High frequency of BRAF mutations in nevi

To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis.

Dizygotic twinning is not associated with methylenetetrahydrofolate reductase haplotypes

Background: Folate metabolism is critical to embryonic development, influencing neural tube defects (NTD) and recurrent early pregnancy loss. Polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR) have been associated with dizygotic (DZ) twinning through pregnancy loss. Methods: The C677T and A1298C polymorphisms in MTHFR were genotyped in 258 Australasian families (1016 individuals) and 118 Dutch families (462 individuals) of mothers of DZ twins and a population sample of 462 adolescent twin families (1861 individuals). Haplotypes were constructed from the alleles, and transmission of the MTHFR haplotypes to mothers of DZ twins and from parents to twins in the adolescent twin families analysed. Results: The C677T and A1298C were common in all three populations (frequencies > 0.29). There was strong linkage disequilibrium (D'=1) between the variants, showing that specific combinations of alleles (haplotypes) were transmitted together. Three haplotypes accounted for nearly all the variation. There was no evidence of any association between MTHFR genotype and twinning in mothers of twins, or of the loss of specific MTHFR genotypes during twin pregnancies. Conclusions: It is concluded that variation in twinning frequency is not associated with MTHFR genotype.

Screening of human primary melanocytes of defined melanocortin-1 receptor genotype: Pigmentation marker, ultrastructural and UV-survival studies

Recent population studies have demonstrated an association with the red-hair and fair-skin phenotype with variant alleles of the melanocortin-1 receptor (MC1R) which result in amino acid substitutions within the coding region leading to an altered receptor activity. In particular, Arg151Cys, Arg160Trp and Asp294His were the most commonly associated variants seen in the south-east Queensland population with at least one of these alleles found in 93% of those with red hair. In order to study the individual effects of these variants on melanocyte biology and melanocytic pigmentation, we established a series of human melanocyte strains genotyped for the MC1R receptor which included wild-type consensus, variant heterozygotes, compound heterozygotes and homozygotes for Arg151Cys, Arg160Trp, Val60Leu and Val92Met alleles. These strains ranged from darkly pigmented to amelanotic, with all strains of consensus sequence having dark pigmentation. UV sensitivity was found not to be associated with either MC1R genotype or the level of pigmentation with a range of sensitivities seen across all genotypes. Ultrastructural analysis demonstrated that while consensus strains contained stage IV melanosomes in their terminal dendrites, Arg151Cys and Arg160Trp homozygote strains contained only stage II melanosomes. This was despite being able to show expression of tyrosinase and tyrosinase-related protein-1 markers, although at reduced levels and an ability to convert exogenous 3,4-dihydroxyphenyl-alanine (DOPA) to melanin in these strains.

Influence of ageing, heat shock treatment and in vivo total antioxidant status on gene-expression profile and protein synthesis in human peripheral lymphocytes

Ageing results in a progressive, intrinsic and generalised imbalance of the control of regulatory systems. A key manifestation of this complex biological process includes the attenuation of the universal stress response. Here we provide the first global assessment of the ageing process as it affects the heat shock response, utilising human peripheral lymphocytes and cDNA microarray analysis. The genomic approach employed in our preliminary study was supplemented with a proteomic approach. In addition, the current study correlates the in vivo total antioxidant status with the age-related differential gene expression as well as the translational kinetics of heat shock proteins (hsps). Most of the genes encoding stress response proteins on the 4224 element microarray used in this study were significantly elevated after heat shock treatment of lymphocytes obtained from both young and old individuals albeit to a greater extent in the young. Cell signaling and signal transduction genes as well as some oxidoreductases showed varied response. Results from translational kinetics of induction of major hsps, from 0 to 24 It recovery period were broadly consistent with the differential expression of HSC 70 and HSP 40 genes. Total antioxidant levels in plasma from old individuals were found to be significantly lower by comparison with young, in agreement with the widely acknowledged role of oxidant homeostasis in the ageing process. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

