Altered gene expression of Staphylococcus aureus upon interaction with human endothelial cells

Staphylococcus aureus is isolated from a substantial number of patients with infective endocarditis who are not known to have predisposing heart abnormalities. It has been suggested that the infection is initiated by the direct binding of S. aureus to human vascular endothelium. To determine the mutual response of the endothelial cells and the bacteria, we studied the interaction between S. aureus and human vascular endothelium. Scanning electron microscopic analyses showed that binding of S. aureus to human umbilical vein endothelial cells (HUVEC) mainly occurred via thread-like protrusions extending from the cell surface. Bound bacteria appeared to be internalized via retraction of the protrusions into newly formed invaginations of the endothelial cell surface. The growth phase of S. aureus had a major impact on the interaction with HUVEC. Logarithmically growing bacteria showed increased binding to, and were more readily internalized by, HUVEC compared to stationary-phase bacteria. To assess the bacterial response to the cellular environments an expression library of S. aureus was used to identify genes whose expression was induced after 4 h of exposure to HUVEC. The identified genes could be divided into different categories based on the functions of the encoded proteins (transport, catabolism, biosynthesis, and DNA repair). Further analyses of five of the S. aureus transposon clones showed that HUVEC as well as human serum are stimuli for triggering gene expression in S. aureus

Een metafysisch perspectief op de verifi catie van maatschappelijke jaarverslagen

In deze bijdrage wordt een controleaanpak uiteengezet voor verificatie van maatschappelijke jaarverslagen die afwijkt van de controleaanpak zoals deze op dit moment veelvuldig wordt gehanteerd en zoals deze in controlestandaard COS 3410N door het Nederlands Instituut van Register Accountants (NIVRA) is uitgewerkt. Bij deze alternatieve aanpak wordt nadrukkelijk ingegaan op (het belang van) de achterliggende ethiek van handelingen beschreven in het maatschappelijk jaarverslag. Wij zet ten uiteen dat deze achterliggende ethiek metafysisch van aard is en dat bij het inrichten van de controle hier nadrukkelijk rekening mee dient te worden gehouden. Door de in deze bijdrage voor gestelde Internal Control for Ethical Conduct (ICEC) als uitgangspunt te nemen, kan een deugdelijke grondslag worden verkregen voor verificatie van kwalitatieve uitspraken in het maatschappelijk jaarverslag en kan zo het gehele maatschappelijk jaarverslag op een holistische manier worden geverifieerd. Hierbij wordt opgemerkt dat dit gevolgen zou kunnen hebben voor de redactie van het maatschappelijk jaarverslag

Does auditor resilience mitigate the effects of multiple team memberships on quality threatening behaviors?

Audit firms rely on audit teams where memberships are frequently shared, shifted, and dissolved. In practice, this means that many auditors are part of multiple engagement teams for a given period of time. This paper examines why and when such multiple team memberships (MTMs) may lead auditors to engage in audit quality-threatening behaviors. We analyze data from a survey of 202 auditors—ranging from assistants to partners—working at Dutch audit firms. Our findings demonstrate that serving on MTMs can undermine auditor learning and in so doing leads auditors to engage in audit quality-threatening behaviors. Analyses show that less resilient auditors—those who are less able to bounce back from experienced difficulties—appear most susceptible to these deleterious effects. In addition, exploratory analyses suggest that the negative effect of serving on many MTMs appears to be more pronounced for field-level auditors than for management-level auditors

Too unsafe to monitor? How board-ceo cognitive conflict and chair leadership shape outside director monitoring

Research into boards of directors has provided mixed support for the view that outside directors\u27 independence or leadership by an independent chair improves monitoring. In this study, we use a micro-level approach to provide a better understanding of why outside directors have difficulty in monitoring the CEO. We highlight that an important reason for this lies in the boardroom dynamics associated with (a) outside directors\u27 cognitive conflict with the CEO and (b) the chair\u27s leadership of the board. Our inductive analyses of video observations of board meetings in five Australian corporations revealed the importance of chair participative leadership during disagreement episodes in the boardroom. Follow-up in-depth interviews of board meeting participants highlighted the importance of psychological safety as a key mechanism explaining why participative board chairs appear so effective in dealing with board-CEO cognitive conflict. We corroborate these results with a second, large-scale survey study involving data on 310 outside directors from 64 Dutch boards. Whereas prior work has mostly focused on the chair\u27s relationship with the CEO, we instead highlight the importance of the chair\u27s role as the leader of the board and identify board psychological safety as an important element shaping director monitoring within the confines of the boardroom

Network Structure and Auditor Compensation: Evidence from a Small World Bipartite Network

This study examines the relationship between auditors’ tacit knowledge transfer and auditor compensation. We exploit a unique proprietary sample and employ small-world theory in social network analysis to capture tacit knowledge transfer among individual auditors. Drawing from an audit firm’s full year of personnel records and data on the assignment of individual auditors to audit engagements throughout the year, we find a statistically significant positive association between tacit knowledge transfer and auditor compensation. Furthermore, we find that this positive association is mainly driven by assistants, audit seniors, and audit managers. Finally, we find that auditor performance is likely to be a valid mechanism linking tacit knowledge transfer and auditor compensation for audit seniors and audit managers. Overall, our results suggest that the social capital embedded within knowledge networks plays an important role in auditor compensation

High titres of pre-existing adenovirus serotype-specific neutralizing antibodies predict viral reactivation after allogeneic stem cell transplantation in children

Transplantation and immunomodulatio

Infection of human endothelial cells with Staphylococcus aureus induces the production of monocyte chemotactic protein-1 (MCP-1) and monocyte chemotaxis

Bacterial infection coincides with migration of leucocytes from the circulation into the bacterium-infected tissue. Recently, we have shown that endothelial cells, upon binding and ingestion of Staphylococcus aureus, exhibit proinflammatory properties including procoagulant activity and increased intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression on the cell surface, resulting in hyperadhesiveness, mainly for monocytes. The enhanced extravasation of monocytes to bacterium-infected sites is facilitated by the local production of chemotactic factors. From another study we concluded that the locally produced chemokine MCP-1 is important in the recruitment of monocytes to the peritoneal cavity in a model of bacterial peritonitis. In the present study we investigated whether cultured human endothelial cells after infection with bacteria produce and release MCP-1, which in turn stimulates monocyte chemotaxis. We observed that endothelial cells released significant amounts of MCP-1 within 48 h after ingestion of S. aureus. This was dependent on the number and the virulence of the bacteria used to infect the endothelial cells. The kinetics as well as the amount of MCP-1 released by S. aureus-infected endothelial cells differed markedly from that released by endothelial cells upon stimulation with IL-1β. Supernatant from S. aureus-infected or IL-1β-stimulated cells promoted monocyte chemotaxis which was almost entirely abrogated in the presence of neutralizing anti-MCP-1 antibody, indicating that most of the chemotactic activity was due to the release of MCP-1 into the supernatant. Our findings support the notion that endothelial cells can actively initiate and sustain an inflammatory response after an encounter with pathogenic microorganisms, without the intervention of macrophage-derived proinflammatory cytokines