RESUMO
Influenza virus induces apoptosis in infected cells to promote viral replication by manipulating the host cell death signaling pathway. Although some Bcl-2 family proteins play a role in the replication of influenza A virus (IAV), the role of cell death pathways in the viral replication cycle is unclear. We investigated whether deficiency of the proapoptotic Bcl-2 family protein, Bik, plays a role in IAV replication. IAV replication was attenuated in mouse airway epithelial cells (MAECs) from bik(-/-) compared with bik(+/+) mice, as indicated by reduced viral titers. Bik(-/-) MAECs showed more stable transepithelial resistance after infection than did bik(+/+) MAECs, were less sensitive to infection-induced cell death, and released fewer copies of viral RNA. Similar results were obtained when Bik expression was suppressed in human airway epithelial cells (HAECs). Bik(+/+) mice lost weight drastically and died within 8 days of infection, whereas 75% of bik(-/-) mice survived infection for 14 days and were 10-fold less likely to die from infection compared with bik(+/+) mice. IAV infection activated caspase 3 in bik(+/+) but not in bik(-/-) MAECs. Cleavage of viral nucleoprotein and M2 proteins were inhibited in bik(-/-) MAECs and when caspase activation was inhibited in HAECs. Furthermore, Bik deficiency impaired cytoplasmic export of viral ribonucleoprotein. These studies suggest a link between Bik-mediated caspase activation and cleavage of viral proteins. Thus, inhibition of proapoptotic host factors such as Bik and downstream mediators of cell death may represent a novel approach to influenza treatment.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 3/metabolismo , Vírus da Influenza A/fisiologia , Influenza Humana/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Infecções por Orthomyxoviridae/metabolismo , Proteínas Virais/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/virologia , Animais , Morte Celular , Embrião de Galinha , Citoplasma/metabolismo , Cães , Ativação Enzimática , Humanos , Influenza Humana/virologia , Células Madin Darby de Rim Canino , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/deficiência , Infecções por Orthomyxoviridae/virologia , Ribonucleoproteínas/metabolismo , Replicação ViralRESUMO
Sonochemistry is the use of ultrasound to generate highly reactive radical species through the inertial collapse of a gas/vapour cavity and is a green alternative for hydrogen production, wastewater treatment, and chemical synthesis and modifications. Yet, current sonochemical reactors often are limited by their design, resulting in low efficacy and yields with slow reaction kinetics. Here, we constructed a novel sonochemical reactor design that creates cylindrically converging ultrasound waves to create an intense localised region of high acoustic pressure amplitudes (15 MPaPKPK) capable of spontaneously nucleating cavitation. Using a novel dosimetry technique, we determined the effect of acoustic parameters on the yield of hydroxyl radicals (HO), HO production rate, and ultimately the sonochemical efficiency (SE) of our reactor. Our reactor design had a significantly higher HO production rate and SE compared to other conventional reactors and across literature.
RESUMO
This study sought to answer how implementing a nontraditional ambulatory registered nurse (RN) residency program impacted confidence, role transition, and retention rates of nursing staff in the outpatient clinical setting. Results demonstrated that the program improved RNs' confidence in communication and perceived preparedness to complete individual professional responsibilities. As a result of this study, implementing a nontraditional RN ambulatory residency program should be considered to support RNs new to the ambulatory setting.