The PPARgamma agonist pioglitazone modifies the vascular sodium-angiotensin II relationship in insulin-resistant rats.

Glitazones are efficient insulin sensitizers that blunt the effects of angiotensin II (ANG II) in the rat. Sodium chloride is another important modulator of the systemic and renal effects of ANG II. Whether glitazones interfere with the interaction between sodium and the response to ANG II is not known. Therefore, we investigated the effects of pioglitazone on the relationship between sodium and the systemic and renal effects of ANG II in rats. Pioglitazone, or vehicle, was administered for 4 wk to 8-wk-old obese Zucker rats. Animals were fed a normal-sodium (NS) or a high-sodium (HS) diet. Intravenous glucose tolerance tests, systemic and renal hemodynamic responses to ANG II, and the renal ANG II binding and expression of ANG II type 1 (AT(1)) receptors were measured. The results of our study were that food intake and body weight increased, whereas blood pressure, heart rate, filtration fraction, and insulin levels decreased significantly with pioglitazone in obese rats on both diets. Pioglitazone blunted the systemic response to ANG II and abolished the increased responsiveness to ANG II induced by a HS diet. Pioglitazone modified the renal hemodynamic response to changes in salt intake while maintaining a lower filtration fraction with ANG II perfusion. These effects were associated with a decrease in the number and expression of the AT(1) receptor in the kidney. In conclusion, these data demonstrate that the peroxisome proliferator-activated receptor-gamma agonist pioglitazone modifies the physiological relationship between sodium chloride and the response to ANG II in insulin-resistant rats.

Fósforo em solos representativos do estado da paraíba: II- disponibilidade de fósforo para plantas de milho

Os laboratórios de fertilidade do solo do Estado da Paraíba utilizam apenas o extrator Mehlich-1 para avaliar o teor de P disponível, independente do grau de intemperismo do solo. Como os solos pouco intemperizados representam a maioria dos solos do Estado, é necessário avaliar a eficiência do Mehlich-1 e de outros extratores usados para avaliação da disponibilidade de P para as plantas. O objetivo deste trabalho foi avaliar a eficiência dos extratores Mehlich-1 (M-1), Mehlich-3 (M-3), Bray-1 (B-1) e resina de troca iônica mista (RTI) na quantificação do P disponível para plantas de milho em solos do Estado da Paraíba. Amostras de 12 solos representativos do Estado da Paraíba foram coletadas na camada de 0-30 cm de profundidade, sendo seis solos mais intemperizados e seis solos menos intemperizados, com ampla variação de características físicas e químicas. Para os solos PA, PVe, LA, RL, TX, SX e RY, aplicaram-se as doses 0; 43,75; 87,5; 175 e 350 mg dm-3 de P. Para os solos PAC e RR, aplicaram-se as doses 0; 37,5; 75; 150 e 300 mg dm-3 de P. Para os solos PVA, PVd e VX, as doses de P foram 0; 51,25; 102,5; 205 e 410 mg dm-3 de P. O experimento foi conduzido em casa de vegetação e as doses de P aplicadas foram homogeneizadas em 100 % do volume de solo de cada vaso (3 dm³). Foi cultivado milho por um período de 35 dias e foram determinados os níveis críticos de P no solo pelos extratores e o nível crítico de P na planta. Independente da dose de P aplicada, o extrator M-3 foi o que extraiu mais P dos solos e o B-1 o que extraiu menos. Quando se aplicaram pequenas doses de P aos solos, o M-1 e a RTI extraíram quantidades semelhantes de P, mas, nas maiores doses, a RTI extraiu mais P que o M-1. Ao contrário do que foi verificado para a planta e para a RTI, para os extratores M-1, M-3 e B-1 a taxa de recuperação do P aplicado ao solo correlacionou-se com o fator capacidade de fósforo (FCP). Por outro lado, os níveis críticos de P no solo pelos extratores M-1, M-3 e B-1 e os níveis críticos de P na planta não se correlacionaram com características do solo relacionadas com o FCP, diferentemente do que foi verificado para os níveis críticos de P no solo pela RTI. Em casa de vegetação, qualquer um dos extratores avaliados mostrou-se eficiente para avaliação da disponibilidade de P para plantas de milho em solos representativos do Estado da Paraíba, uma vez que o P extraído por esses extratores apresentou boa correlação com o P acumulado na planta.

Systemic in vivo lentiviral delivery of miR-15a/16 reduces malignancy in the NZB de novo mouse model of chronic lymphocytic leukemia.

