Respiratory syncytial virus (RSV) is a common cause of childhood lower respiratory tract infections. The recent failure of a vaccine candidate based on recombinant F protein underlines the urgent need to better understand the protective human memory immune response against RSV. Signal transducer and activator of transcription 3 (STAT3) protein is a transcription factor that promotes the maturation of the memory CD8 T cell response in cooperation with IL-10 and IL-21. However, the role of STAT3 in the memory CD8 T cell response during RSV infection remains to be elucidated. We found that in infants with bronchiolitis infected with RSV, the expression of STAT3 detected in nasal washes is reduced when compared to that in infants infected by other viruses. In vitro, RSV impairs STAT3 phosphorylation induced by IL-21 in purified human memory CD8 T cells. In addition, RSV decreases granzyme B production by memory CD8 T cells, reducing its cytotoxic activity against RSV-infected epithelial pulmonary cell lines. Together, these data indicate that RSV modulates the IL-21/STAT3 pathway in human memory CD8 T cells, and this could be a mechanism to be further explored to improve the memory response against the infection.
The generation of memory is a cardinal feature of the adaptive immune response, involving different factors in a complex process of cellular differentiation. This process is essential for protecting the second encounter with pathogens and is the mechanism by which vaccines work. Epigenetic changes play important roles in the regulation of cell differentiation events. There are three types of epigenetic regulation: DNA methylation, histone modification, and microRNA expression. One of these epigenetic changes, DNA methylation, occurs in cytosine residues, mainly in CpG dinucleotides. This brief review aimed to analyse the literature to verify the involvement of DNA methylation during memory T and B cell development. Several studies have highlighted the importance of the DNA methyltransferases, enzymes that catalyse the methylation of DNA, during memory differentiation, maintenance, and function. The methylation profile within different subsets of naïve activated and memory cells could be an interesting tool to help monitor immune memory response.
Software process improvement programs increase the competitiveness of software development organizations. But a critical success factor in this context is the proper alignment between the strategy of such programs and the organization's business strategy. In this paper, we discuss how Quality Function Deployment can be used as a technique to align strategic goals and software process within an organization, presenting results of its application in a small company in Brazil.
The alignment between the strategy of a software process improvement program and the organizations' business strategies has been mentioned as a critical factor of success. However, the main software process reference models do not explicitly guide the companies towards defining processes which meet their strategic goals. Based on this context, the purpose of this paper is to present a process for the strategic alignment of software process improvement programs. Preliminary results indicate benefits beyond the demands of a software process reference model itself, which include the planning and execution of a software process improvement program taking into account the organization's strategic goals in a more systematic way.
O atual investimento despendido em processos de implantação da qualidade inibe a capacitação de processos de software em empresas de pequeno porte. No entanto, a implantação de um modelo pode tornar-se um diferencial estratégico para estas organizações. Deste modo, este artigo relata um projeto de qualidade viabilizado pela interação Universidade-Empresa e sem subsídios financeiros. Desenvolvido no Centro de Inovação/Microsoft, o projeto busca desenvolver alternativas semelhantes para outras organizações de mesma estrutura.
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