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  • Journal article
    Ono M, 2024,

    Unraveling T-cell dynamics using fluorescent timer: Insights from the Tocky system

    , Biophysics and Physicobiology
  • Journal article
    Herzog MK-M, Cazzaniga M, Peters A, Shayya N, Beldi L, Hapfelmeier S, Heimesaat MMM, Bereswill S, Frankel G, Gahan CGM, Hardt W-Det al., 2023,

    Mouse models for bacterial enteropathogen infections: insights into the role of colonization resistance

    , GUT MICROBES, Vol: 15, ISSN: 1949-0976
  • Journal article
    Rosindell J, Manson K, Gumbs R, Pearse WD, Steel Met al., 2023,

    Phylogenetic Biodiversity Metrics Should Account for Both Accumulation and Attrition of Evolutionary Heritage.

    , Syst Biol

    Phylogenetic metrics are essential tools used in the study of ecology, evolution and conservation. Phylogenetic diversity (PD) in particular is one of the most prominent measures of biodiversity, and is based on the idea that biological features accumulate along the edges of phylogenetic trees that are summed. We argue that PD and many other phylogenetic biodiversity metrics fail to capture an essential process that we term attrition. Attrition is the gradual loss of features through causes other than extinction. Here we introduce 'EvoHeritage', a generalisation of PD that is founded on the joint processes of accumulation and attrition of features. We argue that whilst PD measures evolutionary history, EvoHeritage is required to capture a more pertinent subset of evolutionary history including only components that have survived attrition. We show that EvoHeritage is not the same as PD on a tree with scaled edges; instead, accumulation and attrition interact in a more complex non-monophyletic way that cannot be captured by edge lengths alone. This leads us to speculate that the one dimensional edge lengths of classic trees may be insufficiently flexible to capture the nuances of evolutionary processes. We derive a measure of EvoHeritage and show that it elegantly reproduces species richness and PD at opposite ends of a continuum based on the intensity of attrition. We demonstrate the utility of EvoHeritage in ecology as a predictor of community productivity compared with species richness and PD. We also show how EvoHeritage can quantify living fossils and resolve their associated controversy. We suggest how the existing calculus of PD-based metrics and other phylogenetic biodiversity metrics can and should be recast in terms of EvoHeritage accumulation and attrition.

  • Journal article
    González-Ferreras AM, Barquín J, Blyth PSA, Hawksley J, Kinsella H, Lauridsen R, Morris OF, Peñas FJ, Thomas GE, Woodward G, Zhao L, O'Gorman EJet al., 2023,

    Chronic exposure to environmental temperature attenuates the thermal sensitivity of salmonids.

    , Nat Commun, Vol: 14

    Metabolism, the biological processing of energy and materials, scales predictably with temperature and body size. Temperature effects on metabolism are normally studied via acute exposures, which overlooks the capacity for organisms to moderate their metabolism following chronic exposure to warming. Here, we conduct respirometry assays in situ and after transplanting salmonid fish among different streams to disentangle the effects of chronic and acute thermal exposure. We find a clear temperature dependence of metabolism for the transplants, but not the in-situ assays, indicating that chronic exposure to warming can attenuate salmonid thermal sensitivity. A bioenergetic model accurately captures the presence of fish in warmer streams when accounting for chronic exposure, whereas it incorrectly predicts their local extinction with warming when incorporating the acute temperature dependence of metabolism. This highlights the need to incorporate the potential for thermal acclimation or adaptation when forecasting the consequences of global warming on ecosystems.

  • Journal article
    Moriel DG, Piccioli D, Raso MM, Pizza Met al., 2023,

    The overlooked bacterial pandemic.

    , Semin Immunopathol

    The COVID-19 pandemic had a significant economic and health impact worldwide. It also reinforced the misperception that only viruses can pose a threat to human existence, overlooking that bacteria (e.g., plague and cholera) have severely haunted and shaped the course of human civilization. While the world is preparing for the next viral pandemic, it is again overlooking a silent one: antimicrobial resistance (AMR). This review proposes to show the impact of bacterial infections on civilization to remind the pandemic potential. The work will also discuss a few examples of how bacteria can mutate risking global spread and devastating outcomes, the effect on the global burden, and the prophylactic and therapeutic measures. Indeed, AMR is dramatically increasing and if the trend is not reversed, it has the potential to quickly turn into the most important health problem worldwide.

