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  1. Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal dysplasia undermines dominant role of STAT1 in FGFR3 signaling in cartilage.

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    Pavel Krejci

    Full Text Available Activating mutations in FGFR3 tyrosine kinase cause several forms of human skeletal dysplasia. Although the mechanisms of FGFR3 action in cartilage are not completely understood, it is believed that the STAT1 transcription factor plays a central role in pathogenic FGFR3 signaling. Here, we analyzed STAT1 activation by the N540K, G380R, R248C, Y373C, K650M and K650E-FGFR3 mutants associated with skeletal dysplasias. In a cell-free kinase assay, only K650M and K650E-FGFR3 caused activatory STAT1(Y701 phosphorylation. Similarly, in RCS chondrocytes, HeLa, and 293T cellular environments, only K650M and K650E-FGFR3 caused strong STAT1 activation. Other FGFR3 mutants caused weak (HeLa or no activation (293T and RCS. This contrasted with ERK MAP kinase activation, which was strongly induced by all six mutants and correlated with the inhibition of proliferation in RCS chondrocytes. Thus the ability to activate STAT1 appears restricted to the K650M and K650E-FGFR3 mutants, which however account for only a small minority of the FGFR3-related skeletal dysplasia cases. Other pathways such as ERK should therefore be considered as central to pathological FGFR3 signaling in cartilage.

  2. Toxoplasma gondii Inhibits Gamma Interferon (IFN-γ)- and IFN-β-Induced Host Cell STAT1 Transcriptional Activity by Increasing the Association of STAT1 with DNA

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    Rosowski, Emily E.; Nguyen, Quynh P.; Camejo, Ana; Spooner, Eric

    2014-01-01

    The gamma interferon (IFN-γ) response, mediated by the STAT1 transcription factor, is crucial for host defense against the intracellular pathogen Toxoplasma gondii, but prior infection with Toxoplasma can inhibit this response. Recently, it was reported that the Toxoplasma type II NTE strain prevents the recruitment of chromatin remodeling complexes containing Brahma-related gene 1 (BRG-1) to promoters of IFN-γ-induced secondary response genes such as Ciita and major histocompatibility complex class II genes in murine macrophages, thereby inhibiting their expression. We report here that a type I strain of Toxoplasma inhibits the expression of primary IFN-γ response genes such as IRF1 through a distinct mechanism not dependent on the activity of histone deacetylases. Instead, infection with a type I, II, or III strain of Toxoplasma inhibits the dissociation of STAT1 from DNA, preventing its recycling and further rounds of STAT1-mediated transcriptional activation. This leads to increased IFN-γ-induced binding of STAT1 at the IRF1 promoter in host cells and increased global IFN-γ-induced association of STAT1 with chromatin. Toxoplasma type I infection also inhibits IFN-β-induced interferon-stimulated gene factor 3-mediated gene expression, and this inhibition is also linked to increased association of STAT1 with chromatin. The secretion of proteins into the host cell by a type I strain of Toxoplasma without complete parasite invasion is not sufficient to block STAT1-mediated expression, suggesting that the effector protein responsible for this inhibition is not derived from the rhoptries. PMID:24478085

  3. Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma

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    Dimberg Lina Y

    2012-07-01

    Full Text Available Abstract Background Multiple myeloma (MM is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM. Methods To delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS. Results To explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA, geldanamycin (17-AAG, doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered. Conclusion We conclude that Stat1 alters IL-6

  4. Quantitative proteomic analysis reveals that transmissible gastroenteritis virus activates the JAK-STAT1 signaling pathway.

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    An, Kang; Fang, Liurong; Luo, Rui; Wang, Dang; Xie, Lilan; Yang, Jing; Chen, Huanchun; Xiao, Shaobo

    2014-12-05

    Transmissible gastroenteritis virus (TGEV), a porcine enteropathogenic coronavirus, causes lethal watery diarrhea and severe dehydration in piglets. In this study, liquid chromatography-tandem mass spectrometry coupled to isobaric tags for relative and absolute quantification labeling was used to quantitatively identify differentially expressed cellular proteins after TGEV infection in PK-15 cells. In total, 162 differentially expressed cellular proteins were identified, including 60 upregulated proteins and 102 downregulated proteins. These differentially expressed proteins were involved in the cell cycle, cellular growth and proliferation, the innate immune response, etc. Interestingly, many upregulated proteins were associated with interferon signaling, especially signal transducer and activator of transcription 1 (STAT1) and interferon-stimulated genes (ISGs). Immunoblotting and real-time quantitative reverse transcription polymerase chain reaction demonstrated that TGEV infection induces STAT1 phosphorylation and nuclear translocation, as well as ISG expression. This study for the first time reveals that TGEV induces interferon signaling from the point of proteomic analysis.

  5. Activation of transcription factors STAT1 and STAT5 in the mouse median eminence after systemic ciliary neurotrophic factor administration.

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    Severi, Ilenia; Senzacqua, Martina; Mondini, Eleonora; Fazioli, Francesca; Cinti, Saverio; Giordano, Antonio

    2015-10-05

    Exogenously administered ciliary neurotrophic factor (CNTF) causes weight loss in obese rodents and humans through leptin-like activation of the Jak-STAT3 signaling pathway in hypothalamic arcuate neurons. Here we report for the first time that 40min after acute systemic treatment, rat recombinant CNTF (intraperitoneal injection of 0.3mg/kg of body weight) induced nuclear translocation of the tyrosine-phosphorylated forms of STAT1 and STAT5 in the mouse median eminence and other circumventricular organs, including the vascular organ of the lamina terminalis and the subfornical organ. In the tuberal hypothalamus of treated mice, specific nuclear immunostaining for phospo-STAT1 and phospho-STAT5 was detected in ependymal cells bordering the third ventricle floor and lateral recesses, and in median eminence cells. Co-localization studies documented STAT1 and STAT5 activation in median eminence β-tanycytes and underlying radial glia-like cells. A few astrocytes in the arcuate nucleus responded to CNTF by STAT5 activation. The vast majority of median eminence tanycytes and radial glia-like cells showing phospho-STAT1 and phospho-STAT5 immunoreactivity were also positive for phospho-STAT3. In contrast, STAT3 was the sole STAT isoform activated by CNTF in arcuate nucleus and median eminence neurons. Finally, immunohistochemical evaluation of STAT activation 20, 40, 80, and 120min from the injection demonstrated that cell activation was accompanied by c-Fos expression. Collectively, our findings show that CNTF activates STAT3, STAT1, and STAT5 in vivo. The distinctive activation pattern of these STAT isoforms in the median eminence may disclose novel targets and pathways through which CNTF regulates food intake. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. STAT1 pathway mediates amplification of metastatic potential and resistance to therapy.

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    Nikolai N Khodarev

    Full Text Available BACKGROUND: Traditionally IFN/STAT1 signaling is connected with an anti-viral response and pro-apoptotic tumor-suppressor functions. Emerging functions of a constitutively activated IFN/STAT1 pathway suggest an association with an aggressive tumor phenotype. We hypothesized that tumor clones that constitutively overexpress this pathway are preferentially selected by the host microenvironment due to a resistance to STAT1-dependent cytotoxicity and demonstrate increased metastatic ability combined with increased resistance to genotoxic stress. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that clones of B16F1 tumors grown in the lungs of syngeneic C57BL/6 mice demonstrate variable transcriptional levels of IFN/STAT1 pathway expression. Tumor cells that constitutively overexpress the IFN/STAT1 pathway (STAT1(H genotype are selected by the lung microenvironment. STAT1(H tumor cells also demonstrate resistance to IFN-gamma (IFNgamma, ionizing radiation (IR, and doxorubicin relative to parental B16F1 and low expressors of the IFN/STAT1 pathway (STAT1(L genotype. Stable knockdown of STAT1 reversed the aggressive phenotype and decreased both lung colonization and resistance to genotoxic stress. CONCLUSIONS: Our results identify a pathway activated by tumor-stromal interactions thereby selecting for pro-metastatic and therapy-resistant tumor clones. New therapies targeted against the IFN/STAT1 signaling pathway may provide an effective strategy to treat or sensitize aggressive tumor clones to conventional cancer therapies and potentially prevent distant organ colonization.

  7. Sodium azide suppresses LPS-induced expression MCP-1 through regulating IκBζ and STAT1 activities in macrophages.

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    Park, Cho-Yi; Heo, Jae-Nyoung; Suk, Kyoungho; Lee, Won-Ha

    2017-05-01

    Sodium azide (NaN 3 ) is a chemical compound with multiple toxic effects on vascular and neuronal systems, causing hypotension and neurotoxicity, respectively. In order to test its effects on the immune system, human and mouse macrophage-like cell lines were treated with nontoxic doses of NaN 3 and the changes in LPS-induced inflammatory activation was measured. Interestingly, the LPS-induced expression of monocyte chemoattractant protein (MCP)-1 was suppressed by NaN 3 without affecting the expression of IL-8 and TNF-α. Further analysis of cellular signaling mediators involved in the expression of these cytokines revealed that NaN 3 suppressed the LPS-induced activation of signal transducers and activator of transcription (STAT)1 and inhibitor of κB (IκB) ς, which are involved in the LPS-induced expression of MCP-1, while the LPS-induced activation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) was not affected. The LPS-induced expression of MCP-2 and CXCL10, which are also regulated by STAT1, was suppressed by NaN 3 . Similarly, the LPS-induced expression of IL-6, which is regulated by IκBζ, was suppressed by NaN 3 . These results demonstrate that NaN 3 selectively suppresses the LPS-induced expression of pro-inflammatory mediators through the suppression of STAT1 and IκBζ activation. These new findings about the activity of NaN 3 may contribute to the development of specific regulators of macrophage activity during acute and chronic inflammation. Copyright © 2017. Published by Elsevier Inc.

  8. Active Components with Inhibitory Activities on IFN-γ/STAT1 and IL-6/STAT3 Signaling Pathways from Caulis Trachelospermi

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    Xiao-Ting Liu

    2014-08-01

    Full Text Available Initial investigation for new active herbal extract with inhibiting activity on JAK/STAT signaling pathway revealed that the extract of Caulis Trachelospermi, which was separated by 80% alcohol extraction and subsequent HP-20 macroporous resin column chromatography, was founded to strongly inhibit IFN-γ-induced STAT1-responsive luciferase activity (IFN-γ/STAT1 with IC50 value of 2.43 μg/mL as well as inhibiting IL-6-induced STAT3-responsive luciferase activity (IL-6/STAT3 with IC50 value of 1.38 μg/mL. Subsequent study on its active components led to the isolation and identification of two new dibenzylbutyrolactone lignans named 4-demethyltraxillaside (1 and nortrachelogenin 4-O-β-d-glucopyranoside (2, together with six known compounds. The lignan compounds 1–4 together with other lignan compounds isolated in previous study were tested the activities on IFN-γ/STAT1 and IL-6/STAT3 pathways. The following result showed that the main components trachelogenin and arctigenin had corresponding activities on IFN-γ/STAT1 pathway with IC50 values of 3.14 μM and 9.46 μM as well as trachelogenin, arctigenin and matairesinol strongly inhibiting IL-6/STAT3 pathway with IC50 values of 3.63 μM, 6.47 μM and 2.92 μM, respectively.

  9. Engagement of immune effector cells by trastuzumab induces HER2/ERBB2 downregulation in cancer cells through STAT1 activation

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    2014-01-01

    Introduction Trastuzumab has been widely used for the treatment of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer for more than a decade. However, reports on the involvement of HER2 downregulation in trastuzumab’s mechanism of action are inconsistent. The aim of this study is to investigate if the dependence of trastuzumab-mediated cancer cell HER2 downregulation on immune effector cells represents a novel mechanism of action for trastuzumab. Methods HER2 expression was evaluated by Western blotting, flow cytometry, and real-time polymerase chain reaction (PCR) in cell lysates from co-cultures of multiple cancer cell lines with peripheral blood mononuclear cells (PBMCs) in the presence or absence of trastuzumab. The engagement of immune cells by trastuzumab through Fc gamma receptors (FcγRs) was tested using three trastuzumab variants with compromised or no Fc (fragment crystallizable) functions and FcγRs blocking experiments. The engagement of immune cells by trastuzumab in HER2 downregulation was also evaluated in in vivo mouse xenograft tumor models. Results HER2 downregulation of cancer cells by trastuzumab occurred only when trastuzumab was actively engaged with immune cells and cancer cells, as demonstrated consistently in co-cultures of cancer cell lines with PBMCs and in vivo mouse xenograft tumor models. We further demonstrated that HER2 downregulation in cancer cells by immune-cell-engaged trastuzumab was at the transcriptional level, not through the HER2 degradation pathway. Activation of signal transducer and activator of transcription 1 (STAT1) in cancer cells by the increased interferon gamma (IFN-γ) production in immune cells played an important role in downregulating HER2 in cancer cells upon engagement of immune cells by trastuzumab. Furthermore, HER2 downregulation in cancer cells induced by trastuzumab engagement of immune cells was correlated with the antibody’s antitumor efficacy in vivo. Conclusions This

  10. The role of the growth hormone (GH) receptor and JAK1 and JAK2 kinases in the activation of Stats 1, 3, and 5 by GH

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    Smit, L S; Meyer, D J; Billestrup, Nils

    1996-01-01

    GH has been shown to activate the GH receptor (GHR)-associated tyrosine kinase JAK2 and the Src homology 2 domain-containing transcription factors Stats (signal transducers and activators of transcription) 1, 3, and 5. The present work investigates the role of GHR and JAK2 in the activation...... of Stats 1, 3, and 5 by GH. The ability of GH to stimulate the tyrosyl phosphorylation of these Stats was assessed in Chinese hamster ovary (CHO) cells expressing truncated and mutated GHR. GH was observed to stimulate tyrosyl phosphorylation of Stats 1, 3, and 5 in CHO cells expressing GHRs that bind JAK2...... [GHR1-638 (full-length) and GHR1-454 (lacks approximately half of the cytoplasmic domain)] but not in CHO cells expressing GHR that do not bind JAK2 (GHR1-318 or GHR1-294). GH-dependent tyrosyl phosphorylation of Stat5, but not Stats 1 or 3, was reduced in CHO cells expressing GHR1-454. GH...

  11. BANK1 Regulates IgG Production in a Lupus Model by Controlling TLR7-Dependent STAT1 Activation.

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    Ying-Yu Wu

    Full Text Available The purpose of our study was to investigate the effects of the adaptor Bank1 in TLR7 signaling using the B6.Sle1.yaa mouse, a lupus model that develops disease through exacerbated TLR7 expression. Crosses of B6.Sle1.yaa with Bank1-/- mice maintained several B and myeloid cell phenotypes close to normal wild-type levels. Most striking was the reduction in total serum IgG antibodies, but not of IgM, and reduced serum levels of autoantibodies, IL-6, and BAFF. Bank1 deficiency did modify numbers of MZ B cells and total B cell numbers, as well as expression of CXCR4 by follicular helper T cells. Other T cell changes were not observed. Bank1 deficiency did not modify numbers of germinal center B cells or plasma cells or clinical disease outcomes. Purified B cells from Bank1 deficient mice had strongly reduced Ifnb, Ifna4, Irf7, Aicda and Stat1 gene expression following TLR7 agonist stimulation. Interestingly, phosphorylation of Tyr701, but not of Ser727 of STAT1, was impaired in splenic B cells from B6.Sle1.yaa.Bank1-/- mice, as was the nuclear translocation of IRF7 in response to TLR7 agonist stimulation. Further, Bank1 deficiency in B6.Sle1.yaa mice reduced the production of IgG2c after in vitro TLR7 agonist stimulation. Our results demonstrate that Bank1 controls TLR7-mediated type I interferon production. Combined with the control of the nuclear translocation of IRF7, the modulation of STAT1 transcription and phosphorylation, Bank1 contributes to IgG production during development of autoimmune disease.

  12. STAT1 and STAT3 in tumorigenesis

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    Avalle, Lidia; Pensa, Sara; Regis, Gabriella; Novelli, Francesco; Poli, Valeria

    2012-01-01

    The transcription factors STAT1 and STAT3 appear to play opposite roles in tumorigenesis. While STAT3 promotes cell survival/proliferation, motility and immune tolerance and is considered as an oncogene, STAT1 mostly triggers anti-proliferative and pro-apoptotic responses while enhancing anti-tumor immunity. Despite being activated downstream of common cytokine and growth factor receptors, their activation is reciprocally regulated and perturbation in their balanced expression or phosphorylation levels may re-direct cytokine/growth factor signals from proliferative to apoptotic, or from inflammatory to anti-inflammatory. Here we review the functional canonical and non-canonical effects of STAT1 and STAT3 activation in tumorigenesis and their potential cross-regulation mechanisms. PMID:24058752

  13. Human cytomegalovirus IE1 protein elicits a type II interferon-like host cell response that depends on activated STAT1 but not interferon-γ.

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    Theresa Knoblach

    2011-04-01

    Full Text Available Human cytomegalovirus (hCMV is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1 protein, a major transcriptional activator and antagonist of type I interferon (IFN signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-γ and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1 and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-γ-responsive promoters. However, neither synthesis nor secretion of IFN-γ or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity.

  14. Human Cytomegalovirus IE1 Protein Elicits a Type II Interferon-Like Host Cell Response That Depends on Activated STAT1 but Not Interferon-γ

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    Knoblach, Theresa; Grandel, Benedikt; Seiler, Jana

    2011-01-01

    Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major transcriptional activator and antagonist of type I interferon (IFN) signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-γ and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1) and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-γ-responsive promoters. However, neither synthesis nor secretion of IFN-γ or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity. PMID:21533215

  15. PCBP2 enhances the antiviral activity of IFN-α against HCV by stabilizing the mRNA of STAT1 and STAT2.

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    Zhongshuai Xin

    Full Text Available Interferon-α (IFN-α is a natural choice for the treatment of hepatitis C, but half of the chronically infected individuals do not achieve sustained clearance of hepatitis C virus (HCV during treatment with IFN-α alone. The virus can impair IFN-α signaling and cellular factors that have an effect on the viral life cycles. We found that the protein PCBP2 is down-regulated in HCV-replicon containing cells (R1b. However, the effects and mechanisms of PCBP2 on HCV are unclear. To determine the effect of PCBP2 on HCV, overexpression and knockdown of PCBP2 were performed in R1b cells. Interestingly, we found that PCBP2 can facilitate the antiviral activity of IFN-α against HCV, although the RNA level of HCV was unaffected by either the overexpression or absence of PCBP2 in R1b cells. RIP-qRT-PCR and RNA half-life further revealed that PCBP2 stabilizes the mRNA of STAT1 and STAT2 through binding the 3'Untranslated Region (UTR of these two molecules, which are pivotal for the IFN-α anti-HCV effect. RNA pull-down assay confirmed that there were binding sites located in the C-rich tracts in the 3'UTR of their mRNAs. Stabilization of mRNA by PCBP2 leads to the increased protein expression of STAT1 and STAT2 and a consistent increase of phosphorylated STAT1 and STAT2. These effects, in turn, enhance the antiviral effect of IFN-α. These findings indicate that PCBP2 may play an important role in the IFN-α response against HCV and may benefit the HCV clinical therapy.

  16. Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype

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    Murakami, Shunichi; Balmes, Gener; McKinney, Sandra; Zhang, Zhaoping; Givol, David; de Crombrugghe, Benoit

    2004-01-01

    We generated transgenic mice that express a constitutively active mutant of MEK1 in chondrocytes. These mice showed a dwarf phenotype similar to achondroplasia, the most common human dwarfism, caused by activating mutations in FGFR3. These mice displayed incomplete hypertrophy of chondrocytes in the growth plates and a general delay in endochondral ossification, whereas chondrocyte proliferation was unaffected. Immunohistochemical analysis of the cranial base in transgenic embryos showed reduced staining for collagen type X and persistent expression of Sox9 in chondrocytes. These observations indicate that the MAPK pathway inhibits hypertrophic differentiation of chondrocytes and negatively regulates bone growth without inhibiting chondrocyte proliferation. Expression of a constitutively active mutant of MEK1 in chondrocytes of Fgfr3-deficient mice inhibited skeletal overgrowth, strongly suggesting that regulation of bone growth by FGFR3 is mediated at least in part by the MAPK pathway. Although loss of Stat1 restored the reduced chondrocyte proliferation in mice expressing an achondroplasia mutant of Fgfr3, it did not rescue the reduced hypertrophic zone, the delay in formation of secondary ossification centers, and the achondroplasia-like phenotype. These observations suggest a model in which Fgfr3 signaling inhibits bone growth by inhibiting chondrocyte differentiation through the MAPK pathway and by inhibiting chondrocyte proliferation through Stat1. PMID:14871928

  17. AG490 and PF431396 Sensitive Tyrosine Kinase Control the Population Heterogeneity of Basal STAT1 Activity in Ube1l Deficient Cells

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    Now, Hesung; Yoo, Joo-Yeon

    2016-01-01

    A population often contains distinct sub-populations, thereby increasing the complexity of the overall heterogeneity. However, the cellular origin and biological relevance of sub-populations in cell population have not been clearly identified. Here we demonstrated the novel roles of ISGylation, which is an IFN-induced post-translational modification, controlling heterogeneity at the population level in cultured adherent cells. Without UBE1L, an E1 enzyme of ISGylation, mouse embryonic fibroblasts (MEF) exhibited low viral resistance despite high STAT1 and ISG expression compared with the wild-type MEF. We observe that Ube1l−/− MEF populations consist of two behaviorally distinguishable sub-populations with distinct basal STAT1 activity, while wild-type MEF populations are unimodal. This population heterogeneity in Ube1l knock-out cells was perturbed by tyrosine kinase inhibitors, AG490 and PF431396. In contrast, the neutralization of type I IFN did not affect population heterogeneity. Based on these results, we concluded that UBE1L functions to adjust basal immunological states with the regulation of population heterogeneity. PMID:27427993

  18. Interleukin-27 Inhibits Herpes Simplex Virus Type 1 Infection by Activating STAT1 and 3, Interleukin-6, and Chemokines IP-10 and MIG.

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    Heikkilä, Outi; Nygårdas, Michaela; Paavilainen, Henrik; Ryödi, Elina; Hukkanen, Veijo

    2016-11-01

    Interleukin-27 (IL-27) inhibits the replication of many viruses, but the mechanism differs according to virus and cell type. In this study, we observed that IL-27 expression was upregulated in herpes simplex virus type 1 (HSV-1)-infected SJL/J mice, which led us to further investigate the role of IL-27 in HSV-1 infection using epithelial, glioma, and immunological cells as cell models. We showed that in all studied cell lines, the IL-27 messenger RNA (mRNA) level was upregulated due to the HSV-1 infection. When the cells were primed with IL-27 before the virus infection, the virus release was prevented, indicating an antiviral role of IL-27 in HSV-1 infection. Furthermore, we observed that IL-27 secretion to the culture medium was reduced in infected epithelial and immunological cells, but not in glioma cells. Not surprisingly, HSV-1 induced type I, II, and III interferons regardless of cell line, but IL-27 itself caused varying interferon responses dependent on cell type. However, common to all cell types was the IL-27-stimulated secretion of IL-6 and chemokines IP-10 and MIG. In addition, IL-27 stimulation activated STAT1 and STAT3 in HeLa and T98G cells, suggesting that IL-27 engages the STAT1/3 pathway, which then leads to the upregulation of IL-6, IP-10, and MIG.

  19. Involvement of Stat1 in the Phagocytosis of M. avium

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    Sabrina Dominici

    2012-01-01

    Full Text Available Mycobacterium avium is an intracellular pathogen preferentially infecting human macrophages where they activate the JAK/STAT1 pathway. This activation enhances the survival of infected cells, but, at the same time, makes macrophages optimal targets for drugs development against p-tyr701stat1. In this study, we demonstrate that the fast and transient activity of the JAK/STAT1 pathway occurs immediately after macrophages internalization of heat-killed M. avium or inert particles. Furthermore, we show that a persistent Stat1 pathway activation occurs only when an intracellular M. avium infection is established in macrophages. These results strongly indicate different mechanisms of p-tyr701Stat1 activation. In particular, here we report findings aiming at explaining the short-time enhancement of p-tyr701Stat1 and shows its predominant relationship with FcγRs engagement during the internalization process. Furthermore, we demonstrate that opsonized live M. avium is phagocytosed by macrophages involving membrane receptors not related with JAK/STAT1 signalling pathway. On the contrary, heat-inactivated bacilli or latex particles seem to be internalized only after involvement of FcγRs and subsequent Stat1 phosphorylation.

  20. Early activation of rat skeletal muscle IL-6/STAT1/STAT3 dependent gene expression in resistance exercise linked to hypertrophy.

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    Gwénaëlle Begue

    Full Text Available Cytokine interleukin-6 (IL-6 is an essential regulator of satellite cell-mediated hypertrophic muscle growth through the transcription factor signal transducer and activator of transcription 3 (STAT3. The importance of this pathway linked to the modulation of myogenic regulatory factors expression in rat skeletal muscle undergoing hypertrophy following resistance exercise, has not been investigated. In this study, the phosphorylation and nuclear localization of STAT3, together with IL-6/STAT3-responsive gene expression, were measured after both a single bout of resistance exercise and 10 weeks of training. Flexor Digitorum Profundus muscle samples from Wistar rats were obtained 2 and 6 hours after a single bout of resistance exercise and 72 h after the last bout of either 2, 4, or 10 weeks of resistance training. We observed an increase in IL-6 and SOCS3 mRNAs concomitant with phosphorylation of STAT1 and STAT3 after 2 and 6 hours of a single bout of exercise (p<0.05. STAT3-dependent early responsive genes such as CyclinD1 and cMyc were also upregulated whereas MyoD and Myf5 mRNAs were downregulated (p<0.05. BrdU-positive satellite cells increased at 2 and 6 hours after exercise (p<0.05. Muscle fiber hypertrophy reached up to 100% after 10 weeks of training and the mRNA expression of Myf5, c-Myc and Cyclin-D1 decreased, whereas IL-6 mRNA remained upregulated. We conclude that the IL-6/STAT1/STAT3 signaling pathway and its responsive genes after a single bout of resistance exercise are an important event regulating the SC pool and behavior involved in muscle hypertrophy after ten weeks of training in rat skeletal muscle.

  1. IL-17 intensifies IFN-γ-induced NOS2 upregulation in RAW 264.7 cells by further activating STAT1 and NF-κB.

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    Gao, Qiyue; Liu, Yang; Wu, Yan; Zhao, Qiang; Wang, Lijun; Gao, Shanshan; Wen, Wen; Zhang, Weiping; Guo, Ning; Zhou, Juan; Yuan, Zuyi

    2016-02-01

    Interleukin-17 (IL-17) is a signature cytokine of Th17 cells. Previous research has indicated that IL-17 plays a proinflammatory role by exacerbating interferon-γ (IFN-γ)-induced inflammation. However, prior to this study, it was not known whether inducible nitric oxide synthase (iNOS or NOS2), a signature molecule of inflammation, could be intensified by IL-17 when combined with IFN-γ. Thus, we explored the roles and underlying mechanisms of IL-17 and IFN-γ in the regulation of NOS2 expression in RAW 264.7 cells using qPCR, western blot analysis, colorimetric analysis, ChIP assay and statistical analysis. Although IL-17 alone did not induce NOS2 expression or nitric oxide (NO) production, as shown by western blot analysis and colorimetric analysis, it intensified IFN-γ-induced NOS2 upregulation and NO production in RAW 264.7 cells. The alteration of relevant transcription factors demonstrated that a combination of IFN-γ and IL-17 enhanced Tyr701-phosphorylated signal transducer and activator of transcription 1 [p-STAT1(Y701)] and nuclear factor-κB (NF-κB) activation, nuclear translocations and their binding to the NOS2 promoter, compared with IFN-γ alone, as illustrated by the results of the western blot analysis and ChIP assay. Also, using the corresponding inhibitors of STAT1 and NF-κB, we noted downregulation of the expression of NOS2 induced by IFN-γ alone or in combination with IL-17, respectively. In addition, IFN-γ increased phosphorylated (p-)p38 mitogen-activated protein kinase (MAPK), and accelerated the activation of the NF-κB pathway and the expression of NOS2, but phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was reduced by treatment with IFN-γ and IL-17. IL-17 intensified the activation of the NF-κB pathway and NOS2 upregulation induced by IFN-γ by increasing the phosphorylation of p38 MAPK and limiting the phosphorylation of ERK1/2. Taken together, these results suggest that IL-17 intensified IFN-γ-induced NOS2

  2. Nipah and Hendra Virus Nucleoproteins Inhibit Nuclear Accumulation of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT2 by Interfering with Their Complex Formation.

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    Sugai, Akihiro; Sato, Hiroki; Takayama, Ikuyo; Yoneda, Misako; Kai, Chieko

    2017-11-01

    Henipaviruses, such as Nipah (NiV) and Hendra (HeV) viruses, are highly pathogenic zoonotic agents within the Paramyxoviridae family. The phosphoprotein (P) gene products of the paramyxoviruses have been well characterized for their interferon (IFN) antagonist activity and their contribution to viral pathogenicity. In this study, we demonstrated that the nucleoprotein (N) of henipaviruses also prevents the host IFN signaling response. Reporter assays demonstrated that the NiV and HeV N proteins (NiV-N and HeV-N, respectively) dose-dependently suppressed both type I and type II IFN responses and that the inhibitory effect was mediated by their core domains. Additionally, NiV-N prevented the nuclear transport of signal transducer and activator of transcription 1 (STAT1) and STAT2. However, NiV-N did not associate with Impα5, Impβ1, or Ran, which are members of the nuclear transport system for STATs. Although P protein is known as a binding partner of N protein and actively retains N protein in the cytoplasm, the IFN antagonist activity of N protein was not abolished by the coexpression of P protein. This suggests that the IFN inhibition by N protein occurs in the cytoplasm. Furthermore, we demonstrated that the complex formation of STATs was hampered in the N protein-expressing cells. As a result, STAT nuclear accumulation was reduced, causing a subsequent downregulation of interferon-stimulated genes (ISGs) due to low promoter occupancy by STAT complexes. This novel route for preventing host IFN responses by henipavirus N proteins provides new insight into the pathogenesis of these viruses. IMPORTANCE Paramyxoviruses are well known for suppressing interferon (IFN)-mediated innate immunity with their phosphoprotein (P) gene products, and the henipaviruses also possess P, V, W, and C proteins for evading host antiviral responses. There are numerous studies providing evidence for the relationship between viral pathogenicity and antagonistic activities against IFN

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

    Science.gov (United States)

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

    2011-03-01

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

  4. Fatal combined immunodeficiency associated with heterozygous mutation in STAT1.

    Science.gov (United States)

    Sharfe, Nigel; Nahum, Amit; Newell, Andrea; Dadi, Harjit; Ngan, Bo; Pereira, Sergio L; Herbrick, Jo-Anne; Roifman, Chaim M

    2014-03-01

    Mutations in the gene for the signal transducer and activator of transcription 1, STAT1, have been shown to be associated with death at an early age due to overwhelming viral infection (complete STAT1 deficiency) or, more commonly, selective deficiencies to mycobacterial or fungal infection (typically heterozygous STAT1 mutations). To define the molecular basis of progressive combined immunodeficiency in a group of patients with fatal infections. We studied a group of unrelated patients who displayed an unusual progressive form of combined immunodeficiency. Whole exome sequencing assisted in confirming a common genetic defect in this group, which consisted of a heterozygous mutation of the STAT1 gene. STAT1 protein level as well as function was assessed, and a detailed evaluation of the immune system, including analysis of thymus tissue, was performed. Patients were found to carry de novo heterozygous mutations in STAT1 encoding T385A, I294T, or C284R amino acid substitutions. STAT1 expression appeared significantly decreased as a result of these changes but not completely absent, with diminished signaling responses. This group display progressive loss in lymphocyte number and function accompanied by increasing autoimmune features as well as severe, fatal infections. These findings show that some heterozygous aberrations of STAT1 can be associated with progressive combined immunodeficiency, quite distinct from the limited susceptibilities to infection previously reported for heterozygous STAT1 mutations. These mutations were not inherited, rather, arose de novo in each case. Accompanied by significant patient mortality, this finding suggests that this class of STAT1 mutation is ultimately fatal due to overwhelming infection. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  5. The milk protein α-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis.

    Science.gov (United States)

    Bonuccelli, Gloria; Castello-Cros, Remedios; Capozza, Franco; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Tsirigos, Aristotelis; Xuanmao, Jiao; Whitaker-Menezes, Diana; Howell, Anthony; Lisanti, Michael P; Sotgia, Federica

    2012-11-01

    Here, we identified the milk protein α-casein as a novel suppressor of tumor growth and metastasis. Briefly, Met-1 mammary tumor cells expressing α-casein showed a ~5-fold reduction in tumor growth and a near 10-fold decrease in experimental metastasis. To identify the molecular mechanism(s), we performed genome-wide transcriptional profiling. Interestingly, our results show that α-casein upregulates gene transcripts associated with interferon/STAT1 signaling and downregulates genes associated with "stemness." These findings were validated by immunoblot and FACS analysis, which showed the upregulation and hyperactivation of STAT1 and a decrease in the number of CD44(+) "cancer stem cells." These gene signatures were also able to predict clinical outcome in human breast cancer patients. Thus, we conclude that a lactation-based therapeutic strategy using recombinant α-casein would provide a more natural and non-toxic approach to the development of novel anticancer therapies.

  6. Autoimmune Regulator Deficiency Results in a Decrease in STAT1 Levels in Human Monocytes

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    Ofer Zimmerman

    2017-07-01

    Full Text Available Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED is a rare primary immunodeficiency disorder typically caused by biallelic autoimmune regulator (AIRE mutations that manifests with chronic mucocutaneous candidiasis (CMC and autoimmunity. Patients with STAT1 gain-of-function (GOF mutations also develop CMC and autoimmunity; they exhibit increased STAT1 protein levels at baseline and STAT1 phosphorylation (pSTAT1 upon interferon (IFN-γ stimulation relative to healthy controls. AIRE interacts functionally with a protein that directly regulates STAT1, namely protein inhibitor of activated STAT1, which inhibits STAT1 activation. Given the common clinical features between patients with AIRE and STAT1 GOF mutations, we sought to determine whether APECED patients also exhibit increased levels of STAT1 protein and phosphorylation in CD14+ monocytes. We obtained peripheral blood mononuclear cells from 8 APECED patients and 13 healthy controls and assessed the levels of STAT1 protein and STAT1 tyrosine phosphorylation at rest and following IFN-γ stimulation, as well as the levels of STAT1 mRNA. The mean STAT1 protein levels in CD14+ monocytes exhibited a ~20% significant decrease in APECED patients both at rest and after IFN-γ stimulation relative to that of healthy donors. Similarly, the mean peak value of IFN-γ-induced pSTAT1 level was ~20% significantly lower in APECED patients compared to that in healthy controls. The decrease in STAT1 and peak pSTAT1 in APECED patients was not accompanied by decreased STAT1 mRNA or anti-IFN-γ autoantibodies; instead, it correlated with the presence of autoantibodies to type I IFN and decreased AIRE−/− monocyte surface expression of IFN-γ receptor 2. Our data show that, in contrast to patients with STAT1 GOF mutations, APECED patients show a moderate but consistent and significant decrease in total STAT1 protein levels, associated with lower peak levels of pSTAT1 molecules after IFN

  7. Autoimmune Regulator Deficiency Results in a Decrease in STAT1 Levels in Human Monocytes

    Science.gov (United States)

    Zimmerman, Ofer; Rosen, Lindsey B.; Swamydas, Muthulekha; Ferre, Elise M. N.; Natarajan, Mukil; van de Veerdonk, Frank; Holland, Steven M.; Lionakis, Michail S.

    2017-01-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by biallelic autoimmune regulator (AIRE) mutations that manifests with chronic mucocutaneous candidiasis (CMC) and autoimmunity. Patients with STAT1 gain-of-function (GOF) mutations also develop CMC and autoimmunity; they exhibit increased STAT1 protein levels at baseline and STAT1 phosphorylation (pSTAT1) upon interferon (IFN)-γ stimulation relative to healthy controls. AIRE interacts functionally with a protein that directly regulates STAT1, namely protein inhibitor of activated STAT1, which inhibits STAT1 activation. Given the common clinical features between patients with AIRE and STAT1 GOF mutations, we sought to determine whether APECED patients also exhibit increased levels of STAT1 protein and phosphorylation in CD14+ monocytes. We obtained peripheral blood mononuclear cells from 8 APECED patients and 13 healthy controls and assessed the levels of STAT1 protein and STAT1 tyrosine phosphorylation at rest and following IFN-γ stimulation, as well as the levels of STAT1 mRNA. The mean STAT1 protein levels in CD14+ monocytes exhibited a ~20% significant decrease in APECED patients both at rest and after IFN-γ stimulation relative to that of healthy donors. Similarly, the mean peak value of IFN-γ-induced pSTAT1 level was ~20% significantly lower in APECED patients compared to that in healthy controls. The decrease in STAT1 and peak pSTAT1 in APECED patients was not accompanied by decreased STAT1 mRNA or anti-IFN-γ autoantibodies; instead, it correlated with the presence of autoantibodies to type I IFN and decreased AIRE−/− monocyte surface expression of IFN-γ receptor 2. Our data show that, in contrast to patients with STAT1 GOF mutations, APECED patients show a moderate but consistent and significant decrease in total STAT1 protein levels, associated with lower peak levels of pSTAT1 molecules after IFN-γ stimulation

  8. Inborn errors of human STAT1: allelic heterogeneity governs the diversity of immunological and infectious phenotypes

    Science.gov (United States)

    Boisson-Dupuis, Stephanie; Kong, Xiao-Fei; Okada, Satoshi; Cypowyj, Sophie; Puel, Anne; Abel, Laurent; Casanova, Jean-Laurent

    2012-01-01

    The genetic dissection of various human infectious diseases has led to the definition of inborn errors of human STAT1 immunity of four types, including (i) autosomal recessive (AR) complete STAT1 deficiency, (ii) AR partial STAT1 deficiency, (iii) autosomal dominant (AD) STAT1 deficiency, and (iv) AD gain of STAT1 activity. The two types of AR STAT1 defect give rise to a broad infectious phenotype with susceptibility to intramacrophagic bacteria (mostly mycobacteria) and viruses (herpes viruses at least), due principally to the impairment of IFN-γ-mediated and IFN-α/β-mediated immunity, respectively. Clinical outcome depends on the extent to which the STAT1 defect decreases responsiveness to these cytokines. AD STAT1 deficiency selectively predisposes individuals to mycobacterial disease, owing to the impairment of IFN-γ-mediated immunity, as IFN-α/β-mediated immunity is maintained. Finally, AD gain of STAT1 activity is associated with autoimmunity, probably owing to an enhancement of IFN-α/β-mediated immunity. More surprisingly, it is also associated with chronic mucocutaneous candidiasis, through as yet undetermined mechanisms involving an inhibition of the development of IL-17-producing T cells. Thus, germline mutations in human STAT1 define four distinct clinical disorders. Various combinations of viral, mycobacterial and fungal infections are therefore allelic at the human STAT1 locus. These experiments of Nature neatly highlight the clinical and immunological impact of the human genetic dissection of infectious phenotypes. PMID:22651901

  9. Proinflammatory Cytokines IL-6 and TNF-α Increased Telomerase Activity through NF-κB/STAT1/STAT3 Activation, and Withaferin A Inhibited the Signaling in Colorectal Cancer Cells

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    Seyung S. Chung

    2017-01-01

    Full Text Available There are increasing evidences of proinflammatory cytokine involvement in cancer development. Here, we found that two cytokines, IL-6 and TNF-α, activated colorectal cancer cells to be more invasive and stem-like. Combined treatment of IL-6 and TNF-α phosphorylated transcription factors STAT3 in a synergistic manner. STAT3, STAT1, and NF-κB physically interacted upon the cytokine stimulation. STAT3 was bound to the promoter region of human telomerase reverse transcriptase (hTERT. IL-6 and TNF-α stimulation further enhanced STAT3 binding affinity. Stem cell marker Oct-4 was upregulated in colorectal cancer cells upon IL-6 and TNF-α stimulation. Withaferin A, an anti-inflammatory steroidal lactone, inhibited the IL-6- and TNF-α-induced cancer cell invasion and decreased colonosphere formation. Notably, withaferin A inhibited STAT3 phosphorylation and abolished the STAT3, STAT1, and NF-κB interactions. Oct-4 expression was also downregulated by withaferin A inhibition. The binding of STAT3 to the hTERT promoter region and telomerase activity showed reduction with withaferin A treatments. Proinflammatory cytokine-induced cancer cell invasiveness is mediated by a STAT3-regulated mechanism in colorectal cancer cells. Our data suggest that withaferin A could be a promising anticancer agent that effectively inhibits the progression of colorectal cancer.

  10. Menin and RNF20 recruitment is associated with dynamic histone modifications that regulate signal transducer and activator of transcription 1 (STAT1-activated transcription of the interferon regulatory factor 1 gene (IRF1

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    Buro Lauren J

    2010-09-01

    Full Text Available Abstract Background Signal transducer and activator of transcription (STAT activation of gene expression is both rapid and transient, and when properly executed it affects growth, differentiation, homeostasis and the immune response, but when dysregulated it contributes to human disease. Transcriptional activation is regulated by alterations to the chromatin template. However, the role of histone modification at gene loci that are activated for transcription in response to STAT signaling is poorly defined. Results Using chromatin immunoprecipitation, we profiled several histone modifications during STAT1 activation of the interferon regulatory factor 1 gene (IRF1. Methylated lysine histone proteins H3K4me2, H3K4me3, H3K79me3, H3K36me3 and monoubiquitinated histone ubH2B are dynamic and correlate with interferon (IFNγ induction of STAT1 activity. Chemical inhibition of H3K4 methylation downregulates IRF1 transcription and decreases RNA polymerase II (Pol II occupancy at the IRF1 promoter. MEN1, a component of a complex proteins associated with Set1 (COMPASS-like complex and the hBRE1 component, RNF20, are localized to IRF1 in the uninduced state and are further recruited when IRF1 is activated. RNAi-mediated depletion of RNF20 lowers both ubH2B and H3K4me3, but surprisingly, upregulates IFNγ induced IRF1 transcription. The dynamics of phosphorylation in the C-terminal domain (CTD of Pol II are disrupted during gene activation as well. Conclusions H2B monoubiquitination promotes H3K4 methylation, but the E3 ubiquitin ligase, RNF20, is repressive of inducible transcription at the IRF1 gene locus, suggesting that ubH2B can, directly or indirectly, affect Pol II CTD phosphorylation cycling to exert control on ongoing transcription.

  11. Psidium guajava extract inhibits thymus and activation-regulated chemokine (TARC/CCL17) production in human keratinocytes by inducing heme oxygenase-1 and blocking NF-κB and STAT1 activation.

    Science.gov (United States)

    Han, Eun Hee; Hwang, Yong Pil; Choi, Jae Ho; Yang, Ji Hye; Seo, Jong Kwon; Chung, Young Chul; Jeong, Hye Gwang

    2011-09-01

    Psidium guajava (P. guajava) is a food and medicinal plant with antioxidant, anti-inflammatory, and anti-allergic activities that support its traditional uses. The aim of this study was to determine the effects of P. guajava ethyl acetate extract (PGEA) on atopic dermatitis and to investigate the possible mechanisms by which PGEA inhibits cytokine-induced Th2 chemokine expression in HaCaT human keratinocyte cells. We found that PGEA suppressed the IFN-γ/TNF-α-co-induced production of thymus and activation-regulated chemokine (TARC) protein and mRNA in HaCaT cells. Additionally, PGEA inhibited the TNF-α/IFN-γ-co-induced activation of NF-κB and STAT1 and increased the expression of heme oxygenase-1 (HO-1) protein and mRNA. HO-1 inhibitor enhanced the suppressive effects of PGEA on TNF-α/IFN-γ-co-induced TARC production and gene expression. Collectively, these data demonstrate that PGEA inhibits chemokine expression in keratinocytes by inducing HO-1 expression and it suggests a possible therapeutic application in atopic dermatitis and other inflammatory skin diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. The measles virus phosphoprotein interacts with the linker domain of STAT1

    Energy Technology Data Exchange (ETDEWEB)

    Devaux, Patricia, E-mail: devaux.patricia@mayo.edu; Priniski, Lauren; Cattaneo, Roberto

    2013-09-15

    The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway.

  13. The measles virus phosphoprotein interacts with the linker domain of STAT1

    International Nuclear Information System (INIS)

    Devaux, Patricia; Priniski, Lauren; Cattaneo, Roberto

    2013-01-01

    The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway

  14. Molecular cloning and expression analysis of the STAT1 gene from olive flounder, Paralichthys olivaceus

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    Chung Jongkyeong

    2008-06-01

    Full Text Available Abstract Background Signal transducer and activator of transcription 1 (STAT1 is a critical component of interferon (IFN-alpha/beta and IFN-gamma signaling. Although seven isoforms of STAT proteins have been reported from mammals, limited information is available for the STAT genes in fish. We isolated complementary DNA with high similarity to mammalian STAT1 from the olive flounder, Paralichthys olivaceus. Results A DNA fragment containing the conserved SH2 domain was amplified by RT-PCR using degenerate primers designed based on the highly conserved sequences in the SH2 domains of the zebrafish and mammalian STAT1. The complete cDNA sequence was obtained by 5' and 3' RACE. The flounder STAT1 transcript consisted of 2,909 bp that encoded a polypeptide of 749 amino acids. The overall similarity between flounder STAT1 and other STATs was very high, with the highest amino acid sequence identity to snakehead (89%. Phylogenetic analyses reveal that flounder STAT1 is in the same monophyletic group with snakehead STAT1. Quantitative real time RT-PCR and in situ hybridization revealed that STAT1 was expressed in almost all examined organs and tissues, with high expression in gill, spleen, kidney, and heart. The accumulation of STAT1 mRNA in different developmental stages, as determined by real time RT-PCR, increased with development. Conclusion Recent cloning of various cytokine genes and the STAT1 gene of olive flounder here suggest that fish also use the highly specialized JAK-STAT pathway for cytokine signaling. Identification of other STAT genes will elucidate in detail the signal transduction system in this fish.

  15. The role of STAT1 for crosstalk between fibroblasts and colon cancer cells

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    Pawan eKaler

    2014-04-01

    Full Text Available Signaling between tumor cells and the associated stroma has an important impact on cancer initiation and progression. The tumor microenvironment has a paradoxical role in tumor progression and fibroblasts, a major component of the tumor stroma, have been shown to either inhibit or promote cancer development. In this study we established that normal intestinal fibroblasts activate STAT1 signaling in colon cancer cells and, in contrast to cancer- associated fibroblasts, inhibit growth of tumor cells. Treatment of 18Co fibroblasts with the proinflammatory cytokine TNF interfered with their ability to trigger STAT1 signaling in cancer cells. Accordingly, intestinal myofibroblasts isolated from patients with Ulcerative colitis (UC or Crohn’s disease (CD, which are activated and produce high levels of TNF, failed to stimulate STAT1 signaling in tumor cells, demonstrating that activated myofibroblasts lose the ability to trigger growth-inhibitory STAT1 signaling in tumor cells. Finally, we confirmed that silencing of STAT1 in tumor cells alters the crosstalk between tumor cells and fibroblasts, suggesting STAT1 as a novel link between intestinal inflammation and colon cancer. We demonstrated that normal fibroblasts restrain the growth of carcinoma cells, at least in part, through the induction of STAT1 signaling in cancer cells. We showed that changes in the microenvironment, as they occur in inflammatory bowel disease, alter the crosstalk between carcinoma cells and fibroblasts, perturb the homeostasis of intestinal tissue and thereby contribute to tumor progression.

  16. A STAT-1 knockout mouse model for Machupo virus pathogenesis

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    Shurtleff Amy C

    2011-06-01

    Full Text Available Abstract Background Machupo virus (MACV, a member of the Arenaviridae, causes Bolivian hemorrhagic fever, with ~20% lethality in humans. The pathogenesis of MACV infection is poorly understood, and there are no clinically proven treatments for disease. This is due, in part, to a paucity of small animal models for MACV infection in which to discover and explore candidate therapeutics. Methods Mice lacking signal transducer and activator of transcription 1 (STAT-1 were infected with MACV. Lethality, viral replication, metabolic changes, hematology, histopathology, and systemic cytokine expression were analyzed throughout the course of infection. Results We report here that STAT-1 knockout mice succumbed to MACV infection within 7-8 days, and presented some relevant clinical and histopathological manifestations of disease. Furthermore, the model was used to validate the efficacy of ribavirin in protection against infection. Conclusions The STAT-1 knockout mouse model can be a useful small animal model for drug testing and preliminary immunological analysis of lethal MACV infection.

  17. STAT1 and IRF8 in Vascular Inflammation and Cardiovascular Disease: Diagnostic and Therapeutic Potential.

    Science.gov (United States)

    Chmielewski, Stefan; Piaszyk-Borychowska, Anna; Wesoly, Joanna; Bluyssen, Hans A R

    2016-09-02

    Inflammation importantly contributes to the pathophysiology of Cardiovascular Disease (CVD). Signal Transducer and Activator of Transcription (STAT)1 operates at the frontier of innate and adaptive immunity and its involvement in CVD has been widely appreciated. A unique role of STAT1 in cross-talk between the pro-inflammatory cytokine IFNγ and TLR4 activators (TLR4-A) has been uncovered in immune as well as vascular cells increasing inflammation. Interferon Regulatory Factor (IRF)8 whose expression was initially identified in immune cells, controls development and differentiation in close connection with PU.1. In addition, as a STAT1-target, IRF8 accounts for "immune cell-specific" STAT1-dependent functions of IFNγ and LPS. Novel studies prove that also in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), STAT1 and IRF8 orchestrate a transcriptional platform for cross-talk between IFNγ and TLR4-A, which leads to amplified pro-atherogenic responses in the vasculature. In addition to its known immune cell functions, this points to a novel "inflammation-dependent" role of IRF8 in vascular cells. In this review we present a summary of these findings and postulate STAT1- and IRF8-target genes as promising markers of vascular inflammation, and STAT1 and IRF8 as potential targets for the development of new immunosuppressive and anti-inflammatory agents for the treatment of CVD.

  18. The role of the growth hormone (GH) receptor and JAK1 and JAK2 kinases in the activation of Stats 1, 3, and 5 by GH

    DEFF Research Database (Denmark)

    Smit, L S; Meyer, D J; Billestrup, Nils

    1996-01-01

    GH has been shown to activate the GH receptor (GHR)-associated tyrosine kinase JAK2 and the Src homology 2 domain-containing transcription factors Stats (signal transducers and activators of transcription) 1, 3, and 5. The present work investigates the role of GHR and JAK2 in the activation of St...

  19. KAP1 regulates type I interferon/STAT1-mediated IRF-1 gene expression

    International Nuclear Information System (INIS)

    Kamitani, Shinya; Ohbayashi, Norihiko; Ikeda, Osamu; Togi, Sumihito; Muromoto, Ryuta; Sekine, Yuichi; Ohta, Kazuhide; Ishiyama, Hironobu; Matsuda, Tadashi

    2008-01-01

    Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation, and survival in immune responses, hematopoiesis, neurogenesis, and other biological processes. Recently, we showed that KAP1 is a novel STAT-binding partner that regulates STAT3-mediated transactivation. KAP1 is a universal co-repressor protein for the KRAB zinc finger protein superfamily of transcriptional repressors. In this study, we found KAP1-dependent repression of interferon (IFN)/STAT1-mediated signaling. We also demonstrated that endogenous KAP1 associates with endogenous STAT1 in vivo. Importantly, a small-interfering RNA-mediated reduction in KAP1 expression enhanced IFN-induced STAT1-dependent IRF-1 gene expression. These results indicate that KAP1 may act as an endogenous regulator of the IFN/STAT1 signaling pathway

  20. A proteomic study of the regulatory role for STAT-1 in cytokine-induced beta-cell death

    DEFF Research Database (Denmark)

    Rondas, Dieter; Gudmundsdottir, Valborg; D’Hertog, Wannes

    2015-01-01

    PURPOSE: Signal transducer and activator of transcription 1 (STAT-1) plays a crucial role in cytokine-induced beta-cell destruction. However, its precise downstream pathways have not been completely clarified. We performed a proteome analysis of cytokine-exposed C57Bl/6 and STAT-1-/- mouse islets...

  1. High STAT1 mRNA levels but not its tyrosine phosphorylation are associated with macrophage infiltration and bad prognosis in breast cancer

    International Nuclear Information System (INIS)

    Tymoszuk, Piotr; Fiegl, Heidi; Doppler, Wolfgang; Charoentong, Pornpimol; Hackl, Hubert; Spilka, Rita; Müller-Holzner, Elisabeth; Trajanoski, Zlatko; Obrist, Peter; Revillion, Françoise; Peyrat, Jean-Philippe

    2014-01-01

    STAT1 has been attributed a function as tumor suppressor. However, in breast cancer data from microarray analysis indicated a predictive value of high mRNA expression levels of STAT1 and STAT1 target genes belonging to the interferon-related signature for a poor response to therapy. To clarify this issue we have determined STAT1 expression levels and activation by different methods, and investigated their association with tumor infiltration by immune cells. Additionally, we evaluated the interrelationship of these parameters and their significance for predicting disease outcome. Expression of STAT1, its target genes SOCS1, IRF1, CXCL9, CXCL10, CXCL11, IFIT1, IFITM1, MX1 and genes characteristic for immune cell infiltration (CD68, CD163, PD-L1, PD-L2, PD-1, CD45, IFN-γ, FOXP3) was determined by RT-PCR in two independent cohorts comprising 132 breast cancer patients. For a subset of patients, protein levels of total as well as serine and tyrosine-phosphorylated STAT1 were ascertained by immunohistochemistry or immunoblotting and protein levels of CXCL10 by ELISA. mRNA expression levels of STAT1 and STAT1 target genes, as well as protein levels of total and serine-phosphorylated STAT1 correlated with each other in neoplastic tissue. However, there was no association between tumor levels of STAT1 mRNA and tyrosine-phosphorylated STAT1 and between CXCL10 serum levels and CXCL10 expression in the tumor. Tumors with increased STAT1 mRNA amounts exhibited elevated expression of genes characteristic for tumor-associated macrophages and immunosuppressive T lymphocytes. Survival analysis revealed an association of high STAT1 mRNA levels and bad prognosis in both cohorts. A similar prognostically relevant correlation with unfavorable outcome was evident for CXCL10, MX1, CD68, CD163, IFN-γ, and PD-L2 expression in at least one collective. By contrast, activation of STAT1 as assessed by the level of STAT1-Y701 phosphorylation was linked to positive outcome. In multivariate Cox

  2. Modulation of Stat-1 in Human Macrophages Infected with Different Species of Intracellular Pathogenic Bacteria

    Directory of Open Access Journals (Sweden)

    Giuditta Fiorella Schiavano

    2016-01-01

    Full Text Available The infection of human macrophages by pathogenic bacteria induces different signaling pathways depending on the type of cellular receptors involved in the microorganism entry and on their mechanism(s of survival and replication in the host cell. It was reported that Stat proteins play an important role in this process. In the present study, we investigate the changes in Stat-1 activation (phosphorylation in p-tyr701 after uptake of two Gram-positive (Listeria monocytogenes and Staphylococcus aureus and two Gram-negative bacteria (Salmonella typhimurium and Legionella pneumophila characterized by their varying abilities to enter, survive, and replicate in human macrophages. Comparing the results obtained with Gram-negative and Gram-positive bacteria, Stat-1 activation in macrophages does not seem to be related to LPS content. The p-tyr701Stat-1 expression levels were found to be independent of the internalized bacterial number and IFN-γ release. On the contrary, Jak/Stat-1 pathway activation only occurs when an active infection has been established in the host macrophage, and it is plausible that the differences in the expression levels of p-tyr701Stat-1 could be due to different survival mechanisms or to differences in bacteria life cycles within macrophages.

  3. SH2 modified STAT1 induces HLA-I expression and improves IFN-γ signaling in IFN-α resistant HCV replicon cells.

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    Bret Poat

    2010-09-01

    Full Text Available We have developed multiple stable cell lines containing subgenomic HCV RNA that are resistant to treatment with interferon alpha (IFN-α. Characterization of these IFN-α resistant replicon cells showed defects in the phosphorylation and nuclear translocation of STAT1 and STAT2 proteins due to a defective Jak-STAT pathway.In this study, we have developed an alternative strategy to overcome interferon resistance in a cell culture model by improving intracellular STAT1 signaling. An engineered STAT1-CC molecule with double cysteine substitutions in the Src-homology 2 (SH2 domains of STAT1 (at Ala-656 and Asn-658 efficiently phosphorylates and translocates to the nucleus of IFN-resistant cells in an IFN-γ dependent manner. Transfection of a plasmid clone containing STAT1-CC significantly activated the GAS promoter compared to wild type STAT1 and STAT3. The activity of the engineered STAT1-CC is dependent upon the phosphorylation of tyrosine residue 701, since the construct with a substituted phenylalanine residue at position 701 (STAT1-CC-Y701F failed to activate GAS promoter in the replicon cells. Intracellular expression of STAT1-CC protein showed phosphorylation and nuclear translocation in the resistant cell line after IFN-γ treatment. Transient transfection of STAT1-CC plasmid clone into an interferon resistant cell line resulted in inhibition of viral replication and viral clearance in an IFN-γ dependent manner. Furthermore, the resistant replicon cells transfected with STAT1-CC constructs significantly up regulated surface HLA-1 expression when compared to the wild type and Y to F mutant controls.These results suggest that modification of the SH2 domain of the STAT1 molecule allows for improved IFN-γ signaling through increased STAT1 phosphorylation, nuclear translocation, HLA-1 surface expression, and prolonged interferon antiviral gene activation.

  4. STAT1 Inhibits MiR-181a Expression to Suppress Colorectal Cancer Cell Proliferation Through PTEN/Akt.

    Science.gov (United States)

    Zhang, Xingwen; Li, Xiang; Tan, Fengbo; Yu, Nanhui; Pei, Haiping

    2017-10-01

    Signal transducers and activators of transcription 1 (STAT1) exhibits tumor-suppressor properties by inhibiting oncogenic pathways and promoting tumor immunosurveillance. MicroRNAs, a group of non-coding endogenous ones, may regulate gene expression and plays specific roles in tumorigenesis. Recently, miR-181a has been reported to be associated with poor prognosis of colorectal cancer (CRC). Using human colorectal cancer cell lines, we demonstrated that STAT1 suppresses both LoVo and SW480 cell growth by down-regulating miR-181a. STAT1 regulates the expression of miR-181a through binding to the elements in the miR-181a's promoter region. Further, we revealed that miR-181a accelerates CRC cell proliferation through phosphatase and tensin homolog on chromosome ten (PTEN). In addition, PTEN protein was upregulated in response to STAT1 overexpression or miR-181a inhibition, downregulated in response to STAT1 knockdown or miR-181a overexpression. Without changes on the AKT protein level, p-AKT was downregulated by STAT1 overexpression or miR-181a inhibition while upregulated by STAT1 knockdown or miR-181a overexpression, indicating PTEN/Akt pathway activated in STAT1/miR-181a regulation of CRC cell proliferation. Taken together, our findings shed new light on the STAT1/miR-181a/PTEN pathway in colorectal cancer and add new insight regarding the carcinogenesis of colorectal cancer. J. Cell. Biochem. 118: 3435-3443, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1.

    Science.gov (United States)

    Baris, Safa; Alroqi, Fayhan; Kiykim, Ayca; Karakoc-Aydiner, Elif; Ogulur, Ismail; Ozen, Ahmet; Charbonnier, Louis-Marie; Bakır, Mustafa; Boztug, Kaan; Chatila, Talal A; Barlan, Isil B

    2016-10-01

    Loss and gain-of-function (GOF) mutations in human signal transducer and activator of transcription 1 (STAT1) lead to distinct phenotypes. Although recurrent infections are common to both types of STAT1 mutations, GOF mutations are distinguished by chronic mucocutaneous candidiasis and autoimmunity. However, the clinical spectra of STAT1 GOF mutations continue to expand. We here describe two patients with STAT1 GOF mutations presenting early in life with combined immunodeficiency (CID). Clinical data and laboratory findings including immunophenotyping, level of interferon (IFN)-γ/IL-17(+) T cells, interferon-induced STAT1 phosphorylation, and JAK inhibitor assays were evaluated. Sequencing of STAT1 gene was performed by Sanger sequencer. Patient 1 (P1) had persistent oral candidiasis and cytomegalovirus (CMV) infection since 2 months of age and later developed cavitary lung lesions due to Mycobacterium tuberculosis. Patient 2 (P2) presented with oral candidiasis and recurrent pneumonia at 4 months of age and subsequently developed CMV pneumonitis. Both patients suffered heterozygous missense mutations in STAT1, leading to deleterious amino acid substitutions in the DNA binding domain (P1: c.1154C > T; p.T385M; P2. c.971G > T; p.C324F). Circulating CD4(+) T cells of both patients exhibited increased interferon-γ and decreased IL-17 expression as compared to controls. They also exhibited increased IFN-β and -γ-induced STAT1 phosphorylation that was reversed upon treatment with the JAK kinase inhibitor ruxolitinib. STAT1 GOF mutations may present early in life with CID, consistent with the clinical heterogeneity of the disease. JAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation.

  6. STAT1: A Novel Target of miR-150 and miR-223 Is Involved in the Proliferation of HTLV-I–Transformed and ATL Cells

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    Ramona Moles

    2015-05-01

    Full Text Available We have previously reported on the deregulation of cellular microRNAs involved in hematopoiesis and inflammation in human T-cell lymphotropic virus type 1 (HTLV-I–transformed cells. In this study, we demonstrate that miR-150 and miR-223 specifically target the signal transducer and activator of transcription 1 (STAT1 3′ untranslated region, reducing STAT1 expression and dampening STAT1-dependent signaling in human T cells. The effects of miR-150 and miR-223 on endogenous STAT1 were confirmed using inducible cell lines. Our studies also showed that miR-150 expression is upregulated by interleukin-2 signaling in adult T cell leukemia/lymphoma (ATL cells. HTLV-I–transformed and ATL-derived cells have reduced levels of miR150 and miR223 expression, which coincide with increased STAT1 expression and STAT1-dependent signaling. Knockdown of STAT1 by short hairpin RNA demonstrated that the constitutive activation of STAT1 is required for the continuous proliferation of HTLV-I–transformed cells. Our studies further demonstrate that increased expression of STAT1 in ATL cells is associated with higher levels of major histocompatibility complex class I expression. Previous studies have demonstrated that the pressure exerted by natural killer (NK cells in vivo can edit leukemic tumor cells by forcing an increased expression of major histocompatibility complex class I to escape immune clearance. STAT1-expressing tumor cells produce more aggressive tumors because they cannot be eliminated by NK cells. Our results suggest that therapeutic approaches using combined targeting of STAT1 and MHC class I may be an effective approach to activate NK cell–mediated clearance of ATL tumor cells.

  7. Hepatitis C virus core protein inhibits interferon production by a human plasmacytoid dendritic cell line and dysregulates interferon regulatory factor-7 and signal transducer and activator of transcription (STAT) 1 protein expression.

    Science.gov (United States)

    Stone, Amy E L; Mitchell, Angela; Brownell, Jessica; Miklin, Daniel J; Golden-Mason, Lucy; Polyak, Stephen J; Gale, Michael J; Rosen, Hugo R

    2014-01-01

    Plasmacytoid Dendritic Cells (pDCs) represent a key immune cell population in the defense against viruses. pDCs detect viral pathogen associated molecular patterns (PAMPs) through pattern recognition receptors (PRR). PRR/PAMP interactions trigger signaling events that induce interferon (IFN) production to initiate local and systemic responses. pDCs produce Type I and Type III (IFNL) IFNs in response to HCV RNA. Extracellular HCV core protein (Core) is found in the circulation in chronic infection. This study defined how Core modulates PRR signaling in pDCs. Type I and III IFN expression and production following exposure to recombinant Core or β-galactosiade was assessed in human GEN2.2 cells, a pDC cell line. Core suppressed type I and III IFN production in response to TLR agonists and the HCV PAMP agonist of RIG-I. Core suppression of IFN induction was linked with decreased IRF-7 protein levels and increased non-phosphorylated STAT1 protein. Circulating Core protein interferes with PRR signaling by pDCs to suppress IFN production. Strategies to define and target Core effects on pDCs may serve to enhance IFN production and antiviral actions against HCV.

  8. Increased STAT1 signaling in endocrine-resistant breast cancer.

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    Rui Huang

    Full Text Available Proteomic profiling of the estrogen/tamoxifen-sensitive MCF-7 cell line and its partially sensitive (MCF-7/LCC1 and fully resistant (MCF-7/LCC9 variants was performed to identify modifiers of endocrine sensitivity in breast cancer. Analysis of the expression of 120 paired phosphorylated and non-phosphorylated epitopes in key oncogenic and tumor suppressor pathways revealed that STAT1 and several phosphorylated epitopes (phospho-STAT1(Tyr701 and phospho-STAT3(Ser727 were differentially expressed between endocrine resistant and parental controls, confirmed by qRT-PCR and western blotting. The STAT1 inhibitor EGCG was a more effective inhibitor of the endocrine resistant MCF-7/LCC1 and MCF-7/LCC9 lines than parental MCF-7 cells, while STAT3 inhibitors Stattic and WP1066 were equally effective in endocrine-resistant and parental lines. The effects of the STAT inhibitors were additive, rather than synergistic, when tested in combination with tamoxifen in vitro. Expression of STAT1 and STAT3 were measured by quantitative immunofluorescence in invasive breast cancers and matched lymph nodes. When lymph node expression was compared to its paired primary breast cancer expression, there was greater expression of cytoplasmic STAT1 (∼3.1 fold, phospho-STAT3(Ser727 (∼1.8 fold, and STAT5 (∼1.5 fold and nuclear phospho-STAT3(Ser727 (∼1.5 fold in the nodes. Expression levels of STAT1 and STAT3 transcript were analysed in 550 breast cancers from publicly available gene expression datasets (GSE2990, GSE12093, GSE6532. When treatment with tamoxifen was considered, STAT1 gene expression was nearly predictive of distant metastasis-free survival (DMFS, log-rank p = 0.067, while STAT3 gene expression was predictive of DMFS (log-rank p<0.0001. Analysis of STAT1 and STAT3 protein expression in a series of 546 breast cancers also indicated that high expression of STAT3 protein was associated with improved survival (DMFS, p = 0.006. These results suggest

  9. The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii.

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    Daniel P Beiting

    2015-07-01

    Full Text Available The protozoan parasite, Toxoplasma, like many intracellular pathogens, suppresses interferon gamma (IFN-γ-induced signal transducer and activator of transcription 1 (STAT1 activity. We exploited this well-defined host-pathogen interaction as the basis for a high-throughput screen, identifying nine transcription factors that enhance STAT1 function in the nucleus, including the orphan nuclear hormone receptor TLX. Expression profiling revealed that upon IFN-γ treatment TLX enhances the output of a subset of IFN-γ target genes, which we found is dependent on TLX binding at those loci. Moreover, infection of TLX deficient mice with the intracellular parasite Toxoplasma results in impaired production of the STAT1-dependent cytokine interleukin-12 by dendritic cells and increased parasite burden in the brain during chronic infection. These results demonstrate a previously unrecognized role for this orphan nuclear hormone receptor in regulating STAT1 signaling and host defense and reveal that STAT1 activity can be modulated in a context-specific manner by such "modifiers."

