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Journal articleMwima R, Hui T-YJ, Kayondo JK, et al., 2024,
The population genetics of partial diapause, with applications to the aestivating malaria mosquito Anopheles coluzzii.
, Mol Ecol Resour, Vol: 24Diapause, a form of dormancy to delay or halt the reproductive development during unfavourable seasons, has evolved in many insect species. One example is aestivation, an adult-stage diapause enhancing malaria vectors' survival during the dry season (DS) and their re-establishment in the next rainy season (RS). This work develops a novel genetic approach to estimate the number or proportion of individuals undergoing diapause, as well as the breeding sizes of the two seasons, using signals from temporal allele frequency dynamics. Our modelling shows the magnitude of drift is dampened at early RS when previously aestivating individuals reappear. Aestivation severely biases the temporal effective population size ( N e $$ {N}_e $$ ), leading to overestimation of the DS breeding size by 1 / 1 - α 2 $$ 1/{\left(1-\alpha \right)}^2 $$ across 1 year, where α $$ \alpha $$ is the aestivating proportion. We find sampling breeding individuals in three consecutive seasons starting from an RS is sufficient for parameter estimation, and perform extensive simulations to verify our derivations. This method does not require sampling individuals in the dormant state, the biggest challenge in most studies. We illustrate the method by applying it to a published data set for Anopheles coluzzii mosquitoes from Thierola, Mali. Our method and the expected evolutionary implications are applicable to any species in which a fraction of the population diapauses for more than one generation, and are difficult or impossible to sample during that stage.
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Journal articleGuerrero P, Perez-Carrasco R, 2024,
Choice of friction coefficient deeply affects tissue behaviour in stochastic epithelial vertex models.
, Philos Trans R Soc Lond B Biol Sci, Vol: 379To understand the mechanisms that coordinate the formation of biological tissues, the use of numerical implementations is necessary. The complexity of such models involves many assumptions and parameter choices that result in unpredictable consequences, obstructing the comparison with experimental data. Here, we focus on vertex models, a family of spatial models used extensively to simulate the dynamics of epithelial tissues. Usually, in the literature, the choice of the friction coefficient is not addressed using quasi-static deformation arguments that generally do not apply to realistic scenarios. In this manuscript, we discuss the role that the choice of friction coefficient has on the relaxation times and consequently in the conditions of cell cycle progression and division. We explore the effects that these changes have on the morphology, growth rate and topological transitions of the tissue dynamics. These results provide a deeper understanding of the role that an accurate mechanical description plays in the use of vertex models as inference tools. This article is part of a discussion meeting issue 'Causes and consequences of stochastic processes in development and disease'.
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Journal articlevan Thor J, 2024,
Kilohertz Droplet-on-Demand Serial Femtosecond Crystallography at the European XFEL stationFXE
, Structural Dynamics, ISSN: 2329-7778 -
Journal articleWilliams J, Pettorelli N, Hartmann A, et al., 2024,
Decline of a distinct coral reef holobiont community under ocean acidification
, Microbiome, ISSN: 2049-2618Background: Microbes play vital roles across coral reefs both in the environment and inside and upon macrobes (holobionts), where they support critical functions such as nutrition and immune system modulation. These roles highlight the potential ecosystem-level importance of microbes, yet most knowledge of microbial functions on reefs is derived from a small set of holobionts such as corals and sponges. Declining seawater pH - an important global coral reef stressor - can cause ecosystem-level change on coral reefs, providing an opportunity to study the role of microbes at this scale. We use an in situ experimental approach to test the hypothesis that under such ocean acidification (OA) known shifts among macrobe trophic and functional groups may drive a general ecosystem-level response extending across macrobes and microbes, leading to reduced distinctness between the benthic holobiont community microbiome and the environmental microbiome. Results: We test this hypothesis using genetic and chemical data from benthic coral reef community holobionts sampled across a pH gradient from CO2 seeps in Papua New Guinea. We find support for our hypothesis: under OA the microbiome and metabolome of the benthic holobiont community become less compositionally distinct from the sediment microbiome and metabolome, suggesting that benthic macrobe communities are colonized by environmental microbes to a higher degree under OA conditions. We also find a simplification and homogenisation of the benthic photosynthetic community, and an increased abundance of fleshy macroalgae, consistent with previously observed reef microbialisation. Conclusions: We demonstrate a novel structural shift in coral reefs involving macrobes and microbes: that the microbiome of the benthic holobiont community becomes less distinct from the sediment microbiome under OA. Our findings provide evidence that microbialisation and the disruption of macrobe trophic networks are interwoven general responses to envi
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Journal articleChakraborty A, Alsharqi L, Kostrzewa M, et al., 2024,
Intact cell lipidomics using the Bruker MBT lipid Xtract assay allows the rapid detection of glycosyl-inositol-phospho-ceramides from Aspergillus fumigatus.
