Caracterização física e produtividade de acessos de Passiflora nítida no Cerrado do Distrito Federal.

Ref. 71577

Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish

Purpose: Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function in vivo. Methods: Through international collaboration, we identified 22 affected individuals from 16 unrelated families harboring biallelic likely pathogenic or pathogenic in KARS1 variants. Sequencing approaches ranged from disease-specific panels to genome sequencing. We generated loss-of-function alleles in zebrafish. Results: We identify ten new and four known biallelic missense variants in KARS1 presenting with a moderate-to-severe developmental delay, progressive neurological and neurosensory abnormalities, and variable white matter involvement. We describe novel KARS1-associated signs such as autism, hyperactive behavior, pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement. Loss of kars1 leads to upregulation of p53, tissue-specific apoptosis, and downregulation of neurodevelopmental related genes, recapitulating key tissue-specific disease phenotypes of patients. Inhibition of p53 rescued several defects of kars1−/− knockouts. Conclusion: Our work delineates the clinical spectrum associated with KARS1 defects and provides a novel animal model for KARS1-related human diseases revealing p53 signaling components as potential therapeutic targets

Seleção de um modelo de referência de PDP para uma empresa de autopeças através de um método de auxílio à decisão por múltiplos critérios Selection of a PDP reference model to an auto parts company by means of multi-criteria techniques

O processo de desenvolvimento de produtos (PDP) é um fator crítico de sucesso no lançamento de um novo produto para atender os requisitos dos clientes. A adoção de um modelo de referência serve como um guia detalhado para auxiliar as organizações na gestão e sistematização do PDP, através da sequência padronizada de etapas que são adaptadas de acordo com o tipo de produto que a empresa desenvolve. O objetivo deste artigo é selecionar um modelo de referência do processo de desenvolvimento de produtos para uma empresa do ramo de autopeças através de um método de auxílio à decisão por multicritério denominado Analytic Hierarchy Process (AHP). O método de pesquisa utilizado foi a modelagem, que diante de seis alternativas, três critérios e julgamento de cinco especialistas resultou na seleção do modelo de Rozenfeld et al. (2006) como o modelo mais indicado para realizar a análise do PDP da empresa objeto de estudo em pesquisas futuras.<br>The Product Development Process (PDP) is a critical success factor in launching a new product to meet customer requirements. The adoption of a reference model serves as a comprehensive guide to assist organizations in managing and systematization of the PDP, through standardized sequence of steps that are adapted to the type of product that the company develops. The aim of this paper is to select a reference model of the product development process for the auto part sector by establishing an aid to multi-criteria decision known as Analytic Hierarchy Process (AHP). The research method used was modeling, which before six alternatives, three criteria and trial of five experts resulted in the selection of Rozenfeld et al. (2006) reference model as the most suitable model to analyze the company's PDP selected as object of study in future research