Similar to human chronic lymphocytic leukemia (CLL), the de novo New Zealand Black (NZB) mouse model has a genetically determined age-associated increase in malignant B-1 clones and decreased expression of microRNAs miR-15a and miR-16 in B-1 cells. In the present study, lentiviral vectors were employed in vivo to restore miR-15a/16, and both the short-term single injection and long-term multiple injection effects of this delivery were observed in NZB. Control lentivirus without the mir-15a/16 sequence was used for comparison. We found that in vivo lentiviral delivery of mir-15a/16 increased miR-15a/16 expression in cells that were transduced (detected by GFP expression) and in sera when compared with control lentivirus treatment. More importantly, mice treated with the miR-expressing lentivirus had decreased disease. The lentivirus had little systemic toxicity while preferentially targeting B-1 cells. Short-term effects on B-1 cells were direct effects, and only malignant B-1 cells transduced with miR-15a/16 lentivirus had decreased viability. In contrast, long-term studies suggested both direct and indirect effects resulting from miR-15a/16 lentivirus treatment. A decrease in B-1 cells was found in both the transduced and non-transduced populations. Our data support the potential use of systemic lentiviral delivery of miR-15a/16 to ameliorate disease manifestations of CLL.

Premature replacement of mu with alpha immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation.

Sequentially along B cell differentiation, the different classes of membrane Ig heavy chains associate with the Ig alpha/Ig beta heterodimer within the B cell receptor (BCR). Whether each Ig class conveys specific signals adapted to the corresponding differentiation stage remains debated. We investigated the impact of the forced expression of an IgA-class receptor throughout murine B cell differentiation by knocking in the human C alpha Ig gene in place of the S mu region. Despite expression of a functional BCR, homozygous mutant mice showed a partial developmental blockade at the pro-B/pre-BI and large pre-BII cell stages, with decreased numbers of small pre-BII cells. Beyond this stage, peripheral B cell compartments of reduced size developed and allowed specific antibody responses, whereas mature cells showed constitutive activation and a strong commitment to plasma cell differentiation. Secreted IgA correctly assembled into polymers, associated with the murine J chain, and was transported into secretions. In heterozygous mutants, cells expressing the IgA allele competed poorly with those expressing IgM from the wild-type allele and were almost undetectable among peripheral B lymphocytes, notably in gut-associated lymphoid tissues. Our data indicate that the IgM BCR is more efficient in driving early B cell education and in mucosal site targeting, whereas the IgA BCR appears particularly suited to promoting activation and differentiation of effector plasma cells.

Murine alpha1-adrenoceptor subtypes. I. Radioligand binding studies.

Alpha1-adrenoceptors were identified in murine tissues by [3H]prazosin saturation binding studies, with a rank order of cerebral cortex > cerebellum > liver > lung > kidney > heart > spleen, with the spleen not exhibiting detectable expression. Competition binding studies were performed with 5-methylurapidil, BMY 7378, methoxamine, (+)-niguldipine, noradrenaline, SB 216469 and tamsulosin. On the basis of monophasic low-affinity competition by BMY 7378, alpha1D-adrenoceptors were not detected at the protein level in any tissue. On the basis of competition studies with the alpha1A/alpha1B-discriminating drugs, alpha1B-adrenoceptors appeared to be the predominant or even the sole subtype in murine liver, lung and cerebellum, whereas murine cerebral cortex and kidney contained approximately 30% and 50% of alpha1A-adrenoceptors, respectively. The affinities of the various competitors in the murine tissues were quite similar to those reported from other species. The ratio of high- and low-affinity sites for tamsulosin did not in all cases match the percentages of alpha1A- and alpha1B-adrenoceptors detected by the other competitors; however, the low-affinity component of the tamsulosin competition curves was abolished in the cerebral cortex of alpha1B-adrenoceptor knockout mice. Treatment with chloroethylclonidine (10 microM, 30 min, 37 degrees C) inactivated the alpha1-adrenoceptors in all tissues by >75%. When the concentration-dependent inactivation of tissue alpha1B-adrenoceptors (liver) and tissue alpha1A-adrenoceptors (cerebral cortex from alpha1B-adrenoceptor knockout mice) was compared, alpha1A-adrenoceptors were only slightly less sensitive toward chloroethylclonidine than alpha1B-adrenoceptors. We conclude that murine tissues express alpha1A- and alpha1B-adrenoceptors, which are largely similar to those in other species. However, the tissue-specific distribution of subtypes may differ from that of other species.

