Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe

Mechanical Qualification of Green Glued Laminated Timbers From the Congo Basin Towards Preservation of Forest Species Diversity

This study investigates the bending performances of full-size and green glued laminated timber (glulam) beams, manufactured under a tropical climate. Two types of beams were prepared: mono-species and mixed-species glulam. The mono-species glulam with uniform layup were manufactured using abura (Mitragyna ciliata) and dabema (Piptadeniastrum africanum). The mixed-species glulam with balanced layup were manufactured by associating difou (Morus mesozygia) and abura, and tali (Erythrophleum ivorense) and dabema. These species were selected in the framework of a sustainable development of the glulam industry in Congo Basin, and clustering of their technological properties. A one component polyurethane adhesive was used, and the beams were dried artificially using vacuum. Pure bending tests were performed and the results showed an optimal bondlines thickness that ranged from 0.1 to 0.3 mm. Failure occurred in the solid woods indicating a satisfatory bonding quality of the glulam products. The strength properties of the glulam and solid woods presented compatible trends. Findings of this study showed that it is possible to develop high mechanical performance glulam products while improving the valorisation of lesser-known species, thus preserving the forest diversity in the Congo Basin. © Forest Research Institute Malaysi

Contributions of Public Health to nursing practice

Objective: Analyze the perceptions of undergraduate nursing students about the contributions of public health to nursing practice in the Unified Health System. Method: Qualitative Descriptive Study. Data collection was carried out through semi-directed interviews with 15 students. The language material was analyzed according to content and thematic analysis. Results: Thematic categories were established, namely: "Perceptions about Public Health" and "Contribution of Public Health to nursing practice in the Unified Health System". Final considerations: Perceptions about Public Health are diversified, but converge to the recognition of this field as the basis for training nurses qualified to work in the SUS with technical competence, autonomy and focusing on the integrality in health care.Objetivo: Analisar as percepções de alunos do curso de bacharelado em Enfermagem acerca das contribuições da Saúde Coletiva para o trabalho de enfermeiros no Sistema Único de Saúde. Método: Estudo descritivo, com abordagem qualitativa. A coleta de dados foi realizada mediante a técnica da entrevista semidirigida com 15 alunos. O material de linguagem foi analisado segundo a técnica de análise de conteúdo temático-categorial. Resultados: Foram produzidas as categorias temáticas "Percepções acerca da Saúde Coletiva" e "Contribuição da Saúde Coletiva ao trabalho do enfermeiro no Sistema Único de Saúde". Considerações finais: As percepções sobre a Saúde Coletiva são plurais, mas convergem para o reconhecimento desse campo como base de sustentação da formação de enfermeiros habilitados a trabalhar no SUS com competência técnica, autonomia e com foco na integralidade do cuidado em saúde.Univ Fed Sao Paulo, Paulista Sch Nursing, Dept Publ Hlth, Sao Paulo, BrazilUniv Estado Rio de Janeiro, Sch Nursing, Dept Publ Hlth Nursing, Rio De Janeiro, BrazilUniv Estado Rio de Janeiro, Pedro Ernesto Univ Hosp, Nurse Residency Program Neonatol, Rio De Janeiro, BrazilUniv Fed Sao Paulo, Paulista Sch Nursing, Dept Publ Hlth, Sao Paulo, BrazilWeb of Scienc