The impact of natural climate variability on the global distribution of Aedes aegypti : a mathematical modelling study

Kaye, A. R., Obolski, U., Sun, L., Hart, W. S., Hurrell, J. W., Tildesley, M. J. and Thompson, R. N.

Aedes aegypti spread pathogens affecting humans, including dengue, Zika, and yellow fever viruses. Anthropogenic climate change is altering the spatial distribution of Ae aegypti and therefore the locations at risk of vector-borne disease. In addition to climate change, natural climate variability, resulting from internal atmospheric processes and interactions between climate system components (eg, atmosphere–land and atmosphere–ocean interactions), determines climate outcomes. However, the role of natural climate variability in modifying the effects of anthropogenic climate change on future environmental suitability for Ae aegypti has not been assessed fully. In this study, we aim to assess uncertainty arising from natural climate variability in projections of Ae aegypti suitability up to the year 2100. Lancet Planetary Health. December 2024

The time between symptom onset and various clinical outcomes : a statistical analysis of MERS-CoV patients in Saudi Arabia

Althobaity, Yehya, Alkhudaydi, Muhammad, Hill, Edward M., Thompson, Robin N. and Tildesley, Michael J

In this study, we investigate the impact of demographic characteristics on MERS-CoV cases in Saudi Arabia, specifically focusing on the time intervals between symptom onset and key events such as hospitalization, case confirmation, reporting and death. Importantly, we observe age-based differences in the risk of hospitalization and other measures of infection severity, including the probability of death conditional on hospitalization. Careful quantification of epidemiological characteristics, including inference of key epidemiological periods and assessments of differences between cases of different ages, plays a crucial role in understanding the progression of MERS-CoV outbreaks and formulating effective public health strategies to mitigate their impact.

Royal Society Open Society. November 2024

Richard Olumakaiye, Christophe Corre, Fabrizio Alberti

Fungi are talented producers of secondary metabolites with applications in the pharmaceutical and agrochemical sectors. Aspergillus wentii CBS 141173 has gathered research interest due to its ability to produce high-value norditerpenoid compounds, including anticancer molecules. In this study, we aimed to expand the genomic information available for A. wentii to facilitate the identification of terpenoid biosynthetic genes that may be involved in the production of bioactive molecules.

The results provide a scaffold for the future exploration of terpenoid biosynthetic pathways for bioactive molecules in A. wentii. The terpenoid clusters identified in this study are candidates for heterologous gene expression and/or gene disruption experiments. The description and availability of the long-read genome assembly of A. wentii CBS 141173 further provides the basis for downstream genome analysis and biotechnological exploitation of this species.

BMC Genomics. November 2024

Kołodziej, Marta, Tsapras, Panagiotis, Cameron, Alexander and Nezis, Ioannis P

LC3 (microtubule-associated protein 1 light chain 3, called Atg8 in yeast and Drosophila) is one of the most well-studied autophagy-related proteins. LC3 controls the selectivity of autophagic degradation by interacting with LIR (LC3-interacting region) motifs also known as AIM (Atg8-interacting motifs) on selective autophagy receptors that carry cargo for degradation. Although the function of Atg8 family proteins is primarily cytoplasmic, they are also enriched in the nucleus. Here, we used yeast two-hybrid screening, and we identified transcription factor Deformed wings (Dwg) as an Atg8a-interacting protein in Drosophila. Dwg-Atg8a interaction is LIR motif-dependent. We have created Dwg Y129A/I132A LIR mutant flies and shown that they exhibit elevated autophagy, improved resistance to oxidative stress, and starvation. Our results provide novel insights into the transcriptional regulation of autophagy in Drosophila.

Cells. November 2024

Anna Lazar, Richard P Phillips, Stephanie Kivlin, Gary D Bending, Ryan M Mushinski

Although Tetracladium species have traditionally been studied as aquatic saprotrophs, the growing number of metagenomic and metabarcoding reports detecting them in soil environments raises important questions about their ecological adaptability and versatility. We investigated the factors associated with the relative abundance, diversity and ecological dynamics of Tetracladium in temperate forest soils. Collectively, our findings highlight the ecological significance of Tetracladium in temperate forest soils and emphasize the importance of site-specific factors and microbial interactions in shaping their distribution patterns and ecological dynamics.

Environmental Microbiology. November 2024

Claudia Simm, Tzong-Hsien Lee, Harshini Weerasinghe, Dean Walsh, Ioanna T Nakou, Madhu Shankar, Wai Chung Tse, Rebecca Inman, Robert J Mulder, Freya Harrison, Marie-Isabel Aguilar, Gregory L Challis, Ana Traven

Amphotericin B (AmpB) is an effective but toxic antifungal drug.. AmpB disrupts fungal membranes by two proposed mechanisms: ergosterol sequestration from the membrane and pore formation. Whether these two mechanisms operate in conjunction and how they could be potentiated remains to be fully understood. Here, we report that gladiolin, a polyketide antibiotic produced by Burkholderia gladioli, is a strong potentiator of AmpB and acts synergistically against Cryptococcus and Candida species, including drug-resistant C. auris. Gladiolin also synergizes with AmpB against drug-resistant fungal biofilms, while exerting no mammalian cytotoxicity.. Collectively, our findings shed light on AmpB’s mechanism of action and characterize gladiolin as an AmpB potentiator, showing an antifungal mechanism distinct from its proposed antibiotic activity. We shed light on the synergistic mechanism at the membrane, and provide insights into potentiation strategies to improve AmpB’s activity/toxicity relationship.

mBio. November 2024

Chris L B Graham, Jack Bryant, David I Roper, Manuel Banzhaf 

Here we describe a method for in vivo phospholipid labelling by fluorescent imaging in Pseudomonas aeruginosa using a phosphatidylcholine (PC) mimic, “propargyl-choline”(PCho). This click-chemistry liable headgroup mimic is visible by microscopy and allows the covalent labelling of lipids. Fluorescence of the cell membranes, visible in heterogenous patches, is dependent on PCho concentration and is localised in the membrane fraction of cells, demonstrating that it is suitable for membrane labelling and cell imaging.

Access Microbiology. November 2024

Nathan J. Burton, Luís D R. Melo, Michaël F D. Tadesse, Bethany Pearce, Evangelos Vryonis, Antonia P. Sagona

In this study, we produced a cocktail of novel bacteriophages and assessed their viability to eradicate nosocomial staphylococcal biofilms. Here, we used clinical isolates from prosthetic joint infections to isolate and identify four new bacteriophages from sewage effluent. These novel phages were characterized through electron microscopy and full genome sequencing. Subsequently, we combined them into a phage cocktail, which effectively re-sensitized biofilms to vancomycin and flucloxacillin. Notably, this phage cocktail demonstrated low cytotoxicity in vitro to human epithelial cells, even when used alongside antibiotic treatments. These findings highlight the potential of the phage cocktail as a tool to increase antibiotic treatment success in prosthetic joint infections.

