Models to study basic and applied aspects of lysosomal storage disorders

© 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).The lack of available treatments and fatal outcome in most lysosomal storage disorders (LSDs) have spurred research on pathological mechanisms and novel therapies in recent years. In this effort, experimental methodology in cellular and animal models have been developed, with aims to address major challenges in many LSDs such as patient-to-patient variability and brain condition. These techniques and models have advanced knowledge not only of LSDs but also for other lysosomal disorders and have provided fundamental insights into the biological roles of lysosomes. They can also serve to assess the efficacy of classical therapies and modern drug delivery systems. Here, we summarize the techniques and models used in LSD research, which include both established and recently developed in vitro methods, with general utility or specifically addressing lysosomal features. We also review animal models of LSDs together with cutting-edge technology that may reduce the need for animals in the study of these devastating diseases.This work was supported by the Spanish Ministry of Science and Innovation (PID2020-112830RB-I00) (AEI/FEDER, UE) and the NextGeneration EU-CSIC funds (NeuroAging)info:eu-repo/semantics/publishedVersio

Contributos para o desenvolvimento da literacia: a aprendizagem da leitura e da escrita ao longo do 1º ciclo do ensino básico

Este projecto tem por objectivo principal estudar as relações entre a implementação de um programa de promoção de competências de leitura e a aquisição da leitura e da escrita ao longo do primeiro ciclo. O programa foi desenvolvido no ano lectivo 2000/01 junto de um grupo de crianças com 5 anos de idade, envolvendo jardins de infância e famílias. As crianças foram avaliadas no final do ensino pré-escolar e durante o 1º ano de escolaridade. As análises então efectuadas enfatizaram a relação entre a participação da família no programa e o desenvolvimento de competências linguísticas, de descodificação da leitura e codificação da escrita. Durante o ano 2003/04 foram avaliadas cerca de 60 crianças frequentando o 3º ano de escolaridade. Este grupo de crianças incluía aquelas crianças que tinham frequentado o programa atrás citado. Privilegiou-se, nesta fase, a análise dos processos envolvidos na compreensão de textos lidos. Esta comunicação pretende descrever o trabalho efectuado ao longo deste ano lectivo enfatizando os resultados sobre as possíveis relações entre os processos agora avaliados e a participação no programa implementado no final do ensino pré-escolar

Intervenciones para depresión en jóvenes: de la reducción de síntomas al bienestar y funcionamiento óptimo

Depression is a major public health problem in children and adolescents, which makes the identification and implementation of effective interventions an increasing concern. Therefore, the main aim of this article is to discuss theoretically different psychological interventions for depression. In particular, those focused on psychopathology and depressive symptom reduction and the new interventions based on the positive psychology approach, which focus on optimal functioning and wellbeing. Empirically supported interventions for children and adolescents, such as cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT), have focus on symptom reduction, which represents an incomplete vision of youth functioning. In contrast, interventions based on positive psychology promote a more balanced approach that takes into consideration the negative and positive aspects of experience and aims to enhance well-being. We present and discuss new interventions, such as the Optimal Functioning Therapy for Adolescents, which suggest that the focus of interventions for depressed adolescents should integrate symptom reduction and well-being enhancement to achieve optimal functioning. Helping young people be happier and more engaged in their lives is part of a new perspective for clinical psychology practice.La depresión es un problema de salud pública importante en niños y adolescentes, lo que hace que identificar e implementar intervenciones efectivas para su tratamiento sea de creciente interés. Por lo tanto, el objetivo principal de este artículo es discutir teóricamente diferentes intervenciones psicológicas para la depresión. En particular, las que se abordan la psicopatología, la reducción de los síntomas depresivos y las nuevas intervenciones basadas en el enfoque de la psicología positiva, que se centran en el funcionamiento óptimo y el bienestar de la persona. Intervenciones con respaldo empírico para los niños y adolescentes, como la terapia cognitivo-conductual (TCC) y la terapia interpersonal (IPT), tienen un enfoque de reducción de síntomas, lo que representa una visión incompleta de funcionamiento en la juventud. En contraste, las intervenciones basadas en la psicología positiva promueven una aproximación más equilibrada que contempla los aspectos negativos y positivos de la experiencia y tiene como objetivo mejorar el bienestar. En el artículo, se presentan y discuten intervenciones nuevas, como la Terapia del Funcionamiento Óptimo Terapia para Adolescentes, que sugieren que el enfoque de las intervenciones para los adolescentes con depresión debería integrar la reducción de síntomas y la mejora de su bienestar para lograr un funcionamiento óptimo. Ayudar a que los jóvenes sean más felices y más comprometidos en sus vidas es parte de una nueva perspectiva para la práctica de la psicología clínica.info:eu-repo/semantics/publishedVersio

Mutational analysis of MSX1 and PAX9 genes in Portuguese families with maxillary lateral incisor agenesis

The observation that certain patterns of tooth agenesis occur more frequently in individuals of the same family may suggest the existence of predisposing genetic factors. The aim of this study was to search for mutations in the PAX9 and MSX1 genes and to investigate their potential association with the maxillary lateral incisor agenesis (MLIA) phenotype in 12 Portuguese families, a total of 52 individuals, 12 probands and 40 relatives (eight of which had MLIA). Twenty-three of the subjects were male and 29 female with an age range of 10-75 years. The control group comprised random DNA samples of 91 Portuguese individuals. Nucleotide alterations were not detected in the coding regions of the MSX1 gene, analysed by single-strand conformation polymorphism and sequencing; in the PAX9 gene, a polymorphism was found that led to transition of G718 to C, implying a change of alanine 240 for proline. However, the differences in the frequencies of the PAX9 gene polymorphism between the probands (67 per cent) and the control population (56 per cent carrying the c allele) were not statistically significant as determined by chi-square test, and the polymorphism did not clearly segregate with the trait in the families. Aggregating the available data, there does not seem to exist a clear association between the alanine 240 for proline variant in the PAX9 gene and the MLIA phenotype. Further studies are required to clarify the basic genetics of MLIA.The authors would like to thank the families who participated in this study. We are grateful to Pedro Seada for technical support. TP was the recipient of a scholarship from Instituto Superior de Ciencias da Saude Norte/CESPU for her PhD and AS-F is the recipient of a scholarship from FCT (SFRH/BD/15910/2005)

