Branko Rihtman, Alberto Torcello-Requena, Alvetina Mikhaylina, Richard J Puxty, Martha RJ Clokie, Andrew D Millard, David J Scanlan

Phosphorus (P) is a major abiotic control on the marine cyanobacterium Synechococcus. Some viruses infecting Synechococcus have acquired, from their host, a gene encoding a P substrate binding protein (PstS), thought to improve virus replication under phosphate starvation. Yet, pstS is uncommon amongst cyanobacterial viruses. Thus, we asked how infections with viruses lacking PstS are affected by P scarcity. We show that production of infectious virus particles of such viruses is reduced in low P conditions. Our data shows how phage genomes, lacking obvious P-stress related genes, have evolved to exploit their host’s environmental sensing mechanisms to coordinate their own gene expression in response to resource limitation.

ISME Journal. March 2024

Anita Ramesh, Paula Oliveira, Mary Cameron, Priscila M S Castanha, Thomas Walker, Audrey Lenhart, Lucy Impoinvil, Neal Alexander, Zulma Medeiros, André Sá, Abraham Rocha, Wayner V Souza, Amélia Maciel, Cynthia Braga

Lymphatic filariasis (LF) is a leading cause of disability due to infectious disease worldwide. The Recife Metropolitan Region (RMR) is the only remaining focus of LF in Brazil, where the parasite Wuchereria bancrofti is transmitted solely by the mosquito Culex quinquefasciatus. This study reports the results of transmission assessment surveys and molecular xenomonitoring in the city of Olinda, RMR, after nearly 15 years (2015-2016) of interventions for LF elimination. Participants were screened for W. bancrofti antigen via immunochromatographic card tests (ICT), and all 1,170 children from MDA areas and the entire population sample of 990 residents in non-MDA areas were ICT negative. In MDA areas, a total of 3,152 female Cx. quinquefasciatus mosquitoes in 277 households were collected via aspiration. RT-qPCR of 233 pools of mosquitos were negative for W. bancrofti RNA; an independent reference laboratory confirmed these results. These results provide evidence that LF transmission has been halted in this setting.

American Journal of Tropical Medicine & Hygiene. March 2024

Brooks S, Weaver JA, Klomchit A, Alharthi SA, Onlamun T, Nurani R, Vong TK, Alberti F and Greco C

Endophytic fungi constitute a rich source of secondary metabolites that can be manipulated to produce desirable novel analogs for combating current agricultural challenges for crop production, especially controlling plant disease. The endophytic fungus Daldinia eschscholtzii MFLUCC 19-0629, was newly isolated from tropical ancient plants, Oncosperma sp., and displays a broad-spectrum of antifungal and antibacterial activities against several plant pathogens. The discovery that D. eschscholtzii MFLUCC 19-0629 has a broad spectrum of antimicrobial activity against seven major plant pathogenic microorganisms relevant to crop production and its complete genome sequence carries immense importance in the advancement of novel microbial biocontrol agents (MBCAs). This also unveils the prospect of uncovering new compounds that could be utilized for sustainable agriculture and pharmaceutical purposes.

Frontiers in Chemical Biology. March 2024

Kevin D. Whitley, James Grimshaw, David M. Roberts, Eleni Karinou, Phillip J. Stansfeld & Seamus Holden

Bacterial cell division requires septal peptidoglycan (sPG) synthesis by the divisome complex. Treadmilling of the essential tubulin homologue FtsZ has been implicated in septal constriction, though its precise role remains unclear. Here we used live-cell single-molecule imaging of the divisome transpeptidase PBP2B to investigate sPG synthesis dynamics in Bacillus subtilis. In contrast to previous models, we observed a single population of processively moving PBP2B molecules whose motion is driven by peptidoglycan synthesis and is not associated with FtsZ treadmilling. However, despite the asynchronous motions of PBP2B and FtsZ, a partial dependence of PBP2B processivity on FtsZ treadmilling was observed. Additionally, through single-molecule counting experiments we provide evidence that the divisome synthesis complex is multimeric. Our results support a model for B. subtilis division where a multimeric synthesis complex follows a single track dependent on sPG synthesis whose activity and dynamics are asynchronous with FtsZ treadmilling.

Nature Microbiology. March 2024

Talal Al-Yazeedi, Sally Adams, Sophie Tandonnet, Anisa Turner, Jun Kim, Junho Lee, Andre Pires-daSilva

Auanema freiburgense is a nematode with males, females, and selfing hermaphrodites. When XO males mate with XX females, they typically produce a low proportion of XO offspring because they eliminate nullo-X spermatids. This occurs because of an unequal distribution of essential cellular organelles during sperm formation. Intriguingly, the interbreeding of two A. freiburgense strains results in hybrid males capable of producing viable nullo-X sperm. Consequently, when these hybrid males mate with females, they yield a high percentage of male offspring. To uncover the genetic basis of nullo-spermatid elimination and X- chromosome drive, we generated a genome assembly for A. freiburgense, and genotyped the intercrossed lines. This analysis identified a Quantitative Trait Locus spanning several X chromosome genes linked to the non-Mendelian inheritance patterns observed in A. freiburgense. This finding provides valuable clues to the underlying factors involved in asymmetric organelle partitioning during male meiotic division and thus non-Mendelian transmission of the X chromosome and sex ratios.