A rapid method for determining recent sunscreen use in field studies

The role of sunscreens in preventing skin cancer and melanoma is the focus of ongoing research. Currently, there is no objective measure which can be used in field studies to determine whether a person has applied sunscreen to their skin, and researchers must use indirect assessments such as questionnaires. We sought to develop a rapid, non-invasive method for identifying sunscreen on the skin for use in epidemiological studies. Our basic method is to swab the skin, elute any residues which have been adsorbed onto the swab by rinsing in ethanol, and submit the eluted washings for spectrophotometric analysis. In a controlled study, we applied 0.1 ml of sunscreen to a 50 cm(2) grid on both forearms of 21 volunteers. Each forearm was allocated one of 10 different sunscreen brands. The skin was swabbed after intervals of 20 min, 1 h, 2 h and 4 h. In a field study conducted among 12 children aged 2-4 years attending a child care centre, sunscreen was applied to the faces of half the children. Swabs were then taken from the face and back of all children without knowledge of sunscreen status. In the controlled study, sunscreen was clearly detectable up to 2 h after application for all brands containing organic sunscreen, and marginally detectable at 4 h. In the field study, this method correctly identified all children with and without sunscreen. We conclude that spectrophotometric analysis of skin swabs can reliably detect the presence of sunscreen on the skin for up to 2 It after application. (C) 2002 Elsevier Science B.V. All rights reserved.

Induction of metallothionein in human skin by routine exposure to sunlight: Evidence for a systemic response and enhanced induction at certain body sites

Expression of metallothionein, an antioxidant induced by a variety of stimuli including ultraviolet light, was quantitated by immunohistochemistry in the skin of males aged over 50 who had known short- and long-term exposures to sunlight. Skin punch biopsies were taken from two sites in each subject: the hand in all subjects and a range of other sites matched to patients with a previously excised primary melanoma. Metallothionein expression (strongest in the basal layers of the epidermis and primarily nuclear) was associated with both short- and long-term exposure to sunlight. A plateau of staining intensity was reached after 3 h sun exposure, within the previous 3 d before biopsy. Expression was also elevated in the nonexposed skin sites of subjects who had recent sun exposure, indicating a systemic response to exposure of remote sites. Using the skin of the hand to normalize responses to chronic exposure between individuals, the systemically modulated response to sunlight was significantly greater on the unexposed back than on other sites. The possibility of ultraviolet-induced cytokines selectively modifying the response of skin on a site-specific basis was investigated. The circulating leukocytes, but not lymphocytes, of two individuals exposed to 1 minimal erythema dose whole-body solar-simulated ultraviolet showed increased interleukin-6 mRNA 4 h after exposure. Interleukin-6 was not directly induced in these cell populations 4 h after ultraviolet A or ultraviolet B irradiation ex vivo . Leukocytes may therefore contribute to and amplify the systemic effects of ultraviolet-induced interleukin-6 and metallothionein expression.

ATP activates ataxia-telangiectasia mutated (ATM) in vitro - Importance of autophosphorylation

Ataxia-telangiectasia Mutated (ATM), mutated in the human disorder ataxia-telangiectasia, is rapidly activated by DNA double strand breaks. The mechanism of activation remains unresolved, and it is uncertain whether autophosphorylation contributes to activation. We describe an in vitro immunoprecipitation system demonstrating activation of ATM kinase from unirradiated extracts by preincubation with ATP. Activation is both time- and ATP concentration-dependent, other nucleotides fail to activate ATM, and DNA is not required. ATP activation is specific for ATM since it is not observed with kinase-dead ATM, it requires Mn2+, and it is inhibited by wortmannin. Exposure of activated ATM to phosphatase abrogates activity, and repeat cycles of ATP and phosphatase treatment reveal a requirement for autophosphorylation in the activation process. Phosphopeptide mapping revealed similarities between the patterns of autophosphorylation for irradiated and ATP-treated ATM. Caffeine inhibited ATM kinase activity for substrates but did not interfere with ATM autophosphorylation. ATP failed to activate either A-T and rad3-related protein (ATR) or DNA-dependent protein kinase under these conditions, supporting the specificity for ATM. These data demonstrate that ATP can specifically induce activation of ATM by a mechanism involving autophosphorylation. The relationship of this activation to DNA damage activation remains unclear but represents a useful model for understanding in vivo activation.

