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Sample records for survival promoting activity

  1. Timp1 Promotes Cell Survival by Activating the PDK1 Signaling Pathway in Melanoma

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    Mariana Toricelli

    2017-04-01

    Full Text Available High TIMP1 expression is associated with poor prognosis in melanoma, where it can bind to CD63 and β1 integrin, inducing PI3-kinase pathway and cell survival. Phosphatidylinositol (3,4,5-trisphosphate (PIP3, generated under phosphatidylinositol-3-kinase (PI3K activation, enables the recruitment and activation of protein kinase B (PKB/AKT and phosphoinositide-dependent kinase 1 (PDK1 at the membrane, resulting in the phosphorylation of a host of other proteins. Using a melanoma progression model, we evaluated the impact of Timp1 and AKT silencing, as well as PI3K, PDK1, and protein kinase C (PKC inhibitors on aggressiveness characteristics. Timp1 downregulation resulted in decreased anoikis resistance, clonogenicity, dacarbazine resistance, and in vivo tumor growth and lung colonization. In metastatic cells, pAKTThr308 is highly expressed, contributing to anoikis resistance. We showed that PDK1Ser241 and PKCβIISer660 are activated by Timp1 in different stages of melanoma progression, contributing to colony formation and anoikis resistance. Moreover, simultaneous inhibition of Timp1 and AKT in metastatic cells resulted in more effective anoikis inhibition. Our findings demonstrate that Timp1 promotes cell survival with the participation of PDK1 and PKC in melanoma. In addition, Timp1 and AKT act synergistically to confer anoikis resistance in advanced tumor stages. This study brings new insights about the mechanisms by which Timp1 promotes cell survival in melanoma, and points to novel perspectives for therapeutic approaches.

  2. Mycobacterium abscessus induces a limited pattern of neutrophil activation that promotes pathogen survival.

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    Kenneth C Malcolm

    Full Text Available Mycobacterium abscessus is a rapidly growing mycobacterium increasingly detected in the neutrophil-rich environment of inflamed tissues, including the cystic fibrosis airway. Studies of the immune reaction to M. abscessus have focused primarily on macrophages and epithelial cells, but little is known regarding the neutrophil response despite the predominantly neutrophillic inflammation typical of these infections. In the current study, human neutrophils released less superoxide anion in response to M. abscessus than to Staphylococcus aureus, a pathogen that shares common sites of infection. Exposure to M. abscessus induced neutrophil-specific chemokine and proinflammatory cytokine genes. Although secretion of these protein products was confirmed, the quantity of cytokines released, and both the number and level of gene induction, was reduced compared to S. aureus. Neutrophils mediated killing of M. abscessus, but phagocytosis was reduced when compared to S. aureus, and extracellular DNA was detected in response to both bacteria, consistent with extracellular trap formation. In addition, M. abscessus did not alter cell death compared to unstimulated cells, while S. aureus enhanced necrosis and inhibited apoptosis. However, neutrophils augment M. abscessus biofilm formation. The response of neutrophils to M. abscessus suggests that the mycobacterium exploits neutrophil-rich settings to promote its survival and that the overall neutrophil response was reduced compared to S. aureus. These studies add to our understanding of M. abscessus virulence and suggest potential targets of therapy.

  3. Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2/4 Expression and Promote Intracellular Survival

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    Taslima T. Lina

    2016-07-01

    Full Text Available Ehrlichia chaffeensis preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown E. chaffeensis type 1 secreted tandem repeat protein (TRP effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate E. chaffeensis, via the TRP120 effector, activates the canonical Notch signaling pathway to promote intracellular survival. We found that nuclear translocation of the transcriptionally active Notch intracellular domain (NICD occurs in response to E. chaffeensis or recombinant TRP120, resulting in upregulation of Notch signaling pathway components and target genes notch1, adam17, hes, and hey. Significant differences in canonical Notch signaling gene expression levels (>40% were observed during early and late stages of infection, indicating activation of the Notch pathway. We linked Notch pathway activation specifically to the TRP120 effector, which directly interacts with the Notch metalloprotease ADAM17. Using pharmacological inhibitors and small interfering RNAs (siRNAs against γ-secretase enzyme, Notch transcription factor complex, Notch1, and ADAM17, we demonstrated that Notch signaling is required for ehrlichial survival. We studied the downstream effects and found that E. chaffeensis TRP120-mediated activation of the Notch pathway causes inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2 and p38 mitogen-activated protein kinase (MAPK pathways required for PU.1 and subsequent Toll-like receptor 2/4 (TLR2/4 expression. This investigation reveals a novel mechanism whereby E. chaffeensis exploits the Notch pathway to evade the host innate immune response for intracellular survival.

  4. ATF6alpha promotes astroglial activation and neuronal survival in a chronic mouse model of Parkinson's disease.

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    Koji Hashida

    Full Text Available Accumulating evidence suggests a crucial role for the unfolded protein response (UPR in Parkinson's disease (PD. In this study, we investigated the relevance of the UPR in a mouse model of chronic MPTP/probenecid (MPTP/P injection, which causes severe and persistent degeneration of dopaminergic neurons. Enhanced activation of the UPR branches, including ATF6α and PERK/eIF2α/ATF4, was observed after MPTP/P injections into mice. Deletion of the ATF6α gene accelerated neuronal degeneration and ubiquitin accumulation relatively early in the MPTP/P injection course. Surprisingly, astroglial activation was strongly suppressed, and production of the brain-derived neurotrophic factor (BDNF and anti-oxidative genes, such as heme oxygenase-1 (HO-1 and xCT, in astrocytes were reduced in ATF6α -/- mice after MPTP/P injections. Decreased BDNF expression in ATF6α -/- mice was associated with decreased expression of GRP78, an ATF6α-dependent molecular chaperone in the ER. Decreased HO-1 and xCT levels were associated with decreased expression of the ATF4-dependent pro-apoptotic gene CHOP. Consistent with these results, administration of the UPR-activating reagent tangeretin (5,6,7,8,4'-pentamethoxyflavone; IN19 into mice enhanced the expression of UPR-target genes in both dopaminergic neurons and astrocytes, and promoted neuronal survival after MPTP/P injections. These results suggest that the UPR is activated in a mouse model of chronic MPTP/P injection, and contributes to the survival of nigrostriatal dopaminergic neurons, in part, through activated astrocytes.

  5. TNF-mediated survival of CD169(+) cells promotes immune activation during vesicular stomatitis virus infection

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    Shinde, Prashant V; Xu, Haifeng C; Maney, Sathish Kumar

    2017-01-01

    Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169(+) cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169(+) cells during viral infections remain ...

  6. Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

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    Kiran, Shashi; Oddi, Vineesha [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Laboratory of Cancer Cell Biology, Department of Research, Institute of Liver and Biliary Sciences, Delhi 110070 (India)

    2015-02-01

    Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose of doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT

  7. Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF-κB/p65 Activation

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    Qian Liu

    2016-01-01

    Full Text Available Stem cell survival after transplantation determines the efficiency of stem cell treatment, which develops as a novel potential therapy for several central nervous system (CNS diseases in recent decades. The engrafted stem cells face the damage of oxidative stress, inflammation, and immune response at the lesion point in host. Among the damaging pathologies, oxidative stress directs stem cells to apoptosis and even death through several signalling pathways and DNA damage. However, the in-detail mechanism of stem cell survival from oxidative stress has not been revealed clearly. Here, in this study, we used hydrogen peroxide (H2O2 to induce the oxidative damage on neural stem cells (NSCs. The damage was in consequence demonstrated involving the activation of heat shock protein 90 (HSP90 and NF-κB/p65 signalling pathways. Further application of the pharmacological inhibitors, respectively, targeting at each signalling indicated an upper-stream role of HSP90 upon NF-κB/p65 on NSCs survival. Preinhibition of HSP90 with the specific inhibitor displayed a significant protection on NSCs against oxidative stress. In conclusion, inhibition of HSP90 would attenuate NF-κB/p65 activation by oxidative induction and promote NSCs survival from oxidative damage. The HSP90/NF-κB mechanism provides a new evidence on rescuing NSCs from oxidative stress and also promotes the stem cell application on CNS pathologies.

  8. Lipid degradation promotes prostate cancer cell survival

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    Itkonen, Harri M; Brown, Michael; Urbanucci, Alfonso; Tredwell, Gregory; Lau, Chung Ho; Barfeld, Stefan; Hart, Claire; Guldvik, Ingrid J.; Takhar, Mandeep; Heemers, Hannelore V.; Erho, Nicholas; Bloch, Katarzyna; Davicioni, Elai; Derua, Rita; Waelkens, Etienne; Mohler, James L.; Clarke, Noel; Swinnen, Johan V.; Keun, Hector C.; Rekvig, Ole P.; Mills, Ian G.

    2017-01-01

    Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential. PMID:28415728

  9. Notch signaling sustains the expression of Mcl-1 and the activity of eIF4E to promote cell survival in CLL.

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    De Falco, Filomena; Sabatini, Rita; Del Papa, Beatrice; Falzetti, Franca; Di Ianni, Mauro; Sportoletti, Paolo; Baldoni, Stefano; Screpanti, Isabella; Marconi, Pierfrancesco; Rosati, Emanuela

    2015-06-30

    In chronic lymphocytic leukemia (CLL), Notch1 and Notch2 signaling is constitutively activated and contributes to apoptosis resistance. We show that genetic inhibition of either Notch1 or Notch2, through small-interfering RNA, increases apoptosis of CLL cells and is associated with decreased levels of the anti-apoptotic protein Mcl-1. Thus, Notch signaling promotes CLL cell survival at least in part by sustaining Mcl-1 expression. In CLL cells, an enhanced Notch activation also contributes to the increase in Mcl-1 expression and cell survival induced by IL-4.Mcl-1 downregulation by Notch targeting is not due to reduced transcription or degradation by caspases, but in part, to increased degradation by the proteasome. Mcl-1 downregulation by Notch targeting is also accompanied by reduced phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), suggesting that this protein is another target of Notch signaling in CLL cells.Overall, we show that Notch signaling sustains CLL cell survival by promoting Mcl-1 expression and eIF4E activity, and given the oncogenic role of these factors, we underscore the therapeutic potential of Notch inhibition in CLL.

  10. Tumor Necrosis Factor-Mediated Survival of CD169+ Cells Promotes Immune Activation during Vesicular Stomatitis Virus Infection

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    Shinde, Prashant V; Xu, Haifeng C; Maney, Sathish Kumar

    2018-01-01

    Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169(+) cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169(+) cells during viral infections remain...... defense against viral pathogens. CD169(+) macrophages are shown to activate innate and adaptive immunity via "enforced virus replication" a controlled amplification of virus particles. However, factors regulating the CD169(+) macrophages remain to be studied. In this paper, we show that after Vesicular...... stomatitis virus infection, phagocytes produce tumor necrosis factor (TNF) which signals via TNFR1 and promote "enforced virus replication" in CD169(+) macrophages. Consequently, lack of TNF or TNFR1 resulted in defective immune activation and VSV clearance....

  11. DPP in the matrix activates AKT and mTOR signaling pathway to promote preodontoblast survival and differentiation

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    ANNE eGEORGE

    2015-08-01

    Full Text Available Dentin phosphophoryn (DPP is an extracellular matrix protein synthesized by odontoblasts. It is highly acidic and the phosphorylated protein possesses a strong affinity for calcium ions. Therefore, DPP in the extracellular matrix can promote hydroxyapatite nucleation and can regulate the size of the growing crystal. Besides its calcium binding property, DPP can initiate signaling functions from the ECM (Extracellular matrix. The signals that promote the cytodifferentiation of preodontoblasts to fully functional odontoblasts are not known. In this study, we demonstrate that preodontoblasts on a DPP matrix, generates mechanical and biochemical signals. This is initiated by the ligation of the integrins with the RGD containing DPP. The downstream biochemical response observed is the activation of the AKT( protein kinase B and mTOR (mammalian target of rapamycin signaling pathways leading to the activation of the transcription factor NF- κB (Nuclear factor κB . Terminal differentiation of the preodontoblasts was assessed by identifying phosphate and calcium deposits in the matrix using von Kossa and Alizarin red staining respectively. Identifying the signaling pathways initiated by DPP in the dentin matrix would help in devising strategies for dentin tissue engineering.

  12. Activation of focal adhesion kinase by Salmonella suppresses autophagy via an Akt/mTOR signaling pathway and promotes bacterial survival in macrophages.

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    Owen, Katherine A; Meyer, Corey B; Bouton, Amy H; Casanova, James E

    2014-06-01

    Autophagy has emerged as an important antimicrobial host defense mechanism that not only orchestrates the systemic immune response, but also functions in a cell autonomous manner to directly eliminate invading pathogens. Pathogenic bacteria such as Salmonella have evolved adaptations to protect themselves from autophagic elimination. Here we show that signaling through the non-receptor tyrosine kinase focal adhesion kinase (FAK) is actively manipulated by the Salmonella SPI-2 system in macrophages to promote intracellular survival. In wild-type macrophages, FAK is recruited to the surface of the Salmonella-containing vacuole (SCV), leading to amplified signaling through the Akt-mTOR axis and inhibition of the autophagic response. In FAK-deficient macrophages, Akt/mTOR signaling is attenuated and autophagic capture of intracellular bacteria is enhanced, resulting in reduced bacterial survival. We further demonstrate that enhanced autophagy in FAK(-/-) macrophages requires the activity of Atg5 and ULK1 in a process that is distinct from LC3-assisted phagocytosis (LAP). In vivo, selective knockout of FAK in macrophages resulted in more rapid clearance of bacteria from tissues after oral infection with S. typhimurium. Clearance was correlated with reduced infiltration of inflammatory cell types into infected tissues and reduced tissue damage. Together, these data demonstrate that FAK is specifically targeted by S. typhimurium as a novel means of suppressing autophagy in macrophages, thereby enhancing their intracellular survival.

  13. Modification of the association between recreational physical activity and survival after breast cancer by promoter methylation in breast cancer-related genes.

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    McCullough, Lauren E; Chen, Jia; Cho, Yoon Hee; Khankari, Nikhil K; Bradshaw, Patrick T; White, Alexandra J; Teitelbaum, Susan L; Terry, Mary Beth; Neugut, Alfred I; Hibshoosh, Hanina; Santella, Regina M; Gammon, Marilie D

    2017-02-21

    Mechanisms underlying the inverse association between physical activity and survival after breast cancer are unresolved, but DNA methylation may play a role. We hypothesized that promoter methylation of breast cancer-related genes, as well as global methylation, may modify the association between prediagnostic recreational physical activity (RPA) and breast cancer mortality. Using a population-based sample of 1254 women diagnosed with first primary breast cancer, we examined modification of the RPA-mortality association by gene-specific promoter methylation and global methylation. Average lifetime RPA was assessed from menarche to diagnosis through structured in-home interviews. Promoter methylation of 13 breast cancer-related genes was evaluated in archived tumor by methylation-specific polymerase chain reaction and MethyLight assay. Global methylation in white blood cell DNA was determined at long interspersed nucleotide element 1 and by the luminometric methylation assay. After approximately 15 years of follow-up, 486 patients had died, and 186 of the deaths were breast cancer-related. We used Cox proportional hazards regression to estimate HRs and 95% CIs as well as likelihood ratio tests to assess multiplicative interactions. All-cause mortality was lower only among physically active women with methylated promoter of APC (HR 0.60, 95% CI 0.40-0.80), CCND2 (HR 0.56, 95% CI 0.32-0.99), HIN (HR 0.55, 95% CI 0.38-0.80), and TWIST1 (HR 0.28, 95% CI 0.14-0.56) in tumors, but not among those with unmethylated tumors (significant interaction p breast cancer that is associated with RPA may be more pronounced in women with promoter tumor methylation in biologically plausible genes.

  14. TGF-β1 activates the canonical NF-κB signaling to promote cell survival and proliferation in dystrophic muscle fibroblasts in vitro

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    Ma, Zhen-Yu [Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province (China); Department of Neurology, The Second Affiliated Hospital, Guangzhou Medical University, No.250 Changgang East Road, Guangzhou 510260, Guangdong Province (China); Zhong, Zhi-Gang; Qiu, Meng-Yao; Zhong, Yu-Hua [Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province (China); Zhang, Wei-Xi, E-mail: weixizhang@qq.com [Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province (China)

    2016-03-18

    Activated fibroblasts continue to proliferate at injury sites, leading to progressive muscular fibrosis in Duchenne muscular dystrophy (DMD). TGF-β1 is a dominant profibrotic mediator thought to play a critical role in muscle fibrosis; however, the implicated mechanisms are not fully understood. Here we showed that TGF-β1 increased the resistance to apoptosis and stimulated cell cycle progression in dystrophic muscle fibroblasts under serum deprivation conditions in vitro. TGF-β1 treatment activated the canonical NF-κB pathway; and we found that pharmacological inhibition of IKKβ with IMD-0354 and RelA gene knockdown with siRNA attenuated these effects of TGF-β1 on dystrophic muscle fibroblasts. Collectively, our data suggest that TGF-β1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-κB signaling pathway. - Highlights: • TGF-β1 promotes survival and proliferation in dystrophic muscle fibroblasts. • TGF-β1 activated the canonical NF-κB pathway in dystrophic muscle fibroblasts. • Canonical NF-κB pathway mediates these effects of TGF-β1.

  15. Metabolic pathways promoting cancer cell survival and growth.

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    Boroughs, Lindsey K; DeBerardinis, Ralph J

    2015-04-01

    Activation of oncogenes and loss of tumour suppressors promote metabolic reprogramming in cancer, resulting in enhanced nutrient uptake to supply energetic and biosynthetic pathways. However, nutrient limitations within solid tumours may require that malignant cells exhibit metabolic flexibility to sustain growth and survival. Here, we highlight these adaptive mechanisms and also discuss emerging approaches to probe tumour metabolism in vivo and their potential to expand the metabolic repertoire of malignant cells even further.

  16. Activation of AKT signaling promotes cell growth and survival in α7β1 integrin-mediated alleviation of muscular dystrophy.

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    Boppart, Marni D; Burkin, Dean J; Kaufman, Stephen J

    2011-04-01

    Transgenic expression of the α7 integrin can ameliorate muscle pathology in a mouse model of Duchenne muscular dystrophy (mdx/utr(-/-)) and thus can compensate for the loss of dystrophin in diseased mice. In spite of the beneficial effects of the α7 integrin in protecting mice from dystrophy, identification of molecular signaling events responsible for these changes remains to be established. The purpose of this study was to determine a role for signaling in the amelioration of muscular dystrophy by α7 integrin. Activation of PI3K, ILK, AKT, mTOR, p70S6K, BAD, ERK, and p38 was measured in the muscle from wild type (WT), mdx/utr(-/-) and α7BX2-mdx/utr(-/-) mice using in vitro activity assays or phosphospecific antibodies and western blotting. Significant increases in PI3K activity (47%), ILK activity (2.0-fold), mTOR (Ser2448) (57%), p70S6K (Thr389) (11.7-fold), and ERK (Thr202/Tyr204) (66%) were demonstrated in dystrophic mdx/utr(-/-) muscle compared to WT. A significant decrease in p38 phosphorylation (2.9-fold) was also observed. Although most of these signaling events were similar in dystrophic mdx/utr(-/-) mice overexpressing the α7 integrin, the AKT (Ser473):AKT ratio (2-fold vs. WT) and p70S6K phosphorylation (18-fold vs. WT) were higher in α7BX2-mdx/utr(-/-) compared to mdx/utr(-/-) mice. In addition, increased phosphorylation of BAD Serine 112 may contribute to the significant reduction in TUNEL(+) cells observed in α7BX2-mdx/utr(-/-) mice. We conclude that the α7β1 integrin confers a protective effect in dystrophic muscle through the activation of the ILK, AKT, p70S6K and BAD signaling to promote muscle cell survival. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. [Physical activity and cancer survival].

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    Romieu, Isabelle; Touillaud, Marina; Ferrari, Pietro; Bignon, Yves-Jean; Antoun, Sami; Berthouze-Aranda, Sophie; Bachmann, Patrick; Duclos, Martine; Ninot, Grégory; Romieu, Gilles; Sénesse, Pierre; Behrendt, Jan; Balosso, Jacques; Pavic, Michel; Kerbrat, Pierre; Serin, Daniel; Trédan, Olivier; Fervers, Béatrice

    2012-10-01

    Physical activity has been shown in large cohort studies to positively impact survival in cancer survivors. Existing randomized controlled trials showed a beneficial effect of physical activity on physical fitness, quality of life, anxiety and self-esteem; however, the small sample size, the short follow-up and the lack of standardization of physical activity intervention across studies impaired definite conclusion in terms of survival. Physical activity reduces adiposity and circulating estrogen levels and increases insulin sensitivity among other effects. A workshop was conducted at the International Agency for Research on Cancer in April 2011 to discuss the role of physical activity on cancer survival and the methodology to develop multicentre randomized intervention trials, including the type of physical activity to implement and its association with nutritional recommendations. The authors discuss the beneficial effect of physical activity on cancer survival with a main focus on breast cancer and report the conclusions from this workshop.

  18. Increased Sleep Promotes Survival during a Bacterial Infection in Drosophila

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    Kuo, Tzu-Hsing; Williams, Julie A.

    2014-01-01

    Study Objectives: The relationship between sleep and immune function is not well understood at a functional or molecular level. We therefore used a genetic approach in Drosophila to manipulate sleep and evaluated effects on the ability of flies to fight bacterial infection. Setting: Laboratory. Participants: Drosophila melanogaster. Methods and Results: We used a genetic approach to transiently alter neuronal excitability in the mushroom body, a region in the central brain that is known to regulate sleep. Flies with increased sleep for up to two days prior to a bacterial infection showed increased resistance to the infection and improved survival. These flies also had increased expression levels of a subset of anti-microbial peptide mRNA prior to infection, as well as increased NFκB activity during infection as indicated by in vivo luciferase reporter activity. In contrast, flies that experienced reduced sleep for up to two days prior to infection had no effect on survival or on NFκB activity during infection. However, flies with reduced sleep showed an altered defense mechanism, such that resistance to infection was increased, but at the expense of reduced tolerance. This effect was dependent on environmental condition. Conclusions: Increasing sleep enhanced activity of an NFκB transcription factor, increased resistance to infection, and strongly promoted survival. Together, these findings support the hypothesis that sleep is beneficial to the host by maintaining a robust immune system. Citation: Kuo TH, Williams JA. Increased sleep promotes survival during a bacterial infection in Drosophila. SLEEP 2014;37(6):1077-1086. PMID:24882902

  19. Cysteine-linked dimerization of BST-2 confers anoikis resistance to breast cancer cells by negating proapoptotic activities to promote tumor cell survival and growth.

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    Mahauad-Fernandez, Wadie D; Okeoma, Chioma M

    2017-03-16

    Almost all breast tumors express the antiviral protein BST-2 with 67%, 25% and 8.2% containing high, medium or low levels of BST-2, respectively. Breast tumor cells and tissues that contain elevated levels of BST-2 are highly aggressive. Suppression of BST-2 expression reprograms tumorigenic properties of cancer cells and diminishes cancer cell aggressiveness. Using structure/function studies, we report that dimerization of BST-2 through cysteine residues located in the BST-2 extracellular domain (ECD), leads to anoikis resistance and cell survival through proteasome-mediated degradation of BIM-a key proapoptotic factor. Importantly, BST-2 dimerization promotes tumor growth in preclinical breast cancer models in vitro and in vivo. Furthermore, we demonstrate that restoration of the ECD cysteine residues is sufficient to rescue cell survival and tumor growth via a previously unreported pathway-BST-2/GRB2/ERK/BIM/Cas3. These findings suggest that disruption of BST-2 dimerization offers a potential therapeutic approach for breast cancer.

  20. NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus.

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    Onkar Sharma

    2016-03-01

    Full Text Available A global increase in invasive infections due to group A Streptococcus (S. pyogenes or GAS has been observed since the 1980s, associated with emergence of a clonal group of strains of the M1T1 serotype. Among other virulence attributes, the M1T1 clone secretes NAD+-glycohydrolase (NADase. When GAS binds to epithelial cells in vitro, NADase is translocated into the cytosol in a process mediated by streptolysin O (SLO, and expression of these two toxins is associated with enhanced GAS intracellular survival. Because SLO is required for NADase translocation, it has been difficult to distinguish pathogenic effects of NADase from those of SLO. To resolve the effects of the two proteins, we made use of anthrax toxin as an alternative means to deliver NADase to host cells, independently of SLO. We developed a novel method for purification of enzymatically active NADase fused to an amino-terminal fragment of anthrax toxin lethal factor (LFn-NADase that exploits the avid, reversible binding of NADase to its endogenous inhibitor. LFn-NADase was translocated across a synthetic lipid bilayer in vitro in the presence of anthrax toxin protective antigen in a pH-dependent manner. Exposure of human oropharyngeal keratinocytes to LFn-NADase in the presence of protective antigen resulted in cytosolic delivery of NADase activity, inhibition of protein synthesis, and cell death, whereas a similar construct of an enzymatically inactive point mutant had no effect. Anthrax toxin-mediated delivery of NADase in an amount comparable to that observed during in vitro infection with live GAS rescued the defective intracellular survival of NADase-deficient GAS and increased the survival of SLO-deficient GAS. Confocal microscopy demonstrated that delivery of LFn-NADase prevented intracellular trafficking of NADase-deficient GAS to lysosomes. We conclude that NADase mediates cytotoxicity and promotes intracellular survival of GAS in host cells.

  1. Angiopoietin-1 promotes cardiac and skeletal myocyte survival through integrins.

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    Dallabrida, Susan M; Ismail, Nesreen; Oberle, Julianne R; Himes, Blanca E; Rupnick, Maria A

    2005-03-04

    Cardiac myocyte loss, regardless of insult, can trigger compensatory myocardial remodeling leading to heart failure. Identifying mediators of cardiac myocyte survival may advance clinical efforts toward myocardial preservation. Angiopoietin-1 limits ischemia-induced cardiac injury. This benefit is ascribed to angiogenesis because the receptor, tie2, is largely endothelial-specific. We propose that direct, non-tie2 interactions of angiopoietin-1 on cardiac myocytes contribute to this cardioprotection. We found that mouse C2C12 skeletal myocytes lack tie2, yet dose-dependently adhered to angiopoietin-1 and angiopoietin-2 similarly to laminin, fibronectin, vitronectin, and more than to collagen-I, -III, and -IV. Adhesion was divalent cation-mediated (Mn2+, Ca2+, not Mg2+), blocked with EDTA/EGTA, RGD-based peptides, and select integrin subunit antibodies. Similar findings were obtained with human skeletal myocytes (HSMs) and freshly isolated rat neonatal cardiac myocytes (NCMs). Furthermore, angiopoietin-1 conferred significant survival advantage exceeding that of most cell matrices, which was not fully explained by differences in cell adhesion. Angiopoietin-1 promoted survival of serum-starved C2C12, HSM, and NCM (MTT, trypan blue) and prevented taxol-induced apoptosis (caspase-3). Immobilized and soluble angiopoietin-1 phosphorylated Akt(S473) and MAPK(p42/44), (not FAK(Y397)) in C2C12 more than in endothelial cells and more than did angiopoietin-2 or cell matrices. EDTA, RGD-based peptides, and some integrin antibodies blocked these responses. Angiopoietin-1 activated HSM and NCM Akt(S473) and MAPK(p42/44) survival pathways. We propose that this novel function contributes to developmental and cardioprotective actions of angiopoietin-1 presently attributed to vascular effects alone. Angiopoietin-1 may prove therapeutically valuable in cardiac remodeling by supporting myocyte viability and preserving pump function. The full text of this article is available online at

  2. Increasing levels of wild-type CREB up-regulates several activity-regulated inhibitor of death (AID genes and promotes neuronal survival

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    Tan Yan-Wei

    2012-05-01

    Full Text Available Abstract Background CREB (cAMP-response element binding protein is the prototypical signal-regulated transcription factor. In neurons, it is the target of the synaptic activity-induced nuclear calcium-calcium/calmodulin dependent protein kinase (CaMK IV signaling pathway that controls the expression of genes important for acquired neuroprotection as well as other long-lasting adaptive processes in the nervous system. The function of CREB as a transcriptional activator is controlled by its phosphorylation on serine 133, which can be catalyzed by CaMKIV and leads to the recruitment of the co-activator, CREB binding protein (CBP. Activation of CBP function by nuclear calcium-CaMKIV signaling is a second regulatory step required for CREB/CBP-mediated transcription. Results Here we used recombinant adeno-associated virus (rAAV to increase the levels of wild type CREB or to overexpress a mutant version of CREB (mCREB containing a serine to alanine mutation at position amino acid 133 in mouse hippocampal neurons. Increasing the levels of CREB was sufficient to boost neuroprotective activity even under basal conditions (i.e., in the absence of stimulation of synaptic activity. In contrast, overexpression of mCREB increased cell death. The ratio of phospho(serine 133CREB to CREB immunoreactivity in unstimulated hippocampal neurons was similar for endogenous CREB and overexpressed wild type CREB and, as expected, dramatically reduced for overexpressed mCREB. A gene expression analysis revealed that increased expression of CREB but not that of mCREB in hippocampal neurons led to elevated expression levels of bdnf as well as that of several members of a previously characterized set of Activity-regulated Inhibitor of Death (AID genes, which include atf3, btg2, gadd45β, and gadd45γ. Conclusions Our findings indicate that the expression levels of wild type CREB are a critical determinant of the ability of hippocampal neurons to survive harmful conditions

  3. Global Activities and Plant Survival

    DEFF Research Database (Denmark)

    Bandick, Roger

    2014-01-01

    This chapter provides an extensive review of the empirical evidence found for Sweden concerning plant survival. The result reveals that foreign MNE plants and exporting non-MNE plants have the lowest exit rates, followed by purely domestic-oriented plants, and that domestic MNE plants have...... the highest exit rates. Moreover, the exit rates of globally engaged plants seem to be unaffected by increased foreign presence, whereas there appears to be a negative impact on the survival rates of non-exporting non-MNE plants. Finally, the result reveals that the survival ratio of plants of acquired...... exporters, but not other types of plants, improves post acquisition....

  4. Loss of P53 Function Activates JAK2-STAT3 Signaling to Promote Pancreatic Tumor Growth, Stroma Modification, and Gemcitabine Resistance in Mice and Is Associated With Patient Survival.

    Science.gov (United States)

    Wörmann, Sonja M; Song, Liang; Ai, Jiaoyu; Diakopoulos, Kalliope N; Kurkowski, Magdalena U; Görgülü, Kivanc; Ruess, Dietrich; Campbell, Andrew; Doglioni, Claudio; Jodrell, Duncan; Neesse, Albrecht; Demir, Ihsan E; Karpathaki, Angelica-Phaedra; Barenboim, Maxim; Hagemann, Thorsten; Rose-John, Stefan; Sansom, Owen; Schmid, Roland M; Protti, Maria P; Lesina, Marina; Algül, Hana

    2016-07-01

    pancreatic stellate cells in the tumor stroma and altered the types of immune cells that infiltrated tumors. Mice given a combination of gemcitabine and a JAK2 inhibitor formed smaller tumors and survived longer than mice given control agents; the tumor stroma had fewer activated pancreatic stellate cells, lower levels of periostin, and alterations in collagen production and organization. Phosphorylation of STAT3 correlated with P53 mutation and features of infiltrating immune cells in human pancreatic tumors. Patients whose tumors had lower levels of phosphorylated STAT3 and functional P53 had significantly longer survival times than patients with high levels of phosphorylated STAT3 and P53 mutation. In pancreatic tumors of mice, loss of P53 function activates JAK2-STAT3 signaling, which promotes modification of the tumor stroma and tumor growth and resistance to gemcitabine. In human pancreatic tumors, STAT3 phosphorylation correlated with P53 mutation and patient survival time. Inhibitors of this pathway slow tumor growth and stroma formation, alter immune cell infiltration, and prolong survival of mice. Transcript profiling: ArrayExpress accession number: E-MTAB-3278. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  5. Mst-1 deficiency promotes post-traumatic spinal motor neuron survival via enhancement of autophagy flux.

    Science.gov (United States)

    Zhang, Mengting; Tao, Wufan; Yuan, Zengqiang; Liu, Yaobo

    2017-10-01

    The mammalian Ste20-like kinase 1 (Mst-1) is a serine-threonine kinase and a component of the Hippo tumor suppressor pathway, which reacts to pathologically relevant stress and regulates cell death. However, little is known about its role in spinal cord injury. Here, we found that p-Mst-1, the activated form of Mst-1, was induced in the post-traumatic spinal motor neurons. In vivo evidence demonstrated that Mst-1 deficiency promoted post-traumatic spinal motor neuron survival, Basso mouse scale scores, and synapse survival. Moreover, we found that autophagosome formation and autolysosome degradation enhanced by Mst-1 deficiency were crucial to attenuate the death of injured spinal motor neurons. Taken together, our findings demonstrate that Mst-1 deficiency promotes post-traumatic spinal motor neuron survival via enhancement of autophagy flux. © 2017 International Society for Neurochemistry.

  6. Promoting physical activity in schools.

    Science.gov (United States)

    Armstrong, N

    1993-10-01

    Neil Armstrong, director of the Coronary Prevention in Children Project, argues for a comprehensive programme for promoting children's physical activity. The project's survey of adult coronary risk factors in British children revealed a worryingly low level of physical activity among British schoolchildren. Schools are ideally placed to encourage children to take physical exercise, he writes, but parental role models also play an important part.

  7. Repurposing Lesogaberan to Promote Human Islet Cell Survival and β-Cell Replication

    Directory of Open Access Journals (Sweden)

    Jide Tian

    2017-01-01

    Full Text Available The activation of β-cell’s A- and B-type gamma-aminobutyric acid receptors (GABAA-Rs and GABAB-Rs can promote their survival and replication, and the activation of α-cell GABAA-Rs promotes their conversion into β-cells. However, GABA and the most clinically applicable GABA-R ligands may be suboptimal for the long-term treatment of diabetes due to their pharmacological properties or potential side-effects on the central nervous system (CNS. Lesogaberan (AZD3355 is a peripherally restricted high-affinity GABAB-R-specific agonist, originally developed for the treatment of gastroesophageal reflux disease (GERD that appears to be safe for human use. This study tested the hypothesis that lesogaberan could be repurposed to promote human islet cell survival and β-cell replication. Treatment with lesogaberan significantly enhanced replication of human islet cells in vitro, which was abrogated by a GABAB-R antagonist. Immunohistochemical analysis of human islets that were grafted into immune-deficient mice revealed that oral treatment with lesogaberan promoted human β-cell replication and islet cell survival in vivo as effectively as GABA (which activates both GABAA-Rs and GABAB-Rs, perhaps because of its more favorable pharmacokinetics. Lesogaberan may be a promising drug candidate for clinical studies of diabetes intervention and islet transplantation.

  8. Physical activity and survival in breast cancer

    DEFF Research Database (Denmark)

    Ammitzbøll, Gunn; Søgaard, Karen; Karlsen, Randi V

    2016-01-01

    the Diet, Cancer, and Health cohort, all enrolled before diagnosis. Self-reported PA was measured as time per activity, and estimated metabolic equivalent task (MET)-hours per week were summed for each activity. We constructed measures for household, exercise, and total PA. The association between......PURPOSE: Knowledge about lifestyle factors possibly influencing survival after breast cancer (BC) is paramount. We examined associations between two types of postdiagnosis physical activity (PA) and overall survival after BC. PATIENTS AND METHODS: We used prospective data on 959 BC survivors from...... from all causes during the study period. In adjusted analyses, exercise PA above eight MET h/week compared to lower levels of activity was significantly associated with improved overall survival (HR, 0.68; confidence interval [CI]: 0.47-0.99). When comparing participation in exercise to non...

  9. Collagen Promotes Higher Adhesion, Survival and Proliferation of Mesenchymal Stem Cells.

    Directory of Open Access Journals (Sweden)

    Chinnapaka Somaiah

    Full Text Available Mesenchymal stem cells (MSC can differentiate into several cell types and are desirable candidates for cell therapy and tissue engineering. However, due to poor cell survival, proliferation and differentiation in the patient, the therapy outcomes have not been satisfactory. Although several studies have been done to understand the conditions that promote proliferation, differentiation and migration of MSC in vitro and in vivo, still there is no clear understanding on the effect of non-cellular bio molecules. Of the many factors that influence the cell behavior, the immediate cell microenvironment plays a major role. In this context, we studied the effect of extracellular matrix (ECM proteins in controlling cell survival, proliferation, migration and directed MSC differentiation. We found that collagen promoted cell proliferation, cell survival under stress and promoted high cell adhesion to the cell culture surface. Increased osteogenic differentiation accompanied by high active RHOA (Ras homology gene family member A levels was exhibited by MSC cultured on collagen. In conclusion, our study shows that collagen will be a suitable matrix for large scale production of MSC with high survival rate and to obtain high osteogenic differentiation for therapy.

  10. Weight, physical activity and breast cancer survival.

    Science.gov (United States)

    McTiernan, Anne

    2018-02-26

    Weight, weight change and physical activity may affect prognosis among women who are diagnosed with breast cancer. Observational studies show associations between overweight/obesity and weight gain with several measures of reduced prognosis in women with breast cancer, and some suggestions of lower survival in women who are underweight or who experience unexplained weight loss after diagnosis. Observational studies have also shown an association between higher levels of physical activity and reduced breast cancer-specific and all-cause mortality, although a dose-response relationship has not been established. The effects of purposive dietary weight loss and increase in physical activity on survival or recurrence in breast cancer are not yet established, and randomised controlled trials are needed for definitive data. This paper presents the epidemiologic evidence on weight status, weight change, and physical activity and breast cancer survival; suggests potential mediating mechanisms; summarises evidence on weight loss interventions in breast cancer survivors; describes ongoing randomised clinical trials designed to test the effects of weight loss or physical activity on breast cancer survival; and provides information on available guidelines on weight and physical activity for cancer survivors.

  11. Nurse-like cells promote CLL survival through LFA-3/CD2 interactions.

    Science.gov (United States)

    Boissard, Frédéric; Tosolini, Marie; Ligat, Laetitia; Quillet-Mary, Anne; Lopez, Frederic; Fournié, Jean-Jacques; Ysebaert, Loic; Poupot, Mary

    2017-08-08

    In the tumoral micro-environment (TME) of chronic lymphocytic leukemia (CLL), nurse-like cells (NLC) are tumor-associated macrophages which play a critical role in the survival and chemoresistance of tumoral cells. This pro-survival activity is known to involve soluble factors, but few data are available on the relative role of cells cross-talk. Here, we used a transcriptome-based approach to systematically investigate the expression of various receptor/ligand pairs at the surface of NLC/CLL cells. Their relative contribution to CLL survival was assessed both by fluorescent microscopy to identify cellular interactions and by the use of functional tests to measure the impact of uncoupling these pairs with blocking monoclonal antibodies. We found for the first time that lymphocyte function-associated antigen 3 (LFA-3), expressed in CLL at significantly higher levels than in healthy donor B-cells, and CD2 expressed on NLC, were both key for the specific pro-survival signals delivered by NLC. Moreover, we found that NLC/CLL interactions induced the shedding of soluble LFA-3. Importantly, in an exploratory cohort of 60 CLL patients receiving frontline immunochemotherapy, increased levels of soluble LFA-3 were found to correlate with shorter overall survival. Altogether, these data suggest that LFA-3/CD2 interactions promote the survival of CLL cells in the tumor microenvironment.

  12. Acute Sleep Deprivation Enhances Post-Infection Sleep and Promotes Survival during Bacterial Infection in Drosophila

    Science.gov (United States)

    Kuo, Tzu-Hsing; Williams, Julie A.

    2014-01-01

    Study Objectives: Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Setting: Laboratory. Participants: Drosophila melanogaster. Methods and Results: Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Conclusions: Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection. Citation: Kuo TH, Williams JA. Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila. SLEEP 2014;37(5):859-869. PMID:24790264

  13. Blocking LINGO-1 function promotes retinal ganglion cell survival following ocular hypertension and optic nerve transection.

    Science.gov (United States)

    Fu, Qing-Ling; Hu, Bing; Wu, Wutian; Pepinsky, R Blake; Mi, Sha; So, Kwok-Fai

    2008-03-01

    LINGO-1 is a functional member of the Nogo66 receptor (NgR1)/p75 and NgR1/TROY signaling complexes that prevent axonal regeneration through RhoA in the central nervous system. LINGO-1 also promotes cell death after neuronal injury and spinal cord injury. The authors sought to examine whether blocking LINGO-1 function with LINGO-1 antagonists promotes retinal ganglion cell (RGC) survival after ocular hypertension and optic nerve transection. An experimental ocular hypertension model was induced in adult rats using an argon laser to photocoagulate the episcleral and limbal veins. LINGO-1 expression in the retinas was investigated using immunohistochemistry and Western blotting. Soluble LINGO-1 protein (LINGO-1-Fc) and anti-LINGO-1 mAb 1A7 were injected into the vitreous body to examine their effects on RGC survival after ocular hypertension and optic nerve transection. Signal transduction pathways mediating neuroprotective LINGO-1-Fc effects were characterized using Western blotting and specific kinase inhibitors. LINGO-1 was expressed in RGCs and up-regulated after intraocular pressure elevation. Blocking LINGO-1 function with LINGO-1 antagonists, LINGO-1-Fc and 1A7 significantly reduced RGC loss 2 and 4 weeks after ocular hypertension and also promoted RGC survival after optic nerve transection. LINGO-1-Fc treatment blocked the RhoA, JNK pathway and promoted Akt activation. LINGO-1-Fc induced Akt phosphorylation, and the survival effect of LINGO-1 antagonists was abolished by Akt phosphorylation inhibitor. The authors demonstrated that blocking LINGO-1 function with LINGO-1 antagonists rescues RGCs from cell death after ocular hypertension and optic nerve transection. They also delineated the RhoA and PI-3K/Akt pathways as the predominant mediator of LINGO-1-Fc neuroprotection in this paradigm of RGC death.

  14. Early survival factor deprivation in the olfactory epithelium enhances activity-dependent survival

    Directory of Open Access Journals (Sweden)

    Adrien eFrançois

    2013-12-01

    Full Text Available The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs. However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226. We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population towards detection of environmental odorants.

  15. Early survival factor deprivation in the olfactory epithelium enhances activity-driven survival

    Science.gov (United States)

    François, Adrien; Laziz, Iman; Rimbaud, Stéphanie; Grebert, Denise; Durieux, Didier; Pajot-Augy, Edith; Meunier, Nicolas

    2013-01-01

    The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs). However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226). We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population toward detection of environmental odorants. PMID:24399931

  16. International energy-promotion-activities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    Comprehensive promotion of energy and environmental measures are demanded in order to realize improvement in energy demand/supply structures in developing countries where increase in energy demand is anticipated. To achieve this goal, technical transfer related to energy saving technologies and clean coal as well as international energy promotion activities are implemented in China and Indonesia since fiscal 1993. In the field of energy saving, model operations are performed to improve efficiency in such energy consuming fields as steel making, power generation, and oil refining, in addition to cooperation in structuring databases and establishing master plans. In the clean coal field, model operations are conducted to reduce environmental load in coal utilizing areas, in addition to cooperation in establishing master plans for coal utilization. This paper describes feasibility studies on environmentally harmonious coal utilization systems in developing countries, assistance to introduction thereof, and joint verification operations. To rationalize international energy usage, basic surveys on energy utilization efficiency improvement and model operations are carried out mainly in the Asia-Pacific countries.

  17. Niche-derived laminin-511 promotes midbrain dopaminergic neuron survival and differentiation through YAP.

    Science.gov (United States)

    Zhang, Dawei; Yang, Shanzheng; Toledo, Enrique M; Gyllborg, Daniel; Saltó, Carmen; Carlos Villaescusa, J; Arenas, Ernest

    2017-08-22

    Parkinson's disease (PD) is a neurodegenerative disorder in which the loss of dopaminergic neurons in the midbrain (mDA neurons) causes progressive loss of motor control and function. Using embryonic and mDA neurons, midbrain tissue from mice, and differentiated human neural stem cells, we investigated the mechanisms controlling the survival of mDA neurons. We found that the extracellular matrix protein laminin-511 (LM511) promoted the survival and differentiation of mDA neurons. LM511 bound to integrin α3β1 and activated the transcriptional cofactor YAP. LM511-YAP signaling enhanced cell survival by inducing the expression of the microRNA miR-130a, which suppressed the synthesis of the cell death-associated protein PTEN. In addition, LM511-YAP signaling increased the expression of transcription factors critical for mDA identity, such as LMX1A and PITX3, and prevented the loss of mDA neurons in response to oxidative stress, a finding that warrants further investigation to assess therapeutic potential for PD patients. We propose that by enhancing LM511-YAP signaling, it may be possible to prevent mDA neuron degeneration in PD or enhance the survival of mDA neurons in cell replacement therapies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  18. Geothermal activity helps life survive glacial cycles.

    Science.gov (United States)

    Fraser, Ceridwen I; Terauds, Aleks; Smellie, John; Convey, Peter; Chown, Steven L

    2014-04-15

    Climate change has played a critical role in the evolution and structure of Earth's biodiversity. Geothermal activity, which can maintain ice-free terrain in glaciated regions, provides a tantalizing solution to the question of how diverse life can survive glaciations. No comprehensive assessment of this "geothermal glacial refugia" hypothesis has yet been undertaken, but Antarctica provides a unique setting for doing so. The continent has experienced repeated glaciations that most models indicate blanketed the continent in ice, yet many Antarctic species appear to have evolved in almost total isolation for millions of years, and hence must have persisted in situ throughout. How could terrestrial species have survived extreme glaciation events on the continent? Under a hypothesis of geothermal glacial refugia and subsequent recolonization of nongeothermal regions, we would expect to find greater contemporary diversity close to geothermal sites than in nongeothermal regions, and significant nestedness by distance of this diversity. We used spatial modeling approaches and the most comprehensive, validated terrestrial biodiversity dataset yet created for Antarctica to assess spatial patterns of diversity on the continent. Models clearly support our hypothesis, indicating that geothermally active regions have played a key role in structuring biodiversity patterns in Antarctica. These results provide critical insights into the evolutionary importance of geothermal refugia and the history of Antarctic species.

  19. Geothermal activity helps life survive glacial cycles

    Science.gov (United States)

    Fraser, Ceridwen I.; Terauds, Aleks; Smellie, John; Convey, Peter; Chown, Steven L.

    2014-01-01

    Climate change has played a critical role in the evolution and structure of Earth’s biodiversity. Geothermal activity, which can maintain ice-free terrain in glaciated regions, provides a tantalizing solution to the question of how diverse life can survive glaciations. No comprehensive assessment of this “geothermal glacial refugia” hypothesis has yet been undertaken, but Antarctica provides a unique setting for doing so. The continent has experienced repeated glaciations that most models indicate blanketed the continent in ice, yet many Antarctic species appear to have evolved in almost total isolation for millions of years, and hence must have persisted in situ throughout. How could terrestrial species have survived extreme glaciation events on the continent? Under a hypothesis of geothermal glacial refugia and subsequent recolonization of nongeothermal regions, we would expect to find greater contemporary diversity close to geothermal sites than in nongeothermal regions, and significant nestedness by distance of this diversity. We used spatial modeling approaches and the most comprehensive, validated terrestrial biodiversity dataset yet created for Antarctica to assess spatial patterns of diversity on the continent. Models clearly support our hypothesis, indicating that geothermally active regions have played a key role in structuring biodiversity patterns in Antarctica. These results provide critical insights into the evolutionary importance of geothermal refugia and the history of Antarctic species. PMID:24616489

  20. PKC-η-MARCKS Signaling Promotes Intracellular Survival of Unopsonized Burkholderia thailandensis

    Directory of Open Access Journals (Sweden)

    Sofiya N. Micheva-Viteva

    2017-06-01

    Full Text Available Pathogenic Burkholderia rely on host factors for efficient intracellular replication and are highly refractory to antibiotic treatment. To identify host genes that are required by Burkholderia spp. during infection, we performed a RNA interference (RNAi screen of the human kinome and identified 35 host kinases that facilitated Burkholderia thailandensis intracellular survival in human monocytic THP-1 cells. We validated a selection of host kinases using imaging flow cytometry to assess efficiency of B. thailandensis survival in the host upon siRNA-mediated knockdown. We focused on the role of the novel protein kinase C isoform, PKC-η, in Burkholderia infection and characterized PKC-η/MARCKS signaling as a key event that promotes the survival of unopsonized B. thailandensis CDC2721121 within host cells. While infection of lung epithelial cells with unopsonized Gram-negative bacteria stimulated phosphorylation of Ser175/160 in the MARCKS effector domain, siRNA-mediated knockdown of PKC-η expression reduced the levels of phosphorylated MARCKS by >3-fold in response to infection with Bt CDC2721121. We compared the effect of the conventional PKC-α and novel PKC-η isoforms on the growth of B. thailandensis CDC2721121 within monocytic THP-1 cells and found that ≥75% knock-down of PRKCH transcript levels reduced intracellular bacterial load 100% more efficiently when compared to growth in cells siRNA-depleted of the classical PKC-α, suggesting that the PKC-η isoform can specifically mediate Burkholderia intracellular survival. Based on imaging studies of intracellular B. thailandensis, we found that PKC-η function stimulates phagocytic pathways that promote B. thailandensis escape into the cytoplasm leading to activation of autophagosome flux. Identification of host kinases that are targeted by Burkholderia during infection provides valuable molecular insights in understanding Burkholderia pathogenesis, and ultimately, in designing effective

  1. C. elegans AMPKs promote survival and arrest germline development during nutrient stress

    Directory of Open Access Journals (Sweden)

    Masamitsu Fukuyama

    2012-08-01

    Mechanisms controlling development, growth, and metabolism are coordinated in response to changes in environmental conditions, enhancing the likelihood of survival to reproductive maturity. Much remains to be learned about the molecular basis underlying environmental influences on these processes. C. elegans larvae enter a developmentally dormant state called L1 diapause when hatched into nutrient-poor conditions. The nematode pten homologue daf-18 is essential for maintenance of survival and germline stem cell quiescence during this period (Fukuyama et al., 2006; Sigmond et al., 2008, but the details of the signaling network(s in which it functions remain to be elucidated. Here, we report that animals lacking both aak-1 and aak-2, which encode the two catalytic α subunits of AMP-activated protein kinase (AMPK, show reduced viability and failure to maintain mitotic quiescence in germline stem cells during L1 diapause. Furthermore, failure to arrest germline proliferation has a long term consequence; aak double mutants that have experienced L1 diapause develop into sterile adults when returned to food, whereas their continuously fed siblings are fertile. Both aak and daf-18 appear to maintain germline quiescence by inhibiting activity of the common downstream target, TORC1 (TOR Complex 1. In contrast, rescue of the lethality phenotype indicates that aak-2 acts not only in the intestine, as does daf-18, but also in neurons, likely promoting survival by preventing energy deprivation during L1 diapause. These results not only provide evidence that AMPK contributes to survival during L1 diapause in a manner distinct from that by which it controls dauer diapause, but they also suggest that AMPK suppresses TORC1 activity to maintain stem cell quiescence.

  2. An Oncogenic Virus Promotes Cell Survival and Cellular Transformation by Suppressing Glycolysis.

    Directory of Open Access Journals (Sweden)

    Ying Zhu

    2016-05-01

    Full Text Available Aerobic glycolysis is essential for supporting the fast growth of a variety of cancers. However, its role in the survival of cancer cells under stress conditions is unclear. We have previously reported an efficient model of gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV-induced cellular transformation of rat primary mesenchymal stem cells. KSHV-transformed cells efficiently induce tumors in nude mice with pathological features reminiscent of Kaposi's sarcoma tumors. Here, we report that KSHV promotes cell survival and cellular transformation by suppressing aerobic glycolysis and oxidative phosphorylation under nutrient stress. Specifically, KSHV microRNAs and vFLIP suppress glycolysis by activating the NF-κB pathway to downregulate glucose transporters GLUT1 and GLUT3. While overexpression of the transporters rescues the glycolytic activity, it induces apoptosis and reduces colony formation efficiency in softagar under glucose deprivation. Mechanistically, GLUT1 and GLUT3 inhibit constitutive activation of the AKT and NF-κB pro-survival pathways. Strikingly, GLUT1 and GLUT3 are significantly downregulated in KSHV-infected cells in human KS tumors. Furthermore, we have detected reduced levels of aerobic glycolysis in several KSHV-infected primary effusion lymphoma cell lines compared to a Burkitt's lymphoma cell line BJAB, and KSHV infection of BJAB cells reduced aerobic glycolysis. These results reveal a novel mechanism by which an oncogenic virus regulates a key metabolic pathway to adapt to stress in tumor microenvironment, and illustrate the importance of fine-tuning the metabolic pathways for sustaining the proliferation and survival of cancer cells, particularly under stress conditions.

  3. Protein kinase activity of phosphoinositide 3-kinase regulates cytokine-dependent cell survival.

    Directory of Open Access Journals (Sweden)

    Daniel Thomas

    Full Text Available The dual specificity protein/lipid kinase, phosphoinositide 3-kinase (PI3K, promotes growth factor-mediated cell survival and is frequently deregulated in cancer. However, in contrast to canonical lipid-kinase functions, the role of PI3K protein kinase activity in regulating cell survival is unknown. We have employed a novel approach to purify and pharmacologically profile protein kinases from primary human acute myeloid leukemia (AML cells that phosphorylate serine residues in the cytoplasmic portion of cytokine receptors to promote hemopoietic cell survival. We have isolated a kinase activity that is able to directly phosphorylate Ser585 in the cytoplasmic domain of the interleukin 3 (IL-3 and granulocyte macrophage colony stimulating factor (GM-CSF receptors and shown it to be PI3K. Physiological concentrations of cytokine in the picomolar range were sufficient for activating the protein kinase activity of PI3K leading to Ser585 phosphorylation and hemopoietic cell survival but did not activate PI3K lipid kinase signaling or promote proliferation. Blockade of PI3K lipid signaling by expression of the pleckstrin homology of Akt1 had no significant impact on the ability of picomolar concentrations of cytokine to promote hemopoietic cell survival. Furthermore, inducible expression of a mutant form of PI3K that is defective in lipid kinase activity but retains protein kinase activity was able to promote Ser585 phosphorylation and hemopoietic cell survival in the absence of cytokine. Blockade of p110α by RNA interference or multiple independent PI3K inhibitors not only blocked Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also resulted in a block in survival signaling and cell death. Our findings demonstrate a new role for the protein kinase activity of PI3K in phosphorylating the cytoplasmic tail of the GM-CSF and IL-3 receptors to selectively regulate cell survival highlighting the importance of targeting

  4. Functional Screening of Core Promoter Activity.

    Science.gov (United States)

    Even, Dan Y; Kedmi, Adi; Ideses, Diana; Juven-Gershon, Tamar

    2017-01-01

    The core promoter is the DNA sequence that recruits the basal transcription machinery and directs accurate initiation of transcription. It is an active contributor to gene expression that can be rationally designed to manipulate the levels of expression. Core promoter function can be analyzed using different experimental approaches. Here, we describe the qualitative and quantitative analysis of engineered core promoter functions using the EGFP reporter gene that is driven by distinct core promoters. Expression plasmids are transfected into different mammalian cell lines, and the resulting fluorescence is monitored by live cell imaging , as well as by flow cytometry. In order to verify that the transcriptional activity of the examined core promoters is indeed a function of their activity, as opposed to differences in DNA uptake, real-time quantitative PCR analysis is performed. Importantly, the described methodology for functional screening of core promoter activity has enabled the analysis of engineered potent core promoters for extended time periods.

  5. Schwann cell-derived factors support serotoninergic neuron survival and promote neurite outgrowth

    Directory of Open Access Journals (Sweden)

    R Pellitteri

    2009-12-01

    Full Text Available During embryogenesis and the postnatal period, neurons and glia interact in the development and differentiation of specific populations of nerve cells. Both in the peripheral (PNS and in the central nervous system (CNS, glial cells have been shown in various experimental conditions to constitute a favorable substrate for neural adhesion, neural polarity, shape and axonal extension, while numerous soluble molecules secreted by neurons influence the survival and differentiation of the glial cells themselves. The aim of the present work was to investigate the influence of postnatal Schwann cells (SC on embryonic serotoninergic (5-HT neurons of the raphe, in order to study the possible influence of the peripheral glia on the CNS neurons. Cultures of SC from sciatic nerve of postnatal rats and neurons from rat embryonic rhombencephalon were successfully established and cells were immunocytochemically characterized. The number of 5-HT neurons, and the number and length of their branches were quantified in the cultures of 5-HT neurons, in cultures added with Nerve Growth Factor (NGF and Insulin-like Growth Factor I (IGF-I, in co-cultures with SC and in cultures added with conditioned medium obtained from SC cultures. The results indicated that SC have the capacity to promote the survival and growth of 5-HT neurons in culture, and that this activity is mediated by soluble factors. Although the precise nature and mechanism of action of the growth factor or factors produced by SC in the presence of 5-HT neurons was not identified, our results add more data on the possible activity of the peripheral glia in promoting and enhancing the survival and outgrowth of the CNS neurons.

  6. Survival and activity of individual bioaugmentation strains

    DEFF Research Database (Denmark)

    Dueholm, Morten Simonsen; G. Marquesa, Irina; Karst, Søren Michael

    2015-01-01

    Successful application of bioaugmentation for enhanced degradation of environmental pollutants is often limited by the lack of methods to monitor the survival and activity of individual bioaugmentation strains. However, recent advancements in sequencing technologies and molecular techniques now...... allow us to address these limitations. Here a complementing set of general applicable molecular methods are presented that provides detailed information on the performance of individual bioaugmentation strains under in situ conditions. The approach involves genome sequencing to establish highly specific...... qPCR and RT-qPCR tools for cell enumerations and expression of involved genes, stable isotope probing to follow growth on the target compounds and GFP-tagging to visualize the bioaugmentation strains directly in samples, all in combination with removal studies of the target compounds. The concept...

  7. PIAS1-FAK Interaction Promotes the Survival and Progression of Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jerfiz D. Constanzo

    2016-05-01

    Full Text Available The sequence of genomic alterations acquired by cancer cells during tumor progression and metastasis is poorly understood. Focal adhesion kinase (FAK is a non-receptor tyrosine kinase that integrates cytoskeleton remodeling, mitogenic signaling and cell survival. FAK has previously been reported to undergo nuclear localization during cell migration, cell differentiation and apoptosis. However, the mechanism behind FAK nuclear accumulation and its contribution to tumor progression has remained elusive. We report that amplification of FAK and the SUMO E3 ligase PIAS1 gene loci frequently co-occur in non-small cell lung cancer (NSCLC cells, and that both gene products are enriched in a subset of primary NSCLCs. We demonstrate that endogenous FAK and PIAS1 proteins interact in the cytoplasm and the cell nucleus of NSCLC cells. Ectopic expression of PIAS1 promotes proteolytic cleavage of the FAK C-terminus, focal adhesion maturation and FAK nuclear localization. Silencing of PIAS1 deregulates focal adhesion turnover, increases susceptibility to apoptosis in vitro and impairs tumor xenograft formation in vivo. Nuclear FAK in turn stimulates gene transcription favoring DNA repair, cell metabolism and cytoskeleton regulation. Consistently, ablation of FAK by CRISPR/Cas9 editing, results in basal DNA damage, susceptibility to ionizing radiation and impaired oxidative phosphorylation. Our findings provide insight into a mechanism regulating FAK cytoplasm-nuclear distribution and demonstrate that FAK activity in the nucleus promotes NSCLC survival and progression by increasing cell-ECM interaction and DNA repair regulation.

  8. Airway epithelial cells produce neurotrophins and promote the survival of eosinophils during allergic airway inflammation.

    Science.gov (United States)

    Hahn, Christian; Islamian, Ariyan Pirayesh; Renz, Harald; Nockher, Wolfgang Andreas

    2006-04-01

    Eosinophil-epithelial cell interactions make a major contribution to asthmatic airway inflammation. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and other members of the neurotrophin family, originally defined as a class of neuronal growth factors, are now recognized to support the survival and activation of immune cells. Neurotrophin levels are increased in bronchoalveolar lavage fluid during allergic asthma. We sought to investigate the role of neurotrophins as inflammatory mediators in eosinophil-epithelial cell interactions during the allergic immune response. Neurotrophin expression in the lung was investigated by means of immunohistochemistry and ELISA in a mouse model of chronic experimental asthma. Coculture experiments were performed with airway epithelial cells and bronchoalveolar lavage fluid eosinophils. Neurotrophin levels increased continuously during chronic allergic airway inflammation, and airway epithelial cells were the major source of NGF and BDNF within the inflamed lung. Epithelial neurotrophin production was upregulated by IL-1beta, TNF-alpha, and T(H)2 cytokines. Lung eosinophils expressed the BDNF and NGF receptors tropomyosin-related kinase (Trk) A and TrkB, and coculture with airway epithelial cells resulted in enhanced epithelial neurotrophin production, as well as in prolonged survival of eosinophils. Eosinophil survival was completely abolished in the presence of the neurotrophin receptor Trk antagonist K252a. During allergic inflammation, airway epithelial cells express increased amounts of NGF and BDNF that promote the survival of tissue eosinophils. Controlling epithelial neurotrophin production might be an important therapeutic target to prevent allergic airway eosinophilia. Attenuating the release of inflammatory mediators from the activated airway epithelium will become an important strategy to disrupt the pathogenesis of chronic allergic asthma.

  9. Extrusions are phagocytosed and promote Chlamydia survival within macrophages.

    Science.gov (United States)

    Zuck, Meghan; Ellis, Tisha; Venida, Anthony; Hybiske, Kevin

    2017-04-01

    The precise strategies that intracellular pathogens use to exit host cells have a direct impact on their ability to disseminate within a host, transmit to new hosts, and engage or avoid immune responses. The obligate intracellular bacterium Chlamydia trachomatis exits the host cell by two distinct exit strategies, lysis and extrusion. The defining characteristics of extrusions, and advantages gained by Chlamydia within this unique double-membrane structure, are not well understood. Here, we define extrusions as being largely devoid of host organelles, comprised mostly of Chlamydia elementary bodies, and containing phosphatidylserine on the outer surface of the extrusion membrane. Extrusions also served as transient, intracellular-like niches for enhanced Chlamydia survival outside the host cell. In addition to enhanced extracellular survival, we report the key discovery that chlamydial extrusions are phagocytosed by primary bone marrow-derived macrophages, after which they provide a protective microenvironment for Chlamydia. Extrusion-derived Chlamydia staved off macrophage-based killing and culminated in the release of infectious elementary bodies from the macrophage. Based on these findings, we propose a model in which C. trachomatis extrusions serve as "trojan horses" for bacteria, by exploiting macrophages as vehicles for dissemination, immune evasion, and potentially transmission. © 2016 John Wiley & Sons Ltd.

  10. Synthetic Platelets: Intravenous Infusible Nanoparticles to Promote Hemostasis and Survival Following Liver Injury in Swine

    Science.gov (United States)

    2014-08-12

    CONTRACT NUMBER: N62645-12-C-4055 TITLE: Synthetic platelets: Intravenous infusible nanoparticles to promote hemostasis and survival following...SUBTITLE Sa • CONTRACT NOM BER N62645-l2-C-4055 Synthetic Platelets: Intravenous infusible nanoparticles Sb. GRANT NUMBER to promote hemostasis and...one could stop bleeding without triggering complications. 15. SUBJECT TERMS blood loss, hemostasis , internal bleeding, nanomedicine 16. SECURITY

  11. Survival and activity of individual bioaugmentation strains.

    Science.gov (United States)

    Dueholm, Morten S; Marques, Irina G; Karst, Søren M; D'Imperio, Seth; Tale, Vaibhav P; Lewis, Derrick; Nielsen, Per Halkjær; Nielsen, Jeppe Lund

    2015-06-01

    Successful application of bioaugmentation for enhanced degradation of environmental pollutants is often limited by the lack of methods to monitor the survival and activity of individual bioaugmentation strains. However, recent advancements in sequencing technologies and molecular techniques now allow us to address these limitations. Here a complementing set of general applicable molecular methods are presented that provides detailed information on the performance of individual bioaugmentation strains under in situ conditions. The approach involves genome sequencing to establish highly specific qPCR and RT-qPCR tools for cell enumerations and expression of involved genes, stable isotope probing to follow growth on the target compounds and GFP-tagging to visualize the bioaugmentation strains directly in samples, all in combination with removal studies of the target compounds. The concept of the approach is demonstrated through a case study involving degradation of aromatic hydrocarbons in activated sludge augmented with the bioaugmentation strain Pseudomonas monteilii SB3078. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Internal dental school environmental factors promoting faculty survival and success.

    Science.gov (United States)

    Masella, Richard S

    2005-04-01

    A career in dental academics offers ample rewards and challenges. To promote successful careers in dental education, prospective and new dental faculty should possess a realistic view of the dental school work environment, akin to the informed consent so valuable to patients and doctors. Self-assessment of personal strengths and weaknesses provides helpful information in matching faculty applicants with appropriate dental schools. Essential prehiring information also includes a written job description detailing duties and responsibilities, professional development opportunities, and job performance evaluation protocol. Prehiring awareness of what constitutes excellence in job performance will aid new faculty in allotting time to productive venues. New faculty should not rely solely on professional expertise to advance careers. Research and regular peer-reviewed publications are necessary elements in academic career success, along with the ability to secure governmental, private foundation, and corporate grant support. Tactful self-promotion and self-definition to the dental school community are faculty responsibilities, along with substantial peer collaboration. The recruitment period is a singular opportunity to secure job benefits and privileges. It is also the time to gain knowledge of institutional culture and assess administrative and faculty willingness to collaborate on teaching, research, professional development, and attainment of change. Powerful people within dental schools and parent institutions may influence faculty careers and should be identified and carefully treated. The time may come to leave one's position for employment at a different dental school or to step down from full-time academics. Nonetheless, the world of dental and health professional education in 2005 is rapidly expanding and offers unlimited opportunities to dedicated, talented, and informed educators.

  13. CX3CR1-dependent renal macrophage survival promotes Candida control and host survival

    Science.gov (United States)

    Lionakis, Michail S.; Swamydas, Muthulekha; Fischer, Brett G.; Plantinga, Theo S.; Johnson, Melissa D.; Jaeger, Martin; Green, Nathaniel M.; Masedunskas, Andrius; Weigert, Roberto; Mikelis, Constantinos; Wan, Wuzhou; Lee, Chyi-Chia Richard; Lim, Jean K.; Rivollier, Aymeric; Yang, John C.; Laird, Greg M.; Wheeler, Robert T.; Alexander, Barbara D.; Perfect, John R.; Gao, Ji-Liang; Kullberg, Bart-Jan; Netea, Mihai G.; Murphy, Philip M.

    2013-01-01

    Systemic Candida albicans infection causes high morbidity and mortality and is associated with neutropenia; however, the roles of other innate immune cells in pathogenesis are poorly defined. Here, using a mouse model of systemic candidiasis, we found that resident macrophages accumulated in the kidney, the main target organ of infection, and formed direct contacts with the fungus in vivo mainly within the first few hours after infection. Macrophage accumulation and contact with Candida were both markedly reduced in mice lacking chemokine receptor CX3CR1, which was found almost exclusively on resident macrophages in uninfected kidneys. Infected Cx3cr1–/– mice uniformly succumbed to Candida-induced renal failure, but exhibited clearance of the fungus in all other organs tested. Renal macrophage deficiency in infected Cx3cr1–/– mice was due to reduced macrophage survival, not impaired proliferation, trafficking, or differentiation. In humans, the dysfunctional CX3CR1 allele CX3CR1-M280 was associated with increased risk of systemic candidiasis. Together, these data indicate that CX3CR1-mediated renal resident macrophage survival is a critical innate mechanism of early fungal control that influences host survival in systemic candidiasis. PMID:24177428

  14. Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission.

    Science.gov (United States)

    Rao, Sheila; Schieber, Alexandria M Palaferri; O'Connor, Carolyn P; Leblanc, Mathias; Michel, Daniela; Ayres, Janelle S

    2017-01-26

    Sickness-induced anorexia is a conserved behavior induced during infections. Here, we report that an intestinal pathogen, Salmonella Typhimurium, inhibits anorexia by manipulating the gut-brain axis. Inhibition of inflammasome activation by the S. Typhimurium effector, SlrP, prevented anorexia caused by IL-1β-mediated signaling to the hypothalamus via the vagus nerve. Rather than compromising host defenses, pathogen-mediated inhibition of anorexia increased host survival. SlrP-mediated inhibition of anorexia prevented invasion and systemic infection by wild-type S. Typhimurium, reducing virulence while increasing transmission to new hosts, suggesting that there are trade-offs between transmission and virulence. These results clarify the complex and contextual role of anorexia in host-pathogen interactions and suggest that microbes have evolved mechanisms to modulate sickness-induced behaviors to promote health of their host and their transmission at the expense of virulence. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. ANCA-stimulated neutrophils release BLyS and promote B cell survival: a clinically relevant cellular process.

    Science.gov (United States)

    Holden, N J; Williams, J M; Morgan, M D; Challa, A; Gordon, J; Pepper, R J; Salama, A D; Harper, L; Savage, C O S

    2011-12-01

    To determine a role for antineutrophil cytoplasmic antibody (ANCA)-activated neutrophils in promoting B cell survival through the release of B lymphocyte stimulator (BLyS). Neutrophil BLyS expression was measured by flow cytometry. Concentrations of BLyS in cell supernatants and donor serum samples were measured by ELISA. Cell survival assays were carried out using an L3055 cell line and viability measured by flow cytometry. Tumour necrosis factor α and formyl-Met-Leu-Phe (fMLP) treatment of non-primed neutrophils and treatment of primed neutrophils with anti-PR3 ANCA IgG resulted in a significant increase in surface expression of BLyS within 30 min which returned to basal levels by 2 h. Supernatants from ANCA-stimulated neutrophils were shown to contain increased levels of BLyS and to promote the survival of the centroblast cell line L3055. Serum BLyS concentrations are increased in patients with active ANCA-associated systemic vasculitis and these levels are increased further following 1-3 months of treatment with rituximab. ANCA specifically causes the release of BLyS from activated neutrophils which can support B cell survival in vitro. The presence of serum BLyS in active disease and its increase following B cell depletion suggest it is an important factor in disease pathogenesis and may facilitate disease relapse.