Genetics. March 2024

Camus Nimmo, Arturo Torres Ortiz, Cedric C. S. Tan, Juanita Pang, Mislav Acman, James Millard, Nesri Padayatchi, Alison D. Grant, Max O’Donnell, Alex Pym, Ola B. Brynildsrud, Vegard Eldholm, Louis Grandjean, Xavier Didelot, François Balloux & Lucy van Dorp

Drug resistance in tuberculosis (TB) poses a major ongoing challenge to public health. The recent inclusion of bedaquiline into TB drug regimens has improved treatment outcomes, but this advance is threatened by the emergence of strains of Mycobacterium tuberculosis (Mtb) resistant to bedaquiline. Clinical bedaquiline resistance is most frequently conferred by off-target resistance-associated variants (RAVs) in the mmpR5 gene (Rv0678), the regulator of an efflux pump, which can also confer cross-resistance to clofazimine, another TB drug. We compiled a dataset of 3682 Mtb genomes, including 180 carrying variants in mmpR5, and its immediate background (i.e. mmpR5 promoter and adjacent mmpL5 gene), that have been associated to borderline (henceforth intermediate) or confirmed resistance to bedaquiline. We characterised the occurrence of all nonsynonymous mutations in mmpR5 in this dataset and estimated, using time-resolved phylogenetic methods, the age of their emergence.

Genome Medicine. February 2024

Malgorzata Wesoly, Emma Daulton, Sascha Jenkins, Sarah van Amsterdam, John Clarkson and James A. Covington

In this work, we employed Gas chromatography ion-mobility spectrometry (GC-IMS) technology for early detection of Fusarium basal rot in brown onion, red onion, and shallot bulbs and for tracking disease progression during storage. The volatile profiles of the infected and healthy control bulbs were characterized using GC-IMS and gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS). GC-IMS data combined with principal component analysis and supervised methods provided discrimination between infected and healthy control bulbs as early as 1 day after incubation with the pathogen, classification regarding the proportion of infected to healthy bulbs in a sample, and prediction of the infection’s duration with an average R2 = 0.92. Furthermore, GC-TOF-MS revealed several compounds, mostly sulfides and disulfides, that could be uniquely related to Fusarium basal rot infection.

Agricultural and Food Chemistry. February 2024

Ryan Cook​, Nathan Brown​, Branko Rihtman​, Slawomir Michniewski​, Tamsin Redgwell, Martha Clokie​, Dov J. Stekel, Yin Chen​, David J. Scanlan​, Jon L. Hobman, Andrew Nelson​, Michael A. Jones​, Darren Smith​ and Andrew Millard

ecology. Long-read sequencing and hybrid assembly approaches that combine long- and short-read technologies are now being widely implemented in bacterial genomics and metagenomics. However, the use of long-read sequencing to investigate viral communities is still in its infancy. While Nanopore and PacBio technologies have been applied to viral metagenomics, it is not known to what extent different technologies will impact the reconstruction of the viral community. Thus, we constructed a mock bacteriophage community of previously sequenced phage genomes and sequenced them using Illumina, Nanopore and PacBio sequencing technologies and tested a number of different assembly approaches. Overall the best approach was assembly by a combination of Illumina and Nanopore reads, which reduced error rates to levels comparable with short-read-only assemblies. When using a single technology, Illumina only was the best approach. These findings will provide a starting point for others in the choice of reads and assembly algorithms for the analysis of viromes.

Microbial Genomics. February 2024

Dion Garrett, Graham Teakle, Rosemary Collier, James R. Bell, Sergio Cerezo-Medina, Ramiro Morales-Hojas

The currant-lettuce aphid (Nasonovia ribisnigri (Hemiptera: Aphididae) (Mosley)) is a cosmopolitan pest of outdoor lettuce. Until recently, the use of resistant cultivars was an effective method for managing N. ribisnigri. A resistant cultivar containing a single gene (Nr-locus), introduced in the 1980s, conferred complete resistance to feeding. Overreliance of this Nr-locus in lettuce resulted in N. ribisnigri's ability to break resistance mechanism. Our work attempts to understand which candidate gene(s) are associated with this resistance-breaking mechanism. We present two de novo draft assembles for N. ribisnigri genomes, corresponding to both avirulent (Nr-locus susceptible) and virulent (Nr-locus resistant) biotypes.. Out of the 18,872 differentially expressed genes, a single gene/locus was identified in N. ribisnigri that was shared between two resistant-breaking biotypes. This locus was further explored and validated in Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) experiments and has predicted localisations in both the cytoplasm and nucleus. This is the first study to provide evidence that a single gene/locus is likely responsible for the ability of N. ribisnigri to overcome the Nr-locus resistance in the lettuce host.

Insect Molecular Biology. February 2024

Javier Sánchez Romano, Jaione Simón-Santamaria, Peter McCourt, Bård Smedsrød, Kim Erlend Mortensen, Antonia P. Sagona, Karen Kristine Sørensen, Anett Kristin Larsen

Blood-borne phages are believed to be captured by macrophages in the liver and spleen. Since liver sinusoids also consist of specialized scavenger liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), this study investigated the contribution of both cell types in the elimination of Escherichia coli phage K1Fg10b::gfp (K1Fgfp) in mice. The results presented herein contribute to increased knowledge about the pharmacokinetics of the T7-like phage K1F in the mammalian system. The cell types of the liver that are responsible for rapid phage blood clearance are identified. Our results highlight the need for more research about appropriate dose regimens when phage therapy is delivered intravenously and advise essential knowledge about cell systems that should be investigated further for detailed phage pharmacodynamics.

mSphere. February 2024

Elena Fiorin, Charlotte A. Roberts, Marica Baldoni, Erin Connelly, Christina Lee, Claudio Ottoni & Emanuela Cristiani

Leprosy was one of the most outwardly visible diseases in the European Middle Ages, a period during which leprosaria were founded to provide space for the sick. In the present study, microremains and DNA were analysed from the calculus of individuals buried in the late medieval cemetery of St Leonard, a leprosarium located in Peterborough, England. The results show the presence of ginger (Zingiber officinale), a culinary and medicinal ingredient, as well as evidence of consumption of cereals and legumes. This research suggests that affected individuals consumed ingredients mentioned in medieval medical textbooks that were used to treat regions of the body typically impacted by leprosy. To the authors' knowledge, this is the first study which has identified Zingiber officinale in human dental calculus in England or on the wider European continent.

