The scaffold protein IB1/JIP-1 controls the activation of JNK in rat stressed urothelium.

The c-Jun N-terminal kinase (JNK) is critical for cell survival, differentiation, apoptosis and tumorigenesis. This signalling pathway requires the presence of the scaffold protein Islet-Brain1/c-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1). Immunolabeling and in situ hybridisation of bladder sections showed that IB1/JIP-1 is expressed in urothelial cells. The functional role of IB1/JIP-1 in the urothelium was therefore studied in vivo in a model of complete rat bladder outlet obstruction. This parietal stress, which is due to urine retention, reduced the content of IB1/JIP-1 in urothelial cells and consequently induced a drastic increase in JNK activity and AP-1 binding activity. Using a viral gene transfer approach, the stress-induced activation of JNK was prevented by overexpressing IB1/JIP-1. Conversely, the JNK activity was increased in urothelial cells where the IB1/JIP-1 content was experimentally reduced using an antisense RNA strategy. Furthermore, JNK activation was found to be increased in non-stressed urothelial cells of heterozygous mice carrying a selective disruption of the IB1/JIP-1 gene. These data established that mechanical stress in urothelial cells in vivo induces a robust JNK activation as a consequence of regulated expression of the scaffold protein IB1/JIP-1. This result highlights a critical role for that scaffold protein in the homeostasis of the urothelium and unravels a new potential target to regulate the JNK pathway in this tissue.

Sleep deprivation effects on circadian clock gene expression in the cerebral cortex parallel electroencephalographic differences among mouse strains.

Sleep deprivation (SD) results in increased electroencephalographic (EEG) delta power during subsequent non-rapid eye movement sleep (NREMS) and is associated with changes in the expression of circadian clock-related genes in the cerebral cortex. The increase of NREMS delta power as a function of previous wake duration varies among inbred mouse strains. We sought to determine whether SD-dependent changes in circadian clock gene expression parallel this strain difference described previously at the EEG level. The effects of enforced wakefulness of incremental durations of up to 6 h on the expression of circadian clock genes (bmal1, clock, cry1, cry2, csnk1epsilon, npas2, per1, and per2) were assessed in AKR/J, C57BL/6J, and DBA/2J mice, three strains that exhibit distinct EEG responses to SD. Cortical expression of clock genes subsequent to SD was proportional to the increase in delta power that occurs in inbred strains: the strain that exhibits the most robust EEG response to SD (AKR/J) exhibited dramatic increases in expression of bmal1, clock, cry2, csnkIepsilon, and npas2, whereas the strain with the least robust response to SD (DBA/2) exhibited either no change or a decrease in expression of these genes and cry1. The effect of SD on circadian clock gene expression was maintained in mice in which both of the cryptochrome genes were genetically inactivated. cry1 and cry2 appear to be redundant in sleep regulation as elimination of either of these genes did not result in a significant deficit in sleep homeostasis. These data demonstrate transcriptional regulatory correlates to previously described strain differences at the EEG level and raise the possibility that genetic differences underlying circadian clock gene expression may drive the EEG differences among these strains.

Transcriptional activation of the macrophage migration-inhibitory factor gene by the corticotropin-releasing factor is mediated by the cyclic adenosine 3',5'- monophosphate responsive element-binding protein CREB in pituitary cells.

Macrophage migration-inhibitory factor (MIF) has recently been identified as a pituitary hormone that functions as a counterregulatory modulator of glucocorticoid action within the immune system. In the anterior pituitary gland, MIF is expressed in TSH- and ACTH-producing cells, and its secretion is induced by CRF. To investigate MIF function and regulation within pituitary cells, we initiated the characterization of the MIF 5'-regulatory region of the gene. The -1033 to +63 bp of the murine MIF promoter was cloned 5' to a luciferase reporter gene and transiently transfected into freshly isolated rat anterior pituitary cells. This construct drove high basal transcriptional activity that was further enhanced after stimulation with CRF or with an activator of adenylate cyclase. These transcriptional effects were associated with a concomitant rise in ACTH secretion in the transfected cells and by an increase in MIF gene expression as assessed by Northern blot analysis. A cAMP-responsive element (CRE) was identified within the MIF promoter region which, once mutated, abolished the cAMP responsiveness of the gene. Using this newly identified CRE, DNA-binding activity was detected by gel retardation assay in nuclear extracts prepared from isolated anterior pituitary cells and AtT-20 corticotrope tumor cells. Supershift experiments using antibodies against the CRE-binding protein CREB, together with competition assays and the use of recombinant CREB, allowed the detection of CREB-binding activity with the identified MIF CRE. These data demonstrate that CREB is the mediator of the CRF-induced MIF gene transcription in pituitary cells through an identified CRE in the proximal region of the MIF promoter.

Missale ad usum Sancti Cornelii Compendiensis.