  10. Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment

    International Nuclear Information System (INIS)

    Mori, Kazumasa; Haraguchi, Shigeki; Hiori, Miki; Shimada, Jun; Ohmori, Yoshihiro

    2015-01-01

    Tumor-associated macrophages (TAMs) are implicated in the growth, invasion and metastasis of various solid tumors. However, the phenotype of TAMs in premalignant lesions of solid tumors has not been clarified. In the present study, we identify the phenotype of TAMs in leukoplakia, an oral premalignant lesion, by immunohistochemical analysis and investigate the involvement of infiltrated T cells that participate in the polarization of TAMs. The subjects included 30 patients with oral leukoplakia and 10 individuals with normal mucosa. Hematoxylin and eosin slides were examined for the histological grades, and immunohistochemical analysis was carried out using antibodies against CD68 (pan-MΦ), CD80 (M1 MΦ), CD163 (M2 MΦ), CD4 (helper T cells: Th), CD8 (cytotoxic T cells), CXCR3, CCR5 (Th1), CCR4 (Th2), signal transducer and activator of transcription (STAT1), phosphorylated STAT1 (pSTAT1) and chemokine CXCL9. The differences in the numbers of positively stained cells among the different histological grades were tested for statistical significance using the Kruskal-Wallis test. Correlations between different types of immune cells were determined using Spearman’s rank analysis. An increase in the rate of CD163 + TAM infiltration was observed in mild and moderate epithelial dysplasia, which positively correlated with the rate of intraepithelial CD4 + Th cell infiltration. Although CCR4 + cells rarely infiltrated, CXCR3 + and CCR5 + cells were observed in these lesions. Cells positive for STAT1 and chemokine CXCL9, interferon- (IFN)-induced gene products, and pSTAT1 were also observed in the same lesions. Double immunofluorescence staining demonstrated that the cells that were positive for CD163 were also positive for STAT1. CD163 + TAMs in oral premalignant lesions coexpress CD163 and STAT1, suggesting that the TAMs in oral premalignant lesions possess an M1 phenotype in a Th1-dominated micromilieu

  11. Severe epistaxis due to aberrant vasculature in a patient with STAT-1 mutation.

    Science.gov (United States)

    Chang, Michael T; Schwam, Zachary G; Hajek, Michael A; Paskhover, Boris; Judson, Benjamin L

    2016-03-01

    Signal transducer and activator 1 (STAT-1) mutations are rare and have been implicated in combined immunodeficiency, enhanced tumorigenesis, and vascular defects. A 60-year-old woman with a novel STAT-1 mutation and resulting immunodeficiency, squamous cell carcinoma, and vascular disease presented with profuse epistaxis secondary to rupture of an aberrant artery that she developed in part because of this mutation. After unsuccessful posterior packing, embolization was initiated but subsequently aborted because of a bovine origin carotid artery and a history of multiple carotid dissections. After repeat posterior packing, hemostasis was achieved. No additional episodes of epistaxis occurred in the subsequent 13 months. Vascular anomalies can present challenges in epistaxis management. In patients with conditions known to cause vascular anomalies, it is critical to obtain vascular imaging before intervention. © 2015 Wiley Periodicals, Inc.

  12. HDAC Inhibitor-Mediated Beta-Cell Protection Against Cytokine-Induced Toxicity Is STAT1 Tyr701 Phosphorylation Independent

    DEFF Research Database (Denmark)

    Dahllöf, Mattias Salling; Christensen, Dan P; Harving, Mette

    2015-01-01

    inhibition using either IL-1β or IFN-γ alone. Whereas HDAC inhibition has been shown to regulate NFκB-activity, related primarily to IL-1β signaling, it is unknown whether the inhibition of HDACs affect IFN-γ signaling in beta-cells. Further, in non-beta-cells, there is a dispute whether HDAC inhibition...... regulates IFN-γ signaling at the level of STAT1 Tyr701 phosphorylation. Using different small molecule HDAC inhibitors with varying class selectivity, INS-1E wild type and stable HDAC1-3 knockdown pancreatic INS-1 cell lines, we show that IFN-γ-induced Cxcl9 and iNos expression as well as Cxcl9 and GAS...... reporter activity were decreased by HDAC inhibition in a STAT1 Tyr701 phosphorylation-independent fashion. In fact, knockdown of HDAC1 increased IFN-γ-induced STAT1 phosphorylation....

  13. Adenosine A1 Receptor Protects Against Cisplatin Ototoxicity by Suppressing the NOX3/STAT1 Inflammatory Pathway in the Cochlea

    Science.gov (United States)

    Kaur, Tejbeer; Borse, Vikrant; Sheth, Sandeep; Sheehan, Kelly; Ghosh, Sumana; Tupal, Srinivasan; Jajoo, Sarvesh; Mukherjea, Debashree; Rybak, Leonard P.

    2016-01-01

    Cisplatin is a commonly used antineoplastic agent that produces ototoxicity that is mediated in part by increasing levels of reactive oxygen species (ROS) via the NOX3 NADPH oxidase pathway in the cochlea. Recent studies implicate ROS generation in mediating inflammatory and apoptotic processes and hearing loss by activating signal transducer and activator of transcription (STAT1). In this study, we show that the adenosine A1 receptor (A1AR) protects against cisplatin ototoxicity by suppressing an inflammatory response initiated by ROS generation via NOX3 NADPH oxidase, leading to inhibition of STAT1. Trans-tympanic administration of the A1AR agonist R-phenylisopropyladenosine (R-PIA) inhibited cisplatin-induced ototoxicity, as measured by auditory brainstem responses and scanning electron microscopy in male Wistar rats. This was associated with reduced NOX3 expression, STAT1 activation, tumor necrosis factor-α (TNF-α) levels, and apoptosis in the cochlea. In vitro studies in UB/OC-1 cells, an organ of Corti immortalized cell line, showed that R-PIA reduced cisplatin-induced phosphorylation of STAT1 Ser727 (but not Tyr701) and STAT1 luciferase activity by suppressing the ERK1/2, p38, and JNK mitogen-activated protein kinase (MAPK) pathways. R-PIA also decreased the expression of STAT1 target genes, such as TNF-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and reduced cisplatin-mediated apoptosis. These data suggest that the A1AR provides otoprotection by suppressing NOX3 and inflammation in the cochlea and could serve as an ideal target for otoprotective drug therapy. SIGNIFICANCE STATEMENT Cisplatin is a widely used chemotherapeutic agent for the treatment of solid tumors. Its use results in significant and permanent hearing loss, for which no US Food and Drug Administration-approved treatment is currently available. In this study, we targeted the cochlear adenosine A1 receptor (A1AR) by trans-tympanic injections of the agonist R

  14. Sulforaphane exerts its anti-inflammatory effect against amyloid-β peptide via STAT-1 dephosphorylation and activation of Nrf2/HO-1 cascade in human THP-1 macrophages.

    Science.gov (United States)

    An, Ye Won; Jhang, Kyoung A; Woo, So-Youn; Kang, Jihee Lee; Chong, Young Hae

    2016-02-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide, accounting for most cases of dementia in elderly individuals, and effective therapies are still lacking. This study was designed to investigate the anti-inflammatory properties of sulforaphane against Aβ1-42 monomers in human THP-1 microglia-like cells. The results showed that sulforaphane preferentially inhibited cathepsin B- and caspase-1-dependent NLRP3 inflammasome activation induced by mostly Aβ1-42 monomers, an effect that potently reduced excessive secretion of the proinflammatory cytokine interleukin-1β (IL-1β). Subsequent mechanistic studies revealed that sulforaphane mitigated the activation of signal transducer and activator of transcription-1 induced by Aβ1-42 monomers. Sulforaphane also increased nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, which was followed by upregulation of heme-oxygenase 1 (HO-1). The anti-inflammatory effect of sulforaphane on Aβ1-42-induced IL-1β production was diminished by small interfering RNA-mediated knockdown of Nrf2 or HO-1. Moreover, sulforaphane significantly attenuated the levels of microRNA-146a, which is selectively upregulated in the temporal cortex and hippocampus of AD brains. The aforementioned effects of sulforaphane were replicated by the tyrosine kinase inhibitor, herbimycin A, and Nrf2 activator. These results indicate that signal transducer and activator of transcription-1 dephosphorylation, HO-1 and its upstream effector, Nrf2, play a pivotal role in triggering an anti-inflammatory signaling cascade of sulforaphane that results in decreases of IL-1β release and microRNA-146a production in Aβ1-42-stimulated human microglia-like cells. These findings suggest that the phytochemical sulforaphane has a potential application in AD therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent.

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    Jane Q Chen

    Full Text Available Female 129:Stat1-null mice (129S6/SvEvTac-Stat1(tm1Rds homozygous uniquely develop estrogen-receptor (ER-positive mammary tumors. Herein we report that the mammary glands (MG of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment.

  16. Putting the brakes on mammary tumorigenesis: loss of STAT1 predisposes to intraepithelial neoplasias.

    Science.gov (United States)

    Schneckenleithner, Christine; Bago-Horvath, Zsuzsanna; Dolznig, Helmut; Neugebauer, Nina; Kollmann, Karoline; Kolbe, Thomas; Decker, Thomas; Kerjaschki, Dontscho; Wagner, Kay-Uwe; Müller, Mathias; Stoiber, Dagmar; Sexl, Veronika

    2011-12-01

    Multiparous Stat1-/- mice spontaneously develop mammary tumors with increased incidence: at an average age of 12 months, 55% of the animals suffer from mammary cancer, although the histopathology is heterogeneous. We consistently observed mosaic expression or down-regulation of STAT1 protein in wild-type mammary cancer evolving in the control group. Transplantation experiments show that tumorigenesis in Stat1-/- mice is partially influenced by impaired CTL mediated tumor surveillance. Additionally, STAT1 exerts an intrinsic tumor suppressing role by controlling and blocking proliferation of the mammary epithelium. Loss of STAT1 in epithelial cells enhances cell growth in both transformed and primary cells. The increased proliferative capacity leads to the loss of structured acini formation in 3D-cultures. Analogous effects were observed when Irf1-/- epithelial cells were used. Accordingly, the rate of mammary intraepithelial neoplasias (MINs) is increased in Stat1-/- animals: MINs represent the first step towards mammary tumors. The experiments characterize STAT1/IRF1 as a key growth inhibitory and tumor suppressive signaling pathway that prevents mammary cancer formation by maintaining growth control. Furthermore, they define the loss of STAT1 as a predisposing event via enhanced MIN formation.

  17. New primers for methylation-specific polymerase chain reaction enhance specificity of detecting STAT1 methylation

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    Ming-Cheng Chang

    2012-03-01

    Conclusion: Specific primers for methylation-specific PCR are mandatory for the accurate detection of STAT1 gene methylation. Besides, specific primers can generate correct interpretation of STAT1 gene methylation, and its correlation with the clinicopathological characteristics and outcome of cancer patients.

  18. Epigallocatechin-3-gallate Ameliorates Seawater Aspiration-Induced Acute Lung Injury via Regulating Inflammatory Cytokines and Inhibiting JAK/STAT1 Pathway in Rats

    Science.gov (United States)

    Liu, Wei; Dong, Mingqing; Bo, Liyan; Li, Congcong; Liu, Qingqing; Li, Yanyan; Ma, Lijie; Xie, Yonghong; Fu, Enqing; Mu, Deguang; Pan, Lei; Jin, Faguang; Li, Zhichao

    2014-01-01

    Signal transducers and activators of transcriptions 1 (STAT1) play an important role in the inflammation process of acute lung injury (ALI). Epigallocatechin-3-gallate (EGCG) exhibits a specific and strong anti-STAT1 activity. Therefore, our study is to explore whether EGCG pretreatment can ameliorate seawater aspiration-induced ALI and its possible mechanisms. We detected the arterial partial pressure of oxygen, lung wet/dry weight ratios, protein content in bronchoalveolar lavage fluid, and the histopathologic and ultrastructure staining of the lung. The levels of IL-1, TNF-α, and IL-10 and the total and the phosphorylated protein level of STAT1, JAK1, and JAK2 were assessed in vitro and in vivo. The results showed that EGCG pretreatment significantly improved hypoxemia and histopathologic changes, alleviated pulmonary edema and lung vascular leak, reduced the production of TNF-α and IL-1, and increased the production of IL-10 in seawater aspiration-induced ALI rats. EGCG also prevented the seawater aspiration-induced increase of TNF-α and IL-1 and decrease of IL-10 in NR8383 cell line. Moreover, EGCG pretreatment reduced the total and the phosphorylated protein level of STAT1 in vivo and in vitro and reduced the phosphorylated protein level of JAK1 and JAK2. The present study demonstrates that EGCG ameliorates seawater aspiration-induced ALI via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats. PMID:24692852

  19. Transcriptional up-regulation of restin by all-trans retinoic acid through STAT1 in cancer cell differentiation process

    International Nuclear Information System (INIS)

    Fu Haiyan; Yang Guodong; Lu Fan; Wang Ruihua; Yao Libo; Lu Zifan

    2006-01-01

    RESTIN, a member of the melanoma-associated antigen superfamily, is a nuclear protein induced by atRA (all-trans retinoic acid) in HL60 cells. HeLa cells stably transfected with restin results in G1 cell cycle arrest. How this gene is regulated by atRA in the cell differentiation process is still unclear. In this study, we observed that up-regulation of restin was present during the atRA-induced HL60 cell differentiation process, suggesting the functional relevance between RESTIN and atRA-induced cellular effects. In order to further define the transcriptional regulation of restin by atRA, we analyzed the promoter region of restin. About 2.1 kb 5' flanking sequence of this gene was cloned into vector pGL3 and its core promoter region was identified through systemic deletions. Interestingly, restin promoter containing several potential consensus-binding sites of STAT-1α was activated by atRA in ER + MCF-7 cells but not in ER - MDA-MB-231 cells, over-expression of STAT-1α in latter rescued the activation effect of restin promoter in response to atRA and IFNγ. Our evidence supported that STAT-1α plays an important role in the atRA-induced transcriptional up-regulation of restin, which was associated with the atRA-induced HL60 cell differentiation and potentially mediated the downstream effects of atRA signal pathway via STAT-1α in some cancer cells

  20. Tyrosine 110 in the measles virus phosphoprotein is required to block STAT1 phosphorylation

    International Nuclear Information System (INIS)

    Devaux, Patricia; Messling, Veronika von; Songsungthong, Warangkhana; Springfeld, Christoph; Cattaneo, Roberto

    2007-01-01

    The measles virus (MV) P gene encodes three proteins: P, an essential polymerase cofactor, and C and V, which have multiple functions including immune evasion. We show here that the MV P protein also contributes to immune evasion, and that tyrosine 110 is required to block nuclear translocation of the signal transducer and activator of transcription factors (STAT) after interferon type I treatment. In particular, MV P inhibits STAT1 phosphorylation. This is shown not only by transient expression but also by reverse genetic analyses based on a new functional infectious cDNA derived from a MV vaccine vial (Moraten strain). Our study also identifies a conserved sequence around P protein tyrosine 110 as a candidate interaction site with a cellular protein

  1. Autoimmune Regulator Deficiency Results in a Decrease in STAT1 Levels in Human Monocytes

    NARCIS (Netherlands)

    Zimmerman, O.; Rosen, L.B.; Swamydas, M.; Ferre, E.M.N.; Natarajan, M.; Veerdonk, F.L. van de; Holland, S.M.; Lionakis, M.S.

    2017-01-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by biallelic autoimmune regulator (AIRE) mutations that manifests with chronic mucocutaneous candidiasis (CMC) and autoimmunity. Patients with STAT1 gain-of-function

  2. Crimean-Congo Hemorrhagic Fever Virus Subunit Vaccines Induce High Levels of Neutralizing Antibodies But No Protection in STAT1 Knockout Mice

    NARCIS (Netherlands)

    Kortekaas, Jeroen; Vloet, Rianka P M; McAuley, Alexander J; Shen, Xiaoli; Bosch, Berend Jan; de Vries, Laura; Moormann, Rob J M; Bente, Dennis A

    2015-01-01

    Crimean-Congo hemorrhagic fever virus is a tick-borne bunyavirus of the Nairovirus genus that causes hemorrhagic fever in humans with high case fatality. Here, we report the development of subunit vaccines and their efficacy in signal transducer and activator of transcription 1 (STAT1) knockout

  3. The HIV matrix protein p17 subverts nuclear receptors expression and induces a STAT1-dependent proinflammatory phenotype in monocytes.

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    Barbara Renga

    Full Text Available BACKGROUND: Long-term remission of HIV-1 disease can be readily achieved by combinations of highly effective antiretroviral therapy (HAART. However, a residual persistent immune activation caused by circulating non infectious particles or viral proteins is observed under HAART and might contribute to an higher risk of non-AIDS pathologies and death in HIV infected persons. A sustained immune activation supports lipid dysmetabolism and increased risk for development of accelerated atehrosclerosis and ischemic complication in virologically suppressed HIV-infected persons receiving HAART. AIM: While several HIV proteins have been identified and characterized for their ability to maintain immune activation, the role of HIV-p17, a matrix protein involved in the viral replication, is still undefined. RESULTS: Here, we report that exposure of macrophages to recombinant human p17 induces the expression of proinflammatory and proatherogenic genes (MCP-1, ICAM-1, CD40, CD86 and CD36 while downregulating the expression of nuclear receptors (FXR and PPARγ that counter-regulate the proinflammatory response and modulate lipid metabolism in these cells. Exposure of macrophage cell lines to p17 activates a signaling pathway mediated by Rack-1/Jak-1/STAT-1 and causes a promoter-dependent regulation of STAT-1 target genes. These effects are abrogated by sera obtained from HIV-infected persons vaccinated with a p17 peptide. Ligands for FXR and PPARγ counteract the effects of p17. CONCLUSIONS: The results of this study show that HIV p17 highjacks a Rack-1/Jak-1/STAT-1 pathway in macrophages, and that the activation of this pathway leads to a simultaneous dysregulation of immune and metabolic functions. The binding of STAT-1 to specific responsive elements in the promoter of PPARγ and FXR and MCP-1 shifts macrophages toward a pro-atherogenetic phenotype characterized by high levels of expression of the scavenger receptor CD36. The present work identifies p17 as a

  4. Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts

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    Mehrdad Sobhkhez

    2014-01-01

    Full Text Available Mammalian IRF9 and STAT2, together with STAT1, form the ISGF3 transcription factor complex, which is critical for type I interferon (IFN-induced signaling, while IFNγ stimulation is mediated by homodimeric STAT1 protein. Teleost fish are known to possess most JAK and STAT family members, however, description of their functional activity in lower vertebrates is still scarce. In the present study we have identified two different STAT2 homologs and one IRF9 homolog from Atlantic salmon (Salmo salar. Both proteins have domain-like structures with functional motifs that are similar to higher vertebrates, suggesting that they are orthologs to mammalian STAT2 and IRF9. The two identified salmon STAT2s, named STAT2a and STAT2b, showed high sequence identity but were divergent in their transactivation domain (TAD. Like STAT1, ectopically expressed STAT2a and b were shown to be tyrosine phosphorylated by type I IFNs and, interestingly, also by IFNγ. Microscopy analyses demonstrated that STAT2 co-localized with STAT1a in the cytoplasm of unstimulated cells, while IFNa1 and IFNγ stimulation seemed to favor their nuclear localization. Overexpression of STAT2a or STAT2b together with STAT1a activated a GAS-containing reporter gene construct in IFNγ-stimulated cells. The highest induction of GAS promoter activation was found in IFNγ-stimulated cells transfected with IRF9 alone. Taken together, these data suggest that salmon STAT2 and IRF9 may have a role in IFNγ-induced signaling and promote the expression of GAS-driven genes in bony fish. Since mammalian STAT2 is primarily an ISGF3 component and not involved in IFNγ signaling, our finding features a novel role for STAT2 in fish.

  5. Human Cytomegalovirus Immediate-Early 1 Protein Rewires Upstream STAT3 to Downstream STAT1 Signaling Switching an IL6-Type to an IFNγ-Like Response.

    Directory of Open Access Journals (Sweden)

    Thomas Harwardt

    2016-07-01

    Full Text Available The human cytomegalovirus (hCMV major immediate-early 1 protein (IE1 is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445 in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420 deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.

  6. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype

    NARCIS (Netherlands)

    Toubiana, J.; Okada, S.; Hiller, J.; Oleastro, M.; Lagos Gomez, M.; Aldave Becerra, J.C.; Ouachee-Chardin, M.; Fouyssac, F.; Girisha, K.M.; Etzioni, A.; Montfrans, J. van; Camcioglu, Y.; Kerns, L.A.; Belohradsky, B.; Blanche, S.; Bousfiha, A.; Rodriguez-Gallego, C.; Meyts, I.; Kisand, K.; Reichenbach, J.; Renner, E.D.; Rosenzweig, S.; Grimbacher, B.; Veerdonk, F.L. van de; Traidl-Hoffmann, C.; Picard, C.; Marodi, L.; Morio, T.; Kobayashi, M.; Lilic, D.; Milner, J.D.; Holland, S.; Casanova, J.L.; Puel, A.

    2016-01-01

    Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274

  7. The Inflammatory Transcription Factors NFκB, STAT1 and STAT3 Drive Age-Associated Transcriptional Changes in the Human Kidney

    Science.gov (United States)

    O’Brown, Zach K.; Van Nostrand, Eric L.; Higgins, John P.; Kim, Stuart K.

    2015-01-01

    Human kidney function declines with age, accompanied by stereotyped changes in gene expression and histopathology, but the mechanisms underlying these changes are largely unknown. To identify potential regulators of kidney aging, we compared age-associated transcriptional changes in the human kidney with genome-wide maps of transcription factor occupancy from ChIP-seq datasets in human cells. The strongest candidates were the inflammation-associated transcription factors NFκB, STAT1 and STAT3, the activities of which increase with age in epithelial compartments of the renal cortex. Stimulation of renal tubular epithelial cells with the inflammatory cytokines IL-6 (a STAT3 activator), IFNγ (a STAT1 activator), or TNFα (an NFκB activator) recapitulated age-associated gene expression changes. We show that common DNA variants in RELA and NFKB1, the two genes encoding subunits of the NFκB transcription factor, associate with kidney function and chronic kidney disease in gene association studies, providing the first evidence that genetic variation in NFκB contributes to renal aging phenotypes. Our results suggest that NFκB, STAT1 and STAT3 underlie transcriptional changes and chronic inflammation in the aging human kidney. PMID:26678048

  8. Fludarabine inhibits STAT1-mediated up-regulation of caspase-3 expression in dexamethasone-induced osteoblasts apoptosis and slows the progression of steroid-induced avascular necrosis of the femoral head in rats.

    Science.gov (United States)

    Feng, Zhenhua; Zheng, Wenhao; Tang, Qian; Cheng, Liang; Li, Hang; Ni, Wenfei; Pan, Xiaoyun

    2017-08-01

    Steroid-induced avascular necrosis of the femoral head (SANFH) is a major limitation of long-term or excessive clinical administration of glucocorticoids. Fludarabine, which is a compound used to treat various hematological malignancies, such as chronic lymphocytic leukemia, acts by down-regulating signal transducer and activator of transcription 1 (STAT1) by inhibiting STAT1 phosphorylation in both normal and cancer cells. This study assessed the effects of fludarabine in vitro (primary murine osteoblasts) and in vivo (rat SANFH model). In vitro, pretreatment with fludarabine significantly inhibited Dexamethasone (Dex)-induced apoptosis in osteoblasts, which was examined by TUNEL staining. Treatment with Dex caused a remarkable decrease in the expression of Bcl-2; an increase in cytochrome c release; activation of BAX, caspase-9, and caspase-3; and an obvious enhancement in STAT1 phosphorylation. However, treatment resulted in the up-regulation of caspase-3 expression. Enhanced P-STAT1 activity and up-regulation of caspase-3 expression were also observed in osteoblasts. In vivo, the subchondral trabeculae in fludarabine-treated rats exhibited less bone loss and a lower ratio of empty lacunae. Taken together, our results suggest that STAT1-mediated up-regulation of caspase-3 is involved in osteoblast apoptosis induced by Dex and indicates that fludarabine may serve as a potential agent for the treatment of SANFH.

  9. The effect of miR-146a on STAT1 expression and apoptosis in acute lymphoblastic leukemia Jurkat cells.

    Science.gov (United States)

    Yan, Weihong; Guo, Hua; Suo, Feng; Han, Chunling; Zheng, Hua; Chen, Tong

    2017-01-01

    The effect of miR-146a-dependent regulation of STAT1 on apoptosis in acute lymphoblastic leukemia (ALL) Jurkat cells was investigated. The miR-146a mimic and miR-146a inhibitor vectors were constructed in vitro , and experimental grouping was as follows: Control group (untreated Jurkat cells), empty vector group (Jurkat cells transfected with empty vector), agonist group (Jurkat cells transfected with miR-146a mimic) and the inhibitor group (Jurkat cells transfected with miR-146a inhibitor). Western blot analysis was used to observe the expression, respectively, of STAT1, p-STAT1 and Bcl-xL, and flow cytometry was used to test apoptosis in Jurkat cells. STAT1 and p-STAT1 expression in the agonist group was higher than that in the control and empty vector groups, but lower in the inhibitor group, and differences were statistically significant (PJurkat cells.

  10. Anti-Inflammatory Effects of Flavonoids: Genistein, Kaempferol, Quercetin, and Daidzein Inhibit STAT-1 and NF-κB Activations, Whereas Flavone, Isorhamnetin, Naringenin, and Pelargonidin Inhibit only NF-κB Activation along with Their Inhibitory Effect on iNOS Expression and NO Production in Activated Macrophages

    Directory of Open Access Journals (Sweden)

    Mari Hämäläinen

    2007-01-01

    The present study characterises the effects and mechanisms of naturally occurring phenolic compounds on iNOS expression and NO production in activated macrophages. The results partially explain the pharmacological efficacy of flavonoids as anti-inflammatory compounds.

  11. Interactions between Th1 cells and Tregs affect regulation of hepatic fibrosis in biliary atresia through the IFN-γ/STAT1 pathway.

    Science.gov (United States)

    Wen, Jie; Zhou, Ying; Wang, Jun; Chen, Jie; Yan, Wenbo; Wu, Jin; Yan, Junkai; Zhou, Kejun; Xiao, Yongtao; Wang, Yang; Xia, Qiang; Cai, Wei

    2017-06-01

    Regulatory T cells (Tregs) and CD4 + T helper (Th) cells have important roles in bile duct injury of biliary atresia (BA). However, their impacts on liver fibrosis are undefined. Between 2013 and 2016, 146 patients with various stages of BA were enrolled in this study. Peripheral blood, liver biopsy and lymph node samples were collected. Flow cytometry, magnetic cell sorting and immunostaining were used to characterize lymphocytes from BA patients. Deficiency of Tregs was observed along with increased Th1, Th2 and Th17 frequencies in the peripheral blood and livers of BA patients. The levels of peripheral and intrahepatic Th1 cells positively correlated with the stage of liver fibrosis. Furthermore, Th1 cells were located in close proximity to activated hepatic stellate cells (HSCs) and areas of fibrosis in BA livers. In culture, Th1 cells accelerated the proliferation and secretion of profibrogenic markers of HSCs through the IFN-γ/STAT1 pathway. Of note, Tregs blocked the Th1-stimulated effects on HSCs by inhibiting Th1-induced activation of STAT1. Consistent with the results of in vitro study, intrahepatic IFN-γ/STAT1 levels increased in relation to the severity of liver fibrosis in BA patients, and the altered balance between MMP2 and TIMP1 expressions in livers may contribute to increased deposition of extracellular matrix and fibrosis. Finally, to identify the effects of Th1 cells on Tregs, we demonstrated that Th1 cells upregulated the proportion of aTreg cells by secreting IFN-γ cytokine. Thus, aberrant Th1 immune responses in BA promote the proliferation and secretion of HSCs through the IFN-γ/STAT1 pathway. The regulation of HSCs by the interactions between Tregs and Th1 cells might be part of the mechanism underlying progressive liver fibrosis and may be a suitable target for therapy.

  12. MicroRNA-145 targets YES and STAT1 in colon cancer cells

    DEFF Research Database (Denmark)

    Gregersen, Lea H; Jacobsen, Anders B; Frankel, Lisa

    2010-01-01

    BACKGROUND: MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in tumorigenesis. miR-145 is reported to be down-regulated in several cancers, but knowledge of its targets in colon cancer remains limited. METHODOLOGY/PRINCIPAL FINDINGS: To investigate...... miRNA overexpression. Gene Ontology analysis showed an overrepresentation of genes involved in cell death, cellular growth and proliferation, cell cycle, gene expression and cancer. A number of the identified miRNA targets have previously been implicated in cancer, including YES, FSCN1, ADAM17, BIRC2......, VANGL1 as well as the transcription factor STAT1. Both YES and STAT1 were verified as direct miR-145 targets. CONCLUSIONS/SIGNIFICANCE: The study identifies and validates new cancer-relevant direct targets of miR-145 in colon cancer cells and hereby adds important mechanistic understanding of the tumor...

  13. IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression

    DEFF Research Database (Denmark)

    Nielsen, Sebastian Rune; Hammer, Troels; Gibson, Josefine

    2013-01-01

    OBJECTIVE: IL-27 belongs to the IL-12 family of cytokines and is recognized for its role in Th cell differentiation and as an inhibitor of tumor-angiogenesis. The purpose of this study was to investigate the effect of IL-27 on proliferation of lymphatic endothelial cells to gain insight...... into the interplay between the immune system and development of the lymphatic system. METHODS: IL-27-stimulated signal transduction in human dermal lymphatic endothelial cells was measured by western blotting and synthesis of CXCL10 and CXCL11 by use of RT-PCR and ELISA. Proliferation was measured using MTT and Brd......U kits and the role of STAT1 and chemokines was determined by use of siRNA and recombinant proteins. RESULTS: Stimulation of lymphatic endothelial cell cultures with IL-27 induced JAK dependent phosphorylation of STAT1 and STAT3 and inhibited lymphatic endothelial cell proliferation and migration...

  14. Managing Stress through Challenge Activities.

    Science.gov (United States)

    Bunting, Camille J.

    1982-01-01

    Many positive benefits can be obtained through participation in risk, challenge, or adventure activities: (1) emotional release; (2) social interaction; (3) expanded perspective; (4) expanded personal limits; and (5) singleness of mind or attention. Participating in these activities also often helps to develop stress management skills. (CJ)

  15. Stress hormones and physical activity

    Directory of Open Access Journals (Sweden)

    Editorial Office

    1991-07-01

    Full Text Available Hormone secretion during physical activity of specific duration and intensity is part of the stress response. In a study to investigate the secretion of ß-endorphin, leucine enkephalin and other recognised stress hormones during physical exercise, blood samples were taken from fourteen (14 healthy, male athletes who competed in a 21 km roadrace. Blood samples were collected before and after completion of the race. This study shows that ß-endorphin/ß-lipotropin, leucine enkephalin, prolactin, and melatonin may be classified as stress hormones in physical activity of duration 80 to 120 minutes and intensity exceeding 75%-V0₂max. Widespread intra-individual variation in serum cortisol concentrations prevent definite conclusion. The un­expected increase in serum testosterone levels warrants further research.

  16. A fusion cytokine coupling GMCSF to IL9 induces heterologous receptor clustering and STAT1 hyperactivation through JAK2 promiscuity.

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    Pingxin Li

    Full Text Available Cytokine receptors are randomly distributed on the cell surface membrane and are activated upon binding of their extracellular ligands to mediate downstream cellular activities. We hypothesized that pharmaceutical clustering of ligand-bound, activated receptors may lead to heretofore unrealized gain-of-function with therapeutically desirable properties. We here describe an engineered bifunctional cytokine borne of the fusion of Granulocyte Macrophage Colony Stimulating Factor (GMCSF and Interleukin-9 (IL9 (hereafter GIFT9 fusokine and demonstrate that it chaperones co-clustering of the functionally unrelated GMCSF receptor (GMCSFR and IL9 receptor (IL9R on cell surface of target cells. We demonstrate that GIFT9 treatment of MC/9 cells leads to transhyperphosphorylation of IL9R-associated STAT1 by GMCSFR-associated JAK2. We also show that IL9R-associated JAK1 and JAK3 augment phosphorylation of GMCSFR-linked STAT5. The functional relevance of these synergistic JAK/STAT transphosphorylation events translates to an increased mitogenic response by GMCSFR/IL9R-expressing primary marrow mast cells. The notion of inducing heterologous receptor clustering by engineered fusokines such as GIFT9 opens the door to a novel type of biopharmaceutical platform where designer fusokines modulate cell physiology through clustering of targeted receptor complexes.

  17. Impaired Chromatin Remodelling at STAT1-Regulated Promoters Leads to Global Unresponsiveness of Toxoplasma gondii-Infected Macrophages to IFN-γ

    Science.gov (United States)

    Lang, Christine; Hildebrandt, Anke; Brand, Franziska; Opitz, Lennart; Dihazi, Hassan; Lüder, Carsten G. K.

    2012-01-01

    Intracellular pathogens including the apicomplexan and opportunistic parasite Toxoplasma gondii profoundly modify their host cells in order to establish infection. We have shown previously that intracellular T. gondii inhibit up-regulation of regulatory and effector functions in murine macrophages (MΦ) stimulated with interferon (IFN)-γ, which is the cytokine crucial for controlling the parasites' replication. Using genome-wide transcriptome analysis we show herein that infection with T. gondii leads to global unresponsiveness of murine macrophages to IFN-γ. More than 61% and 89% of the transcripts, which were induced or repressed by IFN-γ in non-infected MΦ, respectively, were not altered after stimulation of T. gondii-infected cells with IFN-γ. These genes are involved in a variety of biological processes, which are mostly but not exclusively related to immune responses. Analyses of the underlying mechanisms revealed that IFN-γ-triggered nuclear translocation of STAT1 still occurred in Toxoplasma-infected MΦ. However, STAT1 bound aberrantly to oligonucleotides containing the IFN-γ-responsive gamma-activated site (GAS) consensus sequence. Conversely, IFN-γ did not induce formation of active GAS-STAT1 complexes in nuclear extracts from infected MΦ. Mass spectrometry of protein complexes bound to GAS oligonucleotides showed that T. gondii-infected MΦ are unable to recruit non-muscle actin to IFN-γ-responsive DNA sequences, which appeared to be independent of stimulation with IFN-γ and of STAT1 binding. IFN-γ-induced recruitment of BRG-1 and acetylation of core histones at the IFN-γ-regulated CIITA promoter IV, but not β-actin was diminished by >90% in Toxoplasma-infected MΦ as compared to non-infected control cells. Remarkably, treatment with histone deacetylase inhibitors restored the ability of infected macrophages to express the IFN-γ regulated genes H2-A/E and CIITA. Taken together, these results indicate that Toxoplasma-infected MΦ are

  18. Fibroblast growth factor inhibits interferon gamma-STAT1 and interleukin 6-STAT3 signaling in chondrocytes

    Czech Academy of Sciences Publication Activity Database

    Krejčí, Pavel; Procházková, Jiřina; Bryja, Vítězslav; Jelínková, P.; Pejchalová, K.; Kozubík, Alois; Thompson, L.M.; Wilcox, W.R.

    2009-01-01

    Roč. 21, č. 1 (2009), s. 151-160 ISSN 0898-6568 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : fibroblast growth factor * cartilage * STAT1 Subject RIV: BO - Biophysics Impact factor: 4.094, year: 2009

  19. Experimentally induced stress validated by EMG activity.

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    Rosan Luijcks

    Full Text Available Experience of stress may lead to increased electromyography (EMG activity in specific muscles compared to a non-stressful situation. The main aim of this study was to develop and validate a stress-EMG paradigm in which a single uncontrollable and unpredictable nociceptive stimulus was presented. EMG activity of the trapezius muscles was the response of interest. In addition to linear time effects, non-linear EMG time courses were also examined. Taking into account the hierarchical structure of the dataset, a multilevel random regression model was applied. The stress paradigm, executed in N = 70 subjects, consisted of a 3-minute baseline measurement, a 3-minute pre-stimulus stress period and a 2-minute post-stimulus phase. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. EMG activity during the entire experiment was conform a priori expectations: the pre-stimulus phase showed a significantly higher mean EMG activity level compared to the other two phases, and an immediate EMG response to the stimulus was demonstrated. In addition, the analyses revealed significant non-linear EMG time courses in all three phases. Linear and quadratic EMG time courses were significantly modified by subjective anticipatory stress level, measured just before the start of the stress task. Linking subjective anticipatory stress to EMG stress reactivity revealed that subjects with a high anticipatory stress level responded with more EMG activity during the pre-stimulus stress phase, whereas subjects with a low stress level showed an inverse effect. Results suggest that the stress paradigm presented here is a valid test to quantify individual differences in stress susceptibility. Further studies with this paradigm are required to demonstrate its potential use in mechanistic clinical studies.

  20. Inducibility of STAT 1/SOCS 3 transcripts and proteins by interferon-alpha/gamma in human melanoma cell lines

    Czech Academy of Sciences Publication Activity Database

    Kovařík, Aleš; Fojtová, Miloslava; Boudný, V.; Adamková, L.; Kovařík, J.

    2004-01-01

    Roč. 14, Suppl. 1 (2004), s. S87 ISSN 1107-3756. [World Congress on Advances in Oncology /9./ and International Symposium on Molecular Medicine /7./. 14.10.2004-16.10.2004, Hersonissos] R&D Projects: GA MZd NC7139; GA ČR GA301/03/0370; GA AV ČR IBS5004010 Keywords : melanoma cells * STAT 1 * SOCS 3 Subject RIV: BO - Biophysics

  1. The ebola virus interferon antagonist VP24 directly binds STAT1 and has a novel, pyramidal fold.

    Directory of Open Access Journals (Sweden)

    Adrianna P P Zhang

    2012-02-01

    Full Text Available Ebolaviruses cause hemorrhagic fever with up to 90% lethality and in fatal cases, are characterized by early suppression of the host innate immune system. One of the proteins likely responsible for this effect is VP24. VP24 is known to antagonize interferon signaling by binding host karyopherin α proteins, thereby preventing them from transporting the tyrosine-phosphorylated transcription factor STAT1 to the nucleus. Here, we report that VP24 binds STAT1 directly, suggesting that VP24 can suppress at least two distinct branches of the interferon pathway. Here, we also report the first crystal structures of VP24, derived from different species of ebolavirus that are pathogenic (Sudan and nonpathogenic to humans (Reston. These structures reveal that VP24 has a novel, pyramidal fold. A site on a particular face of the pyramid exhibits reduced solvent exchange when in complex with STAT1. This site is above two highly conserved pockets in VP24 that contain key residues previously implicated in virulence. These crystal structures and accompanying biochemical analysis map differences between pathogenic and nonpathogenic viruses, offer templates for drug design, and provide the three-dimensional framework necessary for biological dissection of the many functions of VP24 in the virus life cycle.

  2. Gain-of-Function Mutations in STAT1: A Recently Defined Cause for Chronic Mucocutaneous Candidiasis Disease Mimicking Combined Immunodeficiencies

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    Sanem Eren Akarcan

    2017-01-01

    Full Text Available Chronic Mucocutaneous Candidiasis (CMC is the chronic, recurrent, noninvasive Candida infections of the skin, mucous membranes, and nails. A 26-month-old girl was admitted with the complaints of recurrent oral Candidiasis, diarrhea, and respiratory infections. Candida albicans grew in oral mucosa swab. CMV and EBV DNA titers were elevated. She had hypergammaglobulinemia; IgE level, percentages of lymphocyte subgroups, and in vitro T-cell proliferation responses were normal. She had parenchymal nodules within the lungs and a calcific nodule in the liver. Chronic-recurrent infections with different pathogens leading to significant morbidity suggested combined immunodeficiency, CMC, or Mendelian susceptibility to mycobacterial diseases. Genetic analysis revealed a predefined heterozygous gain-of-function mutation (GOF (c.1154 C>T, p.Thr385Met in the gene coding STAT1 molecule. Hematopoietic stem cell transplantation (HSCT was planned because of severe recurring infections. Patients with STAT1 GOF mutations may exhibit diverse phenotypes including infectious and noninfectious findings. HSCT should be considered as an early treatment option before permanent organ damage leading to morbidity and mortality develops. This case is presented to prompt clinicians to consider STAT1 GOF mutations in the differential diagnosis of patients with chronic Candidiasis and recurrent infections with multiple organisms, since these mutations are responsible for nearly half of CMC cases reported.

  3. Ciliary neurotrophic factor protects mice against streptozotocin-induced type 1 diabetes through SOCS3: the role of STAT1/STAT3 ratio in β-cell death.

    Science.gov (United States)

    Rezende, Luiz F; Santos, Gustavo J; Carneiro, Everardo M; Boschero, Antonio C

    2012-12-07

    Type 1 diabetes is characterized by a loss of islet β-cells. Ciliary neurotrophic factor (CNTF) protects pancreatic islets against cytokine-induced apoptosis. For this reason, we assessed whether CNTF protects mice against streptozotocin-induced diabetes (a model of type 1 diabetes) and the mechanism for this protection. WT and SOCS3 knockdown C57BL6 mice were treated for 5 days with citrate buffer or 0.1 mg/kg CNTF before receiving 80 mg/kg streptozotocin. Glycemia in non-fasted mice was measured weekly from days 0-28 after streptozotocin administration. Diabetes was defined as a blood glucose > 11.2 mmol/liter. Wild-type (WT) and SOCS3 knockdown MIN6 cells were cultured with CNTF, IL1β, or both. CNTF reduced diabetes incidence and islet apoptosis in WT but not in SOCS3kd mice. Likewise, CNTF inhibited apoptosis in WT but not in SOCS3kd MIN6 cells. CNTF increased STAT3 phosphorylation in WT and SOCS3kd mice and MIN6 cells but reduced STAT1 phosphorylation only in WT mice, in contrast to streptozotocin and IL1β. Moreover, CNTF reduced NFκB activation and required down-regulation of inducible NO synthase expression to exert its protective effects. In conclusion, CNTF protects mice against streptozotocin-induced diabetes by increasing pancreatic islet survival, and this protection depends on SOCS3. In addition, SOCS3 expression and β-cell fate are dependent on STAT1/STAT3 ratio.

  4. Neural activation in stress-related exhaustion

    DEFF Research Database (Denmark)

    Gavelin, Hanna Malmberg; Neely, Anna Stigsdotter; Andersson, Micael

    2017-01-01

    The primary purpose of this study was to investigate the association between burnout and neural activation during working memory processing in patients with stress-related exhaustion. Additionally, we investigated the neural effects of cognitive training as part of stress rehabilitation. Fifty......-five patients with clinical diagnosis of exhaustion disorder were administered the n-back task during fMRI scanning at baseline. Ten patients completed a 12-week cognitive training intervention, as an addition to stress rehabilitation. Eleven patients served as a treatment-as-usual control group. At baseline......, burnout level was positively associated with neural activation in the rostral prefrontal cortex, the posterior parietal cortex and the striatum, primarily in the 2-back condition. Following stress rehabilitation, the striatal activity decreased as a function of improved levels of burnout. No significant...

  5. Cardiovascular Reactivity, Stress, and Physical Activity

    Directory of Open Access Journals (Sweden)

    Chun-Jung eHuang

    2013-11-01

    Full Text Available Psychological stress has been proposed as a major contributor to the progression of cardiovascular disease (CVD. Acute mental stress can activate the sympathetic-adrenal-medullary (SAM axis, eliciting the release of catecholamines (NE and EPI resulting in the elevation of heart rate (HR and blood pressure (BP. Combined stress (psychological and physical can exacerbate these cardiovascular responses, which may partially contribute to the elevated risk of CVD and increased proportionate mortality risks experienced by some occupations (e.g., firefighting and law enforcement. Studies have supported the benefits of physical activity on physiological and psychological health, including the cardiovascular response to acute stress. Aerobically trained individuals exhibit lower sympathetic nervous system (e.g., HR reactivity and enhanced cardiovascular efficiency (e.g., lower vascular reactivity and decreased recovery time in response to physical and/or psychological stress. In addition, resistance training has been demonstrated to attenuate cardiovascular responses and improve mental health. This review will examine stress-induced cardiovascular reactivity and plausible explanations for how exercise training and physical fitness (aerobic and resistance exercise can attenuate cardiovascular responses to stress. This enhanced functionality may facilitate a reduction in the incidence of stroke and myocardial infarction. Finally, this review will also address the interaction of obesity and physical activity on cardiovascular reactivity and CVD.

  6. ICP0 antagonizes Stat 1-dependent repression of herpes simplex virus: implications for the regulation of viral latency

    Directory of Open Access Journals (Sweden)

    Balliet John W

    2006-06-01

    Full Text Available Abstract Background The herpes simplex virus type 1 (HSV-1 ICP0 protein is an E3 ubiquitin ligase, which is encoded within the HSV-1 latency-associated locus. When ICP0 is not synthesized, the HSV-1 genome is acutely susceptible to cellular repression. Reciprocally, when ICP0 is synthesized, viral replication is efficiently initiated from virions or latent HSV-1 genomes. The current study was initiated to determine if ICP0's putative role as a viral interferon (IFN antagonist may be relevant to the process by which ICP0 influences the balance between productive replication versus cellular repression of HSV-1. Results Wild-type (ICP0+ strains of HSV-1 produced lethal infections in scid or rag2-/- mice. The replication of ICP0- null viruses was rapidly repressed by the innate host response of scid or rag2-/- mice, and the infected animals remained healthy for months. In contrast, rag2-/- mice that lacked the IFN-α/β receptor (rag2-/- ifnar-/- or Stat 1 (rag2-/- stat1-/- failed to repress ICP0- viral replication, resulting in uncontrolled viral spread and death. Thus, the replication of ICP0- viruses is potently repressed in vivo by an innate immune response that is dependent on the IFN-α/β receptor and the downstream transcription factor, Stat 1. Conclusion ICP0's function as a viral IFN antagonist is necessary in vivo to prevent an innate, Stat 1-dependent host response from rapidly repressing productive HSV-1 replication. This antagonistic relationship between ICP0 and the host IFN response may be relevant in regulating whether the HSV-1 genome is expressed, or silenced, in virus-infected cells in vivo. These results may also be clinically relevant. IFN-sensitive ICP0- viruses are avirulent, establish long-term latent infections, and induce an adaptive immune response that is highly protective against lethal challenge with HSV-1. Therefore, ICP0- viruses appear to possess the desired safety and efficacy profile of a live vaccine against

  7. Theaflavin Ameliorates Cerebral Ischemia-Reperfusion Injury in Rats Through Its Anti-Inflammatory Effect and Modulation of STAT-1

    Directory of Open Access Journals (Sweden)

    Fei Cai

    2006-01-01

    Full Text Available Theaflavin, a major constituent of black tea, possesses biological functions such as the antioxidative, antiviral, and anti-inflammatory ones. The purpose of this study was to verify whether theaflavin reduces focal cerebral ischemia injury in a rat model of middle cerebral artery occlusion (MCAO. Male Sprague-Dawley rats were anesthetized and subjected to 2 hours of MCAO followed 24 hours reperfusion. Theaflavin administration (5, 10, and 20 mg/kg, IV ameliorated infarct and edema volume. Theaflavin inhibited leukocyte infiltration and expression of ICAM-1, COX-2, and iNOS in injured brain. Phosphorylation of STAT-1, a protein which mediates intracellular signaling to the nucleus, was enhanced 2-fold over that of sham group and was inhibited by theaflavin. Our study demonstrated that theaflavin significantly protected neurons from cerebral ischemia-reperfusion injury by limiting leukocyte infiltration and expression of ICAM-1, and suppressing upregulation of inflammatory-related prooxidative enzymes (iNOS and COX-2 in ischemic brain via, at least in part, reducing the phosphorylation of STAT-1.

  8. Alantolactone from Saussurea lappa Exerts Antiinflammatory Effects by Inhibiting Chemokine Production and STAT1 Phosphorylation in TNF-α and IFN-γ-induced in HaCaT cells.

    Science.gov (United States)

    Lim, Hye-Sun; Jin, Sung-Eun; Kim, Ohn-Soon; Shin, Hyeun-Kyoo; Jeong, Soo-Jin

    2015-07-01

    Skin inflammation is the most common condition seen in dermatology practice and can be caused by various allergic reactions and certain toxins or chemicals. In the present study, we investigated the antiinflammatory effects of Saussurea lappa, a medicinal herb, and its marker compounds alantolactone, caryophyllene, costic acid, costunolide, and dehydrocostuslactone in the HaCaT human keratinocyte cell line. HaCaT cells were stimulated with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and treated with S. lappa or each of five marker compounds. Chemokine production and expression were analyzed by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction, respectively. Phosphorylation of signal transducer and activator of transcription (STAT) 1 was determined by immunoblotting. Stimulation with TNF-α and IFN-γ significantly increased the production of the following chemokines: thymus-regulated and activation-regulated chemokine (TARC): regulated on activation, normal T-cell expressed and secreted (RANTES): macrophage-derived chemokine (MDC): and interleukin-8 (IL-8). By contrast, S. lappa and the five marker compounds significantly reduced the production of these chemokines by TNF-α and IFN-γ-treated cells. S. lappa and alantolactone suppressed the TNF-α and IFN-γ-stimulated increase in the phosphorylation of STAT1. Our results demonstrate that alantolactone from S. lappa suppresses TNF-α and IFN-γ-induced production of RANTES and IL-8 by blocking STAT1 phosphorylation in HaCaT cells. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Arctigenin alleviates ER stress via activating AMPK

    Science.gov (United States)

    Gu, Yuan; Sun, Xiao-xiao; Ye, Ji-ming; He, Li; Yan, Shou-sheng; Zhang, Hao-hao; Hu, Li-hong; Yuan, Jun-ying; Yu, Qiang

    2012-01-01

    Aim: To investigate the protective effects of arctigenin (ATG), a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L (Compositae), against ER stress in vitro and the underlying mechanisms. Methods: A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTT assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKKβ, LKB1, and AMPKα1 genes was achieved by RNA interference (RNAi). An ATP bioluminescent assay kit was employed to measure the intracellular ATP levels. Results: ATG (2.5, 5 and 10 μmol/L) inhibited cell death and unfolded protein response (UPR) in a concentration-dependent manner in cells treated with the ER stress inducer brefeldin A (100 nmol/L). ATG (1, 5 and 10 μmol/L) significantly attenuated protein synthesis in cells through inhibiting mTOR-p70S6K signaling and eEF2 activity, which were partially reversed by silencing AMPKα1 with RNAi. ATG (1-50 μmol/L) reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C (25 μmol/L) rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG (2.5 and 5 μmol/L) efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate (2 mmol/L) in INS-1 β cells. Conclusion: ATG is an effective ER stress alleviator, which protects cells against ER stress through activating AMPK, thus attenuating protein translation and reducing ER load. PMID:22705729

  10. Stress field reconstruction in an active mudslide

    Science.gov (United States)

    Baroň, Ivo; Kernstocková, Markéta; Melichar, Rostislav

    2017-07-01

    Meso-scale structures from gravitational slope deformation observed in landslides and deep-seated gravitational slope failures are very similar to those of endogenous ones. Therefore we applied palaeostress analysis of fault-slip data for reconstructing the stress field of an active mudslide in Pechgraben, Austria. This complex compound landslide has developed in clayey colluvium and shale and was activated after a certain period of dormancy in June 2013. During the active motion on June 12, 2013, 73 fault-slip traces at 9 locations were measured within the landslide body. The heterogeneous fault-slip data were processed in term of palaeostresses, the reconstructed palaeostress tensor being characterized by the orientations of the three principal stress axes and the stress ratio (which provides the shape of the stress ellipsoid). The results of the palaeostress analysis were compared to airborne laser scan digital terrain models that revealed dynamics and superficial displacements of the moving mass prior and after our survey. The results were generally in good agreement with the observed landslide displacement pattern and with the anticipated stress regime according to Mohr-Coulomb failure criteria and Anderson's theory. The compressional regime was mostly registered at the toe in areas, where a compressional stress field is expected during previous mass-movement stages, or at margins loaded by subsequent landslide bodies from above. On the other hand, extension regimes were identified at the head scarps of secondary slides, subsequently on bulged ridges at the toe and in the zone of horst-and-graben structures in the lower central part of the main landslide body, where the basal slip surface probably had locally convex character. Strike-slip regimes, as well as oblique normal or oblique reverse regimes were observed at the lateral margins of the landslide bodies. The directions of principal stresses could be used as markers of landslide movement directions

  11. GYF-21, an Epoxide 2-(2-Phenethyl-Chromone Derivative, Suppresses Innate and Adaptive Immunity via Inhibiting STAT1/3 and NF-κB Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Ran Guo

    2017-05-01

    Full Text Available Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system characterized by demyelinating plaques and axonal loss. Inhibition on over activation of innate and adaptive immunity provides a rationale strategy for treatment of multiple sclerosis. In the present study, we investigated the inhibitory effects of GYF-21, an epoxide 2-(2-phenethyl-chromone derivative isolated from Chinese agarwood, on innate and adaptive immunity for revealing its potential to treat multiple sclerosis. The results showed that GYF-21 markedly inhibited the activation of microglia, and dendritic cells as well as neutrophils, all of which play important roles in innate immunity. Furthermore, GYF-21 significantly suppressed adaptive immunity via inhibiting the differentiation of naive CD4+ T cells into T helper 1 (Th1 and T helper 17 (Th17 cells, and suppressing the activation, proliferation, and IFN-γ secretion of CD8+ T cells. The mechanism study showed that GYF-21 evidently inhibited the activation of STAT1/3 and NF-κB signaling pathways in microglia. In conclusion, we demonstrated that GYF-21 can significantly inhibit innate and adaptive immunity via suppressing STAT1/3 and NF-κB signaling pathways, and has potential to be developed into therapeutic drug for multiple sclerosis.

  12. Parainfluenza Virus 3 Blocks Antiviral Mediators Downstream of the Interferon Lambda Receptor by Modulating Stat1 Phosphorylation.

    Science.gov (United States)

    Eberle, Kirsten C; McGill, Jodi L; Reinhardt, Timothy A; Sacco, Randy E

    2015-12-30

    Parainfluenza viruses are known to inhibit type I interferon (IFN) production; however, there is a lack of information regarding the type III IFN response during infection. Type III IFNs signal through a unique heterodimeric receptor, IFN-λR1/interleukin-10R2 (IL-10R2), which is primarily expressed by epithelial cells. Parainfluenza virus 3 (PIV-3) infection is highly restricted to the airway epithelium. We therefore sought to examine type III IFN signaling pathways during PIV-3 infection of epithelial cells. We used three strains of PIV-3: human PIV-3 (HPIV-3), bovine PIV-3 (BPIV-3), and dolphin PIV-1 (Tursiops truncatus PIV-1, or TtPIV-1). Here, we show that message levels of IL-29 are significantly increased during PIV-3 infection, yet downstream antiviral signaling molecules are not upregulated to levels similar to those of the positive control. Furthermore, in Vero cells infected with PIV-3, stimulation with recombinant IL-29/-28A/-28B does not cause upregulation of downstream antiviral molecules, suggesting that PIV-3 interferes with the JAK/STAT pathway downstream of the IFN-λR1/IL-10R2 receptor. We used Western blotting to examine the phosphorylation of Stat1 and Stat2 in Vero cells and the bronchial epithelial cell line BEAS-2B. In Vero cells, we observed reduced phosphorylation of the serine 727 (S727) site on Stat1, while in BEAS-2B cells Stat1 phosphorylation was decreased at the tyrosine 701 (Y701) site during PIV-3 infection. PIV-3 therefore interferes with the phosphorylation of Stat1 downstream of the type III IFN receptor. These data provide new evidence regarding strategies employed by parainfluenza viruses to effectively circumvent respiratory epithelial cell-specific antiviral immunity. Parainfluenza virus (PIV) in humans is associated with bronchiolitis and pneumonia and can be especially problematic in infants and the elderly. Also seen in cattle, bovine PIV-3 causes respiratory infections in young calves. In addition, PIV-3 is one of a

  13. Preassembly and ligand-induced restructuring of the chains of the IFN-gamma receptor complex: the roles of Jak kinases, Stat1 and the receptor chains.

    Science.gov (United States)

    Krause, Christopher D; Lavnikova, Natasha; Xie, Junxia; Mei, Erwen; Mirochnitchenko, Olga V; Jia, Yiwei; Hochstrasser, Robin M; Pestka, Sidney

    2006-01-01

    We previously demonstrated using noninvasive technologies that the interferon-gamma (IFN-gamma) receptor complex is preassembled (1). In this report we determined how the receptor complex is preassembled and how the ligand-mediated conformational changes occur. The interaction of Stat1 with IFN-gammaR1 results in a conformational change localized to IFN-gammaR1. Jak1 but not Jak2 is required for the two chains of the IFN-gamma receptor complex (IFN-gammaR1 and IFN-gammaR2) to interact; however, the presence of both Jak1 and Jak2 is required to see any ligand-dependant conformational change. Two IFN-gammaR2 chains interact through species-specific determinants in their extracellular domains. Finally, these determinants also participate in the interaction of IFN-gammaR2 with IFN-gammaR1. These results agree with a detailed model of the IFN-gamma receptor that requires the receptor chains to be pre-associated constitutively for the receptor to be active.

  14. Up-regulation of intestinal epithelial cell derived IL-7 expression by keratinocyte growth factor through STAT1/IRF-1, IRF-2 pathway.

    Directory of Open Access Journals (Sweden)

    Yu-Jiao Cai

    Full Text Available BACKGROUND: Epithelial cells(EC-derived interleukin-7 (IL-7 plays a crucial role in control of development and homeostasis of neighboring intraepithelial lymphocytes (IEL, and keratinocyte growth factor (KGF exerts protective effects on intestinal epithelial cells and up-regulates EC-derived IL-7 expression through KGFR pathway. This study was to further investigate the molecular mechanism involved in the regulation of IL-7 expression by KGF in the intestine. METHODS: Intestinal epithelial cells (LoVo cells and adult C57BL/6J mice were treated with KGF. Epithelial cell proliferation was studied by flow cytometry for BrdU-incorporation and by immunohistochemistry for PCNA staining. Western blot was used to detect the changes of expression of P-Tyr-STAT1, STAT1, and IL-7 by inhibiting STAT1. Alterations of nuclear extracts and total proteins of IRF-1, IRF-2 and IL-7 following IRF-1 and IRF-2 RNA interference with KGF treatment were also measured with western blot. Moreover, IL-7 mRNA expressions were also detected by Real-time PCR and IL-7 protein level in culture supernatants was measured by enzyme linked immunosorbent assay(ELISA. RESULTS: KGF administration significantly increased LoVo cell proliferation and also increased intestinal wet weight, villus height, crypt depth and crypt cell proliferation in mice. KGF treatment led to increased levels of P-Tyr-STAT1, RAPA and AG490 both blocked P-Tyr-STAT1 and IL-7 expression in LoVo cells. IRF-1 and IRF-2 expression in vivo and in vitro were also up-regulated by KGF, and IL-7 expression was decreased after IRF-1 and IRF-2 expression was silenced by interfering RNA, respectively. CONCLUSION: KGF could up-regulate IL-7 expression through the STAT1/IRF-1, IRF-2 signaling pathway, which is a new insight in potential effects of KGF on the intestinal mucosal immune system.

  15. [Telomere length, telomerase activity, stress and aging].

    Science.gov (United States)

    Spivak, I M; Mikhelson, V M; Spivak, D L

    The review is dedicated to analysis of data available at present time concerning possible influence of stress upon telomere lengths and telomerase activity, as well as various ways of counteracting it. Present-day telomerase theory of aging gains a new impetus, shedding light upon the influence of psychological state of humans and their ability to counteract stress, upon the process of aging. It also tends to regard telomere shortening and the decrease in the activity of telomerase as a marker of level of the ability to adapt to both inner and outer influences. Both aging and age-dependent diseases are proved to be substantially retarded not only by the administration of drugs, but also by psychological means, which forms a good way towards healthy longevity. With complete understanding of the impossibility to prevent or even to slow down natural senescence itself, these methods allow to remove causes, which accelerate senescence, and to increase the average human longevity.

  16. Thermal stress mitigation by Active Thermal Control

    DEFF Research Database (Denmark)

    Soldati, Alessandro; Dossena, Fabrizio; Pietrini, Giorgio

    2017-01-01

    This work proposes an Active Thermal Control (ATC) of power switches. Leveraging on the fact that thermal stress has wide impact on the system reliability, controlling thermal transients is supposed to lengthen the lifetime of electronic conversion systems. Indeed in some environments......, such as transportation, reliability and lifetime are still obstacles to widespread adoption of electric and electronic actuators, despite a general trend of electrification spreading in many different areas of interest. Active thermal control is attained leaving the electric parameters of load untouched, while acting...... results of control schemes are presented, together with evaluation of the proposed loss models. Experimental proof of the ability of the proposed control to reduce thermal swing and related stress on the device is presented, too....

  17. ZNF198-FGFR1 Transforms Ba/F3 Cells to Growth Factor Independence and Results in High Level Tyrosine Phosphorylation of STATS 1 and 5

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    Damian Smedley

    1999-10-01

    Full Text Available The ZNF198-FGFR1 fusion gene arises as a result of the t(8;13(p11;g12 in the 8p11 myeloproliferative syndrome. To determine the transforming properties of this chimeric protein we transfected ZNF198-FGFR1 into the interleukin (IL-3 dependent cell line Ba/F3. Growth factor independent subclones were obtained in which ZNF198-FGFR1, STAT1, STAT5 were constitutively tyrosine phosphorylated, as determined by immunoprecipitation and Western blot analysis. To test the hypothesis that constitutive activation of ZNF198-FGFR1 tyrosine kinase activity is a result of selfassociation of the fusion protein, we in vitro transcribed and translated ZNF198-FGFR1 and a derivative construct, ZNF198-FGFR1ΔC-myc, in which the C-terminal FGFR1 epitope was replaced by a c-myc tag. As expected, an anti-FGFR1 antibody immunoprecipitated ZNF198-FGFR1 but not ZNF198-FGFR1ΔC-myc. However when both products were translated together, both were coimmunoprecipitated by anti-FGFR1 antisera. Similar results were obtained by using an anti-myc antibody and demonstrated a physical interaction between the two proteins. Analysis of COS-7 cells transfected with ZNF198-FGFR1 demonstrated that the fusion gene, in contrast to normal FGFR1, is located in the cytoplasm. We conclude that ZNF198-FGFRi is a cytoplasmic protein that self-associates and has constitutive transformation activity. These data suggest that ZNF198-FGFR1 plays a primary role in the pathogenesis of the t(8;13 myeloproliferative syndrome and is the first report to implicate STAT proteins in FGFR1-mediated signaling.

  18. Direct interaction of natural and synthetic catechins with signal transducer activator of transcription 1 affects both its phosphorylation and activity

    KAUST Repository

    Menegazzi, Marta

    2013-12-10

    Our previous studies showed that (-)-epigallocatechin-3-gallate (EGCG) inhibits signal transducer activator of transcription 1 (STAT1) activation. Since EGCG may be a promising lead compound for new anti-STAT1 drug design, 15 synthetic catechins, characterized by the (-)-gallocatechin-3-gallate stereochemistry, were studied in the human mammary MDA-MB-231 cell line to identify the minimal structural features that preserve the anti-STAT1 activity. We demonstrate that the presence of three hydroxyl groups of B ring and one hydroxyl group in D ring is essential to preserve their inhibitory action. Moreover, a possible molecular target of these compounds in the STAT1 pathway was investigated. Our results demonstrate a direct interaction between STAT1 protein and catechins displaying anti-STAT1 activity. In particular, surface plasmon resonance (SPR) analysis and molecular modeling indicate the presence of two putative binding sites (a and b) with different affinity. Based on docking data, site-directed mutagenesis was performed, and interaction of the most active catechins with STAT1 was studied with SPR to test whether Gln518 on site a and His568 on site b could be important for the catechin-STAT1 interaction. Data indicate that site b has higher affinity for catechins than site a as the highest affinity constant disappears in the H568ASTAT1 mutant. Furthermore, Janus kinase 2 (JAK2) kinase assay data suggest that the contemporary presence in vitro of STAT1 and catechins inhibits JAK2-elicited STAT1 phosphorylation. The very tight catechin-STAT1 interaction prevents STAT1 phosphorylation and represents a novel, specific and efficient molecular mechanism for the inhibition of STAT1 activation. © Copyright 2014 Federation of European Biochemical Societies. All rights reserved.

  19. Interferon γ is a STAT1-dependent direct inducer of BCL6 expression in imatinib-treated chronic myeloid leukemia cells.

    Science.gov (United States)

    Madapura, H S; Nagy, N; Ujvari, D; Kallas, T; Kröhnke, M C L; Amu, S; Björkholm, M; Stenke, L; Mandal, P K; McMurray, J S; Keszei, M; Westerberg, L S; Cheng, H; Xue, F; Klein, G; Klein, E; Salamon, D

    2017-08-10

    B-cell CLL/lymphoma 6 (BCL6) exerts oncogenic effects in several human hematopoietic malignancies including chronic myeloid leukemia (CML), where BCL6 expression was shown to be essential for CML stem cell survival and self-renewal during imatinib mesylate (IM) treatment. As several lines of evidence suggest that interferon γ (IFNγ) production in CML patients might have a central role in the response to tyrosine kinase inhibitor (TKI) therapy, we analyzed if IFNγ modulates BCL6 expression in CML cells. Although separate IFNγ or IM treatment only slightly upregulated BCL6 expression, combined treatment induced remarkable BCL6 upregulation in CML lines and primary human CD34+ CML stem cells. We proved that during combined treatment, inhibition of constitutive signal transducer and activator of transcription (STAT) 5 activation by IM allowed the specific enhancement of the STAT1 dependent, direct upregulation of BCL6 by IFNγ in CML cells. By using colony-forming assay, we found that IFNγ enhanced the ex vivo colony or cluster-forming capacity of human CML stem cells in the absence or presence of IM, respectively. Furthermore, inhibition of the transcriptional repressor function of BCL6 in the presence of IM and IFNγ almost completely blocked the cluster formation of human CML stem cells. On the other hand, by using small interfering RNA knockdown of BCL6, we demonstrated that in an IM-treated CML line the antiapoptotic effect of IFNγ was independent of BCL6 upregulation. We found that IFNγ also upregulated several antiapoptotic members of the BCL2 and BIRC gene families in CML cells, including the long isoform of MCL1, which proved to be essential for the antiapoptotic effect of IFNγ in an IM-treated CML line. Our results suggest that combination of TKIs with BCL6 and MCL1 inhibitors may potentially lead to the complete eradication of CML stem cells.

  20. Iron Reduces M1 Macrophage Polarization in RAW264.7 Macrophages Associated with Inhibition of STAT1

    Directory of Open Access Journals (Sweden)

    Zhen-Shun Gan

    2017-01-01

    Full Text Available Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions. The aim of this study is to investigate the cross-regulatory interactions between M1 macrophage polarization and iron metabolism. Firstly, we characterized the transcription of genes related to iron homeostasis in M1 RAW264.7 macrophages stimulated by IFN-γ. The molecular signature of M1 macrophages showed high levels of iron storage (ferritin, a low level of iron export (ferroportin, and changes of iron regulators (hepcidin and transferrin receptors, which favour iron sequestration in the reticuloendothelial system and are benefit for inflammatory disorders. Then, we evaluated the effect of iron on M1 macrophage polarization. Iron significantly reduced mRNA levels of IL-6, IL-1β, TNF-α, and iNOS produced by IFN-γ-polarized M1 macrophages. Immunofluorescence analysis showed that iron also reduced iNOS production. However, iron did not compromise but enhanced the ability of M1-polarized macrophages to phagocytose FITC-dextran. Moreover, we demonstrated that STAT1 inhibition was required for reduction of iNOS and M1-related cytokines production by the present of iron. Together, these findings indicated that iron decreased polarization of M1 macrophages and inhibited the production of the proinflammatory cytokines. The results expanded our knowledge about the role of iron in macrophage polarization.

  1. RAC1 in keratinocytes regulates crosstalk to immune cells by Arp2/3-dependent control of STAT1

    DEFF Research Database (Denmark)

    Pedersen, Esben Ditlev Kølle; Wang, Zhipeng; Stanley, Alanna

    2012-01-01

    Crosstalk between keratinocytes and immune cells is crucial for the immunological barrier function of the skin, and aberrant crosstalk contributes to inflammatory skin diseases. Using mice with a keratinocyte-restricted deletion of the RAC1 gene we found that RAC1 in keratinocytes plays an import...... hypersensitive to inflammatory stimuli both in vitro and in vivo, suggesting a major role for RAC1 in regulating the crosstalk between the epidermis and the immune system....... an important role in modulating the interferon (IFN) response in skin. These RAC1 mutant mice showed increased sensitivity in an irritant contact dermatitis model, abnormal keratinocyte differentiation, and increased expression of immune response genes including the IFN signal transducer STAT1. Loss of RAC1......Crosstalk between keratinocytes and immune cells is crucial for the immunological barrier function of the skin, and aberrant crosstalk contributes to inflammatory skin diseases. Using mice with a keratinocyte-restricted deletion of the RAC1 gene we found that RAC1 in keratinocytes plays...