  • Journal article
    Ghani L, Kim S, Ehsan M, Lan B, Poulsen IH, Dev C, Katsube S, Byrne B, Guan L, Loland CJ, Liu X, Im W, Chae PSet al., 2023,

    Melamine-cored glucosides for membrane protein solubilization and stabilization: importance of water-mediated intermolecular hydrogen bonding in detergent performance

    , Chemical Science, Vol: 14, Pages: 13014-13024, ISSN: 2041-6520

    Membrane proteins play essential roles in a number of biological processes, and their structures are important in elucidating such processes at the molecular level and also for rational drug design and development. Membrane protein structure determination is notoriously challenging compared to that of soluble proteins, due largely to the inherent instability of their structures in non-lipid environments. Micelles formed by conventional detergents have been widely used for membrane protein manipulation, but they are suboptimal for long-term stability of membrane proteins, making downstream characterization difficult. Hence, there is an unmet need for the development of new amphipathic agents with enhanced efficacy for membrane protein stabilization. In this study, we designed and synthesized a set of glucoside amphiphiles with a melamine core, denoted melamine-cored glucosides (MGs). When evaluated with four membrane proteins (two transporters and two G protein-coupled receptors), MG-C11 conferred notably enhanced stability compared to the commonly used detergents, DDM and LMNG. These promising findings are mainly attributed to a unique feature of the MGs, i.e., the ability to form dynamic water-mediated hydrogen-bond networks between detergent molecules, as supported by molecular dynamics simulations. Thus, MG-C11 is the first example of a non-peptide amphiphile capable of forming intermolecular hydrogen bonds within a protein-detergent complex environment. Detergent micelles formed via a hydrogen-bond network could represent the next generation of highly effective membrane-mimetic systems useful for membrane protein structural studies.

  • Journal article
    Scopa C, Barnada SM, Cicardi ME, Singer M, Trotti D, Trizzino Met al., 2023,

    JUN upregulation drives aberrant transposable element mobilization, associated innate immune response, and impaired neurogenesis in Alzheimer’s disease

    , Nature Communications, Vol: 14, ISSN: 2041-1723

    Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer’s disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death in AD progenitors and neurons. Notably, inhibiting c-Jun effectively blocks all these downstream molecular processes and rescues neuronal death and the impaired neurogenesis phenotype in AD progenitors. Our findings open new avenues for identifying therapeutic strategies and biomarkers to counteract disease progression and diagnose AD in the early, pre-symptomatic stages.

  • Journal article
    Eberhart-Hertel LJ, Rodrigues LF, Krietsch J, Hertel AG, Cruz-López M, Vázquez-Rojas KA, González-Medina E, Schroeder J, Küpper Cet al., 2023,

    Egg size variation in the context of polyandry: a case study using long-term field data from snowy plovers.

    , Evolution, Vol: 77, Pages: 2590-2605

    Gamete size variation between the sexes is central to the concept of sex roles, however, to what extent gamete size variation within the sexes relates to sex role variation remains unclear. Comparative and theoretical studies suggest that, when clutch size is invariable, polyandry is linked to a reduction of egg size, while increased female-female competition for mates favors early breeding when females cannot monopolize multiple males. To understand whether and how breeding phenology, egg size, and mating behavior are related at the individual level, we studied the reproductive histories of 424 snowy plover females observed in the wild over a 15-year period. Egg size, but not polyandry, were highly repeatable for individual females. Consistent with theoretical predictions, we found that polyandrous females were the earliest breeders and that early clutches contained smaller eggs than clutches initiated later. Neither egg size nor mating behavior showed clear signs of an age-related deterioration, on the contrary, prior experience acquired either through age or local recruitment enabled females to nest early. Taken together, these results suggest that gamete size variation is not linked to mating behavior at the individual level, and, consequently, the adaptive potential of such variation appears to be limited.

  • Journal article
    Kourelis J, 2023,

    Interplay between cell-surface receptor and intracellular NLR-mediated immune responses

    , New Phytologist, Vol: 240, Pages: 2218-2226, ISSN: 0028-646X

    The functional link between cell-surface receptors and intracellular NLR immune receptors is a critical aspect of plant immunity. To establish disease, successful pathogens have evolved mechanisms to suppress cell-surface immune signalling. In response, plants have adapted by evolving NLRs that recognize pathogen effectors involved in this suppression, thereby counteracting their immune-suppressing function. This ongoing co-evolutionary struggle has seemingly resulted in intertwined signalling pathways in some plant species, where NLRs form a separate signalling branch downstream of activated cell-surface receptor complexes essential for full immunity. Understanding these interconnected receptor networks could lead to novel strategies for developing durable disease resistance.