Implementing autonomous maintenance in an automotive components manufacturer

The automotive sector constitutes one of the most demanding activities in the global market, since it requires a constant increase in productivity, both in the automobile industry as well as in the companies whose manufacture its components. This sector is currently set within an economic framework where there is a relentless search for costs reduction and an increase in productivity with minimal investment. In order to meet these requirements, companies have sought to optimise their products and processes to ensure higher profits. This study was developed with the purpose of enhancing procedures in the maintenance sector regarding a company which supplies air-conditioning tubes to the automotive sector. The main objective was to increase its machines and equipment availability through the implementation of autonomous maintenance. Due to the undertaken improvements, there was a 10% increase in the monthly indicator of equipment availability on line AA3 at the company where the study was carried out. This, in turn, resulted in an increase of 8% in OEE (Overall Equipment Effectiveness) during the same time period, which was chiefly due to a reduction both in machine breakdown rates, as well as in the MTTR (Mean Time To Repair) on the same line.info:eu-repo/semantics/publishedVersio

Standardization and optimization of an automotive components production line

Supported by the concepts and definitions of Standard Work methodology, which underpins Lean Thinking philosophy and Kaizen, the study described in this article was developed at a company in the automotive sector, more specifically directed at a production line manufacturing components for air-conditioning systems. The main objectives were to standardize operations, decrease or eliminate the number of activities those are not generating added-value, enhance productivity and associate continuous improvement actions to the processes at hand in order to eliminate waste. After the implementation of a few simple changes - the standardization of operations, adjustments and allocations of workstations – one was able to tailor the production objectives and cycle times to the line’s capacity. The productivity and efficiency of both machines and workers was also increased. Due to the elimination of waste and generation of value, from the customer’s perspective, one was able to raise the OEE (Overall Equipment Effectiveness) general average by 16%, from 70% to 86%.info:eu-repo/semantics/publishedVersio

Improving the coastal record of tsunamis in the ESI-07 Scale : Tsunami Environmental Effects Scale (TEE-16 Scale)

This paper discusses possibilities to improve the Environmental Seismic Intensity Scale (ESI-07 scale), a scale based on the effects of earthquakes in the environment. This scale comprises twelve intensity degrees and considers primary and secondary effects, one of them the occurrence of tsunamis. Terminology and physical tsunami parameters corresponding to different intensity levels are often misleading and confusing. The present work proposes: i) a revised and updated catalogue of environmental and geological effects of tsunamis, gathering all the available information on Tsunami Environmental Effects (TEEs) produced by recent earthquake-tsunamis; ii) a specific intensity scale (TEE-16) for the effects of tsunamis in the natural environment at coastal areas. The proposed scale could be used in future tsunami events and, in historic and paleo-tsunami studies. The new TEE-16 scale incorporates the size specific parameters already considered in the ESI-07 scale, such as wave height, run-up and inland extension of inundation, and a comprehensive and more accurate terminology that covers all the different intensity levels identifiable in the geological record (intensities VI-XII). The TEE-16 scale integrates the description and quantification of the potential sedimentary and erosional features (beach scours, transported boulders and classical tsunamites) derived from different tsunami events at diverse coastal environments (e.g. beaches, estuaries, rocky cliffs,). This new approach represents an innovative advance in relation to the tsunami descriptions provided by the ESI-07 scale, and allows the full application of the proposed scale in paleoseismological studies. The analysis of the revised and updated tsunami environmental damage suggests that local intensities recorded in coastal areas do not correlate well with the TEE-16 intensity (normally higher), but shows a good correlation with the earthquake magnitude (Mw). Tsunamis generated by earthquakes can then be considered efficient processes in the direct transference of the "energy" released by offshore seismogenic sources to the nearest coastal areas, even over distances of hundreds of kilometres (>200km). This scale, as the previous ones, is independent of the earthquake type (i.e. style of faulting) and only focuses on the environmental effects triggered by tsunamis of seismic origin

Molybdenite as a rhenium carrier : first results of a spectroscopic approach using synchrotron radiation

The chemical and physical properties of rhenium render it a highly demanded metal for advanced applications in important industrial fields. This very scarce element occurs mainly in ores of porphyry copper-molybdenum deposits associated with the mineral molybdenite, MoS2, but it has also been found in granite pegmatites and quartz veins as well as in volcanic gases. Molybdenite is a typical polytype mineral which crystal structure is based on the stacking of [S-Mo-S] with molybdenum in prismatic coordination by sulphide anions; however, it is not yet clearly established if rhenium ions replace Mo4+ cations in a disordered way or else, if such replacement gives rise to dispersed nanodomains of a rhenium-rich phase. As a contribution to clarify this question, an X-ray absorption spectroscopy (XANES) study using synchrotron radiation was performed at the Re L3-edge of rhenium-containing molybdenite samples. Obtained results are described and discussed supporting the generally accepted structural perspective that rhenium is mainly carried by molybdenite through the isomorphous replacement of Mo, rather than by the formation of dispersed Re-specific nanophase(s)