The decrease of NAD(P)H:quinone oxidoreductase 1 activity and increase of ROS production by NADPH oxidases are early biomarkers in doxorubicin cardiotoxicity

info:eu-repo/semantics/publishedVersio

Actin cytoskeleton disruption is an early event upon exposure of cerebellar granule neurons to SIN-1-induced oxidative stress

In this work we have studied the alterations of the actin cytoskeleton in cultured cerebellar granule neurons during exposure to the peroxynitritereleasing agent SIN-1 for less than 2 hours. Actin polymerization state was assessed by fluorescence microscopy ratio images using double labelling for actin filaments (phallacidin) and monomers (DNase-I). In addition, agonists and antagonists of L-type Ca2+ channels and NMDA receptors were used in order to find out whether these compounds were able to attenuate or potentiate the effects of oxidative stress on the perturbation of the actin cytoskeleton. The results reveal that a flux of peroxynitrite as low as 0.5 ;M/min during 1h is sufficient to promote alterations of actin dynamics leading to partial actin cytoskeleton disruption and suggest that this is an early event linked to cytosolic calcium concentration changes

Complex I and cytochrome c are molecular targets of flavonoids that inhibit hydrogen peroxide production by mitochondria

AbstractFlavonoids can protect cells from different insults that lead to mitochondria-mediated cell death, and epidemiological data show that some of these compounds attenuate the progression of diseases associated with oxidative stress and mitochondrial dysfunction. In this work, a screening of 5 flavonoids representing major subclasses showed that they display different effects on H2O2 production by mitochondria isolated from rat brain and heart. Quercetin, kaempferol and epicatechin are potent inhibitors of H2O2 production by mitochondria from both tissues (IC50≈1–2μM), even when H2O2 production rate was stimulated by the mitochondrial inhibitors rotenone and antimycin A. Although the rate of oxygen consumption was unaffected by concentrations up to 10μM of these flavonoids, quercetin, kaempferol and apigenin inhibited complex I activity, while up to 100μM epicatechin produced less than 20% inhibition. The extent of this inhibition was found to be dependent on the concentration of coenzyme Q in the medium, suggesting competition between the flavonoids and ubiquinone for close binding sites in the complex. In contrast, these flavonoids did not significantly inhibit the activity of complexes II and III, and did not affect the redox state of complex IV. However, we have found that epicatechin, quercetin and kaempferol are able to stoichiometrically reduce purified cytochrome c. Our results reveal that mitochondria are a plausible main target of flavonoids mediating, at least in part, their reported preventive actions against oxidative stress and mitochondrial dysfunction-associated pathologies

Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability

Plasma membrane calcium ATPases (PMCA) are key proteins in the maintenance of calcium (Ca2+) homeostasis. Dysregulation of PMCA function is associated with several human pathologies, including neurodegenerative diseases, and, therefore, these proteins are potential drug targets to counteract those diseases. Gold compounds, namely of Au(I), are well-known for their therapeutic use in rheumatoid arthritis and other diseases for centuries. Herein, we report the ability of dichloro(2-pyridinecarboxylate)gold(III) (1), chlorotrimethylphosphinegold(I) (2), 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidenegold(I) chloride (3), and chlorotriphenylphosphinegold(I) (4) compounds to interfere with the Ca2+-ATPase activity of pig brain purified PMCA and with membranes from SH-SY5Y neuroblastoma cell cultures. The Au(III) compound (1) inhibits PMCA activity with the IC50 value of 4.9 µM, while Au(I) compounds (2, 3, and 4) inhibit the protein activity with IC50 values of 2.8, 21, and 0.9 µM, respectively. Regarding the native substrate MgATP, gold compounds 1 and 4 showed a non-competitive type of inhibition, whereas compounds 2 and 3 showed a mixed type of inhibition. All gold complexes showed cytotoxic effects on human neuroblastoma SH-SY5Y cells, although compounds 1 and 3 were more cytotoxic than compounds 2 and 4. In summary, this work shows that both Au (I and III) compounds are high-affinity inhibitors of the Ca2+-ATPase activity in purified PMCA fractions and in membranes from SH-SY5Y human neuroblastoma cells. Additionally, they exert strong cytotoxic effects.Projects BFU2017-85723-P (to A.M.M. and C.G.-M.), and PID2020-115512GB-I00 (to A.M.M.) funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”. We acknowledge Fundação para a Ciência e a Tecnologia (FCT) project UIDB/04326/2020, Associate Laboratory for Green Chemistry–LAQV, financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020) and Scientific Employment Stimulus-Institutional Call (CEECINST/00102/2018).info:eu-repo/semantics/publishedVersio

