Software JimenaE allows efficient dynamic simulations of Boolean networks, centrality and system state analysis.

The signal modelling framework JimenaE simulates dynamically Boolean networks. In contrast to SQUAD, there is systematic and not just heuristic calculation of all system states. These specific features are not present in CellNetAnalyzer and BoolNet. JimenaE is an expert extension of Jimena, with new optimized code, network conversion into different formats, rapid convergence both for system state calculation as well as for all three network centralities. It allows higher accuracy in determining network states and allows to dissect networks and identification of network control type and amount for each protein with high accuracy. Biological examples demonstrate this: (i) High plasticity of mesenchymal stromal cells for differentiation into chondrocytes, osteoblasts and adipocytes and differentiation-specific network control focusses on wnt-, TGF-beta and PPAR-gamma signaling. JimenaE allows to study individual proteins, removal or adding interactions (or autocrine loops) and accurately quantifies effects as well as number of system states. (ii) Dynamical modelling of cell-cell interactions of plant Arapidopsis thaliana against Pseudomonas syringae DC3000: We analyze for the first time the pathogen perspective and its interaction with the host. We next provide a detailed analysis on how plant hormonal regulation stimulates specific proteins and who and which protein has which type and amount of network control including a detailed heatmap of the A.thaliana response distinguishing between two states of the immune response. (iii) In an immune response network of dendritic cells confronted with Aspergillus fumigatus, JimenaE calculates now accurately the specific values for centralities and protein-specific network control including chemokine and pattern recognition receptors.

Advanced human mucosal tissue models are needed to improve preclinical testing of vaccines.

Many vaccine candidates with promising results in preclinical testing fail in human trials. New complex human tissue models have the potential to improve the predictability of vaccine safety and efficacy in human clinical trials.

Susceptibility of Human Airway Tissue Models Derived From Different Anatomical Sites to Bordetella pertussis and Its Virulence Factor Adenylate Cyclase Toxin.

To study the interaction of human pathogens with their host target structures, human tissue models based on primary cells are considered suitable. Complex tissue models of the human airways have been used as infection models for various viral and bacterial pathogens. The Gram-negative bacterium Bordetella pertussis is of relevant clinical interest since whooping cough has developed into a resurgent infectious disease. In the present study, we created three-dimensional tissue models of the human ciliated nasal and tracheo-bronchial mucosa. We compared the innate immune response of these models towards the B. pertussis virulence factor adenylate cyclase toxin (CyaA) and its enzymatically inactive but fully pore-forming toxoid CyaA-AC-. Applying molecular biological, histological, and microbiological assays, we found that 1 µg/ml CyaA elevated the intracellular cAMP level but did not disturb the epithelial barrier integrity of nasal and tracheo-bronchial airway mucosa tissue models. Interestingly, CyaA significantly increased interleukin 6, interleukin 8, and human beta defensin 2 secretion in nasal tissue models, whereas tracheo-bronchial tissue models were not significantly affected compared to the controls. Subsequently, we investigated the interaction of B. pertussis with both differentiated primary nasal and tracheo-bronchial tissue models and demonstrated bacterial adherence and invasion without observing host cell type-specific significant differences. Even though the nasal and the tracheo-bronchial mucosa appear similar from a histological perspective, they are differentially susceptible to B. pertussis CyaA in vitro. Our finding that nasal tissue models showed an increased innate immune response towards the B. pertussis virulence factor CyaA compared to tracheo-bronchial tissue models may reflect the key role of the nasal airway mucosa as the first line of defense against airborne pathogens.

Reported bed net ownership and use in social contacts is associated with uptake of bed nets for malaria prevention in pregnant women in Ghana.

BACKGROUND: Despite progress made in the last decades, malaria persists as a pressing health issue in sub-Saharan Africa. Pregnant women are particularly vulnerable to infection and serious health outcomes for themselves and their unborn child. Risk can be mitigated through appropriate use of control measures such as insecticide-treated bed nets. Although social networks can influence uptake of preventive strategies, the role of social influence on bed net ownership has not been explored. During an evaluation of a bed net distribution programme, the influence of non-health care advisors on ownership and use of bed nets by pregnant women in Kumasi, Ghana was examined. METHODS: Data were collected through in-person interviews with 300 pregnant women seeking antenatal care in an urban hospital in Kumasi, Ghana. Participants were asked about their bed net ownership, bed net use, and information about three personal contacts that they go to for pregnancy advice. Information about these advisors was combined into an influence score. Logistic regression models were used to determine the association between the score and bed net ownership. Those who owned a bed net were further assessed to determine if interpersonal influence was associated with self-reported sleeping under the bed net the previous night. RESULTS: Of the 294 women in the analysis, 229 (78%) reported owning bed nets. Of these bed net owners, 139 (61%) reported using a bed net the previous night. A dose response relationship was observed between the interpersonal influence score and bed net ownership and use. Compared to the lowest influence score, those with the highest influence score (>1 SD above the mean) were marginally more likely to own a bed net [OR = 2.37, 95% CI (0.87, 6.39)] and much more likely to use their bed net [5.38, 95% CI (1.89, 15.25)] after adjusting for other factors. CONCLUSIONS: Interpersonal influence appears to have modest impact on ownership and use of bed nets by pregnant women in an urban area of Ghana. Further investigations would need to be conducted to determine if the relationship is causal or if individuals who associate are simply more likely to have similar practices.