Ex-libris "S. Cornelii Compend. Congr. S. Mauri", XVIIe s., f. 1. Compiègne.

O cuidado a pessoas com HIV/aids na perspectiva de profissionais de saúde

Este estudo teve por objetivo compreender o cuidado as pessoas com HIV/aids, na perspectiva de profissionais de saúde, em Portugal. Foi desenvolvido através do método da história oral, de Thompson, com a participação de 22 profissionais de saúde. Os dados foram obtidos através de entrevista semiestruturada e analisados com base na perspectiva de coletânea de narrativas, propostas pelo autor com o apoio do programa QSR NVivo. Os aspectos éticos foram obedecidos ao longo do estudo. O cuidado foi agrupado em três dimensões: cognitiva, afetiva-relacional e técnico-instrumental. A dimensão cognitiva destacou-se no período da revelação do diagnóstico de HIV/aids e ao longo da evolução da doença. A dimensão afetivo-relacional foi transversal e valorizada em todo o processo, desde o diagnóstico até à morte das pessoas com HIV/aids. A dimensão técnico-instrumental foi mais expressiva na fase mais avançada da doença, em situação de dependência e de terminalidade. Diante do exposto, podemos concluir que estas três dimensões são fundamentais para o cuidado à pessoa com HIV/aids.

The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project.

The association between adiposity measures and dyslipidemia has seldom been assessed in a multipopulational setting. 27 populations from Europe, Australia, New Zealand and Canada (WHO MONICA project) using health surveys conducted between 1990 and 1997 in adults aged 35-64 years (n = 40,480). Dyslipidemia was defined as the total/HDL cholesterol ratio >6 (men) and >5 (women). Overall prevalence of dyslipidemia was 25% in men and 23% in women. Logistic regression showed that dyslipidemia was strongly associated with body mass index (BMI) in men and with waist circumference (WC) in women, after adjusting for region, age and smoking. Among normal-weight men and women (BMI<25 kg/m(2)), an increase in the odds for being dyslipidemic was observed between lowest and highest WC quartiles (OR = 3.6, p < 0.001). Among obese men (BMI ≥ 30), the corresponding increase was smaller (OR = 1.2, p = 0.036). A similar weakening was observed among women. Classification tree analysis was performed to assign subjects into classes of risk for dyslipidemia. BMI thresholds (25.4 and 29.2 kg/m(2)) in men and WC thresholds (81.7 and 92.6 cm) in women came out at first stages. High WC (>84.8 cm) in normal-weight men, menopause in women and regular smoking further defined subgroups at increased risk. standard categories of BMI and WC, or their combinations, do not lead to optimal risk stratification for dyslipidemia in middle-age adults. Sex-specific adaptations are necessary, in particular by taking into account abdominal obesity in normal-weight men, post-menopausal age in women and regular smoking in both sexes.

Estimação da média com observações

Neste trabalho abordamos o problema da estimação da média de uma variável aleatória que depende de outra (ou outras) através de um modelo de regressão. O conhecimento completo da amostra permite o tratamento deste problema utilizando os métodos clássicos para a estimação da regressão. Aqui iremos estudar uma solução para o problema quando parte da informação que compõe a amostra se perde, nomeadamente, quando, na amostra que permite o tratamento do problema de regressão, algumas das ordenadas não são conhecidas, mas sim apenas o valor para variável explicativa. A solução mais simples neste caso consistiria em ignorar os pontos correspondentes da amostra. Contudo, aqui, pretende-se estudar um método que tenta tirar partido do conhecimento de que houve uma observação e que o valor desta está relacionado com a abcissa disponível através de um modelo de regressão que será aproximado à custa dos pontos da amostra conhecidos na totalidade. Numa primeira instância introduzimos os métodos não paramétricos de aproximação da regressão, a explorar, regressograma e Nadaraya- Watson. Em capítulos posteriores, descrevemos a adaptação do estimador Nadaraya-Watson ao problema das amostras incompletas. Discutemse ainda adaptações que tentam minimizar as dificuldades deste estimador quando o espaço das abcissas é de dimensão grande, assumindo que parte da função de regressão tem um comportamento linear, portanto paramétrico. Neste trabalho apresentamos resultados que asseguram a normalidade assimptótica dos estimadores definidos.