Scientific Reports. January 2024

Nirwan, Shradha, Chatterjee, Anupriya, Cevik, Volkan, Holub, Eric B., Jones, Jonathan D. G., Tewari, Anand Kumar, Shrivastava, Neeraj, Agnihotri, Abha and Sharma, Pankaj

In an effort to develop resistant plants, Agrobacterium mediated genetic transformation of three B. juncea genotypes viz., susceptible host var. Varuna, along with its doubled haploid mutant lines C66 and C69 (showing moderate tolerance to field isolates of A. candida) was initiated to transfer resistance genes (WRR8Sf-2 and WRR9Hi-0) identified in Arabidopsis thaliana against race Ac2V, that encode for Toll-like/interleukin-1 receptor-nucleotide binding-leucine-rich repeat proteins that recognize effectors of the pathogen races. Our results demonstrate that introduction of resistance genes from a tertiary gene pool by genetic transformation enhances disease resistance in B. juncea genotypes to a highly virulent Ac2V isolate.

Molecular Biology Reports. January 2024

Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes

Y Wan, AC Myall, A Boonyasiri, F Bolt, A Ledda, S Mookerjee, AY Weiße, M Getino, JF Turton, H Abbas, R Prakapaite, A Sabnis, A Abdolrasouli, K Malpartida-Cardenas, L Miglietta, H Donaldson, M Gilchrist, KL Hopkins, MJ Ellington, JA Otter, G Larrouy-Maumus, M Edwards, J Rodriguez-Manzano, X Didelot, M Barahona, AH Holmes, E Jauneikaite, F Davies

Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. Our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.

Journal of Infectious Diseases. January 2024

Genomic epidemiology of the clinically dominant clonal complex 1 in the Listeria monocytogenes population in the UK

Emily T. Fotopoulou​, Claire Jenkins, Clare R. Barker​, Anais Painset​, Xavier Didelot​, Ameze Simbo​, Amy Douglas​, Gauri Godbole​, Frieda Jorgensen​, Saheer Gharbia​, Jim McLauchlin

Listeria monocytogenes is a food-borne pathogen, typically affecting the elderly, immunocompromised patients and pregnant women. The aim of this study was to determine the population structure of L. monocytogenes clonal complex 1 (CC1) in the UK and describe the genomic epidemiology of this clinically significant CC. We interrogated a working dataset of 4073 sequences of L. monocytogenes isolated between January 2015 and December 2020 from human clinical specimens, food and/or foodproduction environments. Analysis of demographic and clinical outcome data identified CC1 as a clinically significant cause of invasive listeriosis in the elderly population and in women of child-bearing age. Phylogenetic analysis revealed the population structure of CC1 in the UK comprised small, sparsely populated genomic clusters. Only clusters containing isolates from an implicated food vehicle, or food processing or farming environments, were resolved, emphasizing the need for clinical, food and animal-health agencies to share sequencing data in real time, and the importance of a One Health approach to public-health surveillance of listeriosis.

Microbial Genomics. January 2024

Arnold W. Lambisia, Nickson Murunga, Martin Mutunga, Robinson Cheruiyot, Grace Maina, Timothy O. Makori, D. James Nokes and Charles N. Agoti

The non-pharmaceutical interventions (NPIs) implemented to curb the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic, substantially disrupted the activity of other respiratory viruses. However, there is limited data from low-and-middle income countries (LMICs) to determine whether these NPIs also impacted the transmission of common enteric viruses. Here, we investigated the changes in the positivity rate of five enteric viruses among hospitalised children who presented with diarrhoea to a referral hospital in coastal Kenya, during COVID-19 pandemic period. Our study finds that in 2020 the transmission of common enteric viruses, especially RVA and astrovirus, in Kilifi Kenya may have been disrupted due to the COVID-19 NPIs. After 2020, local enteric virus transmission patterns appeared to return to pre-pandemic levels coinciding with the removal of most of the government COVID-19 NPIs.

Gut Pathogens. January 2024

O Roth, S Yechezkel, O Serero, A Eliyahu, I Vints, P Tzeela, A Carignano, DP Janacek, V Peters, A Kessel, V Dwivedi, M Carmeli-Weissberg, F Shaya, i Faigenboim-Doron, KL Ung, B Panyella Pedersen, J Riov, E Klavins, C Dawid, Z Hammes, N Ben-Tal, R Napier, E Sadot, R Weinstain

Clonal propagation of plants by induction of adventitious roots (ARs) from stem cuttings is a requisite step in breeding programs. Due to the central role of auxin in organogenesis, indole-3-butyric acid is often used as part of commercial rooting mixtures, yet many recalcitrant plants do not form ARs in response to this treatment. Here we describe the synthesis and screening of a focused library of synthetic auxin conjugates in Eucalyptus grandis cuttings and identify 4-chlorophenoxyacetic acid-L-tryptophan-OMe as a competent enhancer of adventitious rooting in a number of recalcitrant woody plants, including apple and argan. Comprehensive metabolic and functional analyses reveal that this activity is engendered by prolonged auxin signaling due to initial fast uptake and slow release and clearance of the free auxin 4-chlorophenoxyacetic acid. This work highlights the utility of a slow-release strategy for bioactive compounds for more effective plant growth regulation.

Nature Biotechnology. January 2024

Jake Carson, Matt Keeling, David Wyllie, Paolo Ribeca, Xavier Didelot

Here we present a new methodology that can use any number of genomes sampled from a set of individuals to reconstruct their transmission network. Furthermore, we remove the need for the assumption of a complete transmission bottleneck. We use simulated data to show that our method becomes more accurate as more genomes per host are provided, and that it can infer key infectious disease parameters such as the size of the transmission bottleneck, within-host growth rate, basic reproduction number and sampling fraction. We demonstrate the usefulness of our method in applications to real datasets from an outbreak of Pseudomonas aeruginosa amongst cystic fibrosis patients and a nosocomial outbreak of Klebsiella pneumoniae.

Molecular Biology & Evolution. January 2024

Lan X.Y., Liang X.S., Cao M.X., Qin H.M., Chu C.Y., Boltze J., Li S.

The neural cell adhesion molecule (NCAM) promotes neural development and regeneration. Whether NCAM mimetic peptides could synergize with bone marrow mesenchymal stem cells (BMSCs) in stroke treatment deserves investigation. We found that the NCAM mimetic peptide P2 promoted BMSC proliferation, migration, and neurotrophic factor expression, protected neurons from oxygen-glucose deprivation through ERK and PI3K/AKT activation and anti-apoptotic mechanisms in vitro. Following middle cerebral artery occlusion (MCAO) in rats, P2 alone or in combination with BMSCs inhibited neuronal apoptosis and induced the phosphorylation of ERK and AKT. P2 combined with BMSCs enhanced neurotrophic factor expression and BMSC proliferation in the ischemic boundary zone. Moreover, combined P2 and BMSC therapy induced translocation of nuclear factor erythroid 2-related factor, upregulated heme oxygenase-1 expression, reduced infarct volume, and increased functional recovery as compared to monotreatments. Treatment with LY294002 (PI3K inhibitor) and PD98059 (ERK inhibitor) decreased the neuroprotective effects of combined P2 and BMSC therapy in MCAO rats. Collectively, P2 is neuroprotective while P2 and BMSCs work synergistically to improve functional outcomes after ischemic stroke, which may be attributed to mechanisms involving enhanced BMSC proliferation and neurotrophic factor release, anti-apoptosis, and PI3K/AKT and ERK pathways activation.

Journal of Cerebral Blood Flow & Metabolism. January 2024

Ryan M. Mushinski, Yong Zhou, Ayumi Hyodo, Claudio Casola, Thomas W. Boutton

We investigated the interactions between livestock grazing history (none, moderate, heavy) and vegetation cover (grassland, juniper, oak) using a ∼ 70-year grazing experiment in west-central Texas. We explored effects on soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), microbial community composition, and function. The findings highlight how long-term livestock grazing and woody plant encroachment influence soil C, N, P cycles, altering soil microbial community structure and function. This study provides insights for savanna ecosystem management and integrating land cover effects into biogeochemical models for global change scenarios.

Geoderma.  January 2024

Guillermo Friis, Edward G. Smith, Catherine E. Lovelock, Alejandra Ortega, Alyssa Marshell, Carlos M. Duarte, John A. Burt

Biological systems occurring in ecologically heterogeneous and spatially discontinuous habitats provide an ideal opportunity to investigate the relative roles of neutral and selective factors in driving lineage diversification. The grey mangroves (Avicennia marina) of Arabia occur at the northern edge of the species' range and are subject to variable, often extreme, environmental conditions, as well as historic large fluctuations in habitat availability and connectivity resulting from Quaternary glacial cycles. Here, we analyse fully sequenced genomes sampled from 19 locations across the Red Sea, the Arabian Sea and the Persian/Arabian Gulf (PAG) to reconstruct the evolutionary history of the species in the region and to identify adaptive mechanisms of lineage diversification. Our results support a process of rapid diversification resulting from the combined effects of historical factors and ecological selection and reveal mangrove peripheral environments as relevant drivers of lineage diversity.

Molecular Ecology. January 2024

Quantifying microplastic dispersion due to density effects

Stride, Ben, Abolfathi, Soroush, Bending, Gary D. and Pearson, Jonathan M

An experimental study was conducted on how polymer density affects the transport and fate of microplastics in aquatic flows. For the first time, polypropylene (PP), polyethylene (PE), polymethyl methacrylate (PMMA), polyetheretherketone (PEEK), and polyvinyl chloride (PVC) were chemically stained and tested using solute transport techniques and velocities found among rivers in the natural environment (0.016 – 0.361 m/s). Except for PP, in most conditions microplastics exhibited similar transport characteristics to solutes regardless of density and established solute transport models were successfully implemented to predict their transport and fate.. This data is the first to provide microplastic suspension and deposition thresholds based on river velocity and polymer density, making a key contribution to research predicting microplastic fate and organismal exposure.

Journal of Hazardous Materials. January 2024

Distinct biogeographic patterns in Glomeromycotinian and Mucoromycotinian arbuscular mycorrhizal fungi across China: A meta-analysis

Zihao Liu, Jie Fang, Yucheng He, Gary D Bending, Bin Song, Yaping Guo, Xiaojie Wang, Zemin Fang, Jonathan M Adams

Fine root endophytes, recently reclassified as Mucoromycotinian arbuscular mycorrhizal fungi (M-AMF), are now recognized as functionally important as Glomeromycotinian AMF (G-AMF). Here, we investigated the biogeographic assemblies and ecological diversity patterns of both G-AMF and M-AMF, using published 18S rDNA amplicon datasets and associated metadata from 575 soil samples in six ecosystems across China. This study provides solid evidence that the two AMF groups have distinct ecological preferences at the continental scale in China, and also highlights the potential impacts of anthropogenic activities on distributions of AMF. These results advance our knowledge of the ecological differences between the two fungal groups in terrestrial ecosystems, suggesting the need for further field-based investigation that may lead to a more sophisticated understanding of ecosystem function and sustainable management.

