Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods. Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer dev

Detection of High-Energy Gamma-Ray Emission from the Globular Cluster 47 Tucanae with Fermi

Gamma-Ray Pulsar Bonanza Most of the pulsars we know about were detected through their radio emission; a few are known to pulse gamma rays but were first detected at other wavelengths (see the Perspective by Halpern ). Using the Fermi Gamma-Ray Space Telescope, Abdo et al. (p. 840 , published online 2 July; see the cover) report the detection of 16 previously unknown pulsars based on their gamma-ray emission alone. Thirteen of these coincide with previously unidentified gamma-ray sources, solving the 30-year-old mystery of their identities. Pulsars are fast-rotating neutron stars. With time they slow down and cease to radiate; however, if they are in a binary system, they can have their spin rates increased by mass transfer from their companion stars, starting a new life as millisecond pulsars. In another study, Abdo et al. (p. 845 ) report the detection of gamma-ray emission from the globular cluster 47 Tucanae, which is coming from an ensemble of millisecond pulsars in the cluster's core. The data imply that there are up to 60 millisecond pulsars in 47 Tucanae, twice as many as predicted by radio observations. In a further companion study, Abdo et al. (p. 848 , published online 2 July) searched Fermi Large Area Telescope data for pulsations from all known millisecond pulsars outside of stellar clusters, finding gamma-ray pulsations for eight of them. Their properties resemble those of other gamma-ray pulsars, suggesting that they share the same basic emission mechanism. Indeed, both sets of pulsars favor emission models in which the gamma rays are produced in the outer magnetosphere of the neutron star

Tratamento térmico para controle da lanosidade em pêssegos 'Dourado-2' refrigerados Heat treatment to alleviation of woolliness of cold stored 'Dourado-2' peach

O objetivo deste trabalho foi avaliar o efeito de tratamentos térmicos na incidência de lanosidade em pêssegos 'Dourado-2' armazenados a 0ºC e na fisiologia e bioquímica dos frutos. Foram realizados condicionamentos térmicos antes da refrigeração, por meio da exposição dos frutos a 50ºC por 2 horas ou a 20ºC por 48 horas e do aquecimento intermitente durante o armazenamento refrigerado; os frutos foram submetidos a 25ºC durante 24 horas, a cada cinco dias de armazenamento a 0ºC, ou durante 48 horas, a cada dez dias de armazenamento a 0ºC. Frutos continuamente armazenados a 0ºC serviram de controle. Após 30 dias de armazenamento mais três dias de comercialização simulada, foram determinados os efeitos dos tratamentos sobre a incidência de lanosidade, podridões, teor de sólidos solúveis, acidez, teor de ácido ascórbico, coloração, firmeza da polpa, taxa respiratória, produção de etileno, atividade das enzimas poligalacturonase e pectinametilesterase. O aquecimento intermitente com ciclos de cinco ou dez dias e o condicionamento a 20ºC durante 48 horas foram mais eficazes para reduzir a incidência de lanosidade, mas acelerou a perda de firmeza dos frutos. A produção de etileno foi maior nos frutos submetidos a aquecimento intermitente. Os tratamentos térmicos provocaram poucas alterações no teor de sólidos solúveis, acidez, ácido ascórbico, coloração e incidência de podridões.<br>The work was carried out with the objective to verify the effect of heat treatments on the incidence of woolliness in 'Dourado-2' peaches stored at 0ºC. Heat treatments were applied as conditioning temperature (50ºC during 2 hours or 20ºC during 48 hours) before cold storage. In intermittent warming, fruit treatments were warmed each five days at 25ºC during 24 hours or each ten days during 48 hours. Control fruit were continuously stored at 0ºC. The variables evaluated after 30 days at 0ºC (plus three days at room temperature) were: incidence of woolliness and decay, soluble solids content (SSC), acidity, ascorbic acid, skin color, firmness, respiratory rate, ethylene production and activity of polygalacturonase (PG) and pectinmethylesterase (PME). The intermittent warming with cycles of five or ten days and the conditioning temperature at 20ºC during 48 hours before cold storage was the most effective treatment to reduce incidence of woolliness. However, heat treatment hastened fruit softening. Ethylene production was higher in fruits intermittently warmed and this can be related to the higher activity of PG and PME and consequently to alleviation of woolliness of the fruit. Heat treatment caused little variations on SSC, acidity, ascorbic acid and skin color

BRCA1 Protein and Nucleolin Colocalize in Breast Carcinoma Tissue and Cancer Cell Lines

The breast and ovarian cancer susceptibility gene BRCA1 encodes a tumor suppressor. BRCA1 protein, which is involved in DNA damage response, has been thought to be found primarily in cell nuclei. In the present investigation, immunohistological studies of BRCA1 protein in frozen breast cancer tissue and MCF7 and HeLa cell lines revealed BRCA1 expression in both nucleoli and nucleoplasmic foci. Immunoelectron microscopic studies of estrogen-stimulated MCF7 cells demonstrated BRCA1 protein localization in the granular components of the nucleolus. Moreover, immunofluorescence of BRCA1 and nucleolin double-labeling showed colocalization in both nucleoli and nucleoplasmic foci in breast tumor cells and asynchronously growing MCF7 and HeLa cells. Multiparameter analysis of BRCA1 and nucleolin in relation to cell cycle position (DNA content) showed expression during G1−S and persistence of BRCA1 during G2/M. After γ-irradiation of MCF7 cells, BRCA1 protein dispersed from nucleoli and nucleoplasmic foci to other nucleoplasmic sites, which did not colocalize with nucleolin. Small interfering RNA-mediated knockdown of BRCA1 protein resulted in decreased immunofluorescence staining, which was confirmed by Western blotting. The observed colocalization of BRCA1 and nucleolin raises new possibilities for the nucleoplasm-nucleolus pathways of these proteins and their functional significance