On the role of residue phosphorylation in 14-3-3 partners: AANAT as a case study

Twenty years ago, a novel concept in protein structural biology was discovered: the intrinsically disordered regions (IDRs). These regions remain largely unstructured under native conditions and the more are studied, more properties are attributed to them. Possibly, one of the most important is their ability to conform a new type of protein-protein interaction. Besides the classical domain-to-domain interactions, IDRs follow a ´fly-casting´ model including ´induced folding´. Unfortunately, it is only possible to experimentally explore initial and final states. However, the complete movie of conformational changes of protein regions and their characterization can be addressed by in silico experiments. Here, we simulate the binding of two proteins to describe how the phosphorylation of a single residue modulates the entire process. 14-3-3 protein family is considered a master regulator of phosphorylated proteins and from a modern point-of-view, protein phosphorylation is a three component system, with writers (kinases), erasers (phosphatases) and readers. This later biological role is attributed to the 14-3-3 protein family. Our molecular dynamics results show that phosphorylation of the key residue Thr31 in a partner of 14-3-3, the aralkylamine N-acetyltransferase, releases the fly-casting mechanism during binding. On the other hand, the non-phosphorylation of the same residue traps the proteins, systematically and repeatedly driving the simulations into wrong protein-protein conformations.Fil: Masone, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ingeniería; ArgentinaFil: Uhart, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Bustos, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; Argentin

Numerical analysis of the Rayleigh instability in capillary tubes: The influence of surfactant solubility

A two-dimensional (2D) free surface flow model already used to study the Rayleigh instability of thin films lining the interior of capillary tubes under the presence of insoluble surfactants [D. M. Campana, J. Di Paolo, and F. A. Saita, “A 2-D model of Rayleigh instability in capillary tubes. Surfactant effects,” Int. J. Multiphase Flow 30, 431 (2004)] is extended here to deal with soluble solutes. This new version that accounts for the mass transfer of surfactant in the bulk phase, as well as for its interfacial adsorption/desorption, is employed in this work to assess the influence of surfactant solubility on the unstable evolution. We confirm previously reported findings: surfactants do not affect the system stability but the growth rate of the instability [D. R. Otis, M. Johnson, T. J. Pedley, and R. D. Kamm, “The role of pulmonary surfactant in airway closure,” J. Appl. Physiol. 59, 1323 (1993)] and they do not change the successive shapes adopted by the liquid film as the instability develops [S. Kwak and C. Pozrikidis, “Effects of surfactants on the instability of a liquid thread or annular layer. Part I: Quiescent fluids,” Int. J. Multiphase Flow 27, 1 (2001)]. Insoluble surfactants delay the instability process, and the time needed to form liquid lenses disconnecting the gas phase—i.e., the closure time—is four to five times larger than for pure liquids. This retardation effect is considerably reduced when the surfactants are somewhat soluble. For a typical system adopted as a reference case, detailed computed predictions are shown; among them, curves of closure time versus adsorption number are given for solubility values ranging from insoluble to highly soluble conditions. In addition, the evolution of the four mass transport terms appearing in the interfacial mass balance equation—normal and tangential convection, diffusion and sorption—is scrutinized to uncover the mechanisms by which surfactant solubility affects the growth rate of the instability.Fil: Campana, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Saita, Fernando Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

Empirical Evidence of Large-Scale Diversity in API Usage of Object-Oriented Software

In this paper, we study how object-oriented classes are used across thousands of software packages. We concentrate on "usage diversity'", defined as the different statically observable combinations of methods called on the same object. We present empirical evidence that there is a significant usage diversity for many classes. For instance, we observe in our dataset that Java's String is used in 2460 manners. We discuss the reasons of this observed diversity and the consequences on software engineering knowledge and research

Phenomenological research on professsional knowledge and educational relationship building

Following Dewey’s (1997) and Schwab’s (2013) ideas, Clandinin & Connelly (1992) developed their notion of teacher as curriculum maker, it means, the “teacher not so much as a maker of curriculum but as a part of it and to imagine a place for contexts, culture (Dewey´s notion of interaction), and temporality (both past and future contained in Dewey´s notion of continuity)” (p.365). In this way, teachers are not seen as implementers of curricular plans but as part of the curriculum making process. In other words, they understand that students create their curriculum in their experience at school when they interact with teachers and the environment. Therefore, the educational relationship creates the framework where learning can take place and students can build knowledge (Atkinson, 2015); it means, relationships generate meeting places that allow the making and reshaping of curriculum. If teaching takes place in the relationship, it means recognition (and acceptance) of the other person, of the otherness. It supposes trying to come into relation with the other, and it implies also acceptance of the uncertainty that otherness has. Therefore, education Is not about the implementation of an education programme in order to achieve (pre)determined results. It is not about intervention on students, but it is an experience of relationship where each one constructs their own story (Molina, Blanco & Arbiol, 2016). In short, curriculum is made through experiences that are lived in relation and, therefore, we could say that education is an act of relationship (Piussi, 2006). In this way, education does not require that teachers have the most appropriate knowledge and programme for every situation; the educational experience is unpredictable and ineffable, we cannot anticipate or face it completely (Van Manen, 2015). Thus, teaching requires becoming aware of how we build relationships and how we see the other person (Contreras, 2002).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech