71 research outputs found

    Antibody-mediated inhibition of syndecan-4 dimerisation reduces interleukin (IL)-1 receptor trafficking and signalling.

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    OBJECTIVE: Syndecan-4 (sdc4) is a cell-anchored proteoglycan that consists of a transmembrane core protein and glucosaminoglycan (GAG) side chains. Binding of soluble factors to the GAG chains of sdc4 may result in the dimerisation of sdc4 and the initiation of downstream signalling cascades. However, the question of how sdc4 dimerisation and signalling affects the response of cells to inflammatory stimuli is unknown. METHODS: Sdc4 immunostaining was performed on rheumatoid arthritis (RA) tissue sections. Interleukin (IL)-1 induced extracellular signal-regulated kinases (ERK) phosphorylation and matrix metalloproteinase-3 production was investigated. Il-1 binding to sdc4 was investigated using immunoprecipitation. IL-1 receptor (IL1R1) staining on wild-type, sdc4 and IL1R1 knockout fibroblasts was performed in fluorescence-activated cell sorting analyses. A blocking sdc4 antibody was used to investigate sdc4 dimerisation, IL1R1 expression and the histological paw destruction in the human tumour necrosis factor-alpha transgenic mouse. RESULTS: We show that in fibroblasts, the loss of sdc4 or the antibody-mediated inhibition of sdc4 dimerisation reduces the cell surface expression of the IL-1R and regulates the sensitivity of fibroblasts to IL-1. We demonstrate that IL-1 directly binds to sdc4 and in an IL-1R-independent manner leads to its dimerisation. IL-1-induced dimerisation of sdc4 regulates caveolin vesicle-mediated trafficking of the IL1R1, which in turn determines the responsiveness to IL-1. Administration of antibodies (Ab) against the dimerisation domain of sdc4, thus, strongly reduces the expression IL1R1 on arthritic fibroblasts both in vitro and an animal model of human RA. CONCLUSION: Collectively, our data suggest that Ab that specifically inhibit sdc4 dimerisation may support anti-IL-1 strategies in diseases such as inflammatory arthritis

    First results of the air shower experiment KASCADE

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    The main goals of the KASCADE (KArlsruhe Shower Core and Array DEtector) experiment are the determination of the energy spectrum and elemental composition of the charged cosmic rays in the energy range around the knee at ca. 5 PeV. Due to the large number of measured observables per single shower a variety of different approaches are applied to the data, preferably on an event-by-event basis. First results are presented and the influence of the high-energy interaction models underlying the analyses is discussed.Comment: 3 pages, 3 figures included, to appear in the TAUP 99 Proceedings, Nucl. Phys. B (Proc. Suppl.), ed. by M. Froissart, J. Dumarchez and D. Vignau

    Electron, Muon, and Hadron Lateral Distributions Measured in Air-Showers by the KASCADE Experiment

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    Measurements of electron, muon, and hadron lateral distributions of extensive air showers as recorded by the KASCADE experiment are presented. The data cover the energy range from about 5x10^14 eV up to almost 10^17 eV and extend from the inner core region to distances of 200 m. The electron and muon distributions are corrected for mutual contaminations by taking into account the detector properties in the experiment. All distributions are well described by NKG-functions. The scale radii describing the electron and hadron data best are approx. 30 m and 10 m, respectively. We discuss the correlation between scale radii and `age' parameter as well as their dependence on shower size, zenith angle, and particle energy threshold.Comment: 28 pages, 14 figures, Accepted for publication in Astroparticle Physic

    Sustainable peeling of Kapok Tree (Ceiba pentandra) bark by the chimpanzees (Pan troglodytes verus) of Comoé National Park, Ivory Coast

