225 research outputs found

    LPS-induced delayed preconditioning is mediated by hsp90 and involves the heat shock response in mouse kidney.

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    INTRODUCTION: We and others demonstrated previously that preconditioning with endotoxin (LPS) protected from a subsequent lethal LPS challenge or from renal ischemia-reperfusion injury (IRI). LPS is effective in evoking the heat shock response, an ancient and essential cellular defense mechanism, which plays a role in resistance to, and recovery from diseases. Here, by using the pharmacological Hsp90 inhibitor novobiocin (NB), we investigated the role of Hsp90 and the heat shock response in LPS-induced delayed renal preconditioning. METHODS: Male C57BL/6 mice were treated with preconditioning (P: 2 mg/kg, ip.) and subsequent lethal (L: 10 mg/kg, ip.) doses of LPS alone or in combination with NB (100 mg/kg, ip.). Controls received saline (C) or NB. RESULTS: Preconditioning LPS conferred protection from a subsequent lethal LPS treatment. Importantly, the protective effect of LPS preconditioning was completely abolished by a concomitant treatment with NB. LPS induced a marked heat shock protein increase as demonstrated by Western blots of Hsp70 and Hsp90. NB alone also stimulated Hsp70 and Hsp90 mRNA but not protein expression. However, Hsp70 and Hsp90 protein induction in LPS-treated mice was abolished by a concomitant NB treatment, demonstrating a NB-induced impairment of the heat shock response to LPS preconditioning. CONCLUSION: LPS-induced heat shock protein induction and tolerance to a subsequent lethal LPS treatment was prevented by the Hsp90 inhibitor, novobiocin. Our findings demonstrate a critical role of Hsp90 in LPS signaling, and a potential involvement of the heat shock response in LPS-induced preconditioning

    A descriptive study of female suicide deaths from 2005 to 2011 in Van city, Turkey

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    BACKGROUND: Female suicide is an important problem not only for women but for public health in general. METHODS: Autopsy reports from the Van Chief Public Prosecutor’s Office from 2005 to 2011 were reviewed retrospectively in order to analyse female deaths from suicide. RESULTS: Sixty-six female suicide cases were recorded during 2005–2011. The mean age of the cases was 22.64 (sd = 10.09) years, and nine were below the age of 15. The most common method of suicide was hanging (44 cases, 66.7 %). Five (7.6 %) of the cases were under treatment for depression, and 12 (18.2 %) cases had a previous suicide attempt. CONCLUSIONS: Cultural suppression of females and prevention of their socialization in enclave societies are risk factors for female suicides. The number of female suicide attempts, especially recurring attempts, should be reduced via psychiatric scanning, follow-up sessions and therapy for high-risk individuals

    High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model

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    Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon\u27s (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits

    Controlling the degree of branching in vinyl polymerization

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    Branching is an important tool for a synthetic polymer chemist in order to control the macroscopic properties of polymers. In condensation polymers, branching can be controlled by copolymerization of an AB? type monomer with an AB type monomer. However, in Vinyl polymerizations, it was not until very recently that the degree of branching could be controlled. Two different approaches, namely, Self-Condensing Vinyl Polymerization (SCVP) and Atom Transfer Radical Polymerization (ATRP) were developed for controlling the degree of branching in vinyl systems. This review article highlights recent advances in the science and technology in these two industrially very important approaches. A brief summary at the end highlights the advantages and disadvantages of each methodology. (C) 2000 Elsevier Science Ltd. All rights reserved

    Controlling the degree of branching in vinyl polymerization

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    Synthesis and characterization of N-substituted hyperbranched polyureas

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    N,N'-disubstituted hyperbranched polyureas with methyl, benzyl, and allyl substitutents were synthesized starting from AB(2) monomers based on 3,5-diamino benzoic acid. Carbonyl azide approach, which generates isocyanate group in situ on thermal decomposition, was used for the protection of isocyanate functional groups. The N-substituted hyperbranched polymers can be considered as the new class of internally functionalized hyperbranched polyureas wherein the substituent can function either as receptor or as a chemical entity for selective transformations as a tool to tailor the properties. The chain-ends were also modified by attaching long chain aliphatic groups to fully realize the interior functionalization. This approach opens up a possible synthetic route wherein different functional substituents can be used to generate a library of internally functionalized. hyperbranched polymers. All the hyperbranched polyureas were characterized by FTIR, H-1-NMR, DSC, TGA, and size exclusion chromatography. Degree of branching in these N,N'-disubstituted hyperbranched polyureas, as calculated by H-1-NMR spectroscopy using model compounds, was found to be lower than the unsubstituted hyperbranched polyurea and is attributed to the lower reactivity of N-substituted amines compared to that of unsubstituted amines. (C) 2004
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