Search

The aim of the present study was to identify different executive functioning profiles within 2, 6, and 10 scholar grades using a three-step Latent Profile Analysis. In Step 1, unconditional LPA models are estimated, and the selected model is used in the next step. In Step 2, the most likely profile memberships are estimated from the posterior probabilities of the LPA. Furthermore, the profile-classification uncertainties (i.e., measurement error) in the latent profile membership are calculated and used in the next step. In Step 3, the relationships of the most likely latent profile membership with covariates or/and distal outcomes are estimated, considering the measurement error in the estimation of the latent profile membership. In this study, we aimed to examine the prediction of covariates (sex, age, intelligence, and processing speed) on the retained profile solutions in each group. Then, we tested the prediction of intelligence and processing speed on measures of math achievement and reading comprehension) within each retained profile

Proteins are exposed to fluctuating environmental conditions in their cellular context and during their biotechnological production. Disordered regions are susceptible to these fluctuations and may experience solvent-dependent conformational switches that affect their local dynamism and activity. In a recent study, we modeled the influence of pH in the conformational state of IDPs by exploiting a charge–hydrophobicity diagram that considered the effect of solution pH on both variables. However, it was not possible to predict context-dependent transitions for multiple sequences, precluding proteome-wide analysis or the screening of collections of mutants. In this article, we present DispHScan, the first computational tool dedicated to predicting pH-induced disorder–order transitions in large protein datasets. The DispHScan web server allows the users to run pH-dependent disorder predictions of multiple sequences and identify context-dependent conformational transitions. It might provide new insights on the role of pH-modulated conditional disorder in the physiology and pathology of different organisms. The DispHScan web server is freely available for academic users, it is platform-independent and does not require previous registration.

Proteins bearing prion-like domains (PrLDs) are essential players in stress granules (SG) assembly. Analysis of data on heat stress-induced recruitment of yeast PrLDs to SG suggests that this propensity might be connected with three defined protein biophysical features: aggregation propensity, net charge, and the presence of free cysteines. These three properties can be read directly in the PrLDs sequences, and their combination allows to predict protein recruitment to SG under heat stress. On this basis, we implemented SGnn, an online predictor of SG recruitment that exploits a feed-forward neural network for high accuracy classification of the assembly behavior of PrLDs. The simplicity and precision of our strategy should allow its implementation to identify heat stress-induced SG-forming proteins in complete proteomes.

Prions are self‐perpetuating proteins able to switch between a soluble state and an aggregated‐and‐transmissible conformation. These proteinaceous entities have been widely studied in yeast, where they are involved in hereditable phenotypic adaptations. The notion that such proteins could play functional roles and be positively selected by evolution has triggered the development of computational tools to identify prion‐like proteins in different kingdoms of life. These algorithms have succeeded in screening multiple proteomes, allowing the identification of prion‐like proteins in a diversity of unrelated organisms, evidencing that the prion phenomenon is well conserved among species. Interestingly enough, prion‐like proteins are not only connected with the formation of functional membraneless protein–nucleic acid coacervates, but are also linked to human diseases. This review addresses state‐of‐the‐art computational approaches to identify prion‐like proteins, describes proteome‐wide analysis efforts, discusses these unique proteins' functional role, and illustrates recently validated examples in different domains of life., Prions are proteins able to populate two conformational states, one of which is transmissible. The discovery of functional prions in yeast triggered the development of distinct computational approaches to discover prion‐like proteins in other organisms. This review delves into the rationale behind these algorithms and discusses the new insights gathered from proteome‐wide data analysis in different kingdoms of life.

Graphical abstract, The amyloid conformation is considered a fundamental state of proteins and the propensity to populate it a generic property of polypeptides. Multiple proteome-wide analyses addressed the presence of amyloidogenic regions in proteins, nurturing our understanding of their nature and biological implications. However, these analyses focused on highly aggregation-prone and hydrophobic stretches that are only marginally found in intrinsically disordered regions (IDRs). Here, we explore the prevalence of cryptic amyloidogenic regions (CARs) of polar nature in IDRs. CARs are widespread in IDRs and associated with IDPs function, with particular involvement in protein–protein interactions, but their presence is also connected to a risk of malfunction. By exploring this function/malfunction dichotomy, we speculate that ancestral CARs might have evolved into functional interacting regions playing a significant role in protein evolution at the origins of life.

The rapid evolution of resistance in the malaria parasite to every single drug developed against it calls for the urgent identification of new molecular targets. Using a stain specific for the detection of intracellular amyloid deposits in live cells we have detected the presence of abundant protein aggregates in Plasmodium falciparum blood stages and female gametes cultured in vitro, in the blood stages of mice infected by Plasmodium yoelii, and in the mosquito stages of the murine malaria species Plasmodium berghei. Aggregated proteins could not be detected in early rings, the parasite form that starts the intraerythrocytic cycle. A proteomics approach was followed to pinpoint actual aggregating polypeptides in functional P. falciparum blood stages, which resulted in the identification of 369 proteins, with roles particularly enriched in nuclear import-related processes. Five aggregation-prone short peptides selected from this protein pool exhibited different aggregation propensity according to Thioflavin-T fluorescence measurements, and were observed to form amorphous aggregates and amyloid fibrils in transmission electron microscope images. The results presented suggest that generalized protein aggregation might have a functional role in malaria parasites. Future antimalarial strategies based on the upsetting of the pathogen’s proteostasis and therefore affecting multiple gene products could represent the entry to new therapeutic approaches.

An increasing number of human proteins are being found to bear a prion-like domain (PrLD) driving the formation of membraneless compartments through liquid-liquid phase separation. Point mutations in these PrLDs promote the transition to an amyloid-like state. There has been much debate on whether this aberrant aggregation is caused by compositional or sequential changes. A recent extensive mutational study of the ALS-associated prion-like hnRNPA2 protein provides a framework to discriminate the molecular determinants behind pathogenic PrLDs aggregation. The effect of mutations on the aggregation propensity of hnRNPA2 is best predicted by combining their impact on PrLD amino acid composition and sequence-based amyloid propensity. This opens an avenue for the prediction of disease causing mutations in other human prion-like proteins. This article is protected by copyright. All rights reserved.

O objetivo deste estudo é verificar a percepção dos professores sobre o impacto do uso da tecnologia da informação e comunicação (TIC) na aprendizagem dos alunos do Ensino Fundamental. Esta é uma pesquisa qualitativa descritiva feita por meio de estudo de caso único em uma escola de Ensino Fundamental de São Caetano do Sul (SP), tendo sido aplicado questionário semi-estruturado junto a doze professores. Os principais resultados evidenciaram que as ferramentas de TIC introduzidas possibilitaram a consulta, pesquisa e produção de informações, viabilização de comunicação e intercâmbio dessas informações entre os participantes (gestão escolar, professores e alunos), além de permitir o desenvolvimento das disciplinas e projetos. Paradoxalmente, embora a utilização de ferramentas de TIC seja grande, a maior parte dos professores (91,7%) pesquisados não possui formação especializada, o que causa, na opinião dos respondentes, a subutilização das ferramentas.

Summary Polypeptides are exposed to changing environmental conditions that modulate their intrinsic aggregation propensities. Intrinsically disordered proteins (IDPs) constitutively expose their aggregation determinants to the solvent, thus being especially sensitive to its fluctuations. However, solvent conditions are often disregarded in computational aggregation predictors. We recently developed a phenomenological model to predict IDPs' solubility as a function of the solution pH, which is based on the assumption that both protein lipophilicity and charge depend on this parameter. The model anticipated solubility changes in different IDPs accurately. In this application note, we present SolupHred, a web-based interface that implements the aforementioned theoretical framework into a predictive tool able to compute IDPs aggregation propensities as a function of pH. SolupHred is the first dedicated software for the prediction of pH-dependent protein aggregation. Availability and implementation The SolupHred web server is freely available for academic users at: https://ppmclab.pythonanywhere.com/SolupHred. It is platform-independent and does not require previous registration. Supplementary information Supplementary data are available at Bioinformatics online.