Sustainable Microbiology. November 2024

Rawlings, Ngwa Niba, Bailey, Mark, Craig, Peter, Courtenay, Orin

British soldiers undergoing jungle training in Belize typically experience a relatively low risk of developing cutaneous leishmaniasis. However, an uncharacteristically large outbreak of cutaneous leishmaniasis occurred in 2022. This study aimed to determine the cumulative incidence of the disease and highlight potential shortcomings in personal protective measures to mitigate exposure to sand fly vector bites. A retrospective analysis was conducted on medical records of cutaneous leishmaniasis cases between 2005 and 2022, as well as on questionnaire responses regarding personal protective measures administered to cutaneous leishmaniasis cases in 2022. The reasons behind the unusually high numbers of cutaneous leishmaniasis cases and cumulative incidence in 2022 remain unclear, emphasising the need to improve personal protective measures provision and implement a comprehensive health education programme for troops undergoing jungle training in Belize.

Parasite Epidemiology and Control. November 2024

Praneet Prakash, Xue Jiang , Luke Richards, Zoe Schofield, Patrick Schafer Marco Polin, Orkun S. Soyer & Munehiro Asally

Many species of soil fungi grow in the form of branched networks that enable long-range communication and mass flow of nutrient. While there have been investigations on the branching of the fungal networks, their long-term growth dynamics in space and time is still not very well understood. In this study, we monitor the spatio-temporal growth dynamics of the plant-promoting filamentous fungus Serendipita indica for several days in a controlled environment within a microfluidic chamber. We find that S. indica cells display synchronised growth oscillations with the onset of sporulation and at a period of 3 hours. Quantifying this experimental synchronisation of oscillatory dynamics, we show that the synchronisation can be recapitulated by the nearest neighbour Kuramoto model with a millimetre-scale cell-cell coupling.

Royal Society Interface. October 2024

Georgina Benn, Christian Bortolini, David M Roberts, Alice L B Pyne, Seamus Holden, Bart W Hoogenboom

Complement proteins eliminate Gram-negative bacteria in the blood via the formation of membrane attack complex (MAC) pores in the outer membrane. However, it remains unclear how outer membrane poration leads to inner membrane permeation and cell lysis. Using atomic force microscopy (AFM) on living Escherichia coli (E. coli), we probed MAC-induced changes in the cell envelope and correlated these with subsequent cell death. We conclude that bacterial cell lysis is only an indirect effect of MAC formation; outer membrane poration leads to mechanical destabilization of the cell envelope, reducing its ability to contain the turgor pressure, leading to inner membrane permeation and cell death.

EMBO Journal. October 2024

Helen J. Bates, Jamie Pike, R. Jordan Price, Sascha Jenkins, John Connell, Andrew Legg, Andrew Armitage, Richard J. Harrison and John P. Clarkson

This study presents the first genome and transcriptome analyses for Fusarium oxysporum f. sp. lactucae (Fola) which causes Fusarium wilt disease of lettuce. Long-read genome sequencing of three race 1 (Fola1) and three race 4 (Fola4) isolates revealed key differences in putative effector complement between races and with other F. oxysporum ff. spp. following mimp-based bioinformatic analyses.

Frontiers in Plant Science. October 2024

Jack A. Weaver, Duha Alkhder, Panward Prasongpholchai, Michaël D. Tadesse, Emmanuel L. de los Santos, Lijiang Song, Christophe Corre, Fabrizio Alberti

Pleurotin is a meroterpenoid specialized metabolite made by the fungus Hohenbuehelia grisea, and it is a lead anticancer molecule due to its irreversible inhibition of the thioredoxin-thioredoxin reductase system. Total synthesis of pleurotin has been achieved, including through a stereoselective route; however, its biosynthesis has not been characterized. In this study, we used isotope-labeled precursor feeding to show that the nonterpenoid quinone ring of pleurotin and its congeners is derived from phenylalanine. This work sets the foundation to fully elucidate the biosynthesis of pleurotin and its congeners, with long-term potential to optimize their production for therapeutic use and engineer the pathway toward the biosynthesis of valuable analogues.

ACS Chemical Biology. October 2024

Williams G.K., Akkermans J., Lawson M., Syta P., Staelens S., Adhikari M.H., Morton A.J., Nitzsche B., Boltze J., Christou C., Bertoglio D., Ahamed M.

The major goal of our preliminary cross-sectional study is to demonstrate the feasibility and utility of the unique transgenic sheep model of HD (OVT73) in positron emission tomography (PET) imaging. In this first-of-its-kind study, we showed the usefulness and validity of HD sheep model in imaging cerebral glucose metabolism and dopamine uptake using PET imaging. The identification of discrete patterns of metabolic abnormality using [18F]FDG and decline of [18F]FDOPA uptake may provide a useful means of quantifying early HD-related changes in these models, particularly in the transition from presymptomatic to early symptomatic phases of HD.

ACS Chemical Neuroscience. October 2024

Shashank K Pandey, Jay Prakash Maurya, Bibek Aryal, Kamil Drynda, Aswin Nair, Pal Miskolczi, Rajesh Kumar Singh, Xiaobin Wang, Yujiao Ma, Tatiana de Souza Moraes, Emmanuelle M Bayer, Etienne Farcot, George W Bassel, Leah R Band, Rishikesh P Bhalerao

The control of cell–cell communication via plasmodesmata (PD) plays a key role in plant development. In tree buds, low-temperature conditions (LT) induce a switch in plasmodesmata from a closed to an open state, which restores cell-to-cell communication in the shoot apex and releases dormancy. Using genetic and cell-biological approaches, we have identified a previously uncharacterized transcription factor, Low-temperature-Induced MADS-box 1 (LIM1), as an LT-induced, direct upstream activator of the gibberellic acid (GA) pathway. Mathematical modeling and experimental validation suggest that negative feedback regulation of LIM1 by gibberellin could play a crucial role in maintaining the robust temporal regulation of bud responses to low temperature. These results reveal genetic factors linking temperature control of cell–cell communication with regulation of seasonally-aligned growth crucial for adaptation of trees.

EMBO Journal. October 2024

Luke Richards, Kelsey Cremin, Mary Coates, Finley Vigor, Patrick Schäfer, and Orkun S Soyer

Soil microbial communities host a large number of microbial species that support important ecological functions such as biogeochemical cycling and plant nutrition. The extent and stability of these functions are affected by inter-species interactions among soil microorganisms, yet the different mechanisms underpinning microbial interactions in the soil are not fully understood. Here, we study the extent of nutrient-based interactions among two model, plant-supporting soil microorganisms, the fungi Serendipita indica, and the bacteria Bacillus subtilis. Our findings highlight that ammonia based N-sharing can be a previously under-appreciated mechanism underpinning interaction among soil microorganisms and could be influenced by microbial or abiotic alteration of pH in microenvironments.