Science of the Total Environment. December 2023

Rysava, Kristyna and Tildesley, Michael J

Here, we present a quantitative framework using a series of progressively more biologically realistic models of canine rabies in domestic dogs and from dogs to humans, a suitable example system to characterize dynamical changes under varying levels of dog quarantine. We explicitly incorporate health-seeking behaviour data to inform the modelling of contact-tracing and exclusion of rabies suspect and probable dogs that can be identified through bite-histories of patients presenting at anti-rabies clinics. We find that a temporary quarantine of rabies suspect and probable dogs provides a powerful tool to curtail rabies transmission, especially in settings where optimal vaccination coverage is yet to be achieved, providing a critical stopgap to reduce the number of human and animal deaths due to rabid bites.

PLoS Computational Biology. December 2023

Huba L Marton, Apoorva Bhatt, Antonia P Sagona, Peter Kilbride, Matthew I Gibson

Bacteriophages have many biotechnological and therapeutic applications, but as with other biologics, cryopreservation is essential for storage and distribution. Macromolecular cryoprotectants are emerging for a range of biologics, but the chemical space for polymer-mediated phage cryopreservation has not been explored. Here we screen the cryoprotective effect of a panel of polymers against five distinct phages, showing that nearly all the tested polymers provide a benefit. This work shows that phages are amenable to protection with hydrophilic polymers and opens up new opportunities for advanced formulations for future phage therapies and to take advantage of the additional functionality brought by the polymers.

Biomacromolecules. December 2023

Jack Butler, Nicholas Dale

Connexin32 (Cx32) is expressed in myelinating Schwann cells. It forms both reflexive gap junctions, to facilitate transfer of molecules from the outer to the inner myelin layers and hemichannels at the paranode to permit action potential-evoked release of ATP into the extracellular space. Loss of function mutations in Cx32 cause X-linked Charcot Marie Tooth disease (CMTX), a slowly developing peripheral neuropathy. The mechanistic links between Cx32 mutations and CMTX are not well understood. As Cx32 hemichannels can be opened by increases in PCO2, we have examined whether CMTX mutations alter this CO2 sensitivity. We have shown that Schwannoma RT4 D6P2T cells can release ATP in response to elevated PCO2 via the opening of Cx32. This is consistent with the hypothesis that the CO2 sensitivity of Cx32 may be important for maintenance of healthy myelin. Our data, showing a transdominant effect of certain CMTX mutations on CO2 sensitivity, may need to be taken into account in any future gene therapies for this condition.

Frontiers in Cellular Neuroscience. December 2023

Jan Böhning, Miles Graham, Suzanne C. Letham, Luke K. Davis, Ulrike Schulze, Phillip J. Stansfeld, Robin A. Corey, Philip Pearce, Abul K. Tarafder, Tanmay A. M. Bharat

Inoviruses are filamentous phages infecting numerous prokaryotic phyla. Inoviruses can self-assemble into mesoscale structures with liquid-crystalline order, termed tactoids, which protect bacterial cells in Pseudomonas aeruginosa biofilms from antibiotics. Here, we investigate the structural, biophysical, and protective properties of tactoids formed by the P. aeruginosa phage Pf4 and Escherichia coli phage fd. This study provides insights into how filamentous molecules protect bacteria from extraneous substances in biofilms and in host-associated infections.

Nature Communications. December 2023

Mononuclear cell therapy of neonatal hypoxic-ischemic encephalopathy in preclinical versus clinical studies: a systematic analysis of therapeutic efficacy and study design

Scrutton A. M., Ollis F., Boltze J

Hypoxic-ischemic encephalopathy (HIE) is a devastating condition affecting around 8.5 in 1000 newborns globally. Therapeutic hypothermia (TH) can reduce mortality and, to a limited extent, disability after HIE. Nevertheless, there is a need for new and effective treatment strategies. Here, we conducted a systematic review and meta-analysis. and analyzed overall MNC efficacy in preclinical trials, the methodological quality of preclinical trials, and relevant design features in preclinical versus clinical trials. Based on the analyzed data, it is unlikely that therapeutic effect size is massively overestimated in preclinical studies. It is more plausible that the many design differences between preclinical and clinical trials are responsible for the so far lacking proof of the efficacy of MNC treatments in HIE. Additional preclinical and clinical research is required to optimize the application of MNC for experimental HIE treatment.

Neuroprotection. December 2023

MCC950 reduces autophagy and improves cognitive function by inhibiting NLRP3-dependent neuroinflammation in a rat model of Alzheimer's disease

Abdul Naeem, Ravi Prakash, Neha Kumari, Mohsin Ali Khan, Abdul Quaiyoom Khan, Shahab Uddin, Sandeep Verma, Avril AB Robertson, Johannes Boltze, Syed Shadab Raza

In this study, we investigated the potential therapeutic effects of MCC950 on NLRP3-mediated inflammasome-driven inflammation and autophagy in Alzheimer's disease (AD). . MCC950 effectively suppressed STZ-induced cognitive impairment and anxiety by inhibiting NLRP3-dependent neuroinflammation. Moreover, our findings indicate that MCC950 exerts neuroprotective effects by attenuating autophagy in neuronal cells. The inhibiting effects of MCC950 on inflammasome activation and autophagy were reproduced in vitro, provding further mechansistic insights into MCC950 therapeutic action. Our findings suggest that MCC950 impedes the progression of AD and may also improve cognitive function through the mitigation of autophagy and NLRP3 inflammasome.

Brain, Behavior and Immunity. December 2023

María Florencia Mammarella, Leandro Lucero, Nosheen Hussain, Aitor Muñoz-Lopez, Ying Huang, Lucia Ferrero, Guadalupe L Fernandez-Milmanda, Pablo Manavella, Moussa Benhamed, Martin Crespi, Carlos L Ballare, Jose Gutierrez-Marcos, Pilar Cubas, Federico Ariel

The long noncoding RNA (lncRNA) AUXIN-REGULATED PROMOTER LOOP (APOLO) recognizes a subset of target loci across the Arabidopsis thaliana genome by forming RNA–DNA hybrids (R-loops) and modulating local three-dimensional chromatin conformation. Here, we show that APOLO regulates shade avoidance syndrome by dynamically modulating expression of key factors. We show that direct application of APOLO RNA to leaves results in a rapid increase in auxin signaling that is associated with changes in the plant response to far-red light. Collectively, our data support the view that lncRNAs coordinate shade avoidance syndrome in A. thaliana, and reveal their potential as exogenous bioactive molecules. Deploying exogenous RNAs that modulate plant–environment interactions may therefore become a new tool for sustainable agriculture.