  • Journal article
    Ruehr S, Keenan TF, Williams C, Zhou Y, Lu X, Bastos A, Canadell JG, Prentice IC, Sitch S, Terrer Cet al., 2023,

    Publisher Correction: Evidence and attribution of the enhanced land carbon sink (Nature Reviews Earth & Environment, (2023), 4, 8, (518-534), 10.1038/s43017-023-00456-3)

    , Nature Reviews Earth and Environment, Vol: 4

    Correction to: Nature Reviews Earth & Environment, published online 25 July 2023. In the version of the article initially published, the y-axis labels in Fig. 7b, now reading “+” and “–”, read “234” and “254”, respectively. This has been corrected in the HTML and PDF versions of the article.

  • Journal article
    May DA, Taha F, Child MA, Ewald SEet al., 2023,

    How colonization bottlenecks, tissue niches, and transmission strategies shape protozoan infections

    , Trends in Parasitology, Vol: 39, Pages: 1074-1086, ISSN: 0169-4758

    Protozoan pathogens such as Plasmodium spp., Leishmania spp., Toxoplasma gondii, and Trypanosoma spp. are often associated with high-mortality, acute and chronic diseases of global health concern. For transmission and immune evasion, protozoans have evolved diverse strategies to interact with a range of host tissue environments. These interactions are linked to disease pathology, yet our understanding of the association between parasite colonization and host homeostatic disruption is limited. Recently developed techniques for cellular barcoding have the potential to uncover the biology regulating parasite transmission, dissemination, and the stability of infection. Understanding bottlenecks to infection and the in vivo tissue niches that facilitate chronic infection and spread has the potential to reveal new aspects of parasite biology.

  • Journal article
    Martínez-Riaño A, Wang S, Boeing S, Minoughan S, Casal A, Spillane KM, Ludewig B, Tolar Pet al., 2023,

    Author Correction: Long-term retention of antigens in germinal centers is controlled by the spatial organization of the follicular dendritic cell network.

    , Nat Immunol, Vol: 24
  • Journal article
    Budzak J, Goodwin I, Tiengwe C, Rudenko Get al., 2023,

    Imaging of genomic loci in Trypanosoma brucei using an optimised LacO-LacI system

    , Molecular and Biochemical Parasitology, Vol: 256, ISSN: 0166-6851

    Visualisation of genomic loci by microscopy is essential for understanding nuclear organisation, particularly at the single cell level. One powerful technique for studying the positioning of genomic loci is through the Lac Operator-Lac Repressor (LacO-LacI) system, in which LacO repeats introduced into a specific genomic locus can be visualised through expression of a LacI-protein fused to a fluorescent tag. First utilised in Trypanosoma brucei over 20 years ago, we have now optimised this system with short, stabilised LacO repeats of less than 2 kb paired with a constitutively expressed mNeongreen::LacI fusion protein to facilitate visualisation of genomic loci. We demonstrate the compatibility of this system with super-resolution microscopy and propose its suitability for multiplexing with inducible RNAi or protein over expression which will allow analysis of nuclear organisation after perturbation of gene expression.

  • Journal article
    Gonzalez A, Vihervaara P, Balvanera P, Bates AE, Bayraktarov E, Bellingham PJ, Bruder A, Campbell J, Catchen MD, Cavender-Bares J, Chase J, Coops N, Costello MJ, Czúcz B, Delavaud A, Dornelas M, Dubois G, Duffy EJ, Eggermont H, Fernandez M, Fernandez N, Ferrier S, Geller GN, Gill M, Gravel D, Guerra CA, Guralnick R, Harfoot M, Hirsch T, Hoban S, Hughes AC, Hugo W, Hunter ME, Isbell F, Jetz W, Juergens N, Kissling WD, Krug CB, Kullberg P, Le Bras Y, Leung B, Londoño-Murcia MC, Lord J-M, Loreau M, Luers A, Ma K, MacDonald AJ, Maes J, McGeoch M, Mihoub JB, Millette KL, Molnar Z, Montes E, Mori AS, Muller-Karger FE, Muraoka H, Nakaoka M, Navarro L, Newbold T, Niamir A, Obura D, O'Connor M, Paganini M, Pelletier D, Pereira H, Poisot T, Pollock LJ, Purvis A, Radulovici A, Rocchini D, Roeoesli C, Schaepman M, Schaepman-Strub G, Schmeller DS, Schmiedel U, Schneider FD, Shakya MM, Skidmore A, Skowno AL, Takeuchi Y, Tuanmu M-N, Turak E, Turner W, Urban MC, Urbina-Cardona N, Valbuena R, Van de Putte A, van Havre B, Wingate VR, Wright E, Torrelio CZet al., 2023,

    Author Correction: A global biodiversity observing system to unite monitoring and guide action.

