A rationale for non-linear responses to strong electric fields in molecular dynamics simulations

Many approaches for calculation of the field-dependent electric properties of water solutions rely on the Onsager and Kirkwood theories of polar dielectrics. Such basic theories implicitly consider the electric field intensity to fulfill the so-called 'weak field conditions', i.e. to produce a linear response in the system. In this work we made use of molecular dynamics simulations to investigate possible non-linear effects induced by high intensity electric fields, specifically continuous wave bursts with nanosecond duration, comparing them with the ones predicted by the theory. We found that field intensities above 0.15 V nm(-1) produce remarkable nonlinear responses in the whole 100 MHz-100 GHz frequency window considered, with the onset of higher order polarization signals, which are the clear fingerprint of harmonic distorsions. That non-linear response turned out to depend on the considered frequency. We finally show that MD outcomes are consistent with a modelization based on an extended formulation of the Langevin function including a frequency-dependent parameter

Los contenidos del trayecto de formación biológica, en los planes de estudios del Profesorado y Licenciatura en Educación Física, de la Facultad de Humanidades y Ciencias de la Educación, de la Universidad Nacional de La Plata

La línea temática en la que se inscribe el problema de investigación, corresponde a la de “Currículum universitario; problemáticas, desarrollo e innovación”. Considerando que la cuestión central de cualquier teoría del curriculum es, saber qué conocimientos deben ser enseñados, para posteriormente ser expresados en documentos curriculares como contenidos, esta investigación se centrará en los criterios de selección y organización de aquellos que provienen del campo de la biología, y que conforman las asignaturas del trayecto de formación biológica del plan de estudios del profesorado y licenciatura en Educación Física, vigentes desde el año 2000. La investigación indaga sobre los supuestos que justifican el por qué deben ser enseñados los contenidos enunciados en el actual plan de estudios y en los programas vigentes de estas asignaturas; al mismo tiempo considera las formas de organización de los mismos, es decir, el cómo son enseñados. La exploración propone dar respuesta a las siguientes preguntas: ¿Cuáles son los criterios de selección de los contenidos correspondientes a las asignaturas del trayecto de formación biológica en el plan de estudios de las carreras de Educación Física de la Universidad Nacional de La Plata? ¿Cuál es la relación entre los contenidos de estas asignaturas y las incumbencias profesionales planteadas en el plan? ¿Cuáles son las formas de organización y jerarquización de estos contenidos? ¿Cómo se articulan los actuales contenidos del trayecto de formación biológica, con los de los otros ejes y trayectos? ¿Cómo se integran los contenidos hacia el interior del propio trayecto de formación biológica?Facultad de Humanidades y Ciencias de la Educació

Exercise Physiology as a specialization within the field of Physical Education: an analysis from the own institutional context

El propósito de este trabajo es analizar la existencia de una aparente contradicción entre las ideas y creencias que guían la actividad académica de nuestra institución, el Departamento de Educación Física de la Facultad de Humanidades y Ciencias de la Educación de la Universidad Nacional de La Plata, y la implementación de la "Especialización en Fisiología del Ejercicio", como carrera de especialización de posgrado en el campo de la Educación Física.The purpose of this paper is to analyze the existence of an apparent contradiction between the ideas and beliefs that guide our institution's academic activity, the Department of Physical Education,from the Faculty of Humanities and Education Ciences at La Plata National University, and the implementation of the "Exercise Physiology Specialization", a graduate career in the field of Physical Education.Departamento de Educación Físic

Los contenidos del trayecto de formación biológica, en los planes de estudios del Profesorado y Licenciatura en Educación Física, de la Facultad de Humanidades y Ciencias de la Educación, de la Universidad Nacional de La Plata

La línea temática en la que se inscribe el problema de investigación, corresponde a la de “Currículum universitario; problemáticas, desarrollo e innovación”. Considerando que la cuestión central de cualquier teoría del curriculum es, saber qué conocimientos deben ser enseñados, para posteriormente ser expresados en documentos curriculares como contenidos, esta investigación se centrará en los criterios de selección y organización de aquellos que provienen del campo de la biología, y que conforman las asignaturas del trayecto de formación biológica del plan de estudios del profesorado y licenciatura en Educación Física, vigentes desde el año 2000. La investigación indaga sobre los supuestos que justifican el por qué deben ser enseñados los contenidos enunciados en el actual plan de estudios y en los programas vigentes de estas asignaturas; al mismo tiempo considera las formas de organización de los mismos, es decir, el cómo son enseñados. La exploración propone dar respuesta a las siguientes preguntas: ¿Cuáles son los criterios de selección de los contenidos correspondientes a las asignaturas del trayecto de formación biológica en el plan de estudios de las carreras de Educación Física de la Universidad Nacional de La Plata? ¿Cuál es la relación entre los contenidos de estas asignaturas y las incumbencias profesionales planteadas en el plan? ¿Cuáles son las formas de organización y jerarquización de estos contenidos? ¿Cómo se articulan los actuales contenidos del trayecto de formación biológica, con los de los otros ejes y trayectos? ¿Cómo se integran los contenidos hacia el interior del propio trayecto de formación biológica?Facultad de Humanidades y Ciencias de la Educació

A Statistical Analytical Model for Hydrophilic Electropore Characterization: A Comparison Study

