Debundling and Selective Enrichment of SWNTs for Applications in Dye-Sensitized Solar Cells

We present an overview of the recent developments in de-bundling and sorting of Single-Wall Carbon Nanotubes (SWNTs), which are useful for hi-tech applications in dye sensitized solar cells (DSSCs). Applications of SWNTs as transparent and conductive films, catalyst, and scaffold in DSSCs are also reviewed.Peer Reviewe

A plausible identifiable model of the canonical NF-<i>κ</i>B signaling pathway

AbstractAn overwhelming majority of mathematical models of regulatory pathways, including intensively studied NF-κB pathway, remains non-identifiable meaning that their parameters may not be determined by existing data. The existing NF-κB models that are capable to reproduce experimental data, contain non-identifiable parameters, while simplified models with a smaller number of parameters exhibit dynamics that significantly differs from that observed in experiments. Here, we reduce an existing model of the canonical NF-κB pathway by decreasing the number of equations from 15 to 6 in a way that the resulting model exhibits dynamics closely following that of the original model, both for the nominal and the randomly selected parameters. We carried out the sensitivity-based linear analysis and Monte Carlo-based analysis to demonstrate that the resulting model is structurally and practically identifiable based on a simple TNF stimulation protocol in which 5 model variables are measured. The reduced model is capable to reproduce different types of responses characteristic to regulatory motives controlled by negative feedback loops: nearly-perfect adaptation, damped and sustained oscillations. It can serve as a building block of more comprehensive models of immune responses and cancer, where NF-κB plays a decisive role. Our approach, although may not be automatically generalized, suggests that other regulatory pathways models can be transformed to identifiable, while retaining their dynamical features.</jats:p

RSV protects bystander cells against IAV infection by triggering secretion of type I and type III interferons

AbstractWe observed the interference between two prevalent respiratory viruses, respiratory syncytial virus (RSV) and influenza A virus (IAV, H1N1), and characterized its molecular underpinnings in alveolar epithelial cells (A549). We found that RSV induces higher interferon (IFN) β production than IAV and that IFNβ priming confers higher protection against infection with IAV than with RSV. Consequently, we focused on the sequential infection scheme: RSV-then-IAV. Using the A549 WT, IFNAR1 KO, IFNLR1 KO, and IFNAR1–IFNLR1 double KO cell lines we found that both IFNβ and IFNλ are necessary for maximum protection against subsequent infection. Immunostaining revealed that preinfection with RSV partitions the cell population into a subpopulation susceptible to subsequent infection with IAV and an IAV-proof subpopulation. Strikingly, the susceptible cells turned out to be those already compromised and efficiently expressing RSV, whereas the bystander, interferon-primed cells are resistant to IAV infection. Thus, the virus–virus exclusion at the cell population level is not realized through a direct competition for a shared ecological niche (single cell) but rather achieved with the involvement of specific cytokines induced within the host innate immune response.ImportanceThe influenza A virus (IAV) and the respiratory syncytial virus (RSV) are common recurrent respiratory infectants, which show a relatively high coincidence. We demonstrated that preinfection with RSV partitions the cell population into a subpopulation susceptible to subsequent infection with IAV and an IAV-proof subpopulation. The susceptible cells are those already compromised and efficiently expressing RSV, whereas the bystander cells are resistant to IAV infection. The cross-protective effect critically depends on IFNβ and IFNλ signaling and thus ensues when the proportion of cells preinfected with RSV is relatively low yet sufficient to trigger a pervasive antiviral state in bystander cells. Our study suggests that mild, but not severe, respiratory infections may have a short-lasting protective role against more dangerous respiratory viruses, including SARS-CoV-2.</jats:sec

Antagonism between viral infection and innate immunity at the single-cell level.

When infected with a virus, cells may secrete interferons (IFNs) that prompt nearby cells to prepare for upcoming infection. Reciprocally, viral proteins often interfere with IFN synthesis and IFN-induced signaling. We modeled the crosstalk between the propagating virus and the innate immune response using an agent-based stochastic approach. By analyzing immunofluorescence microscopy images we observed that the mutual antagonism between the respiratory syncytial virus (RSV) and infected A549 cells leads to dichotomous responses at the single-cell level and complex spatial patterns of cell signaling states. Our analysis indicates that RSV blocks innate responses at three levels: by inhibition of IRF3 activation, inhibition of IFN synthesis, and inhibition of STAT1/2 activation. In turn, proteins coded by IFN-stimulated (STAT1/2-activated) genes inhibit the synthesis of viral RNA and viral proteins. The striking consequence of these inhibitions is a lack of coincidence of viral proteins and IFN expression within single cells. The model enables investigation of the impact of immunostimulatory defective viral particles and signaling network perturbations that could potentially facilitate containment or clearance of the viral infection

Non-self RNA rewires IFNβ signaling: A mathematical model of the innate immune response

AbstractViral RNA-activated transcription factors IRF3 and NF-κB trigger synthesis of interferons and interleukins. In non-infected bystander cells, the innate immune response is reinforced by secreted interferon β (IFNβ), which induces the expression of interferon-activated genes (ISGs) through activation of STAT1/2. Here, we show that in cells transfected with an analog of viral RNA, poly(I:C), transcriptional activity of STAT1/2 is terminated due to depletion of the IFNβ receptor, IFNAR. We demonstrate that two ISGs, RNase L and PKR, not only hinder replenishment of IFNAR, but also suppress negative regulators of IRF3 and NF-κB, consequently promoting their transcriptional activity. We incorporated these findings into a comprehensive mathematical model of innate immunity. By coupling signaling through the IRF3/NF-κB and the STAT1/2 pathways with activity of RNase L and PKR, the model explains how poly(I:C) switches the transcriptional program from STAT1/2-induced to IRF3/NF-κB-induced, transforming IFNβ-responding cells into IFNβ-secreting cells. Using an ample set of experiments on wild-type and knock-out A549 cell lines for fitting the model, we managed to achieve parameter identifiability.</jats:p

Influence of DVGs on IFN expression and viral progeny (model).

A. The average status of vProteins and IFNe as a function of the percentage of cells infected solely by DVGs at 48 h p.i. Initial MOI: 0.01. B. Same as in panel A, but with the vProteins forward rate coefficient (vProteins_inc) increased 3-fold. Note the different range on the left vertical axis.</p

ELISA data for Fig A panel c in S1 Appendix.

When infected with a virus, cells may secrete interferons (IFNs) that prompt nearby cells to prepare for upcoming infection. Reciprocally, viral proteins often interfere with IFN synthesis and IFN-induced signaling. We modeled the crosstalk between the propagating virus and the innate immune response using an agent-based stochastic approach. By analyzing immunofluorescence microscopy images we observed that the mutual antagonism between the respiratory syncytial virus (RSV) and infected A549 cells leads to dichotomous responses at the single-cell level and complex spatial patterns of cell signaling states. Our analysis indicates that RSV blocks innate responses at three levels: by inhibition of IRF3 activation, inhibition of IFN synthesis, and inhibition of STAT1/2 activation. In turn, proteins coded by IFN-stimulated (STAT1/2-activated) genes inhibit the synthesis of viral RNA and viral proteins. The striking consequence of these inhibitions is a lack of coincidence of viral proteins and IFN expression within single cells. The model enables investigation of the impact of immunostimulatory defective viral particles and signaling network perturbations that could potentially facilitate containment or clearance of the viral infection.</div