ISME Journal. September 2024

Lorenzo Morè, Lucia Privitera, Marcia Lopes, J. Simon C. Arthur, Julie C. Lauterborn, Sonia A.L. Corrêa, Bruno G. Frenguelli

One class of cognitive enhancers, the ampakines, has attracted particular attention by virtue of improving cognition associated with animal models of neurodevelopmental, neurodegenerative, and psychiatric conditions, as well as in age-related cognitive impairment. Ampakines elevate CNS levels of BDNF, and it is through this elevation that their beneficial actions are believed to occur. To establish whether MSK1 converts ampakine-induced elevations of BDNF into cognitive enhancement we tested an ampakine (CX929) in male WT mice and in male mice in which the kinase activity of MSK1 was inactivated. We found that MSK1 is required for the ampakine-dependent improvement in spatial reference memory and cognitive flexibility, and for the elevations of BDNF and the plasticity-related protein Arc associated with ampakines and experience. These observations implicate MSK1 as a key enabler of the beneficial effects of ampakines on cognitive function, and furthermore identify MSK1 as a hub for BDNF-elevating nootropic strategies.

Neuropharmacology. 2024

Keeling, Matthew James and Dyson, Louise

We discuss the invasion of the Omicron BA.1 variant into England as a paradigm for real-time model fitting and projection. Here we use a mixture of simple SIR-type models, analysis of the early data and a more complex age-structure model fit to the outbreak to understand the dynamics. In particular, we highlight that early data shows that the invading Omicron variant had a substantial growth advantage over the resident Delta variant. However, early data does not allow us to reliably infer other key epidemiological parameters - such as generation time and severity - which influence the expected peak hospital numbers. With more complete epidemic data from January 2022 are we able to capture the true scale of the epidemic in terms of both infections and hospital admissions, driven by different infection characteristics of Omicron compared to Delta and a substantial shift in estimated precautionary behaviour during December. This work highlights the challenges of real time forecasting, in a rapidly changing environment with limited information on the variant’s epidemiological characteristics.

PLoS Computational Biology. September 2024

Xiaoning He, Chloé Dias Lopes, Leonardo I Pereyra-Bistrain, Ying Huang, Jing An, Rim Brik Chaouche, Hugo Zalzalé, Qingyi Wang, Xing Ma, Javier Antunez-Sanchez, Catherine Bergounioux, Sophie Piquerez, Sotirios Fragkostefanakis, Yijing Zhang, Shaojian Zheng, Martin Cresp, Magdy M Mahfouz, Olivier Mathieu, Federico Ariel, Jose Gutierrez-Marcos, Xingwang Li, Nicolas Bouché, Cécile Raynaud, David Latrasse, Moussa Benhamed

The 3D chromatin organization plays a major role in the control of gene expression. In this study, employing a combination of genetics and advanced 3D genomics approaches, we demonstrated that a redistribution of facultative heterochromatin marks in regions usually occupied by constitutive heterochromatin marks disrupts the 3D genome compartmentalisation. This disturbance, in turn, triggers novel chromatin interactions between genic and transposable element (TE) regions. Interestingly, our results imply that epigenetic features, constrained by genetic factors, intricately mold the landscape of 3D genome organisation. This study sheds light on the profound genetic-epigenetic interplay that underlies the regulation of gene expression within the intricate framework of the 3D genome. Our findings highlight the complexity of the relationships between genetic determinants and epigenetic features in shaping the dynamic configuration of the 3D genome.

Nucleic Acids Research. September 2024

Mirjam Seeliger, Sally Hilton, George Muscatt, Christopher Walker, David Bass, Felipe Albornoz, Rachel J Standish, Neil D Gray, Louis Mercy, Leonidas Rempelos, Carolin Schneider, Megan H Ryan, Paul E Bilsborrow, Gary D Bending

Arbuscular mycorrhizas (AM) are the most widespread terrestrial symbiosis and are both a key determinant of plant health and a major contributor to ecosystem processes through their role in biogeochemical cycling. Until recently, it was assumed that the fungi which form AM comprise the subphylum Glomeromycotina (G-AMF), and our understanding of the diversity and ecosystem roles of AM is based almost exclusively on this group. However recent evidence shows that fungi which form the distinctive 'fine root endophyte’ (FRE) AM morphotype are members of the subphylum Mucoromycotina (M-AMF), so that AM symbioses are actually formed by two distinct groups of fungi. We investigated the influence of nitrogen (N) addition and wheat variety on the assembly of AM communities under field conditions. The results demonstrate the need to consider both G-AMF and M-AMF when investigating AM communities, and highlight the importance of primer choice when investigating AMF community dynamics.

Environmental Microbiome. September 2024

Lim Chee Liew, Yue You, Lucas Auroux, Marina Oliva, Marta Peirats-Llobet, Sophia Ng, Muluneh Tamiru-Oli, Oliver Berkowitz, Uyen Vu Thuy Hong, Asha Haslem, Tim Stuart, Matthew E. Ritchie, George W. Bassel, Ryan Lister, James Whelan, Quentin Gouil & Mathew G. Lewsey

Here we describe a temporal analysis of the germinating Arabidopsis thaliana embryo at single-cell resolution. We define the highly dynamic cell type-specific patterns of gene expression and how these relate to changing cellular function as germination progresses. Underlying these are unique gene regulatory networks and transcription factor activity. We unexpectedly discover that most embryo cells transition through the same initial transcriptional state early in germination, even though cell identity has already been established during embryogenesis. Cells later transition to cell type-specific gene expression patterns. Furthermore, our analyses support previous findings that the earliest events leading to the induction of seed germination take place in the vasculature. Overall, our study constitutes a general framework with which to characterize Arabidopsis cell transcriptional states through seed germination, allowing investigation of different genotypes and other plant species whose seed strategies may differ. Nature Plants. September 2024

Matthew Higgins, Mojca Kristan, Emma L. Collins, Louisa A. Messenger, Jamille G. Dombrowski, Leen N. Vanheer, Debbie Nolder, Christopher J. Drakeley, William Stone, Almahamoudou Mahamar, Teun Bousema, Michael Delves, Janvier Bandibabone, Sévérin N’Do, Chimanuka Bantuzeko, Bertin Zawadi, Thomas Walker, Colin J. Sutherland, Claudio R. F. Marinho, Mary M. Cameron, Taane G. Clark & Susana Campino

Malaria caused by neglected Plasmodium parasites is often underestimated due to the lack of rapid diagnostic tools that can accurately detect these species. Here, we present a Pan Plasmodium recombinase polymerase amplification lateral flow (RPA–LF) assay, capable of detecting all six human infecting Plasmodium species in low resource settings.. When combined with crude nucleic acid extraction, the assay can serve as a point-of-need tool for molecular xenomonitoring. This utility was demonstrated by screening laboratory-reared Anopheles stephensi mosquitoes fed with Plasmodium-infected blood, as well as field samples of An. funestus s.l. and An. gambiae s.l. collected from central Africa. Overall, our proof-of-concept Pan Plasmodium diagnostic tool has the potential to be applied for clinical and xenomonitoring field surveillance, and after further evaluation, could become an essential tool to assist malaria control and elimination.

