Caveolin interacts with the angiotensin II type 1 receptor during exocytic transport but not at the plasma membrane

The mechanisms involved in angiotensin II type 1 receptor (AT(1)-R) trafficking and membrane localization are largely unknown. In this study, we examined the role of caveolin in these processes. Electron microscopy of plasma membrane sheets shows that the AT(1)-R is not concentrated in caveolae but is clustered in cholesterol-independent microdomains; upon activation, it partially redistributes to lipid rafts. Despite the lack of AT(1)-R in caveolae, AT(1)-R. caveolin complexes are readily detectable in cells co-expressing both proteins. This interaction requires an intact caveolin scaffolding domain because mutant caveolins that lack a functional caveolin scaffolding domain do not interact with AT(1)-R. Expression of an N-terminally truncated caveolin-3, CavDGV, that localizes to lipid bodies, or a point mutant, Cav3-P104L, that accumulates in the Golgi mislocalizes AT(1)-R to lipid bodies and Golgi, respectively. Mislocalization results in aberrant maturation and surface expression of AT(1)-R, effects that are not reversed by supplementing cells with cholesterol. Similarly mutation of aromatic residues in the caveolin-binding site abrogates AT(1)-R cell surface expression. In cells lacking caveolin-1 or caveolin-3, AT(1)-R does not traffic to the cell surface unless caveolin is ectopically expressed. This observation is recapitulated in caveolin-1 null mice that have a 55% reduction in renal AT(1)-R levels compared with controls. Taken together our results indicate that a direct interaction with caveolin is required to traffic the AT(1)-R through the exocytic pathway, but this does not result in AT(1)-R sequestration in caveolae. Caveolin therefore acts as a molecular chaperone rather than a plasma membrane scaffold for AT(1)-R.

The role of melanocortin-1 receptor polymorphism in skin cancer risk phenotypes

We have examined melanocortin-1 receptor (MC1R) variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins to determine statistical associations of pigmentation phenotypes with increased skin cancer risk. This included hair and skin color, freckling, mole count and sun exposed skin reflectance. Nine variants were studied and designated as either strong R (OR = 63; 95% CI 32-140) or weak r (OR = 5; 95% CI 3-11) red hair alleles. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. To assess the interaction of the brown eye color gene BEY2/OCA2 on the phenotypic effects of variant MC1R alleles we imputed OCA2 genotype in the twin collection. A modifying effect of OCA2 on MC1R variant alleles was seen on constitutive skin color, freckling and mole count. In order to study the individual effects of these variants on pigmentation phenotype we have established a series of human primary melanocyte strains genotyped for the MC1R receptor. These include strains which are MC1R wild-type consensus, variant heterozygotes, and homozygotes for strong R alleles Arg151Cys and Arg160Trp. Ultrastructural analysis demonstrated that only consensus strains contained stage III and IV melanosomes in their terminal dendrites whereas Arg151Cys and Arg160Trp homozygous strains contained only immature stage I and II melanosomes. Such genetic association studies combined with the functional analysis of MC1R variant alleles in melanocytic cells should provide a link in understanding the association between pigmentary phototypes and skin cancer risk.

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.

Water sorption into poly[(2-hydroxyethyl methacrylate)-co-(1-vinyl-2-pyrrolidone]at 310 K

Poly(2-hydroxyethyl methacrylate) and copolymers of 2-hydroxyethyl methacrylate (HEMA) and 1-vinyl-2-pyrrolidone (VP) in the form of cylindrical samples (approximate to8mm x 20mm) have been prepared and the sorption of water into these cylinders has been studied by the mass-uptake methods and by magnetic-resonance imaging. The equilibrium water contents for the cylinders were found to vary systematically with the copolymer composition. Diffusion of water into the cylinders was found to follow Fickian behaviour for cylinders with high HEMA contents, with the diffusion coefficients obtained from mass-uptake studies dependent on the copolymer composition, varying from 1.7 x 10(-11) m(2) s(-1) for poly(HEMA) to 2.0 x 10(-11) m(2) s(-1) for poly(HEMA-co-VP) with a composition of 1:1. However, NMR-imaging studies showed that, while the profiles of the water diffusion fronts for cylinders with high HEMA contents were Fickian, that for the 1:1 copolymer was not and indicated that the mechanism was Case III. The polymers which were rich in VP were characterized by a water-sorption process which follows Case-III behaviour. (C) 2003 Society of Chemical Industry.

1-Ethynyl-2-isopropoxy-3-methoxybenzene

The crystal structure of the title compound, C12H14O2, has been determined at 150 K. Significant intermolecular non-conventional C-H...O interactions involving the terminal acetylinic H atom are observed, which result in a zigzag hydrogen-bonded chain in the b direction.

Ludologia (jogo #1/nível #2). em torno da fenomenologia do jogo cerimonial: do lúdico à categoria operatória do sagrado

O objectivo deste artigo é apresentar a distinção fundamental entre os conceitos de «jogo» e de «sagrado» no quadro de uma fenomenologia da cultura e da comunicação. Trata-se de analisar de que modo o jogo e, em particular, a categoria do «lúdico» se relaciona com o conceito de sagrado, partindo do plano do «jogo cerimonial» entre ritos e mitos, tal como se representam nas sociedades arcaicas. Partimos do quadro romântico do século XIX e da noção schellinguiana de Mitologia, passando pela noção de «imersão» no écran que os jogos permitem e da distinção entre «jogo», «sagrado» e «festa», até à análise da estrutura da categoria de sagrado tal como foi desenvolvida por Rudolf Otto e do conceito de «Unheimlich». No parágrafo final mostramos como é diferente o que se passa com essas «máquinas alegóricas» que nos colocam face a Masmorras e Dragões e no centro de um «parque de diversões ontológicas».