EMBO Journal. December 2023

Chaweewan Sirakawin, Dongfa Lin, Ziyue Zhou, Xiaoxin Wang, Rhianne Kelleher, Shangyuan Huang, Weimiao Long, Andre Pires-da Silva, Yu Liu, Jingjing Wang, Ilya A. Vinnikov

Vitamin A (VA) is a micronutrient essential for the physiology of many organisms, but its role in longevity and age-related diseases remains unclear. In this work, we used Caenorhabditis elegans to study the impact of various bioactive compounds on lifespan. We demonstrate that VA extends lifespan and reduces lipofuscin and fat accumulation while increasing resistance to heat and oxidative stress. This resistance can be attributed to high levels of detoxifying enzymes called glutathione S-transferases, induced by the transcription factor skinhead-1 (SKN-1). Notably, VA upregulated the transcript levels of skn-1 or its mammalian ortholog NRF2 in both C. elegans, human cells, and liver tissues of mice. Moreover, the loss-of-function genetic models demonstrated a critical involvement of the SKN-1 pathway in longevity extension by VA. Our study thus provides novel insights into the molecular mechanism of anti-aging and anti-oxidative effects of VA, suggesting that this micronutrient could be used for the prevention and/or treatment of age-related disorders.

Aging Cell. December 2023

Kaisa Thorell, Zilia Y Muñoz-Ramírez, Difei Wang, Santiago Sandoval-Motta, Rajiv Boscolo Agostini, Silvia Ghirotto, Roberto C Torres; HpGP Research Network (inc. Xavier Didelot); Daniel Falush, M Constanza Camargo, Charles S Rabkin

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics.

Nature Communications. December 2023

Genetic and potential antigenic evolution of influenza A(H1N1)pdm09 viruses circulating in Kenya during 2009-2018 influenza seasons

D. Collins Owuor, Zaydah R. de Laurent, Bryan O. Nyawanda, Gideon O. Emukule, Rebecca Kondor, John R. Barnes, D. James Nokes, Charles N. Agoti and Sandra S. Chaves

Influenza viruses undergo rapid evolutionary changes, which requires continuous surveillance to monitor for genetic and potential antigenic changes in circulating viruses that can guide control and prevention decision making. We sequenced and phylogenetically analyzed A(H1N1)pdm09 virus genome sequences obtained from specimens collected from hospitalized patients of all ages with or without pneumonia between 2009 and 2018 from seven sentinel surveillance sites across Kenya. We compared these sequences with recommended vaccine strains during the study period to infer genetic and potential antigenic changes in circulating viruses and associations of clinical outcome. Our study highlights the necessity of timely genomic surveillance to monitor the evolutionary changes of influenza viruses. Routine influenza surveillance with broad geographic representation and whole genome sequencing capacity to inform on prioritization of antigenic analysis and the severity of circulating strains are critical to improved selection of influenza strains for inclusion in vaccines.

Scientific Reports. December 2023

Changes in the global hospitalisation burden or respiratory syncytial virus in young children during the COVID-19 pandemic: a systematic analysis

Bingbing Cong et al inc. D J Nokes.

We aimed to assess the hospitalisation burden of respiratory syncytial virus (RSV)-associated acute lower respiratory infection (ALRI) in children younger than 5 years during the pandemic period and the possible changes in RSV epidemiology from a global perspective. Our finding suggest that the hospitalisation burden of RSV-associated ALRI in children younger than 5 years was significantly reduced during the first year of the COVID-19 pandemic. The rebound in hospitalisation rates to pre-pandemic rates observed in the high-income region but not in the middle-income region by March, 2022, suggests a persistent negative impact of the pandemic on health-care systems and health-care access in the middle-income region. RSV surveillance needs to be established (or re-established) to monitor changes in RSV epidemiology, particularly in low-income and lower-middle-income countries.

Lancet Infectious Diseases. December 2023

Orin Courtenay, José F Marinho-Júnior, Maria Edileuza F Brito, Juliana FCLS Monteiro, Jeffrey J Shaw, Sinval P. Brandão-Filho

Human and wild rodent infection rates with Leishmania (Viannia) braziliensis are needed to differentiate transmission pathways in anthropogenically altered habitats.  In this study, human participants in northeast Brazil were tested by the leishmanin skin test (LST) and inspected for lesions/scars characteristic of American clinical leishmaniasis (ACL). Molecular (PCR/qPCR) test records of free-ranging rodents were available from a concurrent capture–mark–recapture study. Force of Infection (λ) and recovery (ρ) rates were estimated from cross-sectional and longitudinal datasets. The results show human exposure to L. (V.) braziliensis continues to be high despite the substantial drop in reported ACL cases in recent years. Spill-over transmission risk to humans from rodents in peridomestic habitats is likely supported by a rodent infection/transmission corridor linking houses, plantations, and the Atlantic Forest.

Pathogens. December 2023

Esther Ivorra-Molla, Dipayan Akhuli, Martin B. L. McAndrew, William Scott, Lokesh Kumar, Saravanan Palani, Masanori Mishima, Allister Crow & Mohan K. Balasubramanian

StayGold is an exceptionally bright and stable fluorescent protein that is highly resistant to photobleaching. Despite favorable fluorescence properties, use of StayGold as a fluorescent tag is limited because it forms a natural dimer. Here we report the 1.6 Å structure of StayGold and generate a derivative, mStayGold, that retains the brightness and photostability of the original protein while being fully monomeric.