, Mol OmicsGlycosyl-inositol-phospho-ceramides (GIPCs) or glycosylphosphatidylinositol-anchored fungal polysaccharides are major lipids in plant and fungal plasma membranes and play an important role in stress adaption. However, their analysis remains challenging due to the multiple steps involved in their extraction and purification prior to mass spectrometry analysis. To address this challenge, we report here a novel simplified method to identify GIPCs from Aspergillus fumigatus using the new Bruker MBT lipid Xtract assay. A. fumigatus reference strains and clinical isolates were cultured, harvested, heat-inactivated and suspended in double-distilled water. A fraction of this fungal preparation was then dried in a microtube, mixed with an MBT lipid Xtract matrix (Bruker Daltonik, Germany) and loaded onto a MALDI target plate. Analysis was performed using a Bruker MALDI Biotyper Sirius system in the linear negative ion mode. Mass spectra were scanned from m/z 700 to m/z 2 000. MALDI-TOF MS analysis of cultured fungi showed a clear signature of GIPCs in Aspergillus fumigatus reference strains and clinical isolates. Here, we have demonstrated that routine MALDI-TOF in the linear negative ion mode combined with the MBT lipid Xtract is able to detect Aspergillus fumigatus GIPCs.
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Journal articleBradley R, Simon D, Spiga L, et al., 2024,
Laser desorption rapid evaporative ionization mass spectrometry (LD-REIMS) demonstrates a direct impact of hypochlorous acid stress on PQS-mediated quorum sensing in Pseudomonas aeruginosa.
, mSystems, Vol: 9UNLABELLED: To establish infections in human hosts, Pseudomonas aeruginosa must overcome innate immune-generated oxidative stress, such as the hypochlorous acid (HOCl) produced by neutrophils. We set out to find specific biomarkers of oxidative stress through the development of a protocol for the metabolic profiling of P. aeruginosa cultures grown in the presence of different oxidants using a novel ionization technique for mass spectrometry, laser desorption rapid evaporative ionization mass spectrometry (LD-REIMS). We demonstrated the ability of LD-REIMS to classify samples as untreated or treated with a specific oxidant with 100% accuracy and identified a panel of 54 metabolites with significantly altered concentrations after exposure to one or more of the oxidants. Key metabolic changes were conserved in P. aeruginosa clinical strains isolated from patients with cystic fibrosis lung infections. These data demonstrated that HOCl stress impacted the Pseudomonas quinolone signal (PQS) quorum sensing system. Ten 2-alkyl-4-quinolones (AHQs) associated with the PQS system were significantly lower in concentration in HOCl-stressed P. aeruginosa cultures, including 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), the most active signal molecule of the PQS system. The PQS system regulates the production of virulence factors, including pyocyanin and elastase, and their levels were markedly affected by HOCl stress. No pyocyanin was detectable and elastase concentrations were reduced by more than 75% in cultures grown with sub-lethal concentrations of HOCl, suggesting that this neutrophil-derived oxidant may disrupt the ability of P. aeruginosa to establish infections through interference with production of PQS-associated virulence factors. IMPORTANCE: This work demonstrates that a high-throughput ambient ionization mass spectrometry method can be used successfully to study a bacterial stress response. Its application to the opportunistic pathogen Pseudomonas aeruginosa led to the
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Journal articleGriffiths D, Anderson M, Richardson K, et al., 2024,
Cyclic Ion Mobility for Hydrogen/Deuterium Exchange-Mass Spectrometry Applications.
, Anal Chem, Vol: 96, Pages: 5869-5877Hydrogen/deuterium exchange-mass spectrometry (HDX-MS) has emerged as a powerful tool to probe protein dynamics. As a bottom-up technique, HDX-MS provides information at peptide-level resolution, allowing structural localization of dynamic changes. Consequently, the HDX-MS data quality is largely determined by the number of peptides that are identified and monitored after deuteration. Integration of ion mobility (IM) into HDX-MS workflows has been shown to increase the data quality by providing an orthogonal mode of peptide ion separation in the gas phase. This is of critical importance for challenging targets such as integral membrane proteins (IMPs), which often suffer from low sequence coverage or redundancy in HDX-MS analyses. The increasing complexity of samples being investigated by HDX-MS, such as membrane mimetic reconstituted and in vivo IMPs, has generated need for instrumentation with greater resolving power. Recently, Giles et al. developed cyclic ion mobility (cIM), an IM device with racetrack geometry that enables scalable, multipass IM separations. Using one-pass and multipass cIM routines, we use the recently commercialized SELECT SERIES Cyclic IM spectrometer for HDX-MS analyses of four detergent solubilized IMP samples and report its enhanced performance. Furthermore, we develop a novel processing strategy capable of better handling multipass cIM data. Interestingly, use of one-pass and multipass cIM routines produced unique peptide populations, with their combined peptide output being 31 to 222% higher than previous generation SYNAPT G2-Si instrumentation. Thus, we propose a novel HDX-MS workflow with integrated cIM that has the potential to enable the analysis of more complex systems with greater accuracy and speed.