    , Nat Ecol Evol, Vol: 7
  • Journal article
    Beattie JW, Rowland-Jones RC, Farys M, Bettany H, Hilton D, Kazarian SG, Byrne Bet al., 2023,

    Application of Raman spectroscopy to dynamic binding capacity analysis

    , Applied Spectroscopy, Vol: 77, Pages: 1393-1400, ISSN: 0003-7028

    Protein A affinity chromatography is a key step in isolation of biotherapeutics (BTs) containing fragment crystallizable regions, including monoclonal and bispecific antibodies. Dynamic binding capacity (DBC) analysis assesses how much BT will bind to a protein A column. DBC reduces with column usage, effectively reducing the amount of recovered product over time. Drug regulatory bodies mandate chromatography resin lifetime for BT isolation, through measurement of parameters including DBC, so this feature is carefully monitored in industrial purification pipelines. High-performance affinity chromatography (HPAC) is typically used to assess the concentration of BT, which when loaded to the column results in significant breakthrough of BT in the flowthrough. HPAC gives an accurate assessment of DBC and how this changes over time but only reports on protein concentration, requires calibration for each new BT analyzed, and can only be used offline. Here we utilized Raman spectroscopy and revealed that this approach is at least as effective as both HPAC and ultraviolet chromatogram methods at monitoring DBC of protein A resins. In addition to reporting on protein concentration, the chemical information in the Raman spectra provides information on aggregation status and protein structure, providing extra quality controls to industrial bioprocessing pipelines. In combination with partial least square (PLS) analysis, Raman spectroscopy can be used to determine the DBC of a BT without prior calibration. Here we performed Raman analysis offline in a 96-well plate format, however, it is feasible to perform this inline. This study demonstrates the power of Raman spectroscopy as a significantly improved approach to DBC monitoring in industrial pipelines.

  • Journal article
    Peng Y, Prentice IC, Bloomfield KJ, Campioli M, Guo Z, Sun Y, Tian D, Wang X, Vicca S, Stocker BDet al., 2023,

    Global terrestrial nitrogen uptake and nitrogen use efficiency

    , Journal of Ecology, Vol: 111, Pages: 2676-2693, ISSN: 0022-0477

    1. Plant biomass production (BP), nitrogen uptake (Nup) and their ratio, nitrogen use efficiency (NUE), must be quantified to understand how nitrogen (N) cycling constrains terrestrial carbon (C) uptake. But the controls of key plant processes determining Nup and NUE, including BP, C and N allocation, tissue C:N ratios and N resorption efficiency (NRE), remain poorly known. 2. We compiled measurements from 804 forest and grassland sites and derived regression models for each of these processes with growth temperature, vapour pressure deficit, stand age, soil C:N ratio, fAPAR (remotely sensed fraction of photosynthetically active radiation absorbed by green vegetation) and growing-season average daily incident photosynthetic photon flux density (gPPFD) (effectively the seasonal concentration of light availability, which increases polewards) as predictors. An empirical model for leaf N was based on optimal photosynthetic capacity (a function of gPPFD and climate) and observed leaf mass-per-area. The models were used to produce global maps of Nup and NUE. 3. Global BP was estimated as 72 Pg C/yr; Nup as 950 Tg N/yr; and NUE as 76 gC/gN. Forest BP was found to increase with growth temperature and fAPAR and to decrease with stand age, soil C:N ratio and gPPFD. Forest NUE is controlled primarily by climate through its effect on C allocation – especially to leaves, being richer in N than other tissues. NUE is greater in colder climates, where N is less readily available, because belowground allocation is increased. NUE is also greater in drier climates because leaf allocation is reduced. NRE is enhanced (further promoting NUE) in both cold and dry climates. 4. These findings can provide observationally based benchmarks for model representations of C–N cycle coupling. State-of-the-art vegetation models in the TRENDY ensemble showed variable performance against these benchmarks, and models including coupled C–N cycling produced relatively poor simulations o

  • Journal article
    Delabre I, Lyons-White J, Melot C, Veggeberg EI, Alexander A, Schleper MCC, Ewers RMM, Knight ATTet al., 2023,

    Should I stay or should I go? Understanding stakeholder dis/engagement for deforestation-free palm oil

    , Business Strategy and the Environment, Vol: 32, Pages: 5128-5145, ISSN: 0964-4733

