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Kdm1a is a histone demethylase linked to intellectual disability with essential roles during gastrulation and the terminal differentiation of specialized cell types, including neurons, that remains highly expressed in the adult brain. To explore Kdm1a’s function in adult neurons, we develop inducible and forebrain-restricted Kdm1a knockouts. By applying multi-omic transcriptome, epigenome and chromatin conformation data, combined with super-resolution microscopy, we find that Kdm1a elimination causes the neuronal activation of nonneuronal genes that are silenced by the polycomb repressor complex and interspersed with active genes. Functional assays demonstrate that the N-terminus of Kdm1a contains an intrinsically disordered region that is essential to segregate Kdm1a-repressed genes from the neighboring active chromatin environment. Finally, we show that the segregation of Kdm1a-target genes is weakened in neurons during natural aging, underscoring the role of Kdm1a safeguarding neuronal genome organization and gene silencing throughout life.Kdm1a is a histone demethylase implicated in intellectual disability. Here, the authors show that removing Kdm1a in neurons of the adult mouse forebrain disrupts silencing of nonneuronal genes and chromatin organization, emphasizing its role in preserving neuronal genome integrity. [ABSTRACT FROM AUTHOR]

The increasing use of hempseed in food products highlights the need for a comprehensive database for scientific research and industrial applications. In food development, information about the techno-functional properties of raw materials plays a crucial role in determining the suitability of each product for specific applications. Thus, this study aims to characterise three hempseed varieties (Ferimon, Henola and Uso-31), comparing their physicochemical and nutritional compositions. Moreover, the study investigates the impact of hempseed varieties on the techno-functional, physical and thermal properties of the partially defatted hempseed flours (PDHFs) obtained from single screw pressing (SSP) oil extraction. The fatty acid and tocopherol profiles of the dehulled seeds and oil were also analysed. Significant variations in yield and physical properties were observed among hempseed varieties, influenced by genetics, adaptation to agro-climatic conditions and cultivation systems. Despite its lower yield (kg/ha), Uso-31 exhibited superior 1000-seed weight, dehulling yield and larger mean seed size (1.79 ± 0.02 mm). Hempseed oil was rich in unsaturated fatty acids, particularly linoleic (51.2–53.4 g/100 g oil) and α-linolenic (14.88–18.97 g/100 oil) acids, showing variations in γ- and α-tocopherols depending on the variety. The variety also influenced the least gelation concentration (LGC) and techno-functional properties such as water absorption capacity (WAC), emulsifying activity (EA) and emulsion stability (ES). SDS-PAGE and DSC measurements indicated the presence of 11S and 7S globulin proteins with denaturation temperatures above 87.8 °C. These findings confirm that the studied hempseed flours are valuable techno-functional and nutritional ingredients suitable for sustainable food formulations. [ABSTRACT FROM AUTHOR]

Due to the relevance of stockouts in the retail sector together with their significantly negative effect both on retail and the whole supply chain, this paper offers a theoretical review of the stockout definition, rates, its main causes and consequences.

The preservation of The Great Mosque of Córdoba (Spain) as a carrier of Andalusian collective memory requires innovative approaches to assess and maintain its structural health. This research centers on two non-destructive methods: direct ultrasound testing and rebound hammer. Laboratory tests were performed on natural stone provided by the primary material supplier for the Mosque's restoration and rehabilitation works. Non-destructive and destructive tests were carried out over 10 ashlars and 100 cubic and prismatic specimens, which were cut from the ashlars. Tests were conducted in multiple directions to investigate stone anisotropy. Destructive testing indicated isotropy, but ultrasound test results disagreed. Sensitivity analysis of specimen dimensions affected result dispersion, but not average properties. [ABSTRACT FROM AUTHOR]

