112 research outputs found

    Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction

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    Wnt signaling affects fundamental development pathways and, if aberrantly activated, promotes the development of cancers. Wnt signaling is modulated by different factors, but whether the mitochondria! energetic state affects Wnt signaling is unknown. Here, we show that sublethal concentrations of different compounds that decrease mitochondrial ATP production specifically downregulate Wnt/beta-catenin signaling in vitro in colon cancer cells and in vivo in zebrafish reporter lines. Accordingly, fibroblasts from a GRACILE syndrome patient and a generated zebrafish model lead to reduced Wnt signaling. We identify a mitochondria-Wnt signaling axis whereby a decrease in mitochondria! ATP reduces calcium uptake into the endoplasmic reticulum (ER), leading to endoplasmic reticulum stress and to impaired Wnt signaling. In turn, the recovery of the ATP level or the inhibition of endoplasmic reticulum stress restores Wnt activity. These findings reveal a mechanism that links mitochondria! energetic metabolism to the control of the Wnt pathway that may be beneficial against several pathologie

    Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction

    Get PDF
    Wnt signaling affects fundamental development pathways and, if aberrantly activated, promotes the development of cancers. Wnt signaling is modulated by different factors, but whether the mitochondria! energetic state affects Wnt signaling is unknown. Here, we show that sublethal concentrations of different compounds that decrease mitochondrial ATP production specifically downregulate Wnt/beta-catenin signaling in vitro in colon cancer cells and in vivo in zebrafish reporter lines. Accordingly, fibroblasts from a GRACILE syndrome patient and a generated zebrafish model lead to reduced Wnt signaling. We identify a mitochondria-Wnt signaling axis whereby a decrease in mitochondria! ATP reduces calcium uptake into the endoplasmic reticulum (ER), leading to endoplasmic reticulum stress and to impaired Wnt signaling. In turn, the recovery of the ATP level or the inhibition of endoplasmic reticulum stress restores Wnt activity. These findings reveal a mechanism that links mitochondria! energetic metabolism to the control of the Wnt pathway that may be beneficial against several pathologie

    Advanced Television Research Program

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    Contains an introduction and reports on twelve research projects.Advanced Television Research ProgramNational Science Foundation Grant MIP 87-14969National Science Foundation FellowshipKodak Fellowshi

    How to Educate Entrepreneurs?

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    Entrepreneurship education has two purposes: To improve students’ entrepreneurial skills and to provide impetus to those suited to entrepreneurship while discouraging the rest. While entrepreneurship education helps students to make a vocational decision its effects may conflict for those not suited to entrepreneurship. This study shows that vocational and the skill formation effects of entrepreneurship education can be identified empirically by drawing on the Theory of Planned Behavior. This is embedded in a structural equation model which we estimate and test using a robust 2SLS estimator. We find that the attitudinal factors posited by the Theory of Planned Behavior are positively correlated with students’ entrepreneurial intentions. While conflicting effects of vocational and skill directed course content are observed in some individuals, overall these types of content are complements. This finding contradicts previous results in the literature. We reconcile the conflicting findings and discuss implications for the design of entrepreneurship courses

