Impaired modulation of the cardiac L-type Ca2+ channel activity by ahnak-1 after myocardial infarction

Introduction: The L-type cardiac Ca2+ channel (Cav 1.2) is an important determinant of cardiac repolarization and the main source of activator Ca2+ during excitation-contraction coupling in cardiac cells. Its defective regulation is a major cause of arrhythmias and contractile dysfunction. We have recently shown that the cytoskeletal protein ahnak-1 modulates Ca2+ current through Cav 1.2 channels (ICaL) by interacting with the regulatory beta-subunit of the Cav 1.2 channel and that the genetic variant of ahnak-1 I5483T (previously Ile5236Thr), interferes with the beta-adrenergic stimulation of ICaL. Objective: To extend our study of the I5483T variant to ventricular cardiomyocytes dissociated from remodelled infarcted rat hearts (PMI). Methods: The patch-clamp technique was used to record ICaL from enzymatically dissociated ventricular cardiomyocytes from young (2-month-old) and six-month-old sham-operated and PMI rats. Results: Basal ICaL was increased from 11 ± 0.5 A/F in young cardiomyocytes to 14.6 ± 1.1 A/F and 15.7 ± 1 A/F in sham and PMI cardiomyocytes respectively, while isoprenaline (ISO, 1 µmol/L) further increased ICaL by 101 ± 6%, 109 ± 10% and 104 ± 12% respectively. When cells were intracellularly perfused with a peptide containing the mutated ahnak-1 sequence (10 µmol/L) basal ICaL was increased to 20 ± 1 A/F, 22 ± 2 A/F and 21 ± 2 A/F in young, sham and PMI cardiomyocytes respectively. In these cells ISO increased ICaL by 11 ± 4%, 33 ± 6% and 79 ± 12% respectively. Conclusion: Modulation of ICaL by ahnak-1is impaired by myocardial ischemia and remodelling. Since ahnak-1 and Cav 1.2 channels co-localize in the transverse T-tubule system, remodelling of T-tubules could affect the interaction of ahnak-1 with the regulatory beta subunit of these channels

The role of spatial and temporal radiation deposition in inertial fusion chambers: the case of HiPER¿

The first wall armour for the reactor chamber of HiPER will have to face short energy pulses of 5 to 20 MJ mostly in the form of x-rays and charged particles at a repetition rate of 5–10 Hz. Armour material and chamber dimensions have to be chosen to avoid/minimize damage to the chamber, ensuring the proper functioning of the facility during its planned lifetime. The maximum energy fluence that the armour can withstand without risk of failure, is determined by temporal and spatial deposition of the radiation energy inside the material. In this paper, simulations on the thermal effect of the radiation–armour interaction are carried out with an increasing definition of the temporal and spatial deposition of energy to prove their influence on the final results. These calculations will lead us to present the first values of the thermo-mechanical behaviour of the tungsten armour designed for the HiPER project under a shock ignition target of 48 MJ. The results will show that only the crossing of the plasticity limit in the first few micrometres might be a threat after thousands of shots for the survivability of the armour

Modelización de las distribuciones diamétricas en masas de Betula alba L. en el noroeste de España con la función Weibull biparamétrica

