Internalization of Aspergillus fumigatus into pulmonary epithelial cells: joint action of host and pathogen

Aspergillus (A.) fumigatus is een zeer belangrijke opportunistische schimmel. Het veroorzaakt ongeveer 90% van de systemische infecties door Aspergillus. De primaire plaats van infectie is de long. Het proces van de internalisatie van A. fumigatus in longepitheelcellen is een belangrijke stap in de ontwikkeling van aspergillose.Longepitheelcellen fungeren niet alleen als mechanische barrière maar ook als eerste verdedigingslijn van het aangeboren immuunsysteem van de gastheer. Maar tot nu toe zijn de mechanismen die leiden tot de internalisatie van A. fumigatus in longepitheelcellen grotendeels onbekend. Dit proefschrift beschrijft de verschillende moleculen en signaalwegen die betrokken zijn bij dit proces van zowel A. fumigatus als de gastheer.We hebben gevonden dat β-1,3-glucaan en gliotoxine, factoren van A. fumigatus, de internalisatie van A. fumigatus in de longepitheelcellen verhogen door het stimuleren van de fosfolipase D (PLD) van de gastheer. Bovendien is PLD van A. fumigatus zelf een virulentie factor en verbetert internalisatie. Het proefschrift onthult ook dat de fosforyleringsstatus van de actine cytoskelet regulator cofiline de internalisatie in de gastheer bepaalt. DHN-melanine, een ander hoofdbestanddeel van A. fumigatus, regelt de hoeveelheid cAMP in de gastheer en de expressie van de cAMP mediator Epac. Tenslotte bieden we belangrijke gegevens van de dynamiek van genexpressie in longepitheelcellen tijdens A. fumigatus infectie door gebruik te maken van RNA-Seq technologie.Dit proefschrift levert nieuwe belangrijke inzichten om de pathogene mechanismen van A. fumigatus invasie en reacties in de gastheer.Aspergillus (A.) fumigatus is a very important opportunistic fungus. It causes about 90% of the systemic infections due to Aspergillus. The primary site of infection is the lung. The process of A. fumigatus internalization into pulmonary epithelial cells is a key step in the cause of aspergillosis. Pulmonary epithelial cells act not only as mechanical barrier but also as first defense line of the host innate immune system. But until now the mechanisms leading to the internalization of A. fumigatus into pulmonary epithelial cells are largely unknown. In this thesis we studied a subset of molecules and signaling pathways involved in this process from both A. fumigatus and the host. We found that β-1,3-glucan and gliotoxin, factors from A. fumigatus, increase the internalization of A. fumigatus into pulmonary epithelial A549 cells by inducing host cellular phospholipase D (PLD) activation. In addition, PLD of A. fumigatus itself is a virulence factor and improves internalization. The thesis also reveals that the phosphorylation status of the actin regulator cofilin in the host determines internalization. DHN-melanin, another main component of A. fumigatus, regulates the level of host cell cyclic AMP and the expression of its downstream molecule Epac. Finally, we provide important insight into dynamic transcriptome profiles in A549 cells during A. fumigatus infection by using RNA-Seq technology.This thesis provides new important clues to understand the pathogenic mechanisms of A. fumigatus invasion and responses in the host

Luminance Prediction of Paper Model Surface Based on Non-Contact Measurement

The overall appearance perception is affected by luminance perception accuracy and efficiency mostly. The surface luminance prediction correlated with surface angle and surface tone value was performed by measuring and modeling the paper model surface luminance. First, we used a rotating bracket designed to facilitate to set the paper surface angle. Then, we set the surface angle from 5° to 85° at the interval of 5° using the designed rotating bracket. Additionally, the four primary color scales, cyan, magenta, yellow, and black, were printed and set at the designed angle. The angle-ware and tone-ware luminance was measured using spectroradiometer, CS-2000. Finally, we proposed and evaluated a mathematical model to reveal the relationship between luminance and surface angle and surface tone using the least squares method. The results indicated that the surface luminance of paper model could be predicted and obtained quickly and accurately for any surface angles and surface tone values by the proposed prediction model

Proposing Employee Level CSR as an Enabler for Economic Performance: The Role of Work Engagement and Quality of Work-Life