  2. Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture

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    Gunduz Feyza

    2012-08-01

    Full Text Available Abstract Background Hepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC patients. The mechanism of response to interferon-alpha (IFN-α therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV replication and IFN-α antiviral response in a cell culture model. Methods Sub-genomic replicon (S3-GFP and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR. Results FFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response. Conclusion These results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN

  3. Inhibitory effect of moschamine isolated from Carthamus tinctorius on LPS-induced inflammatory mediators via AP-1 and STAT1/3 inactivation in RAW 264.7 macrophages.

    Science.gov (United States)

    Jo, A-Ra; Han, Hee-Soo; Seo, Seunghwan; Shin, Ji-Sun; Lee, Jae Yeol; Kim, Hyoung Ja; Lee, Kyung-Tae

    2017-12-01

    Seeds of Carthamus tinctorius L. (Compositae) have been used in Korean traditional medicines for the treatment of cardiovascular and bone diseases. In this study, we investigated the anti-inflammatory effects of known serotonin derivatives (1-9) isolated from the ethyl acetate (EtOAc) soluble fraction from the seeds of C. tinctorius. Compound 2, identified as moschamine, most potently inhibited lipopolysaccharide (LPS)-induced production of prostaglandin E 2 (PGE 2 ) and nitric oxide (NO) in RAW 264.7 macrophages. Moschamine concentration-dependently inhibited LPS-induced PGE 2 and NO production in RAW 264.7 macrophages. Consistent with these findings, moschamine suppressed the protein and mRNA levels of cyclooxygenase-2 (COX-2), microsomal prostaglandin E 2 synthase (mPGES)-1, and inducible NO synthase (iNOS), interleukin (IL)-6, and IL-1β. In addition, pretreatment of moschamine significantly inhibited LPS-stimulated the transcriptional activity of activator protein-1 (AP-1) and the phosphorylation of signal transducer and activator of transcription (STAT)1/3 in RAW 264.7 macrophages. Moreover, moschamine inhibited LPS-induced the phosphorylation of p38 mitogen-activated protein kinase (p38) and extracellular signal-regulated kinase (ERK), but it had no effect on c-Jun N-terminal kinase (JNK). These results suggest that the mechanism of anti-inflammatory activity of moschamine is associated with the downregulation of COX-2, mPGES-1, iNOS, IL-6, and IL-1β expression through the suppression of AP-1 and STAT1/3 activation in LPS-induced RAW 264.7 macrophages. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Proposed Standards for Variable Harmonization Documentation and Referencing: A Case Study Using QuickCharmStats 1.1.

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    Kristi Winters

    Full Text Available Comparative statistical analyses often require data harmonization, yet the social sciences do not have clear operationalization frameworks that guide and homogenize variable coding decisions across disciplines. When faced with a need to harmonize variables researchers often look for guidance from various international studies that employ output harmonization, such as the Comparative Survey of Election Studies, which offer recoding structures for the same variable (e.g. marital status. More problematically there are no agreed documentation standards or journal requirements for reporting variable harmonization to facilitate a transparent replication process. We propose a conceptual and data-driven digital solution that creates harmonization documentation standards for publication and scholarly citation: QuickCharmStats 1.1. It is free and open-source software that allows for the organizing, documenting and publishing of data harmonization projects. QuickCharmStats starts at the conceptual level and its workflow ends with a variable recording syntax. It is therefore flexible enough to reflect a variety of theoretical justifications for variable harmonization. Using the socio-demographic variable 'marital status', we demonstrate how the CharmStats workflow collates metadata while being guided by the scientific standards of transparency and replication. It encourages researchers to publish their harmonization work by providing researchers who complete the peer review process a permanent identifier. Those who contribute original data harmonization work to their discipline can now be credited through citations. Finally, we propose peer-review standards for harmonization documentation, describe a route to online publishing, and provide a referencing format to cite harmonization projects. Although CharmStats products are designed for social scientists our adherence to the scientific method ensures our products can be used by researchers across the

  5. Levels of occupational stress and stressful activities for nurses working in emergency

    Directory of Open Access Journals (Sweden)

    José Ricardo Ferreira da Fonseca

    2014-12-01

    Full Text Available The study aimed to identify stress levels, areas and their activities identified as stressful by nurses working in the emergence in Manaus, AM, Brazil. It is an epidemiological, cross-sectional design, with 36 emergency nurses from December 2010 to January 2011. The Bianchi Stress Scale with 57 questions was used. The nurses were at risk for high levels of stress. The most stressful areas were the operation of the unit, conditions of work and personnel administration, and the most stressful activity was the request for equipment review and repair. The difference by Friedman test between the areas was significant (p <0.05, Dunn post-test significant (p <0.05 when compared by peers. The accumulation of management activities with the assistance activities can generate higher levels of stress, it is necessary to invest in improving the work environment and management support to minimize the stress experienced at work.

  6. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    Science.gov (United States)

    Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  7. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.

    Science.gov (United States)

    Dues, Dylan J; Andrews, Emily K; Schaar, Claire E; Bergsma, Alexis L; Senchuk, Megan M; Van Raamsdonk, Jeremy M

    2016-04-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage.

  8. Mindfulness-based stress reduction and physiological activity during acute stress: a randomized controlled trial

    NARCIS (Netherlands)

    Nyklicek, I.; Mommersteeg, P.M.; Beugen, S. van; Ramakers, C.; Boxtel, G.J.M. van

    2013-01-01

    OBJECTIVE: The aim was to examine the effects of a Mindfulness-Based Stress Reduction (MBSR) intervention on cardiovascular and cortisol activity during acute stress. METHOD: Eighty-eight healthy community-dwelling individuals reporting elevated stress levels were randomly assigned to the MBSR

  9. Mindfulness-based stress reduction and physiological activity during acute stress : A randomized controlled trial

    NARCIS (Netherlands)

    Nyklicek, I.; Mommersteeg, P.M.C.; van Beugen, S.; Ramakers, C.; van Boxtel, G.J.M.

    2013-01-01

    Objective: The aim was to examine the effects of a Mindfulness-Based Stress Reduction (MBSR) intervention on cardiovascular and cortisol activity during acute stress. Method: Eighty-eight healthy community-dwelling individuals reporting elevated stress levels were randomly assigned to the MBSR

  10. Stress management for optimization oforganizational activity

    Directory of Open Access Journals (Sweden)

    Iuliana Guiţă – Alexandru

    2014-06-01

    Full Text Available Stress is a constant presence in our lives, whether we analyze it in professional, social or family terms. This daily reality creates a state of tension, strain and discomfort, causing significant changes in physical and mental health. Stress at work can affect anyone, at any level, in any sector and in organizations of any size. Stress affects health and safety of individuals and also organizations’ welfare and national economies. There is a definite correlation between the level of stress at work and the changes in organization’s productivity.

  11. Nighttime snacking, stress, and migraine activity.

    Science.gov (United States)

    Turner, Dana P; Smitherman, Todd A; Penzien, Donald B; Porter, John A H; Martin, Vincent T; Houle, Timothy T

    2014-04-01

    Missing meals and fasting have long been reported as headache triggers. Stress also has received attention for its role in precipitating headaches. This study explored the effects of eating behaviors on new-onset headache. Analyzing only the 1070 of 1648 (64.9%) diary days that followed a non-headache day, the study included 34 migraineurs who contributed a median (25th, 75th percentile) of 28 (22, 40) days of diary entries. Multivariable survival modeling with random effects was conducted, and hazards ratios and 95% confidence intervals were calculated. Nighttime snacking was associated with a 40% reduction in the odds of experiencing a headache compared to having no food (p=0.013). Eating a late dinner was associated with a 21% reduction in the odds of headache when compared to no additional food, but this association was not statistically significant (p=0. 22). These results demonstrate the potential for eating behaviors to be targeted in headache management, as regulated eating habits may have the potential to reduce the occurrence of headache. Although no causal relationship can be established, these results indicate that further research into the mechanisms of the association between eating behaviors and headache activity is warranted. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Inertial effects on the stress generation of active fluids

    Science.gov (United States)

    Takatori, S. C.; Brady, J. F.

    2017-09-01

    Suspensions of self-propelled bodies generate a unique mechanical stress owing to their motility that impacts their large-scale collective behavior. For microswimmers suspended in a fluid with negligible particle inertia, we have shown that the virial swim stress is a useful quantity to understand the rheology and nonequilibrium behaviors of active soft matter systems. For larger self-propelled organisms such as fish, it is unclear how particle inertia impacts their stress generation and collective movement. Here we analyze the effects of finite particle inertia on the mechanical pressure (or stress) generated by a suspension of self-propelled bodies. We find that swimmers of all scales generate a unique swim stress and Reynolds stress that impact their collective motion. We discover that particle inertia plays a similar role as confinement in overdamped active Brownian systems, where the reduced run length of the swimmers decreases the swim stress and affects the phase behavior. Although the swim and Reynolds stresses vary individually with the magnitude of particle inertia, the sum of the two contributions is independent of particle inertia. This points to an important concept when computing stresses in computer simulations of nonequilibrium systems: The Reynolds and the virial stresses must both be calculated to obtain the overall stress generated by a system.

  13. Commercial Hy-Line W-36 pullet and laying hen venous blood gas and chemistry profiles utilizing the portable i-STAT?1 analyzer

    OpenAIRE

    Schaal, T. P.; Arango, J.; Wolc, A.; Brady, J. V.; Fulton, J. E.; Rubinoff, I.; Ehr, I. J.; Persia, M. E.; O'Sullivan, N. P.

    2015-01-01

    Venous blood gas and chemistry reference ranges were determined for commercial Hy-Line W-36 pullets and laying hens utilizing the portable i-STAT?1 analyzer and CG8+ cartridges. A total of 632 samples were analyzed from birds between 4 and 110 wk of age. Reference ranges were established for pullets (4 to 15 wk), first cycle laying hens (20 to 68 wk), and second cycle (post molt) laying hens (70 to 110 wk) for the following traits: sodium (Na mmol/L), potassium (K mmol/L), ionized calcium (iC...

  14. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    OpenAIRE

    Dues, Dylan J.; Andrews, Emily K.; Schaar, Claire E.; Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxi...

  15. Functional imaging of sympathetic activation during mental stress.

    Science.gov (United States)

    Fechir, M; Gamer, M; Blasius, I; Bauermann, T; Breimhorst, M; Schlindwein, P; Schlereth, T; Birklein, F

    2010-04-01

    Activation of the sympathetic nervous system (SNS) is essential in adapting to environmental stressors and in maintaining homeostasis. This reaction can also turn into maladaptation, associated with a wide spectrum of stress-related diseases. Up to now, the cortical mechanisms of sympathetic activation in acute mental stress have not been sufficiently characterized. We therefore investigated cerebral activation applying functional magnetic resonance imaging (fMRI) during performance of a mental stress task with graded levels of difficulty, i.e. four versions of a Stroop task (Colour Word Interference Test, CWT) in healthy subjects. To analyze stress-associated sympathetic activation, skin conductance and heart rate were continuously recorded. The results show that sympathetic activation through mental stress is associated with distinct cerebral regions being immediately involved in task performance (visual, motor, and premotor areas). Other activated regions (right insula, dorsolateral superior frontal gyrus, cerebellar regions) are unrelated to task performance. These latter regions have previously been considered to be involved in mediating different stress responses. The results might furthermore serve as a basis for future investigations of the connection between these cortical regions in the generation of stress-related diseases. Copyright 2009 Elsevier Inc. All rights reserved.

  16. Stress relaxation and estimation of activation volume in a ...

    Indian Academy of Sciences (India)

    Unknown

    Stress relaxation and estimation of activation volume in a commercial hard PZT piezoelectric ceramic. B L CHENG and M J REECE*. Department of Materials, Queen Mary and Westfield College, Mile End Road, E1 4NS, London, UK. Abstract. The stress relaxation of ferroelectric/piezoelectric material was studied using ...

  17. Oxidative stress and superoxide dismutase activity in brain of rats ...

    African Journals Online (AJOL)

    The present study was envisaged to investigate the possible role of oxidative stress in permethrin neurotoxicity and to evaluate the protective effect of superoxide dismutase (SOD) activity in brain homogenates of Wistar rats. Oxidative stress measured as thiobarbituric acid reacting substances (TBARS) was found to ...

  18. WATER STRESS RESPONSE ON THE ENZYMATIC ACTIVITY IN COWPEA NODULES

    Directory of Open Access Journals (Sweden)

    Figueiredo Márcia do Vale B.

    2001-01-01

    Full Text Available A greenhouse experiment was carried out aiming to study the effect of water stress on metabolic activity of cowpea nodules at different plant development stages. Cowpea plants were grown in pots with yellow latosol soil under three different matric potentials treatments: -7.0 (control-S1, -70.0 (S2 and <-85.0 KPa (S3. The experimental design was randomized blocks with sub-divided plots, each plot containing a different degree of water stress, divided in sub-plots for the four different developmental stages: E1 (0-15, E2 (15-30, E3 (20-35 and E4 (30-45 days after emmergence. Water stress treatments were applied by monitoring soil water potential using a set of porous cups. The effect of water stress was most harmful to cowpea when it was applied at E2 than at other symbiotic process stages. Shoot/root ratio decreased from 2.61 to 2.14 when matric potential treatment was <-85.0 and -70.0 KPa respectively. There was a reduction in the glutamine synthetase activity and phosphoenolpyruvate carboxilase activity with increased stress, while glutamine synthase activity was the enzyme most sensitive to water stress. Glutamate dehydrogenase activity increased in more negative matric potential, indicating that this enzyme is sufficiently activitye under water stress.

  19. Stress relaxation and estimation of activation volume in a ...

    Indian Academy of Sciences (India)

    Unknown

    ). The testing was carried out in displacement control for stress relaxation testing at a strain rate of 3%/min. An active capacitor transducer measured the displacement of specimen with a sensitivity of 367 µm/V. 3. Results and discussion.

  20. Determining the stress field in active volcanoes using focal mechanisms

    Directory of Open Access Journals (Sweden)

    Bruno Massa

    2016-11-01

    Full Text Available Stress inversion of seismological datasets became an essential tool to retrieve the stress field of active tectonics and volcanic areas. In particular, in volcanic areas, it is able to put constrains on volcano-tectonics and in general in a better understanding of the volcano dynamics. During the last decades, a wide range of stress inversion techniques has been proposed, some of them specifically conceived to manage seismological datasets. A modern technique of stress inversion, the BRTM, has been applied to seismological datasets available at three different regions of active volcanism: Mt. Somma-Vesuvius (197 Fault Plane Solutions, FPSs, Campi Flegrei (217 FPSs and Long Valley Caldera (38,000 FPSs. The key role of stress inversion techniques in the analysis of the volcano dynamics has been critically discussed. A particular emphasis was devoted to performances of the BRTM applied to volcanic areas.

  1. Testosterone suppresses uropathogenic Escherichia coli invasion and colonization within prostate cells and inhibits inflammatory responses through JAK/STAT-1 signaling pathway.

    Science.gov (United States)

    Ho, Chen-Hsun; Fan, Chia-Kwung; Yu, Hong-Jeng; Wu, Chia-Chang; Chen, Kuan-Chou; Liu, Shih-Ping; Cheng, Po-Ching

    2017-01-01

    Prostatitis is a common condition in adult men of all ages. Uropathogenic Escherichia coli (UPEC) are most frequent pathogen involved in bacterial prostatitis by refluxing the infected urine into prostatic ducts and resulting in an ascending urethral infection. However, the study about the mechanisms of UPEC to invade, replicate and persist in normal prostate epithelial cell is only few. Given the fact that UPEC is pathogen most frequently involved in prostatitis and that testosterone has been demonstrated to attenuate prostate inflammation caused by other etiologies. In this study we investigated whether the testosterone reduces the prostatitis and related mechanism by regulating IFN-γ/STAT1 signaling pathway. In the current study aimed to clarify whether testosterone influences the process of UPEC-induced prostate inflammation and invasion into the prostate epithelial cells. In addition, we set up a normal prostate cell model for UPEC infection to evaluate the ability to invade the urothelial cells as well as the colonization of intercellular bacterial communities in vitro. By using the model, we examine the effects of testosterone to suppress effectively the invasion and survival of UPEC in the prostate cells, and inhibit LPS-induced inflammatory responses through the JAK/STAT1 pathway have also been indicated. Our results demonstrated testosterone not only suppressed the invasion and colonization of UPEC, but also inhibited the expression of pro-inflammatory IL-1β, IL-6 and IL-8 cytokines expression induced by UPEC in a dose-dependent manner. We found the effective dose of testosterone to suppress UPEC infect prostate cells may be appropriate under 40μg/ml. Our data also revealed 20μg/ml testosterone treated PZ-HPV-7 cells significantly suppressed the LPS-induced JAK/STAT1 pathway and inflammatory responses, and reached to maximal effects at 40μg/ml treatment. These results indicate that testosterone plays an anti-inflammatory role in LPS-induced prostate

  2. The effects of stress on physical activity and exercise.

    Science.gov (United States)

    Stults-Kolehmainen, Matthew A; Sinha, Rajita

    2014-01-01

    Psychological stress and physical activity (PA) are believed to be reciprocally related; however, most research examining the relationship between these constructs is devoted to the study of exercise and/or PA as an instrument to mitigate distress. The aim of this paper was to review the literature investigating the influence of stress on indicators of PA and exercise. A systematic search of Web of Science, PubMed, and SPORTDiscus was employed to find all relevant studies focusing on human participants. Search terms included "stress", "exercise", and "physical activity". A rating scale (0-9) modified for this study was utilized to assess the quality of all studies with multiple time points. The literature search found 168 studies that examined the influence of stress on PA. Studies varied widely in their theoretical orientation and included perceived stress, distress, life events, job strain, role strain, and work-family conflict but not lifetime cumulative adversity. To more clearly address the question, prospective studies (n = 55) were considered for further review, the majority of which indicated that psychological stress predicts less PA (behavioral inhibition) and/or exercise or more sedentary behavior (76.4 %). Both objective (i.e., life events) and subjective (i.e., distress) measures of stress related to reduced PA. Prospective studies investigating the effects of objective markers of stress nearly all agreed (six of seven studies) that stress has a negative effect on PA. This was true for research examining (a) PA at periods of objectively varying levels of stress (i.e., final examinations vs. a control time point) and (b) chronically stressed populations (e.g., caregivers, parents of children with a cancer diagnosis) that were less likely to be active than controls over time. Studies examining older adults (>50 years), cohorts with both men and women, and larger sample sizes (n > 100) were more likely to show an inverse association. 85.7 % of higher

  3. Connecting local active forces to macroscopic stress in elastic media.

    Science.gov (United States)

    Ronceray, Pierre; Lenz, Martin

    2015-02-28

    In contrast with ordinary materials, living matter drives its own motion by generating active, out-of-equilibrium internal stresses. These stresses typically originate from localized active elements embedded in an elastic medium, such as molecular motors inside the cell or contractile cells in a tissue. While many large-scale phenomenological theories of such active media have been developed, a systematic understanding of the emergence of stress from the local force-generating elements is lacking. In this paper, we present a rigorous theoretical framework to study this relationship. We show that the medium's macroscopic active stress tensor is equal to the active elements' force dipole tensor per unit volume in both continuum and discrete linear homogeneous media of arbitrary geometries. This relationship is conserved on average in the presence of disorder, but can be violated in nonlinear elastic media. Such effects can lead to either a reinforcement or an attenuation of the active stresses, giving us a glimpse of the ways in which nature might harness microscopic forces to create active materials.

  4. Alpha-1 antitrypsin prevents the development of preeclampsia through suppression of oxidative stress

    Directory of Open Access Journals (Sweden)

    Yaling eFeng

    2016-05-01

    Full Text Available Preeclampsia (PE and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

  5. Alpha-1 Antitrypsin Prevents the Development of Preeclampsia Through Suppression of Oxidative Stress.

    Science.gov (United States)

    Feng, Yaling; Xu, Jianjuan; Zhou, Qin; Wang, Rong; Liu, Nin; Wu, Yanqun; Yuan, Hua; Che, Haisha

    2016-01-01

    Preeclampsia (PE) and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT) played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS, and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

  6. Chitin and stress induced protein kinase activation

    DEFF Research Database (Denmark)

    Kenchappa, Chandra Shekar; Azevedo da Silva, Raquel; Bressendorff, Simon

    2017-01-01

    The assays described here are pertinent to protein kinase studies in any plant. They include an immunoblot phosphorylation/activation assay and an in-gel activity assay for MAP kinases (MPKs) using the general protein kinase substrate myelin basic protein. They also include a novel in-gel peptide...... substrate assay for Snf1-related kinase family 2 members (SnRK2s). This kinase family-specific assay overcomes some limitations of in-gel assays and permits the identification of different types of kinase activities in total protein extracts....

  7. The Effects of Stress on Physical Activity and Exercise

    Science.gov (United States)

    Stults-Kolehmainen, Matthew A.; Sinha, Rajita

    2013-01-01

    Background Psychological stress and physical activity (PA) are believed to be reciprocally related; however, most research examining the relationship between these constructs is devoted to the study of exercise and/or PA as an instrument to mitigate distress. Objective The aim of this paper was to review the literature investigating the influence of stress on indicators of PA and exercise. Methods A systematic search of Web of Science, Pub-Med, and SPORTDiscus was employed to find all relevant studies focusing on human participants. Search terms included “stress”, “exercise”, and “physical activity”. A rating scale (0–9) modified for this study was utilized to assess the quality of all studies with multiple time points. Results The literature search found 168 studies that examined the influence of stress on PA. Studies varied widely in their theoretical orientation and included perceived stress, distress, life events, job strain, role strain, and work–family conflict but not lifetime cumulative adversity. To more clearly address the question, prospective studies (n = 55) were considered for further review, the majority of which indicated that psychological stress predicts less PA (behavioral inhibition) and/or exercise or more sedentary behavior (76.4 %). Both objective (i.e., life events) and subjective (i.e., distress) measures of stress related to reduced PA. Prospective studies investigating the effects of objective markers of stress nearly all agreed (six of seven studies) that stress has a negative effect on PA. This was true for research examining (a) PA at periods of objectively varying levels of stress (i.e., final examinations vs. a control time point) and (b) chronically stressed populations (e.g., caregivers, parents of children with a cancer diagnosis) that were less likely to be active than controls over time. Studies examining older adults (>50 years), cohorts with both men and women, and larger sample sizes (n > 100) were more likely

  8. Visceral Inflammation and Immune Activation Stress the Brain

    Science.gov (United States)

    Holzer, Peter; Farzi, Aitak; Hassan, Ahmed M.; Zenz, Geraldine; Jačan, Angela; Reichmann, Florian

    2017-01-01

    Stress refers to a dynamic process in which the homeostasis of an organism is challenged, the outcome depending on the type, severity, and duration of stressors involved, the stress responses triggered, and the stress resilience of the organism. Importantly, the relationship between stress and the immune system is bidirectional, as not only stressors have an impact on immune function, but alterations in immune function themselves can elicit stress responses. Such bidirectional interactions have been prominently identified to occur in the gastrointestinal tract in which there is a close cross-talk between the gut microbiota and the local immune system, governed by the permeability of the intestinal mucosa. External stressors disturb the homeostasis between microbiota and gut, these disturbances being signaled to the brain via multiple communication pathways constituting the gut–brain axis, ultimately eliciting stress responses and perturbations of brain function. In view of these relationships, the present article sets out to highlight some of the interactions between peripheral immune activation, especially in the visceral system, and brain function, behavior, and stress coping. These issues are exemplified by the way through which the intestinal microbiota as well as microbe-associated molecular patterns including lipopolysaccharide communicate with the immune system and brain, and the mechanisms whereby overt inflammation in the GI tract impacts on emotional-affective behavior, pain sensitivity, and stress coping. The interactions between the peripheral immune system and the brain take place along the gut–brain axis, the major communication pathways of which comprise microbial metabolites, gut hormones, immune mediators, and sensory neurons. Through these signaling systems, several transmitter and neuropeptide systems within the brain are altered under conditions of peripheral immune stress, enabling adaptive processes related to stress coping and resilience

  9. Piano Playing Reduces Stress More than Other Creative Art Activities

    Science.gov (United States)

    Toyoshima, Kumiko; Fukui, Hajime; Kuda, Kiyoto

    2011-01-01

    Few studies have been conducted on the physiological effects of creative art activities. In this study, the effects of creative art activities on human stress were investigated, and their effects were compared in 57 healthy college students (27 males and 30 females). Subjects were divided into four groups, each of which participated in 30-minute…

  10. Kohonen Neural Network Stress Detection Using Only Electrodermal Activity Features

    Directory of Open Access Journals (Sweden)

    BORNOIU, I.-V.

    2014-08-01

    Full Text Available This paper presents a method for identifying human stress levels by using a Kohonen neural network. The study focuses on differentiating between a relaxed and a stressed state and it presents a series of parameters (skin conductance response signal power, skin conductance response signal frequency, skin conductance level gradient, response rise time and response amplitude extracted only from the electrodermal activity signal. A very strict recording protocol was used to minimize the artifacts caused by the bad connection between electrodes and skin. A stress inducing method is presented that can be used to replicate results in laboratory conditions.

  11. Emotional Intelligence, Physical Activity and Coping with Stress in Adolescents

    Directory of Open Access Journals (Sweden)

    Ali Aziz Dawood A L S U D A N I

    2015-06-01

    Full Text Available Participation in physical activity seems to be connected with better coping with stress and higher level emotional intelligence. The aim of the study is to check if there are any significant correlations between emotional intelligence, physical activity and style focused on the task in coping with stress. The sample was made by 90 adolesc ents, aged from 19 - 21 from Psychology department at University of Szczecin. To check the level of emotional inteligence was used polish version of Emotional Intelligence Questionaire. To check te level of physical activity was used s hort form of Internati onal Physical Activity Questionaire. To find out what kind of style is used by adolescents with coping with stress was used Polish version of Coping Inventory for Stressful Situations. There were signifficant correlations between physical activity an d task oriented coping, avoidance, social diversion, emotional intelligence (p<0.05. Regression analyses showed that task oriented coping and social diversion are predictors of physical activity. Results of one way Anova showed that the task - oriented copi ng, social diversion, walking, moderate and vigorous intensity physical activity, physical actrivity (in MET/min, emotional intelligence, identifying emotions and using emotions in practice of the high PA group were significantly higher (p<0.05 than in t he low PA group.

  12. Variants in the IFNγ transcription factor genes TBET, STAT1, STAT4, and HLX and the risk of pulmonary tuberculosis in a Colombian population: a case-control study.

    Science.gov (United States)

    Sánchez, Dulfary; Lefebvre, Céline; García, Luis F; Barrera, Luis F

    2013-01-01

    Interferon gamma (IFNγ) is the most potent cytokine involved in the control of Mycobacterium tuberculosis (Mtb), the etiological agent of human tuberculosis (TB). Patients with active TB present reduced levels of IFNγ, which may explain the lack of effective immunity against Mtb in these patients. The diminished expression of or functional alterations in trans-acting factors that regulate IFNγ gene expression may explain the reduced levels of IFNγ in TB patients. To investigate the relationships of genetic variants in the transcription factors TBET, STAT1, STAT4, and HLX to susceptibility/resistance to pulmonary TB. Eight candidate single-nucleotide polymorphisms (SNPs) were selected, and genotyped in 466 unrelated pulmonary TB patients and 300 healthy controls from Colombia, and the allelic and genetic associations with TB were analyzed. The results indicate that no SNP in the transcription factors studied is associated with TB. However, polymorphism rs11650354 in the TBET gene may be associated with a decreased risk of TB; the TT genotype was significantly associated with TB protection in a recessive genetic model (OR=0.089, 95% CI: 0.01-0.73, p=0.0069), although this association was not maintained after multiple test correction (EMP2= 0.61). In this study, the rs11650354 variant of TBET was suggested to promote resistance to TB in a Colombian population. A future replication case-control study using additional samples will be necessary to confirm this suggestive association.

  13. Electrodermal Activity Is Sensitive to Cognitive Stress under Water

    Directory of Open Access Journals (Sweden)

    Hugo F. Posada-Quintero

    2018-01-01

    Full Text Available When divers are at depth in water, the high pressure and low temperature alone can cause severe stress, challenging the human physiological control systems. The addition of cognitive stress, for example during a military mission, exacerbates the challenge. In these conditions, humans are more susceptible to autonomic imbalance. Reliable tools for the assessment of the autonomic nervous system (ANS could be used as indicators of the relative degree of stress a diver is experiencing, which could reveal heightened risk during a mission. Electrodermal activity (EDA, a measure of the changes in conductance at the skin surface due to sweat production, is considered a promising alternative for the non-invasive assessment of sympathetic control of the ANS. EDA is sensitive to stress of many kinds. Therefore, as a first step, we tested the sensitivity of EDA, in the time and frequency domains, specifically to cognitive stress during water immersion of the subject (albeit with their measurement finger dry for safety. The data from 14 volunteer subjects were used from the experiment. After a 4-min adjustment and baseline period after being immersed in water, subjects underwent the Stroop task, which is known to induce cognitive stress. The time-domain indices of EDA, skin conductance level (SCL and non-specific skin conductance responses (NS.SCRs, did not change during cognitive stress, compared to baseline measurements. Frequency-domain indices of EDA, EDASymp (based on power spectral analysis and TVSymp (based on time-frequency analysis, did significantly change during cognitive stress. This leads to the conclusion that EDA, assessed by spectral analysis, is sensitive to cognitive stress in water-immersed subjects, and can potentially be used to detect cognitive stress in divers.

  14. Endoplasmic reticulum stress activates transglutaminase 2 leading to protein aggregation.

    Science.gov (United States)

    Lee, Jin-Haeng; Jeong, Jaeho; Jeong, Eui Man; Cho, Sung-Yup; Kang, Jeong Wook; Lim, Jisun; Heo, Jinbeom; Kang, Hyunsook; Kim, In-Gyu; Shin, Dong-Myung

    2014-04-01

    Aberrant activation of transglutaminase 2 (TGase2) contributes to a variety of protein conformational disorders such as neurodegenerative diseases and age-related cataracts. The accumulation of improperly folded proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), which promotes either repair or degradation of the damaged proteins. Inadequate UPR results in protein aggregation that may contribute to the development of age-related degenerative diseases. TGase2 is a calcium-dependent enzyme that irreversibly modifies proteins by forming cross-linked protein aggregates. Intracellular TGase2 is activated by oxidative stress which generates large quantities of unfolded proteins. However, the relationship between TGase2 activity and UPR has not yet been established. In the present study, we demonstrated that ER stress activated TGase2 in various cell types. TGase2 activation was dependent on the ER stress-induced increase in the intracellular calcium ion concentration but not on the TGase2 protein expression level. Enzyme substrate analysis revealed that TGase2-mediated protein modification promoted protein aggregation concurrently with decreasing water solubility. Moreover, treatment with KCC009, a TGase2 inhibitor, abrogated ER stress-induced TGase2 activation and subsequent protein aggregation. However, TGase2 activation had no effect on ER stress-induced cell death. These results demonstrate that the accumulation of misfolded proteins activates TGase2, which further accelerates the formation of protein aggregates. Therefore, we suggest that inhibition of TGase2 may be a novel strategy by which to prevent the protein aggregation in age-related degenerative diseases.

  15. Market risk stress testing for internationally active financial institutions

    Directory of Open Access Journals (Sweden)

    Marković Petar

    2011-01-01

    Full Text Available The paper develops a comprehensive framework for market risk stress testing in internationally active financial institutions. We begin by defining the scope and type of the stress test and explaining how to select risk factors and the stress time horizon. We then address challenges related to data gathering, followed by in-depth discussion of techniques for developing realistic shock scenarios. Next the process of shock application to a particular portfolio is described, followed by determination of portfolio profit and loss. We conclude by briefly discussing the issue of assigning probability to stress scenarios. We illustrate the framework by considering the development of a ‘worst case’ scenario using global financial market data from Thomson Reuters Datastream.

  16. Sympathetic nerve activity and whole body heat stress in humans.

    Science.gov (United States)

    Low, David A; Keller, David M; Wingo, Jonathan E; Brothers, R Matthew; Crandall, Craig G

    2011-11-01

    We and others have shown that moderate passive whole body heating (i.e., increased internal temperature ∼0.7°C) increases muscle (MSNA) and skin sympathetic nerve activity (SSNA). It is unknown, however, if MSNA and/or SSNA continue to increase with more severe passive whole body heating or whether these responses plateau following moderate heating. The aim of this investigation was to test the hypothesis that MSNA and SSNA continue to increase from a moderate to a more severe heat stress. Thirteen subjects, dressed in a water-perfused suit, underwent at least one passive heat stress that increased internal temperature ∼1.3°C, while either MSNA (n = 8) or SSNA (n = 8) was continuously recorded. Heat stress significantly increased mean skin temperature (Δ∼5°C, P heat stress (Δ core temperature 0.63 ± 0.01°C) when expressed as burst frequency (26 ± 14 to 45 ± 16 bursts/min, P = 0.001), burst incidence (39 ± 13 to 48 ± 14 bursts/100 cardiac cyles, P = 0.03), or total activity (317 ± 170 to 489 ± 150 units/min, P = 0.02) and continued to increase until the end of heat stress (burst frequency: 61 ± 15 bursts/min, P = 0.01; burst incidence: 56 ± 11 bursts/100 cardiac cyles, P = 0.04; total activity: 648 ± 158 units/min, P = 0.01) relative to the mid-heating stage. Similarly, SSNA (total activity) increased midway through the heat stress (normothermia; 1,486 ± 472 to mid heat stress 6,467 ± 5,256 units/min, P = 0.03) and continued to increase until the end of heat stress (11,217 ± 6,684 units/min, P = 0.002 vs. mid-heat stress). These results indicate that both MSNA and SSNA continue to increase as internal temperature is elevated above previously reported values.

  17. Relations of Physical Activity and Stress Vulnerability in University Students

    Science.gov (United States)

    Xu, Furong; Liu, Wenhao; Chepyator-Thomson, Jepkorir Rose; Schmidlein, Robert

    2018-01-01

    There are increased concerns about depression and anxiety among college students. Thus in need of actions to find proper intervention strategies to target this issue. The purpose of this study was to examine association between leisure-time physical activity and stress vulnerability among college students. A modified survey including physical…

  18. Influence of osmotic and metal stresses on nitrogenase activity of ...

    African Journals Online (AJOL)

    SERVER

    2007-08-06

    Aug 6, 2007 ... Influence of osmotic and metal stresses on nitrogenase activity of cyanobacteria ısolated from paddy fields. Gulten OKMEN (Kurucuoglu)1*, Gonul DONMEZ2 and Sedat DONMEZ3. 1Muğla University, Faculty of Science and Arts, Department of Biology, Mugla, Turkıye. 2Ankara University, Faculty of Science ...

  19. Active power decoupling with reduced converter stress for single ...

    Indian Academy of Sciences (India)

    SUJATA BHOWMICK

    The analysis and the simulation results are shown to prove the effectiveness of the topology. Keywords. Single phase; double-frequency ripple; active power decoupling; reduced stress; reliability. 1. Introduction. The single-phase power electronic converters interfacing a. DC storage system or a DC source have the inherent.

  20. Oxidative stress and superoxide dismutase activity in brain of rats ...

    African Journals Online (AJOL)

    JTEkanem

    Oxidative stress and superoxide dismutase activity in brain of rats fed with diet containing permethrin. Olawale OTITOJU1, Ikechukwu N. E. ONWURAH2*, Grace T. O. OTITOJU3 and. Chidiebere E. UGWU4. 1Department of Biochemistry, Faculty of Basic Medical Sciences, University of Uyo, Uyo,. Nigeria. 2 Pollution Control ...

  1. [Modification of plasma blood coagulation factor activity by physical stress].

    Science.gov (United States)

    Lutze, G; Buhl, H; Häcker, R; Socha, C; Socha, U; Urbahn, H

    1986-09-15

    The influence of physical stress (bicycle ergometer and track) on 13 parameters of the plasmatic coagulation system was investigated in trained and untrained test persons. Shortenings of the coagulation times as well as distinct increases of the activity or concentration were observed in the partial thromboplastin time (PTT), the factor VIII activity (VIII:C) and the factor VIII-associated antigen (VIIIR:Ag). The results are discussed with regard to their causes and their clinical importance.

  2. Glia activation and its role in oxidative stress.

    Science.gov (United States)

    Ogundele, Olalekan Michael; Omoaghe, Adams Olalekan; Ajonijebu, Duyilemi Chris; Ojo, Abiodun Ayodele; Fabiyi, Temitope Deborah; Olajide, Olayemi Joseph; Falode, Deborah Tolulope; Adeniyi, Philip Adeyemi

    2014-06-01

    Glia activation and neuroinflamation are major factors implicated in the aetiology of most neurodegenerative diseases (NDDs). Several agents and toxins have been known to be capable of inducing glia activation an inflammatory response; most of which are active substances that can cause oxidative stress by inducing production of reactive oxygen species (ROS). Neurogenesis on the other hand involves metabolic and structural interaction between neurogenic and glia cells of the periventricular zone (PVZ); a region around the third ventricle. This study investigates glia activation (GFAP), cell proliferation (Ki-67) and neuronal metabolism (NSE) during neurogenesis and oxidative stress by comparing protein expression in the PVZ against that of the parietal cortex. Adult Wistar Rats were treated with normal saline and 20 mg/Kg KCN for 7 days. The tissue sections were processed for immunohistochemistry to demonstrate glia cells (anti Rat-GFAP), cell proliferation (anti Rat-Ki-67) and neuronal metabolism (anti Rat-NSE) using the antigen retrieval method. The sections from Rats treated with cyanide showed evidence of neurodegeneration both in the PVZ and cortex. The distribution of glia cells (GFAP), Neuron specific Enolase (NSE) and Ki-67 increased with cyanide treatment, although the increases were more pronounced in the neurogenic cell area (PVZ) when compared to the cortex. This suggests the close link between neuronal metabolism and glia activation both in neurogenesis and oxidative stress.

  3. European standardization activities on residual stress analysis by neutron diffraction

    CERN Document Server

    Youtsos, A G

    2002-01-01

    A main objective of a recently completed European research project, RESTAND - residual stress standard using neutron diffraction, was to develop industrial confidence in the application of the neutron-diffraction technique for residual stress measurement and its principal deliverable was a relevant draft code of practice. In fact this draft standard was jointly developed within RESTAND and VAMAS TWA 20 - an international pre-normative research activity. As no such standard is yet available, on the basis of this draft standard document the European Standards Committee on Non-Destructive Testing (CEN TC/138) has established a new ad hoc Work Group (AHG7). The objective of this group is the development of a European pre-standard on a 'test method for measurement of residual stress by neutron diffraction'. The document contains the proposed protocol for making the measurements. It includes the scope of the method, an outline of the technique, the calibration and measurement procedures recommended, and details of ...

  4. Stress monitoring versus microseismic ruptures in an active deep mine

    Science.gov (United States)

    Tonnellier, Alice; Bouffier, Christian; Bigarré, Pascal; Nyström, Anders; Österberg, Anders; Fjellström, Peter

    2015-04-01

    monitoring data coming from the mine in quasi-real time and facilitates information exchanges and decision making for experts and stakeholders. On the basis of these data acquisition and sharing, preliminary analysis has been started to highlight whether stress variations and seismic sources behaviour might be directly bound with mine working evolution and could improve the knowledge on the equilibrium states inside the mine. Knowing such parameters indeed will be a potential solution to understand better the response of deep mining activities to the exploitation solicitations and to develop, if possible, methods to prevent from major hazards such as rock bursts and other ground failure phenomena.

  5. Mechanical and hypoxia stress can cause chondrocytes apoptosis through over-activation of endoplasmic reticulum stress.

    Science.gov (United States)

    Huang, Ziwei; Zhou, Min; Wang, Qian; Zhu, Mengjiao; Chen, Sheng; Li, Huang

    2017-12-01

    To examine the role of mechanical force and hypoxia on chondrocytes apoptosis and osteoarthritis (OA)-liked pathological change on mandibular cartilage through over-activation of endoplasmic reticulum stress (ERS). We used two in vitro models to examine the effect of mechanical force and hypoxia on chondrocytes apoptosis separately. The mandibular condylar chondrocytes were obtained from three-week-old male Sprague-Dawley rats. Flexcell 5000T apparatus was used to produce mechanical forces (12%, 0.5Hz, 24h vs 20%, 0.5Hz, 24h) on chondrocytes. For hypoxia experiment, the concentration of O 2 was down regulated to 5% or 1%. Cell apoptosis rates were quantified by annexin V and propidium iodide (PI) double staining and FACS analysis. Quantitative real-time PCR and western blot were performed to evaluate the activation of ERS and cellular hypoxia. Then we used a mechanical stress loading rat model to verify the involvement of ERS in OA-liked mandibular cartilage pathological change. Histological changes in mandibular condylar cartilage were assessed via hematoxylin & eosin (HE) staining. Immunohistochemistry of GRP78, GRP94, HIF-1α, and HIF-2α were performed to evaluate activation of the ERS and existence of hypoxia. Apoptotic cells were detected by the TUNEL method. Tunicamycin, 20% mechanical forces and hypoxia (1% O 2 ) all significantly increased chondrocytes apoptosis rates and expression of ERS markers (GRP78, GRP94 and Caspase 12). However, 12% mechanical forces can only increase the apoptotic sensitivity of chondrocytes. Mechanical stress resulted in OA-liked pathological change on rat mandibular condylar cartilage which included thinning cartilage and bone erosion. The number of apoptotic cells increased. ERS and hypoxia markers expressions were also enhanced. Salubrinal, an ERS inhibitor, can reverse these effects in vitro and in vivo through the down-regulation of ERS markers and hypoxia markers. We confirmed that mechanical stress and local hypoxia both

  6. One-dimensional models of thermal activation under shear stress

    CSIR Research Space (South Africa)

    Nabarro, FRN

    2003-01-01

    Full Text Available - dimensional models presented here may illuminate the study of more realistic models. For the model in which as many dislocations are poised for backward jumps as for forward jumps, the experimental activation volume Vye(C27a) under applied stresses close to C...27a is different from the true activation volume V(C27) evaluated at C27 ?C27a. The relations between the two are developed. A model is then discussed in which fewer dislocations are available for backward than for forward jumps. Finally...

  7. Sympathetic activity during passive heat stress in healthy aged humans.

    Science.gov (United States)

    Gagnon, Daniel; Schlader, Zachary J; Crandall, Craig G

    2015-05-01

    Cardiovascular adjustments to heat stress are attenuated in healthy aged individuals, which could contribute to their greater prevalence of heat-related illnesses and deaths during heat waves. The attenuated cardiovascular adjustments in the aged could be due to lower increases in sympathetic nerve activity during heat stress. We examined muscle sympathetic nerve activity (MSNA) and plasma catecholamine concentrations in healthy young and aged individuals during whole-body passive heat stress. The main finding of this study is that increases in MSNA and plasma catecholamine concentrations did not differ between young and aged healthy individuals during passive heating. Furthermore, the increase in these variables did not differ when a cold pressor test and lower body negative pressure were superimposed upon heating. These findings suggest that attenuated cardiovascular adjustments to heat stress in healthy aged individuals are unlikely to be related to attenuated increases in sympathetic activity. Cardiovascular adjustments during heat stress are generally attenuated in healthy aged humans, which could be due to lower increases in sympathetic activity compared to the young. We compared muscle sympathetic nerve activity (MSNA) between 11 young (Y: 28 ± 4 years) and 10 aged (A: 70 ± 5 years) subjects prior to and during passive heating. Furthermore, MSNA responses were compared when a cold pressor test (CPT) and lower body negative pressure (LBNP) were superimposed upon heating. Baseline MSNA burst frequency (Y: 15 ± 4 vs. A: 31 ± 3 bursts min(-1) , P ≤ 0.01) and burst incidence (Y: 26 ± 8 vs. A: 50 ± 7 bursts (100 cardiac cycles (CC))(-1) , P ≤ 0.01) were greater in the aged. Heat stress increased core temperature to a similar extent in both groups (Y: +1.2 ± 0.1 vs. A: +1.2 ± 0.0°C, P = 0.99). Absolute levels of MSNA remained greater in the aged during heat stress (burst frequency: Y: 47 ± 6 vs. A: 63 ± 11

  8. European standardization activities on residual stress analysis by neutron diffraction

    International Nuclear Information System (INIS)

    Youtsos, A.G.; Ohms, C.

    2002-01-01

    A main objective of a recently completed European research project, RESTAND - residual stress standard using neutron diffraction, was to develop industrial confidence in the application of the neutron-diffraction technique for residual stress measurement and its principal deliverable was a relevant draft code of practice. In fact this draft standard was jointly developed within RESTAND and VAMAS TWA 20 - an international pre-normative research activity. As no such standard is yet available, on the basis of this draft standard document the European Standards Committee on Non-Destructive Testing (CEN TC/138) has established a new ad hoc Work Group (AHG7). The objective of this group is the development of a European pre-standard on a 'test method for measurement of residual stress by neutron diffraction'. The document contains the proposed protocol for making the measurements. It includes the scope of the method, an outline of the technique, the calibration and measurement procedures recommended, and details of how the strain data should be analysed to calculate stresses and establish the reliability of the results obtained. (orig.)

  9. European standardization activities on residual stress analysis by neutron diffraction

    Science.gov (United States)

    Youtsos, A. G.; Ohms, C.

    A main objective of a recently completed European research project, RESTAND - residual stress standard using neutron diffraction, was to develop industrial confidence in the application of the neutron-diffraction technique for residual stress measurement and its principal deliverable was a relevant draft code of practice. In fact this draft standard was jointly developed within RESTAND and VAMAS TWA 20 - an international pre-normative research activity. As no such standard is yet available, on the basis of this draft standard document the European Standards Committee on Non-Destructive Testing (CEN TC/138) has established a new ad hoc Work Group (AHG7). The objective of this group is the development of a European pre-standard on a `test method for measurement of residual stress by neutron diffraction'. The document contains the proposed protocol for making the measurements. It includes the scope of the method, an outline of the technique, the calibration and measurement procedures recommended, and details of how the strain data should be analysed to calculate stresses and establish the reliability of the results obtained.

  10. Chronic workplace stress and insufficient physical activity: a cohort study.

    Science.gov (United States)

    Kouvonen, Anne; Vahtera, Jussi; Oksanen, Tuula; Pentti, Jaana; Väänänen, Ari K P; Heponiemi, Tarja; Salo, Paula; Virtanen, Marianna; Kivimäki, Mika

    2013-01-01

    To examine whether exposure to workplace stressors predicts changes in physical activity and the risk of insufficient physical activity. Prospective data from the Finnish Public Sector Study. Repeated exposure to low job control, high job demands, low effort, low rewards and compositions of these (job strain and effort-reward imbalance) were assessed at Time 1 (2000-2002) and Time 2 (2004). Insufficient physical activity (workplace stressors on change in physical activity was examined using fixed-effects (within-subject) logistic regression models (N=6665). In addition, logistic regression analysis was applied to examine the associations between repeated exposure to workplace stressors and insufficient physical activity (N=13 976). In these analyses, coworker assessed workplace stressor scores were used in addition to individual level scores. The proportion of participants with insufficient physical activity was 24% at baseline and 26% at follow-up. 19% of the participants who were sufficiently active at baseline became insufficiently active at follow-up. In the fixed-effect analysis, an increase in workplace stress was weakly related to an increase in physical inactivity within an individual. In between-subjects analysis, employees with repeated exposure to low job control and low rewards were more likely to be insufficiently active at follow-up than those with no reports of these stressors; fully adjusted ORs ranged from 1.11 (95% CI 1.00 to 1.24) to 1.21 (95% CI 1.05 to 1.39). Workplace stress is associated with a slightly increased risk of physical inactivity.

  11. Alanine-scanning mutagenesis of human signal transducer and activator of transcription 1 to estimate loss- or gain-of-function variants.

    Science.gov (United States)

    Kagawa, Reiko; Fujiki, Ryoji; Tsumura, Miyuki; Sakata, Sonoko; Nishimura, Shiho; Itan, Yuval; Kong, Xiao-Fei; Kato, Zenichiro; Ohnishi, Hidenori; Hirata, Osamu; Saito, Satoshi; Ikeda, Maiko; El Baghdadi, Jamila; Bousfiha, Aziz; Fujiwara, Kaori; Oleastro, Matias; Yancoski, Judith; Perez, Laura; Danielian, Silvia; Ailal, Fatima; Takada, Hidetoshi; Hara, Toshiro; Puel, Anne; Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; Casanova, Jean-Laurent; Ohara, Osamu; Okada, Satoshi; Kobayashi, Masao

    2017-07-01

    Germline heterozygous mutations in human signal transducer and activator of transcription 1 (STAT1) can cause loss of function (LOF), as in patients with Mendelian susceptibility to mycobacterial diseases, or gain of function (GOF), as in patients with chronic mucocutaneous candidiasis. LOF and GOF mutations are equally rare and can affect the same domains of STAT1, especially the coiled-coil domain (CCD) and DNA-binding domain (DBD). Moreover, 6% of patients with chronic mucocutaneous candidiasis with a GOF STAT1 mutation have mycobacterial disease, obscuring the functional significance of the identified STAT1 mutations. Current computational approaches, such as combined annotation-dependent depletion, do not distinguish LOF and GOF variants. We estimated variations in the CCD/DBD of STAT1. We mutagenized 342 individual wild-type amino acids in the CCD/DBD (45.6% of full-length STAT1) to alanine and tested the mutants for STAT1 transcriptional activity. Of these 342 mutants, 201 were neutral, 30 were LOF, and 111 were GOF mutations in a luciferase assay. This assay system correctly estimated all previously reported LOF mutations (100%) and slightly fewer GOF mutations (78.1%) in the CCD/DBD of STAT1. We found that GOF alanine mutants occurred at the interface of the antiparallel STAT1 dimer, suggesting that they destabilize this dimer. This assay also precisely predicted the effect of 2 hypomorphic and dominant negative mutations, E157K and G250E, in the CCD of STAT1 that we found in 2 unrelated patients with Mendelian susceptibility to mycobacterial diseases. The systematic alanine-scanning assay is a useful tool to estimate the GOF or LOF status and the effect of heterozygous missense mutations in STAT1 identified in patients with severe infectious diseases, including mycobacterial and fungal diseases. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Lower Electrodermal Activity to Acute Stress in Caregivers of People with Autism Spectrum Disorder: An Adaptive Habituation to Stress

    Science.gov (United States)

    Ruiz-Robledillo, Nicolás; Moya-Albiol, Luis

    2015-01-01

    Caring for a relative with autism spectrum disorder (ASD) entails being under chronic stress that could alter body homeostasis. Electrodermal activity (EDA) is an index of the sympathetic activity of the autonomic nervous system related to emotionality and homeostasis. This study compares EDA in response to acute stress in the laboratory between…

  13. Mechanical stress-controlled tunable active frequency-selective surface

    Science.gov (United States)

    Huang, Bo-Cin; Hong, Jian-Wei; Lo, Cheng-Yao

    2017-01-01

    This study proposes a tunable active frequency-selective surface (AFSS) realized by mechanically expanding or contracting a split-ring resonator (SRR) array. The proposed AFSS transfers mechanical stress from its elastic substrate to the top of the SRR, thereby achieving electromagnetic (EM) modulation without the need for an additional external power supply, meeting the requirements for the target application: the invisibility cloak. The operating mechanism of the proposed AFSS differs from those of other AFSSs, supporting modulations in arbitrary frequencies in the target range. The proposed stress-controlled or strain-induced EM modulation proves the existence of an identical and linear relationship between the strain gradient and the frequency shift, implying its suitability for other EM modulation ranges and applications.

  14. Progranulin causes adipose insulin resistance via increased autophagy resulting from activated oxidative stress and endoplasmic reticulum stress.

    Science.gov (United States)

    Guo, Qinyue; Xu, Lin; Li, Huixia; Sun, Hongzhi; Liu, Jiali; Wu, Shufang; Zhou, Bo

    2017-01-31

    Progranulin (PGRN) has recently emerged as an important regulator for insulin resistance. However, the direct effect of progranulin in adipose insulin resistance associated with the autophagy mechanism is not fully understood. In the present study, progranulin was administered to 3T3-L1 adipocytes and C57BL/6 J mice with/without specific inhibitors of oxidative stress and endoplasmic reticulum stress, and metabolic parameters, oxidative stress, endoplasmic reticulum stress and autophagy markers were assessed. Progranulin treatment increased iNOS expression, NO synthesis and ROS generation, and elevated protein expressions of CHOP, GRP78 and the phosphorylation of PERK, and caused a significant increase in Atg7 and LC3-II protein expression and a decreased p62 expression, and decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and glucose uptake, demonstrating that progranulin activated oxidative stress and ER stress, elevated autophagy and induced insulin insensitivity in adipocytes and adipose tissue of mice. Interestingly, inhibition of iNOS and ER stress both reversed progranulin-induced stress response and increased autophagy, protecting against insulin resistance in adipocytes. Furthermore, the administration of the ER stress inhibitor 4-phenyl butyric acid reversed the negative effect of progranulin in vivo. Our findings showed the clinical potential of the novel adipokine progranulin in the regulation of insulin resistance, suggesting that progranulin might mediate adipose insulin resistance, at least in part, by inducing autophagy via activated oxidative stress and ER stress.

  15. Lifetime physical activity and female stress urinary incontinence.

    Science.gov (United States)

    Nygaard, Ingrid E; Shaw, Janet M; Bardsley, Tyler; Egger, Marlene J

    2015-07-01

    We sought to estimate whether moderate/severe stress urinary incontinence (SUI) in middle-aged women is associated with overall lifetime physical activity (including leisure, household, outdoor, and occupational), as well as lifetime leisure (recreational), lifetime strenuous, and strenuous activity during the teen years. Recruitment for this case-control study was conducted in primary-care-level family medicine and gynecology clinics. A total of 1538 enrolled women ages 39-65 years underwent a Pelvic Organ Prolapse Quantification examination to assess vaginal support. Based on Incontinence Severity Index scores, cases had moderate/severe and controls had no/mild SUI. We excluded 349 with vaginal descent at/below the hymen (pelvic organ prolapse), 194 who did not return questionnaires, and 110 with insufficient activity data for analysis. In all, 213 cases were frequency matched 1:1 by age group to controls. Physical activity was measured using the Lifetime Physical Activity Questionnaire, in which women recall activity from menarche to present. We created separate multivariable logistic regression models for activity measures. SUI odds increased slightly with overall lifetime activity (odds ratio [OR], 1.20 per 70 additional metabolic equivalent of task-h/wk; 95% confidence interval [CI], 1.02-1.41), and were not associated with lifetime strenuous activity (OR, 1.11; 95% CI, 0.99-1.25). In quintile analysis of lifetime leisure activity, which demonstrated a nonlinear pattern, all quintiles incurred about half the odds of SUI compared to reference (second quintile; P = .009). Greater strenuous activity in teen years modestly increased SUI odds (OR, 1.37 per 7 additional h/wk; 95% CI, 1.09-1.71); OR, 1.75; 95% CI, 1.15-2.66 in sensitivity analysis adjusting for measurement error. The predicted probability of SUI rose linearly in women exceeding 7.5 hours of strenuous activity/wk during teen years. Teen strenuous activity had a similar effect on SUI odds when

  16. Vegetation stress and summer fire activity in Portugal

    Science.gov (United States)

    Carlos, DaCamara; Sílvia, Nunes

    2013-04-01

    Fire activity in Mediterranean Europe is closely related to the climatological background where the occurrence of rainy and mild winters, followed by warm and dry summers, may induce high levels of vegetation stress over the different regions making them prone to the occurrence of fire events. The aim of the present study is to investigate whether years of very high or very low levels of fire activity over forests in Portugal are linked to contrasting vegetation cycles associated to high and low degrees of vegetation stress during the summer season. The present study relies on time series of yearly amounts of burned areas provided by Instituto de Conservação da Natureza e das Florestas (ICNF), the national authority for forests as well as on monthly values of NDVI and of brightness temperature as obtained from the Mediterranean Extended Daily One Km AVHRR Data Set (MEDOKADS) product provided by the Free University of Berlin. Both datasets cover the 16-year period from 1990 to 2005. The area of forest is first identified by means of a k-means cluster analysis that is performed on climatological yearly means of NDVI and brightness temperature. Monthly means of NDVI and of brightness temperature are then evaluated over the area of forest and composites are made for severe and mild years of fire activity defined as those with yearly burned areas respectively above the third quartile and below the first quartile. The composite of severe years presents a brightness temperature cycle with values above average during spring and summer together with values of NDVI below average during summer, the behavior of both parameters providing an indication of vegetation stress. In contrast, the composite of mild years of fire activity presents an NDVI cycle with values well below average during spring, an indication of lack of biomass, and a brightness temperature cycle with values below average during spring and summer, an indication that vegetation is not under stress. Results

  17. Sympathetic nerve activity and whole body heat stress in humans

    OpenAIRE

    Low, David A.; Keller, David M.; Wingo, Jonathan E.; Brothers, R. Matthew; Crandall, Craig G.

    2011-01-01

    We and others have shown that moderate passive whole body heating (i.e., increased internal temperature ∼0.7°C) increases muscle (MSNA) and skin sympathetic nerve activity (SSNA). It is unknown, however, if MSNA and/or SSNA continue to increase with more severe passive whole body heating or whether these responses plateau following moderate heating. The aim of this investigation was to test the hypothesis that MSNA and SSNA continue to increase from a moderate to a more severe heat stress. Th...

  18. Low vigorous physical activity is associated with increased adrenocortical reactivity to psychosocial stress in students with high stress perceptions.

    Science.gov (United States)

    Gerber, Markus; Ludyga, Sebastian; Mücke, Manuel; Colledge, Flora; Brand, Serge; Pühse, Uwe

    2017-06-01

    The pathways by which physical activity impacts on participants' health are still not fully understood. The purpose of the present study was to go beyond existing research by combining methods from survey-based and experimental stress research, and by examining whether the potential of vigorous physical activity (VPA) to attenuate physiological and psychological stress responses is moderated by participants' subjective stress perception. The sample consisted of 42 undergraduate students (M=21.2±2.2 years, 52% women). Participants self-reported their stress and wore an accelerometer device for seven consecutive days. To examine differences in the adrenocortical, autonomic and psychological stress reactivity, salivary free cortisol, heart rate, state anxiety, mood and calmness were assessed prior to, during and after the Trier Social Stress Test (TSST). The cut-offs of the American College of Sports Medicine (ACSM) were used to distinguish between students below/above current VPA recommendations. High levels of perceived stress combined with VPA levels below the ACSM's standards (students with high stress/low VPA experienced less favourable affect throughout the entire testing session (pstress-protective potential among undergraduate students with high stress levels. Our findings highlight that promoting VPA in young adults seems to be a promising strategy to increase physiological and psychological stress resilience. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Physical activity, heart rate variability-based stress and recovery, and subjective stress during a 9-month study period.

    Science.gov (United States)

    Föhr, T; Tolvanen, A; Myllymäki, T; Järvelä-Reijonen, E; Peuhkuri, K; Rantala, S; Kolehmainen, M; Korpela, R; Lappalainen, R; Ermes, M; Puttonen, S; Rusko, H; Kujala, U M

    2017-06-01

    The aim of this study was to investigate the association between physical activity (PA) and objective heart rate variability (HRV)-based stress and recovery with subjective stress in a longitudinal setting. Working-age participants (n = 221; 185 women, 36 men) were overweight (body mass index, 25.3-40.1 kg/m 2 ) and psychologically distressed (≥3/12 points on the General Health Questionnaire). Objective stress and recovery were based on HRV recordings over 1-3 work days. Subjective stress was assessed with the Perceived Stress Scale and PA level with a questionnaire. Data were collected at three time points: baseline, 10 weeks post intervention, and at the 36-week follow-up. We adopted a latent growth model to investigate the initial level and change in PA, objective stress and recovery, and subjective stress at the three measurement time points. The results showed that initial levels of PA (P stress (P = 0.001) and recovery (P stress. The results persisted after adjustment for intervention group. The present results suggest that high PA and objectively assessed low stress and good recovery have positive effects on changes in subjective stress in the long-term. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Assessment of brain activities during an emotional stress state using fMRI

    International Nuclear Information System (INIS)

    Hayashi, Takuto; Mizuno-Matsumoto, Yuko; Kawasaki, Aika; Kato, Makoto; Murata, Tsutomu

    2011-01-01

    We investigated cerebrum activation using functional magnetic resonance imaging during a mental stress state. Thirty-four healthy adults participated. Before the experiment, we assessed their stress states using the Stress Self-rating Scale and divided the participants into Stress and Non-stress groups. The experiment consisted of 6 trials. Each trial consisted of a 20-s block of emotional audio-visual stimuli (4-s stimulation x 5 slides) and a fixation point. These processes were performed 3 times continuously (Relaxed, Pleasant, Unpleasant stimuli) in a random order. These results showed that the Non-stress group indicated activation of the amygdala and hippocampus in the Pleasant and Unpleasant stimuli while the Stress group indicated activation of the hippocampus in Pleasant stimuli, and the amygdala and hippocampus in Unpleasant stimuli. These findings suggested that the mental stress state engages the reduction of emotional processing. Also, the responsiveness of the memory system remained during and after the emotional stress state. (author)

  1. Post-traumatic stress disorder, physical activity, and eating behaviors.

    Science.gov (United States)

    Hall, Katherine S; Hoerster, Katherine D; Yancy, William S

    2015-01-01

    Post-traumatic stress disorder (PTSD), a prevalent and costly psychiatric disorder, is associated with high rates of obesity and cardiometabolic diseases. Many studies have examined PTSD and risky behaviors (e.g., smoking, alcohol/substance abuse); far fewer have examined the relationship between PTSD and health-promoting behaviors. Physical activity and eating behaviors are 2 lifestyle factors that impact cardiometabolic risk and long-term health. This comprehensive review of the literature (1980-2014) examined studies that reported physical activity and eating behaviors in adults with PTSD or PTSD symptoms. A systematic search of electronic databases identified 15 articles on PTSD-physical activity and 10 articles on PTSD-eating behaviors in adults. These studies suggest that there may be a negative association among PTSD, physical activity, and eating behaviors. Preliminary evidence from 3 pilot intervention studies suggests that changes in physical activity or diet may have beneficial effects on PTSD symptoms. There was considerable heterogeneity in the study designs and sample populations, and many of the studies had methodological and reporting limitations. More evidence in representative samples, using multivariable analytical techniques, is needed to identify a definitive relationship between PTSD and these health behaviors. Intervention studies for PTSD that examine secondary effects on physical activity/eating behaviors, as well as interventions to change physical activity/eating behaviors that examine change in PTSD, are also of interest. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Decreased Prolidase Activity in Patients with Posttraumatic Stress Disorder.

    Science.gov (United States)

    Demir, Süleyman; Bulut, Mahmut; Atli, Abdullah; Kaplan, İbrahim; Kaya, Mehmet Cemal; Bez, Yasin; Özdemir, Pınar Güzel; Sır, Aytekin

    2016-07-01

    Many neurochemical systems have been implicated in the development of Posttraumatic Stress Disorder (PTSD). The prolidase enzyme is a cytosolic exopeptidase that detaches proline or hydroxyproline from the carboxyl terminal position of dipeptides. Prolidase has important biological effects, and to date, its role in the etiology of PTSD has not been studied. In the present study, we aimed to evaluate prolidase activity in patients with PTSD. The study group consisted of patients who were diagnosed with PTSD after the earthquake that occurred in the province of Van in Turkey in 2011 (n=25); the first control group consisted of patients who experienced the earthquake but did not show PTSD symptoms (n=26) and the second control group consisted of patients who have never been exposed to a traumatic event (n=25). Prolidase activities in the patients and the control groups were determined by the ELISA method using commercial kits. Prolidase activity in the patient group was significantly lower when compared to the control groups. Prolidase activity was also significantly lower in the traumatized healthy subjects compared to the other healthy group (pactivity may have neuroprotective effects in patients with PTSD.

  3. Lower electrodermal activity to acute stress in caregivers of people with autism spectrum disorder: an adaptive habituation to stress.

    Science.gov (United States)

    Ruiz-Robledillo, Nicolás; Moya-Albiol, Luis

    2015-02-01

    Caring for a relative with autism spectrum disorder (ASD) entails being under chronic stress that could alter body homeostasis. Electrodermal activity (EDA) is an index of the sympathetic activity of the autonomic nervous system related to emotionality and homeostasis. This study compares EDA in response to acute stress in the laboratory between parents of people with (n = 30) and without (n = 34) ASD (caregivers and non-caregivers, respectively). Caregivers showed lower EDA in response to acute stress than non-caregivers. They also presented higher trait anxiety, anger, depression, and somatic symptoms than non-caregivers. Higher EDA was related to a worse mood and more severe somatic symptoms only in caregivers. These results could reflect an adaptive habituation to stress and establish that high EDA in response to acute stress depends on caregivers' health.

  4. Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis

    Directory of Open Access Journals (Sweden)

    Duraisamy Kempuraj

    2017-12-01

    Full Text Available Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases

  5. Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis.

    Science.gov (United States)

    Kempuraj, Duraisamy; Selvakumar, Govindhasamy P; Thangavel, Ramasamy; Ahmed, Mohammad E; Zaheer, Smita; Raikwar, Sudhanshu P; Iyer, Shankar S; Bhagavan, Sachin M; Beladakere-Ramaswamy, Swathi; Zaheer, Asgar

    2017-01-01

    Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This

  6. Improving Health by Reducing Stress: An Experiential Activity

    Science.gov (United States)

    Largo-Wight, Erin; Moore, Michele J.; Barr, Elissa M.

    2011-01-01

    Stress is a leading health issue among college students. Managing stress involves enhancing resources necessary to cope with life's demands. Relaxation techniques are especially critical coping strategies when stress is chronic and coping resources are overused and fatigued. Methods: This article describes a research-based relaxation technique…

  7. Stress relaxation and estimation of activation volume in a ...

    Indian Academy of Sciences (India)

    Abstract. The stress relaxation of ferroelectric/piezoelectric material was studied using compression testing. The deformation was produced by the switching of ferroelectric domains. The internal stresses were estimated by decremental stress relaxation during unloading. The results were interpreted in terms of reversible and ...

  8. Mitochondrial Oxidative Stress Corrupts Coronary Collateral Growth by Activating Adenosine Monophosphate Activated Kinase-α Signaling

    Science.gov (United States)

    Pung, Yuh Fen; Sam, Wai Johnn; Stevanov, Kelly; Enrick, Molly; Chen, Chwen-Lih; Kolz, Christopher; Thakker, Prashanth; Hardwick, James P.; Chen, Yeong-Renn; Dyck, Jason R.B.; Yin, Liya; Chilian, William M.

