Early glutathione deficit impairs parvalbumin expression in gaba interneurons and kainate-induced gamma oscillations

An increased oxidative stress and alteration of the antioxidant systems have been observed in schizophrenia. Glutathione (GSH), a major redox regulator, is decreased in patients' cerebrospinal fluid, prefrontal cortex in vivo and striatum post-mortem tissue. Most importantly, there is genetic and functional evidence for the implication of the gene of the glutamate cysteine ligase (GCL) catalytic subunit, the key GSH-synthesizing enzyme. We have developed animal models for a GSH deficit to study the consequences of such deficit on the brain development. A GSH deficit combined with elevated dopamine (DA) during development leads to reduced parvalbumin (PV) expression in a subclass of GABA interneurons in rat anterior cingulate cortex (ACC). Similar changes are observed in postmortem brain tissue of schizophrenic patients. GSH dysregulation increases vulnerability to oxidative stress, that in turn could lead to cortical circuit anomalies in the schizophrenic brain. In the present study, we use a GCL modulatory subunit (GCLM) knock-out (KO) mouse model that presents up to 80% decreased brain GSH levels. During postnatal development, a subgroup of animals from each genotype is exposed to elevated oxidative stress induced by treatment with the DA reuptake inhibitor GBR12909. Results reveal a significant genotype-specific delay International Congress on Schizophrenia Research 136 10. 10. Neuroanatomy, Animal Downloaded from http://schizophreniabulletin.oxfordjournals.org at Bibliotheque Cantonale et Universitaire on June 18, 2010 in cortical PV expression at postnatal day P10 in GCLM-KO mice, as compared to wild-type. This effect seems to be further exaggerated in animals treated with GBR12909 from P5 to P10. At P20, PV expression is no longer significantly reduced in GCLM-KO ACC without GBR but is reduced if GBR is applied from P10 to P20. However, our result show that GCLM-KO mice exhibit increased oxidative stress, cortical altered myelin development as shown by MBP marker, and more specifically impairment of the peri-neuronal net known to modulate PV connectivity. In addition, we also observe a reduced PV expression in the ventro-temporal hippocampus of adult GCLM-KO mice, suggesting that anomalies of the PV interneurons prevail at least in some brain regions throughout the adulthood. Interestingly, the power of kainate-induced gamma oscillations, known to be dependent on proper activation of PV interneuron's, is also lower in hippocampal slices of adult GCLM KO mice. These results suggest that the PV positive GABA interneurons is particularly vulnerable to increased oxidative stress

Alterações no perfil de frações nitrogenadas em calos de cana-de-açúcar induzidas por deficit hídrico

O objetivo deste trabalho foi avaliar o uso de marcadores bioquímicos e fisiológicos, na caracterização do estresse hídrico em calos de cultivares de cana-de-açúcar (Sacharum sp.), RB 72 454 (sensível) e SP 813250 (resistente), contrastantes quanto à resistência à seca em campo. O delineamento experimental foi o inteiramente casualizado, em esquema fatorial de 2x5 [cultivar x doses de polietilenoglicol (PEG)], com dez tratamentos e três repetições. Os calos foram submetidos a concentrações de PEG correspondentes aos potenciais osmóticos de 0, -0,3, -0,6, -0,9 e -1,2 MPa, por 120 horas. A variação no conteúdo relativo de água e na umidade não foi significativamente diferente entre as cultivares. Entretanto, foi observada a tendência de aumento no vazamento de eletrólitos, em conseqüência da diminuição do potencial osmótico na cultivar tolerante. Na cultivar sensível, observou-se tendência de aumento de prolina e, na resistente, diminuição, embora os níveis não tenham sido afetados pelo deficit hídrico. As concentrações de aminoácidos livres foram maiores na sensível. Houve queda nas concentrações de amônia, em ambas cultivares. Os níveis de proteínas não foram afetados pelo PEG. O perfil protéico por SDS-PAGE não mostrou aumento induzido por PEG, na intensidade das bandas correspondentes aos peptídeos entre 14 e 66 kDa. Os marcadores bioquímicos e fisiológicos não foram relacionados ao grau diferencial de resistência observado nas cultivares em condições de campo.

