Molecular determinants of the structural and functional organization of the sarcoplasmic reticulum

AbstractThe endo-sarcoplasmic reticulum of striated muscle cells consists of distinct functional domains that are extremely well organized both in terms of functional specialisation and of spatial organisation. Here we shall review recent evidence on the potential involvement of recently identified novel proteins and of cytoskeletal components in the structural and functional organization of the sarcoplasmic reticulum with respect to the surface membrane/T-tubule system and the contractile apparatus

Solving Parity Games in Scala

Parity games are two-player games, played on directed graphs, whose nodes are labeled with priorities. Along a play, the maximal priority occurring infinitely often determines the winner. In the last two decades, a variety of algorithms and successive optimizations have been proposed. The majority of them have been implemented in PGSolver, written in OCaml, which has been elected by the community as the de facto platform to solve efficiently parity games as well as evaluate their performance in several specific cases. PGSolver includes the Zielonka Recursive Algorithm that has been shown to perform better than the others in randomly generated games. However, even for arenas with a few thousand of nodes (especially over dense graphs), it requires minutes to solve the corresponding game. In this paper, we deeply revisit the implementation of the recursive algorithm introducing several improvements and making use of Scala Programming Language. These choices have been proved to be very successful, gaining up to two orders of magnitude in running time

Amor mundi and politics in Hannah Arendt

Amor mundi es una aptitud existencial y un marco conceptual que caracteriza el trabajo de Arendt. Mundo, según Arendt, se concibe como «mundo de las apariencias» y como «mundo común»: es el espacio en el que los seres humanos pueden vivir y actuar políticamente. Este espacio tiene dimensiones visibles e invisibles. El artículo muestra la relación entre la perspectiva de Arendt, la crítica nietzscheana y heideggeriana de la metafísica, y la reflexión de Merleau-Ponty. Arendt analiza las consecuencias dramáticas de los proyectos políticos que tienen por objeto social la realización de la absoluta transparencia: la transparencia de este tipo coincide con la dominación totalitaria. Por el contrario, la política, cuyo contexto es la visibilidad de la esfera pública, siempre ha de respetar las dimensiones invisibles del mundo y de la vida humanaAmor mundi is an existential aptitude and a conceptual framework which characterizes Arendt’s work. World, according to Arendt, is conceived as «world of appearances» and as «common world»: it is the space in which human beings live and act politically. This space has both visible and invisible dimensions. The article shows the relationship between Arendt’s perspective, Nietzschean and Heideggerian critique of metaphysics, and the reflection of Merleau-Ponty. Arendt analyses the dramatic consequences of political projects which aim at realizing absolute social transparency: that sort of transparency coincides with totalitarian domination. On the contrary politics, whose context is the visibility of public realm, has always to respect the invisible dimensions of the world and of the human lif

Public discussion and transparency of power in Hobbes and Kant

El principio de transparencia política es un elemento constitutivo de los ordenamientos democráticos. Esto es así porque el poder invisible, el recurso al secreto y a la mentira política, no constituye un simple obstáculo a la plena realización de la democracia, sino un factor de verdadera degeneración de tal forma de gobierno. La reflexión sobre las razones, las condiciones y los eventuales riesgos de la transparencia política se sitúa en el corazón de cualquier teoría democrática. El artículo se propone realizar una pequeña contribución a la investigación sobre este tema, proponiendo un análisis relativo de dos clásicos, Hobbes y Kant, cuya obra proporciona instrumentos conceptuales de gran relevancia relativos a la referida reflexión. En particular, en la perspectiva adoptada aquí, la confrontación entre Hobbes y Kant viene a poner de relieve dos dispositivos conceptuales contrapuestos –el primero fundado sobre la correlación entre principio de soberanía, guerra y secreto, el segundo sobre el nexo existente entre la publicidad del poder, el derecho al uso público de la razón y la crítica de la mentira– que representan, hoy más que nunca, un estímulo para que la teoría de la democracia se enfrente a algunas cuestiones ineludibles de carácter filosófico-político.The principle of political transparency is a constitutive element of democratic systems. This is because the invisible power, resort to secrecy and political lie, not a single obstacle to the full realization of democracy, but a factor of real degeneration of this form of government. Thinking about the reasons, conditions and the possible risks of political transparency is at the heart of any democratic theory. The paper aims to make a small contribution to research on this subject, proposing an analysis on two classic, Hobbes and Kant, whose work provides conceptual tools of great importance relative to said reflection. In particular, in the perspective adopted here, the confrontation between Hobbes and Kant comes to highlight two contrasting conceptual devices, –the first based on the correlation between the principle of sovereignty, war and secret; the second on the link between advertising power, the right to public use of reason and criticism of lies– representing, more than ever, a stimulus to the theory of democracy is faced with certain inalienable philosophical matters political