The Mosque of Cordoba (Spain) is an emblem of the rich cultural heritage of Western Andalusia. This research focuses on the mechanical characterization of the natural stone used in the building. Determining its properties is crucial to understanding the structural behaviour of the entire building. An experimental campaign with various mechanical tests, such as density, compression, indirect tensile, and bending tests, was conducted on more than 100 cubic and prismatic specimens obtained from the main quarry that supplies material for the mosque's restoration. The results indicated the stone's isotropic behaviour for the studied properties. Further analysis established correlations between compressive strength (averaging 6 MPa) and other mechanical properties. This preliminary characterization provides valuable information for future in situ testing and more sophisticated lab techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: The temporomandibular joint (TMJ) of dogs is a bilateral joint mainly used for chewing, and subsequently, an area where pathologies are frequently seen. Computed tomography (CT) represents a very important imaging modality used to diagnose TMJ diseases in dogs. A three-dimensional representation of CT images created by a volume rendering method (3DVR) could improve our understanding of the alterations in this joint. In this study, we assessed 3DVR as an ancillary method for the description and diagnosis of TMJ pathologies in dogs. Based on computed tomography (CT) images, volume rendering was used to obtain a three-dimensional representation of data (3DVR). The aims of this study included: describing the bone anatomy of the temporomandibular joint (TMJ) of dogs; comparing the TMJs of each dog by skull type and age; comparing 3DVR images with three-standard-plane CTs; assessing soft tissues adjacent to the TMJ and assessing pathological cases. Multidetector computed tomography scans of bilateral TMJs of 410 dogs were observed. From a ventral view, slight displacements in the positions of the skulls were seen, whereas from a caudal view, differences in amplitude of the articular space were observed. Dolichocephalic and mesaticephalic dogs showed more similar TMJ features than brachycephalic dogs. The shape of the TMJ bones were irregular in dogs under 1 year old. The 3DVR images related to the three-standard-plane CT improved the overall comprehension of the changes in the articular space amplitude and condylar process morphology. The fovea pterygoidea, mandibular fossa and retroarticular process were perfectly shown. A better spatial situation of adjacent soft tissues was obtained. The 3DVR represents an ancillary method to the standard-plane CT that could help in the understanding of the anatomy and diagnoses of different pathologies of the TMJ in dogs. [ABSTRACT FROM AUTHOR]

The paralogous lysine acetyltransferases 3 (KAT3), CBP and P300, play critical roles during neurodevelopment, but their specific roles in neural precursors maintenance and differentiation remain obscure. In fact, it is still unclear whether these proteins are individually or jointly essential in processes such as proliferation of neural precursors, differentiation to specific neural cell types, or both. Here, we use subventricular zone-derived neurospheres as a potential ex vivo developmental model to analyze the proliferation and differentiation of neural stem cells (NSCs) lacking CBP, p300, or both proteins. The results showed that CBP and p300 are not individually essential for maintenance and proliferation of NSCs, although their combined ablation seriously compromised cell division. In turn, the absence of either of the two proteins compromised the differentiation of NSC into the neuronal and astrocytic lineages. Single-nucleus RNA sequencing analysis of neural cell cultures derived from CBP or p300 mutant neurospheres revealed divergent trajectories of neural differentiation upon CBP or p300 ablation, confirming unique functions and nonredundant roles in neural development. These findings contribute to a better understanding of the shared and individual roles of KAT3 proteins in neural differentiation and the etiology of neurodevelopmental disorders caused by their deficiency. [ABSTRACT FROM AUTHOR]

This work summarises the strategy adopted in the European research project PERSISTAH. It aims to increase the resilience of the population, focusing on the existing primary schools in the Algarve (Portugal) and Huelva (Spain) regions. Software was developed to assess the seismic safety of these schools, considering different earthquake scenarios. Seismic retrofitting measures were studied and numerically tested. Some of them were also implemented in the retrofitting activities of two case study schools (one in each country). It was found that the adopted ground motion prediction equations (GMPEs) considerably affect the results obtained with the software, especially for offshore earthquake scenarios. Furthermore, the results show that the masonry buildings would be the most damaged school typologies for all the scenarios considered. Additionally, a set of guidelines was created to support the school community and the technicians related to the construction industry. The goal of these documents is to increase the seismic resilience of the population. Different activities were carried out to train schoolteachers in seismic safety based on the guidelines produced, obtaining positive feedback from them. [ABSTRACT FROM AUTHOR]

Environmental factors and life experiences impinge on brain circuits triggering adaptive changes. Epigenetic regulators contribute to this neuroadaptation by enhancing or suppressing specific gene programs. The paralogous transcriptional coactivators and lysine acetyltransferases CREB binding protein (CBP) and p300 are involved in brain plasticity and stimulus-dependent transcription, but their specific roles in neuroadaptation are not fully understood. Here we investigated the impact of eliminating either CBP or p300 in excitatory neurons of the adult forebrain of mice from both sexes using inducible and cell type-restricted knock-out strains. The elimination of CBP, but not p300, reduced the expression and chromatin acetylation of plasticity genes, dampened activity-driven transcription, and caused memory deficits. The defects became more prominent in elderly mice and in paradigms that involved enduring changes in transcription, such as kindling and environmental enrichment, in which CBP loss interfered with the establishment of activity-induced transcriptional and epigenetic changes in response to stimulus or experience. These findings further strengthen the link between CBP deficiency in excitatory neurons and etiopathology in the nervous system. [ABSTRACT FROM AUTHOR]