The diameter distributions of 125 permanent plots installed in birch dominated (Betula alba L.) stands in Galicia were modelled with the two-parameter Weibull distribution. Four different fitting methods were used: that based on percentiles of the distribution, non linear regression, maximum likelihood and the method of moments. The most accurate fit was obtained with the non linear regression (NLR) approach, considering the following statistics in the comparison: bias, mean absolute error (MAE), mean square error (MSE) and number of plots rejected by the Kolmogoroff-Smirnoff (KS) test. The scale parameter (b) and the shape parameter (c) obtained with the most accurate method (non linear regression), were first modelled with simple linear models and then related to commonly measured prediction variables (quadratic mean diameter, dominant height and stand density) with the parameter prediction model (PPM). The parameters fitted with the method of moments were recovered with the parameter recovery model (PRM) from the first and the second moments of the distribution (mean diameter and variance, respectively). Results indicated that both methods were successful in predicting the diameter frequency distributions. The PRM was more accurate than the PPM method.Las distribuciones diamétricas de 125 parcelas permanentes instaladas en masas puras de abedul (Betula alba L.) en Galicia fueron modelizadas con la distribución Weibull de dos parámetros. Se emplearon cuatro métodos de ajuste: basados en percentiles de la distribución, regresión no lineal, máxima verosimilitud y el método de los momentos. Los ajustes más precisos fueron obtenidos con regresión no lineal, considerando los siguientes estadísticos en la comparación de los resultados: sesgo, error medio absoluto, error medio cuadrático y número de parcelas rechazadas por el test de Kolmogoroff-Smirnoff. El parámetro de escala (b) y el parámetro de forma (c) obtenidos con el método más preciso (regresión no lineal), fueron relacionados con variables de masa de frecuente medición (diámetro medio cuadrático, altura dominante y densidad) mediante modelos lineales sencillos aplicando la metodología de predicción de parámetros. Los parámetros ajustados con el método de los momentos fueron recuperados con modelos de recuperación de parámetros a partir del primer y del segundo momento de la distribución (diámetro medio y varianza, respectivamente). Los resultados indicaron que ambos métodos fueron satisfactorios para predecir las distribuciones de frecuencias de diámetros. El método de recuperación de parámetros fue más preciso que el método de predicción de parámetros

Seasonal cycle of precipitation variability in South America on intraseasonal timescales

The seasonal cycle of the intraseasonal (IS) variability of precipitation in South America is described through the analysis of bandpass filtered outgoing longwave radiation (OLR) anomalies. The analysis is discriminated between short (10--30 days) and long (30--90 days) intraseasonal timescales. The seasonal cycle of the 30--90-day IS variability can be well described by the activity of first leading pattern (EOF1) computed separately for the wet season (October--April) and the dry season (May--September). In agreement with previous works, the EOF1 spatial distribution during the wet season is that of a dipole with centers of actions in the South Atlantic Convergence Zone (SACZ) and southeastern South America (SESA), while during the dry season, only the last center is discernible. In both seasons, the pattern is highly influenced by the activity of the Madden--Julian Oscillation (MJO). Moreover, EOF1 is related with a tropical zonal-wavenumber-1 structure superposed with coherent wave trains extended along the South Pacific during the wet season, while during the dry season the wavenumber-1 structure is not observed. The 10--30-day IS variability of OLR in South America can be well represented by the activity of the EOF1 computed through considering all seasons together, a dipole but with the stronger center located over SESA. While the convection activity at the tropical band does not seem to influence its activity, there are evidences that the atmospheric variability at subtropical-extratropical regions might have a role. Subpolar wavetrains are observed in the Pacific throughout the year and less intense during DJF, while a path of wave energy dispersion along a subtropical wavetrain also characterizes the other seasons. Further work is needed to identify the sources of the 10--30-day-IS variability in South America

Gamma-ray bursts and terrestrial planetary atmospheres

We describe results of modeling the effects on Earth-like planets of long-duration gamma-ray bursts (GRBs) within a few kiloparsecs. A primary effect is generation of nitrogen oxide compounds which deplete ozone. Ozone depletion leads to an increase in solar UVB radiation at the surface, enhancing DNA damage, particularly in marine microorganisms such as phytoplankton. In addition, we expect increased atmospheric opacity due to buildup of nitrogen dioxide produced by the burst and enhanced precipitation of nitric acid. We review here previous work on this subject and discuss recent developments, including further discussion of our estimates of the rates of impacting GRBs and the possible role of short-duration bursts.Comment: 12 pages including 5 figures (4 in color). Added discussion of GRB rates and biological effects. Accepted for publication in New Journal of Physics, for special issue "Focus on Gamma-Ray Bursts