  16. Ribosome hibernation factor promotes Staphylococcal survival and differentially represses translation.

    Science.gov (United States)

    Basu, Arnab; Yap, Mee-Ngan F

    2016-06-02

    In opportunistic Gram-positive Staphylococcus aureus, a small protein called hibernation-promoting factor (HPFSa) is sufficient to dimerize 2.5-MDa 70S ribosomes into a translationally inactive 100S complex. Although the 100S dimer is observed in only the stationary phase in Gram-negative gammaproteobacteria, it is ubiquitous throughout all growth phases in S. aureus The biological significance of the 100S ribosome is poorly understood. Here, we reveal an important role of HPFSa in preserving ribosome integrity and poising cells for translational restart, a process that has significant clinical implications for relapsed staphylococcal infections. We found that the hpf null strain is severely impaired in long-term viability concomitant with a dramatic loss of intact ribosomes. Genome-wide ribosome profiling shows that eliminating HPFSa drastically increased ribosome occupancy at the 5' end of specific mRNAs under nutrient-limited conditions, suggesting that HPFSa may suppress translation initiation. The protective function of HPFSa on ribosomes resides at the N-terminal conserved basic residues and the extended C-terminal segment, which are critical for dimerization and ribosome binding, respectively. These data provide significant insight into the functional consequences of 100S ribosome loss for protein synthesis and stress adaptation. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Shock Wave Therapy Promotes Cardiomyocyte Autophagy and Survival during Hypoxia

    Directory of Open Access Journals (Sweden)

    Ling Du

    2017-06-01

    Full Text Available Background: Autophagy plays an important role in cardiovascular disease. Controversy still exists regarding the effect of autophagy on ischemic/hypoxic myocardium. Cardiac shock wave therapy (CSWT is an effective alternative treatment for refractory ischemic heart disease. Whether CSWT can regulate cardiomyocyte autophagy under hypoxic conditions is not clear. We established a myocardial hypoxia model using the H9c2 cell line and performed shock waves (SWs treatment to evaluate the effect of SW on autophagy. Methods: The H9c2 cells were incubated under hypoxic conditions, and SW treatment was then performed at energies of 0.02, 0.05, or 0.10 mJ/mm2. The cell viability and intracellular ATP level were examined. Western blot analysis was used to assess the expression of LC3B, AMPK, mTOR, Beclin-1, Sirt1, and HIF-1α. Autophagic vacuoles were visualized by monodansylcadaverine staining. Results: After the 24-hour hypoxic period, cardiomyocyte viability and ATP levels were decreased and autophagy was significantly increased in H9c2 cells. SW treatment with an energy of 0.05 mJ/mm2 significantly increased the cellular viability, ATP level, LC3B-II/I, and number of autophagic vacuoles. In addition, phosphorylated AMPK and Sirt1 were increased and phosphorylated mTOR and HIF-1α were decreased after SW treatment. Conclusion: SW treatment can potentially promote cardiomyocyte autophagy during hypoxia and protect cardiomyocyte function by regulating the AMPK/mTOR pathway.

  18. Promotional activities of banks in Serbia

    Directory of Open Access Journals (Sweden)

    Zelenović Vera

    2008-01-01

    Full Text Available The paper is focused on banking sector in Serbia, particulary on promotional activities of banks in public and on media. The authors of paper tried to find cause and effect relationship between business success and working quality on the one hand and investment in promotion activities of bank on the other hand, like important instrument of bank's business policy realization. Promotional activities appear like successful instrument in order to increase satisfaction of the bank's clients, which effect the increase of successfulness of banks' business.

  19. Therapeutic Mechanisms for Cannabinoid-Promoted Survival of Oligodendrocytes

    Science.gov (United States)

    2013-06-21

    to mammals and it can also be found in birds, amphibians, fish, sea urchins , mollusks and leeches, among others (77). In mammals, CB I receptors...CNS, these cells are constantly scanning for foreign pathogens. In case of injury or disease these cells become activated and change their morphology ...ramified morphology to a phagocytosis-capable, "macrophage-like" phenotype (165; 213). Although the initial response of microglia to injury is to

  20. THE PROMOTIONAL ACTIVITY IN THE TOURISTIC SECTOR

    Directory of Open Access Journals (Sweden)

    Costel Iliuta Negricea

    2008-05-01

    Full Text Available The promotion as one of the components of the marketing mix, laying stress, în this regard,on its role în the deployment of the tourism companies’ activity, the structure of the promotional activity în thetouristic sector as well as the use of the promotional strategies în the attainment of the development targets ofthe tourism companies.So, în the paper there have been mentioned the three levels at which it is made the touristic promotionîn Romania, respectively nationally, by the Ministry of the Tourism, under whose subordination it is theTourism National Authority, the second level is the regional/local one, concerning the activity carried out bythe Centers/Offices of Touristic Information from a series of localities, and the last level refers to the microone, respectively at the level of the tourism companies, which promote their offer individually (the most often.The important role of the promotion în the deployment of the activity of the tourism companies isbeing highlighted by the fact that this makes the connection between the activity of an organization and itscustomers (effective or potential, and, în the touristic field, the content of the promotional activity is stronglystressed by the features of this type of services and of the system of creation and delivery, as well as of thepurchasing behaviour.

  1. Public relations as promotional activity

    Directory of Open Access Journals (Sweden)

    Dr.Sc. Almira Curri-Mehmeti

    2011-12-01

    Full Text Available Public relations give opportunity to the organization to present its image and personality to its own “public”- users, supporters, sponsors, donors, local community and other public. It is about transferring the message to the public, but that is a two-way street. You must communicate with your public, but at the same time you must give opportunity to the public to communicate easier with you. The real public relations include dialog – you should listen to the others, to see things through their perspective. This elaborate is made with the purpose to be useful for every organization, not for the sensa-tional promotion of its achievements, but to become more critical towards its work. Seeing the organization in the way that the other see it, you can become better and sure that you are giving to your users the best service possible.

  2. Public Relations as Promotional Activity

    Directory of Open Access Journals (Sweden)

    Almira CURRI-MEMETI

    2011-11-01

    Full Text Available Public relations give opportunity to the organization to present its image and personality to its own “public”- users, supporters, sponsors, donors, local community and other public.It is about transferring the message to the public, but that is a twoway street. You must communicate with your public, but at the same time you must give opportunity to the public to communicate easier with you. The real public relations include dialog – you should listen to the others, to see things through their perspective. This elaborate is made with the purpose to be useful for every organization, not for the sensational promotion of its achievements, but to become more critical towards its work. Seeing the organization in the way that the other see it, you can become better and sure that you are giving to your users the best service possible.

  3. Helicobacter pylori VacA toxin promotes bacterial intracellular survival in gastric epithelial cells.

    Science.gov (United States)

    Terebiznik, M R; Vazquez, C L; Torbicki, K; Banks, D; Wang, T; Hong, W; Blanke, S R; Colombo, M I; Jones, N L

    2006-12-01

    Helicobacter pylori colonizes the gastric epithelium of at least 50% of the world's human population, playing a causative role in the development of chronic gastritis, peptic ulcers, and gastric adenocarcinoma. Current evidence indicates that H. pylori can invade epithelial cells in the gastric mucosa. However, relatively little is known about the biology of H. pylori invasion and survival in host cells. Here, we analyze both the nature of and the mechanisms responsible for the formation of H. pylori's intracellular niche. We show that in AGS cells infected with H. pylori, bacterium-containing vacuoles originate through the fusion of late endocytic organelles. This process is mediated by the VacA-dependent retention of the small GTPase Rab7. In addition, functional interactions between Rab7 and its downstream effector, Rab-interacting lysosomal protein (RILP), are necessary for the formation of the bacterial compartment since expression of mutant forms of RILP or Rab7 that fail to bind each other impaired the formation of this unique bacterial niche. Moreover, the VacA-mediated sequestration of active Rab7 disrupts the full maturation of vacuoles as assessed by the lack of both colocalization with cathepsin D and degradation of internalized cargo in the H. pylori-containing vacuole. Based on these findings, we propose that the VacA-dependent isolation of the H. pylori-containing vacuole from bactericidal components of the lysosomal pathway promotes bacterial survival and contributes to the persistence of infection.

  4. PIAS1-FAK Interaction Promotes the Survival and Progression of Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Constanzo, Jerfiz D; Tang, Ke-Jing; Rindhe, Smita; Melegari, Margherita; Liu, Hui; Tang, Ximing; Rodriguez-Canales, Jaime; Wistuba, Ignacio; Scaglioni, Pier Paolo

    2016-05-01

    The sequence of genomic alterations acquired by cancer cells during tumor progression and metastasis is poorly understood. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that integrates cytoskeleton remodeling, mitogenic signaling and cell survival. FAK has previously been reported to undergo nuclear localization during cell migration, cell differentiation and apoptosis. However, the mechanism behind FAK nuclear accumulation and its contribution to tumor progression has remained elusive. We report that amplification of FAK and the SUMO E3 ligase PIAS1 gene loci frequently co-occur in non-small cell lung cancer (NSCLC) cells, and that both gene products are enriched in a subset of primary NSCLCs. We demonstrate that endogenous FAK and PIAS1 proteins interact in the cytoplasm and the cell nucleus of NSCLC cells. Ectopic expression of PIAS1 promotes proteolytic cleavage of the FAK C-terminus, focal adhesion maturation and FAK nuclear localization. Silencing of PIAS1 deregulates focal adhesion turnover, increases susceptibility to apoptosis in vitro and impairs tumor xenograft formation in vivo. Nuclear FAK in turn stimulates gene transcription favoring DNA repair, cell metabolism and cytoskeleton regulation. Consistently, ablation of FAK by CRISPR/Cas9 editing, results in basal DNA damage, susceptibility to ionizing radiation and impaired oxidative phosphorylation. Our findings provide insight into a mechanism regulating FAK cytoplasm-nuclear distribution and demonstrate that FAK activity in the nucleus promotes NSCLC survival and progression by increasing cell-ECM interaction and DNA repair regulation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Promoting Active Lifestyles--A Multidisciplinary Approach.

    Science.gov (United States)

    Jordan, Deb; And Others

    1993-01-01

    Presents a series of articles that address the theme of promoting active lifestyles through education. Some topics are facilities and equipment, how fear plays a part in limiting participation in physical activity, working with disabled as well as aging persons, the use of water activities, and instructor accountability. (GLR)

  6. Promoting physical activity in socially vulnerable groups

    NARCIS (Netherlands)

    Herens, M.C.

    2016-01-01

    Background:  In the Netherlands, inequalities in physical activity behaviour go hand in hand with socioeconomic inequalities in health. To promote physical activity effectively and equitably, participatory community-based physical activity interventions seem promising and are

  7. N-methyl-D-aspartate promotes the survival of cerebellar granule cells in culture

    DEFF Research Database (Denmark)

    Balázs, R; Jørgensen, Ole Steen; Hack, N

    1988-01-01

    Our previous studies on the survival-promoting influence of elevated concentrations of extracellular K+ ([K+]e) on cultured cerebellar granule cells led to the proposal that depolarization in vitro mimics the effect of the earliest afferent inputs received by the granule cells in vivo. This, in t...

  8. N-methyl-D-aspartate promotes the survival of cerebellar granule cells: pharmacological characterization

    DEFF Research Database (Denmark)

    Balázs, R; Hack, N; Jørgensen, Ole Steen

    1989-01-01

    The survival of cerebellar granule cells in culture is promoted by chronic exposure to N-methyl-D-aspartate (NMDA). The effect is due to the stimulation of 'conventional' NMDA receptor-ionophore complex: it is concentration dependent, voltage dependent and blocked by the selective antagonists D-2...

  9. MicroRNA-22 promotes cell survival upon UV radiation by repressing PTEN

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Guangyun [Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN (United States); Center for Adult Cancer Research, University of Tennessee Health Science Center, Memphis, TN (United States); Jilin Province Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun (China); Shi, Yuling [Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN (United States); Center for Adult Cancer Research, University of Tennessee Health Science Center, Memphis, TN (United States); Wu, Zhao-Hui, E-mail: zwu6@uthsc.edu [Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN (United States); Center for Adult Cancer Research, University of Tennessee Health Science Center, Memphis, TN (United States)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer miR-22 is induced in cells treated with UV radiation. Black-Right-Pointing-Pointer ATM is required for miR-22 induction in response to UV. Black-Right-Pointing-Pointer miR-22 targets 3 Prime -UTR of PTEN to repress its expression in UV-treated cells. Black-Right-Pointing-Pointer Upregulated miR-22 inhibits apoptosis in cells exposed to UV. -- Abstract: DNA damage response upon UV radiation involves a complex network of cellular events required for maintaining the homeostasis and restoring genomic stability of the cells. As a new class of players involved in DNA damage response, the regulation and function of microRNAs in response to UV remain poorly understood. Here we show that UV radiation induces a significant increase of miR-22 expression, which appears to be dependent on the activation of DNA damage responding kinase ATM (ataxia telangiectasia mutated). Increased miR-22 expression may result from enhanced miR-22 maturation in cells exposed to UV. We further found that tumor suppressor gene phosphatase and tensin homolog (PTEN) expression was inversely correlated with miR-22 induction and UV-induced PTEN repression was attenuated by overexpression of a miR-22 inhibitor. Moreover, increased miR-22 expression significantly inhibited the activation of caspase signaling cascade, leading to enhanced cell survival upon UV radiation. Collectively, these results indicate that miR-22 is an important player in the cellular stress response upon UV radiation, which may promote cell survival via the repression of PTEN expression.

  10. Physical activity and health promotion strategies among ...

    African Journals Online (AJOL)

    Background: Physical inactivity has become a global health concern and is among the 10 leading causes of death and disability. Physiotherapists are in a position to combat inactivity and effectively promote physical activity to their clients. Objectives: To establish the relationship between physical activity levels of ...

  11. Physical activity and health promotion strategies among ...

    African Journals Online (AJOL)

    EB

    Abstract. Background: Physical inactivity has become a global health concern and is among the 10 leading causes of death and disability. Physiotherapists are in a position to combat inactivity and effectively promote physical activity to their clients. Objectives: To establish the relationship between physical activity levels of ...

  12. Evaluation of Results from Sales Promotion Activities

    Directory of Open Access Journals (Sweden)

    Olimpia Ban

    2007-02-01

    Full Text Available An essential element of the sales promotion strategy and not only is the evaluation of the results obtained from the activities performed. Due to their nature and applicability, the evaluation of the sales promotion is much easier to be achieved, but it raises some problems. Using a hypothetical example, we have tried to develop a "classic" evaluation model of the specialty literature.

  13. HTLV-1 Tax Stabilizes MCL-1 via TRAF6-Dependent K63-Linked Polyubiquitination to Promote Cell Survival and Transformation

    Science.gov (United States)

    Choi, Young Bong; Harhaj, Edward William

    2014-01-01

    The human T-cell leukemia virus type 1 (HTLV-1) Tax protein hijacks the host ubiquitin machinery to activate IκB kinases (IKKs) and NF-κB and promote cell survival; however, the key ubiquitinated factors downstream of Tax involved in cell transformation are unknown. Using mass spectrometry, we undertook an unbiased proteome-wide quantitative survey of cellular proteins modified by ubiquitin in the presence of Tax or a Tax mutant impaired in IKK activation. Tax induced the ubiquitination of 22 cellular proteins, including the anti-apoptotic BCL-2 family member MCL-1, in an IKK-dependent manner. Tax was found to promote the nondegradative lysine 63 (K63)-linked polyubiquitination of MCL-1 that was dependent on the E3 ubiquitin ligase TRAF6 and the IKK complex. Tax interacted with and activated TRAF6, and triggered its mitochondrial localization, where it conjugated four carboxyl-terminal lysine residues of MCL-1 with K63-linked polyubiquitin chains, which stabilized and protected MCL-1 from genotoxic stress-induced degradation. TRAF6 and MCL-1 played essential roles in the survival of HTLV-1 transformed cells and the immortalization of primary T cells by HTLV-1. Therefore, K63-linked polyubiquitination represents a novel regulatory mechanism controlling MCL-1 stability that has been usurped by a viral oncogene to precipitate cell survival and transformation. PMID:25340740

  14. Changes in growth, survival and digestive enzyme activities of Asian ...

    African Journals Online (AJOL)

    A study was conducted to determine the effects of different dietary treatments on the growth, survival and digestive enzyme activities of Mystus nemurus larvae. Newly hatched larvae were reared for 14 days in twelve 15 L glass aquaria (for growth and survival) and eight 300 L fiberglass tanks (for enzyme samples) at a ...

  15. Intra-graft injection of tacrolimus promotes survival of vascularized composite allotransplantation.

    Science.gov (United States)

    Olariu, Radu; Denoyelle, Julie; Leclère, Franck M; Dzhonova, Dzhuliya V; Gajanayake, Thusitha; Banz, Yara; Hayoz, Michael; Constantinescu, Mihai; Rieben, Robert; Vögelin, Esther; Taddeo, Adriano

    2017-10-01

    Immunosuppressive therapies derived from solid organ transplantation are effective in promoting survival of vascularized composite allotransplantation (VCA), but they cause serious side effects that are difficult to justify for this non-life-saving procedure. Unlike solid organ transplantation, hand and face transplants offer the possibility of site-specific immunosuppression for reducing systemic exposure while increasing intra-graft concentrations of the drug. Therefore, in this study, we tested whether a single intra-graft injection tacrolimus could promote VCA survival. Brown Norway-to-Lewis hind limb transplantations were performed, and animals were left untreated (group I), treated with a daily injection of 1-mg/kg tacrolimus for 21 days (group 2) or injected with 7-mg tacrolimus directly into the transplanted limb on day 1 (group III). Graft rejection was monitored, and animals were sacrificed at grade 3 rejection or 200 days after transplantation. Intra-graft injection of tacrolimus significantly prolonged allograft survival as compared to untreated animals or animals treated with systemic tacrolimus. Half of the intra-graft-treated rats rejected their graft on average at day 70.5. Interestingly, the other half remained rejection-free for more than 200 days without signs of kidney or liver toxicity. In these animals, tacrolimus was detected in the VCA skin but not in the blood until day 200. Long-term survival was not linked to induction of donor-specific tolerance but to a higher level of lymphocyte chimerism. Intra-graft delivery of tacrolimus may promote VCA survival by increasing tissue drug availability and promoting the establishment of transient chimerism and thus long-term graft acceptance. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Increased HDAC1 deposition at hematopoietic promoters in AML and its association with patient survival

    DEFF Research Database (Denmark)

    Tickenbrock, Lara; Klein, Hans-Ulrich; Trento, Cristina

    2011-01-01

    was established, that revealed an AML specific pattern of HDAC1 distribution. Many of the HDAC1-binding altered promoters regulate genes involved in hematopoiesis, transcriptional regulation and signal transduction. HDAC1 binding patterns were associated with patients' event free survival. This is the first study...... to determine HDAC1 modification patterns in a large number of AML and ALL specimens. Our findings suggest that dyslocalization of HDAC1 is a common feature in AML. Importantly, HDAC1 modifications possess prognostic power for patient survival. Our findings suggest that altered HDAC1 localization...

  17. A Three-Dimensional Culture System with Matrigel Promotes Purified Spiral Ganglion Neuron Survival and Function In Vitro.

    Science.gov (United States)

    Yan, Wenqing; Liu, Wenwen; Qi, Jieyu; Fang, Qiaojun; Fan, Zhaomin; Sun, Gaoying; Han, Yuechen; Zhang, Daogong; Xu, Lei; Wang, Mingming; Li, Jianfeng; Chen, Fangyi; Liu, Dong; Chai, Renjie; Wang, Haibo

    2017-03-10

    In vitro culture of spiral ganglion neurons (SGNs) is a useful approach to investigate numerous aspects of neuronal behavior and to identify potential therapeutic targets for SGN protection and regeneration. However, the isolation of SGNs and the long-term maintenance of their structure and function in vitro remain challenging. In this study, we isolated SGNs from Bhlhb5-cre and Rosa26-tdTomato mice with fluorescence-activated cell sorting and determined the cell purity. We then encapsulated the pure SGNs in matrigel and cultured the SGNs in vitro. We found that the three-dimensional (3D)-matrigel culture environment significantly suppressed apoptosis and improved SGN survival in vitro, which enabled the long-term culture of SGNs for up to 6 months. The 3D-matrigel system also significantly promoted neurite outgrowth of the SGNs, increased the cells' polarity, promoted the area of growth cones, and significantly increased the synapse density of the SGNs. More importantly, the 3D-matrigel system helped to maintain and promote the electrophysiological properties of the SGNs. In conclusion, the 3D-matrigel culture system promoted the survival of purified SGNs in vitro and maintained their morphological structure and function and thus could be a useful tool for studying the physiology and pathophysiology of purified SGNs in long-term culture.

  18. Twisted epithelial-to-mesenchymal transition promotes progression of surviving bladder cancer T24 cells with hTERT-dysfunction.

    Science.gov (United States)

    Xue, Yan; Li, Lei; Zhang, Dong; Wu, Kaijie; Chen, Yule; Zeng, Jin; Wang, Xinyang; He, Dalin

    2011-01-01

    Human cancer cells maintain telomeres to protect cells from senescence through telomerase activity (TA) or alternative lengthening of telomeres (ALT) in different cell types. Moreover, cellular senescence can be bypassed by Epithelial-to-mesenchymal transition (EMT) during cancer progression in diverse solid tumors. However, it has not been elucidated the characteristics of telomere maintenance and progression ability after long-term culture in bladder cancer T24 cells with hTERT dysfunction. In this study, by using a dominant negative mutant human telomerase reverse transcriptase (hTERT) vector to inhibit TA in bladder cancer T24 cells, we observed the appearance of long phenotype of telomere length and the ALT-associated PML body (APB) complex after the 27(th) passage, indicating the occurrence of ALT-like pathway in surviving T24/DN868A cells with telomerase inhibition. Meanwhile, telomerase inhibition resulted in significant EMT as shown by change in cellular morphology concomitant with variation of EMT markers. Consistently, the surviving T24/DN868A cells showed increased progression ability in vitro and in vivo. In addition, we found Twist was activated to mediate EMT in surviving T24/DN868A samples. Taken together, our findings indicate that bladder cancer T24 cells may undergo the telomerase-to-ALT-like conversion and promote cancer progression at advanced stages through promoting EMT, thus providing novel possible insight into the mechanism of resistance to telomerase inhibitors in cancer treatment.

  19. Physical activity increases survival after heart valve surgery

    DEFF Research Database (Denmark)

    Lund, K.; Sibilitz, Kirstine Lærum; Kikkenborg Berg, Selina

    2016-01-01

    physical activity levels 6-12 months after heart valve surgery and (1) survival, (2) hospital readmission 18-24 months after surgery and (3) participation in exercise-based cardiac rehabilitation. METHODS: Prospective cohort study with registry data from The CopenHeart survey, The Danish National Patient...... of physical activity after heart valve surgery are positively associated with higher survival rates and participation in cardiac rehabilitation.......OBJECTIVES: Increased physical activity predicts survival and reduces risk of readmission in patients with coronary heart disease. However, few data show how physical activity is associated with survival and readmission after heart valve surgery. Objective were to assess the association between...

  20. Tobacco Control and Health Promotion Activities

    OpenAIRE

    Spasovski, Mome; Donev, Doncho; Arnikov, Aleksandar; Karadzinski, Jaroslav

    2008-01-01

    The use of tobacco is considered as one of the main risk factors for numerous chronic diseases, such as: lung diseases, cancer, and cardiovascular diseases. 4.9 million deaths per year worldwide are tobacco related, having an increasing trend that will lead to double death toll by 2020. WHO is one of the leading organizations in the world actively involved in the health promotion activities related to tobacco consumption reduction and tobacco control. In this regard WHO prepared the Framework...

  1. Promotion of physical activity in children.

    Science.gov (United States)

    Floriani, Victoria; Kennedy, Christine

    2008-02-01

    Promotion of physical activity continues to be recommended as an essential component of obesity treatment and prevention interventions. This review explores recent updates in the area of physical activity promotion and its impact on the physical and mental health consequences of childhood obesity. Despite the availability of opportunities for physical activity in the school environment, namely recess and physical education classes, students do not appear to be meeting activity recommendations at school alone. Access to neighborhood parks may increase levels of physical activity and reduce time spent in sedentary behaviors at home. Less time spent watching television and in other sedentary behaviors such as playing videogames may contribute to higher rates of physical activity. Frequency of physical activity also appears to be related to improved mental health status, although the direction of this relationship warrants further exploration. Physical activity is an evidence-based intervention that offers benefits to both physical and mental health. Pediatric health care providers are encouraged to engage in discussions with patients and families on the topic of physical activity and to assist them in finding ways to incorporate activity into daily life.

  2. Activated macrophage survival is coordinated by TAK1 binding proteins.

    Directory of Open Access Journals (Sweden)

    September R Mihaly

    Full Text Available Macrophages play diverse roles in tissue homeostasis and immunity, and canonically activated macrophages are critically associated with acute inflammatory responses. It is known that activated macrophages undergo cell death after transient activation in some settings, and the viability of macrophages impacts on inflammatory status. Here we report that TGFβ- activated kinase (TAK1 activators, TAK1-binding protein 1 (TAB1 and TAK1-binding protein 2 (TAB2, are critical molecules in the regulation of activated macrophage survival. While deletion of Tak1 induced cell death in bone marrow derived macrophages even without activation, Tab1 or Tab2 deletion alone did not profoundly affect survival of naïve macrophages. However, in lipopolysaccharide (LPS-activated macrophages, even single deletion of Tab1 or Tab2 resulted in macrophage death with both necrotic and apoptotic features. We show that TAB1 and TAB2 were redundantly involved in LPS-induced TAK1 activation in macrophages. These results demonstrate that TAK1 activity is the key to activated macrophage survival. Finally, in an in vivo setting, Tab1 deficiency impaired increase of peritoneal macrophages upon LPS challenge, suggesting that TAK1 complex regulation of macrophages may participate in in vivo macrophage homeostasis. Our results demonstrate that TAB1 and TAB2 are required for activated macrophages, making TAB1 and TAB2 effective targets to control inflammation by modulating macrophage survival.

  3. Arctigenin protects against neuronal hearing loss by promoting neural stem cell survival and differentiation.

    Science.gov (United States)

    Huang, Xinghua; Chen, Mo; Ding, Yan; Wang, Qin

    2017-03-01

    Neuronal hearing loss has become a prevalent health problem. This study focused on the function of arctigenin (ARC) in promoting survival and neuronal differentiation of mouse cochlear neural stem cells (NSCs), and its protection against gentamicin (GMC) induced neuronal hearing loss. Mouse cochlea was used to isolate NSCs, which were subsequently cultured in vitro. The effects of ARC on NSC survival, neurosphere formation, differentiation of NSCs, neurite outgrowth, and neural excitability in neuronal network in vitro were examined. Mechanotransduction ability demonstrated by intact cochlea, auditory brainstem response (ABR), and distortion product optoacoustic emissions (DPOAE) amplitude in mice were measured to evaluate effects of ARC on GMC-induced neuronal hearing loss. ARC increased survival, neurosphere formation, neuron differentiation of NSCs in mouse cochlear in vitro. ARC also promoted the outgrowth of neurites, as well as neural excitability of the NSC-differentiated neuron culture. Additionally, ARC rescued mechanotransduction capacity, restored the threshold shifts of ABR and DPOAE in our GMC ototoxicity murine model. This study supports the potential therapeutic role of ARC in promoting both NSCs proliferation and differentiation in vitro to functional neurons, thus supporting its protective function in the therapeutic treatment of neuropathic hearing loss in vivo. © 2017 Wiley Periodicals, Inc.

  4. Mobile computer application for promoting physical activity.

    Science.gov (United States)

    McMahon, Siobhan; Vankipuram, Mithra; Fleury, Julie

    2013-04-01

    Despite evidence that physical activity reduces the risk of falls and other causes of disability and death, the majority of older adults do not engage in physical activity on a regular basis. Mobile technology applications have emerged as potential resources for promoting physical activity behavior. This article describes features of a new application, Ready∼Steady, highlighting approaches used in its design and development, and implications for clinical practice. Iterative processes enabled the design, development, implementation, and evaluation of the application consistent with the wellness motivation theory, as well as established user-specific strategies and theoretical design principles. Implications in terms of potential benefits and constraints are discussed. Integrating technology that promotes health and wellness in the form of mobile computer applications is a promising adjunct to nursing practice. Copyright 2013, SLACK Incorporated.

  5. Survival Analysis of Faculty Retention and Promotion in the Social Sciences by Gender.

    Directory of Open Access Journals (Sweden)

    Janet M Box-Steffensmeier

    Full Text Available Recruitment and retention of talent is central to the research performance of universities. Existing research shows that, while men are more likely than women to be promoted at the different stages of the academic career, no such difference is found when it comes to faculty retention rates. Current research on faculty retention, however, focuses on careers in science, technology, engineering, and mathematics (STEM. We extend this line of inquiry to the social sciences.We follow 2,218 tenure-track assistant professors hired since 1990 in seven social science disciplines at nineteen U.S. universities from time of hire to time of departure. We also track their time to promotion to associate and full professor. Using survival analysis, we examine gender differences in time to departure and time to promotion. Our methods account for censoring and unobserved heterogeneity, as well as effect heterogeneity across disciplines and cohorts.We find no statistically significant differences between genders in faculty retention. However, we do find that men are more likely to be granted tenure than women. When it comes to promotion to full professor, the results are less conclusive, as the effect of gender is sensitive to model specification.The results corroborate previous findings about gender patterns in faculty retention and promotion. They suggest that advances have been made when it comes to gender equality in retention and promotion, but important differences still persist.

  6. Resistance of Foxp3+ regulatory T cells to Nur77-induced apoptosis promotes allograft survival.

    Directory of Open Access Journals (Sweden)

    Ran Tao

    Full Text Available The NR4A nuclear receptor family member Nur77 (NR4A1 promotes thymocyte apoptosis during negative selection of autoreactive thymocytes, but may also function in mature extrathymic T cells. We studied the effects of over-expression of Nur77 on the apoptosis of murine peripheral T cells, including thymic-derived Foxp3+ regulatory (Treg cells. Overexpression of Nur77 in the T cell lineage decreased numbers of peripheral CD4 and CD8 T cells by approximately 80% compared to wild-type (WT mice. However, the proportions of Treg cells were markedly increased in the thymus (61% of CD4+Foxp3+ singly positive thymocytes vs. 8% in WT and secondary lymphoid organs (40-50% of CD4+Foxp3+ T cells vs. 7-8% in WT of Nur77 transgenic (Nur77Tg mice, and immunoprecipitation studies showed Nur77 was associated with a recently identified HDAC7/Foxp3 transcriptional complex. Upon activation through the T cell receptor in vitro or in vivo, Nur77Tg T cells showed only marginally decreased proliferation but significantly increased apoptosis. Fully allogeneic cardiac grafts transplanted to Nur77Tg mice survived long-term with well-preserved structure, and recipient splenocytes showed markedly enhanced apoptosis and greatly reduced anti-donor recall responses. Allografts in Nur77Tg recipients had significantly increased expression of multiple Treg-associated genes, including Foxp3, Foxp1, Tip60 and HDAC9. Allograft rejection was restored by CD25 monoclonal antibody therapy, indicating that allograft acceptance was dependent upon Treg function in Nur77Tg recipients. These data show that compared to conventional CD4 and CD8 T cells, Foxp3+ Tregs are relatively resistant to Nur77-mediated apoptosis, and that tipping the balance between the numbers of Tregs and responder T cells in the early period post-transplantation can determine the fate of the allograft. Hence, induced expression of Nur77 might be a novel means to achieve long-term allograft survival.

  7. Gene activation regresses atherosclerosis, promotes health, and enhances longevity

    Directory of Open Access Journals (Sweden)

    Luoma Pauli V

    2010-07-01

    Full Text Available Abstract Background Lifestyle factors and pharmacological compounds activate genetic mechanisms that influence the development of atherosclerotic and other diseases. This article reviews studies on natural and pharmacological gene activation that promotes health and enhances longevity. Results Living habits including healthy diet and regular physical activity, and pharmacotherapy, upregulate genes encoding enzymes and apolipoprotein and ATP-binding cassette transporters, acting in metabolic processes that promote health and increase survival. Cytochrome P450-enzymes, physiological factors in maintaining cholesterol homeostasis, generate oxysterols for the elimination of surplus cholesterol. Hepatic CTP:phosphocholine cytidylyltransferase-α is an important regulator of plasma HDL-C level. Gene-activators produce plasma lipoprotein profile, high HDL-C, HDL2-C and HDL-C/cholesterol ratio, which is typical of low risk of atherosclerotic disease, and also of exceptional longevity together with reduced prevalence of cardiovascular, metabolic and other diseases. High HDL contributes to protection against inflammation, oxidation and thrombosis, and associates with good cognitive function in very old people. Avoiding unhealthy stress and managing it properly promotes health and increases life expectancy. Conclusions Healthy living habits and gene-activating xenobiotics upregulate mechanisms that produce lipoprotein pattern typical of very old people and enhance longevity. Lipoprotein metabolism and large HDL2 associate with the process of living a very long life. Major future goals for health promotion are the improving of commitment to both wise lifestyle choices and drug therapy, and further the developing of new and more effective and well tolerated drugs and treatments.

  8. THE CONTROL AND EVALUATION OF PROMOTIONAL ACTIVITIES

    Directory of Open Access Journals (Sweden)

    Felicia Sabou

    2012-01-01

    Full Text Available The paper focused on importance and benefits of control and evaluation of marketing activities. The control of efficiency review the assessment of the resources for marketing activity, checking also the efficiency of the human resources, advertising, promotion activities and distribution activities. In the analyse of human resources the most important ratio are: the average of costumers visits on a day, the number of custom order received from 100 visits, the number of new customers from a period, the number of lost customers from a period, the marketing human expenditures from all the sales.The strategic control is made to check if the objectives and the company strategy are adapted to the marketing environment.

  9. Long-term potentiation promotes proliferation/survival and neuronal differentiation of neural stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Taesup Cho

    Full Text Available Neural stem cell (NSC replacement therapy is considered a promising cell replacement therapy for various neurodegenerative diseases. However, the low rate of NSC survival and neurogenesis currently limits its clinical potential. Here, we examined if hippocampal long-term potentiation (LTP, one of the most well characterized forms of synaptic plasticity, promotes neurogenesis by facilitating proliferation/survival and neuronal differentiation of NSCs. We found that the induction of hippocampal LTP significantly facilitates proliferation/survival and neuronal differentiation of both endogenous neural progenitor cells (NPCs and exogenously transplanted NSCs in the hippocampus in rats. These effects were eliminated by preventing LTP induction by pharmacological blockade of the N-methyl-D-aspartate glutamate receptor (NMDAR via systemic application of the receptor antagonist, 3-[(R-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP. Moreover, using a NPC-neuron co-culture system, we were able to demonstrate that the LTP-promoted NPC neurogenesis is at least in part mediated by a LTP-increased neuronal release of brain-derived neurotrophic factor (BDNF and its consequent activation of tropomysosin receptor kinase B (TrkB receptors on NSCs. Our results indicate that LTP promotes the neurogenesis of both endogenous and exogenously transplanted NSCs in the brain. The study suggests that pre-conditioning of the host brain receiving area with a LTP-inducing deep brain stimulation protocol prior to NSC transplantation may increase the likelihood of success of using NSC transplantation as an effective cell therapy for various neurodegenerative diseases.

  10. Education at the service of man in promoting child survival and development: the special role of primary schools.

    Science.gov (United States)

    Nyamwaya, D

    1987-03-01

    The importance of health education in primary schools is a major concern in Southern and Eastern Africa. Although health education may not always cause changes in behavior that are needed for survival, it is the first crucial step. Parents, especially mothers with just 1 additional year of schooling results in a reduction of 9/1000 in infant mortality. Since 20% of the total population are in primary schools, if their education reaches 2 other people then 1/2 the country's population would be affected. These schools have the infrastructure that can be used to distribute health services. Since teachers are respected, their influence on the community would be taken seriously, and students are likely to participate in many activities outside the school to promote child survival and development. The basic causes for high infant mortality in Africa are malnutrition and communicable diseases; activities necessary for child survival are, growth monitoring, oral rehydration, breast feeding, and immunization. Female education, nutrition and food production, and family planning are also important elements. In addition, components such as water and personal hygiene, environmental sanitation, psychosocial stimulation and development, and maternal health must be monitored. The educational process must be applicable to real life situations and be taught in an environment where students enjoy learning. In addition to the knowledge, behavioral change must be emphasized. Since teachers see themselves as more in academic roles changes will be needed to make them more effective.

  11. C3G overexpression promotes the survival of rat-derived H9C2 cardiomyocytes by p-ERK1/2.

    Science.gov (United States)

    Zhang, Xu; Li, Gang; Zhang, Lei; Yang, Dongyan; Zhang, Zhisheng; Yan, An; Linghu, Hua

    2013-10-01

    Integrin β1 subunit and its downstream molecules, such as integrin-linked kinase and focal adhesion kinase, are imperative for promotion of cell proliferation, survival and anti-apoptosis in cardiomyocytes by activation of their downstream pro-survival signalling molecules, such as the phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2). As a component of the integrin pathway, C3G (Crk-SH3 domain guanine nucleotide exchange factor) protein may be involved in the promotion of cell proliferation and survival and anti-apoptosis in the H9C2 cardiomyocytes. Rat-derived H9C2 cardiomyocytes were transfected with pCXN2-flag-hC3G, a human C3G overexpression eukaryotic recombinant plasmid. Apoptosis, cell proliferation and survival were analysed in the H9C2 cardiomyocytes either treated with hypoxia/reoxygenation (H/R). Human C3G mRNA overexpression significantly elevated C3G protein expression in H9C2 cardiomyocytes whether treated with H/R or not. C3G overexpression promoted proliferation and survival and anti-apoptosis, and attenuated the proliferative and survival inhibition, and apoptosis induced by H/R by activation of its downstream pro-survival signalling molecule, p-ERK1/2. The results suggest that C3G acts as a pro-survival molecule in H9C2 cardiomyocytes by activation of p-ERK1/2. © 2013 International Federation for Cell Biology.

  12. Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival.

    Science.gov (United States)

    Tinkum, Kelsey L; Stemler, Kristina M; White, Lynn S; Loza, Andrew J; Jeter-Jones, Sabrina; Michalski, Basia M; Kuzmicki, Catherine; Pless, Robert; Stappenbeck, Thaddeus S; Piwnica-Worms, David; Piwnica-Worms, Helen

    2015-12-22

    Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.

  13. Using evaluation strategically to promote active learning

    DEFF Research Database (Denmark)

    Münster, Marie

    Rationale: The challenge presented here is how to utilise evaluation to promote active learning. The method used is constructive alignment (Biggs & Tang, 2007) of learning objectives, learning and evaluation along with further considerations including which competences are promoted, the time...... the principle of inductive learning (Prince & Felder, 2006) with the students being presented with the case from the beginning and subsequently achieving the tools to perform the projects. This is both frustrating and motivating for the students as they know why they need to have the tools, but they feel...... they get them too late. The students have formerly been assessed through two group reports (each 25% of final grade) and an individual oral examination (50% of final grade). The students work a lot and learn a lot through working with the reports, but it is also very time consuming to write them as well...

  14. Sox2 promotes survival of satellite glial cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Taro, E-mail: koiket@hirakata.kmu.ac.jp; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

    2015-08-14

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling.

  15. mTOR Promotes Survival and Astrocytic Characteristics Induced by Pten/Akt Signaling in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Xiaoyi Hu

    2005-04-01

    Full Text Available Combined activation of Ras and Akt leads to the formation of astrocytic glioblastoma multiforme (GBM in mice. In human GBMs, AKT is not mutated but is activated in approximately 70% of these tumors, in association with loss of PTEN and/or activation of receptor tyrosine kinases. Mechanistic justification for the therapeutic blockade of targets downstream of AKT, such as mTOR, in these cancers requires demonstration that the oncogenic effect of PTEN loss is through elevated AKT activity. We demonstrate here that loss of Pten is similar to Akt activation in the context of glioma formation in mice. We further delineate the role of mTOR activity downstream of Akt in the maintenance of Akt+KRas-induced GBMs. Blockade of mTOR results in regional apoptosis in these tumors and conversion in the character of surviving tumor cells from astrocytoma to oligodendroglioma. These data suggest that mTOR activity is required for the survival of some cells within these GBMs, and mTOR appears required for the maintenance of astrocytic character in the surviving cells. Furthermore, our study provides the first example of conversion between two distinct tumor types usually thought of as belonging to specific lineages, and provides evidence for signal transduction-mediated transdifferentiation between glioma subtypes.

  16. Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila.

    Science.gov (United States)

    Kuo, Tzu-Hsing; Williams, Julie A

    2014-05-01

    Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Laboratory. Drosophila melanogaster. Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection.

  17. Loyalty Card Promotional Activity in Budget Hotel

    OpenAIRE

    Teng, Fei

    2010-01-01

    Loyalty card is one of the most commonly used promotional activities in business. Thus far, there are some research has been done on luxury hotel, but very few researches are on budget hotel. So, the purpose of the thesis is finding out the Swedish customers’ attitude and behavior towards budget hotel’s loyalty card; getting to know what factors influence Swedish customers’ response towards the loyalty card and budget hotels. In the thesis, the main research problem is “How do Swedish custome...

  18. Exosomes Derived from Squamous Head and Neck Cancer Promote Cell Survival after Ionizing Radiation

    Science.gov (United States)

    Mutschelknaus, Lisa; Peters, Carsten; Winkler, Klaudia; Yentrapalli, Ramesh; Heider, Theresa; Atkinson, Michael John; Moertl, Simone

    2016-01-01

    Exosomes are nanometer-sized extracellular vesicles that are believed to function as intercellular communicators. Here, we report that exosomes are able to modify the radiation response of the head and neck cancer cell lines BHY and FaDu. Exosomes were isolated from the conditioned medium of irradiated as well as non-irradiated head and neck cancer cells by serial centrifugation. Quantification using NanoSight technology indicated an increased exosome release from irradiated compared to non-irradiated cells 24 hours after treatment. To test whether the released exosomes influence the radiation response of other cells the exosomes were transferred to non-irradiated and irradiated recipient cells. We found an enhanced uptake of exosomes isolated from both irradiated and non-irradiated cells by irradiated recipient cells compared to non-irradiated recipient cells. Functional analyses by exosome transfer indicated that all exosomes (from non-irradiated and irradiated donor cells) increase the proliferation of non-irradiated recipient cells and the survival of irradiated recipient cells. The survival-promoting effects are more pronounced when exosomes isolated from irradiated compared to non-irradiated donor cells are transferred. A possible mechanism for the increased survival after irradiation could be the increase in DNA double-strand break repair monitored at 6, 8 and 10 h after the transfer of exosomes isolated from irradiated cells. This is abrogated by the destabilization of the exosomes. Our results demonstrate that radiation influences both the abundance and action of exosomes on recipient cells. Exosomes transmit prosurvival effects by promoting the proliferation and radioresistance of head and neck cancer cells. Taken together, this study indicates a functional role of exosomes in the response of tumor cells to radiation exposure within a therapeutic dose range and encourages that exosomes are useful objects of study for a better understanding of tumor

  19. Survival

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data provide information on the survival of California red-legged frogs in a unique ecosystem to better conserve this threatened species while restoring...

  20. PROMOTION OF ACTIVE MEASURES AND EMPLOYMENT STIMULATION

    Directory of Open Access Journals (Sweden)

    LAVINIA ELISABETA POPP

    2012-01-01

    Full Text Available Researches in the field of the labour market has allowed the identification of certain specific mechanisms for employment promotion; at present, on the Romanian labour market we find passive policies, concretised in financial aids paid to the unemployed, along with active policies, constituting the most efficient social protection activity addressed to the unemployed (they aim at counterbalancing the inefficiencies determined by the granting of financial allowances, help population to find a job by actions of information, professional training and contributing to the encouragement of the labour force mobility. The paper refers to some theoretical considerations related to the influence factors of employment stimulation, as well as to the unemployment – correlated adequate measures synapse. The applied research comprises the analysis of statistic documents; the method used is the case study, i.e. the activity of employment stimulation carried on by the County Agency for Employment Caraş-Severin, in the period 2004-2012. The conclusions highlight the impact of the activity of the institutions involved in the system of social protection and security within the labour market.

  1. GGA3 mediates TrkA endocytic recycling to promote sustained Akt phosphorylation and cell survival

    Science.gov (United States)

    Li, Xuezhi; Lavigne, Pierre; Lavoie, Christine

    2015-01-01

    Although TrkA postendocytic sorting significantly influences neuronal cell survival and differentiation, the molecular mechanism underlying TrkA receptor sorting in the recycling or degradation pathways remains poorly understood. Here we demonstrate that Golgi-localized, γ adaptin-ear–containing ADP ribosylation factor-binding protein 3 (GGA3) interacts directly with the TrkA cytoplasmic tail through an internal DXXLL motif and mediates the functional recycling of TrkA to the plasma membrane. We find that GGA3 depletion by siRNA delays TrkA recycling, accelerates TrkA degradation, attenuates sustained NGF-induced Akt activation, and reduces cell survival. We also show that GGA3’s effect on TrkA recycling is dependent on the activation of Arf6. This work identifies GGA3 as a key player in a novel DXXLL-mediated endosomal sorting machinery that targets TrkA to the plasma membrane, where it prolongs the activation of Akt signaling and survival responses. PMID:26446845

  2. Applying Transtheoretical Model to Promote Physical Activities Among Women

    National Research Council Canada - National Science Library

    Pirzadeh, Asiyeh; Mostafavi, Firoozeh; Ghofranipour, Fazllolah; Feizi, Awat

    2015-01-01

    .... Inadequate regular physical activities among women, the importance of education in promoting the physical activities, and lack of studies on the women using transtheoretical model, persuaded us...

  3. Reconstructing promoter activity from Lux bioluminescent reporters.

    Directory of Open Access Journals (Sweden)

    Mudassar Iqbal

    2017-09-01

    Full Text Available The bacterial Lux system is used as a gene expression reporter. It is fast, sensitive and non-destructive, enabling high frequency measurements. Originally developed for bacterial cells, it has also been adapted for eukaryotic cells, and can be used for whole cell biosensors, or in real time with live animals without the need for euthanasia. However, correct interpretation of bioluminescent data is limited: the bioluminescence is different from gene expression because of nonlinear molecular and enzyme dynamics of the Lux system. We have developed a computational approach that, for the first time, allows users of Lux assays to infer gene transcription levels from the light output. This approach is based upon a new mathematical model for Lux activity, that includes the actions of LuxAB, LuxEC and Fre, with improved mechanisms for all reactions, as well as synthesis and turn-over of Lux proteins. The model is calibrated with new experimental data for the LuxAB and Fre reactions from Photorhabdus luminescens-the source of modern Lux reporters-while literature data has been used for LuxEC. Importantly, the data show clear evidence for previously unreported product inhibition for the LuxAB reaction. Model simulations show that predicted bioluminescent profiles can be very different from changes in gene expression, with transient peaks of light output, very similar to light output seen in some experimental data sets. By incorporating the calibrated model into a Bayesian inference scheme, we can reverse engineer promoter activity from the bioluminescence. We show examples where a decrease in bioluminescence would be better interpreted as a switching off of the promoter, or where an increase in bioluminescence would be better interpreted as a longer period of gene expression. This approach could benefit all users of Lux technology.

  4. Financial Incentives to Promote Active Travel

    Science.gov (United States)

    Martin, Adam; Suhrcke, Marc; Ogilvie, David

    2012-01-01

    Context Financial incentives, including taxes and subsidies, can be used to encourage behavior change. They are common in transport policy for tackling externalities associated with use of motor vehicles, and in public health for influencing alcohol consumption and smoking behaviors. Financial incentives also offer policymakers a compromise between “nudging,” which may be insufficient for changing habitual behavior, and regulations that restrict individual choice. Evidence acquisition The literature review identified studies published between January 1997 and January 2012 of financial incentives relating to any mode of travel in which the impact on active travel, physical activity, or obesity levels was reported. It encompassed macroenvironmental schemes, such as gasoline taxes, and microenvironmental schemes, such as employer-subsidized bicycles. Five relevant reviews and 20 primary studies (of which nine were not included in the reviews) were identified. Evidence synthesis The results show that more-robust evidence is required if policymakers are to maximize the health impact of fiscal policy relating to transport schemes of this kind. Conclusions Drawing on a literature review and insights from the SLOTH (sleep, leisure, occupation, transportation, and home-based activities) time-budget model, this paper argues that financial incentives may have a larger role in promoting walking and cycling than is acknowledged generally. PMID:23159264

  5. Moringa oleifera with promising neuronal survival and neurite outgrowth promoting potentials.

    Science.gov (United States)

    Hannan, Md Abdul; Kang, Ji-Young; Mohibbullah, Md; Hong, Yong-Ki; Lee, Hyunsook; Choi, Jae-Suk; Choi, In Soon; Moon, Il Soo

    2014-02-27

    Moringa oleifera Lam. (Moringaceae) by virtue of its high nutritional as well as ethnomedical values has been gaining profound interest both in nutrition and medicinal research. The leaf of this plant is used in ayurvedic medicine to treat paralysis, nervous debility and other nerve disorders. In addition, research evidence also suggests the nootropic as well as neuroprotective roles of Moringa oleifera leaf in animal models. The aim of the present study was to evaluate the effect of Moringa oleifera leaf in the primary hippocampal neurons regarding its neurotrophic and neuroprotective properties. The primary culture of embryonic hippocampal neurons was incubated with the ethanol extract of Moringa oleifera leaf (MOE). After an indicated time, cultures were either stained directly with a lipophilic dye, DiO, or fixed and immunolabeled to visualize the neuronal morphology. Morphometric analyses for neurite maturation and synaptogenesis were performed using Image J software. Neuronal viability was evaluated using trypan blue exclusion and lactate dehydrogenase assays. MOE promoted neurite outgrowth in a concentration-dependent manner with an optimal concentration of 30 μg/mL. As a very initial effect, MOE significantly promoted the earlier stages of neuronal differentiation. Subsequently, MOE significantly increased the number and length of dendrites, the length of axon, and the number and length of both dendrite and axonal branches, and eventually facilitated synaptogenesis. The β-carotene, one major compound of MOE, promoted neuritogensis, but the increase was not comparable with the effect of MOE. In addition, MOE supported neuronal survival by protecting neurons from naturally occurring cell death in vitro. Our findings indicate that MOE promotes axodendritic maturation as well as provides neuroprotection suggesting a promising pharmacological importance of this nutritionally and ethnomedically important plant for the well-being of nervous system. Copyright

  6. Mineralocorticoid receptor overexpression facilitates differentiation and promotes survival of embryonic stem cell-derived neurons.

    Science.gov (United States)

    Munier, Mathilde; Law, Frédéric; Meduri, Geri; Le Menuet, Damien; Lombès, Marc

    2012-03-01

    Mineralocorticoid receptor (MR), highly expressed in the hippocampus, binds corticosteroid hormones and coordinately participates, with the glucocorticoid receptor, to the control of stress responses, memorization, and behavior. To investigate the impact of MR in neuronal survival, we generated murine embryonic stem (ES) cells that overexpress human MR (hMR) (P1-hMR) and are induced to differentiate into mature neurons. We showed that recombinant MR expression increased throughout differentiation and is 2-fold higher in P1-hMR ES-derived neurons compared with wild-type controls, whereas glucocorticoid receptor expression was unaffected. Although proliferation and early neuronal differentiation were comparable in P1-hMR and wild-type ES cells, MR overexpression was associated with higher late neuronal marker expression (microtubule-associated protein 2 and β-tubulin III). This was accompanied by a shift towards neuron survival with an increased ratio of anti- vs. proapoptotic molecules and 50% decreased caspase 3 activity. Knocking down MR overexpression by small interfering RNA drastically reversed neuroprotective effects with reduced Bcl(2)/Bax ratio and decreased microtubule-associated protein 2 expression. P1-hMR neurons were protected against oxidative stress-induced apoptosis through reduced caspase 3 activation and drastically increased Bcl(2)/Bax ratio and β-tubulin III expression. We demonstrated the involvement of MR in neuronal differentiation and survival and identify MR as an important neuroprotective mediator opening potential pharmacological strategies.

  7. The prohibitin protein complex promotes mitochondrial stabilization and cell survival in hematologic malignancies

    Science.gov (United States)

    Ross, Jeremy A.; Robles-Escajeda, Elisa; Oaxaca, Derrick M.; Padilla, Diana L.; Kirken, Robert A.

    2017-01-01

    Prohibitins (PHB1 and PHB2) have been proposed to play important roles in cancer development and progression, however their oncogenic mechanism of action has not been fully elucidated. Previously, we showed that the PHB1 and PHB2 protein complex is required for mitochondrial homeostasis and survival of normal human lymphocytes. In this study, novel evidence is provided that indicates mitochondrial prohibitins are overexpressed in hematologic tumor cells and promote cell survival under conditions of oxidative stress. Immunofluorescent confocal microscopy revealed both proteins to be primarily confined to mitochondria in primary patient lymphoid and myeloid tumor cells and tumor cell lines, including Kit225 cells. Subsequently, siRNA-mediated knockdown of PHB1 and PHB2 in Kit225 cells significantly enhanced sensitivity to H2O2-induced cell death, suggesting a protective or anti-apoptotic function in hematologic malignancies. Indeed, PHB1 and PHB2 protein levels were significantly higher in tumor cells isolated from leukemia and lymphoma patients compared to PBMCs from healthy donors. These findings suggest that PHB1 and PHB2 are upregulated during tumorigenesis to maintain mitochondrial integrity and therefore may serve as novel biomarkers and molecular targets for therapeutic intervention in certain types of hematologic malignancies. PMID:29029444

  8. Peptides modeled after the alpha-domain of metallothionein induce neurite outgrowth and promote survival of cerebellar granule neurons

    DEFF Research Database (Denmark)

    Asmussen, Johanne Wirenfeldt; Ambjørn, Malene; Bock, Elisabeth

    2009-01-01

    Metallothionein (MT) is a metal-binding protein capable of preventing oxidative stress and apoptotic cell death in the central nervous system of mammals, and hence is of putative therapeutic value in the treatment of neurodegenerative disorders. Recently, we demonstrated that a peptide modeled...... after the beta-domain of MT, EmtinB, induced neurite outgrowth and increased neuronal survival through binding to receptors of the low-density lipoprotein receptor family (LDLR). The present study identified two MT alpha-domain-derived peptide sequences termed EmtinAn and EmtinAc, each consisting of 14...... amino acids, as potent stimulators of neuronal differentiation and survival of primary neurons. In addition, we show that a peptide derived from the N-terminus of the MT beta-domain, EmtinBn, promotes neuronal survival. The neuritogenic and survival promoting effects of EmtinAc, similar to MT and Emtin...

  9. INVESTIGATION INTO CONSUMER RESPONSE TO SALES PROMOTIONAL ACTIVITIES: THE CASE OF UNILEVER GHANA LIMITED

    Directory of Open Access Journals (Sweden)

    Martin Owusu Ansah

    2013-10-01

    Full Text Available The promotional activities have become more sophisticated and an increasing number of companies are using them to ensure their survival in today’s competitive market. Essentially, the study analyzed the nature of sales promotional activities of Unilever Ghana Limited; determined factors that influence the consumption of Unilever products in Kumasi and finally examined the relationship between sales promotions and the consumption of Unilever products. Primary and secondary data sources were used to select 220 consumers of Unilever in Kumasi and an in-depth interview with the Managers of the companies in Kumasi. Convenient sampling technique was employed in the study. Cross tabulation was done on the demographics whilst a regression model was used to establish the relationship between sales promotions and consumption of products. The findings revealed that Personalities in promotions, Prices in promotions, Messages in promotions and Promotional tools have strong influence on consumption but the Medium in promotion did not have influence on consumption during promotions. It was therefore recommended for celebrities to be used in the company’s promotions.

  10. Intact fetal ovarian cord formation promotes mouse oocyte survival and development

    Directory of Open Access Journals (Sweden)

    Pera Renee

    2010-01-01

    Full Text Available Abstract Background Female reproductive potential, or the ability to propagate life, is limited in mammals with the majority of oocytes lost before birth. In mice, surviving perinatal oocytes are enclosed in ovarian follicles for subsequent oocyte development and function in the adult. Before birth, fetal germ cells of both sexes develop in clusters, or germline cysts, in the undifferentiated gonad. Upon sex determination of the fetal gonad, germ cell cysts become organized into testicular or ovarian cord-like structures and begin to interact with gonadal somatic cells. Although germline cysts and testicular cords are required for spermatogenesis, the role of cyst and ovarian cord formation in mammalian oocyte development and female fertility has not been determined. Results Here, we examine whether intact fetal ovarian germ and somatic cell cord structures are required for oocyte development using mouse gonad re-aggregation and transplantation to disrupt gonadal organization. We observed that germ cells from disrupted female gonad prior to embryonic day e13.5 completed prophase I of meiosis but did not survive following transplantation. Furthermore, re-aggregated ovaries from e13.5 to e15.5 developed with a reduced number of oocytes. Oocyte loss occurred before follicle formation and was associated with an absence of ovarian cord structure and ovary disorganization. However, disrupted ovaries from e16.5 or later were resistant to the re-aggregation impairment and supported robust oocyte survival and development in follicles. Conclusions Thus, we demonstrate a critical window of oocyte development from e13.5 to e16.5 in the intact fetal mouse ovary, corresponding to the establishment of ovarian cord structure, which promotes oocyte interaction with neighboring ovarian somatic granulosa cells before birth and imparts oocytes with competence to survive and develop in follicles. Because germline cyst and ovarian cord structures are conserved in the

  11. Stem cell factor expression after renal ischemia promotes tubular epithelial survival.

    Directory of Open Access Journals (Sweden)

    Geurt Stokman

    Full Text Available BACKGROUND: Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration of renal tissue. The cytokine stem cell factor (SCF has been shown to protect the tubular epithelium against apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse model for renal ischemia/reperfusion injury, we studied how expression of c-KIT on tubular epithelium and its ligand SCF protect cells against apoptosis. Administration of SCF specific antisense oligonucleotides significantly decreased specific staining of SCF following ischemia. Reduced SCF expression resulted in impaired renal function, increased tubular damage and increased tubular epithelial apoptosis, independent of inflammation. In an in vitro hypoxia model, stimulation of tubular epithelial cells with SCF activated survival signaling and decreased apoptosis. CONCLUSIONS/SIGNIFICANCE: Our data indicate an important role for c-KIT and SCF in mediating tubular epithelial cell survival via an autocrine pathway.

  12. β-Catenin Signaling Increases during Melanoma Progression and Promotes Tumor Cell Survival and Chemoresistance

    Science.gov (United States)

    Sinnberg, Tobias; Menzel, Moritz; Ewerth, Daniel; Sauer, Birgit; Schwarz, Michael; Schaller, Martin; Garbe, Claus; Schittek, Birgit

    2011-01-01

    Beta-catenin plays an important role in embryogenesis and carcinogenesis by controlling either cadherin-mediated cell adhesion or transcriptional activation of target gene expression. In many types of cancers nuclear translocation of beta-catenin has been observed. Our data indicate that during melanoma progression an increased dependency on the transcriptional function of beta-catenin takes place. Blockade of beta-catenin in metastatic melanoma cell lines efficiently induces apoptosis, inhibits proliferation, migration and invasion in monolayer and 3-dimensional skin reconstructs and decreases chemoresistance. In addition, subcutaneous melanoma growth in SCID mice was almost completely inhibited by an inducible beta-catenin knockdown. In contrast, the survival of benign melanocytes and primary melanoma cell lines was less affected by beta-catenin depletion. However, enhanced expression of beta-catenin in primary melanoma cell lines increased invasive capacity in vitro and tumor growth in the SCID mouse model. These data suggest that beta-catenin is an essential survival factor for metastatic melanoma cells, whereas it is dispensable for the survival of benign melanocytes and primary, non-invasive melanoma cells. Furthermore, beta-catenin increases tumorigenicity of primary melanoma cell lines. The differential requirements for beta-catenin signaling in aggressive melanoma versus benign melanocytic cells make beta-catenin a possible new target in melanoma therapy. PMID:21858114

  13. DUSP4 deficiency caused by promoter hypermethylation drives JNK signaling and tumor cell survival in diffuse large B cell lymphoma

    Science.gov (United States)

    Schmid, Corina A.; Robinson, Mark D.; Scheifinger, Nicole A.; Müller, Sebastian; Cogliatti, Sergio; Tzankov, Alexandar

    2015-01-01

    The epigenetic dysregulation of tumor suppressor genes is an important driver of human carcinogenesis. We have combined genome-wide DNA methylation analyses and gene expression profiling after pharmacological DNA demethylation with functional screening to identify novel tumor suppressors in diffuse large B cell lymphoma (DLBCL). We find that a CpG island in the promoter of the dual-specificity phosphatase DUSP4 is aberrantly methylated in nodal and extranodal DLBCL, irrespective of ABC or GCB subtype, resulting in loss of DUSP4 expression in 75% of >200 examined cases. The DUSP4 genomic locus is further deleted in up to 13% of aggressive B cell lymphomas, and the lack of DUSP4 is a negative prognostic factor in three independent cohorts of DLBCL patients. Ectopic expression of wild-type DUSP4, but not of a phosphatase-deficient mutant, dephosphorylates c-JUN N-terminal kinase (JNK) and induces apoptosis in DLBCL cells. Pharmacological or dominant-negative JNK inhibition restricts DLBCL survival in vitro and in vivo and synergizes strongly with the Bruton’s tyrosine kinase inhibitor ibrutinib. Our results indicate that DLBCL cells depend on JNK signaling for survival. This finding provides a mechanistic basis for the clinical development of JNK inhibitors in DLBCL, ideally in synthetic lethal combinations with inhibitors of chronic active B cell receptor signaling. PMID:25847947

  14. Amiodarone as an autophagy promoter reduces liver injury and enhances liver regeneration and survival in mice after partial hepatectomy

    Science.gov (United States)

    Lin, Chih-Wen; Chen, Yaw-Sen; Lin, Chih-Che; Chen, Yun-Ju; Lo, Gin-Ho; Lee, Po-Huang; Kuo, Po-Lin; Dai, Chia-Yen; Huang, Jee-Fu; Chung, Wang-Long; Yu, Ming-Lung

    2015-01-01

    The deregulation of autophagy is involved in liver regeneration. Here, we investigated the role of autophagy in the regulation of liver regeneration after partial hepatectomy (PHx) and the development of pharmacological interventions for improved liver regeneration after PHx. We show that autophagy was activated in the early stages of liver regeneration following 70% PHx in vivo. Moreover, amiodarone was associated with a significant enhancement of autophagy, liver growth, and hepatocyte proliferation, along with reduced liver injury and the termination of liver regeneration due to decreased transforming growth factor-β1 expression after 70% PHx. The promotion of autophagy appeared to selectively increase the removal of damaged mitochondria. We also found that Atg7 knockdown or pretreatment with chloroquine aggravated the liver injury associated with 70% PHx and reduced liver growth and hepatocyte proliferation. Finally, amiodarone improved liver regeneration, survival, and liver injury after 90% PHx. In conclusion, our results indicate that autophagy plays an important role in mouse liver regeneration and that modulating autophagy with amiodarone may be an effective method of improving liver regeneration, increasing survival, and ameliorating liver injury following PHx. PMID:26515640

  15. Dps promotes survival of nontypeable Haemophilus influenzae in biofilm communities in vitro and resistance to clearance in vivo

    Directory of Open Access Journals (Sweden)

    Bing ePang

    2012-05-01

    Full Text Available Nontypeable Haemophilus influenzae (NTHi is a common airway commensal and opportunistic pathogen that persists within surface-attached biofilm communities. In this study, we tested the hypothesis that bacterial stress-responses are activated within biofilms. Transcripts for several factors associated with bacterial resistance to environmental stress were increased in biofilm cultures as compared to planktonic cultures. Among these, a homolog of the DNA-binding protein from starved cells (dps was chosen for further study. An isogenic NTHi 86-028NP dps mutant was generated and tested for resistance to environmental stress, revealing a significant survival defects in high-iron conditions, which was mediated by oxidative stress and was restored by genetic complementation. As expected, NTHi 86-028NP dps had a general stress-response defect, exhibiting decreased resistance to many types of environmental stress. While no differences were observed in density and structure of NTHi 86-028NP and NTHi 86-028NP dps biofilms, bacterial survival was decreased in NTHi 86-028NP dps biofilms as compared to the parental strain. The role of dps persistence in vivo was tested in animal infection studies. NTHi 86-028NP dps had decreased resistance to clearance after pulmonary infection of elastase-treated mice as compared to NTHi 86-028NP, whereas minimal differences were observed in clearance from mock-treated mice. Similarly, lower numbers of NTHi 86-028NP dps were recovered from middle-ear effusions and bullar homogenates in the chinchilla model for otitis media. Therefore, we conclude that Dps promotes bacterial survival within NTHi biofilm communities both in vitro and in chronic infections in vivo.

  16. δ-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles

    Directory of Open Access Journals (Sweden)

    Chen Yan-Hua

    2009-03-01

    Full Text Available Abstract Background δ-Catenin is a unique member of β-catenin/armadillo domain superfamily proteins and its primary expression is restricted to the brain. However, δ-catenin is upregulated in human prostatic adenocarcinomas, although the effects of δ-catenin overexpression in prostate cancer are unclear. We hypothesized that δ-catenin plays a direct role in prostate cancer progression by altering gene profiles of cell cycle regulation and cell survival. Results We employed gene transfection and small interfering RNA to demonstrate that increased δ-catenin expression promoted, whereas its knockdown suppressed prostate cancer cell viability. δ-Catenin promoted prostate cancer cell colony formation in soft agar as well as tumor xenograft growth in nude mice. Deletion of either the amino-terminal or carboxyl-terminal sequences outside the armadillo domains abolished the tumor promoting effects of δ-catenin. Quantitative RT2 Profiler™ PCR Arrays demonstrated gene alterations involved in cell cycle and survival regulation. δ-Catenin overexpression upregulated cyclin D1 and cdc34, increased phosphorylated histone-H3, and promoted the entry of mitosis. In addition, δ-catenin overexpression resulted in increased expression of cell survival genes Bcl-2 and survivin while reducing the cell cycle inhibitor p21Cip1. Conclusion Taken together, our studies suggest that at least one consequence of an increased expression of δ-catenin in human prostate cancer is the alteration of cell cycle and survival gene profiles, thereby promoting tumor progression.

  17. Does the association between leisure activities and survival in old age differ by living arrangement?

    Science.gov (United States)

    Nilsen, Charlotta; Agahi, Neda; Shaw, Benjamin A

    2018-01-01

    Government policies to promote ageing in place have led to a growing frail population living at home in advanced old age, many of whom live alone. Living alone in old age is associated with adverse health outcomes, but we know little about whether it moderates the health impact of other risk and protective factors. Engagement in leisure activities is considered critical to successful ageing. We investigated whether the association between different types of leisure activities and survival in non-institutionalised older adults (aged 76 and above) differs by living arrangement and gender. We used the Swedish Panel Study of Living Conditions of the Oldest Old study from 2011 and the Swedish Cause of Death Register (until 30 June 2014) to conduct Cox regression analyses (n=669). Incident mortality was 30.2% during the follow-up period. Overall level of leisure activity was not significantly associated with survival in either living arrangement, but some specific leisure activities, and associations, were different across gender and living arrangement. More specifically, certain social activities (participation in organisations and having relatives visit) were associated with longer survival, but only in men living alone. In women, most results were statistically non-significant, with the exception of solving crosswords being associated with longer survival in women living with someone. In order to facilitate engagement with life, interventions focusing on leisure activities in the oldest age groups should take gender and living arrangement into consideration when determining the type of activity most needed. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Cyclic AMP promotes axon regeneration, lesion repair and neuronal survival in lampreys after spinal cord injury.

    Science.gov (United States)

    Lau, Billy Y B; Fogerson, Stephanie M; Walsh, Rylie B; Morgan, Jennifer R

    2013-12-01

    Axon regeneration after spinal cord injury in mammals is inadequate to restore function, illustrating the need to design better strategies for improving outcomes. Increasing the levels of the second messenger cyclic adenosine monophosphate (cAMP) after spinal cord injury enhances axon regeneration across a wide variety of species, making it an excellent candidate molecule that has therapeutic potential. However, several important aspects of the cellular and molecular mechanisms by which cAMP enhances axon regeneration are still unclear, such as how cAMP affects axon growth patterns, the molecular components within growing axon tips, the lesion scar, and neuronal survival. To address these points, we took advantage of the large, identified reticulospinal (RS) neurons in lamprey, a vertebrate that exhibits robust axon regeneration after a complete spinal cord transection. Application of a cAMP analog, db-cAMP, at the time of spinal cord transection increased the number of axons that regenerated across the lesion site. Db-cAMP also promoted axons to regenerate in straighter paths, prevented abnormal axonal growth patterns, increased the levels of synaptotagmin within axon tips, and increased the number of axotomized neurons that survived after spinal cord injury, thereby increasing the pool of neurons available for regeneration. There was also a transient increase in the number of microglia/macrophages and improved repair of the lesion site. Taken together, these data reveal several new features of the cellular and molecular mechanisms underlying cAMP-mediated enhancement of axon regeneration, further emphasizing the positive roles for this conserved pathway. © 2013.

  19. Promoting physical activity at work: A guide for employers

    OpenAIRE

    Public Health Agency

    2010-01-01

    This booklet is the second in a series of short guides aimed at promoting health in the workplace. It outlines to employers the benefits of promoting physical activity at work, how workplaces can be active places through simple activities and changes, what information and facilities can benefit employees,

  20. Archaeal promoter architecture and mechanism of gene activation

    DEFF Research Database (Denmark)

    Peng, Nan; Ao, Xiang; Liang, Yun Xiang

    2011-01-01

    element named ara box directing arabinose-inducible expression and the basal promoter element TATA, serving as the binding site for the TATA-binding protein. Strikingly, these promoters possess a modular structure that allows an essentially inactive basal promoter to be strongly activated. The invoked...