Murciano-Granadina goat performance and methane emission after replacing barley grain with fibrous by-products

[ES] El objetivo de este trabajo fue estudiar los efectos de la sustitución de grano de cebada en la dieta por pulpa de naranja o vainas de soja en el balance de nitrógeno y carbono, las emisiones de metano y el rendimiento de la producción de leche en cabras. Para ello, se seleccionaron doce cabras lecheras Murciano-Granadina y se dividieron en tres grupos basados en un peso corporal similar (42,1 ± 1,2 kg) y la producción de leche (2,16 ± 0,06 kg/cabra/día). El experimento se realizó en un diseño cruzado donde un grupo de cuatro cabras fue alimentado con una ración mixta de grano de cebada, en otro grupo de cuatro cabras se reemplazó el grano de cebada por pulpa de naranja y el último grupo de cuatro cabras se alimentó con soja. Después de la adaptación a las dietas, las cabras se establecieron en jaulas individuales y se analizaron las heces, la orina y la leche. Asimismo, las mediciones de intercambio gaseoso fueron registradas por un sistema móvil de calorimetría en circuito abierto. El consumo de materia seca fue similar en los tres grupos (2,03 kg/d, en promedio). No se observó ninguna influencia de la dieta en el balance energético. Las dietas basadas en pulpa de naranja y cascarilla de soja mostraron una mayor movilización de grasa que en el caso de grano de cebada. El ácido pentadecanoico y el ácido heptadecanoico fueron potenciales biomarcadores de la función del rumen debido a los contenidos más elevados encontrados en la leche de cabras con la dieta de pulpa de naranja y vainas de soja frente al detectado en las cabras con dieta de grano de cebada, lo que sugiere un impacto de estas dietas sobre el metabolismo bacteriano rumen. Esto probablemente esté relacionado con un suministro de nitrógeno inferior en el caso de la dieta de pulpa de naranja para sintetizar proteína microbiana y un mayor contenido de grasa en el caso de la dieta de cascarilla de soja. La sustitución de grano de cereal con subproductos fibrosos no aumentó las emisiones de metano (54,7 L/cabra por día, en promedio). Por lo tanto, se podría utilizar pulpa de naranja y cascarilla de soja en la dieta de las cabras lactantes sin tener un impacto negativo en el rendimiento de la producción de leche.[EN] The aim of this experiment was to study the effects of substituting dietary barley grain with orange pulp or soybean hulls on energy, nitrogen and carbon balance, methane emission and milk performance in dairy goats. Twelve Murciano-Granadina dairy goats in midlactation were selected and divided into three groups based on similar body weight (42.1 +/- 1.2 kg) and milk yield (2.16 +/- 0.060 kg/goat/day). The experiment was conducted in an incomplete crossover design where one group of four goats was fed a mixed ration of barley grain (BRL), another group of four goats replaced barley grain with orange pulp (OP) and the last group of four goats with soybean hulls (SH). After adaptation to diets, the goats were allocated to individual metabolism cages and intake, faeces, urine and milk were recorded and analysed. Then, gas exchange measurements were recorded by a mobile open-circuit indirect calorimetry system using a head box. Dry matter intake was similar for all three groups (2.03 kg/d, on average). No influence of the diet was observed for energy balance and the efficiency of use of metabolizable energy for milk production was 0.61. The OP and SH diets showed greater (P th Symposium on Energy Metabolism. EAAP. Publ. 11. Academic Press, London.Brouwer E (1958) On simple formulae for calculating the heat expenditure and the quantities of carbohydrate and fat metabolized in ruminants, from data on gaseous exchange and urine N. Pages 182–194 in Proc. 1th Symposium on Energy Metabolism. EAAP. Publ. 8. Academic Press, London.Chwalibog, A., Tauson, A.-H., & Thorbek, G. (1997). Quantitative oxidation of nutrients in growing calves. Zeitschrift für Ernährungswissenschaft, 36(4), 313-316. doi:10.1007/bf01617806Casper, D. P., Maiga, H. A., Brouk, M. J., & Schingoethe, D. J. (1999). Synchronization of Carbohydrate and Protein Sources on Fermentation and Passage Rates in Dairy Cows,,. Journal of Dairy Science, 82(8), 1779-1790. doi:10.3168/jds.s0022-0302(99)75408-1Aguilera, J. F., Prieto, C., & FonollÁ, J. (1990). Protein and energy metabolism of lactating Granadina goats. British Journal of Nutrition, 63(2), 165-175. doi:10.1079/bjn19900104Tovar-Luna, I., Puchala, R., Sahlu, T., Freetly, H. C., & Goetsch, A. L. (2010). Effects of stage of lactation and dietary concentrate level on energy utilization by Alpine dairy goats. Journal