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The aim of this work was to study the distribution and cellular localization of GLUT2 in the rat brain by light and electron microscopic immunohistochemistry, whereas our ultrastructural observations will be reported in a second paper. Confirming previous results, we show that GLUT2-immunoreactive profiles are present throughout the brain, especially in the limbic areas and related nuclei, whereas they appear most concentrated in the ventral and medial regions close to the midline. Using cresyl violet counterstaining and double immunohistochemical staining for glial or neuronal markers (GFAp, CAII and NeuN), we show that two limited populations of oligodendrocytes and astrocytes cell bodies and processes are immunoreactive for GLUT2, whereas a cross-reaction with GLUT1 cannot be ruled out. In addition, we report that the nerve cell bodies clearly immunostained for GLUT2 were scarce (although numerous in the dentate gyrus granular layer in particular), whereas the periphery of numerous nerve cells appeared labeled for this transporter. The latter were clustered in the dorsal endopiriform nucleus and neighboring temporal and perirhinal cortex, in the dorsal amygdaloid region, and in the paraventricular and reuniens thalamic nuclei, whereas they were only a few in the hypothalamus. Moreover, a group of GLUT2-immunoreactive nerve cell bodies was localized in the dorsal medulla oblongata while some large multipolar nerve cell bodies peripherally labeled for GLUT2 were scattered in the caudal ventral reticular formation. This anatomical localization of GLUT2 appears characteristic and different from that reported for the neuronal transporter GLUT3 and GLUT4. Indeed, the possibility that GLUT2 may be localized in the sub-plasmalemnal region of neurones and/or in afferent nerve fibres remains to be confirmed by ultrastructural observations. Because of the neuronal localization of GLUT2, and of its distribution relatively similar to glucokinase, it may be hypothesized that this transporter is, at least partially, involved in cerebral glucose sensing.

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Para avaliar o efeito de substratos e da adubação fosfatada sobre a produção de mudas de cacaueiro, bem como definir doses recomendáveis e nível crítico foliar de P, fez-se um experimento fatorial 5 x 5 + 1: cinco substratos (misturas de fibra de coco (FC) e Plantmax florestal estaca®), cinco doses de P no plantio (de 0 a 800 mg dm-3) e um tratamento adicional (P aplicado aos 30 dias). As parcelas iniciais e úteis continham, respectivamente, 27 estacas e 12 mudas (uma estaca/muda por tubete). A partir do 62º dia, aplicaram-se adubações semanais com N e K, e aos 120 dias, com P (20 mg dm-3), em todos os tratamentos. Aos 150 dias foram avaliados: diâmetro, altura, área foliar, massa de matéria seca da parte aérea e das raízes (finas e grossas), concentração e conteúdo de nutrientes na planta. A mortalidade das mudas não foi influenciada pelos tratamentos. A adubação com P em cobertura aumentou sua disponibilidade e sua absorção, mas não o crescimento das mudas. As variáveis biométricas e nutricionais responderam aos tratamentos, sendo os melhores resultados obtidos com 30 a 55 % de FC e doses de P entre 136 e 275 mg dm-3. O nível crítico foliar de P foi de 1,75 g kg-1.

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A rugosidade superficial do solo é uma característica importante, pois influencia a infiltração e a armazenagem de água no solo, a retenção de sedimentos na superfície e a erosão hídrica. Por sua vez, a rugosidade é influenciada pelo preparo, umidade e compactação do solo, pelos resíduos culturais, pelo efeito residual do uso do solo e pela erosividade da chuva. Este trabalho teve o objetivo de quantificar o efeito do tipo de preparo, da compactação do solo e da erosividade da chuva sobre o índice de rugosidade superficial ao acaso modificado (RRM), em um experimento conduzido sob chuva natural em um Cambissolo Húmico Alumínico léptico, com declividade média de 0,03 m m-1, entre setembro e novembro de 2008, em Lages, SC, com os seguintes tratamentos: (1) superfície quase lisa em solo compactado (LIC); (2) superfície quase lisa em solo não compactado (LINC); (3) uma aração e duas gradagens em solo compactado (PCC); (4) uma aração e duas gradagens em solo não compactado (PCNC); (5) uma escarificação em solo compactado (ESC); e (6) uma escarificação em solo não compactado (ESNC). O microrrelevo do solo foi medido com rugosímetro mecânico de varetas, em seis oportunidades: imediatamente antes e imediatamente após instalar os tratamentos; e após a ocorrência de cada um dos valores de erosividade (EI30) da chuva: 136, 190, 630 e 265 MJ mm ha-1 h-1. O preparo do solo com aração e gradagens e com escarificação aumentou o índice RRM em relação a antes do preparo, tanto em solo não compactado quanto em solo compactado. O aumento desse índice foi de 3,72 vezes em aração e gradagens e de 3,88 vezes na escarificação, na média do solo compactado e não compactado. A compactação do solo aumentou o índice RRM, independentemente do tipo de preparo. No caso da aração e gradagens, o aumento nesse índice foi de 4,58 vezes no solo compactado e de 3,04 vezes no não compactado, logo após o preparo; em se tratando da escarificação, em solo compactado o aumento pelo preparo foi de 5,49 vezes e de 2,61 vezes no solo não compactado, também logo após o preparo. A erosividade da chuva diminuiu o índice RRM, independentemente do tipo de preparo e da compactação do solo, cuja relação foi descrita pelo modelo y = ae-bx.

