Regulation of the vapBC-1 Toxin-Antitoxin Locus in Nontypeable Haemophilus influenzae

Nontypeable Haemophilus influenzae (NTHi) are human-adapted commensal bacteria that can cause a number of chronic mucosal infections, including otitis media and bronchitis. One way for these organisms to survive antibiotic therapy and cause recurrent disease is to stop replicating, as most antimicrobials target essential biosynthetic pathways. Toxin-antitoxin (TA) gene pairs have been shown to facilitate entry into a reversible bacteriostatic state. Characteristically, these operons encode a protein toxin and an antitoxin that associate following translation to form a nontoxic complex, which then binds to and regulates the cognate TA promoter. Under stressful conditions, the labile antitoxin is degraded and the complex disintegrates, freeing the stable toxin to facilitate growth arrest. How these events affected the regulation of the TA locus, as well as how the transcription of the operon was subsequently returned to its normal state upon resumption of growth, was not fully understood. Here we show that expression of the NTHi vapBC-1 TA locus is repressed by a complex of VapB-1 and VapC-1 under conditions favorable for growth, and activated by the global transactivator Factor for Inversion Stimulation (Fis) upon nutrient upshift from stationary phase. Further, we demonstrate for the first time that the VapC-1 toxin alone can bind to its cognate TA locus control region and that the presence of VapB-1 directs the binding of the VapBC-1 complex in the transcriptional regulation of vapBC-1

Pervasive melt percolation reactions in ultra-depleted refractory harzburgites at the Mid-Atlantic Ridge, 15° 20′N : ODP Hole 1274A

Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Contributions to Mineralogy and Petrology 153 (2007): 303-319, doi:10.1007/s00410-006-0148-6.ODP Leg 209 Site 1274 mantle peridotites are highly refractory in terms of lack of residual clinopyroxene, olivine Mg# (up to 0.92) and spinel Cr# (~0.5), suggesting high degree of partial melting (>20%). Detailed studies of their microstructures show that they have extensively reacted with a pervading intergranular melt prior to cooling in the lithosphere, leading to crystallization of olivine, clinopyroxene and spinel at the expense of orthopyroxene. The least reacted harzburgites are too rich in orthopyroxene to be simple residues of low-pressure (spinel field) partial melting. Cu-rich sulfides that precipitated with the clinopyroxenes indicate that the intergranular melt was generated by no more than 12% melting of a MORB mantle or by more extensive melting of a clinopyroxene-rich lithology. Rare olivine-rich lherzolitic domains, characterized by relics of coarse clinopyroxenes intergrown with magmatic sulfides, support the second interpretation. Further, coarse and intergranular clinopyroxenes are highly depleted in REE, Zr and Ti. A two-stage partial melting/melt-rock reaction history is proposed, in which initial mantle underwent depletion and refertilization after an earlier high pressure (garnet field) melting event before upwelling and remelting beneath the present-day ridge. The ultra-depleted compositions were acquired through melt re-equilibration with residual harzburgites.Funding for this research was provided by Centre National de la Recherche Scientifique-Institut National des Sciences de l’Univers (Programme Dynamique et Evolution de la Terre Interne)

Origin and ascent history of unusually crystal-rich alkaline basaltic magmas from the western Pannonian Basin

The last eruptions of the monogenetic Bakony-Balaton Highland Volcanic Field (western Pannonian Basin, Hungary) produced unusually crystal- and xenolith-rich alkaline basalts which are unique among the alkaline basalts of the Carpathian- Pannonian Region. Similar alkaline basalts are only rarely known in other volcanic fields of the world. These special basaltic magmas fed the eruptions of two closely located volcanic centres: the Bondoró-hegy and the Füzes-tó scoria cone. Their uncommon enrichment in diverse crystals produced unique rock textures and modified original magma compositions (13.1-14.2 wt.% MgO, 459-657 ppm Cr, 455-564 ppm Ni contents). Detailed mineral-scale textural and chemical analyses revealed that the Bondoró-hegy and Füzes-tó alkaline basaltic magmas have a complex ascent history, and that most of their minerals (~30 vol.% of the rocks) represent foreign crystals derived from different levels of the underlying lithosphere. The most abundant xenocrysts, olivine, orthopyroxene, clinopyroxene and spinel, were incorporated from different regions and rock types of the subcontinental lithospheric mantle. Megacrysts of clinopyroxene and spinel could have originated from pegmatitic veins / sills which probably represent magmas crystallized near the crust-mantle boundary. Green clinopyroxene xenocrysts could have been derived from lower crustal mafic granulites. Minerals that crystallized in situ from the alkaline basaltic melts (olivine with Cr-spinel inclusions, clinopyroxene, plagioclase, Fe-Ti oxides) are only represented by microphenocrysts and overgrowths on the foreign crystals. The vast amount of peridotitic (most common) and mafic granulitic materials indicates a highly effective interaction between the ascending magmas and wall rocks at lithospheric mantle and lower crustal levels. However, fragments from the middle and upper crust are absent from the studied basalts, suggesting a change in the style (and possibly rate) of magma ascent in the crust. These xenocryst- and xenolith-rich basalts yield divers tools for estimating magma ascent rate that is important for hazard forecasting in monogenetic volcanic fields. According to the estimated ascent rates, the Bondoró-hegy and Füzes-tó alkaline basaltic magmas could have reached the surface within hours to few days, similarly to the estimates for other eruptive centres in the Pannonian Basin which were fed by "normal" (crystal- and xenolith-poor) alkaline basalts

