394 research outputs found

    GLUT3 is induced during epithelial-mesenchymal transition and promotes tumor cell proliferation in non-small cell lung cancer.

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    BACKGROUND: Alterations in glucose metabolism and epithelial-mesenchymal transition (EMT) constitute two important characteristics of carcinoma progression toward invasive cancer. Despite an extensive characterization of each of them separately, the links between EMT and glucose metabolism of tumor cells remain elusive. Here we show that the neuronal glucose transporter GLUT3 contributes to glucose uptake and proliferation of lung tumor cells that have undergone an EMT. RESULTS: Using a panel of human non-small cell lung cancer (NSCLC) cell lines, we demonstrate that GLUT3 is strongly expressed in mesenchymal, but not epithelial cells, a finding corroborated in hepatoma cells. Furthermore, we identify that ZEB1 binds to the GLUT3 gene to activate transcription. Importantly, inhibiting GLUT3 expression reduces glucose import and the proliferation of mesenchymal lung tumor cells, whereas ectopic expression in epithelial cells sustains proliferation in low glucose. Using a large microarray data collection of human NSCLCs, we determine that GLUT3 expression correlates with EMT markers and is prognostic of poor overall survival. CONCLUSIONS: Altogether, our results reveal that GLUT3 is a transcriptional target of ZEB1 and that this glucose transporter plays an important role in lung cancer, when tumor cells loose their epithelial characteristics to become more invasive. Moreover, these findings emphasize the development of GLUT3 inhibitory drugs as a targeted therapy for the treatment of patients with poorly differentiated tumors

    Adaptation of Left Ventricular Twist Mechanics in Exercise-Trained Children Is Only Evident after the Adolescent Growth Spurt.

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    The extent of structural cardiac remodeling in response to endurance training is maturity dependent. In adults, this structural adaptation is often associated with the adaptation of left ventricular (LV) twist mechanics. For example, an increase in LV twist often follows an expansion in end-diastolic volume, whereas a reduction in twist may follow a thickening of the LV walls. While structural cardiac remodeling has been shown to be more prominent post-peak height velocity (PHV), it remains to be determined how this maturation-dependent structural remodeling influences LV twist. Therefore, we aimed to (1) compare LV twist mechanics between trained and untrained children pre- and post-PHV and (2) investigate how LV structural variables relate to LV twist mechanics pre- and post-PHV. Left ventricular function and morphology were assessed (echocardiography) in endurance-trained and untrained boys (n = 38 and n = 28, respectively) and girls (n = 39 and n = 34, respectively). Participants were categorized as either pre- or post-PHV using maturity offset to estimate somatic maturation. Pre-PHV, there were no differences in LV twist or torsion between trained and untrained boys (twist: P = .630; torsion: P = .382) or girls (twist: P = .502; torsion: P = .316), and LV twist mechanics were not related with any LV structural variables (P > .05). Post-PHV, LV twist was lower in trained versus untrained boys (P = .004), with torsion lower in trained groups, irrespective of sex (boys: P < .001; girls: P = .017). Moreover, LV torsion was inversely related to LV mass (boys: r = -0.55, P = .001; girls: r = -0.46, P = .003) and end-diastolic volume (boys: r = -0.64, P < .001; girls: r = -0.36, P = .025) in both sexes. A difference in LV twist mechanics between endurance-trained and untrained cohorts is only apparent post-PHV, where structural and functional remodeling were related

    Universal extra dimensions and Z->b bar-b

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    We study, at the one loop level, the dominant contributions from a single universal extra dimension to the process (Z\to b\bar{b}). By resorting to the gaugeless limit of the theory we explain why the result is expected to display a strong dependence on the mass of the top-quark, not identified in the early literature. A detailed calculation corroborates this expectation, giving rise to a lower bound for the compactification scale which is comparable to that obtained from the ρ\rho parameter. An estimate of the subleading corrections is furnished, together with a qualitative discussion on the difference between the present results and those derived previously for the non-universal case.Comment: 16 pages, 4 figures, revtex

    Ultraviolet sensitivity of rare decays in nonuniversal extra dimensional models

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    We consider a nonuniversal five dimensional model in which fermions are localised on a four dimensional brane, while gauge bosons and a scalar doublet can travel in the bulk. As a result of KK number non-conservation at the brane-bulk intersection, the ultraviolet divergence does not cancel out in some physical observables. For example, the Bdl+lB_d \to l^+l^- decay amplitude is linearly divergent, while BB--Bˉ\bar{B} mixing amplitude is log divergent. We attempt to identify the exact source of this nonrenormalizability. We compare and contrast our results with those obtained in the universal five dimensional model where all particles travel in the extra dimension.Comment: Latex, 11 pages, uses axodraw.st

    FCNC Top Quark Decays in Extra Dimensions

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    The flavor changing neutral top quark decay t -> c X is computed, where X is a neutral standard model particle, in a extended model with a single extra dimension. The cases for the photon, X= \gamma,andaStandardModelHiggsboson,X=H,areanalyzedindetailinanonlinear, and a Standard Model Higgs boson, X = H, are analyzed in detail in a non-linearR_\xi gauge. We find that the branching ratios can be enhanced by the dynamics originated in the extra dimension. In the limit where 1/R >> ->, we have found Br(t -> c \gamma) \simeq 10^{-10} for 1/R = 0.5 TeV. For the decay t -> c H, we have found Br(t -> cH) \simeq 10^{-10} for a low Higgs mass value. The branching ratios go to zero when 1/R -> \infty.Comment: Accepted to be published in the Europ. Phys. Jour. C; 16 pages, 2 figure

    Long-term ocean and resource dynamics in a hotspot of climate change

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    Unidad de excelencia María de Maeztu CEX2019-000940-MThe abundance, distribution, and size of marine species are linked to temperature and nutrient regimes and are profoundly affected by humans through exploitation and climate change. Yet little is known about long-term historical links between ocean environmental changes and resource abundance to provide context for current and potential future trends and inform conservation and management. We synthesize >4000 years of climate and marine ecosystem dynamics in a Northwest Atlantic region currently undergoing rapid changes, the Gulf of Maine and Scotian Shelf. This period spans the late Holocene cooling and recent warming and includes both Indigenous and European influence. We compare environmental records from instrumental, sedimentary, coral, and mollusk archives with ecological records from fossils, archaeological, historical, and modern data, and integrate future model projections of environmental and ecosystem changes. This multidisciplinary synthesis provides insight into multiple reference points and shifting baselines of environmental and ecosystem conditions, and projects a near-future departure from natural climate variability in 2028 for the Scotian Shelf and 2034 for the Gulf of Maine. Our work helps advancing integrative end-to-end modeling to improve the predictive capacity of ecosystem forecasts with climate change. Our results can be used to adjust marine conservation strategies and network planning and adapt ecosystem-based management with climate change

    Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

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    A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

    Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

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    Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02
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