    Addressing tropical deforestation in the palm oil sector involves a diverse range of stakeholders who engage or disengage with each other. Palm oil global value chain (GVC) firms (plantation companies, traders and processors, and consumer goods manufacturers and retailers), as well as nongovernmental organisations, financial institutions, consultancies and certification bodies, pursue their respective organisations' agendas through engagement practices, including through coalitions, in a palm oil sustainability network (POSN). Building on interviews with different stakeholder groups, this qualitative study characterises and critically analyses ‘stakeholder engagement’ by examining (1) the priority targets for engagement among different POSN stakeholders, (2) how mechanisms and tools are used in POSN stakeholder engagement or disengagement for addressing deforestation, and (3) the implications of stakeholder engagement or disengagement for addressing deforestation. Engagement and disengagement practices are shaped by and reshape GVC governance, with powerful stakeholders emerging as knowledge brokers and norm setters, raising important challenges for how deforestation is addressed.

  • Journal article
    Chawda MM, Ross S, Lau C-I, Yánez DC, Rowell J, Kilbride P, Crompton Tet al., 2023,

    Cryopreservation of mouse thymus depletes thymocytes but supports immune reconstitution on transplantation.

    , Eur J Immunol, Vol: 53

    Cryopreservation of mouse thymus depletes donor thymocytes but preserves thymus function when transplanted after thawing into athymic mice. No differences in immune reconstitution were observed between fresh and frozen/thawed transplants suggesting that donor thymocyte depletion does not affect outcome. Thus, cryopreservation of thymus may improve outcomes in thymus transplant patients.

  • Journal article
    Keenan TF, Luo X, Stocker BD, De Kauwe MG, Medlyn BE, Prentice IC, Smith NG, Terrer C, Wang H, Zhang Y, Zhou Set al., 2023,

    A constraint on historic growth in global photosynthesis due to rising CO2

    , Nature Climate Change, Vol: 13, Pages: 1376-1381, ISSN: 1758-678X

    Theory predicts that rising CO2 increases global photosynthesis, a process known as CO2 fertilization, and that this is responsible for a large proportion of the current terrestrial carbon sink. The estimated magnitude of the historic CO2 fertilization, however, differs by an order ofmagnitude between long-term proxies, remote sensing-based estimates and terrestrial biosphere models. Here we constrain the likely historic effect of CO2 on global photosynthesis by combining terrestrial biosphere models, ecological optimality theory, remote sensing approaches and an emergent constraint based on global carbon budget estimates. Our analysis suggests that CO2 fertilization increased global annual terrestrial photosynthesis by 13.5 ± 3.5%, or 15.9 ± 2.9 Pg C u(mean ± standard deviation) between 1981 and 2020. Our results help resolve conflicting estimates of the historic sensitivity of global terrestrial photosynthesis to CO2 and highlight the large impact anthropogenic emissions have had on ecosystems worldwide.

  • Journal article
    Matanza XM, Clements A, 2023,

    Pathogenicity and virulence of Shigella sonnei: A highly drug-resistant pathogen of increasing prevalence.

    , Virulence, Vol: 14

    Shigella spp. are the causative agent of shigellosis (or bacillary dysentery), a diarrhoeal disease characterized for the bacterial invasion of gut epithelial cells. Among the 4 species included in the genus, Shigella flexneri is principally responsible for the disease in the developing world while Shigella sonnei is the main causative agent in high-income countries. Remarkably, as more countries improve their socioeconomic conditions, we observe an increase in the relative prevalence of S. sonnei. To date, the reasons behind this change in aetiology depending on economic growth are not understood. S. flexneri has been widely used as a model to study the pathogenesis of the genus, but as more research data are collected, important discrepancies with S. sonnei have come to light. In comparison to S. flexneri, S. sonnei can be differentiated in numerous aspects; it presents a characteristic O-antigen identical to that of one serogroup of the environmental bacterium Plesiomonas shigelloides, a group 4 capsule, antibacterial mechanisms to outcompete and displace gut commensal bacteria, and a poorer adaptation to an intracellular lifestyle. In addition, the World Health Organization (WHO) have recognized the significant threat posed by antibiotic-resistant strains of S. sonnei, demanding new approaches. This review gathers knowledge on what is known about S. sonnei within the context of other Shigella spp. and aims to open the door for future research on understanding the increasing spread of this pathogen.

