Ocular melanoma is not associated with CDKN2A or MC1R variants - a population-based study

Germline variants in the melanocortin 1 receptor gene (MC1R) and the p16 gene (CDKN2A) are associated with an increased risk of cutaneous melanoma. The frequency of these germline variants was examined in a population-based, incident series of 62 ocular melanoma cases and ethnicity-matched population controls. In both cases and controls, 59% of individuals carried at least one MC1R variant and there were no significant differences in the frequency of any of the five most common variants of MC1R. We also found no significant differences between cases and controls in the frequency of any of the four most common variants of CDKN2A, and no melanoma case carried a deleterious germline CDKN2A mutation. Our findings argue against an important predisposing effect of the MC1R and CDKN2A genes for ocular melanoma.

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.

ADH genotype does not modify the effects of alcohol on high-density lipoprotein

Background: Alcohol consumption has beneficial effects on mortality which are mainly due to reduction in cardiovascular disease. These are believed to be due, at least in part, to the increase in plasma high-density lipoprotein (HDL) which is associated with alcohol consumption. It has been proposed that ADH3 genotype modifies the relationships between alcohol intake and cardiovascular disease by altering the HDL response to alcohol. The aim of this paper was to test for effects of ADH2 and ADH3 genotypes on the response of HDL components to habitual alcohol consumption. Methods: Adult male and female subjects were genotyped for ADH2 and ADH3; and plasma HDL cholesterol, apolipoprotein A-I, and apolipoprotein A-II were measured. Nine hundred one subjects had both ADH2 and ADH3 genotypes and HDL cholesterol results, while 753 had both genotypes and all three lipid results. The effect of alcohol intake on the three measured HDL components, and a factor score derived from them, was estimated for each of the ADH2 and ADH3 genotype groups. Results: All the measured components of HDL increased with increasing alcohol consumption over the range of intakes studied, 0-4 drinks per day. There were no significant interactions between alcohol consumption and ADH2 or ADH3 genotypes. Conclusions: The concept that alcohol dehydrogenase genotype and alcohol metabolic rate modify the effects of alcohol on plasma HDL concentration is not supported by our results.

GLUT4 recycles via a trans-Golgi network (TGN) subdomain enriched in Syntaxins 6 and 16 but not TGN38: Involvement of an acidic targeting motif

Insulin stimulates glucose transport in fat and muscle cells by triggering exocytosis of the glucose transporter GLUT4. To define the intracellular trafficking of GLUT4, we have studied the internalization of an epitope-tagged version of GLUT4 from the cell surface. GLUT4 rapidly traversed the endosomal system en route to a perinuclear location. This perinuclear GLUT4 compartment did not colocalize with endosomal markers (endosomal antigen I protein, transferrin) or TGN38, but showed significant overlap with the TGN target (t)-soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) Syntaxins 6 and 16. These results were confirmed by vesicle immunoisolation. Consistent with a role for Syntaxins 6 and 16 in GLUT4 trafficking we found that their expression was up-regulated significantly during adipocyte differentiation and insulin stimulated their movement to the cell surface. GLUT4 trafficking between endosomes and trans-Golgi network was regulated via an acidic targeting motif in the carboxy terminus of GLUT4, because a mutant lacking this motif was retained in endosomes. We conclude that GLUT4 is rapidly transported from the cell surface to a subdomain of the trans-Golgi network that is enriched in the t-SNAREs Syntaxins 6 and 16 and that an acidic targeting motif in the C-terminal tail of GLUT4 plays an important role in this process.

