Glycogen Synthase Kinase 3 Inhibitors in the Next Horizon for Alzheimer's Disease Treatment

Glycogen synthase kinase 3 (GSK-3), a proline/serine protein kinase ubiquitously expressed and involved in many cellular signaling pathways, plays a key role in the pathogenesis of Alzheimer's disease (AD) being probably the link between β-amyloid and tau pathology. A great effort has recently been done in the discovery and development of different new molecules, of synthetic and natural origin, able to inhibit this enzyme, and several kinetics mechanisms of binding have been described. The small molecule called tideglusib belonging to the thiadiazolidindione family is currently on phase IIb clinical trials for AD. The potential risks and benefits of this new kind of disease modifying drugs for the future therapy of AD are discussed in this paper

VIP contribution to the decidualization program: regulatory T cell recruitment

During early pregnancy, the human uterus undergoes profound tissue remodeling characterized by leukocyte invasion and production of proinflammatory cytokines, followed by tissue repair and tolerance maintenance induction. Vasoactive intestinal peptide (VIP) is produced by trophoblast cells and modulates the maternal immune response toward a tolerogenic profile. Here, we evaluated the contribution of the VIP/VPAC to endometrial renewal, inducing decidualization and the recruitment of induced regulatory T cells (iTregs) that accompany the implantation period. For that purpose, we used an in vitro model of decidualization with a human endometrial stromal cell line (HESC) stimulated with progesterone (P4) and lipopolysaccharide (LPS) simulating the inflammatory response during implantation and human iTregs (CD4+CD25+FOXP3+) differentiated from naïve T cells obtained from peripheral blood mononuclear cells of fertile women. We observed that VIP and its receptor VPAC1 are constitutively expressed in HESCs and that P4 increased VIP expression. Moreover, in HESC VIP induced expression of RANTES (CCL5), one of the main chemokines involved in T cell recruitment, and this effect is enhanced by the presence of P4 and LPS. Finally, assays of the migration of iTregs toward conditioned media from HESCs revealed that endogenous VIP production induced by P4 and LPS and RANTES production were involved, as anti-RANTES neutralizing Ab or VIP antagonist prevented their migration. We conclude that VIP may have an active role in the decidualization process, thus contributing to recruitment of iTregs toward endometrial stromal cells by increasing RANTES expression in a P4-dependent manner.Fil: Grasso, Esteban Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Paparini, Daniel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Agüero, Mariana. Universidad de Buenos Aires; ArgentinaFil: Mor, Gil. University of Yale; Estados UnidosFil: Perez Leiros, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Ramhorst, Rosanna Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin

Ankle sprain versus muscle strain injury in professional men's basketball: a 9-year prospective follow-up study

Peer ReviewedPostprint (author's final draft

Low-Cost Piezoelectric Sensors for Time Domain Load Monitoring of Metallic Structures During Operational and Maintenance Processes

The versatility of piezoelectric sensors in measurement techniques and their performance in applications has given rise to an increased interest in their use for structural and manufacturing component monitoring. They enable wireless and sensor network solutions to be developed in order to directly integrate the sensors into machines, fixtures and tools. Piezoelectric sensors increasingly compete with strain-gauges due to their wide operational temperature range, load and strain sensing accuracy, low power consumption and low cost. This research sets out the use of piezoelectric sensors for real-time monitoring of mechanical strength in metallic structures in the ongoing operational control of machinery components. The behaviour of aluminium and steel structures under flexural strength was studied using piezoelectric sensors. Variations in structural behaviour and geometry were measured, and the load and μstrains during operational conditions were quantified in the time domain at a specific frequency. The lead zirconium titanate (PZT) sensors were able to distinguish between material types and thicknesses. Moreover, this work covers frequency selection and optimisation from 20 Hz to 300 kHz. Significant differences in terms of optimal operating frequencies and sensitivity were found in both structures. The influence of the PZT voltage applied was assessed to reduce power consumption without signal loss, and calibration to μstrains and loads was performed.This research was funded by Basque Government, grant number KK-2019/00051-SMARTRESNAK and by the European Commission, grant number 869884- RECLAIM

On Mechanical and Electrical Coupling Determination at Piezoelectric Harvester by Customized Algorithm Modeling and Measurable Properties

Piezoelectric harvesters use the actuation potential of the piezoelectric material to transform mechanical and vibrational energies into electrical power, scavenging energy from their environment. Few research has been focused on the development and understanding of the piezoelectric harvesters from the material themselves and the real piezoelectric and mechanical properties of the harvester. In the present work, the authors propose a behavior real model based on the experimentally measured electromechanical parameters of a homemade PZT bimorph harvester with the aim to predict its Vrms output. To adjust the harvester behavior, an iterative customized algorithm has been developed in order to adapt the electromechanical coupling coefficient, finding the relationship between the harvester actuator and generator behavior. It has been demonstrated that the harvester adapts its elongation and its piezoelectric coefficients combining the effect of the applied mechanical strain and the electrical behavior as a more realistic behavior due to the electromechanical nature of the material. The complex rms voltage output of the homemade bimorph harvester in the frequency domain has been successfully reproduced by the proposed model. The Behavior Real Model, BRM, developed could become a powerful tool for the design and manufacturing of a piezoelectric harvester based on its customized dimensions, configuration, and the piezoelectric properties of the smart materials.This research was funded by the Basque Government, grant number KK-2021/00082-µ4IIoT, and by the European Commission, grant number 869884- RECLAIM

