Integrated signaling pathway and gene expression regulatory model to dissect dynamics of <em>Escherichia coli </em>challenged mammary epithelial cells

AbstractCells transform external stimuli, through the activation of signaling pathways, which in turn activate gene regulatory networks, in gene expression. As more omics data are generated from experiments, eliciting the integrated relationship between the external stimuli, the signaling process in the cell and the subsequent gene expression is a major challenge in systems biology. The complex system of non-linear dynamic protein interactions in signaling pathways and gene networks regulates gene expression.The complexity and non-linear aspects have resulted in the study of the signaling pathway or the gene network regulation in isolation. However, this limits the analysis of the interaction between the two components and the identification of the source of the mechanism differentiating the gene expression profiles. Here, we present a study of a model of the combined signaling pathway and gene network to highlight the importance of integrated modeling.Based on the experimental findings we developed a compartmental model and conducted several simulation experiments. The model simulates the mRNA expression of three different cytokines (RANTES, IL8 and TNFα) regulated by the transcription factor NFκB in mammary epithelial cells challenged with E. coli. The analysis of the gene network regulation identifies a lack of robustness and therefore sensitivity for the transcription factor regulation. However, analysis of the integrated signaling and gene network regulation model reveals distinctly different underlying mechanisms in the signaling pathway responsible for the variation between the three cytokine's mRNA expression levels. Our key findings reveal the importance of integrating the signaling pathway and gene expression dynamics in modeling. Modeling infers valid research questions which need to be verified experimentally and can assist in the design of future biological experiments

Mycelia Growth and Production of Total Flavonoids and 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl- by Schizophyllum commune Using a Bubble Column Bioreactor Considering Aeration Effect and Mass Transfer Study

Higher fungi are a major source of bioactive secondary metabolites, and Schizophyllum commune secreted Schizophyllan that could possess antifungal activity. 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl- (DDMP), a compound with flavonoid fraction, is an important bioactive chemical which exhibited antifungal activity to inhibit growth or spore germination. In view of the potential of DDMP, bench scale production of total flavonoid content (TFC) and DDMP of Schizophyllum commune was carried out in laboratory fermenter at 1.5 L scale. The growth of S. commune was affected by the supply of oxygen during the fermentation. The optimum condition of aeration rate for TFC and DDMP production from S. commune was found to be 4 L min–1. The mass transfer coefficient (kLa) of S. commune was also studied to investigate the oxygen transfer capabilities in the bioreactor by considering the effect of aeration rate. On the other hand, the kLa value increased with increasing the aeration rate and the maximum kLa value (0.0814 s–1) was obtained with aeration rate of 8 L min–1

Determinisitic Writing and Control of the Dark Exciton Spin using Short Single Optical Pulses

We demonstrate that the quantum dot-confined dark exciton forms a long-lived integer spin solid state qubit which can be deterministically on-demand initiated in a pure state by one optical pulse. Moreover, we show that this qubit can be fully controlled using short optical pulses, which are several orders of magnitude shorter than the life and coherence times of the qubit. Our demonstrations do not require an externally applied magnetic field and they establish that the quantum dot-confined dark exciton forms an excellent solid state matter qubit with some advantages over the half-integer spin qubits such as the confined electron and hole, separately. Since quantum dots are semiconductor nanostructures that allow integration of electronic and photonic components, the dark exciton may have important implications on implementations of quantum technologies consisting of semiconductor qubits.Comment: Added two authors, minor edits to figure captions, expanded discussion of dark exciton eigenstate

Reverse genetics in Candida albicans predicts ARF cycling is essential for drug resistance and virulence

Peer reviewedPublisher PD