  1. Pharmacologically active microcarriers for endothelial progenitor cell support and survival.

    Science.gov (United States)

    Musilli, Claudia; Karam, Jean-Pierre; Paccosi, Sara; Muscari, Claudio; Mugelli, Alessandro; Montero-Menei, Claudia N; Parenti, Astrid

    2012-08-01

    The regenerative potential of endothelial progenitor cell (EPC)-based therapies is limited due to poor cell viability and minimal retention following application. Neovascularization can be improved by means of scaffolds supporting EPCs. The aim of the present study was to investigate whether human early EPCs (eEPCs) could be efficiently cultured on pharmacologically active microcarriers (PAMs), made with poly(d,l-lactic-coglycolic acid) and coated with adhesion/extracellular matrix molecules. They may serve as a support for stem cells and may be used as cell carriers providing a controlled delivery of active protein such as the angiogenic factor, vascular endothelial growth factor-A (VEGF-A). eEPC adhesion to fibronectin-coated PAMs (FN-PAMs) was assessed by means of microscopic evaluation and by means of Alamar blue assay. Phospho ERK(1/2) and PARP-1 expression was measured by means of Western blot to assess the survival effects of FN-PAMs releasing VEGF-A (FN-VEGF-PAMs). The Alamar blue assay or a modified Boyden chamber assay was employed to assess proliferative or migratory capacity, respectively. Our data indicate that eEPCs were able to adhere to empty FN-PAMs within a few hours. FN-VEGF-PAMs increased the ability of eEPCs to adhere to them and strongly supported endothelial-like phenotype and cell survival. Moreover, the release of VEGF-A by FN-PAMs stimulated in vitro HUVEC migration and proliferation. These data strongly support the use of PAMs for supporting eEPC growth and survival and for stimulating resident mature human endothelial cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Identification of a Novel Gene Product That Promotes Survival of Mycobacterium smegmatis in Macrophages

    Science.gov (United States)

    Pelosi, Assunta; Smith, Danielle; Brammananth, Rajini; Topolska, Agnieszka; Billman-Jacobe, Helen; Nagley, Phillip

    2012-01-01

    Background Bacteria of the suborder Corynebacterineae include significant human pathogens such as Mycobacterium tuberculosis and M. leprae. Drug resistance in mycobacteria is increasingly common making identification of new antimicrobials a priority. Mycobacteria replicate intracellularly, most commonly within the phagosomes of macrophages, and bacterial proteins essential for intracellular survival and persistence are particularly attractive targets for intervention with new generations of anti-mycobacterial drugs. Methodology/Principal Findings We have identified a novel gene that, when inactivated, leads to accelerated death of M. smegmatis within a macrophage cell line in the first eight hours following infection. Complementation of the mutant with an intact copy of the gene restored survival to near wild type levels. Gene disruption did not affect growth compared to wild type M. smegmatis in axenic culture or in the presence of low pH or reactive oxygen intermediates, suggesting the growth defect is not related to increased susceptibility to these stresses. The disrupted gene, MSMEG_5817, is conserved in all mycobacteria for which genome sequence information is available, and designated Rv0807 in M. tuberculosis. Although homology searches suggest that MSMEG_5817 is similar to the serine:pyruvate aminotransferase of Brevibacterium linens suggesting a possible role in glyoxylate metabolism, enzymatic assays comparing activity in wild type and mutant strains demonstrated no differences in the capacity to metabolize glyoxylate. Conclusions/Significance MSMEG_5817 is a previously uncharacterized gene that facilitates intracellular survival of mycobacteria. Interference with the function of MSMEG_5817 may provide a novel therapeutic approach for control of mycobacterial pathogens by assisting the host immune system in clearance of persistent intracellular bacteria. PMID:22363734

  3. Identification of a novel gene product that promotes survival of Mycobacterium smegmatis in macrophages.

    Directory of Open Access Journals (Sweden)

    Assunta Pelosi

    Full Text Available BACKGROUND: Bacteria of the suborder Corynebacterineae include significant human pathogens such as Mycobacterium tuberculosis and M. leprae. Drug resistance in mycobacteria is increasingly common making identification of new antimicrobials a priority. Mycobacteria replicate intracellularly, most commonly within the phagosomes of macrophages, and bacterial proteins essential for intracellular survival and persistence are particularly attractive targets for intervention with new generations of anti-mycobacterial drugs. METHODOLOGY/PRINCIPAL FINDINGS: We have identified a novel gene that, when inactivated, leads to accelerated death of M. smegmatis within a macrophage cell line in the first eight hours following infection. Complementation of the mutant with an intact copy of the gene restored survival to near wild type levels. Gene disruption did not affect growth compared to wild type M. smegmatis in axenic culture or in the presence of low pH or reactive oxygen intermediates, suggesting the growth defect is not related to increased susceptibility to these stresses. The disrupted gene, MSMEG_5817, is conserved in all mycobacteria for which genome sequence information is available, and designated Rv0807 in M. tuberculosis. Although homology searches suggest that MSMEG_5817 is similar to the serine:pyruvate aminotransferase of Brevibacterium linens suggesting a possible role in glyoxylate metabolism, enzymatic assays comparing activity in wild type and mutant strains demonstrated no differences in the capacity to metabolize glyoxylate. CONCLUSIONS/SIGNIFICANCE: MSMEG_5817 is a previously uncharacterized gene that facilitates intracellular survival of mycobacteria. Interference with the function of MSMEG_5817 may provide a novel therapeutic approach for control of mycobacterial pathogens by assisting the host immune system in clearance of persistent intracellular bacteria.

  4. Ratite oils promote keratinocyte cell growth and inhibit leukocyte activation.

    Science.gov (United States)

    Bennett, Darin C; Leung, Gigi; Wang, Eddy; Ma, Sam; Lo, Blanche K K; McElwee, Kevin J; Cheng, Kimberly M

    2015-09-01

    Traditionally, native Australian aborigines have used emu oil for the treatment of inflammation and to accelerate wound healing. Studies on mice suggest that topically applied emu oil may have anti-inflammatory properties and may promote wound healing. We investigated the effects of ratite oils (6 emu, 3 ostrich, 1 rhea) on immortalized human keratinocytes (HaCaT cells) in vitro by culturing the cells in media with oil concentrations of 0%, 0.5%, and 1.0%. Peking duck, tea tree, and olive oils were used as comparative controls. The same oils at 0.5% concentration were evaluated for their influence on peripheral blood mononuclear cell (PBMC) survival over 48 hr and their ability to inhibit IFNγ production in PBMCs activated by phytohemagglutinin (PHA) in ELISpot assays. Compared to no oil control, significantly shorter population doubling time durations were observed for HaCaT cells cultured in emu oil (1.51×faster), ostrich oil (1.46×faster), and rhea oil (1.64×faster). Tea tree oil demonstrated significant antiproliferative activity and olive oil significantly prolonged (1.35×slower) cell population doubling time. In contrast, almost all oils, particularly tea tree oil, significantly reduced PBMC viability. Different oils had different levels of inhibitory effect on IFNγ production with individual emu, ostrich, rhea, and duck oil samples conferring full inhibition. This preliminary investigation suggests that emu oil might promote wound healing by accelerating the growth rate of keratinocytes. Combined with anti-inflammatory properties, ratite oil may serve as a useful component in bandages and ointments for the treatment of wounds and inflammatory skin conditions. © 2015 Poultry Science Association Inc.

  5. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration.

    Science.gov (United States)

    Chang, Chung-Hsun; Tsai, Wen-Chung; Lin, Miao-Sui; Hsu, Ya-Hui; Pang, Jong-Hwei Su

    2011-03-01

    Pentadecapeptide BPC 157, composed of 15 amino acids, is a partial sequence of body protection compound (BPC) that is discovered in and isolated from human gastric juice. Experimentally it has been demonstrated to accelerate the healing of many different wounds, including transected rat Achilles tendon. This study was designed to investigate the potential mechanism of BPC 157 to enhance healing of injured tendon. The outgrowth of tendon fibroblasts from tendon explants cultured with or without BPC 157 was examined. Results showed that BPC 157 significantly accelerated the outgrowth of tendon explants. Cell proliferation of cultured tendon fibroblasts derived from rat Achilles tendon was not directly affected by BPC 157 as evaluated by MTT assay. However, the survival of BPC 157-treated cells was significantly increased under the H(2)O(2) stress. BPC 157 markedly increased the in vitro migration of tendon fibroblasts in a dose-dependent manner as revealed by transwell filter migration assay. BPC 157 also dose dependently accelerated the spreading of tendon fibroblasts on culture dishes. The F-actin formation as detected by FITC-phalloidin staining was induced in BPC 157-treated fibroblasts. The protein expression and activation of FAK and paxillin were determined by Western blot analysis, and the phosphorylation levels of both FAK and paxillin were dose dependently increased by BPC 157 while the total amounts of protein was unaltered. In conclusion, BPC 157 promotes the ex vivo outgrowth of tendon fibroblasts from tendon explants, cell survival under stress, and the in vitro migration of tendon fibroblasts, which is likely mediated by the activation of the FAK-paxillin pathway.

  6. B-cell lymphoma 6 promotes proliferation and survival of trophoblastic cells.

    Science.gov (United States)

    Muschol-Steinmetz, Cornelia; Jasmer, Britta; Kreis, Nina-Naomi; Steinhäuser, Kerstin; Ritter, Andreas; Rolle, Udo; Yuan, Juping; Louwen, Frank

    2016-01-01

    Preeclampsia is one of the leading causes of maternal and perinatal mortality and morbidity and its pathogenesis is not fully understood. B-cell lymphoma 6 (BCL6), a key regulator of B-lymphocyte development, is altered in preeclamptic placentas. We show here that BCL6 is present in all 3 studied trophoblast cell lines and it is predominantly expressed in trophoblastic HTR-8/SVneo cells derived from a 1(st) trimester placenta, suggestive of its involvement in trophoblast expansion in the early stage of placental development. BCL6 is strongly stabilized upon stress stimulation. Inhibition of BCL6, by administrating either small interfering RNA or a specific small molecule inhibitor 79-6, reduces proliferation and induces apoptosis in trophoblastic cells. Intriguingly, depletion of BCL6 in HTR-8/SVneo cells results in a mitotic arrest associated with mitotic defects in centrosome integrity, indicative of its involvement in mitotic progression. Thus, like in haematopoietic cells and breast cancer cells, BCL6 promotes proliferation and facilitates survival of trophoblasts under stress situation. Further studies are required to decipher its molecular roles in differentiation, migration and the fusion process of trophoblasts. Whether increased BCL6 observed in preeclamptic placentas is one of the causes or the consequences of preeclampsia warrants further investigations in vivo and in vitro.

  7. Lithium promotes DNA stability and survival of ischemic retinal neurocytes by upregulating DNA ligase IV.

    Science.gov (United States)

    Yang, Ying; Wu, Nandan; Tian, Sijia; Li, Fan; Hu, Huan; Chen, Pei; Cai, Xiaoxiao; Xu, Lijun; Zhang, Jing; Chen, Zhao; Ge, Jian; Yu, Keming; Zhuang, Jing

    2016-11-17

    Neurons display genomic fragility and show fragmented DNA in pathological degeneration. A failure to repair DNA breaks may result in cell death or apoptosis. Lithium protects retinal neurocytes following nutrient deprivation or partial nerve crush, but the underlying mechanisms are not well defined. Here we demonstrate that pretreatment with lithium protects retinal neurocytes from ischemia-induced damage and enhances light response in rat retina following ischemia-reperfusion injury. Moreover, we found that DNA nonhomologous end-joining (NHEJ) repair is implicated in this process because in ischemic retinal neurocytes, lithium significantly reduces the number of γ-H2AX foci (well-characterized markers of DNA double-strand breaks in situ) and increases the DNA ligase IV expression level. Furthermore, we also demonstrate that nuclear respiratory factor 1 (Nrf-1) and phosphorylated cyclic AMP-response element binding protein-1 (P-CREB1) bind to ligase IV promoter to cause upregulation of ligase IV in neurocytes. The ischemic upregulation of Nrf-1 and lithium-induced increase of P-CREB1 cooperate to promote transcription of ligase IV. Short hairpin RNAs against Nrf-1 and CREB1 could significantly inhibit the increase in promoter activity and expression of ligase IV observed in the control oligos following lithium treatment in retinal neurocytes. More importantly, ischemic stimulation triggers the expression of ligase IV. Taken together, our results thus reveal a novel mechanism that lithium offers neuroprotection from ischemia-induced damage by enhancing DNA NHEJ repair.

  8. Vasoactive intestinal peptide and nitric oxide promote survival of adult rat myenteric neurons in culture

    DEFF Research Database (Denmark)

    Sandgren, Katarina; Lin, Zhong; Svenningsen, Åsa Fex

    2003-01-01

    adaptation. The aim of this study was to evaluate whether VIP and nitric oxide (NO) influence survival of cultured, dissociated myenteric neurons. Neuronal survival was evaluated after 0, 4, and 8 days in culture. Influence of VIP and NO on neuronal survival was examined after culturing in the presence...

  9. The Typhoid Toxin Promotes Host Survival and the Establishment of a Persistent Asymptomatic Infection

    DEFF Research Database (Denmark)

    Del Bel Belluz, Lisa; Guidi, Riccardo; Pateras, Ioannis S.

    2016-01-01

    analysis confirmed the toxin-mediated suppression of the intestinal inflammatory response. The presence of a functional typhoid toxin further induced an increased frequency of asymptomatic carriers. Our data indicate that the typhoid toxin DNA damaging activity increases host survival and favours long......Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of these effectors during the course of infection remains poorly characterized. To address...... this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine infection. Immunocompetent mice were infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium) strains, encoding either a functional or an inactive typhoid toxin...

  10. Tick-borne pathogens induce differential expression of genes promoting cell survival and host resistance in Ixodes ricinus cells.

    Science.gov (United States)

    Mansfield, Karen L; Cook, Charlotte; Ellis, Richard J; Bell-Sakyi, Lesley; Johnson, Nicholas; Alberdi, Pilar; de la Fuente, José; Fooks, Anthony R

    2017-02-15

    There has been an emergence and expansion of tick-borne diseases in Europe, Asia and North America in recent years, including Lyme disease, tick-borne encephalitis and human anaplasmosis. The primary vectors implicated are hard ticks of the genus Ixodes. Although much is known about the host response to these bacterial and viral pathogens, there is limited knowledge of the cellular responses to infection within the tick vector. The bacterium Anaplasma phagocytophilum is able to bypass apoptotic processes in ticks, enabling infection to proceed. However, the tick cellular responses to infection with the flaviviruses tick-borne encephalitis virus (TBEV) and louping ill virus (LIV), which cause tick-borne encephalitis and louping ill respectively, are less clear. Infection and transcriptional analysis of the Ixodes ricinus tick cell line IRE/CTVM20 with the viruses LIV and TBEV, and the bacterium A. phagocytophilum, identified activation of common and distinct cellular pathways. In particular, commonly-upregulated genes included those that modulate apoptotic pathways, putative anti-pathogen genes, and genes that influence the tick innate immune response, including selective activation of toll genes. These data provide an insight into potential key genes involved in the tick cellular response to viral or bacterial infection, which may promote cell survival and host resistance.

  11. Hair Growth Promotion Activity and Its Mechanism of Polygonum multiflorum

    OpenAIRE

    Yunfei Li; Mingnuan Han; Pei Lin; Yanran He; Jie Yu; Ronghua Zhao

    2015-01-01

    Polygonum multiflorum Radix (PMR) has long history in hair growth promotion and hair coloring in clinical applications. However, several crucial problems in its clinic usage and mechanisms are still unsolved or lack scientific evidences. In this research, C57BL/6J mice were used to investigate hair growth promotion activity and possible mechanism of PMR and Polygonum multiflorum Radix Preparata (PMRP). Hair growth promotion activities were investigated by hair length, hair covered skin ratio,...

  12. TNF-α promotes survival and migration of MSCs under oxidative stress via NF-κB pathway to attenuate intimal hyperplasia in vein grafts.

    Science.gov (United States)

    Bai, Xiao; Xi, Jie; Bi, Yanwen; Zhao, Xin; Bing, Weidong; Meng, Xiangbin; Liu, Yimin; Zhu, Zhonglai; Song, Guangmin

    2017-09-01

    The oxidative stress caused by endothelial injury is involved in intimal hyperplasia (IH) in vein grafts. Mesenchymal stem cells (MSCs) can home to injured intima and promote endothelial repair. However, MSC apoptosis is increased accompanied by decreased functional activity under oxidative stress. Thus, we investigate whether tumour necrosis factor-α (TNF-α) can promote the survival and activity of MSCs under oxidative stress to reduce IH more effectively, and establish what role the NF-κB pathway plays in this. In this study, we preconditioned MSCs with TNF-α ( TNF -α-PC MSCs) for 24 hrs and measured the activation of the IKK/NF-κB pathway. EdU and transwell assays were performed to assess proliferation and migration of TNF -α-PC MSCs. Apoptosis and migration of TNF -α- PC MSCs were evaluated in conditions of oxidative stress by analysis of the expression of Bcl-2 and CXCR4 proteins. TNF -α- PC MSCs were transplanted into a vein graft model, so that cell homing could be tracked, and endothelial apoptosis and IH of vein grafts were measured. The results demonstrated that TNF-α promotes proliferation and migration of MSCs. Furthermore, survival and migration of TNF -α- PC MSCs under oxidative stress were both enhanced. A greater number of MSCs migrated to the intima of vein grafts after preconditioning with TNF-α, and the formation of neointima was significantly reduced. These effects could be partially abolished by IKK XII (NF-κB inhibitor). All these results indicate that preconditioning with TNF-α can promote survival and migration of MSCs under oxidative stress via the NF-κB pathway and thus attenuate IH of vein grafts. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. Hypotonic swelling-induced activation of PKN1 mediates cell survival in cardiac myocytes

    Science.gov (United States)

    Kajimoto, Katsuya; Shao, Dan; Takagi, Hiromitsu; Maceri, Gregorio; Zablocki, Daniela; Mukai, Hideyuki; Ono, Yoshitaka

    2011-01-01

    Hypotonic cell swelling in the myocardium is induced by pathological conditions, including ischemia-reperfusion, and affects the activities of ion transporters/channels and gene expression. However, the signaling mechanism activated by hypotonic stress (HS) is not fully understood in cardiac myocytes. A specialized protein kinase cascade, consisting of Pkc1 and MAPKs, is activated by HS in yeast. Here, we demonstrate that protein kinase N1 (PKN1), a serine/threonine protein kinase and a homolog of Pkc1, is activated by HS (67% osmolarity) within 5 min and reaches peak activity at 60 min in cardiac myocytes. Activation of PKN1 by HS was accompanied by Thr774 phosphorylation and concomitant activation of PDK1, a potential upstream regulator of PKN1. HS also activated RhoA, thereby increasing interactions between PKN1 and RhoA. PP1 (10−5 M), a selective Src family tyrosine kinase inhibitor, significantly suppressed HS-induced activation of RhoA and PKN1. Constitutively active PKN1 significantly increased the transcriptional activity of Elk1-GAL4, an effect that was inhibited by dominant negative MEK. Overexpression of PKN1 significantly increased ERK phosphorylation, whereas downregulation of PKN1 inhibited HS-induced ERK phosphorylation. Downregulation of PKN1 and inhibition of ERK by U-0126 both significantly inhibited the survival of cardiac myocytes in the presence of HS. These results suggest that a signaling cascade, consisting of Src, RhoA, PKN1, and ERK, is activated by HS, thereby promoting cardiac myocyte survival. PMID:21037231

  14. Gastrin activates autophagy and increases migration and survival of gastric adenocarcinoma cells.

    Science.gov (United States)

    Rao, Shalini V; Solum, Guri; Niederdorfer, Barbara; Nørsett, Kristin G; Bjørkøy, Geir; Thommesen, Liv

    2017-01-21

    The peptide hormone gastrin exerts a growth-promoting effect in both normal and malignant gastrointestinal tissue. Gastrin mediates its effect via the cholecystokinin 2 receptor (CCKBR/CCK2R). Although a substantial part of the gastric adenocarcinomas express gastrin and CCKBR, the role of gastrin in tumor development is not completely understood. Autophagy has been implicated in mechanisms governing cytoprotection, tumor growth, and contributes to chemoresistance. This study explores the role of autophagy in response to gastrin in gastric adenocarcinoma cell lines. Immunoblotting, survival assays and the xCELLigence system were used to study gastrin induced autophagy. Chemical inhibitors of autophagy were utilized to assess the role of this process in the regulation of cellular responses induced by gastrin. Further, knockdown studies using siRNA and immunoblotting were performed to explore the signaling pathways that activate autophagy in response to gastrin treatment. We demonstrate that gastrin increases the expression of the autophagy markers MAP1LC3B-II and SQSTM1 in gastric adenocarcinoma cells. Gastrin induces autophagy via activation of the STK11-PRKAA2-ULK1 and that this signaling pathway is involved in increased migration and cell survival. Furthermore, gastrin mediated increase in survival of cells treated with cisplatin is partially dependent on induced autophagy. This study reveals a novel role of gastrin in the regulation of autophagy. It also opens up new avenues in the treatment of gastric cancer by targeting CCKBR mediated signaling and/or autophagy in combination with conventional cytostatic drugs.

  15. Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Diez Soraya

    2010-03-01

    expression of Wnt-11 promoted LNCaP cell invasion. Conclusions These observations suggest that the increased level of Wnt-11 found in prostate cancer contributes to tumour progression by promoting NED, tumour cell survival and cell migration/invasion, and may provide an opportunity for novel therapy in prostate cancer.

  16. Spliced XBP1 promotes macrophage survival and autophagy by interacting with Beclin-1

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Ping-Ge [Southern Medical University, Guangzhou, Guangdong 510515 (China); Jiang, Zhi-Xin [Centre Laboratory, The 305th Hospital of the People' s Liberation Army, Beijing 100017 (China); Li, Jian-Hua [Department of Geriatric Cardiology, Chinese PLA General Hosptial, Beijing 100853 (China); Zhou, Zhe, E-mail: zhouzhe76@126.com [Laboratory of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Zhang, Qing-Hua, E-mail: 1056055170@qq.com [Department of Cardiology, The 305th Hospital of the People' s Liberation Army, Beijing 100017 (China)

    2015-08-07

    Macrophage autophagy plays an important role in the development of atherosclerosis, but the precise mechanism mediating this process is unclear. The potential role of the X-box binding protein 1 (XBP1), a crucial transduction factor that is involved in endoplasmic reticulum stress and the unfolded protein response, in bone marrow-derived macrophage autophagy is unknown. This study mainly explores the roles of XBP1 mRNA splicing in bone marrow-derived macrophage autophagy. The present study shows that the transient overexpression of spliced XBP1 via adenovirus-mediated gene transfer induces autophagy and promotes proliferation in bone marrow-derived macrophages via the down-regulation of Beclin-1, but that the sustained overexpression of spliced XBP1 leads to apoptosis. When XBP1 is down-regulated in bone marrow-derived macrophages using siRNA, rapamycin-induced autophagosome formation is ablated. Furthermore, we have detected the overexpression of XBP1 in areas of atherosclerotic plaques in the arteries of ApoE−/− mice. These results demonstrate that XBP1 mRNA splicing plays an important role in maintaining the function of bone marrow-derived macrophages and provide new insight into the study and treatment of atherosclerosis. - Highlights: • XBP1 was up-regulated in atherosclerotic plaques of ApoE−/− mice. • Transient spliced XBP1 overexpression induced macrophages autophagy via Beclin-1. • Sustained spliced XBP1 overexpression triggered macrophages apoptosis. • Spliced XBP1 plays a key role in maintaining the macrophages survival.

  17. Dennexin peptides modeled after the homophilic binding sites of the neural cell adhesion molecule (NCAM) promote neuronal survival, modify cell adhesion and impair spatial learning

    DEFF Research Database (Denmark)

    Køhler, Lene B; Christensen, Claus; Rossetti, Clara

    2010-01-01

    Neural cell adhesion molecule (NCAM)-mediated cell adhesion results in activation of intracellular signaling cascades that lead to cellular responses such as neurite outgrowth, neuronal survival, and modulation of synaptic activity associated with cognitive processes. The crystal structure...... of the immunoglobulin (Ig) 1-2-3 fragment of the NCAM ectodomain has revealed novel mechanisms for NCAM homophilic adhesion. The present study addressed the biological significance of the so called dense zipper formation of NCAM. Two peptides, termed dennexinA and dennexinB, were modeled after the contact interfaces...... between Ig1 and Ig3 and between Ig2 and Ig2, respectively, observed in the crystal structure. Although the two dennexin peptides differed in amino acid sequence, they both modulated cell adhesion, reflected by inhibition of NCAM-mediated neurite outgrowth. Both dennexins also promoted neuronal survival...

  18. HBx regulates fatty acid oxidation to promote hepatocellular carcinoma survival during metabolic stress.

    Science.gov (United States)

    Wang, Ming-Da; Wu, Han; Huang, Shuai; Zhang, Hui-Lu; Qin, Chen-Jie; Zhao, Ling-Hao; Fu, Gong-Bo; Zhou, Xu; Wang, Xian-Ming; Tang, Liang; Wen, Wen; Yang, Wen; Tang, Shan-Hua; Cao, Dan; Guo, Lin-Na; Zeng, Min; Wu, Meng-Chao; Yan, He-Xin; Wang, Hong-Yang

    2016-02-09

    Due to a high rate of nutrient consumption and inadequate vascularization, hepatocellular carcinoma (HCC) cells constantly undergo metabolic stress during tumor development. Hepatitis B virus (HBV) X protein (HBx) has been implicated in the pathogenesis of HBV-induced HCC. In this study, we investigated the functional roles of HBx in HCC adaptation to metabolic stress. Up-regulation of HBx increased the intracellular ATP and NADPH generation, and induced the resistance to glucose deprivation, whereas depletion of HBx via siRNA abolished these effects and conferred HCC cells sensitive to glucose restriction. Though HBx did not affect the glycolysis and oxidative phosphorylation capacity of HCC cells under normal culture conditions, it facilitated fatty acid oxidation (FAO) in the absence of glucose, which maintained NADPH and ATP levels. Further investigation showed that HBx expression, under glucose deprivation, stimulated phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) via a calcium/CaMKK-dependent pathway, which was required for the activation of FAO. Conversely, inhibition of FAO by etomoxir (ETO) restored the sensitivity of HBx-expressing cells to glucose deficiency in vitro and retarded xenograft tumor formation in vivo. Finally, HBx-induced activation of the AMPK and FAO pathways were also observed in xenograft tumors and HBV-associated HCC specimens. Our data suggest that HBx plays a key role in the maintenance of redox and energy homeostasis by activating FAO, which is critical for HCC cell survival under conditions of metabolic stress and might be exploited for therapeutic benefit.

  19. Classic Ras Proteins Promote Proliferation and Survival Via Distinct Phosphoproteome Alterations in Neurofibromin-Null Malignant Peripheral Nerve Sheath Tumor Cells

    Science.gov (United States)

    Brossier, Nicole M.; Prechtl, Amanda M.; Longo, Jody Fromm; Barnes, Stephen; Wilson, Landon S.; Byer, Stephanie J.; Brosius, Stephanie N.; Carroll, Steven L.

    2015-01-01

    Neurofibromin, the tumor suppressor encoded by the neurofibromatosis type 1 (NF1) gene, potentially suppresses the activation of H-Ras, N-Ras and K-Ras. However, it is not known whether these classic Ras proteins are hyperactivated in NF1-null nerve sheath tumors, how they contribute to tumorigenesis and what signaling pathways mediate their effects. Here we show that H-Ras, N-Ras and K-Ras are coexpressed with their activators, (guanine nucleotide exchange factors), in neurofibromin-null malignant peripheral nerve sheath tumor (MPNST) cells and that all 3 Ras proteins are activated. Dominant negative (DN) H-Ras, a pan-inhibitor of the classic Ras family, inhibited MPNST proliferation and survival, but not migration. However, NF1-null MPNST cells were variably dependent on individual Ras proteins. In some lines, ablation of H-Ras, N-Ras and/or K-Ras inhibited mitogenesis. In others, ablation of a single Ras protein had no effect on proliferation; in these lines, ablation of a single Ras protein resulted in compensatory increases in the activation and/or expression of other Ras proteins. Using mass spectrometry-based phosphoproteomics, we identified 7 signaling networks affecting morphology, proliferation and survival that are regulated by DN H-Ras. Thus, neurofibromin loss activates multiple classic Ras proteins that promote proliferation and survival by regulating several distinct signaling cascades. PMID:25946318

  20. Promoting Physical Activity in Primary Care: Overcoming the barriers

    OpenAIRE

    Singer, Joel; Lindsay, Elizabeth A.; Wilson, Douglas M.C.

    1991-01-01

    The principle barriers preventing health care professionals from promoting physical activity include an incomplete understanding of the evidence linking physical activity and health, difficulty in translating research findings into a feasible and efficacious clinical intervention, resistance to adopting a preventive orientation, and concerns about the risks of physical activity. Low level activities likely provide benefit with little risk.

  1. Physical Activity Promotion, Beliefs, and Barriers Among Australasian Oncology Nurses.

    Science.gov (United States)

    Keogh, Justin W L; Pühringer, Petra; Olsen, Alicia; Sargeant, Sally; Jones, Lynnette M; Climstein, Mike

    2017-03-01

    To describe the physical activity (PA) promotion practices, beliefs, and barriers of Australasian oncology nurses and gain preliminary insight into how PA promotion practices may be affected by the demographics of the nurses.
. Cross-sectional survey.
. Australia and New Zealand.
. 119 registered oncology nurses.
. Self-reported online survey completed once per participant.
. Questions assessed the PA promotion beliefs (e.g., primary healthcare professionals responsible for PA promotion, treatment stage), PA benefits (e.g., primary benefits, evidence base), and PA promotion barriers of oncology nurses.
. Oncology nurses believed they were the major providers of PA advice to their patients. They promoted PA prior to, during, and post-treatment. The three most commonly cited benefits of PA for their patients were improved quality of life, mental health, and activities of daily living. Lack of time, lack of adequate support structures, and risk to patient were the most common barriers to PA promotion. Relatively few significant differences in the oncology nurses' PA promotion practices, beliefs, and barriers were observed based on hospital location or years of experience.
. Despite numerous barriers, Australasian oncology nurses wish to promote PA to their patients with cancer across multiple treatment stages because they believe PA is beneficial for their patients.
. Hospitals may need to better support oncology nurses in promoting PA to their patients and provide better referral pathways to exercise physiologists and physiotherapists.

  2. Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury

    Science.gov (United States)

    2017-09-01

    This application proposes to help improve survival, decrease early dependence on mechanical ventilation, and restore breathing after cervical spinal...complications. This application proposes to help improve survival, decrease early dependence on mechanical ventilation, and restore breathing after...training as cervical SCI is a complicated and difficult surgery and much practice is needed in order to produce consistent injury outcomes

  3. Promote Physical Activity--It's Proactive Guidance

    Science.gov (United States)

    Gartrell, Dan; Sonsteng, Kathleen

    2008-01-01

    Healthy child development relies on physical activity. New curriculum models are effectively integrating physical activity in education programs. The authors describe three such models: S.M.A.R.T. (Stimulating Maturity through Accelerated Readiness Training); Kids in Action, incorporating cardiovascular endurance, muscle strength and endurance,…

  4. Promoting Physical Activity in Afterschool Programs

    Science.gov (United States)

    Beighle, Aaron; Beets, Michael W.; Erwin, Heather E.; Huberty, Jennifer; Moore, Justin B.; Stellino, Megan

    2010-01-01

    Children in the United States are not engaging in sufficient amounts of routine physical activity, and this lack is an emerging public health concern (Strong, Malina, Blimkie, Daniels, Dishman, Gutin, et al., 2005). Efforts to increase the physical activity levels of children and adolescents has become a national priority, attracting attention…

  5. RpoE promotes invasion and intracellular survival by regulating SPI-1 and SPI-2 in Salmonella enterica serovar Typhi.

    Science.gov (United States)

    Zhang, Haifang; Jia, Yanwei; Xie, Xiaofang; Wang, Min; Zheng, Yi; Xu, Shungao; Zhang, Wei; Wang, Qiang; Huang, Xinxiang; Du, Hong

    2016-08-01

    To demonstrate the role of RpoE during the later stage of hyperosmotic stress in Salmonella. Expressions of SPI-1 and SPI-2 under hyperosmotic stress for 120 min were investigated by a microarray, and the invasion and intracellular survival of wild-type and ΔrpoE strains were compared. The global differential expression of bacterial proteins between the wild-type and ΔrpoE strains was examined after 120 min of hyperosmotic stress. SPI-1 and SPI-2 were repressed, and the invasion and intracellular survival were defected in the ΔrpoE strain. Thirteen bacterial-associated proteins and 11 secreted proteins differed significantly between the wild-type and ΔrpoE strains. RpoE may promote invasion and intracellular survival by regulating the expression of SPI-1 and SPI-2.

  6. Bacterial genotoxin functions as immune-modulator and promotes host survival

    Directory of Open Access Journals (Sweden)

    Riccardo Guidi

    2016-07-01

    Full Text Available Bacterial genotoxins are effectors that cause DNA damage in target cells. Many aspects of the biology of these toxins have been characterised in vitro, such as structure, cellular internalisation pathways and effects on the target cells. However, little is known about their function in vivo. Salmonella enterica serovar Typhi (S. Typhi is a Gram-negative, intracellular bacterium that causes typhoid fever, a debilitating disease infecting more than 20 million people every year. S. Typhi produce a genotoxin named typhoid toxin (TT, but its role in the contest of host infection is poorly characterized. The major obstacle in addressing this issue is that S. Typhi is exclusively a human pathogen. To overcome this limitation, we have used as model bacterium S. Typhimurium, and engineered it to produce endogenous levels of an active and inactive typhoid toxin, hereby named as TT (or genotoxic and cdtB (or control, respectively. To our surprise, infection with the genotoxin strain strongly suppressed intestinal inflammation, leading to a better survival of the host during the acute phase of infection, suggesting typhoid toxin may exert a protective role. The presence of a functional genotoxin was also associated with an increased frequency of asymptomatic carriers.

  7. Physical Activity Promotion in Call Centres: Employers' Perspectives

    Science.gov (United States)

    Renton, Sheila J.; Lightfoot, Nancy E.; Maar, Marion A.

    2011-01-01

    This study followed a predominantly qualitative approach to explore the perspectives of employers in Sudbury, Ontario, Canada, call centres (CCs) regarding physical activity (PA) promotion in workplaces, by identifying current practices and employers' motivation to promote PA, as well as perceived facilitators and barriers. In-depth interviews…

  8. Stress-induced nuclear RNA degradation pathways regulate yeast bromodomain factor 2 to promote cell survival.

    Directory of Open Access Journals (Sweden)

    Kevin Roy

    2014-09-01

    Full Text Available Bromodomain proteins are key regulators of gene expression. How the levels of these factors are regulated in specific environmental conditions is unknown. Previous work has established that expression of yeast Bromodomain factor 2 (BDF2 is limited by spliceosome-mediated decay (SMD. Here we show that BDF2 is subject to an additional layer of post-transcriptional control through RNase III-mediated decay (RMD. We found that the yeast RNase III Rnt1p cleaves a stem-loop structure within the BDF2 mRNA to down-regulate its expression. However, these two nuclear RNA degradation pathways play distinct roles in the regulation of BDF2 expression, as we show that the RMD and SMD pathways of the BDF2 mRNA are differentially activated or repressed in specific environmental conditions. RMD is hyper-activated by salt stress and repressed by hydroxyurea-induced DNA damage while SMD is inactivated by salt stress and predominates during DNA damage. Mutations of cis-acting signals that control SMD and RMD rescue numerous growth defects of cells lacking Bdf1p, and show that SMD plays an important role in the DNA damage response. These results demonstrate that specific environmental conditions modulate nuclear RNA degradation pathways to control BDF2 expression and Bdf2p-mediated gene regulation. Moreover, these results show that precise dosage of Bromodomain factors is essential for cell survival in specific environmental conditions, emphasizing their importance for controlling chromatin structure and gene expression in response to environmental stress.

  9. Stress-Induced Nuclear RNA Degradation Pathways Regulate Yeast Bromodomain Factor 2 to Promote Cell Survival

    Science.gov (United States)

    Roy, Kevin; Chanfreau, Guillaume

    2014-01-01

    Bromodomain proteins are key regulators of gene expression. How the levels of these factors are regulated in specific environmental conditions is unknown. Previous work has established that expression of yeast Bromodomain factor 2 (BDF2) is limited by spliceosome-mediated decay (SMD). Here we show that BDF2 is subject to an additional layer of post-transcriptional control through RNase III-mediated decay (RMD). We found that the yeast RNase III Rnt1p cleaves a stem-loop structure within the BDF2 mRNA to down-regulate its expression. However, these two nuclear RNA degradation pathways play distinct roles in the regulation of BDF2 expression, as we show that the RMD and SMD pathways of the BDF2 mRNA are differentially activated or repressed in specific environmental conditions. RMD is hyper-activated by salt stress and repressed by hydroxyurea-induced DNA damage while SMD is inactivated by salt stress and predominates during DNA damage. Mutations of cis-acting signals that control SMD and RMD rescue numerous growth defects of cells lacking Bdf1p, and show that SMD plays an important role in the DNA damage response. These results demonstrate that specific environmental conditions modulate nuclear RNA degradation pathways to control BDF2 expression and Bdf2p-mediated gene regulation. Moreover, these results show that precise dosage of Bromodomain factors is essential for cell survival in specific environmental conditions, emphasizing their importance for controlling chromatin structure and gene expression in response to environmental stress. PMID:25232960

  10. Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

    Science.gov (United States)

    Gu, Lintao; Cui, Xinhua; Wei, Wei; Yang, Jia; Li, Xuezhong

    2017-11-15

    Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Does bedding promote pine survival and growth on ditched wet sands?

    Science.gov (United States)

    Ralph A. Klawitter

    1970-01-01

    Results from a study of prepared beds for planting slash pine on a wet sandy flat in Florida were inconclusive. Early growth was improved, but survival was not; and differences between a bedded site and an unbedded site were slight.

  12. Action of glucocorticoids on survival of nerve cells : Promoting neurodegeneration or neuroprotection?

    NARCIS (Netherlands)

    Abraham, I.; Harkany, T.; Horvath, K.M.; Luiten, P.G.M.

    Extensive studies during the past decades provided compelling evidence that glucocorticoids (GCs) have the potential to affect the development, survival and death of neurones. These observations, however, reflect paradoxical features of GCs, as they may be critically involved in both

  13. Promoting moderate-vigorous physical activity in overweight minority girls

    Science.gov (United States)

    There is limited research on the types of activities that are most effective for promoting moderate-vigorous physical activity (MVPA) in children. The purpose of this study was to assess which types of activities elicit MVPA in overweight minority girls. The sample consisted of 31 overweight Latina ...

  14. Proteomic analysis reveals the mechanisms of Mycena dendrobii promoting transplantation survival and growth of tissue culture seedlings of Dendrobium officinale.

    Science.gov (United States)

    Xu, X B; Ma, X Y; Lei, H H; Song, H M; Ying, Q C; Xu, M J; Liu, S B; Wang, H Z

    2015-06-01

    Dendrobium officinale is an important traditional Chinese medicinal herb. Its seedlings generally show low survival and growth when transferred from in vitro tissue culture to a greenhouse or field environment. In this study, the effect of Mycena dendrobii on the survival and growth of D. officinale tissue culture seedlings and the mechanisms involved was explored. Mycena dendrobii were applied underneath the roots of D. officinale tissue culture seedlings. The seedling survival and growth were analysed. The root proteins induced by M. dendrobii were identified using two-dimensional (2-D) electrophoresis and matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF-MS). Mycena dendrobii treatment significantly enhanced survival and growth of D. officinale seedlings. Forty-one proteins induced by M. dendrobii were identified. Among them, 10 were involved in defence and stress response, two were involved in the formation of root or mycorrhizae, and three were related to the biosynthesis of bioactive constituents. These results suggest that enhancing stress tolerance and promoting new root formation induced by M. dendrobii may improve the survival and growth of D. officinale tissue culture seedlings. This study provides a foundation for future use of M. dendrobii in the large-scale cultivation of Dendrobiums. © 2015 The Society for Applied Microbiology.

  15. ROLE AND IMPORTANCE OF PROMOTIONAL ACTIVITIES IN RESTAURANT BUSINESS

    Directory of Open Access Journals (Sweden)

    Ivica Batinić

    2014-07-01

    Full Text Available Modern restaurant business, as part of a catering business, offers a variety of meals and beverages in restaurants and various related facilities. Promotional activities play a very important role in managing a restaurant and related facilities, because any serious restaurant facility must take all the necessary and effective measures in order to maintain regular guests and approach potential new guests. In this paper, I will write about conceptualizing restaurant business and elementary business systems in restaurant business. In a separate part, I will write about conceptualizing promotions and promotional activities as important factors in achieving better and more efficient communication of restaurants with regular and potential guests.

  16. Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival

    KAUST Repository

    Lambert, Hélène Perreten

    2014-09-18

    Brain activity is energetically costly and requires a steady and highly regulated flow of energy equivalents between neural cells. It is believed that a substantial share of cerebral glucose, the major source of energy of the brain, will preferentially be metabolized in astrocytes via aerobic glycolysis. The aim of this study was to evaluate whether uncoupling proteins (UCPs), located in the inner membrane of mitochondria, play a role in setting up the metabolic response pattern of astrocytes. UCPs are believed to mediate the transmembrane transfer of protons, resulting in the uncoupling of oxidative phosphorylation from ATP production. UCPs are therefore potentially important regulators of energy fluxes. The main UCP isoforms expressed in the brain are UCP2, UCP4, and UCP5. We examined in particular the role of UCP4 in neuron-astrocyte metabolic coupling and measured a range of functional metabolic parameters including mitochondrial electrical potential and pH, reactive oxygen species production, NAD/NADH ratio, ATP/ADP ratio, CO2 and lactate production, and oxygen consumption rate. In brief, we found that UCP4 regulates the intramitochondrial pH of astrocytes, which acidifies as a consequence of glutamate uptake, with the main consequence of reducing efficiency of mitochondrial ATP production. The diminished ATP production is effectively compensated by enhancement of glycolysis. This nonoxidative production of energy is not associated with deleterious H2O2 production. We show that astrocytes expressing more UCP4 produced more lactate, which is used as an energy source by neurons, and had the ability to enhance neuronal survival.

  17. Bisphenol a promotes cell survival following oxidative DNA damage in mouse fibroblasts.

    Directory of Open Access Journals (Sweden)

    Natalie R Gassman

    Full Text Available Bisphenol A (BPA is a biologically active industrial chemical used in production of consumer products. BPA has become a target of intense public scrutiny following concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer. Recent studies link BPA with the generation of reactive oxygen species, and base excision repair (BER is responsible for removing oxidatively induced DNA lesions. Yet, the relationship between BPA and BER has yet to be examined. Further, the ubiquitous nature of BPA allows continuous exposure of the human genome concurrent with the normal endogenous and exogenous insults to the genome, and this co-exposure may impact the DNA damage response and repair. To determine the effect of BPA exposure on base excision repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO3 or laser irradiation as oxidative damaging agents. In experiments with KBrO3, co-treatment with BPA partially reversed the KBrO3-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA. The improvement in cell survival and the increase in oxidatively induced DNA base lesions were reminiscent of previous results with alkyl adenine DNA glycosylase-deficient cells, suggesting that BPA may prevent initiation of repair of oxidized base lesions. With laser irradiation-induced DNA damage, treatment with BPA suppressed DNA repair as revealed by several indicators. These results are consistent with the hypothesis that BPA can induce a suppression of oxidized base lesion DNA repair by the base excision repair pathway.

  18. Promoter Hypermethylation Profiling Identifies Subtypes of Head and Neck Cancer with Distinct Viral, Environmental, Genetic and Survival Characteristics.

    Directory of Open Access Journals (Sweden)

    Javed Hussain Choudhury

    Full Text Available Epigenetic and genetic alteration plays a major role to the development of head and neck squamous cell carcinoma (HNSCC. Consumption of tobacco (smoking/chewing and human papilloma virus (HPV are also associated with an increase the risk of HNSCC. Promoter hypermethylation of the tumor suppression genes is related with transcriptional inactivation and loss of gene expression. We investigated epigenetic alteration (promoter methylation of tumor-related genes/loci in tumor tissues in the context of genetic alteration, viral infection, and tobacco exposure and survival status.The study included 116 tissue samples (71 tumor and 45 normal tissues from the Northeast Indian population. Methylation specific polymerase chain reaction (MSP was used to determine the methylation status of 10 tumor-related genes/loci (p16, DAPK, RASSF1, BRAC1, GSTP1, ECAD, MLH1, MINT1, MINT2 and MINT31. Polymorphisms of CYP1A1, GST (M1 & T1, XRCC1and XRCC2 genes were studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and multiplex-PCR respectively.Unsupervised hierarchical clustering analysis based on methylation pattern had identified two tumor clusters, which significantly differ by CpG island methylator phenotype (CIMP, tobacco, GSTM1, CYP1A1, HPV and survival status. Analyzing methylation of genes/loci individually, we have found significant higher methylation of DAPK, RASSF1, p16 and MINT31 genes (P = 0.031, 0.013, 0.031 and 0.015 respectively in HPV (+ cases compared to HPV (-. Furthermore, a CIMP-high and Cluster-1 characteristic was also associated with poor survival.Promoter methylation profiles reflecting a correlation with tobacco, HPV, survival status and genetic alteration and may act as a marker to determine subtypes and patient outcome in HNSCC.

  19. IL-15 expression on RA synovial fibroblasts promotes B cell survival.

    Directory of Open Access Journals (Sweden)

    Marta Benito-Miguel

    Full Text Available INTRODUCTION: The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib IL-15 expression on B cell survival. METHODS: Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. RESULTS: RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/-8% (p<0.001. IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/-6% (p<0.05. Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. CONCLUSION: IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains.

  20. Characterization of Helicobacter pylori sigma54 promoter-binding activity.

    Science.gov (United States)

    Pereira, Lara E; Brahmachary, Priyanka; Hoover, Timothy R

    2006-06-01

    Several Helicobacter pylori flagellar genes require sigma(54) for their transcription. Predicted H. pylori sigma(54)-dependent promoters display a preference for A at position -23 instead of C or T as occurs in promoters from most other bacteria. Substitution of the A at position -23 of the H. pylori flaB promoter with a C did not effect expression of a flaB'-'xylE reporter gene in H. pylori, whereas T or G substitutions at this position drastically reduced expression. Results of gel mobility shift assays that used DNA probes corresponding to core promoter sequences and a H. pylori sigma(54) protein fused to the Escherichia coli maltose-binding protein suggested that H. pylori sigma(54) has a higher affinity for promoters with an A at the -23 position. The failure to observe an effect on expression for the flaB mutant promoter with the A to C substitution at the -23 position indicates that sequences flanking the core promoter region may assist binding of H. pylori sigma(54) to the mutant flaB promoter. Alternatively, H. pylori RNA polymerase or the sigma(54)-dependent activator FlgR may compensate for the reduced affinity of sigma(54) for the mutant flaB promoter.

  1. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

    Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...... RNA polymerase II-transcribed genes use specialized termination mechanisms to maintain high transcription levels....

  2. The promotion of phisical activity in shockvertising campaigns

    OpenAIRE

    Widawska-Stanisz Agnieszka; Sowier-Kasprzyk Izabella

    2017-01-01

    Preferring passive life style and the problems with obesity eventuating from this fact, have become very common in many countries. According to research, the physical activity of Poles turns out to be under the average for EU countries. (Sport activity of Poles, 2015, p.3) The promotion of physical activity is one of the most important tasks of public health. The publicity of physical activity, habits of caring for health and wellbeing should be realized by national and local authorities, med...

  3. Utilizing elderly free time activities : a study of activities that promote health and wellbeing

    OpenAIRE

    Mbuthia, Ruth Muthoni; Bambot, Gildas

    2011-01-01

    The aim of this study is to investigate free time activities that can promote health and wellbeing among hospitalized elderly people in order to provide information to caregivers. The research questions are: Which activities at free time promote health and wellbeing among hospitalized elderly people from caregivers’ point of view? How do activities at free time promote health and wellbeing among hospitalized elderly people from caregivers’ point of view? Which type of activities can long term...

  4. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) promotes lung fibroblast proliferation, survival and differentiation to myofibroblasts.

    Science.gov (United States)

    Hasaneen, Nadia A; Cao, Jian; Pulkoski-Gross, Ashleigh; Zucker, Stanley; Foda, Hussein D

    2016-02-17

    Idiopathic pulmonary fibrosis (IPF) is a chronic progressively fatal disease. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) is a glycosylated transmembrane protein that induces the expression of some matrix metalloproteinase (MMP) in neighboring stromal cells through direct epithelial-stromal interactions. EMMPRIN is highly expressed in type II alveolar epithelial cells at the edges of the fibrotic areas in IPF lung sections. However, the exact role of EMMPRIN in IPF is unknown. To determine if EMMPRIN contributes to lung fibroblast proliferation, resistance to apoptosis, and differentiation to myofibroblasts, normal Human lung fibroblasts (NHLF) transiently transfected with either EMMPRIN/GFP or GFP were treated with TGF- β1 from 0 to 10 ng/ml for 48 h and examined for cell proliferation (thymidine incorporation), apoptosis (FACS analysis and Cell Death Detection ELISA assay), cell migration (Modified Boyden chamber) and differentiation to myofibroblasts using Western blot for α-smooth actin of cell lysates. The effect of EMMPRIN inhibition on NHLF proliferation, apoptosis, migration and differentiation to myofibroblasts after TGF- β1 treatment was examined using EMMPRIN blocking antibody. We examined the mechanism by which EMMPRIN induces its effects on fibroblasts by studying the β-catenin/canonical Wnt signaling pathway using Wnt luciferase reporter assays and Western blot for total and phosphorylated β-catenin. Human lung fibroblasts overexpressing EMMPRIN had a significant increase in cell proliferation and migration compared to control fibroblasts. Furthermore, EMMPRIN promoted lung fibroblasts resistance to apoptosis. Lung fibroblasts overexpressing EMMPRIN showed a significantly increased expression of α- smooth muscle actin, a marker of differentiation to myofibroblasts compared to control cells. TGF-β1 increased the expression of EMMPRIN in lung fibroblasts in a dose-dependent manner. Attenuation of EMMPRIN expression with the use of an

  5. Comprehensive School-Based Physical Activity Promotion: A Review

    Science.gov (United States)

    Erwin, Heather; Beighle, Aaron; Carson, Russell L.; Castelli, Darla M.

    2013-01-01

    Physical activity (PA) participation levels among youth remain well below national recommendations. Thus, a variety of strategies to promote youth PA have been advocated, including multifaceted, school-based approaches. One identified as having great potential is a comprehensive school physical activity program (CSPAP). The goal of a CSPAP is to…

  6. Promotion of nutrition and physical activity in Dutch general practice

    NARCIS (Netherlands)

    Dillen, van S.; Hiddink, G.J.; Woerkum, van C.M.J.

    2011-01-01

    Introduction: Promotion of nutrition and physical activity is important to slow down the increase of overweight. General practitioners (GPs) are in an unique position to communicate with their patients about nutrition and physical activity, because of the high referral score, high perceived

  7. Ethics Centers' Activities and Role in Promoting Ethics in Universities

    Science.gov (United States)

    Safatly, Lise; Itani, Hiba; El-Hajj, Ali; Salem, Dania

    2017-01-01

    In modern and well-structured universities, ethics centers are playing a key role in hosting, organizing, and managing activities to enrich and guide students' ethical thinking and analysis. This paper presents a comprehensive survey of the goals, activities, and administration of ethics centers, as well as their role in promoting ethical thinking…

  8. Stem Cell Factor Expression after Renal Ischemia Promotes Tubular Epithelial Survival

    NARCIS (Netherlands)

    Stokman, Geurt; Stroo, Ingrid; Claessen, Nike; Teske, Gwendoline J. D.; Weening, Jan J.; Leemans, Jaklien C.; Florquin, Sandrine

    2010-01-01

    Background: Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration

  9. Promoting Physical Activity Among Overweight Young African American Women

    Centers for Disease Control (CDC) Podcasts

    2014-01-15

    This podcast is an interview with Nefertiti Durant, MD, MPH, from the University of Alabama at Birmingham about promoting physical activity among overweight and obese young African American Women using Internet-based tools.  Created: 1/15/2014 by Preventing Chronic Disease (PCD), National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 1/15/2014.

  10. Corporate responsibility for childhood physical activity promotion in the UK.

    Science.gov (United States)

    Leone, Liliana; Ling, Tom; Baldassarre, Laura; Barnett, Lisa M; Capranica, Laura; Pesce, Caterina

    2016-12-01

    The alarming epidemic of obesity and physical inactivity at paediatric age urges societies to rise to the challenge of ensuring an active lifestyle. As one response to this, business enterprises are increasingly engaged in promoting sport and physical activity (PA) initiatives within the frame of corporate social responsibility (CSR). However, comparative analyses among industry sectors of CSR strategies for PA promotion with a particular focus on children are still lacking. This study aimed to explore (i) what are the CSR strategies for PA promotion adopted in different industry sectors and (ii) whether corporate engagement in promoting PA for children is supportive of children's rights to play and be physically active. Corporate pledges pertaining to CSR initiatives to promote PA were analysed. The hypothesis was that companies from different sectors employ different CSR strategies and that companies with a higher profile as regard to public health concerns for children tend to legitimate their action by adopting a compensatory strategy. Results show that the issue of PA promotion is largely represented within CSR commitments. CSR strategies for PA promotion vary across industry sectors and the adoption of a compensatory strategy for rising childhood obesity allows only a limited exploitation of the potential of CSR commitments for the provision of children's rights to play and be physically active. Actors within the fields of public health ethics, human rights and CSR should be considered complementary to develop mainstreaming strategies and improve monitoring systems of PA promotion in children. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Survival advantages conferred to colon cancer cells by E-selectin-induced activation of the PI3K-NFκB survival axis downstream of Death receptor-3

    Directory of Open Access Journals (Sweden)

    Paquet Éric R

    2011-07-01

    Full Text Available Abstract Background Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to endothelial cells. It requires interactions between adhesion receptors on endothelial cells and their counter-receptors on cancer cells. Notably, E-selectin, a major endothelial adhesion receptor, interacts with Death receptor-3 present on metastatic colon carcinoma cells. This interaction confers metastatic properties to colon cancer cells by promoting the adhesion of cancer cells to endothelial cells and triggering the activation of the pro-migratory p38 and pro-survival ERK pathways in the cancer cells. In the present study, we investigated further the mechanisms by which the E-selectin-activated pathways downstream of DR3 confer a survival advantage to colon cancer cells. Methods Cell survival has been ascertained by using the WST-1 assay and by evaluating the activation of the PI3 kinase/NFκB survival axis. Apoptosis has been assayed by determining DNA fragmentation by Hoechst staining and by measuring cleavage of caspases-8 and -3. DR3 isoforms have been identified by PCR. For more precise quantification, targeted PCR reactions were carried out, and the amplified products were analyzed by automated chip-based microcapillary electrophoresis on an Agilent 2100 Bioanalyzer instrument. Results Interaction between DR3-expressing HT29 colon carcinoma cells and E-selectin induces the activation of the PI3K/Akt pathway. Moreover, p65/RelA, the anti-apoptotic subunit of NFκB, is rapidly translocated to the nucleus in response to E-selectin. This translocation is impaired by the PI3K inhibitor LY294002. Furthermore, inhibition of the PI3K/Akt pathway increases the cleavage of caspase 8 in colon cancer cells treated with E-selectin and this effect is still further increased when both ERK and PI3K pathways are concomitantly inhibited. Intriguingly, metastatic colon cancer cell lines such as HT

  12. Hair Growth Promotion Activity and Its Mechanism of Polygonum multiflorum

    Directory of Open Access Journals (Sweden)

    Yunfei Li

    2015-01-01

    Full Text Available Polygonum multiflorum Radix (PMR has long history in hair growth promotion and hair coloring in clinical applications. However, several crucial problems in its clinic usage and mechanisms are still unsolved or lack scientific evidences. In this research, C57BL/6J mice were used to investigate hair growth promotion activity and possible mechanism of PMR and Polygonum multiflorum Radix Preparata (PMRP. Hair growth promotion activities were investigated by hair length, hair covered skin ratio, the number of follicles, and hair color. Regulation effects of several cytokines involved in the hair growth procedure were tested, such as fibroblast growth factor (FGF-7, Sonic Hedgehog (SHH, β-catenin, insulin-like growth factor-1 (IGF-1, and hepatocyte growth factor (HGF. Oral PMR groups had higher hair covered skin ratio (100 ± 0.00% than oral PMRP groups (48%~88%. However, topical usage of PMRP had about 90% hair covered skin ratio. Both oral administration of PMR and topically given PMRP showed hair growth promotion activities. PMR was considered to be more suitable for oral administration, while PMRP showed greater effects in external use. The hair growth promotion effect of oral PMR was most probably mediated by the expression of FGF-7, while topical PMRP promoted hair growth by the stimulation of SHH expression.

  13. Hair Growth Promotion Activity and Its Mechanism of Polygonum multiflorum

    Science.gov (United States)

    Li, Yunfei; Han, Mingnuan; He, Yanran; Zhao, Ronghua

    2015-01-01

    Polygonum multiflorum Radix (PMR) has long history in hair growth promotion and hair coloring in clinical applications. However, several crucial problems in its clinic usage and mechanisms are still unsolved or lack scientific evidences. In this research, C57BL/6J mice were used to investigate hair growth promotion activity and possible mechanism of PMR and Polygonum multiflorum Radix Preparata (PMRP). Hair growth promotion activities were investigated by hair length, hair covered skin ratio, the number of follicles, and hair color. Regulation effects of several cytokines involved in the hair growth procedure were tested, such as fibroblast growth factor (FGF-7), Sonic Hedgehog (SHH), β-catenin, insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF). Oral PMR groups had higher hair covered skin ratio (100 ± 0.00%) than oral PMRP groups (48%~88%). However, topical usage of PMRP had about 90% hair covered skin ratio. Both oral administration of PMR and topically given PMRP showed hair growth promotion activities. PMR was considered to be more suitable for oral administration, while PMRP showed greater effects in external use. The hair growth promotion effect of oral PMR was most probably mediated by the expression of FGF-7, while topical PMRP promoted hair growth by the stimulation of SHH expression. PMID:26294926

  14. Polarized Secretion of PEDF from Human Embryonic Stem Cell–Derived RPE Promotes Retinal Progenitor Cell Survival

    Science.gov (United States)

    Zhu, Danhong; Deng, Xuemei; Spee, Christine; Sonoda, Shozo; Hsieh, Chih-Lin; Barron, Ernesto; Pera, Martin

    2011-01-01

    Purpose. Human embryonic stem cell–derived RPE (hES-RPE) transplantation is a promising therapy for atrophic age-related macular degeneration (AMD); however, future therapeutic approaches may consider co-transplantation of hES-RPE with retinal progenitor cells (RPCs) as a replacement source for lost photoreceptors. The purpose of this study was to determine the effect of polarization of hES-RPE monolayers on their ability to promote survival of RPCs. Methods. The hES-3 cell line was used for derivation of RPE. Polarization of hES-RPE was achieved by prolonged growth on permeable inserts. RPCs were isolated from 16- to 18-week-gestation human fetal eyes. ELISA was performed to measure pigment epithelium–derived factor (PEDF) levels from conditioned media. Results. Pigmented RPE-like cells appeared as early as 4 weeks in culture and were subcultured at 8 weeks. Differentiated hES-RPE had a normal chromosomal karyotype. Phenotypically polarized hES-RPE cells showed expression of RPE-specific genes. Polarized hES-RPE showed prominent expression of PEDF in apical cytoplasm and a marked increase in secretion of PEDF into the medium compared with nonpolarized culture. RPCs grown in the presence of supernatants from polarized hES-RPE showed enhanced survival, which was ablated by the presence of anti-PEDF antibody. Conclusions. hES-3 cells can be differentiated into functionally polarized hES-RPE cells that exhibit characteristics similar to those of native RPE. On polarization, hES-RPE cells secrete high levels of PEDF that can support RPC survival. These experiments suggest that polarization of hES-RPE would be an important feature for promotion of RPC survival in future cell therapy for atrophic AMD. PMID:21087957

  15. Activation of NF-κB drives the enhanced survival of adipose tissue macrophages in an obesogenic environment.

    Science.gov (United States)

    Hill, Andrea A; Anderson-Baucum, Emily K; Kennedy, Arion J; Webb, Corey D; Yull, Fiona E; Hasty, Alyssa H

    2015-10-01

    Macrophage accumulation in adipose tissue (AT) during obesity contributes to inflammation and insulin resistance. Recruitment of monocytes to obese AT has been the most studied mechanism explaining this accumulation. However, recent evidence suggests that recruitment-independent mechanisms may also regulate pro-inflammatory AT macrophage (ATM) numbers. The role of increased ATM survival during obesity has yet to be explored. We demonstrate that activation of apoptotic pathways is significantly reduced in ATMs from diet-induced and genetically obese mice. Concurrently, pro-survival Bcl-2 family member protein levels and localization to the mitochondria is elevated in ATMs from obese mice. This increased pro-survival signaling was associated with elevated activation of the transcription factor, NF-κB, and increased expression of its pro-survival target genes. Finally, an obesogenic milieu increased ATM viability only when NF-κB signaling pathways were functional. Our data demonstrate that obesity promotes survival of inflammatory ATMs, possibly through an NF-κB-regulated mechanism.

  16. ST6Gal-I sialyltransferase promotes tumor necrosis factor (TNF)-mediated cancer cell survival via sialylation of the TNF receptor 1 (TNFR1) death receptor.

    Science.gov (United States)

    Holdbrooks, Andrew T; Britain, Colleen M; Bellis, Susan L

    2018-02-02

    Activation of the tumor necrosis factor receptor 1 (TNFR1) death receptor by TNF induces either cell survival or cell death. However, the mechanisms mediating these distinct outcomes remain poorly understood. In this study, we report that the ST6Gal-I sialyltransferase, an enzyme up-regulated in numerous cancers, sialylates TNFR1 and thereby protects tumor cells from TNF-induced apoptosis. Using pancreatic and ovarian cancer cells with ST6Gal-I knockdown or overexpression, we determined that α2-6 sialylation of TNFR1 had no effect on early TNF-induced signaling events, including the rapid activation of NF-κB, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and Akt (occurring within 15 min). However, upon extended TNF treatment (6-24 h), cells with high ST6Gal-I levels exhibited resistance to TNF-induced apoptosis, as indicated by morphological evidence of cell death and decreased activation of caspases 8 and 3. Correspondingly, at these later time points, high ST6Gal-I expressers displayed sustained activation of the survival molecules Akt and NF-κB. Additionally, extended TNF treatment resulted in the selective enrichment of clonal variants with high ST6Gal-I expression, further substantiating a role for ST6Gal-I in cell survival. Given that TNFR1 internalization is known to be essential for apoptosis induction, whereas survival signaling is initiated by TNFR1 at the plasma membrane, we examined TNFR1 localization. The α2-6 sialylation of TNFR1 was found to inhibit TNF-induced TNFR1 internalization. Thus, by restraining TNFR1 at the cell surface via sialylation, ST6Gal-I acts as a functional switch to divert signaling toward survival. These collective findings point to a novel glycosylation-dependent mechanism that regulates the cellular response to TNF and may promote cancer cell survival within TNF-rich tumor microenvironments. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Promoters active in interphase are bookmarked during mitosis by ubiquitination.

    Science.gov (United States)

    Arora, Mansi; Zhang, Jie; Heine, George F; Ozer, Gulcin; Liu, Hui-wen; Huang, Kun; Parvin, Jeffrey D

    2012-11-01

    We analyzed modification of chromatin by ubiquitination in human cells and whether this mark changes through the cell cycle. HeLa cells were synchronized at different stages and regions of the genome with ubiquitinated chromatin were identified by affinity purification coupled with next-generation sequencing. During interphase, ubiquitin marked the chromatin on the transcribed regions of ∼70% of highly active genes and deposition of this mark was sensitive to transcriptional inhibition. Promoters of nearly half of the active genes were highly ubiquitinated specifically during mitosis. The ubiquitination at the coding regions in interphase but not at promoters during mitosis was enriched for ubH2B and dependent on the presence of RNF20. Ubiquitin labeling of both promoters during mitosis and transcribed regions during interphase, correlated with active histone marks H3K4me3 and H3K36me3 but not a repressive histone modification, H3K27me3. The high level of ubiquitination at the promoter chromatin during mitosis was transient and was removed within 2 h after the cells exited mitosis and entered the next cell cycle. These results reveal that the ubiquitination of promoter chromatin during mitosis is a bookmark identifying active genes during chromosomal condensation in mitosis, and we suggest that this process facilitates transcriptional reactivation post-mitosis.

  18. Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells.

    Science.gov (United States)

    Mendoza, Alejandra; Fang, Victoria; Chen, Cynthia; Serasinghe, Madhavika; Verma, Akanksha; Muller, James; Chaluvadi, V Sai; Dustin, Michael L; Hla, Timothy; Elemento, Olivier; Chipuk, Jerry E; Schwab, Susan R

    2017-06-01

    Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide. Because the production of T cells declines with age, naive T cells must be long-lived. However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer's patches, where T cells search for antigens. The concentration of S1P is higher in circulatory fluids than in lymphoid organs, and the S1P1 receptor (S1P1R) directs the exit of T cells from the spleen into blood, and from lymph nodes and Peyer's patches into lymph. Here we show that S1P is essential not only for the circulation of naive T cells, but also for their survival. Using transgenic mouse models, we demonstrate that lymphatic endothelial cells support the survival of T cells by secreting S1P via the transporter SPNS2, that this S1P signals through S1P1R on T cells, and that the requirement for S1P1R is independent of the established role of the receptor in guiding exit from lymph nodes. S1P signalling maintains the mitochondrial content of naive T cells, providing cells with the energy to continue their constant migration. The S1P signalling pathway is being targeted therapeutically to inhibit autoreactive T cell trafficking, and these findings suggest that it may be possible simultaneously to target autoreactive or malignant cell survival.

  19. IL-7 Promotes T Cell Viability, Trafficking, and Functionality and Improves Survival in Sepsis

    OpenAIRE

    Unsinger, Jacqueline; McGlynn, Margaret; Kasten, Kevin R.; Hoekzema, Andrew S.; Watanabe, Eizo; Muenzer, Jared T.; McDonough, Jacquelyn S.; Tschoep, Johannes; Ferguson, Thomas A.; McDunn, Jonathan E.; Morre, Michel; Hildeman, David A.; Caldwell, Charles C.; Hotchkiss, Richard S.

    2010-01-01

    Sepsis is a highly lethal disorder characterized by widespread apoptosis-induced depletion of immune cells and the development of a profound immunosuppressive state. IL-7 is a potent antiapoptotic cytokine that enhances immune effector cell function and is essential for lymphocyte survival. In this study, recombinant human IL-7 (rhIL-7) efficacy and potential mechanisms of action were tested in a murine peritonitis model. Studies at two independent laboratories showed that rhIL-7 markedly imp...

  20. Oxygen absorption by adventitious roots promotes the survival of completely submerged terrestrial plants.

    Science.gov (United States)

    Ayi, Qiaoli; Zeng, Bo; Liu, Jianhui; Li, Siqi; van Bodegom, Peter M; Cornelissen, Johannes H C

    2016-04-10

    Flooding imposes stress upon terrestrial plants because it results in oxygen deficiency, which is considered a major problem for submerged plants. A common response of terrestrial plants to flooding is the formation of aquatic adventitious roots. Some studies have shown that adventitious roots on submerged plants are capable of absorbing water and nutrients. However, there is no experimental evidence for the possible oxygen uptake function of adventitious roots or for how important this function might be for the survival of plants during prolonged submergence. This study aims to investigate whether adventitious roots absorb oxygen from the water column, and whether this new function is beneficial to the survival of completely submerged plants. TakingAlternanthera philoxeroides(Mart.) Griseb. as a representative species, the profiling of the underwater oxygen gradient towards living and dead adventitious roots on completely submerged plants was conducted, the oxygen concentration in stem nodes with and without adventitious roots was measured, and the growth, survival and non-structural carbohydrate content of completely submerged plants with and without adventitious roots was investigated. Oxygen profiles in the water column of adventitious roots showed that adventitious roots absorbed oxygen from water. It is found that the oxygen concentration in stem nodes having adventitious roots was higher than that in stem nodes without adventitious roots, which implies that the oxygen absorbed by adventitious roots from water was subsequently transported from the roots to other plant tissues. Compared with plants whose adventitious roots had been pruned, those with intact adventitious roots had slower leaf shedding, slower plant mass reduction, more efficient carbohydrate economy and prolonged survival when completely submerged. The adventitious roots ofA. philoxeroidesformed upon submergence can absorb oxygen from ambient water, thereby alleviating the adverse effects of

  1. AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells.

    Science.gov (United States)

    Leaver, S G; Cui, Q; Plant, G W; Arulpragasam, A; Hisheh, S; Verhaagen, J; Harvey, A R

    2006-09-01

    We compared the effects of intravitreal injection of bi-cistronic adeno-associated viral (AAV-2) vectors encoding enhanced green fluorescent protein (GFP) and either ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF) or growth-associated protein-43 (GAP43) on adult retinal ganglion cell (RGC) survival and regeneration following (i) optic nerve (ON) crush or (ii) after ON cut and attachment of a peripheral nerve (PN). At 7 weeks after ON crush, quantification of betaIII-tubulin immunostaining revealed that, compared to AAV-GFP controls, RGC survival was not enhanced by AAV-GAP43-GFP but was increased in AAV-CNTF-GFP (mean RGCs/retina: 17 450+/-358 s.e.m.) and AAV-BDNF-GFP injected eyes (10 200+/-4064 RGCs/retina). Consistent with increased RGC viability in AAV-CNTF-GFP and AAV-BDNF-GFP injected eyes, these animals possessed many betaIII-tubulin- and GFP-positive fibres proximal to the ON crush. However, only in the AAV-CNTF-GFP group were regenerating RGC axons seen in distal ON (1135+/-367 axons/nerve, 0.5 mm post-crush), some reaching the optic chiasm. RGCs were immunoreactive for CNTF and quantitative RT-PCR revealed a substantial increase in CNTF mRNA expression in retinas transduced with AAV-CNTF-GFP. The combination of AAV-CNTF-GFP transduction of RGCs with autologous PN-ON transplantation resulted in even greater RGC survival and regeneration. At 7 weeks after PN transplantation there were 27 954 (+/-2833) surviving RGCs/retina, about 25% of the adult RGC population. Of these, 13 352 (+/-1868) RGCs/retina were retrogradely labelled after fluorogold injections into PN grafts. In summary, AAV-mediated expression of CNTF promotes long-term survival and regeneration of injured adult RGCs, effects that are substantially enhanced by combining gene and cell-based therapies/interventions.

