Brain energy metabolism measured by (13) C magnetic resonance spectroscopy in vivo upon infusion of [3-(13) C]lactate.

The brain uses lactate produced by glycolysis as an energy source. How lactate originated from the blood stream is used to fuel brain metabolism is not clear. The current study measures brain metabolic fluxes and estimates the amount of pyruvate that becomes labeled in glial and neuronal compartments upon infusion of [3-(13) C]lactate. For that, labeling incorporation into carbons of glutamate and glutamine was measured by (13) C magnetic resonance spectroscopy at 14.1 T and analyzed with a two-compartment model of brain metabolism to estimate rates of mitochondrial oxidation, glial pyruvate carboxylation, and the glutamate-glutamine cycle as well as pyruvate fractional enrichments. Extracerebral lactate at supraphysiological levels contributes at least two-fold more to replenish the neuronal than the glial pyruvate pools. The rates of mitochondrial oxidation in neurons and glia, pyruvate carboxylase, and glutamate-glutamine cycles were similar to those estimated by administration of (13) C-enriched glucose, the main fuel of brain energy metabolism. These results are in agreement with primary utilization of exogenous lactate in neurons rather than astrocytes. © 2014 Wiley Periodicals, Inc.

"Quien pone su esperanza en mujer flaca": una lectura de los sonetos de Lope de Vega

En este trabajo se ofrece un análisis de las representaciones femeninas en los sonetos de Lope de Vega a partir de la lectura de tres de sus obras mayores -Rimas (1602), Rimas sacras (1614) y Rimas humanas y divinas del licenciado Tomé de Burguillos (1634)- con el propósito de valorar su relación con la tradición medieval y renacencista, así como la originalidad de su tratamiento.

Konserttiohjelma 1907-06-13 - [Framsidan]

Helsingfors : Esplanad Kapellet 1907, Helsingfors stentryckeri

Ruokalista 1909-02-13 - [Kansi]

[S.l.] 1909

Nuevo marco legal sobre prestaciones económicas: anotaciones críticas a la Ley 13/2006 + despliegue

Las prestaciones económicas son un complemento necesario y, a menudo, un soporte indispensable para los objetivos de inclusión y de autonomía que procura el sistema de Servicios Sociales. El Parlament de Catalunya aprobó hace un año la primera ley que regula específicamente las prestaciones de carácter económico vinculadas al sistema, y que se añade, por tanto, al ordenamiento jurídico de los Servicios Sociales. Este artículo quiere ser una presentación comentada de dicha ley –incluyendo su despliegue hasta la fecha2 – haciendo lo que se podría decir una lectura crítica y desde una perspectiva de Servicios Sociales. El análisis repasa, a grandes rasgos, los aspectos más importantes de la ley, e intenta hacer compatible una exposición pedagógica con una interpretación más personal de búsqueda de significado.

The membrane-permeable calmodulin inhibitors (W-7/W-13) bind to membranes changing the electrostatic surface potential. Dual effect of W-13 on EGFR activation

Membrane-permeable calmodulin inhibitors, such as the napthalenesulfonamide derivatives W-7/W-13, trifluoperazine, and calmidazolium, are used widely to investigate the role of calcium/calmodulin (Ca2+/CaM) in living cells. If two chemically different inhibitors (e.g. W-7 and trifluoperazine) produce similar effects, investigators often assume the effects are due to CaM inhibition. Zeta potential measurements, however, show that these amphipathic weak bases bind to phospholipid vesicles at the same concentrations as they inhibit Ca 2 /CaM; this suggests that they also bind to the inner leaflet of the plasma membrane, reducing its negative electrostatic surface potential. This change will cause electrostatically bound clusters of basic residues on peripheral (e.g. Src and K-Ras4B) and integral (e.g. epidermal growth factor receptor (EGFR)) proteins to translocate from the membrane to the cytoplasm. We measured inhibitor-mediated translocation of a simple basic peptide corresponding to the calmodulin-binding juxtamembrane region of the EGFR on model membranes; W-7/W-13 causes translocation of this peptide from membrane to solution, suggesting that caution must be exercised when interpreting the results obtained with these inhibitors in living cells. We present evidence that they exert dual effects on autophosphorylation of EGFR;W-13 inhibits epidermal growth factordependent EGFR autophosphorylation under different experimental conditions, but in the absence of epidermal growth factor, W-13 stimulates autophosphorylation of the receptor in four different cell types. Our interpretation is that the former effect is due toW-13inhibition of Ca 2 /CaM, but thelatter results could be due to binding of W-13 to the plasma membrane.

