Dihydropyridine Receptors as Voltage Sensors for a Depolarization-evoked, IP3R-mediated, Slow Calcium Signal in Skeletal Muscle Cells

The dihydropyridine receptor (DHPR), normally a voltage-dependent calcium channel, functions in skeletal muscle essentially as a voltage sensor, triggering intracellular calcium release for excitation-contraction coupling. In addition to this fast calcium release, via ryanodine receptor (RYR) channels, depolarization of skeletal myotubes evokes slow calcium waves, unrelated to contraction, that involve the cell nucleus (Jaimovich, E., R. Reyes, J.L. Liberona, and J.A. Powell. 2000. Am. J. Physiol. Cell Physiol. 278:C998–C1010). We tested the hypothesis that DHPR may also be the voltage sensor for these slow calcium signals. In cultures of primary rat myotubes, 10 μM nifedipine (a DHPR inhibitor) completely blocked the slow calcium (fluo-3-fluorescence) transient after 47 mM K+ depolarization and only partially reduced the fast Ca2+ signal. Dysgenic myotubes from the GLT cell line, which do not express the α1 subunit of the DHPR, did not show either type of calcium transient following depolarization. After transfection of the α1 DNA into the GLT cells, K+ depolarization induced slow calcium transients that were similar to those present in normal C2C12 and normal NLT cell lines. Slow calcium transients in transfected cells were blocked by nifedipine as well as by the G protein inhibitor, pertussis toxin, but not by ryanodine, the RYR inhibitor. Since slow Ca2+ transients appear to be mediated by IP3, we measured the increase of IP3 mass after K+ depolarization. The IP3 transient seen in control cells was inhibited by nifedipine and was absent in nontransfected dysgenic cells, but α1-transfected cells recovered the depolarization-induced IP3 transient. In normal myotubes, 10 μM nifedipine, but not ryanodine, inhibited c-jun and c-fos mRNA increase after K+ depolarization. These results suggest a role for DHPR-mediated calcium signals in regulation of early gene expression. A model of excitation-transcription coupling is presented in which both G proteins and IP3 appear as important downstream mediators after sensing of depolarization by DHPR

Evaluation of silicon, calcium and magnesium in liquid fertilizers on sorghum growth in the greenhouse.

Se evaluó el uso de fertilizantes líquidos con Si, Ca o Mg sobre el crecimiento del sorgo (Sorghum bicolor) en un Ultisol bajo invernadero. Se utilizaron 2 silicatos de potasio, carbonato de calcio y óxido de magnesio, todos en líquidos aplicados al suelo en dosis de 2 y 4 ml.pote-1, y un testigo, en un diseño irrestricto al azar con 9 tratamientos y 4 repeticiones. Las variables de crecimiento, evaluadas 45 días después de siembra, fueron peso seco de raíz y de parte aérea. Se realizó un análisis de suelos y de planta al final del ensayo. Las aplicaciones de Ca y de Mg incrementaron de manera significativa el crecimiento y la absorción de nutrimentos del sorgo. El carbonato de calcio promovió los valores más altos de biomasa seca y de absorción de N, P, Ca, S, Cu, Zn, Mn y B. Las fuentes de Si no tuvieron efectos significativos sobre la biomasa del sorgo, a excepción del silicato de K con Ca y Mg en dosis de 4 ml.pote-1, que además produjo un incremento significativo en la absorción de K. El carbonato de calcio y el óxido de magnesio incrementaron significativamente el pH, disminuyeron la acidez y el Al intercambiable, y aumentaron los contenidos de Ca o Mg en el suelo.The effect of liquid fertilizers with Si, Ca or Mg on the growth of sorghum (Sorghum bicolor) was evaluated in an Ultisol under greenhouse conditions. Four liquid fertilizers (two potassium silicates, calcium carbonate and magnesium oxide) were applied into the soil in liquids at doses of 2 and 4 ml.pot-1, plus a control, in a randomized unrestricted design with 9 treatments and 4 replicates. Growth variables, assessed 45 days after sowing, were dry weight of root and aerial parts. Analysis of soil and plant at the end of the test was performed. The application of Ca and Mg significantly increased growth and nutrient uptake of sorghum. Liquid calcium carbonate promoted the highest values of dry biomass and absorption of N, P, Ca, S, Cu, Zn, Mn and B. Si sources had no significant effects on biomass, except for K silicate with Ca and Mg at the dose of 4 ml.pot-1, which also produced a significant increase in K absorption. Calcium carbonate and magnesium oxide significantly increased soil pH and decreased exchangeable acidity and Al, and also increased Ca or Mg content in the soil.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Centro de Investigaciones Agronómicas (CIA

Maquinaria de control numerico computarizado (CNC) y su aplicacion en el proceso de remanufactura maderera