  2. Promoting health in rural Transylvania, Romania. a descriptive analysis of health promotion activities.

    Science.gov (United States)

    Baba, Cătălin O; Brînzaniuc, Alexandra; Sirlincan, Emanuela O; Cherecheş, Răzvan M

    2010-12-01

    Even though efforts are made to reduce health disparities, promote health for all social groups and improve health outcomes, inconsistencies still exist. Existing evidence shows that lack of funding, lack of properly trained workforce, as well as heavy workload on health care workers, are the most employed explanations for the limited number of health promotion interventions in the area. This paper presents the results of a descriptive study that pursues to render a comprehensive image of health promotion efforts undertaken in rural Transylvania, Romania. This descriptive analysis is conducted on data extracted from a larger dataset, obtained through a study which pursues a cross-sectional design, with a quantitative strategy of inquiry on access to health information in rural Transylvania. The instrument used for data collection is a questionnaire administered by telephone to a sample of medical doctors working in rural medical offices in the studied area (n = 226). Results show overall low rates of health promotion activities in the area, as well as low levels of collaboration with other local actors. In the context of behavioral risk factors, this study clearly shows the need of targeted health promotion activities in rural Transylvania in order to improve health outcomes and mitigate health disparities.

  3. Promoting survival: A grounded theory study of consequences of modern health practices in Ouramanat region of Iranian Kurdistan

    Science.gov (United States)

    Mohammadpur, Ahmad; Rezaei, Mehdi; Sadeghi, Rasoul

    2010-01-01

    The aim of this qualitative study is to explore the way people using modern health care perceive its consequences in Ouraman-e-Takht region of Iranian Kurdistan. Ouraman-e-Takht is a rural, highly mountainous and dry region located in the southwest Kurdistan province of Iran. Recently, modern health practices have been introduced to the region. The purpose of this study was to investigate, from the Ouramains' point of view, the impact that modern health services and practices have had on the Ouraman traditional way of life. Interview data from respondents were analyzed by using grounded theory. Promoting survival was the core category that explained the impact that modern health practices have had on the Ouraman region. The people of Ouraman interpreted modern health practices as increasing their quality of life and promoting their survival. Results are organized around this core category in a paradigm model consisting of conditions, interactions, and consequences. This model can be used to understand the impact of change from the introduction of modern health on a traditional society. PMID:20640020

  4. Promoting survival, migration, and integration of transplanted Schwann cells by over-expressing polysialic acid.

    Science.gov (United States)

    Luo, Juan; Bo, Xuenong; Wu, Dongsheng; Yeh, John; Richardson, Peter M; Zhang, Yi

    2011-03-01

    The poor survival and migration of transplanted Schwann cells (SCs) are major drawbacks for their clinical application in cell therapy for neurotrauma. To overcome such drawbacks we genetically modified SCs to over-express polysialic acid (PSA) by lentiviral delivery of polysialyltransferase (PST) to study whether over-expression of PSA could enhance their survival, migration, and integration when transplanted into the spinal cord. It was found that more PSA-expressing SCs (PST/SCs) survived than GFP-expressing SCs (GFP/SCs) after transplantation, although cell loss was still quite significant. PSA expression did not enhance the motility of transplanted SCs in uninjured spinal cord. However, in a spinal cord crush injury model PST/SCs transplanted caudal to the lesion showed that increased number of PST/SCs migrated to the injury site compared with that of GFP/SCs. Induced expression of PSA in spinal cord can further facilitate the infiltration of PST/SCs into the lesion site. PST/SCs were also shown to intermingle well with host spinal cells while GFP/SCs formed boundaries with host tissue. This was confirmed by an in vitro confrontation assay showing that more PST/SCs crossed over to astrocyte territory than GFP/SCs. Furthermore, PST/SCs induced much less expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycan in the surrounding tissues than GFP/SCs, indicating that expression of PSA on SCs do not cause significant stress response of astrocytes. These results demonstrate that expression of PSA on SCs significantly changes their biological properties and makes them more feasible for neural repair after neurotrauma. Copyright © 2010 Wiley-Liss, Inc.

  5. Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Bowerman Melissa

    2012-03-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA is the leading genetic cause of infant death. It is caused by mutations/deletions of the survival motor neuron 1 (SMN1 gene and is typified by the loss of spinal cord motor neurons, muscular atrophy, and in severe cases, death. The SMN protein is ubiquitously expressed and various cellular- and tissue-specific functions have been investigated to explain the specific motor neuron loss in SMA. We have previously shown that the RhoA/Rho kinase (ROCK pathway is misregulated in cellular and animal SMA models, and that inhibition of ROCK with the chemical Y-27632 significantly increased the lifespan of a mouse model of SMA. In the present study, we evaluated the therapeutic potential of the clinically approved ROCK inhibitor fasudil. Methods Fasudil was administered by oral gavage from post-natal day 3 to 21 at a concentration of 30 mg/kg twice daily. The effects of fasudil on lifespan and SMA pathological hallmarks of the SMA mice were assessed and compared to vehicle-treated mice. For the Kaplan-Meier survival analysis, the log-rank test was used and survival curves were considered significantly different at P t test for paired variables and one-way analysis of variance (ANOVA were used to test for differences between samples and data were considered significantly different at P Results Fasudil significantly improves survival of SMA mice. This dramatic phenotypic improvement is not mediated by an up-regulation of Smn protein or via preservation of motor neurons. However, fasudil administration results in a significant increase in muscle fiber and postsynaptic endplate size, and restores normal expression of markers of skeletal muscle development, suggesting that the beneficial effects of fasudil could be muscle-specific. Conclusions Our work underscores the importance of muscle as a therapeutic target in SMA and highlights the beneficial potential of ROCK inhibitors as a therapeutic strategy for SMA

  6. Progranulin is expressed within motor neurons and promotes neuronal cell survival

    Directory of Open Access Journals (Sweden)

    Kay Denis G

    2009-10-01

    Full Text Available Abstract Background Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival. Results In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months. This is mediated at least in part through

  7. Indirect facilitation promotes macrophyte survival and growth in freshwater ecosystems threatened by eutrophication

    OpenAIRE

    Le Bagousse-Pinguet, Yoann; Liancourt, Pierre; Gross, Nicolas; Straile, Dietmar

    2012-01-01

    1. Eutrophication is a major threat for freshwater ecosystems. Submerged aquatic plants (macrophytes) can maintain clear water conditions in eutrophic lakes by competing with phytoplankton for light and nutrients. The interactions between macrophytes and phytoplankton may lead to indirect facilitation among plants and the maintenance of high macrophyte diversities in eutrophicconditions. Nonetheless, the role of indirect facilitation in promoting macrophyte-dominated clear water states under ...

  8. JUNB promotes the survival of Flavopiridol treated human breast cancer cells.

    Science.gov (United States)

    Hicks, Mellissa; Hu, Qiuping; Macrae, Erin; DeWille, James

    2014-07-18

    Chemotherapy resistance is a major obstacle to achieving durable progression-free-survival in breast cancer patients. Identifying resistance mechanisms is crucial to the development of effective breast cancer therapies. Immediate early genes (IEGs) function in the initial cellular reprogramming response to alterations in the extracellular environment and IEGs have been implicated in cancer cell development and progression. The purpose of this study was to investigate the influence of kinase inhibitors on IEG expression in breast cancer cells. The results demonstrated that Flavopiridol (FP), a CDK9 inhibitor, effectively reduced gene expression. FP treatment, however, consistently produced a delayed induction of JUNB gene expression in multiple breast cancer cell lines. Similar results were obtained with Sorafenib, a multi-kinase inhibitor and U0126, a MEK1 inhibitor. Functional studies revealed that JUNB plays a pro-survival role in kinase inhibitor treated breast cancer cells. These results demonstrate a unique induction of JUNB in response to kinase inhibitor therapies that may be among the earliest events in the progression to treatment resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis.

    Science.gov (United States)

    Unsinger, Jacqueline; McGlynn, Margaret; Kasten, Kevin R; Hoekzema, Andrew S; Watanabe, Eizo; Muenzer, Jared T; McDonough, Jacquelyn S; Tschoep, Johannes; Ferguson, Thomas A; McDunn, Jonathan E; Morre, Michel; Hildeman, David A; Caldwell, Charles C; Hotchkiss, Richard S

    2010-04-01

    Sepsis is a highly lethal disorder characterized by widespread apoptosis-induced depletion of immune cells and the development of a profound immunosuppressive state. IL-7 is a potent antiapoptotic cytokine that enhances immune effector cell function and is essential for lymphocyte survival. In this study, recombinant human IL-7 (rhIL-7) efficacy and potential mechanisms of action were tested in a murine peritonitis model. Studies at two independent laboratories showed that rhIL-7 markedly improved host survival, blocked apoptosis of CD4 and CD8 T cells, restored IFN-gamma production, and improved immune effector cell recruitment to the infected site. Importantly, rhIL-7 also prevented a hallmark of sepsis (i.e., the loss of delayed-type hypersensitivity), which is an IFN-gamma- and T cell-dependent response. Mechanistically, rhIL-7 significantly increased the expression of the leukocyte adhesion markers LFA-1 and VLA-4, consistent with its ability to improve leukocyte function and trafficking to the infectious focus. rhIL-7 also increased the expression of CD8. The potent antiapoptotic effect of rhIL-7 was due to increased Bcl-2, as well as to a dramatic decrease in sepsis-induced PUMA, a heretofore unreported effect of IL-7. If additional animal studies support its efficacy in sepsis and if current clinical trials continue to confirm its safety in diverse settings, rhIL-7 should be strongly considered for clinical trials in sepsis.

  10. Methanol-Promoted Lipid Remodelling during Cooling Sustains Cryopreservation Survival of Chlamydomonas reinhardtii.

    Directory of Open Access Journals (Sweden)

    Duanpeng Yang

    Full Text Available Cryogenic treatments and cryoprotective agents (CPAs determine the survival rate of organisms that undergo cryopreservation, but their mechanisms of operation have not yet been characterised adequately. In particular, the way in which membrane lipids respond to cryogenic treatments and CPAs is unknown. We developed comparative profiles of the changes in membrane lipids among cryogenic treatments and between the CPAs dimethyl sulfoxide (DMSO and methanol (MeOH for the green alga Chlamydomonas reinhardtii. We found that freezing in liquid nitrogen led to a dramatic degradation of lipids, and that thawing at warm temperature (35°C induced lipid remodelling. DMSO did not protect membranes, but MeOH significantly attenuated lipid degradation. The presence of MeOH during cooling (from 25°C to -55°C at a rate of 1°C/min sustained the lipid composition to the extent that membrane integrity was maintained; this phenomenon accounts for successful cryopreservation. An increase in monogalactosyldiacylglycerol and a decrease in diacylglycerol were the major changes in lipid composition associated with survival rate, but there was no transformation between these lipid classes. Phospholipase D-mediated phosphatidic acid was not involved in freezing-induced lipid metabolism in C. reinhardtii. Lipid unsaturation changed, and the patterns of change depended on the cryogenic treatment. Our results provide new insights into the cryopreservation of, and the lipid metabolism in, algae.

  11. Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor.

    Science.gov (United States)

    Soto, Raymond; Petersen, Charisse; Novis, Camille L; Kubinak, Jason L; Bell, Rickesha; Stephens, W Zac; Lane, Thomas E; Fujinami, Robert S; Bosque, Alberto; O'Connell, Ryan M; Round, June L

    2017-05-23

    Symbiotic microbes impact the severity of a variety of diseases through regulation of T-cell development. However, little is known regarding the molecular mechanisms by which this is accomplished. Here we report that a secreted factor, Erdr1, is regulated by the microbiota to control T-cell apoptosis. Erdr1 expression was identified by transcriptome analysis to be elevated in splenic T cells from germfree and antibiotic-treated mice. Suppression of Erdr1 depends on detection of circulating microbial products by Toll-like receptors on T cells, and this regulation is conserved in human T cells. Erdr1 was found to function as an autocrine factor to induce apoptosis through caspase 3. Consistent with elevated levels of Erdr1, germfree mice have increased splenic T-cell apoptosis. RNA sequencing of Erdr1-overexpressing cells identified the up-regulation of genes involved in Fas-mediated cell death, and Erdr1 fails to induce apoptosis in Fas-deficient cells. Importantly, forced changes in Erdr1 expression levels dictate the survival of auto-reactive T cells and the clinical outcome of neuro-inflammatory autoimmune disease. Cellular survival is a fundamental feature regulating appropriate immune responses. We have identified a mechanism whereby the host integrates signals from the microbiota to control T-cell apoptosis, making regulation of Erdr1 a potential therapeutic target for autoimmune disease.

  12. Images and Influences in the Promotion of Physical Activity

    Science.gov (United States)

    Overdorf, Virginia

    2005-01-01

    This article presents the author's presentation on the 13th Delphine Hanna Commemorative Lecture in 2004. The presentation examines some of the problems and issues that must be addressed in order to promote physical activity in the academy and beyond. While there is no all embracing prescription, the author hopes to offer some suggestions that…

  13. Predicting Physical Activity Promotion in Health Care Settings.

    Science.gov (United States)

    Faulkner, Guy; Biddle, Stuart

    2001-01-01

    Tested the theory of planned behavior's (TPB) ability to predict stage of change for physical activity promotion among health professionals. Researchers measured attitudes, subjective norms, intentions, perceived behavioral control, and stage of change, then later reassessed stage of change. TPB variables of attitude, subjective norms, perceived…

  14. Health Promotion Guidance Activity of Youth Sports Clubs

    Science.gov (United States)

    Kokko, Sami; Kannas, Lasse; Villberg, Jari; Ormshaw, Michael

    2011-01-01

    Purpose: This paper aims to clarify the extent to which youth sports clubs guide their coaches to recognise health promotion as a part of the coaching practice. The guidance activity of clubs is seen parallel to internal organisational communication. Design/methodology/approach: A survey of 93 (from 120, 78 per cent) youth sports clubs in Finland…

  15. Healthy and Active Ageing: Social Capital in Health Promotion

    Science.gov (United States)

    Koutsogeorgou, Eleni; Davies, John Kenneth; Aranda, Kay; Zissi, Anastasia; Chatzikou, Maria; Cerniauskaite, Milda; Quintas, Rui; Raggi, Alberto; Leonardi, Matilde

    2014-01-01

    Objectives: This paper examines the context of health promotion actions that are focused on/contributing to strengthening social capital by increasing community participation, reciprocal trust and support as the means to achieve better health and more active ageing. Method: The methodology employed was a literature review/research synthesis, and a…

  16. Help Yourself! Activities To Promote Safety and Self-Esteem.

    Science.gov (United States)

    Ross, Kate

    First in a series of books designed to accompany the compact disk "Help Yourself," this book provides suggestions for classroom activities using the CD songs as a springboard into a curriculum for promoting self-esteem and safety skills among preschool children. Each section begins with sheet music and complete lyrics for each of the 12 songs,…

  17. Improving health through policies that promote active travel

    DEFF Research Database (Denmark)

    de Nazelle, Audrey; Nieuwenhuijsen, Mark J; Antó, Josep M

    2011-01-01

    Substantial policy changes to control obesity, limit chronic disease, and reduce air pollution emissions, including greenhouse gasses, have been recommended. Transportation and planning policies that promote active travel by walking and cycling can contribute to these goals, potentially yielding...... further co-benefits. Little is known, however, about the interconnections among effects of policies considered, including potential unintended consequences....

  18. Bone Talk: Activated Osteoblasts Promote Lung Cancer Growth.

    Science.gov (United States)

    Bružas, Emilis; Egeblad, Mikala

    2018-02-02

    Cancer cells can directly stimulate the generation and recruitment of tumor-supportive bone marrow-derived cells (BMDCs), including neutrophils, via secreted factors. A new study demonstrates that lung tumors also remotely activate bone-residing osteoblasts, which in turn promote neutrophil production. This is a multistep mechanism of establishing a supportive tumor microenvironment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. How do general practitioners in Denmark promote physical activity?

    DEFF Research Database (Denmark)

    Jørgensen, Tanja K; Nordentoft, Merete; Krogh, Jesper

    2012-01-01

    The primary objective of this study was to quantify the frequency of advice given on type, frequency, duration, and intensity of exercise during physical activity (PA) promoting sessions by general practitioners. Second, to find GP characteristics associated with high quality of PA counselling....

  20. Wood working elective course promotion by project based activity day

    OpenAIRE

    Jelinčič, Špela

    2014-01-01

    Thesis proposal is intended to provide the lesson plans, which will promote elective subject treatment of materials-wood. As a means to carry out the lesson plans we have chosen an activity day, based on project based teaching. The definition and organization of activity day is given and followed by a review of elective design and technology subjects, where the wood treatment subject is also described in detail. Different inductive teaching methods are described. Here we compare them and choo...

  1. cis Determinants of Promoter Threshold and Activation Timescale

    Directory of Open Access Journals (Sweden)

    Anders S. Hansen

    2015-08-01

    Full Text Available Although the relationship between DNA cis-regulatory sequences and gene expression has been extensively studied at steady state, how cis-regulatory sequences affect the dynamics of gene induction is not known. The dynamics of gene induction can be described by the promoter activation timescale (AcTime and amplitude threshold (AmpThr. Combining high-throughput microfluidics with quantitative time-lapse microscopy, we control the activation dynamics of the budding yeast transcription factor, Msn2, and reveal how cis-regulatory motifs in 20 promoter variants of the Msn2-target-gene SIP18 affect AcTime and AmpThr. By modulating Msn2 binding sites, we can decouple AmpThr from AcTime and switch the SIP18 promoter class from high AmpThr and slow AcTime to low AmpThr and either fast or slow AcTime. We present a model that quantitatively explains gene-induction dynamics on the basis of the Msn2-binding-site number, TATA box location, and promoter nucleosome organization. Overall, we elucidate the cis-regulatory logic underlying promoter decoding of TF dynamics.

  2. Inhibition of cyclophilin D by cyclosporin A promotes retinal ganglion cell survival by preventing mitochondrial alteration in ischemic injury

    Science.gov (United States)

    Kim, S Y; Shim, M S; Kim, K-Y; Weinreb, R N; Wheeler, L A; Ju, W-K

    2014-01-01

    Cyclosporin A (CsA) inhibits the opening of the mitochondrial permeability transition pore (MPTP) by interacting with cyclophilin D (CypD) and ameliorates neuronal cell death in the central nervous system against ischemic injury. However, the molecular mechanisms underlying CypD/MPTP opening-mediated cell death in ischemic retinal injury induced by acute intraocular pressure (IOP) elevation remain unknown. We observed the first direct evidence that acute IOP elevation significantly upregulated CypD protein expression in ischemic retina at 12 h. However, CsA prevented the upregulation of CypD protein expression and promoted retinal ganglion cell (RGC) survival against ischemic injury. Moreover, CsA blocked apoptotic cell death by decreasing cleaved caspase-3 protein expression in ischemic retina. Of interest, although the expression level of Bcl-xL protein did not show a significant change in ischemic retina treated with vehicle or CsA at 12 h, ischemic damage induced the reduction of Bcl-xL immunoreactivity in RGCs. More importantly, CsA preserved Bcl-xL immunoreactivity in RGCs of ischemic retina. In parallel, acute IOP elevation significantly increased phosphorylated Bad (pBad) at Ser112 protein expression in ischemic retina at 12 h. However, CsA significantly preserved pBad protein expression in ischemic retina. Finally, acute IOP elevation significantly increased mitochondrial transcription factor A (Tfam) protein expression in ischemic retina at 12 h. However, CsA significantly preserved Tfam protein expression in ischemic retina. Studies on mitochondrial DNA (mtDNA) content in ischemic retina showed that there were no statistically significant differences in mtDNA content among control and ischemic groups treated with vehicle or CsA. Therefore, these results provide evidence that the activation of CypD-mediated MPTP opening is associated with the apoptotic pathway and the mitochondrial alteration in RGC death of ischemic retinal injury. On the basis

  3. Assessing state-level active living promotion using network analysis.

    Science.gov (United States)

    Buchthal, Opal Vanessa; Taniguchi, Nicole; Iskandar, Livia; Maddock, Jay

    2013-01-01

    Physical inactivity is a growing problem in the United States, one that is being addressed through the development of active living communities. However, active living promotion requires collaboration among organizations that may not have previously shared goals. A network analysis was conducted to assess Hawaii's active living promotion network. Twenty-six organizations playing a significant role in promoting active living in Hawaii were identified and surveyed about their frequency of contact, level of collaboration, and funding flow with other agencies. A communication network was identified linking all agencies. This network had many long pathways, impeding information flow. The Department of Health (DOH) and the State Nutrition and Physical Activity Coalition (NPAC) were central nodes, but DOH connected state agencies while NPAC linked county and voluntary organizations. Within the network, information sharing was common, but collaboration and formal partnership were low. Linkages between county and state agencies, between counties, and between state agencies with different core agendas were particularly low. Results suggest that in the early stages of development, active living networks may be divided by geography and core missions, requiring work to bridge these divides. Network mapping appears helpful in identifying areas for network development.

  4. Active2Gether: Innovative and smart coaching strategies to promote physical activity: A research protocol

    NARCIS (Netherlands)

    Middelweerd, A.; te Velde, S.J.; Klein, M.C.A.; Van Halteren, A.T.; Brug, J.

    Background: Because 67.5 % of Dutch adults is not sufficiently physically active, effective innovative and smart physical activity (PA) promotion is warranted. The ubiquitous nature of smartphones offer new possibilities in PA promotion. Because of their built-in sensors and their ability to connect

  5. Cardiomyocyte Differentiation Promotes Cell Survival During Nicotinamide Phosphoribosyltransferase Inhibition Through Increased Maintenance of Cellular Energy Stores.

    Science.gov (United States)

    Kropp, Erin M; Broniowska, Katarzyna A; Waas, Matthew; Nycz, Alyssa; Corbett, John A; Gundry, Rebekah L

    2017-04-01

    To address concerns regarding the tumorigenic potential of undifferentiated human pluripotent stem cells (hPSC) that may remain after in vitro differentiation and ultimately limit the broad use of hPSC-derivatives for therapeutics, we recently described a method to selectively eliminate tumorigenic hPSC from their progeny by inhibiting nicotinamide phosphoribosyltransferase (NAMPT). Limited exposure to NAMPT inhibitors selectively removes hPSC from hPSC-derived cardiomyocytes (hPSC-CM) and spares a wide range of differentiated cell types; yet, it remains unclear when and how cells acquire resistance to NAMPT inhibition during differentiation. In this study, we examined the effects of NAMPT inhibition among multiple time points of cardiomyocyte differentiation. Overall, these studies show that in vitro cardiomyogenic commitment and continued culturing provides resistance to NAMPT inhibition and cell survival is associated with the ability to maintain cellular ATP pools despite depletion of NAD levels. Unlike cells at earlier stages of differentiation, day 28 hPSC-CM can survive longer periods of NAMPT inhibition and maintain ATP generation by glycolysis and/or mitochondrial respiration. This is distinct from terminally differentiated fibroblasts, which maintain mitochondrial respiration during NAMPT inhibition. Overall, these results provide new mechanistic insight into how regulation of cellular NAD and energy pools change with hPSC-CM differentiation and further inform how NAMPT inhibition strategies could be implemented within the context of cardiomyocyte differentiation. Stem Cells Translational Medicine 2017;6:1191-1201. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  6. C/EBPbeta represses p53 to promote cell survival downstream of DNA damage independent of oncogenic Ras and p19(Arf).

    Science.gov (United States)

    Ewing, S J; Zhu, S; Zhu, F; House, J S; Smart, R C

    2008-11-01

    CCAAT/enhancer-binding protein-beta (C/EBPbeta) is a mediator of cell survival and tumorigenesis. When C/EBPbeta(-/-) mice are treated with carcinogens that produce oncogenic Ras mutations in keratinocytes, they respond with abnormally elevated keratinocyte apoptosis and a block in skin tumorigenesis. Although this aberrant carcinogen-induced apoptosis results from abnormal upregulation of p53, it is not known whether upregulated p53 results from oncogenic Ras and its ability to induce p19(Arf) and/or activate DNA-damage response pathways or from direct carcinogen-induced DNA damage. We report that p19(Arf) is dramatically elevated in C/EBPbeta(-/-) epidermis and that C/EBPbeta represses a p19(Arf) promoter reporter. To determine whether p19(Arf) is responsible for the proapoptotic phenotype in C/EBPbeta(-/-) mice, C/EBPbeta(-/-);p19(Arf-/-) mice were generated. C/EBPbeta(-/-);p19(Arf-/-) mice responded to carcinogen treatment with increased p53 and apoptosis, indicating p19(Arf) is not essential. To ascertain whether oncogenic Ras activation induces aberrant p53 and apoptosis in C/EBPbeta(-/-) epidermis, we generated K14-ER:Ras;C/EBPbeta(-/-) mice. Oncogenic Ras activation induced by 4-hydroxytamoxifen did not produce increased p53 or apoptosis. Finally, when C/EBPbeta(-/-) mice were treated with differing types of DNA-damaging agents, including alkylating chemotherapeutic agents, they displayed aberrant levels of p53 and apoptosis. These results indicate that C/EBPbeta represses p53 to promote cell survival downstream of DNA damage and suggest that inhibition of C/EBPbeta may be a target for cancer cotherapy to increase the efficacy of alkylating chemotherapeutic agents.

  7. The promotion of phisical activity in shockvertising campaigns

    Directory of Open Access Journals (Sweden)

    Widawska-Stanisz Agnieszka

    2017-06-01

    Full Text Available Preferring passive life style and the problems with obesity eventuating from this fact, have become very common in many countries. According to research, the physical activity of Poles turns out to be under the average for EU countries. (Sport activity of Poles, 2015, p.3 The promotion of physical activity is one of the most important tasks of public health. The publicity of physical activity, habits of caring for health and wellbeing should be realized by national and local authorities, media and organisations connected w sport and recreation. Next, there are subjects providing sport- recreation services, which use properly worked out marketing programs, apart from purely business goals, they can also become the promoters of physical activity. The aim of this article is to present shocking advertisement as the part of social campaigns influencing the changing the passive lifestyle for the active one. Shown in this article research was conducted among students of one university. The goal of research was the assessment of emotions which were aroused by showing examples of campaigns and their influence on the willingness to take up physical activities by the youth. The article contains the examples of campaigns and the results of research into using this kind of actions among young people. It was assumed, that the showing shocking messages concerning the consequences of lack physical activity, influences on taking up such activity by young people.

  8. RhoA as a target to promote neuronal survival and axon regeneration

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    Jianli Hu

    2017-01-01

    Full Text Available Paralysis following spinal cord injury (SCI is due to failure of axonal regeneration. It is believed that the capacities of neurons to regrow their axons are due partly to their intrinsic characteristics, which in turn are greatly influenced by several types of inhibitory molecules that are present, or even increased in the extracellular environment of the injured spinal cord. Many of these inhibitory molecules have been studied extensively in recent years. It has been suggested that the small GTPase RhoA is an intracellular convergence point for signaling by these extracellular inhibitory molecules, but due to the complexity of the central nervous system (CNS in mammals, and the limitation of pharmacological tools, the specific roles of RhoA are unclear. By exploiting the anatomical and technical advantages of the lamprey CNS, we recently demonstrated that RhoA knockdown promotes true axon regeneration through the lesion site after SCI. In addition, we found that RhoA knockdown protects the large, identified reticulospinal neurons from apoptosis after their axons were axotomized in spinal cord. Therefore, manipulation of the RhoA signaling pathway may be an important approach in the development of treatments that are both neuroprotective and axon regeneration-promoting, to enhance functional recovery after SCI.

  9. Acetyl-coenzyme A carboxylase alpha promotion of glucose-mediated fatty acid synthesis enhances survival of hepatocellular carcinoma in mice and patients.

    Science.gov (United States)

    Wang, Ming-Da; Wu, Han; Fu, Gong-Bo; Zhang, Hui-Lu; Zhou, Xu; Tang, Liang; Dong, Li-Wei; Qin, Chen-Jie; Huang, Shuai; Zhao, Ling-Hao; Zeng, Min; Wu, Meng-Chao; Yan, He-Xin; Wang, Hong-Yang

    2016-04-01

    Solid tumors often suffer from suboptimal oxygen and nutrient supplies. This stress underlies the requirement for metabolic adaptation. Aberrantly activated de novo lipogenesis is critical for development and progression of human hepatocellular carcinoma (HCC). However, whether de novo lipogenesis influences biological behaviors of HCCs under conditions of metabolic stress are still poorly understood. Here, we show that HCCs display distinct levels of glucose-derived de novo lipogenesis, which are positively correlated with their survival responses to glucose limitation. The enhanced lipogenesis in HCCs is characterized by an increased expression of rate-limiting enzyme acetyl-coenzyme A carboxylase alpha (ACCα). ACCα-mediated fatty acid (FA) synthesis determines the intracellular lipid content that is required to maintain energy hemostasis and inhibit cell death by means of FA oxidation (FAO) during metabolic stress. In accord, overexpression of ACCα facilitates tumor growth. ACCα forms a complex with carnitine palmitoyltransferase 1A (CPT1A) and prevents its mitochondria distribution under nutrient-sufficient conditions. During metabolic stress, phosphorylation of ACCα leads to dissociation of the complex and mitochondria localization of CPT1A, thus promoting FAO-mediated cell survival. Therefore, ACCα could provide both the substrate and enzyme storage for FAO during glucose deficiency. Up-regulation of ACCα is also significantly correlated with poorer overall survival and disease recurrence postsurgery. Multivariate Cox's regression analysis identified ACCα as an effective predictor of poor prognosis. These results present novel mechanistic insight into a pivotal role of ACCα in maintaining HCC survival under metabolic stress. It could be exploited as a novel diagnostic marker and therapeutic target. © 2015 by the American Association for the Study of Liver Diseases.

  10. Epstein-Barr virus promotes human monocyte survival and maturation through a paracrine induction of IFN-alpha.

    Science.gov (United States)

    Salek-Ardakani, Shahram; Lyons, Stephen A; Arrand, John R

    2004-07-01

    The role of monocytes and macrophages during EBV infection is not clear. The interaction of EBV with human monocytes was investigated in terms of cell survival and morphological and phenotypic changes to gain a better understanding of the role of these cells during EBV infection. We show that EBV infection of PBMCs rescues monocytes from undergoing spontaneous apoptosis and dramatically enhances their survival. Results obtained with heat-inactivated virus, neutralizing anti-EBV mAb 72A1 and recombinant gp350, suggest that enhancement of viability by EBV requires both infectious virus and interaction between gp350 and its receptor. IFN-alpha either secreted within 24 h from PBMCs upon infection with EBV or exogenously added to unstimulated monocytes inhibited spontaneous apoptosis, indicating that induction of IFN-alpha is an early important survival signal responsible for the delay in the apoptosis of monocytes. EBV infection also induced acute maturation of monocytes to macrophages with morphological and phenotypic characteristics of potent APCs. Monocytes exposed to EBV became larger in size with increased granularity and expressed considerably higher levels of membrane HLA classes I and II, ICAM-1, CD80, CD86, and CD40 compared with uninfected cultures. These observations provide the first immunoregulatory links among EBV, IFN-alpha, and monocyte survival and maturation and importantly raise the possibility that these cells may serve as a vehicle for the dissemination of the virus as well as being active participants in eliciting anti-EBV T cell responses during acute infection.

  11. Has physical activity anything to do with health promotion?

    DEFF Research Database (Denmark)

    Thing, Lone Friis

    2016-01-01

    Within academic discussions of health promotion related to physical activity an Eliasian perspective is seldom used. Based on a central theoretical theme within Norbert Elias’ sociology of sport (Elias and Dunning 1986), namely the quest for excitement, this article explores the health orientation...... of Danish society as an expression of a continued civilizing of the body. In national governmental health messages sports participation and general physical activity are presented as an essential health-promoting instrument that keeps illness and disease away, thereby prolong life. But the all......-pervading guide to physical activity and sport - often with a focus on quantitative dimensions like frequency, duration and intensity - as measurable effects and risks, has resulted in a rationalisation of many movement cultures for large selections of the population. Health messages are then presented using...

  12. An Ikaros Promoter Element with Dual Epigenetic and Transcriptional Activities.

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    Elizabeth A Perotti

    Full Text Available Ikaros DNA binding factor plays critical roles in lymphocyte development. Changes in Ikaros expression levels during lymphopoiesis are controlled by redundant but also unique regulatory elements of its locus that are critical for this developmental process. We have recently shown that Ikaros binds its own locus in thymocytes in vivo. Here, we evaluated the role of an Ikaros binding site within its major lympho-myeloid promoter. We identified an Ikaros/Ets binding site within a promoter sub-region that was highly conserved in mouse and human. Deletion of this binding site increased the percentage of the reporter-expressing mouse lines, indicating that its loss provided a more permissive chromatin environment. However, once transcription was established, the lack of this site decreased transcriptional activity. These findings implicate a dual role for Ikaros/Ets1 binding on Ikzf1 expression that is exerted at least through its promoter.

  13. Promotion as a Tool in Sustaining the Destination Marketing Activities

    Directory of Open Access Journals (Sweden)

    Ivo Mulec

    2010-01-01

    Full Text Available Promoting the tourism destination in the right and best possible way is today one of vital marketing activities of all Destination Management Organizations. Only successful promotion can entice and attract potential travelers to visit the destination. The number of new destinations is increasing every year and some of them are quite similar. Market segmentation is one of the starting points for devising marketing strategy. Only by presenting the destination to the right segment of potential clients in the right way will a destination maximize the effectiveness of its marketing and promotion. Tourism destination marketers will continue to face considerable challenges in the future: they will have to take account of the needs, wants and expectations of more mature and knowledgeable customers, and the corresponding need for more up-to-date and reliable information upon which to base decision-making. In the future only marketing which includes collaborative dimensions will meet its objectives fully.

  14. Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells.

    Science.gov (United States)

    Cengel, Keith A; Voong, K Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B; Stanbridge, Eric; Kao, Gary D; McKenna, W Gillies; Bernhard, Eric J

    2007-04-01

    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor alpha was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers.

  15. Oncogenic K-Ras Signals through Epidermal Growth Factor Receptor and Wild-Type H-Ras to Promote Radiation Survival in Pancreatic and Colorectal Carcinoma Cells1

    Science.gov (United States)

    Cengel, Keith A.; Voong, K. Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B.; Stanbridge, Eric; Kao, Gary D.; McKenna, W. Gillies; Bernhard, Eric J.

    2007-01-01

    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor α was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers. PMID:17460778

  16. Extracellular Vesicles from Vascular Endothelial Cells Promote Survival, Proliferation and Motility of Oligodendrocyte Precursor Cells.

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    Masashi Kurachi

    Full Text Available We previously examined the effect of brain microvascular endothelial cell (MVEC transplantation on rat white matter infarction, and found that MVEC transplantation promoted remyelination of demyelinated axons in the infarct region and reduced apoptotic death of oligodendrocyte precursor cells (OPCs. We also found that the conditioned medium (CM from cultured MVECs inhibited apoptosis of cultured OPCs. In this study, we examined contribution of extracellular vesicles (EVs contained in the CM to its inhibitory effect on OPC apoptosis. Removal of EVs from the CM by ultracentrifugation reduced its inhibitory effect on OPC apoptosis. To confirm whether EVs derived from MVECs are taken up by cultured OPCs, we labeled EVs with PKH67, a fluorescent dye, and added them to OPC cultures. Many vesicular structures labeled with PKH67 were found within OPCs immediately after their addition. Next we examined the effect of MVEC-derived EVs on OPC behaviors. After 2 days in culture with EVs, there was significantly less pyknotic and more BrdU-positive OPCs when compared to control. We also examined the effect of EVs on motility of OPCs. OPCs migrated longer in the presence of EVs when compared to control. To examine whether these effects on cultured OPCs are shared by EVs from endothelial cells, we prepared EVs from conditioned media of several types of endothelial cells, and tested their effects on cultured OPCs. EVs from all types of endothelial cells we examined reduced apoptosis of OPCs and promoted their motility. Identification of the molecules contained in EVs from endothelial cells may prove helpful for establishment of effective therapies for demyelinating diseases.

  17. Aberrant Lipid Metabolism Promotes Prostate Cancer: Role in Cell Survival under Hypoxia and Extracellular Vesicles Biogenesis

    Directory of Open Access Journals (Sweden)

    Gagan Deep

    2016-07-01

    Full Text Available Prostate cancer (PCa is the leading malignancy among men in United States. Recent studies have focused on the identification of novel metabolic characteristics of PCa, aimed at devising better preventive and therapeutic approaches. PCa cells have revealed unique metabolic features such as higher expression of several enzymes associated with de novo lipogenesis, fatty acid up-take and β-oxidation. This aberrant lipid metabolism has been reported to be important for PCa growth, hormone-refractory progression and treatment resistance. Furthermore, PCa cells effectively use lipid metabolism under adverse environmental conditions for their survival advantage. Specifically, hypoxic cancer cells accumulate higher amount of lipids through a combination of metabolic alterations including high glutamine and fatty acid uptake, as well as decreased fatty acid oxidation. These stored lipids serve to protect cancer cells from oxidative and endoplasmic reticulum stress, and play important roles in fueling cancer cell proliferation following re-oxygenation. Lastly, cellular lipids have also been implicated in extracellular vesicle biogenesis, which play a vital role in intercellular communication. Overall, the new understanding of lipid metabolism in recent years has offered several novel targets to better target and manage clinical PCa.

  18. Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes.

    Science.gov (United States)

    Collins, John A; Wood, Scott T; Nelson, Kimberly J; Rowe, Meredith A; Carlson, Cathy S; Chubinskaya, Susan; Poole, Leslie B; Furdui, Cristina M; Loeser, Richard F

    2016-03-25

    Oxidative stress-mediated post-translational modifications of redox-sensitive proteins are postulated as a key mechanism underlying age-related cellular dysfunction and disease progression. Peroxiredoxins (PRX) are critical intracellular antioxidants that also regulate redox signaling events. Age-related osteoarthritis is a common form of arthritis that has been associated with mitochondrial dysfunction and oxidative stress. The objective of this study was to determine the effect of aging and oxidative stress on chondrocyte intracellular signaling, with a specific focus on oxidation of cytosolic PRX2 and mitochondrial PRX3. Menadione was used as a model to induce cellular oxidative stress. Compared with chondrocytes isolated from young adult humans, chondrocytes from older adults exhibited higher levels of PRX1-3 hyperoxidation basally and under conditions of oxidative stress. Peroxiredoxin hyperoxidation was associated with inhibition of pro-survival Akt signaling and stimulation of pro-death p38 signaling. These changes were prevented in cultured human chondrocytes by adenoviral expression of catalase targeted to the mitochondria (MCAT) and in cartilage explants from MCAT transgenic mice. Peroxiredoxin hyperoxidation was observedin situin human cartilage sections from older adults and in osteoarthritic cartilage. MCAT transgenic mice exhibited less age-related osteoarthritis. These findings demonstrate that age-related oxidative stress can disrupt normal physiological signaling and contribute to osteoarthritis and suggest peroxiredoxin hyperoxidation as a potential mechanism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Autophagy controls an intrinsic host defense to bacteria by promoting epithelial cell survival: a murine model.

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    Sun-Young Chang

    Full Text Available Cell death is a critical host response to regulate the fate of bacterial infections, innate immune responses, and ultimately, disease outcome. Shigella spp. invade and colonize gut epithelium in human and nonhuman primates but adult mice are naturally resistant to intra-gastric Shigella infection. In this study, however, we found Shigella could invade the terminal ileum of the mouse small intestine by 1 hour after infection and be rapidly cleared within 24 h. These early phase events occurred shortly after oral infection resulting in epithelial shedding, degranulation of Paneth cells, and cell death in the intestine. During this process, autophagy proceeded without any signs of inflammation. In contrast, blocking autophagy in epithelial cells enhanced host cell death, leading to tissue destruction and to inflammation, suggesting that autophagic flow relieves cellular stress associated with host cell death and inflammation. Herein we propose a new concept of "epithelial barrier turnover" as a general intrinsic host defense mechanism that increases survival of host cells and inhibits inflammation against enteric bacterial infections, which is regulated by autophagy.

  20. Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination

    Science.gov (United States)

    Zheng, Yu; Miyamoto, David T.; Wittner, Ben S.; Sullivan, James P.; Aceto, Nicola; Jordan, Nicole Vincent; Yu, Min; Karabacak, Nezihi Murat; Comaills, Valentine; Morris, Robert; Desai, Rushil; Desai, Niyati; Emmons, Erin; Milner, John D.; Lee, Richard J.; Wu, Chin-Lee; Sequist, Lecia V.; Haas, Wilhelm; Ting, David T.; Toner, Mehmet; Ramaswamy, Sridhar; Maheswaran, Shyamala; Haber, Daniel A.

    2017-01-01

    Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of β-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4. Depletion of HBB in CTC-derived cultures has minimal effects on primary tumour growth, but it greatly increases apoptosis following ROS exposure, and dramatically reduces CTC-derived lung metastases. These effects are reversed by the anti-oxidant N-Acetyl Cysteine. Conversely, overexpression of HBB is sufficient to suppress intracellular ROS within CTCs. Altogether, these observations suggest that β-globin is selectively deregulated in cancer cells, mediating a cytoprotective effect during blood-borne metastasis. PMID:28181495

  1. Interventions to promote physical activity for adults with intellectual disabilities

    Directory of Open Access Journals (Sweden)

    Viviene A Temple

    2017-07-01

    Full Text Available Objective. To describe interventions designed to promote physical activity for adults with intellectual disabilities and the effects on overall physical activity levels and on health outcomes. Materials and methods. A systematic review of eight databases until January 31, 2015 identified 383 citations. The inclusion criteria were: a the study sample consisted of adults with intellectual disabilities, b the study implemented an intervention to initiate, increase, or maintain physical activity, and c quantitative or qualitative data were used to report the effectiveness of the intervention. Six articles from the 383 citations met this criterion. Results. Three studies resulted in significant increases in physical activity behaviour; however well-controlled trials designed to improve weight status by increasing physical activity did not produce significant effects. Conclusion. Overall, the results indicate that interventions to increase physical activity should simultaneously target the individual with intellectual disability as well as their proximal environment over a sustained period of time.

  2. Applying Transtheoretical Model to Promote Physical Activities Among Women

    Science.gov (United States)

    Pirzadeh, Asiyeh; Mostafavi, Firoozeh; Ghofranipour, Fazllolah; Feizi, Awat

    2015-01-01

    Background: Physical activity is one of the most important indicators of health in communities but different studies conducted in the provinces of Iran showed that inactivity is prevalent, especially among women. Objectives: Inadequate regular physical activities among women, the importance of education in promoting the physical activities, and lack of studies on the women using transtheoretical model, persuaded us to conduct this study with the aim of determining the application of transtheoretical model in promoting the physical activities among women of Isfahan. Materials and Methods: This research was a quasi-experimental study which was conducted on 141 women residing in Isfahan, Iran. They were randomly divided into case and control groups. In addition to the demographic information, their physical activities and the constructs of the transtheoretical model (stages of change, processes of change, decisional balance, and self-efficacy) were measured at 3 time points; preintervention, 3 months, and 6 months after intervention. Finally, the obtained data were analyzed through t test and repeated measures ANOVA test using SPSS version 16. Results: The results showed that education based on the transtheoretical model significantly increased physical activities in 2 aspects of intensive physical activities and walking, in the case group over the time. Also, a high percentage of people have shown progress during the stages of change, the mean of the constructs of processes of change, as well as pros and cons. On the whole, a significant difference was observed over the time in the case group (P < 0.01). Conclusions: This study showed that interventions based on the transtheoretical model can promote the physical activity behavior among women. PMID:26834796

  3. Promoters maintain their relative activity levels under different growth conditions.

    Science.gov (United States)

    Keren, Leeat; Zackay, Ora; Lotan-Pompan, Maya; Barenholz, Uri; Dekel, Erez; Sasson, Vered; Aidelberg, Guy; Bren, Anat; Zeevi, Danny; Weinberger, Adina; Alon, Uri; Milo, Ron; Segal, Eran

    2013-10-29

    Most genes change expression levels across conditions, but it is unclear which of these changes represents specific regulation and what determines their quantitative degree. Here, we accurately measured activities of ~900 S. cerevisiae and ~1800 E. coli promoters using fluorescent reporters. We show that in both organisms 60-90% of promoters change their expression between conditions by a constant global scaling factor that depends only on the conditions and not on the promoter's identity. Quantifying such global effects allows precise characterization of specific regulation-promoters deviating from the global scale line. These are organized into few functionally related groups that also adhere to scale lines and preserve their relative activities across conditions. Thus, only several scaling factors suffice to accurately describe genome-wide expression profiles across conditions. We present a parameter-free passive resource allocation model that quantitatively accounts for the global scaling factors. It suggests that many changes in expression across conditions result from global effects and not specific regulation, and provides means for quantitative interpretation of expression profiles.

  4. Galectin-3 up-regulation in hypoxic and nutrient deprived microenvironments promotes cell survival.

    Directory of Open Access Journals (Sweden)

    Rafael Yamashita Ikemori

    Full Text Available Galectin-3 (gal-3 is a β-galactoside binding protein related to many tumoral aspects, e.g. angiogenesis, cell growth and motility and resistance to cell death. Evidence has shown its upregulation upon hypoxia, a common feature in solid tumors such as glioblastoma multiformes (GBM. This tumor presents a unique feature described as pseudopalisading cells, which accumulate large amounts of gal-3. Tumor cells far from hypoxic/nutrient deprived areas express little, if any gal-3. Here, we have shown that the hybrid glioma cell line, NG97ht, recapitulates GBM growth forming gal-3 positive pseudopalisades even when cells are grafted subcutaneously in nude mice. In vitro experiments were performed exposing these cells to conditions mimicking tumor areas that display oxygen and nutrient deprivation. Results indicated that gal-3 transcription under hypoxic conditions requires previous protein synthesis and is triggered in a HIF-1α and NF-κB dependent manner. In addition, a significant proportion of cells die only when exposed simultaneously to hypoxia and nutrient deprivation and demonstrate ROS induction. Inhibition of gal-3 expression using siRNA led to protein knockdown followed by a 1.7-2.2 fold increase in cell death. Similar results were also found in a human GBM cell line, T98G. In vivo, U87MG gal-3 knockdown cells inoculated subcutaneously in nude mice demonstrated decreased tumor growth and increased time for tumor engraftment. These results indicate that gal-3 protected cells from cell death under hypoxia and nutrient deprivation in vitro and that gal-3 is a key factor in tumor growth and engraftment in hypoxic and nutrient-deprived microenvironments. Overexpression of gal-3, thus, is part of an adaptive program leading to tumor cell survival under these stressing conditions.

  5. p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53-Lys118 acetylation

    Science.gov (United States)

    Gogna, Rajan; Madan, Esha; Khan, Mahmood; Pati, Uttam; Kuppusamy, Periannan

    2013-01-01

    Myocardial infarction, an irreversible cardiac tissue damage, involves progressive loss of cardiomyocytes due to p53-mediated apoptosis. Oxygenation is known to promote cardiac survival through activation of NOS3 gene. We hypothesized a dual role for p53, which, depending on oxygenation, can elicit apoptotic death signals or NOS3-mediated survival signals in the infarct heart. p53 exhibited a differential DNA-binding, namely, BAX-p53RE in the infarct heart or NOS3-p53RE in the oxygenated heart, which was regulated by oxygen-induced, post-translational modification of p53. In the infarct heart, p53 was heavily acetylated at Lys118 residue, which was exclusively reversed in the oxygenated heart, apparently regulated by oxygen-dependent expression of TIP60. The inhibition of Lys118 acetylation promoted the generation of NOS3-promoting prosurvival form of p53. Thus, oxygenation switches p53-DNA interaction by regulating p53 core-domain acetylation, promoting a prosurvival transcription activity of p53. Understanding this novel oxygen-p53 survival pathway will open new avenues in cardioprotection molecular therapy. PMID:24096875

  6. p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53-Lys(118) acetylation.

    Science.gov (United States)

    Gogna, Rajan; Madan, Esha; Khan, Mahmood; Pati, Uttam; Kuppusamy, Periannan

    2013-11-01

    Myocardial infarction, an irreversible cardiac tissue damage, involves progressive loss of cardiomyocytes due to p53-mediated apoptosis. Oxygenation is known to promote cardiac survival through activation of NOS3 gene. We hypothesized a dual role for p53, which, depending on oxygenation, can elicit apoptotic death signals or NOS3-mediated survival signals in the infarct heart. p53 exhibited a differential DNA-binding, namely, BAX-p53RE in the infarct heart or NOS3-p53RE in the oxygenated heart, which was regulated by oxygen-induced, post-translational modification of p53. In the infarct heart, p53 was heavily acetylated at Lys(118) residue, which was exclusively reversed in the oxygenated heart, apparently regulated by oxygen-dependent expression of TIP60. The inhibition of Lys(118) acetylation promoted the generation of NOS3-promoting prosurvival form of p53. Thus, oxygenation switches p53-DNA interaction by regulating p53 core-domain acetylation, promoting a prosurvival transcription activity of p53. Understanding this novel oxygen-p53 survival pathway will open new avenues in cardioprotection molecular therapy. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  7. RELM-β promotes human pulmonary artery smooth muscle cell proliferation via FAK-stimulated surviving

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chunlong, E-mail: lclmd@sina.com; Li, Xiaohui; Luo, Qiong; Yang, Hui; Li, Lun; Zhou, Qiong; Li, Yue; Tang, Hao; Wu, Lifu

    2017-02-01

    Resistin-like molecule-β (RELM-β), focal adhesion kinase (FAK), and survivin may be involved in the proliferation of cultured human pulmonary artery smooth muscle cells (HPAMSCs), which is involved in pulmonary hypertension. HPAMSCs were treated with human recombinant RELM-β (rhRELM-β). siRNAs against FAK and survivin were transfected into cultured HPASMCs. Expression of FAK and survivin were examined by RT-PCR and western blot. Immunofluorescence was used to localize FAK. Flow cytometry was used to examine cell cycle distribution and cell death. Compared to the control group, all rhRELM-β-treated groups demonstrated significant increases in the expression of FAK and survivin (P<0.05). rhRELM-β significantly increased the proportion of HPASMCs in the S phase and decreased the proportion in G0/G1. FAK siRNA down-regulated survivin expression while survivin siRNA did not affect FAK expression. FAK siRNA effectively inhibited FAK and survivin expression in RELM-β-treated HPASMCs and partially suppressed cell proliferation. RELM-β promoted HPASMC proliferation and upregulated FAK and survivin expression. In conclusion, results suggested that FAK is upstream of survivin in the signaling pathway mediating cell proliferation. FAK seems to be important in RELM-β-induced HPASMC proliferation, partially by upregulating survivin expression. - Highlights: • rhRELM-β increased the expression of FAK and survivin. • rhRELM-β increased the proportion of HPASMCs in the S phase. • FAK is upstream of survivin in the signaling pathway mediating cell proliferation. • FAK is important in RELM-β-induced HPASMC proliferation, partly via survivin.

  8. Pancreatic Islet Survival and Engraftment Is Promoted by Culture on Functionalized Spider Silk Matrices.

    Science.gov (United States)

    Johansson, Ulrika; Ria, Massimiliano; Åvall, Karin; Dekki Shalaly, Nancy; Zaitsev, Sergei V; Berggren, Per-Olof; Hedhammar, My

    2015-01-01

    Transplantation of pancreatic islets is one approach for treatment of diabetes, however, hampered by the low availability of viable islets. Islet isolation leads to disruption of the environment surrounding the endocrine cells, which contributes to eventual cell death. The reestablishment of this environment is vital, why we herein investigated the possibility of using recombinant spider silk to support islets in vitro after isolation. The spider silk protein 4RepCT was formulated into three different formats; 2D-film, fiber mesh and 3D-foam, in order to provide a matrix that can give the islets physical support in vitro. Moreover, cell-binding motifs from laminin were incorporated into the silk protein in order to create matrices that mimic the natural cell environment. Pancreatic mouse islets were thoroughly analyzed for adherence, necrosis and function after in vitro maintenance on the silk matrices. To investigate their suitability for transplantation, we utilized an eye model which allows in vivo imaging of engraftment. Interestingly, islets that had been maintained on silk foam during in vitro culture showed improved revascularization. This coincided with the observation of preserved islet architecture with endothelial cells present after in vitro culture on silk foam. Selected matrices were further evaluated for long-term preservation of human islets. Matrices with the cell-binding motif RGD improved human islet maintenance (from 36% to 79%) with preserved islets architecture and function for over 3 months in vitro. The islets established cell-matrix contacts and formed vessel-like structures along the silk. Moreover, RGD matrices promoted formation of new, insulin-positive islet-like clusters that were connected to the original islets via endothelial cells. On silk matrices with islets from younger donors (<35 year), the amount of newly formed islet-like clusters found after 1 month in culture were almost double compared to the initial number of islets

  9. Pancreatic Islet Survival and Engraftment Is Promoted by Culture on Functionalized Spider Silk Matrices

    Science.gov (United States)

    Johansson, Ulrika; Dekki Shalaly, Nancy; Zaitsev, Sergei V.; Berggren, Per-Olof; Hedhammar, My

    2015-01-01

    Transplantation of pancreatic islets is one approach for treatment of diabetes, however, hampered by the low availability of viable islets. Islet isolation leads to disruption of the environment surrounding the endocrine cells, which contributes to eventual cell death. The reestablishment of this environment is vital, why we herein investigated the possibility of using recombinant spider silk to support islets in vitro after isolation. The spider silk protein 4RepCT was formulated into three different formats; 2D-film, fiber mesh and 3D-foam, in order to provide a matrix that can give the islets physical support in vitro. Moreover, cell-binding motifs from laminin were incorporated into the silk protein in order to create matrices that mimic the natural cell environment. Pancreatic mouse islets were thoroughly analyzed for adherence, necrosis and function after in vitro maintenance on the silk matrices. To investigate their suitability for transplantation, we utilized an eye model which allows in vivo imaging of engraftment. Interestingly, islets that had been maintained on silk foam during in vitro culture showed improved revascularization. This coincided with the observation of preserved islet architecture with endothelial cells present after in vitro culture on silk foam. Selected matrices were further evaluated for long-term preservation of human islets. Matrices with the cell-binding motif RGD improved human islet maintenance (from 36% to 79%) with preserved islets architecture and function for over 3 months in vitro. The islets established cell-matrix contacts and formed vessel-like structures along the silk. Moreover, RGD matrices promoted formation of new, insulin-positive islet-like clusters that were connected to the original islets via endothelial cells. On silk matrices with islets from younger donors (<35 year), the amount of newly formed islet-like clusters found after 1 month in culture were almost double compared to the initial number of islets

  10. Glial cell activation, recruitment, and survival of B-lineage cells following MCMV brain infection.

    Science.gov (United States)

    Lokensgard, James R; Mutnal, Manohar B; Prasad, Sujata; Sheng, Wen; Hu, Shuxian

    2016-05-20

    persisted through the latest time tested (60 days post infection). Finally, astrocytes produce BAFF (B cell activating factor of the TNF family) and promote proliferation of B cells via cell-to-cell contact. CXCR3 is the primary chemokine receptor on CD19(+) B cells persisting within the brain, and migration to microglial cell supernatants is mediated through this receptor. Correspondingly, microglial cells produce CXCL9 and CXCL10, but not CXCL13. Reactive astrocytes promote B cell proliferation.

  11. Promoting physical activity in teen girls: insight from focus groups.

    Science.gov (United States)

    Loman, Deborah G

    2008-01-01

    To describe adolescent girls' views about physical activity and explore strategies that nurses can use to promote physical activity. A qualitative study using focus groups and interviews with 28 girls (12-18 years of age) recruited from schools and neighborhood health centers in a Midwest metropolitan area. An interview guide with 15 open-ended questions was used, and data were analyzed using content analysis. Most girls preferred the phrase "physical activity" over "exercise." The benefits most frequently mentioned included positive physical attributes, mental health benefits, and staying healthy. Three major themes were identified: autonomy (ask them what they like to do, and then provide choices), fun (being with friends, variation, and enjoyment), and body image (gaining weight, appearance, and self-confidence). Nursing interventions to promote physical activity and other healthy lifestyle changes that may prevent obesity should include active listening and a focus on the goals of the teen. Nurses need to evaluate their teaching and counseling approach, because the teens emphasized two points: "Don't tell me what to do" and "Don't put me down."

  12. Oncogenic K-Ras Signals through Epidermal Growth Factor Receptor and Wild-Type H-Ras to Promote Radiation Survival in Pancreatic and Colorectal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Keith A. Cengel

    2007-04-01

    Full Text Available Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor o was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFRactivated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers.

  13. Hypothermia activates adipose tissue to promote malignant lung cancer progression.

    Directory of Open Access Journals (Sweden)

    Gangjun Du

    Full Text Available Microenvironment has been increasingly recognized as a critical regulator of cancer progression. In this study, we identified early changes in the microenvironment that contribute to malignant progression. Exposure of human bronchial epithelial cells (BEAS-2B to methylnitrosourea (MNU caused a reduction in cell toxicity and an increase in clonogenic capacity when the temperature was lowered from 37°C to 28°C. Hypothermia-incubated adipocyte media promoted proliferation in A549 cells. Although a hypothermic environment could increase urethane-induced tumor counts and Lewis lung cancer (LLC metastasis in lungs of three breeds of mice, an increase in tumor size could be discerned only in obese mice housed in hypothermia. Similarly, coinjections using differentiated adipocytes and A549 cells promoted tumor development in athymic nude mice when adipocytes were cultured at 28°C. Conversely, fat removal suppressed tumor growth in obese C57BL/6 mice inoculated with LLC cells. Further studies show hypothermia promotes a MNU-induced epithelial-mesenchymal transition (EMT and protects the tumor cell against immune control by TGF-β1 upregulation. We also found that activated adipocytes trigger tumor cell proliferation by increasing either TNF-α or VEGF levels. These results suggest that hypothermia activates adipocytes to stimulate tumor boost and play critical determinant roles in malignant progression.

  14. Hypothermia activates adipose tissue to promote malignant lung cancer progression.

    Science.gov (United States)

    Du, Gangjun; Zhao, Bei; Zhang, Yaping; Sun, Ting; Liu, Weijie; Li, Jiahuan; Liu, Yinghui; Wang, Yingying; Li, Hong; Hou, Xidong

    2013-01-01

    Microenvironment has been increasingly recognized as a critical regulator of cancer progression. In this study, we identified early changes in the microenvironment that contribute to malignant progression. Exposure of human bronchial epithelial cells (BEAS-2B) to methylnitrosourea (MNU) caused a reduction in cell toxicity and an increase in clonogenic capacity when the temperature was lowered from 37°C to 28°C. Hypothermia-incubated adipocyte media promoted proliferation in A549 cells. Although a hypothermic environment could increase urethane-induced tumor counts and Lewis lung cancer (LLC) metastasis in lungs of three breeds of mice, an increase in tumor size could be discerned only in obese mice housed in hypothermia. Similarly, coinjections using differentiated adipocytes and A549 cells promoted tumor development in athymic nude mice when adipocytes were cultured at 28°C. Conversely, fat removal suppressed tumor growth in obese C57BL/6 mice inoculated with LLC cells. Further studies show hypothermia promotes a MNU-induced epithelial-mesenchymal transition (EMT) and protects the tumor cell against immune control by TGF-β1 upregulation. We also found that activated adipocytes trigger tumor cell proliferation by increasing either TNF-α or VEGF levels. These results suggest that hypothermia activates adipocytes to stimulate tumor boost and play critical determinant roles in malignant progression.

  15. Serpins Promote Cancer Cell Survival and Vascular Cooption in Brain Metastasis

    Science.gov (United States)

    Valiente, Manuel; Obenauf, Anna C.; Jin, Xin; Chen, Qing; Zhang, Xiang H.-F.; Lee, Derek J.; Chaft, Jamie E.; Kris, Mark G.; Huse, Jason T.; Brogi, Edi; Massagué, Joan

    2014-01-01

    Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM that metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its deleterious consequences. By protecting cancer cells from death signals and fostering vascular cooption, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers. PMID:24581498

  16. Presentation and exhibition activities for promoting theexportof transport services

    Directory of Open Access Journals (Sweden)

    Darya Vladimirovna Nesterova

    2012-03-01

    Full Text Available Development of presentation and exhibition activities is considered as an important factor in providing new competitive advantages at the strategic markets for exporting of transportation services. A specific role for exhibition activities as a factor to overcome market failures arose from imperfect information and incomplete markets is displayed. Exhibitions are considered as a true reflection of most market parameters, as a means to get correct information concerning market capacity and its borders, as an instrument to access to new markets. At the firm level presentation and branding activities should be considered as a modern technology (especially it concerns Russian companies which provide to hold up already existed markets and to conquer new ones. Presentation and branding activities are an effective technology to promote company trade-mark, competitive advantages for market demand increasing. Comparative analysis of the main exhibitions on transport and logistics issues is fulfilled on the data basecollected by authors. Data observes geographical distribution of transport exhibition and exhibition facilities development at several regions for the last years. The analyses allow to revealing a geographical structure of the exhibitions and its distribution by type of transport. The most promising and economically favorable exhibition areas for the promotion of Russian transport services are shown.

  17. The Analysis of World Experiences in Promoting Export Activity

    Directory of Open Access Journals (Sweden)

    Kotysh Olena M.

    2017-10-01

    Full Text Available This article proposes a theoretical analysis of the scientific approaches to defining concepts such as «exports» and «export activity». The results of the study helped to reveal that these concepts are identical, although this approach is criticized by many scientists. In the publication presented, the export activity is understood as a combination of actions on the part of the enterprises – foreign economic actors, involved in organizational arrangements aimed at preparation and marketing of goods to foreign economic actors. The article calculates the macro indicators in dynamics in order to characterize the status of Ukraine’s export activities. Its main development tendencies have been identified, the main challenges and directions for further development have been indicated. The article provides the international experience in promoting exports worldwide, the main tasks and functions of export promotion institutions have been explained, thus creating possibility to form recommendations for further actions on the part of the State to support and develop the export activity of Ukraine.

  18. Serpins promote cancer cell survival and vascular co-option in brain metastasis.

    Science.gov (United States)

    Valiente, Manuel; Obenauf, Anna C; Jin, Xin; Chen, Qing; Zhang, Xiang H-F; Lee, Derek J; Chaft, Jamie E; Kris, Mark G; Huse, Jason T; Brogi, Edi; Massagué, Joan

    2014-02-27

    Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here, we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM, which metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its metastasis-suppressive effects. By protecting cancer cells from death signals and fostering vascular co-option, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. In Vitro Modulation of TrkB Receptor Signaling upon Sequential Delivery of Curcumin-DHA Loaded Carriers Towards Promoting Neuronal Survival.

    Science.gov (United States)

    Guerzoni, Luis P B; Nicolas, Valérie; Angelova, Angelina

    2017-02-01

    To in vitro investigate the capacity of carrier-free and lipid-nanoparticle (NP)-encapsulated phytochemical compounds to prevent neuronal damage through neurotrophin potentiating activities. Delivery of molecules promoting the neurotrophin receptor signaling in the central nervous system (CNS) present ongoing interest for combination therapy development. Super-resolution Stimulated Emission Depletion (STED) microscopy imaging and flow cytometry analysis were employed to study the expression of the neurotrophin TrkB receptor in a neuronal cell model, which is highly responsive to binding of brain-derived neurotrophic factor (BDNF). Dual drug-loaded nanoparticle formulations, prepared by self-assembly of lyotropic lipids and PEGylated amphiphile derivatives, were delivered to differentiated human neuroblastoma SH-SY5Y cells subjected to degenerative conditions. The expression of BDNF in the intra and extracellular domains was quantified by ELISA and flow cytometry after sequential treatment of the degenerating SH-SY5Y cells by neurotherapeutic formulations. Flow cytometry was also used to assess the phosphorylation of the transcription factor cAMP response element-binding protein (CREB) in the intracellular domain as a result of the treatment by nanoformulations. Over time, dual drug formulations (curcumin and docosahexaenoic acid (DHA)) promoted the neuronal survival and repair processes through enhanced BDNF secretion and increased phosphorylation of CREB as compared to untreated degenerating cells.

  20. The Predictive Factors of the Promotion of Physical Activity by Air Force Squadron Commanders

    National Research Council Canada - National Science Library

    Whelan, Dana

    2001-01-01

    This research examined the relationship between beliefs about physical activity, physical activity levels, age and the promotional practices for physical activity employed by Air Force squadron commanders...

  1. MiR-9, -31, and -182 deregulation promote proliferation and tumor cell survival in colon cancer.

    Science.gov (United States)

    Cekaite, Lina; Rantala, Juha K; Bruun, Jarle; Guriby, Marianne; Agesen, Trude H; Danielsen, Stine A; Lind, Guro E; Nesbakken, Arild; Kallioniemi, Olli; Lothe, Ragnhild A; Skotheim, Rolf I

    2012-09-01

    Several microRNAs (miRNAs) are known to be deregulated in colon cancer, but the mechanisms behind their potential involvement on proliferation and tumor cell survival are unclear. The present study aimed to identify miRNAs with functional implications for development of colon cancer. The cell proliferation and apoptosis were examined following perturbations of miRNA levels by employing a comprehensive miRNA library screen. miRNAs nominated for relevance to colon cancer were validated on expression and functional levels. By integrating the effect of miRNA up-regulation with the endogenous miRNA expression levels within the HT29, HCT116, and SW480 colon cancer cell lines, we identified miRNAs controlling cell proliferation (n = 53) and apoptosis (n = 93). From these functionally nominated miRNAs, we narrowed the list to 10 oncogene- and 20 tumor suppressor-like miRNAs that were also differentially expressed between colon cancer (n = 80) and normal colonic mucosa (n = 20). The differential expressions of miR-9, miR-31, and miR-182 were successfully validated in a series of colon carcinomas (n = 30) and polyps (n = 10) versus normal colonic mucosa (n = 10), whereas the functional effect was confirmed in an in-depth validation using different cell viability and apoptotic markers. Several transcription factors and genes regulating cell proliferation were identified as putative target genes by integrative miRNA/mRNA expression analysis obtained from the same colon cancer patient samples. This study suggests that deregulated expression of miR-9, miR-31, and miR-182 during carcinogenesis plays a significant role in the development of colon cancer by promoting proliferation and tumor cell survival.

  2. MiR-9, -31, and -182 Deregulation Promote Proliferation and Tumor Cell Survival in Colon Cancer12

    Science.gov (United States)

    Cekaite, Lina; Rantala, Juha K; Bruun, Jarle; Guriby, Marianne; Ågesen, Trude H; Danielsen, Stine A; Lind, Guro E; Nesbakken, Arild; Kallioniemi, Olli; Lothe, Ragnhild A; Skotheim, Rolf I

    2012-01-01

    Several microRNAs (miRNAs) are known to be deregulated in colon cancer, but the mechanisms behind their potential involvement on proliferation and tumor cell survival are unclear. The present study aimed to identify miRNAs with functional implications for development of colon cancer. The cell proliferation and apoptosis were examined following perturbations of miRNA levels by employing a comprehensive miRNA library screen. miRNAs nominated for relevance to colon cancer were validated on expression and functional levels. By integrating the effect of miRNA up-regulation with the endogenous miRNA expression levels within the HT29, HCT116, and SW480 colon cancer cell lines, we identified miRNAs controlling cell proliferation (n = 53) and apoptosis (n = 93). From these functionally nominated miRNAs, we narrowed the list to 10 oncogene- and 20 tumor suppressor-like miRNAs that were also differentially expressed between colon cancer (n = 80) and normal colonic mucosa (n = 20). The differential expressions of miR-9, miR-31, and miR-182 were successfully validated in a series of colon carcinomas (n = 30) and polyps (n = 10) versus normal colonic mucosa (n = 10), whereas the functional effect was confirmed in an in-depth validation using different cell viability and apoptotic markers. Several transcription factors and genes regulating cell proliferation were identified as putative target genes by integrative miRNA/mRNA expression analysis obtained from the same colon cancer patient samples. This study suggests that deregulated expression of miR-9, miR-31, and miR-182 during carcinogenesis plays a significant role in the development of colon cancer by promoting proliferation and tumor cell survival. PMID:23019418

  3. MiR-9, -31, and -182 Deregulation Promote Proliferation and Tumor Cell Survival in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Lina Cekaite

    2012-09-01

    Full Text Available Several microRNAs (miRNAs are known to be deregulated in colon cancer, but the mechanisms behind their potential involvement on proliferation and tumor cell survival are unclear. The present study aimed to identify miRNAs with functional implications for development of colon cancer. The cell proliferation and apoptosis were examined following perturbations of miRNA levels by employing a comprehensive miRNA library screen. miRNAs nominated for relevance to colon cancer were validated on expression and functional levels. By integrating the effect of miRNA up-regulation with the endogenous miRNA expression levels within the HT29, HCT116, and SW480 colon cancer cell lines, we identified miRNAs controlling cell proliferation (n = 53 and apoptosis (n = 93. From these functionally nominated miRNAs, we narrowed the list to 10 oncogene- and 20 tumor suppressor-like miRNAs that were also differentially expressed between colon cancer (n = 80 and normal colonic mucosa (n = 20. The differential expressions of miR-9, miR-31, and miR-182 were successfully validated in a series of colon carcinomas (n = 30 and polyps (n = 10 versus normal colonic mucosa (n = 10, whereas the functional effect was confirmed in an in-depth validation using different cell viability and apoptotic markers. Several transcription factors and genes regulating cell proliferation were identified as putative target genes by integrative miRNA/mRNA expression analysis obtained from the same colon cancer patient samples. This study suggests that deregulated expression of miR-9, miR-31, and miR-182 during carcinogenesis plays a significant role in the development of colon cancer by promoting proliferation and tumor cell survival.