of Dairy Science, 93(10), 4818-4828. doi:10.3168/jds.2010-3315Bava, L., Rapetti, L., Crovetto, G. M., Tamburini, A., Sandrucci, A., Galassi, G., & Succi, G. (2001). Effects of a Nonforage Diet on Milk Production, Energy, and Nitrogen Metabolism in Dairy Goats throughout Lactation. Journal of Dairy Science, 84(11), 2450-2459. doi:10.3168/jds.s0022-0302(01)74695-4López, M. C., & Fernández, C. (2013). Energy partitioning and substrate oxidation by Murciano-Granadina goats during mid lactation fed soy hulls and corn gluten feed blend as a replacement for corn grain. Journal of Dairy Science, 96(7), 4542-4552. doi:10.3168/jds.2012-6473Palmquist, D. L., & Jenkins, T. C. (1980). Fat in Lactation Rations : Review. Journal of Dairy Science, 63(1), 1-14. doi:10.3168/jds.s0022-0302(80)82881-5Kebreab E, Strathe AB, Dijkstra J, Mills JAN, Reynolds CK, Crompton LA, et al. (2010) Energy and protein interactions and their effects on nitrogen excretion in dairy cows. Pages 417–426 in Symp. on Energy and Protein Metabolism and Nutrition, Parma, Italy.Chilliard, Y., Ferlay, A., Rouel, J., & Lamberet, G. (2003). A Review of Nutritional and Physiological Factors Affecting Goat Milk Lipid Synthesis and Lipolysis. Journal of Dairy Science, 86(5), 1751-1770. doi:10.3168/jds.s0022-0302(03)73761-8Vlaeminck, B., Fievez, V., Cabrita, A. R. J., Fonseca, A. J. M., & Dewhurst, R. J. (2006). Factors affecting odd- and branched-chain fatty acids in milk: A review. Animal Feed Science and Technology, 131(3-4), 389-417. doi:10.1016/j.anifeedsci.2006.06.017Fievez, V., Colman, E., Castro-Montoya, J. M., Stefanov, I., & Vlaeminck, B. (2012). Milk odd- and branched-chain fatty acids as biomarkers of rumen function—An update. Animal Feed Science and Technology, 172(1-2), 51-65. doi:10.1016/j.anifeedsci.2011.12.008Vlaeminck, B., Gervais, R., Rahman, M. M., Gadeyne, F., Gorniak, M., Doreau, M., & Fievez, V. (2015). Postruminal synthesis modifies the odd- and branched-chain fatty acid profile from the duodenum to milk. Journal of Dairy Science, 98(7), 4829-4840. doi:10.3168/jds.2014-9207Jorjong, S., van Knegsel, A. T. M., Verwaeren, J., Bruckmaier, R. M., De Baets, B., Kemp, B., & Fievez, V. (2015). Milk fatty acids as possible biomarkers to diagnose hyperketonemia in early lactation. Journal of Dairy Science, 98(8), 5211-5221. doi:10.3168/jds.2014-8728Ulbricht, T. L. V., & Southgate, D. A. T. (1991). Coronary heart disease: seven dietary factors. The Lancet, 338(8773), 985-992. doi:10.1016/0140-6736(91)91846-mKnapp, J. R., Laur, G. L., Vadas, P. A., Weiss, W. P., & Tricarico, J. M. (2014). Invited review: Enteric methane in dairy cattle production: Quantifying the opportunities and impact of reducing emissions. Journal of Dairy Science, 97(6), 3231-3261. doi:10.3168/jds.2013-7234Angelidaki, I., & Sanders, W. (2004). Assessment of the anaerobic biodegradability of macropollutants. Reviews in Environmental Science and Bio/Technology, 3(2), 117-129. doi:10.1007/s11157-004-2502-3Velthof, G. L., Nelemans, J. A., Oenema, O., & Kuikman, P. J. (2005). Gaseous Nitrogen and Carbon Losses from Pig Manure Derived from Different Diets. Journal of Environmental Quality, 34(2), 698-706. doi:10.2134/jeq2005.0698Jarret, G., Cozannet, P., Martinez, J., & Dourmad, J. Y. (2011). Effect of different quality wheat dried distiller’s grain solubles (DDGS) in pig diets on composition of excreta and methane production from faeces and slurry. Livestock Science, 140(1-3), 275-282. doi:10.1016/j.livsci.2011.04.006Triolo, J. M., Sommer, S. G., Møller, H. B., Weisbjerg, M. R., & Jiang, X. Y. (2011). A new algorithm to characterize biodegradability of biomass during anaerobic digestion: Influence of lignin concentration on methane production potential. Bioresource Technology, 102(20), 9395-9402. doi:10.1016/j.biortech.2011.07.026Klevenhusen, F., Kreuzer, M., & Soliva, C. R. (2010). Enteric and manure-derived methane and nitrogen emissions as well as metabolic energy losses in cows fed balanced diets based on maize, barley or grass hay. animal, 5(03), 450-461. doi:10.1017/s1751731110001795SPEK, J. W., DIJKSTRA, J., VAN DUINKERKEN, G., & BANNINK, A. (2012). A review of factors influencing milk urea concentration and its relationship with urinary urea excretion in lactating dairy cattle. The Journal of Agricultural Science, 151(3), 407-423. doi:10.1017/s0021859612000561Van Knegsel, A. T. M., van den Brand, H., Dijkstra, J., van Straalen, W. M., Heetkamp, M. J. W., Tamminga, S., & Kemp, B. (2007). Dietary Energy Source in Dairy Cows in Early Lactation: Energy Partitioning and Milk Composition. Journal of Dairy Science, 90(3), 1467-1476. doi:10.3168/jds.s0022-0302(07)71632-

