβ have been found in human cases of normal pressure hydrocephalus (NPH and Alzheimer's disease (AD. Because hydrocephalus occurs frequently in children, we evaluated the expression of Aβ and its transporters and reactive astrocytosis in animals with neonatal hydrocephalus. Methods Hydrocephalus was induced in neonatal rats by intracisternal kaolin injections on post-natal day one, and severe ventriculomegaly developed over a three week period. MRI was performed on post-kaolin days 10 and 21 to document ventriculomegaly. Animals were sacrificed on post-kaolin day 21. For an age-related comparison, tissue was used from previous studies when hydrocephalus was induced in a group of adult animals at either 6 months or 12 months of age. Tissue was processed for immunohistochemistry to visualize LRP-1, RAGE, Aβ, and glial fibrillary acidic protein (GFAP and with quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR to quantify expression of LRP-1, RAGE, and GFAP. Results When 21-day post-kaolin neonatal hydrocephalic animals were compared to adult (6–12 month old hydrocephalic animals, immunohistochemistry demonstrated levels of Aβ, RAGE, and LRP-1 that were substantially lower in the younger animals; in contrast, GFAP levels were elevated in both young and old hydrocephalic animals. When the neonatal hydrocephalic animals were compared to age-matched controls, qRT-PCR demonstrated no significant changes in Aβ, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP

  8. Advanced glycation end products promote differentiation of CD4(+) T helper cells toward pro-inflammatory response.

    Science.gov (United States)

    Han, Xiao-qun; Gong, Zuo-jiong; Xu, San-qing; Li, Xun; Wang, Li-kun; Wu, Shi-min; Wu, Jian-hong; Yang, Hua-fen

    2014-02-01

    This study investigated the effect of advanced glycation end products (AGEs) on differentiation of naïve CD4(+) T cells and the role of the receptor of AGEs (RAGE) and peroxisome proliferator-activated receptors (PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin (BSA) with glucose. Human naïve CD4(+) T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin (sh) RNA knock-down experiment, naïve CD4(+) T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-X(TM) 293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4(+) T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T (Treg) cells was determined by a [(3)H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from naïve CD4(+) T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in naïve CD4(+) T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4(+) T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα PPARγ agonist, PGJ2, inhibited the effect of AGEs on naïve CD4(+) T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It

  9. Advancements in web-database applications for rabies surveillance

    Directory of Open Access Journals (Sweden)

    Bélanger Denise

    2011-08-01

    Full Text Available Abstract Background Protection of public health from rabies is informed by the analysis of surveillance data from human and animal populations. In Canada, public health, agricultural and wildlife agencies at the provincial and federal level are responsible for rabies disease control, and this has led to multiple agency-specific data repositories. Aggregation of agency-specific data into one database application would enable more comprehensive data analyses and effective communication among participating agencies. In Québec, RageDB was developed to house surveillance data for the raccoon rabies variant, representing the next generation in web-based database applications that provide a key resource for the protection of public health. Results RageDB incorporates data from, and grants access to, all agencies responsible for the surveillance of raccoon rabies in Québec. Technological advancements of RageDB to rabies surveillance databases include 1 automatic integration of multi-agency data and diagnostic results on a daily basis; 2 a web-based data editing interface that enables authorized users to add, edit and extract data; and 3 an interactive dashboard to help visualize data simply and efficiently, in table, chart, and cartographic formats. Furthermore, RageDB stores data from citizens who voluntarily report sightings of rabies suspect animals. We also discuss how sightings data can indicate public perception to the risk of racoon rabies and thus aid in directing the allocation of disease control resources for protecting public health. Conclusions RageDB provides an example in the evolution of spatio-temporal database applications for the storage, analysis and communication of disease surveillance data. The database was fast and inexpensive to develop by using open-source technologies, simple and efficient design strategies, and shared web hosting. The database increases communication among agencies collaborating to protect human health from

  10. The Clinical Significances of Soluble Receptor for Advanced Glycation Endproducts in Bronchoscopy Alveolus Lavage Fluid among Patients with COPD%COPD纤维支气管镜肺泡灌洗液中可溶性晚期糖基化终末产物受体水平的临床意义

    Institute of Scientific and Technical Information of China (English)

    杨兴官; 雷超; 胡占升

    2014-01-01

    Objective To discuss the clinical significances of soluble receptor for advanced glycation end-products ( sRAGE)in bronchoscopy alveolus lavage fluid( BALF)in patients with COPD. Methods A total of 40 patients with COPD who were admitted to the department of intensive care unit of the First Hospital Affiliated to Liaoning Medical University from Oc-tober 2012 to May 2013,were selected as the COPD group,meanwhile 40 patients with non-COPD were selected as the non-COPD group,and these COPD patients were divided into mild group(12 cases),moderate group(10 cases),severe group (10 cases),very severe group(8 cases). The sRAGE concentrations in BALF were detected by enzyme-linked immunosor-bent assay(ELISA). Results The concentration of sRAGE in BALF of patients in the COPD group(191 ±71)ng/L was sig-nificantly higher than that in the non-COPD group(55 ±56)ng/L(t=9. 44,P<0. 001). The concentration of sRAGE in BALF of COPD patients in the mild group,moderate group,severe group and very severe group was(111 ± 44) ng/L,(184 ±45)ng/L,(226 ±34)ng/L,and(273 ±30)ng/L,respectively,there were significant differences in concentration of sRAGE among these groups(F=30. 48,P<0. 001),and the concentration of sRAGE in very severe COPD group was signifi-cantly higher than that in severe COPD group,the concentration of sRAGE in severe COPD group was significantly higher than that in moderate group,the concentration of sRAGE in moderate group was significantly higher than that in mild group( P <0. 05 ) . Linear correlation analysis results showed that the concentration of sRAGE in BALF of COPD patients were negatively cor-related with FEV1%(r= -0. 738,P <0. 05). Conclusion The concentration of sRAGE in BALF of COPD patients was higher than that of non-COPD patients;The concentration of sRAGE in BALF is related to severity of COPD,it could be used as an index of the prognosis evaluation of COPD.%目的:探讨纤维支气管镜肺泡灌洗液中可溶性晚期

  11. 黄连多糖对AGEs诱导内皮细胞增殖及其受体表达的作用研究%Effects of Polysaccharides from Coptis Chinensis on HUVECs Proliferation Induced by Advanced Glycation Endproducts and Expression of Its Receptor

    Institute of Scientific and Technical Information of China (English)

    尹登科; 杨晔; 陈松; 李云; 高向东

    2012-01-01

    To study the effects of Coptis Chinensis polysaccharide (CCP) on HUVECs proliferation induced by advanced glycation endproducts(AGEs) and the expression of the receptor for AGEs(RAGE) ,the total CCP was prepared by water extraction, depro-teinized by method of sevag,and alcohol precipitation. HUVECs with 80% confluent were divided into six groups as control (without treatment) ,BSA group ( 200 μg /mL) , AGEs group(200 μg/mL, protein concentration) , AGEs + CCP(25 μg/mL) , AGEs + CCP (50 μg/mL) and AGEs + CCP ( 100 μg/mL) , The proliferation of HUVECs was determined by the method of MTT, Real Time Quantitative Fluorescence RCR was used to analyze the expression of RAGE rnRNA and Western Blot was used to detect the expression of RAGE, The proliferation of HUVECs was increased after treatment with AGEs for 48 h, CCP significantly inhibited the pro-proliferation of HUVECs induced by AGEs in dose-dependent manner. The results of PCR and Western Blot also demonstrated that CCP could decrease the expression of RAGE mRNA and protein. CCP inhibited the activation of HUVECs induced by AGEs through inhibiting the expression of RAGE.%考察黄连多糖对高级糖基化终产物(AGEs)诱导人脐静脉内皮细胞(HUVECs)增殖和AGEs受体(RAGE)表达的作用.采用水提,Sevag法去蛋白,醇沉法获得黄连多糖(CCP);80%汇聚的HUVECs分成6组,分别为空白对照组、BSA对照组(蛋白浓度200μg/mL)、AGEs组(蛋白浓度200μg/mL)、AGEs+ CCP(25μg/mL)、AGEs+ CCP(50 μg/mL)和AGEs+ CCP(100μg/mL),采用MTT法检测黄连多糖对AGEs诱导HUVECs增殖的影响;实时荧光定量PCR检测RAGE mRNA表达;Westem Blot分析RAGE蛋白表达情况.HUVECs经AGEs诱导48h后,其增殖率显著增殖.黄连多糖可以剂量依赖性的抑制AGEs诱导HUVECs早期增殖作用,定量PCR和Western Blot结果表明CCP可以在mRNA和蛋白水平抑制RAGE表达.黄连多糖可通过抑制RAGE表达,降低AGEs对内皮细胞的激活作用.