A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention

PURPOSE: To determine the effects of aggressive lipid lowering on markers of ischemia, resistance vessel function, atherosclerotic burden, and Symptom status in patients with symptomatic coronary artery disease. METHODS: Sixty consecutive patients with coronary artery disease that was unsuitable for revascularization were assigned randomly to either usual therapy of lipids for patients with a low-density lipoprotein (LDL) cholesterol target level <116 mg/dL, or to a, more aggressive lipid-lowering strategy involving up to 80 mg/d of atorvastatin, with a target LDL cholesterol level <77 mg/dL. The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function.(brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, patients in the aggressive therapy group had a significantly greater decrease in mean (+/- SD) LDL cholesterol level than those in the usual care group (29 +/- 38 mg/dL vs. 7 +/- 24 mg/dL, P = 0.03). Patients in the aggressive therapy group had a reduction in the number of ischemic wall segments (mean between-group difference of 1.3; 95% confidence interval: 0.1 to 2.0; P = 0.04), flow-mediated dilatation (mean between-group difference of 5.9%; 95% confidence interval: 2.5% to 9.4%; P = 0.001), and angina score after 12 weeks. There were no significant changes in atherosclerotic burden in either group. CONCLUSION: Patients with symptomatic coronary artery disease who are treated with aggressive lipid lowering have improvement of symptom status and ischemia that appears to reflect improved vascular function but not atheroma burden. Am J Med. 2003;114:445-453. (C) 2003 by Excerpta Medica Inc.

Aging per se does not influence glucose homeostasis - In vivo and in vitro evidence

OBJECTIVE - To assess the effect of age on glucose metabolism by examining 1) glucose metabolism in young and middle-aged subjects when total or regional adiposity is taken into account and 2) in vitro glucose transport in adipose tissue explants from young and middle-aged women paired for total and abdominal adiposity. RESEARCH DESIGN AND METHODS - Study 1: body composition, subcutaneous abdominal and visceral adipose tissue areas, and fasting and oral glucose-stimulated glucose and insulin were measured in 84 young and 81 middle-aged men and in 110 young and 91 middle-aged women. Study 2: glucose uptake in subcutaneous abdominal and visceral adipose tissue explants were measured in eight young and eight middle-aged women. RESULTS - Study 1: young and middle-aged men showed similar subcutaneous abdominal tissue area, whereas fat mass and visceral adipose tissue were greater in middle-aged than in young men (P < 0.01). Fat mass and subcutaneous and visceral adipose tissue areas were greater in middle-aged as compared with young women (P < 0.01). Fasting plasma glucose and the glucose response to an oral glucose tolerance test were significantly higher in middle-aged than in young men and women (P < 0.001). Statistical control for visceral adipose tissue area eliminated the difference seen in glucose response in men and women. Study 2: glucose transport in subcutaneous and omental adipose tissue did not differ between young and middle-aged women. CONCLUSIONS - 1) Visceral obesity, more than age per se, correlates with glucose intolerance in middle-aged subjects; 2) aging does not influence in vitro adipose tissue glucose uptake.

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.

Believing is not enough: Predicting support for the NTEU on an Australian campus

Asurvey-based field study was conducted with 232 members and nonmembers of the National Tertiary Education Union to investigate the psychological processes underpinning union support. Drawing on value-expectancy models and social identity/self-categorisation theory, this study investigated the role that both individual and grouprelated factors play in predicting attitudinal and behavioural support for the union. Variables investigated included instrumental and ideological attitudes, perceptions of a normative climate of union-support, and perceptions of higher education being under threat. Further to support for previous findings for the role of instrumental and ideological attitudes it was found that the perceived workplace norm had the anticipated direct effect on behaviour and evaluation and also moderated the behavioural expression of ideological and instrumental attitudes. The perception of threat to employment and higher education also directly impacted on behaviour and moderated the behavioural expression of ideological beliefs. The implications of these findings for collective action research will he discussed.

