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.

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.

A review of evolution of oviposition guilds in the Bruchidae (Coleoptera)

Three guilds of bruchid beetles oviposit on seeds at different times and in different ways, i. e., in these guilds some species only oviposit on fruits while on the plant (Guild A), other species only oviposit on seeds exposed in fruits while still on the plant (Guild B) and some only oviposit on seeds once they are exposed on the substrate (Guild C). It has been established that one plant species may be oviposited upon by all three guilds, some only by two guilds and some by only one guild. Before and after the inception of this concept many papers have been published that seem to establish that early oviposition behavior of bruchids was probably onto fruits where they burrowed through the fruit wall and fed on seeds (Guild A). Then, as evolution of the fruits developed for dispersal of seeds and possible escape from bruchid predation, bruchids developed to feed in seeds in various other ways (Guilds B and C). Our data show that about 78% of extant bruchids oviposit on fruits, and the other 22% with behavior of Guilds B and C. A review of these papers and new data on oviposition guilds and bruchid evolution are presented and discussed here.

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.

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.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSION: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor.

The homeodomain protein PDX-1, referred as IPF-1/STF-1/IDX-1, is a transcriptional factor that plays a critical role in the control of several genes expressed in the pancreatic islet. PDX-1 gene expression has been previously shown to be reduced in cultured beta-cell lines chronically exposed to high glucose concentrations. As the glucose transporter type 2 (GLUT2) gene expression is selectively decreased in the beta-pancreatic cells of experimental models of diabetes, we postulated that the loss of GLUT2 gene expression in the pancreatic islets of diabetic animals may be due to the loss of PDX-1 transacting function on the GLUT2 gene. We, therefore, investigated the potential role of PDX-1 in the transcriptional control of GLUT2. We have identified a repeat of a TAAT motif (5'-TAATA-ATAACA-3') conserved in the sequence of the human and murine GLUT2 promoters. Recombinant PDX-1 binds to this GLUT2TAAT motif in electrophoretic mobility shift experiments. PDX-1 antiserum detects the formation of the complex of PDX-1 with the GLUT2TAAT motif in nuclear extracts from the pancreatic insulin-secreting cell line, beta TC3. The GLUT2TAAT motif was mutated in the murine GLUT2 promoter (-1308/+49 bp) linked to a luciferase reporter gene and transfected into beta TC3 cells. Compared with the transcriptional activity of the wild type promoter, that of the mutated promoter decreases by 41%. Multiple copies of the GLUT2TAAT motif were ligated 5' to a heterologous promoter and transfected into a PDX-1-expressing cell line (beta TC3) and into cell lines lacking the homeobox factor (InR1-G9 and JEG-3). The GLUT2TAAT motif mediates the activation of the heterologous promoter in the PDX-1-expressing cell line but not in InR1-G9 or JEG-3 cell lines. Furthermore, cotransfection in a PDX-1-deficient cell line with the expression vector encoding PDX-1 transactivates specifically the heterologous promoter containing the multimerized GLUT2TAAT motif. These data demonstrate that the murine GLUT2 promoter is controlled by the PDX-1 homeobox factor through the identified GLUT2TAAT motif.

Nota técnica. Oxígeno disuelto en agua de mar: unidades y conversiones

La concentración de oxígeno disuelto en el agua de mar puede expresarse en diferentes unidades,tales como mL/L, μmol/kg, mg/L o % de saturación. En estudios de carácter oceanográfico, la unidad más empleada en las tres últimas décadas ha sido el mL/L y en la actualidad se ha optado por el mmol/Kg de acuerdo al Sistema Internacional de Unidades publicado en el año 1975 y actualizado en el año 1998 (Thompson y Taylor 2008).