  12. Advanced glycation end-product expression is upregulatedin the gastrointestinal tract of type 2 diabetic rats

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM: To investigate changes in advanced glycation endproducts (AGEs) and their receptor (RAGE) expressionin the gastrointestinal (GI) tract in type 2 diabetic rats.METHODS: Eight inherited type 2 diabetic rats Goto-Kakizak (GK) and ten age-matched normal rats wereused in the study. From 18 wk of age, the body weightand blood glucose were measured every week and 2wk respectively. When the rats reached 32 wk, twocentimetersegments of esophagus, duodenum,jejunum, ileum, and colon were excised and the wetweight was measured. The segments were fixedin 10% formalin, embedded in paraffin and fivemicron sections were cut. The layer thickness wasmeasured in Hematoxylin and Eosin-stained slides.AGE [N epsilon-(carboxymethyl) lysine and N epsilon-(carboxyethyl)lysine] and RAGE were detected byimmunohistochemistry staining and image analysis wasdone using Sigmascan Pro 4.0 image analysis software.RESULTS: The blood glucose concentration (mmol/L)at 18 wk age was highest in the GK group (8.88 ±1.87 vs 6.90 ± 0.43, P 〈 0.001), a difference thatcontinued to exist until the end of the experiment.The wet weight per unit length (mg/cm) increased inesophagus, jejunum and colon from the normal to theGK group (60.64 ± 9.96 vs 68.56 ± 11.69, P 〈 0.05 foresophagus; 87.01 ± 9.35 vs 105.29 ± 15.45, P 〈 0.01for jejunum; 91.37 ± 7.25 vs 97.28 ± 10.90, P 〈 0.05for colon). Histologically, the layer thickness of the GI tract was higher for esophagus, jejunum and colon inthe GK group [full thickness (μm): 575.37 ± 69.22 vs753.20 ± 150.41, P 〈 0.01 for esophagus; 813.51 ±44.44 vs 884.81 ± 45.31, P 〈 0.05 for jejunum; 467.12± 65.92 vs 572.26 ± 93.60, P 〈 0.05 for colon]. Inesophagus, the AGE and RAGE mainly distributed instriated muscle cells and squamous epithelial cells. TheAGE distribution was much stronger in the GK groupcompared to the normal group both in the striatedmuscle layer and mucosa layer

  13. Advanced glycation end products accelerate ischemia/reperfusion injury through receptor of advanced end product/nitrative thioredoxin inactivation in cardiac microvascular endothelial cells.

    Science.gov (United States)

    Liu, Yi; Ma, Yanzhuo; Wang, Rutao; Xia, Chenhai; Zhang, Rongqing; Lian, Kun; Luan, Ronghua; Sun, Lu; Yang, Lu; Lau, Wayne B; Wang, Haichang; Tao, Ling

    2011-10-01

    The advanced glycation end products (AGEs) are associated with increased cardiac endothelial injury. However, no causative link has been established between increased AGEs and enhanced endothelial injury after ischemia/reperfusion. More importantly, the molecular mechanisms by which AGEs may increase endothelial injury remain unknown. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and incubated with AGE-modified bovine serum albumin (BSA) or BSA. After AGE-BSA or BSA preculture, CMECs were subjected to simulated ischemia (SI)/reperfusion (R). AGE-BSA increased SI/R injury as evidenced by enhanced lactate dehydrogenase release and caspase-3 activity. Moreover, AGE-BSA significantly increased SI/R-induced oxidative/nitrative stress in CMECs (as measured by increased inducible nitric oxide synthase expression, total nitric oxide production, superoxide generation, and peroxynitrite formation) and increased SI/R-induced nitrative inactivation of thioredoxin-1 (Trx-1), an essential cytoprotective molecule. Supplementation of EUK134 (peroxynitrite decomposition catalyst), human Trx-1, or soluble receptor of advanced end product (sRAGE) (a RAGE decoy) in AGE-BSA precultured cells attenuated SI/R-induced oxidative/nitrative stress, reduced SI/R-induced Trx-1 nitration, preserved Trx-1 activity, and reduced SI/R injury. Our results demonstrated that AGEs may increase SI/R-induced endothelial injury by increasing oxidative/nitrative injury and subsequent nitrative inactivation of Trx-1. Interventions blocking RAGE signaling or restoring Trx activity may be novel therapies to mitigate endothelial ischemia/reperfusion injury in the diabetic population.

  14. Advanced glycation end products and the progressive course of renal disease.

    Science.gov (United States)

    Heidland, A; Sebekova, K; Schinzel, R

    2001-10-01

    In experimental and human diabetic nephropathy (DN), it has been shown that advanced glycation end products (AGEs), in particular, carboxymethyl-lysine and pentosidine, accumulate with malondialdehyde in glomerular lesions in relation to disease severity and in the presence of an upregulated receptor for AGE (RAGE) in podocytes. Toxic effects of AGEs result from structural and functional alterations in plasma and extracellular matrix (ECM) proteins, in particular, from cross-linking of proteins and interaction of AGEs with their receptors and/or binding proteins. In mesangial and endothelial cells, the AGE-RAGE interaction caused enhanced formation of oxygen radicals with subsequent activation of nuclear factor-kappaB and release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha), growth factors (transforming growth factor-beta1 [TGF-beta1], insulin-like growth factor-1), and adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1). In tubular cells, incubation with AGE albumin was followed by stimulation of the mitogen-activating protein (MAP) kinase pathway and its downstream target, the activating protien-1 (AP-1) complex, TGF-beta1 overexpression, enhanced protein kinase C activity, decreased cell proliferation, and impaired protein degradation rate, in part caused by decreased cathepsin activities. The pathogenic relevance of AGEs was further verified by in vivo experiments in euglycemic rats and mice by the parenteral administration of AGE albumin, leading in the glomeruli to TGF-beta1 overproduction, enhanced gene expression of ECM proteins, and morphological lesions similar to those of DN. Evidence for the pathogenic relevance of AGEs in DN also comes from experimental studies in which the formation and/or action of AGEs was modulated by aminoguanidine, OPB-9195, pyridoxamine, soluble RAGEs, serine protease trypsin, and antioxidants, resulting in improved cell and/or renal function.

  15. High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

    International Nuclear Information System (INIS)

    The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures. (orig.)

  16. Effect of advanced oxidation protein products on the proliferation and osteogenic differentiation of rat mesenchymal stem cells.

    Science.gov (United States)

    Sun, Nan; Yang, Li; Li, Yingbin; Zhang, Hua; Chen, Hong; Liu, Duan; Li, Qingnan; Cai, Dehong

    2013-08-01

    Advanced oxidation protein products (AOPPs) as a novel marker of oxidative stress, are involved in a variety of diseases, including osteoporosis. Although a number of studies have shown the possible functions of AOPPs in biological processes, little is known about the role of AOPPs in the pathogenesis of osteoporosis. In this study, we aimed to investigate the effect of AOPPs on the proliferation and osteogenic differentiation of rat mesenchymal stem cells (MSCs). MSCs, isolated from bone marrow, were cultured in the absence or presence of AOPPs (50, 100, 200 and 400 mg/ml). MTT assay was used to determine the proliferative ability of the cells. Alkaline phosphatase (ALP) activity, the mRNA expression of ALP and collagen I and bone nodule formation were detected to assess osteogenic differentiation. Reactive oxygen species (ROS) generation was analyzed with the probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The expression of receptor of advanced glycation end-products (RAGE) at the mRNA and protein level was detected by real-time PCR and western blot analysis, respectively. Compared with the control group, AOPPs inhibited MSC proliferation in a dose- and time-dependent manner. Moreover, AOPPs induced a significant reduction in ALP activity, as well as a decrease in ALP and collagen I mRNA levels in the MSCs; bone nodule formation was also inhibited. Furthermore, AOPPs increased ROS generation in the MSCs, and upregulated the expression of RAGE at the mRNA and protein level. These results suggest that AOPPs inhibit the proliferation and osteogenic differentiation of MSCs, possibly through the AOPPs-RAGE-ROS pathway; this may be an important mechanism in the development of osteoporosis.