Non-native intermolecular contacts often lead to aberrant protein oligomerization and aggregation. This phenomenon is behind the onset of several human disorders and is a bottleneck for the production of proteins of biotechnological interest. Intrinsically disordered proteins have evolved to avoid aberrant oligomerization, but mutations or aging-promoted degeneration of the protein quality machinery might result in their aggregation. Folded globular proteins are not completely protected from aggregation, mostly because the physicochemical properties stabilizing their tertiary and/or quaternary structures are very similar to those leading to non-native oligomerization. Once these properties are known, it becomes feasible to predict the aggregation propensities of proteins and to design them to disfavor aggregation-prone contacts. In this chapter, we describe how computational approaches can assist the identification of the aggregation-prone sequential or structural regions leading to aberrant oligomerization and how these tools can be employed to predict pathogenic mutations or to design biotherapeutics with optimized solubility.

Protein aggregation is associated with an increasing number of human disorders and premature aging. Moreover, it is a central concern in the manufacturing of recombinant proteins for biotechnological and therapeutic applications. Nevertheless, the unique architecture of protein aggregates is also exploited by nature for functional purposes, from bacteria to humans. The relevance of this process in health and disease has boosted the interest in understanding and controlling aggregation, with the concomitant development of a myriad of algorithms aimed to predict aggregation propensities. However, most of these programs are blind to the protein environment and, in particular, to the influence of the pH. Here, we developed an empirical equation to model the pH-dependent aggregation of intrinsically disordered proteins (IDPs) based on the assumption that both the global protein charge and lipophilicity depend on the solution pH. Upon its parametrization with a model IDP, this simple phenomenological approach showed unprecedented accuracy in predicting the dependence of the aggregation of both pathogenic and functional amyloidogenic IDPs on the pH. The algorithm might be useful for diverse applications, from large-scale analysis of IDPs aggregation properties to the design of novel reversible nanofibrillar materials.

Protein aggregation is a hallmark of a growing number of human disorders and constitutes a major bottleneck in the manufacturing of therapeutic proteins. Therefore, there is a strong need of in-silico methods that can anticipate the aggregative properties of protein variants linked to disease and assist the engineering of soluble protein-based drugs. A few years ago, we developed a method for structure-based prediction of aggregation properties that takes into account the dynamic fluctuations of proteins. The method has been made available as the Aggrescan3D (A3D) web server and applied in numerous studies of protein structure-aggregation relationship. Here, we present a major update of the A3D web server to version 2.0. The new features include: extension of dynamic calculations to significantly larger and multimeric proteins, simultaneous prediction of changes in protein solubility and stability upon mutation, rapid screening for functional protein variants with improved solubility, a REST-ful service to incorporate A3D calculations in automatic pipelines, and a new, enhanced web server interface. A3D 2.0 is freely available at: http://biocomp.chem.uw.edu.pl/A3D2/

Proteins with prion-like behavior are attracting an increasing interest, since accumulating evidences indicate that they play relevant roles both in health and disease. The self-assembly of these proteins into insoluble aggregates is associated with severe neuropathological processes such as amyotrophic lateral sclerosis (ALS). However, in normal conditions, they are known to accomplish a wide range of functional roles. The conformational duality of prion-like proteins is often encoded in specific protein regions, named prion-like domains (PrLDs). PrLDs are usually long and disordered regions of low complexity. We have shown that PrLDs might contain soft-amyloid cores that contribute significantly to trigger their aggregation, as well as to support their propagation. Further exploration of the role of these sequences in the conformational conversion of prion-like proteins might provide novel insights into the mechanism of action and regulation of these polypeptides, enabling the future development of therapeutic strategies. Here, we describe a set of methodologies aimed to identify and characterize these short amyloid stretches in a protein or proteome of interest, ranging from in silico detection to in vitro and in vivo evaluation and validation.

The aggregation of proteins compromises cell fitness, either because it titrates functional proteins into non-productive inclusions or because it results in the formation of toxic assemblies. Accordingly, computational proteome-wide analyses suggest that prevention of aggregation upon misfolding plays a key role in sequence evolution. Most proteins spend their lifetimes in a folded state, therefore, it is conceivable that, in addition to sequences, protein structures would have also evolved to minimize the risk of aggregation in their natural environments. By exploiting the AGGRESCAN3D structure-based approach to predict the aggregation propensity of &gt, 600 Escherichia coli proteins, we show that the structural aggregation propensity of globular proteins is connected with their abundance, length, essentiality, subcellular location and quaternary structure. These data suggest that the avoidance of protein aggregation has contributed to shape the structural properties of proteins in bacterial cells.