Genetic disruption of the growth hormone receptor does not influence motoneuron survival in the developing mouse

In the rodent central nervous system (CNS) during the five days prior to birth, both growth hormone (GH) and its receptor (GHR) undergo transient increases in expression to levels considerably higher than those found postnatally. This increase in expression coincides with the period of neuronal programmed cell death (PCD) in the developing CNS. To evaluate the involvement of growth hormone in the process of PCD, we have quantified the number of motoneurons in the spinal cord and brain stem of wild type and littermate GHR-deficient mice at the beginning and end of the neuronal PCD period. We found no change in motoneuron survival in either the brachial or lumbar lateral motor columns of the spinal cord or in the trochlear, trigeminal, facial or hypoglossal nuclei in the brain stem. We also found no significant differences in spinal cord volume, muscle fiber diameter, or body weight of GHR-deficient fetal mice when compared to their littermate controls. Therefore, despite considerable in vitro evidence for GH action on neurons and glia, genetic disruption of GHR signalling has no effect on prenatal motoneuron number in the mouse, under normal physiological conditions. This may be a result of compensation by the signalling of other neurotrophic cytokines.

A sociologia de Max Weber: sua import??ncia para a teoria e a pr??tica da administra????o

A tradu????o integral da obra de Max Weber ??? Wirtschaft und Gesellschaft ??? empreendida pela editora mexicana ??? Fondo de Cultura Econ??mica, sob a esclarecida dire????o de Jos?? Medina Echavarr??a, ?? um acontecimento a cuja magnitude esta Revista n??o pode permanecer indiferente. ?? esta a primeira vez que a referida obra aparece em l??ngua diferente da original, pois a anunciada tradu????o do seu primeiro volume, realizada por Parsons-Henderson, n??o foi editada at?? o presente e, ao que me consta, circula mimeografada, em restritos centros de estudo dos Estados Unidos. Apesar de inacabada e fragment??ria e de ser um livro p??stumo, publicado gra??as ?? dedica????o e compet??ncia de Marianna Weber, esposa do autor, Economia e Sociedade ?? a obra n??o s?? onde se re??nem os temas centrais de Max Weber, como tamb??m onde ele exp??e o seu sistema de sociologia.

Museu e escola : espaços de sentidos

Esta pesquisa procurou compreender como o Museu de Arte do Espírito Santo (MAES) atua na produção de sentidos dos estudantes, a partir das relações estabelecidas com a escola, e, nesse proceder, como o museu compreende a arte e a escola como destinatária de suas ações. Os sujeitos da pesquisa foram 98 crianças, do 5º ano do Ensino Fundamental I, de uma escola privada de Vitória. A pesquisa teve como corpus os discursos verbo-visuais produzidos pelas crianças nessa relação museu e escola, bem como as performances discursivas do Programa de Ação Educativa do Museu, no que concerne à formação de educadores e ao programa ciclo de palestras. Como metodologia de pesquisa, utilizou-se o estudo exploratório, e o aporte teórico foi a semiótica discursiva. A coleta de dados ocorreu no museu e na escola. No Museu, a partir de eventos que nortearam a exposição “Meu País Tropical”, da artista alemã, Heidi Lieberman, e das ações educativas propostas pelo MAES; na Escola, com o mapeamento inicial para compreender como e quais os sentidos eram apontados pelas crianças quanto ao conhecimento delas sobre a arte e sobre um museu de arte (antes da realização de sua primeira visita a esse espaço, o que elas sabem e qual a compreensão que elas têm da arte), bem como, nas produções plásticas e verbo-visuais produzidas por elas após a visita à instituição museal. Os resultados da pesquisa apontam que a metodologia analítica da semiótica discursiva contribuiu, de forma significativa, para desvelar os sentidos apontados pelas crianças no museu e na escola. Por meio dos discursos verbo-visuais produzidos por elas, compreendeu-se que uma educação pelo sensível, em consonância com relações de bons encontros no museu e na escola, pode propiciar uma experiência singular e significativa, que aguce a sensibilidade e reencante a educação.