  17. S100B as a Potential Biomarker and Therapeutic Target in Multiple Sclerosis.

    Science.gov (United States)

    Barateiro, Andreia; Afonso, Vera; Santos, Gisela; Cerqueira, João José; Brites, Dora; van Horssen, Jack; Fernandes, Adelaide

    2016-08-01

    Multiple sclerosis (MS) pathology is characterized by neuroinflammation and demyelination. Recently, the inflammatory molecule S100B was identified in cerebrospinal fluid (CSF) and serum of MS patients. Although seen as an astrogliosis marker, lower/physiological levels of S100B are involved in oligodendrocyte differentiation/maturation. Nevertheless, increased S100B levels released upon injury may induce glial reactivity and oligodendrocyte demise, exacerbating tissue damage during an MS episode or delaying the following remyelination. Here, we aimed to unravel the functional role of S100B in the pathogenesis of MS. Elevated S100B levels were detected in the CSF of relapsing-remitting MS patients at diagnosis. Active demyelinating MS lesions showed increased expression of S100B and its receptor, the receptor for advanced glycation end products (RAGE), in the lesion area, while chronic active lesions displayed increased S100B in demyelinated areas with lower expression of RAGE in the rim. Interestingly, reactive astrocytes were identified as the predominant cellular source of S100B, whereas RAGE was expressed by activated microglia/macrophages. Using an ex vivo demyelinating model, cerebral organotypic slice cultures treated with lysophosphatidylcholine (LPC), we observed a marked elevation of S100B upon demyelination, which co-localized mostly with astrocytes. Inhibition of S100B action using a directed antibody reduced LPC-induced demyelination, prevented astrocyte reactivity and abrogated the expression of inflammatory and inflammasome-related molecules. Overall, high S100B expression in MS patient samples suggests its usefulness as a diagnostic biomarker for MS, while the beneficial outcome of its inhibition in our demyelinating model indicates S100B as an emerging therapeutic target in MS. PMID:26184632

  18. Interaction between S100P and the anti-allergy drug cromolyn

    Energy Technology Data Exchange (ETDEWEB)

    Penumutchu, Srinivasa R. [Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Chou, Ruey-Hwang [Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China); Yu, Chin, E-mail: cyu.nthu@gmail.com [Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan (China); The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005 (China)

    2014-11-21

    Highlights: • The interaction between S100P–cromolyn was investigated by fluorescence spectroscopy. • The interfacial residues on S100P and cromolyn contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • S100P–cromolyn complex model was generated from NMR restraints using HADDOCK program. • The stability of the S100P–cromolyn complex was studied using molecular dynamics simulations. - Abstract: The S100P protein has been known to mediate cell proliferation by binding the receptor for advanced glycation end products (RAGE) to activate signaling pathways, such as the extracellular regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. S100P/RAGE signaling is involved in a variety of diseases, such as cancer, metastasis, and diabetes. Cromolyn is an anti-allergy drug that binds S100P to block the interaction between S100P and RAGE. In the present study, we characterized the properties of the binding between cromolyn and calcium-bound S100P using various biophysical techniques. The binding affinity for S100P and cromolyn was measured to be in the millimolar range by fluorescence spectroscopy. NMR-HSQC titration experiments and HADDOCK modeling was employed to determine the spatial structure of the proposed heterotetramer model of the S100P–cromolyn complex. Additional MD simulation results revealed the important properties in the complex stability and conformational flexibility of the S100P–cromolyn complex. This proposed model has provided an understanding of the molecular level interactions of S100P–cromolyn complex.

  19. A Study on Affective Cognition of Children with Different Aggression/Victim Groups%不同攻击/受欺儿童的情感认知特征研究

    Institute of Scientific and Technical Information of China (English)

    李亚真; 桑标

    2012-01-01

    The study made an inquiry on affective cognition differences among different aggression/victim groups, with five kinds of emotions as cheer, rage, sad, fear and awkward mood, including three indices such as facial expression recognition, affective attribution and sensitivity to affective perception. The results indicated that scores of non-involved children's were the best or second best. There were specific characteristics in sad and rage affective cognition of pure aggressive children and victims' The overal perfor- mance of aggressive victim children was poor, especially their sensitivity to affective perception was the worst. In addition, they consistently had low level of fear and rage affective cognition in facial expression recognition, affective attribution.%本研究以喜怒哀惧尴五种情绪为代表,从表情识别、情绪归因能力、情感觉知敏感性三个方面考察不同攻击/受欺类型儿童的情感认知特征。结果表明:未卷入儿童在各类情绪的表情识别、归因和觉知上都是次高或最高的;单纯攻击和受欺负儿童对愤怒和悲伤的情感认知呈现特殊性;攻击—受欺儿童的情感认知整体表现较差,尤其是该群体的情感觉知敏感性最差,在表情识别和情绪归因上则一致地表现出对愤怒和害怕情感的低水平认知。

  20. High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

    Energy Technology Data Exchange (ETDEWEB)

    Gizewski, Elke R. [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Maderwald, Stefan [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Linn, Jennifer; Bochmann, Katja [LMU Munich, Department of Neuroradiology, Munich (Germany); Dassinger, Benjamin [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Justus-Liebig-University Giessen, Department of Neuroradiology, Giessen (Germany); Forsting, Michael [University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Ladd, Mark E. [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany)

    2014-03-15

    The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures. (orig.)

  1. Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain β-amyloid through PPARY activation

    Institute of Scientific and Technical Information of China (English)

    Li-ping LIU; Tian-hua YAN; Li-ying JIANG; Wei HU; Meng HU; Chao WANG; Qian ZHANG

    2013-01-01

    Aim:To examine the effects of pioglitazone,a PPARY agonist,on memory performance and brain amyloidogenesis in streptozotocin (STZ)-induced diabetic mice.Methods:ICR male mice were injected with STZ (150 mg/kg,iv) to induce experimental diabetes.Pioglitazone (9 and 18 mg·kg1-d-1,po) was administered for 6 weeks.Passive avoidance and Morris water maze (MWM) tests were used to evaluate cognitive function.The blood glucose and serum insulin levels were detected using the glucose oxidase method and an ELISA assay,respectively.β-amyloid (Aβ),β-amyloid precursor protein (APP),β-amyloid precursor protein cleaving enzyme 1 (BACE1),NF-κB p65,the receptor for advanced glycation end products (RAGE) and PPARy in the brains were analyzed using Western blotting assays.Results:The STZ-induced diabetic mice characterized by hyperglycemia and hypoinsulinemia performed poorly in both the passive avoidance and MWM tests,accompanied by increased Aβ1-40/Aβ1-42,APP,BACE1,NF-κB p65 and RAGE levels and decreased PPARy level in the hippocampus and cortex.Chronic pioglitazone treatment significantly ameliorated the memory deficits of STZ-induced diabetic mice,and suppressed expression of APP,BACE1,RAGE and NF-κB p65,and activated PPARy in the hippocampus and cortex.However,pioglitazone did not significantly affect blood glucose and insulin levels.Conclusion:Pioglitazone ameliorates memory deficits in STZ-induced diabetic mice by reducing brain Aβ level via activation of PPARy,which is independent of its effects on blood glucose and insulin levels.The results suggest that pioglitazone may be used for treating the cognitive dysfunction in type 1 diabetes mellitus.

  2. Glucagon-like peptide-1 counteracts the detrimental effects of Advanced Glycation End-Products in the pancreatic beta cell line HIT-T 15

    Energy Technology Data Exchange (ETDEWEB)

    Puddu, A., E-mail: alep100@hotmail.com [University of Genova, Department of Internal Medicine and Medical Specialties, Viale Benedetto XV, 16132 Genova (Italy); Storace, D.; Durante, A.; Odetti, P.; Viviani, G.L. [University of Genova, Department of Internal Medicine and Medical Specialties, Viale Benedetto XV, 16132 Genova (Italy)

    2010-07-30

    Research highlights: {yields} GLP-1 prevents AGEs-induced cell death. {yields} GLP-1 prevents AGEs-induced oxidative stress. {yields} GLP-1 ameliorated AGEs-induced cell dysfunction. {yields} GLP-1 attenuates AGEs-induced RAGE increment. {yields} GLP-1 counteracts AGEs-induced pancreatic cell death and dysfunction. -- Abstract: Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases proinsulin biosynthesis, stimulates insulin secretion, and improves pancreatic beta-cell viability. The aim of this work was to investigate the effects of GLP-1 on the function and viability of HIT-T 15 cells cultured with AGEs. HIT-T 15 cells were cultured for 5 days in presence of AGEs alone, or supplemented with 10 nmol/l GLP-1. Cell viability, insulin secretion, redox balance, and expression of the AGEs receptor (RAGE) were then determined. The results showed that GLP-1 protected beta cell against AGEs-induced cell death preventing both apoptosis and necrosis. Moreover, addition of GLP-1 to the AGEs culture medium restored the redox balance, improved the responsiveness to glucose, and attenuated AGEs-induced RAGE expression. These findings provide evidence that GLP-1 protects beta cells from the dangerous effects of AGEs.

