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"Williams, Charlotte A."
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Vertical mixing alleviates autumnal oxygen deficiency in the central North Sea
There is an immediate need to better understand and monitor shelf sea dissolved oxygen (O2) concentrations. Here we use high-resolution glider observations of turbulence and O2 concentrations to directly estimate the vertical O2 flux into the bottom mixed layer (BML) immediately before the autumn breakdown of stratification in a seasonally stratified shelf sea. We present a novel method to resolve the oxycline across sharp gradients due to slow optode response time and optode positioning in a flow “shadow zone” on Slocum gliders. The vertical O2 flux to the low-O2 BML was found to be between 2.5 to 6.4 mmol m−2 d−1. Episodic intense mixing events were responsible for the majority (up to 90 %) of this oxygen supply despite making up 40 % of the observations. Without these intense mixing events, BML O2 concentrations would approach ecologically concerning levels by the end of the stratified period. Understanding the driving forces behind episodic mixing and how these may change under future climate scenarios and renewable energy infrastructure is key for monitoring shelf sea health.
Journal Article
Whole-genome sequencing of ocular Chlamydia trachomatis isolates from Gadarif State, Sudan
Background
Trachoma, caused by ocular
Chlamydia trachomatis
, is the leading infectious cause of blindness worldwide. Sudan first reported trachoma in the 1930s and has since been consistently endemic. Ocular
C. trachomatis
previously isolated from trachoma patients in Sudan in 1963 was antigenically identical to an isolate from Saudi Arabia (A/SA1). No contemporary ocular
C. trachomatis
whole genome sequences have been reported from Sudan.
Methods
This study sequenced twenty ocular
C. trachomatis
isolates to improve understanding of pathogen diversity in North-East Africa and examine for genomic variation specific to Sudan, possibly related to the persistence of trachoma in surveyed communities. High quality, whole genome sequences were obtained from 12/20 isolates.
Results
All isolates were serovar A and had
tarP
and
trpA
sequences typical of classical, ocular
C. trachomatis
isolates. The Sudanese isolates formed a closely related subclade within the T2-trachoma clade of
C. trachomatis
phylogeny distinct from geographically disparate ocular isolates, with little intra-population diversity. We found 333 SNPs that were conserved in Sudanese ocular isolates but rare compared to other ocular
C. trachomatis
populations, which were focused in two genomic loci (
CTA0172-CTA0173
and
CTA0482
).
Conclusions
Limited intra-population diversity and geographical clustering of ocular
C. trachomatis
suggests minimal transmission between and slow diversification within trachoma-endemic communities. However, diversity may have been higher pre-treatment in these communities. Over-representation of Sudan-specific SNPs in three genes suggests they may have an impact on
C. trachomatis
growth and transmission in this population.
Journal Article
The tumour microenvironment of pilocytic astrocytoma evolves over time via enrichment for microglia
Pilocytic astrocytoma (PA) is the commonest low-grade tumour affecting children and is frequently experienced as a chronic disease associated with extended treatment, periods of regrowth, and long-term disability. This contrasts with the view of PA as a benign tumour with positive clinical outcomes and raises the fundamental question of biologically driven change over time within these tumours, which will impact diagnosis, stratification, and management. To investigate the molecular, cellular, and pathological stability of PA we performed RNA sequencing, methylation array profiling, immunohistochemistry, and targeted panel DNA sequencing on a cohort of 15 PA patients with matched primary/longitudinal samples at a mean sampling interval of 2.7 years. Through pairwise analysis of primary versus longitudinal tumour samples we identified changes to immune-related pathways within the expression and methylation profiles of longitudinal PA. Further interrogation of these changes revealed an enrichment over time for microglial cell populations, which was validated by immunohistochemistry against common monocyte/microglial markers. Moreover, immunohistochemical characterisation revealed concurrent increases in the expression of M2-like and anti-inflammatory markers. Microglial enrichments were consistent across the cohort and were not adequately explained by a range of potential confounders, including receipt of adjuvant therapy. Taken together, these data challenge the idea of pilocytic astrocytoma as a static entity and indicate that they consistently accumulate microglia over time, potentially co-opting the immune microenvironment towards an anti-inflammatory phenotype that may affect the natural course and treatment response of the tumours.