Capacity curves obtained from nonlinear static analyses are widely used to perform seismic assessments of structures as an alternative to dynamic analysis. This paper presents a novel 'en masse' method to assess the seismic vulnerability of urban areas swiftly and with the accuracy of mechanical methods. At the core of this methodology is the calculation of the capacity curves of low-rise reinforced concrete buildings using neural networks, where no modeling of the building is required. The curves are predicted with minimal error, needing only basic geometric and material parameters of the structures to be specified. As a first implementation, a typology of prismatic buildings is defined and a training set of more than 7000 structures generated. The capacity curves are calculated through push-over analysis using SAP2000. The results feature the prediction of 100-point curves in a single run of the network while maintaining a very low mean absolute error. This paper proposes a method that improves current seismic assessment tools by providing a fast and accurate calculation of the vulnerability of large sets of buildings in urban environments. [ABSTRACT FROM AUTHOR]

Background: COVID-19 vaccine hesitancy seems to be universal across countries and subgroups, and so are its determinants. We studied the willingness and factors associated with the decision to be vaccinated against COVID-19 in healthcare workers (HCW) in a Spanish tertiary hospital. Furthermore, we compared the percentage of willingness to vaccinate against COVID with actual vaccination rates among HCW in our hospital. Methods: From December 21, 2020 to January 4, 2021, before initiation of the COVID-19 HCW vaccination campaign at Germans Trias i Pujol University Hospital (HUGTiP), an anonymous self-administered questionnaire was administered to HCW. Univariate and multivariate logistic regression of the association of variables with the outcome "intention to receive the COVID-19 vaccine as soon as possible" was conducted. Vaccination rates were extracted from the hospital information systems. Results: Forty-four percent of HCW included in the study declared a willingness to be vaccinated against COVID-19 as soon as possible. This was associated with male sex [1.66 (95%CI 1.13–2.43); p = 0.009], older age [1.02 (95%CI 1.00–1.03); p = 0.014], belonging to the occupational groups "physician" or "other" [5.76 (95%CI 3.44–9.63) and 2.15 (95%CI 1.25–3.70); p<0.001], respectively, and reporting influenza vaccination during the last three seasons or at least one of the last three seasons [3.84 (95%CI 2.56–5.75) and 2.49 (95%CI 1.71–3.63); p<0.001]. One in ten hospital workers reported they were unwilling to receive COVID-19 vaccination. Actual COVID-19 vaccination uptake among HCW was higher (80.4%) than the percentage of willingness to vaccinate estimated from the questionnaire. Physicians not only had the highest vaccination rate, but also the highest correlation between the reported intention to vaccinate and the final decision to receive COVID-19 vaccination. Conclusions: COVID-19 vaccination uptake was higher than previously estimated according to the stated intentions of HCW. Doubts and fears must be addressed, particularly in persons less inclined to be vaccinated: females, younger people and those not vaccinated against influenza in recent seasons. The study of barriers and strategies aimed at promoting COVID-19 vaccination must be adapted in relation to occupational groups' attitudes, understanding their idiosyncrasies with respect to this and other vaccines. [ABSTRACT FROM AUTHOR]

The article analyzes The Scratchware Manifesto (2000), considering the development of indie games and the transformations in the production and creation of games in neoliberal capitalism. Therefore, we approach the textual genre manifesto as a sociocultural practice of transformation that presents limitations because of its Eurocentric nature, and the debate of The Scratchware Manifesto was held in dialogue with other manifestos, such as the Manifesto of the Communist Party (MARX; ENGELS, 2012) and Rise of the Videogame Zinesters (ANTROPY, 2012), among others. In addition, we point out some processes of creation, production and circulation of indie games, from their alignment or not with the market, as well as the labor precariousness. Finally, we indicate initiatives that are promoting alternative relationships of indie game creation, as well as other relationships with work in the video game industry. [ABSTRACT FROM AUTHOR]