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    Primates often consume either bark or cambium (inner bark) as a fallback food to complete their diet during periods of food scarcity. Wild chimpanzees exhibit great behavioral diversity across Africa, as studies of new populations frequently reveal. Since 2014, we have been using a combination of camera traps and indirect signs to study the ecology and behavior of wild chimpanzees (Pan troglodytes verus) in Comoé National Park, Ivory Coast, to document and understand the behavioral adaptations that help them to survive in a savanna–forest mosaic landscape. We found that Comoé chimpanzees peel the bark of the buttresses of kapok tree (Ceiba pentandra) trees to eat the cambium underneath. Individuals of all sex/age classes across at least six neighboring communities peeled the bark, but only during the late rainy season and beginning of the dry season, when cambium may represent an important fallback food. Baboons (Papio anubis) also target the same trees but mainly eat the bark itself. Most of the bark-peeling wounds on Ceiba trees healed completely within 2 years, seemingly without any permanent damage. We recorded chimpanzees visiting trees in early stages of wound recovery but leaving them unpeeled. Only 6% of peeled trees (N = 53) were reexploited after a year, suggesting that chimpanzees waited for the rest of the trees to regrow the bark fully before peeling them again, thus using them sustainably. Many human groups of hunter-gatherers and herders exploited cambium sustainably in the past. The observation that similar sustainable bark-peeling behavior evolved in both chimpanzees and humans suggests that it has an important adaptive value in harsh environments when other food sources become seasonally scarce, by avoiding the depletion of the resource and keeping it available for periods of scarcity

    Cosmic ray physics around the knee with the KASCADE experiment

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    KASCADE (KArlsruhe Shower Core and Array DEtector) is a multidetector setup to observe the electromagnetic, muonic and hadronic air shower components simultaneously for the primary energy region around the knee. The large body of observables per single shower allows to follow the main aims of the experiment in analyses on an event-by-event basis, mainly: 1) slopes and structures of the primary energy spectrum; 2) the energy dependence of the chemical composition of the primaries; 3) tests of the air shower simulation tools underlying the analyses, in particular of the Monte Carlo generators based on different high-energy interaction models; 4) examinations of the air shower development in the atmosphere. Examples and results of different analysis methods are presented for the different subjects

    Abundância e sazonalidade de cigarrinhas (Hemiptera, Cicadellidae, Cicadellinae) em vegetação herbácea de pomar de laranja doce, no município de Montenegro, Estado do Rio Grande do Sul, Brasil.

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    O presente estudo teve por objetivo conhecer a flutuação populacional e a constância de cicadelíneos presentes na vegetação herbácea de um pomar de laranja doce (Citrus sinensis (L.) Osbeck), variedade Valência, em Montenegro, RS. O levantamento foi realizado com a metodologia da rede-de-varredura, tendo início em fevereiro de 2001 e finalizando-se em janeiro de 2002. Mensalmente foram coletadas dez amostras, sendo cada uma destas composta por 50 golpes de rede em movimento de avanço sobre a vegetação herbácea e cultura intercalar nas entrelinhas do pomar (n = 500 golpes/ocasião de coleta). No total foram coletados 928 cicadelíneos,pertencentes a nove espécies: Bucephalogonia xanthophis (Berg, 1879), Diedrocephala variegata(Fabricius, 1775), Hortensia similis(Walker, 1851), Macugonalia leucomelas (Walker, 1851), Parathona gratiosa (Blanchard, 1840), Plesiommata corniculata Young,1977, Sibovia sagata (Signoret, 1854), Sonesimia grossa (Signoret, 1854) e Tapajosa rubromarginata (Signoret, 1855). O período de maior abundância da comunidade de cicadelíneos foi durante a primavera e o verão. Hortensia similis e M. leucomelas foram as únicas espécies consideradas constantes durante o levantamento. A menor abundância dos cicadelíneos em abril e dezembro provavelmente devese a efeitos causados por fatores abióticos (pluviosidade) e aqueles relativos à estrutura da vegetação (altura das plantas) sobre a comunidade

    Pharmacological treatment options for mast cell activation disease

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    Laryngeale Varizella zoster Virus-(VZV-)Infektion: ein Fallbericht

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