The Fur regulon in anaerobically grown Salmonella enterica sv. Typhimurium: identification of new Fur targets

<p>Abstract</p> <p>Background</p> <p>The Ferric uptake regulator (Fur) is a transcriptional regulator that controls iron homeostasis in bacteria. Although the regulatory role of Fur in <it>Escherichia coli </it>is well characterized, most of the studies were conducted under routine culture conditions, i.e., in ambient oxygen concentration. To reveal potentially novel aspects of the Fur regulon in <it>Salmonella enterica </it>serovar Typhimurium under oxygen conditions similar to that encountered in the host, we compared the transcriptional profiles of the virulent wild-type strain (ATCC 14028s) and its isogenic Δ<it>fur </it>strain under anaerobic conditions.</p> <p>Results</p> <p>Microarray analysis of anaerobically grown Δ<it>fur S</it>. Typhimurium identified 298 differentially expressed genes. Expression of several genes controlled by Fnr and NsrR appeared to be also dependent on Fur. Furthermore, Fur was required for the activity of the cytoplasmic superoxide disumutases (MnSOD and FeSOD). The regulation of FeSOD gene, <it>sodB</it>, occurred via small RNAs (i.e., the <it>ryhB </it>homologs, <it>rfrA </it>and <it>rfrB</it>) with the aid of the RNA chaperone Hfq. The transcription of <it>sodA </it>was increased in Δ<it>fur; </it>however, the enzyme was inactive due to the incorporation of iron instead of manganese in SodA. Additionally, in Δ<it>fur</it>, the expression of the gene coding for the ferritin-like protein (<it>ftnB</it>) was down-regulated, while the transcription of the gene coding for the nitric oxide (NO^·) detoxifying flavohemoglobin (<it>hmpA</it>) was up-regulated. The promoters of <it>ftnB </it>and <it>hmpA </it>do not contain recognized Fur binding motifs, which indicated their probable indirect regulation by Fur. However, Fur activation of <it>ftnB </it>was independent of Fnr. In addition, the expression of the gene coding for the histone-like protein, H-NS (<it>hns</it>) was increased in Δ<it>fur</it>. This may explain the observed down-regulation of the <it>tdc </it>operon, responsible for the anaerobic degradation of threonine, and <it>ftnB </it>in Δ<it>fur</it>.</p> <p>Conclusions</p> <p>This study determined that Fur is a positive factor in <it>ftnB </it>regulation, while serving to repress the expression of <it>hmpA</it>. Furthermore, Fur is required for the proper expression and activation of the antioxidant enzymes, FeSOD and MnSOD. Finally, this work identified twenty-six new targets of Fur regulation, and demonstrates that H-NS repressed genes are down-regulated in Δ<it>fur</it>.</p

Analysis of the ArcA regulon in anaerobically grown Salmonella enterica sv. Typhimurium

<p>Abstract</p> <p>Background</p> <p><it>Salmonella enterica </it>serovar Typhimurium (<it>S</it>. Typhimurium) is a Gram-negative pathogen that must successfully adapt to the broad fluctuations in the concentration of dissolved dioxygen encountered in the host. In <it>Escherichia coli</it>, ArcA (Aerobic Respiratory Control) helps the cells to sense and respond to the presence of dioxygen. The global role of ArcA in <it>E. coli </it>is well characterized; however, little is known about its role in anaerobically grown <it>S</it>. Typhimurium.</p> <p>Results</p> <p>We compared the transcriptional profiles of the virulent wild-type (WT) strain (ATCC 14028s) and its isogenic <it>arcA </it>mutant grown under anaerobic conditions. We found that ArcA directly or indirectly regulates 392 genes (8.5% of the genome); of these, 138 genes are poorly characterized. Regulation by ArcA in <it>S</it>. Typhimurium is similar, but distinct from that in <it>E</it>. <it>coli</it>. Thus, genes/operons involved in core metabolic pathways (e.g., succinyl-CoA, fatty acid degradation, cytochrome oxidase complexes, flagellar biosynthesis, motility, and chemotaxis) were regulated similarly in the two organisms. However, genes/operons present in both organisms, but regulated differently by ArcA in <it>S</it>. Typhimurium included those coding for ethanolamine utilization, lactate transport and metabolism, and succinate dehydrogenases. <it>Salmonella</it>-specific genes/operons regulated by ArcA included those required for propanediol utilization, flagellar genes (<it>mcpAC</it>, <it>cheV</it>), Gifsy-1 prophage genes, and three SPI-3 genes (<it>mgtBC</it>, <it>slsA</it>, STM3784). In agreement with our microarray data, the <it>arcA </it>mutant was non-motile, lacked flagella, and was as virulent in mice as the WT. Additionally, we identified a set of 120 genes whose regulation was shared with the anaerobic redox regulator, Fnr.</p> <p>Conclusion(s)</p> <p>We have identified the ArcA regulon in anaerobically grown <it>S</it>. Typhimurium. Our results demonstrated that in <it>S</it>. Typhimurium, ArcA serves as a transcriptional regulator coordinating cellular metabolism, flagella biosynthesis, and motility. Furthermore, ArcA and Fnr share in the regulation of 120 <it>S</it>. Typhimurium genes.</p

