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PGC-1α plays a central role in maintaining mitochondrial and energy metabolism homeostasis, linking external stimuli to transcriptional co-activation of genes involved in adaptive and age-related pathways. The carboxyl-terminus encodes a serine/arginine-rich (RS) region and an RNA recognition motif, however the RNA-processing function(s) were poorly investigated over the past 20 years. Here, we show that the RS domain of human PGC-1α directly interacts with RNA and the nuclear RNA export receptor NXF1. Inducible depletion of PGC-1α and expression of RNAi-resistant RS-deleted PGC-1α further demonstrate that its RNA/NXF1-binding activity is required for the nuclear export of some canonical mitochondrial-related mRNAs and mitochondrial homeostasis. Genome-wide investigations reveal that the nuclear export function is not strictly linked to promoter-binding, identifying in turn novel regulatory targets of PGC-1α in non-homologous end-joining and nucleocytoplasmic transport. These findings provide new directions to further elucidate the roles of PGC-1α in gene expression, metabolic disorders, aging and neurodegeneration. PGC-1α is a master regulator activating the transcription of key genes controlling the cell’s energy production. Here the authors show that PGC-1α has a function in the NXF1-dependent nuclear export of mRNAs.

From the investigations performed, this study showed that technical equipment surveillance is a weakness displayed by the majority of the industrial companies in Romania. An efficient management of fleet equipment in production quality assurance approach is involving technical fleet equipment tracking, requiring a high reliability of each device and obtaining of maximum equipment efficiency. History of preventive interventions made and accidental failure history are essential elements in managing industrial equipment. These could be defined periodically and content of preventive actions of maintenance can be made.

In the conditions of the current crisis, there is an increase in the importance of ensuring the management of material resources. A strategy to ensure the necessary material resources on the suppliers' market is mandatory as a result of the growing role that this function holds in the present economic conditions and of its integration into the strategic activity of organizations. A strategic and proactive function of ensuring material resources can offer your organization a competitive advantage by reducing costs in the value chain. Nevertheless, resource-ensuring strategies cannot be developed in isolation, as they must be integrated into the overall strategy of the company so as to fit harmoniously in order to be able to achieve their goals and to contribute to the success of the whole system of the organization. [PUBLICATION ABSTRACT]

In this article the authors aim to address key issues regarding pricing decision substantiation in a crisis context and to create an overview of the elements that should underlie such substantiation. We can say that making price decisions is both a science and an art, based on precise calculations and sound economic reasoning. But, especially in a crisis context, such reasoning and calculations should not exclude intuition, flair, hunches, and experience and so on, all instruments belonging to the art of management. A solid reasoning assumes that those involved ask the right questions and understand all the factors that determine the success of some price decisions and failure of others. [PUBLICATION ABSTRACT]

This article aims to analyze how the performance management of the process of procurement and management of material resources contributes to its continuous improvement and to achieve the long-lasting success of the organization. In this sense, through a quality management approach, the authors will examine the monitoring, measurement and analysis methods used in evaluating the performances of the process of procurement and management of material resources, to measure its efficiency and effectiveness in relation to the strategy and objectives of the organization.

We propose the addition of usability validation to the extended V3 framework, now “V3+”, and describe a pragmatic approach to ensuring that sensor-based digital health technologies can be used optimally at scale by diverse users. Alongside the original V3 components (verification; analytical validation; clinical validation), usability validation will ensure user-centricity of digital measurement tools, paving the way for more inclusive, reliable, and trustworthy digital measures within clinical research and clinical care.

The price plays a decisive role in achieving the company's objectives, no matter what they are and, generally speaking, in ensuring the success of the company's overall strategy, its proper level relative to the product's quality being the crucial aspect, considering that the situations in which wrong price decisions compromised the overall company strategy were not rare. The substantiation of the price decisions is a science and an art in the same time, being based on precise calculations and sound reasoning, which doesn't exclude elements based on intuition, flair, presentiments, experience, elements that relate to the management seen as art. A sound reasoning implies the right types of questions from the persons involved, and an understanding of the overall factors that determine the success of some price decisions and the failure of others.

Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA to activate gene expression. The role of neurogenic pioneer factor ASCL1 in shaping chromatin landscape in human neurogenesis remains unclear. Here we show that ASCL1 acts as a pioneer transcription factor in a transient population of progenitors. Using an in vitro ASCL1 knockout model we show it drives progenitor differentiation by cis-regulation both as a classical pioneer factor and as a non-pioneer remodeler, where ASCL1 binds permissive chromatin to induce chromatin conformation changes. We find ASCL1 directly interacts with mammalian BAF SWI/SNF chromatin remodeling complexes, essential for neurogenesis and involved in multiple neurodevelopmental disorders. ASCL1 acts as a non-pioneer chromatin remodeler to regulate gene expression at a subset of loci, requiring mBAF SWI/SNF's ATPase activity for cis-regulation of gene expression. Our findings demonstrate that ASCL1 is a key chromatin remodeler in human neurogenesis, uncovering an alternative mechanism of remodeling function dependent on partner ATPase activity. Competing Interest Statement The authors have declared no competing interest.

In this article, we identify opportunities for improvement of the process of procurement and management of material resources based on results of analysis of information from monitoring, measurement and testing, to contribute to the lasting success of the organization. Improvement of the process of procurement and management of material resources must be carried out in a structured manner, following the \"Plan-Do-Check-Act\" methodology (PDCA). Analysis of the opportunities for improvement of the process of procurement and management of material resources will be done through an approach based on the integrated quality management system.

A specialised set of transcription factors called pioneer factors are able to bind their targets in previously inaccessible chromatin and upon binding create accessible regions of DNA. Their activity allows non-pioneer transcription factors to also bind their targets, regulate downstream gene expression and establish gene regulatory networks during development. In the developing mammalian cortex, one of the most illustrative examples of a stable yet versatile system, proneural transcription factors of the bHLH family represent key determinants of neural cell fate and differentiation. Among the proneural proteins, ASCL1 has been proposed to act as a pioneer transcription factor by programming the epigenome and establishing new transcriptional networks during development and cellular reprogramming in both mouse and human models. The mSWI/SNF ATP-dependent chromatin remodelling complexes play critical roles in controlling chromatin dynamics, therefore facilitating rapid transcriptional events. Proper functioning of the mSWI/SNF complexes is essential for the establishment, maintenance and functionality of neural cells during development. The overlapping activity of ASCL1 and mSWI/SNF remodellers during neurogenesis led us to investigate the hypothesis of a mutual interaction between them. Using an in vitro model of human cortical neuronal differentiation from iPSCs, I have established that ASCL1 interacts physically with multiple subunits of the mSWI/SNF complexes. To further characterise this interaction, I investigated whether ASCL1 requires the mSWI/SNF remodellers to regulate its targets. By comparing the DNA binding landscapes of ASCL1 and mSWI/SNF core subunit SMARCB1, I found that approximately 70% of ASCL1 binding sites are also genomic targets of SMARCB1. This finding suggests that ASCL1 may functionally interact with mSWI/SNF complexes in order to regulate a large subset of its targets. I then performed reciprocal disruption of ASCL1 and mSWI/SNF assemblies at different time points during corticogenesis to investigate the mutual requirement of ASCL1 for mSWI/SNF recruitment. Correlation of DNA binding and chromatin accessibility in ASCL1 knockout, mSWI/SNF-lacking and wild-type neuronal cells re- vealed that approximately one third of ASCL1 direct targets are also direct targets of the mSWI/SNF remodellers. In addition, 55% of the ASCL1-dependent genes are also misregulated upon mSWI/SNF removal. Association of ASCL1-mSWI/SNF direct genomic targets with the transcriptional changes observed in the two mutants led to the identification of 61 ASCL1-mSWI/SNF-dependent genes with essential roles during cortical neuronal differentiation whose regulation is linked to the sites where ASCL1 and SMARCB1 bind to regulate chromatin accessibility. However, more than 80% of the ASCL1-mSWI/SNF direct targets represent distal genomic sites with enhancer-specific histone modification signatures. As a consequence, looking at the nearest annotated promoter to associate these genomic regions with their transcriptional output might only explain a subset of the ASCL1-dependent genes. More extensive bioinformatics approaches that take into consideration the 3D organisation of the genome are likely to link these distal regulatory regions with a larger proportion of the ASCL1-mSWI/SNF-dependent genes. Overall, this work advances our understanding of the mechanisms behind ASCL1 pioneer activity. The essential roles of both ASCL1 and mSWI/SNF remodellers during cortical development point towards their interaction having vast implications for human health and disease.