Journal Article
Application of a new net primary production methodology: a daily to annual-scale data set for the North Sea, derived from autonomous underwater gliders and satellite Earth observation
Shelf seas play a key role in both the global carbon cycle and coastal marine ecosystems through the draw-down and fixing of carbon, as measured through phytoplankton net primary production (NPP). Measuring NPP in situ and extrapolating this to the local, regional, and global scale presents challenges however because of limitations with the techniques utilised (e.g. radiocarbon isotopes), data sparsity, and the inherent biogeochemical heterogeneity of coastal and open-shelf waters. Here, we introduce a new data set generated using a technique based on the synergistic use of in situ glider profiles and satellite Earth observation measurements which can be implemented in a real-time or delayed-mode system (https://doi.org/10.5285/e6974644-2026-0f94-e053-6c86abc00109; Loveday and Smyth, 2022). We apply this system to a fleet of gliders successively deployed over a 19-month time frame in the North Sea, generating an unprecedented fine-scale time series of NPP in the region. At a large scale, this time series gives close agreement with existing satellite-based estimates of NPP for the region and previous in situ estimates. What has not been elucidated before is the high-frequency, small-scale, depth-resolved variability associated with bloom phenology, mesoscale phenomena, and mixed layer dynamics.
Journal Article
Whole-genome Sequencing Provides Data for Stratifying Infection Prevention and Control Management of Nosocomial Influenza A
Influenza A virus causes annual epidemics in humans and is associated with significant morbidity and mortality. Haemagglutinin (HA) and neuraminidase (NA) gene sequencing have traditionally been used to identify the virus genotype, although their utility in detecting outbreak clusters is still unclear. The objective of this study was to determine the utility, if any, of whole-genome sequencing over HA/NA sequencing for infection prevention and control (IPC) in hospitals.
We obtained all clinical samples from influenza (H1N1)-positive patients at the Great Ormond Street Hospital between January and March 2016. Samples were sequenced using targeted enrichment on an Illumina MiSeq sequencer. Maximum likelihood trees were computed for both whole genomes and concatenated HA/NA sequences. Epidemiological data was taken from routine IPC team activity during the period.
Complete genomes were obtained for 65/80 samples from 38 patients. Conventional IPC analysis recognized 1 outbreak, involving 3 children, and identified another potential cluster in the haemato-oncology ward. Whole-genome and HA/NA phylogeny both accurately identified the previously known outbreak cluster. However, HA/NA sequencing additionally identified unrelated strains as part of this outbreak cluster. A whole-genome analysis identified a further cluster of 2 infections that had been previously missed and refuted suspicions of transmission in the haemato-oncology wards.
Whole-genome sequencing is better at identifying outbreak clusters in a hospital setting than HA/NA sequencing. Whole-genome sequencing could provide a faster and more reliable method for outbreak monitoring and supplement routine IPC team work to allow the prevention of transmission.
Journal Article
Norovirus Transmission Dynamics in a Pediatric Hospital Using Full Genome Sequences
Norovirus genome sequencing identified 33% of patients whose sequences were linked phylogenetically to those of another patient in the study. An additional 24% of nosocomially infected patients had unlinked sequences, suggesting infection from unsampled sources. Genome sequencing identifies unsuspected nosocomial norovirus infection.
Abstract
Background
Norovirus is a leading cause of worldwide and nosocomial gastroenteritis. The study aim was to assess the utility of molecular epidemiology using full genome sequences compared to routine infection prevention and control (IPC) investigations.
Methods
Norovirus genomes were generated from new episodes of norovirus at a pediatric tertiary referral hospital over a 19-month period (n = 182). Phylogeny identified clusters of related sequences that were verified using epidemiological and clinical data.
Results
Twenty-four clusters of related norovirus sequences (\"sequence clusters\") were observed, including 8 previously identified by IPC investigations (\"IPC outbreaks\"). Seventeen sequence clusters (involving 77/182 patients) were corroborated by epidemiological data (\"epidemiologically supported clusters\"), suggesting transmission between patients. Linked infections were identified among 44 patients who were missed by IPC investigations. Thirty-three percent of norovirus sequences were linked, suggesting nosocomial transmission; 24% of patients had nosocomial infections from an unknown source; and 43% were norovirus positive on admission.