Spatially heterogeneous argon-isotope systematics and apparent ⁴⁰Ar/³⁹Ar ages in perlitised obsidian

In situ laser ablation Ar-isotope analyses of variably hydrated and devitrified obsidian from the ~ 27 Ma Cochetopa Dome, San Juan, USA, reveal complex interplay between degassing of initial Ar and absorption of atmospheric Ar. These processes have locally modified the Ar-isotope composition of the obsidian and led to spurious, spatially-heterogeneous Ar-isotope and 40Ar/39Ar age data. Small perlite beads exhibit older apparent Ar-ages at the rims than the cores. This is interpreted as an apparent excess of 40Ar at the rims, produced either by a) diffusion of excess 40Ar into the bead during flushing of the lava with excess 40Ar-bearing volcanic gas, or by b) isotopic fractionation during degassing of initial Ar, causing preferential loss of 36Ar over 40Ar at the bead rims. The second interpretation is favoured by a relative enrichment of 36Ar in the core of a perlite bead along a microlite-free (poorly degassed) flow band, and by a lack of age variation in a larger, fresh, well-degassed perlite bead. These isotopic gradients were later overprinted during glass hydration by absorption of Ar with near-atmospheric composition, resulting in elevated 36Ar and reduced radiogenic 40Ar* yields at the rims of perlite beads. These complex interactions essentially represent the mixing of three distinct Ar reservoirs: initial trapped Ar that may or may not be fractionated, an isotopically atmospheric Ar component introduced during hydration, and radiogenic 40Ar*. Such reservoir mixing is the underlying reason for poor correlations on isotope correlation diagrams and the difficulties in validating the composition of the non-radiogenic Ar component. We thus suggest that high 36Ar yields are a combination of the incomplete degassing of initial (possibly magmatic) Ar and the gain of Ar during interaction between the obsidian and meteoric/atmospheric fluids. Our analyses emphasise the challenging nature of 40Ar/39Ar dating obsidian samples, but also point to possible solutions by careful sample characterisation and selection of highly degassed samples

Aerosol delivery to ventilated newborn infants: historical challenges and new directions

There are several aerosolized drugs which have been used in the treatment of neonatal respiratory illnesses, such as bronchodilators, diuretics, and surfactants. Preclinical in vitro and in vivo studies identified a number of variables that affect aerosol efficiency, including particle size, aerosol flows, nebulizer choice, and placement. Nevertheless, an optimized aerosol drug delivery system for mechanically ventilated infants still does not exist. Increasing interest in this form of drug delivery requires more controlled and focused research of drug/device combinations appropriate for the neonatal population. In the present article, we review the research that has been conducted thus far and discuss the next steps in developing the optimal aerosol delivery system for use in mechanically ventilated neonates

Exploring PERMA in spectator sport: Applying positive psychology to examine the individual-level benefits of sport consumption

Sport spectating provides numerous benefits for sport organisations and individuals. In this paper we use a positive psychology approach to examine the individual-level benefits of sport consumption in order to investigate the activation of five domains of well-being: positive emotions, engagement, relationships, meaning, and accomplishment (PERMA). Using a two-study panel research design, we collected qualitative data from a sample of Australian Rules Football consumers. In the first study, we explored how the PERMA domains were activated during the season. Study two included a follow-up interview with eight initial respondents in the off-season. We found evidence of four PERMA domains that were activated in the sport spectator context by a variety of consumer experiences. The emergence of these domains in both studies suggests sport marketers would benefit from actions including: creating more social spaces within their stadiums, hosting regular off-season events, and creating social-media based competitions which promote fan engagement and interactions throughout the calendar year

Social Justice and Technocracy: Tracing the Narratives of Inclusive Education in the United States