Molecular dynamics (MD) simulations have proved to be a useful tool for unveiling many aspects of pore formation in lipid membranes under the influence of external electric fields. In order to compare the size-related properties of pores in bilayers of various compositions, generated and maintained under different physical and chemical conditions, reference metrics are needed for characterizing pore geometry and its evolution over time. In the present paper three different methodologies for evaluating electropore geometrical behavior will be compared: (i) the first allows analysis of the dimensions of the pore through an algorithm that uses a Monte Carlo simulated annealing procedure to find the best route for a sphere with variable radius to squeeze through the pore channel; (ii) a more recent procedure extracts pore volume from an integration of a three-dimensional model of the irregular shape of the pore; (III) a new method based on a statistical approach (following essential dynamics principles) describes pore geometrical fluctuations in a robust and reproducible way. For the same pore height of 2 nm the three methods give rise to mean electropore radii up to 3-fold different. The three approaches described here are not system-specific, i.e. the methods can be generalized for any kind of pore for which appropriate structural information is available

Effects of environmental and electric perturbations on the pKa of thioredoxin cysteine 35: a computational study

Here we present a theoretical-computational study dealing with the evaluation of the pKa of the Cysteine residues in Thioredoxin (TRX) and in its complex with the Thioredoxin-interacting protein (TXNIP). The free energy differences between the anionic and neutral form of the Cysteine 32 and 35 have been evaluated by means of the Perturbed Matrix Method with classical perturbations due to both the environment and an exogenous electric field as provided by Molecular Dynamics (MD) simulations. The evaluation of the free energies allowed us to show that the effect of the perturbing terms is to lower the pKa of Cysteine 32 and Cysteine 35 with respect to the free amino-acid. On the other hand, in the complex TRX-TXNIP, our data show an enhanced stabilization of the neutral reduced form of Cys 35. These results suggest that external electric stimuli higher than 0.02 V/nm can modulate the Cysteine pKa, which can be connected to the tight regulation of the TRX acting as an antioxidant agent

Nanosecond Pulsed Electric Signals Can Affect Electrostatic Environment of Protiens Below the Threshold of Conformational Effects: The Case Study of SOD1 With a Molecular Simulation Study

Electric fields can be a powerful tool to interact with enzymes or proteins, with an intriguing perspective to allow protein manipulation. Recently, researchers have focused the interest on intracellular enzyme modifications triggered by the application of nanosecond pulsed electric fields. These findings were also supported by theoretical predictions from molecular dynamics simulations focussing on significant variations in protein secondary structures. In this work, a theoretical study utilizing molecular dynamics simulations is proposed to explore effects of electric fields of high intensity and very short nanosecond duration applied to the superoxide dismutase (Cu/Zn-SOD or SOD-1), an important enzyme involved in the cellular antioxidant defence mechanism. The effects of 100-nanosecond pulsed electric fields, with intensities ranging from 108 to 7x108 V/m, on a single SOD1 enzyme are presented. We demonstrated that the lowest intensity of 108 V/m, although not inducing structural changes, can produce electrostatic modifications on the reaction centre of the enzyme, as apparent from the dipolar response and the electric field distribution of the protein active site. Electric pulses above 5x108 V/m produced a fast transition between the folded and a partially denatured state, as inferred by the secondary structures analysis. Finally, for the highest field intensity used (7x108 V/m), a not reversible transition toward an unfolded state was observed

Stimulation of S1PR5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington's disease

Huntington's disease (HD) is themost common neurodegenerative disorder for which no effective cure is yet available. Although several agents have been identified to provide benefits so far, the number of therapeutic options remains limited with only symptomatic treatment available. Over the past few years, we have demonstrated that sphingolipid-based approachesmay open the door to newandmore targeted treatments for the disease. In this study, we investigated the therapeutic potential of stimulating sphingosine-1-phosphate (S1P) receptor 5 by the new selective agonist A-971432 (provided by AbbVie) in R6/2mice, a widely used HD animalmodel. Chronic administration of low-dose (0.1mg/kg) A-971432 slowed down the progression of the disease and significantly prolonged lifespan in symptomatic R6/2mice. Such beneficial effects were associated with activation of pro-survival pathways (BDNF, AKT and ERK) and with reduction of mutant huntingtin aggregation. A-971432 also protected blood-brain barrier (BBB) homeostasis in the same mice. Interestingly, when administered early in the disease, before any overt symptoms, A-971432 completely protected HDmice fromthe classic progressivemotor deficit and preserved BBB integrity. Beside representing a promising strategy to take into consideration for the development of alternative therapeutic options for HD, selective stimulation of S1P receptor 5may be also seen as an effective approach to target brain vasculature defects in the disease

Agri-Food Waste from Apple, Pear, and Sugar Beet as a Source of Protective Bioactive Molecules for Endothelial Dysfunction and Its Major Complications

Endothelial damage is recognized as the initial step that precedes several cardiovascular diseases (CVD), such as atherosclerosis, hypertension, and coronary artery disease. It has been demonstrated that the best treatment for CVD is prevention, and, in the frame of a healthy lifestyle, the consumption of vegetables, rich in bioactive molecules, appears effective at reducing the risk of CVD. In this context, the large amount of agri-food industry waste, considered a global problem due to its environmental and economic impact, represents an unexplored source of bioactive compounds. This review provides a summary regarding the possible exploitation of waste or by-products derived by the processing of three traditional Italian crops—apple, pear, and sugar beet—as a source of bioactive molecules to protect endothelial function. Particular attention has been given to the bioactive chemical profile of these pomaces and their efficacy in various pathological conditions related to endothelial dysfunction. The waste matrices of apple, pear, and sugar beet crops can represent promising starting material for producing “upcycled” products with functional applications, such as the prevention of endothelial dysfunction linked to cardiovascular diseases