Earth: Atmospheric Evolution of a Habitable Planet

Our present-day atmosphere is often used as an analog for potentially habitable exoplanets, but Earth's atmosphere has changed dramatically throughout its 4.5 billion year history. For example, molecular oxygen is abundant in the atmosphere today but was absent on the early Earth. Meanwhile, the physical and chemical evolution of Earth's atmosphere has also resulted in major swings in surface temperature, at times resulting in extreme glaciation or warm greenhouse climates. Despite this dynamic and occasionally dramatic history, the Earth has been persistently habitable--and, in fact, inhabited--for roughly 4 billion years. Understanding Earth's momentous changes and its enduring habitability is essential as a guide to the diversity of habitable planetary environments that may exist beyond our solar system and for ultimately recognizing spectroscopic fingerprints of life elsewhere in the Universe. Here, we review long-term trends in the composition of Earth's atmosphere as it relates to both planetary habitability and inhabitation. We focus on gases that may serve as habitability markers (CO2, N2) or biosignatures (CH4, O2), especially as related to the redox evolution of the atmosphere and the coupled evolution of Earth's climate system. We emphasize that in the search for Earth-like planets we must be mindful that the example provided by the modern atmosphere merely represents a single snapshot of Earth's long-term evolution. In exploring the many former states of our own planet, we emphasize Earth's atmospheric evolution during the Archean, Proterozoic, and Phanerozoic eons, but we conclude with a brief discussion of potential atmospheric trajectories into the distant future, many millions to billions of years from now. All of these 'Alternative Earth' scenarios provide insight to the potential diversity of Earth-like, habitable, and inhabited worlds.Comment: 34 pages, 4 figures, 4 tables. Review chapter to appear in Handbook of Exoplanet

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

Initial results of coring at Prees, Cheshire Basin, UK (ICDP JET project): towards an integrated stratigraphy, timescale, and Earth system understanding for the Early Jurassic

