Excision of Titin's Cardiac Pevk Spring Element Abolishes PKCα-Induced Increases in Myocardial Stiffness

Protein Kinase C-alpha (PKCalpha) was recently reported to increase myocardial stiffness, an effect that was proposed to be due to phosphorylation of two highly conserved sites (S11878 and S12022) within the proline-gluatamic acid-valine-lysine (PEVK) rich spring element of titin. To test this proposal we investigated the effect of PKCalpha on phosphorylation and passive stiffness in a mouse model lacking the titin exons that contain these two phosphorylation sites, the PEVK knockout (KO). We used skinned, gelsolin-extracted, left ventricular, myocardium from wildtype and PEVK KO mice. Consistent with previous work we found that PKCalpha increased passive stiffness in the WT myocardium by 27 +/-6%. Importantly, this effect was completely abolished in KO myocardium. In addition, increases in the elastic and viscous moduli at a wide range of frequencies (properties important in diastolic filling) following PKCalpha incubation (27 +/-3% and 20 +/-4%, respectively) were also ablated in the KO. Back phosphorylation assays showed that titin phosphorylation following incubation with PKCalpha was significantly reduced by 36+/-12% in skinned PEVK KO myocardial tissues. The remaining phosphorylation in the KO suggests that PKCalpha sites exist in the titin molecule outside the PEVK region; these sites are not involved in increasing passive stiffness. Our results firmly support that the PEVK region of cardiac titin is phosphorylated by PKCalpha and that this increases passive tension. Thus, the PEVK spring element is the critical site of PKCalpha's involvement in passive myocardial stiffness

Titin-Actin Interaction: PEVK-Actin-Based Viscosity in a Large Animal

Titin exhibits an interaction between its PEVK segment and the actin filament resulting in viscosity, a speed dependent resistive force, which significantly influences diastolic filling in mice. While diastolic disease is clinically pervasive, humans express a more compliant titin (N2BA:N2B ratio ~0.5–1.0) than mice (N2BA:N2B ratio ~0.2). To examine PEVK-actin based viscosity in compliant titin-tissues, we used pig cardiac tissue that expresses titin isoforms similar to that in humans. Stretch-hold experiments were performed at speeds from 0.1 to 10 lengths/s from slack sarcomere lengths (SL) to SL of 2.15 μm. Viscosity was calculated from the slope of stress-relaxation vs stretch speed. Recombinant PEVK was added to compete off native interactions and this found to reduce the slope by 35%, suggesting that PEVK-actin interactions are a strong contributor of viscosity. Frequency sweeps were performed at frequencies of 0.1–400 Hz and recombinant protein reduced viscous moduli by 40% at 2.15 μm and by 50% at 2.25 μm, suggesting a SL-dependent nature of viscosity that might prevent SL “overshoot” at long diastolic SLs. This study is the first to show that viscosity is present at physiologic speeds in the pig and supports the physiologic relevance of PEVK-actin interactions in humans in both health and disease

To what extent is Gluon Confinement an empirical fact?

Experimental verifications of Confinement in hadron physics have established the absence of charges with a fraction of the electron's charge by studying the energy deposited in ionization tracks at high energies, and performing Millikan experiments with charged droplets at rest. These experiments test only the absence of particles with fractional charge in the asymptotic spectrum, and thus "Quark" Confinement. However what theory suggests is that Color is confined, that is, all asymptotic particles are color singlets. Since QCD is a non-Abelian theory, the gluon force carriers (indirectly revealed in hadron jets) are colored. We empirically examine what can be said about Gluon Confinement based on the lack of detection of appropriate events, aiming at an upper bound for high-energy free-gluon production.Comment: 14 pages, 12 figures, version accepted at Few Body Physic

Evaluación Automática de Resultados de Aprendizaje como un Nuevo Paradigma en la enseñanza de un Curso de Programación: La ingeniería en la sociedad 5.0

Programming education goes through the transition from the content model to the learning outcomes model and the integration of technology, where automatic assessment tools allow students to support them in practice; This makes learning inclusive by proposing a transversal approach so that the necessary programming skills are achieved. In this sense, this paper presents a strategy that evaluates the source code and analyzes it using software metrics to identify students' learning results in a programming course. A strategy was developed that integrates an automatic source code evaluation tool, which allowed us to identify How an evaluation-based approach supports the learning process, time, and impact in a computer programming course? The results show that the strategy helps the transition from a programming course to a learning outcomes model and reduces the evaluation time without affecting students' grades, compared to the traditional way. Finally, it is essential to highlight that the development of strategies that integrate tools that support the teaching-learning and evaluation process in programming courses has a positive impact on academic training and decision-making, seeking to improve students' weaknesses through the analysis of the outcomes obtained

Quality of live and quality of work life in organic versus conventional farmers

Quality of life (QOL) and quality of work life (QOWL) play a key role in the overall concept of sustainability. In this paper we analyze QOL and QOWL variables in relation to the type of livestock farm (organic/conventional) and the use of some quality label (PDO Protected Designation of Origin, PGI Protected Geographical Indication). Data were collected through regular visits in 2011 to 70 small ruminant farms in Spain using five-point Likert items with 1-5 range. Of all the 70 farms, 6 are organics, 39 have a quality label and 17 use traditional manufacturing methods. The possession of quality labels in the small ruminant farms analyzed seems not to be related with the quality of life and work. Farmers with traditional production show higher valuation of quality of life but not of quality of work. Organic farms provide quality of life and quality of work significantly better than conventional ones

Conectividad del paisaje para tipos de hábitat zonales de interés comunitario en España

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