  4. The cytoprotective protein clusterin is overexpressed in hypergastrinemic rodent models of oxyntic preneoplasia and promotes gastric cancer cell survival.

    Directory of Open Access Journals (Sweden)

    Pål Vange

    Full Text Available The cytoprotective protein clusterin is often dysregulated during tumorigenesis, and in the stomach, upregulation of clusterin marks emergence of the oxyntic atrophy (loss of acid-producing parietal cells-associated spasmolytic polypeptide-expressing metaplasia (SPEM. The hormone gastrin is important for normal function and maturation of the gastric oxyntic mucosa and hypergastrinemia might be involved in gastric carcinogenesis. Gastrin induces expression of clusterin in adenocarcinoma cells. In the present study, we examined the expression patterns and gastrin-mediated regulation of clusterin in gastric tissue from: humans; rats treated with proton pump (H+/K+-ATPase inhibitors and/or a gastrin receptor (CCK2R antagonist; H+/K+-ATPase β-subunit knockout (H/K-β KO mice; and Mongolian gerbils infected with Helicobacter pylori and given a CCK2R antagonist. Biological function of secretory clusterin was studied in human gastric cancer cells. Clusterin was highly expressed in neuroendocrine cells in normal oxyntic mucosa of humans and rodents. In response to hypergastrinemia, expression of clusterin increased significantly and its localization shifted to basal groups of proliferative cells in the mucous neck cell-chief cell lineage in all animal models. That shift was partially inhibited by antagonizing the CCK2R in rats and gerbils. The oxyntic mucosa of H/K-β KO mice contained areas with clusterin-positive mucous cells resembling SPEM. In gastric adenocarcinomas, clusterin mRNA expression was higher in diffuse tumors containing signet ring cells compared with diffuse tumors without signet ring cells, and clusterin seemed to be secreted by tumor cells. In gastric cancer cell lines, gastrin increased secretion of clusterin, and both gastrin and secretory clusterin promoted survival after starvation- and chemotherapy-induced stress. Overall, our results indicate that clusterin is overexpressed in hypergastrinemic rodent models of oxyntic

  5. ERLIN2 promotes breast cancer cell survival by modulating endoplasmic reticulum stress pathways

    Directory of Open Access Journals (Sweden)

    Wang Guohui

    2012-06-01

    Full Text Available Abstract Background Amplification of the 8p11-12 region has been found in approximately 15% of human breast cancer and is associated with poor prognosis. Previous genomic analysis has led us to identify the endoplasmic reticulum (ER lipid raft-associated 2 (ERLIN2 gene as one of the candidate oncogenes within the 8p11-12 amplicon in human breast cancer, particularly in the luminal subtype. ERLIN2, an ER membrane protein, has recently been identified as a novel mediator of ER-associated degradation. Yet, the biological roles of ERLIN2 and molecular mechanisms by which ERLIN2 coordinates ER pathways in breast carcinogenesis remain unclear. Methods We established the MCF10A-ERLIN2 cell line, which stably over expresses ERLIN2 in human nontransformed mammary epithelial cells (MCF10A using the pLenti6/V5-ERLIN2 construct. ERLIN2 over expressing cells and their respective parental cell lines were assayed for in vitro transforming phenotypes. Next, we knocked down the ERLIN2 as well as the ER stress sensor IRE1α activity in the breast cancer cell lines to characterize the biological roles and molecular basis of the ERLIN2 in carcinogenesis. Finally, immunohistochemical staining was performed to detect ERLIN2 expression in normal and cancerous human breast tissues Results We found that amplification of the ERLIN2 gene and over expression of the ERLIN2 protein occurs in both luminal and Her2 subtypes of breast cancer. Gain- and loss-of-function approaches demonstrated that ERLIN2 is a novel oncogenic factor associated with the ER stress response pathway. The IRE1α/XBP1 axis in the ER stress pathway modulated expression of ERLIN2 protein levels in breast cancer cells. We also showed that over expression of ERLIN2 facilitated the adaptation of breast epithelial cells to ER stress by supporting cell growth and protecting the cells from ER stress-induced cell death. Conclusions ERLIN2 may confer a selective growth advantage for breast cancer cells by

  6. Glycine Receptor α2 Subunit Activation Promotes Cortical Interneuron Migration

    Directory of Open Access Journals (Sweden)

    Ariel Avila

    2013-08-01

    Full Text Available Glycine receptors (GlyRs are detected in the developing CNS before synaptogenesis, but their function remains elusive. This study demonstrates that functional GlyRs are expressed by embryonic cortical interneurons in vivo. Furthermore, genetic disruption of these receptors leads to interneuron migration defects. We discovered that extrasynaptic activation of GlyRs containing the α2 subunit in cortical interneurons by endogenous glycine activates voltage-gated calcium channels and promotes calcium influx, which further modulates actomyosin contractility to fine-tune nuclear translocation during migration. Taken together, our data highlight the molecular events triggered by GlyR α2 activation that control cortical tangential migration during embryogenesis.

  7. Cytoplasmic ATR Activation Promotes Vaccinia Virus Genome Replication

    Directory of Open Access Journals (Sweden)

    Antonio Postigo

    2017-05-01

    Full Text Available In contrast to most DNA viruses, poxviruses replicate their genomes in the cytoplasm without host involvement. We find that vaccinia virus induces cytoplasmic activation of ATR early during infection, before genome uncoating, which is unexpected because ATR plays a fundamental nuclear role in maintaining host genome integrity. ATR, RPA, INTS7, and Chk1 are recruited to cytoplasmic DNA viral factories, suggesting canonical ATR pathway activation. Consistent with this, pharmacological and RNAi-mediated inhibition of canonical ATR signaling suppresses genome replication. RPA and the sliding clamp PCNA interact with the viral polymerase E9 and are required for DNA replication. Moreover, the ATR activator TOPBP1 promotes genome replication and associates with the viral replisome component H5. Our study suggests that, in contrast to long-held beliefs, vaccinia recruits conserved components of the eukaryote DNA replication and repair machinery to amplify its genome in the host cytoplasm.

  8. Interventions to promote physical activity for youth with intellectual disabilities

    Directory of Open Access Journals (Sweden)

    Georgia C Frey

    2017-07-01

    Full Text Available Objective. To describe interventions designed to promote physical activity for youth with intellectual disabilities. Materials and methods. A systematic review of nine databases until January 31, 2015 identified 213 citations. The inclusion criteria were: a the study sample consisted of youth with intellectual disabilities, b the study implemented an intervention to initiate, increase, or maintain physical activity, and c quantitative or qualitative data were used to report the effectiveness of the intervention. Eleven articles from the 213 citations met this criterion. Results. Nine studies reported significant increases in physical activity behavior. Conclusions. Conclusions cannot be made regarding intervention components that impacted outcome variables, if the observed effects were specifically due to the intervention or if interventions could be maintained long-term. To advance the knowledge base in this area, a concerted effort should be made to increase rigor in study conceptualization and research design.

  9. SLC25A22 Promotes Proliferation and Survival of Colorectal Cancer Cells With KRAS Mutations and Xenograft Tumor Progression in Mice via Intracellular Synthesis of Aspartate.

    Science.gov (United States)

    Wong, Chi Chun; Qian, Yun; Li, Xiaona; Xu, Jiaying; Kang, Wei; Tong, Joanna H; To, Ka-Fai; Jin, Ye; Li, Weilin; Chen, Huarong; Go, Minnie Y Y; Wu, Jian-Lin; Cheng, Ka Wing; Ng, Simon S M; Sung, Joseph J Y; Cai, Zongwei; Yu, Jun

    2016-11-01

    regeneration of oxidized nicotinamide adenine dinucleotide and reduced nicotinamide adenine dinucleotide phosphate. Reduced oxidized nicotinamide adenine dinucleotide inhibited glycolysis and decreased levels of adenosine triphosphate, which inactivated mitogen-activated protein kinase kinase and extracellular signal-regulated kinase signaling via activation of AMP-activated protein kinase. An increased ratio of oxidized nicotinamide adenine dinucleotide phosphate to reduced nicotinamide adenine dinucleotide phosphate induced oxidative stress and glutathione oxidation, which suppressed cell proliferation. Asparagine synthetase mediated synthesis of asparagine from aspartate to promote cell migration. SLC25A22 promotes proliferation and migration of CRC cells with mutations KRAS, and formation and metastasis of CRC xenograft tumors in mice. Patients with colorectal tumors that express increased levels of SLC25A22 have shorter survival times than patients whose tumors have lower levels. SLC25A22 induces intracellular synthesis of aspartate, activation of mitogen-activated protein kinase kinase and extracellular signal-regulated kinase signaling and reduces oxidative stress. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. Vampire bat salivary plasminogen activator (desmoteplase): a unique fibrinolytic enzyme that does not promote neurodegeneration.

    Science.gov (United States)

    Liberatore, Gabriel T; Samson, André; Bladin, Christopher; Schleuning, Wolf-Dieter; Medcalf, Robert L

    2003-02-01

    Tissue-type plasminogen activator (tPA) promotes excitotoxic and ischemic injury within the brain. These findings have implications for the use of tPA in the treatment of acute ischemic stroke. The plasminogen activator from vampire bat (Desmodus rotundus) saliva (D rotundus salivary plasminogen activator [DSPA]; desmoteplase) is an effective plasminogen activator but, in contrast to tPA, is nearly inactive in the absence of a fibrin cofactor. The purpose of this study was to compare the ability of DSPA and tPA to promote kainate- and N-methyl-D-aspartate (NMDA)-induced neurodegeneration in tPA-/- mice and wild-type mice, respectively. tPA-/- mice were infused intracerebrally with either tPA or DSPA. The degree of neuronal survival after hippocampal injection of kainate was assessed histochemically. Wild-type mice were used to assess the extent of neuronal damage after intrastriatal injection of NMDA in the presence of tPA or DSPA. Immunohistochemistry and fibrin zymography were used to evaluate DSPA and tPA antigen or activity. Infusion of tPA into tPA-/- mice restored sensitivity to kainate-mediated neurotoxicity and activation of microglia. DSPA was incapable of conferring sensitivity to kainate treatment, even when infused at 10-fold higher molar concentration than tPA. The presence of tPA also increased the lesion volume induced by NMDA injection into the striatum of wild-type mice, whereas DSPA had no effect. DSPA does not promote kainate- or NMDA-mediated neurotoxicity in vivo. These results provide significant impetus to evaluate DSPA in patients with ischemic stroke.

  11. Human mediator subunit MED15 promotes transcriptional activation.

    Science.gov (United States)

    Nakatsubo, Takuya; Nishitani, Saori; Kikuchi, Yuko; Iida, Satoshi; Yamada, Kana; Tanaka, Aki; Ohkuma, Yoshiaki

    2014-10-01

    In eukaryotes, the Mediator complex is an essential transcriptional cofactor of RNA polymerase II (Pol II). In humans, it contains up to 30 subunits and consists of four modules: head, middle, tail, and CDK/Cyclin. One of the subunits, MED15, is located in the tail module, and was initially identified as Gal11 in budding yeast, where it plays an essential role in the transcriptional regulation of galactose metabolism with the potent transcriptional activator Gal4. For this reason, we investigated the function of the human MED15 subunit (hMED15) in transcriptional activation. First, we measured the effect of hMED15 knockdown on cell growth in HeLa cells. The growth rate was greatly reduced. By immunostaining, we observed the colocalization of hMED15 with the general transcription factors TFIIE and TFIIH in the nucleus. We measured the effects of siRNA-mediated knockdown of hMED15 on transcriptional activation using two different transcriptional activators, VP16 and SREBP1a. Treatment with siRNAs reduced transcriptional activation, and this reduction could be rescued by overexpression of HA/Flag-tagged, wild-type hMED15. To investigate hMED15 localization, we treated human MCF-7 cells with the MDM2 inhibitor Nutlin-3, thus inducing p21 transcription. We found that hMED15 localized to both the p53 binding site and the p21 promoter region, along with TFIIE and TFIIH. These results indicate that hMED15 promotes transcriptional activation.

  12. Mycobacterium tuberculosis 19-kDa lipoprotein promotes neutrophil activation.

    Science.gov (United States)

    Neufert, C; Pai, R K; Noss, E H; Berger, M; Boom, W H; Harding, C V

    2001-08-01

    Certain microbial substances, e.g., LPS, can activate neutrophils or prime them to enhance their response to other activating agents, e.g., fMLP. We investigated the role of the Mycobacterium tuberculosis (MTB) 19-kDa lipoprotein in activation of human neutrophils. MTB 19-kDa lipoprotein initiated phenotypic changes characteristic of neutrophil activation, including down-regulation of CD62 ligand (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1). In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced the subsequent oxidative burst in response to fMLP as assessed by oxidation of dihydrorhodamine 123 (determined by flow cytometry). LPS also produced these effects with similar kinetics, but an oligodeoxynucleotide containing a CpG motif failed to induce any priming or activation response. Although the effects of LPS required the presence of serum, neutrophil activation by MTB 19-kDa lipoprotein occurred independently of serum factors, suggesting the involvement of different receptors and signaling mechanisms for LPS and MTB 19-kDa lipoprotein. Thus, MTB 19-kDa lipoprotein serves as a pathogen-associated molecular pattern that promotes neutrophil priming and activation.

  13. Maternal exercise during pregnancy promotes physical activity in adult offspring.

    Science.gov (United States)

    Eclarinal, Jesse D; Zhu, Shaoyu; Baker, Maria S; Piyarathna, Danthasinghe B; Coarfa, Cristian; Fiorotto, Marta L; Waterland, Robert A

    2016-07-01

    Previous rodent studies have shown that maternal voluntary exercise during pregnancy leads to metabolic changes in adult offspring. We set out to test whether maternal voluntary exercise during pregnancy also induces persistent changes in voluntary physical activity in the offspring. Adult C57BL/6J female mice were randomly assigned to be caged with an unlocked (U) or locked (L) running wheel before and during pregnancy. Maternal running behavior was monitored during pregnancy, and body weight, body composition, food intake, energy expenditure, total cage activity, and running wheel activity were measured in the offspring at various ages. U offspring were slightly heavier at birth, but no group differences in body weight or composition were observed at later ages (when mice were caged without access to running wheels). Consistent with our hypothesis, U offspring were more physically active as adults. This effect was observed earlier in female offspring (at sexual maturation). Remarkably, at 300 d of age, U females achieved greater fat loss in response to a 3-wk voluntary exercise program. Our findings show for the first time that maternal physical activity during pregnancy affects the offspring's lifelong propensity for physical activity and may have important implications for combating the worldwide epidemic of physical inactivity and obesity.-Eclarinal, J. D., Zhu, S., Baker, M. S., Piyarathna, D. B., Coarfa, C., Fiorotto, M. L., Waterland, R. A. Maternal exercise during pregnancy promotes physical activity in adult offspring. © FASEB.

  14. Strategies for promoting physical activity in clinical practice.

    Science.gov (United States)

    Sallis, Robert; Franklin, Barry; Joy, Liz; Ross, Robert; Sabgir, David; Stone, James

    2015-01-01

    The time has come for healthcare systems to take an active role in the promotion of physical activity (PA). The connection between PA and health has been clearly established and exercise should be viewed as a cost effective medication that is universally prescribed as a first line treatment for virtually every chronic disease. While there are potential risks associated with exercise, these can be minimized with a proper approach and are far outweighed by the benefits. Key to promoting PA in the clinical setting is the use of a PA Vital Sign in which every patient's exercise habits are assessed and recorded in their medical record. Those not meeting the recommended 150min per week of moderate intensity PA should be encouraged to increase their PA levels with a proper exercise prescription. We can improve compliance by assessing our patient's barriers to being more active and employing new and evolving technology like accelerometers and smart phones applications, along with various websites and programs that have proven efficacy. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

    Science.gov (United States)

    Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

    2016-08-19

    Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

  16. Eplerenone promotes alternative activation in human monocyte-derived macrophages.

    Science.gov (United States)

    Łabuzek, Krzysztof; Liber, Sebastian; Bułdak, Łukasz; Machnik, Grzegorz; Liber, Justyna; Okopień, Bogusław

    2013-01-01

    In this study, we have analyzed the response of human monocyte-derived macrophages to mineralocorticoid axis modulators. Human monocyte-derived macrophages were incubated with aldosterone alone, eplerenone alone, and the combination of aldosterone and eplerenone. The analyzed variables were nitric oxide and reactive oxygen species production, and the gene and protein expression of inducible nitric oxide synthase, arginase I, and mannose receptor. We showed that aldosterone promotes a classic inflammatory response in macrophages, whereas its antagonist, eplerenone, attenuates aldosterone-induced activity. Eplerenone did not quantitatively weaken the response of macrophages to aldosterone but instead qualitatively changed their behavior.

  17. Why and how physical activity promotes experience-induced brain plasticity

    Directory of Open Access Journals (Sweden)

    Gerd eKempermann

    2010-12-01

    Full Text Available Adult hippocampal neurogenesis is an unusual case of brain plasticity, since new neurons (and not just neurites and synapses are added to the network in an activity-dependent way. At the behavioral level the plasticity-inducing stimuli include both physical and cognitive activity. In reductionistic animal studies these types of activity can be studied separately in paradigms like voluntary wheel running and environmental enrichment. In both of these, adult neurogenesis is increased but the net effect is primarily due to different mechanisms at the cellular level. Locomotion appears to stimulate the precursor cells, from which adult neurogenesis originates, to increased proliferation and maintenance over time, whereas environmental enrichment, as well as learning, predominantly promotes survival of immature neurons, that is the progeny of the proliferating precursor cells. Surprisingly, these effects are additive: boosting the potential for adult neurogenesis by physical activity increases the recruitment of cells following cognitive stimulation in an enriched environment. Why is that? We argue that locomotion actually serves as an intrinsic feedback mechanism, signaling to the brain, including its neural precursor cells, that the likelihood of cognitive challenges increases. In the wild (other than in front of a TV, no separation of physical and cognitive activity occurs. Physical activity might thus be much more than a generally healthy garnish to leading an active life but an evolutionarily fundamental aspect of activity, which is needed to provide the brain and its systems of plastic adaptation with the appropriate regulatory input and feedback.

  18. Listeria monocytogenes virulence factor Listeriolysin O favors bacterial growth in co-culture with the ciliate Tetrahymena pyriformis, causes protozoan encystment and promotes bacterial survival inside cysts

    Directory of Open Access Journals (Sweden)

    Ermolaeva Svetlana A

    2010-01-01

    Full Text Available Abstract Background The gram-positive pathogenic bacterium Listeria monocytogenes is widely spread in the nature. L. monocytogenes was reported to be isolated from soil, water, sewage and sludge. Listeriolysin O (LLO is a L. monocytogenes major virulence factor. In the course of infection in mammals, LLO is required for intracellular survival and apoptosis induction in lymphocytes. In this study, we explored the potential of LLO to promote interactions between L. monocytogenes and the ubiquitous inhabitant of natural ecosystems bacteriovorous free-living ciliate Tetrahymena pyriformis. Results Wild type L. monocytogenes reduced T. pyriformis trophozoite counts and stimulated encystment. The effects were observed starting from 48 h of co-incubation. On the day 14, trophozoites were eliminated from the co-culture while about 5 × 104 cells/ml remained in the axenic T. pyriformis culture. The deficient in the LLO-encoding hly gene L. monocytogenes strain failed to cause mortality among protozoa and to trigger protozoan encystment. Replenishment of the hly gene in the mutant strain restored toxicity towards protozoa and induction of protozoan encystment. The saprophytic non-haemolytic species L. innocua transformed with the LLO-expressing plasmid caused extensive mortality and encystment in ciliates. During the first week of co-incubation, LLO-producing L. monocytogenes demonstrated higher growth rates in association with T. pyriformis than the LLO-deficient isogenic strain. At latter stages of co-incubation bacterial counts were similar for both strains. T. pyriformis cysts infected with wild type L. monocytogenes caused listerial infection in guinea pigs upon ocular and oral inoculation. The infection was proved by bacterial plating from the internal organs. Conclusions The L. monocytogenes virulence factor LLO promotes bacterial survival and growth in the presence of bacteriovorous ciliate T. pyriformis. LLO is responsible for L. monocytogenes

  19. Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts.

    LENUS (Irish Health Repository)

    Burke, J P

    2012-02-01

    BACKGROUND: Fibroblasts play a critical role in intestinal wound healing. Lipopolysaccharide (LPS) is a cell wall component of commensal gut bacteria. The effects of LPS on intestinal fibroblast activation were characterized. METHODS: Expression of the LPS receptor, toll-like receptor (TLR) 4, was assessed in cultured primary human intestinal fibroblasts using flow cytometry and confocal microscopy. Fibroblasts were treated with LPS and\\/or transforming growth factor (TGF) beta1. Nuclear factor kappaB (NFkappaB) pathway activation was assessed by inhibitory kappaBalpha (IkappaBalpha) degradation and NFkappaB promoter activity. Fibroblast contractility was measured using a fibroblast-populated collagen lattice. Smad-7, a negative regulator of TGF-beta1 signalling, and connective tissue growth factor (CTGF) expression were assessed using reverse transcriptase-polymerase chain reaction and western blot. The NFkappaB pathway was inhibited by IkappaBalpha transfection. RESULTS: TLR-4 was present on the surface of intestinal fibroblasts. LPS treatment of fibroblasts induced IkappaBalpha degradation, enhanced NFkappaB promoter activity and increased collagen contraction. Pretreatment with LPS (before TGF-beta1) significantly increased CTGF production relative to treatment with TGF-beta1 alone. LPS reduced whereas TGF-beta1 increased smad-7 expression. Transfection with an IkappaBalpha plasmid enhanced basal smad-7 expression. CONCLUSION: Intestinal fibroblasts express TLR-4 and respond to LPS by activating NFkappaB and inducing collagen contraction. LPS acts in concert with TGF-beta1 to induce CTGF. LPS reduces the expression of the TGF-beta1 inhibitor, smad-7.

  20. Promoting active community environments through land use and transportation planning.

    Science.gov (United States)

    Aytur, Semra A; Rodriguez, Daniel A; Evenson, Kelly R; Catellier, Diane J; Rosamond, Wayne D

    2007-01-01

    To examine the role of land use and transportation plans as policy instruments for promoting active community environments. Cross-sectional analysis using multilevel models to examine whether active community environment scores were associated with leisure and transportation-related physical activity (PA) and whether associations varied by household income. 67 North Carolina counties Adults (n = 6694) from pooled 2000 and 2002 North Carolina Behavioral Risk Factor Surveillance System (BRFSS) surveys. Active community environment scores, derived from a 2003 survey of planning directors, representing the presence of nonmotorized transportation improvements, mixed land use classification, and comprehensiveness of implementation tools. Dependent variables were self-reported PA measures from the BRFSS. Sociodemographic variables were derived from the 2000 U.S. Census of Population. After adjustment for sociodemographic factors, more favorable active community environment scores were significantly associated with leisure PA (p = .001), transportation PA (p land use and transportation planning. Plans may provide a means to incorporate community support for active living into public policy.

  1. [Can sports and physical activity promote young peoples' psychosocial health?].

    Science.gov (United States)

    Ommundsen, Y

    2000-11-30

    Sport and physical activity is generally believed to be beneficial to young people's psychosocial health, but the scientific evidence seems equivocal. This article gives a narrative review of recent developments in the literature on psychosocial health effects of physical activity and sport among children and adolescents. Based on a narrative review of a selection of metaanalytical and key studies, results in four areas of psychosocial functioning are presented. Findings support an association between involvement in physical activity and sport and well-being. Physical activity is associated with lower levels of mental health problems, and seems to promote self-esteem. Physical activity as a treatment of mental health problems for this age group is underexplored and no firm conclusions can be made. The evidence with respect to effects on cognitive and academic functioning is weak. Further, the evidence that juvenile delinquency and antisocial development could be counteracted is equivocal. There is a paucity of studies that can confirm any causal effects. Future research would benefit particularly from studying the role of sports and physical activity mode as well as the psychological and social context in which it may produce beneficial psychosocial outcomes.

  2. Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases*

    Science.gov (United States)

    Song, Xiao; Ding, Yanping; Liu, Gang; Yang, Xiao; Zhao, Ruifang; Zhang, Yinlong; Zhao, Xiao; Anderson, Gregory J.; Nie, Guangjun

    2016-01-01

    Tumor-associated macrophages (TAM) play pivotal roles in cancer initiation and progression. Monocytes, the precursors of TAMs, normally undergo spontaneous apoptosis within 2 days, but can subsist in the inflammatory tumor microenvironment for continuous survival and generation of sufficient TAMs. The mechanisms underlying tumor-driving monocyte survival remain obscure. Here we report that cancer cell-derived exosomes were crucial mediators for monocyte survival in the inflammatory niche. Analysis of the survival-promoting molecules in monocytes revealed that cancer cell-derived exosomes activated Ras and extracellular signal-regulated kinases in the mitogen-activated protein kinase (MAPK) pathway, resulting in the prevention of caspase cleavage. Phosphorylated receptor tyrosine kinases (RTKs), such as phosphorylated epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), were abundantly expressed in cancer cell-derived exosomes. Knock-out of EGFR or/and HER-2, or alternatively, inhibitors against their phosphorylation significantly disturbed the exosome-mediated activation of the MAPK pathway, inhibition of caspase cleavage, and increase in survival rate in monocytes. Moreover, the deprived survival-stimulating activity of exosomes due to null expression of EGFR and HER-2 could be restored by activation of another RTK, insulin receptor. Overall, our study uncovered a mechanism of tumor-associated monocyte survival and demonstrated that cancer cell-derived exosomes can stimulate the MAPK pathway in monocytes through transport of functional RTKs, leading to inactivation of apoptosis-related caspases. This work provides insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. PMID:26895960

  3. Bee bread increases honeybee haemolymph protein and promote better survival despite of causing higher Nosema ceranae abundance in honeybees.

    Science.gov (United States)

    Basualdo, Marina; Barragán, Sergio; Antúnez, Karina

    2014-08-01

    Adequate protein nutrition supports healthy honeybees and reduces the susceptibility to disease. However little is known concerning the effect of the diet on Nosema ceranae development, an obligate intracellular parasite that disturbs the protein metabolism of honeybees (Apis mellifera). Here we tested the effect of natural (bee bread) and non-natural protein diets (substitute) on haemolymph proteins titers of honeybee and N. ceranae spore production. The natural diet induced higher levels of protein and parasite development, but the survival of bees was also higher than with non-natural diets. The data showed that the administration of an artificially high nutritious diet in terms of crude protein content is not sufficient to promote healthy bees; rather the protein ingested should be efficiently assimilated. The overall results support the idea that the physiological condition of the bees is linked to protein levels in the haemolymph, which affects the tolerance to parasite; consequently the negative impact of the parasite on host fitness is not associated only with the level of infection. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. CDKN3 expression is negatively associated with pathological tumor stage and CDKN3 inhibition promotes cell survival in hepatocellular carcinoma.

    Science.gov (United States)

    Dai, Wei; Miao, Huilai; Fang, Shuo; Fang, Tao; Chen, Nianping; Li, Mingyi

    2016-08-01

    Aberrant expression of CDKN3 may be involved in carcinogenesis of liver cancer. The effect of CDKN3 on tumorigenesis and the molecular mechanisms involved have not been fully elucidated. Immunohistochemistry was performed to detect CDKN3 expression levels in tumor tissues. CDKN3 siRNA was used to knockdown CDKN3 in QGY7701 hepatocellular carcinoma (HCC) cells. Colony formation assay was used to measure the clonogenic capacity of the tumor cells. Cell viability was determined by MTT assay. Logistic regression was performed to analyze the association between CDKN3 expression level and the HCC clinical pathology index. The CDKN3 expression level was significantly decreased in HCC tumor tissues compared with normal liver tissue and liver cirrhosis tissue. Additionally, CDKN3 expression was negatively‑associated with the pathological stage of the tumor. Inhibition of CKDN3 promoted the clonogenic capacity and chemotherapeutic tolerance in HCC tissues compared with controls. Knockdown of CDKN3 resulted in downregulation of p53 and p21 protein levels, whereas, AKT serine/threonine kinase 1 expression was upregulated. Thus, CDKN3 expression may reduce the survival of tumor cells and alter the sensitivity to therapeutic agents via the AKT/P53/P21 signaling pathway. Therefore, CDKN3 may be involved in tumor differentiation and self-renewal.

  5. Magnetic fields promote a pro-survival non-capacitative Ca2+ entry via phospholipase C signaling.

    Science.gov (United States)

    Cerella, Claudia; Cordisco, Sonia; Albertini, Maria Cristina; Accorsi, Augusto; Diederich, Marc; Ghibelli, Lina

    2011-03-01

    The ability of magnetic fields (MFs) to promote/increase Ca(2+) influx into cells is widely recognized, but the underlying mechanisms remain obscure. Here we analyze how static MFs of 6 mT modulates thapsigargin-induced Ca(2+) movements in non-excitable U937 monocytes, and how this relates to the anti-apoptotic effect of MFs. Magnetic fields do not affect thapsigargin-induced Ca(2+) mobilization from endoplasmic reticulum, but significantly increase the resulting Ca(2+) influx; this increase requires intracellular signal transduction actors including G protein, phospholipase C, diacylglycerol lipase and nitric oxide synthase, and behaves as a non-capacitative Ca(2+) entry (NCCE), a type of influx with an inherent signaling function, rather than a capacitative Ca(2+) entry (CCE). All treatments abrogating the extra Ca(2+) influx also abrogate the anti-apoptotic effect of MFs, demonstrating that MF-induced NCCE elicits an anti-apoptotic survival pathway. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Neural stem/progenitor cell-laden microfibers promote transplant survival in a mouse transected spinal cord injury model.

    Science.gov (United States)

    Sugai, Keiko; Nishimura, Soraya; Kato-Negishi, Midori; Onoe, Hiroaki; Iwanaga, Shintaroh; Toyama, Yoshiaki; Matsumoto, Morio; Takeuchi, Shoji; Okano, Hideyuki; Nakamura, Masaya

    2015-12-01

    Previous studies have demonstrated that transplantation of neural stem/progenitor cells (NS/PCs) into the lesioned spinal cord can promote functional recovery following incomplete spinal cord injury (SCI) in animal models. However, this strategy is insufficient following complete SCI because of the gap at the lesion epicenter. To obtain functional recovery in a mouse model of complete SCI, this study uses a novel collagen-based microfiber as a scaffold for engrafted NS/PCs. We hypothesized that the NS/PC-microfiber combination would facilitate lesion closure as well as transplant survival in the transected spinal cord. NS/PCs were seeded inside the novel microfibers, where they maintained their capacity to differentiate and proliferate. After transplantation, the stumps of the transected spinal cord were successfully bridged by the NS/PC-laden microfibers. Moreover, the transplanted cells migrated into the host spinal cord and differentiated into three neural lineages (astrocytes, neurons, and oligodendrocytes). However, the NS/PC-laden scaffold could not achieve a neural connection between the rostral end of the injury and the intact caudal area of the spinal cord, nor could it achieve recovery of motor function. To obtain optimal functional recovery, a microfiber design with a modified composition may be useful. Furthermore, combinatorial therapy with rehabilitation and/or medications should also be considered for practical success of biomaterial/cell transplantation-based approaches to regenerative medicine. © 2015 Wiley Periodicals, Inc.

  7. Saposin C promotes survival and prevents apoptosis via PI3K/Akt-dependent pathway in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Lee Tae-Jin

    2004-11-01

    Full Text Available Abstract Background In addition to androgens, growth factors are also implicated in the development and neoplastic growth of the prostate gland. Prosaposin is a potent neurotrophic molecule. Homozygous inactivation of prosaposin in mice has led to the development of a number of abnormalities in the male reproductive system, including atrophy of the prostate gland and inactivation of mitogen-activated protein kinase (MAPK and Akt in prostate epithelial cells. We have recently reported that prosaposin is expressed at a higher level by androgen-independent (AI prostate cancer cells as compared to androgen-sensitive prostate cancer cells or normal prostate epithelial and stromal cells. In addition, we have demonstrated that a synthetic peptide (prosaptide TX14A, derived from the trophic sequence of the saposin C domain of prosaposin, stimulated cell proliferation, migration and invasion and activated the MAPK signaling pathway in prostate cancer cells. The biological significances of saposin C and prosaposin in prostate cancer are not known. Results Here, we report that saposin C, in a cell type-specific and dose-dependent manner, acts as a survival factor, activates the Akt-signaling pathway, down-modulates caspase-3, -7, and -9 expression and/or activity, and decreases the cleaved nuclear substrate of caspase-3 in prostate cancer cells under serum-starvation stress. In addition, prosaptide TX14A, saposin C, or prosaposin decreased the growth-inhibitory effect, caspase-3/7 activity, and apoptotic cell death induced by etoposide. We also discovered that saposin C activates the p42/44 MAP kinase pathway in a pertussis toxin-sensitive and phosphatidylinositol 3-kinase (PI3K /Akt-dependent manner in prostate cancer cells. Our data also show that the anti-apoptotic activity of saposin C is at least partially mediated via PI3K/Akt signaling pathway. Conclusion We postulate that as a mitogenic, survival, and anti-apoptotic factor for prostate cancer cells

  8. Active fantasy sports: rationale and feasibility of leveraging online fantasy sports to promote physical activity.

    Science.gov (United States)

    Moller, Arlen C; Majewski, Sara; Standish, Melanie; Agarwal, Pooja; Podowski, Aleksandra; Carson, Rebecca; Eyesus, Biruk; Shah, Aakash; Schneider, Kristin L

    2014-11-25

    The popularity of active video games (AVGs) has skyrocketed over the last decade. However, research suggests that the most popular AVGs, which rely on synchronous integration between players' activity and game features, fail to promote physical activity outside of the game or for extended periods of engagement. This limitation has led researchers to consider AVGs that involve asynchronous integration of players' ongoing physical activity with game features. Rather than build an AVG de novo, we selected an established sedentary video game uniquely well suited for the incorporation of asynchronous activity: online fantasy sports. The primary aim of this study was to explore the feasibility of a new asynchronous AVG-active fantasy sports-designed to promote physical activity. We conducted two pilot studies of an active fantasy sports game designed to promote physical activity. Participants wore a low cost triaxial accelerometer and participated in an online fantasy baseball (Study 1, n=9, 13-weeks) or fantasy basketball (Study 2, n=10, 17-weeks) league. Privileges within the game were made contingent on meeting weekly physical activity goals (eg, averaging 10,000 steps/day). Across the two studies, the feasibility of integrating physical activity contingent features and privileges into online fantasy sports games was supported. Participants found the active fantasy sports game enjoyable, as or more enjoyable than traditional (sedentary) online fantasy sports (Study 1: t8=4.43, P<.01; Study 2: t9=2.09, P=.07). Participants in Study 1 increased their average steps/day, t8=2.63, P<.05, while participants in Study 2 maintained (ie, did not change) their activity, t9=1.57, P=.15). In postassessment interviews, social support within the game was cited as a key motivating factor for increasing physical activity. Preliminary evidence supports potential for the active fantasy sports system as a sustainable and scalable intervention for promoting adult physical activity.

  9. A Social Identity Approach to Understanding and Promoting Physical Activity.

    Science.gov (United States)

    Stevens, Mark; Rees, Tim; Coffee, Pete; Steffens, Niklas K; Haslam, S Alexander; Polman, Remco

    2017-10-01

    Against the backdrop of a global physical inactivity crisis, attempts to both understand and positively influence physical activity behaviours are characterized by a focus on individual-level factors (e.g. cognitions, attitudes, motivation). We outline a new perspective, drawn from an emerging body of work exploring the applicability of social identity and self-categorization theories to domains of sport and health, from which to understand and address this pervasive problem. This social identity approach suggests that the groups to which people belong can be, and often are, incorporated into their sense of self and, through this, are powerful determinants of physical activity-related behaviour. We start by reviewing the current state of physical activity research and highlighting the potential for the social identity approach to help understand how social factors influence these behaviours. Next, we outline the theoretical underpinnings of the social identity approach and provide three key examples that speak to the analytical and practical value of the social identity approach in physical activity settings. Specifically, we argue that social identity (1) can be harnessed to promote engagement in physical activity, (2) underpins exercise group behaviour, and (3) underpins effective leadership in exercise settings. We conclude by identifying prospects for a range of theory-informed research developments.

  10. Active Aging Promotion: Results from the Vital Aging Program

    Directory of Open Access Journals (Sweden)

    Mariagiovanna Caprara

    2013-01-01

    Full Text Available Active aging is one of the terms in the semantic network of aging well, together with others such as successful, productive, competent aging. All allude to the new paradigm in gerontology, whereby aging is considered from a positive perspective. Most authors in the field agree active aging is a multidimensional concept, embracing health, physical and cognitive fitness, positive affect and control, social relationships and engagement. This paper describes Vital Aging, an individual active aging promotion program implemented through three modalities: Life, Multimedia, and e-Learning. The program was developed on the basis of extensive evidence about individual determinants of active aging. The different versions of Vital Aging are described, and four evaluation studies (both formative and summative are reported. Formative evaluation reflected participants’ satisfaction and expected changes; summative evaluations yielded some quite encouraging results using quasi-experimental designs: those who took part in the programs increased their physical exercise, significantly improved their diet, reported better memory, had better emotional balance, and enjoyed more cultural, intellectual, affective, and social activities than they did before the course, thus increasing their social relationships. These results are discussed in the context of the common literature within the field and, also, taking into account the limitations of the evaluations accomplished.

  11. System for Observing Staff Promotion of Activity and Nutrition (SOSPAN).

    Science.gov (United States)

    Weaver, R Glenn; Beets, Michael W; Webster, Collin; Huberty, Jennifer

    2014-01-01

    Frontline-staff are critical to achieving policies related to child physical activity and nutrition (PAaN) in out-of-school-time programs (OSTP). Recent policies call upon staff to demonstrate behaviors related to PAaN. Currently, no instrument exists to measure these behaviors. This study fills the gap between policy mandates and staff behaviors by describing the development of the System for Observing Staff Promotion of Activity and Nutrition (SOSPAN) in OSTP. SOSPAN items were aligned with existing OSTP policies. Reliability and validity data of SOSPAN were collected across 8 OSTP: 4 summer day camps and 4 afterschool programs. Validity of SOSPAN staff behaviors/management of PA was established using the percent of children active measured concurrently via direct observation. A total of 6437 scans were performed. Interrater percent agreement ranged from 74%-99% across PAaN behaviors. Children's activity was associated with staff facilitative behaviors/management, such as playing with the children and providing 2 or more activities for children to choose, while prohibitive behaviors/management, such as waiting in line were related to increased sedentary behavior. Staff nutrition behaviors were observed in less than 0.6% of scans. SOSPAN is a reliable and valid tool to assess staff behaviors/management of PAaN in OSTPs.

  12. Therapeutic intraspinal stimulation to generate activity and promote long-term recovery

    Directory of Open Access Journals (Sweden)

    Sarah E. Mondello

    2014-02-01

    Full Text Available Neuroprosthetic approaches have tremendous potential for the treatment of injuries to the brain and spinal cord by inducing appropriate neural activity in otherwise disordered circuits. Substantial work has demonstrated that stimulation applied to both the central and peripheral nervous system leads to immediate and in some cases sustained benefits after injury. Here we focus on cervical intraspinal microstimulation (ISMS as a promising method of activating the spinal cord distal to an injury site, either to directly produce movements or more intriguingly to improve subsequent volitional control of the paretic extremities. Incomplete injuries to the spinal cord are the most commonly observed in human patients, and these injuries spare neural tissue bypassing the lesion that could be influenced by neural devices to promote recovery of function. In fact, recent results have demonstrated that therapeutic ISMS leads to modest but sustained improvements in forelimb function after an incomplete spinal cord injury. This therapeutic spinal stimulation may promote long-term recovery of function by providing the necessary electrical activity needed for neuron survival, axon growth, and synaptic stability.

  13. SPINK6 Promotes Metastasis of Nasopharyngeal Carcinoma via Binding and Activation of Epithelial Growth Factor Receptor.

    Science.gov (United States)

    Zheng, Li-Sheng; Yang, Jun-Ping; Cao, Yun; Peng, Li-Xia; Sun, Rui; Xie, Ping; Wang, Meng-Yao; Meng, Dong-Fang; Luo, Dong-Hua; Zou, Xiong; Chen, Ming-Yuan; Mai, Hai-Qiang; Guo, Ling; Guo, Xiang; Shao, Jian-Yong; Huang, Bi-Jun; Zhang, Wei; Qian, Chao-Nan

    2017-01-15

    Nasopharyngeal carcinoma has the highest rate of metastasis among head and neck cancers, and distant metastasis is the major reason for treatment failure. The underlying molecular mechanisms of nasopharyngeal carcinoma metastasis are not fully understood. Here, we report the identification of serine protease inhibitor Kazal-type 6 (SPINK6) as a functional regulator of nasopharyngeal carcinoma metastasis via EGFR signaling. SPINK6 mRNA was upregulated in tumor and highly metastatic nasopharyngeal carcinoma cells. Immunohistochemical staining of 534 nasopharyngeal carcinomas revealed elevated SPINK6 expression as an independent unfavorable prognostic factor for overall, disease-free, and distant metastasis-free survival. Ectopic SPINK6 expression promoted in vitro migration and invasion as well as in vivo lymph node metastasis and liver metastasis of nasopharyngeal carcinoma cells, whereas silencing SPINK6 exhibited opposing effects. SPINK6 enhanced epithelial-mesenchymal transition by activating EGFR and the downstream AKT pathway. Inhibition of EGFR with a neutralizing antibody or erlotinib reversed SPINK6-induced nasopharyngeal carcinoma cell migration and invasion. Erlotinib also inhibited SPINK6-induced metastasis in vivo Notably, SPINK6 bound to the EGFR extracellular domain independent of serine protease-inhibitory activity. Overall, our results identified a novel EGFR-activating mechanism in which SPINK6 has a critical role in promoting nasopharyngeal carcinoma metastasis, with possible implications as a prognostic indicator in nasopharyngeal carcinoma patients. Cancer Res; 77(2); 579-89. ©2016 AACR. ©2016 American Association for Cancer Research.

  14. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle

    DEFF Research Database (Denmark)

    Hunter, Roger W; Treebak, Jonas Thue; Wojtaszewski, Jørgen

    2011-01-01

    OBJECTIVE During energy stress, AMP-activated protein kinase (AMPK) promotes glucose transport and glycolysis for ATP production, while it is thought to inhibit anabolic glycogen synthesis by suppressing the activity of glycogen synthase (GS) to maintain the energy balance in muscle. Paradoxically...

  15. Survival and activity of Streptococcus faecalis and Escherichia coli in tropical freshwater

    Energy Technology Data Exchange (ETDEWEB)

    Muniz, I.; Jimenez, L.; Toranzos, G.A.; Hazen, T.C. [Univ. of Puerto Rico, Rio Piedras (Puerto Rico)

    1988-12-31

    The survival of Streptococcus facecalis and Escherichia coli was studied in situ in a tropical rain forest watershed using membrane diffusion chambers. Densities were determined by acridine orange direct count and Coulter Counter. Population activity was determined by microautoradiography, cell respiration, and by nucleic acid composition. Densities of S. facecalis and E. coli decreased less than 1 log unit after 105 h as measured by direct count methods. Activity as measured by respiration, acridine orange activity, and microautoradiography indicated that both bacteria remained moderately active during the entire study. After 12 h, E. coli was more active than S. faecalis as measured by nucleic acid composition. E. coli and S. faecalis survived and remained active for more than 5 days. Consequently, both would seem to be unsuitable as indicators of recent fecal contamination in tropical waters.

  16. S100A4 is upregulated in injured myocardium and promotes growth and survival of cardiac myocytes

    DEFF Research Database (Denmark)

    Schneider, Mikael; Kostin, Sawa; Strøm, Claes C

    2007-01-01

    and immunoblotting that S100A4 mRNA and protein is upregulated in hypertrophic rat and human hearts and show by way of confocal microscopy that S100A4 protein, but not mRNA, appears in cardiac myocytes only in the border zone after an acute ischemic event in rat and human hearts. In normal rat and human hearts, S100...... after injury. Promisingly, recombinant S100A4 protein elicited a robust hypertrophic response and increased the number of viable cells in cardiac myocyte cultures by inhibiting apoptosis. We also found that ERK1/2 activation was necessary for both the hypertrophy and survival effects of S100A4 in vitro...

  17. Physical activity and health promotion in Italian university students.

    Science.gov (United States)

    Teleman, Adele Anna; de Waure, Chiara; Soffiani, Valentina; Poscia, Andrea; Di Pietro, Maria Luisa

    2015-01-01

    Physical activity, diet plans, the mantainment of a certain Body Mass Index (BMI) and the use of various types of supplementation are common elements in the search for disease prevention, health promotion and well-being. We analyzed the data regarding Italian university students' BMI, dieting behaviour, personal body perception, exercise habits, and use of dietary supplements and of doping substances. 13.7% resulted being underweight, 75.1% was in the normal range, 9.8% was overweight, and 1.4% was obese. 11.0% were on a diet. 25.8% of the students reported never doing any type of physical activity. 0.9% admitted consuming doping substances. The percentage of overweight/obese students increases from 8.8% of the 18-21 year olds to 18.1% of the 25-30 year olds. Similarly, the prevalence of overweight/obesity was 18.5% among male population and 7.5% among the female one. The data deriving from this questionnaire showed that while the majority of university students has a BMI in the normal range, 11.2% of the study population is overweight/obese. Males present a higher risk of being overweight or obese. An important part of the population showed to be sedentary even though data coming from our study are aligned to further evidence. The most important concern arising from the questionnaire is represented by physical inactivity. Indeed, it is necessary to encourage and plan initiatives aimed at promoting physical activity in university students.

  18. Physical activity and health promotion in Italian university students

    Directory of Open Access Journals (Sweden)

    Adele Anna Teleman

    2015-06-01

    Full Text Available INTRODUCTION: Physical activity, diet plans, the mantainment of a certain Body Mass Index (BMI and the use of various types of supplementation are common elements in the search for disease prevention, health promotion and well-being. MATERIALS AND METHODS: We analyzed the data regarding Italian university students' BMI, dieting behaviour, personal body perception, exercise habits, and use of dietary supplements and of doping substances. RESULTS: 13.7% resulted being underweight, 75.1% was in the normal range, 9.8% was overweight, and 1.4% was obese. 11.0% were on a diet. 25.8% of the students reported never doing any type of physical activity. 0.9% admitted consuming doping substances. The percentage of overweight/obese students increases from 8.8% of the 18-21 year olds to 18.1% of the 25-30 year olds. Similarly, the prevalence of overweight/obesity was 18.5% among male population and 7.5% among the female one. DISCUSSION: The data deriving from this questionnaire showed that while the majority of university students has a BMI in the normal range, 11.2% of the study population is overweight/obese. Males present a higher risk of being overweight or obese. An important part of the population showed to be sedentary even though data coming from our study are aligned to further evidence. CONCLUSION: The most important concern arising from the questionnaire is represented by physical inactivity. Indeed, it is necessary to encourage and plan initiatives aimed at promoting physical activity in university students.

  19. Promoting Moderate-Vigorous Physical Activity in Overweight Minority Girls

    Directory of Open Access Journals (Sweden)

    Norma Olvera

    2010-01-01

    Full Text Available There is limited research on the types of activities that are most effective for promoting MVPA in children. Purpose. To assess which types of activities elicit MVPA in overweight minority girls. Methods. Sample consisted of 31 overweight (BMI≥85th percentile Latina and African-American girls (mean age 10.3±1.2 years. Participants wore an Actical accelerometer each day for 8 hours for 15 days to assess engagement in MVPA during their participation in a three-week activity intervention that included traditional fitness, sport skills, games, dancing, and flexibility sessions. Results. On average 62% of participants met the MVPA recommended guidelines (60 min/5d/wk with an average of 68.5±14 minutes of MVPA across the three weeks. Traditional fitness sessions elicited the highest percent of MVPA (mean time spent in MVPA=32%, followed by dancing and games (mean time spent in MVPA=21%, sports skills (mean time spent in MVPA=18%, and flexibility (mean time spent in MVPA=7%. Step aerobics and rumba fitness elicited the highest proportions of MVPA. Conclusion. Traditional fitness activities were identified as the most successful in eliciting MVPA in overweight Latina and African American girls.

  20. Insulin Promotes Survival of Amyloid-Beta Oligomers Neuroblastoma Damaged Cells via Caspase 9 Inhibition and Hsp70 Upregulation

    Directory of Open Access Journals (Sweden)

    M. Di Carlo

    2010-01-01

    Full Text Available Alzheimer's disease (AD and type 2 diabetes are connected in a way that is still not completely understood, but insulin resistance has been implicated as a risk factor for developing AD. Here we show an evidence that insulin is capable of reducing cytotoxicity induced by Amyloid-beta peptides (A-beta in its oligomeric form in a dose-dependent manner. By TUNEL and biochemical assays we demonstrate that the recovery of the cell viability is obtained by inhibition of intrinsic apoptotic program, triggered by A-beta and involving caspase 9 and 3 activation. A protective role of insulin on mitochondrial damage is also shown by using Mito-red vital dye. Furthermore, A-beta activates the stress inducible Hsp70 protein in LAN5 cells and an overexpression is detectable after the addition of insulin, suggesting that this major induction is the necessary condition to activate a cell survival program. Together, these results may provide opportunities for the design of preventive and therapeutic strategies against AD.

  1. Hair growth promoting activity of discarded biocomposite keratin extract.

    Science.gov (United States)

    Akanda, Md Rashedunnabi; Kim, Hak-Yong; Park, Mira; Kim, In-Shik; Ahn, Dongchoon; Tae, Hyun-Jin; Park, Byung-Yong

    2017-08-01

    Keratin biomaterial has been used in regenerative medicine owing to its in-vivo and in-vitro biocompatibility. The present study was aimed to investigate the hair growth promoting activity of keratin extract and its mechanism of action. Keratin extract was topically applied on the synchronized depilated dorsal skin of telogenic C57BL/6 mice and promoted hair growth by inducing the anagen phase. The histomorphometric observation indicated significantly increases the number, shaft of hair follicles and deep subcutis area in the keratin extract treated group in contrast to the control group, which was considered an indication of anagen phase induction. Subsequently, the quantitative real-time polymerase chain reaction analysis revealed that fibroblast growth factor-10, vascular endothelial growth factor, insulin-like growth factor-1, β-catenin, and Shh were expressed earlier in the keratin extract-treated group than in the control group. Besides, keratin extract has been observed to be biocompatible when analyzed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 4',6-diamidino-2-phenylindole staining using immortalized human keratinocyte cells, showing more than 90% cell viability. Our study demonstrated that keratin extract stimulating hair follicle growth by inducing the growth phase; anagen in telogenic C57BL/6 mice and thus the topical application of keratin extract may represent a promising biomaterial for the management and applications of hair follicle disorder.

  2. The gadolinium-based contrast agent Omniscan® promotes in vitro fibroblast survival through in situ precipitation.

    Science.gov (United States)

    Feng, Min; Fan, Yun-Zhou; Ma, Xiao-Jie; Li, Jin-Xia; Yang, Xiao-Gai

    2015-07-01

    The current study aims to explore how the gadolinium (Gd)-based contrast agent (GBCA) Omniscan® enhanced cell viability of murine fibroblasts. The results of scanning electron microscopy showed that Omniscan® can precipitate in cell culture media and deposit on cell membranes. Energy-dispersive X-ray analysis and Fourier-transform infrared spectroscopy demonstrated the presence of Gd and phosphates in the agglomerated particles. By filtering the Omniscan®-containing medium through a 220 nm filter, it can be clearly found that the increased cell viability should be mainly attributed to the insoluble species of gadolinium rather than to chelated gadolinium. Moreover, the effects of other gadolinium-based contrast agents, Magnevist® and Dotarem®, were compared with that of Omniscan®. It is noted that the three contrast agents differed in their ability to induce cell viability, which is possibly ascribed to the different chemical stabilities of gadolinium chelates as demonstrated by the attenuation in cell growth upon the addition of excess ligands to the compounds. The results of flow cytometry analysis also showed that Omniscan® can promote cell growth via an increase in the S-phase cell population as evidenced by the elevated levels of cell cycle associated proteins cyclin D, cyclin A and the phosphorylated Rb protein. Furthermore, our results revealed that integrin-mediated signaling may play an important role in both Omniscan® and Magnevist®-enhanced focal adhesion formation since the blockade of integrins decreased the level of ERK phosphorylation induced by the two GBCAs. Taken together, these data suggested that in situ gadolinium phosphate precipitation formation mediated Omniscan®-promoted fibroblast survival, which is similar to that of gadolinium chloride. It was demonstrated that the application of GBCAs with more stable thermodynamic stability may cause less dissociation of the gadolinium ion and thus resulted in less precipitation, finally

  3. [Actively promote the development of neuro-ophthalmology in China].

    Science.gov (United States)

    Wei, Shi-hui; Zhao, Jia-liang

    2010-12-01

    Neuro-ophthalmology is a medical subspecialty concerned on the nervous system diseases with ocular manifestations, this could be both sensory and motor, including ocular movements, papillary responses, and the structure changes of the brain and nervous system with ocular manifestations. Although neuro-ophthalmology in China has achieved some progress, certain problems still exist, such as the professional neuro-ophthalmology team and related academic organization are still absent in China; neuro-ophthalmology knowledge has not been popularized; the new technologies for diagnosis and treatment in neuro-ophthalmology have not been absorbed and applied; the coordination and cooperation with other related disciplines are not enough. We should actively promote the development of neuro-ophthalmology in China, including organization of a professional team of neuro-ophthalmology, popularization of neuro-ophthalmology knowledge to the ophthalmologists, development of research work in neuro-ophthalmology and the collaboration with international neuro-ophthalmologists.

  4. The oncoprotein SF2/ASF promotes non-small cell lung cancer survival by enhancing survivin expression.

    Science.gov (United States)

    Ezponda, Teresa; Pajares, María J; Agorreta, Jackeline; Echeveste, José I; López-Picazo, José M; Torre, Wenceslao; Pio, Ruben; Montuenga, Luis M

    2010-08-15

    SF2/ASF is a splicing factor recently described as an oncoprotein. In the present work, we examined the role of SF2/ASF in human non-small cell lung cancer (NSCLC) and analyzed the molecular mechanisms involved in SF2/ASF-related carcinogenesis. SF2/ASF protein levels were analyzed in 81 NSCLC patients by immunohistochemistry. SF2/ASF downregulation cellular models were generated using small interfering RNAs, and the effects on proliferation and apoptosis were evaluated. Survivin and SF2/ASF expression in lung tumors was analyzed by Western blot and immunohistochemistry. Survival curves and log-rank test were used to identify the association between the expression of the proteins and time to progression. Overexpression of SF2/ASF was found in most human primary NSCLC tumors. In vitro downregulation of SF2/ASF induced apoptosis in NSCLC cell lines. This effect was associated with a reduction in the expression of survivin, an antiapoptotic protein widely upregulated in cancer. In fact, SF2/ASF specifically bound survivin mRNA and enhanced its translation, via a mammalian target of rapamycin complex 1 (mTORC1) pathway-dependent mechanism, through the phosphorylation and inactivation of the translational repressor 4E-BP1. Moreover, SF2/ASF promoted the stability of survivin mRNA. A strong correlation was observed between the expression of SF2/ASF and survivin in tumor biopsies from NSCLC patients, supporting the concept that survivin expression levels are controlled by SF2/ASF. Furthermore, combined expression of these proteins was associated with prognosis. This study provides novel data on the mTORC1- and survivin-dependent mechanisms of SF2/ASF-related carcinogenic potential, and shows that SF2/ASF and survivin expression is involved in NSCLC progression.

  5. Hydrogen-promoted oxygen activation by free gold cluster cations.

    Science.gov (United States)

    Lang, Sandra M; Bernhardt, Thorsten M; Barnett, Robert N; Yoon, Bokwon; Landman, Uzi

    2009-07-01

    Small gas-phase gold cluster cations are essentially inert toward molecular oxygen. Preadsorption of molecular hydrogen, however, is found to cooperatively activate the binding of O(2) to even-size Au(x)(+) (x = 2, 4, 6) clusters. Measured temperature- and reaction-time-dependent ion intensities, obtained by ion trap mass spectrometry, in conjunction with first-principles density-functional theory calculations, reveal promotion and activation of molecular oxygen by preadsorbed hydrogen. These processes lead to the formation of a hydroperoxo intermediate on Au(4)(+) and Au(6)(+) and culminate in the dissociation of O(2) via the release of H(2)O. Langmuir-Hinshelwood reaction mechanisms involving the coadsorption of both of the reactant molecules are discussed for both cluster sizes, and an alternative Eley-Rideal mechanism involving hydrogen molecules adsorbed on a Au(6)(+) cluster reacting with an impinging gaseous oxygen molecule is analyzed. Structural fluctionality of the gold hexamer cation, induced by the adsorption of hydrogen molecules, and resulting in structural isomerization from a ground-state triangular structure to an incomplete hexagonal one, is theoretically predicted. Bonding of H(2) on cationic gold clusters is shown to involve charge transfer to the clusters. This serves to promote the bonding of coadsorbed oxygen through occupation of the antibonding 2pi* orbitals, resulting in excess electronic charge accumulation on the adsorbed molecule and weakening of the O-O bond. The theoretical results for hydrogen saturation coverages and reaction characteristics between the coadsorbed hydrogen and oxygen molecules are found to agree with the experimental findings. The joint investigations provide insights regarding hydrogen and oxygen cooperative adsorption effects and consequent reaction mechanisms.

  6. Spectral effects in activation of the human immunodeficiency virus promoter by psoralens plus ultraviolet A treatment.

    Science.gov (United States)

    Miller, S A; Beer, J Z; Strickland, A G; Zmudzka, B Z

    The effects of PUVA treatment on HIV promoter activation and cell killing in HIV cat/HeLa cells were studied using two UV sources, a UVASUN sunlamp and a UVAR Photoactivation Chamber. A 4 to 5 times higher dose of ultraviolet radiation was required from the UVASUN lamp than from the UVAR lamps: 1) to activate the HIV promoter in the presence of 0.1 or 1.0 microgram/ml 8-MOP and 2) to reduce cell survival to a level of 10%, in the presence of 0.1 or 1.0 microgram/ml 8-MOP. In addition, exposures performed with a fixed dose of 20 kJ/m2 at varying concentrations of 8-MOP, required a 4.7 times higher combined PUVA dose from the UVASUN lamp than from the UVAR lamps. Two possible sources of these differences were analyzed: (1) the presence of UVB + UVA2 (280-340 nm) in the radiation emitted by the UVAR, but not the UVASUN lamp, and its potential biological activity independent of 8-MOP, and (2) the difference in the overlap of the emission spectra of the two lamps with the absorption spectrum of 8-MOP. The area of overlap was higher for the UVAR lamp than for the UVASUN lamp by a factor of 4.6, which is close to the difference between these two lamps in induction of the HIV promoter and killing HeLa cells. This indicates that the effectiveness of a particular UVA source used in combination with 8-MOP can be predicted by its congruence to the absorption spectrum of the photosensitizing drug.

  7. Implanted spike wave electric stimulation promotes survival of the bone marrow mesenchymal stem cells and functional recovery in the spinal cord injured rats.

    Science.gov (United States)

    Wu, Wenliang; Zhao, Hua; Xie, Bin; Liu, Haichun; Chen, Yunzhen; Jiao, Guangjun; Wang, Hongliang

    2011-03-10

    Transplantation of bone marrow-derived mesenchymal stromal cells (BMSCs) into the injured spinal cord may provide therapeutic benefit, but its application is limited by their poor survival and low differentiation rate into neurons. Electrical stimulation (ES) has been reported to promote survival and differentiation of the BMSCs. Therefore we investigated whether implanted spike wave ES could improve survival of BMSCs after transplantation and result in functional improvement in animals with spinal cord injury. Our results showed that the number and ratio of survived BMSCs near the lesion site were significantly increased in the BMSCs+ES-treated group as compared to BMSCs transplantation or ES treatment alone group. Furthermore, results from BBB scales, SSEP and DTI demonstrated a significant improved functional recovery in the BMSCs+ES group. This indicated that implanted spike wave ES could promote the bioactivity of BMSCs and their survival. This represents a new therapeutic potential of the combination of BMSCs transplantation with implanted spike wave ES to treat spinal cord injury. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Transit-Related Walking to Work in Promoting Physical Activity.

    Science.gov (United States)

    Yu, Chia-Yuan; Lin, Hsien-Chang

    2015-04-01

    Transit-related walking to work is a potential strategy for incorporating physical activity into daily life and promoting health benefits. This study estimated the transit-related walking time for work trips on the journey to and from work and examined the predictors of transit users who walked to/from transit and the workplace and those who walked 30 minutes or more per day. This study used the 2009 National Household Travel Survey and identified 772 subjects who took transit to/from work, 355 subjects who walked to/from transit and the workplace, and 145 subjects who walked 30 minutes or more per day among the 40,659 workers. Weighted logistic regressions were used for the analysis. Of the people who walked to/from transit and the workplace, 40.9% walked 30 minutes or more per day. The weighted logistic regressions revealed that low-income groups and workers living in high population density areas were more likely to walk to/from transit and the workplace. Workers living in high population density areas were more likely to walk 30 minutes or more per day. Transit-related walking to work provides an opportunity to increase physical activity levels and to meet the physical activity recommendations.

  9. Predicting survival of Salmonella in low-water activity foods: an analysis of literature data.

    Science.gov (United States)

    Santillana Farakos, Sofia M; Schaffner, Donald W; Frank, Joseph F

    2014-09-01

    Factors such as temperature, water activity (aw), substrate, culture media, serotype, and strain influence the survival of Salmonella in low-aw foods. Predictive models for Salmonella survival in low-aw foods at temperatures ranging from 21 to 80(u) C and water activities below 0.6 were previously developed. Literature data on survival of Salmonella in low-aw foods were analyzed in the present study to validate these predictive models and to determine global influencing factors. The results showed the Weibull model provided suitable fits to the data in 75% of the curves as compared with the log-linear model. The secondary models predicting the time required for log-decimal reduction (log δ) and shape factor (log β) values were useful in predicting the survival of Salmonella in low-aw foods. Statistical analysis indicated overall fail-safe secondary models, with 88% of the residuals in the acceptable and safe zones (survival kinetics of Salmonella in low-aw foods and its influencing factors.

  10. Promoting Uranium Immobilization by the Activities of Microbial Phosphatases

    Energy Technology Data Exchange (ETDEWEB)

    Robert J. Martinez; Melanie J. Beazley; Samuel M. Webb; Martial Taillefert (co-PI); and Patricia A. Sobecky

    2007-04-19

    The overall objective of this project is to examine the activity of nonspecific phosphohydrolases present in naturally occurring subsurface microorganisms for the purpose of promoting the immobilization of radionuclides through the production of uranium [U(VI)] phosphate precipitates. Specifically, we hypothesize that the precipitation of U(VI) phosphate minerals may be promoted through the microbial release and/or accumulation of PO4 3- as a means to detoxify radionuclides and heavy metals. An experimental approach was designed to determine the extent of phosphatase activity in bacteria previously isolated from contaminated subsurface soils collected at the ERSP Field Research Center (FRC) in Oak Ridge, TN. Screening of 135 metal resistant isolates for phosphatase activity indicated the majority (75 of 135) exhibited a phosphatase-positive phenotype. During this phase of the project, a PCR based approach has also been designed to assay FRC isolates for the presence of one or more classes of the characterized non-specific acid phophastase (NSAP) genes likely to be involved in promoting U(VI) precipitation. Testing of a subset of Pb resistant (Pbr) Arthrobacter, Bacillus and Rahnella strains indicated 4 of the 9 Pbr isolates exhibited phosphatase phenotypes suggestive of the ability to bioprecipitate U(VI). Two FRC strains, a Rahnella sp. strain Y9602 and a Bacillus sp. strain Y9-2, were further characterized. The Rahnella sp. exhibited enhanced phosphatase activity relative to the Bacillus sp. Whole-cell enzyme assays identified a pH optimum of 5.5, and inorganic phosphate accumulated in pH 5.5 synthetic groundwater (designed to mimic FRC conditions) incubations of both strains in the presence of a model organophosphorus substrate provided as the sole C and P source. Kinetic experiments showed that these two organisms can grow in the presence of 200 μM dissolved uranium and that Rahnella is much more efficient in precipitating U(VI) than Bacillus sp. The

  11. Survival of bacteria in nuclear waste buffer materials. The influence of nutrients, temperature and water activity

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, K.; Motamedi, M. [Goeteborg Univ. (Sweden). Dept. of General and Marine Microbiology; Karnland, O. [Clay Technology AB, Lund (Sweden)

    1995-12-01

    The concept of deep geological disposal of spent fuel is common to many national nuclear waste programs. Long-lived radioactive waste will be encapsulated in canisters made of corrosion resistant materials e.g. copper and buried several hundred meters below ground in a geological formation. Different types of compacted bentonite clay, or mixtures with sand, will be placed as a buffer around the waste canisters. A major concern for the performance of the canisters is that sulphate-reducing bacteria (SRB) may be present in the clay and induce corrosion by production of hydrogen sulphide. This report presents data on viable counts of SRB in the bedrock of Aespoe hard rock laboratory. A theoretical background on the concept water activity is given, together with basic information about SRB. Some results on microbial populations from a full scale buffer test in Canada is presented. These results suggested water activity to be a strong limiting factor for survival of bacteria in compacted bentonite. As a consequence, experiments were set up to investigate the effect from water activity on survival of SRB in bentonite. Here we show that survival of SRB in bentonite depends on the availability of water and that compacting a high quality bentonite to a density of 2.0 g/cm{sup 3}, corresponding to a water activity (a{sub w}) of 0.96, prevented SRB from surviving in the clay. 24 refs.

  12. Recreational physical activity, body mass index, and survival in women with colorectal cancer

    NARCIS (Netherlands)

    Kuiper, J.; Phipps, A.I.; Neuhouser, M.L.; Chlebowski, R.T.; Thomson, C.A.; Irwin, M.L.; Lane, D.S.; Wactawski-Wende, J.; Hou, L.; Jackson, R.D.; Kampman, E.; Newcomb, P.A.

    2012-01-01

    Previous studies have shown that physical inactivity and obesity are risk factors for the development of colorectal cancer. However, controversy exists regarding the influence of these factors on survival in colorectal cancer patients. We evaluated the impact of recreational physical activity and

  13. Impact of diet, body mass index and physical activity on cancer survival

    NARCIS (Netherlands)

    Kampman, E.; Vrieling, A.; Duijnhoven, van F.J.B.; Winkels, R.M.

    2012-01-01

    With the increase in the number of cancer patients worldwide in the coming years, the need for knowledge on the influence of lifestyle factors on cancer survival is increasing. In this paper, the current knowledge on diet, body mass index, and physical activity in relation to cancer outcome is

  14. Non-exercise physical activity and survival: English longitudinal study of ageing.

    Science.gov (United States)

    Hamer, Mark; de Oliveira, Cesar; Demakakos, Panayotes

    2014-10-01

    The activity patterns of older adults include more light/mild-intensity or "non-exercise" activity and less moderate- to vigorous-intensity activity. The health benefits of this type of activity pattern remain unclear. To examine dose-response associations between physical activity and survival using time-varying analysis to understand the importance of "non-exercise" activity for survival in older adults. Participants (N=10,426) were drawn from The English Longitudinal Study of Ageing, a representative sample of men and women aged ≥50 years living in England. Participant data were linked with death records from the National Health Service registries from 2002 to 2011. Analyses were conducted in 2013. Cox proportional hazards models were used to estimate the risk of death according to time-varying estimates of physical activity. Over an average follow-up of 7.8 years (median follow-up, 8.5 years), there were 1,896 deaths. In models adjusted for comorbidities, psychosocial factors, smoking, and obesity, there was a dose-response association between time-varying physical activity and mortality, with the greatest survival benefit in vigorously active participants. However, participating in mild ("non-exercise")-intensity physical activity was also associated with a lower risk of all-cause mortality (hazard ratio [HR]=0.76, 95% CI=0.69, 0.83); cardiovascular mortality (HR=0.74, 95% CI=0.64, 0.85); and death by other causes (HR=0.67, 95% CI=0.58, 0.78). Time-varying models produced stronger, more robust estimates than models using a single measurement of physical activity at baseline. Older adults gain health benefits from participating in regular "non-exercise" physical activity, although the greatest benefits are observed for more vigorous activity. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  15. CD4+IL-21+T cells are correlated with regulatory T cells and IL-21 promotes regulatory T cells survival during HIV infection.

    Science.gov (United States)

    Zhang, Zi-Ning; Bai, Li-Xin; Fu, Ya-Jing; Jiang, Yong-Jun; Shang, Hong

    2017-03-01

    IL-21 enhances T and natural killer cells survival and antiviral functions without promoting T cell activation during HIV infection, which makes it a better adjuvant in anti-HIV immunotherapy. Due to the pleiotropy and redundancy of cytokines, it is vital to have a comprehensive knowledge of the role of IL-21 in the regulation of immune responses. Regulatory T cells (Tregs) play an important role in immune regulation and are a determinant of immune therapeutic efficacy in certain circumstances. In this study, we explored the direct effect of IL-21 on Tregs during HIV infection, which has not been addressed before. Thirty-four HIV treatment-naïve patients were enrolled and the relationship between CD4 + IL-21 + T cells and Tregs were studied. The effects of IL-21 on CD4 + CD25 + CD127 low Tregs' apoptosis, proliferation, and CTLA-4 and TGF-β expression in HIV-infected patients was investigated and compared with the effect of other common γ-chain cytokines. We found the percentage and absolute numbers of CD4 + IL-21 + T cells were positively related to the frequency or absolute numbers of CD4 + CD25 + or CD4 + CD25 + CD127 low Tregs. Compared with the media-alone control, IL-21, IL-7, and IL-15 could significantly reduce apoptosis of Tregs (pHIV infected patients. There were no significant differences of the fold induction of apoptosis, proliferation, or CTLA-4 and TGF-β expression by Tregs from HIV-infected patients and normal controls after IL-21 treatment. In vitro experiment showed that pretreatment with IL-21 significantly enhanced the suppressive effect of Tregs on CD8+ T cells' IFN-γ expression. We conclude that IL-21 promotes the survival and CTLA-4 expression of Tregs and enhanced the suppressive capacity of Tregs during HIV infection. These results broaden the understanding of HIV pathogenesis and provide critical information for HIV interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Fibroblast growth factor signaling pathway in endothelial cells is activated by BMPER to promote angiogenesis.