The aim of this paper is to propose a classification of the barriers of continuous improvement and identify the different profiles of companies based on it. First, a literature review was done in order to identify the main barriers; second, some of them were included in a survey based on experts' opinions; third, a survey was conducted among people responsible for implementing continuous improvement; and finally factorial and cluster analysis were applied. Based on the results, two main factors were identified: 'pre-implementation barriers' and 'during implementation barriers'. Additionally, four clusters were analysed 'informal companies', 'disoriented companies', 'unaware companies' and 'slightly-hindered companies'. As many companies still struggle when implementing continuous improvement, the results of this study can help all them to focus on the most important aspects in order to guarantee the sustainability of the continuous improvement system. From a theoretical point of view, this work contributes to the continuous improvement field by analysing the nature of the main barriers companies can find when implementing these initiatives. Thus, not only does this study provide a hierarchy of the most important barriers, but also classifies them. As far as authors are concerned, this is the first attempt to categorise continuous improvement barriers. [ABSTRACT FROM AUTHOR]

Previous research has indicated that many European buildings are vulnerable to moderate-magnitude earthquakes. For example, during the L´Aquila (Italia, Mw 6.3, 2009) and Lorca (Spain, Mw 5.9, 2011) earthquakes, many old buildings were severely damaged and some of them collapsed. In specific, significant damage has been found in several school buildings after past earthquakes in Europe. This is due to the fact that many of them were constructed prior to the current seismic codes, thus considering only gravitational loads and with no seismic design whatsoever. Primary schools are even more vulnerable than other typologies because of their low adult/child ratio. The seismic activity of the Iberian Peninsula is low-moderate. However, the Algarve and Huelva regions, which are situated in the south-west, are influenced by large faults which have caused major earthquakes of long-return periods. The European project PERSISTAH (Projetos de Escolas Resilientes aos SISmos no Território do Algarve e de Huelva, in Portuguese) aims to cooperatively evaluate the seismic vulnerability of primary schools in the Algarve (Portugal) and Huelva (Spain) regions. The present work is framed under this project. The objective of this paper is to determine the most effective retrofitting scheme for a typical primary school building in this area, considering structural, architectural and constructive parameters. The scheme could be applied to several buildings of the same typology, decreasing costs and time. An existing reinforced concrete frame building has been selected for the study. This is one of the most commonly used typologies for primary schools in this area. A nonlinear static analysis has been carried out in order to study its seismic behaviour. The performance point of the building has been obtained through the capacity-demand spectrum method. The preliminary results have confirmed the poor seismic behaviour of this building. Specifically, soft-story behaviour has been identified in the ground floor and short columns have been observed in the upper floors. Therefore, specific seismic retrofitting solutions have been proposed and evaluated in order to identify the one that is the most efficient. The combination of reinforcements has been done considering the structural and architectural impact and constructive parameters. The calculations have shown that steel X-bracings are the best solution for preventing the formation of a soft-storey in the ground floor. Unfortunately, this scheme increases the deformation in the upper floor columns. The best solution for the upper floors' short columns has been the use of steel jackets. The results have also shown that this combination produces an important reduction of the expected general damage level. The resulting retrofitting scheme can be extrapolated to other buildings with a similar typology. [ABSTRACT FROM AUTHOR]

The multiplicity of functions, substrates, and molecular partners of the two KAT3 proteins defines a complex cat's cradle of relationships. • CBP and p300 (KAT3s) interact with dozens of TFs and acetylate hundreds of substrates. • KAT3s have both unique and overlapping functions during neural development. • The relative importance of KAT3s decreases along the neuronal differentiation process. • Scaffolding and KAT functions are both part of the same mechanism of transactivation. • Novel tools can address outstanding questions regarding the neuronal role of KAT3s. The paralogous transcriptional co-activators CBP and p300 (aka KAT3A and KAT3B, respectively) contain a characteristic and promiscuous lysine acetyltransferase (KAT) domain and multiple independent protein-binding domains that enable them to interact with hundreds of proteins, possibly promoting the acetylation of thousands of target lysine residues. Both proteins play critical roles during the development of the nervous system and may also regulate stimuli-driven transcription and plasticity in postmitotic neurons. The multiplicity of functions, substrates, and molecular partners, together with the redundancy and singularity of the two KAT3 paralogs, define a complex cat's cradle of relationships. In this review, we discuss the role of the KAT3 proteins in neurons and integrate recent information regarding their function and mode of action. [ABSTRACT FROM AUTHOR]