RpoE fine tunes expression of a subset of SsrB-regulated virulence factors in Salmonella enterica serovar Typhimurium

<p>Abstract</p> <p>Background</p> <p>The survival of <it>Salmonella enterica </it>within the intracellular host niche requires highly co-ordinated expression of virulence effectors predominantly regulated by the SsrAB two-component regulatory system. <it>S. enterica </it>serovar Typhimurium mutants lacking the <it>ssrAB </it>genes are avirulent in mice, highlighting the importance of this regulatory system <it>in vivo</it>. Mutants lacking the gene encoding the alternative sigma factor σ^E(<it>rpoE</it>) are also highly attenuated for intracellular survival, pointing to a potential connection with the SsrAB regulatory system.</p> <p>Results</p> <p>In this study we demonstrate that RpoE is involved in fine-tuning the expression of a subset of SsrB-regulated genes found in the <it>Salmonella </it>pathogenicity island-2 (SPI-2) genetic locus that encodes a horizontally acquired type III secretion system, and unlinked genes integrated into this regulon that are required for virulence in host animals.</p> <p>Conclusion</p> <p>These data point to a potential connection between the virulence phenotype of strains lacking <it>ssrB </it>and <it>rpoE</it>, and highlight new transcriptional regulation that might be essential for appropriate temporal and spatial control of the virulence-associated type III secretion system during host infection.</p

Evaluating Equality, Diversity, and Inclusion activities within Creative Industries Clusters: A report from Creative Informatics

In 2018 UK Research and Innovation (UKRI) created the Creative Industries Clusters Programme (CICP), which has funded nine large-scale Creative Research and Development Partnerships (CRDPs) across the UK, including Creative Informatics. Creative Informatics (2018–2024) focuses on supporting the Creative Industries in Edinburgh and the South-East Scotland Region to use data to innovate in the production of goods and services. With a network of over 6000 people, and leading to 352 new and safeguarded jobs, Creative Informatics has had a huge impact on the creative industries in its region. But has this been done in a way that advances Equality, Diversity and Inclusion?This report evaluates the Equality, Diversity &amp; Inclusion (ED&amp;I) activities (based on data published up to July 2023) of Creative Informatics (CI) in the context of other funding, policy and research organisations also operating in the space of the Creative Industries. These organisations are Clwstwr, Bristol + Bath Creative Research + Development, and XR Stories and the associated Research England-funded project, SIGN, which are three other regional beneficiaries of the Creative Industries Clusters Programme (CICP), and the Creative Industries Policy &amp; Evidence Centre, which is also part of the CICP. We also offer an overview of ED&amp;I activities by Creative Scotland as a comparable Scottish funder of the Creative Industries.Each of these organisations publishes its own material about ED&amp;I aims, priorities, actions, accountability and reporting, and in this report we introduce the organisations and their self-stated objectives and targets. We then discuss their data collection activities as part of their monitoring practices as well as their reasons for collecting specific data, their comparisons of these data against benchmarks, and how they incorporate intersectionality. Next we look at the collaborators and beneficiaries of projects funded by these organisations and finally we address three recurring issues raised by many of the organisations: how to achieve continued improvement, change at senior levels, and socio-economic inequalities. All of this is placed in the context of wider ED&amp;I activities within the Creative Industries. After introducing this overview of each organisation's activities, our discussion section draws out some common themes and, finally, we offer some recommendations for how to expand upon the evidence and knowledge already circulating in the Creative Industries

Diversity and inclusion in the data-driven creative economy:An analysis of Creative Industries Clusters Programme approaches

What is the role of data in our understanding of diversity and inclusion in the creative economy? How can decision-making be supported by the available data we have about the different characteristics of those employed, and innovating, in the creative economy? Focusing on the activities of Creative Informatics and other clusters in the Creative Industries Clusters Programme, this chapter will establish the importance of attending to the intersection of race, class and gender in the creative sectors and show how data can inform our understanding of mechanisms of exclusion in creative occupations. It will particularly focus on what we know about the makeup of the data-driven cultural economy and make recommendations on what we must do to ensure that both a diverse workforce and audience can engage in digital aspects of the creative industries

So near and yet so far: Harmonic radar reveals reduced homing ability of nosema infected honeybees