    Science.gov (United States)

    Esser, Jennifer S; Rahner, Susanne; Deckler, Meike; Bode, Christoph; Patterson, Cam; Moser, Martin

    2015-02-01

    Previously, we have identified bone morphogenetic protein endothelial cell precursor-derived regulator (BMPER) to increase the angiogenic activity of endothelial cells in a concentration-dependent manner. In this project, we now investigate how BMPER acts in concert with key molecules of angiogenesis to promote blood vessel formation. To assess the effect of BMPER on angiogenesis-related signaling pathways, we performed an angiogenesis antibody array with BMPER-stimulated endothelial cells. We detected increased basic fibroblast growth factor (bFGF/FGF-2) expression after BMPER stimulation and decreased expression of thrombospondin-1. Additionally, FGF receptor-1 expression, phosphorylation, FGF signaling pathway activity, and cell survival were increased. Consistently, silencing of BMPER by small interfering RNA decreased bFGF and FGF receptor-1 expression and increased thrombospondin-1 expression and cell apoptosis. Next, we investigated the interaction of BMPER and the FGF signaling pathway in endothelial cell function. BMPER stimulation increased endothelial cell angiogenic activity in migration, Matrigel, and spheroid assays. To block FGF signaling, an anti-bFGF antibody was used, which effectively inhibited the proangiogenic BMPER effect. Accordingly, BMPER-silenced endothelial cells under bFGF stimulation showed decreased angiogenic activity compared with bFGF control. We confirmed these findings in vivo by subcutaneous Matrigel injections with and without bFGF in C57BL/6_Bmper(+/-) mice. Aortic ring assays of C57BL/6_Bmper(+/-) mice confirmed a specific effect for bFGF but not for vascular endothelial growth factor. Taken together, the proangiogenic BMPER effect in endothelial cells is mediated by inhibition of antiangiogenic thrombospondin-1 and enhanced expression and activation of the FGF signaling pathway that is crucial in the promotion of angiogenesis. © 2014 American Heart Association, Inc.

  17. FGFR3 stimulates stearoyl CoA desaturase 1 activity to promote bladder tumor growth.

    Science.gov (United States)

    Du, Xiangnan; Wang, Qian-Rena; Chan, Emily; Merchant, Mark; Liu, Jinfeng; French, Dorothy; Ashkenazi, Avi; Qing, Jing

    2012-11-15

    Fibroblast growth factor receptor 3 (FGFR3) belongs to a family of receptor tyrosine kinases that control cell proliferation, differentiation, and survival. Aberrant activation of FGFR3 via overexpression or mutation is a frequent feature of bladder cancer; however, its molecular and cellular consequences and functional relevance to carcinogenesis are not well understood. Through transcriptional profiling of bladder carcinoma cells subjected to short hairpin RNA knockdown of FGFR3, we identified a gene-signature linking FGFR3 signaling with de novo sterol and lipid biosynthesis and metabolism. We found that FGFR3 signaling promotes the cleavage and activation of the master transcriptional regulator of lipogenesis, sterol regulatory element-binding protein 1(SREBP1/SREBF1), in a PI3K-mTORC1-dependent fashion. In turn, SREBP1 regulates the expression of key lipogenic enzymes, including stearoyl CoA desaturase 1 (SCD1/SCD). SCD1 is the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids and is crucial for lipid homeostasis. In human bladder cancer cell lines expressing constitutively active FGFR3, knockdown of SCD1 by siRNA markedly attenuated cell-cycle progression, reduced proliferation, and induced apoptosis. Furthermore, inducible knockdown of SCD1 in a bladder cancer xenograft model substantially inhibited tumor progression. Pharmacologic inhibition of SCD1 blocked fatty acid desaturation and also exerted antitumor activity in vitro and in vivo. Together, these findings reveal a previously unrecognized role of FGFR3 in regulating lipid metabolism to maintain tumor growth and survival, and also identify SCD1 as a potential therapeutic target for FGFR3-driven bladder cancer. ©2012 AACR.

  18. International Association for Promoting Geoethics (IAPG): an update on activities

    Science.gov (United States)

    Di Capua, Giuseppe; Bobrowsky, Peter; Kieffer, Susan; Peppoloni, Silvia; Tinti, Stefano

    2016-04-01

    The International Association for Promoting Geoethics (IAPG: http://www.geoethics.org) was founded on August 2012 to unite global geoscientists to raise the awareness of the scientific community regarding the importance of the ethical, social and cultural implications of geoscience research, education, and practice. IAPG is an international, multidisciplinary and scientific platform for discussion on ethical problems and dilemmas in Earth Sciences, promoting geoethical themes through scientific publications and conferences, strengthening the research base on geoethics, and focusing on case-studies as models for the development of effective and operative strategies. IAPG is legally recognized as a not-for-profit organization. It is a non-governmental, non-political, non-party institution, at all times free from racial, gender, religious or national prejudices. Its network continues to grow with more than 900 members in 103 countries, including 20 national sections. IAPG operates exclusively through donations and personal funds of its members. The results achieved since inception have been recognized by numerous international organizations. In particular, IAPG has obtained the status of affiliated organization by the International Union of Geological Sciences (IUGS), American Geosciences Institute (AGI), Geological Society of America (GSA), and the Geological Society of London (GSL). IAPG has enlarged its official relationships also through agreements on collaboration with other organizations, such as the American Geophysical Union (AGU), EuroGeoSurveys (EGS), European Federation of Geologists (EFG), Association of Environmental & Engineering Geologists (AEG), International Geoscience Education Organisation (IGEO), African Association of Women in Geosciences (AAWG), and others. IAPG considers publications as an indispensable activity to strengthen geoethics from a scientific point of view, so members are active in the publication of articles and editing of books on

  19. Critical success factors for physical activity promotion through community partnerships.

    Science.gov (United States)

    Lucidarme, Steffie; Marlier, Mathieu; Cardon, Greet; De Bourdeaudhuij, Ilse; Willem, Annick

    2014-02-01

    To define key factors of effective evidence-based policy implementation for physical activity promotion by use of a partnership approach. Using Parent and Harvey's model for sport and physical activity community-based partnerships, we defined determinants of implementation based on 13 face-to-face interviews with network organisations and 39 telephone interviews with partner organisations. Furthermore, two quantitative data-sets (n = 991 and n = 965) were used to measure implementation. In total, nine variables were found to influence implementation. Personal contact was the most powerful variable since its presence contributed to success while its absence led to a negative outcome. Four contributed directly to success: political motive, absence of a metropolis, high commitment and more qualified staff. Four others resulted in a less successful implementation: absence of positive merger effects, exposure motive and governance, and dispersed leadership. Community networks are a promising instrument for the implementation of evidence-based policies. However, determinants of both formation and management of partnerships influence the implementation success. During partnership formation, special attention should be given to partnership motives while social skills are of utmost importance for the management.

  20. Promoting Physical Activity through Priming the Content of Motivation.

    Science.gov (United States)

    St Quinton, Tom

    2017-01-01

    Non-conscious processes are important in influencing the performance of a number of behaviors, such as physical activity. One way that such processes can be influenced is through priming. Despite this, approaches within health psychology have predominantly focused on reflective processes with a number of psychological theories dedicated to identifying the predictors of intention. In doing so, critical beliefs and thoughts are first identified and then altered within interventions. Such work has shown limited effectiveness, however, with a gap apparent between what one intends to do and what subsequently ensues. Although there have been attempts to bridge this gap, such as theoretical integration, recent efforts include priming implicit processes. The aim of this commentary is to demonstrate the potential effectiveness of priming non-conscious processes and to suggest that the content of motivation should also succumb to priming influences. This brief review suggests that priming one of the most influential conscious processes, that of self-efficacy, could demonstrate particular effectiveness in promoting physical activity. Thus, the main purpose of the article is to suggest that the content of implicit processes as well their more traditional conscious counterparts may provide useful intervention targets. To achieve this, the article will first introduce the role of non-conscious processes and behavioral priming. Following this, the more common reflective processes will be outlined as well as attempts at theoretical integration. Finally, the article will identify studies priming non-conscious processes and will then suggest priming self-efficacy.

  1. Promoting Physical Activity through Priming the Content of Motivation

    Directory of Open Access Journals (Sweden)

    Tom St Quinton

    2017-09-01

    Full Text Available Non-conscious processes are important in influencing the performance of a number of behaviors, such as physical activity. One way that such processes can be influenced is through priming. Despite this, approaches within health psychology have predominantly focused on reflective processes with a number of psychological theories dedicated to identifying the predictors of intention. In doing so, critical beliefs and thoughts are first identified and then altered within interventions. Such work has shown limited effectiveness, however, with a gap apparent between what one intends to do and what subsequently ensues. Although there have been attempts to bridge this gap, such as theoretical integration, recent efforts include priming implicit processes. The aim of this commentary is to demonstrate the potential effectiveness of priming non-conscious processes and to suggest that the content of motivation should also succumb to priming influences. This brief review suggests that priming one of the most influential conscious processes, that of self-efficacy, could demonstrate particular effectiveness in promoting physical activity. Thus, the main purpose of the article is to suggest that the content of implicit processes as well their more traditional conscious counterparts may provide useful intervention targets. To achieve this, the article will first introduce the role of non-conscious processes and behavioral priming. Following this, the more common reflective processes will be outlined as well as attempts at theoretical integration. Finally, the article will identify studies priming non-conscious processes and will then suggest priming self-efficacy.

  2. Sense oligonucleotide competition for gene promoter binding and activation.

    Science.gov (United States)

    Cutroneo, Kenneth R; Chiu, Jen-Fu

    2003-01-01

    Considerable evidence has ensued on the importance of growth factors during regeneration both for cell replication and for stimulation of reparative cells to synthesize and secrete extracellular matrix components. During the healing process if the growth factor concentration is too high because of over-expression, abnormal wound healing and tissue fibrosis will occur. The growth factor concentration at the wound site may be controlled by gene therapy and the titration of gene dosage. However, if there is a narrow window between the beneficial effects and adverse effects of gene therapy, oligonucleotide approaches may be used concurrently with gene therapy to control growth factor concentration(s) at the wound site. Antisense oligos offer a method to control the concentration of growth factors at the level of translation. A novel method using sense oligos to the proalpha1 (I) collagen gene to inhibit gene transcription and collagen synthesis has recently been reported. The exogenous modified oligodeoxynucleotide competes with the cis-element (i.e. the transforming growth factor-beta (TGF-beta) element) in the distal 5'-flanking region of the proalpha1 (I) collagen gene for the trans-acting factor (i.e. the TGF-beta activator protein complex), thereby down regulating promoter activity of the proalpha1 (I) collagen gene and inhibiting type I collagen synthesis. The oligonucleotide approaches, both antisense and sense therapies, may be used to regulate over-expression of growth factors and thereby either eliminate or lessen the potential adverse effects of gene therapy.

  3. JunD/AP-1 Antagonizes the Induction of DAPK1 To Promote the Survival of v-Src-Transformed Cells.

    Science.gov (United States)

    Maślikowski, Bart M; Wang, Lizhen; Wu, Ying; Fielding, Ben; Bédard, Pierre-André

    2017-01-01

    The increase in AP-1 activity is a hallmark of cell transformation by tyrosine kinases. Previously, we reported that blocking AP-1 using the c-Jun dominant negative mutant TAM67 induced senescence, adipogenesis, or apoptosis in v-Src-transformed chicken embryo fibroblasts (CEFs) whereas inhibition of JunD by short hairpin RNA (shRNA) specifically induced apoptosis. To investigate the role of AP-1 in Src-mediated transformation, we undertook a gene profiling study to characterize the transcriptomes of v-Src-transformed CEFs expressing either TAM67 or the JunD shRNA. Our study revealed a cluster of 18 probe sets upregulated exclusively in response to AP-1/JunD impairment and v-Src transformation. Four of these probe sets correspond to genes involved in the interferon pathway. One gene in particular, death-associated protein kinase 1 (DAPK1), is a C/EBPβ-regulated mediator of apoptosis in gamma interferon (IFN-γ)-induced cell death. Here, we show that inhibition of DAPK1 abrogates cell death in v-Src-transformed cells expressing the JunD shRNA. Chromatin immunoprecipitation data indicated that C/EBPβ was recruited to the DAPK1 promoter while the expression of a dominant negative mutant of C/EBPβ abrogated the induction of DAPK1 in response to the inhibition of AP-1. In contrast, as determined by chromatin immunoprecipitation (ChIP) assays, JunD was not detected on the DAPK1 promoter under any conditions, suggesting that JunD promotes survival by indirectly antagonizing the expression of DAPK1 in v-Src transformed cells. Transformation by the v-Src oncoprotein causes extensive changes in gene expression in primary cells such as chicken embryo fibroblasts. These changes, determining the properties of transformed cells, are controlled in part at the transcriptional level. Much attention has been devoted to transcription factors such as AP-1 and NF-κB and the control of genes associated with a more aggressive phenotype. In this report, we describe a novel mechanism

  4. Phosphorylation by Cdc28 Activates the Cdc20-Dependent Activity of the Anaphase-Promoting Complex

    OpenAIRE

    Rudner, Adam D.; MURRAY, ANDREW W.

    2000-01-01

    Budding yeast initiates anaphase by activating the Cdc20-dependent anaphase-promoting complex (APC). The mitotic activity of Cdc28 (Cdk1) is required to activate this form of the APC, and mutants that are impaired in mitotic Cdc28 function have difficulty leaving mitosis. This defect can be explained by a defect in APC phosphorylation, which depends on mitotic Cdc28 activity in vivo and can be catalyzed by purified Cdc28 in vitro. Mutating putative Cdc28 phosphorylation sites in three compone...

  5. Purple sweet potato color alleviates D-galactose-induced brain aging in old mice by promoting survival of neurons via PI3K pathway and inhibiting cytochrome C-mediated apoptosis.

    Science.gov (United States)

    Lu, Jun; Wu, Dong-mei; Zheng, Yuan-lin; Hu, Bin; Zhang, Zi-feng

    2010-05-01

    Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, protects brain function against oxidative stress induced by D-galactose (D-gal) (Sigma-Aldrich, St. Louis, MO, USA). Our data showed that PSPC enhanced open-field activity, decreased step-through latency, and improved spatial learning and memory ability in D-gal-treated old mice by decreasing advanced glycation end-products' (AGEs) formation and the AGE receptor (RAGE) expression, and by elevating Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (Sigma-Aldrich) and catalase (CAT) expression and activity. Cleavage of caspase-3 and increased terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling (TUNEL)-positive cells in D-gal-treated old mice were inhibited by PSPC, which might be attributed to its antioxidant property. PSPC also suppressed the activation of c-Jun NH(2)-terminal kinase (JNK) and the release of cytochrome c from mitochondria that counteracted the onset of neuronal apoptosis in D-gal-treated old mice. Furthermore, it was demonstrated that phosphoinositide 3-kinase (PI3K) activation was required for PSPC to promote the neuronal survival accompanied with phosphorylation and activation of Akt and p44/42 mitogen-activated protein kinase (MAPK) by using PI3K inhibitor LY294002 (Cell Signaling Technology, Inc., Beverly, MA, USA), implicating a neuronal survival mechanism. The present results suggest that neuronal survival promoted by PSPC may be a potentially effective method to enhance resistance of neurons to age-related disease.

  6. The survival of fetal and bone marrow monocyte-derived alveolar macrophages is promoted by CD44 and its interaction with hyaluronan.

    Science.gov (United States)

    Dong, Y; Poon, G F T; Arif, A A; Lee-Sayer, S S M; Dosanjh, M; Johnson, P

    2017-10-25

    Alveolar macrophages maintain lung homeostasis by performing important roles in immunosurveillance and lung surfactant catabolism. They express high levels of CD44 and are one of the few macrophage populations that constitutively bind hyaluronan, a ligand for CD44 and component of pericellular and extracellular matrices. Using adoptive transfer experiments and a mouse model of inflammation, we found that alveolar macrophages are initially depleted after an inflammatory insult then rapidly self-renew and return to original numbers after the resolution phase. Monocytes recruited to an inflamed lung differentiate and contribute to the alveolar macrophage pool, but this occurs over a much slower time frame than alveolar macrophage self-renewal. CD44 expression on both fetal and bone marrow-derived alveolar macrophages promoted their survival and provided a competitive advantage over CD44-deficient alveolar macrophages at homeostasis and after inflammation. CD44-mediated hyaluronan binding was induced by the alveolar environment, and this interaction promoted alveolar macrophage survival both ex vivo and in vivo. Without CD44, alveolar macrophages lacked a hyaluronan coat, were more susceptible to death, and were present at lower numbers in the alveolar space. This demonstrates a new role for CD44 and hyaluronan in promoting alveolar macrophage survival.Mucosal Immunology advance online publication 25 October 2017. doi:10.1038/mi.2017.83.

  7. TYK2 activity promotes ligand-induced IFNAR1 proteolysis.

    Science.gov (United States)

    Marijanovic, Zrinka; Ragimbeau, Josiane; Kumar, K G Suresh; Fuchs, Serge Y; Pellegrini, Sandra

    2006-07-01

    The type I IFNR (interferon receptor) is a heterodimer composed of two transmembrane chains, IFNAR1 (interferon-alpha receptor 1 subunit) and IFNAR2, which are associated with the tyrosine kinases Tyk2 and Jak1 (Janus kinase 1) respectively. Ligand-induced down-regulation of the type I IFNR is a major mechanism of negative regulation of cellular signalling and involves the internalization and lysosomal degradation of IFNAR1. IFNalpha promotes the phosphorylation of IFNAR1 on Ser535, followed by recruitment of the E3 ubiquitin ligase, beta-TrCP2 (beta-transducin repeats-containing protein 2), ubiquitination of IFNAR1 and proteolysis. The non-catalytic role of Tyk2 in sustaining the steady-state IFNAR1 level at the plasma membrane is well documented; however, little is known about the function of Tyk2 in the steps that precede and succeed serine phosphorylation and ubiquitination of IFNAR1 in response to ligand binding. In the present study, we show that catalytic activation of Tyk2 is not essential for IFNAR1 internalization, but is required for ligand-induced IFNAR1 serine phosphorylation, ubiquitination and efficient lysosomal proteolysis.

  8. Parent participation plays an important part in promoting physical activity

    Directory of Open Access Journals (Sweden)

    Anna-Karin Lindqvist

    2015-08-01

    Full Text Available Although physical activity (PA is an important and modifiable determinant of health, in Sweden only 15% of boys and 10% of girls aged 15 years old achieve the recommended levels of PA 7 days per week. Adolescents’ PA levels are associated with social influence exerted by parents, friends, and teachers. The purpose of this study was to describe parents’ experiences of being a part of their adolescents’ empowerment-inspired PA intervention. A qualitative interview study was performed at a school in the northern part of Sweden. A total of 10 parents were interviewed, and the collected data were analyzed with qualitative content analysis. Three subthemes were combined into one main theme, demonstrating that parents are one important part of a successful PA intervention. The life of an adolescent has many options and demands that make it difficult to prioritize PA. Although parents felt that they were important in supporting their adolescent, a successful PA intervention must have multiple components. Moreover, the parents noted that the intervention had a positive effect upon not only their adolescents’, but also their own PA. Interventions aimed at promoting PA among adolescents should include measures to stimulate parent participation, have an empowerment approach, and preferably be school-based.

  9. An inducible and secreted eukaryote-like serine/threonine kinase of Salmonella enterica serovar Typhi promotes intracellular survival and pathogenesis.

    Science.gov (United States)

    Theeya, Nagaraja; Ta, Atri; Das, Sayan; Mandal, Rahul S; Chakrabarti, Oishee; Chakrabarti, Saikat; Ghosh, Amar N; Das, Santasabuj

    2015-02-01

    Eukaryote-like serine/threonine kinases (eSTKs) constitute an important family of bacterial virulence factors. Genome analysis had predicted putative eSTKs in Salmonella enterica serovar Typhi, although their functional characterization and the elucidation of their role in pathogenesis are still awaited. We show here that the primary sequence and secondary structure of the t4519 locus of Salmonella Typhi Ty2 have all the signatures of eukaryotic superfamily kinases. t4519 encodes a ∼39-kDa protein (T4519), which shows serine/threonine kinase activities in vitro. Recombinant T4519 (rT4519) is autophosphorylated and phosphorylates the universal substrate myelin basic protein. Infection of macrophages results in decreased viability of the mutant (Ty2Δt4519) strain, which is reversed by gene complementation. Moreover, reactive oxygen species produced by the macrophages signal to the bacteria to induce T4519, which is translocated to the host cell cytoplasm. That T4519 may target a host substrate(s) is further supported by the activation of host cellular signaling pathways and the induction of cytokines/chemokines. Finally, the role of T4519 in the pathogenesis of Salmonella Typhi is underscored by the significantly decreased mortality of mice infected with the Ty2Δt4519 strain and the fact that the competitive index of this strain for causing systemic infection is 0.25% that of the wild-type strain. This study characterizes the first eSTK of Salmonella Typhi and demonstrates its role in promoting phagosomal survival of the bacteria within macrophages, which is a key determinant of pathogenesis. This, to the best of our knowledge, is the first study to describe the essential role of eSTKs in the in vivo pathogenesis of Salmonella spp. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. TERT promoter mutation and its interaction with IDH mutations in glioma: Combined TERT promoter and IDH mutations stratifies lower-grade glioma into distinct survival subgroups-A meta-analysis of aggregate data.

    Science.gov (United States)

    Vuong, Huy Gia; Altibi, Ahmed M A; Duong, Uyen N P; Ngo, Hanh T T; Pham, Thong Quang; Chan, Aden Ka-Yin; Park, Chul-Kee; Fung, Kar-Ming; Hassell, Lewis

    2017-12-01

    The clinical significance of telomerase reverse transcriptase (TERT) promoter mutation in glioma remains unclear. The aim of our meta-analysis is to investigate the prognostic impact TERT promoter mutation in glioma patients and its interaction with other molecular markers, particularly Isocitrate Dehydrogenase (IDH) mutation from aggregate level data. Relevant articles were searched in four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library. Pooled HRs were calculated using random effect model weighted by inverse variance method. From 1010 studies, we finally included 28 studies with 11519 patients for meta-analyses. TERT mutation is significantly associated with compromised overall survival (OS) (HR=1.38; 95% CI=1.15-1.67) and progression-free survival (PFS) (HR=1.31; 95% CI=1.06-1.63) in glioma patients. In studying its reaction with IDH, TERT promoter mutation was associated with reduced OS in both IDH-mutant (IDH-mut) and IDH-wild type (IDH-wt) glioblastomas but shown to have inverse effects on IDH-mut and IDH-wt grade II/III tumors. Our analysis categorized WHO grade II/III glioma patients into four distinct survival subgroups with descending survival as follow: TERT-mut/IDH-mut≫TERT-wt/IDH-mut≫TERT-wt/IDH-wt≫TERT-mut/IDH-wt. Prognostic value of TERT promoter mutations in gliomas is dependent on tumor grade and the IDH mutational status. With the same tumor grade in WHO grade II and III tumors and the same IDH mutation status, TERT-mut is a prognostic factor. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Analysis of promoter activity in transgenic plants by normalizing ...

    Indian Academy of Sciences (India)

    Variations in transgene expression due to position effect and copy number are normalized when analysing and comparing the strengths of different promoters. In such experiments, the promoter to be tested is placed upstream to a reporter gene and a second expression cassette is introduced in a linked fashion in the same ...

  12. Evaluation of tumor-specific promoter activities in melanoma

    NARCIS (Netherlands)

    Lu, B; Makhija, SK; Nettelbeck, DM; Rivera, AA; Komarova, S; Zhou, F; Yamamoto, M; Haisma, HJ; Alvarez, RD; Curiel, DT; Zhu, ZB

    Gene therapy is a novel therapy for melanoma. To date, however, there is still no powerful tumor specific promoter (TSP) to restrict the transgene expression in melanoma cells. In order to define a useful TSP for targeting in the context of melanoma gene therapy, four promoters, the cyclooxygenase-2

  13. Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival

    Directory of Open Access Journals (Sweden)

    Hsieh Fu-Chuan

    2008-10-01

    Full Text Available Abstract Background Constitutive activation of signal transducer and activator of transcription 3 (Stat3 signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer. Results We found that elevated Stat3 phosphorylation in 19 of 100 (19% bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC. The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin and a cell cycle regulating gene (cyclin D1 was associated with the cell growth inhibition and apoptosis. Conclusion These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.

  14. Promotion of invasion by mutant RAS is dependent on activation of the WASF3 metastasis promoter gene.

    Science.gov (United States)

    Teng, Yong; Ngoka, Lambert; Cowell, John K

    2017-06-01

    Metastasis represents an end stage in the evolution of cancer progression and has been related to specific genetic pathways. Overexpression of mutant RAS in particular appears to promote invasion and metastasis, although exactly how this occurs has not been well characterized. It was previously showed that activation of the WASF3 protein regulates actin cytoskeleton dynamics that promote invasion. In this report, how WASF3 overexpression interacts with mutant RAS to increase invasion and metastasis was investigated. The ability of RAS to promote invasion and metastasis was shown to be dependent on WASF3 activation in a PI3K and AKT dependent manner. Proteomics analysis demonstrates the presence of AKT in the WASF3 immunocomplex which is enhanced by overexpression of mutant RAS. During these processes activation of ERK1/2 is not affected by loss of WASF3 expression. Analysis of the relative involvement of p85 and p110 in the WASF3 complex demonstrates that mutant RAS promotes dissociation of p85 promoting activation of p110. These studies provide a deeper understanding of the critical role for WASF3 in facilitating increased invasion potential in cancer cells expressing mutant RAS and supports the idea that targeting WASF3 in metastatic cells overexpressing RAS may be used to suppress invasion and metastasis. © 2017 Wiley Periodicals, Inc.

  15. Plant growth-promoting potential of bacteria isolated from active volcano sites of Barren Island, India.

    Science.gov (United States)

    Amaresan, N; Kumar, K; Sureshbabu, K; Madhuri, K

    2014-02-01

    To elucidate the biodiversity of plant growth-promoting (PGP) bacteria in active volcano sites of Barren Island, India, a total of 102 bacteria were isolated and screened for their multifunctional PGP properties. The results revealed that 21 isolates (20.6%) survived heat shock at 72°C and 11 (10.8%) isolates were able to grow exposed to 25% NaCl (w/v). In assaying for PGP properties, 59 (57.8%) isolates shown indole acetic acid (IAA) like substances production, 57 isolates (55.9%) produced siderophore and 34 (33.3%) solubilized inorganic phosphate qualitatively. Whereas in the production of extracellular enzymes, 42 isolates (41.2%) produced protease and amylase, 26 (25.5%) isolates produced lipase and 24 (23.5%) isolates produced cellulase. In antagonistic activity, 30 isolates (29.4%) were found antagonistic against Macrophomina sp., 20 isolates (19.6%) against Rhizoctonia solani and 15 isolates (14.7%) against Sclerotium rolfsii. The results based on 16 rRNA gene sequencing revealed that the PGP bacteria belonged to 22 different species comprising 13 genera. Based on multifunctional properties, nine isolates were further selected to determine the PGP in brinjal and chilli seeds. Of the bacteria tested, the isolate BAN87 showed increased root and shoot length of both the crops followed in plant growth promotion by BAN86 and BAN43. The outcome of this research proves plausible practical applicability of these PGPB for crop production in soils of saline and arid environments. The present research shows diverse plant growth-promoting (PGP) bacteria could be isolated from the active volcano site and suggests that volcano sites represent an ecological niche, which harbours a diverse and hitherto largely uncharacterized microbial population with yet unknown and untapped potential biotechnological applications, for example, plant growth promoters, as evidenced from this study. The outcome of this research may have a practical effect on crop production methodologies in

  16. MiRNA-486 regulates angiogenic activity and survival of mesenchymal stem cells under hypoxia through modulating Akt signal

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Xue-Feng [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining 810001 (China); Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Department of Respiration, Qinghai Provincial People' s Hospital, Xining (China); Wang, Hua; Xiao, Feng-Jun [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Yin, Yue [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Department of Hematology, Peking University First Hospital, Beijing (China); Xu, Qin-Qin [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining 810001 (China); Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Ge, Ri-Li, E-mail: geriligao@hotmail.com [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining 810001 (China); Wang, Li-Sheng, E-mail: wangls@bmi.ac.cn [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)

    2016-02-12

    MicroRNA-486 (miR-486) was first identified from human fetal liver cDNA library and validated as a regulator of hematopoiesis. Its roles in regulating the biological function of bone marrow-derived mesnechymal stem cells (BM-MSCs) under hypoxia have not been explored yet. In this study, we demonstrated that exposure to hypoxia upregulates miR-486 expression in BM-MSCs. Lentivirus-mediated overexpression of miR-486 resulted in increase of hepatocyte growth factor (HGF) and vascular endothelial growth factor(VEGF) in both mRNA and protein levels. MiR-486 expression also promotes proliferation and reduces apoptosis of BM-MSCs. Whereas MiR-486 knockdown downregulated the secretion of HGF and VEGF and induced apoptosis of BM-MSCs. Furthermore, PTEN-PI3K/AKT signaling was validated to be involved in changes of BM-MSC biological functions regulated by miR-486. These results suggested that MiR-486 mediated the hypoxia-induced angiogenic activity and promoted the proliferation and survival of BM-MSCs through regulating PTEN-PI3K/AKT signaling. These findings might provide a novel understanding of effective therapeutic strategy for hypoxic-ischemic diseases. - Highlights: • miR-486 is a hypoxia-induced miRNA. • miR-486 regulates the secretion of HGF and VEGF, promotes proliferation, and inhibits apoptosis of BM-MSCs. • miR-486 enhances PI3K/AKT activity signaling by targeting PTEN molecule.

  17. Rac1 selective activation improves retina ganglion cell survival and regeneration.

    Directory of Open Access Journals (Sweden)

    Erika Lorenzetto

    Full Text Available In adult mammals, after optic nerve injury, retinal ganglion cells (RGCs do not regenerate their axons and most of them die by apoptosis within a few days. Recently, several strategies that activate neuronal intracellular pathways were proposed to prevent such degenerative processes. The rho-related small GTPase Rac1 is part of a complex, still not fully understood, intracellular signaling network, mediating in neurons many effects, including axon growth and cell survival. However, its role in neuronal survival and regeneration in vivo has not yet been properly investigated. To address this point we intravitreally injected selective cell-penetrating Rac1 mutants after optic nerve crush and studied the effect on RGC survival and axonal regeneration. We injected two well-characterized L61 constitutively active Tat-Rac1 fusion protein mutants, in which a second F37A or Y40C mutation confers selectivity in downstream signaling pathways. Results showed that, 15 days after crush, both mutants were able to improve survival and to prevent dendrite degeneration, while the one harboring the F37A mutation also improved axonal regeneration. The treatment with F37A mutant for one month did not improve the axonal elongation respect to 15 days. Furthermore, we found an increase of Pak1 T212 phosphorylation and ERK1/2 expression in RGCs after F37A treatment, whereas ERK1/2 was more activated in glial cells after Y40C administration. Our data suggest that the selective activation of distinct Rac1-dependent pathways could represent a therapeutic strategy to counteract neuronal degenerative processes in the retina.

  18. Nrf1 CNC-bZIP protein promotes cell survival and nucleotide excision repair through maintaining glutathione homeostasis.

    Science.gov (United States)

    Han, Weinong; Ming, Mei; Zhao, Rui; Pi, Jingbo; Wu, Chunli; He, Yu-Ying

    2012-05-25

    Skin cancer is the most common cancer in the United States. Its major environmental risk factor is UVB radiation in sunlight. In response to UVB damage, epidermal keratinocytes activate a specific repair pathway, i.e. nucleotide excision repair, to remove UVB-induced DNA lesions. However, the regulation of UVB response is not fully understood. Here we show that the long isoform of the nuclear factor erythroid 2-related factor 1 (Nrf1, also called NFE2L1), a cytoprotective transcription factor critical for the expression of multiple antioxidant response element-dependent genes, plays an important role in the response of keratinocytes to UVB. Nrf1 loss sensitized keratinocytes to UVB-induced apoptosis by up-regulating the expression of the proapoptotic Bcl-2 family member Bik through reducing glutathione levels. Knocking down Bik reduced UVB-induced apoptosis in Nrf1-inhibited cells. In UVB-irradiated surviving cells, however, disruption of Nrf1 impaired nucleotide excision repair through suppressing the transcription of xeroderma pigmentosum C (XPC), a factor essential for initiating the global genome nucleotide excision repair by recognizing the DNA lesion and recruiting downstream factors. Nrf1 enhanced XPC expression by increasing glutathione availability but was independent of the transcription repressor of XPC. Adding XPC or glutathione restored the DNA repair capacity in Nrf1-inhibited cells. Finally, we demonstrate that Nrf1 levels are significantly reduced by UVB radiation in mouse skin and are lower in human skin tumors than in normal skin. These results indicate a novel role of Nrf1 in UVB-induced DNA damage repair and suggest Nrf1 as a tumor suppressor in the skin.

  19. Survival and activity of Streptococcus faecalis and Escherichia coli in petroleum-contaminated tropical marine waters

    Energy Technology Data Exchange (ETDEWEB)

    Santo Domingo, J.W.; Fuentes, F.A.; Hazen, T.C. [Univ. of Puerto Rico, Rio Piedras (Puerto Rico). Microbial Ecology Lab.

    1987-12-31

    The in situ survival and activity of Streptococcus faecalis and Escherichia coli were studied using membrane diffusion chambers in tropical marine waters receiving oil refinery effluents. Protein synthesis, DNA synthesis, respiration or fermentation, INT reduced per cell, and ATP per cell were used to measure physiological activity. Cell densities decreased significantly over time at both sites for both S. faecalis and E. coli; however, no significant differences in survival pattern were observed between S. faecalis and E.coli. Differences in protein synthesis between the two were only observed at a study site which was not heavily oiled. Although fecal streptococci have been suggested as a better indicator of fecal contamination than fecal coliforms in marine waters, in this study both E. coli and S. faecalis survived and remained physiologically active for extended periods of time. These results suggest that the fecal streptococci group is not a better indicator of fecal contamination in tropical marine waters than the fecal coliform group, especially when that environment is high in long-chained hydrocarbons.

  20. Interferon-γ links UV to melanocyte activation and promotes melanomagenesis

    Science.gov (United States)

    Zaidi, M. Raza; Davis, Sean; Noonan, Frances P.; Graff-Cherry, Cari; Hawley, Teresa S.; Walker, Robert L.; Feigenbaum, Lionel; Fuchs, Elaine; Lyakh, Lyudmila; Young, Howard A.; Hornyak, Thomas J.; Arnheiter, Heinz; Trinchieri, Giorgio; Meltzer, Paul S.; De Fabo, Edward C.; Merlino, Glenn

    2010-01-01

    Cutaneous malignant melanoma is a highly aggressive and frequently chemoresistant cancer, whose incidence continues to rise. Epidemiological studies reveal that the major etiological melanoma risk factor is ultraviolet (UV) solar radiation, with the highest risk associated with intermittent burning doses, especially during childhood1,2. We have experimentally validated these epidemiological findings using the hepatocyte growth factor/scatter factor (HGF/SF) transgenic mouse model, which develops lesions in stages highly reminiscent of human melanoma with respect to biological, genetic and etiologic criteria, but only when irradiated as neonatal pups with UVB, not UVA3,4. However, mechanisms underlying UVB-initiated, neonatal-specific melanomagenesis remain largely unknown. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-γ (IFN-γ), but not type-I interferons. IFN-γ was produced by macrophages recruited to neonatal skin by UVB-induced ligands to the chemokine receptor Ccr2. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-γ blockade abolished macrophage-enhanced melanoma growth and survival. IFN-γ-producing macrophages were also identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-γ in promoting melanocytic cell survival/immunoevasion, and suggest that IFN-γ-R signaling represents a novel therapeutic melanoma target. PMID:21248750

  1. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis.

    Science.gov (United States)

    Bollrath, Julia; Phesse, Toby J; von Burstin, Vivian A; Putoczki, Tracy; Bennecke, Moritz; Bateman, Trudie; Nebelsiek, Tim; Lundgren-May, Therese; Canli, Ozge; Schwitalla, Sarah; Matthews, Vance; Schmid, Roland M; Kirchner, Thomas; Arkan, Melek C; Ernst, Matthias; Greten, Florian R

    2009-02-03

    Although gastrointestinal cancers are frequently associated with chronic inflammation, the underlying molecular links have not been comprehensively deciphered. Using loss- and gain-of-function mice in a colitis-associated cancer model, we establish here a link comprising the gp130/Stat3 transcription factor signaling axis. Mutagen-induced tumor growth and multiplicity are reduced following intestinal epithelial cell (IEC)-specific Stat3 ablation, while its hyperactivation promotes tumor incidence and growth. Conversely, IEC-specific Stat3 deficiency enhances susceptibility to chemically induced epithelial damage and subsequent mucosal inflammation, while excessive Stat3 activation confers resistance to colitis. Stat3 has the capacity to mediate IL-6- and IL-11-dependent IEC survival and to promote proliferation through G1 and G2/M cell-cycle progression as the common tumor cell-autonomous mechanism that bridges chronic inflammation to tumor promotion.

  2. Promoting active visits to parks: models and strategies for transdisciplinary collaboration

    Science.gov (United States)

    David M. Buchner; Paul H. Gobster

    2007-01-01

    The purpose of this paper is to discuss the shared interest of the public health and parks and recreation sectors in promoting active visits to parks. At the institutional level, both sectors have missions to promote physical activity and view parks as key components in attaining physical activity goals. While some balancing among park goals may be necessary to avoid...

  3. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.

    Science.gov (United States)

    Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D; Moriggl, Richard; Kenner, Lukas; Tse, William

    2015-08-21

    AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties.

  4. The basic helix-loop-helix transcription factor Nex-1/Math-2 promotes neuronal survival of PC12 cells by modulating the dynamic expression of anti-apoptotic and cell cycle regulators.

    Science.gov (United States)

    Uittenbogaard, Martine; Chiaramello, Anne

    2005-02-01

    The basic helix-loop-helix transcription factor Nex1/Math-2 belongs to the NeuroD subfamily, which plays a critical role during neuronal differentiation and maintenance of the differentiated state. Previously, we demonstrated that Nex1 is a key regulatory component of the nerve growth factor (NGF) pathway. Further supporting this hypothesis, this study shows that Nex1 has survival-inducing properties similar to NGF, as Nex1-overexpressing PC12 cells survive in the absence of trophic factors. We dissected the molecular mechanism by which Nex1 confers neuroprotection upon serum removal and found that constitutive expression of Nex1 maintained the expression of specific G1 phase cyclin-dependent kinase inhibitors and concomitantly induced a dynamic expression profile of key anti-apoptotic regulators. This study provides the first evidence of the underlying mechanism by which a member of the NeuroD-subfamily promotes an active anti-apoptotic program essential to the survival of neurons. Our results suggest that the survival program may be viewed as an integral component of the intrinsic programming of the differentiated state.

  5. HDAC Activity Is Required for Efficient Core Promoter Function at the Mouse Mammary Tumor Virus Promoter

    Directory of Open Access Journals (Sweden)

    Sang C. Lee

    2011-01-01

    Full Text Available Histone deacetylases (HDACs have been shown to be required for basal or inducible transcription at a variety of genes by poorly understood mechanisms. We demonstrated previously that HDAC inhibition rapidly repressed transcription from the mouse mammary tumor virus (MMTV promoter by a mechanism that does not require the binding of upstream transcription factors. In the current study, we find that HDACs work through the core promoter sequences of MMTV as well as those of several cellular genes to facilitate transcriptional initiation through deacetylation of nonhistone proteins.

  6. Interleukin-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium

    Science.gov (United States)

    Liu, Rebecca; Lauridsen, Holly M.; Amezquita, Robert A.; Pierce, Richard W.; Jane-wit, Dan; Fang, Caodi; Pellowe, Amanda S.; Kirkiles-Smith, Nancy C.; Gonzalez, Anjelica L.; Pober, Jordan S.

    2016-01-01

    A classical hallmark of acute inflammation is neutrophil infiltration of tissues, a multi-step process that involves sequential cell-cell interactions of circulating leukocytes with interleukin (IL)-1- or tumor necrosis factor-α (TNF)-activated microvascular endothelial cells (ECs) and pericytes (PCs) that form the wall of the postcapillary venules. The initial infiltrating cells accumulate perivascularly in close proximity to PCs. IL-17, a pro-inflammatory cytokine that acts on target cells via a heterodimeric receptor formed by IL-17RA and IL-17RC subunits, also promotes neutrophilic inflammation but its effects on vascular cells are less clear. We report that both cultured human ECs and PCs strongly express IL-17RC and, while neither cell type expresses much IL-17RA, PCs express significantly more than ECs. IL-17, alone or synergistically with TNF, significantly alters inflammatory gene expression in cultured human PCs but not ECs. RNA-seq analysis identifies many IL-17-induced transcripts in PCs encoding proteins known to stimulate neutrophil-mediated immunity. Conditioned media (CM) from IL-17-activated PCs, but not ECs, induce pertussis toxin-sensitive neutrophil polarization, likely mediated by PC-secreted chemokines, and also stimulate neutrophil production of pro-inflammatory molecules, including TNF, IL-1α, IL-1β, and IL-8. Furthermore, IL-17-activated PCs but not ECs can prolong neutrophil survival by producing G-CSF and GM-CSF, delaying the mitochondria outer membrane permeabilization and caspase 9 activation. Importantly, neutrophils exhibit enhanced phagocytic capacity after activation by CM from IL-17-treated PCs. We conclude that PCs, not ECs, are the major target of IL-17 within the microvessel wall and that IL-17-activated PCs can modulate neutrophil functions within the perivascular tissue space. PMID:27534549

  7. Coaches' Perceptions of French Sports Clubs: Health-Promotion Activities, Aims and Coach Motivation

    Science.gov (United States)

    Van Hoye, Aurélie; Sarrazin, Philippe; Heuzé, Jean-Philippe; Kokko, Sami

    2015-01-01

    Background: Given the benefits of participating in sport, sports clubs have been recognised as health promoting organizations. To examine health-promotion activities in Finnish sports clubs, Kokko et al. developed a set of standards for health-promoting sports clubs (HPSC). Objective: The present study extends this line of research, by (1)…

  8. Health promotion activities for elderly foreigners : a study about third sector organization and their health promotional activities for elderly foreigners in the Ostrobothnia region

    OpenAIRE

    Hägg, Jane; Zheng, Haixia

    2011-01-01

    The objective of this study is to find out the presence of available activities offered by the Third Sector Organizations for elderly from minorities in the Ostrobothnia Region. This study aims at raising awareness of health promotion and well-being. Therefore, the intention was to increase the knowledge and awareness about the Third Sector organizations and their health promotional activities in the Ostrobothnia Region. The qualitative method was used and the respondents have conducted se...

  9. Crocetin Reduces Activation of Hepatic Apoptotic Pathways and Improves Survival in Experimental Hemorrhagic Shock

    Science.gov (United States)

    Yang, Rongjie; Vernon, Kathy; Thomas, Ann; Morrison, David; Qureshi, Nilofer; Van Way, Charles W

    2014-01-01

    Background Hemorrhagic shock results in cellular damage and cell death. A primary mechanism is cellular apoptosis from mitochondrial damage. This study demonstrated that administration of crocetin to experimental animals during resuscitation from shock significantly improved postshock survival and reduced apoptosis. Crocetin is a component of saffron and has long been used in traditional medicine in Asia. Methods Male Sprague-Dawley rats (350 ± 30g) were randomly assigned to 1 of 4 groups of 8 animals. Hemorrhagic shock was induced by withdrawing blood until the mean arterial pressure was 35–40 mm Hg, and blood pressure was maintained at that level for 60 minutes with further withdrawals as needed. Resuscitation was carried out by administration of 21 mL/kg lactated Ringer’s solution and return of shed blood, with or without concurrent administration of crocetin (2 mg/kg). Control animals were sham-treated with surgical preparation, without shock or resuscitation, and with and without crocetin. Rats were sacrificed 24 hours after completion of resuscitation. The extent of activation of hepatic apoptosis was established by measuring levels of hepatic cytosolic cytochrome c, caspase-3, and bcl-2. A separate group of 53 animals treated identically was used to assess survival. Results Crocetin administration during resuscitation resulted in less extensive activation of hepatic apoptosis and significantly increased survival relative to controls. Conclusions Crocetin administration to experimental animals during resuscitation post hemorrhage increased survival, at least in part by protecting the liver from activation of apoptotic cell death. This agent continues to show promise as a potential treatment strategy for hemorrhagic shock. PMID:21224437

  10. A university system-wide qualitative investigation into student physical activity promotion conducted on college campuses.

    Science.gov (United States)

    Milroy, Jeffrey J; Wyrick, David L; Bibeau, Daniel L; Strack, Robert W; Davis, Paul G

    2012-01-01

    This study aimed to examine college student physical activity promotion. A cross-sectional approach to qualitative research was used. Southeastern state university system. Fourteen of 15 (93%) universities recruited were included in this study; 22 university employees participated in a semistructured interview. Nonprobabilistic purposive and snowball sampling strategies were used to recruit individuals who were likely to be engaged in physical activity promotion efforts on their respective campuses. Thematic analyses lead to the identification of emerging themes that were coded and analyzed using NVivo software. Themes informed three main areas: key personnel responsible for promoting physical activity to students, actual physical activity promotion efforts implemented, and factors that influence student physical activity promotion. Results suggest that ecological approaches to promote physical activity on college campuses are underused, the targeting of mediators of physical activity in college students is limited, and values held by university administration influence campus physical activity promotion. Findings support recommendations for future research and practice. Practitioners should attempt to implement social ecological approaches that target scientifically established mediators of physical activity in college students. Replication of this study is needed to compare these findings with other types of universities, and to investigate the relationship between promotion activities (type and exposure) and physical activity behaviors of college students.

  11. Bacterial Genotoxins Promote Inside-Out Integrin β1 Activation, Formation of Focal Adhesion Complexes and Cell Spreading

    Science.gov (United States)

    Levi, Laura; Toyooka, Tatsushi; Patarroyo, Manuel; Frisan, Teresa

    2015-01-01

    Integrins are membrane bound receptors that regulate several cellular processes, such as cell adhesion, migration, survival and proliferation, and may contribute to tumor initiation/progression in cells exposed to genotoxic stress. The extent of integrin activation and its role in cell survival upon intoxication with bacterial genotoxins are still poorly characterized. These toxins induce DNA strand breaks in the target cells and activate the DNA damage response (DDR), coordinated by the Ataxia Telangectasia Mutated (ATM) kinase. In the present study, we demonstrate that induction of DNA damage by two bacterial genotoxins promotes activation of integrin β1, leading to enhanced assembly of focal adhesions and cell spreading on fibronectin, but not on vitronectin. This phenotype is mediated by an ATM-dependent inside-out integrin signaling, and requires the actin cytoskeleton remodeler NET1. The toxin-mediated cell spreading and anchorage-independent survival further relies on ALIX and TSG101, two components of the endosomal sorting complex required for transport (ESCRT), known to regulate integrin intracellular trafficking. These data reveal a novel aspect of the cellular response to bacterial genotoxins, and provide new tools to understand the carcinogenic potential of these effectors in the context of chronic intoxication and infection. PMID:25874996

  12. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension

    Science.gov (United States)

    Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E.; Arons, Elena; Zaman, Paula; Polach, Kevin J.; Matar, Majed; Yung, Lai-Ming; Yu, Paul B.; Bowman, Frederick P.; Opotowsky, Alexander R.; Waxman, Aaron B.; Loscalzo, Joseph; Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10−9 to 10−7 M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor–small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro. Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo. Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.—Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery

  13. Physiotypic Plasticity and Survival of Arido-active Euphorbia triaculeata (Euphorbiaceae in its Natural Habitat

    Directory of Open Access Journals (Sweden)

    Turki A. Al-Turki

    2014-12-01

    Full Text Available Leafless stem succulent Euphorbia triaculeata Forssk. is abundant in arid regions southwest of the Arabian Peninsula. These regions are characterized by short wet season with erratic rainfall and long dry season with high temperature and high irradiance. Field observations indicated that the plant survives the long dry season and acquires a red stem colour under high irradiance and protracted drought. Our work aimed at investigating survival of this arido-active species in its natural habitat by studying diurnal and seasonal changes in stomatal conductance, cell sap acidity, and chlorophyll fluorescence. Results showed that E. triaculeata is obligate crassulacean acid metabolism (CAM plant. Under protracted drought, low stomatal conductance and dampening of CAM denoted a shift to CAM-idling. Observed stress-induced reduction of Photosystem II activity occurred in concomitance with increased non-photochemical quenching of chlorophyll fluorescence and increased anthocyanin content. These results reflected operation of a photoprotective mechanism involving interplay of non-photochemical energy dissipation via xanthophyll cycle and alleviation of oxidative stress by anthocyanin. It was concluded that E. triaculeata survives in its arid habitat by performing obligate CAM, shifting to CAM-idling under protracted drought, increasing non-photochemical excess energy dissipation, and accumulating anthocyanin pigment for its antioxidant attributes.

  14. Does the benefit on survival from leisure time physical activity depend on physical activity at work?

    DEFF Research Database (Denmark)

    Holtermann, Andreas; Marott, Jacob Louis; Gyntelberg, Finn

    2013-01-01

    To investigate if persons with high physical activity at work have the same benefits from leisure time physical activity as persons with sedentary work.......To investigate if persons with high physical activity at work have the same benefits from leisure time physical activity as persons with sedentary work....

  15. Prostaglandin E2 promotes features of replicative senescence in chronically activated human CD8+ T cells.

    Directory of Open Access Journals (Sweden)

    Jennifer P Chou

    Full Text Available Prostaglandin E2 (PGE2, a pleiotropic immunomodulatory molecule, and its free radical catalyzed isoform, iso-PGE2, are frequently elevated in the context of cancer and chronic infection. Previous studies have documented the effects of PGE2 on the various CD4+ T cell functions, but little is known about its impact on cytotoxic CD8+ T lymphocytes, the immune cells responsible for eliminating virally infected and tumor cells. Here we provide the first demonstration of the dramatic effects of PGE2 on the progression of human CD8+ T cells toward replicative senescence, a terminal dysfunctional state associated multiple pathologies during aging and chronic HIV-1 infection. Our data show that exposure of chronically activated CD8+ T cells to physiological levels of PGE2 and iso-PGE2 promotes accelerated acquisition of markers of senescence, including loss of CD28 expression, increased expression of p16 cell cycle inhibitor, reduced telomerase activity, telomere shortening and diminished production of key cytotoxic and survival cytokines. Moreover, the CD8+ T cells also produced higher levels of reactive oxygen species, suggesting that the resultant oxidative stress may have further enhanced telomere loss. Interestingly, we observed that even chronic activation per se resulted in increased CD8+ T cell production of PGE2, mediated by higher COX-2 activity, thus inducing a negative feedback loop that further inhibits effector function. Collectively, our data suggest that the elevated levels of PGE2 and iso-PGE2, seen in various cancers and HIV-1 infection, may accelerate progression of CD8+ T cells towards replicative senescence in vivo. Inhibition of COX-2 activity may, therefore, provide a strategy to counteract this effect.

  16. GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy.

    Directory of Open Access Journals (Sweden)

    Shvetank Sharma

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a known outcome of hepatosteatosis. Free fatty acids (FFA induce the unfolded protein response (UPR or endoplasmic reticulum (ER stress that may induce apoptosis. Recent data indicate ER stress to be a major player in the progression of fatty liver to more aggressive lesions. Autophagy on the other hand has been demonstrated to be protective against ER stress-induced cell death. We hypothesized that exendin-4 (GLP-1 analog treatment of fat loaded hepatocytes can reduce steatosis by autophagy which leads to reduced ER stress-related hepatocyte apoptosis.Primary human hepatocytes were loaded with saturated, cis- and trans-unsaturated fatty acids (palmitic, oleic and elaidic acid respectively. Steatosis, induced with all three fatty acids, was significantly resolved after exendin-4 treatment. Exendin-4 sustained levels of GRP78 expression in fat-loaded cells when compared to untreated fat-loaded cells alone. In contrast, CHOP (C/EBP homologous protein; the penultimate protein that leads to ER stress-related cell death was significantly decreased by exendin-4 in hepatocytes loaded with fatty acids. Finally, exendin-4 in fat loaded hepatocytes clearly promoted gene products associated with macroautophagy as measured by enhanced production of both Beclin-1 and LC3B-II, markers for autophagy; and visualized by transmission electron microscopy (TEM. Similar observations were made in mouse liver lysates after mice were fed with high fat high fructose diet and treated with a long acting GLP-1 receptor agonist, liraglutide.GLP-1 proteins appear to protect hepatocytes from fatty acid-related death by prohibition of a dysfunctional ER stress response; and reduce fatty acid accumulation, by activation of both macro-and chaperone-mediated autophagy. These findings provide a novel role for GLP-1 proteins in halting the progression of more aggressive lesions from underlying steatosis in humans afflicted with NAFLD.

  17. L-arginine, an active component of salmon milt nucleoprotein, promotes thermotolerance via Sirtuin in Caenorhabditis elegans.

    Science.gov (United States)

    Furuhashi, Tsubasa; Matsunaga, Masaji; Asahara, Yuji; Sakamoto, Kazuichi

    2016-03-25

    We previously showed that salmon milt nucleoprotein (NP) promotes thermotolerance in Caenorhabditis elegans; however, the active component and physiological mechanism of this effect has remained unclear. l-arginine (AR) is a major component of protamine and thus it has been proposed as the possible active component of NP. In this study, the viability of C. elegans treated with AR under heat stress was assessed and AR was shown to extend the survival term of the heat-stressed organisms. Additionally, AR was shown to restore the thrashing movement of the worms that is suppressed by heat stress. Treatment with AR was furthermore shown to promote thermotolerance in a DAF-16- and SIR-2.1-dependent manner, where DAF-16 and SIR-2.1 are homologs of FoxO and SirT1, respectively. Taken together, these data suggest that AR is one of the active components of NP and promotes thermotolerance via the activation of DAF-16 and SIR-2.1. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Loss of Endogenous Interleukin-12 Activates Survival Signals in Ultraviolet-Exposed Mouse Skin and Skin Tumors

    Directory of Open Access Journals (Sweden)

    Syed M. Meeran

    2009-09-01

    Full Text Available Interleukin-12 (IL-12-deficiency promotes photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. Here, we report that long-term exposure to ultraviolet (UV radiation resulted in enhancement of the levels of cell survival kinases, such as phosphatidylinositol 3-kinase (PI3K, Akt (Ser473, p-ERK1/2, and p-p38 in the skin of IL-12p40 knockout (IL-12 KO mice compared with the skin of wild-type mice. UV-induced activation of nuclear factor-κB (NF-κB/p65 in the skin of IL-12 KO mice was also more prominent. The levels of NF-κB-targeted proteins, such as proliferating cell nuclear antigen (PCNA, cyclooxygenase-2, cyclin D1, and inducible nitric oxide synthase, were higher in the UV-exposed skin of IL-12 KO mice than the UV-exposed skin of wild types. In short-term UV irradiation experiments, subcutaneous treatment of IL-12 KO mice with recombinant IL-12 (rIL-12 or topical treatment with oridonin, an inhibitor of NF-κB, resulted in the inhibition of UV-induced increases in the levels of PCNA, cyclin D1, and NF-κB compared with non-rIL-12- or non-oridonin-treated IL-12 KO mice. UV-induced skin tumors of IL-12 KO mice had higher levels of PI3K, p-Akt (Ser473, p-ERK1/2, p-p38, NF-κB, and PCNA and fewer apoptotic cells than skin tumors of wild types. Together, these data suggest that the loss of endogenous IL-12 activates survival signals in UV-exposed skin and that may lead to the enhanced photocarcinogenesis in mice.

  19. Promoting extracellular matrix remodeling via ascorbic acid enhances the survival of primary ovarian follicles encapsulated in alginate hydrogels.

    Science.gov (United States)

    Tagler, David; Makanji, Yogeshwar; Tu, Tao; Bernabé, Beatriz Peñalver; Lee, Raymond; Zhu, Jie; Kniazeva, Ekaterina; Hornick, Jessica E; Woodruff, Teresa K; Shea, Lonnie D

    2014-07-01

    The in vitro growth of ovarian follicles is an emerging technology for fertility preservation. Various strategies support the culture of secondary and multilayer follicles from various species including mice, non-human primate, and human; however, the culture of early stage (primary and primordial) follicles, which are more abundant in the ovary and survive cryopreservation, has been limited. Hydrogel-encapsulating follicle culture systems that employed feeder cells, such as mouse embryonic fibroblasts (MEFs), stimulated the growth of primary follicles (70-80 µm); yet, survival was low and smaller follicles (ascorbic acid based on its role in extracellular matrix (ECM) deposition/remodeling for other applications. The selection of ascorbic acid was further supported by a microarray analysis that suggested a decrease in mRNA levels of enzymes within the ascorbate pathway between primordial, primary, and secondary follicles. The supplementation of ascorbic acid (50 µg/mL) significantly enhanced the survival of primary follicles (<80 µm) cultured in alginate hydrogels, which coincided with improved structural integrity. Follicles developed antral cavities and increased to diameters exceeding 250 µm. Consistent with improved structural integrity, the gene/protein expression of ECM and cell adhesion molecules was significantly changed. This research supports the notion that modifying the culture environment (medium components) can substantially enhance the survival and growth of early stage follicles. © 2013 Wiley Periodicals, Inc.

  20. Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo

    DEFF Research Database (Denmark)

    Jørgensen, Jesper Roland; Fransson, Anette; Fjord-Larsen, Lone

    2012-01-01

    properties in vitro, combined with the restricted inner ear expression during development, we further investigated Cometin in relation to deafness. In neomycin deafened guinea pigs, two weeks intracochlear infusion of recombinant Cometin supports spiral ganglion neuron survival and function. In contrast......Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved...... protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.5 also in dorsal root ganglions and inner ear but apparently not in the adult nervous system. In vitro, Cometin promotes neurite outgrowth from dorsal root ganglion cells which can be blocked...

  1. Apparent survival of the salamander Salamandra salamandra is low because of high migratory activity

    Directory of Open Access Journals (Sweden)

    Schaub Michael

    2007-09-01

    Full Text Available Abstract Background Understanding the demographic processes underlying population dynamics is a central theme in ecology. Populations decline if losses from the population (i.e., mortality and emigration exceed gains (i.e., recruitment and immigration. Amphibians are thought to exhibit little movement even though local populations often fluctuate dramatically and are likely to go exinct if there is no rescue effect through immigration from nearby populations. Terrestrial salamanders are generally portrayed as amphibians with low migratory activity. Our study uses demographic analysis as a key to unravel whether emigration or mortality is the main cause of "losses" from the population. In particular, we use the analysis to challenge the common belief that terrestrial salamanders show low migratory activity. Results The mark-recapture analysis of adult salamanders showed that monthly survival was high (> 90% without a seasonal pattern. These estimates, however, translate into rather low rates of local annual survival of only ~40% and suggest that emigration was important. The estimated probability of emigration was 49%. Conclusion Our analysis shows that terrestrial salamanders exhibit more migratory activity than commonly thought. This may be due either because the spatial extent of salamander populations is underestimated or because there is a substantial exchange of individuals between populations. Our current results are in line with several other studies that suggest high migratory activity in amphibians. In particular, many amphibian populations may be characterized by high proportions of transients and/or floaters.

  2. Apparent survival of the salamander Salamandra salamandra is low because of high migratory activity.

    Science.gov (United States)

    Schmidt, Benedikt R; Schaub, Michael; Steinfartz, Sebastian

    2007-09-06

    Understanding the demographic processes underlying population dynamics is a central theme in ecology. Populations decline if losses from the population (i.e., mortality and emigration) exceed gains (i.e., recruitment and immigration). Amphibians are thought to exhibit little movement even though local populations often fluctuate dramatically and are likely to go exinct if there is no rescue effect through immigration from nearby populations. Terrestrial salamanders are generally portrayed as amphibians with low migratory activity. Our study uses demographic analysis as a key to unravel whether emigration or mortality is the main cause of "losses" from the population. In particular, we use the analysis to challenge the common belief that terrestrial salamanders show low migratory activity. The mark-recapture analysis of adult salamanders showed that monthly survival was high (> 90%) without a seasonal pattern. These estimates, however, translate into rather low rates of local annual survival of only ~40% and suggest that emigration was important. The estimated probability of emigration was 49%. Our analysis shows that terrestrial salamanders exhibit more migratory activity than commonly thought. This may be due either because the spatial extent of salamander populations is underestimated or because there is a substantial exchange of individuals between populations. Our current results are in line with several other studies that suggest high migratory activity in amphibians. In particular, many amphibian populations may be characterized by high proportions of transients and/or floaters.

  3. Oxidative stress-mediated NFκB phosphorylation upregulates p62/SQSTM1 and promotes retinal pigmented epithelial cell survival through increased autophagy.

    Directory of Open Access Journals (Sweden)

    Chunjuan Song

    Full Text Available p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied the effect of hydrogen peroxide (H2O2-mediated oxidative stress and NFκB signaling on p62 expression in the retinal pigment epithelium (RPE and investigated its role in regulation of autophagy and RPE survival against oxidative damage. Cultured human RPE cell line ARPE-19 and primary human adult and fetal RPE cells were exposed to H2O2-induced oxidative stress. The human apolipoprotein E4 targeted-replacement (APOE4 mouse model of AMD was used to study expression of p62 and other autophagy proteins in the retina. p62, NFκB p65 (total, phosphorylated, nuclear and cytoplasmic and ATG10 expression was assessed by mRNA and protein analyses. Cellular ROS and mitochondrial superoxide were measured by CM-H2DCFDA and MitoSOX staining respectively. Mitochondrial viability was determined using MTT activity. qPCR-array system was used to investigate autophagic genes affected by p62. Nuclear and cytoplasmic levels of NFκB p65 were evaluated after cellular fractionation by Western blotting. We report that p62 is up-regulated in RPE cells under H2O2-induced oxidative stress and promotes autophagic activity. Depletion of endogenous p62 reduces autophagy by downregulation of ATG10 rendering RPE more susceptible to oxidative damage. NFκB p65 phosphorylation at Ser-536 was found to be critical for p62 upregulation in response to oxidative stress. Proteasome inhibition by H2O2 causes p62-NFκB signaling as antioxidant pre-treatment reversed p62 expression and p65 phosphorylation when RPE was challenged by H2O2 but not when by Lactacystin. p62 protein but not RNA levels are elevated in APOE4-HFC AMD mouse model, suggesting reduction of autophagic flux in disease conditions. Our findings suggest that p62 is necessary for RPE cytoprotection

  4. Activation of nuclear factor-kappa B via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons

    NARCIS (Netherlands)

    Fernyhough, P; Smith, DR; Schapansky, J; Van Der Ploeg, R; Gardiner, NJ; Tweed, CW; Kontos, A; Freeman, L; Purves-Tyson, TD; Glazner, GW

    2005-01-01

    Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and cultured embryonic DRG neurons require exogenous neurotrophic factors that activate the neuroprotective transcription factor nuclear factor-kappaB(NF-kappaB) for survival. In contrast, adult DRG neurons survive

  5. The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

    LENUS (Irish Health Repository)

    Sernbo, Sandra

    2011-09-24

    Abstract Background The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking. Methods SOX11 expression and clinicopathological data was compared using χ2 test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation. Results SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5\\'-Aza-2\\'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11. Conclusions SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.

  6. The Role of Physical Educators in Helping Classroom Teachers to Promote Physical Activity

    Science.gov (United States)

    Russ, Laura

    2015-01-01

    Elementary classroom teachers are an increasingly important constituency in school-based physical activity promotion. This article situates the need for classroom teacher physical-activity promotion at the intersection of what we know about teacher actions, what informs those actions, and what recent research has uncovered. Recommendations are…

  7. Promoting Physical Activity in Secondary Schools: Growing Expectations, "Same Old" Issues?

    Science.gov (United States)

    Cale, Lorraine; Harris, Jo; Duncombe, Rebecca

    2016-01-01

    There are growing expectations on schools to promote health and physical activity and helping schools to effectively do so is considered a priority. This paper reports on selected findings from a research project that was concerned with supporting secondary schools in the effective promotion of physical activity and establishing their needs in…

  8. Activating Public Space: How to Promote Physical Activity in Urban Environment

    Science.gov (United States)

    Kostrzewska, Małgorzata

    2017-10-01

    Physical activity is an essential component of a healthy lifestyle. The quality and equipment of urban public space plays an important role in promoting physical activity among people (residents, tourists). In order for recreation and sports activities to be undertaken willingly, in a safe and comprehensive manner, certain spatial conditions and requirements must be met. The distinctive feature of contemporary large cities is the disappearance of local, neighbourly relations, and the consequent loneliness, alienation, and atomization of the residents. Thus, the design of public spaces should be an expression of the values of social inclusion and integration. A properly designed urban space would encourage people to leave their homes and integrate, also by undertaking different forms of physical activities. This, in turn, can lead to raising the quality of the space, especially in the context of its “familiarization” and “domestication”. The aim of the research was to identify the architectural and urban features of the public spaces of contemporary cities that can contribute to the promotion of physical activity. The paper presents the research results and the case studies of such spatial solutions and examples of good practices, which invite residents to undertake different forms of physical activities in public spaces. The issue of the integrating, inclusionary, and social function of physical recreation and sport is discussed as well, and so are the possibilities of translating these values into physical characteristics of an urban space. The main conclusions are that taking into account the diverse needs of different social groups, participation in the design and construction process, aesthetic and interesting design, vicinity of the residence, open access for all age groups and the disabled would be the most important spatial determinants of a properly designed, physically activating public space. Strategies of planning the sports and recreation

  9. Salmonella Survival Kinetics on Pecans, Hazelnuts, and Pine Nuts at Various Water Activities and Temperatures.

    Science.gov (United States)

    Santillana Farakos, Sofia; Pouillot, Régis; Keller, Susanne E

    2017-04-17

    The impact of temperature, water activity (a w ), and nut composition on Salmonella survival on tree nuts has not been thoroughly examined. The aim of this study was to determine the effect of temperature, a w , and nut composition on the survival of Salmonella on tree nuts and develop predictive models. Pecans, hazelnuts, and pine nuts were chosen based on differences in their typical fat content. Nuts were inoculated with a cocktail of five Salmonella serotypes (11 log CFU/mL) and then were dried and stored at 4, 10, and 25°C at 0.41 ± 0.06 and 0.60 ± 0.05 a w for 1 year. Ten-gram quantities were removed at different intervals up to 364 days to test for surviving Salmonella populations (plating on selective and nonselective media) and a w . Experiments were carried out in triplicate. Salmonella populations were relatively stable over a year at 4 and 10°C at both a w levels with Salmonella survival at 4 and 10°C was a log-linear model with a D-value for each tree nut and a w combination. Significant declines in Salmonella levels were observed at 25°C, where the best fit was a Weibull model with a fixed ρ for all tree nuts (ρ = 0.86), a δ value for each tree nut and a w combination, and a random factor to account for variability among replicates. The time for the first log reduction at 25°C and 0.37 ± 0.009 a w was estimated at 24 ± 2 weeks for hazelnuts, 34 ± 3 weeks for pecans, and 52 ± 7 weeks for pine nuts. At the same temperature, but with 0.54 ± 0.009 a w , the mean estimated time for the first log reduction decreased to 9 ± 1 weeks for hazelnuts, 10 ± 1 weeks for pecans, and 16 ± 1 weeks for pine nuts. Tree nut, a w , and temperature were shown to have a statistically significant effect on survival (P survival was observed. The results of this study can be used to predict changes in Salmonella levels on pecans, hazelnuts, and pine nuts after storage at the different temperatures and a w values.

  10. Diabetes mellitus: preliminary health-promotion activity based on ...

    African Journals Online (AJOL)

    Objectives: To investigate the effects of a service-learning-based health promotion elective in influencing knowledge of diabetes mellitus (DM) and ways to prevent it. Method: A computer-based quiz, an information poster, interactive models and a take-home information leaflet on DM were developed as part of an exhibit ...

  11. Hair Growth Promotant Activity of Petroleum Ether Root Extract of ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of Glycyrrhiza glabra root extract on hair growth in female Wistar rats. Methods: Female Wistar rats were used for the hair growth promotion studies. They were divided into three groups(n = 6) and their dorsal skin was completely denuded to completely remove hair. Paraffin oil (control), 2 ...

  12. Viability in delivering oral health promotion activities within the ...

    African Journals Online (AJOL)

    Interventions could include promotion of a healthy diet, oral health education, tobacco cessation, safe water and sanitation, water fluoridation, tooth brushing and fluoride rinsing programmes.[2]. Schools in South Africa (SA) are graded according to quintiles, which range from quintile 1 (the poorest) to quintile 5 (least poor).

  13. Differential survival of leukocyte subsets mediated by synovial, bone marrow, and skin fibroblasts: site-specific versus activation-dependent survival of T cells and neutrophils.