    2015-01-01

    Objective Our goal was to determine the mechanism by which mitochondrial oxidative stress impairs collateral growth in the heart. Approach and Results Rats were treated with rotenone (mitochondrial complex I inhibitor that increases reactive oxygen species production) or sham-treated with vehicle and subjected to repetitive ischemia protocol for 10 days to induce coronary collateral growth. In control rats, repetitive ischemia increased flow to the collateral-dependent zone; however, rotenone treatment prevented this increase suggesting that mitochondrial oxidative stress compromises coronary collateral growth. In addition, rotenone also attenuated mitochondrial complex I activity and led to excessive mitochondrial aggregation. To further understand the mechanistic pathway(s) involved, human coronary artery endothelial cells were treated with 50 ng/ mL vascular endothelial growth factor, 1 µmol/L rotenone, and rotenone/vascular endothelial growth factor for 48 hours. Vascular endothelial growth factor induced robust tube formation; however, rotenone completely inhibited this effect (Pmediated by the activation of AMPK-α. Conversely, expression of a constitutively active AMPK-α blocked tube formation. Conclusions We conclude that activation of AMPK-α during mitochondrial oxidative stress inhibits mammalian target of rapamycin signaling, which impairs phenotypic switching necessary for the growth of blood vessels. PMID:23788766

  9. Oxidative stress inhibition and oxidant activity by fibrous clays.

    Science.gov (United States)

    Cervini-Silva, Javiera; Nieto-Camacho, Antonio; Gómez-Vidales, Virginia

    2015-09-01

    Fibrous clays (sepiolite, palygorskite) are produced at 1.2m tonnes per year and have a wide range of industrial applications needing to replace long-fibre length asbestos. However, information on the beneficial effects of fibrous clays on health remains scarce. This paper reports on the effect of sepiolite (Vallecas, Spain) and palygorskite (Torrejón El Rubio, Spain) on cell damage via oxidative stress (determined as the progress of lipid peroxidation, LP). The extent of LP was assessed using the Thiobarbituric Acid Reactive Substances assay. The oxidant activity by fibrous clays was quantified using Electron-Paramagnetic Resonance. Sepiolite and palygorskite inhibited LP, whereby corresponding IC50 values were 6557±1024 and 4250±289μgmL(-1). As evidenced by dose-response experiments LP inhibition by palygorskite was surface-controlled. Fibrous clay surfaces did not stabilize HO species, except for suspensions containing 5000μgmL(-1). A strong oxidant (or weak anti-oxidant) activity favours the inhibition of LP by fibrous clays. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Lead stress effects on physiobiochemical activities of higher plants.

    Science.gov (United States)

    Sengar, Rakesh Singh; Gautam, Madhu; Sengar, Rajesh Singh; Garg, Sanjay Kumar; Sengar, Kalpana; Chaudhary, Reshu

    2008-01-01

    Lead is a metallic pollutant emanating from various environmental sources including industrial wastes, combustion of fossil fuels, and use of agrochemicals. Lead may exist in the atmosphere as dusts, fumes, mists, and vapors, and in soil as a mineral. Soils along roadsides are rich in lead because vehicles burn leaded gasoline, which contributes to environmental lead pollution. Other important sources of lead pollution are geological weathering, industrial processing of ores and minerals, leaching of lead from solid wastes, and animal and human excreta. Lead is nondegradable, readily enters the food chain, and can subsequently endanger human and animal health. Lead is one of the most important environment pollutants and deserves the increasing attention it has received in recent decades. The present effort was undertaken to review lead stress effects on the physiobiochemical activity of higher plants. Lead has gained considerable attention as a potent heavy metal pollutant because of growing anthropogenic pressure on the environment. Lead-contaminated soils show a sharp decline in crop productivity. Lead is absorbed by plants mainly through the root system and in minor amounts through the leaves. Within the plants, lead accumulates primarily in roots, but some is translocated to aerial plant parts. Soil pH, soil particle size, cation-exchange capacity, as well as root surface area, root exudation, and mycorrhizal transpiration rate affect the availability and uptake of lead by plants. Only a limited amount of lead is translocated from roots to other organs because there are natural plant barriers in the root endodermis. At lethal concentrations, this barrier is broken and lead may enter vascular tissues. Lead in plants may form deposits of various sizes, present mainly in intercellular spaces, cell walls, and vacuoles. Small deposits of this metal are also seen in the endoplasmic reticulum, dictyosome, and dictyosome-derived vesicles. After entering the cells, lead

  11. Monitoring eruption activity using temporal stress changes at Mount Ontake volcano.

    Science.gov (United States)

    Terakawa, Toshiko; Kato, Aitaro; Yamanaka, Yoshiko; Maeda, Yuta; Horikawa, Shinichiro; Matsuhiro, Kenjiro; Okuda, Takashi

    2016-02-19

    Volcanic activity is often accompanied by many small earthquakes. Earthquake focal mechanisms represent the fault orientation and slip direction, which are influenced by the stress field. Focal mechanisms of volcano-tectonic earthquakes provide information on the state of volcanoes via stresses. Here we demonstrate that quantitative evaluation of temporal stress changes beneath Mt. Ontake, Japan, using the misfit angles of focal mechanism solutions to the regional stress field, is effective for eruption monitoring. The moving average of misfit angles indicates that during the precursory period the local stress field beneath Mt. Ontake was deviated from the regional stress field, presumably by stress perturbations caused by the inflation of magmatic/hydrothermal fluids, which was removed immediately after the expulsion of volcanic ejecta. The deviation of the local stress field can be an indicator of increases in volcanic activity. The proposed method may contribute to the mitigation of volcanic hazards.

  12. Determining stress management activities for various Myers-Briggs personality types.

    Directory of Open Access Journals (Sweden)

    Ghidella, J.

    2017-07-01

    Full Text Available Stress, a component of everyday life, can be detrimental to health. Previous research has shown an increase in studies on stress in recent years, but little on linking stress and personality type. Because of this, new and innovative research in stress management is of utmost importance. This study combined the personality type theory of Myers-Briggs with de-stressing activities to determine which personality types found which de-stressing activities the most effective. The study focused on teenagers to bring more light to their stress management. There were different correlations, but they were insignificant. A conclusive statement cannot be made about the original research question, but a plethora of useful information was still discovered. While the results were varied, the conclusion of this study was that it was possible to determine which activities would most benefit people with certain personality types.

  13. Pituitary adenylate cyclase activating polypeptide (PACAP), stress, and sex hormones.

    Science.gov (United States)

    King, S Bradley; Toufexis, Donna J; Hammack, Sayamwong E

    2017-09-01

    Stressor exposure is associated with the onset and severity of many psychopathologies that are more common in women than men. Moreover, the maladaptive expression and function of stress-related hormones have been implicated in these disorders. Evidence suggests that PACAP has a critical role in the stress circuits mediating stress-responding, and PACAP may interact with sex hormones to contribute to sex differences in stress-related disease. In this review, we describe the role of the PACAP/PAC1 system in stress biology, focusing on the role of stress-induced alterations in PACAP expression and signaling in the development of stress-induced behavioral change. Additionally, we present more recent data suggesting potential interactions between stress, PACAP, and circulating estradiol in pathological states, including PTSD. These studies suggest that the level of stress and circulating gonadal hormones may differentially regulate the PACAPergic system in males and females to influence anxiety-like behavior and may be one mechanism underlying the discrepancies in human psychiatric disorders.

  14. Perceived Stress Predicts Lower Physical Activity in African-American Boys, but not Girls.

    Science.gov (United States)

    McGlumphy, Kellye C; Shaver, Erika R; Ajibewa, Tiwaloluwa A; Hasson, Rebecca E

    2018-03-01

    The purpose of this study was to examine cross-sectional relationships of psychological stress, stress coping, and minutes of moderate-to-vigorous physical activity (MVPA) in Amer- ican-American (AA) boys and girls. A community-based sample of 139 AA adolescents (mean age 14.7 years; SD = 1.8 years; 64.7% girls; 30% obese) from Washtenaw County, Michigan was included in this analysis. Psychological stress was assessed using the Daily Stress Inventory and the Perceived Stress Scale. Coping strategies were evaluated using the Schoolager's Coping Strategies questionnaire. Physical activity was measured objectively via accelerometry. Compared to boys, girls participated in approximately 13 fewer minutes of MVPA (p < .001) per day and reported significantly higher levels of daily stress (p = .03) and perceived stress (p < .001). In addition, girls reported using a greater number of coping strategies (p = .01) at a greater frequency (p = .04) compared to boys. However, perceived stress significantly predicted lower levels of MVPA (p = .03) in boys only. There are important gender differences in how AA girls perceive, experience, and cope with stress compared to AA boys. Although AA girls reported higher levels of stress and employed more coping strategies, perceived stress was associated with physical inactivity in AA boys, but not girls. Additional research is warranted to better understand the influence of stress on the choice to be physically active in AA youth.

  15. The importance of physical activity and sleep for affect on stressful days: Two intensive longitudinal studies.

    Science.gov (United States)

    Flueckiger, Lavinia; Lieb, Roselind; Meyer, Andrea H; Witthauer, Cornelia; Mata, Jutta

    2016-06-01

    We investigated the potential stress-buffering effect of 3 health behaviors-physical activity, sleep quality, and snacking-on affect in the context of everyday life in young adults. In 2 intensive longitudinal studies with up to 65 assessment days over an entire academic year, students (Study 1, N = 292; Study 2, N = 304) reported stress intensity, sleep quality, physical activity, snacking, and positive and negative affect. Data were analyzed using multilevel regression analyses. Stress and positive affect were negatively associated; stress and negative affect were positively associated. The more physically active than usual a person was on a given day, the weaker the association between stress and positive affect (Study 1) and negative affect (Studies 1 and 2). The better than usual a person's sleep quality had been during the previous night, the weaker the association between stress and positive affect (Studies 1 and 2) and negative affect (Study 2). The association between daily stress and positive or negative affect did not differ as a function of daily snacking (Studies 1 and 2). On stressful days, increasing physical activity or ensuring high sleep quality may buffer adverse effects of stress on affect in young adults. These findings suggest potential targets for health-promotion and stress-prevention programs, which could help reduce the negative impact of stress in young adults. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  16. Stress.

    Science.gov (United States)

    Chambers, David W

    2008-01-01

    We all experience stress as a regular, and sometimes damaging and sometimes useful, part of our daily lives. In our normal ups and downs, we have our share of exhaustion, despondency, and outrage--matched with their corresponding positive moods. But burnout and workaholism are different. They are chronic, dysfunctional, self-reinforcing, life-shortening habits. Dentists, nurses, teachers, ministers, social workers, and entertainers are especially susceptible to burnout; not because they are hard-working professionals (they tend to be), but because they are caring perfectionists who share control for the success of what they do with others and perform under the scrutiny of their colleagues (they tend to). Workaholics are also trapped in self-sealing cycles, but the elements are ever-receding visions of control and using constant activity as a barrier against facing reality. This essay explores the symptoms, mechanisms, causes, and successful coping strategies for burnout and workaholism. It also takes a look at the general stress response on the physiological level and at some of the damage American society inflicts on itself.

  17. Social stress, obesity, and depression among women: clarifying the role of physical activity.

    Science.gov (United States)

    Lincoln, Karen D

    2017-07-01

    This study examined the role of stress in the association among physical activity, obesity, and depression among women. The extent to which physical activity moderated these relationships was also examined. Data from the National Survey of American Life (N = 3235) and multivariable regression analyses were used to examine the effects of chronic stress, material hardship, racial discrimination, and physical activity on obesity and depression among African American, Caribbean Black and White women. Stress was not related to body mass index (BMI) for African American or White women, but chronic stress was associated with higher BMI for Caribbean Black women. Stress was associated with depressive symptoms, but there was variation by the type of stressor under consideration. Physical activity was associated with fewer depressive symptoms and lower BMI, but the relationships varied by type of stressor and race/ethnicity. Physical activity moderated the effect of chronic stress on depressive symptoms and BMI, but only for African American women who reported high levels of chronic stress. Among White women, physical activity moderated the effect of racial discrimination on BMI for those who reported experiencing both high and low levels of discrimination. This study was the first to document physical activity as a moderator in the relationship among stress, depression, and obesity using a nationally representative sample of racially/ethnically diverse women. Findings provide insight into the role of stress in relation to depression and obesity while highlighting heterogeneity among Black Americans.

  18. Restraint stress increases hemichannel activity in hippocampal glial cells and neurons.

    Science.gov (United States)

    Orellana, Juan A; Moraga-Amaro, Rodrigo; Díaz-Galarce, Raúl; Rojas, Sebastián; Maturana, Carola J; Stehberg, Jimmy; Sáez, Juan C

    2015-01-01

    Stress affects brain areas involved in learning and emotional responses, which may contribute in the development of cognitive deficits associated with major depression. These effects have been linked to glial cell activation, glutamate release and changes in neuronal plasticity and survival including atrophy of hippocampal apical dendrites, loss of synapses and neuronal death. Under neuro-inflammatory conditions, we recently unveiled a sequential activation of glial cells that release ATP and glutamate via hemichannels inducing neuronal death due to activation of neuronal NMDA/P2X7 receptors and pannexin1 hemichannels. In the present work, we studied if stress-induced glia activation is associated to changes in hemichannel activity. To this end, we compared hemichannel activity of brain cells after acute or chronic restraint stress in mice. Dye uptake experiments in hippocampal slices revealed that acute stress induces opening of both Cx43 and Panx1 hemichannels in astrocytes, which were further increased by chronic stress; whereas enhanced Panx1 hemichannel activity was detected in microglia and neurons after acute/chronic and chronic stress, respectively. Moreover, inhibition of NMDA/P2X7 receptors reduced the chronic stress-induced hemichannel opening, whereas blockade of Cx43 and Panx1 hemichannels fully reduced ATP and glutamate release in hippocampal slices from stressed mice. Thus, we propose that gliotransmitter release through hemichannels may participate in the pathogenesis of stress-associated psychiatric disorders and possibly depression.

  19. Relationships among self-esteem, stress, and physical activity in college students.

    Science.gov (United States)

    Hubbs, Allison; Doyle, Eva I; Bowden, Rodney G; Doyle, Robert D

    2012-04-01

    The purpose of this study was to identify population and sex-specific relationships between perceived stress, self-esteem, and physical activity in college students. 90 students, ages 18 and older and enrolled in five sections of a health and human behavior class during the spring 2010 semester, were contacted for this study with 74 consenting to serve as study participants. Each participant completed three surveys: the Rosenberg Self-Esteem Scale, the Perceived Stress Scale, and the International Physical Activity Questionnaire. Significant correlations were observed between perceived stress and self-esteem in men, and in women. Physical activity was not significantly correlated with perceived stress or self-esteem.

  20. The contribution of activated processes to Q. [stress corrosion cracking in seismic wave attenuation

    Science.gov (United States)

    Spetzler, H. A.; Getting, I. C.; Swanson, P. L.

    1980-01-01

    The possible role of activated processes in seismic attenuation is investigated. In this study, a solid is modeled by a parallel and series configuration of dashpots and springs. The contribution of stress and temperature activated processes to the long term dissipative behavior of this system is analyzed. Data from brittle rock deformation experiments suggest that one such process, stress corrosion cracking, may make a significant contribution to the attenuation factor, Q, especially for long period oscillations under significant tectonic stress.

  1. Stress determination in active thrust belts: An alternative leak-off pressure interpretation

    Science.gov (United States)

    Couzens-Schultz, Brent A.; Chan, Alvin W.

    2010-08-01

    In thrust belts, fluid flow through critically stressed fractures will occur at pressures less than the overburden stress, which is the minimum stress. We propose that low leak-off pressures obtained in active thrust belts may result from this mechanism, leading workers to infer that apparent minimum stresses are 30-60% less than the overburden stress in some compressional settings. Traditionally, leak-off pressure data have been used to constrain the magnitude of minimum stress, assuming that the rock is dilating against the minimum stress during a leak-off test. In our new interpretation, we constrain the stress state by assuming that the leak-off test causes shear failure along pre-existing weaknesses rather than tensile opening. While this mechanism has been discussed in a small number of borehole stability and hydraulic fracture papers, it has not been directly applied to leak-off tests. We considered this interpretation because we observed that some leak-off tests imply an apparent contradiction between the stress states from the standard interpretation of leak-off tests versus the stress state inferred from geologic and geophysical evidence in tectonically active thrust belts. We present two examples with one in an onshore fold-thrust belt and one in a deepwater fold-thrust belt. Our new interpretation of stresses based on shear failure resolves the contradiction and also provides a constraint on the maximum horizontal stress in the fold-thrust belts.

  2. The Effect of Psychological Stress on Mucosal IL-6 and Helicobacter pylori Activity in Functional Dyspepsia.

    Science.gov (United States)

    Darwin, Eryati; Murni, Arina Widya; Nurdin, Adnil E

    2017-04-01

    pathophysiology of functional dyspepsia remains poorly understood. Many factors such as gastric motility disorder, visceral hypersensitivity, Helicobacter pylori (Hp) infection, psychological stress and excessive gastric acid secretion play roles in this symptom. Psychological stress may promote peptic ulcer and has an effect on ulcers-associated Hp. This study aimed to determine Helicobacter pylori activity and expression of mucosal IL-6 and their association with psychological stress. a cross-sectional study was done among 40 outpatients with dyspeptic syndromes in M. Djamil General Hospital and two-community health centers in Padang. The subjects were divided into two groups, with and without psychological stress, which were identified using DASS 42. Gastric biopsy specimens and peripheral blood samples were taken while performing esophagogastroduodenoscopy. Immunohistochemistry methods was used to determine the expression of IL-6 and Hp in gastric mucosa. The correlation of each variable in the group experiencing psychological stress and non-stress was analyzed using Chi-square test. there were 40 patients with functional dyspepsia with average age of 37.58(SD 11.82) years old. The cortisol levels were significantly different between both groups (non-stress vs. stress groups); moreover, morning cortisol level in psychological stress group was higher beyond normal limit. Inter-Leukin-6 expression, as the evidence of inflammatory activity, seemed higher in non-stress group than the group with psychological stress (8.25% vs. 7.25%). Helicobacter pylori activity was seemed to be increased in the stress group as characterized by higher numbers of invasion to the sub mucosa epithelium compared to the non-stress group (11 vs. 7 subjects). psychological stress seems to have no correlation with IL-6 in gastric mucous of patients with functional dyspepsia; however, there is an evidence of increasing activity of Helicobacter pylori.

  3. Association between Physical Activity and Perceived Psychological Stress in Adults in Bucaramanga

    Directory of Open Access Journals (Sweden)

    Paula Camila Ramírez Muñoz

    2016-01-01

    Full Text Available Introduction: Increased stress levels became a problem for the general population’s health. Research studies show that individuals engaging regular physical activity have a decreased percep­tion of psychological stress. The relationship between physical activity and perceived psychological stress has been suggested to vary across domains of physical activity and across population groups. Objective: To establish the association between physical activity and perceived psychological stress in adults living in neighborhoods of the 2nd and 3rd socio-economic strata of Bucaramanga. Materials and methods: This observational analytical cross-sectional study was conducted in a population of 502 adult residents in the city of Bucaramanga. Individuals were interviewed to obtain information about physical activity and their level of perceived psychological stress. Data analysis will account for socio-demographic and behavior patterns using linear regression models, and it was performed in stata® 11.0. Results: Meeting the physical activity recommendations was associated with a decrease in psychological stress levels in study participants (β = -1,90 IC 95 % -3,73 a -0,06; P = 0,043. Conclusions: Complying with the recommendations of physical activity was associated with a decrease in the psychological stress level in the participants, who had an average -1.9 points lower PSS score than those who do not comply.

  4. Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli.

    Science.gov (United States)

    Oei, Nicole Y L; Both, Stephanie; van Heemst, Diana; van der Grond, Jeroen

    2014-01-01

    Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain's "reward system", and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PET studies indicate that the stress hormone cortisol may be crucial in the interaction between stress and dopaminergic actions. In the present study we therefore investigated whether cortisol mediated the effect of stress on DA-related responses to -subliminal-presentation of reward cues using the Trier Social Stress Test (TSST), which is known to reliably enhance cortisol levels. Young healthy males (n = 37) were randomly assigned to the TSST or control condition. After stress induction, brain activation was assessed using fMRI during a backward-masking paradigm in which potentially rewarding (sexual), emotionally negative and neutral stimuli were presented subliminally, masked by pictures of inanimate objects. A region of interest analysis showed that stress decreased activation in the NAcc in response to masked sexual cues (voxel-corrected, pcortisol levels were related to stronger NAcc activation, showing that cortisol acted as a suppressor variable in the negative relation between stress and NAcc activation. The present findings indicate that cortisol is crucially involved in the relation between stress and the responsiveness of the reward system. Although generally stress decreases activation in the NAcc in response to rewarding stimuli, high stress-induced cortisol levels suppress this relation, and are associated with stronger NAcc activation. Individuals with a high cortisol response to stress might on one hand be protected against reductions in reward sensitivity, which has been linked to anhedonia and depression, but they may ultimately be more vulnerable to increased reward

  5. Physical Activity, Mindfulness Meditation, or Heart Rate Variability Biofeedback for Stress Reduction: A Randomized Controlled Trial

    OpenAIRE

    van der Zwan, Judith Esi; de Vente, Wieke; Huizink, Anja C.; B?gels, Susan M.; de Bruin, Esther I.

    2015-01-01

    In contemporary western societies stress is highly prevalent, therefore the need for stress-reducing methods is great. This randomized controlled trial compared the efficacy of self-help physical activity (PA), mindfulness meditation (MM), and heart rate variability biofeedback (HRV-BF) in reducing stress and its related symptoms. We randomly allocated 126 participants to PA, MM, or HRV-BF upon enrollment, of whom 76 agreed to participate. The interventions consisted of psycho-education and a...

  6. Maternal stress, physical activity, and body mass index during new mothers' first year postpartum.

    Science.gov (United States)

    Vernon, Marlo M; Young-Hyman, Deborah; Looney, Stephen W

    2010-09-01

    We evaluated associations of parenting stress, including depressive symptoms, with 51 first-time mothers' light and moderate physical activity and body mass index during the first year postpartum. The Parenting Stress Index and 24-hour physical activity recalls were completed during the first year postpartum (mean time elapsed since birth: 6 months). Direct relationships between identified variables were tested, and then hierarchical linear regression was used to assess hypothesized relationships among body mass index, physical activity, and parenting stress. Effects of parenting stress on the relationships between postpartum body mass index, light physical activity, and moderate physical activity were evaluated after controlling for factors known to be associated with overweight and low levels of physical activity in women. Mean postpartum body mass index = 27.4 kg/m² ± 7.7, range = 18-50 kg/m². Mean reported hours of light physical activity = 11.2 ± 3.0, and moderate physical activity = 4.5 ± 3.0 per day. Postpartum body mass index was not associated with parenting stress, but was positively related to higher pre-pregnancy body mass index (r = .89, p body mass index (β = .27, p body mass index (β = -.27, p body mass index (R² = .89, p body mass index (β = .99, p stress and depressive symptoms in addition to physical activity are needed to prevent development of overweight in new mothers.

  7. Determining adrenocortical activity as a measure of stress in African ...

    African Journals Online (AJOL)

    Little is known about the levels of stress experienced by African buffalos affected by injury, disease, or socio-ecological and anthropogenic factors. To be able to start filling this gap, we examined the suitability of two 11-oxoaetiocholanolone enzyme-immunoassays (EIAs) detecting 11,17 dioxoandrostanes (11,17-DOA) as ...

  8. Increased oxidative stress in pemphigus vulgaris is related to disease activity and HLA-association.

    Science.gov (United States)

    Shah, Amit Aakash; Dey-Rao, Rama; Seiffert-Sinha, Kristina; Sinha, Animesh A

    2016-06-01

    Pemphigus vulgaris (PV) is a rare blistering skin disorder characterized by the disadhesion of keratinocytes due to autoantibody attack against epidermal targets including desmoglein (Dsg) 3, Dsg 1 and possibly other adhesion and non-adhesion molecules. The mechanisms leading to immune-mediated pathology in PV are multifactorial and not fully understood. Recently, oxidative stress (antioxidant/oxidant disequilibrium) has been proposed as a contributory mechanism of autoimmune skin diseases, including PV. In this study, we directly assessed oxidative stress via measurement of total antioxidant capacity (TAC) using ELISA in 47 PV patients, 25 healthy controls and 18 bullous pemphigoid (BP) patients. We also performed microarray gene expression analysis on a separate set of 21 PV patients and 10 healthy controls to evaluate transcriptional dysregulation in oxidative stress-related pathways. Our data indicate that there is a significant reduction in TAC levels in PV patients compared with healthy controls, as well as BP patients. Furthermore, PV patients with active disease have significantly lower TAC levels than PV patients in remission. We also find that HLA allele status has a significant influence on oxidative stress. These findings are corroborated by microarray analysis showing differentially expressed genes involved in oxidative stress between the aforementioned groups. Collectively, our findings provide support for a role of oxidative stress in PV. Whether increased oxidative stress leads to disease manifestation and/or activity, or if disease activity leads to increased oxidative stress remains unknown. Future longitudinal studies may help to further elucidate the relationship between PV and oxidative stress.

  9. Vigorous physical activity, mental health, perceived stress, and socializing among college students.

    Science.gov (United States)

    Vankim, Nicole A; Nelson, Toben F

    2013-01-01

    To examine cross-sectional associations between vigorous physical activity, mental health, perceived stress, and socializing among 4-year college students. A national cross-sectional sample of 4-year colleges in the United States. Ninety-four 4-year colleges in the United States. A total of 14,804 undergraduate students. Self-report vigorous physical activity, perceived stress (measured using the Cohen Perceived Stress Scale), mental health (measured using the SF-36), and socializing (assessed using self-report number of friends and hours spent socializing). Logistic regression models accounting for clustering within schools were estimated to examine the association between vigorous physical activity, mental health, perceived stress, and socializing. Adjusted models included high school vigorous physical activity and sociodemographic characteristics. Students who met vigorous physical activity recommendations were less likely to report poor mental health (adjusted odds ratio [OR]: .79; 95% confidence interval [CI]: .69, .90) and perceived stress (adjusted OR: .75; 95% CI: .67, .83) than students who did not meet recommendations. In addition, socializing partially mediated the relationship between vigorous physical activity, mental health, and perceived stress; however, race and sex did not moderate the relationship. Interventions aiming to improve mental well-being of college students should also consider promoting physical activity. At least some of the positive benefits of physical activity may arise from social interactions.

  10. A study on level of physical activity, depression, anxiety and stress symptoms among adolescents.

    Science.gov (United States)

    Tajik, Esra; Abd Latiff, Latiffah; Adznam, Siti N; Awang, Hamidin; Yit Siew, Chin; Abu Bakar, Azrin S

    2017-10-01

    Inadequate physical activity has adverse health consequences among adolescents. Mental health problem can be developed by lack of physical activity however it is controversial. The current study aimed to examine the association between level of physical activity with depression, anxiety and stress symptoms among adolescents. A representative sample of 1747 adolescents (13-14 years) was randomly selected from 6 schools in a south part of Malaysia. Respondents were asked to fill consent form, and questionnaires including Depression Anxiety and Stress Scale-21 and Physical Activity Questionnaire for Adolescents. Majority of respondents (71.9%) was Malay and more than half of the adolescents had low physical activity. About 40% had depression symptoms, followed by anxiety symptoms (65.9%) and stress symptoms (38.5%). Level of physical activity was significantly associated with gender, anxiety and stress (P<0.001). There were no associations with race, religion and depression symptom. This study provides some evidence among school-going adolescents related to anxiety and stress symptoms and low physical activities. Further studies are needed to show the protection effects of higher physical activity for depression, anxiety and stress symptoms in adolescents.

  11. Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yao Zhu

    2016-08-01

    Full Text Available Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Salidroside (SAL, one of the main effective constituents of Rhodiola rosea, has been reported to suppress oxidative stress-induced cardiomyocyte injury and necrosis by promoting transcription of nuclear factor E2-related factor 2 (Nrf2-regulated genes such as heme oxygenase-1 (HO-1 and NAD(PH dehydrogenase (quinone1 (NQO1. However, it has not been indicated whether SAL might ameliorate endothelial injury induced by oxidative stress. Here, our study demonstrated that SAL might suppress HUVEC cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. The results of our study indicated that SAL decreased the levels of intercellular reactive oxygen species (ROS and malondialdehyde (MDA, and improved the activities of superoxide dismutase (SOD and catalase (CAT, resulting in protective effects against oxidative stress-induced cell damage in HUVECs. It suppressed oxidative stress damage by inducing Nrf2 nuclear translocation and activating the expression of Nrf2-regulated antioxidant enzyme genes such as HO-1 and NQO1 in HUVECs. Knockdown of Nrf2 with siRNA abolished the cytoprotective effects against oxidative stress, decreased the expression of Nrf2, HO-1, and NQO1, and inhibited the nucleus translocation of Nrf2 in HUVECs. This study is the first to demonstrate that SAL suppresses HUVECs cell injury induced by oxidative stress through activating the Nrf2 signaling pathway.

  12. Stress analysis of the modified Pulsed Neutron Activation system downstream shield support structure

    Energy Technology Data Exchange (ETDEWEB)

    Mosby, W.R.

    1980-05-28

    The modified LOFT Pulsed Neutron Activation (PNA) System downstream shielding support structure was stress analyzed for deadweight and worst-case LOCE loads. No deficiencies were found in the structure. This stress analysis was performed for the PNA Shielding Configuration that has been used on Test L3-2 and that is to be used on Test L3-7.

  13. Physical activity, mindfulness meditation, or heart rate variability biofeedback for stress reduction: a randomized controlled trial

    NARCIS (Netherlands)

    van der Zwan, J.E.; de Vente, W.; Huizink, A.C.; Bögels, S.M.; de Bruin, E.I.

    2015-01-01

    In contemporary western societies stress is highly prevalent, therefore the need for stress-reducing methods is great. This randomized controlled trial compared the efficacy of self-help physical activity (PA), mindfulness meditation (MM), and heart rate variability biofeedback (HRV-BF) in reducing

  14. The nutrient stress-induced small GTPase Rab5 contributes to the activation of vesicle trafficking and vacuolar activity.

    Science.gov (United States)

    Nakatsukasa, Kunio; Kanada, Akira; Matsuzaki, Mariko; Byrne, Stuart D; Okumura, Fumihiko; Kamura, Takumi

    2014-07-25

    Rab family small GTPases regulate membrane trafficking by spatiotemporal recruitment of various effectors. However, it remains largely unclear how the expression and functions of Rab proteins are regulated in response to extracellular or intracellular stimuli. Here we show that Ypt53, one isoform of Rab5 in Saccharomyces cerevisiae, is up-regulated significantly under nutrient stress. Under non-stress conditions, Vps21, a constitutively expressed Rab5 isoform, is crucial to Golgi-vacuole trafficking and to vacuolar hydrolase activity. However, when cells are exposed to nutrient stress for an extended period of time, the up-regulated Ypt53 and the constitutive Vps21 function redundantly to maintain these activities, which, in turn, prevent the accumulation of reactive oxygen species and maintain mitochondrial respiration. Together, our results clarify the relative roles of these constitutive and nutrient stress-inducible Rab5 proteins that ensure adaptable vesicle trafficking and vacuolar hydrolase activity, thereby allowing cells to adapt to environmental changes.

  15. Transient stress control of aeroengine disks based on active thermal management

    International Nuclear Information System (INIS)

    Ding, Shuiting; Wang, Ziyao; Li, Guo; Liu, Chuankai; Yang, Liu

    2016-01-01

    Highlights: • The essence of cooling in turbine system is a process of thermal management. • Active thermal management is proposed to control transient stress of disks. • The correlation between thermal load and transient stress of disks is built. • Stress level can be declined by actively adjusting the thermal load distribution. • Artificial temperature gradient can be used to counteract stress from rotating. - Abstract: The physical essence of cooling in the turbine system is a process of thermal management. In order to overcome the limits of passive thermal management based on thermal protection, the concept of active thermal management based on thermal load redistribution has been proposed. On this basis, this paper focuses on a near real aeroengine disk during a transient process and studies the stress control mechanism of active thermal management in transient conditions by a semi-analytical method. Active thermal management is conducted by imposing extra heating energy on the disk hub, which is represented by the coefficient of extra heat flow η. The results show that the transient stress level can be effectively controlled by actively adjusting the thermal load distribution. The decline ratio of the peak equivalent stress of the disk hub can be 9.0% for active thermal management load condition (η = 0.2) compared with passive condition (η = 0), even at a rotation speed of 10,000 r/min. The reason may be that the temperature distribution of the disk turns into an artificial V-shape because of the extra heating energy on the hub, and the resulting thermal stresses induced by the negative temperature gradients counteract parts of the stress from rotating.

  16. Maternal Type 1 diabetes activates stress response in early placenta.

    Science.gov (United States)

    Gauster, Martin; Majali-Martinez, Alejandro; Maninger, Sabine; Gutschi, Elisabeth; Greimel, Patrick H; Ivanisevic, Marina; Djelmis, Josip; Desoye, Gernot; Hiden, Ursula

    2017-02-01

    Human pregnancy and in particular the first trimester, is a period highly susceptible towards adverse insults such as oxidative stress, which may lead to inadequate embryonic and feto-placental development. Diabetes mellitus is associated with increased oxidative stress caused by hyperglycemia, reactive oxygen species (ROS) production and inflammatory signals. In pregnancy, diabetes elevates the risk for early pregnancy loss, preeclampsia and fetal growth restriction, pathologies that origin from early placental maldevelopment. We hypothesized that maternal Type 1 diabetes mellitus (T1DM) induces oxidative stress in the first trimester human placenta. We quantified stress induced, cytoprotective proteins, i.e. heat shock protein (HSP)70 and heme oxygenase (HO)-1 and determined protein modifications as markers for oxidation and glycation, i.e. levels of 4-hydroxynonenal (HNE) or Nε-(carboxymethyl)lysine (CML) modified proteins. Moreover, we measured expression levels of enzymes involved in antioxidant defense in the first trimester (week 7-9) placenta of normal and T1DM women by immunoblot and real-time qPCR. Primary human trophoblasts were isolated from first trimester placenta and the effects of oxygen, hyperglycemia and the pro-inflammatory cytokine tumor necrosis factor (TNF)-α on levels of HSP70 and HO-1 were analyzed. HSP70 (+19.9± 10.1%) and HO-1 (+63.5± 14.5%) were elevated (p placenta of T1DM women when compared to normal women. However, levels of HNE or CML modified proteins were unchanged. Also, expression of most antioxidant enzymes was unchanged, with only superoxide dismutase 3 (SOD3) being upregulated by 3.0-fold (p placenta of T1DM women may contribute to disturbances in placental development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Stress-Induced Out-of-Context Activation of Memory

    Czech Academy of Sciences Publication Activity Database

    Ježek, Karel; Lee, B.B.; Kelemen, E.; McCarthy, K.; McEwen, B.S.; Fenton, André Antonio

    2010-01-01

    Roč. 8, č. 12 (2010), e1000570-13 ISSN 1544-9173 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GP309/04/P206 Grant - others:EC(XE) QLG3-CT-1999-00192 Institutional research plan: CEZ:AV0Z50110509 Keywords : memory * stress * hippocampus Subject RIV: ED - Physiology Impact factor: 12.469, year: 2010

  18. Stress and happiness among adolescents with varying frequency of physical activity.

    Science.gov (United States)

    Moljord, Inger Elise Opheim; Moksnes, Unni Karin; Eriksen, Lasse; Espnes, Geir Arild

    2011-10-01

    The aim of this cross-sectional study was to investigate associations between physical activity, stress, and happiness, as well as possible sex and age differences on these variables in a survey of 1,508 adolescent pupils (13 to 18 yr.) in middle Norway. Adolescents who reported they participated in physical activity 2 to 3 times per week or more scored significantly lower on stress and higher on happiness than those who participated in physical activity 1 day per week or less. There was no significant difference on stress and happiness between those being physically active 2 or 3 times a week and those being active almost every day. There was no sex difference in physical activity frequency. Girls had higher mean scores on stress, and boys scored higher on happiness. Adolescents 15 to 16 years old showed higher stress scores than those 17 to 18 years old, but there were no significant differences between the different age groups when looking at happiness and physical activity. A statistically significant two-way interaction of sex by age was found on both stress and happiness.

  19. Stress-induced alterations of left-right electrodermal activity coupling indexed by pointwise transinformation

    Czech Academy of Sciences Publication Activity Database

    Světlák, M.; Bob, P.; Roman, R.; Ježek, S.; Damborská, A.; Chládek, Jan; Shaw, D. J.; Kukleta, M.

    2013-01-01

    Roč. 62, č. 6 (2013), s. 711-719 ISSN 0862-8408 Institutional support: RVO:68081731 Keywords : electrodermal activity * pointwise trasinformation * autonomic nervous system * asymmetry * stress Subject RIV: CE - Biochemistry Impact factor: 1.487, year: 2013

  20. Synergistic induction of CX3CL1 by TNF alpha and IFN gamma in osteoblasts from rheumatoid arthritis: involvement of NF-kappa B and STAT-1 signaling pathways

    Directory of Open Access Journals (Sweden)

    Kuninobu Wakabayashi

    2008-10-01

    Full Text Available Takeo Isozaki, Tsuyoshi Kasama, Ryo Takahashi, Tsuyoshi Odai, Kuninobu Wakabayashi, Hirohito Kanemitsu, Kyoko Nohtomi, Hiroko T Takeuchi, Satoshi Matsukura, Masakazu TezukaDivision of Rheumatology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan, and the Department of Orthopedics, Denencyofu Central Hospital, Tokyo, JapanAbstract: To explore the regulation of CX3CL1 in inflammatory bone diseases, CX3CL1 expression by osteoblasts (OB was examined. Human OB isolated from rheumatoid arthritis (RA patients, osteoarthritis patients, and normal individuals were incubated in the presence of cytokines. Soluble CX3CL1 levels were determined with an enzyme-linked immunosorbent assay. Expression of CX3CL1 mRNA was examined using quantitative real-time polymerase chain reaction. Although tumor necrosis factor (TNF-α or interferon (IFN-γ alone RA OB induced negligible CX3CL1 secretion, the combination of TNF-α and IFN-γ induced dramatic increases in both soluble CX3CL1 protein and mRNA transcripts. This synergistic effect was more pronounced in OB from RA than in OB from either osteoarthritis or normal individuals. The expression of CX3CL1 was markedly reduced by specific inhibitors of the nuclear factor-κB (NF-κB or STAT-1 transcription factor. These findings suggest that osteoblasts are an important cellular source of CX3CL1 and may play roles in inflammatory bone/joint diseases.Keywords: osteoblast, CX3CL1, chemokine, NF-κB, STAT-1

  1. Salivary alpha amylase activity in human beings of different age groups subjected to psychological stress.

    Science.gov (United States)

    Sahu, Gopal K; Upadhyay, Seema; Panna, Shradha M

    2014-10-01

    Salivary alpha-amylase (sAA) has been proposed as a sensitive non-invasive biomarker for stress-induced changes in the body that reflect the activity of the sympathetic nervous system. Though several experiments have been conducted to determine the validity of this salivary component as a reliable stress marker in human subjects, the effect of stress induced changes on sAA level in different age groups is least studied. This article reports the activity of sAA in human subjects of different age groups subjected to psychological stress induced through stressful video clip. Differences in sAA level based on sex of different age groups under stress have also been studied. A total of 112 subjects consisting of both the male and female subjects, divided into two groups on basis of age were viewed a video clip of corneal transplant surgery as stressor. Activity of sAA from saliva samples of the stressed subjects were measured and compared with the activity of the samples collected from the subjects before viewing the clip. The age ranges of subjects were 18-25 and 40-60 years. The sAA level increased significantly in both the groups after viewing the stressful video. The increase was more pronounced in the younger subjects. The level of sAA was comparatively more in males than females in the respective groups. No significant change in sAA activity was observed after viewing the soothed video clip. Significant increase of sAA level in response to psychological stress suggests that it might act as a reliable sympathetic activity biochemical marker in different stages of human beings.

  2. Virtual nature environment with nature sound exposure induce stress recovery by enhanced parasympathetic activity

    DEFF Research Database (Denmark)

    Annerstedt, Matilda; Jönsson, Peter; Wallergård, Mattias

    2013-01-01

    Experimental research on stress recovery in natural environments is limited, as is study of the effect of sounds of nature. After inducing stress by means of a virtual stress test, we explored physiological recovery in two different virtual natural environments (with and without exposure to sounds...... of nature) and in one control condition. Cardiovascular data and saliva cortisol were collected. Repeated ANOVA measurements indicated parasympathetic activation in the group subjected to sounds of nature in a virtual natural environment, suggesting enhanced stress recovery may occur in such surroundings....... The group that recovered in virtual nature without sound and the control group displayed no particular autonomic activation or deactivation. The results demonstrate a potential mechanistic link between nature, the sounds of nature, and stress recovery, and suggest the potential importance of virtual reality...

  3. Shallow Lunar Seismic Activity and the Current Stress State of the Moon

    Science.gov (United States)

    Watters, Thomas R.; Weber, Renee C.; Collins, Geoffrey C.; Johnson, Catherine L.

    2017-01-01

    A vast, global network of more than 3200 lobate thrust fault scarps has been revealed in high resolution Lunar Reconnaissance Orbiter Camera (LROC) images. The fault scarps are very young, less than 50 Ma, based on their small scale and crisp appearance, crosscutting relations with small-diameter impact craters, and rates of infilling of associated small, shallow graben and may be actively forming today. The population of young thrust fault scarps provides a window into the recent stress state of the Moon and offers insight into the origin of global lunar stresses. The distribution of orientations of the fault scarps is non-random, inconsistent with isotropic stresses from late-stage global contraction as the sole source of stress. Modeling shows that tidal stresses contribute significantly to the current stress state of the lunar crust. Tidal stresses (orbital recession and diurnal tides) superimposed on stresses from global contraction result in non-isotropic compressional stress and may produce thrust faults consistent with lobate scarp orientations. At any particular point on the lunar surface, peak compressive stress will be reached at a certain time in the diurnal cycle. Coseismic slip events on currently active thrust faults are expected to be triggered when peak stresses are reached. Analysis of the timing of the 28 the shallow moonquakes recorded by the Apollo seismic network shows that 19 indeed occur when the Moon is closer to apogee, while only 9 shallow events occur when the Moon is closer to perigee. Here we report efforts to refine the model for the current stress state of the Moon by investigating the contribution of polar wander. Progress on relocating the epicentral locations of the shallow moonquakes using an algorithm designed for sparse networks is also reported.

  4. The interplay between neuroendocrine activity and psychological stress-induced exacerbation of allergic asthma.

    Science.gov (United States)

    Miyasaka, Tomomitsu; Dobashi-Okuyama, Kaori; Takahashi, Tomoko; Takayanagi, Motoaki; Ohno, Isao

    2018-01-01

    Psychological stress is recognized as a key factor in the exacerbation of allergic asthma, whereby brain responses to stress act as immunomodulators for asthma. In particular, stress-induced enhanced type 2 T-helper (Th2)-type lung inflammation is strongly associated with asthma pathogenesis. Psychological stress leads to eosinophilic airway inflammation through activation of the hypothalamic-pituitary-adrenal pathway and autonomic nervous system. This is followed by the secretion of stress hormones into the blood, including glucocorticoids, epinephrine, and norepinephrine, which enhance Th2 and type 17 T-helper (Th17)-type asthma profiles in humans and rodents. Recent evidence has shown that a defect of the μ-opioid receptor in the brain along with a defect of the peripheral glucocorticoid receptor signaling completely disrupted stress-induced airway inflammation in mice. This suggests that the stress response facilitates events in the central nervous and endocrine systems, thus exacerbating asthma. In this review, we outline the recent findings on the interplay between stress and neuroendocrine activities followed by stress-induced enhanced Th2 and Th17 immune responses and attenuated regulatory T (Treg) cell responses that are closely linked with asthma exacerbation. We will place a special focus on our own data that has emphasized the continuity from central sensing of psychological stress to enhanced eosinophilic airway inflammation. The mechanism that modulates psychological stress-induced exacerbation of allergic asthma through neuroendocrine activities is thought to involve a series of consecutive pathological events from the brain to the lung, which implies there to be a "neuropsychiatry phenotype" in asthma. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  5. Active stress along the ne external margin of the Apennines: the Ferrara arc, northern Italy

    Science.gov (United States)

    Montone, Paola; Mariucci, M. Teresa

    1999-09-01

    We have analysed borehole breakout data from 12 deep wells in order to constrain the direction of the minimum and maximum horizontal stress in a part of the Po Plain, northern Italy, characterised by a ˜N-S prevailing compressional stress regime, and in order to shed light on the regional state of stress and on the correlation between the active stress field and the orientation of tectonic structures. The results have been compared with seismological data relating to 1988-1995 crustal seismicity (2.5Reggio Emilia ( Ms=5.1) events. Plio-Pleistocene mesostructural data are also described in order to better define the present-day stress field and to understand the active tectonic processes in particular stress provinces. The borehole breakout analysis, in accordance with the seismicity and mesostructural data, shows the presence of a predominant compression area, characterised by approximately N-S maximum horizontal stress, along the outer thrust of the Ferrara arc. Particularly, the breakout analysis indicates a minimum horizontal stress, N81W±22° relative to a total of eleven analysed wells, with 3746 m cumulative total length of breakout zones. Among these, nine wells are located in the same tectonic structure, consisting of an arc of asymmetric folds overthrust towards the NE. The breakout results for these wells are quite similar in terms of minimum horizontal stress direction (˜E-W oriented). The other two wells are located in the outside sector of the arc and one of them shows a different minimum horizontal stress direction, probably distinctive of another tectonic unit. On the basis of these new reliable stress indicators, the active compressive front in this area is located along the termination of the external northern Apenninic arc.

  6. Activity of ethanol-stressed Oenococcus oeni cells: a flow cytometric approach

    NARCIS (Netherlands)

    Silveira, da M.G.; Abee, T.

    2009-01-01

    Aims: To study the effect of ethanol on Oenococcus oeni activity at the single cell level. Methods and Results: The active extrusion of the fluorescent probe carboxy fluorescein (cF) was used to assess the metabolic activity of ethanol-stressed O. oeni cells. Subsequent flow cytometric analysis

  7. Stress !!!

    OpenAIRE

    Fledderus, M.

    2012-01-01

    Twee op de vijf UT-studenten hebben last van ernstige studiestress, zo erg zelfs dat het ze in hun privéleven belemmert. Die cijfers komen overeen met het landelijk beeld van stress onder studenten. Samen met 14 andere universiteits- en hogeschoolbladen enquêteerde UT Nieuws bijna 5500 studenten. Opvallend is dat mannelijke studenten uit Twente zich veel minder druk lijken te maken over hun studie. Onder vrouwen ligt de stress juist erg hoog ten opzichte van het landelijk gemiddelde.

  8. Stress

    DEFF Research Database (Denmark)

    Keller, Hanne Dauer

    2015-01-01

    Kapitlet handler om stress som følelse, og det trækker primært på de få kvalitative undersøgelser, der er lavet af stressforløb.......Kapitlet handler om stress som følelse, og det trækker primært på de få kvalitative undersøgelser, der er lavet af stressforløb....

  9. HIV protease inhibitors disrupt lipid metabolism by activating endoplasmic reticulum stress and inhibiting autophagy activity in adipocytes.

    Directory of Open Access Journals (Sweden)

    Beth S Zha

    Full Text Available HIV protease inhibitors (PI are core components of Highly Active Antiretroviral Therapy (HAART, the most effective treatment for HIV infection currently available. However, HIV PIs have now been linked to lipodystrophy and dyslipidemia, which are major risk factors for cardiovascular disease and metabolic syndrome. Our previous studies have shown that HIV PIs activate endoplasmic reticulum (ER stress and disrupt lipid metabolism in hepatocytes and macrophages. Yet, little is known on how HIV PIs disrupt lipid metabolism in adipocytes, a major cell type involved in the pathogenesis of metabolic syndrome.Cultured and primary mouse adipocytes and human adipocytes were used to examine the effect of frequently used HIV PIs in the clinic, lopinavir/ritonavir, on adipocyte differentiation and further identify the underlying molecular mechanism of HIV PI-induced dysregulation of lipid metabolism in adipocytes. The results indicated that lopinavir alone or in combination with ritonavir, significantly activated the ER stress response, inhibited cell differentiation, and induced cell apoptosis in adipocytes. In addition, HIV PI-induced ER stress was closely linked to inhibition of autophagy activity. We also identified through the use of primary adipocytes of CHOP(-/- mice that CHOP, the major transcriptional factor of the ER stress signaling pathway, is involved in lopinavir/ritonavir-induced inhibition of cell differentiation in adipocytes. In addition, lopinavir/ritonavir-induced ER stress appears to be associated with inhibition of autophagy activity in adipocytes.Activation of ER stress and impairment of autophagy activity are involved in HIV PI-induced dysregulation of lipid metabolism in adipocytes. The key components of ER stress and autophagy signaling pathways are potential therapeutic targets for HIV PI-induced metabolic side effects in HIV patients.

  10. Physical activity intervention effects on perceived stress in working mothers: the role of self-efficacy.

    Science.gov (United States)

    Mailey, Emily L; McAuley, Edward

    2014-01-01

    Working mothers often report elevated stress, and efforts to improve their coping resources are needed to buffer the detrimental effects of stress on health. This study examined the impact of changes in physical activity, self-efficacy, and self-regulation across the course of a brief intervention on subsequent levels of stress in working mothers. Participants (N = 141) were randomly assigned to an intervention or control condition (2:1 ratio). The intervention was conducted in Illinois between March 2011 and January 2012 and consisted of two group-mediated workshop sessions with content based on social cognitive theory. Participants completed measures of physical activity, self-efficacy, self-regulation, and perceived stress at baseline, immediately postintervention, and 6-month follow-up. Stress levels declined across the 6-month period in both groups. Changes in stress were negatively associated with changes in self-efficacy and self-regulation among intervention participants only. Regression analyses revealed the intervention elicited short-term increases in physical activity, self-efficacy, and self-regulation, but only changes in self-efficacy predicted perceived stress at 6-month follow-up. These results suggest that enhancing self-efficacy is likely to improve working mothers' perceived capabilities to cope with stressors in their lives. Future interventions should continue to focus on increasing self-efficacy to promote improvements in physical activity and psychological well-being in this population.

  11. Stress through the mind of the beholder: preliminary differences in child and maternal perceptions of child stress in relation to child cortisol and cardiovascular activity.

    Science.gov (United States)

    Allwood, Maureen A; Gaffey, Allison E; Vergara-Lopez, Chrystal; Stroud, Laura R

    2017-07-01

    The present study examined associations among parent and child reports of youth's stressful life events (SLEs), perceived stress, and biological measures of stress activity (i.e. cortisol and cardiovascular activity). Examining these aspects of youth stress presents several challenges. Unlike adult studies of individual differences in which information regarding SLEs, perceptions of events, and biological activity are gathered from one individual, assessment of individual differences among children usually involves other informants (e.g. parent). However, parent and child reports of SLEs and the child's psychological response to such events are often discordant. Moreover, examinations of youth perception of stress are hampered by limitations of child cognitive processes, as well as parents' limited knowledge of their child's perception of stress. In a preliminary effort to unscramble the complex effects of youth SLEs and perceived stress in relation to biological response to acute stressors, this study examined 51 boys and girls aged 7-16, with no history of psychopathology or medical concerns. Contrary to hypotheses, findings revealed that compared to actual experiences of stress, perceived stress has greater associations with both cortisol and cardiovascular activity. That is, perceived stress is more biologically salient relative to actual stress. Results also suggest that informant differences may explain some previous inconsistent findings in studies of youth's stress reactivity. The current findings mirror the adult studies that show appraisal and perception of traumatic and stressful events may be more predictive of negative health and mental health outcomes than the severity of the events. Further studies are needed to understand the impact of youth's perceptions of stress on their biological stress reactions and later health outcomes such as clinical disorders.

  12. Activity-based anorexia: relationship to gender and activity-stress ulcers.

    Science.gov (United States)

    Doerries, L E; Stanley, E Z; Aravich, P F

    1991-11-01

    The phenomena of activity-based anorexia (ABA) and the activity-stress ulcer (ASU) both involve paradigms in which the food intake of rats is restricted and the animals are allowed voluntary exercise in a running wheel. This study determined the susceptibility of male and female rats to ABA and ASU following 25- and 30-percent losses of their original body weights. Male rats reached both weight loss criteria in a fewer number of days than did female rats. None of the male and female rats sacrificed at the 25% weight loss criterion evidenced gastric lesions; 52% of the animals sacrificed at the 30% weight loss criterion had one or more lesions. No gender differences with respect to gastric lesions were observed at the 30% weight loss criterion; however, at both weight loss criteria, females ate and ran more than males. It is concluded that ASUs are a consequence rather than a cause of ABA, and that there is a sexually "dimorphic" susceptibility to ABA but not ASUs. The utility of using a 25% weight loss criterion for defining ABA is also discussed.

  13. A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed Cells during Development.

    Directory of Open Access Journals (Sweden)

    Kwonyoon Kang

    Full Text Available Eukaryotic cells have evolved signaling pathways that help to restore cellular homeostasis in response to various physiological or pathological conditions. ATF4 is a transcription factor whose mRNA translation is stimulated in response to stress-activated eIF2alpha kinases. Established conditions that activate eIF2alpha phosphorylation and ATF4 translation include excessive stress in the endoplasmic reticulum (ER and amino acid deprivation. ATF4 is activated through a unique translational activation mechanism that involves multiple upstream open reading frames (uORFs in the 5'-untranslated region (UTR, which is conserved from yeast to mammals. Taking advantage of this, we developed a translational activation reporter of ATF4 in Drosophila, in which the dsRed reporter coding sequence was placed downstream of the Drosophila ATF4 5' UTR. This reporter remained inactive in most tissues under normal conditions, but showed dsRed expression when starved, or when challenged with conditions that imposed ER stress. In normally developing flies, a small number of cell types showed reporter expression even without exogenous stress, which included the salivary gland, gut, the male reproductive organ, and the photoreceptor cells, suggestive of inherent stress during the normal development of these cell types. These results establish a new tool to study ATF4-mediated stress response in Drosophila development and disease.

  14. Acute stress enhances learning and memory by activating acid-sensing ion channels in rats.

    Science.gov (United States)

    Ye, Shunjie; Yang, Rong; Xiong, Qiuju; Yang, Youhua; Zhou, Lianying; Gong, Yeli; Li, Changlei; Ding, Zhenhan; Ye, Guohai; Xiong, Zhe

    2018-04-15

    Acute stress has been shown to enhance learning and memory ability, predominantly through the action of corticosteroid stress hormones. However, the valuable targets for promoting learning and memory induced by acute stress and the underlying molecular mechanisms remain unclear. Acid-sensing ion channels (ASICs) play an important role in central neuronal systems and involves in depression, synaptic plasticity and learning and memory. In the current study, we used a combination of electrophysiological and behavioral approaches in an effort to explore the effects of acute stress on ASICs. We found that corticosterone (CORT) induced by acute stress caused a potentiation of ASICs current via glucocorticoid receptors (GRs) not mineralocorticoid receptors (MRs). Meanwhile, CORT did not produce an increase of ASICs current by pretreated with GF109203X, an antagonist of protein kinase C (PKC), whereas CORT did result in a markedly enhancement of ASICs current by bryostatin 1, an agonist of PKC, suggesting that potentiation of ASICs function may be depended on PKC activating. More importantly, an antagonist of ASICs, amiloride (10 μM) reduced the performance of learning and memory induced by acute stress, which is further suggesting that ASICs as the key components involves in cognitive processes induced by acute stress. These results indicate that acute stress causes the enhancement of ASICs function by activating PKC signaling pathway, which leads to potentiated learning and memory. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Economic stress and low leisure-time physical activity: Two life course hypotheses

    Directory of Open Access Journals (Sweden)

    Martin Lindström

    2018-04-01

    Full Text Available The aim was to investigate associations between economic stress in childhood and adulthood, and low leisure-time physical activity (LTPA in adulthood from two life course perspectives. The public health survey in Scania in the southernmost part of Sweden in 2012 is a cross-sectional study based on a stratified random sample with 28,029 respondents aged 18–80 (51.7% response rate. Associations between childhood and adult economic stress, and low LTPA were analyzed with logistic regressions. A 14.8% prevalence of men and 13.5% of women had low LTPA (sedentary lifestyle. Low LTPA was associated with higher age, being born abroad, low socioeconomic status, low trust, smoking, poor self-rated health, and economic stress in childhood and adulthood. The odds ratios of low LTPA increased with more accumulated economic stress across the life course in a dose-response relationship. There was no specific critical period (childhood or adulthood, because economic stress in childhood and adulthood were both associated with low LTPA but the associations were attenuated after the introduction of smoking and self-rated health. The accumulation hypothesis was supported because the odds ratios of low LTPA indicated a graded response to life course economic stress. The critical period hypothesis was thus not supported. Economic stress across the life course seems to be associated with low LTPA in adulthood. Keywords: Economic stress, Leisure-time physical activity, Accumulation, Critical period, Social capital, Sweden

  16. Silica nanoparticles induce endoplasmic reticulum stress response and activate mitogen activated kinase (MAPK signalling

    Directory of Open Access Journals (Sweden)

    Verena Christen

    Full Text Available Humans may be exposed to engineered silica nanoparticles (SiO2-NPs but potential adverse effects are poorly understood, in particular in relation to cellular effects and modes of action. Here we studied effects of SiO2-NPs on cellular function in human hepatoma cells (Huh7. Exposure for 24 h to 10 and 50 μg/ml SiO2-NPs led to induction of endoplasmic reticulum (ER stress as demonstrated by transcriptional induction of DNAJB9, GADD34, CHOP, as well as CHOP target genes BIM, CHAC-1, NOXA and PUMA. In addition, CHOP protein was induced. In addition, SiO2-NPs induced an inflammatory response as demonstrated by induction of TNF-α and IL-8. Activation of MAPK signalling was investigated employing a PCR array upon exposure of Huh7 cells to SiO2-NPs. Five of 84 analysed genes, including P21, P19, CFOS, CJUN and KSR1 exhibited significant transcriptional up-regulation, and 18 genes a significant down-regulation. Strongest down-regulation occurred for the proto-oncogene BRAF, MAPK11, one of the four p38 MAPK genes, and for NFATC4. Strong induction of CFOS, CJUN, FRA1 and CMYC was found after exposure to 50 μg/ml SiO2-NPs for 24 h. To analyse for effects derived from up-regulation of TNF-α, Huh7 cells were exposed to SiO2-NPs in the presence of the TNF-α inhibitor sauchinone, which reduced the induction of the TNF-α transcript by about 50%. These data demonstrate that SiO2-NPs induce ER stress, MAPK pathway and lead to inflammatory reaction in human hepatoma cells. Health implications of SiO2-NPs exposure should further be investigated for a risk assessment of these frequently used nanoparticles. Keywords: Silica nanoparticles, Endoplasmic reticulum stress, MAPK, TNF-α, Huh7 cells

  17. Is Political Activism on Social Media an initiator of Psychological Stress?

    Science.gov (United States)

    Hisam, Aliya; Safoor, Iqra; Khurshid, Nawal; Aslam, Aakash; Zaid, Farhan; Muzaffar, Ayesha

    2017-01-01

    To find out the association of psychological stress with political activism on social networking sites (SNS) in adults. To find association of psychological stress and political activism with age, gender and occupational status. A descriptive cross-sectional study of 8 months (Aug 2014 to March 2015) was conducted on young adults between age group of 20-40 years of different universities of Rawalpindi, Pakistan. Closed ended standardized questionnaires (i.e. Cohen Perceived Stress-10) were distributed via non-probability convenient sampling among a total sample size of 237. Sample size was calculated using WHO sample size calculator and data was analyzed in STATA version 12. The mean age of participants was 21.06±1.425 years. Out of the 237 participants, 150 (63.3%) were males and 87 (36.7%) females. Regarding their occupation, 13 (51.9%) were military cadets, 8 (3.4%) were consultant, 47 (19.8%) medical officer, 3 (1.3%) PG students and 56 (23.6%) MBBS students. Significant association of occupation was established with both political activism and psychological stress (p=0.4 and p=0.002 respectively). Among 237 individuals, 91 (38.4%) were stressed out and 146 (61.6%) were not. Among whole sample, political activists on SNS were found to be 23 (9.7%). Out of these 23 individuals who were politically active, 15 (65.2%) were stressed out and 8 (34.7%) were not. A significant association between stress and political activism was established (p=0.005). Political activism via social networking sites is playing significant role on adult person's mental health in terms of stress among different occupation.

  18. Stress-induced alterations of left-right electrodermal activity coupling indexed by pointwise transinformation.

    Science.gov (United States)

    Světlák, M; Bob, P; Roman, R; Ježek, S; Damborská, A; Chládek, J; Shaw, D J; Kukleta, M

    2013-01-01

    In this study, we tested the hypothesis that experimental stress induces a specific change of left-right electrodermal activity (EDA) coupling pattern, as indexed by pointwise transinformation (PTI). Further, we hypothesized that this change is associated with scores on psychometric measures of the chronic stress-related psychopathology. Ninety-nine university students underwent bilateral measurement of EDA during rest and stress-inducing Stroop test and completed a battery of self-report measures of chronic stress-related psychopathology. A significant decrease in the mean PTI value was the prevalent response to the stress conditions. No association between chronic stress and PTI was found. Raw scores of psychometric measures of stress-related psychopathology had no effect on either the resting levels of PTI or the amount of stress-induced PTI change. In summary, acute stress alters the level of coupling pattern of cortico-autonomic influences on the left and right sympathetic pathways to the palmar sweat glands. Different results obtained using the PTI, EDA laterality coefficient, and skin conductance level also show that the PTI algorithm represents a new analytical approach to EDA asymmetry description.

  19. Job stressors and job stress among teachers engaged in nursing activity.

    Science.gov (United States)

    Muto, Shigeki; Muto, Takashi; Seo, Akihiko; Yoshida, Tsutomu; Taoda, Kazushi; Watanabe, Misuzu

    2007-01-01

    Teachers and staff members engaged in nursing activity experience more stress than other workers. However, it is unknown whether teachers engaged in nursing activity in schools for handicapped children experience even greater stress. This study evaluated job stressors and job stress among such teachers using a cross-sectional study design. The subjects were all 1,461 teachers from all 19 prefectural schools for handicapped children in Shizuoka Prefecture, Japan. We used a brief job stress questionnaire for the survey and 831 teachers completed the questionnaire. Job stressors among teachers engaged in nursing activity were compared with those among teachers not engaged in nursing activity. Job stress among such teachers was estimated by the score for total health risk, and was compared with the score in the Japanese general population. Male and female teachers engaged in nursing activity had a significantly higher level of job stressors for physical work load and job control compared with those not engaged in nursing activity. The scores for total health risk among male and female teachers engaged in nursing activity were 102 points and 98 points, respectively. These scores were not markedly above 100 points which is the mean score in the Japanese general population.

  20. LPS-Induced Macrophage Activation and Plasma Membrane Fluidity Changes are Inhibited Under Oxidative Stress.

    Science.gov (United States)

    de la Haba, Carlos; Morros, Antoni; Martínez, Paz; Palacio, José R

    2016-12-01

    Macrophage activation is essential for a correct and efficient response of innate immunity. During oxidative stress membrane receptors and/or membrane lipid dynamics can be altered, leading to dysfunctional cell responses. Our aim is to analyze membrane fluidity modifications and cell function under oxidative stress in LPS-activated macrophages. Membrane fluidity of individual living THP-1 macrophages was evaluated by the technique two-photon microscopy. LPS-activated macrophage function was determined by TNFα secretion. It was shown that LPS activation causes fluidification of macrophage plasma membrane and production of TNFα. However, oxidative stress induces rigidification of macrophage plasma membrane and inhibition of cell activation, which is evidenced by a decrease of TNFα secretion. Thus, under oxidative conditions macrophage proinflammatory response might develop in an inefficient manner.

  1. CK2-dependent phosphorylation positively regulates stress-induced activation of Msn2 in Saccharomyces cerevisiae.

    Science.gov (United States)

    Cho, Bo-Ram; Hahn, Ji-Sook

    2017-06-01

    CK2 is a highly conserved Ser/Thr protein kinase involved in a large number of cellular processes. Here, we demonstrate that CK2-dependent phosphorylation positively regulates Msn2/4, the general stress response transcriptional activators in Saccharomyces cerevisiae, in response to various types of environmental stress conditions. CK2 overexpression elicits hyperactivation of Msn2/4, whereas deletion of one of the CK2 catalytic subunits, especially CKA2, leads to reduced transcriptional activity of Msn2/4 in response to glucose starvation, H 2 O 2, and lactic acid. The CKA2 deletion mutant also shows increased stress sensitivity. CK2 phosphorylates Ser194 and Ser638 in Msn2 and replacement of Ser638 with alanine leads to reduced Msn2 activity upon stress and reduced tolerance to H 2 O 2 and lactic acid. CKA2 deletion mutant shows shorter nuclear retention time of Msn2 upon lactic acid stress, suggesting that CK2 might regulate nuclear localization of Msn2. However, Msn2 S194A, S638A mutant shows normal nuclear import and export patterns upon stress, suggesting that CK2 might positively regulate the general stress response not only by direct phosphorylation of Msn2/4, but also by regulating cellular translocation machinery. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Protective Activity Against Oxidative Stress of Plants Indigenous to Korea

    International Nuclear Information System (INIS)

    Yoo, B.S.; Yang, Y.T.; Jung, M.S.; Kang, K.A.; Zhang, Rui; Chae, S.W.; Lee, N.H.; Park, J.W.; Hyun, J.W.

    2005-01-01

    We have screened the cytoprotective effect against Ha, Oa, and γ-ray radiation induced oxidative stress from 32 Korean plants. Betula ermani var, saitoana (caulis, leaves), Rosa wichuraiana (caulis), Sorbus commixta (caulis), Weigela florida (leaves), Cirsium rhinoceros (whole plant), and Viburnum erosum (caulis) were found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and intracellular reactive oxygen species (ROS). As a result, extracts of six plants reduced cell death of Chinese hamster lung fibroblast (V79-4) cells induced by Ha,Oa, treatment. In addition, these extracts protected cell death of V79-4 cells damaged by γ-ray radiation. In addition, these extracts scavenged ROS generated by radiation. Taken together, the results suggest that Betula ermani var. saitoana, Rosa wichuraiana, Sorbus commixta, Weigela florida, Cirsium rhinoceros, and Viburnum erosum protect V79-4 cells against oxidative damage by radiation through scavenging ROS

  3. The Different Roles of Perceived Stress in the Association Between Older Adults’ Physical Activity and Physical Health

    Science.gov (United States)

    Rueggeberg, Rebecca; Wrosch, Carsten; Miller, Gregory E.

    2011-01-01

    This 4-yr longitudinal study examined the different roles of perceived stress in the association between older adults’ physical activities and physical health. We hypothesized that physical activities would exert beneficial effects on physical health by preventing chronically high levels of perceived stress. Design and Measures We assessed baseline levels of physical activities and repeated measures of perceived stress and physical symptoms in three waves of data from a sample of 157 older adults. Results Among participants with high (but not low) baseline levels of perceived stress, physical activity predicted a 2-yr reduction of perceived stress and a 4-yr prevention of physical health symptoms. Moreover, the interaction effect on 4-yr changes in physical symptoms was mediated by 2-yr changes in perceived stress. Conclusions Physical health benefits of physical activity are particularly pronounced among older adults who perceive high levels of stress, and this effect is mediated by a prevention of chronically high perceptions of stress. PMID:21875206

  4. Stress Incontinence

    Science.gov (United States)

    Stress incontinence Overview Urinary incontinence is the unintentional loss of urine. Stress incontinence happens when physical movement or activity — such ... coughing, sneezing, running or heavy lifting — puts pressure (stress) on your bladder. Stress incontinence is not related ...

  5. Activation of the low molecular weight protein tyrosine phosphatase in keratinocytes exposed to hyperosmotic stress.

    Directory of Open Access Journals (Sweden)

    Rodrigo A Silva

    Full Text Available Herein, we provide new contribution to the mechanisms involved in keratinocytes response to hyperosmotic shock showing, for the first time, the participation of Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP activity in this event. We reported that sorbitol-induced osmotic stress mediates alterations in the phosphorylation of pivotal cytoskeletal proteins, particularly Src and cofilin. Furthermore, an increase in the expression of the phosphorylated form of LMWPTP, which was followed by an augment in its catalytic activity, was observed. Of particular importance, these responses occurred in an intracellular milieu characterized by elevated levels of reduced glutathione (GSH and increased expression of the antioxidant enzymes glutathione peroxidase and glutathione reductase. Altogether, our results suggest that hyperosmostic stress provides a favorable cellular environment to the activation of LMWPTP, which is associated with increased expression of antioxidant enzymes, high levels of GSH and inhibition of Src kinase. Finally, the real contribution of LMWPTP in the hyperosmotic stress response of keratinocytes was demonstrated through analysis of the effects of ACP1 gene knockdown in stressed and non-stressed cells. LMWPTP knockdown attenuates the effects of sorbitol induced-stress in HaCaT cells, mainly in the status of Src kinase, Rac and STAT5 phosphorylation and activity. These results describe for the first time the participation of LMWPTP in the dynamics of cytoskeleton rearrangement during exposure of human keratinocytes to hyperosmotic shock, which may contribute to cell death.

  6. Inbreeding alters activities of the stress-related enzymes chitinases and β-1,3-glucanases.

    Science.gov (United States)

    Leimu, Roosa; Kloss, Lena; Fischer, Markus

    2012-01-01

    Pathogenesis-related proteins, chitinases (CHT) and β-1,3-glucanases (GLU), are stress proteins up-regulated as response to extrinsic environmental stress in plants. It is unknown whether these PR proteins are also influenced by inbreeding, which has been suggested to constitute intrinsic genetic stress, and which is also known to affect the ability of plants to cope with environmental stress. We investigated activities of CHT and GLU in response to inbreeding in plants from 13 Ragged Robin (Lychnis flos-cuculi) populations. We also studied whether activities of these enzymes were associated with levels of herbivore damage and pathogen infection in the populations from which the plants originated. We found an increase in pathogenesis-related protein activity in inbred plants from five out of the 13 investigated populations, which suggests that these proteins may play a role in how plants respond to intrinsic genetic stress brought about by inbreeding in some populations depending on the allele frequencies of loci affecting the expression of CHT and the past levels of inbreeding. More importantly, we found that CHT activities were higher in plants from populations with higher levels of herbivore or pathogen damage, but inbreeding reduced CHT activity in these populations disrupting the increased activities of this resistance-related enzyme in populations where high resistance is beneficial. These results provide novel information on the effects of plant inbreeding on plant-enemy interactions on a biochemical level.

  7. Inbreeding alters activities of the stress-related enzymes chitinases and β-1,3-glucanases.

    Directory of Open Access Journals (Sweden)

    Roosa Leimu

    Full Text Available Pathogenesis-related proteins, chitinases (CHT and β-1,3-glucanases (GLU, are stress proteins up-regulated as response to extrinsic environmental stress in plants. It is unknown whether these PR proteins are also influenced by inbreeding, which has been suggested to constitute intrinsic genetic stress, and which is also known to affect the ability of plants to cope with environmental stress. We investigated activities of CHT and GLU in response to inbreeding in plants from 13 Ragged Robin (Lychnis flos-cuculi populations. We also studied whether activities of these enzymes were associated with levels of herbivore damage and pathogen infection in the populations from which the plants originated. We found an increase in pathogenesis-related protein activity in inbred plants from five out of the 13 investigated populations, which suggests that these proteins may play a role in how plants respond to intrinsic genetic stress brought about by inbreeding in some populations depending on the allele frequencies of loci affecting the expression of CHT and the past levels of inbreeding. More importantly, we found that CHT activities were higher in plants from populations with higher levels of herbivore or pathogen damage, but inbreeding reduced CHT activity in these populations disrupting the increased activities of this resistance-related enzyme in populations where high resistance is beneficial. These results provide novel information on the effects of plant inbreeding on plant-enemy interactions on a biochemical level.

  8. Stress !!!

    NARCIS (Netherlands)

    Fledderus, M.

    2012-01-01

    Twee op de vijf UT-studenten hebben last van ernstige studiestress, zo erg zelfs dat het ze in hun privéleven belemmert. Die cijfers komen overeen met het landelijk beeld van stress onder studenten. Samen met 14 andere universiteits- en hogeschoolbladen enquêteerde UT Nieuws bijna 5500 studenten.

  9. Overcrowding stress decreases macrophage activity and increases Salmonella Enteritidis invasion in broiler chickens.

    Science.gov (United States)

    Gomes, A V S; Quinteiro-Filho, W M; Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Baskeville, E; Akamine, A T; Astolfi-Ferreira, C S; Ferreira, A J P; Palermo-Neto, J

    2014-01-01

    Overcrowding stress is a reality in the poultry industry. Chickens exposed to long-term stressful situations present a reduction of welfare and immunosuppression. We designed this experiment to analyse the effects from overcrowding stress of 16 birds/m(2) on performance parameters, serum corticosterone levels, the relative weight of the bursa of Fabricius, plasma IgA and IgG levels, intestinal integrity, macrophage activity and experimental Salmonella Enteritidis invasion. The results of this study indicate that overcrowding stress decreased performance parameters, induced enteritis and decreased macrophage activity and the relative bursa weight in broiler chickens. When the chickens were similarly stressed and infected with Salmonella Enteritidis, there was an increase in feed conversion and a decrease in plasma IgG levels in the stressed and Salmonella-infected birds. We observed moderate enteritis throughout the duodenum of chickens stressed and infected with Salmonella. The overcrowding stress decreased the macrophage phagocytosis intensity and increased Salmonella Enteritidis counts in the livers of birds challenged with the pathogenic bacterium. Overcrowding stress via the hypothalamic-pituitary-adrenal axis that is associated with an increase in corticosterone and enteritis might influence the quality of the intestinal immune barrier and the integrity of the small intestine. This effect allowed pathogenic bacteria to migrate through the intestinal mucosa, resulting in inflammatory infiltration and decreased nutrient absorption. The data strengthen the hypothesis that control of the welfare of chickens and avoidance of stress from overcrowding in poultry production are relevant factors for the maintenance of intestinal integrity, performance and decreased susceptibility to Salmonella infection.

  10. Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Aisha, M.D. [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); Nor-Ashikin, M.N.K. [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); DDH, Universiti Teknologi MARA, ShahAlam 40450, Selangor (Malaysia); Sharaniza, A.B.R. [DDH, Universiti Teknologi MARA, ShahAlam 40450, Selangor (Malaysia); Nawawi, H. [Center for Pathology Diagnostic and Research Laboratories, Clinical Training Center, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); I-PPerForM, Universiti Teknologi MARA, Selayang 47000 Selangor (Malaysia); Froemming, G.R.A., E-mail: gabriele@salam.uitm.edu.my [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); I-PPerForM, Universiti Teknologi MARA, Selayang 47000 Selangor (Malaysia)

    2015-09-10

    Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases. - Highlights: • OFS stress transmits anabolic signals to osteoblasts. • Actin and tubulin fibers are rearranged under OFS stress. • OFS stress increases mitochondrial metabolism and proliferation. • Reduced RANKL/OPG ratio in response to OFS inhibits osteoclastogenesis. • OFS stress prevents apoptosis and stimulates ALP and OCN.

  11. Polyamines and plant stress - Activation of putrescine biosynthesis by osmotic shock

    Science.gov (United States)

    Flores, H. E.; Galston, A. W.

    1982-01-01

    The putrescine content of oat leaf cells and protoplasts increases up to 60-fold within 6 hours of exposure to osmotic stress (0.4 to 0.6 molar sorbitol). Barley, corn, wheat, and wild oat leaves show a similar response. Increased arginine decarboxylase activity parallels the rise in putrescine, whereas ornithine decarboxylase remains unchanged. DL-alpha-Difluoromethylarginine, a specific irreversible inhibitor of arginine decarboxylase, prevents the stress-induced rise in increase in arginine decarboxylase activity and putrescine synthesis, indicating the preferential activation of this pathway.

  12. A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress

    KAUST Repository

    Ritho, Joan

    2015-07-23

    SUMOylation has been implicated in cellular stress adaptation, but its role in regulating liver kinase B1 (LKB1), a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), is unknown. Here, we show that energy stress triggers an increase in SUMO1 modification of LKB1, despite a global reduction in both SUMO1 and SUMO2/3 conjugates. During metabolic stress, SUMO1 modification of LKB1 lysine 178 is essential in promoting its interaction with AMPK via a SUMO-interacting motif (SIM) essential for AMPK activation. The LKB1 K178R SUMO mutant had defective AMPK signaling and mitochondrial function, inducing death in energy-deprived cells. These results provide additional insight into how LKB1-AMPK signaling is regulated during energy stress, and they highlight the critical role of SUMOylation in maintaining the cell’s energy equilibrium.

  13. Effects of stress and adrenalectomy on activity-regulated cytoskeleton protein (Arc) gene expression

    DEFF Research Database (Denmark)

    Mikkelsen, Jens D; Larsen, Marianne Hald

    2006-01-01

    Activity-regulated cytoskeletal-associated protein (Arc) is an effector immediate early gene induced by novelty and involved in consolidation of long-term memory. Since activation of glucocorticoid receptors is a prerequisite for memory consolidation, we therefore aimed to study the effect of acute...... restraint stress on Arc gene expression in adrenalectomized rats. Acute stress produced a significant increase in Arc gene expression in the medial prefrontal cortex, but not in the parietal cortex or in the pyramidal cell layer of the hippocampus. The basal level of Arc mRNA in adrenalectomized animals...... was high in the medial prefrontal cortex and unaffected by acute stress in these animals. These data are consistent with the role of Arc as an integrative modulator of synaptic plasticity by emphasizing the potential role of stress and glucocorticoids in the control of Arc gene expression....

  14. Differential regulation of protease activated receptor-1 and tissue plasminogen activator expression by shear stress in vascular smooth muscle cells

    Science.gov (United States)

    Papadaki, M.; Ruef, J.; Nguyen, K. T.; Li, F.; Patterson, C.; Eskin, S. G.; McIntire, L. V.; Runge, M. S.

    1998-01-01

    Recent studies have demonstrated that vascular smooth muscle cells are responsive to changes in their local hemodynamic environment. The effects of shear stress on the expression of human protease activated receptor-1 (PAR-1) and tissue plasminogen activator (tPA) mRNA and protein were investigated in human aortic smooth muscle cells (HASMCs). Under conditions of low shear stress (5 dyn/cm2), PAR-1 mRNA expression was increased transiently at 2 hours compared with stationary control values, whereas at high shear stress (25 dyn/cm2), mRNA expression was decreased (to 29% of stationary control; Pmuscle cells, indicating that the effects of shear stress on human PAR-1 were not species-specific. Flow cytometry and ELISA techniques using rat smooth muscle cells and HASMCs, respectively, provided evidence that shear stress exerted similar effects on cell surface-associated PAR-1 and tPA protein released into the conditioned media. The decrease in PAR-1 mRNA and protein had functional consequences for HASMCs, such as inhibition of [Ca2+] mobilization in response to thrombin stimulation. These data indicate that human PAR-1 and tPA gene expression are regulated differentially by shear stress, in a pattern consistent with their putative roles in several arterial vascular pathologies.

  15. Stress, Sleep and Depressive Symptoms in Active Duty Military Personnel.

    Science.gov (United States)

    Chou, Han-Wei; Tzeng, Wen-Chii; Chou, Yu-Ching; Yeh, Hui-Wen; Chang, Hsin-An; Kao, Yu-Chen; Huang, San-Yuan; Yeh, Chin-Bin; Chiang, Wei-Shan; Tzeng, Nian-Sheng

    2016-08-01

    The military is a unique occupational group and, because of this, military personnel face different kinds of stress than civilian populations. Sleep problems are an example. The purpose of this study was to investigate the relationship between sleep problems, depression level and coping strategies among military personnel. In this cross-sectional study, military personnel completed the Beck Depression Inventory, the Pittsburgh Sleep Quality Index and the Jalowiec Coping Scale. An evaluation of the test scores showed that officers had better sleep quality and fewer depressive symptoms than enlisted personnel. Military personnel with higher educational levels and less physical illness also had fewer depressive symptoms. Officers and noncommissioned officers preferred problem-focused strategies. Those with higher Beck Depression Inventory and Pittsburgh Sleep Quality Index scores and those who drank alcohol frequently preferred affective-focused strategies. Our results revealed that sleep quality, physical illness and alcohol consumption were associated with the mental health of military personnel. Treating these factors may improve the mental health of military personnel and enhance effective coping strategies. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  16. Activity of earthworm in Latosol under simulated acid rain stress.

    Science.gov (United States)

    Zhang, Jia-En; Yu, Jiayu; Ouyang, Ying

    2015-01-01

    Acid rain is still an issue of environmental concerns. This study investigated the impacts of simulated acid rain (SAR) upon earthworm activity from the Latosol (acidic red soil). Laboratory experiment was performed by leaching the soil columns grown with earthworms (Eisenia fetida) at the SAR pH levels ranged from 2.0 to 6.5 over a 34-day period. Results showed that earthworms tended to escape from the soil and eventually died for the SAR at pH = 2.0 as a result of acid toxicity. The catalase activity in the earthworms decreased with the SAR pH levels, whereas the superoxide dismutases activity in the earthworms showed a fluctuate pattern: decreasing from pH 6.5 to 5.0 and increasing from pH 5.0 to 4.0. Results implied that the growth of earthworms was retarded at the SAR pH ≤ 3.0.

  17. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

    Directory of Open Access Journals (Sweden)

    Andreas Stengel

    2017-04-01

    Full Text Available Corticotropin-releasing factor (CRF is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

  18. Perceived and measured physical activity and mental stress levels in obstetricians.

    Science.gov (United States)

    Martinez de Tejada, Begoña; Jastrow, Nicole; Poncet, Antoine; Le Scouezec, Iona; Irion, Olivier; Kayser, Bengt

    2013-11-01

    Obstetric work generates important subjective and objective mental stress and is perceived as a physically demanding activity by obstetricians. The aim of this study was to quantify physical and mental stress levels in obstetricians at work and during leisure activities to investigate their association with overall physical activity levels and professional experience. 18 obstetricians at the maternity unit of the University of Geneva Hospitals were enrolled in a prospective observational study. Physical activity and stress levels were measured in two different activity sectors (delivery room and outpatient clinic) and outside work. Physical activity was assessed by questionnaire, visual analogue scale (VAS), and accelerometer. Mental stress levels were assessed by validated questionnaires, VAS, measurement of urine catecholamines and salivary cortisol, and night-time heart rate variability indices. Daily stress levels were higher at work compared to outside work (all, P = 0.002). Adrenalin (P = 0.002) and dopamine (P = 0.09) levels were elevated after a labour suite shift and a trend was observed for reduced heart rate variability during the night after this shift. The median average daily number of steps was 7132 (range, 5283-8649). Subjects reached a median of 32 min (range, 19-49 min) of moderate or higher intensity (≥ 1952 counts/min) daily physical activity. Contrary to perception, obstetrics work is not physically demanding. It is, however, accompanied by important subjective and objective mental stress that may have a negative impact on health when combined with a lack of regular daily physical activity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Obesity-induced metabolic disturbance drives oxidative stress and complement activation in the retinal environment.

    Science.gov (United States)

    Natoli, Riccardo; Fernando, Nilisha; Dahlenburg, Tess; Jiao, Haihan; Aggio-Bruce, Riemke; Barnett, Nigel L; Chao de la Barca, Juan Manuel; Tcherkez, Guillaume; Reynier, Pascal; Fang, Johnny; Chu-Tan, Joshua A; Valter, Krisztina; Provis, Jan; Rutar, Matt

    2018-01-01

    Systemic increases in reactive oxygen species, and their association with inflammation, have been proposed as an underlying mechanism linking obesity and age-related macular degeneration (AMD). Studies have found increased levels of oxidative stress biomarkers and inflammatory cytokines in obese individuals; however, the correlation between obesity and retinal inflammation has yet to be assessed. We used the leptin-deficient (ob/ob) mouse to further our understanding of the contribution of obesity to retinal oxidative stress and inflammation. Retinas from ob/ob mice were compared to age-matched wild-type controls for retinal function (electroretinography) and gene expression analysis of retinal stress ( Gfap ), oxidative stress ( Gpx3 and Hmox1 ), and complement activation ( C3 , C2 , Cfb , and Cfh ). Oxidative stress was further quantified using a reactive oxygen species and reactive nitrogen species (ROS and RNS) assay. Retinal microglia and macrophage migration to the outer retina and complement activation were determined using immunohistochemistry for IBA1 and C3, respectively. Retinas and sera were used for metabolomic analysis using QTRAP mass spectrometry. Retinal function was reduced in ob/ob mice, which correlated to changes in markers of retinal stress, oxidative stress, and inflammation. An increase in C3-expressing microglia and macrophages was detected in the outer retinas of the ob/ob mice, while gene expression studies showed increases in the complement activators ( C2 and Cfb ) and a decrease in a complement regulator ( Cfh ). The expression of several metabolites were altered in the ob/ob mice compared to the controls, with changes in polyunsaturated fatty acids (PUFAs) and branched-chain amino acids (BCAAs) detected. The results of this study indicate that oxidative stress, inflammation, complement activation, and lipid metabolites in the retinal environment are linked with obesity in ob/ob animals. Understanding the interplay between these

  20. Recovery from activity-stress ulcer by ad lib feeding in rats.

    Science.gov (United States)

    Hirao, M; Tanaka, M; Emoto, H; Ishii, H; Yokoo, H; Yoshida, M; Tsuda, A

    1997-12-31

    In order to investigate the recovery from activity-stress ulcers by ad lib-feeding and/or cessation of running, male Wistar rats were exposed to the activity-stress paradigm, and the rats that revealed hypothermia (their rectal temperature fell below 36 degrees C) were sacrificed either immediately or after several 24 h periods of healing. Rats that were sacrificed immediately after the appearance of hypothermia and those that were exposed to restricted feeding plus cessation of running revealed severe activity-stress ulcers, whereas few ulcers were observed in rats given ad lib-feeding and those that were given ad lib-feeding plus cessation of running. Although no significant differences in relative weights of spleen and thymus were obtained among the different recovery conditions, the relative weights of the adrenal glands were highest in the restricted feeding plus cessation of running group, whereas, the other animals exposed to the activity-stress paradigm showed no differences. These results indicate that activity-stress ulcers recover under conditions of ad lib-feeding within 24 h, but they are not influenced by cessation of running. These data also suggest that organ weights are not affected by any manipulations employed in the present study.

  1. Evaluation of physical activity habits in patients with posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Marcio Antonio de Assis

    2008-01-01

    Full Text Available OBJECTIVE: In this study, we present data from a survey that aimed to assess the physical activity habits of adult Brazilian patients with Posttraumatic Stress Disorder. METHOD: Fifty male and female patients with Posttraumatic Stress Disorder participated in this study. The mean age at onset was 37±12 years, and the mean time between diagnosis and follow-up was 3.6±4.2 years. RESULTS: Substantial changes in physical activity habits were observed following the onset of PTSD. While more than half of the patients participated in physical activities prior to Posttraumatic Stress Disorder onset, there was a significant reduction in their participation afterwards. The justifications for stopping physical activities or sport participation were lack of time and lack of motivation. DISCUSSION: Several studies have shown that physical exercise decreases reverts symptoms of psychiatric disorders such as depression, anxiety and social isolation. We could therefore hypothesize that patients with Posttraumatic Stress Disorder who exercise should experience the same benefits. CONCLUSION: Our findings demonstrated that patients with Posttraumatic Stress Disorder have low levels of participation in sports or physical activities.

  2. Replication stress activates DNA repair synthesis in mitosis

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Ying, Songmin; Bjerregaard, Victoria A

    2015-01-01

    into mitotic prophase triggers the recruitment of MUS81 to CFSs. The nuclease activity of MUS81 then promotes POLD3-dependent DNA synthesis at CFSs, which serves to minimize chromosome mis-segregation and non-disjunction. We propose that the attempted condensation of incompletely duplicated loci in early...

  3. Influence of osmotic and metal stresses on nitrogenase activity of ...

    African Journals Online (AJOL)

    Samples were collected from paddy fields in Corum-Turk.ye. Nitrogen-free BG-11 medium was used for isolation of nitrogen fixing cyanobacteria. Acetylene reduction technique was used to determine the effects of different chemical agents on the nitrogenase activities of the cyanobacteria, which were identified at the genus ...

  4. Activity of the Hypothalamic-Pituitary-Adrenal System in Prenatally Stressed Male Rats on the Experimental Model of Post-Traumatic Stress Disorder.

    Science.gov (United States)

    Pivina, S G; Rakitskaya, V V; Akulova, V K; Ordyan, N E

    2016-03-01

    Using the experimental model of post-traumatic stress disorder (stress-restress paradigm), we studied the dynamics of activity of the hypothalamic-pituitary-adrenal system (HPAS) in adult male rats, whose mothers were daily subjected to restraint stress on days 15-19 of pregnancy. Prenatally stressed males that were subjected to combined stress and subsequent restress exhibited not only increased sensitivity of HPAS to negative feedback signals (manifested under restress conditions), but also enhanced stress system reactivity. These changes persisted to the 30th day after restress. Under basal conditions, the number of cells in the hypothalamic paraventricular nucleus of these animals expressing corticotropin-releasing hormone and vasopressin was shown to decrease progressively on days 1-30. By contrast, combined stress and restress in control animals were followed by an increase in the count of CRH-immunopositive cells in the magnocellular and parvocellular parts of the paraventricular nucleus and number of vasopressin-immunopositive cells in the magnocellular part of the nucleus (to the 10th day after restress). Our results indicate a peculiar level of functional activity of HPAS in prenatally stressed males in the stress-restress paradigm: decreased activity under basal conditions and enhanced reactivity during stress.

  5. Emergency department noise: mental activation or mental stress?

    Science.gov (United States)

    Folscher, Lindy-Lee; Goldstein, Lara Nicole; Wells, Mike; Rees, David

    2015-06-01

    Healthcare professionals working in emergency medicine are often exposed to noisy environments. We determined if there is any difference in cognitive task performance required for clinical decision-making of healthcare professionals in a quiet compared with noisy environment and to assess the subjective experience of participants with regard to performance in a noisy environment. This was a prospective cross-over study conducted at three academic hospitals in Johannesburg, South Africa. 41 doctors involved in the emergency management of patients were administered six matched and prevalidated medical questions over a 30-min period. Each doctor completed half of the questions with exposure to ambient noise (range 40-52 dB(A)) and the other half with exposure to pre-recorded background emergency department noise at 80-85 dB(A). The questions were completed in alternating quiet and noise: half of the physicians answered the odd questions in noise and half answered even numbered questions in noise. Each question was scored out of 10 and the time taken to complete each question was recorded. Overall median test scores in quiet and noise were 18.5/30 and 20/30 (p=0.2), respectively; time for test completion was longer in quiet (836 s in quiet and 819 s in noise (p=0.006)). While there was no statistically significant difference in task performance, 65% of the doctors found the noise distracting with 88% experiencing varying degrees of stress. Performance of mental tasks is maintained during noise exposure but noise exposure is associated with significant degrees of self-reported distress. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Interferon-alpha signalling in bovine adrenal chromaffin cells: involvement of signal-transducer and activator of transcription 1 and 2, extracellular signal-regulated protein kinases 1/2 and serine 31 phosphorylation of tyrosine hydroxylase.

    Science.gov (United States)

    Douglas, S A; Bunn, S J

    2009-03-01

    Adrenal medullary chromaffin cells are an integral part of the neuroendocrine system, playing an important role in the physiological adaptation to stress. In response to a wide variety of stimuli, including acetylcholine released from the splanchnic nerve, hormones such as angiotensin II or paracrine signals such as prostaglandins, chromaffin cells synthesise and secrete catecholamines and a number of biologically active peptides. This adrenal medullary output mediates a complex and diverse stress response. We report that chromaffin cells also respond both acutely and chronically to interferon (IFN)-alpha, thus providing a mechanism of interaction between the immune system and the stress response. Incubation of isolated bovine chromaffin cells maintained in culture, with IFN-alpha resulted in a rapid, transient activation of the extracellular signal-regulated protein kinase (ERK)1/2, which was maximal after 5 min. IFN-alpha mediated activation of ERK1/2 appeared to be responsible for the increased phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This tyrosine hydroxylase phosphorylation was exclusively on serine 31, with no change in the phosphorylation of serine 19 or 40. This increase in the serine 31 phosphorylation of tyrosine hydroxylase was prevented by inhibition of protein kinase C or ERK1/2 activation. Incubation with IFN-alpha also resulted in a time- and concentration-dependent phosphorylation and nuclear translocation of signal transducer and activator of transcription proteins (STAT)1 and 2. This response was maximal after approximately 60 min. Prolonged treatment with IFN-alpha (12-48 h) resulted in increased expression of STAT1 and, to a lesser extent, STAT2. Thus, these findings demonstrate that adrenal medullary chromaffin cells are responsive to IFN-alpha and provide a possible cellular mechanism by which this immune-derived signal can potentially influence and integrate with the stress response.

  7. Glycolytic enzyme activities and gene expression in Cicer arietinum exposed to water-deficit stress.

    Science.gov (United States)

    Khanna, Suruchi M; Taxak, Pooja Choudhary; Jain, Pradeep K; Saini, Raman; Srinivasan, R

    2014-08-01

    The specific activities and transcript levels of glycolytic enzymes were examined in shoots of chickpea (Cicer arietinum L.) cultivars, Pusa362 (drought tolerant) and SBD377 (drought sensitive), subjected to water-deficit stress 30 days after sowing. Water-deficit stress resulted in decrease in relative water content, chlorophyll content, plant dry weight, and NADP/NADPH ratio and increase in NAD/NADH ratio in both the cultivars. A successive decline in the specific activities of fructose-1,6-bisphosphate aldolase (aldolase), 3-phosphoglycerate kinase (PGK), and NADP-glyceraldehyde-3-phosphate dehydrogenase (NADP-GAPDH) and elevation in the specific activities of phosphoglycerate mutase (PGM) and triosephosphate isomerase (TPI) was observed in both the cultivars under stress as compared to their respective control plants. The specific activities of hexokinase, fructose-6-phosphate kinase (PFK), and NAD-GAPDH were least affected. The transcript levels of PGK and NADP-GAPDH decreased and that of glucose-6-phosphate isomerase (GPI), PGM, and PFK increased in response to water-deficit stress while water-deficit stress had no effect on the steady-state transcript levels of hexokinase, aldolase, TPI, and NAD-GAPDH. The results suggest that under water-deficit stress, the activities and transcript levels of most of the glycolytic enzymes are not significantly affected, except the increased activity and transcript level of PGM and decreased activities and transcript levels of PGK and NADP-GAPDH. Further, the glycolytic enzymes do not show much variation between the tolerant and sensitive cultivars under water deficit.

  8. [Leisure activities, resilience and mental stress in adolescents].

    Science.gov (United States)

    Karpinski, Norbert; Popal, Narges; Plück, Julia; Petermann, Franz; Lehmkuhl, Gerd

    2017-01-01

    To date, the factors contributing to emergence of resilience in different stages of adolescence have yet to be sufficiently examined. This study looks at the influence of extracurricular activities on resilience. The sample consists of 413 adolescents (f = 14.8) reporting personal problems (mood, concentration problems, behavior). The effect of extracurricular activities on resilience (gathered by the RS25) was analyzed by linear regression models. Predictor variables in these models were extracurricular activities (sport, hobbies, club memberships, household duties) and the subscales of the SDQ (Strengths and Difficulties Questionnaire). Because of the lack of homoscedasticity, two different regression models (model A: Realschule and Grammar School. Model B: Hauptschule) were specified. The explained variance of both models (model A: R = .516; model B: R = .643) is satisfactory. In both models “prosocial behavior” (SDQ) turns out to be a significant positive predictor for resilience (model A: b = 2.815; model B; b = 3.577) and emotional symptoms (model A: b = -1.697; model B: b = -2.596) are significant negative predictors for resilience. In addition, model A presents significant positive influences of sport (b = 16,314) and significant negative influences of “hyperactivity” (SDQ). In contrast, in model B “club memberships” (b = 15.775) and” peer relationship problems” (b = 1.508) are additional positive predictors. The results of the study demonstrate the important role of prosocial behavior and emotional competence in the manifestation of resilience. The effect of extracurricular activities proves to depend on the social environment (type of school). Thus, these results could form the basis for further more specific developmental programs.

  9. Moderate Thermal Stress Causes Active and Immediate Expulsion of Photosynthetically Damaged Zooxanthellae (Symbiodinium from Corals.

    Directory of Open Access Journals (Sweden)

    Lisa Fujise

    Full Text Available The foundation of coral reef biology is the symbiosis between corals and zooxanthellae (dinoflagellate genus Symbiodinium. Recently, coral bleaching, which often results in mass mortality of corals and the collapse of coral reef ecosystems, has become an important issue around the world as coral reefs decrease in number year after year. To understand the mechanisms underlying coral bleaching, we maintained two species of scleractinian corals (Acroporidae in aquaria under non-thermal stress (27°C and moderate thermal stress conditions (30°C, and we compared the numbers and conditions of the expelled Symbiodinium from these corals. Under non-thermal stress conditions corals actively expel a degraded form of Symbiodinium, which are thought to be digested by their host coral. This response was also observed at 30°C. However, while the expulsion rates of Symbiodinium cells remained constant, the proportion of degraded cells significantly increased at 30°C. This result indicates that corals more actively digest and expel damaged Symbiodinium under thermal stress conditions, likely as a mechanism for coping with environmental change. However, the increase in digested Symbiodinium expulsion under thermal stress may not fully keep up with accumulation of the damaged cells. There are more photosynthetically damaged Symbiodinium upon prolonged exposure to thermal stress, and corals release them without digestion to prevent their accumulation. This response may be an adaptive strategy to moderate stress to ensure survival, but the accumulation of damaged Symbiodinium, which causes subsequent coral deterioration, may occur when the response cannot cope with the magnitude or duration of environmental stress, and this might be a possible mechanism underlying coral bleaching during prolonged moderate thermal stress.

  10. Moderate Thermal Stress Causes Active and Immediate Expulsion of Photosynthetically Damaged Zooxanthellae (Symbiodinium) from Corals.

    Science.gov (United States)

    Fujise, Lisa; Yamashita, Hiroshi; Suzuki, Go; Sasaki, Kengo; Liao, Lawrence M; Koike, Kazuhiko

    2014-01-01

    The foundation of coral reef biology is the symbiosis between corals and zooxanthellae (dinoflagellate genus Symbiodinium). Recently, coral bleaching, which often results in mass mortality of corals and the collapse of coral reef ecosystems, has become an important issue around the world as coral reefs decrease in number year after year. To understand the mechanisms underlying coral bleaching, we maintained two species of scleractinian corals (Acroporidae) in aquaria under non-thermal stress (27°C) and moderate thermal stress conditions (30°C), and we compared the numbers and conditions of the expelled Symbiodinium from these corals. Under non-thermal stress conditions corals actively expel a degraded form of Symbiodinium, which are thought to be digested by their host coral. This response was also observed at 30°C. However, while the expulsion rates of Symbiodinium cells remained constant, the proportion of degraded cells significantly increased at 30°C. This result indicates that corals more actively digest and expel damaged Symbiodinium under thermal stress conditions, likely as a mechanism for coping with environmental change. However, the increase in digested Symbiodinium expulsion under thermal stress may not fully keep up with accumulation of the damaged cells. There are more photosynthetically damaged Symbiodinium upon prolonged exposure to thermal stress, and corals release them without digestion to prevent their accumulation. This response may be an adaptive strategy to moderate stress to ensure survival, but the accumulation of damaged Symbiodinium, which causes subsequent coral deterioration, may occur when the response cannot cope with the magnitude or duration of environmental stress, and this might be a possible mechanism underlying coral bleaching during prolonged moderate thermal stress.

  11. Work related perceived stress and muscle activity during standardized computer work among female computer users

    DEFF Research Database (Denmark)

    Larsman, P; Thorn, S; Søgaard, K

    2009-01-01

    The current study investigated the associations between work-related perceived stress and surface electromyographic (sEMG) parameters (muscle activity and muscle rest) during standardized simulated computer work (typing, editing, precision, and Stroop tasks). It was part of the European case......-control study, NEW (Neuromuscular assessment in the Elderly Worker). The present cross-sectional study was based on a questionnaire survey and sEMG measurements among Danish and Swedish female computer users aged 45 or older (n=49). The results show associations between work-related perceived stress...... and trapezius muscle activity and rest during standardized simulated computer work, and provide partial empirical support for the hypothesized pathway of stress induced muscle activity in the association between an adverse psychosocial work environment and musculoskeletal symptoms in the neck and shoulder....

  12. Extracurricular activities associated with stress and burnout in preclinical medical students.

    Science.gov (United States)

    Fares, Jawad; Saadeddin, Zein; Al Tabosh, Hayat; Aridi, Hussam; El Mouhayyar, Christopher; Koleilat, Mohamad Karim; Chaaya, Monique; El Asmar, Khalil

    2016-09-01

    This study aims to assess the prevalence of stress and burnout among preclinical medical students in a private university in Beirut, Lebanon, and evaluate the association between extracurricular involvement and stress and burnout relief in preclinical medical students. A cross-sectional survey was conducted on a random sample of 165 preclinical medical students. Distress level was measured using the 12-item General Health Questionnaire (GHQ-12) while that of burnout was measured through the Maslach Burnout Inventory-Student Survey (MBI-SS). The MBI-SS assesses three interrelated dimensions: emotional exhaustion, cynicism, and academic efficacy. Extracurricular activities were divided into four categories: physical exercise, music, reading, and social activities. All selected participants responded. A substantial proportion of preclinical medical students suffered from stress (62%) and burnout (75%). Bivariate and multivariate regression analyses revealed that being a female or a 1st year medical student correlated with higher stress and burnout. Music-related activities were correlated with lower burnout. Social activities or living with parents were associated with lower academic efficacy. The high stress and burnout levels call for action. Addressing the studying conditions and attending to the psychological wellbeing of preclinical medical students are recommendations made in the study. Copyright © 2015 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  13. Extracurricular activities associated with stress and burnout in preclinical medical students

    Directory of Open Access Journals (Sweden)

    Jawad Fares

    2016-09-01

    Full Text Available This study aims to assess the prevalence of stress and burnout among preclinical medical students in a private university in Beirut, Lebanon, and evaluate the association between extracurricular involvement and stress and burnout relief in preclinical medical students. A cross-sectional survey was conducted on a random sample of 165 preclinical medical students. Distress level was measured using the 12-item General Health Questionnaire (GHQ-12 while that of burnout was measured through the Maslach Burnout Inventory-Student Survey (MBI-SS. The MBI-SS assesses three interrelated dimensions: emotional exhaustion, cynicism, and academic efficacy. Extracurricular activities were divided into four categories: physical exercise, music, reading, and social activities. All selected participants responded. A substantial proportion of preclinical medical students suffered from stress (62% and burnout (75%. Bivariate and multivariate regression analyses revealed that being a female or a 1st year medical student correlated with higher stress and burnout. Music-related activities were correlated with lower burnout. Social activities or living with parents were associated with lower academic efficacy. The high stress and burnout levels call for action. Addressing the studying conditions and attending to the psychological wellbeing of preclinical medical students are recommendations made in the study.

  14. Does oxidative stress affect the activity of the sodium-proton exchanger?

    Science.gov (United States)

    Bober, Joanna; Kedzierska, Karolina; Kwiatkowska, Ewa; Stachowska, Ewa; Gołembiewska, Edyta; Mazur, Olech; Staniewicz, Zdzisław; Ciechanowski, Kazimierz; Chlubek, Dariusz

    2010-01-01

    Accumulation of reactive oxygen species (ROS) takes place in patients with chronic renal failure (CRF). Oxidative stress causes disorders in the activity of the sodium-proton exchanger (NHE). Studies on NHE in CRF produced results that are discrepant and difficult to interpret. The aim of this study was to demonstrate that oxidative stress had an effect on the activity of NHE. We enrolled 87 subjects divided into 4 groups: patients with CRF treated conservatively; patients with CRF hemodialyzed without glucose--HD-g(-); patients with CRF hemodialyzed with glucose--HD-g(+); controls (C). The activity of NHE, the rate of proton efflux V(max), Michaelis constant (Km), and the concentration of thiobarbituric acid-reactive substances (TBARS, an indicator of oxidative stress) in plasma, as well as the concentration of reduced glutathione in blood were determined. The concentration of TBARS was significantly higher in hemodialyzed patients before and after dialysis and in patients with CRF on conservative treatment in comparison with group C. TBARS in plasma correlated negatively with VpH(i)6.4 in group C and with V(max) and VpH(i)6.4 after HD in group HD-g(-). We found that the concentration of creatinine correlated with TBARS (p < 0.0001; r = +0.51) in the conservatively treated group. We observed a marked oxidative stress and decreased NHE activity when dialysis was done without glucose, whereas patients dialyzed with glucose demonstrated a relatively low intensity of oxidative stress.

  15. Psychosocial Stress Increases Salivary Alpha-Amylase Activity Independently from Plasma Noradrenaline Levels.

    Directory of Open Access Journals (Sweden)

    Liubov Petrakova

    Full Text Available Salivary alpha-amylase activity (sAA and plasma noradrenaline (NA concentrations are often considered to be surrogate markers of sympathetic activation in response to stress. However, despite accumulating evidence for a close association between sAA and noradrenaline and other indicators of sympathetic activity, reliability and generality of this relation remains unclear. We employed the Trier Social Stress Test (TSST in order to directly compare the responses in sAA and NA to psychological stress in healthy volunteers (n = 23. The TSST significantly increased sAA and NA plasma levels with no significant differences in females and males. However, when subjects were divided according to their NA responses into low versus high responders, both groups did not significantly differ in their sAA before, during or after stress exposure. These data suggest that in response to acute psychological stress both plasma NA levels and sAA reflect sympathetic activity, however seemed to increase independently from each other.

  16. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

    Science.gov (United States)

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-01-01

    ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297

  17. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy.

    Science.gov (United States)

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-08-02

    Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation.

  18. The stressed female brain: neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress.

    Science.gov (United States)

    Maeng, Lisa Y; Shors, Tracey J

    2013-01-01

    Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD), indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA) is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC) during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL) and infralimbic (IL) subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. About 24 h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similarly to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful life

  19. The Stressed Female Brain: Neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress

    Directory of Open Access Journals (Sweden)

    Lisa Y. Maeng

    2013-12-01

    Full Text Available Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD, indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL and infralimbic (IL subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. 24h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similar to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful

  20. A pleasant familiar odor influences perceived stress and peripheral nervous system activity during normal aging

    Directory of Open Access Journals (Sweden)

    Pauline eJoussain

    2014-02-01

    Full Text Available Effects of smells on stress have been demonstrated in animals and humans, suggesting that inhaling certain odorants may counteract the negative effects of stress. Because stress plays a key role in cerebral aging, the present study set out to examine whether positive odor effects on perceived stress can be achieved in elderly individuals. To this end, two groups of aged individuals (n=36 women, aged from 55 to 65 years, were tested. The first group was exposed for 5 days to a pleasant and, by end of exposure, familiar odor (exposure odor, whereas the other was exposed to a non-scented control stimulus. Stress and mood states were assessed before and after the 5-day odor exposure period. Psychophysiological markers were also assessed at the end of exposure, in response to the exposure odor and to a new odor. Results revealed that stress on this second exposure was decreased and zygomatic EMG activity was increased specifically in the group previously exposed to the odor (p< 0.05. Taken as a whole, these findings offer a new look at the relationship between perceived stress, olfaction and normal aging, opening up new research perspectives on the effect of olfaction on quality of life and well-being in aged individuals.

  1. Hypercholesterolemia aggravates myocardial ischemia reperfusion injury via activating endoplasmic reticulum stress-mediated apoptosis.

    Science.gov (United States)

    Wu, Nan; Zhang, Xiaowen; Jia, Pengyu; Jia, Dalin

    2015-12-01

    The effect of hypercholesterolemia on myocardial ischemia reperfusion injury (MIRI) is in controversy and the underlying mechanism is still not well understood. In the present study, we firstly detected the effects of hypercholesterolemia on MIRI and the role of endoplasmic reticulum (ER) stress-mediated apoptosis pathway in this process. The infarct size was determined by TTC staining, and apoptosis was measured by the TUNEL method. The marker proteins of ER stress response and ER stress-mediated apoptosis pathway were detected by Western blot. The results showed that high cholesterol diet-induced hypercholesterolemia significantly increased the myocardial infarct size, the release of myocardium enzyme and the ratio of apoptosis, but did not affect the recovery of cardiac function. Moreover, hypercholesterolemia also remarkably up-regulated the expressions of ER stress markers (glucose-regulated protein 78 and calreticulin) and critical molecules in ER stress-mediated apoptosis pathway (CHOP, caspase 12, phospho-JNK). In conclusion, our study demonstrated that hypercholesterolemia enhanced myocardial vulnerability/sensitivity to ischemia reperfusion injury involved in aggravation the ER stress and activation of ER stress-mediated apoptosis pathway and it gave us a new insight into the underlying mechanisms associated with hypercholesterolemia-induced exaggerated MIRI and also provided a novel target for preventing MIRI in the presence of hypercholesterolemia. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Physical activity, mindfulness meditation, or heart rate variability biofeedback for stress reduction: a randomized controlled trial.

    Science.gov (United States)

    van der Zwan, Judith Esi; de Vente, Wieke; Huizink, Anja C; Bögels, Susan M; de Bruin, Esther I

    2015-12-01

    In contemporary western societies stress is highly prevalent, therefore the need for stress-reducing methods is great. This randomized controlled trial compared the efficacy of self-help physical activity (PA), mindfulness meditation (MM), and heart rate variability biofeedback (HRV-BF) in reducing stress and its related symptoms. We randomly allocated 126 participants to PA, MM, or HRV-BF upon enrollment, of whom 76 agreed to participate. The interventions consisted of psycho-education and an introduction to the specific intervention techniques and 5 weeks of daily exercises at home. The PA exercises consisted of a vigorous-intensity activity of free choice. The MM exercises consisted of guided mindfulness meditation. The HRV-BF exercises consisted of slow breathing with a heart rate variability biofeedback device. Participants received daily reminders for their exercises and were contacted weekly to monitor their progress. They completed questionnaires prior to, directly after, and 6 weeks after the intervention. Results indicated an overall beneficial effect consisting of reduced stress, anxiety and depressive symptoms, and improved psychological well-being and sleep quality. No significant between-intervention effect was found, suggesting that PA, MM, and HRV-BF are equally effective in reducing stress and its related symptoms. These self-help interventions provide easily accessible help for people with stress complaints.

  3. Activation of endoplasmic reticulum stress response during the development of ischemic heart disease.

    Science.gov (United States)

    Azfer, Asim; Niu, Jianli; Rogers, Linda M; Adamski, Frances M; Kolattukudy, Pappachan E

    2006-09-01

    Endoplasmic reticulum (ER) stress has been found to be associated with neurodegenerative diseases and diabetes mellitus. Whether ER stress is involved in the development of heart disease is not known. Cardiac-specific expression of monocyte chemoattractant protein-1 (MCP-1) in mice causes the development of ischemic heart disease. Here we report that microarray analysis of gene expression changes in the heart of these transgenic mice revealed that a cluster of ER stress-related genes was transcriptionally activated in the heart during the development of ischemic heart disease. The gene array results were verified by quantitative real-time PCR that showed highly elevated transcript levels of genes involved in unfolded protein response such as ER and cytoplasmic chaperones, oxidoreductases, protein disulfide isomerase (PDI) family, and ER-associated degradation system such as ubiquitin. Immunoblot analysis confirmed the expression of chaperones, PDI, and ubiquitin. Immunohistochemical analyses showed that ER stress proteins were associated mainly with the degenerating cardiomyocytes. A novel ubiquitin fold modifier (Ufm1) that has not been previously associated with ER stress and not found to be induced under any condition was also found to be upregulated in the hearts of MCP mice (transgenic mice that express MCP-1 specifically in the heart). The present results strongly suggest that activation of ER stress response is involved in the development of ischemic heart disease in this murine model.

  4. Rank, job stress, psychological distress and physical activity among military personnel

    Science.gov (United States)

    2013-01-01

    Background Physical fitness is one of the most important qualities in armed forces personnel. However, little is known about the association between the military environment and the occupational and leisure-time dimensions of the physical activity practiced there. This study assessed the association of rank, job stress and psychological distress with physical activity levels (overall and by dimensions). Methods This a cross-sectional study among 506 military service personnel of the Brazilian Army examined the association of rank, job stress and psychological distress with physical activity through multiple linear regression using a generalized linear model. Results The adjusted models showed that the rank of lieutenant was associated with most occupational physical activity (β = 0.324; CI 95% 0.167; 0.481); “high effort and low reward” was associated with more occupational physical activity (β = 0.224; CI 95% 0.098; 0.351) and with less physical activity in sports/physical exercise in leisure (β = −0.198; CI 95% −0.384; −0.011); and psychological distress was associated with less physical activity in sports/exercise in leisure (β = −0.184; CI 95% −0.321; −0.046). Conclusions The results of this study show that job stress and rank were associated with higher levels of occupational physical activity. Moreover job stress and psychological distress were associated with lower levels of physical activity in sports/exercises. In the military context, given the importance of physical activity and the psychosocial environment, both of which are related to health, these findings may offer input to institutional policies directed to identifying psychological distress early and improving work relationships, and to creating an environment more favorable to increasing the practice of leisure-time physical activity. PMID:23914802

  5. Reduction of free edge peeling stress of laminated composites using active piezoelectric layers.

    Science.gov (United States)

    Huang, Bin; Kim, Heung Soo

    2014-01-01

    An analytical approach is proposed in the reduction of free edge peeling stresses of laminated composites using active piezoelectric layers. The approach is the extended Kantorovich method which is an iterative method. Multiterms of trial function are employed and governing equations are derived by taking the principle of complementary virtual work. The solutions are obtained by solving a generalized eigenvalue problem. By this approach, the stresses automatically satisfy not only the traction-free boundary conditions, but also the free edge boundary conditions. Through the iteration processes, the free edge stresses converge very quickly. It is found that the peeling stresses generated by mechanical loadings are significantly reduced by applying a proper electric field to the piezoelectric actuators.

  6. Reduction of Free Edge Peeling Stress of Laminated Composites Using Active Piezoelectric Layers

    Directory of Open Access Journals (Sweden)

    Bin Huang

    2014-01-01

    Full Text Available An analytical approach is proposed in the reduction of free edge peeling stresses of laminated composites using active piezoelectric layers. The approach is the extended Kantorovich method which is an iterative method. Multiterms of trial function are employed and governing equations are derived by taking the principle of complementary virtual work. The solutions are obtained by solving a generalized eigenvalue problem. By this approach, the stresses automatically satisfy not only the traction-free boundary conditions, but also the free edge boundary conditions. Through the iteration processes, the free edge stresses converge very quickly. It is found that the peeling stresses generated by mechanical loadings are significantly reduced by applying a proper electric field to the piezoelectric actuators.

  7. Humanin directly protects cardiac mitochondria against dysfunction initiated by oxidative stress by decreasing complex I activity.

    Science.gov (United States)

    Thummasorn, Savitree; Shinlapawittayatorn, Krekwit; Khamseekaew, Juthamas; Jaiwongkam, Thidarat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2018-01-01

    Humanin (HN) is an endogenous peptide that exerts cytoprotection against oxidative stress and apoptosis. We recently reported that Humanin analogue (HNG) pretreatment can reduce reactive oxygen species production in the heart subjected to ischemia/reperfusion (I/R) injury via attenuating mitochondrial dysfunction. However, it is unclear if HNG has direct effects on mitochondrial function against oxidative stress. Thus, we sought to determine the effects of HNG on mitochondrial function under hydrogen peroxide (H 2 O 2 ) induced oxidative stress in isolated cardiac mitochondria. We found that HNG has direct protective effects on cardiac mitochondrial function against H 2 O 2 induced oxidative stress through decreasing complex I activity. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  8. Delayed healing of a navicular stress fracture, following limited weight-bearing activity.

    Science.gov (United States)

    Robinson, Matthew; Fulcher, Mark

    2014-03-11

    This report describes a 21-year-old man, a semiprofessional football (soccer) player, with a navicular stress fracture. It highlights the difficulty in diagnosing the condition and the complications arising from inadequate management. The case discusses the optimal management of these stress fractures and the detrimental role of weight-bearing recovery. The diagnosis of navicular stress fractures is challenging, and a high index of suspicion is required. The available literature indicates that limited weightbearing is not an appropriate treatment for navicular stress injuries. Non-weight-bearing (NWB) cast immobilisation for 6-8 weeks appears to be the gold standard treatment; however, open reduction with internal fixation (ORIF) has similar success rates and an equal return-to-play time but should also be followed by a period of NWB. NWB cast immobilisation for 6 weeks remains a good second option at any time following failed limited weight-bearing activity.

  9. Reactive Oxygene Species and Thioredoxin Activity in Plants at Development of Hypergravity and Oxidative Stresses

    Science.gov (United States)

    Jadko, Sergiy

    Early increasing of reactive oxygen species (ROS) content, including H2O2, occurs in plant cells under various impacts and than these ROS can function as signaling molecules in starting of cell stress responses. At the same time thioredoxins (TR) are significant ROS and H2O2 sensors and transmitters to activation of various redox sensitive proteins, transcription factors and MAP kinases. This study was aimed to investigate early increasing of ROS and H2O2 contents and TR activity in the pea roots and in tissue culture under hypergravity and oxidative stresses. Pea roots of 3-5 days old seedlings and 12-14 days old tissue culture of Arabidopsis thaliana were studied. The pea seedlings were grown on wet filter paper and the tissue culture was grown on MS medium in dark conditions under 24oC. Hypergravity stress was induced by centrifugation at 10 and 15 g. Chemiluminescence (ChL) intensity for ROS concentration, H2O2 content and TR activity were determined. All experiments were repeated by 3-5 times. Early and reliable increasing of ChL intensity and H2O2 contents in the pea roots and in the tissue culture took place under hypergravity and oxidative stresses to 30, 60 and 90 min. At the same time TR activity increased on 11 and 19 percents only to 60 and 90 min. Thus under hypergravity and oxidative stresses in both investigated plants take place early increasing of ROS and H2O2 contents which as second messengers lead to increasing of TR activity with creating of ROS-TR stress signaling pathway.

  10. Hippocampal activation of microglia may underlie the shared neurobiology of comorbid posttraumatic stress disorder and chronic pain.

    Science.gov (United States)

    Sun, Rao; Zhang, Zuoxia; Lei, Yishan; Liu, Yue; Lu, Cui'e; Rong, Hui; Sun, Yu'e; Zhang, Wei; Ma, Zhengliang; Gu, Xiaoping

    2016-01-01

    The high comorbidity rates of posttraumatic stress disorder and chronic pain have been widely reported, but the underlying mechanisms remain unclear. Emerging evidence suggested that an excess of inflammatory immune activities in the hippocampus involved in the progression of both posttraumatic stress disorder and chronic pain. Considering that microglia are substrates underlying the initiation and propagation of the neuroimmune response, we hypothesized that stress-induced activation of hippocampal microglia may contribute to the pathogenesis of posttraumatic stress disorder-pain comorbidity. We showed that rats exposed to single prolonged stress, an established posttraumatic stress disorder model, exhibited persistent mechanical allodynia and anxiety-like behavior, which were accompanied by increased activation of microglia and secretion of pro-inflammatory cytokines in the hippocampus. Correlation analyses showed that hippocampal activation of microglia was significantly correlated with mechanical allodynia and anxiety-like behavior. Our data also showed that both intraperitoneal and intra-hippocampal injection of minocycline suppressed single prolonged stress-induced microglia activation and inflammatory cytokines accumulation in the hippocampus, and attenuated both single prolonged stress-induced mechanical allodynia and anxiety-like behavior. Taken together, the present study suggests that stress-induced microglia activation in the hippocampus may serve as a critical mechanistic link in the comorbid relationship between posttraumatic stress disorder and chronic pain. The novel concept introduces the possibility of cotreating chronic pain and posttraumatic stress disorder. © The Author(s) 2016.

  11. Evidence for ACD5 ceramide kinase activity involvement in Arabidopsis response to cold stress.

    Science.gov (United States)

    Dutilleul, Christelle; Chavarria, Heidy; Rézé, Nathalie; Sotta, Bruno; Baudouin, Emmanuel; Guillas, Isabelle

    2015-12-01

    Although sphingolipids emerged as important signals for plant response to low temperature, investigations have been limited so far to the function of long-chain base intermediates. The formation and function of ceramide phosphates (Cer-Ps) in chilled Arabidopsis were explored. Cer-Ps were analysed by thin layer chromatography (TLC) following in vivo metabolic radiolabelling. Ceramide kinase activity, gene expression and growth phenotype were determined in unstressed and cold-stressed wild type (WT) and Arabidopsis ceramide kinase mutant acd5. A rapid and transient formation of Cer-P occurs in cold-stressed WT Arabidopsis plantlets and cultured cells, which is strongly impaired in acd5 mutant. Although concomitant, Cer-P formation is independent of long-chain base phosphate (LCB-P) formation. No variation of ceramide kinase activity was measured in vitro in WT plantlets upon cold stress but the activity in acd5 mutant was further reduced by cold stress. At the seedling stage, acd5 response to cold was similar to that of WT. Nevertheless, acd5 seed germination was hypersensitive to cold and abscisic acid (ABA), and ABA-dependent gene expression was modified in acd5 seeds when germinated at low temperature. Our data involve for the first time Cer-P and ACD5 in low temperature response and further underline the complexity of sphingolipid signalling operating during cold stress. © 2015 John Wiley & Sons Ltd.

  12. An investigation on some medicinal compounds and PAL activity in two olive cultivars under cold stress

    Directory of Open Access Journals (Sweden)

    Davood Bakhshi

    2014-03-01

    Full Text Available Olive (Olea europaea L. is an evergreen tree, traditionally cultivated in the Mediterranean area. Olive tree cultivation is curtailed in cold areas because they can rarely tolerate temperatures at and below -12°C. In recent years, because of high demands for olive oil and its fruit, the cultivation of olive trees has been increased in Iran. To investigate the impact of cold stress on the content of total phenol, antioxidant activity and three major phenolic compounds including oleuropein, hydroxyl tyrosol and tyrosol and also phenylalanine ammonialyase (PAL activity, one-year old olive cultivars of Sevillana and Frantoio were exposed to low temperatures of 10, 5, 0, -5, -10, -15, -20 and control 20°C for 12 h, gradually. The results indicated that total phenol content, antioxidant activity and PAL activity were increased under cold stress in both investigated cultivars. However, PAL activity in Sevillana showed significant decrease at and below -5°C while in Frantoio cultivar there was significant dwindling blew -10°C. Oleuropein content significantly increased during cold stress but, tyrosol and hydroxy tyrosol content decreased in both cultivars compared with the controls. According to the current results, Frantoio and Sevillana showed different resistance under cold stress, so that Frantoio was more resistant than Sevillana.

  13. Effects of psychosocial stress on psychophysiological activity during risky decision-making in male adolescents.

    Science.gov (United States)

    Stankovic, Aleksandra; Fairchild, Graeme; Aitken, Michael R F; Clark, Luke

    2014-07-01

    Adolescence is characterized by increases in both perceived stress and risk-taking, although the effects of stress on risk-sensitive decision-making have received little attention in adolescent groups. We report psychophysiological data from the healthy control group of a larger project examining neuroendocrine and neuropsychological function in boys with conduct disorder. The present analysis focussed on healthy male adolescents (n = 66) performing a decision-making task that involved selection between two wheel-of-fortune gambles. The task was completed in a neutral state, and again following a psychosocial stress induction that robustly increased salivary cortisol levels and baseline autonomic arousal. Task-related changes in electrodermal activity (EDA) and heart rate (HR) were monitored during the receipt of win and loss outcomes. On gamble choice, stress attenuated the difference in risk taking between the losses-only and wins-only trials (the 'reflection effect') and reduced risk-taking on one further gamble type (i.e. a stress × gamble type interaction). In the neutral condition, EDA and HR deceleration responses were significantly greater for losses compared to wins. This physiological differentiation of losses and wins was reduced under stress, with a significant attenuation of the HR deceleration response. In addition, higher trait impulsivity scores predicted reduced EDA differentiation of the outcomes, and reduced EDA stress reactivity. As a limitation, the order of neutral and stress sessions was not counter-balanced. Reduced psychophysiological discrimination between positive and negative outcomes may contribute to the effects of stress on risky decision-making in adolescents. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Free convection in parallelogram-shaped enclosures with isothermal active walls: viscous shear stress in active systems

    Energy Technology Data Exchange (ETDEWEB)

    Baieri, A; Zarco-Pernia, E; Laraqi, N [Laboratoire de Thermique Interfaces Environnement, LTIE-GTE EA 4415, Universite Paris Ouest, 50 Rue de Sevres, F-92410 Ville d' Avray (France); Garcia de Maria, J-M, E-mail: abairi@u-paris10.fr, E-mail: e.zarcopernia@yahoo.fr, E-mail: nlaraqi@u-paris10.fr, E-mail: juanmario.garcia@upm.es [Departamento de Fisica Aplicada, Universidad Politecnica de Madrid, Ronda de Valencia 3, E-28012 Madrid (Spain)

    2012-10-01

    Thermocouples are often used for thermoregulation of active thermal systems. When the junctions of these sensors are under a natural convection flow, it is necessary to take into account the viscous stress that can affect the measurement of temperature and therefore the regulation set points. The main objective of this work is to study the viscous shear stress taking place close to the active hot wall in closed air-filled cavities of parallelogrammic shape. The influence of shear stress is examined for different inclination angles of the cavity and large Rayleigh numbers which are usual in thermal applications. The local stress distributions are presented for the steady state for all the geometric configurations considered. The Nusselt number at the hot wall as well as the temperature and stream function distributions in the cavities are also included. The findings obtained from the numerical simulation using the finite volume method are validated by thermal measurements on an experimental cavity. This study confirms the need to properly choose the location of thermocouples in the reference cell used for controlling the active system. (paper)

  15. The Nutrient Stress-induced Small GTPase Rab5 Contributes to the Activation of Vesicle Trafficking and Vacuolar Activity*

    Science.gov (United States)

    Nakatsukasa, Kunio; Kanada, Akira; Matsuzaki, Mariko; Byrne, Stuart D.; Okumura, Fumihiko; Kamura, Takumi

    2014-01-01

    Rab family small GTPases regulate membrane trafficking by spatiotemporal recruitment of various effectors. However, it remains largely unclear how the expression and functions of Rab proteins are regulated in response to extracellular or intracellular stimuli. Here we show that Ypt53, one isoform of Rab5 in Saccharomyces cerevisiae, is up-regulated significantly under nutrient stress. Under non-stress conditions, Vps21, a constitutively expressed Rab5 isoform, is crucial to Golgi-vacuole trafficking and to vacuolar hydrolase activity. However, when cells are exposed to nutrient stress for an extended period of time, the up-regulated Ypt53 and the constitutive Vps21 function redundantly to maintain these activities, which, in turn, prevent the accumulation of reactive oxygen species and maintain mitochondrial respiration. Together, our results clarify the relative roles of these constitutive and nutrient stress-inducible Rab5 proteins that ensure adaptable vesicle trafficking and vacuolar hydrolase activity, thereby allowing cells to adapt to environmental changes. PMID:24923442

  16. Adrenal stress hormones, amygdala activation, and memory for emotionally arousing experiences.

    Science.gov (United States)

    Roozendaal, Benno; Barsegyan, Areg; Lee, Sangkwan

    2008-01-01

    Extensive evidence indicates that stress hormones released from the adrenal glands are critically involved in memory consolidation of emotionally arousing experiences. Epinephrine or glucocorticoids administered after exposure to emotionally arousing experiences enhance the consolidation of long-term memories of these experiences. Our findings indicate that adrenal stress hormones influence memory consolidation via interactions with arousal-induced activation of noradrenergic mechanisms within the amygdala. In turn, the amygdala regulates memory consolidation via its efferent projections to many other brain regions. In contrast to the enhancing effects on consolidation, high circulating levels of stress hormones impair memory retrieval and working memory. Such effects also require noradrenergic activation of the amygdala and interactions with other brain regions.

  17. [Association between occupational stress and aminotransferase activity in patients with metabolic syndrome].

    Science.gov (United States)

    Zhao, H; Song, L; Qiang, Y; Liu, H R; Qiu, F Y; Li, X Z; Song, H

    2016-12-20

    Objective: To investigate the association between occupational stress and activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in patients with metabolic syndrome. Methods: A case-control study was performed. According to inclusion and exclusion criteria, among the staff members of enterprises and public institutions aged 20~60 years who underwent physical examination in The Affiliated Hospital of Ningxia Medical University and The People's Hospital of Wuzhong from October 2011 to October 2012, 622 patients with metabolic syndrome who did not have a blood relationship with each other were enrolled as case group, and 600 healthy staff members who also did not have a blood relationshipwith each otherwere enrolled as control group. Questionnaire investigation, chronic occupational stress investigation, physical examination, and laboratory tests were performed for all subjects. Results: Compared with the control group, the case group had significantly higher serum levels and abnormal rates of AST and ALT ( t =-4.338 and-5.485, χ(2)=11.168 and 34.302, all P level and abnormal rate of AST between the subgroups with different occupational stresses in both groups ( F =2.192 and 2.567, χ(2)=2.694 and 5.402, all P >0.05) , but there were significant differencesbetween the subgroups in all subjects ( F =5.005, χ(2)=6.398, all P level and abnormal rate of ALT between thesubgroups with different occupational stresses in the case group, the control group, and all subjects ( F =0.845, 0.450, and 1.416, χ(2)=2.564, 1.344, and 3.147, all P >0.05) . The partial correlation analysis showed that the total score of occupational stress was positively correlated withthe serum level of AST ( r =0.071, P level of ALT ( r =-0.044, P >0.05) , and that the serum level of AST was positively correlated with that of ALT ( r =0.736, P stress was positively correlated with the serum level of AST ( r =0.069, P level of ALT ( r =-0.042, P >0.05) , and the serum level

  18. Oxidative stress and antioxidant activity in orbital fibroadipose tissue in Graves' ophthalmopathy.

    Science.gov (United States)

    Hondur, Ahmet; Konuk, Onur; Dincel, Aylin Sepici; Bilgihan, Ayse; Unal, Mehmet; Hasanreisoglu, Berati

    2008-05-01

    To investigate the oxidative stress and antioxidant activity in the orbit in Graves' ophthalmopathy (GO). Orbital fibroadipose tissue samples were obtained from 13 cases during orbital fat decompression surgery. All cases demonstrated features of moderate or severe GO according to the European Group on Graves' Orbitopathy classification. The disease activity was evaluated with the Clinical Activity Score, and the clinical features of GO were evaluated with the Ophthalmopathy Index. Orbital fibroadipose tissue samples of 8 patients without any thyroid or autoimmune disease were studied as controls. In the tissue samples, lipid hydroperoxide level was examined to determine the level of oxidative stress; glutathione level to determine antioxidant level; superoxide dismutase, glutathione reductase, and glutathione peroxidase activities to determine antioxidant activity. Lipid hydroperoxide level and all three antioxidant enzyme activities were found to be significantly elevated, while glutathione level significantly diminished in tissue samples from GO cases compared to controls (p < 0.05). Glutathione levels in tissue samples of GO cases showed negative correlation with Ophthalmopathy Index (r = -0.59, p < 0.05). The antioxidant activity in the orbit is enhanced in GO. However, the oxidative stress appears to be severe enough to deplete the tissue antioxidants and leads to oxidative tissue damage. This study may support the possible value of antioxidant treatment in GO.

  19. Changes in gene expression and catalase activity in Oryza sativa L. under abiotic stress.

    Science.gov (United States)

    Vighi, I L; Benitez, L C; do Amaral, M N; Auler, P A; Moraes, G P; Rodrigues, G S; da Maia, L C; Pinto, L S; Braga, E J B

    2016-11-03

    Different rice (Oryza sativa L.) genotypes were subjected to high salinity and low temperature (150 mM NaCl and 13°C, respectively) for 0, 6, 24, 48, or 72 h. We evaluated the simultaneous expression of the genes OsCATA, OsCATB, and OsCATC, correlated gene expression with enzyme activity, and verified the regulation of these genes through identification of cis-elements in the promoter region. The hydrogen peroxide content increased in a tolerant genotype and decreased in a sensitive genotype under both stress conditions. Lipid peroxidation increased in the tolerant genotype when exposed to cold, and in the sensitive genotype when exposed to high salinity. Catalase activity significantly increased in both genotypes when subjected to 13°C. In the tolerant genotype, OsCATA and OsCATB were the most responsive to high salinity and cold, while in the sensitive genotype, OsCATA and OsCATC responded positively to saline stress, as did OsCATA and OsCATB to low temperature. Cis-element analysis identified different regulatory sequences in the catalase promoter region of each genotype. The sensitive genotype maintained a better balance between hydrogen oxyacid levels, catalase activity, and lipid peroxidation under low temperature than the resistant genotype. OsCATA and OsCATB were the most responsive in the salt-tolerant genotype to cold, OsCATA and OsCATC were the most responsive to saline stress, and OsCATA and OsCATB were the most responsive to chilling stress in the sensitive genotype. There were positive correlations between catalase activity and OsCATB expression in the tolerant genotype under saline stress and in the sensitive genotype under cold stress.

  20. Palm kernel cake extract exerts hepatoprotective activity in heat-induced oxidative stress in chicken hepatocytes.

    Science.gov (United States)

    Oskoueian, Ehsan; Abdullah, Norhani; Idrus, Zulkifli; Ebrahimi, Mahdi; Goh, Yong Meng; Shakeri, Majid; Oskoueian, Armin

    2014-10-02

    Palm kernel cake (PKC), the most abundant by-product of oil palm industry is believed to contain bioactive compounds with hepatoprotective potential. These compounds may serve as hepatoprotective agents which could help the poultry industry to alleviate adverse effects of heat stress on liver function in chickens. This study was performed to evaluate the hepatoprotective potential of PKC extract in heat-induced oxidative stress in chicken hepatocytes. The nature of the active metabolites and elucidation of the possible mechanism involved were also investigated. The PKC extract possessed free radical scavenging activity with values significantly (p < 0.05) lower than silymarin as the reference antioxidant. Heat-induced oxidative stress in chicken hepatocyte impaired the total protein, lipid peroxidation and antioxidant enzymes activity significantly (p < 0.05). Treatment of heat-induced hepatocytes with PKC extract (125 μg/ml) and silymarin as positive control increased these values significantly (p < 0.05). The real time PCR and western blot analyses revealed the significant (p < 0.05) up-regulation of oxidative stress biomarkers including TNF-like, IFN-γ and IL-1β genes; NF-κB, COX-2, iNOS and Hsp70 proteins expression upon heat stress in chicken hepatocytes. The PKC extract and silymarin were able to alleviate the expression of all of these biomarkers in heat-induced chicken hepatocytes. The gas chromatography-mass spectrometry analysis of PKC extract showed the presence of fatty acids, phenolic compounds, sugar derivatives and other organic compounds such as furfural which could be responsible for the observed hepatoprotective activity. Palm kernel cake extract could be a potential agent to protect hepatocytes function under heat induced oxidative stress.

  1. Changes of Germination Properties, Photosynthetic Pigments and Anti Oxidant Enzymes Activity of Safflower as Affected by Drought and Salinity Stresses

    Directory of Open Access Journals (Sweden)

    A Sirousmehr

    2015-01-01

    Full Text Available To evaluate the effects of drought and salinity stresses on some germination characteristics, contents of photosynthetic pigments and antioxidant enzymes (CAT, APX and GPX in the leaves of safflower, a factorial experiment based on CRD was conducted during 2012 at both laboratory and greenhouse of Zabol University with four replications. To expose the plants to drought (0, -6 and -8 bars and salinity stresses (5, 10 and 15 ds.m-1 PEG 6000 and NaCl were used respectively. The results indicated that the effects of factors on germination percentage and rate, chlorophyll a and b contents and antioxidants enzymes activities were significant. The result of laboratory study revealed a reduction in percentage and speed of germination when plants exposed to negative osmotic potential. Photosynthetic pigments of plant leaves grown in greenhouse significantly decreased by increasing drought and salinity stresses. Increasing drought stress along with soluble salts changed the activity of some antioxidant enzymes. Enzymes’ activity of both CAT and GPX were increased when the plants expose to PEG drought stress, but decreased against the levels of salt stress. APX activity also increased due to drought stress. Interactive effects of drought×salinity stresses indicated that under lower stress GPX enzymes increased salinity, and under severe stress APX was highly increased. It means the production and activity of plant defensive system like these enzymes in recent tensions and leads to protect or make plants tolerate against oxidative stress induced by drought and salinity.

  2. Does pulsed low intensity ultrasound allow early return to normal activities when treating stress fractures? A review of one tarsal navicular and eight tibial stress fractures.

    Science.gov (United States)

    Brand, J C; Brindle, T; Nyland, J; Caborn, D N; Johnson, D L

    1999-01-01

    We sought to evaluate the efficacy of daily pulsed low intensity ultrasound (LIUS) with early return to activities for the treatment of lower extremity stress fractures. Eight patients (2 males, 6 females) with radiographic and bone scan confirmed tibial stress fractures participated in this study. Additionally, a case report of a tarsal navicular stress fracture is described. All patients except one were involved in athletics. Prior to the study, subjects completed a 5 question, 10 cm visual analog scale (VAS) regarding pain level (10 = extreme pain, 1 = no pain) and were assessed for functional performance. Subjects received 20-minute LIUS treatments 5 times a week for 4 weeks. Subjects maintained all functional activities during the treatment period. Seven patients with posterior-medial stress fractures participated without a brace. Subjects were re-tested after 4 weeks of treatment. Mann-Whitney U tests (VAS data) and paired t-tests (functional tests) assessed statistical significance (psports was prescribed for the patients with the tibial stress fractures. The patient with the anterior tibial stress fracture underwent tibial intramedullary nailing at the conclusion of a season of play. In this uncontrolled experience, treatment of tibial stress fractures with daily pulsed LIUS was effective in pain relief and early return to vigorous activity without bracing for the patients with posterior-medial stress fractures.

  3. Glucocorticoid receptor number predicts increase in amygdala activity after severe stress

    NARCIS (Netherlands)

    Geuze, Elbert; van Wingen, Guido A.; van Zuiden, Mirjam; Rademaker, Arthur R.; Vermetten, Eric; Kavelaars, Annemieke; Fernández, Guillén; Heijnen, Cobi J.

    2012-01-01

    Introduction: Individuals who are exposed to a traumatic event are at increased risk of developing psychiatric disorders such as posttraumatic stress disorder (PTSD). Studies have shown that increased amygdala activity is frequently found in patients with PTSD. In addition, pre-trauma glucocorticoid

  4. About the activation volume for cross-slip in Cu at high stresses

    Czech Academy of Sciences Publication Activity Database

    Couteau, O.; Kruml, Tomáš; Martin, J. L.

    2011-01-01

    Roč. 59, 10 (2011), s. 4207-4215 ISSN 1359-6454 Institutional research plan: CEZ:AV0Z20410507 Keywords : Cross-slip * Thermally activated processes * Stress relaxation technique Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.755, year: 2011

  5. Physical Activity Attenuates Intermittent Hypoxia-induced Spatial Learning Deficits and Oxidative Stress

    OpenAIRE

    Gozal, David; Nair, Deepti; Goldbart, Aviv D.

    2010-01-01

    Rationale: Exposure to intermittent hypoxia (IH), such as occurs in sleep-disordered breathing, is associated with substantial cognitive impairments, oxidative stress and inflammation, and increased neuronal cell losses in brain regions underlying learning and memory in rats. Physical activity (PA) is now recognized as neuroprotective in models of neuronal injury and degeneration.

  6. Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5.

    Science.gov (United States)

    Kino, Tomoshige; Takatori, Hiroaki; Manoli, Irini; Wang, Yonghong; Tiulpakov, Anatoly; Blackman, Marc R; Su, Yan A; Chrousos, George P; DeCherney, Alan H; Segars, James H

    2009-02-10

    Extracellular hyperosmolarity, or osmotic stress, generally caused by differences in salt and macromolecule concentrations across the plasma membrane, occurs in lymphoid organs and at inflammatory sites. The response of immune cells to osmotic stress is regulated by nuclear factor of activated T cells 5 (NFAT5), a transcription factor that induces the expression of hyperosmolarity-responsive genes and stimulates cytokine production. We report that the guanine nucleotide exchange factor (GEF) Brx [also known as protein kinase A-anchoring protein 13 (AKAP13)] is essential for the expression of nfat5 in response to osmotic stress, thus transmitting the extracellular hyperosmolarity signal and enabling differentiation of splenic B cells and production of immunoglobulin. This process required the activity of p38 mitogen-activated protein kinase (MAPK) and NFAT5 and involved a physical interaction between Brx and c-Jun N-terminal kinase (JNK)-interacting protein 4 (JIP4), a scaffold molecule specific to activation of the p38 MAPK cascade. Our results indicate that Brx integrates the responses of immune cells to osmotic stress and inflammation by elevating intracellular osmolarity and stimulating the production of cytokines.

  7. Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis

    Directory of Open Access Journals (Sweden)

    Maria Razzoli

    2016-01-01

    Conclusion: Our findings demonstrate that thermogenesis and BAT function are determinant of the resilience or vulnerability to stress-induced obesity. Our data support a model in which adrenergic and purinergic pathways exert complementary/synergistic functions in BAT, thus suggesting an alternative to βARs agonists for the activation of human BAT.

  8. On the Eulerian formulation of a stress induced platelet activation function

    Czech Academy of Sciences Publication Activity Database

    Bodnár, Tomáš

    2014-01-01

    Roč. 257, November (2014), s. 91-95 ISSN 0025-5564 Institutional support: RVO:61388998 Keywords : blood flow * platelet * stress * activation Subject RIV: BK - Fluid Dynamics Impact factor: 1.303, year: 2014 http://www.sciencedirect.com/science/article/pii/S0025556414001163

  9. Evaluation of oxidative stress parameters and metabolic activities of nurses working day and night shifts

    Directory of Open Access Journals (Sweden)

    Turgay Ulas

    Full Text Available The aim of this study was to evaluate the oxidative stress and metabolic activities of nurses working day and night shifts. Intensive care unit (ICU (n=70 and ordinary service (OS nurses (n=70 were enrolled in the study. Just before and the end of the shifts, blood samples were obtained to measure the participants' oxidative stress parameters. Metabolic activities were analyzed using the SenseWear Armband. Oxidative stress parameters were increased at the end of the shifts for all OS and ICU nurses compared to the beginning of the shifts. Compared to the OS nurses, the ICU nurses' TAS, TOS, and OSI levels were not significantly different at the end of the day and night shifts. The metabolic activities of the OS and ICU nurses were found to be similar. As a result, the OS and ICU nurses' oxidative stress parameters and metabolic activities were not different, and all of the nurses experienced similar effects from both the day and night shifts.

  10. Microscopic origins of anisotropic active stress in motor-driven nematic liquid crystals.

    Science.gov (United States)

    Blackwell, Robert; Sweezy-Schindler, Oliver; Baldwin, Christopher; Hough, Loren E; Glaser, Matthew A; Betterton, M D

    2016-03-14

    The cytoskeleton, despite comprising relatively few building blocks, drives an impressive variety of cellular phenomena ranging from cell division to motility. These building blocks include filaments, motor proteins, and static crosslinkers. Outside of cells, these same components can form novel materials exhibiting active flows and nonequilibrium contraction or extension. While dipolar extensile or contractile active stresses are common in nematic motor-filament systems, their microscopic origin remains unclear. Here we study a minimal physical model of filaments, crosslinking motors, and static crosslinkers to dissect the microscopic mechanisms of stress generation in a two-dimensional system of orientationally aligned rods. We demonstrate the essential role of filament steric interactions which have not previously been considered to significantly contribute to active stresses. With this insight, we are able to tune contractile or extensile behavior through the control of motor-driven filament sliding and crosslinking. This work provides a roadmap for engineering stresses in active liquid crystals. The mechanisms we study may help explain why flowing nematic motor-filament mixtures are extensile while gelled systems are contractile.

  11. The influence of motor activity on the development of cardiac arrhythmias during experimental emotional stress

    Science.gov (United States)

    Ulyaninskiy, L. S.; Urmancheyeva, T. G.; Stepanyan, Y. P.; Fufacheva, A. A.; Gritsak, A. V.; Kuznetsova, B. A.; Kvitka, A. A.

    1982-01-01

    Experimental emotional stress which can produce various disorders of cardiac rhythm: sinus tachycardia, atrial fibrillation, ventricular, extrasystoles and paroxysmal ventricular tachysystoles was studied. In these conditions the adrenalin content in the blood and myocardium is increased 3 to 4 times. It is found that moderate motor activity leads to a relative decrease of adrenalin in the myocardium and arrest of cardiac arrhythmias.

  12. Steady activity of microfractures on geological faults loaded by mining stress

    CSIR Research Space (South Africa)

    Naoi, M

    2015-05-01

    Full Text Available -scale irregularities of the interface. On the other hand, many other mapped faults near the planar AE clusters were not accompanied by AE activities, despite the fact that these quiet faults were subjected to a similar stress history. The presence or absence of AE...

  13. The effects of drought stress on the activity of acid phosphatase and ...

    African Journals Online (AJOL)

    A model of drought was created on pigweed and the effects of drought stress on the activity of acid phosphatase and its protective enzymes were examined. The pot-cultured pigweeds were divided into 4 groups (ten plants per group) when they reached 6 leaves. (1) In the control group, the culture media contained 70 ...

  14. Effects of Aluminum Stress on Protective Enzyme Activity in Tie Guanyin leaves

    Science.gov (United States)

    Sun, JingWei; Du, NaiChen; Zhang, YunFeng

    2018-01-01

    The experiment was adopted to study the change of SOD, CAT and POD activity of Tie guanyin (new leaf and old leaf blade of different concentrations of aluminum stress; in this paper, 0 (CK), 40, 200, four gradients of 400mg/L concentration of Al3+ in acidic conditions, Tieguanyin tea leaf SOD, cat and POD activity changes. The results showed that high concentrations of aluminum stress on antioxidant enzyme system activity cannot continue to increase; at the same time showed that SOD is sensitive to aluminum toxicity concentration change, its sensitivity is higher than CAT and POD, SOD and CAT activity and the aging and decline of plant There was a positive correlation.

  15. Influence of Oxidative Stress on Biocontrol Activity ofCryptococcus laurentiiagainst Blue Mold on Peach Fruit.

    Science.gov (United States)

    Zhang, Zhanquan; Chen, Jian; Li, Boqiang; He, Chang; Chen, Yong; Tian, Shiping

    2017-01-01

    The limitations of chemical fungicides for the control of postharvest diseases have recently become more apparent. The utilization of antagonistic microorganisms is a promising alternative to that of fungicides to control postharvest decay. In previous studies, the antagonistic yeast Cryptococcus laurentii has shown excellent effects of biocontrol and great potential for practical application. Adverse conditions, such as oxidative stress, limit the practical application of antagonistic yeast. In this study, we investigated the oxidative stress tolerance of C. laurentii and the associated mechanisms. The results indicated that exogenous oxidative stress has a significant effect on the viability and biocontrol efficiency of C. laurentii . H 2 O 2 -induced oxidative stress led to the accumulation of reactive oxygen species. The results of flow cytometric analysis suggested that apoptosis is responsible for the reduced survival rate of C. laurentii under oxidative stress. Using tests of antioxidant activity, we found that C. laurentii could employ enzymatic systems to resist exogenous oxidative stress. The addition of exogenous glutathione, a non-enzymatic antioxidant, to the media can significantly enhance oxidative tolerance and biocontrol efficiency of C. laurentii .

  16. Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase

    DEFF Research Database (Denmark)

    Sayed, M; Kim, S O; Salh, B S

    2000-01-01

    Protein kinase CK2 has been implicated in the regulation of a wide range of proteins that are important in cell proliferation and differentiation. Here we demonstrate that the stress signaling agents anisomycin, arsenite, and tumor necrosis factor-alpha stimulate the specific enzyme activity of CK2...... to be an allosteric mechanism. Furthermore, we demonstrate that anisomycin- and tumor necrosis factor-alpha-induced phosphorylation of p53 at Ser-392, which is important for the transcriptional activity of this growth suppressor protein, requires p38 MAP kinase and CK2 activities....

  17. Discovery of a Stress-Activated Protein Kinase Inhibitor for Lymphatic Filariasis.

    Science.gov (United States)

    Tummalapalli, Sreedhar R; Bhat, Rohit; Chojnowski, Agnieszka; Prorok, Monika; Kreiss, Tamara; Goldberg, Ronald; Canan, Stacie; Hawryluk, Natalie; Mortensen, Deborah; Khetani, Vikram; Zeldis, Jerome; Siekierka, John J; Rotella, David P

    2018-03-08

    Lymphatic filariasis infects over 120 million people worldwide and can lead to significant disfigurement and disease. Resistance is emerging with current treatments, and these therapies have dose limiting adverse events; consequently new targets are needed. One approach to achieve this goal is inhibition of parasitic protein kinases involved in circumventing host defense mechanisms. This report describes structure-activity relationships leading to the identification of a potent, orally bioavailable stress activated protein kinase inhibitor that may be used to investigate this hypothesis.

  18. Validating the Heat Stress Indices for Using In Heavy Work Activities in Hot and Dry Climates.

    Science.gov (United States)

    Hajizadeh, Roohalah; Golbabaei, Farideh; Farhang Dehghan, Somayeh; Beheshti, Mohammad Hossein; Jafari, Sayed Mohammad; Taheri, Fereshteh

    2016-01-01

    Necessity of evaluating heat stress in the workplace, require validation of indices and selection optimal index. The present study aimed to assess the precision and validity of some heat stress indices and select the optimum index for using in heavy work activities in hot and dry climates. It carried out on 184 workers from 40 brick kilns workshops in the city of Qom, central Iran (as representative hot and dry climates). After reviewing the working process and evaluation the activity of workers and the type of work, environmental and physiological parameters according to standards recommended by International Organization for Standardization (ISO) including ISO 7243 and ISO 9886 were measured and indices were calculated. Workers engaged in indoor kiln experienced the highest values of natural wet temperature, dry temperature, globe temperature and relative humidity among studied sections (Pstress index (HSI) indices had the highest correlation with other physiological parameters among the other heat stress indices. Relationship between WBGT index and carotid artery temperature (r=0.49), skin temperature (r=0.319), and oral temperature (r=0.203) was statistically significant (P=0.006). Since WBGT index, as the most applicable index for evaluating heat stress in workplaces is approved by ISO, and due to the positive features of WBGT such as ease of measurement and calculation, and with respect to some limitation in application of HSI; WBGT can be introduced as the most valid empirical index of heat stress in the brick workshops.

  19. Hsp70-GlcNAc-binding activity is released by stress, proteasome inhibition, and protein misfolding

    International Nuclear Information System (INIS)

    Guinez, Celine; Mir, Anne-Marie; Leroy, Yves; Cacan, Rene; Michalski, Jean-Claude; Lefebvre, Tony

    2007-01-01

    Numerous recent works strengthen the idea that the nuclear and cytosolic-specific O-GlcNAc glycosylation protects cells against injuries. We have first investigated O-GlcNAc level and Hsp70-GlcNAc-binding activity (HGBA) behaviour after exposure of HeLa and HepG 2 cells to a wide variety of stresses. O-GlcNAc and HGBA responses were different according to the stress and according to the cell. HGBA was released for almost all stresses, while O-GlcNAc level was modified either upwards or downwards, depending to the stress. Against all expectations, we demonstrated that energy charge did not significantly vary with stress whereas UDP-GlcNAc pools were more dramatically affected even if differences in UDP-GlcNAc contents were not correlated with O-GlcNAc variations suggesting that O-GlcNAc transferase is itself finely regulated during cell injury. Finally, HGBA could be triggered by proteasome inhibition and by L-azetidine-2-carboxylic acid (a proline analogue) incorporation demonstrating that protein misfolding is one of the key-activator of this Hsp70 property

  20. Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging.

    Science.gov (United States)

    Gambino, Valentina; De Michele, Giulia; Venezia, Oriella; Migliaccio, Pierluigi; Dall'Olio, Valentina; Bernard, Loris; Minardi, Simone Paolo; Della Fazia, Maria Agnese; Bartoli, Daniela; Servillo, Giuseppe; Alcalay, Myriam; Luzi, Lucilla; Giorgio, Marco; Scrable, Heidi; Pelicci, Pier Giuseppe; Migliaccio, Enrica

    2013-06-01

    Oxidative stress is a determining factor of cellular senescence and aging and a potent inducer of the tumour-suppressor p53. Resistance to oxidative stress correlates with delayed aging in mammals, in the absence of accelerated tumorigenesis, suggesting inactivation of selected p53-downstream pathways. We investigated p53 regulation in mice carrying deletion of p66, a mutation that retards aging and confers cellular resistance and systemic resistance to oxidative stress. We identified a transcriptional network of ~200 genes that are repressed by p53 and encode for determinants of progression through mitosis or suppression of senescence. They are selectively down-regulated in cultured fibroblasts after oxidative stress, and, in vivo, in proliferating tissues and during physiological aging. Selectivity is imposed by p66 expression and activation of p44/p53 (also named Delta40p53), a p53 isoform that accelerates aging and prevents mitosis after protein damage. p66 deletion retards aging and increases longevity of p44/p53 transgenic mice. Thus, oxidative stress activates a specific p53 transcriptional response, mediated by p44/p53 and p66, which regulates cellular senescence and aging. © 2013 John Wiley & Sons Ltd and the Anatomical Society.

  1. Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells.

    Directory of Open Access Journals (Sweden)

    Li Fang

    Full Text Available Albuminuria contributes to the progression of tubulointerstitial fibrosis. Although it has been demonstrated that ongoing albuminuria leads to tubular injury manifested by the overexpression of numerous proinflammatory cytokines, the mechanism remains largely unknown. In this study, we found that the inflammasome activation which has been recognized as one of the cornerstones of intracellular surveillance system was associated with the severity of albuminuria in the renal biopsies specimens. In vitro, bovine serum albumin (BSA could also induce the activation of NLRP3 inflammasome in the cultured kidney epithelial cells (NRK-52E. Since there was a significant overlap of NLRP3 with the ER marker calreticulin, the ER stress provoked by BSA seemed to play a crucial role in the activation of inflammasome. Here, we demonstrated that the chemical chaperone taurine-conjugated ursodeoxycholic acid (TUDCA which was proved to be an enhancer for the adaptive capacity of ER could attenuate the inflammasome activation induced by albuminuria not only in vitro but also in diabetic nephropathy. Taken together, these data suggested that ER stress seemed to play an important role in albuminuria-induced inflammasome activation, elimination of ER stress via TUDCA might hold promise as a novel avenue for preventing inflammasome activation ameliorating kidney epithelial cells injury induced by albuminuria.

  2. SIRT1 deacetylase activity and the maintenance of protein homeostasis in response to stress: an overview.

    Science.gov (United States)

    Monteiro, Jomar Patricio; Cano, Maria Isabel Nogueira

    2011-02-01

    The present review intends to summarize the, yet preliminary, but very important emerging data underlining the functions exerted by the nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase SIRT1 on protein homeostasis. The main focus of the discussion is the cooperation between SIRT1 and the heat shock factor 1 (HSF1) responsible for activating the transcription of molecular chaperones, the protein-protective factors that resolve damaged/misfolded and aggregated proteins generated by heat stress or metabolism. SIRT1, a mammalian ortholog of the yeast silent information regulator 2, is a stress activated protein deacetylase that contributes to life-span extension by regulating different cell survival pathways, including replicative senescence, inflammation and resistance to hypoxic and heat stress. Phosphorylation is the major mechanism controlling the level and function of SIRT1 required for normal cell cycle progression and cell survival under stress conditions. Phosphorylated SIRT1 deacetylates and coactivates different substrates, including HSF1. Deacetylated HSF1 binds to the heat shock promoter element found upstream of genes encoding molecular chaperones. Overexpression of SIRT1 in cultured cells also helps them to survive exposure to heat stress. Conversely, its down-regulation accelerates the attenuation of the heat shock response promoting the release of HSF1 from its cognate promoter element. Very recently, in a mouse model for Alzheimer's disease, SIRT1 deacetylase activity was also found activating the transcription of α-secretase, the enzyme responsible for inhibiting the formation of aggregates of neuronal β-amyloid plaques. How SIRT1 activity protects cells from the deleterious effects of damaged/misfolded proteins and the implication of these findings on age-related pathologies are discussed.

  3. Endoplasmic reticulum stress-sensing mechanism is activated in Entamoeba histolytica upon treatment with nitric oxide.

    Directory of Open Access Journals (Sweden)

    Julien Santi-Rocca

    Full Text Available The Endoplasmic Reticulum stores calcium and is a site of protein synthesis and modification. Changes in ER homeostasis lead to stress responses with an activation of the unfolded protein response (UPR. The Entamoeba histolytica endomembrane system is simple compared to those of higher eukaryotes, as a canonical ER is not observed. During amoebiasis, an infection of the human intestine and liver by E. histolytica, nitric oxide (NO triggers an apoptotic-like event preceded by an impairment of energy production and a loss of important parasite pathogenic features. We address the question of how this ancient eukaryote responds to stress induced by immune components (i.e. NO and whether stress leads to ER changes and subsequently to an UPR. Gene expression analysis suggested that NO triggers stress responses marked by (i dramatic up-regulation of hsp genes although a bona fide UPR is absent; (ii induction of DNA repair and redox gene expression and iii up-regulation of glycolysis-related gene expression. Enzymology approaches demonstrate that NO directly inhibits glycolysis and enhance cysteine synthase activity. Using live imaging and confocal microscopy we found that NO dramatically provokes extensive ER fragmentation. ER fission in E. histolytica appears as a protective response against stress, as it has been recently proposed for neuron self-defense during neurologic disorders. Chronic ER stress is also involved in metabolic diseases including diabetes, where NO production reduces ER calcium levels and activates cell death. Our data highlighted unique cellular responses of interest to understand the mechanisms of parasite death during amoebiasis.

  4. Stress recovery and cyclic behaviour of an Fe-Mn-Si shape memory alloy after multiple thermal activation

    Science.gov (United States)

    Hosseini, E.; Ghafoori, E.; Leinenbach, C.; Motavalli, M.; Holdsworth, S. R.

    2018-02-01

    The stress recovery and cyclic deformation behaviour of Fe-17Mn-5Si-10Cr-4Ni-1(V,C) shape memory alloy (Fe-SMA) strips, which are often used for pre-stressed strengthening of structural members, were studied. The evolution of recovery stress under different constraint conditions was studied. The results showed that the magnitude of the tensile stress in the Fe-SMA member during thermal activation can have a signification effect on the final recovery stress. The higher the tensile load in the Fe-SMA (e.g., caused by dead load or thermal expansion of parent structure during heating phase), the lower the final recovery stress. Furthermore, this study investigated the cyclic behaviour of the activated SMA followed by a second thermal activation. Although the magnitude of the recovery stress decreased during the cyclic loading, the second thermal activation could retrieve a significant part of the relaxed recovery stress. This observation suggests that the relaxation of recovery stress during cyclic loading is due to a reversible phase transformation-induced deformation (i.e., forward austenite-to-martensite transformation) rather than an irreversible dislocation-induced plasticity. Retrieval of the relaxed recovery stress by the reactivation process has important practical implications as the prestressing loss in pre-stressed civil structures can be simply recovered by reheating of the Fe-SMA elements.

  5. Activation of the Amino Acid Response Pathway Blunts the Effects of Cardiac Stress.

    Science.gov (United States)

    Qin, Pu; Arabacilar, Pelin; Bernard, Roberta E; Bao, Weike; Olzinski, Alan R; Guo, Yuanjun; Lal, Hind; Eisennagel, Stephen H; Platchek, Michael C; Xie, Wensheng; Del Rosario, Julius; Nayal, Mohamad; Lu, Quinn; Roethke, Theresa; Schnackenberg, Christine G; Wright, Fe; Quaile, Michael P; Halsey, Wendy S; Hughes, Ashley M; Sathe, Ganesh M; Livi, George P; Kirkpatrick, Robert B; Qu, Xiaoyan A; Rajpal, Deepak K; Faelth Savitski, Maria; Bantscheff, Marcus; Joberty, Gerard; Bergamini, Giovanna; Force, Thomas L; Gatto, Gregory J; Hu, Erding; Willette, Robert N

    2017-05-09

    The amino acid response (AAR) is an evolutionarily conserved protective mechanism activated by amino acid deficiency through a key kinase, general control nonderepressible 2. In addition to mobilizing amino acids, the AAR broadly affects gene and protein expression in a variety of pathways and elicits antifibrotic, autophagic, and anti-inflammatory activities. However, little is known regarding its role in cardiac stress. Our aim was to investigate the effects of halofuginone, a prolyl-tRNA synthetase inhibitor, on the AAR pathway in cardiac fibroblasts, cardiomyocytes, and in mouse models of cardiac stress and failure. Consistent with its ability to inhibit prolyl-tRNA synthetase, halofuginone elicited a general control nonderepressible 2-dependent activation of the AAR pathway in cardiac fibroblasts as evidenced by activation of known AAR target genes, broad regulation of the transcriptome and proteome, and reversal by l-proline supplementation. Halofuginone was examined in 3 mouse models of cardiac stress: angiotensin II/phenylephrine, transverse aortic constriction, and acute ischemia reperfusion injury. It activated the AAR pathway in the heart, improved survival, pulmonary congestion, left ventricle remodeling/fibrosis, and left ventricular function, and rescued ischemic myocardium. In human cardiac fibroblasts, halofuginone profoundly reduced collagen deposition in a general control nonderepressible 2-dependent manner and suppressed the extracellular matrix proteome. In human induced pluripotent stem cell-derived cardiomyocytes, halofuginone blocked gene expression associated with endothelin-1-mediated activation of pathologic hypertrophy and restored autophagy in a general control nonderepressible 2/eIF2α-dependent manner. Halofuginone activated the AAR pathway in the heart and attenuated the structural and functional effects of cardiac stress. © 2017 The Authors and GlaxoSmithKline. Published on behalf of the American Heart Association, Inc., by Wiley.

  6. MORPHOMETRIC CHARACTERISTIC OF RATS LIVER UNDER PRE-SLAUGHTER STRESS AND USAGE OF BIOLOGICALLY ACTIVE SUBSTANCES

    Directory of Open Access Journals (Sweden)

    Grabovskyi S. S.

    2015-04-01

    Full Text Available We have studied morphometric parameters of rats’ liver under stress conditions using the biologically active substances of plant and animal origin: spleen, Echinacea and Chinese lemon extracts, sprouted grain. Aerosol introduction of spleen extract to the rats feed for five days before slaughter was caused to liver morphological state moderate deviation, indicating the antistressors properties of polyamines contained in this extract. The results of model experiment on rats can be used in research of farm animals for correction of pre-slaughter stress influence and getting the receiving of quality industrial production.

  7. Utilization of shear stress for determination of activation energy of the defects created by neutron irradiation

    International Nuclear Information System (INIS)

    Gonzalez, Hector C.; Miralles, Monica

    1996-01-01

    This paper describes an experimental technique used for the determination thermodynamical parameters such as activation energy using the thermal annealing of increments of Critical resolved Shear Stress of the defects created by neutron irradiation at 77 K. The doses chosen for this work was 3.1 x 10 16 n/cm 2 since the defects are stable to plastic deformation and the cascades of atomic displacements do not overlap. Specimens without any prior deformation were used allowing then the single addition of the initial stress to that due to the created defects. (author)

  8. How a retrotransposon exploits the plant's heat stress response for its activation.

    Directory of Open Access Journals (Sweden)

    Vladimir V Cavrak

    2014-01-01

    Full Text Available Retrotransposons are major components of plant and animal genomes. They amplify by reverse transcription and reintegration into the host genome but their activity is usually epigenetically silenced. In plants, genomic copies of retrotransposons are typically associated with repressive chromatin modifications installed and maintained by RNA-directed DNA methylation. To escape this tight control, retrotransposons employ various strategies to avoid epigenetic silencing. Here we describe the mechanism developed by ONSEN, an LTR-copia type retrotransposon in Arabidopsis thaliana. ONSEN has acquired a heat-responsive element recognized by plant-derived heat stress defense factors, resulting in transcription and production of full length extrachromosomal DNA under elevated temperatures. Further, the ONSEN promoter is free of CG and CHG sites, and the reduction of DNA methylation at the CHH sites is not sufficient to activate the element. Since dividing cells have a more pronounced heat response, the extrachromosomal ONSEN DNA, capable of reintegrating into the genome, accumulates preferentially in the meristematic tissue of the shoot. The recruitment of a major plant heat shock transcription factor in periods of heat stress exploits the plant's heat stress response to achieve the transposon's activation, making it impossible for the host to respond appropriately to stress without losing control over the invader.

  9. Ultrafine particles from diesel engines induce vascular oxidative stress via JNK activation.

    Science.gov (United States)

    Li, Rongsong; Ning, Zhi; Cui, Jeffery; Khalsa, Bhavraj; Ai, Lisong; Takabe, Wakako; Beebe, Tyler; Majumdar, Rohit; Sioutas, Constantinos; Hsiai, Tzung

    2009-03-15

    Exposure to particulate air pollution is linked to increased incidences of cardiovascular diseases. Ambient ultrafine particles (UFP) from diesel vehicle engines have been shown to be proatherogenic in ApoE knockout mice and may constitute a major cardiovascular risk in humans. We posited that circulating nano-sized particles from traffic pollution sources induce vascular oxidative stress via JNK activation in endothelial cells. Diesel UFP were collected from a 1998 Kenworth truck. Intracellular superoxide assay revealed that these UFP dose-dependently induced superoxide (O(2)(-)) production in human aortic endothelial cells (HAEC). Flow cytometry showed that UFP increased MitoSOX red intensity specific for mitochondrial superoxide. Protein carbonyl content was increased by UFP as an indication of vascular oxidative stress. UFP also up-regulated heme oxygenase-1 (HO-1) and tissue factor (TF) mRNA expression, and pretreatment with the antioxidant N-acetylcysteine significantly decreased their expression. Furthermore, UFP transiently activated JNK in HAEC. Treatment with the JNK inhibitor SP600125 and silencing of both JNK1 and JNK2 with siRNA inhibited UFP-stimulated O(2)(-) production and mRNA expression of HO-1 and TF. Our findings suggest that JNK activation plays an important role in UFP-induced oxidative stress and stress response gene expression.

  10. Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2+ overload.

    Science.gov (United States)

    Li, Wei; Wang, Yue-peng; Gao, Ling; Zhang, Peng-pai; Zhou, Qing; Xu, Quan-fu; Zhou, Zhi-wen; Guo, Kai; Chen, Ren-hua; Yang, Huang-tian; Li, Yi-gang

    2013-09-01

    To investigate whether resveratrol suppressed oxidative stress-induced arrhythmogenic activity and Ca(2+) overload in ventricular myocytes and to explore the underlying mechanisms. Hydrogen peroxide (H2O2, 200 μmol/L)) was used to induce oxidative stress in rabbit ventricular myocytes. Cell shortening and calcium transients were simultaneously recorded to detect arrhythmogenic activity and to measure intracellular Ca(2+) ([Ca(2+)]i). Ca(2+)/calmodulin-dependent protein kinases II (CaMKII) activity was measured using a CaMKII kit or Western blotting analysis. Voltage-activated Na(+) and Ca(2+) currents were examined using whole-cell recording in myocytes. H2O2 markedly prolonged Ca(2+) transient duration (CaTD), and induced early afterdepolarization (EAD)-like and delayed afterdepolarization (DAD)-like arrhythmogenic activity in myocytes paced at 0.16 Hz or 0.5 Hz. Application of resveratrol (30 or 50 μmol/L) dose-dependently suppressed H2O2-induced EAD-like arrhythmogenic activity and attenuated CaTD prolongation. Co-treatment with resveratrol (50 μmol/L) effectively prevented both EAD-like and DAD-like arrhythmogenic activity induced by H2O2. In addition, resveratrol markedly blunted H2O2-induced diastolic [Ca(2+)]i accumulation and prevented the myocytes from developing hypercontracture. In whole-cell recording studies, H2O2 significantly enhanced the late Na(+) current (I(Na,L)) and L-type Ca(2+) current (I(Ca,L)) in myocytes, which were dramatically suppressed or prevented by resveratrol. Furthermore, H2O2-induced ROS production and CaMKII activation were significantly prevented by resveratrol. Resveratrol protects ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca(2+) overload through inhibition of I(Na,L)/I(Ca,L), reduction of ROS generation, and prevention of CaMKII activation.

  11. Dynamic of bioelectric activity back hypothalamus changes in conditions of pyroxan application on the background of stress-reaction developmen

    Directory of Open Access Journals (Sweden)

    T. G. Chaus

    2005-04-01

    Full Text Available The dynamic of changes of capacity of electroencephalogram’s rhythms back hypothalamus at animals of control group and group in stress conditions in parallel with rats who on a background of stress development accepted pyroxan is analyzed. The submitted results have shown influence of a pharmacological preparation pyroxan on bioelectric activity of back hypothalamus in stress conditions that restoration of electric activity under action of this preparation was more shown at 3 weeks of its application.

  12. Posterior midline activation during symptom provocation in acute stress disorder: An fMRI study

    Directory of Open Access Journals (Sweden)

    Jan Christopher Cwik

    2014-05-01

    Full Text Available Functional imaging studies of patients with Posttraumatic Stress Disorder showed wide-spread activation of mid-line cortical areas during symptom provocation i.e., exposure to trauma-related cues. The present study aimed at investigating neural activation during exposure to trauma-related pictures in patients with Acute Stress Disorder (ASD shortly after the traumatic event. Nineteen ASD patients and 19 healthy control participants were presented with individualized pictures of the traumatic event and emotionally neutral control pictures during the acquisition of whole-brain data with a 3-T fMRI scanner. Compared to the control group and to control pictures, ASD patients showed significant activation in mid-line cortical areas in response to trauma-related pictures including precuneus, cuneus, postcentral gyrus and pre-supplementary motor area. The results suggest that the trauma-related pictures evoke emotionally salient self-referential processing in ASD patients.

  13. Effect of astaxanthin supplementation on paraoxonase 1 activities and oxidative stress status in young soccer players.

    Science.gov (United States)

    Baralic, Ivana; Djordjevic, Brizita; Dikic, Nenad; Kotur-Stevuljevic, Jelena; Spasic, Slavica; Jelic-Ivanovic, Zorana; Radivojevic, Nenad; Andjelkovic, Marija; Pejic, Snezana

    2013-10-01

    The purpose of the study was to examine the effects of astaxanthin (Asx) on paraoxonase (PON1) activities and oxidative stress status in soccer players. Forty soccer players were randomly assigned in a double-blind fashion to Asx and placebo (P) group. Blood samples were obtained before, 45 and 90 days after supplementation. PON1 activity was assessed by using two substrates: paraoxon and diazoxon. The oxidative stress biomarkers were also examined: total sulphydryl group content (-SH groups), thiobarbituric acid-reactive substances (TBARS), advanced oxidation protein products and redox balance. The significant interaction effect of supplementation and training (p Asx group after 90 days (p Asx group (supplementation and training, p Asx supplementation might increase total SH groups content and improve PON1 activity through protection of free thiol groups against oxidative modification. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Regulation of activity and localization of the WNK1 protein kinase by hyperosmotic stress

    Science.gov (United States)

    Zagórska, Anna; Pozo-Guisado, Eulalia; Boudeau, Jérôme; Vitari, Alberto C.; Rafiqi, Fatema H.; Thastrup, Jacob; Deak, Maria; Campbell, David G.; Morrice, Nick A.; Prescott, Alan R.; Alessi, Dario R.

    2007-01-01

    Mutations within the WNK1 (with-no-K[Lys] kinase-1) gene cause Gordon's hypertension syndrome. Little is known about how WNK1 is regulated. We demonstrate that WNK1 is rapidly activated and phosphorylated at multiple residues after exposure of cells to hyperosmotic conditions and that activation is mediated by the phosphorylation of its T-loop Ser382 residue, possibly triggered by a transautophosphorylation reaction. Activation of WNK1 coincides with the phosphorylation and activation of two WNK1 substrates, namely, the protein kinases STE20/SPS1-related proline alanine–rich kinase (SPAK) and oxidative stress response kinase-1 (OSR1). Small interfering RNA depletion of WNK1 impairs SPAK/OSR1 activity and phosphorylation of residues targeted by WNK1. Hyperosmotic stress induces rapid redistribution of WNK1 from the cytosol to vesicular structures that may comprise trans-Golgi network (TGN)/recycling endosomes, as they display rapid movement, colocalize with clathrin, adaptor protein complex 1 (AP-1), and TGN46, but not the AP-2 plasma membrane–coated pit marker nor the endosomal markers EEA1, Hrs, and LAMP1. Mutational analysis suggests that the WNK1 C-terminal noncatalytic domain mediates vesicle localization. Our observations shed light on the mechanism by which WNK1 is regulated by hyperosmotic stress. PMID:17190791

  15. Effect of aging on performance, muscle activation and perceived stress during mentally demanding computer tasks

    DEFF Research Database (Denmark)

    Alkjaer, Tine; Pilegaard, Marianne; Bakke, Merete

    2005-01-01

    ' perception of the stress and difficulty related to the tasks. RESULTS: Performance decreased significantly in both groups during the color word test in comparison with performance on the reference task. However, the performance reduction was more pronounced in the elderly group than in the young group......OBJECTIVES: This study examined the effects of age on performance, muscle activation, and perceived stress during computer tasks with different levels of mental demand. METHODS: Fifteen young and thirteen elderly women performed two computer tasks [color word test and reference task] with different....... Likewise, a higher level of self-reported stress was found for the elderly participants after the color word test. During the reference task higher electromyographic levels and reported difficulty were recorded for the elderly group than for the young group. CONCLUSIONS: The findings suggest that mental...

  16. Effect of aging on performance, muscle activation and perceived stress during mentally demanding computer tasks

    DEFF Research Database (Denmark)

    Alkjaer, Tine; Pilegaard, Marianne; Bakke, Merete

    2005-01-01

    OBJECTIVES: This study examined the effects of age on performance, muscle activation, and perceived stress during computer tasks with different levels of mental demand. METHODS: Fifteen young and thirteen elderly women performed two computer tasks [color word test and reference task] with different......' perception of the stress and difficulty related to the tasks. RESULTS: Performance decreased significantly in both groups during the color word test in comparison with performance on the reference task. However, the performance reduction was more pronounced in the elderly group than in the young group....... Likewise, a higher level of self-reported stress was found for the elderly participants after the color word test. During the reference task higher electromyographic levels and reported difficulty were recorded for the elderly group than for the young group. CONCLUSIONS: The findings suggest that mental...

  17. Dichloroacetate Decreases Cell Health and Activates Oxidative Stress Defense Pathways in Rat Alveolar Type II Pneumocytes

    Directory of Open Access Journals (Sweden)

    Alexis Valauri-Orton

    2015-01-01

    Full Text Available Dichloroacetate (DCA is a water purification byproduct that is known to be hepatotoxic and hepatocarcinogenic and to induce peripheral neuropathy and damage macrophages. This study characterizes the effects of the haloacetate on lung cells by exposing rat alveolar type II (L2 cells to 0–24 mM DCA for 6–24 hours. Increasing DCA concentration and the combination of increasing DCA concentration plus longer exposures decrease measures of cellular health. Length of exposure has no effect on oxidative stress biomarkers, glutathione, SOD, or CAT. Increasing DCA concentration alone does not affect total glutathione or its redox ratio but does increase activity in the SOD/CAT oxidative stress defense pathway. These data suggest that alveolar type II cells rely on SOD and CAT more than glutathione to combat DCA-induced stress.

  18. Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines

    International Nuclear Information System (INIS)

    Pan, Mu-Yun; Shen, Yuh-Chiang; Lu, Chien-Hsing; Yang, Shu-Yi; Ho, Tsing-Fen; Peng, Yu-Ta; Chang, Chia-Che

    2012-01-01

    Prodigiosin is a bacterial tripyrrole pigment with potent cytotoxicity against diverse human cancer cell lines. Endoplasmic reticulum (ER) stress is initiated by accumulation of unfolded or misfolded proteins in the ER lumen and may induce cell death when irremediable. In this study, the role of ER stress in prodigiosin-induced cytotoxicity was elucidated for the first time. Comparable to the ER stress inducer thapsigargin, prodigiosin up-regulated signature ER stress markers GRP78 and CHOP in addition to activating the IRE1, PERK and ATF6 branches of the unfolded protein response (UPR) in multiple human breast carcinoma cell lines, confirming prodigiosin as an ER stress inducer. Prodigiosin transcriptionally up-regulated CHOP, as evidenced by its promoting effect on the CHOP promoter activity. Of note, knockdown of CHOP effectively lowered prodigiosin's capacity to evoke PARP cleavage, reduce cell viability and suppress colony formation, highlighting an essential role of CHOP in prodigiosin-induced cytotoxic ER stress response. In addition, prodigiosin down-regulated BCL2 in a CHOP-dependent manner. Importantly, restoration of BCL2 expression blocked prodigiosin-induced PARP cleavage and greatly enhanced the survival of prodigiosin-treated cells, suggesting that CHOP-dependent BCL2 suppression mediates prodigiosin-elicited cell death. Moreover, pharmacological inhibition of JNK by SP600125 or dominant-negative blockade of PERK-mediated eIF2α phosphorylation impaired prodigiosin-induced CHOP up-regulation and PARP cleavage. Collectively, these results identified ER stress-mediated cell death as a mode-of-action of prodigiosin's tumoricidal effect. Mechanistically, prodigiosin engages the IRE1–JNK and PERK–eIF2α branches of the UPR signaling to up-regulate CHOP, which in turn mediates BCL2 suppression to induce cell death. Highlights: ► Prodigiosin is a bacterial tripyrrole pigment with potent anticancer effect. ► Prodigiosin is herein identified as an

  19. Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Mu-Yun [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Shen, Yuh-Chiang [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); National Research Institute of Chinese Medicine, Taipei, Taiwan (China); Lu, Chien-Hsing [Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Yang, Shu-Yi [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Ho, Tsing-Fen [Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan (China); Peng, Yu-Ta [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chang, Chia-Che, E-mail: chia_che@dragon.nchu.edu.tw [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China)

    2012-12-15

    Prodigiosin is a bacterial tripyrrole pigment with potent cytotoxicity against diverse human cancer cell lines. Endoplasmic reticulum (ER) stress is initiated by accumulation of unfolded or misfolded proteins in the ER lumen and may induce cell death when irremediable. In this study, the role of ER stress in prodigiosin-induced cytotoxicity was elucidated for the first time. Comparable to the ER stress inducer thapsigargin, prodigiosin up-regulated signature ER stress markers GRP78 and CHOP in addition to activating the IRE1, PERK and ATF6 branches of the unfolded protein response (UPR) in multiple human breast carcinoma cell lines, confirming prodigiosin as an ER stress inducer. Prodigiosin transcriptionally up-regulated CHOP, as evidenced by its promoting effect on the CHOP promoter activity. Of note, knockdown of CHOP effectively lowered prodigiosin's capacity to evoke PARP cleavage, reduce cell viability and suppress colony formation, highlighting an essential role of CHOP in prodigiosin-induced cytotoxic ER stress response. In addition, prodigiosin down-regulated BCL2 in a CHOP-dependent manner. Importantly, restoration of BCL2 expression blocked prodigiosin-induced PARP cleavage and greatly enhanced the survival of prodigiosin-treated cells, suggesting that CHOP-dependent BCL2 suppression mediates prodigiosin-elicited cell death. Moreover, pharmacological inhibition of JNK by SP600125 or dominant-negative blockade of PERK-mediated eIF2α phosphorylation impaired prodigiosin-induced CHOP up-regulation and PARP cleavage. Collectively, these results identified ER stress-mediated cell death as a mode-of-action of prodigiosin's tumoricidal effect. Mechanistically, prodigiosin engages the IRE1–JNK and PERK–eIF2α branches of the UPR signaling to up-regulate CHOP, which in turn mediates BCL2 suppression to induce cell death. Highlights: ► Prodigiosin is a bacterial tripyrrole pigment with potent anticancer effect. ► Prodigiosin is herein identified

  20. Methyl jasmonate enhances memory performance through inhibition of oxidative stress and acetylcholinesterase activity in mice.

    Science.gov (United States)

    Eduviere, Anthony T; Umukoro, S; Aderibigbe, Adegbuyi O; Ajayi, Abayomi M; Adewole, Folashade A

    2015-07-01

    Current research effort focuses on the development of safer natural compounds with multipronged mechanisms of action that could be used to ameliorate memory deficits in patients with Alzheimer's disease, as cure for the disease still remains elusive. In this study, we evaluated the effect of methyl jasmonate (MJ), a naturally occurring bioactive compound on memory, acetylcholinesterase activity and biomarkers of oxidative stress in mice. Male Swiss mice were treated with intraperitoneal injection of MJ (10-40 mg/kg) alone or in combination with scopolamine (3mg/kg) once daily for 7 days. Thirty minutes after the last treatment, memory functions were assessed using Y-maze and object recognition tests. Thereafter, acetylcholinesterase activity and levels of biomarkers of oxidative stress were assessed in mice brains using standard biochemical procedures. MJ significantly enhanced memory performance and reversed scopolamine-induced cognitive impairment in mice. MJ demonstrated significant inhibition of acetylcholinesterase activity suggesting increased cholinergic neurotransmission. It further decreased malondialdehyde concentrations in mouse brain indicating antioxidant activity. Moreover, MJ significantly increased glutathione levels and activity of antioxidant enzymes (catalase and superoxide dismutase) in mice brains. The increased oxidative stress; evidenced by elevated levels of malondialdehyde and decreased antioxidant defense systems in scopolamine-treated mice was attenuated by MJ. The results of this study suggest that MJ may be useful in conditions associated with memory dysfunctions or age-related cognitive decline. The positive effect of MJ on memory may be related to inhibition of oxidative stress and enhancement of cholinergic neurotransmission through inhibition of acetylcholinesterase activity. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. The Impact of Perceived Stress, Social Support, and Home-Based Physical Activity on Mental Health among Older Adults

    Science.gov (United States)

    Kwag, Kyung Hwa; Martin, Peter; Russell, Daniel; Franke, Warren; Kohut, Marian

    2011-01-01

    This study investigated how perceived stress, social support, and home-based physical activity affected older adults' fatigue, loneliness, and depression. We also explored whether social support and physical activity mediated the relationships between stress and mental health problems. The data of 163 older participants were analyzed in this…

  2. Assessing physical activity in people with posttraumatic stress disorder: feasibility and concurrent validity of the International Physical Activity Questionnaire--short form and actigraph accelerometers

    NARCIS (Netherlands)

    Rosenbaum, S.; Tiedemann, A.; Sherrington, C.; van der Ploeg, H.P.

    2014-01-01

    Background: Posttraumatic stress disorder (PTSD) is reportedly associated with lower rates of physical activity participation despite the known benefits of regular physical activity for improving both mental and physical health. However, no studies have evaluated the validity or feasibility of

  3. Acid-induced autophagy protects human lung cancer cells from apoptosis by activating ER stress.

    Science.gov (United States)

    Xie, Wen-Yue; Zhou, Xiang-Dong; Li, Qi; Chen, Ling-Xiu; Ran, Dan-Hua

    2015-12-10

    An acidic tumor microenvironment exists widely in solid tumors. However, the detailed mechanism of cell survival under acidic stress remains unclear. The aim of this study is to clarify whether acid-induced autophagy exists and to determine the function and mechanism of autophagy in lung cancer cells. We have found that acute low pH stimulated autophagy by increasing LC3-positive punctate vesicles, increasing LC3 II expression levels and reducing p62 protein levels. Additionally, autophagy was inhibited by the addition of Baf or knockdown of Beclin 1, and cell apoptosis was increased markedly. In mouse tumors, the expression of cleaved caspase3 and p62 was enhanced by oral treatment with sodium bicarbonate, which can raise the intratumoral pH. Furthermore, the protein levels of ER stress markers, including p-PERK, p-eIF2α, CHOP, XBP-1s and GRP78, were also increased in response to acidic pH. The antioxidant NAC, which reduces ROS accumulation, alleviated acid-mediated ER stress and autophagy, and knocking down GRP78 reduced autophagy activation under acidic conditions, which suggests that autophagy was induced by acidic pH through ER stress. Taken together, these results indicate that the acidic microenvironment in non-small cell lung cancer cells promotes autophagy by increasing ROS-ER stress, which serves as a survival adaption in this setting. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. NOX3 NADPH oxidase couples transient receptor potential vanilloid 1 to signal transducer and activator of transcription 1-mediated inflammation and hearing loss.

    Science.gov (United States)

    Mukherjea, Debashree; Jajoo, Sarvesh; Sheehan, Kelly; Kaur, Tejbeer; Sheth, Sandeep; Bunch, Jennifer; Perro, Christopher; Rybak, Leonard P; Ramkumar, Vickram

    2011-03-15

    Transient receptor potential vanilloid 1 (TRPV1) is implicated in cisplatin ototoxicity. Activation of this channel by cisplatin increases reactive oxygen species generation, which contribute to loss of outer hair cells in the cochlea. Knockdown of TRPV1 by short interfering RNA protected against cisplatin ototoxicity. In this study, we examined the mechanism underlying TRPV1-mediated ototoxicity using cultured organ of Corti transformed cells (UB/OC-1) and rats. Trans-tympanic injections of capsaicin produced transient hearing loss within 24 h, which recovered by 72 h. In UB/OC-1 cells, capsaicin increased NOX3 NADPH oxidase activity and activation of signal transducer and activator of transcription 1 (STAT1). Intratympanic administration of capsaicin transiently increased STAT1 activity and expression of downstream proinflammatory molecules. Capsaicin produced a transient increase in CD14-positive inflammatory cells into the cochlea, which mimicked the temporal course of STAT1 activation but did not alter the expression of apoptotic genes or damage to outer hair cells. In addition, trans-tympanic administration of STAT1 short interfering RNA protected against capsaicin-induced hearing loss. These data suggest that activation of TRPV1 mediates temporary hearing loss by initiating an inflammatory process in the cochlea via activation of NOX3 and STAT1. Thus, these proteins represent reasonable targets for ameliorating hearing loss.

  5. Relationship between physical activity and markers of oxidative stress in independent community-living elderly individuals.

    Science.gov (United States)

    Fraile-Bermúdez, A B; Kortajarena, M; Zarrazquin, I; Maquibar, A; Yanguas, J J; Sánchez-Fernández, C E; Gil, J; Irazusta, A; Ruiz-Litago, F

    2015-10-01

    The aim of the present study was to examine the relationship between objective data of physical activity and markers of oxidative stress in older men and women. Participants were old adults, aged≥60years (61 women and 34 men) who were all capable of performing basic daily activities by themselves and lived on their own. To describe physical activity we used objective data measured by accelerometers which record active and sedentary periods during everyday life for five days. Determination of oxidative stress was conducted from three perspectives: determination plasma total antioxidant status (TAS), plasma antioxidant enzyme activities, i.e., glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD), and membrane lipid peroxidation (TBARS). In the group of women, those who met physical activity recommendations (WR) had lower level of TAS. In addition, the moderate to vigorous physical activity (MVPA) was negatively correlated with TAS. Simultaneously, MVPA was correlated with increase in the GPx antioxidant enzyme activity, and the counts per minute were positively correlated with CAT activity. In the group of men, the cpm and the MVPA were negatively correlated with lipid peroxidation while lifestyle physical activity was positively correlated with CAT activity. These findings suggest that MVPA in the elderly although it is related to a decrease in the TAS in women, induces adaptive increase in antioxidant enzyme activity and decreases lipid peroxidation in both women and men. These results suggest that at this time of life, it is not only the amount of physical activity performed that is important but also its intensity. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Activation of antioxidant defenses in whole saliva by psychosocial stress is more manifested in young women than in young men.

    Directory of Open Access Journals (Sweden)

    Viktoriia Tsuber

    Full Text Available Psychosocial stress has been long known to have deleterious effects on health. Nevertheless, an exposure to moderate stressors enhances resilience and promotes health benefits. Male and female organisms differ in many aspects of health and disease. The aim of this study was to investigate antioxidant activity and oxidative damage in saliva in a psychosocial stress paradigm in men and women. Here, we show that an acute stressor of moderate strength augments antioxidant activity and decreases oxidative damage in whole saliva of young people. An examination stress caused a significant increase of catalase activity, accompanied by a decrease of levels of oxidized proteins. Levels of thiobarbituric acid-reacting substances did not increase at stress, indicating that lipid peroxidation was not activated. The stress-induced alterations were more manifested in young women compared to young men. Thus, antioxidant protective mechanisms are more activated by a moderate stressor in young women than in young men.

  7. Activation of antioxidant defenses in whole saliva by psychosocial stress is more manifested in young women than in young men.

    Science.gov (United States)

    Tsuber, Viktoriia; Kadamov, Yunus; Tarasenko, Lydia

    2014-01-01

    Psychosocial stress has been long known to have deleterious effects on health. Nevertheless, an exposure to moderate stressors enhances resilience and promotes health benefits. Male and female organisms differ in many aspects of health and disease. The aim of this study was to investigate antioxidant activity and oxidative damage in saliva in a psychosocial stress paradigm in men and women. Here, we show that an acute stressor of moderate strength augments antioxidant activity and decreases oxidative damage in whole saliva of young people. An examination stress caused a significant increase of catalase activity, accompanied by a decrease of levels of oxidized proteins. Levels of thiobarbituric acid-reacting substances did not increase at stress, indicating that lipid peroxidation was not activated. The stress-induced alterations were more manifested in young women compared to young men. Thus, antioxidant protective mechanisms are more activated by a moderate stressor in young women than in young men.

  8. Aberrant mTOR activation in senescence and aging: A mitochondrial stress response?

    Science.gov (United States)

    Nacarelli, Timothy; Azar, Ashley; Sell, Christian

    2015-08-01

    Unexpected activation of mTOR signaling, measured by ribosomal S6 phosphorylation or ribosomal S6 kinase (p70S6K) activity, has been reported in aging-related settings. Evidence of elevated mTOR activity has been reported in the heart and muscle tissue in aged mice and humans, mouse models of progeria, and senescent human fibroblasts. We explore these reports and the possibility that activation of the mTOR/p70S6K kinase pathway may represent a ROS-mediated response to mitochondrial stress leading to the activation of senescence. This activation is a hallmark of both aged tissue and senescent human cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Genetic activation of Nrf2 protects against fasting-induced oxidative stress in livers of mice.

    Directory of Open Access Journals (Sweden)

    Yu-Kun Jennifer Zhang

    Full Text Available Acute fasting causes elevated oxidative stress. The current study investigated the effects of the nuclear factor erythoid 2-related factor 2 (Nrf2, the sensor of oxidative stress in cells, on energy homeostasis and liver pathophysiology during fasting. Feed was removed from mice possessing none (Nrf2-null, normal (wild-type, WT, enhanced (Keap1-knockdown, K1-KD, and maximum (hepatocyte-specific Keap1-knockout, K1-HKO Nrf2 activity in liver for 24 h. Body weight, blood glucose, and blood lipid profiles were similar among mice with graded Nrf2 activity under either fed or fasted conditions. Fasting reduced liver size in mice expressing Nrf2, but not in Nrf2-null mice. Nrf2-null mice accumulated more non-esterified free fatty acids and triglycerides in liver after fasting than the other genotypes of mice. Fatty acids are mainly catabolized in mitochondria, and Nrf2-null mice had lower mitochondrial content in liver under control feeding conditions, which was further reduced by fasting. In contrast, mitochondrial contents in mice with enhanced Nrf2 activity were not affected by fasting. Oxidative stress, determined by staining of free radicals and quantification of malondialdehyde equivalents, was highest in Nrf2-null and lowest in K1-HKO mice after fasting. The exacerbated oxidative stress in livers of Nrf2-null mice is predicted to lead to damages to mitochondria, and therefore diminished oxidation and increased accumulation of lipids in livers of Nrf2-null mice. In summary, the Nrf2-regulated signaling pathway is critical in protecting mitochondria from oxidative stress during feed deprivation, which ensures efficient utilization of fatty acids in livers of mice.

  10. CRANIOFACIAL STRESS PATTERNS AND DISPLACEMENTS AFTER ACTIVATION OF HYRAX DEVICE: FINITE ELEMENT MODELLING

    Directory of Open Access Journals (Sweden)

    Sergei Bosiakov

    2017-12-01

    Full Text Available Rapid maxillary expansion is employed for the treatment of cross-bite and deficiency of transversal dimension of the maxilla in patients with and without cleft of palate and lip. For this procedure, generally, different orthodontic appliances and devices generating significant transversal forces are used. The aim of this study is the finite-element analysis of stresses and displacements of the skull without palate cleft and the skull with unilateral and bilateral cleft after activation of the Hyrax orthodontic device. Two different constructions of the orthodontic device Hyrax with different positions of the screw relative palate are considered. In the first case, the screw is in the occlusal horizontal plane, and in the other, the screw is located near the palate. Activation of the orthodontic device corresponds to the rotation of the screw on one-quarter turn. It is established that the screw position significantly affects the distributions of stresses in skull and displacements of the cranium without palate cleft and with unilateral or bilateral palate cleft. Stresses in the bone structures of the craniums without cleft and with cleft are transferred from the maxilla to the pterygoid plate and pharyngeal tubercle if the screw displaces from the occlusal plane to the palate. Depending on the construction of the orthodontic appliance, the maxilla halves in the transversal plane are unfolded or the whole skull is entirely rotated in the sagittal plane. The stresses patterns and displacements of the skull with bilateral palate cleft are almost unchanged after activation of the orthodontic devices with different positions of the screw, only magnitudes of stresses and displacements are changed. The obtained results can be used for design of orthodontic appliances with the Hyrax screw, as well as for planning of osteotomies during the surgical assistance of the rapid maxillary expansion.

  11. Maternal stress, nutrition and physical activity: Impact on immune function, CNS development and psychopathology.

    Science.gov (United States)

    Marques, Andrea Horvath; Bjørke-Monsen, Anne-Lise; Teixeira, Antônio L; Silverman, Marni N

    2015-08-18

    Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying

  12. Blueberry polyphenols prevent cardiomyocyte death by preventing calpain activation and oxidative stress.

    Science.gov (United States)

    Louis, Xavier Lieben; Thandapilly, Sijo Joseph; Kalt, Wilhelmina; Vinqvist-Tymchuk, Melinda; Aloud, Basma Milad; Raj, Pema; Yu, Liping; Le, Hoa; Netticadan, Thomas

    2014-08-01

    The purpose of this study was to examine the efficacy of an aqueous wild blueberry extract and five wild blueberry polyphenol fractions on an in vitro model of heart disease. Adult rat cardiomyocytes were pretreated with extract and fractions, and then exposed to norepinephrine (NE). Cardiomyocyte hypertrophy, cell death, oxidative stress, apoptosis and cardiomyocyte contractile function as well as the activities of calpain, superoxide dismutase (SOD) and catalase (CAT) were measured in cardiomyocytes treated with and without NE and blueberry fraction (BF). Four of five blueberry fractions prevented cell death and cardiomyocyte hypertrophy induced by NE. Total phenolic fraction was used for all further analysis. The NE-induced increase in oxidative stress, nuclear condensation, calpain activity and lowering of SOD and CAT activities were prevented upon pretreatment with BF. Reduced contractile function was also significantly improved with BF pretreatment. Blueberry polyphenols prevent NE-induced adult cardiomyocyte hypertrophy and cell death. The protective effects of BF may be in part attributed to a reduction in calpain activity and oxidative stress.

  13. Impact of exogenous ascorbic acid on biochemical activities of rice callus treated with salt stress

    Science.gov (United States)

    Alhasnawi, Arshad Naji; Zain, Che Radziah Che Mohd; Kadhimi, Ahsan A.; Isahak, Anizan; Mohamad, Azhar; Ashraf, Mehdi Farshad; Doni, Febri; Yusoff, Wan Mohtar Wan

    2016-11-01

    The application of in vitro systems can lead to new methods of crop amelioration. This method has been widely utilized for breeding tenacities, particularly for stress tolerance selection. Salinity causes oxidative stress in callus by enhancing the production of Reactive Oxygen Species (ROS), resulting in an efficient antioxidant system. The exogenous application of ascorbic acid (AsA) is an important requirement for tolerance. The present study aimed to examine in vitro selection strategy for callus induction in rice mature embryo culture on MS culture medium and to produce salt-tolerant callus under sodium chloride (NaCl) and AsA conditions in callus rice variety, MR269. This study also highlights changes in the activities of proline and antioxidants peroxidase (POD), catalase (CAT) and superoxide dismutase (SOD) of callus under NaCl stress to understand their possible role in salt tolerance. However, various levels of exogenously applied AsA under saline conditions improved callus, and the antioxidant enzyme activities of AsA are related to resistance to oxidative stress. Our results provide strong support for the hypothesis that AsA-dependent antioxidant enzymes play a significant role in the salinity tolerance of callus rice.

  14. Effects of early life stress on brain activity: implications from maternal separation model in rodents.

    Science.gov (United States)

    Nishi, Mayumi; Horii-Hayashi, Noriko; Sasagawa, Takayo; Matsunaga, Wataru

    2013-01-15

    Adverse experiences in early life can affect the formation of neuronal circuits during postnatal development and exert long-lasting influences on neural function. Many studies have shown that daily repeated maternal separation (RMS), an animal model of early life stress, can modulate the hypothalamic-pituitary-adrenal axis (HPA-axis) and can affect subsequent brain function and emotional behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not been completely elucidated. In this mini-review, we introduce various cases of maternal separation in rodents and illustrate the alterations in HPA-axis activity by focusing on corticosterone (CORT), an end-product of the HPA-axis in rodents. We then present the characterization of the brain regions affected by various patterns of MS, including RMS and single time maternal separation (SMS) at various stages before weaning, by investigating c-Fos expression, a biological marker of neuronal activity. These CORT and c-Fos studies suggest that repeated early life stress may affect neuronal function in region- and temporal-specific manners, indicating a critical period for habituation to early life stress. Furthermore, we introduce changes in behavioral aspects and gene expression in adult mice exposed to RMS. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Peripheral and central effects of repeated social defeat stress: monocyte trafficking, microglial activation, and anxiety.

    Science.gov (United States)

    Reader, B F; Jarrett, B L; McKim, D B; Wohleb, E S; Godbout, J P; Sheridan, J F

    2015-03-19

    The development and exacerbation of depression and anxiety are associated with exposure to repeated psychosocial stress. Stress is known to affect the bidirectional communication between the nervous and immune systems leading to elevated levels of stress mediators including glucocorticoids (GCs) and catecholamines and increased trafficking of proinflammatory immune cells. Animal models, like the repeated social defeat (RSD) paradigm, were developed to explore this connection between stress and affective disorders. RSD induces activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis activation, increases bone marrow production and egress of primed, GC-insensitive monocytes, and stimulates the trafficking of these cells to tissues including the spleen, lung, and brain. Recently, the observation that these monocytes have the ability to traffic to the brain perivascular spaces and parenchyma have provided mechanisms by which these peripheral cells may contribute to the prolonged anxiety-like behavior associated with RSD. The data that have been amassed from the RSD paradigm and others recapitulate many of the behavioral and immunological phenotypes associated with human anxiety disorders and may serve to elucidate potential avenues of treatment for these disorders. Here, we will discuss novel and key data that will present an overview of the neuroendocrine, immunological and behavioral responses to social stressors. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. PML is a ROS sensor activating p53 upon oxidative stress.

    Science.gov (United States)

    Niwa-Kawakita, Michiko; Ferhi, Omar; Soilihi, Hassane; Le Bras, Morgane; Lallemand-Breitenbach, Valérie; de Thé, Hugues

    2017-11-06

    Promyelocytic leukemia (PML) nuclear bodies (NBs) recruit partner proteins, including p53 and its regulators, thereby controlling their abundance or function. Investigating arsenic sensitivity of acute promyelocytic leukemia, we proposed that PML oxidation promotes NB biogenesis. However, physiological links between PML and oxidative stress response in vivo remain unexplored. Here, we identify PML as a reactive oxygen species (ROS) sensor. Pml -/- cells accumulate ROS, whereas PML expression decreases ROS levels. Unexpectedly, Pml -/- embryos survive acute glutathione depletion. Moreover, Pml -/- animals are resistant to acetaminophen hepatotoxicity or fasting-induced steatosis. Molecularly, Pml -/- animals fail to properly activate oxidative stress-responsive p53 targets, whereas the NRF2 response is amplified and accelerated. Finally, in an oxidative stress-prone background, Pml -/- animals display a longevity phenotype, likely reflecting decreased basal p53 activation. Thus, similar to p53, PML exerts basal antioxidant properties but also drives oxidative stress-induced changes in cell survival/proliferation or metabolism in vivo. Through NB biogenesis, PML therefore couples ROS sensing to p53 responses, shedding a new light on the role of PML in senescence or stem cell biology. © 2017 Niwa-Kawakita et al.

  17. Associations among self-perceived work and life stress, trouble sleeping, physical activity, and body weight among Canadian adults.

    Science.gov (United States)

    Sampasa-Kanyinga, Hugues; Chaput, Jean-Philippe

    2017-03-01

    We investigated the associations among self-perceived work and life stress, trouble sleeping, physical activity and body weight among Canadian adults, and tested whether trouble sleeping and physical activity moderated the relationship between work/life stress and body weight, and whether work/life stress and physical activity moderated the relationship between trouble sleeping and body weight. Data on 13,926 Canadian adults aged 20years and older were derived from the nationally representative 2012 Canadian Community Health Survey. After adjusting for age, sex, education level, household income, marital status and job insecurity, self-perceived work and life stress and trouble sleeping were associated with a higher BMI. The associations of work and life stress with higher BMI were independent of trouble sleeping and physical activity in addition to other covariates, while that of trouble sleeping and higher BMI was independent of work and life stress. Results further indicated that trouble sleeping among inactive participants was related to a higher BMI; however, this relationship was almost null for adults who self-reported being physically active for about 8h/week. These findings suggest that work and life stress are both associated with excess weight in adults, regardless of physical activity level, while the link of trouble sleeping with BMI varies by physical activity level. Future research is necessary to determine whether reducing work and life stress and improving sleep habits would benefit the prevention of weight gain and obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats.

    Science.gov (United States)

    Bowman, R E; Ferguson, D; Luine, V N

    2002-01-01

    Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167-170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279-289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased homovanillic acid levels in the prefrontal cortex, an effect not previously observed in stressed intact females. Estradiol treatment increased norepinephrine levels in CA3 region of the hippocampus, mitigating stress-dependent changes. Both stress and estradiol decreased dentate gyrus levels of 5-hydroxyindole acetic acid. In summary, the current

  19. Thermally activated low temperature creep and primary water stress corrosion cracking of NiCrFe alloys

    International Nuclear Information System (INIS)

    Hall, M.M. Jr.