Pathogens may gain a fitness advantage through manipulation of the behaviour of their hosts. Likewise, host behavioural changes can be a defence mechanism, counteracting the impact of pathogens on host fitness. We apply harmonic radar technology to characterize the impact of an emerging pathogen - Nosema ceranae (Microsporidia) - on honeybee (Apis mellifera) flight and orientation performance in the field. Honeybees are the most important commercial pollinators. Emerging diseases have been proposed to play a prominent role in colony decline, partly through sub-lethal behavioural manipulation of their hosts. We found that homing success was significantly reduced in diseased (65.8%) versus healthy foragers (92.5%). Although lost bees had significantly reduced continuous flight times and prolonged resting times, other flight characteristics and navigational abilities showed no significant difference between infected and non-infected bees. Our results suggest that infected bees express normal flight characteristics but are constrained in their homing ability, potentially compromising the colony by reducing its resource inputs, but also counteracting the intra-colony spread of infection. We provide the first high-resolution analysis of sub-lethal effects of an emerging disease on insect flight behaviour. The potential causes and the implications for both host and parasite are discussed

So near and yet so far: Harmonic radar reveals reduced homing ability of nosema infected honeybees

Pathogens may gain a fitness advantage through manipulation of the behaviour of their hosts. Likewise, host behavioural changes can be a defence mechanism, counteracting the impact of pathogens on host fitness. We apply harmonic radar technology to characterize the impact of an emerging pathogen - Nosema ceranae (Microsporidia) - on honeybee (Apis mellifera) flight and orientation performance in the field. Honeybees are the most important commercial pollinators. Emerging diseases have been proposed to play a prominent role in colony decline, partly through sub-lethal behavioural manipulation of their hosts. We found that homing success was significantly reduced in diseased (65.8%) versus healthy foragers (92.5%). Although lost bees had significantly reduced continuous flight times and prolonged resting times, other flight characteristics and navigational abilities showed no significant difference between infected and non-infected bees. Our results suggest that infected bees express normal flight characteristics but are constrained in their homing ability, potentially compromising the colony by reducing its resource inputs, but also counteracting the intra-colony spread of infection. We provide the first high-resolution analysis of sub-lethal effects of an emerging disease on insect flight behaviour. The potential causes and the implications for both host and parasite are discussed

Analysis of phosphatases in ER-negative breast cancers identifies DUSP4 as a critical regulator of growth and invasion.

Estrogen receptor (ER)-negative cancers have a poor prognosis, and few targeted therapies are available for their treatment. Our previous analyses have identified potential kinase targets critical for the growth of ER-negative, progesterone receptor (PR)-negative and HER2-negative, or "triple-negative" breast cancer (TNBC). Because phosphatases regulate the function of kinase signaling pathways, in this study, we investigated whether phosphatases are also differentially expressed in ER-negative compared to those in ER-positive breast cancers. We compared RNA expression in 98 human breast cancers (56 ER-positive and 42 ER-negative) to identify phosphatases differentially expressed in ER-negative compared to those in ER-positive breast cancers. We then examined the effects of one selected phosphatase, dual specificity phosphatase 4 (DUSP4), on proliferation, cell growth, migration and invasion, and on signaling pathways using protein microarray analyses of 172 proteins, including phosphoproteins. We identified 48 phosphatase genes are significantly differentially expressed in ER-negative compared to those in ER-positive breast tumors. We discovered that 31 phosphatases were more highly expressed, while 11 were underexpressed specifically in ER-negative breast cancers. The DUSP4 gene is underexpressed in ER-negative breast cancer and is deleted in approximately 50&nbsp;% of breast cancers. Induced DUSP4 expression suppresses both in vitro and in vivo growths of breast cancer cells. Our studies show that induced DUSP4 expression blocks the cell cycle at the G1/S checkpoint; inhibits ERK1/2, p38, JNK1, RB, and NFkB p65 phosphorylation; and inhibits invasiveness of TNBC cells. These results suggest that that DUSP4 is a critical regulator of the growth and invasion of triple-negative breast cancer cells

Pathogenic Adaptation of Intracellular Bacteria by Rewiring a Cis-Regulatory Input Function

The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones