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Cellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxia-dependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia.

Our understanding of how the course of opportunistic bacterial infection is influenced by the microenvironment is limited. We demonstrate that the pathogenicity of Pseudomonas aeruginosa strains derived from acute clinical infections is higher than that of strains derived from chronic infections, where tissues are hypoxic. Exposure to hypoxia attenuated the pathogenicity of strains from acute (but not chronic) infections, implicating a role for hypoxia in regulating bacterial virulence. Mass spectrometric analysis of the secretome of P. aeruginosa derived from an acute infection revealed hypoxia-induced repression of multiple virulence factors independent of altered bacterial growth. Pseudomonas aeruginosa lacking the Pseudomonas prolyl-hydroxylase domain–containing protein, which has been implicated in bacterial oxygen sensing, displays reduced virulence factor expression. Furthermore, pharmacological hydroxylase inhibition reduces virulence factor expression and pathogenicity in a murine model of pneumonia. We hypothesize that hypoxia reduces P. aeruginosa virulence at least in part through the regulation of bacterial hydroxylases.

In this paper we propose a technique to adapt a convolutional neural network (CNN) based object counter to additional visual domains and object types while still preserving the original counting function. Domain-specific normalisation and scaling operators are trained to allow the model to adjust to the statistical distributions of the various visual domains. The developed adaptation technique is used to produce a singular patch-based counting regressor capable of counting various object types including people, vehicles, cell nuclei and wildlife. As part of this study a challenging new cell counting dataset in the context of tissue culture and patient diagnosis is constructed. This new collection, referred to as the Dublin Cell Counting (DCC) dataset, is the first of its kind to be made available to the wider computer vision community. State-of-the-art object counting performance is achieved in both the Shanghaitech (parts A and B) and Penguins datasets while competitive performance is observed on the TRANCOS and Modified Bone Marrow (MBM) datasets, all using a shared counting model.