    1993-01-01

    A phenomenological SCC-CGR model is developed based on an apriori assumption that the SCC-CGR is controlled by low temperature creep (LTC). This mode of low temperature time dependent deformation occurs at stress levels above the athermal flow stress by a dislocation glide mechanism that is thermally activated and may be environmentally assisted. The SCC-CGR model equations developed contain thermal activation parameters descriptive of the dislocation creep mechanism. Thermal activation parameters are obtained by fitting the CGR model to SCC-CGR data obtained on Alloy 600 and Alloy X-750. These SCC-CGR activation parameters are compared to LTC activation parameters obtained from stress relaxation tests. When the high concentration of hydrogen at the tip of an SCC crack is considered, the SCC-CGR activation energies and rate sensitivities are shown to be quantitatively consistent with hydrogen reducing the activation energy and increasing the strain rate sensitivity in LTC stress relaxation tests. Stress dependence of SCC-CGR activation energy consistent with that found for the LTC activation energy. Comparisons between temperature dependence of the SCC-CGR stress sensitivity and LTC stress sensitivity provide a basis for speculation on effects of hydrogen and solute carbon on SCC crack growth rates

  20. Active stress from earthquake focal mechanisms along the Padan-Adriatic side of the Northern Apennines (Italy), with considerations on stress magnitudes and pore-fluid pressures

    Science.gov (United States)

    Boncio, Paolo; Bracone, Vito

    2009-10-01

    The active tectonic regime along the outer Northern Apennines (Padan-Adriatic area) is a matter of debate. We analyse the active tectonic regime by systematically inverting earthquake focal mechanisms in terms of their driving stress field, comparing two different stress inversion methods. Earthquakes within the area often deviate from Andersonian conditions, being characterized by reverse or transpressional slip on high-angle faults even if the regime is almost purely thrust faulting (e.g. Reggio Emilia 1996 and Faenza 2000 earthquakes). We analyse the stress conditions at faulting for the Reggio Emilia and Faenza earthquakes in order to infer the stress magnitudes and the possible role of fluid pressures. The stress analysis defines a consistent pattern of sub-horizontal active deviatoric compression arranged nearly perpendicular to the eastern front of the Padan-Adriatic fold-and-thrust system, independent of the stress inversion method used. The results are consistent with active compression operating within the Padan-Adriatic belt. The stress field is thrust faulting (sub-vertical σ3), except for the Cesena-Forlì and Ancona areas, where a strike-slip regime (sub-vertical or steeply-plunging σ2) operates. The strike-slip regimes are interpreted as being caused by the superposition of local tensional stresses due to oroclinal bending (i.e. rotations of the belt about vertical axes) on the regional compressional stress field. Kinematic complexities characterize the 1996 Reggio Emilia seismic sequence. The distribution of these complexities is not random, suggesting that they are due to local variations of the regional stress field within the unfaulted rocks surrounding the coseismic rupture. The stress conditions at faulting for the Reggio Emilia 1996 and Faenza 2000 earthquakes, coupled with the observation that seismicity in the Padan-Adriatic area often occurs in swarms, suggest that high pore-fluid pressures (Pf ≥ 70% of the lithostatic load) operate

  1. Oxidative stress and changes in adenosine deaminase activity of cattle experimentally infected by Fasciola hepatica.

    Science.gov (United States)

    DA Silva, Aleksandro S; Baldissera, Matheus D; Bottari, Nathieli B; Gabriel, Matheus E; Rhoden, Leandro A; Piva, Manoela M; Christ, Ricardo; Stedille, Fernanda A; Gris, Anderson; Morsch, Vera M; Schetinger, Maria Rosa; Mendes, Ricardo E

    2017-04-01

    The aim of this study was to evaluate the oxidative stress in serum and liver and adenosine deaminase (ADA) activity of cattle experimentally infected by Fasciola hepatica. The group A consisted of five healthy animals (uninfected), and the group B was composed of five animals orally infected with 200 metacercariae of F. hepatica. On days 20, 40, 60 and 80 post-infection (PI) serum was collected to measure oxidative stress variables. On day 100 PI, animals were humanely euthanized and liver samples were collected. Infected animals showed lower (P hepatic reactive oxygen species (ROS) were higher (P Hepatic thiobarbituric acid reactive substances were higher (P hepatic damage, and that increased in hepatic ADA activity may contribute to the inflammatory process.

  2. Stress-restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus

    DEFF Research Database (Denmark)

    Harvey, Brian H; Oosthuizen, Frasia; Brand, Linda

    2004-01-01

    . The NOS isoform involved, and the role of stress-mediated corticosterone release in NOS activation, was verified with the administration of selective iNOS and nNOS inhibitors, aminoguanidine (50 mg/kg/day i.p.) and 7-nitroindazole (12.5 mg/kg/day i.p.), and the steroid synthesis inhibitor, ketoconazole...... (24 mg/kg/day i.p.), administered for 21 days prior to and during the stress procedure. RESULTS: Stress evoked a sustained increase in NOS activity, but reduced NMDA receptor density and total GABA levels. Aminoguanidine or ketoconazole, but not 7-nitroindazole or saline, blocked stress-induced NOS...

  3. Acute stress reduces wound-induced activation of microbicidal potential of ex vivo isolated human monocyte-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Ulrike Kuebler

    Full Text Available BACKGROUND: Psychological stress delays wound healing but the precise underlying mechanisms are unclear. Macrophages play an important role in wound healing, in particular by killing microbes. We hypothesized that (a acute psychological stress reduces wound-induced activation of microbicidal potential of human monocyte-derived macrophages (HMDM, and (b that these reductions are modulated by stress hormone release. METHODS: Fourty-one healthy men (mean age 35 ± 13 years were randomly assigned to either a stress or stress-control group. While the stress group underwent a standardized short-term psychological stress task after catheter-induced wound infliction, stress-controls did not. Catheter insertion was controlled. Assessing the microbicidal potential, we investigated PMA-activated superoxide anion production by HMDM immediately before and 1, 10 and 60 min after stress/rest. Moreover, plasma norepinephrine and epinephrine and salivary cortisol were repeatedly measured. In subsequent in vitro studies, whole blood was incubated with norepinephrine in the presence or absence of phentolamine (norepinephrine blocker before assessing HMDM microbicidal potential. RESULTS: Compared with stress-controls, HMDM of the stressed subjects displayed decreased superoxide anion-responses after stress (p's <.05. Higher plasma norepinephrine levels statistically mediated lower amounts of superoxide anion-responses (indirect effect 95% CI: 4.14-44.72. Norepinephrine-treated HMDM showed reduced superoxide anion-production (p<.001. This effect was blocked by prior incubation with phentolamine. CONCLUSIONS: Our results suggest that acute psychological stress reduces wound-induced activation of microbicidal potential of HMDM and that this reduction is mediated by norepinephrine. This might have implications for stress-induced impairment in wound healing.

  4. Parenting stress: a cross-sectional analysis of associations with childhood obesity, physical activity, and TV viewing.

    Science.gov (United States)

    Walton, Kathryn; Simpson, Janis Randall; Darlington, Gerarda; Haines, Jess

    2014-10-01

    Parents influence their children's obesity risk through feeding behaviours and modeling of weight-related behaviours. Little is known about how the general home environment, including parental stress, may influence children's weight. The objective of this study was to explore the association between parenting stress and child body mass index (BMI) as well as obesity risk factors, physical activity and television (TV) viewing. We used cross-sectional data from 110 parent-child dyads participating in a community-based parenting intervention. Child heights and weights were measured by trained research assistants. Parents (93% mothers) reported level of parenting stress via the Parenting Stress Index- Short Form (PSI-3-SF) as well as children's activity behaviours and TV viewing. This was an ethnically diverse (55% Hispanic/Latino, 22% Black), low-income (64% earning < $45,000/year) sample. Level of parenting stress was not associated with children's risk of being overweight/obese. Children with highly stressed parents were less likely to meet physical activity guidelines on weekdays than children with normally stressed parents (OR = 0.33, 95% CI, 0.12-0.95). Parents experiencing high stress were less likely to set limits on the amount of TV their children watched (OR = 0.32, 95% CI, 0.11, 0.93). Results suggest stress specific to parenting may not be associated with increased obesity risk among children. However, future interventions may need to address stress as a possible underlying factor associated with unhealthful behaviours among preschoolers.

  5. Stress hormone levels in a freshwater turtle from sites differing in human activity.

    Science.gov (United States)

    Polich, Rebecca L

    2016-01-01

    Glucocorticoids, such as corticosterone (CORT), commonly serve as a measure of stress levels in vertebrate populations. These hormones have been implicated in regulation of feeding behaviour, locomotor activity, body mass, lipid metabolism and other crucial behaviours and physiological processes. Thus, understanding how glucocorticoids fluctuate seasonally and in response to specific stressors can yield insight into organismal health and the overall health of populations. I compared circulating CORT concentrations between two similar populations of painted turtle, Chrysemys picta, which differed primarily in the level of exposure to human recreational activities. I measured basal CORT concentrations as well as the CORT stress response and did not find any substantive difference between the two populations. This similarity may indicate that painted turtles are not stressed by the presence of humans during the nesting season. The results of this study contribute to our understanding of CORT concentrations in freshwater reptiles, a group that is historically under-represented in studies of circulating hormone concentrations; specifically, studies that seek to use circulating concentrations of stress hormones, such as CORT, as a measure of the effect of human activities on wild populations. They also give insight into how these species as a whole may respond to human recreational activities during crucial life-history stages, such as the nesting season. Although there was no discernable difference between circulating CORT concentrations between the urban and rural populations studied, I did find a significant difference in circulating CORT concentrations between male and female C. picta. This important finding provides better understanding of the sex differences between male and female painted turtles and adds to our understanding of this species and other species of freshwater turtle.

  6. Effect of L-carnitine on oxidative stress and platelet activation after major surgery.

    Science.gov (United States)

    Pignatelli, P; Tellan, G; Marandola, M; Carnevale, R; Loffredo, L; Schillizzi, M; Proietti, M; Violi, F; Chirletti, P; Delogu, G

    2011-09-01

    The surgical/anesthesia trauma is associated with an increased production of reactive oxygen species (ROS). This enhanced oxidative stress leads to cell damage resulting in various complications such as sepsis, myocardial injury and increased mortality. The aim of this study was to investigate the role of antioxidant treatment with l-carnitine in oxidative stress and platelet activation in patients undergoing major abdominal surgery. Forty patients scheduled for abdominal surgery were randomly allocated to l-carnitine, administered with a rapid infusion (0.05 g/kg) diluted in 250 ml of saline solution, vs. placebo treatment just before the surgical intervention. At baseline and after treatment, oxidative stress was evaluated by detection of circulating levels of soluble NOX2-derived peptide (sNOX2-dp), a marker of NADPH oxidase activation, and by analyzing platelet ROS formation. Platelet activation was studied by dosing sCD40L. We observed an increase of soluble sNOX2-dp, sCD40L and ROS production in the placebo group compared with the baseline after the surgical intervention. Conversely, in the l-carnitine-treated group, sNOX2-dp, sCD40L and ROS production did not significantly differ from the baseline. A linear correlation analysis showed that Δ of ROS correlated with Δ of sNOX2 (R(s) =0.817; Pl-carnitine could be helpful in modulating oxidative stress and platelet activation during major abdominal surgery-dependent oxidative damage. © 2011 The Authors. Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.

  7. Management of the endoplasmic reticulum stress by activation of the heat shock response in yeast

    DEFF Research Database (Denmark)

    Hou, Jin; Tang, Hongting; Liu, Zihe

    2014-01-01

    In yeast Saccharomyces cerevisiae, accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates the unfolded protein response (UPR), which is mediated by Hac1p. The heat shock response (HSR) mediated by Hsf1p, mainly regulates cytosolic processes and protects...... and secretion. We also find that HSR coordinates multiple stress–response pathways, including the repression of the overall transcription and translation....

  8. Expression and Enzyme Activity of Catalase in Chilo suppressalis (Lepidoptera: Crambidae) Is Responsive to Environmental Stresses.

    Science.gov (United States)

    Lu, Yanhui; Bai, Qi; Zheng, Xusong; Lu, Zhongxian

    2017-08-01

    Catalase (CAT) is an important antioxidant enzyme that protects organisms against oxidative stresses by eliminating hydrogen peroxide. In this study, we cloned and characterized a full-length cDNA of CAT from Chilo suppressalis (CsCAT) and examined the influence of environmental stresses on CsCAT expression and enzyme activity. The cDNA contains a 1659-bp open reading frame encoding a polypeptide of 553 amino acids most closely related (90.14%) to Papilio polytes catalases. The CsCAT was expressed in all developmental stages with the highest expression in the fat body, and the CsCAT enzyme activity closely mirrored its observed mRNA expression patterns. The CsCAT mRNA was up-regulated when the larvae were exposed to high temperature (≥30 °C), insecticides (abamectin and chlorantraniliprole), chemicals (H2O2, CHP, CdCl2, and CuSO4), and a dead-end trap plant (vetiver grass), and the CsCAT enzyme activity again mirrored the observed CsCAT expression patterns. These results suggest that up-regulation of CsCAT may enhance the defense response of C. suppressalis by weakening the effects of environmental stresses, and provide insight into the role of CsCAT during development of C. suppressalis. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Inhibition of TGFbeta1 Signaling Attenutates ATM Activity inResponse to Genotoxic Stress

    Energy Technology Data Exchange (ETDEWEB)

    Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose; Ravani, Shraddha A.; Glick, Adam B.; Lavin, Martin J.; Koslov, Sergei; Shiloh, Yosef; Barcellos-Hoff, Mary Helen

    2006-09-15

    Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta}1 (TGF{beta}), which is activated by radiation, is a potent and pleiotropic mediator of physiological and pathological processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}1 null murine epithelial cells or human epithelial cells treated with a small molecule inhibitor of TGF{beta} type I receptor kinase exhibit decreased phosphorylation of Chk2, Rad17 and p53, reduced {gamma}H2AX radiation-induced foci, and increased radiosensitivity compared to TGF{beta} competent cells. We determined that loss of TGF{beta} signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. Addition of TGF{beta} restored functional ATM and downstream DNA damage responses. These data reveal a heretofore undetected critical link between the microenvironment and ATM that directs epithelial cell stress responses, cell fate and tissue integrity. Thus, TGF{beta}1, in addition to its role in homoeostatic growth control, plays a complex role in regulating responses to genotoxic stress, the failure of which would contribute to the development of cancer; conversely, inhibiting TGF{beta} may be used to advantage in cancer therapy.

  10. vmPFC activation during a stressor predicts positive emotions during stress recovery.

    Science.gov (United States)

    Yang, Xi; Garcia, Katelyn M; Jung, Youngkyoo; Whitlow, Christopher T; McRae, Kateri; Waugh, Christian E

    2018-03-01

    Despite accruing evidence showing that positive emotions facilitate stress recovery, the neural basis for this effect remains unclear. To identify the underlying mechanism, we compared stress recovery for people reflecting on a stressor while in a positive emotional context with that for people in a neutral context. While blood-oxygen-level dependent data were being collected, participants (N = 43) performed a stressful anagram task, which was followed by a recovery period during which they reflected on the stressor while watching a positive or neutral video. Participants also reported positive and negative emotions throughout the task as well as retrospective thoughts about the task. Although there was no effect of experimental context on emotional recovery, we found that ventromedial prefrontal cortex (vmPFC) activation during the stressor predicted more positive emotions during recovery, which in turn predicted less negative emotions during recovery. In addition, the relationship between vmPFC activation and positive emotions during recovery was mediated by decentering-the meta-cognitive detachment of oneself from one's feelings. In sum, successful recovery from a stressor seems to be due to activation of positive emotion-related regions during the stressor itself as well as to their downstream effects on certain cognitive forms of emotion regulation.

  11. Plasma Homocysteine Is Associated with Increased Oxidative Stress and Antioxidant Enzyme Activity in Welders

    Directory of Open Access Journals (Sweden)

    Hung-Hsin Liu

    2013-01-01

    Full Text Available The purpose of this study was to examine the association of vitamin B6 status and plasma homocysteine with oxidative stress and antioxidant capacities in welders. Workers were divided into either the welding exposure group (n=57 or the nonexposure controls (n=42 based on whether they were employed as welders. There were no significant differences in vitamin B6 status and plasma homocysteine concentration between the welding exposure group and the nonexposure controls. The welding exposure group had significantly higher levels of oxidized low-density lipoprotein cholesterol and lower erythrocyte glutathione concentration and superoxide dismutase (SOD activities when compared to nonexposure controls. Plasma pyridoxal 5′-phosphate concentration did not correlate with oxidative stress indicators or antioxidant capacities in either group. However, plasma homocysteine significantly correlated with total antioxidant capacity (TAC (partial rs=-0.34, P<0.05 and erythrocyte SOD activities (partial rs=0.29, P<0.05 after adjusting for potential confounders in the welding exposure group. In the welding exposure group, adequate vitamin B6 status was not associated with oxidative stress or antioxidant capacities. However, elevated plasma homocysteine seemed to be a major contributing factor to antioxidant capacities (TAC and erythrocyte SOD activities in welders.

  12. Exposure to Forced Swim Stress Alters Local Circuit Activity and Plasticity in the Dentate Gyrus of the Hippocampus

    Directory of Open Access Journals (Sweden)

    Mouna Maroun

    2008-02-01

    Full Text Available Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience.

  13. Exposure to Forced Swim Stress Alters Local Circuit Activity and Plasticity in the Dentate Gyrus of the Hippocampus

    Science.gov (United States)

    Yarom, Orli; Maroun, Mouna; Richter-Levin, Gal

    2008-01-01

    Studies have shown that, depending on its severity and context, stress can affect neural plasticity. Most related studies focused on synaptic plasticity and long-term potentiation (LTP) of principle cells. However, evidence suggests that following high-frequency stimulation, which induces LTP in principal cells, modifications also take place at the level of complex interactions with interneurons within the dentate gyrus, that is, at the local circuit level. So far, the possible effects of stress on local circuit activity and plasticity were not studied. Therefore, we set out to examine the possible alterations in local circuit activity and plasticity following exposure to stress. Local circuit activity and plasticity were measured by using frequency dependant inhibition (FDI) and commissural modulation protocols following exposure to a 15 minute-forced swim trial. Exposure to stress did not alter FDI. The application of theta-burst stimulation (TBS) reduced FDI in both control and stressed rats, but this type of plasticity was greater in stressed rats. Commissural-induced inhibition was significantly higher in stressed rats both before and after applying theta-burst stimulation. These findings indicate that the exposure to acute stress affects aspects of local circuit activity and plasticity in the dentate gyrus. It is possible that these alterations underlie some of the behavioral consequences of the stress experience. PMID:18301720

  14. Physical activity, job demand-control, perceived stress-energy, and salivary cortisol in white-collar workers

    DEFF Research Database (Denmark)

    Hansen, Ase Marie; Blangsted, Anne Katrine; Hansen, Ernst Albin

    2010-01-01

    PURPOSE: The aim of the present study is to examine the association between physical activity and perceived job demand, job control, perceived stress and energy, and physiological arousal reflected by morning and evening concentrations of cortisol in saliva among white-collar workers. METHODS...... active at leisure time and perceiving higher energy showed higher evening saliva cortisol. CONCLUSION: Physically active employees perceive less stress and more energy. The association between stress-energy and salivary cortisol was affected by vigorous physical activity. No association between job...... control-demand and the degree of physical activity was found. Based on the present data, we recommend office workers-exposed to high job strain and inactivity at the job-to perform physical activity, preferably of high intensity, in order to reduce stress and increase energy....

  15. Vaginal cone use in passive and active phases in patients with stress urinary incontinence

    Directory of Open Access Journals (Sweden)

    Jorge Milhem Haddad

    2011-01-01

    Full Text Available OBJECTIVE: To evaluate vaginal cone therapy in two phases, passive and active, in women with stress urinary incontinence. METHODS: A prospective study was conducted at the Department of Obstetrics and Gynecology, São Paulo University, Brazil. Twenty-four women with a clinical and urodynamic diagnosis of stress urinary incontinence were treated with vaginal cones in a passive phase (without voluntary contractions of the pelvic floor and an active phase (with voluntary contractions, each of which lasted three months. Clinical complaints, a functional evaluation of the pelvic floor, a pad test, and bladder neck mobility were analyzed before and after each phase. RESULTS: Twenty-one patients completed the treatment. The reduction in absolute risk with the pad test was 0.38 (p<0.034 at the end of the passive phase and 0.67 (p<0.0001 at the end of the active phase. The reduction in absolute risk with the pelvic floor evaluation was 0.62 (p<0.0001 at the end of the passive phase and 0.77 (p<0.0001 at the end of the active phase. The reduction in absolute risk of bladder neck mobility was 0.38 (p<0.0089 at the end of the passive phase and 0.52 (p<0.0005 at the end of the active phase. Complete reversal of symptomatology was observed in 12 (57.1% patients, and satisfaction was expressed by 19 (90.4%. CONCLUSION: Using vaginal cones in the passive phase, as other researchers did, was effective. Inclusion of the active phase led to additional improvement in all of the study parameters evaluated in women with stress urinary incontinence. Randomized studies are needed, however, to confirm these results.

  16. Activation of stress signaling molecules in bat brain during arousal from hibernation.

    Science.gov (United States)

    Lee, Moonyong; Choi, Inho; Park, Kyoungsook

    2002-08-01

    Induction of glucose-regulated proteins (GRPs) is a ubiquitous intracellular response to stresses such as hypoxia, glucose starvation and acidosis. The induction of GRPs offers some protection against these stresses in vitro, but the specific role of GRPs in vivo remains unclear. Hibernating bats present a good in vivo model to address this question. The bats must overcome local high oxygen demand in tissue by severe metabolic stress during arousal thermogenesis. We used brain tissue of a temperate bat Rhinolopus ferrumequinum to investigate GRP induction by high metabolic oxygen demand and to identify associated signaling molecules. We found that during 30 min of arousal, oxygen consumption increased from nearly zero to 11.9/kg/h, which was about 8.7-fold higher than its active resting metabolic rate. During this time, body temperature rose from 7 degrees C to 35 degrees C, and levels of TNF-alpha and lactate in brain tissue increased 2-2.5-fold, indicating a high risk of oxygen shortage. Concomitantly, levels of GRP75, GRP78 and GRP94 increased 1.5-1.7-fold. At the same time, c-Jun N-terminal protein kinase (JNK) activity increased 6.4-fold, and extracellular signal-regulated protein kinase (ERK) activity decreased to a similar degree (6.1-fold). p38 MAPK activity was very low and remained unchanged during arousal. In addition, survival signaling molecules protein kinase B (Akt) and protein kinase C (PKC) were activated 3- and 5-fold, respectively, during arousal. Taken together, our results showed that bat brain undergoes high oxygen demand during arousal from hibernation. Up-regulation of GRP proteins and activation of JNK, PKCgamma and Akt may be critical for neuroprotection and the survival of bats during the repeated process.

  17. Cocaine-mediated induction of microglial activation involves the ER stress-TLR2 axis.

    Science.gov (United States)

    Liao, Ke; Guo, Minglei; Niu, Fang; Yang, Lu; Callen, Shannon E; Buch, Shilpa

    2016-02-09

    Neuroinflammation associated with advanced human immunodeficiency virus (HIV)-1 infection is often exacerbated by chronic cocaine abuse. Cocaine exposure has been demonstrated to mediate up-regulation of inflammatory mediators in in vitro cultures of microglia. The molecular mechanisms involved in this process, however, remain poorly understood. In this study, we sought to explore the underlying signaling pathways involved in cocaine-mediated activation of microglial cells. BV2 microglial cells were exposed to cocaine and assessed for toll-like receptor (TLR2) expression by quantitative polymerase chain reaction (qPCR), western blot, flow cytometry, and immunofluorescence staining. The mRNA and protein levels of cytokines (TNFα, IL-6, MCP-1) were detected by qPCR and ELISA, respectively; level of reactive oxygen species (ROS) production was examined by the Image-iT LIVE Green ROS detection kit; activation of endoplasmic reticulum (ER)-stress pathways were detected by western blot. Chromatin immunoprecipitation (ChIP) assay was employed to discern the binding of activating transcription factor 4 (ATF4) with the TLR2 promoter. Immunoprecipitation followed by western blotting with tyrosine antibody was used to determine phosphorylation of TLR2. Cocaine-mediated up-regulation of TLR2 expression and microglial activation was validated in cocaine-injected mice. Exposure of microglial cells to cocaine resulted in increased expression of TLR2 with a concomitant induction of microglial activation. Furthermore, this effect was mediated by NADPH oxidase-mediated rapid accumulation of ROS with downstream activation of the ER-stress pathways as evidenced by the fact that cocaine exposure led to up-regulation of pPERK/peIF2α/ATF4 and TLR2. The novel role of ATF4 in the regulation of TLR2 expression was confirmed using genetic and pharmacological approaches. xThe current study demonstrates that cocaine-mediated activation of microglia involves up-regulation of TLR2 through the

  18. Impaired cardiac SIRT1 activity by carbonyl stress contributes to aging-related ischemic intolerance.

    Directory of Open Access Journals (Sweden)

    Chunhu Gu

    Full Text Available Reactive aldehydes can initiate protein oxidative damage which may contribute to heart senescence. Sirtuin 1 (SIRT1 is considered to be a potential interventional target for I/R injury management in the elderly. We hypothesized that aldehyde mediated carbonyl stress increases susceptibility of aged hearts to ischemia/reperfusion (I/R injury, and elucidate the underlying mechanisms with a focus on SIRT1. Male C57BL/6 young (4-6 mo and aged (22-24 mo mice were subjected to myocardial I/R. Cardiac aldehyde dehydrogenase (ALDH2, SIRT1 activity and protein carbonyls were assessed. Our data revealed that aged heart exhibited increased endogenous aldehyde/carbonyl stress due to impaired ALDH2 activity concomitant with blunted SIRT1 activity (P<0.05. Exogenous toxic aldehydes (4-HNE exposure in isolated cardiomyocyte verified that aldehyde-induced carbonyl modification on SIRT1 impaired SIRT1 activity leading to worse hypoxia/reoxygenation (H/R injury, which could all be rescued by Alda-1 (ALDH2 activator (all P<0.05. However, SIRT1 inhibitor blocked the protective effect of Alda-1 on H/R cardiomyocyte. Interestingly, myocardial I/R leads to higher carbonylation but lower activity of SIRT1 in aged hearts than that seen in young hearts (P<0.05. The application of Alda-1 significantly reduced the carbonylation on SIRT1 and markedly improved the tolerance to in vivo I/R injury in aged hearts, but failed to protect Sirt1(+/- knockout mice against myocardial I/R injury. This was verified by Alda-1 treatment improved postischemic contractile function recovery in ex vivo perfused aged but not in Sirt1(+/- hearts. Thus, aldehyde/carbonyl stress is accelerated in aging heart. These results provide a new insight that impaired cardiac SIRT1 activity by carbonyl stress plays a critical role in the increased susceptibility of aged heart to I/R injury. ALDH2 activation can restore this aging-related myocardial ischemic intolerance.

  19. Extension joints: a tool to infer the active stress field orientation (case study from southern Italy)

    Science.gov (United States)

    De Guidi, Giorgio; Caputo, Riccardo; Scudero, Salvatore; Perdicaro, Vincenzo

    2013-04-01

    An intense tectonic activity in eastern Sicily and southern Calabria is well documented by the differential uplift of Late Quaternary coastlines and by the record of the strong historical earthquakes. The extensional belt that crosses this area is dominated by a well established WNW-ESE-oriented extensional direction. However, this area is largely lacking of any structural analysis able to define the tectonics at a more local scale. In the attempt to fill this gap of knowledge, we carried out a systematic analysis of extension joint sets. In fact, the systematic field collection of these extensional features, coupled with an appropriate inversion technique, allows to determine the characteristic of the causative tectonic stress field. Joints are defined as outcrop-scale mechanical discontinuities showing no evidence of shear motion and being originated as purely extensional fractures. Such tectonic features are one of the most common deformational structures in every tectonic environment and particularly abundant in the study area. A particular arrangement of joints, called "fracture grid-lock system", and defined as an orthogonal joint system where mutual abutting and crosscutting relationships characterize two geologically coeval joint sets, allow to infer the direction and the magnitude of the tectonic stress field. We performed the analyses of joints only on Pleistocene deposits of Eastern Sicily and Southern Calabria. Moreover we investigated only calcarenite sediments and cemented deposits, avoiding claysh and loose matrix-supported clastic sediments where the deformation is generally accomodated in a distributed way through the relative motion between the single particles. In the selection of the sites, we also took into account the possibility to clearly observe the geometric relationships among the joints. For this reason we chose curvilinear road cuts or cliffs, wide coastal erosional surfaces and quarries. The numerical inversions show a similar stress

  20. Electro dermal activity as maker of psychophysiology and work stressed variations; L`attivita` elettrodermica come maker di variazioni psicofisiologiche e stress da lavoro

    Energy Technology Data Exchange (ETDEWEB)

    Cenni, P. [ENEA, Centro Ricerche `Ezio Clementel`, Bologna, Bologna (Italy). Dip. Ambiente; Arduini, R. [Azienda USL, Citta` di Bologna, Bologna (Italy); Palomba, D. [Padova Univ., Padua (Italy). Dipartimento di Psicologia Generale; Tuozzi, G. [Bologna Univ., Bologna (Italy). Dipartimento di Psicologia

    1996-10-01

    In this report an approach is described on the use of work psychophysiology in stress research. Such a contribution may have its main impact on the organizational factors and on the identification and prevention of stress related diseases. Physiological parameters such a heart rate, muscular activity, peripheral temperature and electrodermal activity are investigated in a combined laboratory-field framework, in order to quantify changes in functions mostly regulated by autonomic nervous system and verify whether they can be caused by negative influence of environmental organizational or psycho social factors. In particular, the authors present the electrodermal activity as an interesting index related to clinical and emotional aspects and very significant for the experimental data recorded in a research on bus-drivers stress carried out at the Occupational Medicine Service, ENEA, Bologna.

  1. The effect of water and salt stresses on the phosphorus content and acid phosphatase activity in oilseed rape

    Directory of Open Access Journals (Sweden)

    Stanisław Flasiński

    2014-01-01

    Full Text Available Oilseed rape plants responded to water and salt stresses (-0.5 MPa, PEG 6000 and NaCI by reduction of the fresh and dry weights of shoots and roots. When PEG was used, the ratio of dry weights of roots:shoots surpassed that of controls. The leaf protein content increased considerably. The phosphorus content decreased only in the roots, most significantly after three days of stress. Immediately after the stresses were induced, an increase in the acid phosphatase (AP activity was noted. Water and salt stresses caused four- and two-fold increases in AP activity in leaves, respectively. Changes in the enzyme activity were negligible in stems and roots. There are nine forms of AP in young leaves of oilseed rape. In the stressed plants, from No. 5 revealed lower activity and forms Nos 8 and 9, higher activities than in the control. The increase in AP activity was directly accompanied by the decrease in the water potential of the tissues. Oilseed rape is considerably less sensitive to salt stress than to water stress, which is manifested as the lower inhibition of plant growth and also by a smaller increase in acid phosphatase activity.

  2. Plasma Prolidase Activity and Oxidative Stress in Patients with Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Akhilesh Kumar Verma

    2015-01-01

    Full Text Available Prolidase deficiency has been related to mental retardation and oxidative stress. The study aimed to observe plasma prolidase activity (PPA, total oxidant status (TOS, total antioxidant status (TAS, and oxidative stress index (OSI in patients with Parkinson’s disease (PD. 240 subjects with PD and 150 healthy volunteers were considered as cases and controls, respectively. PPA, TOS, TAS, and OSI were measured spectrophotometrically. PPA and TAS in cases were more significantly decreased than controls (P<0.01, while TOS and OSI were significantly increased (P<0.001. In cases, nonsignificant, positive correlation was observed between PPA and TOS and OSI while significant, negative correlation was observed between PPA and TAS (P=0.047. PPA in cases was nonsignificantly decreased with increased duration of PD (P=0.747 while TAS was significantly decreased (P<0.001 and TOS and OSI were significantly increased (P<0.001. It was observed that higher age groups had decreased PPA, and TAS and increased TOS and OSI compared to lower age groups in cases. In summary, patients with PD have decreased PPA and increased oxidative stress compared to healthy volunteers. PPA was associated with oxidative stress markers in patients with PD. Decreased PPA and TAS and increased TOS and OSI were associated with progression of disease and higher age.

  3. Management of sleep-time masticatory muscle activity using stabilisation splints affects psychological stress.

    Science.gov (United States)

    Takahashi, H; Masaki, C; Makino, M; Yoshida, M; Mukaibo, T; Kondo, Y; Nakamoto, T; Hosokawa, R

    2013-12-01

    To treat sleep bruxism (SB), symptomatic therapy using stabilisation splints (SS) is frequently used. However, their effects on psychological stress and sleep quality have not yet been examined fully. The objective of this study was to clarify the effects of SS use on psychological stress and sleep quality. The subjects (11 men, 12 women) were healthy volunteers. A crossover design was used. Sleep measurements were performed for three consecutive days or longer without (baseline) or with an SS or palatal splint (PS), and data for the final day were evaluated. We measured masseter muscle activity during sleep using portable electromyography to evaluate SB. Furthermore, to compare psychological stress before and after sleep, assessments were made based on STAI-JYZ and the measurement of salivary chromogranin A. To compare each parameter among the three groups (baseline, SS and PS), Friedman's and Dunn's tests were used. From the results of the baseline measurements, eight subjects were identified as high group and 15 as low group. Among the high group, a marked decrease in the number of bruxism events per hour and an increase in the difference in the total STAI Y-1 scores were observed in the SS group compared with those at baseline (P sleep stages. SS use may be effective in reducing the number of SB events, while it may increase psychological stress levels, and SS use did not apparently influence sleep stages. © 2013 John Wiley & Sons Ltd.

  4. Variantes en los factores de transcripción para IFNγ, TBET, STAT1, STAT4 y HLX, y el riesgo de desarrollar tuberculosis pulmonar en un estudio de casos y controles de una población colombiana

    Directory of Open Access Journals (Sweden)

    María Dulfary Sánchez

    2013-06-01

    Full Text Available Introducción. El interferón gama (IFNγ es la citocina más potente para controlar la infección por Mycobacterium tuberculosis, el agente etiológico de la tuberculosis humana. Los pacientes con tuberculosis activa presentan reducción de los niveles de IFNγ, lo cual parece explicar la inmunidad poco efectiva contra el bacilo. La disminución de su expresión o alteraciones funcionales de los factores transactivadores del promotor del gen de IFNγ, podrían explicar la reducción de los niveles de IFNγ enlos pacientes con tuberculosis. Objetivo. Determinar la asociación de variantes genéticas en los factores de transcripción TBET,STAT1, STAT4 y HLX con sensibilidad o resistencia a tuberculosis pulmonar. Materiales y métodos. Se seleccionaron ocho polimorfismos de un solo nucleótido (Single-NucleotidePolymorphism, SNP y se estableció su genotipo, en 466 pacientes con tuberculosis pulmonar y 300 controles sanos en Colombia; además, se hizo un análisis de asociación alélica y genética. Resultados. Los resultados indican que los SNP de los factores de transcripción estudiados no están asociados con tuberculosis; sin embargo, el polimorfismo rs11650354 en TBET puede estar implicado en la disminución de riesgo de tuberculosis. El genotipo TT de TBET se asoció significativamente con protección contra tuberculosis usando un modelo genético recesivo (OR=0,089; CI95%: 0,01-0,73;p=0,0069; sin embargo, la corrección mediante pruebas múltiples de ajuste abolió esta asociación (Empirical P Value, EMP2=0,61. Conclusión. En este estudio se sugiere un efecto de la variante rs11650354 de TBET sobre la resistencia a la tuberculosis en la población colombiana. Es necesario desarrollar un estudio de replicación usando muestras adicionales para confirmar esta asociación sugestiva. doi: http://dx.doi.org/10.7705/biomedica.v33i2.790

  5. Nrf2 activation involves an oxidative-stress independent pathway in tetrafluoroethylcysteine-induced cytotoxicity.

    Science.gov (United States)

    Ho, Han K; White, Collin C; Fernandez, Carolina; Fausto, Nelson; Kavanagh, Terrance J; Nelson, Sidney D; Bruschi, Sam A

    2005-08-01

    Tetrafluoroethylcysteine (TFEC), a metabolite of the industrial gas tetrafluoroethylene, can cause both nephrotoxicity and limited hepatotoxicity in animal models, and this is associated with the covalent modification of specific intramitochondrial proteins including heat shock protein 60 (HSP60), mitochondrial HSP70 (mtHSP70), aspartate aminotransferase (AST), aconitase, and alpha-ketoglutarate dehydrogenase (alphaKGDH). Using the murine TAMH cell line as a useful in vitro model for TFEC toxicity, we demonstrate a rapid and sustained induction of Nrf2, a member of the "cap-and-collar" transcription factor family, following exposure to cytotoxic concentrations of TFEC. A functional correlate was also established with the rapid translocation of cytosolic Nrf2 into the nucleus. In addition, transcriptional and translational upregulation of known Nrf2 regulated genes including glutamate cysteine ligase (GCL), both catalytic and modulatory subunits, heme oxygenase-1, and glutathione S-transferase (GST) isoforms were detected. While Nrf2 activation is often linked to perturbation of cellular thiol status and/or oxidative stress, we were unable to detect any significant depletion of cellular glutathione or oxidation of mitochondrial membrane cardiolipin or increases in reactive oxygen species (ROS). These data suggest Nrf2 activation is likely independent of classical oxidative stress or, at best, a result of a transient, low-level redox stress. Moreover, supporting evidence indicates an early endoplasmic reticular (ER) stress response after TFEC treatment, with a time-dependent upregulation of the ER responsive genes gadd34, gadd45, gadd153, and ndr1 . These findings suggest an alternative pathway for Nrf2 activation, i.e., Nrf2 phosphorylation through ER-mediated protein kinases such as PKR-like endoplasmic reticular kinase (PERK). Overall, the results implicate a role for Nrf2 in the cellular response to TFEC toxicity and suggest a previously unrecognized role for the

  6. Gene expression and activity of antioxidant enzymes in rice plants, cv. BRS AG, under saline stress.

    Science.gov (United States)

    Rossatto, Tatiana; do Amaral, Marcelo Nogueira; Benitez, Letícia Carvalho; Vighi, Isabel Lopes; Braga, Eugenia Jacira Bolacel; de Magalhães Júnior, Ariano Martins; Maia, Mara Andrade Colares; da Silva Pinto, Luciano

    2017-10-01

    The rice cultivar ( Oryza sativa L.) BRS AG, developed by Embrapa Clima Temperado, is the first cultivar designed for purposes other than human consumption. It may be used in ethanol production and animal feed. Different abiotic stresses negatively affect plant growth. Soil salinity is responsible for a serious reduction in productivity. Therefore, the objective of this study was to evaluate the gene expression and the activity of antioxidant enzymes (SOD, CAT, APX and GR) and identify their functions in controlling ROS levels in rice plants, cultivar BRS AG, after a saline stress period. The plants were grown in vitro with two NaCl concentrations (0 and 136 mM), collected at 10, 15 and 20 days of cultivation. The results indicated that the activity of the enzymes evaluated promotes protection against oxidative stress. Although, there was an increase of reactive oxygen species, there was no increase in MDA levels. Regarding genes encoding isoforms of antioxidant enzymes, it was observed that OsSOD3 - CU/Zn , OsSOD2 - Cu/Zn , OsSOD - Cu/Zn , OsSOD4 - Cu/Zn , OsSODCc1 - Cu/Zn , OsSOD - Fe , OsAPX1 , OsCATB and OsGR2 were the most responsive. The increase in the transcription of all genes among evaluated isoforms, except for OsAPX6 , which remained stable, contributed to the increase or the maintenance of enzyme activity. Thus, it is possible to infer that the cv. BRS AG has defense mechanisms against salt stress.

  7. Activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.

    Science.gov (United States)

    Xu, Jun; Wu, Liang; Zhang, Yiming; Gu, Huijie; Huang, Zhongyue; Zhou, Kaifeng; Yin, Xiaofan

    2017-12-22

    The present study tested the potential effect of OSU53, a novel AMPK activator, against hydrogen peroxide (H2O2)-induced spinal cord neuron damages. Treatment with OSU53 attenuated H2O2-induced death and apoptosis of primary murine spinal cord neurons. OSU53 activated AMPK signaling, which is required for its actions in spinal cord neurons. The AMPK inhibitor Compound C or AMPKα1 siRNA almost abolished OSU53-mediated neuroprotection against H2O2. On the other hand, sustained-activation of AMPK by introducing the constitutive-active AMPKα1 mimicked OSU53's actions, and protected spinal cord neurons from oxidative stress. OSU53 significantly attenuated H2O2-induced reactive oxygen species production, lipid peroxidation and DNA damages in spinal cord neurons. Additionally, OSU53 increased NADPH content and heme oxygenase-1 mRNA expression in H2O2-treated spinal cord neurons. Together, we indicate that targeted-activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.

  8. Oxidative stress plays a role in high glucose-induced activation of pancreatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Gyeong Ryul; Lee, Esder; Chun, Hyun-Ji; Yoon, Kun-Ho; Ko, Seung-Hyun; Ahn, Yu-Bae; Song, Ki-Ho, E-mail: kihos@catholic.ac.kr

    2013-09-20

    Highlights: •High glucose increased production of reactive oxygen species in cultured pancreatic stellate cells. •High glucose facilitated the activation of these cells. •Antioxidant treatment attenuated high glucose-induced activation of these cells. -- Abstract: The activation of pancreatic stellate cells (PSCs) is thought to be a potential mechanism underlying islet fibrosis, which may contribute to progressive β-cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants reduced islet fibrosis in an animal model of type 2 diabetes. However, there is no in vitro study demonstrating that high glucose itself can induce oxidative stress in PSCs. Thus, PSCs were isolated and cultured from Sprague Dawley rats, and treated with high glucose for 72 h. High glucose increased the production of reactive oxygen species. When treated with high glucose, freshly isolated PSCs exhibited myofibroblastic transformation. During early culture (passage 1), PSCs treated with high glucose contained an increased number of α-smooth muscle actin-positive cells. During late culture (passages 2–5), PSCs treated with high glucose exhibited increases in cell proliferation, the expression of fibronectin and connective tissue growth factor, release of interleukin-6, transforming growth factor-β and collagen, and cell migration. Finally, the treatment of PSCs with high glucose and antioxidants attenuated these changes. In conclusion, we demonstrated that high glucose increased oxidative stress in primary rat PSCs, thereby facilitating the activation of these cells, while antioxidant treatment attenuated high glucose-induced PSC activation.

  9. Oxidative stress plays a role in high glucose-induced activation of pancreatic stellate cells

    International Nuclear Information System (INIS)

    Ryu, Gyeong Ryul; Lee, Esder; Chun, Hyun-Ji; Yoon, Kun-Ho; Ko, Seung-Hyun; Ahn, Yu-Bae; Song, Ki-Ho

    2013-01-01

    Highlights: •High glucose increased production of reactive oxygen species in cultured pancreatic stellate cells. •High glucose facilitated the activation of these cells. •Antioxidant treatment attenuated high glucose-induced activation of these cells. -- Abstract: The activation of pancreatic stellate cells (PSCs) is thought to be a potential mechanism underlying islet fibrosis, which may contribute to progressive β-cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants reduced islet fibrosis in an animal model of type 2 diabetes. However, there is no in vitro study demonstrating that high glucose itself can induce oxidative stress in PSCs. Thus, PSCs were isolated and cultured from Sprague Dawley rats, and treated with high glucose for 72 h. High glucose increased the production of reactive oxygen species. When treated with high glucose, freshly isolated PSCs exhibited myofibroblastic transformation. During early culture (passage 1), PSCs treated with high glucose contained an increased number of α-smooth muscle actin-positive cells. During late culture (passages 2–5), PSCs treated with high glucose exhibited increases in cell proliferation, the expression of fibronectin and connective tissue growth factor, release of interleukin-6, transforming growth factor-β and collagen, and cell migration. Finally, the treatment of PSCs with high glucose and antioxidants attenuated these changes. In conclusion, we demonstrated that high glucose increased oxidative stress in primary rat PSCs, thereby facilitating the activation of these cells, while antioxidant treatment attenuated high glucose-induced PSC activation

  10. Midlife stress alters memory and mood-related behaviors in old age: Role of locally activated glucocorticoids.

    Science.gov (United States)

    Wheelan, Nicola; Kenyon, Christopher J; Harris, Anjanette P; Cairns, Carolynn; Al Dujaili, Emad; Seckl, Jonathan R; Yau, Joyce L W

    2018-03-01

    Chronic exposure to stress during midlife associates with subsequent age-related cognitive decline and may increase the vulnerability to develop psychiatric conditions. Increased hypothalamic-pituitary-adrenal (HPA) axis activity has been implicated in pathogenesis though any causative role for glucocorticoids is unestablished. This study investigated the contribution of local glucocorticoid regeneration by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), in persisting midlife stress-induced behavioral effects in mice. Middle-aged (10 months old) 11β-HSD1-deficient mice and wild-type congenic controls were randomly assigned to 28 days of chronic unpredictable stress or left undisturbed (non-stressed). All mice underwent behavioral testing at the end of the stress/non-stress period and again 6-7 months later. Chronic stress impaired spatial memory in middle-aged wild-type mice. The effects, involving a wide spectrum of behavioral modalities, persisted for 6-7 months after cessation of stress into early senescence. Enduring effects after midlife stress included impaired spatial memory, enhanced contextual fear memory, impaired fear extinction, heightened anxiety, depressive-like behavior, as well as reduced hippocampal glucocorticoid receptor mRNA expression. In contrast, 11β-HSD1 deficient mice resisted both immediate and enduring effects of chronic stress, despite similar stress-induced increases in systemic glucocorticoid activity during midlife stress. In conclusion, chronic stress in midlife exerts persisting effects leading to cognitive and affective dysfunction in old age via mechanisms that depend, at least in part, on brain glucocorticoids generated locally by 11β-HSD1. This finding supports selective 11β-HSD1 inhibition as a novel therapeutic target to ameliorate the long-term consequences of stress-related psychiatric disorders in midlife. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Delta-aminolevulinate dehydratase activity and oxidative stress markers in preeclampsia.

    Science.gov (United States)

    de Lucca, Leidiane; Rodrigues, Fabiane; Jantsch, Letícia B; Kober, Helena; Neme, Walter S; Gallarreta, Francisco M P; Gonçalves, Thissiane L

    2016-12-01

    Preeclampsia is an important pregnancy-specific multisystem disorder characterized by the onset of hypertension and proteinuria. It is of unknown etiology and involves serious risks for the pregnant women and fetus. One of the main factors involved in the pathophysiology of preeclampsia is oxidative stress, where excess free radicals produce harmful effects, including damage to macromolecules such as lipids, proteins and DNA. In addition, the sulfhydryl delta-aminolevulinate dehydratase enzyme (δ-ALA-D) that is part of the heme biosynthetic pathway in pro-oxidant conditions can be inhibited, which may result in the accumulation of 5-aminolevulinic acid (ALA), associated with the overproduction of free radicals, suggesting it to be an indirect marker of oxidative stress. As hypertensive pregnancy complications are a major cause of morbidity and mortality maternal and fetal where oxidative stress appears to be an important factor involved in preeclampsia, the aim of this study was to evaluate the activity of δ-ALA-D and classic oxidative stress markers in the blood of pregnant women with mild and severe preeclampsia. The analysis and quantification of the following oxidative stress markers were performed: thiobarbituric acid-reactive species (TBARS); presence of protein and non-protein thiol group; quantification of vitamin C; Catalase and δ-ALA--D activities in samples of blood of pregnant women with mild preeclampsia (n=25), with severe preeclampsia (n=30) and in a control group of healthy pregnant women (n=30). TBARS was significantly higher in women with preeclampsia, while the presence of thiol groups, levels of vitamin C, catalase and δ-ALA-D activity were significantly lower in groups of pregnant women with preeclampsia compared with healthy women. In addition, the results showed no significant difference between groups of pregnant women with mild and severe preeclampsia. The data suggest a state of increased oxidative stress in pregnant women with

  12. Evidence of Bidirectional Associations Between Perceived Stress and Symptom Activity: A Prospective Longitudinal Investigation in Inflammatory Bowel Disease.

    Science.gov (United States)

    Sexton, Kathryn A; Walker, John R; Graff, Lesley A; Bernstein, Matthew T; Beatie, Brooke; Miller, Norine; Sargent, Michael; Targownik, Laura E

    2017-03-01

    Our aim was to explore the relationships among perceived stress, intestinal inflammation, and inflammatory bowel disease (IBD) symptoms over time. Participants were recruited from a population-based registry of persons with IBD and assessed at months 0, 3, and 6. Key dependent measures were the Manitoba IBD Index (symptom activity), Cohen's Perceived Stress Scale, and fecal calprotectin in stool (intestinal inflammation). Complete data were available for 417 participants at months 0; 369 provided follow-up data. Active symptoms were reported by 54% of those with Crohn's disease (CD) and 40% of those with ulcerative colitis (UC) and approximately one-third consistently had fecal calprotectin measures ≥250 μg/g, suggestive of active inflammation. A significant proportion of participants had indications of inflammation but no active symptoms over the 6 months. Correlations of month 0 perceived stress and disease activity measures with values at months 3 and 6 for both CD and UC indicated strong temporal stability. In hierarchical multiple regression analyses, month 0 symptom activity was thus a strong predictor of later symptom activity for CD and UC. Perceived stress predicted change in symptom activity from 0 to 3 months for CD, as did use of prednisone for UC. Comparably, month 0 perceived stress was a strong predictor of later perceived stress for CD and UC, while month 0 symptom activity predicted change in perceived stress from 0 to 3 months for both CD and UC. The analysis revealed prospective bidirectional relationships between perceived stress and IBD symptoms but no relationship between perceived stress and change in intestinal inflammation as assessed by fecal calprotectin.

  13. Being stressed and active!? An analysis of different aspects of the relationship between physical activity, individual perceived stress, and individual health

    OpenAIRE

    Reiner, Miriam

    2014-01-01

    Die sportwissenschaftliche Forschung zeigt deutlich, dass Sport und körperliche Aktivität positive Effekte für die Gesundheit haben, im Gegensatz dazu aber erlebter Stress negative Folgen hat. Es stellt sich die Frage, welche Rollen und Effekte Sport im Stress-Gesundheit Kontext spielen kann. In drei Studien wurde der Moderatoreffekt von Sport auf den Zusammenhang zwischen Stress und Beschwerden sowie der Effekt von erlebtem Stress auf die Sportaktivität selbst untersucht.

  14. Effect of short-term salt stress on oxidative stress markers and antioxidant enzymes activity in tocopherol-deficient Arabidopsis thaliana plants.

    Science.gov (United States)

    Semchuk, N M; Vasylyk, Y V; Lushchak, O V; Lushchak, V I

    2012-01-01

    Changes of carotenoids and anthocyanins content, lipid peroxidation, and activity of antioxidant enzymes were studied in wild type and tocopherol-deficient lines vte1 and vte4 of Arabidopsis thaliana subjected to 200 mM NaCI during 24 h. The salt stress enhanced the intensity of lipid peroxidation to different extent in all three plant lines. Salt stress resulted in an increase of carotenoid content and activity of catalase, ascorbate peroxidase, guaiacol peroxidase and glutathione reductase in wild type and tocopherol-deficient vte1 mutant. However, the increase in anthocyanins concentration was observed in vte1 mutants only. In vte4 mutant, which contain gamma-tocopherol instead of alpha-tocopherol, the response to salt stress occurred via coordinative action of superoxide dismutase and enzymes of ascorbate-glutathione cycle, in particular, ascorbate peroxidase, glutathione reductase, dehydroascorbate reductase, and glutathione-S-transferase. It can be concluded, that salt stress was accompanied by oxidative stress in three studied lines, however different mechanisms involved in adaptation of wild type and tocopherol-deficient lines to salt stress.

  15. Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex.

    Science.gov (United States)

    Toledo-Rodriguez, Maria; Pitiot, Alain; Paus, Tomáš; Sandi, Carmen

    2012-07-01

    Adolescence is characterized by major developmental changes that may render the individual vulnerable to stress and the development of psychopathologies in a sex-specific manner. Earlier we reported lower anxiety-like behavior and higher risk-taking and novelty seeking in rats previously exposed to peri-pubertal stress. Here we studied whether peri-pubertal stress affected the acquisition and extinction of fear memories and/or the associated functional engagement of various brain regions, as assessed with 2-deoxyglucose. We showed that while peri-pubertal stress reduced freezing during the acquisition of fear memories (training) in both sexes, it had a sex-specific effect on extinction of these memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices showed higher metabolic rates during extinction in rats exposed to peri-pubertal stress. Interestingly, activation of the infralimbic cortex was negatively correlated with freezing during extinction only in control males, while only males stressed during puberty showed a significant correlation between behavior during extinction and metabolic activation of hippocampus, amygdala and paraventricular nucleus. No correlations between brain activation and behavior during extinction were observed in females (control or stress). These results indicate that exposure to peri-pubertal stress affects behavior and brain metabolism when the individual is exposed to an additional stressful challenge. Some of these effects are sex-specific. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Bufotalin-induced apoptosis in osteoblastoma cells is associated with endoplasmic reticulum stress activation.

    Science.gov (United States)

    Zhu, Yun-Rong; Xu, Yong; Fang, Jian-Feng; Zhou, Feng; Deng, Xiong-Wei; Zhang, Yun-Qing

    2014-08-15

    The search for novel and more efficient chemo-agents against malignant osteoblastoma is important. In this study, we examined the potential anti-osteoblastoma function of bufotalin, and studied the underlying mechanisms. Our results showed that bufotalin induced osteoblastoma cell death and apoptosis in dose- and time-dependent manners. Further, bufotalin induced endoplasmic reticulum (ER) stress activation in osteoblastoma cells, the latter was detected by the induction of C/EBP homologous protein (CHOP), phosphorylation of inositol-requiring enzyme 1 (IRE1) and PKR-like endoplasmic reticulum kinase (PERK), as well as caspase-12 activation. Conversely, the ER stress inhibitor salubrinal, the caspase-12 inhibitor z-ATAD-fmk as well as CHOP depletion by shRNA significantly inhibited bufotalin-induced osteoblastoma cell death and apoptosis. Finally, by using a mice xenograft model, we demonstrated that bufotalin inhibited U2OS osteoblastoma cell growth in vivo. In summary, our results suggest that ER stress contributes to bufotalin-induced apoptosis in osteoblastoma cells. Bufotalin might be investigated as a novel anti-osteoblastoma agent. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Participation in recreational activities buffers the impact of perceived stress on quality of life in adults with autism spectrum disorder.

    Science.gov (United States)

    Bishop-Fitzpatrick, Lauren; Smith DaWalt, Leann; Greenberg, Jan S; Mailick, Marsha R

    2017-05-01

    As the number of adults with autism spectrum disorder (ASD) grows, the need to identify modifiable correlates of positive outcomes and quality of life (QoL) gains in importance. Research indicates that perceived stress is significantly correlated with QoL in adults with ASD. Studies in the general population of individuals without disabilities indicate that greater participation in social and recreational activities may lessen the negative impact of perceived stress on well-being, and this association may also hold among adults with ASD. We hypothesized that: (1) perceived stress would be negatively associated with QoL; and (2) higher frequency of participation in social activities and recreational activities would moderate the relationship between perceived stress and QoL. We used data collected from 60 adults with ASD aged 24-55 and their mothers to address our hypotheses. Findings indicate that adults with ASD with higher perceived stress are likely to have poorer QoL. Furthermore, greater participation in recreational activities buffers the impact of perceived stress on QoL, but no buffering effect was observed for participation in social activities. These findings suggest that interventions and services that provide supports and opportunities for participation in recreational activities may help adults with ASD manage their stress and lead to better QoL. Autism Res 2017, 10: 973-982. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

  18. Classical and alternative macrophage activation in the lung following ozone-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Sunil, Vasanthi R., E-mail: sunilva@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States); Patel-Vayas, Kinal; Shen, Jianliang [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States)

    2012-09-01

    Ozone is a pulmonary irritant known to cause oxidative stress, inflammation and tissue injury. Evidence suggests that macrophages play a role in the pathogenic response; however, their contribution depends on the mediators they encounter in the lung which dictate their function. In these studies we analyzed the effects of ozone-induced oxidative stress on the phenotype of alveolar macrophages (AM). Exposure of rats to ozone (2 ppm, 3 h) resulted in increased expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG), as well as heme oxygenase-1 (HO-1) in AM. Whereas 8-OHdG was maximum at 24 h, expression of HO-1 was biphasic increasing after 3 h and 48–72 h. Cleaved caspase-9 and beclin-1, markers of apoptosis and autophagy, were also induced in AM 24 h post-ozone. This was associated with increased bronchoalveolar lavage protein and cells, as well as matrix metalloproteinase (MMP)-2 and MMP-9, demonstrating alveolar epithelial injury. Ozone intoxication resulted in biphasic activation of the transcription factor, NFκB. This correlated with expression of monocyte chemotactic protein‐1, inducible nitric oxide synthase and cyclooxygenase‐2, markers of proinflammatory macrophages. Increases in arginase-1, Ym1 and galectin-3 positive anti-inflammatory/wound repair macrophages were also observed in the lung after ozone inhalation, beginning at 24 h (arginase-1, Ym1), and persisting for 72 h (galectin-3). This was associated with increased expression of pro-surfactant protein-C, a marker of Type II cell proliferation and activation, important steps in wound repair. These data suggest that both proinflammatory/cytotoxic and anti-inflammatory/wound repair macrophages are activated early in the response to ozone-induced oxidative stress and tissue injury. -- Highlights: ► Lung macrophages are highly sensitive to ozone induced oxidative stress. ► Ozone induces autophagy and apoptosis in lung macrophages. ► Proinflammatory and wound repair macrophages are activated

  19. Active stress field and seismotectonic features in Intra-Carpathian region of Romania

    Science.gov (United States)

    Oros, Eugen; Popa, Mihaela; Diaconescu, Mihai; Radulian, Mircea

    2017-04-01

    The Romanian Intra-Carpathian Region is located on the eastern half of Tisa-Dacia geodynamic block from the Neogene Carpathian-Pannonian Basin. The distribution of seismicity displays clear clusters and narrower zones with seismogenic potential confirmed by the damaging earthquakes recoded in the region, e.g. July 01, 1829 (Mw=6.2), October 10, 1834 (Mw=5.6), January 26, 1916 (Mw=6.4), July 12, 1991 (Mw=5.7), December 2, 1991 (Mw=5.5). The state of recent stress and deformation appears to be controlled by the interaction of plate-boundary and intraplate forces, which include the counterclockwise rotation and N-NE-directed indentation of the Adria microplate and buoyancy forces associated with differential topography and lithospheric heterogeneities. The stress field and tectonic regime are investigated at regional and local scales by the formal inversion of focal mechamisms. There can be observed short-scale lateral changes of i) tectonic regimes from compressive (reverse and strike-slip faultings) to pure extensive (normal faultings) and ii) variation of stress directions (SHmax) from NE-SW to EW and WNW-ESE towards Southern Carpathians and NS within Easter Carpathians. The changes in stress directions occur over a distance that is comparable to or smaller than the thickness of the lithosphere. A comparative analysis of stress tensor with GPS velocity/displacememt vectors shows variations from paralellism to orthogonality, suggesting different mechanisms of crustal deformations.The major seismic activity (Mw≥5.0) appears to be generally concentrated along the faults systems bordering de Tisa-Dacia Block, intersections of faults of different ages, internal shear zones and with the border of the former structural terrains, old rifts and neostructures.

  20. Relationship between perceived stress and dietary and activity patterns in older adults participating in the Boston Puerto Rican Health Study

    Science.gov (United States)

    Background: Previous research supports a relationship between psychological stress and chronic disease, particularly in low-income minority populations. Stress may affect health, in part, through its influence on dietary and physical activity patterns. Objective: To probe this hypothesis, we examin...

  1. Mind magic: a pilot study of preventive mind-body-based stress reduction in behaviorally inhibited and activated children

    NARCIS (Netherlands)

    Jellesma, F.C.; Cornelis, J.

    2012-01-01

    Purpose of study: The aim of this pilot study was to examine a mind-body-based preventive intervention program and to determine relationships between children's behavioral inhibition system (BIS) and behavioral activation system, stress, and stress reduction after the program. Design of study:

  2. Correction of stress-depended changes of glucoproteid platelet receptors activity by electromagnetic radiation of terahertz range

    Directory of Open Access Journals (Sweden)

    V.F. Kirichuk

    2010-09-01

    Full Text Available The research goal is correction of stress-depended changes of glucoproteid (Gp platelet receptors activity by electromagnetic radiation of terahertz range. Influence of electromagnetic waves of terahertz range at the frequency of molecular spectrum of radiation and absorption of nitrogen oxide on lectin-induced platelet aggregation of white rats in the stressed condition was investigated

  3. ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response

    Directory of Open Access Journals (Sweden)

    Jarom Heijmans

    2013-04-01

    Full Text Available Stem cells generate rapidly dividing transit-amplifying cells that have lost the capacity for self-renewal but cycle for a number of times until they exit the cell cycle and undergo terminal differentiation. We know very little of the type of signals that trigger the earliest steps of stem cell differentiation and mediate a stem cell to transit-amplifying cell transition. We show that in normal intestinal epithelium, endoplasmic reticulum (ER stress and activity of the unfolded protein response (UPR are induced at the transition from stem cell to transit-amplifying cell. Induction of ER stress causes loss of stemness in a Perk-eIF2α-dependent manner. Inhibition of Perk-eIF2α signaling results in stem cell accumulation in organoid culture of primary intestinal epithelium. Our findings show that the UPR plays an important role in the regulation of intestinal epithelial stem cell differentiation.

  4. Earthquake lights and the stress-activation of positive hole charge carriers in rocks

    Science.gov (United States)

    St-Laurent, F.; Derr, J.S.; Freund, F.T.

    2006-01-01

    Earthquake-related luminous phenomena (also known as earthquake lights) may arise from (1) the stress-activation of positive hole (p-hole) charge carriers in igneous rocks and (2) the accumulation of high charge carrier concentrations at asperities in the crust where the stress rates increase very rapidly as an earthquake approaches. It is proposed that, when a critical charge carrier concentration is reached, the p-holes form a degenerated solid state plasma that can break out of the confined rock volume and propagate as a rapidly expanding charge cloud. Upon reaching the surface the charge cloud causes dielectric breakdown at the air-rock interface, i.e. corona discharges, accompanied by the emission of light and high frequency electromagnetic radiation. ?? 2006 Elsevier Ltd. All rights reserved.

  5. Hypoxia increases the behavioural activity of schooling herring: a response to physiological stress or respiratory distress?

    DEFF Research Database (Denmark)

    Herbert, Neill A.; Steffensen, John F.

    2006-01-01

    Atlantic herring, Clupea harengus, increase their swimming speed during low O2 (hypoxia) and it has been hypothesised that the behavioural response is modulated by the degree of "respiratory distress" (i.e. a rise in anaerobic metabolism and severe physiological stress). To test directly whether...... response reflects a hypoxia-induced shift in metabolic fuel-use rather than respiratory distress per se. The significance of this behavioural-physiological reaction is discussed in terms of behavioural-energetic trade-offs, schooling dynamics and the hypoxia tolerance of herring. Udgivelsesdato: August...... a deviation in physiological homeostasis is associated with any change in behavioural activity, we exposed C. harengus in a school to a progressive stepwise decline in water oxygen pressure  and measured fish swimming speed and valid indicators of primary and secondary stress (i.e. blood cortisol, lactate...

  6. Lateral prefrontal cortex activity during cognitive control of emotion predicts response to social stress in schizophrenia

    Directory of Open Access Journals (Sweden)

    Laura M. Tully, PhD

    2014-01-01

    Full Text Available LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9 during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative mood on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia.

  7. Inhibiting the Physiological Stress Effects of a Sustained Attention Task on Shoulder Muscle Activity

    Directory of Open Access Journals (Sweden)

    Fiona Wixted

    2018-01-01

    Full Text Available Objective: The objective of this study was to investigate if a breathing technique could counteract the effects of hyperventilation due to a sustained attention task on shoulder muscle activity. Background: The trend towards higher levels of automation in industry is increasing. Consequently, manufacturing operators often monitor automated process for long periods of their work shift. Prolonged monitoring work requires sustained attention, which is a cognitive process that humans are typically poor at and find stressful. As sustained attention becomes an increasing requirement of manufacturing operators’ job content, the resulting stress experienced could contribute to the onset of many health problems, including work related musculoskeletal disorders (WRMSDs. Methods: The SART attention test was completed by a group of participants before and after a breathing intervention exercise. The effects of the abdominal breathing intervention on breathing rate, upper trapezius muscle activity and end-tidal CO2 were evaluated. Results: The breathing intervention reduced the moderation effect of end-tidal CO2 on upper trapezius muscle activity. Conclusions: Abdominal breathing could be a useful technique in reducing the effects of sustained attention work on muscular activity. Application: This research can be applied to highly-automated manufacturing industries, where prolonged monitoring of work is widespread and could, in its role as a stressor, be a potential contributor to WRMSDs.

  8. Punica granatum juice effects on oxidative stress in severe physical activity.

    Science.gov (United States)

    Naghizadeh-Baghi, Abbas; Mazani, Mohammad; Shadman-Fard, Ali; Nemati, Ali

    2015-02-01

    The aim of this study was to investigate Punica granatum juice effects on oxidative stress in young healthy males during severe physical activity. Our subjects were selected from healthy males at 18 - 24 years. They were enrolled and randomly distributed into control and supplemented groups. 240 ml of Punica granatum juice and tap water were given to supplement and control groups daily for two weeks, respectively. Fasting blood samples were taken at the starting and the end of two weeks of intervention. Subjects were given once severe physical activity and then fasting blood samples were taken. Fasting blood samples were used for testing of oxidative and antioxidative factors. Data were analyzed using descriptive statistical tests, paired samples t-test, and independent samples t-test. The levels of arylesterase, superoxide dismutase, glutathione peroxidase and total antioxidant capacity after severe physical activity in supplement group were significantly increased (pPunica granatum juice significantly modulates oxidative stress and thus protects against severe physical activity oxidative injury in young healthy males.

  9. Face cooling reveals a relative inability to increase cardiac parasympathetic activation during passive heat stress.

    Science.gov (United States)

    Schlader, Zachary J; O'Leary, Morgan C; Sackett, James R; Johnson, Blair D

    2018-02-15

    We tested the hypothesis that passive heat stress attenuates the increase in cardiac parasympathetic stimulation, vascular resistance, and blood pressure evoked by face cooling. During normothermia and when intestinal temperature was elevated by 1.0 ± 0.2°C, eleven healthy young adults underwent 3 min of face cooling. Face cooling was accomplished by placing a 2.5 L bag of ice water (0 ± 0°C) over the cheeks, eyes, and forehead. Primary variables included forehead skin temperature, mean arterial pressure, and systemic, forearm and cutaneous vascular resistances. Indices of heart rate variability in the time domain provided an index of cardiac parasympathetic activity. The magnitude of reductions in forehead skin temperature during face cooling was slightly greater during normothermia (-17.6 ± 1.9°C vs. -16.3 ± 3.0°C, P = 0.03). Increases in heart rate variability evoked by face cooling were attenuated during heat stress. Changes in systemic, forearm, and cutaneous vascular resistances during face cooling were virtually abolished lower during heat stress (P < 0.01). However, when forearm and vascular data were reported as conductance, differences between normothermia and heat stress were not apparent (P ≥ 0.62). Nevertheless, the increase in mean arterial pressure was attenuated during heat stress with face cooling (at 3 min: 2 ± 7 mmHg) compared to normothermia (at 3 min: 19 ± 7 mmHg, P < 0.01). These data indicate that passive heat stress attenuates face cooling evoked increases in cardiac parasympathetic activation, vascular resistance, and blood pressure. However, they also indicate that changes in indices of vascular resistance do not always reflect equivalent changes in conductance. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Chronic Vortioxetine Treatment Reduces Exaggerated Expression of Conditioned Fear Memory and Restores Active Coping Behavior in Chronically Stressed Rats.

    Science.gov (United States)

    Hatherall, Lauren; Sánchez, Connie; Morilak, David A

    2017-04-01

    Stress is a risk factor for depression and anxiety disorders, disrupting neuronal processes leading to exaggerated fear and compromised coping behaviors. Current antidepressants are only partially effective. Vortioxetine, a novel multimodal antidepressant, is a serotonin transporter inhibitor; 5-HT3, 5-HT7, and 5-HT1D receptor antagonist; 5-HT1B partial agonist; and 5-HT1A agonist. We have shown that chronic dietary vortioxetine administration reversed stress-induced deficits in cognitive flexibility. In the present studies, we investigated the generality of vortioxetine's effects on other stress-related behavioral changes after different types of chronic stress. In experiment 1, rats were fear-conditioned by pairing a tone with footshock, then exposed to chronic plus acute prolonged stress. In experiment 2, rats were exposed to chronic unpredictable stress. In both experiments, beginning on day 4 of chronic stress, vortioxetine was given in the diet (24 mg/kg/d). In experiment 1, effects of vortioxetine were tested on stress-induced changes in retention and extinction of cue-conditioned fear, and in experiment 2, on coping behavior on the shock probe defensive burying test after chronic stress. Chronic stress exaggerated the expression of conditioned fear memory. Vortioxetine restored fear memory to control levels and rendered extinction in stressed rats comparable with that in controls. In experiment 2, chronic unpredictable stress caused a shift from active to passive coping behavior, and vortioxetine restored active coping. Vortioxetine reduced exaggerated expression of conditioned fear and restored adaptive coping behavior following 2 different types of chronic stress, adding to the evidence of its therapeutic potential in the management of depression and anxiety disorders.

  11. Stress affects theta activity in limbic networks and impairs novelty-induced exploration and familiarization

    Directory of Open Access Journals (Sweden)

    Luis eJacinto

    2013-10-01

    Full Text Available Exposure to a novel environment triggers the response of several brain areas that regulate emotional behaviors. Here, we studied theta oscillations within the hippocampus (HPC-amygdala (AMY-medial prefrontal cortex (mPFC network in exploration of a novel environment and subsequent familiarization through repeated exposures to that same environment; in addition, we assessed how concomitant stress exposure could disrupt this activity and impair both behavioral processes. Local field potentials were simultaneously recorded from dorsal and ventral hippocampus (dHPC and vHPC respectively, basolateral amygdala (BLA and mPFC in freely behaving rats while they were exposed to a novel environment, then repeatedly re-exposed over the course of 3 weeks to that same environment and, finally, on re-exposure to a novel unfamiliar environment. A longitudinal analysis of theta activity within this circuit revealed a reduction of vHPC and BLA theta power and vHPC-BLA theta coherence through familiarization which was correlated with a return to normal exploratory behavior in control rats. In contrast, a persistent over-activation of the same brain regions was observed in stressed rats that displayed impairments in novel exploration and familiarization processes. Importantly, we show that stress also affected intra-hippocampal synchrony and heightened the coherence between vHPC and BLA. In summary, we demonstrate that modulatory theta activity in the aforementioned circuit, namely in the vHPC and BLA, is correlated with the expression of anxiety in novelty-induced exploration and familiarization in both normal and pathological conditions.

  12. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

    International Nuclear Information System (INIS)

    Mercado, Nicolas; Thimmulappa, Rajesh; Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E.; Biswal, Shyam; Ito, Kazuhiro; Barnes, Peter J.

    2011-01-01

    Research highlights: → Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. → HDAC inhibition decreases Nrf2 protein stability. → HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. → HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H 2 O 2 ) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H 2 O 2 -induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

  13. HMGB1 mediates depressive behavior induced by chronic stress through activating the kynurenine pathway.

    Science.gov (United States)

    Wang, Bo; Lian, Yong-Jie; Su, Wen-Jun; Peng, Wei; Dong, Xin; Liu, Lin-Lin; Gong, Hong; Zhang, Ting; Jiang, Chun-Lei; Wang, Yun-Xia

    2017-11-28

    Our previous study has reported that the proactive secretion and role of central high mobility group box 1 (HMGB1) in lipopolysaccharide-induced depressive behavior. Here, the potential mechanism of HMGB1 mediating chronic-stress-induced depression through the kynurenine pathway (KP) was further explored both in vivo and in vitro. Depression model was established with the 4-week chronic unpredictable mild stress (CUMS). Sucrose preference and Barnes maze test were performed to reflect depressive behaviors. The ratio of kynurenine (KYN)/tryptophan (Trp) represented the enzyme activity of indoleamine-2,3-dioxygenase (IDO). Gene transcription and protein expression were assayed by real-time RT-PCR and western-blot or ELISA kit respectively. Along with depressive behaviors, HMGB1 concentrations in the hippocampus and serum substantially increased post 4-week CUMS exposure. Concurrent with the upregulated HMGB1 protein, the regulator of translocation of HMGB1, sirtuin 1 (SIRT1) concentration in the hippocampus remarkably increased. In addition to HMGB1 and SIRT1, IDO, the rate limiting enzyme of KP, was upregulated at the level of mRNA expression and enzyme activity in stressed hippocampi and LPS/HMGB1-treated hippocampal slices. The gene transcription of kynurenine monooxygenase (KMO) and kynureninase (KYNU) in the downstream of KP also increased both in vivo and in vitro. Mice treated with ethyl pyruvate (EP), the inhibitor of HMGB1 releasing, were observed with lower tendency of developing depressive behaviors and reduced activation of enzymes in KP. All of these experiments demonstrate that the role of HMGB1 on the induction of depressive behavior is mediated by KP activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Mercado, Nicolas [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Thimmulappa, Rajesh [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States); Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E. [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Biswal, Shyam [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States); Ito, Kazuhiro [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Barnes, Peter J., E-mail: p.j.barnes@imperial.ac.uk [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom)

    2011-03-11

    Research highlights: {yields} Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. {yields} HDAC inhibition decreases Nrf2 protein stability. {yields} HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. {yields} HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H{sub 2}O{sub 2}) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H{sub 2}O{sub 2}-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

  15. Impaired activity of phagocytic cells in Candida albicans infection after exposure to chronic varied stress.

    Science.gov (United States)

    Rodriguez-Galán, M C; Correa, S G; Cejas, H; Sotomayor, C E

    2001-01-01

    Candidiasis is a prototypic opportunistic fungal disease that may follow severe modulations of the immune system of the host. The purpose of this study was to evaluate which innate immune mechanisms involved in the protection against fungal invasion are impaired under stress conditions. Wistar rats were infected intraperitoneally with Candida albicans and immediately exposed to chronic varied stress (CVS) over 10 days (CVS; Ca-S); the fungal burden (CFU), histopathological lesion and ACTH levels were evaluated. Additionally, functional assessment of peritoneal cells (PC) included the phagocytic and anticandidacidal activities and the production of H(2)O(2) and NO. In the only infected animals (Ca), C. albicans colonization stimulated an efficient inflammatory response, while in Ca-S rats poor tissue reactions were associated with increased CFU in livers and kidneys (p process was not modified, the candidacidal activity of PC was significantly decreased after the application of CVS (p < 0.001, Ca vs. Ca-S). The H(2)O(2) production by macrophages and neutrophils was downregulated by the infection, and while at early intervals these cells possessed a residual oxidative capacity, by day 10, the production of this metabolite was blocked. Spontaneous NO production by macrophages was significantly increased in both Ca and Ca-S animals (p < 0.001), but in stressed rats, this reactive nitrogen intermediate was noticeably downregulated (p < 0.05, Ca vs. Ca-S). The hyperactivity of hypothalamus-pituitary-adrenal axis after exposure to stress was confirmed by an increase in baseline plasma ACTH levels. These results show that during infection with C. albicans, the exposure to CVS contributes to the spread of the fungus and downregulates critical functions of phagocytic cells involved in the control of this opportunistic pathogen. Copyright 2002 S. Karger AG, Basel

  16. Tracking Stress and Hydrothermal Activity Along Oceanic Spreading Centers Using Tomographic Images of Seismic Anisotropy

    Science.gov (United States)

    Dunn, R. A.; Conder, J. A.; Canales, J. P.

    2014-12-01

    Marine controlled-source seismic tomography experiments now utilize 50+ ocean-bottom seismographs and source grids consisting of many tens of seismic lines with shot spacing. These dense experiments focus on the upper 10 km of the lithosphere over areas approaching 9000 sq-km. Because of the dense sampling and large azimuthal coverage of ray paths (200,000+ travel time measurements possible), it is now feasible to solve for 3-D images of P-wave azimuthal anisotropy with resolving lengths approaching 1km. Recent examples include the L-SCAN and MARINER experiments, performed at the Eastern Lau Spreading Center and Mid-Atlantic Ridge (36N), respectively. In each case, background anisotropy of ~4% is found in the upper 3-4 km of lithosphere and is consistent with pervasive stress-aligned cracks and microcracks. The fast axes are generally oriented parallel to the trend of the spreading center, as expected for cracks that form in association with seafloor spreading. Three-dimensional images of anisotropy magnitude and orientation reveal variations interpreted as arising from changes in the ambient stress field. Near the ends of ridge segments, where the ridge axis jumps from one spreading center to the next, anisotropy is high with orientations that are out of alignment relative to the background trend. This agrees with numerical models and seafloor morphology that suggest tensile stress concentration and brittle crack formation in these areas. Anisotropy also increases in areas along the ridges where the underlying magma supply and hydrothermal output are greater. This is opposite the trend expected if simple tectonic stress models govern anisotropy. Increased hydrothermal activity, due to increased magma supply, can explain higher anisotropy via increased pore pressure and hydrofracturing. These studies provide the first evidence that images of seismic anisotropy can be used to map variations in hydrologic activity along the crests of oceanic spreading centers.

  17. Midazolam more effectively suppresses sympathetic activations and reduces stress feelings during mental arithmetic task than propofol.

    Science.gov (United States)

    Tsugayasu, Rie; Handa, Toshiyuki; Kaneko, Yuzuru; Ichinohe, Tatsuya

    2010-03-01

    The aim of the present study was to examine the effect of intravenous midazolam and propofol sedation on autonomic nervous activities during psychological stress, and whether these results are associated with changes in subjective stress feelings. Seven healthy male volunteers were included in a randomized crossover manner. The heart rate (HR), HR variability, arterial oxygen saturation, and bispectral index value were continuously monitored. A mental arithmetic task for 7 minutes was given with or without intravenous sedation with midazolam or propofol. A bispectral index value of 75 to 85 and an Observer's Assessment of Alertness/Sedation score of 4 were the targeted sedation level in both groups. HR variability was assessed using the power spectral analysis (low-frequency [LF] and high-frequency [HF] components and LF/HF ratio). The faces anxiety scale was used to grade their stress feelings after each mental arithmetic task. During the mental arithmetic task with intravenous sedation, no differences were found in the bispectral index values, arterial oxygen saturation, or the results of the mental arithmetic task between the 2 groups. The HR, LF/HF ratio, and normalized unit LF increased, and the normalized unit HF decreased in both groups. However, the percentage of changes in LF/HF ratio, normalized unit LF, and normalized unit HF were smaller in the midazolam group. In addition, the reduction in faces anxiety scale was greater in the midazolam group. These results suggest that midazolam more effectively suppresses sympathetic nervous activation and reduces subjective stress feelings during a mental arithmetic task than propofol. Copyright (c) 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Stem cell factor (SCF) protects osteoblasts from oxidative stress through activating c-Kit-Akt signaling

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Lei [Department of Orthopedics, Changzhou Wujin People’s Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou (China); Wu, Zhong [Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Yin, Gang; Liu, Haifeng; Guan, Xiaojun; Zhao, Xiaoqiang [Department of Orthopedics, Changzhou Wujin People’s Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou (China); Wang, Jianguang, E-mail: jianguangwang@163.com [Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Zhu, Jianguo, E-mail: gehujianguo68@163.com [Department of Orthopedics, Changzhou Wujin People’s Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou (China)

    2014-12-12

    Highlights: • SCF receptor c-Kit is functionally expressed in primary and transformed osteoblasts. • SCF protects primary and transformed osteoblasts from H{sub 2}O{sub 2}. • SCF activation of c-Kit in osteoblasts, required for its cyto-protective effects. • c-Kit mediates SCF-induced Akt activation in cultured osteoblasts. • Akt activation is required for SCF-regulated cyto-protective effects in osteoblasts. - Abstract: Osteoblasts regulate bone formation and remodeling, and are main target cells of oxidative stress in the progression of osteonecrosis. The stem cell factor (SCF)-c-Kit pathway plays important roles in the proliferation, differentiation and survival in a range of cell types, but little is known about its functions in osteoblasts. In this study, we found that c-Kit is functionally expressed in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. Its ligand SCF exerted significant cyto-protective effects against hydrogen peroxide (H{sub 2}O{sub 2}). SCF activated its receptor c-Kit in osteoblasts, which was required for its cyto-protective effects against H{sub 2}O{sub 2}. Pharmacological inhibition (by Imatinib and Dasatinib) or shRNA-mediated knockdown of c-Kit thus inhibited SCF-mediated osteoblast protection. Further investigations showed that protection by SCF against H{sub 2}O{sub 2} was mediated via activation of c-Kit-dependent Akt pathway. Inhibition of Akt activation, through pharmacological or genetic means, suppressed SCF-mediated anti-H{sub 2}O{sub 2} activity in osteoblasts. In summary, we have identified a new SCF-c-Kit-Akt physiologic pathway that protects osteoblasts from H{sub 2}O{sub 2}-induced damages, and might minimize the risk of osteonecrosis caused by oxidative stress.

  19. Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions

    Directory of Open Access Journals (Sweden)

    Salvadore Christopher

    2004-09-01

    Full Text Available Abstract Background The mitogen-activated protein kinases (MAPKs have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2 has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6, were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE binding (CREB protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined. Results A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3 were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold. Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex areas. Conclusions Swim stress specifically and markedly

  20. ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval.

    Science.gov (United States)

    Li, Shijia; Weerda, Riklef; Milde, Christopher; Wolf, Oliver T; Thiel, Christiane M

    2015-02-01

    Noradrenaline interacts with stress hormones in the amygdala and hippocampus to enhance emotional memory consolidation, but the noradrenergic-glucocorticoid interaction at retrieval, where stress impairs memory, is less understood. We used a genetic neuroimaging approach to investigate whether a genetic variation of the noradrenergic system impacts stress-induced neural activity in amygdala and hippocampus during recognition of emotional memory. This study is based on genotype-dependent reanalysis of data from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two healthy male volunteers were genotyped for the ADRA2B gene encoding the α2B-adrenergic receptor. Ten deletion carriers and 12 noncarriers performed an emotional face recognition task, while their brain activity was measured with fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour later, they underwent either an acute stress (Trier Social Stress Test) or a control procedure which was followed immediately by the retrieval session, where participants had to discriminate between 100 old and 50 new faces. A genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus. Deletion carriers showed decreased neural activity in the amygdala when recognizing emotional faces in control condition and increased amygdala activity under stress. Noncarriers showed no differences in emotional modulated amygdala activation under stress or control. Instead, stress-induced increases during recognition of emotional faces were present in the right hippocampus. The genotype-dependent effects of acute stress on neural activity in amygdala and hippocampus provide evidence for noradrenergic-glucocorticoid interaction in emotional memory retrieval.

  1. Acute stress evokes sexually dimorphic, stressor-specific patterns of neural activation across multiple limbic brain regions in adult rats.

    Science.gov (United States)

    Sood, Ankit; Chaudhari, Karina; Vaidya, Vidita A

    2018-03-01

    Stress enhances the risk for psychiatric disorders such as anxiety and depression. Stress responses vary across sex and may underlie the heightened vulnerability to psychopathology in females. Here, we examined the influence of acute immobilization stress (AIS) and a two-day short-term forced swim stress (FS) on neural activation in multiple cortical and subcortical brain regions, implicated as targets of stress and in the regulation of neuroendocrine stress responses, in male and female rats using Fos as a neural activity marker. AIS evoked a sex-dependent pattern of neural activation within the cingulate and infralimbic subdivisions of the medial prefrontal cortex (mPFC), lateral septum (LS), habenula, and hippocampal subfields. The degree of neural activation in the mPFC, LS, and habenula was higher in males. Female rats exhibited reduced Fos positive cell numbers in the dentate gyrus hippocampal subfield, an effect not observed in males. We addressed whether the sexually dimorphic neural activation pattern noted following AIS was also observed with the short-term stress of FS. In the paraventricular nucleus of the hypothalamus and the amygdala, FS similar to AIS resulted in robust increases in neural activation in both sexes. The pattern of neural activation evoked by FS was distinct across sexes, with a heightened neural activation noted in the prelimbic mPFC subdivision and hippocampal subfields in females and differed from the pattern noted with AIS. This indicates that the sex differences in neural activation patterns observed within stress-responsive brain regions are dependent on the nature of stressor experience.

  2. The Stress-Metabolic Syndrome Relationship in Adolescents: An Examination of the Moderating Potential of Physical Activity.

    Science.gov (United States)

    Holmes, Megan E; Pivarnik, Jim; Pfeiffer, Karin; Maier, Kimberly S; Eisenmann, Joey C; Ewing, Martha

    2016-10-01

    The role of psychosocial stress in the development of obesity and metabolic syndrome is receiving increased attention and has led to examination of whether physical activity may moderate the stress-metabolic syndrome relationship. The current study examined relationships among physical activity, stress, and metabolic syndrome in adolescents. Participants (N = 126; 57 girls, 69 boys) were assessed for anthropometry, psychosocial stress, physical activity, and metabolic syndrome variables; t tests were used to examine sex differences, and regression analysis was used to assess relationships among variables controlling for sex and maturity status. Mean body mass index approached the 75th percentile for both sexes. Typical sex differences were observed for systolic blood pressure, time spent in moderate and vigorous physical activity, and perceived stress. Although stress was not associated with MetS (β = -.001, P = .82), a modest, positive relationship was observed with BMI (β = .20, P = .04). Strong relationships between physical activity and stress with MetS or BMI were not found in this sample. Results may be partially explained by overall good physical health status of the participants. Additional research in groups exhibiting varying degrees of health is needed.

  3. Is Oxidative Stress Associated with Activation and Pathogenesis of Inflammatory Bowel Disease?

    Directory of Open Access Journals (Sweden)

    Yuksel Mahmut

    2017-08-01

    Full Text Available Background: We aimed to determine the levels of total antioxidant status (TAS, total oxidant status (TOS, oxidative stress index (OSI and paraoxonase1/arylesterase levels in inflammatory bowel disease (IBD, and the relation be - tween these molecules and the activity index of the disease. Methods: Eighty IBD patients (ulcerative colitis (UC/Crohn disease (CD 40/40 and 80 control group participants were included in the study. Oxidative stress parameters were measured using the colorimetric method. As disease activity indexes, the endoscopic activity index (EAI was used for UC and the CD activity index (CDAI was used for CD. Results: In IBD patients, mean TAS (1.3±0.2 vs 1.9±0.2, respectively; p<0.001 and arylesterase (963.9±232.2 vs 1252.9±275, respectively; p<0.001 levels were found to be lower and TOS level (5.6±1.6 vs 4.0±1.0, respectively; p<0.001 and OSI rate (4.5±1.6 vs 2.2±0.8, respectively; p<0.001 were found to be higher compared to the control group. A strong positive correlation was found between EAI and TOS levels (r=0.948, p<0.001 and OSI rate (r=0.894, p<0.001 for UC patients. A very strong positive correlation was found between EAI and TOS levels (r=0.964, p<0.001 and OSI rate (r=0.917, p<0.001 for CD patients. It was found in a stepwise regression model that C-reactive protein, OSI and arylesterase risk factors were predictors of IBD compared to the control group. Conclusion: Increased oxidative stress level in IBD patients and the detection of OSI rate as an independent predictor for disease activity indexes lead to the idea that oxidative stress might be related to the pathogenesis of IBD.

  4. Serum paraoxonase activity and oxidative stress levels in patients with cutaneous anthrax.

    Science.gov (United States)

    Karadas, S; Aslan, M; Ceylan, M R; Sunnetcioglu, M; Bozan, N; Kara, H; Demir, H

    2017-07-01

    Anthrax is a bacterial disease caused by the aerobic sporeforming bacterium Bacillus anthracis. It has been suggested that oxidative stress plays an important role in the pathogenesis of B. anthracis. The aim of this study was to investigate serum paraoxonase 1 (PON1) activity, catalase activity, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) levels in patients with cutaneous anthrax. Fifteen patients with cutaneous anthrax and 15 healthy controls were enrolled in this study. The serum MDA levels, SOD levels, paraoxonase, arylesterase, and catalase activities were measured using a spectrophotometer. The serum SOD levels, paraoxonase, arylesterase, and catalase activities were significantly lower in patients with cutaneous anthrax than in controls (for all, p paraoxonase activity, arylesterase activity, SOD levels, and MDA levels (all, p > 0.05) in patients with cutaneous anthrax. The current study was the first to show decreased antioxidant levels and increased oxidant levels in patients with cutaneous anthrax. Therefore, decreased PON1 activity may play a role in the pathogenesis of cutaneous anthrax.

  5. Activation of Antioxidant Defenses in Whole Saliva by Psychosocial Stress Is More Manifested in Young Women than in Young Men

    OpenAIRE

    Tsuber, Viktoriia; Kadamov, Yunus; Tarasenko, Lydia

    2014-01-01

    Psychosocial stress has been long known to have deleterious effects on health. Nevertheless, an exposure to moderate stressors enhances resilience and promotes health benefits. Male and female organisms differ in many aspects of health and disease. The aim of this study was to investigate antioxidant activity and oxidative damage in saliva in a psychosocial stress paradigm in men and women. Here, we show that an acute stressor of moderate strength augments antioxidant activity and decreases o...

  6. Lactate Dehydrogenase and Oxidative Stress Activity in Primary Open-Angle Glaucoma Aqueous Humour

    Directory of Open Access Journals (Sweden)

    Predrag Jovanović

    2010-02-01

    Full Text Available Lactate dehydrogenase (LDH and lactate are some of the hypoxy biochemical parameters. Extracellular activity of this enzyme increases under the condition of oxidative stress, since the cell integrity can be disrupted during the lipid peroxidation process. Subsequently that leads to the increase level of the lactic acid and lactic acid salts. The objective of this investigation is establishing the level of LDH, LDH1 (HBDH and the lactate concentration in aqueous humour in patients with primary open-angle glaucoma.Biochemical analysis have been made by enzymatic-colometric method (lactate and UV-kinetic method (LDH and HBDH in aqueous humour of 30 patients (42 eyes with primary open-angle glaucoma (POAG and 30 patients (40 eyes with cataract (the control group.The increased values of lactate and the activity of LDH and HBDH enzyme in aqueous humour of POAG patients in correlation with the control group are the results not only of oxidative stress but also of hypoxy and the mitochondry oxidative function (p<0,001.The increased activity of the examined biochemical parameters in the aqueous humour of the POAG patients points to the fact that other mechanisms, besides IOP, have a role in glaucoma pathogenesis.

  7. Restoration of acetylcholinesterase activity by Euphorbia hirta in discrete brain regions of chronically stressed rats.

    Science.gov (United States)

    Anuradha, H; Srikumar, B N; Deepti, N; Shankaranarayana Rao, B S; Lakshmana, M

    2010-05-01

    Several drugs of herbal origin are known to possess anxiolytic and antidepressant effects. In a recent study, we showed that extracts from Euphorbia hirta L. (Euphorbiaceae) (Eh) demonstrated anxiolytic effects in rats subjected to chronic immobilization stress (CIS) but not in rats that underwent forced swim stress (FSS). Acetylcholine and the cholinergic system are known to be involved in anxiety. However, whether the cholinergic system is involved in the anxiolytic actions of Eh are not known. In the current study, we evaluated the effects of Eh treatment of rats subjected to either CIS or FSS on acetylcholinesterase (AChE) activity in the frontal cortex, hippocampus, and septum. CIS increased the AChE activity in all three regions, while Eh treatment restored it to normal levels. FSS increased the AChE activity only in the septum, and Eh treatment marginally restored this to normal levels. Thus, these results indicate the involvement of the cholinergic system in the behavioral effects of Euphorbia hirta.

  8. Methionine oxidation activates a transcription factor in response to oxidative stress.

    Science.gov (United States)

    Drazic, Adrian; Miura, Haruko; Peschek, Jirka; Le, Yan; Bach, Nina C; Kriehuber, Thomas; Winter, Jeannette

    2013-06-04

    Oxidant-mediated antibacterial response systems are broadly used to control bacterial proliferation. Hypochlorite (HOCl) is an important component of the innate immune system produced in neutrophils and specific epithelia. Its antimicrobial activity is due to damaging cellular macromolecules. Little is known about how bacteria escape HOCl-inflicted damage. Recently, the transcription factor YjiE was identified that specifically protects Escherichia coli from HOCl killing. According to its function, YjiE is now renamed HypT (hypochlorite-responsive transcription factor). Here we unravel that HypT is activated by methionine oxidation to methionine sulfoxide. Interestingly, so far only inactivation of cellular proteins by methionine oxidation has been reported. Mutational analysis revealed three methionines that are essential to confer HOCl resistance. Their simultaneous substitution by glutamine, mimicking the methionine sulfoxide state, increased the viability of E. coli cells upon HOCl stress. Triple glutamine substitution generates a constitutively active HypT that regulates target genes independently of HOCl stress and permanently down-regulates intracellular iron levels. Inactivation of HypT depends on the methionine sulfoxide reductases A/B. Thus, microbial protection mechanisms have evolved along the evolution of antimicrobial control systems, allowing bacteria to survive within the host environment.

  9. ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells.

    Science.gov (United States)

    Arduino, Daniela M; Esteves, A Raquel; Domingues, A Filipa; Pereira, Claudia M F; Cardoso, Sandra M; Oliveira, Catarina R

    2009-11-30

    Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

  10. Sleep duration moderates the association between insula activation and risky decisions under stress in adolescents and adults.

    Science.gov (United States)

    Uy, Jessica Phuong; Galván, Adriana

    2017-01-27

    Insufficient sleep has been associated with increased risk-taking and poor decision-making, enhanced physiological responses to stress, and attenuated anterior insula (AI) activity to risk. The AI has also been linked to risky decision-making under acute stress. However, it is yet unknown how naturalistic sleep habits affect risky decision-making and AI activity when individuals feel stressed. In the current study, a daily diary approach was used to document participants' daily stress. Adolescents and adults reported their recent sleep duration and completed two fMRI visits during which they performed a risky decision-making task: once each when they endorsed a high and low level of stress. Results revealed that, regardless of age, individuals who reported receiving more sleep took fewer non-advantageous risks during high stress relative to those who reported receiving fewer hours of sleep per night while sleep duration was not associated with risky behavior under low stress. Among individuals who reported less sleep, those who exhibited reduced AI activation during risk-taking under high stress also took more disadvantageous risks whereas this effect was attenuated for those who reported longer sleep duration. Moreover, longer sleep duration was associated with greater functional coupling between the AI and dorsolateral prefrontal cortex (DLPFC) under high stress whereas sleep duration was not associated with AI-DLPFC functional coupling under low stress. These findings suggest that naturalistic sleep duration may amplify the effects of daily stress and alter risky decision-making behavior through interactions with the AI. Copyright © 2016. Published by Elsevier Ltd.

  11. Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress*♦

    Science.gov (United States)

    Benoit, Stéphane L.; Maier, Robert J.

    2016-01-01

    Catalase, a conserved and abundant enzyme found in all domains of life, dissipates the oxidant hydrogen peroxide (H2O2). The gastric pathogen Helicobacter pylori undergoes host-mediated oxidant stress exposure, and its catalase contains oxidizable methionine (Met) residues. We hypothesized catalase may play a large stress-combating role independent of its classical catalytic one, namely quenching harmful oxidants through its recyclable Met residues, resulting in oxidant protection to the bacterium. Two Helicobacter mutant strains (katAH56A and katAY339A) containing catalase without enzyme activity but that retain all Met residues were created. These strains were much more resistant to oxidants than a catalase-deletion mutant strain. The quenching ability of the altered versions was shown, whereby oxidant-stressed (HOCl-exposed) Helicobacter retained viability even upon extracellular addition of the inactive versions of catalase, in contrast to cells receiving HOCl alone. The importance of the methionine-mediated quenching to the pathogen residing in the oxidant-rich gastric mucus was studied. In contrast to a catalase-null strain, both site-change mutants proficiently colonized the murine gastric mucosa, suggesting that the amino acid composition-dependent oxidant-quenching role of catalase is more important than the well described H2O2-dissipating catalytic role. Over 100 years after the discovery of catalase, these findings reveal a new non-enzymatic protective mechanism of action for the ubiquitous enzyme. PMID:27605666

  12. Cold stress increases reactive oxygen species formation via TRPA1 activation in A549 cells.

    Science.gov (United States)

    Sun, Wenwu; Wang, Zhonghua; Cao, Jianping; Cui, Haiyang; Ma, Zhuang

    2016-03-01

    Reactive oxygen species (ROS) are responsible for lung damage during inhalation of cold air. However, the mechanism of the ROS production induced by cold stress in the lung is still unclear. In this work, we measured the changes of ROS and the cytosolic Ca(2+) concentration ([Ca(2+)]c) in A549 cell. We observed that cold stress (from 20 to 5 °C) exposure of A549 cell resulted in an increase of ROS and [Ca(2+)]c, which was completely attenuated by removing Ca(2+) from medium. Further experiments showed that cold-sensing transient receptor potential subfamily member 1 (TRPA1) agonist (allyl isothiocyanate, AITC) increased the production of ROS and the level of [Ca(2+)]c in A549 cell. Moreover, HC-030031, a TRPA1 selective antagonist, significantly inhibited the enhanced ROS and [Ca(2+)]c induced by AITC or cold stimulation, respectively. Taken together, these data demonstrated that TRPA1 activation played an important role in the enhanced production of ROS induced by cold stress in A549 cell.

  13. Baroreflex modulation of sympathetic nerve activity to muscle in heat-stressed humans

    Science.gov (United States)

    Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

    2002-01-01

    To identify whether whole body heating alters arterial baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA and beat-by-beat arterial blood pressure were recorded in seven healthy subjects during acute hypotensive and hypertensive stimuli in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature (P 0.05). During both normothermic and heat stress conditions, MSNA increased and then decreased significantly when blood pressure was lowered and then raised via intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure during heat stress (-128.3 +/- 13.9 U x beats(-1) x mmHg(-1)) was similar (P = 0.31) with normothermia (-140.6 +/- 21.1 U x beats(-1) x mmHg(-1)). Moreover, no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that arterial baroreflex modulation of MSNA and heart rate are not altered by whole body heating, with the exception of an upward shift of these baroreflex curves to accommodate changes in these variables that occur with whole body heating.

  14. Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

    Directory of Open Access Journals (Sweden)

    Michael A Petrie

    Full Text Available Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat and mechanical stress (vibration on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction.The purpose of this study is to examine whether active mechanical stress (muscle contraction, passive mechanical stress (vibration, or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair.Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus to analyze mRNA gene expression.We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold, PGC-1α (5.46 fold, and ABRA (5.98 fold; and repressed MSTN (0.56 fold. Heat stress repressed PGC-1α (0.74 fold change; p < 0.05; while vibration induced FOXK2 (2.36 fold change; p < 0.05. Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05, but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05 while heat stress repressed PGC-1α (0.74 fold and ANKRD1 genes (0.51 fold; p < 0.05.These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell

  15. Plants in water-controlled ecosystems: active role in hydrologic processes and response to water stress. III. Vegetation water stress

    Science.gov (United States)

    Porporato, A.; Laio, F.; Ridolfi, L.; Rodriguez-Iturbe, I.

    The reduction of soil moisture content during droughts lowers the plant water potential and decreases transpiration; this in turn causes a reduction of cell turgor and relative water content which brings about a sequence of damages of increasing seriousness. A review of the literature on plant physiology and water stress shows that vegetation water stress can be assumed to start at the soil moisture level corresponding to incipient stomatal closure and reach a maximum intensity at the wilting point. The mean crossing properties of these soil moisture levels crucial for water stress are derived analytically for the stochastic model of soil moisture dynamics described in Part II (F. Laio, A. Porporato, L. Ridolfi, I. Rodriguez-Iturbe. Adv. Water Res. 24 (7) (2001) 707-723). These properties are then used to propose a measure of vegetation water stress which combines the mean intensity, duration, and frequency of periods of soil water deficit. The characteristics of vegetation water stress are then studied under different climatic conditions, showing how the interplay between plant, soil, and environment can lead to optimal conditions for vegetation.

  16. A facilitator of leisure activities for stress-related growth experience among middle-aged Korean women with depression.

    Science.gov (United States)

    Kim, Junhyoung; Kim, Jung-Hyun

    2014-01-01

    Leisure may serve as a coping resource following negative life events that facilitate positive changes. Previous studies on leisure have mainly focused on stress-related growth among individuals living in Western cultures. This study aimed to capture the role of leisure involvement as a facilitator of stress-related growth among middle-aged Korean women with depression. Three main themes were identified as an outcome of participation in leisure activities: (a) strengthening meaningful relationships, (b) improving positive emotions, and (c) facilitating personal strength. By participating in leisure activities, individuals with depression may develop the ability to cope with stress and experience positive changes.

  17. An Action Research Inquiry into the Relationship Among Aerobic Activities, Memory, and Stress with Students Identified as Gifted

    Science.gov (United States)

    Ford, Denise Marie

    Students identified as gifted come from varying socio-economic strata and nationalities with a range of talents and temperaments comprising a diverse community. They may experience stress for a variety of reasons. Although a certain amount of stress can enhance the learning process, too much stress can impede learning, especially memory. Strategies have been offered for relieving stress, yet the benefits of physical activities as stress reducers for the gifted have frequently been overlooked. The purpose of this study was to investigate the relationship among aerobic activity, stress, and memory ability in students in an elementary school gifted program. An exceptional aspect of this research was that the students were an integral part of their own study. As co-researchers they had a vested interest in what they were doing, enhancing the significance of the experience and heightening learning. This action research project conducted in a mid-western school district with fourth and fifth grade students examined the impact of aerobic movement on physical indicators of stress and memory. The study lasted twelve weeks with data collected on physical indicators of stress, memory test scores, parent observations, interviews with students, a parent focus group session, observational data, student comments, and investigator/teacher journal. By infusing regular exercise into curricula, stress levels in students identified as gifted were examined. Students' scores on declarative memory tasks conducted with and without an accompanying aerobic activity were documented. Students learned of the delicate relationship between stress and memory as they studied the physiology of the brain. Twenty-four hour retention rates of declarative memory items were higher when a 20-minute aerobic activity intervention preceded the memory activity. Perceived stress levels were lowered for 14 of the 16 co-researchers. Students indicated a positive attitude toward physical activity and its

  18. SIGNALING TO THE P53 TUMOR SUPPRESSOR THROUGH PATHWAYS ACTIVATED BY GENOTOXIC AND NON-GENOTOXIC STRESSES.

    Energy Technology Data Exchange (ETDEWEB)

    ANDERSON,C.W.APPELLA,E.

    2002-07-01

    The p53 tumor suppressor is a tetrameric transcription factor that is post-translational modified at {approx}18 different sites by phosphorylation, acetylation, or sumoylation in response to various cellular stress conditions. Specific posttranslational modifications, or groups of modifications, that result from the activation of different stress-induced signaling pathways are thought to modulate p53 activity to regulate cell fate by inducing cell cycle arrest, apoptosis, or cellular senescence. Here we review the posttranslational modifications to p53 and the pathways that produce them in response to both genotoxic and non-genotoxic stresses.

  19. Stress-Activated Electric Currents in the Earth Crust: How they Can and Cannot Flow (Invited)

    Science.gov (United States)

    Freund, F. T.; Bleier, T. E.; Bortnik, J.; Dahlgren, R.

    2010-12-01

    Dormant electronic charge carriers exist in rocks. They “wake up” when stresses are applied: electrons e’ and positive holes, h., the latter being defect electrons in the oxygen anion sublattice of minerals [1, 2]. The h. can flow out of the stressed subvolume. They can spread into the unstressed surrounding, turning the rocks into p-type semiconductors. They travel fast and far using energy levels at the upper edge of the valence bands. Contrary to the h., the co-activated electrons e’ cannot flow out and propagate through unstressed rocks: they are stuck in the activation volume. The situation is akin to that in an electrochemical battery except that, in the “rock battery”, the positive charge carriers are not cations but positive holes h.. In the laboratory it is easy to close the battery circuit by offering the electrons a metal contact and connecting the stressed and unstressed rock with a metal wire. This is useful to demonstrate the functioning of the “rock battery”. In the field the h. outflow from a stressed rock volume is restricted as long as there is no return path. This is an important point when we try to understand why pre-earthquake EM emission is widely considered “unreliable” [3, 4]. However, there are at least three conditions, under which circuit closure can be achieved in the field under realistic pre-earthquake situations: (i) via n-type conducting rocks; (ii) via electrolytic conductivity of water; and (iii) via the air when the air above the epicentral region becomes highly ionized. We report on examples where these three conditions might have allowed large currents to flow and strong EM signals to be emitted. [1] Freund, F.T. et al.: Electric currents streaming out of stressed igneous rocks - A step towards understanding pre-earthquake low frequency EM emissions, Phys. Chem. Earth 31, 389-396 (2006). [2] Freund, F.T.: Charge generation and propagation in rocks, J. Geodyn. 33, 545-572 (2002). [3] Johnston, M.J.S. and

  20. The effect of psychosocial stress on muscle activity during computer work: Comparative study between desktop computer and mobile computing products.

    Science.gov (United States)

    Taib, Mohd Firdaus Mohd; Bahn, Sangwoo; Yun, Myung Hwan

    2016-06-27

    The popularity of mobile computing products is well known. Thus, it is crucial to evaluate their contribution to musculoskeletal disorders during computer usage under both comfortable and stressful environments. This study explores the effect of different computer products' usages with different tasks used to induce psychosocial stress on muscle activity. Fourteen male subjects performed computer tasks: sixteen combinations of four different computer products with four different tasks used to induce stress. Electromyography for four muscles on the forearm, shoulder and neck regions and task performances were recorded. The increment of trapezius muscle activity was dependent on the task used to induce the stress where a higher level of stress made a greater increment. However, this relationship was not found in the other three muscles. Besides that, compared to desktop and laptop use, the lowest activity for all muscles was obtained during the use of a tablet or smart phone. The best net performance was obtained in a comfortable environment. However, during stressful conditions, the best performance can be obtained using the device that a user is most comfortable with or has the most experience with. Different computer products and different levels of stress play a big role in muscle activity during computer work. Both of these factors must be taken into account in order to reduce the occurrence of musculoskeletal disorders or problems.

  1. Early and later life stress alter brain activity and sleep in rats.

    Directory of Open Access Journals (Sweden)

    Jelena Mrdalj

    Full Text Available Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2-14 male rats were exposed to either long maternal separation (180 min or brief maternal separation (10 min. Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.

  2. Loss of catalase increases malignant mouse keratinocyte cell growth through activation of the stress activated JNK pathway.

    Science.gov (United States)

    Hanke, Neale T; Finch, Joanne S; Bowden, G Timothy

    2008-05-01

    A cell line that produces mouse squamous cell carcinoma (6M90) was modified to develop a cell line with an introduced Tet-responsive catalase transgene (MTOC2). We have previously reported that the overexpressed catalase in the MTOC2 cells reverses the malignant phenotype in part by decreasing epidermal growth factor receptor (EGFR) signaling. With this work we expanded the investigation into the differences between these two cell lines. We found that the decreased EGFR pathway activity of the MTOC2 cells is not because of reduced autocrine secretion of an epidermal growth factor (EGF) ligand but rather because of lower basal receptor activity. Phosphorylated levels of the mitogen-activated protein kinase (MAPK) members JNK and p38 were both higher in the 6M90 cells with low catalase when compared with the MTOC2 cell line. Although treatment with an EGFR inhibitor, AG1478, blocked the increased activity of JNK in the 6M90 cells, a similar effect was not observed for p38. Basal levels of downstream c-jun transcription were also found to be higher in the 6M90 cells versus MTOC2 cells. Activated p38 was found to down-regulate the JNK MAPK pathway in the 6M90 cells. However, the 6M90 cells contain constitutively high levels of phosphorylated JNK, generating higher levels of phosphorylated c-jun and total c-jun than those in the MTOC2 cells. Inhibition of JNK activity in the 6M90 cells reduced AP-1 transcription and cell proliferation. The data confirm the inhibitory effects of catalase on tumor cell growth, specifically through a ligand-independent decrease in the stress activated JNK pathway. (c) 2007 Wiley-Liss, Inc.

  3. Telomerase activity and its association with psychological stress, mental disorders, lifestyle factors and interventions: A systematic review.

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    Deng, W; Cheung, S T; Tsao, S W; Wang, X M; Tiwari, A F Y

    2016-02-01

    To summarise and discuss the association between telomerase activity and psychological stress, mental disorders and lifestyle factors. A systematic review was carried out to identify prospective or retrospective studies and interventions published up to June 2015 that reported associations between telomerase activity and psychological stress, mental disorders and lifestyle factors. Electronic data bases of PubMed, ProQuest, CINAHL and Google Scholar were searched. Twenty six studies on humans measured telomerase activity in peripheral blood mononuclear cells (PBMCs) or leukocytes and examined its association with psychological stress, mental disorders and lifestyle factors. Of those studies, three reported significantly decreased telomerase activity in individuals under chronic psychological stress. Interestingly, one of the three studies found that acute laboratory psychological stress significantly increased telomerase activity. Nine studies reported mixed results on association between mental disorders and telomerase activity. Of the nine studies, five reported that major depressive disorder (MDD) was associated with significantly increased telomerase activity. In thirteen out of fourteen studies on lifestyle factors, it was reported that physical exercise, diet micronutrient supplementation, mindfulness meditation, Qigong practice or yoga mediation resulted in increase in telomerase activity. In addition, two studies on animal models showed that depression-like behaviour was associated with decreased hippocampus telomerase activity. Five animal studies showed that physical exercise increased telomerase activity by cell-type-specific and genotype-specific manners. Although multi-facet results were reported on the association between telomerase activity and psychological stress, mental disorders and lifestyle factors, there were some consistent findings in humans such as (1) decreased telomerase activity in individuals under chronic stress, (2) increased

  4. Oxidative stress (glutathionylation and Na,K-ATPase activity in rat skeletal muscle.

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    Carsten Juel

    Full Text Available Changes in ion distribution across skeletal muscle membranes during muscle activity affect excitability and may impair force development. These changes are counteracted by the Na,K-ATPase. Regulation of the Na,K-ATPase is therefore important for skeletal muscle function. The present study investigated the presence of oxidative stress (glutathionylation on the Na,K-ATPase in rat skeletal muscle membranes.Immunoprecipitation with an anti-glutathione antibody and subsequent immunodetection of Na,K-ATPase protein subunits demonstrated 9.0±1.3% and 4.1±1.0% glutathionylation of the α isoforms in oxidative and glycolytic skeletal muscle, respectively. In oxidative muscle, 20.0±6.1% of the β1 units were glutathionylated, whereas 14.8±2.8% of the β2-subunits appear to be glutathionylated in glycolytic muscle. Treatment with the reducing agent dithiothreitol (DTT, 1 mM increased the in vitro maximal Na,K-ATPase activity by 19% (P<0.05 in membranes from glycolytic muscle. Oxidized glutathione (GSSG, 0-10 mM increased the in vitro glutathionylation level detected with antibodies, and decreased the in vitro maximal Na,K-ATPase activity in a dose-dependent manner, and with a larger effect in oxidative compared to glycolytic skeletal muscle.This study demonstrates the existence of basal glutathionylation of both the α and the β units of rat skeletal muscle Na,K-ATPase. In addition, the study suggests a negative correlation between glutathionylation levels and maximal Na,K-ATPase activity.Glutathionylation likely contributes to the complex regulation of Na,K-ATPase function in skeletal muscle. Especially, glutathionylation induced by oxidative stress may have a role in Na,K-ATPase regulation during prolonged muscle activity.

  5. Early-Life Stress Affects Stress-Related Prefrontal Dopamine Activity in Healthy Adults, but Not in Individuals with Psychotic Disorder.

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    Zuzana Kasanova

    Full Text Available Early life stress may have a lasting impact on the developmental programming of the dopamine (DA system implicated in psychosis. Early adversity could promote resilience by calibrating the prefrontal stress-regulatory dopaminergic neurotransmission to improve the individual's fit with the predicted stressful environment. Aberrant reactivity to such match between proximal and distal environments may, however, enhance psychosis disease risk. We explored the combined effects of childhood adversity and adult stress by exposing 12 unmedicated individuals with a diagnosis of non-affective psychotic disorder (NAPD and 12 healthy controls (HC to psychosocial stress during an [18F]fallypride positron emission tomography. Childhood trauma divided into early (ages 0-11 years and late (12-18 years was assessed retrospectively using a questionnaire. A significant group x childhood trauma interaction on the spatial extent of stress-related [18F]fallypride displacement was observed in the mPFC for early (b = -8.45, t(1,23 = -3.35, p = .004 and late childhood trauma (b = -7.86, t(1,23 = -2.48, p = .023. In healthy individuals, the spatial extent of mPFC DA activity under acute psychosocial stress was positively associated with the severity of early (b = 7.23, t(11 = 3.06, p = .016 as well as late childhood trauma (b = -7.86, t(1,23 = -2.48, p = .023. Additionally, a trend-level main effect of early childhood trauma on subjective stress response emerged within this group (b = -.7, t(11 = -2, p = .07, where higher early trauma correlated with lower subjective stress response to the task. In the NAPD group, childhood trauma was not associated with the spatial extent of the tracer displacement in mPFC (b = -1.22, t(11 = -0.67, nor was there a main effect of trauma on the subjective perception of stress within this group (b = .004, t(11 = .01, p = .99. These findings reveal a potential mechanism of neuroadaptation of prefrontal DA transmission to early life stress

  6. Influence of stress systems and physical activity on different dimensions of fatigue in female fibromyalgia patients.

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    Doerr, Johanna M; Fischer, Susanne; Nater, Urs M; Strahler, Jana

    2017-02-01

    Fatigue is a defining characteristic and one of the most debilitating features of fibromyalgia syndrome (FMS). The mechanisms underlying different dimensions of fatigue in FMS remain unclear. The aim of the current study was to test whether stress-related biological processes and physical activity modulate fatigue experience. Using an ambulatory assessment design, 26 female FMS patients reported general, mental, and physical fatigue levels at six time points per day for 14 consecutive days. Salivary cortisol and alpha-amylase were analyzed as markers of neuroendocrine functioning. Participants wore wrist actigraphs for the assessment of physical activity. Lower increases in cortisol after awakening predicted higher mean daily general and physical fatigue levels. Additionally, mean daily physical activity positively predicted next-day mean general fatigue. Levels of physical fatigue at a specific time point were positively associated with momentary cortisol levels. The increase in cortisol after awakening did not mediate the physical activity - fatigue relationship. There were no associations between alpha-amylase and fatigue. Our findings imply that both changes in hypothalamic-pituitary-adrenal axis activity and physical activity contribute to variance in fatigue in the daily lives of patients with FMS. This study helps to paint a clearer picture of the biological and behavioral underpinnings of fatigue in FMS and highlight the necessity of interdisciplinary treatment approaches targeting biological, behavioral and psychological aspects of FMS. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Potato responds to salt stress by increased activity of antioxidant enzymes.

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    Aghaei, Keyvan; Ehsanpour, Ali Akber; Komatsu, Setsuko

    2009-12-01

    To understand the response of potato to salt stress, antioxidant enzyme activities and ion content were analyzed for a sensitive and a tolerant cultivar. Nodal cuttings of the tolerant cultivar, Kennebec, and the sensitive cultivar, Concord, were exposed to media without or with 30, 60, 90 or 120 mmol/L NaCl for 4 weeks. On exposure to NaCl, the length and fresh and dry weight of both shoots and roots of Concord showed greater decrease than those of Kennebec. The decrease in shoot growth was more severe than that of the root for both cultivars. The K(+) content of shoots and roots of both cultivars was reduced in a dose-dependent manner by exposure to NaCl; the Na(+) content increased. Activities of ascorbate peroxidase, catalase and glutathione reductase were increased in NaCl-exposed shoots of Kennebec; the corresponding activities in NaCl-exposed shoots of Concord were decreased. Roots of both cultivars showed similar changes in the activities of these enzymes on exposure to NaCl. These studies established that enzyme activities in Concord shoots are inversely related to the NaCl concentration, whereas those in Kennebec do not show a dose dependency, which is also the case for the roots of both cultivars. Our findings suggest that an increase in activity of antioxidant enzymes, such as ascorbate peroxidase, catalase and glutathione reductase, can contribute to salt tolerance in Kennebec, a salt resistant cultivar of potato.

  8. Desiccating Stress-Induced MMP Production and Activity Worsens Wound Healing in Alkali-Burned Corneas

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    Bian, Fang; Pelegrino, Flavia S. A.; Pflugfelder, Stephen C.; Volpe, Eugene A.; Li, De-Quan; de Paiva, Cintia S.

    2015-01-01

    Purpose To evaluate the effects of dry eye on ocular surface protease activity and sight threatening corneal complications following ocular surface chemical injury. Methods C57BL/6 mice were subjected to unilateral alkali burn (AB) with or without concomitant dry eye for 2 or 5 days. Mice were observed daily for appearance of corneal perforation. Whole corneas were harvested and lysed for RNA extraction. Quantitative real-time PCR was performed to measure expression of inflammation cytokines, matrix metalloproteinases (MMP). Matrix metalloproteinase–9 activity, gelatinase activity, and myeloperoxidase (MPO) activity were evaluated in corneal lysates. Presence of infiltrating neutrophils was evaluated by immunohistochemistry and flow cytometry. Results Eyes subjected to the combined model of AB and dry eye (CM) had 20% sterile corneal perforation rate as soon as 1 day after the initial injury, which increased to 35% by 5 days, delayed wound closure and increased corneal opacity. Increased levels of IL-1β, -6, and MMPs-1, -3, -8, -9, and -13, and chemokine (C-X-C motif) ligand 1 (CSCL1) transcripts were found after 2 days in CM compared with AB corneas. Increased MMP-1, -3, -9, and -13 immunoreactivity and gelatinolytic activity were seen in CM corneas compared with AB. Increased neutrophil infiltration and MPO activity was noted in the CM group compared with AB 2 days post injury. Conclusions Desiccating stress worsens outcome of ocular AB, creating a cytokine and protease storm with greater neutrophil infiltration, increasing the risk of corneal perforation. PMID:26225631

  9. Hypoxia mediated pulmonary edema: potential influence of oxidative stress, sympathetic activation and cerebral blood flow.

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    Khademi, Shadi; Frye, Melinda A; Jeckel, Kimberly M; Schroeder, Thies; Monnet, Eric; Irwin, Dave C; Cole, Patricia A; Bell, Christopher; Miller, Benjamin F; Hamilton, Karyn L

    2015-10-09

    Neurogenic pulmonary edema (NPE) is a non-cardiogenic form of pulmonary edema that can occur consequent to central neurologic insults including stroke, traumatic brain injury, and seizure. NPE is a public health concern due to high morbidity and mortality, yet the mechanism(s) are unknown. We hypothesized that NPE, evoked by cerebral hypoxia in the presence of systemic normoxia, would be accompanied by sympathetic activation, oxidative stress, and compensatory antioxidant mechanisms. Thirteen Walker hounds were assigned to cerebral hypoxia (SaO2 ~ 55 %) with systemic normoxia (SaO2 ~ 90 %) (CH; n = 6), cerebral and systemic (global) hypoxia (SaO2 ~ 60 %) (GH; n = 4), or cerebral and systemic normoxia (SaO2 ~ 90 %) (CON; n = 3). Femoral venous (CH and CON) perfusate was delivered via cardiopulmonary bypass to the brain and GH was induced by FiO2 = 10 % to maintain the SaO2 at ~60 %. Lung wet to lung dry weight ratios (LWW/LDW) were assessed as an index of pulmonary edema in addition to hemodynamic measurements. Plasma catecholamines were measured as markers of sympathetic nervous system (SNS) activity. Total glutathione, protein carbonyls, and malondialdehyde were assessed as indicators of oxidative stress. Brain and lung compensatory antioxidants were measured with immunoblotting. Compared to CON, LWW/LDW and pulmonary artery pressure were greater in CH and GH. Expression of hemeoxygenase-1 in brain was higher in CH compared to GH and CON, despite no group differences in oxidative damage in any tissue. Catecholamines tended to be higher in CH and GH. Cerebral hypoxia, with systemic normoxia, is not systematically associated with an increase in oxidative stress and compensatory antioxidant enzymes in lung, suggesting oxidative stress did not contribute to NPE in lung. However, increased SNS activity may play a role in the induction of NPE during hypoxia.

  10. Anti-stress and Adaptogenic Activity of l-Arginine Supplementation

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    Vanita Gupta

    2005-01-01

    Full Text Available In the present study, oral supplementation of l-arginine in rats was evaluated for its anti-stress and adaptogenic activity using the cold (5°C–hypoxia (428 mmHg–restraint (C-H-R animal model. A dose-dependent study of l-arginine was carried out at doses of 12.5, 25.0, 50.0, 100.0, 200.0 and 500.0 mg/kg body weight, administered orally 30 min prior to C-H-R exposure. The time taken by the rat to attain a rectal temperature of 23°C (Trec 23°C during C-H-R exposure and its recovery to Trec 37°C at normal atmospheric pressure and 32 ± 1°C were used as biomarkers of anti-stress and adaptogenic activity. Biochemical parameters related to lipid peroxidation, anti-oxidants, cell membrane permeability, nitric oxide and stress, with and without administration of the least effective l-arginine dose, were measured in rats on attaining Trec 23°C and Trec 37°C. The least effective adaptogenic dose of l-arginine was 100.0 mg/kg body weight. The C-H-R exposure of control rats, on attaining Trec 23°C, resulted in a significant increase in plasma malondialdehyde (MDA, blood lactate dehydrogenase (LDH and a decrease in blood catalase (CAT and plasma testosterone levels. On recovery (Trec 37°C of control rats, there was a further decrease in CAT and plasma testosterone, and an increase in LDH. l-Arginine supplementation resulted in a significant decrease in plasma MDA, an increase in blood superoxide dismutase (SOD, CAT levels maintained at control values and a lower increase in LDH compared with controls (45.3 versus 58.5% and 21.5 versus 105.2% on attaining Trec 23°C during C-H-R exposure and on recovery to Trec 37°C. The results suggested that l-arginine possesses potent anti-stress activity during C-H-R exposure and recovery from C-H-R-induced hypothermia.

  11. Heat stress impairs performance parameters, induces intestinal injury, and decreases macrophage activity in broiler chickens.

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    Quinteiro-Filho, W M; Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Sakai, M; Sá, L R M; Ferreira, A J P; Palermo-Neto, J

    2010-09-01

    Studies on environmental consequences of stress on animal production have grown substantially in the last few years for economic and animal welfare reasons. Physiological, hormonal, and immunological deficits as well as increases in animals' susceptibility to diseases have been reported after different stressors in broiler chickens. The aim of the current experiment is to describe the effects of 2 different heat stressors (31 +/- 1 and 36 +/- 1 degrees C/10 h per d) applied to broiler chickens from d 35 to 42 of life on the corticosterone serum levels, performance parameters, intestinal histology, and peritoneal macrophage activity, correlating and discussing the obtained data under a neuroimmune perspective. In our study, we demonstrated that heat stress (31 +/- 1 and 36 +/- 1 degrees C) increased the corticosterone serum levels and decreased BW gain and food intake. Only chickens submitted to 36 +/- 1 degrees C, however, presented a decrease in feed conversion and increased mortality. We also showed a decrease of bursa of Fabricius (31 +/- 1 and 36 +/- 1 degrees C), thymus (36 +/- 1 degrees C), and spleen (36 +/- 1 degrees C) relative weights and of macrophage basal (31 +/- 1 and 36 +/- 1 degrees C) and Staphylococcus aureus-induced oxidative burst (31 +/- 1 degrees C). Finally, mild multifocal acute enteritis characterized by an increased presence of lymphocytes and plasmocytes within the jejunum's lamina propria was also observed. The stress-induced hypothalamic-pituitary-adrenal axis activation was taken as responsible for the negative effects observed on the chickens' performance and immune function and also the changes of the intestinal mucosa. The present obtained data corroborate with others in the field of neuroimmunomodulation and open new avenues for the improvement of broiler chicken welfare and production performance.

  12. Physiological responses of Brassica napus to fulvic acid under water stress: Chlorophyll a fluorescence and antioxidant enzyme activity

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    Ramin Lotfi

    2015-10-01

    Full Text Available The ameliorative effect of fulvic acid (0, 300, and 600 mg L− 1 on photosystem II and antioxidant enzyme activity of the rapeseed (Brassica napus L. plant under water stress (60, 100, and 140 mm evaporation from class A pan was studied using split plots in a randomized complete block design with three replications. Results indicated that application of fulvic acid (FA improved the maximum quantum efficiency of PSII (Fv/Fm and performance index (PI of plants under both well-watered and limited-water conditions. The time span from Fo to Fm and the energy necessary for the closure of all reaction centers was significantly increased, but the size of the plastoquinone pool was reduced with increasing water stress levels. Plants treated with FA had higher peroxidase and catalase activities under all irrigation conditions. Activities of ascorbate peroxidase and superoxide dismutase in plants increased with increasing water stress. Malondialdehyde increased under severe water stress, but application of FA significantly decreased lipid peroxidation. Production of reactive oxygen species (ROS is a common phenomenon in plants under stress. Under this condition, the balance between the production of ROS and the quenching activity of antioxidants is upset, often resulting in oxidative damage. In this study, application of FA significantly increased fluorescence of chlorophyll a, inhibiting ROS production and enhancing antioxidant enzymes activity that destroyed ROS. Thus, ROS in plant cells was reduced under water stress by application of FA and consequently lipid peroxidation was reduced.

  13. Elevated temperature altered photosynthetic products in wheat seedlings and organic compounds and biological activity in rhizopshere soil under cadmium stress.

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    Jia, Xia; Zhao, YongHua; Wang, WenKe; He, Yunhua

    2015-09-23

    The objective of this study was to investigate the effects of slightly elevated atmospheric temperature in the spring on photosynthetic products in wheat seedlings and on organic compounds and biological activity in rhizosphere soil under cadmium (Cd) stress. Elevated temperature was associated with increased soluble sugars, reducing sugars, starch, and total sugars, and with decreased amino acids in wheat seedlings under Cd stress. Elevated temperature improved total soluble sugars, free amino acids, soluble phenolic acids, and organic acids in rhizosphere soil under Cd stress. The activity of amylase, phenol oxidase, invertase, β-glucosidase, and l-asparaginase in rhizosphere soil was significantly improved by elevated temperature under Cd stress; while cellulase, neutral phosphatase, and urease activity significantly decreased. Elevated temperature significantly improved bacteria, fungi, actinomycetes, and total microorganisms abundance and fluorescein diacetate activity under Cd stress. In conclusion, slightly elevated atmospheric temperature in the spring improved the carbohydrate levels in wheat seedlings and organic compounds and biological activity in rhizosphere soil under Cd stress in the short term. In addition, elevated atmospheric temperature in the spring stimulated available Cd by affecting pH, DOC, phenolic acids, and organic acids in rhizosphere soil, which resulted in the improvement of the Cd uptake by wheat seedlings.

  14. Changes in neuronal CycD/Cdk4 activity affect aging, neurodegeneration, and oxidative stress.

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    Icreverzi, Amalia; de la Cruz, Aida Flor A; Walker, David W; Edgar, Bruce A

    2015-10-01

    Mitochondrial dysfunction has been implicated in human diseases, including cancer, and proposed to accelerate aging. The Drosophila Cyclin-dependent protein kinase complex cyclin D/cyclin-dependent kinase 4 (CycD/Cdk4) promotes cellular growth by stimulating mitochondrial biogenesis. Here, we examine the neurodegenerative and aging consequences of altering CycD/Cdk4 function in Drosophila. We show that pan-neuronal loss or gain of CycD/Cdk4 increases mitochondrial superoxide, oxidative stress markers, and neurodegeneration and decreases lifespan. We find that RNAi-mediated depletion of the mitochondrial transcription factor, Tfam, can abrogate CycD/Cdk4's detrimental effects on both lifespan and neurodegeneration. This indicates that CycD/Cdk4's pathological consequences are mediated through altered mitochondrial function and a concomitant increase in reactive oxygen species. In support of this, we demonstrate that CycD/Cdk4 activity levels in the brain affect the expression of a set of 'oxidative stress' genes. Our results indicate that the precise regulation of neuronal CycD/Cdk4 activity is important to limit mitochondrial reactive oxygen species production and prevent neurodegeneration. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  15. Stress responses in flavivirus-infected cells: activation of unfolded protein response and autophagy

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    Ana-Belén eBlázquez

    2014-06-01

    Full Text Available The Flavivirus is a genus of RNA viruses that includes multiple long known human, animal and zoonotic pathogens such as Dengue virus, yellow fever virus, West Nile virus or Japanese encephalitis virus, as well as other less known viruses that represent potential threats for human and animal health such as Usutu or Zika viruses. Flavivirus replication is based on endoplasmic reticulum-derived structures. Membrane remodeling and accumulation of viral factors induce endoplasmic reticulum stress that results in activation of a cellular signaling response termed unfolded protein response (UPR, which can be modulated by the viruses for their own benefit. Concomitant with the activation of the UPR, an upregulation of the autophagic pathway in cells infected with different flaviviruses has also been described. This review addresses the current knowledge of the relationship between endoplasmic reticulum stress, UPR and autophagy in flavivirus-infected cells and the growing evidences for an involvement of these cellular pathways in the replication and pathogenesis of these viruses.

  16. Analgesic activity of piracetam: effect on cytokine production and oxidative stress.

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    Navarro, Suelen A; Serafim, Karla G G; Mizokami, Sandra S; Hohmann, Miriam S N; Casagrande, Rubia; Verri, Waldiceu A

    2013-04-01

    Piracetam is a prototype of nootropic drugs used to improve cognitive impairment. However, recent studies suggest that piracetam can have analgesic and anti-inflammatory effects. Inflammatory pain is the result of a process that depends on neutrophil migration, cytokines and prostanoids release and oxidative stress. We analyze whether piracetam has anti-nociceptive effects and its mechanisms. Per oral pretreatment with piracetam reduced in a dose-dependent manner the overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone, formalin and complete Freund's adjuvant. Piracetam also diminished carrageenin-induced mechanical and thermal hyperalgesia, myeloperoxidase activity, and TNF-α-induced mechanical hyperalgesia. Piracetam presented analgesic effects as post-treatment and local paw treatment. The analgesic mechanisms of piracetam were related to inhibition of carrageenin- and TNF-α-induced production of IL-1β as well as prevention of carrageenin-induced decrease of reduced glutathione, ferric reducing ability and free radical scavenging ability in the paw. These results demonstrate that piracetam presents analgesic activity upon a variety of inflammatory stimuli by a mechanism dependent on inhibition of cytokine production and oxidative stress. Considering its safety and clinical use for cognitive function, it is possible that piracetam represents a novel perspective of analgesic. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Cathepsin D inhibits oxidative stress-induced cell death via activation of autophagy in cancer cells.

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    Hah, Young-Sool; Noh, Hae Sook; Ha, Ji Hye; Ahn, Jin Sook; Hahm, Jong Ryeal; Cho, Hee Young; Kim, Deok Ryong

    2012-10-28

    Cathepsin D (CatD), a lysosomal aspartic protease, plays an essential role in tumor progression and apoptosis. However, the function of CatD in cell death is not yet fully understood. In this study, we identified CatD as one of up-regulated proteins in human malignant glioblastoma M059J cells that lack the catalytic subunit of DNA-PK compared with its isogenic M059K cells with normal DNA-PK activity. M059J cells were relatively more resistant to genotoxic stress than M059K cells. Overexpression of wild-type CatD but not catalytically inactive mutant CatD (D295N) inhibited H(2)O(2)-induced cell death in HeLa cells. Furthermore, knockdown of CatD expression abolished anti-apoptotic effect by CatD in the presence of H(2)O(2). Interestingly, high expression of CatD in HeLa cells significantly activated autophagy: increase of acidic autophagic vacuoles, LC3-II formation, and GFP-LC3 puncta. These results suggest that CatD can function as an anti-apoptotic mediator by inducing autophagy under cellular stress. In conclusion, inhibition of autophagy could be a novel strategy for the adjuvant chemotherapy of CatD-expressing cancers. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Independent association between lower level of social support and higher coagulation activity before and after acute psychosocial stress.

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    Wirtz, Petra H; Redwine, Laura S; Ehlert, Ulrike; von Känel, Roland

    2009-01-01

    To investigate the relationship between social support and coagulation parameter reactivity to mental stress in men and to determine if norepinephrine is involved. Lower social support is associated with higher basal coagulation activity and greater norepinephrine stress reactivity, which in turn, is linked with hypercoagulability. However, it is not known if low social support interacts with stress to further increase coagulation reactivity or if norepinephrine affects this association. These findings may be important for determining if low social support influences thrombosis and possible acute coronary events in response to acute stress. We investigated the relationship between social support and coagulation parameter reactivity to mental stress in men and determined if norepinephrine is involved. We measured perceived social support in 63 medication-free nonsmoking men (age (mean +/- standard error of the mean) = 36.7 +/- 1.7 years) who underwent an acute standardized psychosocial stress task combining public speaking and mental arithmetic in front of an audience. We measured plasma D-dimer, fibrinogen, clotting Factor VII activity (FVII:C), and plasma norepinephrine at rest as well as immediately after stress and 20 minutes after stress. Independent of body mass index, mean arterial pressure, and age, lower social support was associated with higher D-dimer and fibrinogen levels at baseline (p social support and stress on fibrinogen, D-dimer, and norepinephrine (p social support and the coagulation measures D-dimer and fibrinogen. Our results suggest that lower social support is associated with greater coagulation activity before and after acute stress, which was unrelated to norepinephrine reactivity.

  19. Effect of cycocel on photosynthetic activity and essential oil of fennel (Foeniculum vulgare Mill. under drought stress

    Directory of Open Access Journals (Sweden)

    Fatemeh Nouri

    2014-12-01

    Full Text Available Drought stress is one of the most important and most common environmental stresses that limit plant growth. Photosynthesis is the main determinant of plant growth and its retention ability under environmental stress condition is important for preservation of growth stability. To study the effect of spraying CCC on photosynthesis activity and essential oil content on 'Foeniculum vulgare', an experiment was done in split plot design based on complete block with four replications in research field of University of Zanjan in 2011. Levels of drought stress included, control, soft stress (when 30% of available water was out of soil, severe stress (when 90% of available water was out of soil, and three concentration of CCC 0, 1500 and 3000 mg/L. The results showed that between rates foliar application on physiologic characteristics as photosynthesis rate, transpiration severity, RWC and TΔ intercellular (Ci, stomata conductivity, mesophyll conductivity and essential oil content was significant. By spraying 3000 mg/L CCC, balanced the plant position against drought stress and could reduce negative effect. Foliar application of CCC caused significant increase in photosynthesis rate, mesophyll conductivity and significant decrease stomata conductivity, transpiration severity under drought stress and could increase essential oil content under soft stress. In this study, foliar application of CCC to content 3000 mg/L had the highest effect on this characters.

  20. Exogenous Tryptophan Promotes Cutaneous Wound Healing of Chronically Stressed Mice through Inhibition of TNF-α and IDO Activation

    Science.gov (United States)

    Bandeira, Luana Graziella; Bortolot, Beatriz Salari; Cecatto, Matheus Jorand; Monte-Alto-Costa, Andréa; Romana-Souza, Bruna

    2015-01-01

    Stress prolongs the inflammatory response compromising the dermal reconstruction and wound closure. Acute stress-induced inflammation increases indoleamine 2, 3-dioxygenase-stimulated tryptophan catabolism. To investigate the role of indoleamine 2, 3-dioxygenase expression and tryptophan administration in adverse effects of stress on cutaneous wound healing, mice were submitted to chronic restraint stress and treated with tryptophan daily until euthanasia. Excisional lesions were created on each mouse and 5 or 7 days later, the lesions were analyzed. In addition, murine skin fibroblasts were exposed to elevated epinephrine levels plus tryptophan, and fibroblast activity was evaluated. Tryptophan administration reversed the reduction of the plasma tryptophan levels and the increase in the plasma normetanephrine levels induced by stress 5 and 7 days after wounding. Five days after wounding, stress-induced increase in the protein levels of tumor necrosis factor-α and indoleamine 2, 3-dioxygenase, and this was inhibited by tryptophan. Stress-induced increase in the lipid peroxidation and the amount of the neutrophils, macrophages and T cells number was reversed by tryptophan 5 days after wounding. Tryptophan administration inhibited the reduction of myofibroblast density, collagen deposition, re-epithelialization and wound contraction induced by stress 5 days after wounding. In dermal fibroblast culture, the tryptophan administration increased the cell migration and AKT phosphorylation in cells treated with high epinephrine levels. In conclusion, tryptophan-induced reduction of inflammatory response and indoleamine 2, 3-dioxygenase expression may have accelerated cutaneous wound healing of chronically stressed mice. PMID:26057238