Positive feedback and noise activate the stringent response regulator Rel in mycobacteria

Phenotypic heterogeneity in an isogenic, microbial population enables a subset of the population to persist under stress. In mycobacteria, stresses like nutrient and oxygen deprivation activate the stress response pathway involving the two-component system MprAB and the sigma factor, SigE. SigE in turn activates the expression of the stringent response regulator, rel. The enzyme polyphosphate kinase 1 (PPK1) regulates this pathway by synthesizing polyphosphate required for the activation of MprB. The precise manner in which only a subpopulation of bacterial cells develops persistence, remains unknown. Rel is required for mycobacterial persistence. Here we show that the distribution of rel expression levels in a growing population of mycobacteria is bimodal with two distinct peaks corresponding to low (L) and high (H) expression states, and further establish that a positive feedback loop involving the mprAB operon along with stochastic gene expression are responsible for the phenotypic heterogeneity. Combining single cell analysis by flow cytometry with theoretical modeling, we observe that during growth, noise-driven transitions take a subpopulation of cells from the L to the H state within a "window of opportunity" in time preceding the stationary phase. We find evidence of hysteresis in the expression of rel in response to changing concentrations of PPK1. Our results provide, for the first time, evidence that bistability and stochastic gene expression could be important for the development of "heterogeneity with an advantage" in mycobacteria.Comment: Accepted for publication in PLoS On

Genotyping of Streptococcus agalactiae (group B streptococci) isolated from vaginal and rectal swabs of women at 35-37 weeks of pregnancy

<p>Abstract</p> <p>Background</p> <p>Group B streptococci (GBS), or <it>Streptococcus agalactiae</it>, are the leading bacterial cause of meningitis and bacterial sepsis in newborns. Here we compared different culture media for GBS detection and we compared the occurrence of different genotypes and serotypes of GBS isolates from the vagina and rectum.</p> <p>Methods</p> <p><it>Streptococcus agalactiae </it>was cultured separately from both rectum and vagina, for a total of 150 pregnant women, i) directly onto Columbia CNA agar, or indirectly onto ii) Granada agar resp. iii) Columbia CNA agar, after overnight incubation in Lim broth.</p> <p>Results</p> <p>Thirty six women (24%) were colonized by GBS. Of these, 19 harbored GBS in both rectum and vagina, 9 only in the vagina and 8 exclusively in the rectum. The combination of Lim broth and subculture on Granada agar was the only culture method that detected all GBS positive women. Using RAPD-analysis, a total of 66 genotypes could be established among the 118 isolates from 32 women for which fingerprinting was carried out. Up to 4 different genotypes in total (rectal + vaginal) were found for 4 women, one woman carried 3 different genotypes vaginally and 14 women carried two 2 different genotypes vaginally. Only two subjects were found to carry strains with the same genotype, although the serotype of both of these strains was different.</p> <p>Eighteen of the 19 subjects with GBS at both sites had at least one vaginal and one rectal isolate with the same genotype.</p> <p>We report the presence of two to four different genotypes in 22 (61%) of the 36 GBS positive women and the presence of identical genotypes in both sites for all women but one.</p> <p>Conclusion</p> <p>The combination of Lim broth and subculture on Granada medium provide high sensitivity for GBS detection from vaginal and rectal swabs from pregnant women. We established a higher genotypic diversity per individual than other studies, with up to four different genotypes among a maximum of 6 isolates per individual picked. Still, 18 of the 19 women with GBS from both rectum and vagina had at least one isolate from each sampling site with the same genotype.</p

Lange-termijnveranderingen van chemie en biologie van vennen in relatie tot veranderingen van atmosferische depositie

verkrijgbaar bij AquaSense TEC, Martine van Nugteren Postbus 95125, 1090 HC Amsterdam fax 020 - 592 2249De voornaamste veranderingen in de chemie en biologie van drie vennen in de loop van 16 jaar zijn gemeten. Deze gegevens werden vergeleken met oudere waarnemingen (1912-1970) om verbanden te leggen tussen deze veranderingen en de veranderingen van de atmosferische depositie, in het bijzonder van zwavel- en stikstofverbindingen. Modelberekeningen werden toegepast. Tussen 1979 en 1994 is in twee van de drie onderzochte vennen het sulfaatgehalte sterk gedaald. Uit modelberekingen bleek dat dit veroorzaakt werd door de sterke afname van depositie van zwavelverbindingen in die periode. Dit had zeer positieve gevolgen voor de soortensamenstelling van de kiezelwieren, die sterk indicatief zijn voor de verzuringstoestand. Uit de modelberekingen blijkt dat er geen goede meetresultaten zijn van de depositie van stikstofverbindingen op oppervlaktewateren. Het is zeer noodzakelijk dat hiervoor metingen worden uitgevoerd.Major changes in chemistry and biota of three moorland pools have been registered in the period 1979 - 1994 in view of the acidification and eutrophication by atmospheric deposition. The data have been compared with data from the period 1912-1970. By model calculations the changes in these periods were studied with regard to particularly sulphur and nitrogen compounds. Recommendations for future monitoring are made, tailored to the needs of environmental policy.DGM/L

Image retrieval based on effective feature extraction and diffusion process

Feature extraction and its matching are two critical tasks in image retrieval. This paper presents a new methodology for content-based image retrieval by integrating three features, and then optimizing feature metric by diffusion process. To boost the discriminative power, the color histogram, local directional pattern, and dense SIFT features based on bag of features (BoF) are selected. Then diffusion process is applied to seek a global optimization for image matching based on fused multi-features. The diffusion process can capture the intrinsic manifold structure on a dataset, and thus enhance the overall retrieval performance significantly. Finally, a new search strategy is explored to make the diffusion process work even better when the number of retrieval images is small. In order to validate our proposed approach, four benchmark databases are used, and the results of experiments show that the proposed approach outperforms all other existing approaches

A new fusion approach for content based image retrieval with color histogram and local directional pattern

In this paper, we propose a novel color image retrieval approach by using an effective fusion of two types of histograms extracted from color and local directional pattern (LDP), respectively. First, we describe the extraction process of color histogram and LDP. Secondly we present these two features and then develop an effective fusion procedure including feature normalization and a new similarity metric. Thirdly, this new approach is validated after extensive comparisons with several existing state of the art approaches on two benchmark datasets including the Wang’s dataset and large size of the Corel-10000 dataset. Finally, a friendly interface for this proposed retrieval system is designed and used to show some retrieval results