Prospects for observations of high-energy cosmic tau neutrinos

We study prospects for the observations of high-energy cosmic tau neutrinos (E \geq 10^6 GeV) originating from proton acceleration in the cores of active galactic nuclei. We consider the possibility that vacuum flavor neutrino oscillations induce a tau to muon neutrino flux ratio greatly exceeding the rather small value expected from intrinsic production. The criterias and event rates for under water/ice light Cerenkov neutrino telescopes are given by considering the possible detection of downgoing high-energy cosmic tau neutrinos through characteristic double shower events.Comment: 10 pages, Revtex, 3 figures included with eps

GRBs Neutrinos as a Tool to Explore Quantum Gravity induced Lorentz Violation

Lorentz Invariance Violation (LIV) arises in various quantum-gravity theories. As the typical energy for quantum gravity is the Planck mass, $M_{pl}$, LIV will, most likely, be manifested at very high energies that are not accessible on Earth in the foreseeable future. One has to turn to astronomical observations. Time of flight measurement from different astronomical sources set current limits on the energy scale of possible LIV to $> 0.01 M_{pl}$ (for n=1 models) and $> 10^{-9} M_{pl}$ (for n=2). According to current models Gamma-Ray Bursts (GRBs) are accompanied by bursts of high energy (\gsim 100TeV) neutrinos. At this energy range the background level of currently constructed neutrino detectors is so low that a detection of a single neutrino from the direction of a GRB months or even years after the burst would imply an association of the neutrino with the burst and will establish a measurement of a time of flight delay. Such time of flight measurements provide the best way to observe (or set limits) on LIV. Detection of a single GRB neutrino would open a new window on LIV and would improve current limits by many orders of magnitude

Bayesian analysis of the association between casein complex haplotype variants and milk yield, composition, and curve shape parameters in murciano-granadina goats

Considering casein haplotype variants rather than SNPs may maximize the understanding of heritable mechanisms and their implication on the expression of functional traits related to milk production. Effects of casein complex haplotypes on milk yield, milk composition, and curve shape parameters were used using a Bayesian inference for ANOVA. We identified 48 single nucleotide polymorphisms (SNPs) present in the casein complex of 159 unrelated individuals of diverse ancestry, which were organized into 86 haplotypes. The Ali and Schaeffer model was chosen as the best fitting model for milk yield (Kg), protein, fat, dry matter, and lactose (%), while parabolic yield-density was chosen as the best fitting model for somatic cells count (SCC × 103 sc/mL). Peak and persistence for all traits were computed respectively. Statistically significant differences (p < 0.05) were found for milk yield and components. However, no significant difference was found for any curve shape parameter except for protein percentage peak. Those haplotypes for which higher milk yields were reported were the ones that had higher percentages for protein, fat, dry matter, and lactose, while the opposite trend was described by somatic cells counts. Conclusively, casein complex haplotypes can be considered in selection strategies for economically important traits in dairy goats

Software-automatized individual lactation model fitting, peak and persistence and Bayesian criteria comparison for milk yield genetic studies in Murciano-Granadina goats

SPSS model syntax was defined and used to evaluate the individual performance of 49 linear and non-linear models to fit the lactation curve of 159 Murciano-Granadina goats selected for genotyping analyses. Lactation curve shape, peak and persistence were evaluated for each model using 3107 milk yield controls with an average of 3.78 ± 2.05 lactations per goat. Best fit (Adjusted R2) values (0.47) were reached by the five-parameter logarithmic model of Ali and Schaeffer. Three main possibilities were detected: non-fitting (did not converge), standard (Adjusted R2 over 75%) and atypical curves (Adjusted R2 below 75%). All the goats fitted for 38 models. The ability to fit different possible functional forms for each goat, which progressively increased with the number of parameters comprised in each model, translated into a higher sensitivity to explaining curve shape individual variability. However, for models for which all goats fitted, only moderate increases in explanatory and predictive potential (AIC, AICc or BIC) were found. The Ali and Schaeffer model reported the best fitting results to study the genetic variability behind goat milk yield and perhaps enhance the evaluation of curve parameters as trustable future selection criteria to face the future challenges offered by the goat dairy industry