Background Around 1% of human proteins are predicted to contain a disordered and low complexity prion-like domain (PrLD). Mutations in PrLDs have been shown promote a transition towards an aggregation-prone state in several diseases. Results Recently, we have shown that an algorithm that considers the effects of mutations on PrLDs composition, as well as on localized amyloid propensity can predict the impact of these amino acid changes on protein intracellular aggregation. In this application note, we implement this concept into the AMYCO web server, a refined algorithm that forecasts the influence of amino acid changes in prion-like proteins aggregation propensity better than state-of-the-art predictors. Conclusions The AMYCO web server allows for a fast and automated evaluation of the effect of mutations on the aggregation properties of prion-like proteins. This might uncover novel disease-linked amino acid changes in the sequences of human prion-like proteins. Additionally, it can find application in the in silico design of synthetic prion-like proteins with tuned aggregation propensities for different purposes. AMYCO does not require previous registration and is freely available to all users at: http://bioinf.uab.cat/amyco/. Electronic supplementary material The online version of this article (10.1186/s12859-019-2601-3) contains supplementary material, which is available to authorized users.

Studies have noted the influence of commercials aired by the electronic media consumption behavior of children, especially television. Thus, this work proposes to study the behavior of the child consumer in Brazil, analyzing how the actions of marketing and media may influence the behavior of early consumption of children aged between six and nine years. We used a mixed approach, with the application of an instrument with open and closed questions and multiple choice, about consumer preferences applied to 141 children six to nine years old. It was found that going to the mall and watching television is part of everyday life that the consumer market, the survey also revealed that the most consumed products are toys for children (71.63%), the largest source of product knowledge that arouse desire are the advertisements on television (80.85%) and the infant admiring the appearance of these cartoon television advertisements (36.99%). It appears that the marketing and the media influence the behavior of the child consumer through advertisements on TV, advertisements on Internet and showcase the stores, especially if they are inserted in the malls, once consisting of a tour of great enjoyment for children. Key words: Marketing, Consumer market, Consumer behavior, Child consumer.

The aberrant or misfolded forms of the prion protein have been described as the causative agents of rare transmissible spongiform encephalopathies. In addition, proteins associated with frequently occurring neurodegenerative disorders, such as Alzheimer's and Parkinson's, are shown to share prion-like properties and to spread the disease in the brain. Areas covered: Interest in the prion phenomenon has crystallized in a series of computational methods aimed at uncovering prion-like proteins at the proteome level. These programs rely on the identification of sequence signatures similar to those of yeast prions, whose structural conversion is driven by specific domains enriched in glutamine/asparagine residues. A myriad of prion-like candidates, similar to those in yeast, are predicted to exist in organisms across all kingdoms of life. We review here the role of prions, prionoids and prion-like proteins in health and disease, with a special focus on the algorithms and databases developed for their prediction and classification. Expert commentary: Computational approaches provide novel insights into prion-like protein functions, their regulation and their role in disease.

Prion-like behaviour is attracting much attention due to the growing evidences that amyloid-like self-assembly may reach beyond neurodegeneration and be a conserved functional mechanism. The best characterized functional prions correspond to a subset of yeast proteins involved in translation or transcription. Their conformational promiscuity is encoded in Prion Forming Domains (PFDs), usually long and intrinsically disordered protein segments of low complexity. The compositional bias of these regions seems to be important for the transition between soluble and amyloid-like states. We have proposed that the presence of cryptic soft amyloid cores embedded in yeast PFDs can also be important for their assembly and demonstrated their existence and self-propagating abilities. Here, we used an orthogonal approach in the search of human domains that share yeast PFDs compositional bias and exhibit a predicted nucleating core, identifying 535 prion-like candidates. We selected seven proteins involved in transcriptional or translational regulation and associated to disease to characterize the properties of their amyloid cores. All of them self-assemble spontaneously into amyloid-like structures able to propagate their polymeric state. This provides support for the presence of short sequences able to trigger conformational conversion in prion-like human proteins, potentially regulating their functionality. This work was funded supported by the Spanish Ministry of Economy and Competitiveness [BIO2016-783-78310-R to S.V] and by ICREA [ICREA-Academia 2015 to S.V.]