Estudo taxonômico de Leschenaultia Robineau-Desvoidy (Diptera, Tachinidae)

Taxonomic study of Leschenaultia Robineau-Desvoidy (Diptera, Tachinidae). The genus Leschenaultia Robineau-Desvoidy, 1830 is redescribed. Two genera are considered as its junior synonyms: Echinomasicera Townsend, 1915 syn. nov. and Parachaetopsis Blanchard, 1959 syn. nov. Thirty two especies are treated, as follows: 18 described as new, Leschenaultia aldrichi, sp. nov. (Brazil, Santa Catarina), L. arnaudi sp. nov. (Haiti, La Salle), L. bergenstammi sp. nov. (Peru, San Martin), L. bessi sp. nov. (Brazil, Santa Catarina), L. bigoti sp. nov. (Peru, Huanuco), L. blanchardi sp. nov. (Equador, Cuenca), L. braueri sp. nov. (Brazil, Mato Grosso), L. brooksi sp. nov. (Brazil, Rio de Janeiro), L. coquilletti sp. nov. (Brazil, Santa Catarina); L. cortesi sp. nov. (Venezuela, Maracay), L. currani sp. nov. (Brazil, São Paulo), L. loewi sp. nov. (Mexico, Vera Cruz), L. macquarti sp. nov. (U. S. A., Arizona), L. reinhardi sp. nov. (Canada, Quebec), L. sabroskyi sp. nov. from (U. S. A., California), L. schineri sp. nov. (U. S. A., California), L. thompsoni sp. nov. (Mexico, Mexico City), L. townsendi sp. nov. (Mexico, Puebla), and 14 known species, for these, diagnoses are given: L. adusta (Loew, 1872); L. americana (Brauer & Bergenstamm, 1893); L. bicolor (Macquart, 1846) = L. fusca (Townsend, 1916) syn. nov.; = Parachaetopsis proseni Blanchard, 1959 syn. nov.; L. ciliata (Macquart, 1848); L. exul (Townsend, 1892); L. fulvipes (Bigot, 1887); L. grossa Brooks, 1947; L. halisidotae Brooks, 1947; L. hospita Reinhard, 1952; L. hystrix (Townsend, 1915) comb. nov., L. jurinioides (Townsend, 1895); L. leucophrys (Wiedemann, 1830) = Leschenaultia latifrons (Walker, 1852) syn. nov. = Parachaeta nigricalyptrata (Macquart, 1855) syn. nov.; L. montagna (Townsend, 1912); L. nuda Thompson, 1963. One species was not examined, Leschenaultia nigrisquamis (Townsend, 1892), and two were not recognized, L. trichopsis (Bigot, 1887) and L. hirta Robineau-Desvoidy, 1830. Keys for Nearctic and Neotropical species (only for males) are provided, as well as geographical distribution and illustrations for each species.

Riqueza de formigas (Hymenoptera, Formicidae) epigéicas em povoamentos de Eucalyptus spp. (Myrtaceae) de diferentes idades no Rio Grande do Sul, Brasil

Este estudo descreve as comunidades de formigas de solo em povoamentos de eucalipto implantados em ecossistema de restinga no Rio Grande do Sul. As coletas de formigas foram feitas em seis povoamentos de Eucalyptus grandis Hill ex Maiden e de Eucalyptus saligna Smith com idades de 31, 19, sete e cinco anos. Para as coletas de formigas, foram selecionados ao acaso 24 talhões, quatro por povoamento. Em cada talhão, foram traçados três transectos com 100 m de comprimento, afastados entre si 12 m. Ao longo dos transectos, foram enterradas 30 armadilhas, tipo pitfall, com iscas de sardinha, afastadas entre si 10 m e mantidas por 24 horas. Foi coletado um total de 21.033 formigas pertencentes a cinco subfamílias, 12 tribos, 19 gêneros e 49 espécies. De acordo com o estimador de riqueza jackknife de primeira ordem, não houve diferenças significativas entre as riquezas das comunidades de formigas considerando as espécies de eucalipto (U = 81,500; g.l.=1; P=0,582) e as idades dos povoamentos (U=2,504; g.l.=3; P=0,547). Os resultados indicam que a riqueza de espécies de formigas não está relacionada à espécie de eucalipto e/ou à idade do povoamento implantado na restinga.

Abundância e riqueza de espécies de Syrphidae (Diptera) em áreas de borda e interior de floresta no Parque Estadual de Vila Velha, Ponta Grossa, Paraná, Brasil