Scientific Reports. August 2024

Overview of the MOSAiC expedition: Ecosystem

Allison A. Fong, Clara J. M. Hoppe et al. (incl. H Schafer)

The international and interdisciplinary sea-ice drift expedition “The Multidisciplinary drifting Observatory for the Study of Arctic Climate” (MOSAiC) was conducted from October 2019 to September 2020. The aim of MOSAiC was to study the interconnected physical, chemical, and biological characteristics and processes from the atmosphere to the deep sea of the central Arctic system. The ecosystem team addressed current knowledge gaps and explored unknown biological properties over a complete seasonal cycle focusing on three major research areas: biodiversity, biogeochemical cycles, and linkages to the environment. This article provides a detailed overview of the sampling approaches used to address the three main science objectives. It highlights the core sampling program and provides examples of habitat- or process-specific sampling. The initial results presented include high biological activities in wintertime and the discovery of biological hotspots in underexplored habitats. The unique interconnectivity of the coordinated sampling efforts also revealed insights into cross-disciplinary interactions like the impact of biota on Arctic cloud formation. This overview further presents both lessons learned from conducting such a demanding field campaign and an outlook on spin-off projects to be conducted over the next years.

Elementa: Science of the Anthropocene. August 2024  

Microbial assimilatory sulfate reduction-mediated H2S: an overlooked role in Crohn's disease development

H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota. The study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD. Microbiome. August 2024

de Klerk, Joanna N., Tildesley, Michael J., Labuschagne, Karien and Gorsich, Erin E

Culicoides biting midges exhibit a global spatial distribution and are the main vectors of several viruses of veterinary importance, including bluetongue (BT) and African horse sickness (AHS). The aim of this study was to model distributions for two primary vectors for BT and AHS (Culicoides imicola and Culicoides bolitinos) using random forest (RF) machine learning and explore the relative importance of environmental and anthropological factors in a region of South Africa with frequent AHS and BT outbreaks. This study yielded novel insight into the spatial abundance and drivers of abundance of competent vectors of BT and AHS. It also provided valuable data to inform mathematical models exploring disease outbreaks so that Culicoides-transmitted diseases in South Africa can be further analysed.

Parasites & Vectors. August 2024

Christian Vanhille-Campos, Kevin D. Whitley, Philipp Radler, Martin Loose, Seamus Holden & Anđela Šarić

Filaments in the cell commonly treadmill. Driven by energy consumption, they grow on one end while shrinking on the other, causing filaments to appear motile even though individual proteins remain static. This process is characteristic of cytoskeletal filaments and leads to collective filament self-organization. Here we show that treadmilling drives filament nematic ordering by dissolving misaligned filaments. Taking the bacterial FtsZ protein involved in cell division as an example, we show that this mechanism aligns FtsZ filaments in vitro and drives the organization of the division ring in living Bacillus subtilis cells. We find that ordering via local dissolution also allows the system to quickly respond to chemical and geometrical biases in the cell, enabling us to quantitatively explain the ring formation dynamics in vivo. Beyond FtsZ and other cytoskeletal filaments, our study identifies a mechanism for self-organization via constant birth and death of energy-consuming filaments.

Nature Physics. August 2024

Mireia Montaner, Jessica Denom, Vincent Simon, Wanqing Jiang, Marie K. Holt, Daniel I. Brierley, Claude Rouch, Ewout Foppen, Nadim Kassis, David Jarriault, Dawood Khan, Louise Eygret, Francois Mifsud, David J. Hodson, Johannes Broichhagen, Lukas Van Oudenhove, Xavier Fioramonti, Victor Gault, Daniela Cota, Frank Reimann, Fiona M. Gribble, Stephanie Migrenne-Li, Stefan Trapp, Hirac Gurden & Christophe Magnan

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS.

Nature Communications. August 2024

Huba L. Marton, Antonia P. Sagona, Peter Kilbride and Matthew I. Gibson

Poly(carboxylic acids) have been reported to inhibit phages’ ability to infect their bacterial hosts and hence offer an exciting route to discover additives to prevent infection. Here, we report the role of pH in inactivating phages to determine if the polymers are unique or simply acidic. It is shown that lower pH (= 3) triggered by either acidic polymers or similar changes in pH using HCl lead to inhibition. There is no inhibitory activity at higher pHs (in growth media). It is also shown that poly(acrylic acid) leads to reversible deactivation of phage, but when the pH is adjusted using HCl alone the phage is irreversibly deactivated. Further experiments using metal binders ruled out ion depletion as the mode of action.  These results show that polymeric phage inhibitors may work by unique mechanisms of action and that pH alone cannot explain the observed effects whilst also placing constraints on the practical utility of poly(acrylic acid).

RSC Applied Polymers. August 2024

Prioritising older individuals for COVID-19 booster vaccination leads to optimal public health outcomes in a range of socio-economic settings

Bouros, Ioana, Hill, Edward M., Keeling, Matt J., Moore, Sam and Thompson, Robin N.

The rapid development of vaccines against SARS-CoV-2 altered the course of the COVID-19 pandemic. In most countries, vaccinations were initially targeted at high-risk populations, including older individuals and healthcare workers. Policy makers must now determine how to deploy booster vaccinations, particularly when constraints in vaccine supply, delivery and cost mean that booster vaccines cannot be administered to everyone. A key question is whether older individuals should again be prioritised for vaccination, or whether alternative strategies (e.g. offering booster vaccines to the individuals who have most contacts with others and therefore drive infection) can instead offer indirect protection to older individuals. Here, we use mathematical modelling to address this question, considering SARS-CoV-2 transmission in a range of countries with different socio-economic backgrounds. We show that the population structures of different countries can have a pronounced effect on the impact of booster vaccination, even when identical booster vaccination targeting strategies are adopted. However, under the assumed transmission model, prioritising older individuals for booster vaccination consistently leads to the most favourable public health outcomes in every setting considered. PLoS Computational Biology. August 2024

Modelling timelines to elimination of sleeping sickness in the Democratic Republic of Congo, accounting for possible cryptic human and animal transmission