  • Journal article
    Maretvadakethope S, Hazel AL, Vasiev B, Bearon RNet al., 2023,

    The interplay between bulk flow and boundary conditions on the distribution of microswimmers in channel flow

    , Journal of Fluid Mechanics, Vol: 976, ISSN: 0022-1120

    While previous experimental and numerical studies of dilute microswimmer suspensions have focused on the behaviours of swimmers in the bulk flow and near boundaries, models typically do not account for the interplay between bulk flow and the choice of boundary conditions imposed in continuum models. In our work, we highlight the effect of boundary conditions on the bulk flow distributions, such as through the development of boundary layers or secondary peaks of cell accumulation in bulk-flow swimmer dynamics. For the case of a dilute swimmer suspension in Poiseuille flow, we compare the distribution (in physical and orientation space) obtained from individual-based stochastic models with those from continuum models, and identify under what conditions it is mathematically sensible to use specific continuum boundary conditions to capture different physical scenarios (i.e. specular reflection, uniform random reflection and absorbing boundaries). We identify that the spread of preferred cell orientations is dependent on the interplay between rotation driven by the shear flow (Jeffery orbits) and rotational diffusion. We find that in the absence of hydrodynamic wall interactions, swimmers preferentially approach the walls perpendicular to the surface in the presence of high rotational diffusion, and that the preferential approach of swimmers to the walls is shape-dependent at low rotational diffusion (when suspensions tend towards a fully deterministic case). In the latter case, the preferred orientations are nearly parallel to the surface for elongated swimmers and nearly perpendicular to the surface for near-spherical swimmers. Furthermore, we highlight the effects of swimmer geometries and shear throughout the bulk-flow on swimmer trajectories and show how the full history of bulk-flow dynamics affects the orientation distributions of microswimmer wall incidence.

  • Journal article
    Merali N, Chouari T, Terroire J, Jessel M-D, Liu DSK, Smith J-H, Wooldridge T, Dhillon T, Jiménez JI, Krell J, Roberts KJ, Rockall TA, Velliou E, Sivakumar S, Giovannetti E, Demirkan A, Annels NE, Frampton AEet al., 2023,

    Bile microbiome signatures associated with pancreatic ductal adenocarcinoma compared to benign disease: a UK pilot study

    , International Journal of Molecular Sciences, Vol: 24, ISSN: 1422-0067

    Pancreatic ductal adenocarcinoma (PDAC) has a very poor survival. The intra-tumoural microbiome can influence pancreatic tumourigenesis and chemoresistance and, therefore, patient survival. The role played by bile microbiota in PDAC is unknown. We aimed to define bile microbiome signatures that can effectively distinguish malignant from benign tumours in patients presenting with obstructive jaundice caused by benign and malignant pancreaticobiliary disease. Prospective bile samples were obtained from 31 patients who underwent either Endoscopic Retrograde Cholangiopancreatography (ERCP) or Percutaneous Transhepatic Cholangiogram (PTC). Variable regions (V3-V4) of the 16S rRNA genes of microorganisms present in the samples were amplified by Polymerase Chain Reaction (PCR) and sequenced. The cohort consisted of 12 PDAC, 10 choledocholithiasis, seven gallstone pancreatitis and two primary sclerosing cholangitis patients. Using the 16S rRNA method, we identified a total of 135 genera from 29 individuals (12 PDAC and 17 benign). The bile microbial beta diversity significantly differed between patients with PDAC vs. benign disease (Permanova p = 0.0173). The separation of PDAC from benign samples is clearly seen through unsupervised clustering of Aitchison distance. We found three genera to be of significantly lower abundance among PDAC samples vs. benign, adjusting for false discovery rate (FDR). These were Escherichia (FDR = 0.002) and two unclassified genera, one from Proteobacteria (FDR = 0.002) and one from Enterobacteriaceae (FDR = 0.011). In the same samples, the genus Streptococcus (FDR = 0.033) was found to be of increased abundance in the PDAC group. We show that patients with obstructive jaundice caused by PDAC have an altered microbiome composition in the bile compared to those with benign disease. These bile-based microbes could be developed into potential diagnostic and prognostic biomarkers for PDAC and warrant further investigation.

  • Journal article
    Stępień P, Świątek S, Robles MYY, Markiewicz-Mizera J, Balakrishnan D, Inaba-Inoue S, De Vries AH, Beis K, Marrink SJ, Heddle JGet al., 2023,

    CRAFTing Delivery of Membrane Proteins into Protocells using Nanodiscs.