  3. Glucagon-like peptide-1 counteracts the detrimental effects of Advanced Glycation End-Products in the pancreatic beta cell line HIT-T 15

    International Nuclear Information System (INIS)

    Research highlights: → GLP-1 prevents AGEs-induced cell death. → GLP-1 prevents AGEs-induced oxidative stress. → GLP-1 ameliorated AGEs-induced cell dysfunction. → GLP-1 attenuates AGEs-induced RAGE increment. → GLP-1 counteracts AGEs-induced pancreatic cell death and dysfunction. -- Abstract: Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases proinsulin biosynthesis, stimulates insulin secretion, and improves pancreatic beta-cell viability. The aim of this work was to investigate the effects of GLP-1 on the function and viability of HIT-T 15 cells cultured with AGEs. HIT-T 15 cells were cultured for 5 days in presence of AGEs alone, or supplemented with 10 nmol/l GLP-1. Cell viability, insulin secretion, redox balance, and expression of the AGEs receptor (RAGE) were then determined. The results showed that GLP-1 protected beta cell against AGEs-induced cell death preventing both apoptosis and necrosis. Moreover, addition of GLP-1 to the AGEs culture medium restored the redox balance, improved the responsiveness to glucose, and attenuated AGEs-induced RAGE expression. These findings provide evidence that GLP-1 protects beta cells from the dangerous effects of AGEs.

  4. Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilator-associated pneumonia: a retrospective observational study

    Directory of Open Access Journals (Sweden)

    Lutter Rene

    2009-12-01

    Full Text Available Abstract Background Despite consensus criteria, diagnosing acute lung injury, or its more severe form acute respiratory distress syndrome (ALI/ARDS remains challenging. Adding objective measures, such as plasma levels of biological markers could facilitate recognition of ALI/ARDS. This study was designed to assess and compare the diagnostic accuracy of biological markers for ALI/ARDS with ventilator-associated pneumonia (VAP. Methods We performed serial measurements of Clara cell protein (CC16, soluble receptor for advanced glycation end products (sRAGE, surfactant protein D (SP-D and Krebs von den Lungen (KL-6 in plasma of patients with VAP and mechanically ventilated control patients without VAP. ALI/ARDS was diagnosed using the criteria of the North-American European consensus conference. Results Thirty-seven patients were enrolled - 22 patients with VAP and 15 control patients. Ten patients with pneumonia met the ALI/ARDS consensus criteria. Control patients never met these criteria. Plasma CC16 had a good diagnostic capacity for ALI/ARDS as shown by the receiver operating characteristic curve with an area under the curve of 0.91 (95% confidence interval (CI 0.79 - 1.00; p p = 0.02. The diagnostic accuracies of KL-6 and sRAGE were low. Conclusion Plasma CC16 seems a potential biological marker for ALI/ARDS in patients with VAP. Plasma levels of sRAGE, SP-D and KL-6 have limited discriminative power for diagnosing ALI/ARDS in VAP.

  5. Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Yii Michael

    2011-09-01

    Full Text Available Abstract Background Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE in men with coronary artery disease. Methods We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction. Results All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E', consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red, or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyllysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis. Conclusions Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the

  6. MicroRNA-218 modulates activities of glioma cells by targeting HMGB1

    Science.gov (United States)

    Gu, Jianjun; Xu, Rong; Li, Yaxing; Zhang, Jianhe; Wang, Shousen

    2016-01-01

    To explore the effects of microRNA-218 (miR-218) on glioma cell lines and the related mechanism. U251 and U87 cells were transfected with negative control, miR-218 mimic or miR-218 inhibitor using lipofectamine 2000. The expressions of mRNA and proteins were detected with qRT-PCR and Western blotting. The cell proliferation, apoptosis, migration and invasion were studied using MTT, flow cytometry, Transwell assay and scratch-wound assay, respectively. The targeting effect of HMGB1 by miR-218 was measured with luciferase reporter assay. The results showed that miR-218 was significantly downregulated while HMGB1 was upregulated in both glioma cell lines. Transfection of miR-218 significantly reduced the cell viability and colony formation, increased cell apoptosis and arrested cell in G0/G1 phase. Transfection of miR-218 also decreased the invasion and migration of glioma cells. The expressions of HMGB1, RAGE, cyclin D1 and MMP-9 were downregulated while the expression of caspase-9 was upregulated by miR-218. Silencing HMGB1 increased the expression of RAGE, cyclin D1, MMP-9 but decreased the expression of caspase-9 in U251 and U87 cells. Co-transfection with pcHMGB1 and miR-218 significantly decreased the growth inhibition and increased the apoptosis of glioma cells while these effects were abolished in glioma cells co-transfected with HMGB1 siRNA and miR-218 inhibitor. In addition, co-transfection with pcHMGB1 and miR-218 inhibitor increased the invasiveness of U251 and U87 cells. These findings suggested that miR-218 may negatively regulate HMGB-mediated suppression of RAGE to regulate cell proliferation, apoptosis and invasion, and that intervention of miR-218-HMGB1-RAGE may be useful for developing potential clinical strategies. PMID:27725858

  7. Expression of receptor for advanced glycation endproducts and nuclear factor κB in brain hippocampus of rat with chronic fluorosis

    Institute of Scientific and Technical Information of China (English)

    张凯琳

    2014-01-01

    Objective To investigate the expressions of receptor for advanced glycation endproducts(RAGE)and nuclear factorκB(NF-κB)in brain hippocampus of rat with chronic fluorosis,and to reveal the mechanism of brain damage resulted from chronic fluorosis.Methods Sixty clean grade SD rats were randomly divided to three groups(20 rats in each group,10 female and 10 male)fed with different contents of fluoride,control group with normal tap-water(<0.5 mg/L fluoride),

  8. Nuclear industry review

    International Nuclear Information System (INIS)

    This review examines the consequences of projected excess electrical generating capacity for the maintenance of an independent nuclear power capability in Canada. Although consumption of electricity will continue to grow at rages well below historical averages, significant additions to capacity will be required in all parts of Canada in the 1990s. CANDU reactors are an attractive option for meeting load growth, particularly east of Manitoba. However, the absence of domestic orders in the 1980s may threaten the maintenance of this option. Even the most optimistic projections indicate that only one supplier of each component will remain in the nuclear business in the 1990s

  9. The objective qualification of non-international armed conflicts: A Colombian case study

    OpenAIRE

    Sebastian Machado; Guillermo Otálora Lozano

    2012-01-01

    Armed conflict has raged in Colombia since at least the 1960’s, involving governmental forces, rebel groups, and paramilitary forces. The Uribe government (2002-2010) declared that Colombia was not in a ‘state of armed conflict’ but was rather facing a ‘terrorist threat’. This declaration was done in fear of conferring a political status to the armed groups, and most particularly, in fear that a recognition of armed conflict would open the possibility of endowing the Revolutionary Ar...

  10. A European Culture War in the Twentieth Century? Antic-Catholicism and Anti-Bolshevism between Moscow, Berlin, and the Vatican 1922 to 1933

    OpenAIRE

    Weir, Todd

    2015-01-01

    The term “culture war” has become a generic expression for secular-catholic conflicts across nineteenth-century Europe. Yet, if measured by acts of violence, anticlericalism peaked in the years between 1927 and 1939, when thousands of Catholic priests and believers were imprisoned or executed and hundreds of churches razed in Mexico, Spain and Russia. This essay argues that not only in these three countries, but indeed across Europe a culture war raged in the interwar period. It takes, as a c...

  11. Eleonora Pasotti, Political branding in cities. The decline of machine politics in Bogotá, Naples, and Chicago

    Directory of Open Access Journals (Sweden)

    Gilles Pinson

    2011-11-01

    Full Text Available Au travers de cet ouvrage, Eleonora Pasotti, professeure de science politique à l’Université de Californie à Santa Cruz, renoue avec la grande tradition nord-américaine des travaux de science politique qui aborde la grande ville comme lieu d’invention et de repérage des nouvelles formes d’échange politique et de lien entre gouvernants et gouvernés. Le livre articule une analyse des nouveaux comportements électoraux et des nouvelles logiques de mobilisation électorale, d’une part, et une analy...

  12. L'information-documentation et sa mise en scène au quotidien : la culture informationnelle en questions

    OpenAIRE

    Maury, Yolande; Etévé, Christiane

    2010-01-01

    Rapport final ERTé Culture informationnelle et curriculum documentaire, Equipe de Paris, 15 p. Cette recherche étudie les pratiques ordinaires d'information-documentation. Son objectif est de dégager " l'aire de pertinence " de la culture informationnelle, à partir du repérage des éléments structurants de cette culture, telle qu'elle est abordée, au quotidien, en contexte scolaire (élèves, enseignants-documentalistes, éventuellement enseignants ; en collège et lycée). Les savoirs en inform...