Renovação do carbono-13 em figueiras 'Roxo de Valinhos'

O objetivo do trabalho foi determinar a taxa de renovação do carbono-13 ("turnover"), dos diferentes órgãos da figueira 'Roxo de Valinhos'. O experimento foi conduzido no pomar da Faculdade de Ciências Agronômicas, FCA/UNESP, Câmpus de Botucatu-SP. Determinou-se previamente, através das trocas gasosas com um medidor aberto portátil de fotossíntese, IRGA, a principal folha fotossinteticamente ativa. Essa folha foi colocada em uma câmara onde ocorreu a injeção do gás enriquecido. O tempo de enriquecimento da folha foi de 30 minutos. Os tratamentos foram constituídos por sete plantas de figueira, que foram retiradas do solo após: 6; 24; 48; 72; 120; 168 e 360 horas do enriquecimento com 13C, e suas partes seccionadas em: gema apical, folha jovem, folhas adultas (fotossinteticamente ativas), brotações laterais, frutos e ramo. Os resultados obtidos permitiram o estabelecimento da sequência de metabolização do carbono-13 nas partições estudadas: Folhas novas > Frutos > Brotações > Folhas Adultas > Gema Apical > Ramo > Folha marcada. Plantas de figueira 'Roxo de Valinhos' apresentam reciclagem do 13C de 24 horas e um tempo de meia-vida de duração do carbono-13 inferior a 11 horas.

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Summary and conclusion: One of the main challenges facing the Swiss health care system remains continued fragmentation as a consequence of the federal structure and the division of responsibilities. This constitutes a major barrier for the implementation of a nationwide public health strategy and a more rational organization of health care. Much of the health reform agenda during the past decade was driven by cost-containment efforts. Despite the absence of a national regulatory framework targeting prevention and care of chronic diseases, national strategies and programmes have been developed within a growing recognition of the need to address chronic disease in the health care system. In addition, several small-scale pilot and preliminary structured care programmes have been implemented in selected localities. The latter are however still too few and limited in scope to cover the needs of the majority of patients with chronic diseases residing in Switzerland. Given the continued high satisfaction with the system among health care users, of around 80%, pressure to actually initiate larger scale changes might not yet be sufficiently strong.

Metabolic and structural rearrangement during dark-induced autophagy in soybean (Glycine max L.) nodules: An electron microscopy and P-31 and C-13 nuclear magnetic resonance study

The effects of dark-induced stress on the evolution of the soluble metabolites present in senescent soybean (Glycine max L.) nodules were analysed in vitro using C-13- and P-31-NMR spectroscopy. Sucrose and trehalose were the predominant soluble storage carbons. During dark-induced stress, a decline in sugars and some key glycolytic metabolites was observed. Whereas 84% of the sucrose disappeared, only one-half of the trehalose was utilised. This decline coincides with the depletion of Gln, Asn, Ala and with an accumulation of ureides, which reflect a huge reduction of the N-2 fixation. Concomitantly, phosphodiesters and compounds like P-choline, a good marker of membrane phospholipids hydrolysis and cell autophagy, accumulated in the nodules. An autophagic process was confirmed by the decrease in cell fatty acid content. In addition, a slight increase in unsaturated fatty acids (oleic and linoleic acids) was observed, probably as a response to peroxidation reactions. Electron microscopy analysis revealed that, despite membranes dismantling, most of the bacteroids seem to be structurally intact. Taken together, our results show that the carbohydrate starvation induced in soybean by dark stress triggers a profound metabolic and structural rearrangement in the infected cells of soybean nodule which is representative of symbiotic cessation.

Direct noninvasive estimation of myocardial tricarboxylic acid cycle flux in vivo using hyperpolarized (13)C magnetic resonance.

BACKGROUND: The heart relies on continuous energy production and imbalances herein impair cardiac function directly. The tricarboxylic acid (TCA) cycle is the primary means of energy generation in the healthy myocardium, but direct noninvasive quantification of metabolic fluxes is challenging due to the low concentration of most metabolites. Hyperpolarized (13)C magnetic resonance spectroscopy (MRS) provides the opportunity to measure cellular metabolism in real time in vivo. The aim of this work was to noninvasively measure myocardial TCA cycle flux (VTCA) in vivo within a single minute. METHODS AND RESULTS: Hyperpolarized [1-(13)C]acetate was administered at different concentrations in healthy rats. (13)C incorporation into [1-(13)C]acetylcarnitine and the TCA cycle intermediate [5-(13)C]citrate was dynamically detected in vivo with a time resolution of 3s. Different kinetic models were established and evaluated to determine the metabolic fluxes by simultaneously fitting the evolution of the (13)C labeling in acetate, acetylcarnitine, and citrate. VTCA was estimated to be 6.7±1.7μmol·g(-1)·min(-1) (dry weight), and was best estimated with a model using only the labeling in citrate and acetylcarnitine, independent of the precursor. The TCA cycle rate was not linear with the citrate-to-acetate metabolite ratio, and could thus not be quantified using a ratiometric approach. The (13)C signal evolution of citrate, i.e. citrate formation was independent of the amount of injected acetate, while the (13)C signal evolution of acetylcarnitine revealed a dose dependency with the injected acetate. The (13)C labeling of citrate did not correlate to that of acetylcarnitine, leading to the hypothesis that acetylcarnitine formation is not an indication of mitochondrial TCA cycle activity in the heart. CONCLUSIONS: Hyperpolarized [1-(13)C]acetate is a metabolic probe independent of pyruvate dehydrogenase (PDH) activity. It allows the direct estimation of VTCA in vivo, which was shown to be neither dependent on the administered acetate dose nor on the (13)C labeling of acetylcarnitine. Dynamic (13)C MRS coupled to the injection of hyperpolarized [1-(13)C]acetate can enable the measurement of metabolic changes during impaired heart function.