Sleeping sickness (gambiense human African trypanosomiasis, gHAT) is a vector-borne disease targeted for global elimination of transmission (EoT) by 2030. There are, however, unknowns that have the potential to hinder the achievement and measurement of this goal. These include asymptomatic gHAT infections (inclusive of the potential to self-cure or harbour skin-only infections) and whether gHAT infection in animals can contribute to the transmission cycle in humans. Using modelling, we explore how cryptic (undetected) transmission impacts the monitoring of progress towards and the achievement of the EoT goal. This study is the first to simulate an (as-yet-to-be available) screen-and-treat strategy and found that removing a parasitological confirmation step was predicted to have a more noticeable benefit to transmission reduction under the asymptomatic model compared with the others. Our simulations suggest vector control could greatly impact all transmission routes in all models, although this resource-intensive intervention should be carefully prioritised. Parasites & Vectors. August 2024

Jake Brooks, James Everett, Emily Hill, Kharmen Billimoria, Christopher M. Morris, Peter J. Sadler, Neil Telling & Joanna F. Collingwood

Neuromelanin-pigmented neurons of the substantia nigra are selectively lost during the progression of Parkinson’s disease. These neurons accumulate iron in the disease state, and iron-mediated neuron damage is implicated in cell death. Here, scanning transmission x-ray microscopy (STXM) is used to probe iron foci in relation to the surrounding ultrastructure in melanised neurons of human substantia nigra from a confirmed Parkinson’s case. The findings show that STXM is a powerful label-free tool for the in situ, nanoscale chemical characterisation of both organic and inorganic intracellular components. Future applications are likely to shed new light on incompletely understood biochemical mechanisms, such as metal dysregulation and morphological changes to cell nucleoli, that are important in understanding the pathogenesis of Parkinson’s.

Communications Biology. August 2024

Collette S. Guy, James A. Gott, Jonathan Ramírez-Cárdenas, Christopher de Wolf, Christopher M. Furze, Geoff West, Juan C. Muñoz-García, Jesus Angulo and Elizabeth Fullam 

The sensitive, rapid and accurate diagnosis of Mycobacterium tuberculosis (Mtb) infection is a central challenge in controlling the global tuberculosis (TB) pandemic. Yet the detection of mycobacteria is often made difficult by the low sensitivity of current diagnostic tools, with over 3.6 million TB cases missed each year. To overcome these limitations there is an urgent need for next-generation TB diagnostic technologies. Here we report the use of a discrete panel of native 19F-trehalose (F-Tre) analogues to label and directly visualise Mtb by exploiting the uptake of fluorine-modified trehalose analogues via the mycobacterial trehalose LpqY-SugABC ATP-binding cassette (ABC) importer.. This rapid one-step labelling approach facilitates the direct visualisation of F-Tre-labelled Mtb by Focused Ion Beam (FIB) Secondary Ion Mass Spectrometry (SIMS), enabling detection of the Mtb pathogen. Collectively, our findings highlight that F-Tre analogues have potential as tools to probe and unravel Mtb biology and can be exploited to detect and image TB

Chemical Science.August 2024

Peter Wotherspoon, Hannah Johnston, David J. Hardy, Rachel Holyfield, Soi Bui, Giedrė Ratkevičiūtė, Pooja Sridhar, Jonathan Colburn, Charlotte B. Wilson, Adam Colyer, Benjamin F. Cooper, Jack A. Bryant, Gareth W. Hughes, Phillip J. Stansfeld, Julien R. C. Bergeron & Timothy J. Knowles

The Maintenance of Lipid Asymmetry (Mla) pathway is a multicomponent system found in all gram-negative bacteria that contributes to virulence, vesicle blebbing and preservation of the outer membrane barrier function. Here, we report the structure of E. coli MlaC in complex with the MlaD hexamer in two distinct stoichiometries. Utilising in vivo complementation assays, an in vitro fluorescence-based transport assay, and molecular dynamics simulations, we confirm key residues, identifying the MlaD β6-β7 loop as essential for MlaCD function. We also provide evidence that phospholipids pass between the C-terminal helices of the MlaD hexamer to reach the central pore, providing insight into the trajectory of GPL transfer between MlaC and MlaD.

Nature Communications. July 2024

Habib Bashour, Eva Smorodina, Matteo Pariset, Jahn Zhong, Rahmad Akbar, Maria Chernigovskaya, Khang Lê Quý, Igor Snapkow, Puneet Rawat, Konrad Krawczyk, Geir Kjetil Sandve, Jose Gutierrez-Marcos, Daniel Nakhaee-Zadeh Gutierrez, Jan Terje Andersen & Victor Greiff

Designing effective monoclonal antibody (mAb) therapeutics faces a multi-parameter optimization challenge known as “developability”, which reflects an antibody’s ability to progress through development stages based on its physicochemical properties. To chart natural and engineered DP landscapes, we computed 40 sequence- and 46 structure-based DPs of over two million native and human-engineered single-chain antibody sequences. We show that sequence DPs are more predictable than structure-based ones across different machine-learning tasks and embeddings, indicating a constrained sequence-based design space. Human-engineered antibodies localize within the developability and sequence landscapes of natural antibodies, suggesting that human-engineered antibodies explore mere subspaces of the natural one. Our work quantifies the plasticity of antibody developability, providing a fundamental resource for multi-parameter therapeutic mAb design.

Communications Biology July 2024

Okinaka Y, Maeda M, Kataoka Y, Nakagomi T, Doi A, Boltze J, Claussen C, Gul S, Taguchi A

Intravascularly transplanted bone marrow cells, including bone marrow mononuclear cells (BM-MNC) and mesenchymal stem cells, transfer water-soluble molecules to cerebral endothelial cells via gap junctions. Following transplantation of BM-MNC, this fosters hippocampal neurogenesis and enhancement of neuronal function. Herein, we report the impact of transplanted BM-MNC on neural stem cells (NSC) in the brain. Surprisingly, direct transfer of water-soluble molecules from transplanted BM-MNC and peripheral mononuclear cells to NSC in the hippocampus was observed already 10 minutes after cell transplantation, and transfer from BM-MNC to GFAP-positive cortical astrocytes was also observed. In-vitro investigations revealed that BM-MNC abolish the expression of HIF1α in astrocytes. We suggest that the transient and direct transfer of water-soluble molecules between cells in circulation and NSC in the brain may be one of the biological mechanisms underlying repair of brain function.

Stem Cells & Development. July 2024

Behzad Dehghani, Christopher D. A. Rodrigues

During spore development in bacteria, a polar septum separates two transcriptionally distinct cellular compartments, the mother cell and the forespore. The conserved serine phosphatase SpoIIE is known for its critical role in the formation of this septum and activation of compartment-specific transcription in the forespore. Signaling between the mother cell and forespore then leads to activation of mother cell transcription and a phagocytic-like process called engulfment, which involves dramatic remodeling of the septum and requires a balance between peptidoglycan synthesis and hydrolysis to ensure septal stability and compartmentalization. Using Bacillus subtilis, we identify an additional role for SpoIIE in maintaining septal stability and compartmentalization at the onset of engulfment. Our data support a model whereby SpoIIE and its interactions with the peptidoglycan synthetic machinery contribute to the stabilization of the asymmetric septum early in engulfment, thereby ensuring compartmentalization during spore development.