Constitutive activity and inverse agonism at the alpha1adrenoceptors.

Mutations of G protein-coupled receptors (GPCR) can increase their constitutive (agonist-independent) activity. Some of these mutations have been artificially introduced by site-directed mutagenesis, others occur spontaneously in human diseases. The alpha(1B)adrenoceptor was the first GPCR in which point mutations were shown to trigger receptor activation. This article briefly summarizes some of the findings reported in the last several years on constitutive activity of the alpha(1)adrenoceptor subtypes, the location where mutations have been found in the receptors, the spontaneous activity of native receptors in recombinant as well as physiological systems. In addition, it will highlight how the analysis of the pharmacological and molecular properties of the constitutively active adrenoceptor mutants provided an important contribution to our understanding of the molecular mechanisms underlying the mechanism of receptor activation and inverse agonism.

Insulin and insulin-like growth factor I receptors utilize different G protein signaling components.

We examined the role of heterotrimeric G protein signaling components in insulin and insulin-like growth factor I (IGF-I) action. In HIRcB cells and in 3T3L1 adipocytes, treatment with the Galpha(i) inhibitor (pertussis toxin) or microinjection of the Gbetagamma inhibitor (glutathione S-transferase-betaARK) inhibited IGF-I and lysophosphatidic acid-stimulated mitogenesis but had no effect on epidermal growth factor (EGF) or insulin action. In basal state, Galpha(i) and Gbeta were associated with the IGF-I receptor (IGF-IR), and after ligand stimulation the association of IGF-IR with Galpha(i) increased concomitantly with a decrease in Gbeta association. No association of Galpha(i) was found with either the insulin or EGF receptor. Microinjection of anti-beta-arrestin-1 antibody specifically inhibited IGF-I mitogenic action but had no effect on EGF or insulin action. beta-Arrestin-1 was associated with the receptors for IGF-I, insulin, and EGF in a ligand-dependent manner. We demonstrated that Galpha(i), betagamma subunits, and beta-arrestin-1 all play a critical role in IGF-I mitogenic signaling. In contrast, neither metabolic, such as GLUT4 translocation, nor mitogenic signaling by insulin is dependent on these protein components. These results suggest that insulin receptors and IGF-IRs can function as G protein-coupled receptors and engage different G protein partners for downstream signaling.

Hereditary diffuse leukoencephalopathy with axonal spheroids: More than just a rare disease.

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a progressive white matter disease with a wide range of clinical symptoms including dementia, behavioral changes, seizures, pyramidal signs, ataxia, and parkinsonism.(1-3) Affected individuals develop symptoms in their early 40s with an average survival time of 10 years. HDLS is inherited as an autosomal dominant trait. Recently, mutations in the colony-stimulating factor 1 receptor gene (CSF-1R) were identified as the genetic cause of HDLS.(4) White matter lesions, easily demonstrated on MRI studies, involve predominantly the frontal lobes and corpus callosum with subsequent cortical atrophy. MRI abnormalities are present prior to symptom onset.(5,6) Histopathology shows widespread myelin and axon destruction with axonal dilations termed spheroids, as well as pigmented macrophages.

Physical quality of an Oxisol under an integrated crop-livestock-forest system in the Brazilian Cerrado

Soil physical quality is an important factor for the sustainability of agricultural systems. Thus, the aim of this study was to evaluate soil physical properties and soil organic carbon in a Typic Acrudox under an integrated crop-livestock-forest system. The experiment was carried out in Mato Grosso do Sul, Brazil. Treatments consisted of seven systems: integrated crop-livestock-forest, with 357 trees ha-1 and pasture height of 30 cm (CLF357-30); integrated crop-livestock-forest with 357 trees ha-1 and pasture height of 45 cm (CLF357-45); integrated crop-livestock-forest with 227 trees ha-1 and pasture height of 30 cm (CLF227-30); integrated crop-livestock-forest with 227 trees ha-1 and pasture height of 45 cm (CLF227-45); integrated crop-livestock with pasture height of 30 cm (CL30); integrated crop-livestock with pasture height of 45 cm (CL45) and native vegetation (NV). Soil properties were evaluated for the depths of 0-10 and 10-20 cm. All grazing treatments increased bulk density (r b) and penetration resistance (PR), and decreased total porosity (¦t) and macroporosity (¦ma), compared to NV. The values of r b (1.18-1.47 Mg m-3), ¦ma (0.14-0.17 m³ m-3) and PR (0.62-0.81 MPa) at the 0-10 cm depth were not restrictive to plant growth. The change in land use from NV to CL or CLF decreased soil organic carbon (SOC) and the soil organic carbon pool (SOCpool). All grazing treatments had a similar SOCpool at the 0-10 cm depth and were lower than that for NV (17.58 Mg ha-1).