Brazilian maize genotypes sensitivity to water deficit estimated through a simple crop yield model

The objective of this work was to determine the sensitivity of maize (Zea mays) genotypes to water deficit, using a simple agrometeorological crop yield model. Crop actual yield and agronomic data of 26 genotypes were obtained from the Maize National Assays carried out in ten locations, in four Brazilian states, from 1998 to 2006. Weather information for each experimental location and period were obtained from the closest weather station. Water deficit sensitivity index (Ky) was determined using the crop yield depletion model. Genotypes can be divided into two groups according to their resistance to water deficit. Normal resistance genotypes had Ky ranging from 0.4 to 0.5 in vegetative period, 1.4 to 1.5 in flowering, 0.3 to 0.6 in fruiting, and 0.1 to 0.3 in maturing period, whereas the higher resistance genotypes had lower values, respectively 0.2-0.4, 0.7-1.2, 0.2-0.4, and 0.1-0.2. The general Ky for the total growing season was 2.15 for sensitive genotypes and 1.56 for the resistant ones. Model performance was acceptable to evaluate crop actual yield, whose average errors estimated for each genotype ranged from -5.7% to +5.8%, and whose general mean absolute error was 960 kg ha-1 (10%).

Indicadores fisiológicos da interação entre deficit hídrico e acidez do solo em cana-de-açúcar

O objetivo deste trabalho foi avaliar os indicadores fisiológicos da interação entre deficit hídrico e acidez do solo em plantas jovens de cana-de-açúcar. As plantas foram submetidas a três tratamentos de disponibilidade hídrica, medidos em percentagem de capacidade de campo (CC) - sem estresse (70% CC), estresse moderado (55% CC) e estresse severo (40% CC); e três tratamentos de acidez no solo, medidos em termos de saturação por bases (V) - baixa acidez (V = 55%), média acidez (V = 33%) e alta acidez (V = 23%). O experimento foi realizado em casa de vegetação a 29,7±4,3ºC e 75±10% UR. O delineamento experimental utilizado foi o de blocos ao acaso, em esquema fatorial 3x3, com quatro repetições. Após 60 dias, foram determinados os teores de solutos compatíveis - trealose, glicina betaína e prolina - na folha diagnóstico e o crescimento inicial da parte aérea. Os solutos compatíveis trealose, glicina betaína e prolina são indicadores do efeito da interação dos estresses hídrico e ácido no solo. O acúmulo dos solutos compatíveis nos tecidos foliares das plantas não é capaz de impedir a redução na produção de matéria seca da cana-de-açúcar, resultante do agravamento nas condições de disponibilidade hídrica e de acidez no solo.

Metabolic alterations in the cortex of a mouse model with glutathione deficit - relevance to schizophrenia

Background: Glutathione (GSH) is a major redox regulator and antioxidant and is decreased in cerebrospinal fluid and prefrontal cortex of schizophrenia patients [Do et al. (2000) Eur J Neurosci 12:3721]. The genes of the key GSH-synthesizing enzyme, glutamate- cysteine ligase catalytic (GCLC) and modifier (GCLM) subunits, are associated with schizophrenia, suggesting that the deficit in GSH synthesis is of genetic origin [Gysin et al. (2007) PNAS 104:16621]. GCLM knock-out (KO) mice, which display an 80% decrease in brain GSH levels, have abnormal brain morphology and function [Do et al. (2009) Curr Opin Neurobiol 19:220]. Developmental redox deregulation by impaired GSH synthesis and environmental risk factors generating oxidative stress may have a central role in schizophrenia. Here, we used GCLM KO mice to investigate the impact of a genetically dysregulated redox system on the neurochemical profile of the developing brain. Methods: The neurochemical profile of the anterior and posterior cortical areas of male and female GCLM KO and wild-type mice was determined by in vivo 1H NMR spectroscopy on postnatal days 10, 20, 30, 60 and 90, under 1 to 1.5% isoflurane anaesthesia. Localised 1H NMR spectroscopy was performed on a 14.1 T, 26 cm VNMRS spectrometer (Varian, Magnex) using a home-built 8 mm diameter quadrature surface coil (used both for RF excitation and signal reception). Spectra were acquired using SPECIAL with TE of 2.8 ms and TR of 4 s from VOIs placed in anterior or posterior regions of the cortex [Mlynárik et al. (2006) MRM 56:965]. LCModel analysis allowed in vivo quantification of a neurochemical profile composed of 18 metabolites. Results: GCLM KO mice displayed nearly undetectable GSH levels as compared to WT mice, demonstrating their drastic redox deregulation. Depletion of GSH triggered alteration of metabolites related to its synthesis, namely increase of glycine and glutamate levels during development (P20 and P30). Concentrations of glutamine and aspartate that are produced from glutamate were also increased in GCLM KO animals relative to WT. In addition, GCLM KO mice also showed higher levels of N-acetylaspartate that originates from the acetylation of aspartate. These metabolites are particularly implicated in neurotransmission processes and in mitochondrial oxidative metabolism. Their increase may indicate impaired mitochondrial metabolism with concomitant accumulation of lactate in the adult mice (P60 and P90). In addition, the GSH depletion triggers reduction of GABA concentration in anterior cortex of the P60 mice, which is in accordance with known impairment of GABAergic interneurons in that area. Changes were generally more pronounced in males than in females at P60, which is consistent with earlier disease onset in male patients. Discussion: In conclusion, the observed metabolic alterations in the cortex of a mouse model of redox deregulation suggest impaired mitochondrial metabolism and altered neurotransmission. The results also highlight the age between P20 and P30 as a sensitive period during the development for these alterations.