This is the final version. Available on open access from Copernicus Publications via the DOI in this recordData availability: Full core scan data (https://doi.org/10.5285/91392f09-25d4-454c-aece-56bde0dbf3ba, BGS Core Scanning Facility, 2022) will be available after 1 November 2024 via the Natural Environment Research Council (NERC) National Geoscience Data Centre (https://webapps.bgs.ac.uk/services/ngdc/accessions/index.html#, last access: 12 October 2023). Downhole logging data (https://doi.org/10.5880/ICDP.5065.001​​​​​​​, Wonik, 2023) will be made available via the ICDP (https://www.icdp-online.org/projects/by-continent/europe/jet-uk/, last access: 12 October 2023). The JET Operational Report is published as Hesselbo et al. (2023); full information about the operational dataset, the logging dataset, data availability and the explanatory remarks is available on the ICPD-JET project website: https://www.icdp-online.org/projects/by-continent/europe/jet-uk/ (last access: 12 October 2023). A subset of data, additional biostratigraphic tables, and vector graphics files for Figs. 3–5 are included as the Supplement. Supplementary Data File 1 tabulates the corrected depth scale for Prees 2C. Supplementary Data File 2 summarizes the ammonite-based chronostratigraphy of the Prees 2 cores (ammonite identifications by Kevin N. Page). Supplementary Data File 3 summarizes the ammonite-based chronostratigraphy for the Hettangian to Early Pliensbachian of the Llanbedr (Mochras Farm) borehole (updated by Kevin N. Page). Supplementary Data File 4 tabulates the organic carbon-isotope ratios, TOC, and carbonate content of low-resolution samples taken at the Prees drill site; TOC and carbonate data are calculated using calibration based on portable XRF (Supplementary Data File 5) and a gas source isotope ratio mass spectrometer (Supplementary Data File 6). Supplementary Data File 5 tabulates portable XRF results for bulk rock powders of low-resolution samples taken at the Prees drill site; uncertainties stated in the table are given for the fit to the raw data and do not reflect the true reproducibility of the data. Empty fields indicate values under the detection limit. Sample SSK116001 acted as a repeat sample which was measured 70 times over the course of the data acquisition to determine the repeatability and drift of the instrument. LE stands for “light elements”. Supplementary Data File 6 tabulates gas source isotope ratio mass spectrometry (GS-IRMS) data (oxygen- and carbon-isotope ratios of carbonate as well as carbonate content calculated as calcite) for a set of 24 samples covering the entire core length and reflecting a representative spread of carbonate content. Comparison of GS-IRMS data with p-XRF data was used to create a calibration curve to calculate the carbonate (and TOC) content of all low-resolution samples. Supplementary Data File 7 tabulates pyrolysis data (Rock-Eval 6) for Prees 1 well cuttings and Wilkesley borehole samples. Supplementary Data File 8 contains vector graphics files (.svg) for Figs. 3–5.Drilling for the International Continental Scientific Drilling Program (ICDP) Early Jurassic Earth System and Timescale project (JET) was undertaken between October 2020 and January 2021. The drill site is situated in a small-scale synformal basin of the latest Triassic to Early Jurassic age that formed above the major Permian–Triassic half-graben system of the Cheshire Basin. The borehole is located to recover an expanded and complete succession to complement the legacy core from the Llanbedr (Mochras Farm) borehole drilled through 1967–1969 on the edge of the Cardigan Bay Basin, North Wales. The overall aim of the project is to construct an astronomically calibrated integrated timescale for the Early Jurassic and to provide insights into the operation of the Early Jurassic Earth system. Core of Quaternary age cover and Early Jurassic mudstone was obtained from two shallow partially cored geotechnical holes (Prees 2A to 32.2 m below surface (m b.s.) and Prees 2B to 37.0 m b.s.) together with Early Jurassic and Late Triassic mudstone from the principal hole, Prees 2C, which was cored from 32.92 to 651.32 m (corrected core depth scale). Core recovery was 99.7 % for Prees 2C. The ages of the recovered stratigraphy range from the Late Triassic (probably Rhaetian) to the Early Jurassic, Early Pliensbachian (Ibex Ammonoid Chronozone). All ammonoid chronozones have been identified for the drilled Early Jurassic strata. The full lithological succession comprises the Branscombe Mudstone and Blue Anchor formations of the Mercia Mudstone Group, the Westbury and Lilstock formations of the Penarth Group, and the Redcar Mudstone Formation of the Lias Group. A distinct interval of siltstone is recognized within the Late Sinemurian of the Redcar Mudstone Formation, and the name “Prees Siltstone Member” is proposed. Depositional environments range from playa lake in the Late Triassic to distal offshore marine in the Early Jurassic. Initial datasets compiled from the core include radiography, natural gamma ray, density, magnetic susceptibility, and X-ray fluorescence (XRF). A full suite of downhole logs was also run. Intervals of organic carbon enrichment occur in the Rhaetian (Late Triassic) Westbury Formation and in the earliest Hettangian and earliest Pliensbachian strata of the Redcar Mudstone Formation, where up to 4 % total organic carbon (TOC) is recorded. Other parts of the succession are generally organic-lean, containing less than 1 % TOC. Carbon-isotope values from bulk organic matter have also been determined, initially at a resolution of ∼ 1 m, and these provide the basis for detailed correlation between the Prees 2 succession and adjacent boreholes and Global Stratotype Section and Point (GSSP) outcrops. Multiple complementary studies are currently underway and preliminary results promise an astronomically calibrated biostratigraphy, magnetostratigraphy, and chemostratigraphy for the combined Prees and Mochras successions as well as insights into the dynamics of background processes and major palaeo-environmental changes.ICDPNatural Environment Research Council (NERC)German Research FoundationHungarian Scientific Research FundNational Science Centre, PolandPolish Geological Institut

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study

Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding UK Research and Innovation and National Institute for Health Research