  13. Set this house on fire: the self-analysis of Raymond Carver.

    Science.gov (United States)

    Tutter, Adele

    2011-10-01

    The convergence of features of Raymond Carver's short-story oeuvre and of psychoanalytic methodology suggests that Carver's writing served as the fulcrum and focus of a self-analytic experience. Within this model, his stories function as container and mirror of myriad aspects of the writer's self. Tracing the developmental arc of the contextual meanings of one motif--fire--through six stories and their ur-texts demonstrates gains comparable to certain analytic goals, including enhanced integration, accountability, and self-awareness. Over time, Carver's narratives of rage, impotence, and despair give way to a new story: of mourning, forgiveness, and the rekindling of hope. PMID:22034681

  14. Where the Runners Went: British Motivations Behind Postal Policy and Allocation in Colonial India

    OpenAIRE

    Bharat, Sheetal

    2012-01-01

    British presence has had a profound influence on economic development in British and independent India, and the debate on the nature of this influence has been raging for decades. At one end is the imperialist view that India benefitted from British rule and at the other is the nationalist view that India is still struggling from the burden of misrule. This debate has been enriched by in-depth research on the railways, among other topics; yet the closely related postal network has received ...

  15. Report of the independent review commissioned by the Royal College of Radiologists into brachial plexus neuropathy following radiotherapy for breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bates, Thelma; Evans, R.G.B.

    1995-12-31

    Brachial plexus neuropathy (BPN) is a rare but serious side effect of radiotherapy for operable breast carcinoma. It was identified in 48 of a sample of 126 patients (38%) who agreed to cooperate out of 249 members of RAGE, who were treated during the 14 year period 1980 to 1993 at 15 cancer centres. A conservative estimate of the total number of patients with operable breast cancer receiving radiotherapy at these centres during this time is 65,000. The incidence of BPN due to radiotherapy (BPN/RT) appears to be falling. From the first 7 years we found 41 cases and from the second 7 years only 7 cases. (author).

  16. Rabies.

    Science.gov (United States)

    Burnett, Nark

    2013-01-01

    Rabies has been a scourge of mankind since antiquity. The name itself, ?rabies? is derived from the ancient Sanskrit rabhas meaning ?to do violence? and has been found described in medical writings several thousand years old. The rabies virus is an RNA virus of the family Rhabdoviridae (Greek for ?rod-shaped virus?), genus Lyssavirus (Lyssa being the Greek God of frenzy and rage). Rabies infections have a worldwide spread, with only a few, mostly island nations laying claim to being ?rabies free.? PMID:24049000

  17. Le médicin des sauvages: le jongleur

    Directory of Open Access Journals (Sweden)

    Aldo Trucchio

    2015-06-01

    Full Text Available The term «jongleur» is currently employed in Quebequois French with reference to the shaman‐healer of the Amerindians. The authors explore the history of the peculiar conflation between a typical medieval character and the doctor of the «savages», through the texts and images that first provided its description between the XVI and XVIII Centuries. Their aim is to show how the representations of this character result from the encounter of different pre‐existing iconographic traditions and, especially, how they express the political and religious conflicts raging in Europe at the time.

  18. Dickens’s Global Art: Cultural and Ecological Legacy in Pictures from Italy

    OpenAIRE

    John, Juliet

    2016-01-01

    In today’s Dickens Studies, “Global Dickens” is all the critical rage. Yet the landmark work on global Dickens by Nisbet, Jordan, Gagnier and others focuses on the international dissemination and reception of Dickens’s work as opposed to Dickens’s own conception of his art. There is no doubt that Dickens saw himself as a global writer from the outset, using metaphors like “the ocean of humanity” to describe his target audience (Letter to W. C. Macready (14 January 1853)). But the travelogues ...

  19. Intracranial aneurysm formation in type-one diabetes rats.

    Directory of Open Access Journals (Sweden)

    Tao Yan

    Full Text Available BACKGROUND & OBJECTIVE: Diabetes mellitus (DM plays an important role in the pathogenesis of vascular complications including arteriosclerosis and ischemic stroke. Whether DM impacts intracranial aneurysm (IA formation has not been extensively investigated. In this study, we tested the underlying mechanism of type one DM (T1DM induced IA formation in rats. EXPERIMENTAL APPROACHES: T1DM was induced by streptozotocin injection. Rats were euthanized at 0, 4 and 10 weeks after T1DM induction. To evaluate cerebral vascular perfusion, Fluorescein isothiocyanate - dye was injected at 5 min prior to euthanasia. Vascular perfusion was measured by laser scanning confocal microscopy. Trichrome, Elastica van Gieson, alpha-smooth muscle actin (a-SMA and receptor of advanced glycation end-products (RAGE, toll-like receptor 4 (TLR4 and matrix metalloproteinase 9 (MMP9 immunostaining were performed. The IA formation was classified by 0-3 stages: 0: Normal; 1: Endothelial damage; 2: Moderate protrusion; and 3: Saccular aneurysm formation. RESULTS: T1DM significantly increased IA formation identified by the classification of aneurysmal changes compared with non-DM rats (p<0.05. However, T1DM induced IA formations were classified as stage 1 and stage 2, but not stage 3. Cerebral vascular perfusion was significantly decreased in T1DM rats compared to non-DM rats (p<0.01. DM10W rats exhibited a significant decrease of cerebral vascular perfusion compared to DM4W rats (p<0.05. T1DM rats also significantly increased the internal carotid artery (ICA intimae and media thickness, and decreased the internal carotid artery diameter compared to non-DM rats. RAGE, MMP9 and TLR4 expression were significantly increased in T1DM rats compared to non-DM rats. The increased RAGE, TLR4 and MMP9 significantly correlated with IA formation (p<0.05. CONCLUSION: T1DM increases IA formation. The increased RAGE, MMP9 and TLR4 expressions might contribute to IA formation in T1DM rats.

  20. Characterization of Static/Dynamic Topological Routing For Grid Networks

    DEFF Research Database (Denmark)

    Gutierrez Lopez, Jose Manuel; Cuevas, Ruben; Riaz, M. Tahir;

    2009-01-01

    Grid or 2D Mesh structures are becoming one of the most attractive network topologies to study. They can be used in many different fields raging from future broadband networks to multiprocessors structures. In addition, the high requirements of future services and applications demand more flexible...... and adaptive networks. Topological routing in grid networks is a simple and efficient alternative to traditional routing techniques, e.g. routing tables, and the paper extends this kind of routing providing a "Dynamic" attribute. This new property attempts to improve the overall network performance for future...

  1. Financial Derivatives Market and Storage Management

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    It's known to all that under ideal condition the s to rage cost is kept in lower level when storage management be arranged by Economic Order Quantity(EOQ).Does this mean that any companies should set up their own storing system in proportion to the scale of the commodities' producing or sell ing Furthermore, even if they manage storage in EOQ, because of different oper ation scale, geographical condition or ability borrowing money from financial ma rket, different companies pay unequal cost in storing the...

  2. Seduction and revenge in Virginia Woolf's Orlando.

    Science.gov (United States)

    McNamara, Susan

    2011-07-01

    Virginia Woolf's Orlando was characterized by Nigel Nicolson as a "charming love letter" to his mother, Vita Sackville-West. The fictional biography was actually an attempt by Woolf to organize herself after the unbearable humiliation of Vita's abandoning her for another woman. In imagining, writing, and publishing Orlando, Woolf turns her despair about Vita's betrayal into a monument of revenge, defending against disorganizing feelings of humiliation, powerlessness, rage, and loss by creating her own scathing portrait of Vita. In the novel, Woolf also intermittently merges herself with Orlando/Vita to create a permanent tie to the woman who--like her mother and sister--excited and rejected her.

  3. The sound and the fury: tre sguardi letterari sull’11-S tra rabbia, incredulità e metaletteratura

    OpenAIRE

    Simone Cattaneo

    2011-01-01

    The aim of the article is to offer three different versions of the 11-S terrorist attacks, showing how Juan Manuel de Prada (Baracaldo, 1970), Ray Loriga (Madrid, 1967) and Enrique Vila-Matas (Barcelona, 1948) reproduce that tragic event in some of their novels – La vida invisible, El hombre que inventó Manhattan and El Mal de Montano – employing different techniques and approaches. In that way it’s possible to recognize in their pages an interesting spectrum of emotions that goes from rage t...

  4. “You Killed Our Baby!”: Cristina Yang and the Breaking of the Abortion Taboo in Grey’s Anatomy

    OpenAIRE

    Levy, Elizabeth

    2015-01-01

    In 2011, a rare event occurred on American television: Cristina Yang, one of the main characters of Grey’s Anatomy, a widely popular TV show, decided to have an abortion and went through with her decision. In light of the fact that the pro-life/pro-choice debate has been raging in the United States since 1973 and has been tightly informed by religious views, this paper attempts to determine how the abortion plotline was organized in that regard. It becomes clear that Cristina’s decision is ne...

  5. Blah,Blah,Blog

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    It's the nature of Internet manias: they tend to leave almost as fast as they come, with only the rarest of rages sticking around for the long haul. Of the Internet "in things" that have remained "in," perhaps the most surprising is the humble Web log, or blog. This is a kind of digital diary, a Web page to which a writer posts chronological entries on a particular topic. The main difference between a blog and a regular Web site is that the blog's information is updated frequently, often several times a day or more.

