Estimation and validation of InSAR-derived surface displacements at temperate raised peatlands

Peatland surface motion derived from satellite-based Interferometry of Synthetic Aperture Radar (InSAR) is potentially a proxy for groundwater level variations and greenhouse gas emissions from peat soils. Ground validation of these motions at equivalent temporal resolution has proven problematic, either because of limitations of traditional surveying methods or because of limitations with past InSAR time-series approaches. Novel camera-based instrumentation has enabled in-situ measurement of peat surface from mid-2019 to mid-2022 at two large temperate raised bogs undergoing restoration – Cors Fochno and Cors Caron, in mid-Wales, United Kingdom. The cameras provided continuous measurements at sub-millimetre precision and sub-daily temporal resolution. From these data and Sentinel-1 acquisitions spanning mid-2015 to early-2023, we demonstrate that accurate peat surface motion can be derived by InSAR when a combination of interferometric networks with long and short temporal baselines is used. The InSAR time series data closely match the in-situ data at both bogs, and in particular recover well the annual peat surface oscillations of 10-40 mm. Pearson's values for the point-wise correlation of in-situ and InSAR displacements are 0.8–0.9, while 76% of differences are < ±5 mm and 93% are < ±10 mm. RMSE values between multi-annual in-situ and InSAR peat surface displacement rates are ~7 mm·yr−1 and decrease to ∼3.5 mm for individual peat surface motion measurements. Larger differences mainly occur during drought periods. Multi-annual displacement velocities rates based on InSAR indicate long-term subsidence at Cors Caron (maximum −7 mm·yr−1), while Cors Fochno exhibits subsidence at the centre and uplift at the margins (−9 mm·yr−1 to +5 mm·yr−1). Because of the annual peat surface oscillations, however, more robust ground validation of the long-term peat surface motion rates derived from InSAR requires longer time-series of in-situ measurements than are presently available. Nonetheless, the InSAR-derived surface motion rates correlate well spatially with both peat dome elevation and peat thickness. In addition, the annual oscillations in surface motion are synchronous with or lag slightly behind groundwater level changes. A coarse ratio of 10:1 is observed between annual changes in groundwater level and peat surface displacement. Satellite-based InSAR derived from a fusion of short- and long-term temporal baseline networks can thus enable accurate monitoring of hydrologically driven surface motions of moderately degraded to intact temperate raised peatlands

A rise in the frequency of lasR mutant Pseudomonas aeruginosa among keratitis isolates between 1993 and 2021

IntroductionPseudomonas aeruginosa causes vision threatening keratitis. The LasR transcription factor regulates virulence factors in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone. P. aeruginosa isolates with lasR mutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone. A previous study demonstrated 22% (n=101) of P. aeruginosa keratitis isolates from India between 2010 and 2016 were sheen positive lasR mutants, and the sheen phenotype correlated with worse clinical outcomes for patients. In this study, a longitudinal collection of P. aeruginosa keratitis isolates from Eastern North America were screened for lasR mutations by the sheen phenotype and sequencing of the lasR gene.MethodsKeratitis isolates (n=399) were classified by sheen phenotype. The lasR gene was cloned from a subset of isolates, sequenced, and tested for loss of function or dominant-negative status based on an azocasein protease assay. A retrospective chart review compared outcomes of keratitis patients infected by sheen positive and negative isolates.ResultsA significant increase in sheen positive isolates was observed between 1993 and 2021. Extracellular protease activity was reduced among the sheen positive isolates and a defined lasR mutant. Cloned lasR alleles from the sheen positive isolates were loss of function or dominant negative and differed in sequence from previously reported ocular lasR mutant alleles. Retrospective analysis of patient information suggested significantly better visual outcomes for patients infected by sheen positive isolates.DiscussionThese results indicate an increase in lasR mutations among keratitis isolates in the United States and suggest that endemic lasR mutants can cause keratitis

Genetic mechanisms of critical illness in Covid-19.

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs). We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 [Formula: see text] 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 [Formula: see text] 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 [Formula: see text] 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 [Formula: see text] 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P &lt; 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Xylose-Inducible Promoter Tools for <i>Pseudomonas</i> Species and Their Use in Implicating a Role for the Type II Secretion System Protein XcpQ in the Inhibition of Corneal Epithelial Wound Closure

Pseudomonas species are enormously important in human infections, in biotechnology, and as model systems for investigating basic science questions. In this study, we have developed a xylose-inducible promoter system, evaluated it in P. aeruginosa and P. fluorescens , and found it to be suitable for the strong induction of gene expression. Furthermore, we have demonstrated its efficacy in controlled gene expression to show that a type II secretion system protein from P. aeruginosa , XcpQ, is important for host-pathogen interactions in a corneal wound closure model. </jats:p

Generation of Xylose-inducible promoter tools for<i>Pseudomonas</i>species and their use in implicating a role for the Type II secretion system protein XcpQ in inhibition of corneal epithelial wound closure

ABSTRACTTunable control of gene expression is an invaluable tool for biological experiments. In this study, we describe a new xylose-inducible promoter system and evaluate it in bothPseudomonas aeruginosaandP. fluorescens. ThePxutpromoter derived from theP. flurorescens xutoperon was incorporated into a broad host-range pBBR1-based plasmid and compared to theEscherichia coli-derivedPBADpromoter usinggfpas a reporter. GFP-fluorescence from thePxutpromoter was inducible in bothPseudomonasspecies, but not inE. coli,which may facilitate cloning of toxic genes usingE. colito generate plasmids. ThePxutpromoter was expressed at a lower inducer concentration thanPBADinP. fluorescensand highergfplevels were achieved usingPxut. Flow cytometry analysis indicated thatPxutwas more leaky thanPBADin the testedPseudomonasspecies, but was expressed in a higher proportion of cells when induced. D-xylose did not support growth ofP. aeruginosaorP. fluorescensas a sole carbon source and is less expensive than many other commonly used inducers which could facilitate large scale applications. The efficacy of this system aided in demonstrating a role for theP. aeruginosatype II secretion system gene fromxcpQin bacterial inhibition of corneal epithelial cell wound closure. This study introduces a new inducible promoter system for gene expression for use inPseudomonasspecies.ImportancePseudomonasspecies are enormously important in human infections, biotechnology, and as a model system for interrogating basic science questions. In this study we have developed a xylose-inducible promoter system and evaluated it inP. aeruginosaandP. fluorescensand found it to be suitable for the strong induction of gene expression. Furthermore, we have demonstrated its efficacy in controlled gene expression to show that a type 2 secretion system protein fromP. aeruginosa, XcpQ, is important for host-pathogen interactions in a corneal wound closure model.</jats:sec