Schrödinger Equation with Position-Dependent Mass: Staggered Mass Distributions

The Point canonical transformation method is applied for solving the Schrödinger equation with position-dependent mass. This class of problem has been solved for continuous mass distributions. In this work, a staggered mass distribution for the case of a free particle in an infinite square well potential has been proposed. The continuity conditions as well as normalization for the wave function are also considered. The proposal can be used for dealing with other kind of staggered mass distributions in the Schrödinger equation with different quantum potentials

Generation of a porous scaffold with a starting composition in the CaO-SiO2-MgO-P2O5 system in a simulated physiological environment

Magnesium-based ceramics are involved in orthopedic applications such as bone scaffolds or implant coatings. They provide structural support to cells for bone ingrowth, but highly porous matrices cannot resist severe mechanical stress during implantation. In this study, the laser floating zone (LFZ) technique is used to prepare a dense crystalline material with composition in the CaO-SiO2-MgO-P2O5 system. This material, under physiological conditions, is able to generate a porous scaffold controlled by the dissolution of the MgO phase, meeting the mechanical advantages of a dense material and the biological features of a porous scaffold. FESEM (Field emission scanning electron microscopy), XRD (X-ray Diffraction), EDS (Energy Dispersive X-rays spectroscopy), and ICP ((Inductively Coupled Plasma) analysis were carried out in order to characterize the samples before and after immersion in simulated body fluid (SBF)

High-throughput screening methodology to identify alpha-synuclein aggregation inhibitors

An increasing number of neurodegenerative diseases are being found to be associated with the abnormal accumulation of aggregated proteins in the brain. In Parkinson’s disease, this process involves the aggregation of alpha-synuclein (a-syn) into intraneuronal inclusions. Thus, compounds that inhibit a-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of a-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein. However, the in vitro aggregation of a-syn is exceedingly slow and highly irreproducible, therefore precluding fast high throughput anti-aggregation drug screening. Here, we present a simple and easy-to-implement in-plate method for screening large chemical libraries in the search for a-syn aggregation modulators. It allows us to monitor aggregation kinetics with high reproducibility, while being faster and requiring lower protein amounts than conventional aggregation assays. We illustrate how the approach enables the identification of strong aggregation inhibitors in a library of more than 14, 000 compounds

Design, synthesis and structure-activity evaluation of novel 2-pyridone-based inhibitors of a-synuclein aggregation with potentially improved BBB permeability

The treatment of Parkinson''s disease (PD), the second most common neurodegenerative human disorder, continues to be symptomatic. Development of drugs able to stop or at least slowdown PD progression would benefit several million people worldwide. SynuClean-D is a low molecular weight 2-pyridone-based promising drug candidate that inhibits the aggregation of a-synuclein in human cultured cells and prevents degeneration of dopaminergic neurons in a Caenorhabditis elegans model of PD. Improving SynuClean-D pharmacokinetic/pharmacodynamic properties, performing structure/activity studies and testing its efficacy in mammalian models of PD requires the use of gr-amounts of the compound. However, not enough compound is on sale, and no synthetic route has been reported until now, which hampers the molecule progress towards clinical trials. To circumvent those problems, we describe here an efficient and economical route that enables the synthesis of SynuClean-D with good yields as well as the synthesis of SynuClean-D derivatives. Structure-activity comparison of the new compounds with SynuClean-D reveals the functional groups of the molecule that can be disposed of without activity loss and those that are crucial to interfere with a-synuclein aggregation. Several of the derivatives obtained retain the parent''s compound excellent in vitro anti-aggregative activity, without compromising its low toxicity. Computational predictions and preliminary testing indicate that the blood brain barrier (BBB) permeability of SynuClean-D is low. Importantly, several of the newly designed and obtained active derivatives are predicted to display good BBB permeability. The synthetic route developed here will facilitate their synthesis for BBB permeability determination and for efficacy testing in mammalian models of PD. © 2021 The Author

Recycled wastewater as a potential source of microplastics in irrigated soils from an arid-insular territory (Fuerteventura, Spain)

In this work, the occurrence of microplastics (MPs) in irrigation recycled wastewaters (RWWs) and a desalinated brackish water (DBW) from the arid territory of Fuerteventura (Canary Islands, Spain) was studied. Besides, the presence of MPs in two types of soils (sandy-loam and clay-loamy; with no mulch film or fertilization with sewage sludge applied) irrigated with both water qualities was addressed. Results showed the prevalence presence of cellulosic and polyester microfibers (between 84.4 and 100%) of blue and transparent colors (up to 55.6 and 33.3%, respectively), with an average length of 786.9 ± 812.1 μm in the water samples. DBW had the lowest MP concentration (2.0 ± 2.0 items·L−1) while RWW showed concentrations up to 40.0 ± 19.0 items·L−1. Similarities were also observed between the MPs types and sizes found in both soils top layer (0–5 cm), with an average concentration three times greater in soil irrigated with RWW than in soil under DBW irrigation (159 ± 338 vs. 46 ± 92 items·kg−1, respectively). In addition, no MPs were extracted from non-irrigated/non-cultivated soils, suggesting agricultural activities as the unique source of MPs in soils of this arid area. Results show that RWWs constitute a potential source of MPs in irrigated soils that should be considered among other pros and cons linked to the use of this water quality in agricultural arid land