    Lymphatic vessels assessment in feline mammary tumours

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    BACKGROUND: The lymphatic vessels play a crucial role in a variety of human cancers since tumour cell lymphatic invasion significantly influences prognosis. It is not known if pre-existing lymphatics are enough for tumour dissemination or de novo development is necessary. VEGFR-3 is an angiogenetic mediator for both lymphatic and blood vessels during embryonic development, and only for lymphatics after birth. VEGF is a mediator of both vasculogenesis and angiogenesis, regulates the growth of lymphatics in various experimental models, and is produced in many solid tumours. CD44 mediates hyaluronic acid (HA)-dependent cell adhesion: besides promoting invasion, this interaction also supports neoangiogenesis that indirectly stimulates tumour cell proliferation. The expression of VEGF-C (Vascular Endothelial Growth Factor – C), its receptor VEGFR-3 and CD44, were studied on feline mammary samples to assess the importance of lymphangiogenesis and lymphangiotrophism in neoplasia. METHODS: Samples were taken from six normal mammary glands (NMG), ten benign (BT) and 32 malignant (MT) tumours. Immunohistochemical laminin/VEGFR-3 double stain, VEGF-C and CD44 stains were applied to 4 μm-thick sections, and their expression evaluated in intratumoral/extratumoral and intramammary/extramammary fields. RESULTS: All groups revealed a higher number of lymphatics in the extratumoral/extramammary areas. VEGF-C expression in the epithelium paralleled the number of positive vessels in the NMG, BT and MT, whereas VEGF-C higher expression was noted in the intratumoral fields only in infiltrating MT. CD44 score was lower in extratumoral than intratumoral fields in tumours and showed a significant increase in extramammary/extratumoral fields from NMG to MT. Pearson test showed a significant and inversely proportional correlation between CD44 expression and the number of lymphatic vessels with VEGFR-3 in malignant infiltrating tumours. CONCLUSION: The number of both VEGFR-3 positive and negative lymphatics in the extratumoral and extramammary stroma was significantly higher than intratumoral and intramammary fields respectively in the NMG, BT and MT. This suggests a scant biological importance of intratumoral lymphatics while their higher number is due to the concentration of existing vessels following compression of the extratumoral stroma in spite of a non demonstrable increase from NMG to MT. The tumour model employed provided no evidence of lymphangiogenesis, and metastasis in the regional lymph node develops following the spread through the pre-existing lymphatic network

    Strange particle production in proton-proton collisions at s=0.9\sqrt{s}=0.9 TeV with ALICE at the LHC

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    The production of mesons containing strange quarks (Ks0^0_s, ϕ\phi) and both singly and doubly strange baryons (Λ\Lambda, Anti-Λ\Lambda, and Ξ\Xi+Anti-Ξ\Xi) are measured at central rapidity in pp collisions at s\sqrt{s} = 0.9 TeV with the ALICE experiment at the LHC. The results are obtained from the analysis of about 250 k minimum bias events recorded in 2009. Measurements of yields (dN/dy) and transverse momentum spectra at central rapidities for inelastic pp collisions are presented. For mesons, we report yields () of 0.184 ±\pm 0.002 stat. ±\pm 0.006 syst. for Ks0^0_s and 0.021 ±\pm 0.004 stat. ±\pm 0.003 syst. for ϕ\phi. For baryons, we find = 0.048 ±\pm 0.001 stat. ±\pm 0.004 syst. for Λ\Lambda, 0.047 ±\pm 0.002 stat. ±\pm 0.005 syst. for Anti-Λ\Lambda and 0.0101 ±\pm 0.0020 stat. ±\pm 0.0009 syst. for Ξ\Xi+Anti-Ξ\Xi. The results are also compared with predictions for identified particle spectra from QCD-inspired models and provide a baseline for comparisons with both future pp measurements at higher energies and heavy-ion collisions.Comment: 33 pages, 21 captioned figures, 10 tables, authors from page 28, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/387

    Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

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    The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

    Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

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    The yield of charged particles associated with high-pTp_{\rm T} trigger particles (8<pT<158 < p_{\rm T} < 15 GeV/cc) is measured with the ALICE detector in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV relative to proton-proton collisions at the same energy. The conditional per-trigger yields are extracted from the narrow jet-like correlation peaks in azimuthal di-hadron correlations. In the 5% most central collisions, we observe that the yield of associated charged particles with transverse momenta pT>3p_{\rm T}> 3 GeV/cc on the away-side drops to about 60% of that observed in pp collisions, while on the near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/350

    Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

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    Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at sNN\sqrt{s_{_{\rm NN}}} = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in η<0.8|\eta|<0.8 and 0.3<pT<200.3 < p_T < 20 GeV/cc are compared to the expectation in pp collisions at the same sNN\sqrt{s_{\rm NN}}, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor RAAR_{\rm AA}. The result indicates only weak medium effects (RAAR_{\rm AA} \approx 0.7) in peripheral collisions. In central collisions, RAAR_{\rm AA} reaches a minimum of about 0.14 at pT=6p_{\rm T}=6-7GeV/cc and increases significantly at larger pTp_{\rm T}. The measured suppression of high-pTp_{\rm T} particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98
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