Respostas biométricas e fisiológicas ao deficit hídrico em cana-de-açúcar em diferentes fases fenológicas

O objetivo deste trabalho foi avaliar as respostas biométricas e fisiológicas de cana-de-açúcar (Saccharum spp.) ao deficit hídrico (DH), em diferentes fases fenológicas. Os genótipos IACSP 94-2094 e IACSP 96-2042 foram submetidos a DH nas fases de crescimento inicial, crescimento máximo e de acúmulo de sacarose no colmo. O delineamento experimental foi inteiramente casualizado. A suscetibilidade ao DH foi determinada pela redução de matéria seca do colmo e do conteúdo de sólidos solúveis no caldo. O deficit hídrico causou redução nas trocas gasosas, nas três fases fenológicas, em ambos os genótipos. Foi observada menor altura das plantas, menor acúmulo de matéria seca do colmo e de sólidos solúveis, e redução no número e comprimento de entrenós, apenas na fase de crescimento inicial, no clone IACSP 96-2042. Na fase de crescimento inicial, observou-se tolerância ao DH no genótipo IACSP 94-2094, com evidências de aclimatação fisiológica, e redução na produção de fitomassa e de sólidos solúveis no genótipo IACSP 96-2042, como resposta à menor condutância estomática e à menor eficiência aparente de carboxilação da fotossíntese. Independentemente da fase fenológica, o genótipo IACSP 94-2094 foi tolerante ao deficit hídrico, pois manteve a produção de fitomassa mesmo com redução das trocas gasosas.

Deficit hídrico e secamento parcial do sistema radicular em pomar de lima ácida

O objetivo deste trabalho foi avaliar o efeito do deficit hídrico associado ao secamento parcial do sistema radicular ("partial rootzone drying", PRD) na produção e eficiência de uso de água, em pomar de lima ácida 'Tahiti', na Região do Semiárido baiano. Utilizou-se o delineamento de blocos ao acaso, com seis tratamentos e seis repetições. Os tratamentos com PRD foram realizados pela alternância periódica (7, 14 ou 21 dias) dos lados em que o microaspersor localizava-se em relação às plantas. Esses tratamentos foram conduzidos com lâmina d'água equivalente a 50% da evapotranspiração da cultura (ETc) e comparados ao tratamento com deficit hídrico de 50% da ETc com microaspersor fixo em um dos lados das plantas, e ao tratamento 100% da ETc, com aspersores de ambos os lados das plantas. Avaliou-se também o PRD (21 dias) com diminuição da irrigação em 25% da ETc. O PRD com 50% da ETc não difere do tratamento com esse mesmo deficit e sem alternância de lados da irrigação, em termos de produtividade, eficiência do uso da água, e diâmetro e peso dos frutos, independentemente do período de alternância dos lados de irrigação. O PRD com diminuição da irrigação em 25% da ETc não causa perdas em relação à condição sem deficit e sem localização da irrigação.