  6. The Organization of Work: Changes and Their Consequences

    OpenAIRE

    Avner Ben-Ner; Fanmin Kong; Tzu-Shian Han; Nien-Chi Liu; Yong-Seung Park

    2001-01-01

    This paper documents the changes in human resource practices from the early 1980s to the middle of the 1990s, using a unique and comprehensive data set concerning a sample of about 800 firms from a wide rage of industries in the state of Minnesota. A major aspect in these changes concerns the widespread adoption of practices that emphasize employee involvement in decision-making and in firm financial returns. Focusing on cross-sectional data the paper examines the determinants of human resour...

  7. Conducción y sustancias psicoactivas (alcohol, drogas y medicamentos): de la magnitud del problema a la intervención en seguridad vial.

    OpenAIRE

    Fierro Lorenzo, María Inmaculada

    2015-01-01

    Con la investigación realizada para el presente trabajo se analizan diferentes aspectos del “factor humano” relacionados con la conducción, como son, el consumo de sustancias por parte de los conductores (alcohol, drogas ilegales y medicamentos) y la agresividad vial (Road rage). Respecto al consumo, se ha analizado la prevalencia de sustancias en conductores y además, en el caso del alcohol y el THC, se ha analizado su relación con la prevalencia de signos de deterioro, dependiendo de la con...

  8. Systemic biomarkers of neutrophilic inflammation, tissue injury and repair in COPD patients with differing levels of disease severity.

    Directory of Open Access Journals (Sweden)

    Debra A Cockayne

    Full Text Available The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research. The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls. Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-α and HB-EGF showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups. Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV(1, FEV(1/FVC and DLCO. Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin predicted 21% of the variability in DLCO values. To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile. While analytes related to neutrophil function (EN-RAGE, NGAL, MPO grouped together to form a cluster associated with FEV(1 related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-α formed another cluster associated with both DLCO and FEV(1 related parameters. Associations of Fibrinogen with DLCO and MPO with FEV(1/FVC were stronger in patients without metabolic syndrome (r  =  -0.52, p  =  0.005 and r  =  -0.61, p =  0.023, respectively compared to patients with coexisting metabolic syndrome (r  =  -0.25, p  =  0.47 and r  =  -0.15, p  =  0.96, respectively, and may be driving overall associations in the general cohort. In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV(1, FEV(1/FVC and DLCO. These data highlight systemic

  9. Who calls the tune?

    Directory of Open Access Journals (Sweden)

    Claude Chastagner

    2011-04-01

    Full Text Available The real action was taking place behind the scenes.Irwin Pincus, music publisherA couple of weeks ago, while researching for this paper, I decided to read again Chronicles, Bob Dylan’s autobiography. Chapter 4 deals with the recording in a rented New Orleans mansion of Oh Mercy, the 1989 album produced by Daniel Lanois, unanimously hailed as Dylan’s resurrection. Dylan insists on the significant impact Lanois had on his own artistry. Through conversations, flashes of rage and frustration, and...

  10. Shock-to-Detonation Transition simulations

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-14

    Shock-to-detonation transition (SDT) experiments with embedded velocity gauges provide data that can be used for both calibration and validation of high explosive (HE) burn models. Typically, a series of experiments is performed for each HE in which the initial shock pressure is varied. Here we describe a methodology for automating a series of SDT simulations and comparing numerical tracer particle velocities with the experimental gauge data. Illustrative examples are shown for PBX 9502 using the HE models implemented in the xRage ASC code at LANL.

  11. WHO’S WHO Scientists and Thinkers of the 20th Century

    Institute of Scientific and Technical Information of China (English)

    时林

    2004-01-01

    PSYCHOANALYST Sigmund Freud He opened a window on the unconscious--where,he said,lust,rage andrepression battle for supremacy-and changed the way we view ourselves.精神分析学家——西格蒙德·弗洛伊德(1881-1939) 他打开了无意识之窗——他说,在人的无意识中,欲望、愤怒和压抑心理都在争夺着控制大权——从而改变了我们看待自己的方式。

  12. 2D-vektoripohjainen tasosuunnittelu Unity 3D:llä

    OpenAIRE

    Birkström, Patrik

    2014-01-01

    Tasosuunnittelu on hyvin tärkeä osa lähes jokaista peliprojektia. Hyvä tasosuunnittelu voi pelastaa muuten huonosti suunnitellun pelin ja huono tasosuunnittelu voi taas pilata muuten hyvän pelinautinnon. Tämä opinnäytetyö keskittyy nimenomaan 2D –tasosuunnittelun perusteisiin ja testaa RageSpline–työkalun toimivuutta Unity 3D –peliprojektissa. Tarve opinnäytetyölle syntyi Kuutti Entertainment Oy:ltä, joka kehitti Moped Mania –nimistä mobiilipeliä Unity 3D:llä. Unity on pääasiassa tarkoite...

  13. Search (Non-)Neutrality and Impact on Innovation

    OpenAIRE

    L'Ecuyer, Pierre; MAILLÉ, Patrick; Stier-Moses, Nicolás; Tuffin, Bruno

    2016-01-01

    The search neutrality debate, as a parallel to the network neutrality debate, is raging worldwide, with search engines accused of biasing the ranking of their organic links to provide a competitive advantage to their own content. In a recent paper, we have designed a model and determined the optimal ranking policy for a search engine as a trade-off between short-term revenue (based on the potential immediate gain from high-ranked links) and long-term revenue (based on the satisfaction of user...

  14. Validation of the presence of comorbidities in a Danish clinical cohort of children with tourette syndrome

    DEFF Research Database (Denmark)

    Debes, N.M.M.M.; Hjalgrim, H.; Skov, L.

    2008-01-01

    attacks, Sleeping disturbances, and depressive Symptoms in a Danish clinical cohort of 314 children with TS using Validated diagnostic instruments. For the assessment of symptoms of seasonal affective disorder and Stuttering, WC Used a nonvalidated systematic interview. In total, only 10.......2% of the children did not have anycomorbid symptoms at all. IfADHD and/or obsessive-compulsive disorder were present, the rates of the comorbidities rage, symptoms of seasonal affective disorder, Sleep disturbances, and depressive symptoms were significantly higher than if AMI) and/or obsessive-compulsive disorder...

  15. FTW (For the Win / Fuck the World)

    OpenAIRE

    Summers, Francis; Minkin, Louisa

    2012-01-01

    Participation in the group exhibition curated by Bernice Donszelmann, Tim Renshaw and Mary McLean. Exhibited the work FTW (For the Win / Fuck the World) made in collaboration with Louisa Minkin. Here we use the format of the triumphal procession to pose questions around the twinned states of glory and nihilism. FTW! (For The Win / Fuck The World) is a banner that combines a letter to a generic addressee alongside a selection of internet memes, rage comic figures and images of disaster and cel...

  16. Short-term effects of dietary advanced glycation end products in rats

    DEFF Research Database (Denmark)

    Poulsen, Malene Wibe; Andersen, Jeanette Marker; Hedegaard, Rikke Susanne Vingborg;

    2016-01-01

    excretion of N ε -carboxymethyl-lysine increased with increasing proportion of heat-treated milk powder in the HMW and LMW diets but was unrelated to gene expression. There was no difference in insulin sensitivity, F2-isoprostaglandins, food intake, water intake, body weight or body composition between......) dietary AGE on insulin sensitivity, expression of the receptor for AGE (RAGE), the AGE receptor 1 (AGER1) and TNF-α, F2-isoprostaglandins, body composition and food intake. For 2 weeks, thirty-six Sprague-Dawley rats were fed a diet containing 20 % milk powder with different proportions of this being...

  17. 读物注释

    Institute of Scientific and Technical Information of China (English)

    郑绪林

    2011-01-01

    Water,Water Everywhere ( 1 )You may know how you got your name.( 2 ) But do you know how some oceans and seas got their names? (3)The Pacific Ocean was named by an explorer from Spain,Ferdinand Magellan.(4) When Magellan sailed on the ocean,it was peaceful.In Spanish,the word for peaceful is " pacifico" -pacific.But that doesn' t mean that the Pacific Ocean is always peaceful.(5) Raging typhoons and tidal waves (6) batter the coastlines of the Pacific many times during the year.(7)Magellan just didn' t see any bad storms (8) there,probably.

  18. 读物注释

    Institute of Scientific and Technical Information of China (English)

    郑绪林

    2011-01-01

    water,water everywhere ( 1 )you may know how you got your name.( 2 ) but do you know how some oceans and seas got their names? (3)the pacific ocean was named by an explorer from spain,ferdinand magellan.(4) when magellan sailed on the ocean,it was peaceful.in spanish,the word for peaceful is " pacifico" -pacific.but that doesn' t mean that the pacific ocean is always peaceful.(5) raging typhoons and tidal waves (6) batter the coastlines of the pacific many times during the year.(7)magellan just didn' t see any bad storms (8) there,probably.

