Cellular and molecular phenotypes depending upon the RNA repair system RtcAB of Escherichia coli

Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J00717X/1]; Medical Research Council (MRC) [MR/M017672/1]; Queen's Fellowship (Queen's University Belfast, UK) (to C.E.); Antimicrobial Resistance Cross Council Initiative. Funding for open access charge: BBSRC [BB/J00717X/1]; MRC [MR/M017672/1]

The route to transcription initiation determines the mode of transcriptional bursting in E. coli

Transcription is fundamentally noisy, leading to significant heterogeneity across bacterial populations. Noise is often attributed to burstiness, but the underlying mechanisms and their dependence on the mode of promotor regulation remain unclear. Here, we measure E. coli single cell mRNA levels for two stress responses that depend on bacterial sigma factors with different mode of transcription initiation (σ70 and σ54). By fitting a stochastic model to the observed mRNA distributions, we show that the transition from low to high expression of the σ70-controlled stress response is regulated via the burst size, while that of the σ54-controlled stress response is regulated via the burst frequency. Therefore, transcription initiation involving σ54 differs from other bacterial systems, and yields bursting kinetics characteristic of eukaryotic systems

CA 125 regression after two completed cycles of chemotherapy: lack of prediction for long-term survival in patients with advanced ovarian cancer

The prognostic influence of CA 125 regression between the time point before surgery and after two completed courses of chemotherapy was studied in 210 patients with advanced ovarian cancer, and was compared to other well established prognostic factors. CA 125 blood samples were collected preoperatively (CA 125 pre) and 3 months after surgery (CA 125 3 mo) (at the beginning of the 3rd cycle of chemotherapy). The parameter CA 125 regression defined as log10 (CA 125 3 mo/CA 125 pre) was used for statistical analysis. In a survival analysis using a Cox proportional hazards model, CA 125 regression (P = 0.0001), residual tumour (P = 0.0001), age (P = 0.0095) and grading (P = 0.044) were independent variables, whereas stage of disease, histology, ascites and type of surgery failed to retain significance. Using log10 (CA 125 3 mo/CA 125 pre) as simple covariate in a Cox model showed a hazard ratio of 1.70 (95% confidence interval 1.32–2.19, P = 0.0001). However, a detailed analysis of the interaction of time with the prognostic factor CA 125 regression on survival revealed a strong time-dependent effect with a hazard ratio of more than 6 immediately after two courses of chemotherapy, whereas within approximately 1 year the hazard ratio for the surviving patients dropped quickly to the neutral level of 1. In summary, CA 125 regression is an independent prognostic factor for survival of women with advanced ovarian cancer and allows an identification of a high-risk population among patients with advanced ovarian cancer. However, the discriminating power of serial CA 125 for long-term survival seems to be temporary and prediction of individual patients outcome is far less precise. © 1999 Cancer Research Campaig

On the Calibration of a Size-Structured Population Model from Experimental Data

The aim of this work is twofold. First, we survey the techniques developed in (Perthame, Zubelli, 2007) and (Doumic, Perthame, Zubelli, 2008) to reconstruct the division (birth) rate from the cell volume distribution data in certain structured population models. Secondly, we implement such techniques on experimental cell volume distributions available in the literature so as to validate the theoretical and numerical results. As a proof of concept, we use the data reported in the classical work of Kubitschek [3] concerning Escherichia coli in vitro experiments measured by means of a Coulter transducer-multichannel analyzer system (Coulter Electronics, Inc., Hialeah, Fla, USA.) Despite the rather old measurement technology, the reconstructed division rates still display potentially useful biological features

An integral equation method for the inverse conductivity problem

We present an image reconstruction algorithm for the Inverse Conductivity Problem based on reformulating the problem in terms of integral equations. We use as data the values of injected electric currents and of the corresponding induced boundary potentials, as well as the boundary values of the electrical conductivity. We have used a priori information to find a regularized conductivity distribution by first solving a Fredholm integral equation of the second kind for the Laplacian of the potential, and then by solving a first order partial differential equation for the regularized conductivity itself. Many of the calculations involved in the method can be achieved analytically using the eigenfunctions of an integral operator defined in the paper.Comment: 15 pages, 8 figure

Molecular origins of transcriptional heterogeneity in diazotrophic Klebsiella oxytoca.

Phenotypic heterogeneity in clonal bacterial batch cultures has been shown for a range of bacterial systems; however, the molecular origins of such heterogeneity and its magnitude are not well understood. Under conditions of extreme low-nitrogen stress in the model diazotroph Klebsiella oxytoca, we found remarkably high heterogeneity of nifHDK gene expression, which codes for the structural genes of nitrogenase, one key enzyme of the global nitrogen cycle. This heterogeneity limited the bulk observed nitrogen-fixing capacity of the population. Using dual-probe, single-cell RNA fluorescent in situ hybridization, we correlated nifHDK expression with that of nifLA and glnK-amtB, which code for the main upstream regulatory components. Through stochastic transcription models and mutual information analysis, we revealed likely molecular origins for heterogeneity in nitrogenase expression. In the wild type and regulatory variants, we found that nifHDK transcription was inherently bursty, but we established that noise propagation through signaling was also significant. The regulatory gene glnK had the highest discernible effect on nifHDK variance, while noise from factors outside the regulatory pathway were negligible. Understanding the basis of inherent heterogeneity of nitrogenase expression and its origins can inform biotechnology strategies seeking to enhance biological nitrogen fixation. Finally, we speculate on potential benefits of diazotrophic heterogeneity in natural soil environments

Numerical studies of the Lagrangian approach for reconstruction of the conductivity in a waveguide

We consider an inverse problem of reconstructing the conductivity function in a hyperbolic equation using single space-time domain noisy observations of the solution on the backscattering boundary of the computational domain. We formulate our inverse problem as an optimization problem and use Lagrangian approach to minimize the corresponding Tikhonov functional. We present a theorem of a local strong convexity of our functional and derive error estimates between computed and regularized as well as exact solutions of this functional, correspondingly. In numerical simulations we apply domain decomposition finite element-finite difference method for minimization of the Lagrangian. Our computational study shows efficiency of the proposed method in the reconstruction of the conductivity function in three dimensions