Over the past two decades, the percentage of American students with disabilities educated in general classrooms with their nondisabled peers has risen by approximately fifty percent. This gradual but steady policy shift has been driven by two distinct narratives of organisational change. The social justice narrative espouses principles of equality and caring across human differences. The narrative of technocracy creates top-down, administrative pressure through hierarchical systems based on quantitative performance data. This article examines these two primary policy narratives of inclusive education in the United States, exploring the conceptual features of each and initiating an analysis of their application in the public schools

Comparative Transmissibility of SARS-CoV-2 Variants Delta and Alpha in New England, USA

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant quickly rose to dominance in mid-2021, displacing other variants, including Alpha. Studies using data from the United Kingdom and India estimated that Delta was 40-80% more transmissible than Alpha, allowing Delta to become the globally dominant variant. However, it was unclear if the ostensible difference in relative transmissibility was due mostly to innate properties of Delta\u27s infectiousness or differences in the study populations. To investigate, we formed a partnership with SARS-CoV-2 genomic surveillance programs from all six New England US states. By comparing logistic growth rates, we found that Delta emerged 37-163% faster than Alpha in early 2021 (37% Massachusetts, 75% New Hampshire, 95% Maine, 98% Rhode Island, 151% Connecticut, and 163% Vermont). We next computed variant-specific effective reproductive numbers and estimated that Delta was 58-120% more transmissible than Alpha across New England (58% New Hampshire, 68% Massachusetts, 76% Connecticut, 85% Rhode Island, 98% Maine, and 120% Vermont). Finally, using RT-PCR data, we estimated that Delta infections generate on average ∼6 times more viral RNA copies per mL than Alpha infections. Overall, our evidence indicates that Delta\u27s enhanced transmissibility could be attributed to its innate ability to increase infectiousness, but its epidemiological dynamics may vary depending on the underlying immunity and behavior of distinct populations

Comparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA.

The SARS-CoV-2 Delta variant rose to dominance in mid-2021, likely propelled by an estimated 40%-80% increased transmissibility over Alpha. To investigate if this ostensible difference in transmissibility is uniform across populations, we partner with public health programs from all six states in New England in the United States. We compare logistic growth rates during each variant\u27s respective emergence period, finding that Delta emerged 1.37-2.63 times faster than Alpha (range across states). We compute variant-specific effective reproductive numbers, estimating that Delta is 63%-167% more transmissible than Alpha (range across states). Finally, we estimate that Delta infections generate on average 6.2 (95% CI 3.1-10.9) times more viral RNA copies per milliliter than Alpha infections during their respective emergence. Overall, our evidence suggests that Delta\u27s enhanced transmissibility can be attributed to its innate ability to increase infectiousness, but its epidemiological dynamics may vary depending on underlying population attributes and sequencing data availability

Work productivity in rhinitis using cell phones:The MASK pilot study

Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI: AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS-work >50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P <0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI: AS (Rho=0.53, P <0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptom

Evidence for Type Ia Supernova Diversity from Ultraviolet Observations with the Hubble Space Telescope

We present ultraviolet (UV) spectroscopy and photometry of four Type Ia supernovae (SNe 2004dt, 2004ef, 2005M, and 2005cf) obtained with the UV prism of the Advanced Camera for Surveys on the Hubble Space Telescope. This dataset provides unique spectral time series down to 2000 Angstrom. Significant diversity is seen in the near maximum-light spectra (~ 2000--3500 Angstrom) for this small sample. The corresponding photometric data, together with archival data from Swift Ultraviolet/Optical Telescope observations, provide further evidence of increased dispersion in the UV emission with respect to the optical. The peak luminosities measured in uvw1/F250W are found to correlate with the B-band light-curve shape parameter dm15(B), but with much larger scatter relative to the correlation in the broad-band B band (e.g., ~0.4 mag versus ~0.2 mag for those with 0.8 < dm15 < 1.7 mag). SN 2004dt is found as an outlier of this correlation (at > 3 sigma), being brighter than normal SNe Ia such as SN 2005cf by ~0.9 mag and ~2.0 mag in the uvw1/F250W and uvm2/F220W filters, respectively. We show that different progenitor metallicity or line-expansion velocities alone cannot explain such a large discrepancy. Viewing-angle effects, such as due to an asymmetric explosion, may have a significant influence on the flux emitted in the UV region. Detailed modeling is needed to disentangle and quantify the above effects.Comment: 17 pages, 13 figures, accepted by Ap