254 research outputs found
Time resolved depression of isometric force by Mavacamten in single myofibrils from rabbit psoas and human cardiac muscle
Mavacamten has a differential impact on force generation in myofibrils from rabbit psoas and human cardiac muscle
The relation between sarcomere energetics and the rate of isometric tension relaxation in healthy and diseased cardiac muscle
The Relaxation Properties of Myofibrils Are Compromised by Amino Acids that Stabilize α-Tropomyosin
We investigated the functional impact of α-tropomyosin (Tm) substituted with one (D137L) or two (D137L/G126R) stabilizing amino acid substitutions on the mechanical behavior of rabbit psoas skeletal myofibrils by replacing endogenous Tm and troponin (Tn) with recombinant Tm mutants and purified skeletal Tn. Force recordings from myofibrils (15°C) at saturating [Ca(2+)] showed that Tm-stabilizing substitutions did not significantly affect the maximal isometric tension and the rates of force activation (k(ACT)) and redevelopment (k(TR)). However, a clear effect was observed on force relaxation: myofibrils with D137L/G126R or D137L Tm showed prolonged durations of the slow phase of relaxation and decreased rates of the fast phase. Both Tm-stabilizing substitutions strongly decreased the slack sarcomere length (SL) at submaximal activating [Ca(2+)] and increased the steepness of the SL-passive tension relation. These effects were reversed by addition of 10 mM 2,3-butanedione 2-monoxime. Myofibrils also showed an apparent increase in Ca(2+) sensitivity. Measurements of myofibrillar ATPase activity in the absence of Ca(2+) showed a significant increase in the presence of these Tms, indicating that single and double stabilizing substitutions compromise the full inhibition of contraction in the relaxed state. These data can be understood with the three-state (blocked-closed-open) theory of muscle regulation, according to which the mutations increase the contribution of the active open state in the absence of Ca(2+) (M(−)). Force measurements on myofibrils substituted with C-terminal truncated TnI showed similar compromised relaxation effects, indicating the importance of TnI-Tm interactions in maintaining the blocked state. It appears that reducing the flexibility of native Tm coiled-coil structure decreases the optimum interactions of the central part of Tm with the C-terminal region of TnI. This results in a shift away from the blocked state, allowing myosin binding and activity in the absence of Ca(2+). This work provides a basis for understanding the effects of disease-producing mutations in muscle proteins
Innovative Virtual Lab for Improving Safety and Port Operations
Computer simulation makes it possible to reproduce real systems and processes in a synthetic environment. In this way virtual analysis turn to be possible and it complex scenarios are suitable to be simulated. In the proposed paper is presented a port system where to study the behavior respect operations and accidents and to consider interaction among multiple players. The simulation is applied to create a Virtual Lab able to evaluate and investigate the development of new procedures, contingency plans during crises. The development of models to be used in simulations is clearly a critical aspect, since the consistency of the simulation depend on the quality of the models and their interaction; in this case the authors used their experience in the field to guarantee a successful Verification and Validation. In this case study, models are used for simulations of phenomena related to port accidents and crises with particular attention to dispersion system of liquid contaminant on sea surface and dispersion of toxic gases into atmosphere. These models have been tested in the Alacres2 simulator in order to create as an effective tool to observe and study the evolution and impact of dangerous situations, as well as a decision-making support to define response plans crises
Strong fisheries management and governance positively impact ecosystem status
Fisheries have had major negative impacts on marine ecosystems, and effective fisheries management and governance are needed to achieve sustainable fisheries, biodiversity conservation goals and thus good ecosystem status. To date, the IndiSeas programme (Indicators for the Seas) has focussed on assessing the ecological impacts of fishing at the ecosystem scale using ecological indicators. Here, we explore fisheries Management Effectiveness' and Governance Quality' and relate this to ecosystem health and status. We developed a dedicated expert survey, focused at the ecosystem level, with a series of questions addressing aspects of management and governance, from an ecosystem-based perspective, using objective and evidence-based criteria. The survey was completed by ecosystem experts (managers and scientists) and results analysed using ranking and multivariate methods. Results were further examined for selected ecosystems, using expert knowledge, to explore the overall findings in greater depth. Higher scores for Management Effectiveness' and Governance Quality' were significantly and positively related to ecosystems with better ecological status. Key factors that point to success in delivering fisheries and conservation objectives were as follows: the use of reference points for management, frequent review of stock assessments, whether Illegal, Unreported and Unregulated (IUU) catches were being accounted for and addressed, and the inclusion of stakeholders. Additionally, we found that the implementation of a long-term management plan, including economic and social dimensions of fisheries in exploited ecosystems, was a key factor in successful, sustainable fisheries management. Our results support the thesis that good ecosystem-based management and governance, sustainable fisheries and healthy ecosystems go together.IOC-UNESCO; EuroMarine; European FP7 MEECE research project; European Network of Excellence Eur-Oceans; FRB EMIBIOS project [212085]info:eu-repo/semantics/publishedVersio
Effects of Chronic Atrial Fibrillation on Active and Passive Force Generation in Human Atrial Myofibrils
Rationale: Chronic atrial fibrillation (cAF) is associated with atrial contractile dysfunction. Sarcomere remodeling may contribute to this contractile disorder.
Objective: Here, we use single atrial myofibrils and fast solution switching techniques to directly investigate the impact of cAF on myofilament mechanical function eliminating changes induced by the arrhythmia in atrial myocytes membranes and extracellular components. Remodeling of sarcomere proteins potentially related to the observed mechanical changes is also investigated.
Methods and Results: Myofibrils were isolated from atrial samples of 15 patients in sinus rhythm and 16 patients with cAF. Active tension changes following fast increase and decrease in [Ca2+] and the sarcomere length\u2013passive tension relation were determined in the 2 groups of myofibrils. Compared to sinus rhythm myofibrils, cAF myofibrils showed (1) a reduction in maximum tension and in the rates of tension activation and relaxation; (2) an increase in myofilament Ca2+ sensitivity; (3) a reduction in myofibril passive tension. The slow \u3b2-myosin heavy chain isoform and the more compliant titin isoform N2BA were up regulated in cAF myofibrils. Phosphorylation of multiple myofilament proteins was increased in cAF as compared to sinus rhythm atrial myocardium.
Conclusions: Alterations in active and passive tension generation at the sarcomere level, explained by translational and post-translational changes of multiple myofilament proteins, are part of the contractile dysfunction of human cAF and may contribute to the self-perpetuation of the arrhythmia and the development of atrial dilatation
Design of Biocompatible Liquid Cristal Elastomers Reproducing the Mechanical Properties of Human Cardiac Muscle
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