    Science.gov (United States)

    Filer, Andrew; Parsonage, Greg; Smith, Emily; Osborne, Chloe; Thomas, Andrew M C; Curnow, S John; Rainger, G Ed; Raza, Karim; Nash, Gerard B; Lord, Janet; Salmon, Mike; Buckley, Christopher D

    2006-07-01

    Synovial fibroblasts share a number of phenotype markers with fibroblasts derived from bone marrow. In this study we investigated the role of matched fibroblasts obtained from 3 different sources (bone marrow, synovium, and skin) to test the hypothesis that synovial fibroblasts share similarities with bone marrow-derived fibroblasts in terms of their ability to support survival of T cells and neutrophils. Matched synovial, bone marrow, and skin fibroblasts were established from 8 different patients with rheumatoid arthritis who were undergoing knee or hip surgery. Resting or activated fibroblasts were cocultured with either CD4 T cells or neutrophils, and the degree of leukocyte survival, apoptosis, and proliferation were measured. Fibroblasts derived from all 3 sites supported increased survival of CD4 T cells, mediated principally by interferon-beta. However, synovial and bone marrow fibroblasts shared an enhanced site-specific ability to maintain CD4 T cell survival in the absence of proliferation, an effect that was independent of fibroblast activation or proliferation but required direct T cell-fibroblast cell contact. In contrast, fibroblast-mediated neutrophil survival was less efficient, being independent of the site of origin of the fibroblast but dependent on prior fibroblast activation, and mediated solely by soluble factors, principally granulocyte-macrophage colony-stimulating factor. These results suggest an important functional role for fibroblasts in the differential accumulation of leukocyte subsets in a variety of tissue microenvironments. The findings also provide a potential explanation for site-specific differences in the pattern of T cell and neutrophil accumulation observed in chronic inflammatory diseases.

  14. Activated Akt and Erk expression and survival after surgery in pancreatic carcinoma.

    Science.gov (United States)

    Chadha, Krishdeep S; Khoury, Thaer; Yu, Jihnhee; Black, Jennifer D; Gibbs, John F; Kuvshinoff, Boris W; Tan, Dongfeng; Brattain, Michael G; Javle, Milind M

    2006-07-01

    Long-term survival of surgically resectable pancreatic cancer patients is uncommon. The epidermal growth factor receptor (EGFR) and the phosphoinositol-3-kinase pathways are often activated in pancreatic cancer, and an understanding of their role in resected cases may help refine adjuvant therapy. We investigated the expression of EGFR, Erk, Akt, and their phosphoforms (p-) in pancreatectomy specimens and correlated these with survival. Thirty-nine consecutive surgically resected pancreatic adenocarcinoma cases were included. Immunohistochemical staining of paraffin-embedded blocks was performed by using monoclonal antibodies against EGFR, Erk, p-Erk, Akt, and p-Akt. A standard immunoperoxidase technique was used to detect the avidin-biotin peroxidase complex. Immunostaining was visually scored with the histoscore method by two surgical pathologists. Patient characteristics were as follows: 17 men and 22 women; median age, 66 years; and American Joint Committee on Cancer stage I, 5 patients; stage II, 4 patients; stage III, 27 patients; and stage IV, 3 patients. The tumor was World Health Organization grade 1 in 4, grade 2 in 17, and grade 3 in 18 cases. Adjuvant therapies were chemotherapy (n = 6), radiotherapy (n = 1), and chemoradiotherapy (n = 17). Immunohistochemistry revealed positive expression of EGFR in 30.8%, Erk in 92.3%, p-Erk in 45.9%, Akt in 71.8%, and p-Akt in 20.5% of cases. On univariate analyses, tumor grade (P = .0098), p-Akt (P = .0003), and p-Erk (P = .0052) expression correlated with survival. On multivariate analyses, age (P = .0002; hazard ratio [HR], 1.8), grade (P = .00318; HR, 3.0), Akt (P = .0433; HR, .4), p-Akt (P = .0002; HR, .2), and p-Erk (P = .0003; HR, 3.5) expression correlated significantly with survival. p-Erk and p-Akt expression may have prognostic and therapeutic implications in pancreatic cancer.

  15. Integration of ALV intoCTDSPLandCTDSPL2genes in B-cell lymphomas promotes cell immortalization, migration and survival.

    Science.gov (United States)

    Winans, Shelby; Flynn, Alyssa; Malhotra, Sanandan; Balagopal, Vidya; Beemon, Karen L

    2017-08-22

    Avian leukosis virus induces tumors in chickens by integrating into the genome and altering expression of nearby genes. Thus, ALV can be used as an insertional mutagenesis tool to identify novel genes involved in tumorigenesis. Deep sequencing analysis of viral integration sites has identified CTDSPL and CTDSPL2 as common integration sites in ALV-induced B-cell lymphomas, suggesting a potential role in driving oncogenesis. We show that in tumors with integrations in these genes, the viral promoter is driving the expression of a truncated fusion transcript. Overexpression in cultured chick embryo fibroblasts reveals that CTDSPL and CTDSPL2 have oncogenic properties, including promoting cell migration. We also show that CTDSPL2 has a previously uncharacterized role in protecting cells from apoptosis induced by oxidative stress. Further, the truncated viral fusion transcripts of both CTDSPL and CTDSPL2 promote immortalization in primary cell culture.

  16. Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity.

    Science.gov (United States)

    Zhang, Cunzhen; Liu, Fenghua; Chen, Haiyang; Li, Nan; Luo, Zaili; Guo, Weixing; Huang, Dandan; Tang, Shanhua; Wang, Honggang; Cheng, Shuqun; Li, Zhong; Wang, Hongyang

    2017-01-01

    Tumor metastasis is the process by which tumor cells disseminate from tumors and enter nearby and distant microenvironments for new colonization. Bif-1 (BAX-interacting factor 1), which has a BAR domain and an SH3 domain, has been reported to be involved in cell growth, apoptosis and autophagy. However, the influence of Bif-1 on metastasis has been less studied. To understand the role of Bif-1 in metastasis, we studied the expression levels of Bif-1 in human HCC specimens using immunohistochemistry, a tissue microarray and quantitative PCR. The function of Bif-1 was assessed in migration and translocation assays and the pulmonary metastatic animal model. The relationship between Bif-1 and the Rho family was determined using immunoblot analyses and chromatin immunoprecipitation. The results showed that the expression of Bif-1 was higher in hepatocellular carcinoma (HCC) than matched adjacent non-tumor liver tissues. Increased Bif-1 expression was associated with tumor size and the intercellular spread and metastasis of HCC. Analysis of the relationship between Bif-1 expression and patients' clinical characteristics revealed that patients with higher levels of Bif-1 had shorter disease-free and overall survival rates. Knockdown of Bif-1 with RNAi suppressed the migration of HCC cells and pulmonary metastasis and decreased the expression of Cdc42, a member of the Rho family. Bif-1 localized to the cytosol and nucleus and interacted with the promoter transcription region of Cdc42, which may regulate Cdc42 expression. Our results demonstrate a novel role of Bif-1 in HCC, in which Bif-1 promotes cell metastasis by regulating Cdc42 expression and activity.

  17. Survival Potential and Photosynthetic Activity of Lichens Under Mars-Like Conditions: A Laboratory Study

    Science.gov (United States)

    de Vera, Jean-Pierre; Möhlmann, Diedrich; Butina, Frederike; Lorek, Andreas; Wernecke, Roland; Ott, Sieglinde

    2010-03-01

    Lichens were repetitively exposed over 22 days to thermophysical Mars-like conditions at low-and mid-latitudes. The simulated parameters and the experimental setup are described. Natural samples of the lichen Xanthoria elegans were used to investigate their ability to survive the applied Mars-like conditions. The effects of atmospheric pressure, CO2 concentration, low temperature, water availability, and light on Mars were also studied. The results of these experiments indicate that - no significant decrease in the vitality of the lichen occurred after exposure to simulated martian conditions, which was demonstrated by confocal laser scanning microscopy analysis, and - a 95% CO2 atmosphere with 100% humidity, low pressure (partial pressure of CO2 was 600 Pa), and low temperature has a balancing effect on photosynthetic activity as a function of temperature. This means a starting low photosynthetic activity at high CO2 concentrations with Earth-like pressure has a reduction of 60%. But, if the simulated atmospheric pressure is reduced to Mars-like conditions with the maintenance of the same Mars-like 95% CO2 concentration, the photosynthetic activity increases and again reaches similar values as those exhibited under terrestrial atmospheric pressure and concentration. Based on these results, we presume that, in any region on Mars where liquid water might be available, even for short periods of time, a eukaryotic symbiotic organism would have the ability to survive, at least over weeks, and to temporarily photosynthesize.

  18. Mediation analysis of the relationship between institutional research activity and patient survival

    DEFF Research Database (Denmark)

    Rochon, Justine; du Bois, Andreas; Lange, Theis

    2014-01-01

    BACKGROUND: Recent studies have suggested that patients treated in research-active institutions have better outcomes than patients treated in research-inactive institutions. However, little attention has been paid to explaining such effects, probably because techniques for mediation analysis exis......, we have shown that the research activity of a hospital contributes to superior patient survival through better use of surgery and chemotherapy. This methodology may be applied to analyze direct and indirect natural effects for almost any combination of variable types....... the 133 patients treated in non-trial hospitals. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.58 (95% confidence interval: 0.42 to 0.79). This effect was decomposed into a direct effect of research activity of 0.67 and two indirect effects of 0.93 each...

  19. CmeABC Multidrug Efflux Pump Contributes to Antibiotic Resistance and Promotes Campylobacter jejuni Survival and Multiplication in Acanthamoeba polyphaga

    Science.gov (United States)

    Vieira, Ana; Ramesh, Amritha; Seddon, Alan M.

    2017-01-01

    ABSTRACT Campylobacter jejuni is a foodborne pathogen that is recognized as the leading cause of human bacterial gastroenteritis. The widespread use of antibiotics in medicine and in animal husbandry has led to an increased incidence of antibiotic resistance in Campylobacter. In addition to a role in multidrug resistance (MDR), the Campylobacter CmeABC resistance-nodulation-division (RND)-type efflux pump may be involved in virulence. As a vehicle for pathogenic microorganisms, the protozoan Acanthamoeba is a good model for investigations of bacterial survival in the environment and the molecular mechanisms of pathogenicity. The interaction between C. jejuni 81-176 and Acanthamoeba polyphaga was investigated in this study by using a modified gentamicin protection assay. In addition, a possible role for the CmeABC MDR pump in this interaction was explored. Here we report that this MDR pump is beneficial for the intracellular survival and multiplication of C. jejuni in A. polyphaga but is dispensable for biofilm formation and motility. IMPORTANCE The endosymbiotic relationship between amoebae and microbial pathogens may contribute to persistence and spreading of the latter in the environment, which has significant implications for human health. In this study, we found that Campylobacter jejuni was able to survive and to multiply inside Acanthamoeba polyphaga; since these microorganisms can coexist in the same environment (e.g., on poultry farms), the latter may increase the risk of infection with Campylobacter. Our data suggest that, in addition to its role in antibiotic resistance, the CmeABC MDR efflux pump plays a role in bacterial survival within amoebae. Furthermore, we demonstrated synergistic effects of the CmeABC MDR efflux pump and TetO on bacterial resistance to tetracycline. Due to its role in both the antibiotic resistance and the virulence of C. jejuni, the CmeABC MDR efflux pump could be considered a good target for the development of antibacterial

  20. CmeABC multidrug efflux pump contributes to antibiotic resistance and promotes Campylobacter jejuni survival and multiplication in Acanthamoeba polyphaga.

    Science.gov (United States)

    Vieira, Ana; Ramesh, Amritha; Seddon, Alan M; Karlyshev, Andrey V

    2017-09-15

    Campylobacter jejuni is a foodborne pathogen recognized as the leading cause of human bacterial gastroenteritis. The wide use of antibiotics in medicine and in animal husbandry has led to an increased incidence of antibiotic resistance in Campylobacter In addition to a role in multidrug resistance, the Campylobacter CmeABC RND-type efflux pump, which is associated with multidrug resistance (MDR), may also be involved in virulence. As a vehicle of pathogenic microorganisms, the protozoan Acanthamoeba is a good model for the investigation of bacterial survival in the environment and molecular mechanisms of pathogenicity. The interaction between C. jejuni 81-176 and A. polyphaga was investigated in this study by using a modified gentamicin protection assay. In addition, a possible role for the CmeABC MDR pump in this interaction was explored. Here we report that this MDR pump is beneficial for the intracellular survival and multiplication of C. jejuni in A. polyphaga, but is dispensable for biofilm formation and motility.Importance The endosymbiotic relationship between amoebae and microbial pathogens may contribute to persistence and spreading of the latter in the environment, which has significant implications to human health. In this study we found that Campylobacter jejuni was able to survive and multiply inside Acanthamoeba. polyphaga Since these microorganisms can co-exist in the same environment (e.g. in poultry farms), the latter may increase the risk of infection with Campylobacter Our data suggests that, in addition to its role in antibiotic resistance, the CmeABC MDR efflux pump also plays a role in bacterial survival within amoebae. Furthermore, we demonstrated a synergistic effect of the CmeABC MDR efflux pump and TetO on bacterial resistance to tetracycline. Due to its role both in antibiotic resistance and virulence of C. jejuni, the CmeABC MDR efflux pump could be considered as a good target for the development of antibacterial drugs against this

  1. Berberine promotes glucose consumption independently of AMP-activated protein kinase activation.

    Directory of Open Access Journals (Sweden)

    Miao Xu

    Full Text Available Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK pathway has been proposed as mechanism for berberine's action. This study aimed to examine whether AMPK activation was necessary for berberine's glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1 inhibition of AMPK activity by Compound C, (2 suppression of AMPKα expression by siRNA, and (3 blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation.

  2. An Enriched Environment Promotes Shelter-Seeking Behaviour and Survival of Hatchery-Produced Juvenile European Lobster (Homarus gammarus.

    Directory of Open Access Journals (Sweden)

    Stian Aspaas

    Full Text Available The high loss of newly released hatchery-reared European lobster (Homarus gammarus juveniles for stock enhancement is believed to be the result of maladaptive anti-predator behaviour connected to deprived stimuli in the hatchery environment. Our objective was to learn if an enriched hatchery environment enhances shelter-seeking behaviour and survival. In the "naïve" treatment, the juveniles were raised in single compartments without substrate and shelter whereas juveniles in the "exposed" treatment experienced substrate, shelter and interactions with conspecifics. Three experiments with increasing complexity were conducted. Few differences in shelter-seeking behaviour were found between treatments when one naïve or one exposed juvenile were observed alone. When observing interactions between one naïve and one exposed juvenile competing for shelter, naïve juveniles more often initiated the first aggressive encounter. The third experiment was set up to simulate a release for stock enhancement. Naïve and exposed juveniles were introduced to a semi-natural environment including substrate, a limited number of shelters and interactions with conspecifics. Shelter occupancy was recorded three times during a period of 35 days. Exposed juveniles occupied more shelters, grew larger and had higher survival compared with naïve juveniles. Our results demonstrate that experience of environmental complexity and social interactions increase shelter-seeking ability and survival in hatchery reared lobster juveniles.

  3. An Enriched Environment Promotes Shelter-Seeking Behaviour and Survival of Hatchery-Produced Juvenile European Lobster (Homarus gammarus).

    Science.gov (United States)

    Aspaas, Stian; Grefsrud, Ellen Sofie; Fernö, Anders; Jensen, Knut Helge; Trengereid, Henrik; Agnalt, Ann-Lisbeth

    2016-01-01

    The high loss of newly released hatchery-reared European lobster (Homarus gammarus) juveniles for stock enhancement is believed to be the result of maladaptive anti-predator behaviour connected to deprived stimuli in the hatchery environment. Our objective was to learn if an enriched hatchery environment enhances shelter-seeking behaviour and survival. In the "naïve" treatment, the juveniles were raised in single compartments without substrate and shelter whereas juveniles in the "exposed" treatment experienced substrate, shelter and interactions with conspecifics. Three experiments with increasing complexity were conducted. Few differences in shelter-seeking behaviour were found between treatments when one naïve or one exposed juvenile were observed alone. When observing interactions between one naïve and one exposed juvenile competing for shelter, naïve juveniles more often initiated the first aggressive encounter. The third experiment was set up to simulate a release for stock enhancement. Naïve and exposed juveniles were introduced to a semi-natural environment including substrate, a limited number of shelters and interactions with conspecifics. Shelter occupancy was recorded three times during a period of 35 days. Exposed juveniles occupied more shelters, grew larger and had higher survival compared with naïve juveniles. Our results demonstrate that experience of environmental complexity and social interactions increase shelter-seeking ability and survival in hatchery reared lobster juveniles.

  4. IL-23 activates innate lymphoid cells to promote neonatal intestinal pathology.

    Science.gov (United States)

    Chen, Lili; He, Zhengxiang; Slinger, Erik; Bongers, Gerold; Lapenda, Taciana L S; Pacer, Michelle E; Jiao, Jingjing; Beltrao, Monique F; Soto, Alan J; Harpaz, Noam; Gordon, Ronald E; Ochando, Jordi C; Oukka, Mohamed; Iuga, Alina Cornelia; Chensue, Stephen W; Blander, Julie Magarian; Furtado, Glaucia C; Lira, Sergio A

    2015-03-01

    Interleukin-23 (IL-23) responsive group 3 innate lymphoid cells (ILC3s) have been implicated in immune homeostasis and pathogenesis in the adult, but little is known about their roles in the newborn. Here we show that IL-23 promotes conversion of embryonic intestinal Lin(-)IL-23R(+)Thy1(+) cells into IL-22-producing Thy1(+)Sca-1(hi) ILC3s in vitro. Gut-specific expression of IL-23 also activated and expanded Thy1(+)Sca-1(hi) ILC3s, which produced IL-22, IL-17, interferon gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) and were distinct from canonical CD4(+) lymphoid tissue inducer (LTi) cells. These ILC3s accumulated under the epithelium in intercellular adhesion molecule (ICAM)-1-positive cell aggregates together with neutrophils that disrupted the epithelium, leading to the formation of discrete intestinal erosions, bleeding, and neonatal death. Genetic and antibody depletion of ILC3s rescued the mice from neonatal death. Antibiotic treatment of pregnant mothers and offspring prolonged survival of IL-23 transgenic mice, suggesting a role for the commensal flora on ILC3-induced pathogenesis. Our results reveal a novel role for the IL-23-ILC3s axis in the pathogenesis of neonatal intestinal inflammation.

  5. Ameloginins promote an alternatively activated macrophage phenotype in vitro

    DEFF Research Database (Denmark)

    Almqvist, S; Werthen, M; Lyngstadas, SP

    2011-01-01

    Amelogenins are extracellular matrix proteins used for the topical treatment of chronically inflamed tissues. The influence of amelogenins on human monocyte-derived macrophages was studied by measuring the concentrations of cytokines in culture supernatants. The interactions of cells and protein ...... increased the macrophage release of key cell mediators involved in tissue repair. The effect was independent of phagocytosis, implying a receptor-mediated signal. The markedly increased levels of AMAC-1 suggest that amelogenins promote a reparative macrophage phenotype....

  6. Chinese tobacco industry promotional activity on the microblog Weibo.

    Science.gov (United States)

    Wang, Fan; Zheng, Pinpin; Yang, Dongyun; Freeman, Becky; Fu, Hua; Chapman, Simon

    2014-01-01

    Although China ratified the WHO Framework Convention on Tobacco Control [FCTC] in 2005, the partial ban on tobacco advertising does not cover the internet. Weibo is one of the most important social media channels in China, using a format similar to its global counterpart, Twitter. The Weibo homepage is a platform to present products, brands and corporate culture. There is great potential for the tobacco industry to exploit Weibo to promote products. Seven tobacco industry Weibo accounts that each had more than 5000 fans were selected to examine the content of Weibos established by tobacco companies or their advertising agents. Of the 12073 posts found on the seven accounts, 92.3% (11143) could be classified into six main themes: traditional culture, popular culture, social and business affairs, advertisement, public relations and tobacco culture. Posts under the theme of popular culture accounted for about half of total posts (49%), followed by 'advertisement' and 'tobacco culture' (both at 12%), 'traditional culture' and 'public relations' (both at 11%), and finally 'social and business affairs' (5%). 33% of posts included the words 'cigarette' or 'smoking' and 53% of posts included the tobacco brand name, indicating that tobacco companies carefully construct the topic and content of posts. Weibo is an important new online marketing tool for the Chinese tobacco industry. Tobacco industry use of Weibo to promote brands and normalize smoking subverts China's ratification of the WHO FCTC. Policy to control tobacco promotion needs reforming to address this widespread circumvention of China's tobacco advertising ban.

  7. Efficacy of breast cancer appeals for promoting physical activity.

    Science.gov (United States)

    Jalleh, Geoffrey; Donovan, Robert J; Slevin, Terry; Lin, Chad Y

    2009-01-01

    We investigated the efficacy of breast cancer prevention messages in increasing intentions to be more active. We randomly assigned 200 females aged 30-60 years to a breast cancer and physical activity message or a cardiovascular disease and physical activity message. The breast cancer message was more believable and slightly more motivating to increase physical activity than the cardiovascular disease message, and 72% of respondents in the breast cancer condition increased their intention to increase their physical activity. The benefit of reducing the risk of breast cancer can be used to motivate increased physical activity in women.

  8. Implications of subzero metabolic activity on long-term microbial survival in terrestrial and extraterrestrial permafrost.

    Science.gov (United States)

    Amato, Pierre; Doyle, Shawn M; Battista, John R; Christner, Brent C

    2010-10-01

    The survival of microorganisms over extended time frames in frozen subsurface environments may be limited by chemical (i.e., via hydrolysis and oxidation) and ionizing radiation-induced damage to chromosomal DNA. In an effort to improve estimates for the survival of bacteria in icy terrestrial and extraterrestrial environments, we determined rates of macromolecular synthesis at temperatures down to -15°C in bacteria isolated from Siberian permafrost (Psychrobacter cryohalolentis K5 and P. arcticus 273-4) and the sensitivity of P. cryohalolentis to ionizing radiation. Based on experiments conducted over ≈400 days at -15°C, the rates of protein and DNA synthesis in P. cryohalolentis were <1 to 16 proteins cell(-1) d(-1) and 83 to 150 base pairs (bp) cell(-1) d(-1), respectively; P. arcticus synthesized DNA at rates of 20 to 1625 bp cell(-1) d(-1) at -15°C under the conditions tested. The dose of ionizing radiation at which 37% of the cells survive (D(37)) of frozen suspensions of P. cryohalolentis was 136 Gy, which was ∼2-fold higher (71 Gy) than identical samples exposed as liquid suspensions. Laboratory measurements of [(3)H]thymidine incorporation demonstrate the physiological potential for DNA metabolism at -15°C and suggest a sufficient activity is possible to offset chromosomal damage incurred in near-subsurface terrestrial and martian permafrost. Thus, our data imply that the longevity of microorganisms actively metabolizing within permafrost environments is not constrained by chromosomal DNA damage resulting from ionizing radiation or entropic degradation over geological time.

  9. The physical therapist's role in physical activity promotion

    NARCIS (Netherlands)

    Verhagen, E.; Engbers, L.

    2009-01-01

    Clinicians are increasingly confronted with the diseases of physical inactivity. Paradoxically, a promising strategy to motivate sedentary individuals to become more active is the opportunity to encourage physical activity related behavioural change when individuals encounter health professionals.

  10. Active Commuting to School as a Source of Health Promotion ...

    African Journals Online (AJOL)

    The students were predominantly passive commuters and their commuting pattern was linked to sociodemographic characteristics while barriers and facilitators of active commuting included family, societal, environmental and school factors. KEYWORDS: adolescents health, attitudes, physical activity, sociodemographic ...

  11. Survival of Salmonella in Cookie and Cracker Sandwiches Containing Inoculated, Low-Water Activity Fillings.

    Science.gov (United States)

    Beuchat, Larry R; Mann, David A

    2015-10-01

    A study was done to determine the rate of inactivation of Salmonella in cookie and cracker snack sandwiches. Two cookie bases (chocolate and vanilla) and cheese crackers, along with high-sugar chocolate and peanut butter-based crème cookie fillings and peanut butter- and cheese-based cracker fillings, were obtained from commercial sources. Fillings and sandwiches containing fillings that had been dry- or wet-inoculated with Salmonella were stored at 25°C for 1, 6, 21, 35, 70, 112, and 182 days (6 months). At initial populations of 3.4 and 3.6 log CFU/g of cookie sandwiches containing chocolate crème and peanut butter crème fillings, respectively, Salmonella survived for at least 182 days; initially at 0.36 log CFU/g, the pathogen survived for at least 35 and 70 days. Initially at 2.9 and 3.4 log CFU/g of cracker sandwiches containing peanut butter- and cheese-based fillings, respectively, Salmonella survived for at least 182 and 112 days; initially at 0.53 log CFU/g, the pathogen survived for at least 6 and 35 days. Inactivation of Salmonella was more rapid in wet-inoculated peanut butter crème cookie filling than in dry-inoculated filling but was less affected by type of inoculum in peanut butter-based cracker filling. Chocolate cookie base (water activity [aw] 0.39) and chocolate crème filling (aw 0.30) components of sandwiches equilibrated to aw 0.38 within 15 days at 25°C; vanilla cookie base (aw 0.21) and peanut butter-based crème filling (aw 0.27) equilibrated to aw 0.24 between 50 and 80 days. Cheese cracker (aw 0.14) and peanut butter-based filling (aw 0.31) or cheese-based filling (aw 0.33) components of sandwiches equilibrated to aw 0.33 in 80 days. The ability of Salmonella to survive for at least 182 days in fillings of cookie and cracker sandwiches demonstrates a need to assure that filling ingredients do not contain the pathogen and that contamination does not occur during manufacture.

  12. International Approaches to Whole-of-School Physical Activity Promotion

    Science.gov (United States)

    McMullen, Jaimie; Ní Chróinín, Déirdre; Tammelin, Tuija; Pogorzelska, Malgorzata; van der Mars, Hans

    2015-01-01

    Increasing physical activity opportunities in schools has emerged as a global priority among school-aged youth. As a result, many countries have designed and implemented whole-of-school physical activity initiatives that seek to increase physical activity opportunities that are available to school-aged children before, during, and after school.…

  13. Promoting Physical Activity: Addressing Barriers and Moving Forward

    Science.gov (United States)

    Beighle, Aaron; Morrow, James R.

    2014-01-01

    The barriers that keep individuals from adopting and maintaining active lifestyles are very complex. Strategies for overcoming these barriers and to incentivize and assist inactive individuals to benefit from physical activity are necessary. In addition, it is important to examine the impact of public policy on active living. As youth physical…

  14. Promoting physical activity in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Berg, Machteld Heleen van den

    2007-01-01

    The aim of the thesis was to study: 1. The engagement of patients with RA in various forms of physical activity and their preferences regarding the delivery of physical activity interventions; 2. The evidence regarding the effectiveness of physical activity interventions delivered by means of the

  15. School-Based Health Promotion Initiative Increases Children's Physical Activity

    Science.gov (United States)

    Cluss, Patricia; Lorigan, Devin; Kinsky, Suzanne; Nikolajski, Cara; McDermott, Anne; Bhat, Kiran B.

    2016-01-01

    Background: Childhood obesity increases health risk, and modest physical activity can impact that risk. Schools have an opportunity to help children become more active. Purpose: This study implemented a program offering extra school-day activity opportunities in a rural school district where 37% of students were obese or overweight in 2005 and…

  16. Promoting physical activity: A low cost intervention programme for ...

    African Journals Online (AJOL)

    Physical activity guidelines recommend that children accumulate at least 60 minutes of moderate-to-vigorous physical activity (MVPA) daily. In South Africa, children from historically black communities and schools, previously disadvantaged by apartheid, have limited physical activity opportunities due to the marginalization ...

  17. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice.

    Science.gov (United States)

    Hong, Zhen-Yi; Yu, Shuang-Shuang; Wang, Zhi-Jun; Zhu, Yi-Zhun

    2015-08-07

    SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson's disease and Alzheimer's disease (AD). In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1) double-transgenic mice without affecting amyloid-β (Aβ) burden. In addition, decreases in cAMP-response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA) inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  18. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice

    Directory of Open Access Journals (Sweden)

    Zhen-Yi Hong

    2015-08-01

    Full Text Available SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson’s disease and Alzheimer’s disease (AD. In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1 double-transgenic mice without affecting amyloid-β (Aβ burden. In addition, decreases in cAMP-response element-binding protein (CREB phosphorylation, brain-derived neurotrophic factor (BDNF and tropomyosin-related kinase B (TrkB phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.

  19. Streptolysin O and NAD-Glycohydrolase Prevent Phagolysosome Acidification and Promote Group A Streptococcus Survival in Macrophages

    Science.gov (United States)

    Bastiat-Sempe, Benedicte; Love, John F.; Lomayesva, Natalie

    2014-01-01

    ABSTRACT Group A Streptococcus (GAS, Streptococcus pyogenes) is an ongoing threat to human health as the agent of streptococcal pharyngitis, skin and soft tissue infections, and life-threatening conditions such as necrotizing fasciitis and streptococcal toxic shock syndrome. In animal models of infection, macrophages have been shown to contribute to host defense against GAS infection. However, as GAS can resist killing by macrophages in vitro and induce macrophage cell death, it has been suggested that GAS intracellular survival in macrophages may enable persistent infection. Using isogenic mutants, we now show that the GAS pore-forming toxin streptolysin O (SLO) and its cotoxin NAD-glycohydrolase (NADase) mediate GAS intracellular survival and cytotoxicity for macrophages. Unexpectedly, the two toxins did not inhibit fusion of GAS-containing phagosomes with lysosomes but rather prevented phagolysosome acidification. SLO served two essential functions, poration of the phagolysosomal membrane and translocation of NADase into the macrophage cytosol, both of which were necessary for maximal GAS intracellular survival. Whereas NADase delivery to epithelial cells is mediated by SLO secreted from GAS bound to the cell surface, in macrophages, the source of SLO and NADase is GAS contained within phagolysosomes. We found that transfer of NADase from the phagolysosome to the macrophage cytosol occurs not by simple diffusion through SLO pores but rather by a specific translocation mechanism that requires the N-terminal translocation domain of NADase. These results illuminate the mechanisms through which SLO and NADase enable GAS to defeat macrophage-mediated killing and provide new insight into the virulence of a major human pathogen. PMID:25227466

  20. Promoting responsible conduct in research through "survival skills" workshops: some mentoring is best done in a crowd.

    Science.gov (United States)

    Fischer, B A; Zigmond, M J

    2001-07-01

    For graduate students to succeed as professionals, they must develop a set of general "survival skills". These include writing research articles, making oral presentations, obtaining employment and funding, supervising, and teaching. Traditionally, graduate programs have offered little training in many of these skills. Our educational model provides individuals with formal instruction in each area, including their ethical dimensions. Infusion of research ethics throughout a professional skills curriculum helps to emphasize that responsible conduct is integral to succeeding as a researcher. It also leads to the consideration of ethical dimensions of professional life not covered in traditional ethics courses.

  1. Chinese tobacco industry promotional activity on the microblog Weibo.

    Directory of Open Access Journals (Sweden)

    Fan Wang

    Full Text Available BACKGROUND: Although China ratified the WHO Framework Convention on Tobacco Control [FCTC] in 2005, the partial ban on tobacco advertising does not cover the internet. Weibo is one of the most important social media channels in China, using a format similar to its global counterpart, Twitter. The Weibo homepage is a platform to present products, brands and corporate culture. There is great potential for the tobacco industry to exploit Weibo to promote products. METHODS: Seven tobacco industry Weibo accounts that each had more than 5000 fans were selected to examine the content of Weibos established by tobacco companies or their advertising agents. RESULTS: Of the 12073 posts found on the seven accounts, 92.3% (11143 could be classified into six main themes: traditional culture, popular culture, social and business affairs, advertisement, public relations and tobacco culture. Posts under the theme of popular culture accounted for about half of total posts (49%, followed by 'advertisement' and 'tobacco culture' (both at 12%, 'traditional culture' and 'public relations' (both at 11%, and finally 'social and business affairs' (5%. 33% of posts included the words 'cigarette' or 'smoking' and 53% of posts included the tobacco brand name, indicating that tobacco companies carefully construct the topic and content of posts. CONCLUSIONS: Weibo is an important new online marketing tool for the Chinese tobacco industry. Tobacco industry use of Weibo to promote brands and normalize smoking subverts China's ratification of the WHO FCTC. Policy to control tobacco promotion needs reforming to address this widespread circumvention of China's tobacco advertising ban.

  2. Salidroside, A Natural Antioxidant, Improves β-Cell Survival and Function via Activating AMPK Pathway

    Directory of Open Access Journals (Sweden)

    Linjie Ju

    2017-10-01

    Full Text Available Aim: The enhanced oxidative stress contributes to progression of type 2 diabetes mellitus (T2DM and induces β-cell failure. Salidroside is a natural antioxidant extracted from medicinal food plant Rhodiola rosea. This study was aimed to evaluate protective effects of salidroside on β-cells against diabetes associated oxidative stress.Methods and Results: In diabetic db/db and high-fat diet-induced mice, we found salidroside ameliorated hyperglycemia and relieved oxidative stress. More importantly, salidroside increased β-cell mass and β-cell replication of diabetic mice. Mechanism study in Min6 cells revealed that, under diabetic stimuli, salidroside suppressed reactive oxygen species production and restore mitochondrial membrane potential (ΔΨm via reducing NOX2 expression and inhibiting JNK–caspase 3 apoptotic cascade subsequently to protect β-cell survival. Simultaneously, diabetes associated oxidative stress also activated FOXO1 and triggered nuclear exclusion of PDX1 which resulted in β-cell dysfunction. This deleterious result was reversed by salidroside by activating AMPK-AKT to inhibit FOXO1 and recover PDX1 nuclear localization. The efficacy of salidroside in improving β-cell survival and function was further confirmed in isolated cultured mouse islets. Moreover, the protective effects of salidroside on β-cells against diabetic stimuli can be abolished by an AMPK inhibitor compound C, which indicated functions of salidroside on β-cells were AMPK activation dependent.Conclusion: These results confirmed beneficial metabolic effects of salidroside and identified a novel role for salidroside in preventing β-cell failure via AMPK activation. Our finding highlights the potential value of Rhodiola rosea as a dietary supplement for diabetes control.

  3. Salidroside, A Natural Antioxidant, Improves β-Cell Survival and Function via Activating AMPK Pathway.

    Science.gov (United States)

    Ju, Linjie; Wen, Xiaohua; Wang, Chunjun; Wei, Yingjie; Peng, Yunru; Ding, Yongfang; Feng, Liang; Shu, Luan

    2017-01-01

    Aim: The enhanced oxidative stress contributes to progression of type 2 diabetes mellitus (T2DM) and induces β-cell failure. Salidroside is a natural antioxidant extracted from medicinal food plant Rhodiola rosea. This study was aimed to evaluate protective effects of salidroside on β-cells against diabetes associated oxidative stress. Methods and Results: In diabetic db/db and high-fat diet-induced mice, we found salidroside ameliorated hyperglycemia and relieved oxidative stress. More importantly, salidroside increased β-cell mass and β-cell replication of diabetic mice. Mechanism study in Min6 cells revealed that, under diabetic stimuli, salidroside suppressed reactive oxygen species production and restore mitochondrial membrane potential (ΔΨm) via reducing NOX2 expression and inhibiting JNK-caspase 3 apoptotic cascade subsequently to protect β-cell survival. Simultaneously, diabetes associated oxidative stress also activated FOXO1 and triggered nuclear exclusion of PDX1 which resulted in β-cell dysfunction. This deleterious result was reversed by salidroside by activating AMPK-AKT to inhibit FOXO1 and recover PDX1 nuclear localization. The efficacy of salidroside in improving β-cell survival and function was further confirmed in isolated cultured mouse islets. Moreover, the protective effects of salidroside on β-cells against diabetic stimuli can be abolished by an AMPK inhibitor compound C, which indicated functions of salidroside on β-cells were AMPK activation dependent. Conclusion: These results confirmed beneficial metabolic effects of salidroside and identified a novel role for salidroside in preventing β-cell failure via AMPK activation. Our finding highlights the potential value of Rhodiola rosea as a dietary supplement for diabetes control.

  4. Comparative analysis of the activity of two promoters in insect cells

    African Journals Online (AJOL)

    Jane

    2011-08-15

    Aug 15, 2011 ... expressing prion protein in insect cells. To systematically compare the activity of these two promoters in same backbone, we replaced the OpIE2 promoter with the hr5-. IE1 promoter sequences in the pIB/V5-His vector and named this new vector pIEX-B. A gene encoding β- galactosidase was cloned into ...

  5. A novel baculovirus-derived promoter with high activity in the baculovirus expression system

    Directory of Open Access Journals (Sweden)

    María Martínez-Solís

    2016-06-01

    Full Text Available The baculovirus expression vector system (BEVS has been widely used to produce a large number of recombinant proteins, and is becoming one of the most powerful, robust, and cost-effective systems for the production of eukaryotic proteins. Nevertheless, as in any other protein expression system, it is important to improve the production capabilities of this vector. The orf46 viral gene was identified among the most highly abundant sequences in the transcriptome of Spodoptera exigua larvae infected with its native baculovirus, the S. exigua multiple nucleopolyhedrovirus (SeMNPV. Different sequences upstream of the orf46 gene were cloned, and their promoter activities were tested by the expression of the GFP reporter gene using the Autographa californica nucleopolyhedrovirus (AcMNPV vector system in different insect cell lines (Sf21, Se301, and Hi5 and in larvae from S. exigua and Trichoplusia ni. The strongest promoter activity was defined by a 120 nt sequence upstream of the ATG start codon for the orf46 gene. On average, GFP expression under this new promoter was more than two fold higher than the expression obtained with the standard polyhedrin (polh promoter. Additionally, the orf46 promoter was also tested in combination with the polh promoter, revealing an additive effect over the polh promoter activity. In conclusion, this new characterized promoter represents an excellent alternative to the most commonly used baculovirus promoters for the efficient expression of recombinant proteins using the BEVS.

  6. Measuring the activity of BioBrick promoters using an in vivo reference standard.

    Science.gov (United States)

    Kelly, Jason R; Rubin, Adam J; Davis, Joseph H; Ajo-Franklin, Caroline M; Cumbers, John; Czar, Michael J; de Mora, Kim; Glieberman, Aaron L; Monie, Dileep D; Endy, Drew

    2009-03-20

    The engineering of many-component, synthetic biological systems is being made easier by the development of collections of reusable, standard biological parts. However, the complexity of biology makes it difficult to predict the extent to which such efforts will succeed. As a first practical example, the Registry of Standard Biological Parts started at MIT now maintains and distributes thousands of BioBrick standard biological parts. However, BioBrick parts are only standardized in terms of how individual parts are physically assembled into multi-component systems, and most parts remain uncharacterized. Standardized tools, techniques, and units of measurement are needed to facilitate the characterization and reuse of parts by independent researchers across many laboratories. We found that the absolute activity of BioBrick promoters varies across experimental conditions and measurement instruments. We choose one promoter (BBa_J23101) to serve as an in vivo reference standard for promoter activity. We demonstrated that, by measuring the activity of promoters relative to BBa_J23101, we could reduce variation in reported promoter activity due to differences in test conditions and measurement instruments by approximately 50%. We defined a Relative Promoter Unit (RPU) in order to report promoter characterization data in compatible units and developed a measurement kit so that researchers might more easily adopt RPU as a standard unit for reporting promoter activity. We distributed a set of test promoters to multiple labs and found good agreement in the reported relative activities of promoters so measured. We also characterized the relative activities of a reference collection of BioBrick promoters in order to further support adoption of RPU-based measurement standards. Relative activity measurements based on an in vivoreference standard enables improved measurement of promoter activity given variation in measurement conditions and instruments. These improvements are

  7. Measuring the activity of BioBrick promoters using an in vivo reference standard

    Directory of Open Access Journals (Sweden)

    Kelly Jason R

    2009-03-01

    Full Text Available Abstract Background The engineering of many-component, synthetic biological systems is being made easier by the development of collections of reusable, standard biological parts. However, the complexity of biology makes it difficult to predict the extent to which such efforts will succeed. As a first practical example, the Registry of Standard Biological Parts started at MIT now maintains and distributes thousands of BioBrick™ standard biological parts. However, BioBrick parts are only standardized in terms of how individual parts are physically assembled into multi-component systems, and most parts remain uncharacterized. Standardized tools, techniques, and units of measurement are needed to facilitate the characterization and reuse of parts by independent researchers across many laboratories. Results We found that the absolute activity of BioBrick promoters varies across experimental conditions and measurement instruments. We choose one promoter (BBa_J23101 to serve as an in vivo reference standard for promoter activity. We demonstrated that, by measuring the activity of promoters relative to BBa_J23101, we could reduce variation in reported promoter activity due to differences in test conditions and measurement instruments by ~50%. We defined a Relative Promoter Unit (RPU in order to report promoter characterization data in compatible units and developed a measurement kit so that researchers might more easily adopt RPU as a standard unit for reporting promoter activity. We distributed a set of test promoters to multiple labs and found good agreement in the reported relative activities of promoters so measured. We also characterized the relative activities of a reference collection of BioBrick promoters in order to further support adoption of RPU-based measurement standards. Conclusion Relative activity measurements based on an in vivoreference standard enables improved measurement of promoter activity given variation in measurement

  8. Adolescents' Physical Activity at Recess and Actions to Promote a Physically Active School Day in Four Finnish Schools

    Science.gov (United States)

    Haapala, H. L.; Hirvensalo, M. H.; Laine, K.; Laakso, L.; Hakonen, H.; Lintunen, T.; Tammelin, T. H.

    2014-01-01

    The national Finnish Schools on the Move programme support schools with their individual plans to promote school-based physical activity (PA). We examined the changes in adolescents' recess and overall PA in four lower secondary schools and described the school actions to promote students' PA and the local contact persons' perceptions of the…

  9. Transcriptional Activity of the FUT1 Gene Promoter Region in Pigs

    Directory of Open Access Journals (Sweden)

    Chen Zi

    2013-12-01

    Full Text Available This study aims to provide a theoretical basis on the regulatory mechanism of the α-l,2-fucosyltransferase (FUT1 gene in pigs by analyzing the transcriptional activity of its promoter region. On the basis of the previously obtained promoter sequence, primers upstream and downstream of the gene were designed using the restriction endonucleases KpnI and HindIII respectively, and the recombinant plasmids of the pGL3-promoter were constructed by inserting promoter sequences with partially missing regions. The resultant mutants were observed by transient transfection assay into HEK293 cells, and the transcriptional activity of the promoter region was determined by luciferase activity. The 5'-flanking region of the FUT1 gene (−1150 to +50 bp exhibited promoter activity. The −1150-bp to −849-bp region showed negative regulation of the gene. The recombinant plasmid pGL3-898 showed the strongest luciferase activity, and the activity showed a decreasing trend when the deleted region was increased. Recombinant plasmids were successfully constructed, verified, and the positive and negative regulation areas and core promoter region were detected, providing a deeper insight into the transcriptional regulatory mechanism of the FUT1 gene.

  10. Promoting Physical Activity and Exercise among Children. ERIC Digest.

    Science.gov (United States)

    Summerfield, Liane M.

    This Digest discusses the importance of and ways to foster activity and exercise in children. Following an introduction, the Digest is organized into four sections. The first section deals with the significant health benefits of physical activity, including: reduction in chronic disease risk; lowered risk of colon cancer; increase in bone density;…

  11. Videogames to Promote Physical Activity in Older Adults with Schizophrenia.

    Science.gov (United States)

    Leutwyler, Heather; Hubbard, Erin M; Vinogradov, Sophia; Dowling, Glenna A

    2012-10-01

    Older adults with schizophrenia need physical activity interventions to improve their physical health. The purpose of this report is to describe the preliminary acceptability of a videogame-based physical activity program using the Kinect™ for Xbox 360 game system (Microsoft, Redmond, WA) in older adults with schizophrenia.

  12. Green care farms promote activity among elderly people with dementia

    NARCIS (Netherlands)

    Bruin, de S.R.; Oosting, S.J.; Kuin, Y.; Hoefnagels, E.C.M.; Blauw, Y.H.; Groot, de C.P.G.M.; Schols, J.M.G.A.

    2009-01-01

    In the Netherlands, an increasing number of green care farms are providing day care to community-dwelling elderly people with dementia. Currently, it is unknown whether activities, activity participation, and facility use of elderly people with dementia at green care farms differ from those at

  13. Promoting Healthy Lifestyle Behaviors: The Heart Smart Discussion Activity

    Science.gov (United States)

    McCalla, Judith R.; Juarez, Cheryl L.; Williams, Lucia E.; Brown, Judy; Chipungu, Katie; Saab, Patrice G.

    2012-01-01

    The health habits of high school students affect not only their current health but also their future risk for obesity and cardiovascular disease. The "Heart Smart Discussion Activity" was developed to provide information about heart health, good nutrition, physical activity, and stress management. It encourages students to discuss…

  14. Promoting Physical Activity among International Students in Higher Education: A Peer-Education Approach

    Science.gov (United States)

    Yan, Zi; Cardinal, Bradley J.

    2013-01-01

    International students have become an important and growing group in U.S. higher education. Although many universities offer various types of support to international students, little attention is given to preventive health services or health promotion efforts, such as the promotion of physical activity. This article outlines a theory-based…

  15. Collegewide Promotion of E-Learning/Active Learning and Faculty Development

    Science.gov (United States)

    Ogawa, Nobuyuki; Shimizu, Akira

    2016-01-01

    Japanese National Institutes of Technology have revealed a plan to strongly promote e-Learning and active learning under the common schematization of education in over 50 campuses nationwide. Our e-Learning and ICT-driven education practiced for more than fifteen years were highly evaluated, and is playing a leading role in promoting e-Learning…

  16. 75 FR 22357 - Center for Nutrition Policy and Promotion; Agency Information Collection Activities; Current...

    Science.gov (United States)

    2010-04-28

    ..., students, technology professionals and gamers). Estimated Number of Innovations for Healthy Kids Challenge...; ] DEPARTMENT OF AGRICULTURE Center for Nutrition Policy and Promotion; Agency Information Collection Activities; Current Collection: Comment Request--Innovations for Healthy Kids Challenge To Promote the Open Government...

  17. Use of SPARK to promote after-school physical activity.

    Science.gov (United States)

    Herrick, Heidi; Thompson, Hannah; Kinder, Jennifer; Madsen, Kristine A

    2012-10-01

    The after-school period is potentially an important venue for increasing physical activity for youth. We sought to assess the effectiveness of the Sports, Play, and Recreation for Youth (SPARK) program to increase physical activity and improve cardiorespiratory fitness and weight status among elementary students after school. This quasi-experimental controlled study compared change in moderate to vigorous physical activity (MVPA), body mass index (BMI) z-score, and cardiorespiratory fitness (VO(2) ) over 5 months between students in after-school programs exposed to SPARK versus controls. Participants were fifth grade students at 3 intervention schools (N = 48) and 3 control schools (N = 52). There was no difference between groups in mean change in MVPA, BMI z-score, or cardiorespiratory fitness. After-school time dedicated to physical activity did not increase with the implementation of SPARK. Intervention students' self-assessment of their activity levels relative to their peers significantly increased compared to control students (p = .011). In this 5-month study, the SPARK program did not increase MVPA in the after-school setting. Increasing the amount of time dedicated to physical activity may be as important as the curriculum used to effectively increase physical activity after school. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

  18. Recreational physical activity and survival in African-American women with ovarian cancer.

    Science.gov (United States)

    Abbott, Sarah E; Camacho, Fabian; Peres, Lauren C; Alberg, Anthony J; Bandera, Elisa V; Bondy, Melissa; Cote, Michele L; Funkhouser, Ellen; Moorman, Patricia G; Peters, Edward S; Qin, Bo; Schwartz, Ann G; Barnholtz-Sloan, Jill; Terry, Paul; Schildkraut, Joellen M

    2018-01-01

    While recreational physical activity (RPA) has been associated with reduced mortality in breast, colorectal, and prostate cancers, evidence for epithelial ovarian cancer (EOC) is limited. Most EOC studies have been in predominantly white populations, although inactivity is more prevalent and survival is poorer among African-American (AA) women. We examined RPA before and after EOC diagnosis and associations with survival among AA women. We analyzed data from 264 EOC survivors enrolled in a population-based, case-control study who completed surveys that included questions about pre- and post-diagnosis RPA. Data were collected on RPA frequency, intensity, and duration before diagnosis and approximately 1 year after the baseline interview. We calculated metabolic equivalent of task (MET)-hours/week for pre- and post-diagnosis RPA, and evaluated associations with risk of mortality using Cox proportional hazards models. RPA before diagnosis was not associated with mortality. Hazard ratios (HRs) for post-diagnosis RPA were  0-9 MET-hours/week and 0.53 (95% CI 0.21, 1.35) for > 9 MET-hours/week. Our results suggest that RPA may be inversely associated with mortality among AA women with ovarian cancer, although it is possible that the present study was underpowered to detect an association. There is a clear need for more studies of RPA after diagnosis in EOC survivors with attention to potential differences by race.

  19. HIGD1A Regulates Oxygen Consumption, ROS Production, and AMPK Activity during Glucose Deprivation to Modulate Cell Survival and Tumor Growth

    Directory of Open Access Journals (Sweden)

    Kurosh Ameri

    2015-02-01

    Full Text Available Hypoxia-inducible gene domain family member 1A (HIGD1A is a survival factor induced by hypoxia-inducible factor 1 (HIF-1. HIF-1 regulates many responses to oxygen deprivation, but viable cells within hypoxic perinecrotic solid tumor regions frequently lack HIF-1α. HIGD1A is induced in these HIF-deficient extreme environments and interacts with the mitochondrial electron transport chain to repress oxygen consumption, enhance AMPK activity, and lower cellular ROS levels. Importantly, HIGD1A decreases tumor growth but promotes tumor cell survival in vivo. The human Higd1a gene is located on chromosome 3p22.1, where many tumor suppressor genes reside. Consistent with this, the Higd1a gene promoter is differentially methylated in human cancers, preventing its hypoxic induction. However, when hypoxic tumor cells are confronted with glucose deprivation, DNA methyltransferase activity is inhibited, enabling HIGD1A expression, metabolic adaptation, and possible dormancy induction. Our findings therefore reveal important new roles for this family of mitochondrial proteins in cancer biology.

  20. Mitochondrial stress and activation of PI3K and Akt survival pathway in bladder ischemia

    Directory of Open Access Journals (Sweden)

    Yang JH

    2017-06-01

    behavior and cystometric changes in bladder ischemia were associated with significant decrease in DNA binding activity of Nrf2, significant increase in cellular levels of stress protein Hsp70 and mitochondrial stress protein GRP75, and significant decrease in mitochondrial oxygen consumption and upregulation of PI3K and Akt expression. Conclusion: Chronic bladder ischemia may be a mediating variable in the development of detrusor overactivity in the non-obstructive bladder. The mechanism may involve ischemia-induced cellular stress, Nrf2 functional deficit, depression of mitochondrial respiration, and upregulation of PI3K/Akt cell survival signaling pathway. Keywords: atherosclerosis, blood flow, redox, cellular stress, detrusor overactivity, survival signaling 

  1. Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss.

    Science.gov (United States)

    He, Qiang; Jia, Zhanwei; Zhang, Ying; Ren, Xiumin

    2017-03-01

    We aimed to investigate the effect of morin hydrate on neural stem cells (NSCs) isolated from mouse inner ear and its potential in protecting neuronal hearing loss. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays were employed to assess the effect of morin hydrate on the viability and proliferation of in vitro NSC culture. The NSCs were then differentiated into neurons, in which neurosphere formation and differentiation were evaluated, followed by neurite outgrowth and neural excitability measurements in the subsequent in vitro neuronal network. Mechanotransduction of cochlea ex vivo culture and auditory brainstem responses threshold and distortion product optoacoustic emissions amplitude in mouse ototoxicity model were also measured following gentamicin treatment to investigate the protective role of morin hydrate against neuronal hearing loss. Morin hydrate improved viability and proliferation, neurosphere formation and neuronal differentiation of inner ear NSCs, and promoted in vitro neuronal network functions. In both ex vivo and in vivo ototoxicity models, morin hydrate prevented gentamicin-induced neuronal hearing loss. Morin hydrate exhibited potent properties in promoting growth and differentiation of inner ear NSCs into functional neurons and protecting from gentamicin ototoxicity. Our study supports its clinical potential in treating neuronal hearing loss. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. Transport on prescription: How can GPs contribute to the promotion of active transport?

    Science.gov (United States)

    Pistoll, Chance; Furler, John

    2017-10-01

    Active transport (ie walking, cycling, using public transport) can play a part in reducing non-communicable diseases (NCDs). Very little is known about how general practitioners (GPs) can contribute to promoting active transport. We explored GPs' ideas around active transport, and potential barriers and facilitators to its promotion in the clinical setting. Using a maximal variation sample, we conducted 10 semi-structured interviews with GPs in Victoria, Australia. The socioecological model informed data collection and analysis. The idea of active transport resonated with GPs. Limited awareness around active transport and safety concerns regarding commuter cycling were barriers to clinical promotion. GPs believed patients' health, cultural norms, socioeconomic position and access to supportive environments could facilitate participation. Future efforts should prioritise awareness of active transport among GPs. The perspectives of GPs would be valuable to policymakers, particularly in designing programs to mitigate inequalities around active transport access and use.

  3. Activity monitor intervention to promote physical activity of physicians-in-training: randomized controlled trial.

    Science.gov (United States)

    Thorndike, Anne N; Mills, Sarah; Sonnenberg, Lillian; Palakshappa, Deepak; Gao, Tian; Pau, Cindy T; Regan, Susan

    2014-01-01

    Physicians are expected to serve as role models for healthy lifestyles, but long work hours reduce time for healthy behaviors. A hospital-based physical activity intervention could improve physician health and increase counseling about exercise. We conducted a two-phase intervention among 104 medical residents at a large hospital in Boston, Massachusetts. Phase 1 was a 6-week randomized controlled trial comparing daily steps of residents assigned to an activity monitor displaying feedback about steps and energy consumed (intervention) or to a blinded monitor (control). Phase 2 immediately followed and was a 6-week non-randomized team steps competition in which all participants wore monitors with feedback. Phase 1 outcomes were: 1) median steps/day and 2) proportion of days activity monitor worn. The Phase 2 outcome was mean steps/day on days monitor worn (≥500 steps/day). Physiologic measurements were collected at baseline and study end. Median steps/day were compared using Wilcoxon rank-sum tests. Mean steps were compared using repeated measures regression analyses. In Phase 1, intervention and control groups had similar activity (6369 vs. 6063 steps/day, p = 0.16) and compliance with wearing the monitor (77% vs. 77% of days, p = 0.73). In Phase 2 (team competition), residents recorded more steps/day than during Phase 1 (CONTROL: 7,971 vs. 7,567, p = 0.002; 7,832 vs. 7,739, p = 0.13). Mean compliance with wearing the activity monitor decreased for both groups during Phase 2 compared to Phase 1 (60% vs. 77%, pmonitor intervention did not have a major impact on activity or health, the high participation rates of busy residents and modest changes in steps, blood pressure, and HDL suggest that more intensive hospital-based wellness programs have potential for promoting healthier lifestyles among physicians. Clinicaltrials.gov NCT01287208.

  4. Biofilms promote survival and virulence of Salmonella enterica sv. Tennessee during prolonged dry storage and after passage through an in vitro digestion system.

    Science.gov (United States)

    Aviles, Bryan; Klotz, Courtney; Eifert, Joseph; Williams, Robert; Ponder, Monica

    2013-04-01

    Salmonella enterica serotypes have been linked to outbreaks associated with low water activity foods. While the biofilm-forming abilities of Salmonella improve its survival during thermal processing and sanitation it is unclear whether biofilms enhance survival to desiccation and gastric stresses. The purpose of this study was to quantify the effect of physiological state (planktonic versus biofilm) and prior exposure to desiccation and storage in dry milk powder on Salmonella survival and gene expression after passage through an in vitro digestion model. Planktonic cells of Salmonella enterica serotype Tennessee were deposited onto membranes while biofilms were formed on glass beads. The cells were subsequently dried at room temperature and stored in dried milk powder (a(w)=0.3) for up to 30 days. Salmonella survival was quantified by serial dilution onto Brilliant Green Agar before desiccation, after desiccation, after 1-day storage and after 30-day storage. At each sampling period both physiological states were tested for survival through a simulated gastrointestinal system. RNA was extracted at the identical time points and Quantitative Real-Time PCR was used to determine relative expression for genes associated with stress response (rpoS, otsB), virulence (hilA, invA, sipC) and a housekeeping gene 16S rRNA. The physiological state and length of storage affected the survival and gene expression of Salmonella within the desiccated milk powder environment and after passage through an in vitro digestion system (pSalmonella genomes detected by qPCR were not significantly different suggesting entry of the planktonic cells of S. Tennessee into a viable but non-culturable state. The increased expression of stress response genes rpoS and otsB correlated with survival, indicating cross-protection to low water activity and acid stress. Increased expression of virulence-associated genes was seen in cells exposed to dry storage for short periods, however the largest amount

  5. Promoting social skills of mexican high school students through virtual activities in the Moodle platform

    National Research Council Canada - National Science Library

    Laura Yolanda RODRÍGUEZ MATAMOROS; María Luz CACHEIRO GONZÁLEZ; Juan Antonio GIL PASCUAL

    2014-01-01

    With the intention of promoting social skills of Mexican high school students based on the graduate profile of this level, virtual activities were implemented in the Moodle platform to 169 students...

  6. Promoting Uranium Immobilization by the Activities of Microbial Phosphatases

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Robert J.; Beazley, Melanie J.; Wilson, Jarad J.; Taillefert, Martial; Sobecky, Patricia A.

    2005-04-05

    The overall goal of this project is to examine the role of nonspecific phosphohydrolases present in naturally occurring subsurface microorganisms for the purpose of promoting the immobilization of radionuclides through the production of uranium [U(VI)] phosphate precipitates. Specifically, we hypothesize that the precipitation of U(VI) phosphate minerals may be promoted through the microbial release and/or accumulation of PO{sub 4}{sup 3-}. During this phase of the project we have been conducting assays to determine the effects of pH, inorganic anions and organic ligands on U(VI) mineral formation and precipitation when FRC bacterial isolates were grown in simulated groundwater medium. The molecular characterization of FRC isolates has also been undertaken during this phase of the project. Analysis of a subset of gram-positive FRC isolates cultured from FRC soils (Areas 1, 2 and 3) and background sediments have indicated a higher percentage of isolates exhibiting phosphatase phenotypes (i.e., in particular those surmised to be PO{sub 4}{sup 3-}-irrepressible) relative to isolates from the reference site. A high percentage of strains that exhibited such putatively PO{sub 4}{sup 3-}-irrepressible phosphatase phenotypes were also resistant to the heavy metals lead and cadmium. Previous work on FRC strains, including Arthrobacter, Bacillus and Rahnella spp., has demonstrated differences in tolerance to U(VI) toxicity (200 {micro}M) in the absence of organophosphate substrates. For example, Arthrobacter spp. exhibited the greatest tolerance to U(VI) while the Rahnella spp. have been shown to facilitate the precipitation of U(VI) from solution and the Bacillus spp. demonstrate the greatest sensitivity to acidic conditions and high concentrations of U(VI). PCR-based detection of FRC strains are being conducted to determine if non-specific acid phosphatases of the known molecular classes [i.e., classes A, B and C] are present in these FRC isolates. Additionally, these

  7. Natural variation of macrophage activation as disease-relevant phenotype predictive of inflammation and cancer survival.

    Science.gov (United States)

    Buscher, Konrad; Ehinger, Erik; Gupta, Pritha; Pramod, Akula Bala; Wolf, Dennis; Tweet, George; Pan, Calvin; Mills, Charles D; Lusis, Aldons J; Ley, Klaus

    2017-07-24

    Although mouse models exist for many immune-based diseases, the clinical translation remains challenging. Most basic and translational studies utilize only a single inbred mouse strain. However, basal and diseased immune states in humans show vast inter-individual variability. Here, focusing on macrophage responses to lipopolysaccharide (LPS), we use the hybrid mouse diversity panel (HMDP) of 83 inbred strains as a surrogate for human natural immune variation. Since conventional bioinformatics fail to analyse a population spectrum, we highlight how gene signatures for LPS responsiveness can be derived based on an Interleukin-12β and arginase expression ratio. Compared to published signatures, these gene markers are more robust to identify susceptibility or resilience to several macrophage-related disorders in humans, including survival prediction across many tumours. This study highlights natural activation diversity as a disease-relevant dimension in macrophage biology, and suggests the HMDP as a viable tool to increase translatability of mouse data to clinical settings.

  8. Nattokinase-promoted tissue plasminogen activator release from human cells.

    Science.gov (United States)

    Yatagai, Chieko; Maruyama, Masugi; Kawahara, Tomoko; Sumi, Hiroyuki

    2008-01-01

    When heated to a temperature of 70 degrees C or higher, the strong fibrinolytic activity of nattokinase in a solution was deactivated. Similar results were observed in the case of using Suc-Ala-Ala-Pro-Phe-pNA and H-D-Val-Leu-Lys-pNA, which are synthetic substrates of nattokinase. In the current study, tests were conducted on the indirect fibrinolytic effects of the substances containing nattokinase that had been deactivated through heating at 121 degrees C for 15 min. Bacillus subtilis natto culture solutions made from three types of bacteria strain were heat-treated and deactivated, and it was found that these culture solutions had the ability to generate tissue plasminogen activators (tPA) from vascular endothelial cells and HeLa cells at certain concentration levels. For example, it was found that the addition of heat-treated culture solution of the Naruse strain (undiluted solution) raises the tPA activity of HeLa cells to about 20 times that of the control. Under the same conditions, tPA activity was raised to a level about 5 times higher for human vascular endothelial cells (HUVEC), and to a level about 24 times higher for nattokinase sold on the market. No change in cell count was observed for HeLa cells and HUVEC in the culture solution at these concentrations, and the level of activity was found to vary with concentration. Copyright 2009 S. Karger AG, Basel.

  9. Genetic variation in the proximal promoter of ABC and SLC superfamilies: liver and kidney specific expression and promoter activity predict variation.

    Directory of Open Access Journals (Sweden)

    Stephanie E Hesselson

    2009-09-01

    Full Text Available Membrane transporters play crucial roles in the cellular uptake and efflux of an array of small molecules including nutrients, environmental toxins, and many clinically used drugs. We hypothesized that common genetic variation in the proximal promoter regions of transporter genes contribute to observed variation in drug response. A total of 579 polymorphisms were identified in the proximal promoters (-250 to +50 bp and flanking 5' sequence of 107 transporters in the ATP Binding Cassette (ABC and Solute Carrier (SLC superfamilies in 272 DNA samples from ethnically diverse populations. Many transporter promoters contained multiple common polymorphisms. Using a sliding window analysis, we observed that, on average, nucleotide diversity (pi was lowest at approximately 300 bp upstream of the transcription start site, suggesting that this region may harbor important functional elements. The proximal promoters of transporters that were highly expressed in the liver had greater nucleotide diversity than those that were highly expressed in the kidney consistent with greater negative selective pressure on the promoters of kidney transporters. Twenty-one promoters were evaluated for activity using reporter assays. Greater nucleotide diversity was observed in promoters with strong activity compared to promoters with weak activity, suggesting that weak promoters are under more negative selective pressure than promoters with high activity. Collectively, these results suggest that the proximal promoter region of membrane transporters is rich in variation and that variants in these regions may play a role in interindividual variation in drug disposition and response.

  10. Mobile Health Applications to Promote Active and Healthy Ageing.

    Science.gov (United States)

    Helbostad, Jorunn L; Vereijken, Beatrix; Becker, Clemens; Todd, Chris; Taraldsen, Kristin; Pijnappels, Mirjam; Aminian, Kamiar; Mellone, Sabato

    2017-03-18

    The European population is ageing, and there is a need for health solutions that keep older adults independent longer. With increasing access to mobile technology, such as smartphones and smartwatches, the development and use of mobile health applications is rapidly growing. To meet the societal challenge of changing demography, mobile health solutions are warranted that support older adults to stay healthy and active and that can prevent or delay functional decline. This paper reviews the literature on mobile technology, in particular wearable technology, such as smartphones, smartwatches, and wristbands, presenting new ideas on how this technology can be used to encourage an active lifestyle, and discusses the way forward in order further to advance development and practice in the field of mobile technology for active, healthy ageing.

  11. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone

    Science.gov (United States)

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Wang, Lin; Adams, Ralf H.

    2014-03-01

    Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.

  12. Promoting Cartilage Stem Cell Activity to Improve Recovery from Joint Fracture

    Science.gov (United States)

    2012-09-01

    stages of human osteoarthritis . Cell Stem Cell 2009;4(4):324-35. 26. Klune JR, Dhupar R, Cardinal J, Billiar TR, Tsung A. HMGB1: endogenous danger...AD_________________ Award Number: W81XWH-10-1-0702 TITLE: Promoting Cartilage Stem Cell Activity to...SUBTITLE Promoting Cartilage Stem Cell Activity to Improve Recovery from Joint iInjuryFracture 5a. CONTRACT NUMBER 5b. GRANT

  13. Impact of Physical Activity on Cancer-Specific and Overall Survival of Patients with Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Gaetan Des Guetz

    2013-01-01

    Full Text Available Background. Physical activity (PA reduces incidence of colorectal cancer (CRC. Its influence on cancer-specific (CSS and overall survival (OS is controversial. Methods. We performed a literature-based meta-analysis (MA of observational studies, using keywords “colorectal cancer, physical activity, and survival” in PubMed and EMBASE. No dedicated MA was found in the Cochrane Library. References were cross-checked. Pre- and postdiagnosis PA levels were assessed by MET. Usually, “high” PA was higher than 17 MET hour/week. Hazard ratios (HRs for OS and CSS were calculated, with their 95% confidence interval. We used more conservative adjusted HRs, since variables of adjustment were similar between studies. When higher PA was associated with improved survival, HRs for detrimental events were set to <1. We used EasyMA software and fixed effect model whenever possible. Results. Seven studies (8056 participants were included, representing 3762 men and 4256 women, 5210 colon and 1745 rectum cancers. Mean age was 67 years. HR CSS for postdiagnosis PA (higher PA versus lower was 0.61 (0.44–0.86. The corresponding HR OS was 0.62 (0.54–0.71. HR CSS for prediagnosis PA was 0.75 (0.62–0.91. The corresponding HR OS was 0.74 (0.62–0.89. Conclusion. Higher PA predicted a better CSS. Sustained PA should be advised for CRC. OS also improved (reduced cardiovascular risk.

  14. Impact of Physical Activity on Cancer-Specific and Overall Survival of Patients with Colorectal Cancer

    Science.gov (United States)

    Des Guetz, Gaetan; Uzzan, Bernard; Bouillet, Thierry; Nicolas, Patrick; Chouahnia, Kader; Zelek, Laurent; Morere, Jean-François

    2013-01-01

    Background. Physical activity (PA) reduces incidence of colorectal cancer (CRC). Its influence on cancer-specific (CSS) and overall survival (OS) is controversial. Methods. We performed a literature-based meta-analysis (MA) of observational studies, using keywords “colorectal cancer, physical activity, and survival” in PubMed and EMBASE. No dedicated MA was found in the Cochrane Library. References were cross-checked. Pre- and postdiagnosis PA levels were assessed by MET. Usually, “high” PA was higher than 17 MET hour/week. Hazard ratios (HRs) for OS and CSS were calculated, with their 95% confidence interval. We used more conservative adjusted HRs, since variables of adjustment were similar between studies. When higher PA was associated with improved survival, HRs for detrimental events were set to <1. We used EasyMA software and fixed effect model whenever possible. Results. Seven studies (8056 participants) were included, representing 3762 men and 4256 women, 5210 colon and 1745 rectum cancers. Mean age was 67 years. HR CSS for postdiagnosis PA (higher PA versus lower) was 0.61 (0.44–0.86). The corresponding HR OS was 0.62 (0.54–0.71). HR CSS for prediagnosis PA was 0.75 (0.62–0.91). The corresponding HR OS was 0.74 (0.62–0.89). Conclusion. Higher PA predicted a better CSS. Sustained PA should be advised for CRC. OS also improved (reduced cardiovascular risk). PMID:24222762

  15. Creativity in the English Class: Activities to Promote EFL Learning

    Directory of Open Access Journals (Sweden)

    Hernán A. Avila

    2015-10-01

    Full Text Available This article introduces a pedagogical intervention that includes a set of creative activities designed to improve the oral and written production of students in the English classroom, especially those who have shown a lack of interest or attention. It was observed that participants initially seemed careless about studying the language. Eventually they responded to the proposed methods positively and were more willing and motivated to participate in chain games, creative writing, and screenwriting exercises. The activities helped develop the students’ fluency in both oral and written production and improved their understanding of English grammar and structure.

  16. Survival of patients with melanoma brain metastasis treated with stereotactic radiosurgery and active systemic drug therapies.

    Science.gov (United States)

    Choong, Ee Siang; Lo, Serigne; Drummond, Martin; Fogarty, Gerald B; Menzies, Alexander M; Guminski, Alexander; Shivalingam, Brindha; Clarke, Kathryn; Long, Georgina V; Hong, Angela M

    2017-04-01

    With new systemic therapies demonstrating activity in melanoma brain metastasis, most of the previously reported stereotactic radiosurgery (SRS) data are superseded. In this study, we report the outcomes (overall survival [OS] and brain control [BC]) and identify factors that associate with such outcomes in the era of modern systemic therapy. A total of 108 patients treated with SRS from 2010 to 2015 were included. Systemic treatment use within 6 weeks of SRS was noted. OS was defined as time from SRS to death or last follow-up, and BC was defined as absence of any active intracranial disease during follow-up. Univariate and multivariate Cox proportional hazard analyses were performed on clinico-pathological prognostic features associated with OS and BC. The median age was 64.3 years, and the median follow-up was 8.6 months. Seventy-nine (73.1%) patients received systemic treatment. The median OS were as follows: anti-CTLA4 - 7.5 months (95% CI: 4.4-15.6), anti-PD1 - 20.4 months (95% CI: 8.8 - N/A) and BRAF inhibitor (BRAFi) ± MEK inhibitor (MEKi) - 17.8 months (95% CI: 11.8 - N/A). Median BC was as follows: anti-CTLA4 - 7.5 months (95% CI: 4.0-15.6), anti-PD1 - 12.7 months (95% CI: 5.5 - N/A) and BRAFi ± MEKi - 12.7 months (95% CI: 8.3-18.5). In multivariate analysis, age and type of systemic therapy were strongly associated with OS. Age, Eastern Cooperative Oncology Group performance status, Graded Prognostic Assessment (GPA) score, and presence of symptoms were associated with BC. Favourable outcomes are seen in patients treated with SRS and with the best survival seen in patients treated with anti-PD1. Known independent prognostic factors for survival such as age and performance status and GPA score remain relevant in this setting. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. EBV induces persistent NF-κB activation and contributes to survival of EBV-positive neoplastic T- or NK-cells.