Isotopic evidence for mobility in the Copper and Bronze Age Cemetery of Humanejos (Parla, Madrid): a diachronic approach using biological and archaeological variables

Over the last several decades, the application of aDNA and strontium isotope analyses on archaeologically recovered human remains has provided new avenues for the investigation of mobility in past societies. Data on human mobility can be valuable in the reconstruction of prehistoric residential patterns and kinship systems, which are at the center of human social organization and vary across time and space. In this paper, we aim to contribute to our understanding of mobility, residence, and kinship patterns in late Prehistoric Iberia (c. 3300–1400BC) by providing new strontium data on 44 individuals from the site of Humanejos (Parla, Madrid). The study presented here is multi-proxy and looks at these new data by interweaving biological, chronological, and archaeological information. This analysis found that 7/44 individuals buried at Humanejos could be identified as non-local to the necropolis. Although more men (n = 5) than women (n = 2) were found in the non-local category, and more non-local individuals were identified in the pre-Bell Beaker (n = 5) than in Bell Beaker (n = 1) or Bronze Age (n = 1), we find no statistically significant differences concerning sex or time period. This contrasts with other archaeological datasets for late prehistoric Europe which suggest higher female mobility, female exogamy, and male-centered residential patterns were common. At Humanejos, we have also identified one non-local female whose exceptional Beaker grave goods suggest she was an individual of special status, leading to additional questions about the relationships between gender, mobility, and social position in this region and time periodThe project leading to this publication has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No 891776, project “WOMAM. Women, Men and Mobility: Understanding Gender Inequality in Prehistory.” This article was also supported by the Spanish Ministerio de Ciencia e Innovación Grants No. PID2019-105690 GB-I00 and HAR2013- 47776-R, the Dirección General de Patrimonio Cultural (Comunidad de Madrid) and the SFB 1070 “Ressourcenkulturen” (DFG

Inhibition of a-Synuclein Aggregation and Mature Fibril Disassembling With a Minimalistic Compound, ZPDm

Synucleinopathies are a group of disorders characterized by the accumulation of a-Synuclein amyloid inclusions in the brain. Preventing a-Synuclein aggregation is challenging because of the disordered nature of the protein and the stochastic nature of fibrillogenesis, but, at the same time, it is a promising approach for therapeutic intervention in these pathologies. A high-throughput screening initiative allowed us to discover ZPDm, the smallest active molecule in a library of more than 14.000 compounds. Although the ZPDm structure is highly related to that of the previously described ZPD-2 aggregation inhibitor, we show here that their mechanisms of action are entirely different. ZPDm inhibits the aggregation of wild-type, A30P, and H50Q a-Synuclein variants in vitro and interferes with a-Synuclein seeded aggregation in protein misfolding cyclic amplification assays. However, ZPDm distinctive feature is its strong potency to dismantle preformed a-Synuclein amyloid fibrils. Studies in a Caenorhabditis elegans model of Parkinson’s Disease, prove that these in vitro properties are translated into a significant reduction in the accumulation of a-Synuclein inclusions in ZPDm treated animals. Together with previous data, the present work illustrates how different chemical groups on top of a common molecular scaffold can result in divergent but complementary anti-amyloid activities

Field analysis of solar PV-based collective systems for rural electrification.

This article analyses the long-term performance of collective off-grid photovoltaic (PV) systems in rural areas. The use of collective PV systems for the electrification of small medium-size villages in developing countries has increased in the recent years. They are basically set up as stand-alone installations (diesel hybrid or pure PV) with no connection with other electrical grids. Their particular conditions (isolated) and usual installation places (far from commercial/industrial centers) require an autonomous and reliable technology. Different but related factors affect their performance and the energy supply; some of them are strictly technical but others depend on external issues like the solar energy resource and users’ energy and power consumption. The work presented is based on field operation of twelve collective PV installations supplying the electricity to off-grid villages located in the province of Jujuy, Argentina. Five of them have PV generators as unique power source while other seven include the support of diesel groups. Load demand evolution, energy productivity and fuel consumption are analyzed. Besides, energy generation strategies (PV/diesel) are also discussed

A phylogenetic study of covid-19 data from Aragon and Catalonia over a year: learning bioinformatics during a world pandemic

Presentamos aquí un análisis de variabilidad durante un año del virus SARS-CoV-2 en el área de Aragón, comparándolo con la vecina Cataluña y centrándonos en la variante del Reino Unido. La investigación se realizó dentro de un curso de Bioinformática. Se extrajeron tanto una evaluación detallada sobre el valor de esta metodología como conclusiones novedosas de la investigación