The aim of the current research is to foster the economic performance of a hotel enterprise through employee-level corporate social responsibility (CSR) activities with the mediating effect of work engagement (W.E) and quality of work-life (QWL). A hypothesized model was developed for this purpose. The data were collected from the hotel employees of a developing economy (n = 396). The hypothesized relations were tested by employing the structural equation modeling technique. The current work’s statistical outcomes validated CSR’s seminal role to influence W.E and QWL perceptions of hotel employees, which eventually contribute to the economic performance of a hotel enterprise. The findings of the current analysis have different theoretical and practical implications. To the extent of theory, the current work advances the fields of enterprise management and employee wellbeing from an individual-level perspective of CSR. Practically, the current study helps the hotel management to realize that a carefully planned CSR strategy not only improves the economic performance of a hotel enterprise through employees but also helps to fulfill its social responsibility, hence leading a hotel enterprise towards a win-win situation

A data-driven mathematical model of multi-drug resistant Acinetobacter baumannii transmission in an intensive care unit

Major challenges remain when attempting to quantify and evaluate the impacts of contaminated environments and heterogeneity in the cohorting of health care workers (HCWs) on hospital infections. Data on the detection rate of multidrug-resistant Acinetobacter baumannii (MRAB) in a Chinese intensive care unit (ICU) were obtained to accurately evaluate the level of environmental contamination and also to simplify existing models. Data-driven mathematical models, including mean-field and pair approximation models, were proposed to examine the comprehensive effect of integrated measures including cohorting, increasing nurse-patient ratios and improvement of environmental sanitation on MRAB infection. Our results indicate that for clean environments and with strict cohorting, increasing the nurse-patient ratio results in an initial increase and then a decline in MRAB colonization. In contrast, in contaminated environments, increasing the nurse-patient ratio may lead to either a consistent increase or an initial increase followed by a decline of MRAB colonization, depending on the level of environmental contamination and the cohorting rate. For developing more effective control strategies, the findings suggest that increasing the cohorting rate and nurse-patient ratio are effective interventions for relatively clean environments, while cleaning the environment more frequently and increasing hand washing rate are suitable measures in contaminated environments

High prevalence and clonal dissemination of OXA-72-producing Acinetobacter baumannii in a Chinese hospital:a cross sectional study

Background: Carbapenem resistance in Acinetobacter baumannii in China was mainly mediated by OXA-23-like carbapenemases, while OXA-24/40-like carbapenemases were rarely identified. OXA-72 is one variant of OXA-24/40-like carbapenemases. This study aimed to demonstrate the epidemiology and characterizations of OXA-72-producing A. baumannii in a Chinese hospital. Methods: A total of 107 clinical A. calcoaceticus-A. baumannii (Acb) complex isolates were collected in a Chinese hospital during between 2014 and 2016. These isolates were identified using Vitek 2 system and gyrB multiplex PCR. Vitek 2 system was used for antibiotic susceptibility testing. Genes encoding for major classes of carbapenemases were investigated by PCR. Rep-PCR was used for genotyping of all the A. baumannii isolates. The risk factors for carriage of OXA-72-producing or OXA-23-producing A. baumannii were analyzed through univariate and multivariate logistic regression. Results: Of the 107 Acb isolates collected, 101 isolates (94.4%) and 6 isolates (5.6%) were identified as A. baumannii and A. pittii, respectively. 78 A. baumannii isolates (77.2%) were carbapenem resistant and mainly cultured from intensive care unit (ICU). blaOXA-72 and blaOXA-23 genes were identified in 45(57.7%) and 33(42.3%) carbapenem-resistant A. baumannii (CRAB), respectively. Multivariate risk factor analyses showed that prior carbapenem usage and nasogastric intubation were significantly associated with carriage of OXA-72-producing A. baumannii or OXA-23-producing A. baumannii. Rep-PCR analysis showed that 9 and 22 Rep-PCR types were assigned to 78 CRAB isolates and 23 carbapenem-susceptible A. baumannii (CSAB) isolates, respectively. A higher diverstiy of Rep-PCR patterns was observed among OXA-72-producing A. baumannii isolates than OXA-23-producing A. baumannii isolates, but all of them belonged to the same clone complex. MLST analysis suggested that the OXA-72 isolates from this study correspond to CC92/CC2 clone complex. Conclusions: This study demonstrates high prevalence and potential clonal spread of closely related genotypes of OXA-72-producing A. baumannii within a Chinese hospital. Continuous surveillance is necessary to monitor the dissemination of these strains in other healthcare settings to guide infection control policies in order to curb the spread of this bacterium