On optimal dividend strategies with deficit or incomplete information

Rapport de synthèse Cette thèse consiste en trois essais sur les stratégies optimales de dividendes. Chaque essai correspond à un chapitre. Les deux premiers essais ont été écrits en collaboration avec les Professeurs Hans Ulrich Gerber et Elias S. W. Shiu et ils ont été publiés; voir Gerber et al. (2006b) ainsi que Gerber et al. (2008). Le troisième essai a été écrit en collaboration avec le Professeur Hans Ulrich Gerber. Le problème des stratégies optimales de dividendes remonte à de Finetti (1957). Il se pose comme suit: considérant le surplus d'une société, déterminer la stratégie optimale de distribution des dividendes. Le critère utilisé consiste à maximiser la somme des dividendes escomptés versés aux actionnaires jusqu'à la ruine2 de la société. Depuis de Finetti (1957), le problème a pris plusieurs formes et a été résolu pour différents modèles. Dans le modèle classique de théorie de la ruine, le problème a été résolu par Gerber (1969) et plus récemment, en utilisant une autre approche, par Azcue and Muler (2005) ou Schmidli (2008). Dans le modèle classique, il y a un flux continu et constant d'entrées d'argent. Quant aux sorties d'argent, elles sont aléatoires. Elles suivent un processus à sauts, à savoir un processus de Poisson composé. Un exemple qui correspond bien à un tel modèle est la valeur du surplus d'une compagnie d'assurance pour lequel les entrées et les sorties sont respectivement les primes et les sinistres. Le premier graphique de la Figure 1 en illustre un exemple. Dans cette thèse, seules les stratégies de barrière sont considérées, c'est-à-dire quand le surplus dépasse le niveau b de la barrière, l'excédent est distribué aux actionnaires comme dividendes. Le deuxième graphique de la Figure 1 montre le même exemple du surplus quand une barrière de niveau b est introduite, et le troisième graphique de cette figure montre, quand à lui, les dividendes cumulés. Chapitre l: "Maximizing dividends without bankruptcy" Dans ce premier essai, les barrières optimales sont calculées pour différentes distributions du montant des sinistres selon deux critères: I) La barrière optimale est calculée en utilisant le critère usuel qui consiste à maximiser l'espérance des dividendes escomptés jusqu'à la ruine. II) La barrière optimale est calculée en utilisant le second critère qui consiste, quant à lui, à maximiser l'espérance de la différence entre les dividendes escomptés jusqu'à la ruine et le déficit au moment de la ruine. Cet essai est inspiré par Dickson and Waters (2004), dont l'idée est de faire supporter aux actionnaires le déficit au moment de la ruine. Ceci est d'autant plus vrai dans le cas d'une compagnie d'assurance dont la ruine doit être évitée. Dans l'exemple de la Figure 1, le déficit au moment de la ruine est noté R. Des exemples numériques nous permettent de comparer le niveau des barrières optimales dans les situations I et II. Cette idée, d'ajouter une pénalité au moment de la ruine, a été généralisée dans Gerber et al. (2006a). Chapitre 2: "Methods for estimating the optimal dividend barrier and the probability of ruin" Dans ce second essai, du fait qu'en pratique on n'a jamais toute l'information nécessaire sur la distribution du montant des sinistres, on suppose que seuls les premiers moments de cette fonction sont connus. Cet essai développe et examine des méthodes qui permettent d'approximer, dans cette situation, le niveau de la barrière optimale, selon le critère usuel (cas I ci-dessus). Les approximations "de Vylder" et "diffusion" sont expliquées et examinées: Certaines de ces approximations utilisent deux, trois ou quatre des premiers moments. Des exemples numériques nous permettent de comparer les approximations du niveau de la barrière optimale, non seulement avec les valeurs exactes mais également entre elles. Chapitre 3: "Optimal dividends with incomplete information" Dans ce troisième et dernier essai, on s'intéresse à nouveau aux méthodes d'approximation du niveau de la barrière optimale quand seuls les premiers moments de la distribution du montant des sauts sont connus. Cette fois, on considère le modèle dual. Comme pour le modèle classique, dans un sens il y a un flux continu et dans l'autre un processus à sauts. A l'inverse du modèle classique, les gains suivent un processus de Poisson composé et les pertes sont constantes et continues; voir la Figure 2. Un tel modèle conviendrait pour une caisse de pension ou une société qui se spécialise dans les découvertes ou inventions. Ainsi, tant les approximations "de Vylder" et "diffusion" que les nouvelles approximations "gamma" et "gamma process" sont expliquées et analysées. Ces nouvelles approximations semblent donner de meilleurs résultats dans certains cas.

