12 research outputs found

    Gastrin stabilises ÎČ-catenin protein in mouse colorectal cancer cells

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    As gastrin may play a role in the pathophysiology of gastrointestinal (GI) malignancies, the elucidation of the mechanisms governing gastrin-induced proliferation has recently gained considerable interest. Several studies have reported that a large percentage of colorectal tumours overexpress or stabilise the ÎČ-catenin oncoprotein. We thus sought to determine whether gastrin might regulate ÎČ-catenin expression in colorectal tumour cells. Amidated gastrin-17 (G-17), one of the major circulating forms of gastrin, not only enhanced ÎČ-catenin protein expression, but also one of its target genes, cyclin D1. Furthermore, activation of ÎČ-catenin-dependent transcription by gastrin was confirmed by an increase in LEF-1 reporter activity, as well as enhanced cyclin D1 promoter activity. Finally, G-17 prolonged the τ1/2 of ÎČ-catenin protein, demonstrating that gastrin appears to exert its mitogenic effects on colorectal tumour cells, at least in part, by stabilising ÎČ-catenin

    Global urban environmental change drives adaptation in white clover

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    Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

    Inactivation of LEF1 in T-cell acute lymphoblastic leukemia

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    To further unravel the molecular pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL), we performed high-resolution array comparative genomic hybridization on diagnostic specimens from 47 children with T-ALL and identified monoallelic or biallelic LEF1 microdeletions in 11% (5 of 47) of these primary samples. An additional 7% (3 of 44) of the cases harbored nonsynonymous sequence alterations of LEF1, 2 of which produced premature stop codons. Gene expression microarrays showed increased expression of MYC and MYC targets in cases with LEF1 inactivation, as well as differentiation arrest at an early cortical stage of thymocyte development characterized by expression of CD1B, CD1E, and CD8, with absent CD34 expression. LEF1 inactivation was associated with a younger age at the time of T-ALL diagnosis, as well as activating NOTCH1 mutations, biallelic INK4a/ARF deletions, and PTEN loss-of-function mutations or activating mutations of PI3K or AKT genes. These cases generally lacked overexpression of the TAL1, HOX11, HOX11L2, or the HOXA cluster genes, which have been used to define separate molecular pathways leading to T-ALL. Our findings suggest that LEF1 inactivation is an important step in the molecular pathogenesis of T-ALL in a subset of young children

    Measurement of the J/ψ\psi photoproduction cross section over the full near-threshold kinematic region

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    We report the total and differential cross sections for J / ψ photoproduction with the large acceptance GlueX spectrometer for photon beam energies from the threshold at 8.2 GeV up to 11.44 GeV and over the full kinematic range of momentum transfer squared, t . Such coverage facilitates the extrapolation of the differential cross sections to the forward ( t = 0 ) point beyond the physical region. The forward cross section is used by many theoretical models and plays an important role in understanding J / ψ photoproduction and its relation to the J / ψ -proton interaction. These measurements of J / ψ photoproduction near threshold are also crucial inputs to theoretical models that are used to study important aspects of the gluon structure of the proton, such as the gluon generalized parton distribution of the proton, the mass radius of the proton, and the trace anomaly contribution to the proton mass. We observe possible structures in the total cross section energy dependence and find evidence for contributions beyond gluon exchange in the differential cross section close to threshold, both of which are consistent with contributions from open-charm intermediate states

    Radiative decays of the Sigma(0)(1385) and Lambda(1520) hyperons

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    The electromagnetic decays of the Sig0(1385) and Lambda(1520) hyperons were studied in photon-induced reactions gamma p -> K+ Lambda(1116)gamma in the CLAS detector at the Thomas Jefferson National Accelerator Facility. We report the first observation of the radiative decay of the Sig0(1385) and a measurement of the Lambda(1520) radiative decay width. For the Sig0(1385) -> Lambda(1116)gamma transition, we measured a partial width of 479+/-120(stat)+81-100(sys) keV, larger than all of the existing model predictions. For the Lambda(1520) -> Lambda(1116)gamma transition, we obtained a partial width of 167+/-43(stat)+26-12(sys) keV

    Global urban environmental change drives adaptation in white clover

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    Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

    Global urban environmental change drives adaptation in white clover

    No full text
    Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale
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