167 p.Los actuales mercados cada vez son mas exigentes tanto en cantidad como en calidad de productos. Para cumplir estas exigencias se hace cada vez mas necesario el uso de la automatización, existiendo dentro de esta ultima el uso de las maquinas de Control Numérico Computarizado (CNC). Esta tecnología se aplica en la industria de fabricación de piezas, partes y conjuntos para distintas áreas de producción, incluidas la industria secundaria de la madera. Las maquinas CNC pueden fabricar las mas complejas piezas con la precisión requerida. Todo bajo las Ordenes de un computador de uso exclusivo, el que se programa en un lenguaje propio. Lamentablemente son muy pocas las empresas nacionales que han podido incorporar maquinas CNC a sus procesos. Una de las causas de esto es el poco conocimiento del tema. Por lo anterior la presente Memoria esta destinada a la descripción de los principales aspectos del funcionamiento y uso de las maquinas CNC. Para esto, además de la revisión bibliografiíta, se visitaron empresas y se realizo un contacto directo con personas expertas en el tema, quienes entregaron información de las maquinas, características del personal que las usa, el apoyo computacional y la generación de los programas de trabajo. Se entrega además una visión general actual y futura de la tecnología CNC en la remanufactura maderera, considerando los problemas que existen actualmente en la industria nacional y las soluciones a algunos de estos problemas. También se analizan globalmente las ventajas y desventajas del uso de esta tecnología

Strengthening self-regulation and reducing poverty to prevent adolescent depression and anxiety: rationale, approach and methods of the ALIVE interdisciplinary research collaboration in Colombia, Nepal and South Africa

Aims Depression and anxiety are the leading contributors to the global burden of disease among young people, accounting for over a third (34.8%) of years lived with disability. Yet there is limited evidence for interventions that prevent adolescent depression and anxiety in low- and middle-income countries (LMICs), where 90% of adolescents live. This article introduces the ‘Improving Adolescent mentaL health by reducing the Impact of poVErty (ALIVE)’ study, its conceptual framework, objectives, methods and expected outcomes. The aim of the ALIVE study is to develop and pilot-test an intervention that combines poverty reduction with strengthening self-regulation to prevent depression and anxiety among adolescents living in urban poverty in Colombia, Nepal and South Africa. Methods This aim will be achieved by addressing four objectives: (1) develop a conceptual framework that identifies the causal mechanisms linking poverty, self-regulation and depression and anxiety; (2) develop a multi-component selective prevention intervention targeting self-regulation and poverty among adolescents at high risk of developing depression or anxiety; (3) adapt and validate instruments to measure incidence of depression and anxiety, mediators and implementation parameters of the prevention intervention; and (4) undertake a four-arm pilot cluster randomised controlled trial to assess the feasibility, acceptability and cost of the selective prevention intervention in the three study sites. Results The contributions of this study include the active engagement and participation of adolescents in the research process; a focus on the causal mechanisms of the intervention; building an evidence base for prevention interventions in LMICs; and the use of an interdisciplinary approach. Conclusions By developing and evaluating an intervention that addresses multidimensional poverty and self-regulation, ALIVE can make contributions to evidence on the integration of mental health into broader development policy and practice

Catalases Are NAD(P)H-Dependent Tellurite Reductases

Reactive oxygen species damage intracellular targets and are implicated in cancer, genetic disease, mutagenesis, and aging. Catalases are among the key enzymatic defenses against one of the most physiologically abundant reactive oxygen species, hydrogen peroxide. The well-studied, heme-dependent catalases accelerate the rate of the dismutation of peroxide to molecular oxygen and water with near kinetic perfection. Many catalases also bind the cofactors NADPH and NADH tenaciously, but, surprisingly, NAD(P)H is not required for their dismutase activity. Although NAD(P)H protects bovine catalase against oxidative damage by its peroxide substrate, the catalytic role of the nicotinamide cofactor in the function of this enzyme has remained a biochemical mystery to date. Anions formed by heavy metal oxides are among the most highly reactive, natural oxidizing agents. Here, we show that a natural isolate of Staphylococcus epidermidis resistant to tellurite detoxifies this anion thanks to a novel activity of its catalase, and that a subset of both bacterial and mammalian catalases carry out the NAD(P)H-dependent reduction of soluble tellurite ion (TeO(3) (2−)) to the less toxic, insoluble metal, tellurium (Te°), in vitro. An Escherichia coli mutant defective in the KatG catalase/peroxidase is sensitive to tellurite, and expression of the S. epidermidis catalase gene in a heterologous E. coli host confers increased resistance to tellurite as well as to hydrogen peroxide in vivo, arguing that S. epidermidis catalase provides a physiological line of defense against both of these strong oxidizing agents. Kinetic studies reveal that bovine catalase reduces tellurite with a low Michaelis-Menten constant, a result suggesting that tellurite is among the natural substrates of this enzyme. The reduction of tellurite by bovine catalase occurs at the expense of producing the highly reactive superoxide radical

SELNET clinical practice guidelines for bone sarcoma

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context

Measurement of the W-boson mass in pp collisions at √s=7 TeV with the ATLAS detector

A measurement of the mass of the W boson is presented based on proton–proton collision data recorded in 2011 at a centre-of-mass energy of 7 TeV with the ATLAS detector at the LHC, and corresponding to 4.6 fb−1 of integrated luminosity. The selected data sample consists of 7.8×106 candidates in the W→μν channel and 5.9×106 candidates in the W→eν channel. The W-boson mass is obtained from template fits to the reconstructed distributions of the charged lepton transverse momentum and of the W boson transverse mass in the electron and muon decay channels, yielding mW=80370±7 (stat.)±11(exp. syst.) ±14(mod. syst.) MeV =80370±19MeV, where the first uncertainty is statistical, the second corresponds to the experimental systematic uncertainty, and the third to the physics-modelling systematic uncertainty. A measurement of the mass difference between the W+ and W−bosons yields mW+−mW−=−29±28 MeV

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.