  19. The conservation and dissemination of information - A democratic issue

    International Nuclear Information System (INIS)

    The societal function of the historians are pointed out, to describe and explain, in cooperation with the archives, the chain of political, economic, social and cultural events that has shaped the country's history. The lessons of the past, whether pleasant or unpleasant, should be passed on to the posterity. Open information is an important element in a democratic society and is normally one of the criteria that distinguishes democracy from autocracy. In the closed and controlled information society all that is hushed up and covered up leads to bitterness and rage among the citizens

  20. 听觉耐受下降与耳鸣%Decreased sound tolerance and tinnitus

    Institute of Scientific and Technical Information of China (English)

    祝晓宇; 张剑宁; 李明

    2012-01-01

    Summary Decreased sound tolerance includes hyperacusis and/or misophonia (phonophobia). As a commonly subjective symptom, tinnitus is defined to be a sound perceived in the ear or head without corresponding sound or electrical stimulus in the surrounding environment. It is usually occured with or without hearing loss or harmful psychic reaction, which includes dyssomnia, annoy, rage, anxiety, depress, hard to concentrate, etc. Frequently, tinnitus is accompied by decreased sound tolerance, while this text is aimed to review the corelated concepts of decreased sound tolerance,and focus on the hyperacusis which is a more common symptom.

  1. Theological reflections on empire

    Directory of Open Access Journals (Sweden)

    Allan A. Boesak

    2009-11-01

    Full Text Available Since the meeting of the World Alliance of Reformed Churches in Accra, Ghana (2004, and the adoption of the Accra Declaration, a debate has been raging in the churches about globalisation, socio-economic justice, ecological responsibility, political and cultural domination and globalised war. Central to this debate is the concept of empire and the way the United States is increasingly becoming its embodiment. Is the United States a global empire? This article argues that the United States has indeed become the expression of a modern empire and that this reality has considerable consequences, not just for global economics and politics but for theological refl ection as well.

  2. Study on the Phase Behavior of Coating Matrix in Supercritical or Sub—critical Carbon Dioxide

    Institute of Scientific and Technical Information of China (English)

    曹维良; 徐金龙; 张敬畅

    2003-01-01

    The high-pressure phase behavior of coating -solvent-supercritical or sub-critical carbon dioxide system was investigated experimentally.The coating matrix used was 108-acrylic resin at concentration raging from 10% to 50%(by mass) in mixtures with n-butyl acetate ,The experiments were conducted in a high-pressure view cell for temperatures from 35℃to 65 ℃ and for pressures from 3.0 MPa to 8.0 MPa ,The effect of temperature,pressure and content of every component on the phase behavior of the systems was observed,Finally ,the ternary phase diagram for resin-solvent-CO2 was plotted.

  3. Recognition and management of Shaken Baby Syndrome

    LENUS (Irish Health Repository)

    Nicholson, Alf

    2016-04-01

    Abusive head trauma (previously referred to as Shaken Baby Syndrome) consists of a triad of findings which included subdural haemorrhage, retinal haemorrhages and encephalopathy after receiving a shake injury or blunt trauma to the head. Debate rages regarding the exact mechanism. Previously published reports on abusive head trauma (AHT) highlight the young age of the victims (median 4 months of age), the significant preponderance of male infants (3:1 in most series), the high rate of probable male perpetrators (just over 50%), and relatively high rates of mortality and morbidity

  4. In Search of the jüdische Typus: A Proposed Benchmark to Test the Genetic Basis of Jewishness Challenges Notions of “Jewish Biomarkers”

    OpenAIRE

    Elhaik, E.

    2016-01-01

    The debate as to whether Jewishness is a biological trait inherent from an “authentic” “Jewish type” (jüdische Typus) ancestor or a system of beliefs has been raging for over two centuries. While the accumulated biological and anthropological evidence support the latter argument, recent genetic findings, bolstered by the direct-to-consumer genetic industry, purport to identify Jews or quantify one’s Jewishness from genomic data. To test the merit of claims that Jews and non-Jews are genetical...

  5. Epidemiological characteristics of multiple sclerosis in Tomsk Region and their dynamics for last 30 years

    Directory of Open Access Journals (Sweden)

    V. M. Alifirova

    2016-03-01

    Full Text Available The Tomsk Region is a zone of average risk multiple sclerosis (MS, prevalence makes 27.1 cases on 100 000 people. During the period with 1980 for 2010 variety of morbidity from 0.4 (1992 to 4.1 (2003 on 100 000 people. The lowest morbidity was in period with 1991 for 1995 and makes 1.8 on 100 000 people, and the highest in the rage from 2001 for 2005 — 3.1 on 100 000 people. Last 5 years in the TomskRegion to increase ofmorbidityis observed.

  6. Hitler: a neurohistorical formulation.

    Science.gov (United States)

    Martindale, C; Hasenfus, N; Hines, D

    1976-01-01

    It is hypothesized that Adolf Hitler suffered from a constitutional left-side weakness that allowed his cerebral hemisphere to exert a strong influence on his thought and behavior. Physical characteristics such as trembling of the left extremities, lack of a left testicle, and tendency to exhibit leftward eye movements are interpreted as supportive of the hypothesis. Right hemisphere dominance is consistent with a number of Hitler's personal traits such as praise of the irrational, automatic speech, auditory hallucinations, hypochondriasis, uncontrolled rages, and spatial and musical interests. Right hemisphere dominated thought may also have formed a basis for his two basic political policies: Lebensraum and anti-Semitism.

  7. Elemental magic, v.2 the technique of special effects animation

    CERN Document Server

    Gilland, Joseph

    2012-01-01

    Design beautiful, professional-level animated effects with these detailed step-by-step tutorials from former Disney animator and animated effects expert Joseph Gilland. Filled with beautiful, full-color artwork, Elemental Magic, Volume II, breaks down the animated effect process from beginning to end-including booming explosions, gusting winds, magical incantations, and raging fires. He also breaks down the process of effects ""clean-up,"" as well as timing and frame rates. The companion website includes real-time footage of the author lecturing as he animates the drawings from the

  8. Multi-modal ultra-high resolution structural 7-Tesla MRI data repository

    OpenAIRE

    Forstmann, Birte U.; Keuken, Max C.; Schafer, Andreas; Bazin, Pierre-Louis; Alkemade, Anneke; Turner, Robert

    2014-01-01

    Structural brain data is key for the understanding of brain function and networks, i.e., connectomics. Here we present data sets available from the ‘atlasing of the basal ganglia (ATAG)’ project, which provides ultra-high resolution 7 Tesla (T) magnetic resonance imaging (MRI) scans from young, middle-aged, and elderly participants. The ATAG data set includes whole-brain and reduced field-of-view MP2RAGE and T2*-weighted scans of the subcortex and brainstem with ultra-high resolution at a sub...

  9. Clinical and the demographic characteristics of patients with alopecia areata

    OpenAIRE

    Mustafa Arıca; Roza Zelal Abdioğlu; Ruken Azizoğlu Anlı; Sibel Yorgancılar

    2013-01-01

    Background and Design: In this study, our aim was to determine clinical and the demographical characteristics of the patients with alopecia areata in our region.Materials and Metods: In the study, 100 patients who received alopecia areata diagnosis with ages raging from 2 to 52 and who applied to the polyclinic of ………… Medical Faculty Dermatology Department between October and November 2009 were evaluated.Results: Of 100 patients included into the study 44 (44%) were female and 56 (56%) male....

  10. Micro-Structural Brain Alterations in Aviremic HIV+ Patients with Minor Neurocognitive Disorders: A Multi-Contrast Study at High Field.

    OpenAIRE

    Cristina Granziera; Alessandro Daducci; Samanta Simioni; Matthias Cavassini; Alexis Roche; Djalel Meskaldji; Tobias Kober; Melanie Metral; Alexandra Calmy; Gunther Helms; Bernard Hirschel; François Lazeyras; Reto Meuli; Gunnar Krueger; Du Pasquier, Renaud A.

    2013-01-01

    OBJECTIVE: Mild neurocognitive disorders (MND) affect a subset of HIV+ patients under effective combination antiretroviral therapy (cART). In this study, we used an innovative multi-contrast magnetic resonance imaging (MRI) approach at high-field to assess the presence of micro-structural brain alterations in MND+ patients. METHODS: We enrolled 17 MND+ and 19 MND- patients with undetectable HIV-1 RNA and 19 healthy controls (HC). MRI acquisitions at 3T included: MP2RAGE for T1 relaxation time...

