Genome-Wide Screen of Three Herpesviruses for Protein Subcellular Localization and Alteration of PML Nuclear Bodies

Herpesviruses are large, ubiquitous DNA viruses with complex host interactions, yet many of the proteins encoded by these viruses have not been functionally characterized. As a first step in functional characterization, we determined the subcellular localization of 234 epitope-tagged proteins from herpes simplex virus, cytomegalovirus, and Epstein–Barr virus. Twenty-four of the 93 proteins with nuclear localization formed subnuclear structures. Twelve of these localized to the nucleolus, and five at least partially localized with promyelocytic leukemia (PML) bodies, which are known to suppress viral lytic infection. In addition, two proteins disrupted Cajal bodies, and 19 of the nuclear proteins significantly decreased the number of PML bodies per cell, including six that were shown to be SUMO-modified. These results have provided the first functional insights into over 120 previously unstudied proteins and suggest that herpesviruses employ multiple strategies for manipulating nuclear bodies that control key cellular processes

Impact of intravenous infusion time on AAV8 vector pharmacokinetics, safety, and liver transduction in cynomolgus macaques

Systemically delivered adeno-associated viral (AAV) vectors are now in early-phase clinical trials for a variety of diseases. While there is a general consensus on inclusion and exclusion criteria for each of these trials, the conditions under which vectors are infused vary significantly. In this study, we evaluated the impact of intravenous infusion rate of AAV8 vector in cynomolgus macaques on transgene expression, vector clearance from the circulation, and potential activation of the innate immune system. The dose of AAV8 vector in terms of genome copies per kilogram body weight and its concentration were fixed, while the rate of infusion varied to deliver the entire dose over different time periods, including 1, 10, or 90 minutes. Analyses during the in-life phase of the experiment included sequential evaluation of whole blood for vector genomes and appearance of proinflammatory cytokines. Liver tissues were analyzed at the time of necropsy for enhanced green fluorescent protein (eGFP) expression and vector genomes. The data were remarkable with a relative absence of any statistically significant effect of infusion time on vector transduction, safety, and clearance. However, some interesting and unexpected trends did emerge

Características clínicas e psicossociais do paciente com insuficiência cardíaca que interna por descompensação clínica Características clínicas y psicosociales del paciente con insuficiencia cardiaca ingresado en hospital por descompensación clínica Clinical and psycossocial features of heart failure patients admitted for clinical decompensation

Este estudo teve como objetivo identificar perfil sociodemográfico e clínico, história de hospitalizações por Insuficiência Cardíaca (IC) e seguimento (consultas regulares, tratamento medicamentoso, fatores facilitadores e dificultadores do seguimento) do paciente internado por quadro de descompensação clínica. Foram entrevistados 61 pacientes com idade média de 58,1 (&plusmn; 15,9) anos, 3,5 (&plusmn; 4,4) anos de estudo e renda individual de 1,3 (&plusmn; 2,4) salários-mínimos. A maioria dos sujeitos se encontrava em classe funcional III ou IV da New York Heart Association, tendo como causa mais freqüente de hospitalização, os sinais/sintomas da forma congestiva da IC. 75,4% dos sujeitos relataram acompanhamento clínico, porém de periodicidade irregular. Constatou-se utilização de terapêutica medicamentosa em proporção inferior à recomendada pela literatura. Os achados devem auxiliar a identificação dos pacientes com maior risco de descompensação da IC e assim, desenhar e implementar intervenções específicas visando a redução das re-hospitalizações por IC.<br>Este estudio tuvo como objetivo identificar el perfil sociodemográfico y clínico, la historia de hospitalizaciones por Insuficiencia Cardiaca (IC) y el seguimiento (consultas regulares, tratamiento medicamentoso, y, los factores facilitadores y dificultadores del seguimiento) del paciente internado por cuadro de descompensación clínica. Fueron entrevistados 61 pacientes con edad promedio de 58,1(&plusmn;15,9) años, 3,5 (&plusmn;4,4) años de estudio y renta individual de 1,3 (&plusmn;2,4) salarios mínimos. La mayoría de los sujetos se encontraba en la clase funcional III o IV de la New York Heart Asociation, teniendo como causa más frecuente de hospitalización las señales/síntomas de la forma con-gestiva de la IC; 75,4% de los sujetos relataron acompañamiento clínico, sin embargo este era de una periodicidad irregular. Se constató la utilización de terapéutica medicamentosa en proporción inferior a la recomendada por la literatura. Lo encontrado debe auxiliar a identificar los pacientes con mayor riesgo de descompensación de la IC, y así, proyectar e imple-mentar intervenciones específicas que tengan como objetivo la reducción de las hospitalizaciones por IC.<br>This study had the purpose to identify the sociodemographic and clinical profiles, history of hospitalizations due to Heart Failure (HF) and follow-ups (regular appointments, drug treatment, facilities and difficulties for follow-up) of patients admitted for clinical decompensation. Interviews were held with 61 patients, with average age of 58.1 (&plusmn; 15.9) years, 3.5 (&plusmn; 4.4) years of education and individual income of 1.3 (&plusmn; 2.4) times the minimum wage. Most subjects were in functional classes III or IV of the New York Heart Association, having signs and symptoms of the congestive form of HF as the most frequent cause of hospitalization. Of all subjects, 75.4% reported clinical follow-ups, although they tended to be irregular. The use of drug therapy occurred in lower ratios than that recommended in the literature. The findings must help to identify patients with higher risk of HC decompensation, and, as such, design and implement specific interventions aiming at reducing re-admittances due to HF

Controlled thermo-catalytic modification of regenerated cellulosic fibres using magnesium chloride Lewis acid

The Lewis-acid catalytic reactions of magnesium chloride with regenerated cellulosic fibres under baking conditions can be interpreted using existing semi-crystalline morphological models. Reaction at 180 °C is associated with chain scission, which takes place randomly within the accessible regions of the fibre structure. This causes a rapid reduction in the cellulose degree of polymerization, which stabilizes at a limiting value, analogous to that observed with wet-state mineral acid catalysed hydrolysis. A slower scission-reaction is also observed, believed to be due to the liberation of single glucan units from crystallite ends, again analogous to wet-state mineral acid hydrolysis. Dry-state catalysis is promoted by thermal molecular motion, allowing migration of catalyst ions and also conformational flexing of the cellulose polymer, which also induces a small amount of recrystallisation at crystallite lateral surfaces. Differences in the dry-state reaction have been observed for lyocell, viscose and modal regenerated fibres, which can be related to differences in crystallinity and resulting accessibility of the magnesium chloride catalyst. For lyocell the accessibility towards magnesium chloride is lower than found with mineral acids, which may be significant in the development of treatments to promote mechanical fibrillation, without sacrificing fibre tensile properties