Inhibition of SERCA and PMCA Ca2+-ATPase activities by polyoxotungstates

Plasma membrane calcium ATPases (PMCA) and sarco(endo) reticulum calcium ATPases (SERCA) are key proteins in the maintenance of calcium homeostasis. Herein, we compare for the first time the inhibition of SERCA and PMCA calcium pumps by several polyoxotungstates (POTs), namely by Wells-Dawson phospho-tungstate anions [P2W18O62]6-(intact, {P2W18}), [P2W17O61]10-(monolacunary, {P2W17}), [P2W15O56]12-(trilacunary, {P2W15}), [H2P2W12O48]12-(hexalacunary, {P2W12}), [H3P2W15V3O62]6- (trivanadium-substituted, {P2W15V3}) and by Preyssler-type anion [NaP5W30O110]14-({P5W30}). The speciation in the solu-tions of tested POTs was investigated by 31P and 51V NMR spectroscopy. The tested POTs inhibited SERCA Ca2+- ATPase activity, whereby the Preyssler POT showed the strongest effect, with an IC50 value of 0.37 mu M. For {P2W17} and {P2W15V3} higher IC50 values were determined: 0.72 and 0.95 mu M, respectively. The studied POTs showed to be more potent inhibitors of PMCA Ca2+-ATPase activity, with lower IC50 values for {P2W17}, {P5W30} and {P2W15V3}.info:eu-repo/semantics/publishedVersio

Cytochrome c stimulates the superoxide anion production by cytochrome b5 reductase in neuronal synaptic plasma membrane vesicles

info:eu-repo/grantAgreement/FCT/5876/147258/PT Work financed by Grants FCT/MEC (UID/Multi/04378/2013). POCI-01-0145-FEDER-007728 and BFU2014-53641-P of the Spanish Ministerio de Economia y Competitividad co-financed by FEDER.authorsversionpublishe

Estimulación del pensamiento crítico y habilidades blandas mediante la metodología “leo, pienso y aprendo” en el asentamiento humano las torres de San Borja - Moche - Trujillo - La Libertad - Perú, 2019

RESUMEN El presente proyecto se desarrolló en el marco continuo del proyecto “Biblioteca para todos” este es un proyecto de responsabilidad social que fue implementado en UPN 2018 2 en el AA. HH. Las Torres de San Borja, Distrito de Moche, con la finalidad de compartir nuevas formas de educar a los niños. Con este nuevo proyecto se decidió trabajar a través del sistema educativo canadiense moderno 6Cs colaboración, comunicación, contenido, pensamiento crítico, confianza, creatividad. Con este modelo educativo se enfocó en enseñarles la importancia de la lectura en su desarrollo mental y educativo. Asimismo, se buscó, incentivar el buen uso de la biblioteca, fomentando hábitos de lectura, cuidado de los libros y mejora de la comprensión lectora en los niños, a través de dinámicas y actividades participativas donde ellos puedan relacionarse con los libros de la biblioteca. Gracias al proyecto “UNIONES”, los estudiantes de la Universidad Privada del Norte pudimos desarrollar “BIBLIOTECA PARA TODOS”, a través del taller “Estimulación del pensamiento crítico y habilidades blandas mediante la metodología “Leo, pienso y Aprendo” Palabras clave: Responsabilidad social, bibliotec

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results