  11. Mortality investigation

    Science.gov (United States)

    Work, Thierry M.; Franson, J. Christian; Friend, Milton; Gibbs, Samantha E.J.; Wild, Margaret A.

    2015-01-01

    Wildlife mortality events usually occur unannounced and may find management agencies unaware. These events can become highly visible and politically charged affairs, depending upon the scale or species involved. The public, media, and (or) politicians may pressure managers, field investigators, and diagnosticians to quickly identify the cause or to comment on potential causes, the significance of the event, what is being done about it, and a resolution. It may be common during such events for speculation to rage, and for conflicting theories to be advanced to explain either the environmental conditions that led to the mortality or the actual cause of death.

  12. EFFECTS OF DIFFERENT NUMERICAL INTERFACE METHODS ON HYDRODYNAMICS INSTABILITY

    Energy Technology Data Exchange (ETDEWEB)

    FRANCOIS, MARIANNE M. [Los Alamos National Laboratory; DENDY, EDWARD D. [Los Alamos National Laboratory; LOWRIE, ROBERT B. [Los Alamos National Laboratory; LIVESCU, DANIEL [Los Alamos National Laboratory; STEINKAMP, MICHAEL J. [Los Alamos National Laboratory

    2007-01-11

    The authors compare the effects of different numerical schemes for the advection and material interface treatments on the single-mode Rayleigh-Taylor instability, using the RAGE hydro-code. The interface growth and its surface density (interfacial area) versus time are investigated. The surface density metric shows to be better suited to characterize the difference in the flow, than the conventional interface growth metric. They have found that Van Leer's limiter combined to no interface treatment leads to the largest surface area. Finally, to quantify the difference between the numerical methods they have estimated the numerical viscosity in the linear-regime at different scales.

  13. Privacy and Big Data

    CERN Document Server

    Craig, Terence

    2011-01-01

    Much of what constitutes Big Data is information about us. Through our online activities, we leave an easy-to-follow trail of digital footprints that reveal who we are, what we buy, where we go, and much more. This eye-opening book explores the raging privacy debate over the use of personal data, with one undeniable conclusion: once data's been collected, we have absolutely no control over who uses it or how it is used. Personal data is the hottest commodity on the market today-truly more valuable than gold. We are the asset that every company, industry, non-profit, and government wants. Pri

  14. Penile Replantation After Five Hours of Warm Ischemia

    Directory of Open Access Journals (Sweden)

    Fernando N. Facio Jr.

    2015-05-01

    Full Text Available Although a rare occurrence, this event may occur as a result of self-mutilation among individuals with psychiatric disturbances or due to work-related accidents, iatrogenic injuries or the actions of individuals motivated by jealously, rage and feelings of betrayal. In western societies, most penile amputations are the result of self-aggression during a psychotic episode, the treatment of victims involves resuscitation, stabilization and immediate psychiatric support. The amputated tissue must be preserved under hypothermic conditions. Micro-surgery is currently the most widely employed method for penile replantation. This paper describes a successful case of penile replantation following 5 hours of warm ischemia.

  15. Expanding horizons

    OpenAIRE

    Editor

    2009-01-01

    Dear Friends, The debate of whether Stem Cell Therapy is a hype or hope has been raging for quite some time and has been rekindled in the current year. Stem Cell Scientists have been particularly enthused by the bold standard taken by Barack Obama in passing an Executive Order that lifted the ban on federal funding of Research on Embryonic Stem Cell (ESC) lines created after August 9, 2001. With the lifting of the ban more money is expected to be poured into ESC and Stem Cell Research in gene...

  16. Une utilisation inattendue des outils de télédétection disponibles sur internet : l’identification des sujets de deux aquarelles du peintre William Turner.

    Directory of Open Access Journals (Sweden)

    Roland Courtot

    2008-05-01

    Full Text Available Internet nous fournit maintenant des cartes, des images satellitaires et des photographies aériennes pour la quasi totalité des surfaces terrestres du globe : les modèles numériques de terrain permettent d’observer le relief en trois dimensions, et s’appliquent à des surfaces de plus en plus importantes. Ces outils, on le sait, permettent des repérages sur le terrain et des analyses d’espaces géographiques et de paysages de plus en plus détaillés. Ils sont depuis longtemps les outils du géogr...

  17. Fracture of tibial tuberosity in an adult

    OpenAIRE

    Rodrigo Pires e Albuquerque; Campos, André Siqueira; de Araújo, Gabriel Costa Serrão; Gameiro, Vinícius Schott

    2013-01-01

    The fracture of tibial tuberosity is a rare lesion and still more unusual in adults. We describe a case in an adult who suffered a left knee injury due to a fall from height. No risk factors were identified. The lesion was treated with surgical reduction and internal fixation. The rehabilitation method was successful, resulting in excellent function and rage of motion of the knee. The aim of this study was to present an unusual case of direct trauma of the tibial tuberosity in an adult and th...

  18. Nurturing Prodigy Pianists

    Institute of Scientific and Technical Information of China (English)

    ZHANGJINGDE

    2005-01-01

    CHINA's piano craze has raged for 20 years and shows no sign of flagging. China has the world's biggest piano production and is also home to most prodigy pianists.French pianist Michel Rourdoncle says that it is possible to hear infants playing excellent piano in every province. This craze is apparent in cosmopolitan Beijing and Shanghai as well as far-flung Tibet and Xinjiang. Piano tuition in China is generally 100 yuan (US $ 12) per hour - not at all cheap when taking into account the average monthly income of a couole of thousand vuan It is,

  19. The conservation and dissemination of information - A democratic issue

    Energy Technology Data Exchange (ETDEWEB)

    Torbacke, J. [Stockholm Univ. (Sweden). Dept. of History

    1996-12-01

    The societal function of the historians are pointed out, to describe and explain, in cooperation with the archives, the chain of political, economic, social and cultural events that has shaped the country`s history. The lessons of the past, whether pleasant or unpleasant, should be passed on to the posterity. Open information is an important element in a democratic society and is normally one of the criteria that distinguishes democracy from autocracy. In the closed and controlled information society all that is hushed up and covered up leads to bitterness and rage among the citizens.

  20. 缺氧后内皮细胞早期生长反应因子-1活化的信号机制%The Signaling Mechanism Involved in Hypoxia-induced Upregulation of Early Growth Response-1 in Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    黄春; 杨明; 施晓芸; 陈晓春

    2012-01-01

    目的 观察缺氧对内皮细胞早期生长反应因子(Egr-1)表达的影响及晚期糖基化终末产物(AGEs)及其受体(RAGE)对上述效应的可能调控机制.方法 以培养小鼠主动脉内皮细胞(MAECs)为模型,根据缺氧时间和缺氧前预处理方式,分为不同缺氧时间组[缺氧0(对照组),5,10,15,30,60,120 min组]、anti-AGE预处理组、可溶性RAGE(sRAGE)预处理组和蛋白激酶C(PKC)β抑制剂组,实时定量PCR法检测缺氧后Egr-1 mRNA含量、ELISA法检测细胞裂解液中AGEs含量、蛋白印迹法检测细胞膜蛋白中PKC各异构体的活化.结果 缺氧15 min组Egr-1 mRNA表达上调,为对照组的(14.13±0.77)倍(P=0.000 0);缺氧10~60 min内皮细胞裂解液中AGEs堆积;缺氧15 min组MAECs膜蛋白中PKCβⅡ含量为(30.57±1.86),显著高于对照组的含量(9.22±1.05)(P=0.002);anti-AGE、sRAGE和PKCβ抑制剂预处理减少缺氧诱导的Egr-1 mRNA表达上调(P=0.000 0);anti-AGE和sRAGE预处理显著减少缺氧对PKCβⅡ的活化(P=0.000 0).结论 急性缺氧诱导内皮细胞AGEs堆积、PKCβⅡ活化和Egr-1mRNA高表达,AGEs-RAGE和PKCβII信号参与急性缺氧后Egr-1诱导表达的调控.%Objective To observe the impact of hypoxia on the expression of early growth response-1 (Egr-1) in mouse aortic endothelial cells(MAECs) , and to study the underlying signaling mechanism involving advanced glycation end-products (AGEs) and its receptor (receptor for AGEs, RAGE). Methods MAECs were subjected to hypoxia treatment with a (6.0+0.5)% oxygen concentration for various periods (0, 5, 10, 15, 30, 60 or 120 min) , or -were first pre-incubated -with anti-AGEs or soluble RAGE (sRAGE) for 2 h, or LY379196 for 45 min respectively, and then subsequently exposed to hypoxia for 15 min. Egr-1 mRNA levels -were detected by real time PCR (RT-PCR), AGEs in cell lysate -were monitored by ELISA, and PKC isoformates in membrane fraction were examined by western blot. MAECs cultured -with normoxia -were