    Directory of Open Access Journals (Sweden)

    Honami Takada

    Full Text Available Epstein-Barr virus (EBV has been detected in several T- and NK-cell neoplasms such as extranodal NK/T-cell lymphoma nasal type, aggressive NK-cell leukemia, EBV-positive peripheral T-cell lymphoma, systemic EBV-positive T-cell lymphoma of childhood, and chronic active EBV infection (CAEBV. However, how this virus contributes to lymphomagenesis in T or NK cells remains largely unknown. Here, we examined NF-κB activation in EBV-positive T or NK cell lines, SNT8, SNT15, SNT16, SNK6, and primary EBV-positive and clonally proliferating T/NK cells obtained from the peripheral blood of patients with CAEBV. Western blotting, electrophoretic mobility shift assays, and immunofluorescent staining revealed persistent NF-κB activation in EBV-infected cell lines and primary cells from patients. Furthermore, we investigated the role of EBV in infected T cells. We performed an in vitro infection assay using MOLT4 cells infected with EBV. The infection directly induced NF-κB activation, promoted survival, and inhibited etoposide-induced apoptosis in MOLT4 cells. The luciferase assay suggested that LMP1 mediated NF-κB activation in MOLT4 cells. IMD-0354, a specific inhibitor of NF-κB that suppresses NF-κB activation in cell lines, inhibited cell survival and induced apoptosis. These results indicate that EBV induces NF-κB-mediated survival signals in T and NK cells, and therefore, may contribute to the lymphomagenesis of these cells.

  18. EBV induces persistent NF-κB activation and contributes to survival of EBV-positive neoplastic T- or NK-cells.

    Science.gov (United States)

    Takada, Honami; Imadome, Ken-Ichi; Shibayama, Haruna; Yoshimori, Mayumi; Wang, Ludan; Saitoh, Yasunori; Uota, Shin; Yamaoka, Shoji; Koyama, Takatoshi; Shimizu, Norio; Yamamoto, Kouhei; Fujiwara, Shigeyoshi; Miura, Osamu; Arai, Ayako

    2017-01-01

    Epstein-Barr virus (EBV) has been detected in several T- and NK-cell neoplasms such as extranodal NK/T-cell lymphoma nasal type, aggressive NK-cell leukemia, EBV-positive peripheral T-cell lymphoma, systemic EBV-positive T-cell lymphoma of childhood, and chronic active EBV infection (CAEBV). However, how this virus contributes to lymphomagenesis in T or NK cells remains largely unknown. Here, we examined NF-κB activation in EBV-positive T or NK cell lines, SNT8, SNT15, SNT16, SNK6, and primary EBV-positive and clonally proliferating T/NK cells obtained from the peripheral blood of patients with CAEBV. Western blotting, electrophoretic mobility shift assays, and immunofluorescent staining revealed persistent NF-κB activation in EBV-infected cell lines and primary cells from patients. Furthermore, we investigated the role of EBV in infected T cells. We performed an in vitro infection assay using MOLT4 cells infected with EBV. The infection directly induced NF-κB activation, promoted survival, and inhibited etoposide-induced apoptosis in MOLT4 cells. The luciferase assay suggested that LMP1 mediated NF-κB activation in MOLT4 cells. IMD-0354, a specific inhibitor of NF-κB that suppresses NF-κB activation in cell lines, inhibited cell survival and induced apoptosis. These results indicate that EBV induces NF-κB-mediated survival signals in T and NK cells, and therefore, may contribute to the lymphomagenesis of these cells.

  19. Promoting physical activity in rheumatoid arthritis: a narrative review of behaviour change theories.

    Science.gov (United States)

    Larkin, Louise; Kennedy, Norelee; Gallagher, Stephen

    2015-01-01

    Despite physical activity having significant health benefits for people with rheumatoid arthritis (RA), current levels of physical activity in this population are suboptimal. Changing behaviour is challenging and interventions aimed at increasing physical activity in this context have had varying levels of success. This review provides an overview of common behaviour change theories used in interventions to promote physical activity and their application for promoting physical activity in people with RA. A scoping, narrative review was conducted of English language literature, using the search terms "physical activity/exercise" and keywords, which are associated with behaviour change interventions. The theoretical basis of such interventions in people with RA was assessed using the "theory coding scheme". Six theories which have been used in physical activity research are discussed. Further, four studies which aimed to increase physical activity levels in people with RA are explored in detail. To date, behaviour change interventions conducted in RA populations to increase physical activity levels have not had a strong theoretical underpinning. It is proposed that an intervention utilising the theory of planned behaviour is developed with the aim of increasing physical activity in people with RA. Implications for Rehabilitation Interventions to promote physical activity in the rheumatoid arthritis (RA) population have failed to change participants' behaviour. A small number of studies have used behaviour change theories in the development and delivery of interventions. The theory of planned behaviour is recommended as the theoretical basis for an intervention to promote physical activity in the RA population.

  20. Healhy Ageing in People with Profound Intellectual and Multiple Disabilities : Promoting Physical Activity

    NARCIS (Netherlands)

    van Alphen, Helena; Bossink, Leontien; Schalen, Gertruud Henrike; van der Putten, Annette

    2016-01-01

    Physical activity is beneficial, also for people who are characterized by profound intellectual and severe motor disabilities. However, these people are totally dependent on others to participate in physical activities. To date, promoting physical activity in people with these profound disabilities

  1. The Role of Platelet-Derived ADP and ATP in Promoting Pancreatic Cancer Cell Survival and Gemcitabine Resistance

    Directory of Open Access Journals (Sweden)

    Omar Elaskalani

    2017-10-01

    Full Text Available Platelets have been demonstrated to be vital in cancer epithelial-mesenchymal transition (EMT, an important step in metastasis. Markers of EMT are associated with chemotherapy resistance. However, the association between the development of chemoresistance, EMT, and the contribution of platelets to the process, is still unclear. Here we report that platelets regulate the expression of (1 human equilibrative nucleoside transporter 1 (hENT1 and (2 cytidine deaminase (CDD, markers of gemcitabine resistance in pancreatic cancer. Human ENT1 (hENT1 is known to enable cellular uptake of gemcitabine while CDD deactivates gemcitabine. Knockdown experiments demonstrate that Slug, a mesenchymal transcriptional factor known to be upregulated during EMT, regulates the expression of hENT1 and CDD. Furthermore, we demonstrate that platelet-derived ADP and ATP regulate Slug and CDD expression in pancreatic cancer cells. Finally, we demonstrate that pancreatic cancer cells express the purinergic receptor P2Y12, an ADP receptor found mainly on platelets. Thus ticagrelor, a P2Y12 inhibitor, was used to examine the potential therapeutic effect of an ADP receptor antagonist on cancer cells. Our data indicate that ticagrelor negated the survival signals initiated in cancer cells by platelet-derived ADP and ATP. In conclusion, our results demonstrate a novel role of platelets in modulating chemoresistance in pancreatic cancer. Moreover, we propose ADP/ATP receptors as additional potential drug targets for treatment of pancreatic cancer.

  2. Development and oversight of ethical health promotion quality assurance and evaluation activities involving human participants.

    Science.gov (United States)

    Sainsbury, Peter

    2015-12-01

    This paper considers the role of ethics and ethics review processes in the development of health promotion quality assurance and evaluation activities involving human participants. The Australian National Health and Medical Research Council (NHMRC) National Statement on Ethical Conduct in Human Research and associated documents provide the framework for the ethical conduct and independent review of research (including quality assurance and evaluation) involving humans in Australia. Identifying the level of risk to which participants may be exposed by participation in quality assurance and evaluation activities is essential for health promotion workers undertaking such activities. Organisations can establish processes other than review by a Human Research Ethics Committee for negligible and low risk research activities. Health promotion quality assurance and evaluation activities often involve negligible and low risk to participants. Seven triggers that indicate the need for ethics review of quality assurance and evaluation activities and a procedural checklist for developing ethical quality assurance and evaluation activities are provided. Health promotion workers should be familiar with the NHMRC's National Statement on Ethical Conduct in Human Research. When ethical considerations underpin the planning and conduct of all quality assurance and evaluation from the very beginning, the activity is the better for it, independent 'ethics approval' can mostly be secured without much trouble and workers' frustration levels are reduced. So what? Health promotion quality assurance and evaluation activities must be ethically justified. Health promotion workers should be familiar with the NHMRC's National Statement on Ethical Conduct in Human Research and should use it when developing health promotion quality assurance and evaluation activities.

  3. Linking the Belowground Microbial Composition, Diversity and Activity to Soilborne Disease Suppression and Growth Promotion of Tomato Amended with Biochar.

    Science.gov (United States)

    Jaiswal, Amit K; Elad, Yigal; Paudel, Indira; Graber, Ellen R; Cytryn, Eddie; Frenkel, Omer

    2017-03-13

    Biochar, in addition to sequestering carbon, ameliorating soil, and improving plant performance, can impact foliar and soilborne plant diseases. Nevertheless, the mechanisms associated with suppression of soilborne diseases and improved plant performances are not well understood. This study is designed to establish the relationships between biochar-induced changes in rhizosphere microbial community structure, taxonomic and functional diversity, and activity with soilborne disease suppression and enhanced plant performance in a comprehensive fashion. Biochar suppressed Fusarium crown and root-rot of tomato and simultaneously improved tomato plant growth and physiological parameters. Furthermore, biochar reduced Fusarium root colonization and survival in soil, and increased the culturable counts of several biocontrol and plant growth promoting microorganisms. Illumina sequencing analyses of 16S rRNA gene revealed substantial differences in rhizosphere bacterial taxonomical composition between biochar-amended and non-amended treatments. Moreover, biochar amendment caused a significant increase in microbial taxonomic and functional diversity, microbial activities and an overall shift in carbon-source utilization. High microbial taxonomic and functional diversity and activity in the rhizosphere has been previously associated with suppression of diseases caused by soilborne pathogens and with plant growth promotion, and may collectively explain the significant reduction of disease and improvement in plant performance observed in the presence of biochar.

  4. Promoting direct interspecies electron transfer with activated carbon

    DEFF Research Database (Denmark)

    Liu, Fanghua; Rotaru, Amelia-Elena; Shrestha, Pravin M.

    2012-01-01

    Granular activated carbon (GAC) is added to methanogenic digesters to enhance conversion of wastes to methane, but the mechanism(s) for GAC’s stimulatory effect are poorly understood. GAC has high electrical conductivity and thus it was hypothesized that one mechanism for GAC stimulation...

  5. Active Commuting to School as a Source of Health Promotion ...

    African Journals Online (AJOL)

    user

    and mobility challenges were excluded from the study. The selected students were provided with packets containing the consent forms to be completed by the students and their parents; and the active commuting questionnaire to be completed by the students. A total of 926 (84.2%) out of the 1100 students who received the ...

  6. Student training for promoting collaborative agency: the monitoring activities

    NARCIS (Netherlands)

    Cunha Jr., Fernando Rezende da

    This study aims at understanding how student training contributes to the success and sustainability of a school intervention project and how collaborative agency emerges from that process among students and teachers. All activities developed in the intervention were based on Cultural Historical

  7. Antifungal activity of plant growth-promoting rhizobacteria isolates ...

    African Journals Online (AJOL)

    Strains WPR-51, WPR-42 and WM-30 were selected to test in planta antagonistic activity on two wheat verities infected with R. solani. These three strains belonging to Azotobacter and Azospirillum produced IAA ranging from 19.4 to 30.2 ug/ml and possessed phosphorus solublization capability. Out of these three strains ...

  8. Health-Promoting Physical Activity and Extra-Curricular Sport

    Science.gov (United States)

    Curtner-Smith, Matthew; Sofo, Seidu; Chouinard, Jeremy; Wallace, Sheila

    2007-01-01

    The primary purpose of this exploratory study was to determine the percentage of time in which school pupils coached by teachers were engaged in moderate to vigorous physical activity (MVPA) during extra-curricular sport practices. Three secondary purposes of the study were to determine (a) the percentage of time allocated by teachers for pupils…

  9. A manual for promoting health activity at work

    NARCIS (Netherlands)

    Wynne, R.; Clarkin, N.; Urlings, I.; Gründemann, R.W.M.; Jorda, C.; Moncada, S.; Lundberg, B.

    1996-01-01

    This methodology has been developed to help organisations increase their level of health activity in a planned and systematic way. There are many good reasons for undertaking health improvement actions in the workplace, not all of them related to the benefits of improved health. Research undertaken

  10. Creativity in the English Class: Activities to Promote EFL Learning

    Science.gov (United States)

    Avila, Hernán A.

    2016-01-01

    This article introduces a pedagogical intervention that includes a set of creative activities designed to improve the oral and written production of students in the English classroom, especially those who have shown a lack of interest or attention. It was observed that participants initially seemed careless about studying the language. Eventually…

  11. Maternal exercise during pregnancy promotes physical activity in adult offspring

    Science.gov (United States)

    Previous rodent studies have shown that maternal voluntary exercise during pregnancy leads to metabolic changes in adult offspring. We set out to test whether maternal voluntary exercise during pregnancy also induces persistent changes in voluntary physical activity in the offspring. Adult C57BL/6J ...

  12. Forming a Learning Culture to Promote Fracture Prevention Activities

    Science.gov (United States)

    Hjalmarson, Helene V.; Strandmark, Margaretha

    2012-01-01

    Purpose: The purpose of this paper is to explore interprofessional experiences of incorporating fracture prevention activities in clinical practice inspired by an empowerment approach. Design/methodology/approach: Data collection consisted primarily of focus groups interviews, systematized and analyzed by the grounded theory method. The study took…

  13. Promotion of physically active lifestyle among South African youth ...

    African Journals Online (AJOL)

    Physical inactivity is one of the major underlying causes of mortality in the world. Various studies have proven that a moderate amount of physical activity can help to reduce various chronic diseases of lifestyle. The current article reviews literature pertaining to the prevalence of chronic diseases of lifestyle in South Africa, ...

  14. Growth promotion and elicitor activity of salicylic acid in Achillea ...

    African Journals Online (AJOL)

    ... with a consequent improvement of the antioxidant activity of the plant extract. It can be concluded that SA application constitutes an advantageous management practice for commercial production of Achillea millefolium, increasing the nutraceutical and medicinal values of this species. Key words: Photosynthetic pigments, ...

  15. Diabetes mellitus: preliminary health-promotion activity based on ...

    African Journals Online (AJOL)

    Predominantly school students visited the exhibit and took part in the quiz and other educational activities. Results: The majority of the 119 junior and 332 senior quiz participants were male students attending government schools in the Eastern Cape, South Africa. After an educational intervention, there was significant ...

  16. Does HOPSports Promote Youth Physical Activity in Physical Education Classes?

    Science.gov (United States)

    West, Stephanie T.; Shores, Kindal A.

    2014-01-01

    This study investigated how a technological intervention, HOPSports (HOPS), impacted youth physical activity (PA) in a physical education (PE) class. Research indicates rising levels of youth television watching and video game use, physical inactivity, and related overweight. One approach to increase youth PA is to use technology-based…

  17. Promoting Technology-Assisted Active Learning in Computer Science Education

    Science.gov (United States)

    Gao, Jinzhu; Hargis, Jace

    2010-01-01

    This paper describes specific active learning strategies for teaching computer science, integrating both instructional technologies and non-technology-based strategies shown to be effective in the literature. The theoretical learning components addressed include an intentional method to help students build metacognitive abilities, as well as…

  18. Plasminogen activator promotes recovery following spinal cord injury.

    Science.gov (United States)

    Seeds, Nicholas; Mikesell, Steve; Vest, Rebekah; Bugge, Thomas; Schaller, Kristin; Minor, Kenneth

    2011-08-01

    Plasminogen activators play an important role in synaptic plasticity associated with the crossed phrenic phenomenon (CPP) and recovery of respiratory function after spinal cord injury. A genetic approach using knockout mice lacking various genes in the plasminogen activator/plasmin system has shown that induction of urokinase plasminogen activator (uPA) is required during the first hour after a C2-hemisection for the acquisition of the CPP response. The uPA knockout mice do not show the structural remodeling of phrenic motor neuron synapses characteristic of the CPP response. As shown here uPA acts in a cell signaling manner via binding to its receptor uPAR rather than as a protease, since uPAR knockout mice or knock-in mice possessing a modified uPA that is unable to bind to uPAR both fail to generate a CPP and recover respiratory function. Microarray data and real-time PCR analysis of mRNAs induced in the phrenic motor nucleus after C2-hemisection in C57Bl/6 mice as compared to uPA knockout mice indicate a potential cell signaling cascade downstream possibly involving β-integrin and Src, and other pathways. Identification of these uPA-mediated signaling pathways may provide the opportunity to pharmacologically upregulate the synaptic plasticity necessary for recovery of phrenic motoneuron activity following cervical spinal cord injury.

  19. Measuring the Effectiveness of Sales Promotion Activities on Brand Loyalty: A Study on COCA COLA

    Directory of Open Access Journals (Sweden)

    Uma Shankar Singh

    2017-03-01

    Full Text Available The study is descriptive in nature measuring the effect and relationship in between sales promotion activities and brand loyalty. The study is done on COCA COLA brand in the open market. The research problem observed here as to measure the efficiency of sales promotion and brand loyalty to get the real effectiveness on sales promotion activities. The research objectives formulated are to know the importance of component of sales promotion activities, to know the effect of advertising on sales promotion activities, to realize the importance of brand loyalty on sales promotion activities. A quantitative method was used to accomplish the purpose of the study. A survey instrument developed taking items to measure all variables with five points likert scale. A sample size of 159 (from 210 incorporated in the study having the reliability of 0.851(more than 0.7. The data analyzed using SPSS for descriptive statistics and regression to measure the effect of independent variable on dependent variable. It is recommend that COCA COLA should improve more on its different activities and produce different product and with tasty fast food or build up different production of equipment to expand its business in the whole world’s market .

  20. Combining balneotherapy and health promotion to promote active and healthy ageing: the Balaruc-MACVIA-LR® approach.

    Science.gov (United States)

    Blain, H; Bernard, P L; Canovas, G; Raffort, N; Desfour, H; Soriteau, L; Noguès, M; Camuzat, T; Mercier, J; Dupeyron, A; Quéré, I; Laffont, I; Hérisson, C; Solimene, H; Bousquet, J

    2016-12-01

    Scaling up and replication of successful innovative integrated care models for chronic diseases is one of the targets of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). MACVIA-LR® (MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon) is a Reference Site of the EIP on AHA. The main objective of MACVIA-LR® is to develop innovative solutions in order to (1) improve the care of patients affected by chronic diseases, (2) reduce avoidable hospitalization and (3) scale up the innovation to regions of Europe. The MACVIA-LR® project also aims to assess all possible aspects of medicine-including non-pharmacologic approaches-in order to maintain health and prevent chronic diseases. These approaches include hydrotherapy and balneotherapy which can be of great importance if health promotion strategies are considered. Balneotherapy at Balaruc-les-Bains focusses on musculoskeletal diseases and chronic venous insufficiency of the lower limbs. Each year, over 46,000 people attend an 18-day course related to a new falls prevention initiative combining balneotherapy and education. On arrival, each person receives a flyer providing information on the risk of fall and, depending on this risk, a course is proposed combining education and physical activity. A pilot study assesses the impact of the course 6 and 12 months later. This health promotion strategy for active and healthy ageing follows the FEMTEC (World Federation of Hydrotherapy and Climatotherapy) concept.

  1. Dog ownership and dog walking to promote physical activity and health in patients.

    Science.gov (United States)

    Epping, Jacqueline N

    2011-07-01

    Lack of physical activity is a significant risk factor for many chronic diseases and conditions and is associated with significant medical costs. Approximately half of adults and more than a third of adolescents and youth in the United States do not achieve recommended levels of physical activity. Effective population-level strategies are needed to promote activities that are practical, accessible, and sustainable and that can reach a large proportion of the population. Dog walking may be such a strategy. Walking is popular, easy, and sustainable and has a low risk of injury. Owning dogs confers many health benefits, and dog walking, in particular, can help promote physical activity and improve health. Physicians and other health care providers can play a unique and integral role in promoting physical activity among patients by recommending dog walking both to dog owners and to non-dog owners as a purposeful, enjoyable, and sustainable form of regular physical activity.

  2. SUSTAINABLE DEVELOPMENT OF DORNA BASIN, BY PROMOTING TOURISM ACTIVITIES IN RURAL AREAS

    Directory of Open Access Journals (Sweden)

    Andrei Lucian VINTILĂ

    2013-01-01

    Full Text Available Any strategy of diversification of non-agricultural economic activities and development of micro-enterprises in rural areas, aims to increase farms’ side incomes from non-agricultural activities, to create new job opportunities, new services for local people, to promote entrepreneurship and development of rural tourism. Sustainable developmentby promoting tourism should have as objective, besides recovery and sustainable promotion of cultural heritage the natural resources with tourism potential as well and the use of local products, which are marketed not only as raw materials but also as products with added value.

  3. Enhancing survival of Escherichia coli by expression of azoreductase AZR possessing quinone reductase activity.

    Science.gov (United States)

    Liu, Guangfei; Zhou, Jiti; Jin, Ruofei; Zhou, Mi; Wang, Jing; Lu, Hong; Qu, Yuanyuan

    2008-09-01

    Quinone reductase activity of azoreductase AZR from Rhodobacter sphaeroides was reported. High homologies were found in the cofactor/substrate-binding regions of quinone reductases from different domains. 3D structure comparison revealed that AZR shared a common overall topology with mammal NAD(P)H/quinone oxidoreductase NQO1. With menadione as substrate, the optimal pH value and temperature were pH 8-9 and 50 degrees C, respectively. Following the ping-pong kinetics, AZR transferred two electrons from NADPH to quinone substrate. It could reduce naphthoquinones and anthraquinones, such as menadione, lawsone, anthraquinone-2-sulfonate, and anthraquinone-2,6-disulfonate. However, no activity was detected with 1,4-benzoquinone. Dicoumarol competitively inhibited AZR's quinone reductase activity with respect to NADPH, with an obtained K (i) value of 87.6 microM. Significantly higher survival rates were obtained in Escherichia coli YB overexpressing AZR than in the control strain when treated by heat shock and oxidative stressors such as H(2)O(2) and menadione.

  4. Mesenchymal stem cells promote liver regeneration and prolong survival in small-for-size liver grafts: involvement of C-Jun N-terminal kinase, cyclin D1, and NF-κB.

    Directory of Open Access Journals (Sweden)

    Weijie Wang

    Full Text Available BACKGROUND: The therapeutic potential of mesenchymal stem cells (MSCs has been highlighted recently for treatment of acute or chronic liver injury, by possibly differentiating into hepatocyte-like cells, reducing inflammation, and enhancing tissue repair. Despite recent progress, exact mechanisms of action are not clearly elucidated. In this study, we attempted to explore whether and how MSCs protected hepatocytes and stimulated allograft regeneration in small-for-size liver transplantation (SFSLT. METHODS: SFSLT model was established with a 30% partial liver transplantation (30PLT in rats. The differentiation potential and characteristics of bone marrow derived MSCs were explored in vitro. MSCs were infused transvenously immediately after graft implantation in therapy group. Expressions of apoptosis-, inflammatory-, anti-inflammatory-, and growth factor-related genes were measured by RT-PCR, activities of transcription factors AP-1 and NF-κB were analyzed by EMSA, and proliferative responses of the hepatic graft were evaluated by immunohistochemistry and western blot. RESULTS: MSCs were successfully induced into hepatocyte-like cells, osteoblasts and adipocytes in vitro. MSCs therapy could not only alleviate ischemia reperfusion injury and acute inflammation to promote liver regeneration, but also profoundly improve one week survival rate. It markedly up-regulated the mRNA expressions of HGF, Bcl-2, Bcl-XL, IL-6, IL-10, IP-10, and CXCR2, however, down-regulated TNF-α. Increased activities of AP-1 and NF-κB, as well as elevated expressions of p-c-Jun, cyclin D1, and proliferating cell nuclear antigen (PCNA, were also found in MSCs therapy group. CONCLUSION: These data suggest that MSCs therapy promotes hepatocyte proliferation and prolongs survival in SFSLT by reducing ischemia reperfusion injury and acute inflammation, and sustaining early increased expressions of c-Jun N-terminal Kinase, Cyclin D1, and NF-κB.

  5. Active audiodescription to promote speaking skills in online environments

    Directory of Open Access Journals (Sweden)

    Noa Talaván

    2016-12-01

    Full Text Available Research on the use of audiovisual translation in foreign language education has considerably increased over the last decade. However, it has mainly covered the use of subtitles as a support, and the use of active subtitling and dubbing as a task. This paper introduces the pedagogical use of another AVT mode: active audiodescription --the oral description of visual information for blind and visually impaired people-- to enhance speaking skills in distance learning education The quasi-experimental study, developed in an online setting, involved 30 Spanish students of English for Specific Purposes (level B1. Participants were required to write the audiodescription of two tourist advertisements collaboratively online and then record their voices using the web platform ClipFlair. Reasonably valid conclusions that shed some light on the pedagogical benefits of audiodescription were obtained and they invite further research on the possibilities of revoicing techniques in L2 contexts.

  6. AAV-mediated transfer of RhoA shRNA and CNTF promotes retinal ganglion cell survival and axon regeneration.

    Science.gov (United States)

    Cen, Ling-Ping; Liang, Jia-Jian; Chen, Jian-Huan; Harvey, Alan R; Ng, Tsz Kin; Zhang, Mingzhi; Pang, Chi Pui; Cui, Qi; Fan, You-Ming

    2017-02-20

    The aim of the present study was to determine whether adeno-associated viral vector (AAV) mediated transfer of ciliary neurotrophic factor (CNTF) and RhoA shRNA has additive effects on promoting the survival and axon regeneration of retinal ganglion cells (RGCs) after optic nerve crush (ONC). Silencing effects of AAV-RhoA shRNA were confirmed by examining neurite outgrowth in PC12 cells, and by quantifying RhoA expression levels with western blotting. Young adult Fischer rats received an intravitreal injection of (i) saline, (ii) AAV green fluorescent protein (GFP), (iii) AAV-CNTF, (iv) AAV-RhoA shRNA, or (v) a combination of both AAV-CNTF and AAV-RhoA shRNA. Two weeks later, the ON was completely crushed. Three weeks after ONC, RGC survival was estimated by counting βIII-tubulin-positive neurons in retinal whole mounts. Axon regeneration was evaluated by counting GAP-43-positive axons in the crushed ON. It was found that AAV-RhoA shRNA decreased RhoA expression levels and promoted neurite outgrowth in vitro. In the ONC model, AAV-RhoA shRNA by itself had only weak beneficial effects on RGC axon regeneration. However, when combined with AAV-CNTF, AAV-RhoA shRNA significantly improved the therapeutic effect of AAV-CNTF on axon regeneration by nearly two fold, even though there was no significant change in RGC viability. In sum, this combination of vectors increases the regenerative response and can lead to more successful therapeutic outcomes following neurotrauma. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Paxillin promotes tumor progression and predicts survival and relapse in oral cavity squamous cell carcinoma by microRNA-218 targeting.

    Science.gov (United States)

    Wu, De-Wei; Chuang, Chun-Yi; Lin, Wea-Long; Sung, Wen-Wei; Cheng, Ya-Wen; Lee, Huei

    2014-08-01

    High-risk human papillomavirus (HPV) 16-infected oral cavity squamous cell carcinoma (OCSCC) differs significantly from non-HPV-infected OCSCC. However, the molecular pathogenesis of HPV-infected OCSCC remains unclear. Paxillin (PXN) has been reported to promote lung tumor progression by miR-218 targeting. In addition, expression of miR-218 has been shown to be reduced by HPV16 E6 in cervical cancer. We thus asked whether PXN can promote tumor progression by E6-reduced miR-218 in OCSCC, especially in HPV-infected OCSCC. Mechanistic studies demonstrated that PXN expression increased markedly upon E6-mediated reductions in miR-218, resulting in increased colony formation and invasion capabilities in HPV-infected OCSCC cells. Among tumor specimens, HPV16/18 infection was negatively associated with miR-218 expression and positively associated with PXN expression. Kaplan-Meier and Cox regression models demonstrated that patients with low-miR-218 tumors or high-PXN tumors exhibited shorter overall survival (OS) and relapse-free survival (RFS) than those with high-miR-218 tumors or low-PXN tumors. Interestingly, HPV-infected patients with low-miR-218, high-PXN tumors and both combinations exhibited the worst OS and RFS compared with patients in their counterparts. These observations in patients were consistent with the findings from the cell model. Therefore, we suggest that PXN might be targeted to suppress tumor progression and consequently to improve outcomes in OCSCC, especially in HPV-infected OCSCC. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Fnr, a global transcriptional regulator of Escherichia coli, activates the Vitreoscilla hemoglobin (VHb) promoter and intracellular VHb expression increases cytochrome d promoter activity.

    Science.gov (United States)

    Tsai, P S; Kallio, P T; Bailey, J E

    1995-01-01

    The oxygen-regulated promoter (Pvhb) of the Vitreoscilla hemoglobin gene has been applied to direct high-level expression of several cloned proteins, including Vitreoscilla hemoglobin (VHb), which improves productivity of many aerobic processes. In an effort to gain a better understanding of the regulation of Pvhb, and to guide further optimization of this technology, we investigated whether the Escherichia coli global regulatory molecules Fnr and the Arc system (ArcA and ArcB), which control the expression of various genes under either aerobic or anaerobic conditions, also regulate Pvhb activity in E. coli. The activity of Pvhb and the expression of VHb in E. coli were activated by Fnr, but were relatively unaffected by the Arc system under microaerobic conditions (DO less than 2% air saturation). We also examined the possibility of VHb affecting cytochrome d promoter activity during microaerobiosis. The presence of VHb increased the activity of beta-galactosidase from a cytochrome d promoter-lacZ fusion by 1.5-fold. This indicates that VHb affects oxygen-regulated transcription of E. coli genes and may contribute to the modified physiology observed in VHb-expressing E. coli.

  9. Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Liyan; Liu, Xiaolin [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zhang, Yuelin [Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong (China); Liang, Xiaoting; Ding, Yue [Pudong District Clinical Translational Medical Research Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai (China); Xu, Yan; Fang, Zhen [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zhang, Fengxiang, E-mail: njzfx6@njmu.edu.cn [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2016-05-15

    Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted into the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease.

  10. Xanthine dehydrogenase-1 silencing inAedes aegyptimosquitoes promotes a blood feeding-induced adulticidal activity.

    Science.gov (United States)

    Isoe, Jun; Petchampai, Natthida; Isoe, Yurika E; Co, Katrina; Mazzalupo, Stacy; Scaraffia, Patricia Y

    2017-06-01

    Aedes aegypti has 2 genes encoding xanthine dehydrogenase (XDH). We analyzed XDH1 and XDH2 gene expression by real-time quantitative PCR in tissues from sugar- and blood-fed females. Differential XDH1 and XDH2 gene expression was observed in tissues dissected throughout a time course. We next exposed females to blood meals supplemented with allopurinol, a well-characterized XDH inhibitor. We also tested the effects of injecting double-stranded RNA (dsRNA) against XDH1, XDH2, or both. Disruption of XDH by allopurinol or XDH1 by RNA interference significantly affected mosquito survival, causing a disruption in blood digestion, excretion, oviposition, and reproduction. XDH1-deficient mosquitoes showed a persistence of serine proteases in the midgut at 48 h after blood feeding and a reduction in the uptake of vitellogenin by the ovaries. Surprisingly, analysis of the fat body from dsRNA-XDH1-injected mosquitoes fell into 2 groups: one group was characterized by a reduction of the XDH1 transcript, whereas the other group was characterized by an up-regulation of several transcripts, including XDH1, glutamine synthetase, alanine aminotransferase, catalase, superoxide dismutase, ornithine decarboxylase, glutamate receptor, and ammonia transporter. Our data demonstrate that XDH1 plays an essential role and that XDH1 has the potential to be used as a metabolic target for Ae. aegypti vector control.-Isoe, J., Petchampai, N., Isoe, Y. E., Co, K., Mazzalupo, S., Scaraffia, P. Y. Xanthine dehydrogenase-1 silencing in Aedes aegypti mosquitoes promotes a blood feeding-induced adulticidal activity. © FASEB.

  11. Policy brief on promoting physical activity among adolescents

    Directory of Open Access Journals (Sweden)

    Leila Mounesan

    2012-01-01

    Full Text Available Regular physical activity (PA is an underlying factor since childhood and adolescence for having a healthy and active future for life. The aim of this stud y was to review the evidence on increasing the youth PA to develop the national program at country level. At first, the databases were searched using the sensitive keywords, and systematic reviews of the relevant databases were extracted. The studies were evaluated in terms of relevance and methodological quality for effective interventions that were detected. These cases were also identified in the effective interventions: disadvantages, benefits, costs, methods, and limitations of early studies, which were based on systematic review of the studies. Three interventions were identified as physical education curriculum reform, the creation of extra-curricular activities, as well as approaches to environmental and social support. Evidences showed that the relative impact of these interventions were not high. Thus, a combination of all three options of integrated approach is recommended for reducing the sedentary lifestyle of youths.

  12. Hepatitis B Virus Activates Signal Transducer and Activator of Transcription 3 Supporting Hepatocyte Survival and Virus ReplicationSummary

    Directory of Open Access Journals (Sweden)

    Marianna Hösel

    2017-11-01

    Full Text Available Background & Aims: The human hepatitis B virus (HBV is a major cause of chronic hepatitis and hepatocellular carcinoma, but molecular mechanisms driving liver disease and carcinogenesis are largely unknown. We therefore studied cellular pathways altered by HBV infection. Methods: We performed gene expression profiling of primary human hepatocytes infected with HBV and proved the results in HBV-replicating cell lines and human liver tissue using real-time polymerase chain reaction and Western blotting. Activation of signal transducer and activator of transcription (STAT3 was examined in HBV-replicating human hepatocytes, HBV-replicating mice, and liver tissue from HBV-infected individuals using Western blotting, STAT3-luciferase reporter assay, and immunohistochemistry. The consequences of STAT3 activation on HBV infection and cell survival were studied by chemical inhibition of STAT3 phosphorylation and small interfering RNA–mediated knockdown of STAT3. Results: Gene expression profiling of HBV-infected primary human hepatocytes detected no interferon response, while genes encoding for acute phase and antiapoptotic proteins were up-regulated. This gene regulation was confirmed in liver tissue samples of patients with chronic HBV infection and in HBV-related hepatocellular carcinoma. Pathway analysis revealed activation of STAT3 to be the major regulator. Interleukin-6–dependent and –independent activation of STAT3 was detected in HBV-replicating hepatocytes in cell culture and in vivo. Prevention of STAT3 activation by inhibition of Janus tyrosine kinases as well as small interfering RNA–mediated knockdown of STAT3-induced apoptosis and reduced HBV replication and gene expression. Conclusions: HBV activates STAT3 signaling in hepatocytes to foster its own replication but also to prevent apoptosis of infected cells. This very likely supports HBV-related carcinogenesis. Keywords: Hepatitis B Virus Infection, STAT3 Signaling

  13. Cognitive brain responses during circadian wake-promotion: evidence for sleep-pressure-dependent hypothalamic activations.

    Science.gov (United States)

    Reichert, Carolin F; Maire, Micheline; Gabel, Virginie; Viola, Antoine U; Götz, Thomas; Scheffler, Klaus; Klarhöfer, Markus; Berthomier, Christian; Strobel, Werner; Phillips, Christophe; Salmon, Eric; Cajochen, Christian; Schmidt, Christina

    2017-07-17

    The two-process model of sleep-wake regulation posits that sleep-wake-dependent homeostatic processes interact with the circadian timing system to affect human behavior. The circadian timing system is fundamental to maintaining stable cognitive performance, as it counteracts growing homeostatic sleep pressure during daytime. Using magnetic resonance imaging, we explored brain responses underlying working memory performance during the time of maximal circadian wake-promotion under varying sleep pressure conditions. Circadian wake-promoting strength was derived from the ability to sleep during an evening nap. Hypothalamic BOLD activity was positively linked to circadian wake-promoting strength under normal, but not under disproportionally high or low sleep pressure levels. Furthermore, higher hypothalamic activity under normal sleep pressure levels predicted better performance under sleep loss. Our results reappraise the two-process model by revealing a homeostatic-dose-dependent association between circadian wake-promotion and cognition-related hypothalamic activity.

  14. Nonsteroidal anti-inflammatory drugs repress β-secretase gene promoter activity by the activation of PPARγ

    Science.gov (United States)

    Sastre, Magdalena; Dewachter, Ilse; Rossner, Steffen; Bogdanovic, Nenad; Rosen, Evan; Borghgraef, Peter; Evert, Bernd O.; Dumitrescu-Ozimek, Lucia; Thal, Dietmar R.; Landreth, Gary; Walter, Jochen; Klockgether, Thomas; van Leuven, Fred; Heneka, Michael T.

    2006-01-01

    Epidemiological evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the risk for Alzheimer's disease (AD). Certain NSAIDs can activate the peroxisome proliferator-activated receptor-γ (PPARγ), which is a nuclear transcriptional regulator. Here we show that PPARγ depletion potentiates β-secretase [β-site amyloid precursor protein cleaving enzyme (BACE1)] mRNA levels by increasing BACE1 gene promoter activity. Conversely, overexpression of PPARγ, as well as NSAIDs and PPARγ activators, reduced BACE1 gene promoter activity. These results suggested that PPARγ could be a repressor of BACE1. We then identified a PPARγ responsive element (PPRE) in the BACE1 gene promoter. Mutagenesis of the PPRE abolished the binding of PPARγ to the PPRE and increased BACE1 gene promoter activity. Furthermore, proinflammatory cytokines decreased PPARγ gene transcription, and this effect was supressed by NSAIDs. We also demonstrate that in vivo treatment with PPARγ agonists increased PPARγ and reduced BACE1 mRNA and intracellular β-amyloid levels. Interestingly, brain extracts from AD patients showed decreased PPARγ expression and binding to PPRE in the BACE1 gene promoter. Our data strongly support a major role of PPARγ in the modulation of amyloid-β generation by inflammation and suggest that the protective mechanism of NSAIDs in AD involves activation of PPARγ and decreased BACE1 gene transcription. PMID:16407166

  15. Statins Activate Human PPAR Promoter and Increase PPAR mRNA Expression and Activation in HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Makoto Seo

    2008-01-01

    Full Text Available Statins increase peroxisome proliferator-activated receptor (PPAR mRNA expression, but the mechanism of this increased PPAR production remains elusive. To examine the regulation of PPAR production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin on human PPAR promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1 Majority of statins enhanced PPAR promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPAR promoter. This enhancement may be mediated by statin-induced HNF-4. (2 PPAR mRNA expression was increased by statin treatment. (3 The PPAR levels in nuclear fractions were increased by statin treatment. (4 Simvastatin, pravastatin, and cerivastatin markedly enhanced transcriptional activity in 293T cells cotransfected with acyl-coenzyme A oxidase promoter and PPAR/RXR expression vectors. In summary, these data demonstrate that PPAR production and activation are upregulated through the PPAR promoter activity by statin treatment.

  16. Construction and evaluation of a maize (Zea mays) chimaeric promoter with activity in kernel endosperm and embryo.

    Science.gov (United States)

    Shepherd, Colin T; Scott, M Paul

    2009-03-01

    Chimaeric promoters contain DNA sequences from different promoters. Chimaeric promoters are developed to increase the level of recombinant protein expression, to precisely control transgene activity or to combat homology-based gene silencing. Sets of chimaeric promoters, each containing different lengths of DNA from maize (Zea mays) 27zn (27 kDa gamma-zein) endosperm-specific promoter and the Glb1 (Globulin-1) embryo-specific promoter were created and tested in a transient expression assay of GFP (green fluorescent protein). Promoter fragments with the highest activity were combined to create the chimaeric promoter A27znGlb1. In the context of the chimaeric promoter, the selected Glb1 promoter fragment was necessary and sufficient to activate expression in embryo tissue and was functionally equivalent to the native Glb1 promoter. Similarly, the selected 27zn promoter fragment in the chimaeric promoter was necessary and sufficient to activate expression in endosperm tissue and was functionally equivalent to the native 27zn promoter. Maize transgenic plants containing the A27znGlb1 chimaeric promoter fused to GFP were produced to characterize this promoter in vivo. Quantitative reverse-transcriptase PCR was used to determine that the promoter was active in the embryo, endosperm, pericarp and immature leaf tissues. GFP activity in plants containing the chimaeric promoter was not significantly different in endosperm than the activity of GFP fused to the full-length 27zn promoter, nor was it different in embryo from the activity of GFP fused to the full-length Glb1 promoter. Transgene copy numbers were shown to be between 4 and 12 copies in different events.

  17. Activity monitor intervention to promote physical activity of physicians-in-training: randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Anne N Thorndike

    Full Text Available Physicians are expected to serve as role models for healthy lifestyles, but long work hours reduce time for healthy behaviors. A hospital-based physical activity intervention could improve physician health and increase counseling about exercise.We conducted a two-phase intervention among 104 medical residents at a large hospital in Boston, Massachusetts. Phase 1 was a 6-week randomized controlled trial comparing daily steps of residents assigned to an activity monitor displaying feedback about steps and energy consumed (intervention or to a blinded monitor (control. Phase 2 immediately followed and was a 6-week non-randomized team steps competition in which all participants wore monitors with feedback. Phase 1 outcomes were: 1 median steps/day and 2 proportion of days activity monitor worn. The Phase 2 outcome was mean steps/day on days monitor worn (≥500 steps/day. Physiologic measurements were collected at baseline and study end. Median steps/day were compared using Wilcoxon rank-sum tests. Mean steps were compared using repeated measures regression analyses.In Phase 1, intervention and control groups had similar activity (6369 vs. 6063 steps/day, p = 0.16 and compliance with wearing the monitor (77% vs. 77% of days, p = 0.73. In Phase 2 (team competition, residents recorded more steps/day than during Phase 1 (CONTROL: 7,971 vs. 7,567, p = 0.002;7,832 vs. 7,739, p = 0.13. Mean compliance with wearing the activity monitor decreased for both groups during Phase 2 compared to Phase 1 (60% vs. 77%, p<0.001. Mean systolic blood pressure decreased (p = 0.004 and HDL cholesterol increased (p<0.001 among all participants at end of study compared to baseline.Although the activity monitor intervention did not have a major impact on activity or health, the high participation rates of busy residents and modest changes in steps, blood pressure, and HDL suggest that more intensive hospital-based wellness programs have potential for

  18. l-Arginine Uptake by Cationic Amino Acid Transporter Promotes Intra-Macrophage Survival of Leishmania donovani by Enhancing Arginase-Mediated Polyamine Synthesis

    Directory of Open Access Journals (Sweden)

    Abhishek Mandal

    2017-07-01

    Full Text Available The survival of intracellular protozoan parasite, Leishmania donovani, the causative agent of Indian visceral leishmaniasis (VL, depends on the activation status of macrophages. l-Arginine, a semi-essential amino acid plays a crucial regulatory role for activation of macrophages. However, the role of l-arginine transport in VL still remains elusive. In this study, we demonstrated that intra-macrophage survival of L. donovani depends on the availability of extracellular l-arginine. Infection of THP-1-derived macrophage/human monocyte-derived macrophage (hMDM with Leishmania, resulted in upregulation of l-arginine transport. While investigating the involvement of the transporters, we observed that Leishmania survival was greatly impaired when the transporters were blocked either using inhibitor or siRNA-mediated downregulation. CAT-2 was found to be the main isoform associated with l-arginine transport in L. donovani-infected macrophages. l-arginine availability and its transport regulated the host arginase in Leishmania infection. Arginase and inducible nitric oxide synthase (iNOS expression were reciprocally regulated when assayed using specific inhibitors and siRNA-mediated downregulation. Interestingly, induction of iNOS expression and nitric oxide production were observed in case of inhibition of arginase in infected macrophages. Furthermore, inhibition of l-arginine transport as well as arginase resulted in decreased polyamine production, limiting parasite survival inside macrophages. l-arginine availability and transport regulated Th1/Th2 cytokine levels in case of Leishmania infection. Upregulation of l-arginine transport, induction of host arginase, and enhanced polyamine production were correlated with increased level of IL-10 and decreased level of IL-12 and TNF-α in L. donovani-infected macrophages. Our findings provide clear evidence for targeting the metabolism of l-arginine and l-arginine-metabolizing enzymes as an important

  19. l-Arginine Uptake by Cationic Amino Acid Transporter Promotes Intra-Macrophage Survival of Leishmania donovani by Enhancing Arginase-Mediated Polyamine Synthesis.

    Science.gov (United States)

    Mandal, Abhishek; Das, Sushmita; Kumar, Ajay; Roy, Saptarshi; Verma, Sudha; Ghosh, Ayan Kumar; Singh, Ruby; Abhishek, Kumar; Saini, Savita; Sardar, Abul Hasan; Purkait, Bidyut; Kumar, Ashish; Mandal, Chitra; Das, Pradeep

    2017-01-01

    The survival of intracellular protozoan parasite, Leishmania donovani, the causative agent of Indian visceral leishmaniasis (VL), depends on the activation status of macrophages. l-Arginine, a semi-essential amino acid plays a crucial regulatory role for activation of macrophages. However, the role of l-arginine transport in VL still remains elusive. In this study, we demonstrated that intra-macrophage survival of L. donovani depends on the availability of extracellular l-arginine. Infection of THP-1-derived macrophage/human monocyte-derived macrophage (hMDM) with Leishmania, resulted in upregulation of l-arginine transport. While investigating the involvement of the transporters, we observed that Leishmania survival was greatly impaired when the transporters were blocked either using inhibitor or siRNA-mediated downregulation. CAT-2 was found to be the main isoform associated with l-arginine transport in L. donovani-infected macrophages. l-arginine availability and its transport regulated the host arginase in Leishmania infection. Arginase and inducible nitric oxide synthase (iNOS) expression were reciprocally regulated when assayed using specific inhibitors and siRNA-mediated downregulation. Interestingly, induction of iNOS expression and nitric oxide production were observed in case of inhibition of arginase in infected macrophages. Furthermore, inhibition of l-arginine transport as well as arginase resulted in decreased polyamine production, limiting parasite survival inside macrophages. l-arginine availability and transport regulated Th1/Th2 cytokine levels in case of Leishmania infection. Upregulation of l-arginine transport, induction of host arginase, and enhanced polyamine production were correlated with increased level of IL-10 and decreased level of IL-12 and TNF-α in L. donovani-infected macrophages. Our findings provide clear evidence for targeting the metabolism of l-arginine and l-arginine-metabolizing enzymes as an important therapeutic and

  20. Cloning the Horse RNA Polymerase I Promoter and Its Application to Studying Influenza Virus Polymerase Activity

    Directory of Open Access Journals (Sweden)

    Gang Lu

    2016-05-01

    Full Text Available An influenza virus polymerase reconstitution assay based on the human, dog, or chicken RNA polymerase I (PolI promoter has been developed and widely used to study the polymerase activity of the influenza virus in corresponding cell types. Although it is an important member of the influenza virus family and has been known for sixty years, no studies have been performed to clone the horse PolI promoter or to study the polymerase activity of equine influenza virus (EIV in horse cells. In our study, the horse RNA PolI promoter was cloned from fetal equine lung cells. Using the luciferase assay, it was found that a 500 bp horse RNA PolI promoter sequence was required for efficient transcription. Then, using the developed polymerase reconstitution assay based on the horse RNA PolI promoter, the polymerase activity of two EIV strains was compared, and equine myxovirus resistance A protein was identified as having the inhibiting EIV polymerase activity function in horse cells. Our study enriches our knowledge of the RNA PolI promoter of eukaryotic species and provides a useful tool for the study of influenza virus polymerase activity in horse cells.

  1. Perceiving Promotion Activities İn Politic Marketing By Gazi University’ Students

    Directory of Open Access Journals (Sweden)

    Ahmet ÇATLI

    2013-06-01

    Full Text Available Political parties determine the marketing strategies about affecting electors, who have customer property. What, when and how do they want? After they can meet these wantings, needs and can subordinate other parties. Promotion activities also can be defined as election drive, is an mix of marketing. But as the seen changing of electors' wantings also in politic marketing, kinds and variations of promotion activities, especially in our technological age are more important than classic promotions. With this project inquiry work that consists of 9 parts also has done to know about how the university students are affected and which promotion activities affect the students more. İnquiry appliers are students in University of Gazi TTEF. In the inquiry, questioned to students that students' gender, incomes, the place they live, their enroling in political parties, being affected by promotion activities, if they are affected, by which promotion activity and how much they are affected, advertsement, public relations,personal marketing and marketing development.

  2. CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion

    Science.gov (United States)

    2011-01-01

    Background Chemotherapy heavily relies on apoptosis to kill breast cancer (BrCa) cells. Many breast tumors respond to chemotherapy, but cells that survive this initial response gain resistance to subsequent treatments. This leads to aggressive cell variants with an enhanced ability to migrate, invade and survive at secondary sites. Metastasis and chemoresistance are responsible for most cancer-related deaths; hence, therapies designed to minimize both are greatly needed. We have recently shown that CCR9-CCL25 interactions promote BrCa cell migration and invasion, while others have shown that this axis play important role in T cell survival. In this study we have shown potential role of CCR9-CCL25 axis in breast cancer cell survival and therapeutic efficacy of cisplatin. Methods Bromodeoxyuridine (BrdU) incorporation, Vybrant apoptosis and TUNEL assays were performed to ascertain the role of CCR9-CCL25 axis in cisplatin-induced apoptosis of BrCa cells. Fast Activated Cell-based ELISA (FACE) assay was used to quantify In situ activation of PI3Kp85, AktSer473, GSK-3βSer9 and FKHRThr24 in breast cancer cells with or without cisplatin treatment in presence or absence of CCL25. Results CCR9-CCL25 axis provides survival advantage to BrCa cells and inhibits cisplatin-induced apoptosis in a PI3K-dependent and focal adhesion kinase (FAK)-independent fashion. Furthermore, CCR9-CCL25 axis activates cell-survival signals through Akt and subsequent glycogen synthase kinase-3 beta (GSK-3β) and forkhead in human rhabdomyosarcoma (FKHR) inactivation. These results show that CCR9-CCL25 axis play important role in BrCa cell survival and low chemotherapeutic efficacy of cisplatin primarily through PI3K/Akt dependent fashion. PMID:21539750

  3. CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion

    Directory of Open Access Journals (Sweden)

    Lillard James W

    2011-05-01

    Full Text Available Abstract Background Chemotherapy heavily relies on apoptosis to kill breast cancer (BrCa cells. Many breast tumors respond to chemotherapy, but cells that survive this initial response gain resistance to subsequent treatments. This leads to aggressive cell variants with an enhanced ability to migrate, invade and survive at secondary sites. Metastasis and chemoresistance are responsible for most cancer-related deaths; hence, therapies designed to minimize both are greatly needed. We have recently shown that CCR9-CCL25 interactions promote BrCa cell migration and invasion, while others have shown that this axis play important role in T cell survival. In this study we have shown potential role of CCR9-CCL25 axis in breast cancer cell survival and therapeutic efficacy of cisplatin. Methods Bromodeoxyuridine (BrdU incorporation, Vybrant apoptosis and TUNEL assays were performed to ascertain the role of CCR9-CCL25 axis in cisplatin-induced apoptosis of BrCa cells. Fast Activated Cell-based ELISA (FACE assay was used to quantify In situ activation of PI3Kp85, AktSer473, GSK-3βSer9 and FKHRThr24 in breast cancer cells with or without cisplatin treatment in presence or absence of CCL25. Results CCR9-CCL25 axis provides survival advantage to BrCa cells and inhibits cisplatin-induced apoptosis in a PI3K-dependent and focal adhesion kinase (FAK-independent fashion. Furthermore, CCR9-CCL25 axis activates cell-survival signals through Akt and subsequent glycogen synthase kinase-3 beta (GSK-3β and forkhead in human rhabdomyosarcoma (FKHR inactivation. These results show that CCR9-CCL25 axis play important role in BrCa cell survival and low chemotherapeutic efficacy of cisplatin primarily through PI3K/Akt dependent fashion.

  4. CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion.

    Science.gov (United States)

    Johnson-Holiday, Crystal; Singh, Rajesh; Johnson, Erica L; Grizzle, William E; Lillard, James W; Singh, Shailesh

    2011-05-03

    Chemotherapy heavily relies on apoptosis to kill breast cancer (BrCa) cells. Many breast tumors respond to chemotherapy, but cells that survive this initial response gain resistance to subsequent treatments. This leads to aggressive cell variants with an enhanced ability to migrate, invade and survive at secondary sites. Metastasis and chemoresistance are responsible for most cancer-related deaths; hence, therapies designed to minimize both are greatly needed. We have recently shown that CCR9-CCL25 interactions promote BrCa cell migration and invasion, while others have shown that this axis play important role in T cell survival. In this study we have shown potential role of CCR9-CCL25 axis in breast cancer cell survival and therapeutic efficacy of cisplatin. Bromodeoxyuridine (BrdU) incorporation, Vybrant apoptosis and TUNEL assays were performed to ascertain the role of CCR9-CCL25 axis in cisplatin-induced apoptosis of BrCa cells. Fast Activated Cell-based ELISA (FACE) assay was used to quantify In situ activation of PI3Kp85, AktSer473, GSK-3βSer9 and FKHRThr24 in breast cancer cells with or without cisplatin treatment in presence or absence of CCL25. CCR9-CCL25 axis provides survival advantage to BrCa cells and inhibits cisplatin-induced apoptosis in a PI3K-dependent and focal adhesion kinase (FAK)-independent fashion. Furthermore, CCR9-CCL25 axis activates cell-survival signals through Akt and subsequent glycogen synthase kinase-3 beta (GSK-3β) and forkhead in human rhabdomyosarcoma (FKHR) inactivation. These results show that CCR9-CCL25 axis play important role in BrCa cell survival and low chemotherapeutic efficacy of cisplatin primarily through PI3K/Akt dependent fashion.

  5. SALSA: SAving Lives Staying Active to Promote Physical Activity and Healthy Eating

    Directory of Open Access Journals (Sweden)

    Rebecca E. Lee

    2011-01-01

    Full Text Available Physical inactivity, poor dietary habits, and obesity are vexing problems among minorities. SAving Lives, Staying Active (SALSA was an 8-week randomized controlled crossover design, pilot study to promote regular physical activity (PA and fruit and vegetable (FV consumption as a means to preventing weight gain among women of color. Participants completed measures of demographics, PA, and dietary habits. Women (=50;=42 years who participated were overweight (BMI=29.7 kg/m2; bodyfat=38.5% and reported low levels of leisure time PA (=10.7 MET-min/wk and FV consumption (=4.2 servings/day. All were randomized to a four-week (1 semiweekly Latin dance group or (2 internet-based dietary education group. All participants reported a significant increase in weekly leisure time PA from baseline (=10.7 MET-min/wk to follow up (=34.0 MET-min/wk, <.001, and FV consumption increased over time by group (=.02. Data suggest that Latin dance interventions to improve PA and web-based interventions to improve dietary habits show promise for improving health among women of color.

  6. MAGEB2 is activated by promoter demethylation in head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Kavita M Pattani

    Full Text Available PURPOSE: Although promoter hypermethylation has been an accepted means of tumor suppressor gene inactivation, activation of otherwise normally repressed proto-oncogenes by promoter demethylation has been infrequently documented. EXPERIMENTAL DESIGN: In this study we performed an integrative, whole-genome analysis for discovery of epigenetically activated proto-oncogenes in head and neck cancer tumors. We used the 47K GeneChip U133 Plus 2.0 Affymetrix expression microarray platform to obtain re-expression data from 5-aza treated normal cell line and expression data from primary head and neck squamous cell carcinoma (HNSCC tumor tissues and normal mucosa tissues. We then investigated candidate genes by screening promoter regions for CpG islands and bisulfite sequencing followed by QUMSP and RT PCR for the best candidate genes. Finally, functional studies were performed on the top candidate gene. RESULTS: From the top 178 screened candidates 96 had CpG islands in their promoter region. Seven candidate genes showed promoter region methylation in normal mucosa samples and promoter demethylation in a small cohort of primary HNSCC tissues. We then studied the demethylation of the top 3 candidate genes in an expanded cohort of 76 HNSCC tissue samples and 17 normal mucosa samples. We identified MAGEB2 as having significant promoter demethylation in primary head and neck squamous cell carcinoma tissues. We then found significantly higher expression of MAGEB2 in tumors in a separate cohort of 73 primary HNSCC tissues and 31 normal tissues. Finally, we found that MAGEB2 has growth promoting effects on minimally transformed oral keratinocyte cell lines but not a definite effect on HNSCC cell lines. CONCLUSION: In conclusion, we identified MAGEB2 as activated by promoter demethylation in HNSCCand demonstrates growth promoting effects in a minimally transformed oral keratinocyte cell line. More studies are needed to evaluate MAGBE2's exact role in HNSCC.

  7. DNA hypomethylation-mediated activation of Cancer/Testis Antigen 45 (CT45) genes is associated with disease progression and reduced survival in epithelial ovarian cancer.

    Science.gov (United States)

    Zhang, Wa; Barger, Carter J; Link, Petra A; Mhawech-Fauceglia, Paulette; Miller, Austin; Akers, Stacey N; Odunsi, Kunle; Karpf, Adam R

    2015-01-01

    Epithelial ovarian cancer (EOC) is a highly lethal malignancy due to a lack of early detection approaches coupled with poor outcomes for patients with clinically advanced disease. Cancer-testis (CT) or cancer-germline genes encode antigens known to generate spontaneous anti-tumor immunity in cancer patients. CT45 genes are a recently discovered 6-member family of X-linked CT genes with oncogenic function. Here, we determined CT45 expression in EOC and fully defined its epigenetic regulation by DNA methylation. CT45 was silent and hypermethylated in normal control tissues, but a large subset of EOC samples showed increased CT45 expression in conjunction with promoter DNA hypomethylation. In contrast, copy number status did not correlate with CT45 expression in the TCGA database for EOC. CT45 promoter methylation inversely correlated with both CT45 mRNA and protein expression, the latter determined using IHC staining of an EOC TMA. CT45 expression was increased and CT45 promoter methylation was decreased in late-stage and high-grade EOC, and both measures were associated with poor survival. CT45 hypomethylation was directly associated with LINE-1 hypomethylation, and CT45 was frequently co-expressed with other CT antigen genes in EOC. Decitabine treatment induced CT45 mRNA and protein expression in EOC cells, and promoter transgene analyses indicated that DNA methylation directly represses CT45 promoter activity. These data verify CT45 expression and promoter hypomethylation as possible prognostic biomarkers, and suggest CT45 as an immunological or therapeutic target in EOC. Treatment with decitabine or other epigenetic modulators could provide a means for more effective immunological targeting of CT45.

  8. Natural lecithin promotes neural network complexity and activity.

    Science.gov (United States)

    Latifi, Shahrzad; Tamayol, Ali; Habibey, Rouhollah; Sabzevari, Reza; Kahn, Cyril; Geny, David; Eftekharpour, Eftekhar; Annabi, Nasim; Blau, Axel; Linder, Michel; Arab-Tehrany, Elmira

    2016-05-27

    Phospholipids in the brain cell membranes contain different polyunsaturated fatty acids (PUFAs), which are critical to nervous system function and structure. In particular, brain function critically depends on the uptake of the so-called "essential" fatty acids such as omega-3 (n-3) and omega-6 (n-6) PUFAs that cannot be readily synthesized by the human body. We extracted natural lecithin rich in various PUFAs from a marine source and transformed it into nanoliposomes. These nanoliposomes increased neurite outgrowth, network complexity and neural activity of cortical rat neurons in vitro. We also observed an upregulation of synapsin I (SYN1), which supports the positive role of lecithin in synaptogenesis, synaptic development and maturation. These findings suggest that lecithin nanoliposomes enhance neuronal development, which may have an impact on devising new lecithin delivery strategies for therapeutic applications.

  9. Activating lay health influencers to promote tobacco cessation.

    Science.gov (United States)

    Muramoto, Myra L; Hall, John R; Nichter, Mark; Nichter, Mimi; Aickin, Mikel; Connolly, Tim; Matthews, Eva; Campbell, Jean Z; Lando, Harry A

    2014-05-01

    To evaluate the effect of tobacco cessation brief-intervention (BI) training for lay "health influencers," on knowledge, self-efficacy and the proportion of participants reporting BI delivery post-training. Randomized, community-based study comparing In-person or Web-based training, with mailed materials. In-person and Web-training groups had significant post-training cessation knowledge and self-efficacy gains. All groups increased the proportion of individuals reporting BIs at follow-up, with no significant between-group differences. Irrespective of participants' prior intervention experience, 80%-86% reported BIs within the past 90 days; 71%-79% reported >1 in the past 30. Web and In-person training significantly increase health influencer cessation knowledge and self-efficacy. With minimal prompting and materials, even persons without BI experience can be activated to encourage tobacco cessation.

  10. Promoting Active Learning in Electrical Engineering Basic Studies

    Directory of Open Access Journals (Sweden)

    Anu Lehtovuori

    2013-05-01

    Full Text Available Active learning, project-based teaching, and student collaboration are current trends in engineering education. Incorporating these have also been the goal of the basic studies development project EPOP started at the Aalto University School of Electrical Engineering in 2011. In the project, two obligatory basic courses in circuit analysis and electromagnetic field theory have been taught using interactive engagement during the spring of 2012. This paper presents the implementation of the teaching, including methods and evaluation with several concrete examples. As a result of the novel teaching, motivation and the engagement of students were at a high level during the whole course and learning results were better than those of the students participating the traditional lecture course.

  11. Biomineralization of Uranium by PhoY Phosphatase Activity Aids Cell Survival in Caulobacter crescentus

    Energy Technology Data Exchange (ETDEWEB)

    Yung, M C [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Jiao, Y [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2014-07-22

    Caulobacter crescentus is known to tolerate high levels of uranium [U(VI)], but its detoxification mechanism is poorly understood. Here we show that C. crescentus is able to facilitate U(VI) biomineralization through the formation of U-Pi precipitates via its native alkaline phosphatase activity. The U-Pi precipitates, deposited on the cell surface in the form of meta-autunite structures, have a lower U/Pi ratio than do chemically produced precipitates. The enzyme that is responsible for the phosphatase activity and thus the biomineralization process is identified as PhoY, a periplasmic alkaline phosphatase with broad substrate specificity. Furthermore, PhoY is shown to confer a survival advantage on C. crescentus toward U(VI) under both growth and nongrowth conditions. Results obtained in this study thus highlight U(VI) biomineralization as a resistance mechanism in microbes, which not only improves our understanding of bacterium-mineral interactions but also aids in defining potential ecological niches for metal-resistant bacteria.

  12. Changes in the expression of pituitary adenylate cyclase-activating polypeptide in the human placenta during pregnancy and its effects on the survival of JAR choriocarcinoma cells.

    Science.gov (United States)

    Brubel, R; Boronkai, A; Reglodi, D; Racz, B; Nemeth, J; Kiss, P; Lubics, A; Toth, G; Horvath, G; Varga, T; Szogyi, D; Fonagy, E; Farkas, J; Barakonyi, A; Bellyei, Sz; Szereday, L; Koppan, M; Tamas, A

    2010-11-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide with survival-promoting actions, has been observed in endocrine organs and is thought to play a role in reproductive functions, including pregnancy. PACAP occurs in two forms, 27 and 38 amino acid residues, with PACAP38 being the predominant form in human tissues. In the present study, we determined the concentrations of PACAP38 and PACAP27 in first-trimester and full-term human placentas using radioimmunoassay. We found high levels of PACAP38 and lower levels of PACAP27 in different parts of the full-term human placenta. PACAP38 content increased in the placenta during pregnancy, both on the maternal side and on the fetal side. The effects of PACAP on the survival of JAR human choriocarcinoma cells were investigated using flow cytometry and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) cell viability assay in cells exposed to the widely used chemotherapeutic agent methotrexate (MTX). It was found that PACAP neither influenced the survival of JAR cytotrophoblast cells nor affected cellular response to the death-inducing effect of the chemotherapeutic agent MTX. The present observations further support the significance of PACAP in the human placenta. The observation that PACAP did not influence the effects of MTX may have future clinical importance, showing that PACAP does not decrease the effects of certain chemotherapeutic agents.

  13. HIV-1 matrix protein p17 promotes lymphangiogenesis and activates the endothelin-1/endothelin B receptor axis.

    Science.gov (United States)

    Caccuri, Francesca; Rueckert, Christine; Giagulli, Cinzia; Schulze, Kai; Basta, Daniele; Zicari, Sonia; Marsico, Stefania; Cervi, Edoardo; Fiorentini, Simona; Slevin, Mark; Guzman, Carlos A; Caruso, Arnaldo

    2014-04-01

    AIDS-related lymphomas are high grade and aggressively metastatic with poor prognosis. Lymphangiogenesis is essential in supporting proliferation and survival of lymphoma, as well as tumor dissemination. Data suggest that aberrant lymphangiogenesis relies on action of HIV-1 proteins rather than on a direct effect of the virus itself. HIV-1 matrix protein p17 was found to accumulate and persist in lymph nodes of patients even under highly active antiretroviral therapy. Because p17 was recently found to exert a potent proangiogenic activity by interacting with chemokine (C-X-C motif) receptors 1 and 2, we tested the prolymphangiogenic activity of the viral protein. Human primary lymph node-derived lymphatic endothelial cells were used to perform capillary-like structure formation, wound healing, spheroids, and Western blot assays after stimulation with or without p17. Here, we show that p17 promotes lymphangiogenesis by binding to chemokine (C-X-C motif) receptor-1 and chemokine (C-X-C motif) receptor-2 expressed on lymph node-derived lymphatic endothelial cells and activating the Akt/extracellular signal-regulated kinase signaling pathway. In particular, it was found to induce capillary-like structure formation, sprout formation from spheroids, and increase lymph node-derived lymphatic endothelial cells motility. The p17 lymphangiogenic activity was, in part, sustained by activation of the endothelin-1/endothelin receptor B axis. A Matrigel plug assay showed that p17 was able to promote the outgrowth of lymphatic vessels in vivo, demonstrating that p17 directly regulates lymphatic vessel formation. Our results suggest that p17 may generate a prolymphangiogenic microenvironment and plays a role in predisposing the lymph node to lymphoma growth and metastasis. This finding offers new opportunities to identify treatment strategies in combating AIDS-related lymphomas.

  14. Saturation mutagenesis of the TATA box and upstream activator sequence in the haloarchaeal bop gene promoter.

    Science.gov (United States)

    Baliga, N S; DasSarma, S

    1999-04-01

    Degenerate oligonucleotides were used to randomize 21 bp of the 53-bp minimal bop promoter in three 7-bp segments, including the putative TATA box and the upstream activator sequence (UAS). The mutagenized bop promoter and the wild-type structural gene and transcriptional terminator were inserted into a shuttle plasmid capable of replication in the halophilic archaeon Halobacterium sp. strain S9. Active promoters were isolated by screening transformants of an orange (Pum- bop) Halobacterium mutant for purple (Pum+ bop+) colonies on agar plates and analyzed for bop mRNA and/or bacteriorhodopsin content. Sequence analysis yielded the consensus sequence 5'-tyT(T/a)Ta-3', corresponding to the promoter TATA box element 30 to 25 bp 5' of the transcription start site. A putative UAS, 5'-ACCcnactagTTnG-3', located 52 to 39 bp 5' of the transcription start site was found to be conserved in active promoters. This study provides direct evidence for the requirement of the TATA box and UAS for bop promoter activity.

  15. RNF183 promotes proliferation and metastasis of colorectal cancer cells via activation of NF-κB-IL-8 axis.

    Science.gov (United States)

    Geng, Rong; Tan, Xin; Wu, Jiangxue; Pan, Zhizhong; Yi, Min; Shi, Wei; Liu, Ranyi; Yao, Chen; Wang, Gaoyuan; Lin, Jiaxin; Qiu, Lin; Huang, Wenlin; Chen, Shuai

    2017-08-10

    Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, which is a heterogeneous disease and main risk factors are associated with inflammation, family history, genetic mutations, epigenetics, and so on. Ring finger domain proteins have been reported involved in carcinogenesis, whereas their roles in CRC are rarely studied. Here, we reanalyzed the expression of 202 RNF family members in CRC using published microarray data from GEO database and found that RNF183 is markedly upregulated in tumor tissues. RNF183 high expression is significantly associated with tumor size (P=0.012), tumor invasive depth (P=0.004), TNM stage (P=0.01), and distant metastasis (P=0.009). CRC patients with high expression of RNF183 have poor overall survival (P8. Blockage of NF-κB by small molecule inhibitor or depletion of IL-8 by siRNA attenuates the function of RNF183 to promote cell migration. Moreover, the regulation of RNF183 on IL-8 transcription and cell viability/motility is dependent on its E3 ubiquitin ligase activity. Our study provided proof of principle to show that RNF183 promotes proliferation and metastasis of CRC cells via activation of NF-κB-IL-8 axis.

  16. Promotion of physical activity among senior high school students by applying educational counseling at school

    OpenAIRE

    Indriūnienė, Vinga

    2013-01-01

    Physical activity is one of the key factors in strengthening health. Yet, in Lithuania as well as in the whole world, the physical activity among youngsters is insufficient. The sudden decrease of physical activity during this period is becoming a huge