Natureza, princípios e fundamentos das práticas e relações profissionais-doentes no contexto do Gabinete de Sub-visão do Instituto Dr. Gama Pinto

A institucionalização do direito à saúde, na constituição de 1976, como direito social e humano não parece ter conseguido, na prática dos profissionais de saúde, abalar a relação paternalista que coloca o doente numa situação de submissão face à dominância do poder/saber médico central ou periférico que o doente, nos termos de Parsons, deve acatar humildemente como “um bom doente”. É este papel de passividade e submissão do doente que nos propomos problematizar nos meandros dos direitos humanos/direitos sociais de cidadania como campo de construção social assente em práticas norteadas por direitos e deveres que, nos termos de Foucault, submetem os cidadãos a constrangimentos inerentes às relações de poder.

Suplementação materna com retinil palmitato no pós-parto imediato: consumo potencial por lactentes

OBJETIVO: Avaliar o efeito da suplementação materna com dose única de retinil palmitato no pós-parto para o fornecimento de vitamina A ao lactente. MÉTODOS: Ensaio clínico realizado em Natal (RN), entre março e dezembro de 2007, com 85 mulheres aleatoriamente distribuídas em dois grupos. As suplementações de retinil palmitato no pós-parto corresponderam à dose única de 200.000 (grupo experimento) UI e 0 UI (grupo controle). A quantificação do nível de retinol no leite foi obtida pelo método de cromatografia líquida de alta eficiência. Com base nas concentrações de retinol obtidas no leite materno e por meio de simulações, foi calculado o consumo de vitamina A dos lactentes nos momentos 24h e 30 dias pós-parto. RESULTADOS: No momento 24h pós-parto, o fornecimento diário de retinol ao recém-nascido via colostro foi de 1,63 µmol para o grupo controle e 2,9 µmol para o grupo experimento, considerando ingestão adequada de 1,40 µmol/dia e volume de leite consumido de 500 mL/dia. Trinta dias pós-parto, esses valores corresponderam a 0,64 µmol/dia (controle) e 0,89 µmol/dia (experimento), um aumento de 39% na concentração de retinol no grupo experimento em relação ao grupo controle ou 64% da recomendação para lactentes de zero a seis meses de idade. CONCLUSÕES: A suplementação materna com 200.000 UI de retinil palmitato no pós-parto imediato e a promoção de práticas de aleitamento materno são eficientes para melhorar o estado nutricional em vitamina A do binômio mãe-filho.

Simulation and theory of hybrid aligned liquid crystal films

We present a study of the effects of nanoconfinement on a system of hard Gaussian overlap particles interacting with planar substrates through the hard-needle-wall potential, extending earlier work by two of us [D. J. Cleaver and P. I. C. Teixeira, Chem. Phys. Lett. 338, 1 (2001)]. Here, we consider the case of hybrid films, where one of the substrates induces strongly homeotropic anchoring, while the other favors either weakly homeotropic or planar anchoring. These systems are investigated using both Monte Carlo simulation and density-functional theory, the latter implemented at the level of Onsager's second-virial approximation with Parsons-Lee rescaling. The orientational structure is found to change either continuously or discontinuously depending on substrate separation, in agreement with earlier predictions by others. The theory is seen to perform well in spite of its simplicity, predicting the positional and orientational structure seen in simulations even for small particle elongations.

O papel do educador no modelo curricular do movimento da escola moderna: reflexão em torno da construção da prática profissional supervisionada

Relatório da Prática Profissional Supervisionada Mestrado Em Educação Pré-Escolar