332 research outputs found

    Metal enrichment in elliptical galaxies and globular clusters through the study of iron and H-beta spectral indices

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    Chemical evolution of elliptical galaxies and globular clusters is addressed through a combined study of the iron indices at 5270 and 5335 A, and of the H-Beta line strength. The observational database of 74 standard stars (both dwarfs and giants) referred to in a previous paper (Buzzoni et al. (1992)) complemented with the data of Faber et al. (1985) and Gorgas et al. (1993) allowed us to explore here Fe and H-Beta index dependence on stellar temperature, gravity, and metallicity. The derived fitting functions were then included into Buzzoni's (1989) code for population synthesis in order to derive expected integrated indices for simple stellar populations and compare with observations. Partition of metals in the current chemical mix of galaxies and globulars has been constrained supporting the claim that light alpha elements might be enhanced in the globular cluster metal-poor population. An alternative conclusion resting on the standard framework with (alpha/Fe) = 0 would require a systematically larger age, about 18-20 Gyr. Iron and magnesium in ellipticals are found in average solar but a systematic trend of (Mg/Fe) vs global metallicity does exist with iron more deficient with respect to magnesium at high Z. We conclude that this effect might indicate that Fe abundance per unit mass in the galaxies is constant (suggesting a constant rate per unit mass of SN I events) while light metals supplied by SNe II should have been more effectively enriched with increasing galactic total mass

    Proteomic analysis of dopamine and \u3b1-synuclein interplay in a cellular model of Parkinson's disease pathogenesis

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    Altered dopamine homeostasis is an accepted mechanism in the pathogenesis of Parkinson\u2019s disease. a-Synuclein overexpression and impaired disposal contribute to this mechanism. However, biochemical alterations associated with the interplay of cytosolic dopamine and increased a-synuclein are still unclear. Catecholaminergic SH-SY5Y human neuroblastoma cells are a suitable model for investigating dopamine toxicity. In the present study, we report the proteomic pattern of SH-SY5Y cells overexpressing a-synuclein (1.6-fold induction) after dopamine exposure. Dopamine itself is able to upregulate a-synuclein expression. However, the effect is not observed in cells that already overexpress a-synuclein as a consequence of transfection. The proteomic analysis highlights significant changes in 23 proteins linked to specific cellular processes, such as cytoskeleton structure and regulation, mitochondrial function, energetic metabolism, protein synthesis, and neuronal plasticity. A bioinformatic network enrichment procedure generates a significant model encompassing all proteins and allows us to enrich functional categories associated with the combination of factors analyzed in the present study (i.e. dopamine together with a-synuclein). In particular, the model suggests a potential involvement of the nuclear factor kappa B pathway that is experimentally confirmed. Indeed, a-synuclein significantly reduces nuclear factor kappa B activation, which is completely quenched by dopamine treatment.Altered dopamine homeostasis is an accepted mechanism in the pathogenesis of Parkinson's disease. \u3b1-Synuclein overexpression and impaired disposal contribute to this mechanism. However, biochemical alterations associated with the interplay of cytosolic dopamine and increased \u3b1-synuclein are still unclear. Catecholaminergic SH-SY5Y human neuroblastoma cells are a suitable model for investigating dopamine toxicity. In the present study, we report the proteomic pattern of SH-SY5Y cells overexpressing \u3b1-synuclein (1.6-fold induction) after dopamine exposure. Dopamine itself is able to upregulate \u3b1-synuclein expression. However, the effect is not observed in cells that already overexpress \u3b1-synuclein as a consequence of transfection. The proteomic analysis highlights significant changes in 23 proteins linked to specific cellular processes, such as cytoskeleton structure and regulation, mitochondrial function, energetic metabolism, protein synthesis, and neuronal plasticity. A bioinformatic network enrichment procedure generates a significant model encompassing all proteins and allows us to enrich functional categories associated with the combination of factors analyzed in the present study (i.e. dopamine together with \u3b1-synuclein). In particular, the model suggests a potential involvement of the nuclear factor kappa B pathway that is experimentally confirmed. Indeed, \u3b1-synuclein significantly reduces nuclear factor kappa B activation, which is completely quenched by dopamine treatment. \ua9 2010 The Authors Journal compilation \ua9 2010 FEBS

    Role of the p53/p21 system in the response of human colon carcinoma cells to Doxorubicin

