Latest Publications
Spatio-temporal surveillance and early detection of SARS-CoV-2 variants of concern: a retrospective analysis
Massimo Cavallaro, Louise Dyson, Michael J Tildesley, Dan Todkill, Matt J Keeling
The SARS-CoV-2 pandemic has been characterized by the repeated emergence of genetically distinct virus variants of increased transmissibility and immune evasion compared to pre-existing lineages. Here we study the spatial invasion and early spread of the Alpha, Delta and Omicron (BA.1 and BA.2) variants in England from September 2020 to February 2022 using the random neighbourhood covering (RaNCover) method. This is a statistical technique for the detection of aberrations in spatial point processes, which we tailored here to community PCR (polymerase-chain-reaction) test data where the TaqPath kit provides a proxy measure of the switch between variants. Retrospectively, RaNCover detected the earliest signals associated with the four novel variants that led to large infection waves in England. With suitable data our method therefore has the potential to rapidly detect outbreaks of future SARS-CoV-2 variants, thus helping to inform targeted public health interventions.
Microplastic transport dynamics in surcharging and overflowing manholes
Ben Stride, Charlotte Dykes, Soroush Abolfathi, Modupe Jimoh, Gary D Bending, Jonathan Pearson
The transport of microplastics within urban water systems remains poorly understood, with little prior research on their behaviour within manhole configurations. This study represents the first to measure and model the transport dynamics of microplastics within circular and square manholes under different hydraulic scenarios. The transport and fate of polyethylene (PE) was quantified and compared to solutes (Rhodamine WT dye) using energy losses, residence time distributions (RTDs), and mixing models within surcharging and overflowing manholesThis establishes the deconvolution method as the most accurate and appropriate model to accurately predict microplastic mixing in manholes and urban drainage systems.
Post operative fibrinogen to albumin ratio acting as an indicator of futile recanalization in patients with successful thrombectomy
Tang T., Li D., Fan T.P., Guo L.J., Lan X.Y., Bi C.J., Boltze J., Thomas A.M., Zhao X.S., Mo M., Zhao M.H., Ji X., Li S
Timely recognition of futile recanalization might enable a prompter response and thus improve outcomes in patients receiving successful thrombectomy. This study aims to evaluate whether postoperative fibrinogen-to-albumin ratio (FAR) could act as an indicator of futile recanalization.This is a single-center, retrospective analysis of patients with acute anterior circulation large-vessel occlusion and successful thrombectomy between May 2019 and June 2022. A total of 255 patients were enrolled, amongst which 34.1% had high postoperative FAR. Futile recanalization was more prevalent among patients with high FAR compared to those with low FAR. After adjusting for potential confounders, high postoperative FAR was found to independently correspond with the occurrence of futile. This association was consistently observed regardless of prior antithrombotic therapy, treatment of intravenous thrombolysis, occlusion site, time from symptom onset to groin puncture, and reperfusion status. Our findings support high postoperative FAR serving as an indicator of futile recanalization in patients with anterior circulation large-vessel occlusion and successful thrombectomy.
Microbial hitchhikers harbouring antimicrobial-resistance genes in the riverine plastisphere
Vinko Zadjelovic, Robyn J. Wright, Chiara Borsetto, Jeannelle Quartey, Tyler N. Cairns, Morgan G. I. Langille, Elizabeth M. H. Wellington & Joseph A. Christie-Oleza
In- and ex-situ incubations were used to characterise the riverine plastisphere taxonomically and functionally in order to determine whether antibiotics within the water influenced the ARG profiles in these microbiomes and how these compared to those on natural surfaces such as wood and their planktonic counterparts. Our results provide insights into the capacity of the riverine plastisphere to harbour a distinct set of potentially pathogenic bacteria and function as a reservoir of ARGs. The environmental impact that plastics pose if they act as a reservoir for either pathogenic bacteria or ARGs is aggravated by the persistence of plastics in the environment due to their recalcitrance and buoyancy. Nevertheless, the high similarities with microbiomes growing on natural co-occurring materials and even more worrisome microbiome observed in the surrounding water highlights the urgent need to integrate the analysis of all environmental compartments when assessing risks and exposure to pathogens and ARGs in anthropogenically-impacted ecosystems.
Mechanism of substrate binding and transport in BASS transporters
Patrick Becker, Fiona B. Naughton, Deborah H. Brotherton, Raul Pacheco-Gomez, Oliver Beckstein, Alexander D. Cameron
The bile acid sodium symporter (BASS) family transports a wide array of molecules across membranes, including bile acids in humans, and small metabolites in plants. These transporters, many of which are sodium-coupled, have been shown to use an elevator mechanism of transport, but exactly how substrate binding is coupled to sodium ion binding and transport is not clear. Here, we solve the crystal structure at 2.3 Å of a transporter from Neisseria meningitidis (ASBTNM) in complex with pantoate, a potential substrate of ASBTNM.. Comparison of structures in the presence and absence of pantoate demonstrates that pantoate elicits a conformational change in one of the cross-over helices. This modifies the interface between the two domains that move relative to one another to elicit the elevator mechanism. These results have implications, not only for ASBTNM but for the BASS family as a whole and indeed other transporters that work through the elevator mechanism.
Ceg1 depletion reveals mechanisms governing degradation of non-capped RNAs in Saccharomyces cerevisiae
Onofrio Zanin, Matthew Eastham, Kinga Winczura, Mark Ashe, Rocio T. Martinez-Nunez, Daniel Hebenstreit and Pawel Grzechnik
Most functional eukaryotic mRNAs contain a 5’ 7-methylguanosine (m7 G) cap. Although capping is essential for many biological processes,the fate of uncapped transcripts has not been studied extensively. Here, we employed fast nuclear depletion of the capping enzymes in Saccharomyces cerevisiae to uncover the turnover of the transcripts that failed to be capped. We show that although the degradation of cap-deficient mRNA is dominant, the levels of hundreds of non-capped mRNAs increase upon depletion of the capping enzymes. Overall, the abundance of non-capped mRNAs is inversely correlated to the expression levels, altogether resembling the effects observed in cells lacking the cytoplasmic 5’-3’ exonuclease Xrn1 and indicating differential degradation fates of non-capped mRNAs. Our data indicate that the cap presence is essential to initiate the Xrn1-dependent degradation of mRNAs underpinning the role of 5’ cap in the Xrn1-dependent buffering of the cellular mRNA levels.