    , ACS Appl Mater Interfaces, Vol: 15, Pages: 56689-56701

    For the successful generative engineering of functional artificial cells, a convenient and controllable means of delivering membrane proteins into membrane lipid bilayers is necessary. Here we report a delivery system that achieves this by employing membrane protein-carrying nanodiscs and the calcium-dependent fusion of phosphatidylserine lipid membranes. We show that lipid nanodiscs can fuse a transported lipid bilayer with the lipid bilayers of small unilamellar vesicles (SUVs) or giant unilamellar vesicles (GUVs) while avoiding recipient vesicles aggregation. This is triggered by a simple, transient increase in calcium concentration, which results in efficient and rapid fusion in a one-pot reaction. Furthermore, nanodiscs can be loaded with membrane proteins that can be delivered into target SUV or GUV membranes in a detergent-independent fashion while retaining their functionality. Nanodiscs have a proven ability to carry a wide range of membrane proteins, control their oligomeric state, and are highly adaptable. Given this, our approach may be the basis for the development of useful tools that will allow bespoke delivery of membrane proteins to protocells, equipping them with the cell-like ability to exchange material across outer/subcellular membranes.

  • Journal article
    Dimitrov D, Xu X, Su X, Shrestha N, Liu Y, Kennedy JD, Lyu L, Nogués-Bravo D, Rosindell J, Yang Y, Fjeldså J, Liu J, Schmid B, Fang J, Rahbek C, Wang Zet al., 2023,

    Diversification of flowering plants in space and time.

    , Nat Commun, Vol: 14

    The rapid diversification and high species richness of flowering plants is regarded as 'Darwin's second abominable mystery'. Today the global spatiotemporal pattern of plant diversification remains elusive. Using a newly generated genus-level phylogeny and global distribution data for 14,244 flowering plant genera, we describe the diversification dynamics of angiosperms through space and time. Our analyses show that diversification rates increased throughout the early Cretaceous and then slightly decreased or remained mostly stable until the end of the Cretaceous-Paleogene mass extinction event 66 million years ago. After that, diversification rates increased again towards the present. Younger genera with high diversification rates dominate temperate and dryland regions, whereas old genera with low diversification dominate the tropics. This leads to a negative correlation between spatial patterns of diversification and genus diversity. Our findings suggest that global changes since the Cenozoic shaped the patterns of flowering plant diversity and support an emerging consensus that diversification rates are higher outside the tropics.

  • Journal article
    Xu H, Wang H, Prentice IC, Harrison SPet al., 2023,

    Leaf carbon and nitrogen stoichiometric variation alongenvironmental gradients

    , Biogeosciences, Vol: 20, Pages: 4511-4525, ISSN: 1726-4170

    Leaf stoichiometric traits are central to ecosystem function and biogeochemical cycling, yet no accepted theory predicts their variation along environmental gradients. Using data in the China Plant Trait Database version 2, we aimed to characterize variation in leaf carbon and nitrogen per unit mass (Cmass, Nmass) and their ratio, and to test an eco-evolutionary optimality model for Nmass. Community-mean trait values were related to climate variables by multiple linear regression. Climatic optima and tolerances of major genera were estimated; Pagel’s λ was used to quantify phylogenetic controls, and Bayesian phylogenetic linear mixed models to assess the contributions of climate, species identity and phylogeny. Optimality-based predictions of community-mean Nmass were compared to observed values. All traits showed strong phylogenetic signals. Climate explained only 18 % of C : N ratio variation among species but 45 % among communities, highlighting the role of taxonomic replacement in mediating community-level responses. Geographic distributions of deciduous taxa separated primarily by moisture, evergreens by temperature. Cmass increased with irradiance, but decreased with moisture and temperature. Nmass declined with all three variables. C : N ratio variations were dominated by Nmass. The coefficients relating Nmass to the ratio of maximum carboxylation capacity at 25 °C (Vcmax25) and leaf mass per area (Ma) were influenced by leaf area index. The optimality model captured 68 % and 53 % of variation between communities for Vcmax25 and Ma respectively, and 30 % for Nmass. We conclude that stoichiometric variations along climate gradients are achieved largely by environmental selection among species and clades with different characteristic trait values. Variations in leaf C : N ratio are mainly determined by Nmass, and optimality-based modelling shows useful predictive ability for community-mean Nmass. These findings should help to improve the repres

  • Journal article
    Brazeau M, Castiello M, El Fassi El Fehri A, Hamilton L, Ivanov AO, Johanson Z, Friedman Met al., 2023,