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    BACKGROUND: Colon adenocarcinomas are refractory to a number of widely used anticancer agents. Multifactorial mechanisms have been implicated in this intrinsically resistant phenotype, including deregulation of cell death pathways. In this regard, the p53 protein has a well established role in the control of tumor cell response to DNA damaging agents; however, the relationship between p53-driven genes and drug sensitivity remains controversial. The present study investigates the role of the p53/p21 system in the response of human colon carcinoma cells to treatment with the cytotoxic agent doxorubicin (DOX) and the possibility to modify the therapeutic index of DOX by modulation of p53 and/or p21 protein levels. METHODS: The relationship between p53 and p21 protein levels and the cytotoxic effect of DOX was investigated, by MTT assay and western blot analysis, in HCT116 (p53-positive) and HT29 (p53-negative) colon cancer cells. We then assessed the effects of DOX in two isogenic cell lines derived from HCT116 by abrogating the expression and/or function of p53 and p21 (HCT116-E6 and HCT116 p21-/-, respectively). Finally, we evaluated the effect of pre-treatment with the piperidine nitroxide Tempol (TPL), an agent that was reported to induce p21 expression irrespective of p53 status, on the cytotoxicity of DOX in the four cell lines. Comparisons of IC50 values and apoptotic cell percentages were performed by ANOVA and Bonferroni's test for independent samples. C.I. calculations were performed by the combination Index method. RESULTS: Our results indicate that, in the colon carcinoma cell lines tested, sensitivity to DOX is associated with p21 upregulation upon drug exposure, and DOX cytotoxicity is potentiated by pre-treatment with TPL, but only in those cell lines in which p21 can be upregulated. CONCLUSIONS: p21 induction may significantly contribute to the response of colon adenocarcinomas cells to DOX treatment; and small molecules that can exploit p53-independent pathways for p21 induction, such as TPL, may find a place in chemotherapeutic protocols for the clinical management of colorectal cancer, where p53 function is often lost, due to genetic or epigenetic defects or to post-transcriptional inactivating mechanisms

    Fracture Toughness And Microstructure In AA 2XXX Aluminum Alloys

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    The paper presents the toughness properties of forgings made of two AA 2xxx series aluminium alloys with different microstructural conditions. Fracture toughness tests in crack opening mode I were performed on compact tension specimens machined from the forgings in different orientations. The tests were performed both at room temperature and at 130?C. Fracture toughness properties were related to microstructural and fractographic features of the alloys in order to discuss on their failure mechanisms. The effect of the coarse intermetallic phases within grains or at their boundaries in the different conditions was underlined. The testing temperature, within the range here investigated, neither affected fracture toughness properties nor failure mechanisms

    Population Genetics of Franciscana Dolphins (Pontoporia blainvillei): Introducing a New Population from the Southern Edge of Their Distribution

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    Due to anthropogenic factors, the franciscana dolphin, Pontoporia blainvillei, is the most threatened small cetacean on the Atlantic coast of South America. Four Franciscana Management Areas have been proposed: Espiritu Santo to Rio de Janeiro (FMA I), São Paulo to Santa Catarina (FMA II), Rio Grande do Sul to Uruguay (FMA III), and Argentina (FMA IV). Further genetic studies distinguished additional populations within these FMAs. We analyzed the population structure, phylogeography, and demographic history in the southernmost portion of the species range. From the analysis of mitochondrial DNA control region sequences, 5 novel haplotypes were found, totalizing 60 haplotypes for the entire distribution range. The haplotype network did not show an apparent phylogeographical signal for the southern FMAs. Two populations were identified: Monte Hermoso (MH) and Necochea (NC)+Claromecó (CL)+Río Negro (RN). The low levels of genetic variability, the relative constant size over time, and the low levels of gene flow may indicate that MH has been colonized by a few maternal lineages and became isolated from geographically close populations. The apparent increase in NC+CL+RN size would be consistent with the higher genetic variability found, since genetic diversity is generally higher in older and expanding populations. Additionally, RN may have experienced a recent split from CL and NC; current high levels of gene flow may be occurring between the latter ones. FMA IV would comprise four franciscana dolphin populations: Samborombón West+Samborombón South, Cabo San Antonio+Buenos Aires East, NC+CL+Buenos Aires Southwest+RN and MH. Results achieved in this study need to be taken into account in order to ensure the long-term survival of the species.Fil: Gariboldi, María Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Tunez, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Luján; ArgentinaFil: Dejean, Cristina Beatriz. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropológicas. Sección Antropología Biológica; ArgentinaFil: Failla, Mauricio. Fundación Cethus; ArgentinaFil: Vitullo, Alfredo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Negri, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; ArgentinaFil: Cappozzo, Humberto Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; Argentin
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