Schizophrenia: glutathione deficit as a new vulnerability factor for disconnectivity syndrome

(from the journal abstract) Schizophrenia, a major psychiatric disease, affects individuals in the centre of their personality. Its aetiology is not clearly established. In this review, we will present evidence that patients suffering of schizophrenia present a brain deficit in glutathione, a major endogenous redox regulator and antioxidant. We will also show that, in experimental models, a decrease in glutathione, particularly during development, induces morphological, electrophysiological and behavioural anomalies consistent with those observed in the disease. In the cerebrospinal fluid of drug-naive schizophrenics, glutathione level was decreased by 27% and its direct metabolite of glutathione by 16%. Glutathione level in prefrontal cortex of patients, measured by magnetic resonance spectroscopy, was 52% lower than in controls. Patients' fibroblasts reveal a decrease in mRNA levels of the two glutathione synthesising enzymes, glutamatecysteine ligase modulatory subunit (GCLM) and glutathione synthetase. GCLM expression level in fibroblasts correlates negatively with symptoms severity. Glutathione is an important endogenous redox regulator and neuroactive substance. It is protecting cells from damage by reactive oxygen species generated, among others, by dopamine metabolism. A glutathione deficit-induced oxidative stress would lead to lipid peroxidation and micro-lesions at the level of dendritic spines, a synaptic damage responsible for abnormal nervous connections or structural disconnectivity. On the other hand, a glutathione deficit could also lead to a functional disconnectivity by depressing NMDA neurotransmission, in analogy to phencyclidine effects. Present experimental data are consistent with the proposed hypothesis: decreasing pharmacologically glutathione level in experimental models, with or without blocking dopamine (DA) uptake (GBR12909), induces morphological, electrophysiological and behavioural changes similar to those observed in patients. In summary, a deficit of glutathione and/or glutathione-related enzymes during early development would lead to both a functional and a structural disconnectivity, which could be at the basis of some perceptive, cognitive and behavioural troubles of the disease. It could constitute a major vulnerability factor for schizophrenia. Attempts to restore physiological glutathione functions could open new therapeutic avenues. This translational research, made possible by a close interaction between clinicians and neuroscientists, should also pave the way to the identification of biological markers for schizophrenia. In turn, they should allow early diagnostic and hopefully preventive intervention to this devastating disease. (PsycINFO Database Record (c) 2005 APA, all rights reserved)

Transpiração e crescimento foliar de plantas de mandioca em resposta ao deficit hídrico no solo

O objetivo deste trabalho foi determinar a transpiração e o crescimento foliar de duas cultivares de mandioca, em resposta ao conteúdo de água disponível no solo representado pela fração de água transpirável no solo (FATS). Foram realizados dois experimentos, em vasos de 8 L, com as cultivares Fécula Branca e Fepagro RS 13. O plantio foi feito em 11/9/2009 e 8/9/2010, em delineamento experimental inteiramente casualizado. A água disponível, a transpiração e o crescimento foliar foram medidos diariamente, em cada experimento,durante o período de imposição da deficiência hídrica. A FATS crítica, em que a transpiração começa a serreduzida, foi de 0,45 para 'Fécula Branca' e 0,50 para 'Fepagro RS 13'. A redução do crescimento foliar começou quando a FATS atingiu 0,51 para 'Fécula Branca' e 0,49 para 'Fepagro RS 13'. A FATS crítica para transpiração e crescimento foliar difere em condições de atmosfera com baixa e com alta demanda evaporativa do ar, conforme a cultivar de mandioca utilizada.

Transpiration response of upland rice to water deficit changed by different levels of eucalyptus biochar

The objective of this work was to evaluate the effect of eucalyptus biochar on the transpiration rate of upland rice 'BRSMG Curinga' as an alternative means to decrease the effect of water stress on plant growth and development. Two-pot experiments were carried out using a completely randomized block design, in a split-plot arrangement, with six replicates. Main plots were water stress (WS) and no-water stress (NWS), and the subplots were biochar doses at 0, 6, 12 and 24% in growing medium (sand). Total transpirable soil water (TTSW), the p factor - defined as the average fraction of TTSW which can be depleted from the root zone before water stress limits growth -, and the normalized transpiration rate (NTR) were determined. Biochar addition increased TTSW and the p factor, and reduced NTR. Consequently, biochar addition was able to change the moisture threshold (p factor) of the growing medium, up to 12% maximum concentration, delaying the point where transpiration declines and affects yield.