Evaluation pré-post d'une intervention de prévention du VIH auprès des hommes qui ont des rapports sexuels avec des hommes, Suisse 2012

Contexte: L'intervention "Break The Chains" 2012 de l'OFSP a l'intention des gays visait à informer sur la primo-infection et a inciter a un test de dépistage VIH. Design: L'évaluation a recouru a un design Pre-Post avec 2 dispositifs: A) enquête par questionnaire Internet avec une vague avant la campagne et une après (transversal repete); B) 1) relevé centré sur le canton de Zurich du nombre de test effectues par des gays durant le premier semestre 2012 utilisant des données récoltées par Sentinella, par les centres de test utilisant l'application BerDa et auprès des praticiens de HIV-Prakt; et 2) recueil d'information par le questionnaire internet post-intervention des intentions d'effectuer un test VIH. Résultats: 366 HSH ont répondu au questionnaire de la phase pré-, et 964 à la phase post-intervention. 69.8% ont entendu parler de la campagne. Parmi les répondants ayant identifie le message, 48.6% se sont sentis concernes. Avant la campagne, 34.2% des répondants identifiaient les 4 symptômes de la primo-infection, 46.4% se sentaient bien informes et 79.2% connaissaient le délai minimum pour qu'un test informe sur une absence d'infection; après la campagne, ces proportions étaient 39.6%, 62.0% et 85.2%. 17.1% des répondants ont déclaré avoir fait/avoir l'intention de faire, un test VIH suite à la campagne. Le nombre de tests effectues par les répondants Internet montre effectivement un pic dans le 2e trimestre 2012; les données BerDa montrent une stabilité du nombre total de tests. Les données épidémiologiques montrent une augmentation de la proportion et du nombre d'infections récentes détectées durant ce 2e trimestre, mais une diminution des infections anciennes. Conclusions: L'intervention BTC a amélioré légèrement les connaissances relatives à la phase de primo-infection du VIH et a la nécessité d'effectuer un test VIH. Elle semble avoir incite le public cible à effectuer un test VIH qui n'aurait pas été réalisé autrement et a peut-être ainsi contribuer a la détection d'infections récentes.

Plants and tortoises: mutations in the Arabidopsis jasmonate pathway increase feeding in a vertebrate herbivore.

Photosynthetic tissues, the major food source of many invertebrates and vertebrates, are well defended. Many defence traits in leaves are controlled via the jasmonate signalling pathway in which jasmonate acts as a hormone by binding to a receptor to activate responses that lead to increased resistance to invertebrate folivores. We predicted that mutations in jasmonate synthesis might also increase the vulnerability of leaves to vertebrate folivores and tested this hypothesis using the Eastern Hermann's tortoise (Eurotestudo boettgeri) and an Arabidopsis thaliana (Brassicaceae) allene oxide synthase (aos) mutant unable to synthesize jasmonate. Tortoises preferred the aos mutant over the wild type (WT). Based on these results, we then investigated the effect of mutating jasmonate perception using a segregating population of the recessive A. thaliana jasmonate receptor mutant coronatine insensitive1-1 (coi1-1). Genotyping of these plants after tortoise feeding revealed that the homozygous coi1-1 receptor mutant was consumed more readily than the heterozygous mutant or the WT. Therefore, the plant's ability to synthesize or perceive jasmonate reduces feeding by a vertebrate herbivore. We also tested whether or not tortoise feeding behaviour was influenced by glucosinolates, the principal defence chemicals in Arabidopsis leaves with known roles in defence against many generalist insects. However, in contrast to what has been observed with such insects, leaves in which the levels of these compounds were reduced genetically were consumed at a similar rate to those of the WT.

A.A.V.V.: Montbarbat (1978-1986), Lloret de Mar, 1996

Debe reconocerse que en estos años próximos al fin del milenio la publicación de estudios sobre el mundo ibérico goza de excelente salud, cuando menos en volumen. Artículos, ponencias y comunicaciones amenazan con abrumar al lector más impenitente. Por ello resulta aleccionador acudir al meritorio trabajo de Fernando Quesada: "La cultura ibérica: una aproximación bibliográfica (1992-1993)", RE/b, 1, 1994, 335-377, que reúne la producción en revistas y series no excesivamente locales -imposibles de controlar, por otro lado-, y comprobar un balance de unos doscientos títulos anuales. Ahora bien, si consideramos el número de monografías, nos situaremos en un plano selectivo, que rondará la docena al año. Diversos factores -y entre ellos la desidia de diferentes niveles administrativos y académicos- parecen confabularse para que no se disponga de un conjunto de memorias impresas proporcional al volumen de excavaciones realizadas en las dos últimas décadas.

« Genealogie de Bourbon », et histoire des accroissements territoriaux de cette famille, par ETIENNE LEBLANC.

Au fol. 5, miniature dans laquelle l'auteur est représenté offrant son ouvrage à Louise de Savoie. Ce volume, pour l'ornementation comme pour l'écriture, semble être de la même main que celui qui porte le n° 5715. Elle a été composée sur la demande de Louise de Savoie, ainsi que l'auteur le déclare dans sa dédicace (fol. 5). Elle commence (fol. 1) avant cette dédicace par : « Pour plus facillement entendre le contenu en ce present livre, au commencement d'iceluy ay mys ceste presente genealogie de la maison de Bourbon. Monsieur sainct Loys, roy de France... » et finit (fol. 30) par : «... esquelz escriptz toute foy doit estre adjoustée ». La seconde partie de l'ouvrage (fol. 23-30) est consacrée à saint Louis : « Probation que monseigneur sainct Loys ne destruisit point le royaume pour le sainct voyaige qu'il feist oultre mer ». L'auteur pour justifier saint Louis d'avoir ruiné le royaume pour le payement de sa rançon, lors de sa première croisade, énumère (fol. 23-24) les reliques acquises par ce roi, donne, en passant (fol. 24-25), les noms des « roys de France qui ont été en Terre saincte », indique (fol. 25-26) à combien monta la rançon de saint Louis, et montre qu'elle ne fut pas disproportionnée eu égard au temps et à la qualité du prisonnier du Soudan ; passe ensuite en revue (fol. 26-27) les églises et hôpitaux fondés après le payement de cette rançon par le saint roi, sans avoir recours à aucune taille, aide ni subside ; montre (fol. 27-28) que saint Louis ne fit jamais de monnaie de cuir et que c'est longtemps après son décès que les gabelles (fol. 28-29) furent établies. En dernier lieu, il parle (fol. 29-30) de la canonisation de saint Louis, proclamée en 1297 par les soins et aux frais de Philippe le Bel son petit-fils. Miniature, encadrement, lettres ornées.

« Genealogie de Bourbon », et histoire des accroissements territoriaux de cette famille, par ETIENNE LEBLANC.

Au fol. 5, miniature dans laquelle l'auteur est représenté offrant son ouvrage à Louise de Savoie. Ce volume, pour l'ornementation comme pour l'écriture, semble être de la même main que celui qui porte le n° 5715. Elle a été composée sur la demande de Louise de Savoie, ainsi que l'auteur le déclare dans sa dédicace (fol. 5). Elle commence (fol. 1) avant cette dédicace par : « Pour plus facillement entendre le contenu en ce present livre, au commencement d'iceluy ay mys ceste presente genealogie de la maison de Bourbon. Monsieur sainct Loys, roy de France... » et finit (fol. 30) par : «... esquelz escriptz toute foy doit estre adjoustée ». La seconde partie de l'ouvrage (fol. 23-30) est consacrée à saint Louis : « Probation que monseigneur sainct Loys ne destruisit point le royaume pour le sainct voyaige qu'il feist oultre mer ». L'auteur pour justifier saint Louis d'avoir ruiné le royaume pour le payement de sa rançon, lors de sa première croisade, énumère (fol. 23-24) les reliques acquises par ce roi, donne, en passant (fol. 24-25), les noms des « roys de France qui ont été en Terre saincte », indique (fol. 25-26) à combien monta la rançon de saint Louis, et montre qu'elle ne fut pas disproportionnée eu égard au temps et à la qualité du prisonnier du Soudan ; passe ensuite en revue (fol. 26-27) les églises et hôpitaux fondés après le payement de cette rançon par le saint roi, sans avoir recours à aucune taille, aide ni subside ; montre (fol. 27-28) que saint Louis ne fit jamais de monnaie de cuir et que c'est longtemps après son décès que les gabelles (fol. 28-29) furent établies. En dernier lieu, il parle (fol. 29-30) de la canonisation de saint Louis, proclamée en 1297 par les soins et aux frais de Philippe le Bel son petit-fils. Miniature, encadrement, lettres ornées.