Com o objetivo de caracterizar a fauna local de insetos foram obtidas amostras semanais, de setembro/1999 a agosto/2000, utilizando-se armadilhas Malaise instaladas na borda da floresta e no seu interior. Uma análise temporal foi realizada com as espécies de Syrphidae coletadas há, aproximadamente, dezessete anos no mesmo local, dentro da floresta. A abundância e a riqueza de espécies também foram avaliadas. Tanto a riqueza quanto a abundância foram maiores na borda da floresta. Comparando-se os dados atuais com aqueles obtidos em 1986/1987, observa-se um decréscimo na abundância e também na riqueza de espécies de Syrphidae. A espécie mais abundante na borda foi Allograpta neotropica Curran, 1936 e no interior (1999/2000), Ocyptamus sativus (Curran, 1941). Os espécimens de Toxomerus Macquart, 1855 foram os mais abundantes na armadilha localizada na borda da floresta e os de Ocyptamus Macquart, 1834 no interior. Noventa e cinco espécies foram identificadas em 22 gêneros. Ocyptamus foi o gênero com maior riqueza de espécies (23). Na seqüência estão Copestylum Macquart, 1846 (15), Toxomerus (15) e Microdon Meigen, 1803 (10). Sete espécies foram comuns aos três levantamentos: Allograpta neotropica; Copestylum selectum (Curran, 1939); Leucopodella gracilis (Williston, 1891); Mixogaster polistes Hull, 1954; Ocyptamus funebris Macquart, 1834; Toxomerus procrastinatus Metz, 2001 e Toxomerus tibicen (Wiedemann, 1830). Três novas espécies de Microdon, uma de Toxomerus, uma de Aristosyrphus Curran, 1941 e uma de Myolepta Newman, 1838 foram identificadas.

Riqueza de formigas de solo na praia da Pedreira, Parque Estadual de Itapuã, Viamão, RS, Brasil

Neste trabalho são listadas as espécies de formigas de solo encontradas em três ambientes (mata nativa, barreira pedregosa e areias da orla) na praia da Pedreira, localizada na Zona de Uso Intensivo do Parque Estadual de Itapuã, município de Viamão, RS. No total, foram identificadas 60 espécies representantes de 24 gêneros, 18 tribos e oito subfamílias (Dolichoderinae, Ecitoninae, Ectatomminae, Formicinae, Heteroponerinae, Myrmicinae, Ponerinae e Pseudomyrmecinae). Dos três ambientes amostrados, de acordo com o estimador de riqueza jackknife de primeira ordem, a mata nativa apresentou a maior riqueza (Sest= 37,5), seguindo-se a barreira pedregosa (Sest= 8,9) e as areias da orla (Sest= 5,9). Apenas Acromyrmex laticeps, Crematogaster sp. e Solenopsis invicta foram comuns aos três ambientes. Neste trabalho é feito o primeiro registro de ocorrência de Pachycondyla crenata e Pachycondyla laevigata (Ponerinae) para o Rio Grande do Sul.

BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF.

B cell homeostasis has been shown to critically depend on BAFF, the B cell activation factor from the tumor necrosis factor (TNF) family. Although BAFF is already known to bind two receptors, BCMA and TACI, we have identified a third receptor for BAFF that we have termed BAFF-R. BAFF-R binding appears to be highly specific for BAFF, suggesting a unique role for this ligand-receptor interaction. Consistent with this, the BAFF-R locus is disrupted in A/WySnJ mice, which display a B cell phenotype qualitatively similar to that of the BAFF-deficient mice. Thus, BAFF-R appears to be the principal receptor for BAFF-mediated mature B cell survival.

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Autosomal Recessive Posterior Microphthalmos/Nanophthalmos is Caused by Loss-of-function Mutations in LOC646960, a Novel Gene Encoding a Trypsin-like Serine Protease

Purpose: Posterior microphthalmos (MCOP)/nanophthalmos (NNO) is a developmental anomaly characterized by extreme hyperopia due to short axial length. The population of the Faroe Islands shows a high prevalence of an autosomal recessive form (arMCOP). The gene mutated in arMCOP is not yet known.Methods: Genetic mapping by linkage analysis using microsatellite and single nucleotide polymorphisms, mutation analysis by PCR and sequencing, molecular modellingResults: Having refined the position of the disease locus (MCOP6) in an interval of 250 kb in chromosome 2q37.1 in Faroese families, we detected 3 mutations in a novel gene, LOC646960: Patients of 10 different Faroese families were either homozygous (n=22) for c.926G>C (p.Trp309Ser) or compound heterozygous (n=6) for c.926G>C and c.526C>G (p.Arg176Gly), whereas a homozygous 1 bp duplication (c.1066dupC) was identified in patients with arNNO from a Tunisian family. In two unrelated patients with MCOP, no LOC646960 mutation was found. LOC646960 is expressed in the human adult retina and RPE. The expression of the mouse homologue in the eye can be first detected at E17 and is highest in adults. The predicted protein is a 603 amino acid long secreted trypsin-like serine peptidase. c.1066dupC should result in a functional null allele. Molecular modelling of the p.Trp309Ser mutant suggests that both affinity and reactivity of the enzyme towards in vivo substrates are substantially reduced.Conclusions: Postnatal growth of the eye is important for proper development of the refractive components (emmetropization), and is mainly due to elongation of the posterior segment from 10-11 mm at birth to 15-16 mm at the age of 13 years. Optical defocus leads to changes in axial length by moving the retina towards the image plane. arMCOP may theoretically be explained, in line with the expression pattern of LOC646960, by a postnatal growth retardation of the posterior segment.