Gene expression can be noisy, as can the growth of single cells. Such cell-to-cell variation has been implicated in survival strategies for bacterial populations. However, it remains unclear how single cells couple gene expression with growth to implement these strategies. Here, we show how noisy expression of a key stress-response regulator, RpoS, allows E. coli to modulate its growth dynamics to survive future adverse environments. We reveal a dynamic positive feedback loop between RpoS and growth rate that produces multi-generation RpoS pulses. We do so experimentally using single-cell, time-lapse microscopy and microfluidics and theoretically with a stochastic model. Next, we demonstrate that E. coli prepares for sudden stress by entering prolonged periods of slow growth mediated by RpoS. This dynamic phenotype is captured by the RpoS-growth feedback model. Our synthesis of noisy gene expression, growth, and survival paves the way for further exploration of functional phenotypic variability.

To determine the degree of association of age at school entry with reading failure, the Basic Skills Assessment Program (BSAP) reading test scores for all South Carolina students in Grades 1, 2, 3, and 6 were analyzed. The study found that the proportions of students failing to meet the standards on BSAP reading tests were higher for younger, male, black, and lunch-assisted students than for older, female, non-black, and full-paying students. Adjusted odds ratios from logistic regression indicated that risk of failure for younger students was greater than for older students in all grades when controlled for race, sex, and lunch-payment status (α = .05). However, the odds ratios as well as estimates of attributable risk showed that the effect of age at school entry, though significant through Grade 6, was minor compared to the risk associated with race, sex, or lunch-payment status.

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Background Transcription in mammalian cells is a complex stochastic process involving shuttling of polymerase between genes and phase-separated liquid condensates. It occurs in bursts, which results in vastly different numbers of an mRNA species in isogenic cell populations. Several factors contributing to transcriptional bursting have been identified, usually classified as intrinsic, in other words local to single genes, or extrinsic, relating to the macroscopic state of the cell. However, some possible contributors have not been explored yet. Here, we focus on processes at the 3 ′ and 5 ′ ends of a gene that enable reinitiation of transcription upon termination. Results Using Bayesian methodology, we measure the transcriptional bursting in inducible transgenes, showing that perturbation of polymerase shuttling typically reduces burst size, increases burst frequency, and thus limits transcriptional noise. Analysis based on paired-end tag sequencing (PolII ChIA-PET) suggests that this effect is genome wide. The observed noise patterns are also reproduced by a generative model that captures major characteristics of the polymerase flux between the ends of a gene and a phase-separated compartment. Conclusions Interactions between the 3 ′ and 5 ′ ends of a gene, which facilitate polymerase recycling, are major contributors to transcriptional noise.

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National governments spend significant amounts of money supporting public research. However, in an era where the international economic climate has led to budget cuts, policymakers increasingly are looking to justify the returns from public investments, including in science and innovation. The so-called 'impact agenda' which has emerged in many countries around the world is part of this response; an attempt to understand and articulate for the public what benefits arise from the research that is funded. The United Kingdom is the most progressed in implementing this agenda and in 2014 the national research assessment exercise, the Research Excellence Framework, for the first time included the assessment of research impact as a component. For the first time within a dual funding system, funding would be awarded not only on the basis of the academic quality of research, but also on the wider impacts of that research. In this paper we outline the context and approach taken by the UK government, along with some of the core challenges that exist in implementing such an exercise. We then synthesise, together for the first time, the results of the only two national evaluations of the exercise and offer reflections for future exercises both in the UK and internationally.

When uninfected mouse cell DNA is cleaved with restriction endonuclease EcoRll, a DNA fragment of 14.0 kilobases can be identified by hybridization to cloned DNA containing sarcoma specific sequences of Moloney mouse sarcoma virus (M-MSVsr). The Murine sarcoma viruses can induce cellular transformation in cultured fibroblasts and fibrosarcomas in animals (1). Moloney murine sarcoma virus (M-MSV) was isolated by passage of Moloney murine leukemia virus (M-MLV) through BALB/c mice (2). The genome of a M-MSV (clone 124) has been extensively analyzed and appears to have been derived by recombination between M-MLV and cellular genes (1,3,4). Hybridization studies have shown the presence of MSV-specific nucleotide sequences in the cellular DNA obtained from uninfected mouse cells (5). Recently, we have cloned unintegrated M-MSV circular DNA in bacteriophage X (6). A DNA fragment encompassing the sarcoma (src) specific region of the M-MSV genome was further subcloned in bacterial plasmid pBR322. The plasmid containing the M-MSVsrc fragment showed no hybridization to the helper M-MLV genomic RNA. When uninfected mouse cell DNA was cleaved with restriction endonuclease EcoRI and analyzed on Southern blotting gels (7) by hybridization to cloned M-MSV~c probe, a band migrating with a size of 14.0 kilobases (kb) can be detected. The 14.0-kb band contained the entire M-MSVrc specific sequences. We have cloned the 14.0-kb EcoRI fragment in bacteriophage X and characterized it by restriction endonuclease mapping, electron microscopy, and nuclease S1 mapping. The results indicate that the 14.0-kb EcoRI fragment contains an uninterrupted stretch of about 1000 nucleotides that is homologous to the src specific region of the M-MSV genome.MATERIALS AND METHODS Preparation of High Molecular Weight Cellular DNA. The procedure described by Van der Putten et al. (8) Cloning. Subcloning of M-MSVsrc specific fragment. Unintegrated M-MSV circular viral DNA was cloned in bacteriophage X and subsequently sublconed in plasmid pBR322 (6). The plasmid (p-MSV-1), containing the entire M-MSV genome and an additional copy of the long terminal redundancy, was cleaved with restriction endonucleases HindIII and Xba I and fractionated on agarose gels. The HindIII/Xba I fragment was excised, DNA was extracted, and a stretch of 20-30 dC residues was incorporated by using terminal transferase. The plasmid pBR322 was cleaved with restriction endonuclease Pst I, and a stretch of 8-20 dG residues was added as described (9). The dC-tailed insert and dG-tailed plasmid were annealed and used to transform Escherichia coli C600SF as described (9). The colonies were screened for drug resistance and ampicillinsensitive, tetracycline-resistant (AmpSTetR) colonies were further screened by hybridization to M-MSV cDNA as described (10

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