O programa de formação contínua em matemática para professores do 1º e 2º ciclo do ensino básico

Este artigo faz um balanço do desenvolvimento do Programa de Formação Contínua em Matemática para professores do 1.º e 2.º ciclo (PFCM), desde a sua criação em 2005 até à totalidade. O artigo começa por caracterizar o PFCM, especificando os seus objectivos e princípios orientadores, a sua organização e a caracterização e intenção dos diferentes tipos de sessões. É feito um balanço quantitativo e qualitativo do desenvolvimento do PFCM nos últimos quatro anos, bem como enunciados os aspectos considerados mais positivos e aqueles que se consideram menos conseguidos. O artigo termina com um balanço global do PFCM bem como dos desafios que enfrenta.

Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotype

Aims Obesity and asthma are widely prevalent and associated disorders. Recent studies of our group revealed that Substance P (SP) is involved in pathophysiology of obese-asthma phenotype in mice through its selective NK1 receptor (NK1-R). Lymphangiogenesis is impaired in asthma and obesity, and SP activates contractile and inflammatory pathways in lymphatics. Our aim was to study whether NK1-R expression was involved in lymphangiogenesis on visceral (VAT) and subcutaneous (SAT) adipose tissues and in the lungs, in obese-allergen sensitized mice. Main methods Diet-induced obese and ovalbumin (OVA)-sensitized Balb/c mice were treated with a selective NK1-R antagonist (CJ 12,255, Pfizer Inc., USA) or placebo. Lymphatic structures (LYVE-1 +) and NK1-R expression were analyzed by immunohistochemistry. A semi-quantitative score methodology was used for NK1-R expression. Key findings Obesity and allergen-sensitization together increased the number of LYVE-1 + lymphatics in VAT and decreased it in SAT and lungs. NK1-R was mainly expressed on adipocyte membranes of VAT, blood vessel areas of SAT, and in lung epithelium. Obesity and allergen-sensitization combined increased the expression of NK1-R in VAT, SAT and lungs. NK1-R antagonist treatment reversed the effects observed in lymphangiogenesis in those tissues. Significance The obese-asthma phenotype in mice is accompanied by increased expression of NK1-R on adipose tissues and lung epithelium, reflecting that SP released during inflammation may act directly on these tissues. Blocking NK1-R affects lymphangiogenesis, implying a role of SP, with opposite physiological consequences in VAT, and in SAT and lungs. Our results provide a clue for a novel SP role in the obese-asthma phenotype.

Unesp Informa, 2010, ano 1, número 2

Boletim elaborado pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2009, ano 1, número 2

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Cálculo flexível e o raciocínio quantitativo aditivo em alunos dos 1.º e 2.º anos

Esta comunicação insere-se no Projeto “Pensamento numérico e cálculo flexível: Aspetos críticos”. Começa por discutir o que se entende por flexibilidade de cálculo e raciocínio quantitativo aditivo, discutindo depois os resultados de entrevistas individuais realizadas com quatro alunos (dois do 1.º ano e dois do 2.º ano) quando lhes foram propostas tarefas onde aqueles aspetos estavam presentes. Trata-se de um estudo exploratório cujo principal objetivo é compreender o raciocínio dos alunos quando resolvem tarefas numéricas envolvendo situações aditivas, e ainda identificar aspetos associados à flexibilidade de cálculo e ao raciocínio quantitativo. Os resultados mostram que, no caso dos alunos do 1.º ano, o seu desempenho parece estar relacionado com o seu desenvolvimento do sentido do número e com as relações que dominam. Para os alunos do 2.º ano, o raciocínio inversivo constituiu um aspeto crítico, que conseguiram mobilizar depois de superadas as dificuldades iniciais. Os resultados sugerem, ainda, que estes alunos concebem a diferença como uma relação invariante numérica.

Prática de ensino supervisionado no 1.º e 2.º ciclo do ensino básico: o jogo e o desenvolvimento da consciência linguística

Relatório de Estágio apresentado à Escola Superior de Educação de Lisboa para obtenção de grau de mestre em Ensino do 1.º e 2.º Ciclo do Ensino Básico

Prática de ensino supervisionado no 1.º e 2.º ciclo do ensino básico: contributo das atividades práticas e experimentais em ciências para o aumento da motivação dos alunos

Relatório de Estágio apresentado à Escola Superior de Educação de Lisboa para obtenção de grau de mestre em Ensino do 1º e 2º Ciclo do Ensino Básico

Prática de ensino supervisionado no 1.º e 2.º ciclo do ensino básico: de que forma o ensino explícito das estratégias de leitura contribui para uma melhor produção escrita do texto descritivo

Relatório de Estágio apresentado à Escola Superior de Educação de Lisboa para obtenção de grau de mestre em Ensino do 1.º e 2.º Ciclos do Ensino Básico

Prática de ensino supervisionado no 1.º e 2.º ciclo do ensino básico: desenvolver competências de recolha e tratamento da informação na aprendizagem da História e Geografia no 1.º e 2.º CEB

Relatório de investigação apresentado à Escola Superior de Educação de Lisboa para obtenção de grau de mestre no Mestrado em Ensino do 1.º e 2.º Ciclo do Ensino Básico