Prion-like proteins can switch between a soluble intrinsically disordered conformation and a highly ordered amyloid assembly. This conformational promiscuity is encoded in specific sequence regions, known as prion domains (PrDs). Prions are best known as the causative factors of neurological diseases in mammals. However, bioinformatics analyses reveal that proteins bearing PrDs are present in all kingdoms of life, including bacteria, thus supporting the idea that they serve conserved beneficial cellular functions. Despite the proportion of predicted prion-like proteins in bacterial proteomes is generally low, pathogenic species seem to have a higher prionic load, suggesting that these malleable proteins may favor pathogenic traits. In the present work, we performed a stringent computational analysis of the Clostridium botulinum pathogen proteome in the search for prion-like proteins. A total of 54 candidates were predicted for this anaerobic bacterium, including the transcription termination Rho factor. This RNA-binding protein has been shown to play a crucial role in bacterial adaptation to changing environments. We show here that the predicted disordered PrD domain of this RNA-binding protein contains an inner, highly polar, asparagine-rich short sequence able to spontaneously self-assemble into amyloid-like structures, bearing thus the potential to induce a Rho factor conformational switch that might rewire gene expression in response to environmental conditions.

Este estudo objetiva a comparação dos perfis de usuários dos softwares nas escolas de administração de negócios, comparados com aqueles das escolas de informática, tendo como alvo confirmar o modelo da ruptura de leis de copyright do software, de um ponto de vista ético. A escola da administração foi escolhida desde que seu syllabus cobre uma escala larga de aspectos financeiros de maximização, visando os objetivos dos proprietários, considerando riscos mensuráveis e a escola de informática que é voltada para a tecnologia de programação, e marketing e os problemas do copyright. Fizemos um exame tendo por base a Universidade Metodista de São Paulo, como um argumento para a pesquisa, primeiro porque é situada em uma área metropolitana brasileira industrializada e, em segundo, principalmente, porque os avanços tecnológicos e, conseqüentemente, o uso ou os abusos dos softwares poderiam, facilmente, ser propagados nesta região, devido à acessibilidade e ao padrão de vida mais elevado. Para auxiliar nas realizações dos objetivos, nós extraímos duas hipótese: a) o preparo dos governos locais e modalidade de seus atos privativos para coibir o abuso de tecnologias não está acompanhando a taxa em que os desenvolvedores estão trazendo de novos produtos e, também, não acompanha a habilidade dos usuários em violar atos da privacidade; b) os estudantes da escola da administração de negócio e aqueles da escola da informática devem convergir nos pontos de vista, quando vem ao pensamento,questões morais e éticas. Baseado em nossos achados, concluimos que os estudantes que usam sempre os softwares instalados com licença válida usariam, raramente, os softwares instalados sem licença válida e, também, nunca instalariam softwares sem a licença, independentemente do preço negociável.

This paper presents a software aimed at making easier the design of customized products in accor- dance with consumers' expectations. It is based on a user-centered design methodology which combines techniques provided by Kansei Engineering, Sen- sory Analysis, and Soft Computing. Consumers' expectations are naturally expressed in the form of vague assessments related to human perceptions. Soft Computing techniques, namely Fuzzy Logic, can assist both Sensory Analysis and Kansei Engi- neering in the design and customization of products because of: (1) their suitability for computing with perceptions, and (2) their ability to tackle with im- precision and uncertainty in system identification. The utility of the software has been illustrated with a case study related to gin packaging.

The article examines issues involving the social dimension of sustainability. The survey compares the territorial development indicators in Brazil, as the level of economic development, through the Gross Domestic Product and the Human Development Index. The objective is to verify the actual level of socioeconomic development of regions. The methodology consists of a descriptive quantitative, with secondary data collection. Data analysis indicates that social indicators should be well researched and analyzed in order to complete on improving the quality of life and that the specific IDH’s not explain consistently the overall HDI of the States, being the object of analysis further the variable component of these elements and their regional crossings.