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OBJECTIVE: High-dose methotrexate (MTX) exposure during pregnancy is associated with embryopathy. The teratogenic potential of MTX at dosages typically used in the treatment of rheumatic diseases remains uncertain. The aim of this study was to evaluate the risk of spontaneous abortion, major birth defects, elective termination of pregnancy, shortened gestational age at delivery, and reduced birth weight in women exposed to MTX. METHODS: Pregnancy outcome in women taking MTX (≤30 mg/week) either after conception or within the 12 weeks before conception was evaluated in a prospective observational multicenter cohort study. Pregnancy outcomes in the MTX group were compared to outcomes in a group of disease-matched women and a group of women without autoimmune diseases (neither group was exposed to MTX). RESULTS: The study sample included 324 MTX-exposed pregnancies (188 exposed post-conception, 136 exposed pre-conception), 459 disease-matched comparison women, and 1,107 comparison women without autoimmune diseases. In the post-conception cohort, the cumulative incidence of spontaneous abortion was 42.5% (95% confidence interval [95% CI] 29.2-58.7), which was significantly higher than the incidence of spontaneous abortion in either comparison group. The risk of major birth defects (7 of 106 [6.6%]) was elevated compared to both the cohort of women without autoimmune diseases (29 of 1,001 [2.9%]) (adjusted odds ratio [OR] 3.1 [95% CI 1.03-9.5]) and the disease-matched cohort (14 of 393 [3.6%]) (adjusted OR 1.8 [95% CI 0.6-5.7]). None of the malformations were clearly consistent with MTX embryopathy. Neither the cumulative incidence of spontaneous abortion (14.4% [95% CI 8.0-25.3]) nor the risk of major birth defects (4 of 114 [3.5%]) was increased in the pre-conception cohort. Elective termination rates were increased in both of the MTX-exposed cohorts. There were no other significant differences among groups in other study end points. CONCLUSION: Post-conception administration of MTX at dosages typically used in the treatment of rheumatic diseases was associated with an increased risk of major birth defects and spontaneous abortion. Such evidence was not found among women in our pre-conception cohort.

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Socrates' serene attitude before his death -although this is questioned-, as described by Xenophon in his Apologia Socratis becomes for the playwright Rodolf Sirera a useful reference in an effort to reflect boldly on the limits of theatrical fiction in another clear example of the Classical Tradition, including that derived from Baroque Tragedy. However, in this case, it is judged severely to make us more conscious of the risk of turning life into a mere theatrical performance and human beings into actors and actresses in a play they did not write.

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Socrates' serene attitude before his death -although this is questioned-, as described by Xenophon in his Apologia Socratis becomes for the playwright Rodolf Sirera a useful reference in an effort to reflect boldly on the limits of theatrical fiction in another clear example of the Classical Tradition, including that derived from Baroque Tragedy. However, in this case, it is judged severely to make us more conscious of the risk of turning life into a mere theatrical performance and human beings into actors and actresses in a play they did not write.

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The effects of the thyroid hormones on target cells are mediated through nuclear T3 receptors. In the peripheral nervous system, nuclear T3 receptors were previously detected with the monoclonal antibody 2B3 mAb in all the primary sensory neurons throughout neuronal life and in peripheral glia at the perinatal period only (Eur. J. Neurosci. 5, 319, 1993). To determine whether these nuclear T3 receptors correspond to functional ones able to bind T3, cryostat sections and in vitro cell cultures of dorsal root ganglion (DRG) or sciatic nerve were incubated with 0.1 nM [125I]-labeled T3, either alone to visualize the total T3-binding sites or added with a 10(3) fold excess of unlabeled T3 to estimate the part due to the non-specific T3-binding. After glutaraldehyde fixation, radioautography showed that the specific T3-binding sites were largely prevalent. The T3-binding capacity of peripheral glia in DRG and sciatic nerve was restricted to the perinatal period in vivo and to Schwann cells cultured in vitro. In all the primary sensory neurons, specific T3-binding sites were disclosed in foetal as well as adult rats. The detection of the T3-binding sites in the nucleus indicated that the nuclear T3 receptors are functional. Moreover the concomitant presence of both T3-binding sites and T3 receptors alpha isoforms in the perikaryon of DRG neurons infers that: 1) [125I]-labeled T3 can be retained on the T3-binding 'E' domain of nascent alpha 1 isoform molecules newly-synthesized on the perikaryal ribosomes; 2) the alpha isoforms translocated to the nucleus are modified by posttranslational changes and finally recognized by 2B3 mAb as nuclear T3 receptor. In conclusion, the radioautographic visualization of the T3-binding sites in peripheral neurons and glia confirms that the nuclear T3 receptors are functional and contributes to clarify the discordant intracellular localization provided by the immunocytochemical detection of nuclear T3 receptors and T3 receptor alpha isoforms.