Criticism, truth and argumentation in the last Foucault

Contra todo normativismo abstracto, Foucault ha contrapuesto con fuerza la instancia de una crítica entendida como ética, es decir, como trabajo sobre el propio estilo de vida: un trabajo sobre la forma de relacionarse con uno mismo y con los otros, que tiene una dimensión, al mismo tiempo, individual e interpersonal, reflexiva y material, política y espiritual. Una prática del la libertad consciente de sus propios límites y llamada a «gobernar» una constelación de aspiraciones y experiencias que no se dejan sintetizar fácilmente. Desde esta perspectiva, Foucault vuelve a pensar el papel de la filosofía: un papel ético, que él reencuentra en el origen histórico de este saber y que consiste en plantearla como una práctica de problematización centrada sobre la compleja, frágil y a veces arriesgada correlación entre logos y bios.Against all normativismo abstract, Foucault has strongly opposed the request of a criticism as understood as ethics, that is, as work on their own lifestyle: a work on how to interact with oneself and with others who have an dimension, while individual and interpersonal, and reflective material, political and spiritual. A practice of freedom conscious their own limits and call to «govern» a constellation of aspirations and experiences that can not be easily synthesized. From this perspective, Foucault once again think the role of philosophy: an ethical role, that the reunion in the historical origins of this knowledge and that is to raise it as a practice of problematization focused on the complex, fragile and sometimes risky correlation between logos e bios

Thermodynamic cost of coherent oscillations in stochastic systems

openVerrà presentata una congettura nell'ambito degli orologi biochimici. Verranno esposti alcuni risultati che connettono lo spettro di una matrice di transizione con altre proprietà. Verrà esplicitato il caso analitico di un sistema uniciclico a rates costanti. Verrà studiata la connessione tra la congettura ed i risultati prima presentati

FKBP12 associates tightly with the skeletal muscle type 1 ryanodine receptor, but not with other intracellular calcium release channels

AbstractThis study compared the relative levels of ryanodine receptor (RyR) isoforms, inositol 1,4,5-trisphosphate receptor (IP3R) isoforms, and calcineurin, plus their association with FKBP12 in brain, skeletal and cardiac tissue. FKBP12 demonstrated a very tight, high affinity association with skeletal muscle microsomes, which was displaced by FK506. In contrast, FKBP12 was not tightly associated with brain or cardiac microsomes and did not require FK506 for removal from these organelles. Furthermore, of the proteins solubilised from skeletal muscle, cardiac muscle and brain microsomes, only skeletal muscle RyR1 bound to an FKBP12–glutathione-S-transferase fusion protein, in a high affinity FK506 displaceable manner. These results suggest that RyR1 has distinctive FKBP12 binding properties when compared to RyR2, RyR3, all IP3R isoforms and calcineurin

Improving parity games in practice

Parity games are infinite-round two-player games played on directed graphs whose nodes are labeled with priorities. The winner of a play is determined by the smallest priority (even or odd) that is encountered infinitely often along the play. In the last two decades, several algorithms for solving parity games have been proposed and implemented in PGSolver, a platform written in OCaml. PGSolver includes the Zielonka’s recursive algorithm (RE, for short) which is known to be the best performing one over random games. Notably, several attempts have been carried out with the aim of improving the performance of RE in PGSolver, but with small advances in practice. In this work, we deeply revisit the implementation of RE by dealing with the use of specific data structures and programming languages such as Scala, Java, C++, and Go. Our empirical evaluation shows that these choices are successful, gaining up to three orders of magnitude in running time over the classic version of the algorithm implemented in PGSolver

Binding of an ankyrin-1 isoform to obscurin suggests a molecular link between the sarcoplasmic reticulum and myofibrils in striated muscles

Assembly of specialized membrane domains, both of the plasma membrane and of the ER, is necessary for the physiological activity of striated muscle cells. The mechanisms that mediate the structural organization of the sarcoplasmic reticulum with respect to the myofibrils are, however, not known. We report here that ank1.5, a small splice variant of the ank1 gene localized on the sarcoplasmic reticulum membrane, is capable of interacting with a sequence of 25 aa located at the COOH terminus of obscurin. Obscurin is a giant sarcomeric protein of ∼800 kD that binds to titin and has been proposed to mediate interactions between myofibrils and other cellular structures. The binding sites and the critical aa required in the interaction between ank1.5 and obscurin were characterized using the yeast two-hybrid system, in in vitro pull-down assays and in experiments in heterologous cells. In differentiated skeletal muscle cells, a transfected myc-tagged ank1.5 was found to be selectively restricted near the M line region where it colocalized with endogenous obscurin. The M line localization of ank1.5 required a functional obscurin-binding site, because mutations of this domain resulted in a diffused distribution of the mutant ank1.5 protein in skeletal muscle cells. The interaction between ank1.5 and obscurin represents the first direct evidence of two proteins that may provide a direct link between the sarcoplasmic reticulum and myofibrils

Localization of lipopolysaccharide from Escherichia Coli into human atherosclerotic plaque

Experimental studies showed that gut-derived lipopolysaccharide (LPS) is pro-atherogenic, however, its relationship with human atherosclerosis is still to be defined. We investigate if gut-derived LPS from Escherichia Coli localizes in human carotid plaque and its potential role as pro-inflammatory molecule in the atherosclerotic lesion. LPS from Escherichia Coli and Toll-like receptor 4 (TLR4) were studied in specimens from carotid and thyroid arteries of 10 patients undergoing endarterectomy and 15 controls matched for demographic and clinical characteristics. Blood LPS were significantly higher in patients compared to controls. Immunochemistry analysis revealed positivity for antibodies against LPS and TLR4 coincidentally with positivity for CD68 only in the atherosclerotic plaque of carotid arteries but not in thyroid arteries; the positivity for LPS and TLR4 was greater in the area with activated macrophages. LPS concentration similar to that detected in atherosclerotic plaque resulted in a dose-dependent TLR4-mediated Nox2 up-regulation by human monocytes. These data provide the first evidence that LPS from Escherichia Coli localizes in human plaque and may contribute to atherosclerotic damage via TLR4-mediated oxidative stress