Journal of Bacteriology. July 2024

Eleanor L. Dearlove, David Chandler, Steve Edgington, Shaun D. Berry, Gareth Martin, Claus Svendsen & Helen Hesketh

Management of T. vaporariorum is problematic because of widespread pesticide resistance, and many greenhouse growers rely on biological control agents to regulate T. vaporariorum populations. However, these are often slow and vary in efficacy, leading to subsequent application of chemical insecticides when pest populations exceed threshold levels. In this study, we evaluated co-applications of the entomopathogenic fungi (EPF) Beauveria bassiana and Cordyceps farinosa and the chemical insecticide spiromesifen in laboratory bioassays. Results indicate the potential for combined applications of EPF and spiromesifen as an effective integrated pest management strategy and demonstrate the applicability of the MixTox model to describe complex mixture interactions.

Scientific Reports. July 2024

Michelle Kendall, Luca Ferretti, Chris Wymant, Daphne Tsallis, James Petrie, Andrea di Francia, Franceso di Lauro, Lucie Abeler-Dorner, Harrison Manley, Jasmina Panovska-Griffiths, Alice Ledda, Xavier Didelot and Christophe Fraser

Understanding the drivers of respiratory pathogen spread is challenging, particularly in a timely manner during an ongoing epidemic. Here we present insights obtained using daily data from the NHS COVID-19 app for England and Wales and shared with health authorities in almost real time. Our indicator of the reproduction number R(t) was available days earlier than other estimates, with a novel capability to decompose R(t) into contact rates and probabilities of infection. When Omicron arrived, the main epidemic driver switched from contacts to transmissibility. We separate contacts and transmissions by day of exposure and setting, finding pronounced variability over days of the week and during Christmas holidays and events. As an example, during the Euro football tournament in 2021, days with England matches showed sharp spikes in exposures and transmissibility. Digital contact tracing technologies can help control epidemics not only by directly preventing transmissions but also by enabling rapid analysis at scale and with unprecedented resolution.  

Science. July 2024

Tailise Carolina de Souza-Guerreiro, Letícia Huan Bacellar, Thyerre Santana da Costa, Conor LA Edwards, Ljubica Tasic & Munehiro Asally

Membrane potential is a useful marker for antimicrobial susceptibility testing (AST) due to the fundamental characteristic of vital cells. However, the difficulties associated with measuring the membrane potential in microbes restrict its broad application. In this study, we present Bioelectrical AST (BeAST) using the model fungus Saccharomyces cerevisiae . The results suggest that BeAST holds promise for screening anti-fungal compounds, offering a valuable approach to tackling antimicrobial resistance.

mBio. July 2024

When should lockdown be implemented? Devising cost-effective strategies for managing epidemics amid vaccine uncertainty

Doyle, Nathan, Cumming, Fergus, Thompson, Robin N. and Tildesley, Michael J.

We combine features of existing models to develop a novel model for vectorial capacity that considers both climate and vector control. This model considers how vector control tools affect vectors at each stage of their feeding cycle, and incorporates host availability and preference. Applying this model to arboviruses of veterinary importance in Europe, we show that African horse sickness virus (AHSV) has a higher peak predicted vectorial capacity than bluetongue virus (BTV), Schmallenberg virus (SBV), and epizootic haemorrhagic disease virus (EHDV). However, AHSV has a shorter average infectious period due to high mortality; therefore, the overall basic reproduction number of AHSV is similar to BTV. Overall, this model can be used to consider both climate and vector control interventions either currently utilised or for potential use in an outbreak, and could help guide policy makers seeking to mitigate the impact of climate change on disease control. PLoS Computational Biology. July 2024

Modelling the Influence of Climate and Vector Control Interventions on Arbovirus Transmission

We combine features of existing models to develop a novel model for vectorial capacity that considers both climate and vector control. This model considers how vector control tools affect vectors at each stage of their feeding cycle, and incorporates host availability and preference. Applying this model to arboviruses of veterinary importance in Europe, we show that African horse sickness virus (AHSV) has a higher peak predicted vectorial capacity than bluetongue virus (BTV), Schmallenberg virus (SBV), and epizootic haemorrhagic disease virus (EHDV). However, AHSV has a shorter average infectious period due to high mortality; therefore, the overall basic reproduction number of AHSV is similar to BTV. Overall, this model can be used to consider both climate and vector control interventions either currently utilised or for potential use in an outbreak, and could help guide policy makers seeking to mitigate the impact of climate change on disease control. Viruses. July 2024

Shefeeq M. Theparambil, Olga Kopach, Alice Braga, Shereen Nizari, Patrick S. Hosford, Virag Sagi-Kiss, Anna Hadjihambi, Christos Konstantinou, Noemi Esteras, Ana Gutierrez Del Arroyo, Gareth L. Ackland, Anja G. Teschemacher, Nicholas Dale, Tobias Eckle, Petros Andrikopoulos, Dmitri A. Rusakov, Sergey Kasparov & Alexander V. Gourine

Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply. Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism, but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood. Here we show, using experimental in vitro and in vivo animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulator adenosine acting on astrocytic A2B receptors. The data identifies the adenosine A2B receptor as an astrocytic sensor of neuronal activity and show that cAMP signalling in astrocytes tunes brain energy metabolism to support its fundamental functions such as sleep and memory.

Nature. July 2024

Michael Hymas, Sopida Wongwas, Simin Roshan, Abigail L. Whittock, Christophe Corre, Reza Omidyan and Vasilios G. Stavros

Mycosporine glycine (MyG) was produced by the fermentation of a purposely engineered bacterial strain and isolated from this sustainable source. The ultrafast spectroscopy of MyG was then investigated in its native, zwitterionic form (MyGzwitter), via femtosecond transient electronic absorption spectroscopy. Complementary nonadiabatic (NAD) simulations suggest that, upon photoexcitation to the lowest excited singlet state (S1), MyGzwitter undergoes efficient nonradiative decay to repopulate the electronic ground state (S0). We propose an initial ultrafast ring-twisting mechanism toward an S1/S0 conical intersection, followed by internal conversion to S0 and subsequent vibrational cooling. This study illuminates the workings of the archetype mycosporine, providing photoprotection, in the UV–B range, to organisms such as corals, macroalgae, and cyanobacteria. This study also contributes to our growing understanding of the photoprotection mechanisms of life.

Journal of Physical Chemistry Letters. July 2024

Joshua C. Macdonald, Hayriye Gulbudak, Brianna Beechler, Erin E. Gorsich, Simon Gubbins, Eva Pérez-Martin and Anna E. Jolles

We investigated within-host dynamics and among-host transmission of three strains (SAT-1, -2, -3) of foot-and-mouth disease viruses (FMDVs) in their wildlife host, African buffalo. Our data reveals contrasting within-host dynamics among viral strains, with SAT-2 eliciting more rapid and effective immune responses than SAT-1 and SAT-3. Within-host viral fitness was overwhelmingly determined by variation among hosts in immune response activation rates but not by variation among individual hosts in viral growth rate. Our analyses investigating across-scale linkages indicate that viral replication rate in the host correlates with transmission rates among buffalo and that adaptive immune activation rate determines the infectious period. These parameters define the virus’s relative basic reproductive number (ℛ0), suggesting that viral invasion potential may be predictable from within-host dynamics.

American Naturalist. July 2024

Nicole Pereira, Kathryn R. Hales, Andrew Mead, Lauren H. K. Chappell, Guy C. Barker, John P. Clarkson

In Europe, cavity spot disease continues to have a major impact on marketable yield. The lack of reliable inoculation methods for these Pythium pathogens has, for many years, hampered the identification of new effective crop protection products or carrot varieties that are resistant to the disease. In this research, inoculation methods were developed for P. violae using mycelium or oospores, each of which successfully induced typical cavity spot symptoms in both pot- and field-grown carrots as well as consistent root stunting in the former. These methods were also used to successfully identify carrot cultivars with resistance to cavity spot and confirmed the efficacy of the fungicide metalaxylM against the disease. Results therefore demonstrated that the inoculation methods should be reliable for identifying the efficacy of crop protection products, assessing cavity spot resistance and for further studies investigating the biology and epidemiology of the pathogen.

Plant Pathology. July 2024

Jing An, Rim Brik Chaouche, Leonardo I Pereyra-Bistraín, Hugo Zalzalé, Qingyi Wang, Ying Huang, Xiaoning He, Chloé Dias Lopes, Javier Antunez-Sanchez, Catherine Bergounioux, Claire Boulogne, Cynthia Dupas, Cynthia Gillet, José Manuel Pérez-Pérez, Olivier Mathieu, Nicolas Bouché, Sotirios Fragkostefanakis, Yijing Zhang, Shaojian Zheng, Martin Crespi, Magdy M Mahfouz, Federico Ariel, Jose Gutierrez-Marcos, Cécile Raynaud, David Latrasse, Moussa Benhamed

In recent years, the exploration of genome three-dimensional (3D) conformation has yielded profound insights into the regulation of gene expression and cellular functions in both animals and plants. Employing advanced high-throughput sequencing and microscopy techniques, we investigated the landscape of 26 histone modifications and RNA polymerase II distribution in tomato (Solanum lycopersicum). Our study unveiled a rich and nuanced epigenetic landscape, shedding light on distinct chromatin states associated with heterochromatin formation and gene silencing. Moreover, we elucidated the intricate interplay between these chromatin states and the overall topology of the genome. Employing a genetic approach, we delved into the role of the histone modification H3K9ac in genome topology. Notably, our investigation revealed that the ectopic deposition of this chromatin mark triggered a reorganization of the 3D chromatin structure, defining different TAD-like borders. Our work emphasizes the critical role of H3K9ac in shaping the topology of the tomato genome, providing valuable insights into the epigenetic landscape of this agriculturally significant crop species.

PNAS. July 2024

Perioperative stroke deteriorates white matter integrity by enhancing cytotoxic CD8 + T‐cell activation

Yuxi Zhou, Xin Wang, Wen Yin, Yan Li, Yunlu Guo, Chen Chen, Johannes Boltze, Arthur Liesz, Tim Sparwasser, Daxiang Wen, Weifeng Yu, and Peiying Li

Here we explore the regulatory mechanisms of microglia‐mediated cytotoxic CD8+ T‐cell infiltration in the white matter injury of perioperative stroke (PIS). We found surgery aggravated white matter injury and deteriorated sensorimotor deficits up to 28 days following PIS. The PIS mice exhibited significantly increased activation of peripheral and central CD8+ T cells, while significantly reduced numbers of mature oligodendrocytes compared to IS mice. Neutralizing CD8+ T cells partly reversed the aggravated demyelination following PIS. Pharmacological blockage or genetic deletion of receptor‐interacting protein kinase 1 (RIPK1) activity could alleviate CD8+ T‐cell infiltration and demyelination in PIS mice. Surgery exacerbates demyelination and worsens neurological function by promoting infiltration of CD8+ T cells and microglia necroptosis, suggesting that modulating interactions of CD8+ T cells and microglia could be a novel therapeutic target of long‐term neurological deficits of PIS.. CNS Neuroscience and Therapeutics. July 2024

The association between air pollutant exposure and cerebral small vessel disease imaging markers with modifying effects of PRS-defined genetic susceptibility

Studies have highlighted a possible link between air pollution and cerebral small vessel disease (CSVD) imaging markers. However, the exact association and effects of polygenic risk score (PRS) defined genetic susceptibility remains unclear. This cross-sectional study used data from the UK Biobank. Participants aged 40–69 years were recruited between the year 2006 and 2010. The annual average concentrations of NOX, NO2, PM2.5, PM2.5–10, PM2.5 absorbance, and PM10, were estimated, and joint exposure to multiple air pollutants was reflected in the air pollution index (APEX). Air pollutant exposure was classified into the low (T1), intermediate (T2), and high (T3) tertiles.. Our study demonstrated that air pollutant exposure may be associated with CSVD imaging markers, with females being more susceptible, and that PRS-defined genetic susceptibility may modify the associations of air pollutants.

Toxicology and Environmental Safety. June 2024

Mojgan Rabiey, Emily R. Grace, Paulina Pawlos, Muscab Bihi, Haleem Ahmed, Georgina E. Hampson, Amna Al Riyami, Leena Alharbi, Rosa Sanchez-Lucas, Naina Korotania, Maria Laura Ciusa, Olivia Mosley, Michelle T. Hulin, Laura Baxter, Sabrine Dhaouadi, Diana Vinchira-Villarraga, Robert W. Jacks

Pseudomonas syringae pathovar syringae (Pss) is a major pathogen of cherry (Prunus avium) causing bacterial canker of the stem, leaf and fruit, impacting productivity and leading to a loss of trees. In an attempt to find a treatment for this disease, naturally occurring bacteriophage (phage) that specifically target Pss is being investigated as a biocontrol strategy. However, before using them as a biocontrol treatment, it is important to both understand their efficacy in reducing the bacterial population and determine if the bacterial pathogens can evolve resistance to evade phage infection. To investigate this, killing curve assays of five MR phages targeting Pss showed that phage resistance rapidly emerges in vitro, even when using a cocktail of the five phages together. This study shows that understanding the genetic mechanisms of bacterial pathogen resistance to phages is important for helping to design a more effective approach to kill the bacteria while minimizing the opportunity for phage resistance to manifest.