Ni es “nuestra Ciencia y nuestra Tecnología”, ni son “nuestros Derechos Humanos”

El propósito de este trabajo es contribuir a cuestionar la atribución a la civilización judeocristiana, en exclusiva, del origen de la ciencia moderna, así como de la implantación y defensa de los Derechos Humanos. Se pretende con ello salir al paso de la supuesta superioridad cultural de dicha civilización, utilizada como justificación de inaceptables privilegios y causa de conflictos que impiden avanzar en la transición a sociedades sostenibles, respetuosas con el conjunto de Derechos Humanos Universales

Las prácticas de laboratorio de física en la formación del profesorado. Un análisis crítico.

We have proposed and founded the hypothesis that practical works done by future physics teachers in their university physics courses and in the teachers training centers do not give a correct view of a scientific approach. Results of the analysis of 91 lab guides, 54 estudents repports and some professors  interviews are in accordance with this hypothesis, showing the need of a deep reestructure of the usual orientation of the practical works proposed to future physics teachers. </p

Electrical Response Analysis of a Piezoelectric Energy Harvester Power Source Based on Electromechanical Parameters

A piezoelectric energy harvester generator is a device capable of transforming environmental mechanical energy into electrical energy. The piezoelectric electromechanical parameters determine the maximum electrical power which is able to be transferred to an electric load. In this research work, an exhaustive study of the electromechanical parameters related to the piezoelectric material is carried out, modeling them as components of an electrical circuit, in order to analyze their influence on the transmitted power. On the other hand, some electrical loads are simulated to determine different matrix scenarios for a model developed by state-space equations in the Laplace transform domain. The results obtained have allowed to know how the piezoelectric material properties and mechanical characteristics influence the electrical power output of the energy harvester generator and the energy transmission behavior for different electric loads. The conclusions show how the different electromechanical parameters are related to each other, and how their combination transforms the mechanical environmental energy into the required electrical energy. The novelty of this research is the presentation of a model capable of obtaining the optimized working point of the harvester, taking into account not only the electric loads and current demands but also the piezoelectric material parameters.This research was funded by the European Commission, grant number 869884-RECLAIM

Multiphoton imaging of melanoma 3D models with plasmonic nanocapsules

We report the synthesis of plasmonic nanocapsules and the cellular responses they induce in 3D melanoma models for their perspective use as a photothermal therapeutic agent. The wall of the nanocapsules is composed of polyelectrolytes. The inner part is functionalized with discrete gold nanoislands. The cavity of the nanocapsules contains a fluorescent payload to show their ability for loading a cargo. The nanocapsules exhibit simultaneous two-photon luminescent, fluorescent properties and X-ray contrasting ability. The average fluorescence lifetime (τ) of the nanocapsules measured with FLIM (0.3 ns) is maintained regardless of the intracellular environment, thus proving their abilities for bioimaging of models such as 3D spheroids with a complex architecture. Their multimodal imaging properties are exploited for the first time to study tumorspheres cellular responses exposed to the nanocapsules. Specifically, we studied cellular uptake, toxicity, intracellular fate, generation of reactive oxygen species, and effect on the levels of hypoxia by using multi-photon and confocal laser scanning microscopy. Because of the high X-ray attenuation and atomic number of the gold nanostructure, we imaged the nanocapsule-cell interactions without processing the sample. We confirmed maintenance of the nanocapsules’ geometry in the intracellular milieu with no impairment of the cellular ultrastructure. Furthermore, we observed the lack of cellular toxicity and no alteration in oxygen or reactive oxygen species levels. These results in 3D melanoma models contribute to the development of these nanocapsules for their exploitation in future applications as agents for imaging-guided photothermal therapy. Statement of Significance: The novelty of the work is that our plasmonic nanocapsules are multimodal. They are responsive to X-ray and to multiphoton and single-photon excitation. This allowed us to study their interaction with 2D and 3D cellular structures and specifically to obtain information on tumor cell parameters such as hypoxia, reactive oxygen species, and toxicity. These nanocapsules will be further validated as imaging-guided photothermal probe

Ciudad Compacta, Espacio Público y Población Flotante en el Eje Ambiental del Centro de Bogotá

El ejercicio de investigación es la suma de cuatro propuestas desde diferentes disciplinas y dimensiones, que intentan dar solución a la baja densidad poblacional del centro de Bogotá y su incidencia en la dispersión urbana