Combining stochastic and deterministic approaches within high efficiency molecular simulations

Generalized Shadow Hybrid Monte Carlo (GSHMC) is a method for molecular simulations that rigorously alternates Monte Carlo sampling from a canonical ensemble with integration of trajectories using Molecular Dynamics (MD). While conventional hybrid Monte Carlo methods completely re-sample particle's velocities between MD trajectories, our method suggests a partial velocity update procedure which keeps a part of the dynamic information throughout the simulation. We use shadow (modified) Hamiltonians, the asymptotic expansions in powers of the discretization parameter corresponding to timestep, which are conserved by symplectic integrators to higher accuracy than true Hamiltonians. We present the implementation of this method into the highly efficient MD code GROMACS and demonstrate its performance and accuracy on computationally expensive systems like proteins in comparison with the molecular dynamics techniques already available in GROMACS. We take advantage of the state-of-the-art algorithms adopted in the code, leading to an optimal implementation of the method. Our implementation introduces virtually no overhead and can accurately recreate complex biological processes, including rare event dynamics, saving much computational time compared with the conventional simulation methods

Concepciones de los estudiantes sobre una magnitud "olvidada" en la enseñanza de la química : la cantidad de sustancia

The main objective of this paper is the identification of the students' representations about the idea of substance quantity and to see to what extent the establised Chemistry teaching in Secondary schools contributes to giving them a more atomist view of matter. The results obtained in this work confirm that students, upon completing their studies, have practically not changed their 'globalist' conception of substance quantity, and only half of those that studied chemistry master the necessary activity to be able to understand the mole concept

Molecular dynamics simulations of iron- and aluminum-loaded serum transferrin: Protonation of tyr188 is necessary to prompt metal release

Serum transferrin (sTf) carries iron in blood serum and delivers it into cells by receptor-mediated endocytosis. The protein can also bind other metals, including aluminum. The crystal structures of the metal-free and metal-loaded protein indicate that the metal release process involves an opening of the protein. In this process, Lys206 and Lys296 lying in the proximity of each other form the dilysine pair or, so-called, dilysine trigger. It was suggested that the conformational change takes place due to variations of the protonation state of the dilysine trigger at the acidic endosomal pH. In 2003, Rinaldo and Field (Biophys. J. 85, 3485-3501) proposed that the dilysine trigger alone can not explain the opening and that the protonation of Tyr188 is required to prompt the conformational change. However, no evidence was supplied to support this hypothesis. Here, we present several 60 ns molecular dynamics simulations considering various protonation states to investigate the complexes formed by sTf with Fe(III) and Al(III). The calculations demonstrate that only in those systems where Tyr188 has been protonated does the protein undergo the conformational change and that the dilysine trigger alone does not lead to the opening. The simulations also indicate that the metal release process is a stepwise mechanism, where the hinge-bending motion is followed by the hinge-twisting step. Therefore, the study demonstrates for the first time that the protonation of Tyr188 is required for the release of metal from the metal loaded sTf and provides valuable information about the whole process

Tubulin and Tubulin Posttranslational Modifications in Alzheimer’s Disease and Vascular Dementia

Copyright \ua9 2021 Santiago-Mujika, Luthi-Carter, Giorgini, Kalaria and Mukaetova-Ladinska. Alzheimer’s disease (AD) and vascular dementia (VaD) are the two most common forms of dementia in older people. Although these two dementia types differ in their etiology, they share many pathophysiological and morphological features, including neuronal loss, which is associated with the microtubule (MT) destabilization. Stabilization of MTs is achieved in different ways: through interactions with MT binding proteins (MTBP) or by posttranslational modifications (PTMs) of tubulin. Polyglutamylation and tyrosination are two foremost PTMs that regulate the interaction between MTs and MTBPs, and play, therefore, a role in neurodegeneration. In this review, we summarize key information on tubulin PTMs in relation to AD and VaD and address the importance of studying further the tubulin code to reveal sites of potential intervention in development of novel and effective dementia therapy

SEOM clinical guideline for the management of cutaneous melanoma (2020)

Tractament adjuvant; Melanoma; EscenificacióAdjuvant treatment; Melanoma; StagingTratamiento adyuvante; Melanoma; EscenificaciónMelanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I–III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available

Diseño de estrategias centradas en el aprendizaje para las visitas escolares a los museos de ciencias

Las visitas a los Museos de Ciencias pueden constituir un complemento al aprendizaje de las ciencias realizado en la Escuela. Sin embargo, los Museos de Ciencias son entornos de aprendizaje no formal donde los profesores solemos tener poco control sobre las ideas implicadas o las experiencias que los estudiantes realizan. En el caso de visitas escolares, para que el Museo constituya un auténtico instrumento de aprendizaje son necesarios enfoques y estrategias centrados en el aprendizaje de los estudiantes más que en tareas de manipulación de módulos. Será necesario, diseñar materiales para la visita al Museo que integren el aprendizaje en la Escuela y en el Museo, que estimulen el interés y curiosidad de los estudiantes promoviendo un aprendizaje autónomo mediante trabajo en grupo orientado por el profesor. En este trabajo se explica cómo hemos elaborado estos materiales y sus principales características.Palabras clave: aprendizaje no formal, estrategias centradas en el aprendizaje, manipulación de módulos, museos de Ciencia, visitas escolares.Design of strategies focused on learning for school visits to science museumsVisits to the Science Museums can be a complement to Science learning at the School. However, Science Museums are non-formal learning environments where teachers tend to have little control over the ideas involved or the experiences that the students make. In the case of school visits, in order for the Museum to constitute a true learning instrument, it is necessary to focus on strategies and strategies focused on student learning rather than on module manipulation tasks. It will be necessary to design materials for the visit to the Museum that integrate the learning in the School and in the Museum, that stimulate the interest and curiosity of the students promoting an autonomous learning through work in group guided by the teacher. This paper explains how we have developed these materials and their main characteristics.Key words: non-formal learning, strategies focused on learning, manipulation of modules, science museums, school visits

Diseño de estrategias centradas en el aprendizaje para las visitas escolares a los museos de ciencias

Las visitas a los Museos de Ciencias pueden constituir un complemento al aprendizaje de las ciencias realizado en la Escuela. Sin embargo, los Museos de Ciencias son entornos de aprendizaje no formal donde los profesores solemos tener poco control sobre las ideas implicadas o las experiencias que los estudiantes realizan. En el caso de visitas escolares, para que el Museo constituya un auténtico instrumento de aprendizaje son necesarios enfoques y estrategias centrados en el aprendizaje de los estudiantes más que en tareas de manipulación de módulos. Será necesario, diseñar materiales para la visita al Museo que integren el aprendizaje en la Escuela y en el Museo, que estimulen el interés y curiosidad de los estudiantes promoviendo un aprendizaje autónomo mediante trabajo en grupo orientado por el profesor. En este trabajo se explica cómo hemos elaborado estos materiales y sus principales características

SEOM clinical guideline for the management of cutaneous melanoma (2020)

Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I-III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available