Microbial Biotechnology. June 20204

Rodrigo Barquera, Oana Del Castillo-Chávez, Kathrin Nägele, Patxi Pérez-Ramallo, Diana Iraíz Hernández-Zaragoza, András Szolek, Adam Benjamin Rohrlach, Pablo Librado, Ainash Childebayeva, Raffaela Angelina Bianco, Bridget S. Penman, Victor Acuña-Alonzo, Mary Lucas, Julio César Lara-Riegos, María Ermila Moo-Mezeta, Julio César Torres-Romero, Patrick Roberts, Oliver Kohlbacher, Christina Warinner & Johannes Krause

Here we present genome-wide data obtained from 64 subadult individuals dating to around AD 500-900 that were found in a subterranean mass burial near the Sacred Cenote (sinkhole) in the ceremonial centre of Chichén Itzá. Genetic analyses showed that all analysed individuals were male and several individuals were closely related, including two pairs of monozygotic twins. Twins feature prominently in Mayan and broader Mesoamerican mythology, where they embody qualities of duality among deities and heroes, but until now they had not been identified in ancient Mayan mortuary contexts. Genetic comparison to present-day people in the region shows genetic continuity with the ancient inhabitants of Chichén Itzá, except at certain genetic loci related to human immunity, including the human leukocyte antigen complex, suggesting signals of adaptation due to infectious diseases introduced to the region during the colonial period. Nature. June 2024

Carvalho, Bruno M., Maia, Carla, Courtenay, Orin, Llabrés-Brustenga, Alba, Lotto Batista, Martín, Moirano, Giovenale, van Daalen, Kim R., Semenza, Jan C. and Lowe, Rachel

Leishmaniases are neglected diseases transmitted by sand flies. The aim of this modelling study was to develop an indicator that tracks climatic suitability for Leishmania infantum transmission in Europe at the subnational level. Historical records of sand fly vectors, human leishmaniasis, bioclimatic indicators, and environmental variables were integrated in a machine learning framework (XGBoost) to predict suitability in two past periods (2001–2010 and 2011–2020. This study demonstrates how key epidemiological data can be combined with open-source climatic and environmental information to develop an indicator that effectively tracks spatiotemporal changes in climatic suitability and disease risk. The positive association between the model predictions and human disease incidence demonstrates that this indicator could help target leishmaniasis surveillance to transmission hotspots.

The Lancet Regional Health - Europe. June 2024

Stuart Middlemiss, Matthieu Blandenet, David M. Roberts, Andrew McMahon, James Grimshaw, Joshua M. Edwards, Zikai Sun, Kevin D. Whitley, Thierry Blu, Henrik Strahl & Seamus Holden

Most rod-shaped bacteria elongate by inserting new cell wall material into the inner surface of the cell sidewall. This is performed by class A penicillin binding proteins (PBPs) and a highly conserved protein complex, the elongasome, which moves processively around the cell circumference and inserts long glycan strands that act as barrel-hoop-like reinforcing structures, thereby giving rise to a rod-shaped cell. However, it remains unclear how elongasome synthesis dynamics and termination events are regulated to determine the length of these critical cell-reinforcing structures. To address this, we developed a method to track individual elongasome complexes around the entire circumference of Bacillus subtilis cells for minutes-long periods using single-molecule fluorescence microscopy. Our results demonstrate that molecular motor tug-of-war is a key regulator of elongasome dynamics in B. subtilis, which likely also regulates the cell shape via modulation of elongasome processivity.

Nature Communications. June 2024

Laura Reyes-Haro, Gillian Prince, Rommel Santiago Granja-Travez, David Chandler

The diamondback moth (DBM) (Plutella xylostella) causes large losses to global crop production. Conventional insecticides are losing effectiveness due to resistance. Consequently, there is a growing interest in sustainable control methods like entomopathogenic fungi (EPF) in Integrated Pest Management. However, the field efficacy of fungi varies due to environmental influences. In this study, a group of 50 Beauveria strains sourced from different locations were characterized by genotype and phenotype with respect to their conidial production, temperature and UV-B radiation tolerance, and virulence against DBM. Survival under environmental conditions is crucial for EPF-based commercial products against DBM. Results suggest strain tolerance to environmental stressors is more tied to specific micro-climatic factors than geographical origin. Each strain exhibited unique characteristics; for example, the most virulent strain (#29) was highly UV-sensitive. Therefore, characterizing diverse strains provides essential genotypic and phenotypic insights, which are fundamental for understanding their role as biocontrol agents while facilitating efficient biopesticide product development and uptake

Pest Management Science. June 2024

Deborah H. Brotherton, Sarbjit Nijjar, Christos G. Savva, Nicholas Dale, Alexander D. Cameron

Connexins allow intercellular communication by forming gap junction channels (GJCs) between juxtaposed cells. Connexin26 (Cx26) can be regulated directly by CO2. This is proposed to be mediated through carbamylation of K125. We show that mutating K125 to glutamate, mimicking the negative charge of carbamylation, causes Cx26 GJCs to be constitutively closed. Through cryo-EM we observe that the K125E mutation pushes a conformational equilibrium towards the channel having a constricted pore entrance, similar to effects seen on raising the partial pressure of CO2. In previous structures of connexins, the cytoplasmic loop, important in regulation and where K125 is located, is disordered. Through further cryo-EM studies we trap distinct states of Cx26 and observe density for the cytoplasmic loop. The interplay between the position of this loop, the conformations of the transmembrane helices and the position of the N-terminal helix, which controls the aperture to the pore, provides a mechanism for regulation.

eLife. June 2023

Harrison Manley,Thomas Bayley,Gabriel Danelian, Lucy Burton, Thomas Finnie, Andre Charlett, Nicholas A. Watkins, Paul Birrell, Daniela De Angelis, Matt Keeling, Sebastian Funk, Graham Medley, Lorenzo Pellis, Marc Baguelin, Graeme J. Ackland, Johanna Hutchinson, Steven Riley and Jasmina Panovska-Griffiths

Mathematical modelling has played an important role in offering informed advice during the COVID-19 pandemic. In England, a cross government and academia collaboration generated medium-term projections (MTPs) of possible epidemic trajectories over the future 4–6 weeks from a collection of epidemiological models. In this article, we outline this collaborative modelling approach and evaluate the accuracy of the combined and individual model projections against the data over the period Learning from our experience of ensemble modelling during the COVID-19 epidemic, our findings highlight the importance of developing cross-institutional multi-model infectious disease hubs for future outbreak control.

Royal Society Open Science. May 2024