Nature Biotechnology. December 2023

Amol M Bhandare, Nicholas Dale

While central autonomic, cardiac, and/or respiratory dysfunction underlies sudden unexpected death in epilepsy (SUDEP), the specific neural mechanisms that lead to SUDEP remain to be determined. In this study, we took advantage of single-cell neuronal Ca2+ imaging and intrahippocampal kainic acid (KA)-induced chronic epilepsy in mice to investigate progressive changes in key cardiorespiratory brainstem circuits during chronic epilepsy. Our findings establish a dysfunctional breathing phenotype with its RTN neuronal correlate in mice with chronic epilepsy and suggest that the assessment of respiratory chemosensitivity may have the potential for identifying people at risk of SUDEP.

Frontiers in Cellular Neuroscience. December 2023

Emily Skates, Hadrien Delattre, Zoe Schofield, Munehiro Asally, Orkun S. Soyer

Recently, the fluorescent benzothiazole dye thioflavin T (ThT) was shown to indicate membrane potential in bacteria due to its cationic nature. This finding prompted a question whether ThT fluorescence is linked to the membrane potential in mammalian cells, which would be important for appropriate utilization of ThT in research and diagnosis. Here, we show that ThT localizes into the mitochondria of HeLa cells in a membrane-potential-dependent manner. The results show that ThT can act as a mitochondrial membrane potential indicator in mammalian cells, when used at low concentrations and with low blue light exposure. However, it causes dissipation of the mitochondrial membrane potential depending additively on its concentrations and blue light exposure. This conclusion motivates a re-evaluation of ThT’s use at micromolar range in live-cell analyses and indicates that this dye can enable future studies on the potential connections between mitochondrial membrane potential dynamics and protein aggregation.

Biophysical Reports. December 2023

Taguchi A., Okinaka Y., Takeda A., Okamoto T., Boltze J., Claussen C., Gul S

It is proposed that age-related brain dysfunction may not necessarily result from the accumulation of uncontrollable disorders, but rather the natural deterioration of brain function following expiration of the limited innate program to preserve the brain in a healthy condition. We now have identified a means by which this process could potentially be mitigated or even partially reversed by applying stem cell therapy. Furthermore, we propose that the activation of neurogenesis in the hippocampus, also through stem cell therapy, is a promising therapeutic target in AD.

Neuroprotection. November 2023

George Muscatt, Ryan Cook, Andrew Millard, Gary D Bending, Eleanor Jameson

To investigate viral communities throughout the soil depth profile, we leveraged a publicly available metagenomic data set sampled from grassland soil in Northern California. In total, 10,196 non-redundant viral operational taxonomic units were recovered from soil between 20 cm and 115 cm below the surface. Viral diversity was assessed at both the population level and strain level to reveal diverse ecological and evolutionary patterns of virus-host interactions in surface and subsurface soils. Investigating viral microdiversity uncovered potential patterns of antagonistic co-evolution across both surface and subsurface soils. We have provided evidence for the potential of soil viruses to augment the remineralization of soil carbon. While we continue to yield a more comprehensive understanding of soil viral ecology, our work appeals to future researchers to further investigate subsurface viral communities.

Microbial Ecology. November 2023

T. Bertie Ansell, Wanling Song, Claire E. Coupland, Loic Carrique, Robin A. Corey, Anna L. Duncan, C. Keith Cassidy, Maxwell M. G. Geurts, Tim Rasmussen, Andrew B. Ward, Christian Siebold, Phillip J. Stansfeld, Mark S. P. Sansom

Cryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures.

Nature Communications. November 2023

McKendrick, James, Tennant, Warren S. D. and Tildesley, Michael J.

Lassa fever (Lf) is a viral haemorrhagic disease endemic to West Africa and is caused by the Lassa mammarenavirus. The rodent Mastomys natalensis serves as the primary reservoir and its ecology and behaviour have been linked to the distinct spatial and temporal patterns in the incidence of Lf. While previous research has modelled the case seasonality within Nigeria, this did not capture the seasonal variation in the reproduction of the zoonotic reservoir and its effect on case numbers. To this end, we introduce an approximate Bayesian computation scheme to fit our model to the case data from 2018–2020 supplied by the NCDC. In this study we used a periodically forced seasonal nonautonomous system of ordinary differential equations as a vector model to demonstrate that the population dynamics of the rodent reservoir may be responsible for the spikes in the number of observed cases in humans.

PLoS Neglected Tropical Diseases.November 2023

A quantitative morphospace of multicellular organ design in the plant Arabidopsis

Salva Duran-Nebreda, Matthew D.B. Jackson, George W. Bassel

The investigation of cellular organization can provide insight into organ function following structure-function relationships. Here, we investigate the extent to which properties in cellular organization can arise ‘‘for free’’ as an emergent property of embedding cells in space versus those that are actively generated by patterning processes. A 3D cellular-resolution digital tissue atlas for the model plant species Arabidopsis was generated, and the extent to which the organs in this organism conform to the default configurations was established through statistical comparisons with digital tissue models. This work establishes a quantitative morphospace to understand the principles of organ construction and its diversity within a single organism.

Current Biology. November 2023

Toward uncovering an operating system in plant organs

Gwendolyn V Davis, Tatiana de Souza Moraes, Swanand Khanapurkar, Hannah Dromiack, Zaki Ahmad, Emmanuelle M Bayer, Rishikesh P Bhalerao, Sara I Walker, George W Bassel

Molecular motifs can explain information processing within single cells, while how assemblies of cells collectively achieve this remains less well understood. Plant fitness and survival depend upon robust and accurate decision-making in their decentralised multicellular organ systems. Mobile agents, including hormones, metabolites, and RNAs, have a central role in coordinating multicellular collective decision-making, yet mechanisms describing how cell-cell communication scales to organ-level transitions is poorly understood. Here, we explore how unified outputs may emerge in plant organs by distributed information processing across different scales and using different modalities. Mathematical and computational representations of these events are also explored toward understanding how these events take place and are leveraged to manipulate plant development in response to the environment.