Entre rios, praias e planetas : travessias do congo da Barra do Jucu

O Espírito Santo abriga grande diversidade de expressões populares tradicionais que se dividem em grupos, saberes e celebrações. Uma das práticas mais evidentes são as bandas de Congo que abrangem grande parte do Estado e ganham cada vez mais notoriedade. A Barra do Jucu é uma das comunidades mais antigas do Espírito Santo, uma vila de pescadores que séculos atrás compunha parte da grande fazenda Araçatiba fundada pelos Jesuítas e administrada no século XIX pelo coronel Sebastião Vieira Machado. A diversidade cultural dessa região habitada por africanos, indígenas e europeus, propiciou o surgimento de práticas populares como a Marujada, a Folia de Reis e as Bandas de Congo, que persistem até hoje nos municípios de Cariacica, Vila Velha, Guarapari e Viana, no passado, pertencentes à grande fazenda Araçatiba. A formação do Congo na Barra do Jucu é resultado de rodas informais realizadas por conguistas de comunidades ribeirinhas vizinhas, promovidas principalmente pelo senhor Ignácio Vieira Machado, descendente do coronel Sebastião e lideradas por Alcides Gomes da Silva, descendente de negros africanos e açorianos habitantes da fazenda Araçatiba. Durante muito tempo essa prática foi marginalizada, mas atualmente o Congo é considerado um ícone da cultura capixaba. Essa ressignificação está ligada a um processo de valorização e projeção midiática que se iniciou nos anos 1980 e se intensificou nas décadas seguintes. Boa parte dos movimentos e eventos que estimularam esse processo ocorreu na comunidade da Barra do Jucu. Por outro lado, políticos, empresários, indústria do entretenimento e outros setores sociais, aproveitam cada vez mais dessa ascensão do Congo utilizando os grupos tradicionais para fins lucrativos e promocionais. De prática marginal até se tornar ícone cultural, o Congo da Barra do Jucu passou por fazendas, rios, praias e planetas. E sobre essas travessias não só geográficas, mas sociais, culturais e políticas é que este trabalho pretende refletir, além das práticas tradicionais dos grupos e seus usos, buscando trazer à tona as relações entre conguistas, instituições públicas e privadas, mídia e público.

Profundidade de semeadura e superação de dormência no crescimento inicial de sementes de Brachiaria dictyoneura (Fig. & De Not.) Stapf (1919) cv. Llanero

O Brasil é o maior produtor, consumidor e exportador de sementes de espécies forrageiras de clima tropical. Objetivou-se, com este estudo, avaliar o desenvolvimento inicial de Brachiaria dictyoneura cv. Llanero, em função da profundidade de semeadura e dos métodos de superação de dormência. O trabalho foi realizado em casa de vegetação, em blocos casualizados, com quatro repetições e em esquema de parcela subdividida. Os tratamentos aplicados às parcelas foram cinco, com as profundidades de semeadura de 0,0; 2,0; 4,0; 6,0 e 8,0 cm e, nas subparcelas, os métodos de superação da dormência com e sem escarificação. Cada parcela experimental foi constituída de 25 sementes. A partir do 10º dia de semeadura iniciou-se a contagem de plantas emergidas, a fim de se determinar o índice de velocidade de emergência e, aos 35 dias posteriores à semeadura, avaliou-se a emergência das plântulas, a altura de plantas e a matéria seca da parte aérea. As sementes de B. dictioneura semeadas em torno de 4,0 cm de profundidade e submetidas à escarificação mecânica apresentaram melhor desenvolvimento em todos os parâmetros avaliados. A semeadura superficial e aquela em profundidades abaixo de 4,0 cm mostraram-se ineficientes para o desenvolvimento inicial de B. dictioneura.

Knowledge and policy action in urban development: if we know so much, why is the urban condition not improving?

In spite of the wealth generation potential of the world's large metropolitan cities, poor living conditions for much of the world's urban population persist. Although the city has been widely studied, urban policy often remains ineffective. The paper adopts a policy process approach to analyze the relationship between knowledge and governmental action. Impediments to improving urban policy are found in the inadequate capacity of government to act and in the politics of democratic decision-making. The paper recommends that a pragmatic view of knowledge generation be adopted.

Budgeting and resource allocation in universities: a public choice approach

The calls for colleges and universities to improve their productivity are coming thick and fast in Brazil. Many studies are suggesting evaluation systems and external criteria to control the quality of teaching and research in universities. Since universities and colleges are not profit-oriented organizations (considering only the legitimate and serious research and teaching organizations, of course), the traditional microeconomics and administrative variables used to measure efficiency do not have any direct function. An alternative would be to create an "as if" market control system to evaluate performance in universities and colleges. Internal budget and resources allocation mechanism can be used as incentive instruments to improve quality and productivity. It will be the main issue of this article.