Physiological function as regulation of large transcriptional programs: the cellular response to genotoxic stress

The responses to ionizing radiation and other genotoxic environmental stresses are complex and are regulated by a number of overlapping molecular pathways. One such stress signaling pathway involves p53, which regulates the expression of over 100 genes already identified. It is also becoming increasingly apparent that the pattern of stress gene expression has some cell type specificity. It may be possible to exploit these differences in stress gene responsiveness as molecular markers through the use of a combined informatics and functional genomics approach. The techniques of microarray analysis potentially offer the opportunity to monitor changes in gene expression across the entire set of expressed genes in a cell or organism. As an initial step in the development of a functional genomics approach to stress gene analysis, we have recently demonstrated the utility of cDNA microarray hybridization to measure radiation-stress gene responses and identified a number of previously unknown radiation-regulated genes. The responses of some of these genes to DNA-damaging agents vary widely in cell lines from different tissues of origin and different genetic backgrounds. While this again highlights the importance of a cellular context to genotoxic stress responses, it also raises the prospect of expression-profiling of cell lines, tissues, and tumors. Such profiles may have a predictive value if they can define regions of ‘expression space’ that correlate with important endpoints, such as response to cancer therapy regimens, or identification of exposures to environmental toxins.     

Mapping of noninvasion TnphoA mutations on the Escherichia coli O18:K1:H7 chromosome

Abstract The most virulent newborn meningitis-associated Escherichia coli are of the serotype O18: K1: H7. We previously isolated a large number of E. coli O18:K1:H7 mutants resulting from transposon Tn phoA mutagenesis that fail to invade brain microvascular endothelial cells. We have now determined the locations of 45 independent insertions. Twelve were localized to the 98 min region, containing a 120 kb segment that is characteristic of E. coli O18:K1:H7. Another, the previously described insertion ibe -10::Tn phoA , was localized to the 87 min region, containing a 20 kb segment found in this E. coli . These noninvasion mutations may define new O18:K1:H7 pathogenicity islands carrying genes for penetration of the blood-brain barrier of newborn mammals.     

Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients

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Candidate Cancer Driver Mutations in Distal Regulatory Elements and Long-Range Chromatin Interaction Networks

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Domestication of the Emblematic White Cheese-Making Fungus Penicillium camemberti and Its Diversification into Two Varieties

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A critical rebuttal of the proposed division of the genus Arcobacter into six genera using comparative genomic,phylogenetic, and phenotypic criteria

The proposal to restructure the genus Arcobacter into six distinct genera was critically examined using: comparative analyses of up to 80 Epsilonproteobacterial genome sequences (including 26 arcobacters); phylogenetic analyses of three housekeeping genes and also 342 core genes; and phenotypic criteria. Genome sequences were analysed with tools to calculate Percentage of Conserved Proteins, Average Amino-acid Identity, BLAST-based Average Nucleotide Identity, in silico DNA–DNA hybridisation values, genome-wide Average Nucleotide Identity, Alignment Fractions and G + C percentages. Genome analyses revealed the genus Arcobacter sensu lato to be relatively homogenous, and phylogenetic analyses clearly distinguished the group from other Epsilonproteobacteria. Genomic distinction of the genera proposed by Pérez-Cataluña et al. [2018] was not supported by any of the measures used and a subsequent risk of strain misidentification clearly identified. Similarly, phenotypic analyses supported the delineation of Arcobacter sensu lato but did not justify the position of the proposed novel genera. The present polyphasic taxonomic study strongly supports the continuance of the classification of “aerotolerant campylobacters” as Arcobacter and refutes the proposed genus-level subdivision of Pérez-Cataluña et al. [2018].