Trends in Plant Science. November 2023

Reno Roberts, Robert T.R. Huckstepp

Sleep apnea (SA) is a major threat to physical health and carries a significant economic burden. These impacts are worsened by its interaction with, and induction of, its comorbidities. SA holds a bidirectional relationship with hypertension, which drives atherosclerosis/arteriolosclerosis, ultimately culminating in vascular dementia. To enable a better understanding of these sequelae of events, we investigated innate SA and its effects on cognition in adult-aged spontaneously hypertensive rats, which have a range of cardiovascular disorders. Spontaneously hypertensive rats displayed a higher degree of sleep-disordered breathing, which emanates from poor vascular health leading to a loss of preBötzinger Complex neurons. These rats also display small vessel white matter disease, a form of vascular dementia, which may be exacerbated by the SA-induced neuroinflammation in the hippocampus to worsen the related deficits in both long- and short-term memories.

Stroke. November 2023

Jacqueline L. Stroud, Simon J. Kemp, Craig J. Sturrock

In this study, new and traditional organic wastes (green waste compost, farmyard manure (FYM), anaerobic digestate or straw) were ploughed into an arable field experiment at a range of rates (1–3 t C ha−1) and under spring and winter cropping rotations for 5 years. The stability of the soil surface structure (<5 cm) was assessed in Years 3, 4 and 5 to guide the use of organic wastes in arable field management. In conclusion, to achieve a stable soil surface structure, a 150% improvement in aggregate stability would be needed here and ploughing in organic wastes was not a successful management approach on these arable field experiments.

Soil Use and Management. November 2023

Yenew, B., et al. (incl. Didelot, X)

The Mycobacterium tuberculosis complex (MTBC) includes several human- and animal-adapted pathogens. It is thought to have originated in East Africa from a recombinogenic Mycobacterium canettii-like ancestral pool. Here, we describe the discovery of a clinical tuberculosis strain isolated in Ethiopia that shares archetypal phenotypic and genomic features of M. canettii strains, but represents a phylogenetic branch much closer to the MTBC clade than to the M. canettii strains. Analysis of genomic traces of horizontal gene transfer in this isolate and previously identified M. canettii strains indicates a persistent albeit decreased recombinogenic lifestyle near the emergence of the MTBC. Our findings support that the MTBC emergence from its putative free-living M. canettii-like progenitor is evolutionarily very recent, and suggest the existence of a continuum of further extant derivatives from ancestral stages, close to the root of the MTBC, along the Great Rift Valley.

Nature Communications. November 2023

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.

Journal of the Royal Society Interface. November 2023

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.

Science of the Total Environment. November 2023

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.

Brain & Behavior. November 2023

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.

Microbiome. November 2023

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.

eLife. November 2023

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.

Communications Biology. November 2023

Megan L. Purchase, Gary D. Bending and Ryan M. Mushinski

Volatile reactive nitrogen oxides (NOy) are significant atmospheric pollutants, including NOx (nitric oxide [NO] + nitrogen dioxide [NO2]) and NOz (nitrous acid [HONO] + nitric acid [HNO3] + nitrogen trioxide [NO3] + ...). NOy species are products of nitrogen (N) cycle processes, particularly nitrification and denitrification. Biogenic sources, including soil, account for over 50% of natural NOy emissions to the atmosphere, yet emissions from soils are generally not included in atmospheric models as a result of a lack of mechanistic data. This work is a unique investigation of NOy fluxes on a landscape scale, taking a comprehensive set of land-use types, human influence, and seasonality into account to determine large-scale heterogeneity to provide a basis for future modeling and hypothesis generation

Environmental Science &Technology. October 2023

Holly Acford-Palmer, Monica Campos, Janvier Bandibabone, Sévérin N’Do, Chimanuka Bantuzeko, Bertin Zawadi, Thomas Walker, Jody E. Phelan, Louisa A. Messenger, Taane G. Clark & Susana Campino

Vector control strategies have been successful in reducing the number of malaria cases and deaths globally, but the spread of insecticide resistance represents a significant threat to disease control. To support the continuous efficacy of vector control strategies, it is essential to monitor insecticide resistance using molecular surveillance tools. In this study, we developed an amplicon sequencing (“Amp-seq”) approach targeting An. funestus, and using multiplex PCR, dual index barcoding, and next-generation sequencing for high throughput and low-cost applications. Overall, our panel represents an extendable and much-needed method for the molecular surveillance of insecticide resistance in An. funestus populations.

Scientific Reports. October 2023

Dennis Alexander Tebbe, Charlotte Gruender, Leon Dlugosch, Kertu Lõhmus, Sönke Rolfes, Martin Könneke, Yin Chen, Bert Engelen and Hendrik Schaefer

Saltmarshes are highly productive environments, exhibiting high abundances of organosulfur compounds. Dimethylsulfoniopropionate (DMSP) is produced in large quantities by algae, plants, and bacteria and is a potential precursor for dimethylsulfoxide (DMSO) and dimethylsulfide (DMS). DMSO serves as electron acceptor for anaerobic respiration leading to DMS formation, which is either emitted or can be degraded by methylotrophic prokaryotes. Major products of these reactions are trace gases with positive (CO2, CH4) or negative (DMS) radiative forcing with contrasting effects on the global climate. Here, we investigated organic sulfur cycling in saltmarsh sediments and followed DMSO reduction in anoxic batch experiments. Compared to previous measurements from marine waters, DMSO concentrations in the saltmarsh sediments were up to ~300 fold higher.

ISME journal. October 2023