Conclusions
We show there are frequent introductions of multiple norovirus strains with extensive onward nosocomial transmission of norovirus in a pediatric hospital with a high proportion of immunosuppressed patients nursed in isolation. Phylogenetic analysis using full genome sequences is more sensitive than classic IPC investigations for identifying linked cases and should be considered when investigating norovirus nosocomial transmission. Sampling of staff, visitors, and the environment may be required for complete understanding of infection sources and transmission routes in patients with nosocomial infections not linked to other patients and among patients with phylogenetically linked cases but no evidence of direct contact.
Journal Article
A set of dual promoter vectors for high throughput cloning, screening, and protein expression in eukaryotic and prokaryotic systems from a single plasmid
Background
The ability to produce the same recombinant protein in both prokaryotic and eukaryotic cells offers many experimental opportunities. However, the cloning of the same gene into multiple plasmids is required, which is time consuming, laborious and still may not produce soluble, stable protein in sufficient quantities. We have developed a set of expression vectors that allows for ligation-independent cloning and rapid functional screening for protein expression in both
E. coli
and
S. cerevisiae.
Results
A set of expression vectors was made that can express the same open reading frame in
E. coli
(via the T7 phage promoter) and in
S. cerevisiae
(via the
CUP1
or
MET25
promoter). These plasmids also contain the essential elements for replication and selection in both cell types and have several advantages: they allow for cloning of genes by homologous recombination in yeast, protein expression can be determined before plasmid isolation and sequencing, and a GST-fusion tag is added to aid in soluble expression and purification. We have also included a TEV recognition site that allows for the specific cleavage of the fusion proteins to yield native proteins.
Conclusions
The dual promoter vectors can be used for rapid cloning, expression, and purification of target proteins from both prokaryotic and eukaryotic systems with the ability to study post-translation modifications.
Journal Article
Whole genome sequencing of Herpes Simplex Virus 1 directly from human cerebrospinal fluid reveals selective constraints in neurotropic viruses
Herpes Simplex Virus type 1 (HSV-1) chronically infects over 70 per cent of the global population. Clinical manifestations are largely restricted to recurrent epidermal vesicles. However, HSV-1 also leads to encephalitis, the infection of the brain parenchyma, with high associated rates of mortality and morbidity. In this study, we performed target enrichment followed by direct sequencing of HSV-1 genomes, using target enrichment methods on the cerebrospinal fluid (CSF) of clinical encephalitis patients and from skin swabs of epidermal vesicles on non-encephalopathic patients. Phylogenetic analysis revealed high inter-host diversity and little population structure. In contrast, samples from different lesions in the same patient clustered with similar patterns of allelic variants. Comparison of consensus genome sequences shows HSV-1 has been freely recombining, except for distinct islands of linkage disequilibrium (LD). This suggests functional constraints prevent recombination between certain genes, notably those encoding pairs of interacting proteins. Distinct LD patterns characterised subsets of viruses recovered from CSF and skin lesions, which may reflect different evolutionary constraints in different body compartments. Functions of genes under differential constraint related to immunity or tropism and provide new hypotheses on tissue-specific mechanisms of viral infection and latency.
Journal Article
A solution for autonomous, adaptive monitoring of coastal ocean ecosystems: Integrating ocean robots and operational forecasts
This study presents a proof-of-concept for a fully automated and adaptive observing system for coastal ocean ecosystems. Such systems present a viable future observational framework for oceanography, reducing the cost and carbon footprint of marine research. An autonomous ocean robot (an ocean glider) was deployed for 11 weeks in the western English Channel and navigated by exchanging information with operational forecasting models. It aimed to track the onset and development of the spring phytoplankton bloom in 2021. A stochastic prediction model combined the real-time glider data with forecasts from an operational numerical model, which in turn assimilated the glider observations and other environmental data, to create high-resolution probabilistic predictions of phytoplankton and its chlorophyll signature. A series of waypoints were calculated at regular time intervals, to navigate the glider to where the phytoplankton bloom was most likely to be found. The glider successfully tracked the spring bloom at unprecedented temporal resolution, and the adaptive sampling strategy was shown to be feasible in an operational context. Assimilating the real-time glider data clearly improved operational biogeochemical forecasts when validated against independent observations at a nearby time series station, with a smaller impact at a more distant neighboring station. Remaining issues to be addressed were identified, for instance relating to quality control of near-real time data, accounting for differences between remote sensing and in situ observations, and extension to larger geographic domains. Based on these, recommendations are made for the development of future smart observing systems.
Journal Article