    Fossil evidence for a pharyngeal origin of the vertebrate pectoral girdle

    , Nature, Vol: 623, Pages: 550-554, ISSN: 0028-0836

    The origin of vertebrate paired appendages is one of the most investigated and debated examples of evolutionary novelty. Paired appendages are widely considered key innovations that allowed new opportunities for controlled swimming and gill ventilation and were prerequisites for the eventual transition from water to land. The last 150 years of debate has been shaped by two contentious theories: the ventrolateral fin-fold hypothesis and the archipterygium hypothesis. The latter proposes that fins and girdles evolved from an ancestral gill arch. Although tantalizing developmental evidence has revived interest in this idea, it is apparently unsupported by fossil evidence. Here we present fossil evidence of a pharyngeal basis for the vertebrate shoulder girdle. We use CT scanning to reveal details of the braincase of Kolymaspis sibirica, a placoderm fish from the Early Devonian of Siberia that suggests a pharyngeal component of the shoulder. We combine these findings with refreshed comparative anatomy of placoderms and jawless outgroups to place the origin of the shoulder girdle on the sixth branchial arch. These findings provide a novel framework for understanding the origin of the pectoral girdle. Our new evidence clarifies the location of the presumptive head-trunk interface in jawless fishes and explains the constraint on branchial arch number in gnathostomes. The results revive a key aspect of the archipterygium hypothesis, but also reconciles it with the ventrolateral fin fold model.

  • Journal article
    Davydova S, Liu J, Kandul NP, Braswell WE, Akbari OS, Meccariello Aet al., 2023,

    Next-generation genetic sexing strain establishment in the agricultural pest Ceratitis capitata.

    , Sci Rep, Vol: 13

    Tephritid fruit fly pests pose an increasing threat to the agricultural industry due to their global dispersion and a highly invasive nature. Here we showcase the feasibility of an early-detection SEPARATOR sex sorting approach through using the non-model Tephritid pest, Ceratitis capitata. This system relies on female-only fluorescent marker expression, accomplished through the use of a sex-specific intron of the highly-conserved transformer gene from C. capitata and Anastrepha ludens. The herein characterized strains have 100% desired phenotype outcomes, allowing accurate male-female separation during early development. Overall, we describe an antibiotic and temperature-independent sex-sorting system in C. capitata, which, moving forward, may be implemented in other non-model Tephritid pest species. This strategy can facilitate the establishment of genetic sexing systems with endogenous elements exclusively, which, on a wider scale, can improve pest population control strategies like sterile insect technique.

  • Other
    Blackford KR, Kasoar M, Burton C, Burke E, Prentice IC, Voulgarakis Aet al., 2023,

    Supplementary material to "INFERNO-peat v1.0.0: A representation of northern high latitude peat fires in the JULES-INFERNO global fire model"

  • Journal article
    Jones H, Willis J, Firth L, Giachello C, Gilestro Get al., 2023,

    A reductionist paradigm for high-throughput behavioural fingerprinting in Drosophila melanogaster

    , eLife, ISSN: 2050-084X
  • Journal article
    Mwima R, Hui T-YJ, Nanteza A, Burt A, Kayondo JKet al., 2023,

    Potential persistence mechanisms of the major Anopheles gambiae species complex malaria vectors in sub-Saharan Africa: a narrative review

    , Malaria Journal, Vol: 22, ISSN: 1475-2875

    The source of malaria vector populations that re-establish at the beginning of the rainy season is still unclear yet knowledge of mosquito behaviour is required to effectively institute control measures. Alternative hypotheses like aestivation, local refugia, migration between neighbouring sites, and long-distance migration (LDM) are stipulated to support mosquito persistence. This work assessed the malaria vector persistence dynamics and examined various studies done on vector survival  via these hypotheses; aestivation, local refugia, local or long-distance migration across sub-Saharan Africa, explored a range of methods used, ecological parameters and highlighted the knowledge trends and gaps. The results about a particular persistence mechanism that supports the re-establishment of Anopheles gambiae, Anopheles coluzzii or Anopheles arabiensis in sub-Saharan Africa were not conclusive given that each method used had its limitations. For example, the Mark-Release-Recapture (MRR) method whose challenge is a low recapture rate that affects its accuracy, and the use of time series analysis through field collections whose challenge is the uncertainty about whether not finding mosquitoes during the dry season is a weakness of the conventional sampling methods used or because of hidden shelters. This, therefore, calls for further investigations emphasizing the use of ecological experiments under controlled conditions in the laboratory or semi-field, and genetic approaches, as they are known to complement each other. This review, therefore, unveils and assesses the uncertainties that influence the different malaria vector persistence mechanisms and provides recommendations for future studies.

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