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Résumé Dans la maladie de Crohn, le clinicien ne dispose pas toujours d'études prospectives randomisées ou autres preuves solides sur lesquelles appuyer sa décision thérapeutique. Pour pallier ce manque, la méthode RAND, qui combine une revue détaillée de la littérature et une synthèse méthodique de l'opinion d'experts, a été utilisée pour développer des critères détaillés d'adéquation de traitements pour les différentes présentations cliniques de la maladie de Crohn. La présente étude a eu pour but d'examiner la faisabilité d'une utilisation rétrospective de ces critères dans une cohorte de patients souffrant de maladie de Crohn. Les dossiers médicaux des patients ayant consulté leur spécialiste au moins une fois dans les 6 mois précédents ont été revus à la recherche des éléments établis par les experts. Pour les dossiers contenant tous les éléments nécessaires, l'adéquation des divers traitements a été évaluée. Les dossiers médicaux de 260 patients suivis par 22 gastro-entérologues ont été examinés. 116 patients ont été exclus pour absence de consultation dans les 6 mois précédents. 136 patients (53%) représentant 148 consultations ont été retenus. Dans plus de 90% des cas, les éléments nécessaires à l'évaluation de l'adéquation du traitement étaient disponibles, cette proportion variant quelque peu selon la catégorie de la maladie. En appliquant les critères lorsque les éléments nécessaires étaient présents dans le dossier médical, 18% des indications aux traitements étaient appropriées, 29% inappropriées et pour 38% l'indication était incertaine. Pour 15% des cas, la situation clinique rencontrée n'avait pas été explicitement évaluée par les experts. Les informations nécessaires à l'évaluation des indications aux divers traitements de la maladie de Crohn sont disponibles dans la très grande majorité des dossiers médicaux, permettant ainsi l'évaluation de l'adéquation des traitements. Cette étude ouvre la voie à l'utilisation prospective de ces critères.

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Lors de l'apprentissage d'une langue étrangère, l'apprenant ne s'interroge guère sur la légitimité d'appréhender la langue cible via sa langue maternelle. En témoignent l'achat et l'utilisation rarement questionnés du dictionnaire bilingue. Pourtant, sur le long terme, ces pratiques sont loin d'être exemptes d'écueils. Cet article examinera quelques-uns des inconvénients d'une telle stratégie d'apprentissage.

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In Arabidopsis, interplay between nuclear auxin perception and trans-cellular polar auxin transport determines the transcriptional auxin response. In brevis radix (brx) mutants, this response is impaired, probably indirectly because of disturbed crosstalk between the auxin and brassinosteroid pathways. Here we provide evidence that BRX protein is plasma membrane-associated, but translocates to the nucleus upon auxin treatment to modulate cellular growth, possibly in conjunction with NGATHA class B3 domain-type transcription factors. Application of the polar auxin transport inhibitor naphthalene phthalamic acid (NPA) resulted in increased BRX abundance at the plasma membrane. Thus, nuclear translocation of BRX could depend on cellular auxin concentration or on auxin flux. Supporting this idea, NPA treatment of wild-type roots phenocopied the brx root meristem phenotype. Moreover, BRX is constitutively turned over by the proteasome pathway in the nucleus. However, a stabilized C-terminal BRX fragment significantly rescued the brx root growth phenotype and triggered a hypocotyl gain-of-function phenotype, similar to strong overexpressors of full length BRX. Therefore, although BRX activity is required in the nucleus, excess activity interferes with normal development. Finally, similar to the PIN-FORMED 1 (PIN1) auxin efflux carrier, BRX is polarly localized in vascular cells and subject to endocytic recycling. Expression of BRX under control of the PIN1 promoter fully rescued the brx short root phenotype, suggesting that the two genes act in the same tissues. Collectively, our results suggest that BRX might provide a contextual readout to synchronize cellular growth with the auxin concentration gradient across the root tip.