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Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease with a mean survival time of three years. The 97% of the cases have TDP-43 nuclear depletion and cytoplasmic aggregation in motor neurons. TDP-43 prevents non-conserved cryptic exon splicing in certain genes, maintaining transcript stability, including ATG4B, which is crucial for autophagosome maturation and Microtubule-associated proteins 1A/1B light chain 3B (LC3B) homeostasis. In ALS mice (G93A), Atg4b depletion worsens survival rates and autophagy function. For the first time, we observed an elevation of LC3ylation in the CNS of both ALS patients and atg4b−/− mouse spinal cords. Furthermore, LC3ylation modulates the distribution of ATG3 across membrane compartments. Antisense oligonucleotides (ASOs) targeting cryptic exon restore ATG4B mRNA in TARDBP knockdown cells. We further developed multi-target ASOs targeting TDP-43 binding sequences for a broader effect. Importantly, our ASO based in peptide-PMO conjugates show brain distribution post-IV administration, offering a non-invasive ASO-based treatment avenue for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

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The article presents a theoretical generalisation and solution of a current scientific and applied problem which develops theoretical principles, methodological approaches and scientific and practical recommendations for improving the mechanism of labour efficiency management in terms of innovation-oriented development of enterprises. It is substantiated that in the conditions of innovation-oriented development of ecosystems, including enterprises, the disclosure of the essence of labour efficiency requires introduction of a dual quantitative–qualitative approach: on the one hand, labour efficiency reflects the ratio of the manufactured products (tangible and intangible benefits) and corresponding living labour costs (quantitative aspect) and, on the other hand, it is the result of using productive abilities of people, characterised by manufactured products of a particular consumer quality with the creation of added value (qualitative aspect). Conceptual bases of improvement of the mechanism of labour efficiency management at enterprises were developed. They are based on certain tasks, functions, principles, methods of labour efficiency management and the formed system of factors of influence and the revealed factors and reserves of an increase in labour efficiency. They presuppose development and realisation of the corresponding programme, which aims to: optimise total labour costs; improve quality of products at a constant mass and satisfaction with the work process of all its participants; ensure positive changes in material well-being and quality of life on the basis of the formation of modern innovation infrastructure of the enterprise. [ABSTRACT FROM AUTHOR]

This article delves into the escalating frequency of financial crises and their repercussions on national economies, emphasizing the imperative need for both the global community and individual nations to establish mechanisms that can effectively counter financial shocks. The primary line of defence within banking institutions is their own capital. Consequently, the adequacy of a country's own capital plays a pivotal role in determining the robustness of its banking system. The article presents an in-depth analysis of the dynamics of fundamental capital types, including own and borrowed capital, and other economic indicators, with a specific focus on the proportion of own capital within these factors in Portugal, an integral part of the European community. The study employs correlation-regression analysis to explore the interdependencies among capital, liabilities, assets, income, and Gross Domestic Product (GDP). Regression models are developed to investigate the influence on a bank's own capital. The analysis substantiates the hypothesis regarding the interconnections among these key indicators. Based on the findings, recommendations are made for the implementation of a mechanism to ascertain capital sufficiency. The article places significant emphasis on identifying and utilizing instruments that facilitate the achievement of this objective, ultimately contributing to bolstering financial resilience in Portugal and beyond. [ABSTRACT FROM AUTHOR]

The instruments that are constituted by inquiries that intend to investigate the opinions, behaviors and attitudes, instead of putting the person to the test, intend to find out how they would act in a given situation. Although there are no right or wrong answers, there is a tendency to respond in a socially acceptable way, even if the answer does not correspond to reality. This problem can be overcome through the Q-sort methodology that combines quantitative and qualitative data and analytical techniques that are not present in other methods. In this way, it consists of presenting the participants with a set of statements on a given topic and asking them to classify them according to their opinion, according to a predefined distribution, which is generally approximately normal. This methodology forces participants to distribute the score among the items on the scale, thus avoiding the constraints associated with social desirability and the tendency to respond in the same way or always through the midpoint to different questions. Another advantage is that it provides linearity and nearnormality to the scale, which makes it possible to compare subjects more easily. Nevertheless, its advantages, Q-sort methodology also has negative points because forced-choice measures produce ipsative data that lead to distorted scales and problematic psychometric properties. As the data are obtained by ordering a set of items or by forcefully choosing one item over another, it is impossible to achieve very high or very low values on all scales, which gives rise to a large number of negative values that, in turn, result in an average correlation between the scales, which is also negative. In view of the above, it was considered relevant to apply the Q-sort methodology to a personality inventory, whose data were collected from 175 university students attending the Portuguese higher education institution which specializes in the area of economic and business sciences. The Q-sort methodology plays a crucial role in personality inventories by offering a subjective and personalized approach to assessing personality traits. It enables a more thorough and contextual analysis of individual traits, thereby contributing to a deeper and more comprehensive understanding of the human personality. The results of the empirical study showed that despite the mean values being negative or very close to zero, they allowed the grouping of respondents according to their similarities in terms of their personality traits depending on the course they attend. [ABSTRACT FROM AUTHOR]