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Journal articleZhang-Zheng H, Adu-Bredu S, Duah-Gyamfi A, et al., 2024,
Contrasting carbon cycle along tropical forest aridity gradients in West Africa and Amazonia
, Nature Communications, ISSN: 2041-1723 -
Journal articleChia K-S, Kourelis J, Teulet A, et al., 2024,
The N-terminal domains of NLR immune receptors exhibit structural and functional similarities across divergent plant lineages
, The Plant Cell, ISSN: 1040-4651<jats:title>Abstract</jats:title> <jats:p>Nucleotide-binding domain and leucine-rich repeat (NLR) proteins are a prominent class of intracellular immune receptors in plants. However, our understanding of plant NLR structure and function is limited to the evolutionarily young flowering plant clade. Here, we describe an extended spectrum of NLR diversity across divergent plant lineages and demonstrate the structural and functional similarities of N-terminal domains that trigger immune responses. We show that the broadly distributed coiled-coil (CC) and toll/interleukin-1 receptor (TIR) domain families of non-flowering plants retain immune-related functions through trans-lineage activation of cell death in the angiosperm Nicotiana benthamiana. We further examined a CC subfamily specific to non-flowering lineages and uncovered an essential N-terminal MAEPL motif that is functionally comparable to motifs in resistosome-forming CC-NLRs. Consistent with a conserved role in immunity, the ectopic activation of CCMAEPL in the non-flowering liverwort Marchantia polymorpha led to profound growth inhibition, defense gene activation, and signatures of cell death. Moreover, comparative transcriptomic analyses of CCMAEPL activity delineated a common CC-mediated immune program shared across evolutionarily divergent non-flowering and flowering plants. Collectively, our findings highlight the ancestral nature of NLR-mediated immunity during plant evolution that dates its origin to at least ∼500 million years ago.</jats:p>
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Journal articleFlo V, Joshi J, Sabot M, et al., 2024,
Incorporating photosynthetic acclimation improves stomatal optimisation models
, Plant, Cell and Environment, ISSN: 0140-7791 -
Journal articleDelhaye G, van der Linde S, Bauman D, et al., 2024,
Ectomycorrhizal fungi are influenced by ecoregion boundaries across Europe
, Global Ecology and Biogeography, ISSN: 1466-822X<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>Ecoregions and the distance decay in community similarity are fundamental concepts in biogeography and conservation biology that are well supported across plants and animals, but not fungi. Here we test the relevance of these concepts for ectomycorrhizal (ECM) fungi in temperate and boreal regions.</jats:p></jats:sec><jats:sec><jats:title>Location</jats:title><jats:p>Europe.</jats:p></jats:sec><jats:sec><jats:title>Time Period</jats:title><jats:p>2008–2015.</jats:p></jats:sec><jats:sec><jats:title>Major Taxa Studied</jats:title><jats:p>Ectomycorrhizal fungi.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used a large dataset of ~24,000 ectomycorrhizas, assigned to 1350 operational taxonomic units, collected from 129 forest plots via a standardized protocol. We investigated the relevance of ecoregion delimitations for ECM fungi through complementary methodological approaches based on distance decay models, multivariate analyses and indicator species analyses. We then evaluated the effects of host tree and climate on the observed biogeographical distributions.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Ecoregions predict large‐scale ECM fungal biodiversity patterns. This is partly explained by climate differences between ecoregions but independent from host tree distribution. Basidiomycetes in the orders Russulales and Atheliales and producing epigeous fruiting bodies, with potentially short‐distance dispersal, show the best agreement with ecoregion boundaries. Host tree distribution and fungal abundance (as opposed to presence/absence only) are important to uncover biogeographical patterns in mycorrhizas.</jats:p>&l
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Journal articleMiao A, Luo T, Hsieh B, et al., 2024,
Brain clearance is reduced during sleep and anesthesia
, Nature Neuroscience, ISSN: 1097-6256 -
Journal articleStiller J, Feng S, Chowdhury A-A, et al., 2024,
Complexity of avian evolution revealed by family-level genomes.
, NatureDespite tremendous efforts in the past decades, relationships among main avian lineages remain heavily debated without a clear resolution. Discrepancies have been attributed to diversity of species sampled, phylogenetic method, and the choice of genomic regions 1-3. Here, we address these issues by analyzing genomes of 363 bird species 4 (218 taxonomic families, 92% of total). Using intergenic regions and coalescent methods, we present a well-supported tree but also a remarkable degree of discordance. The tree confirms that Neoaves experienced rapid radiation at or near the Cretaceous-Paleogene (K-Pg) boundary. Sufficient loci rather than extensive taxon sampling were more effective in resolving difficult nodes. Remaining recalcitrant nodes involve species that challenge modeling due to extreme GC content, variable substitution rates, incomplete lineage sorting, or complex evolutionary events such as ancient hybridization. Assessment of the impacts of different genomic partitions showed high heterogeneity across the genome. We discovered sharp increases in effective population size, substitution rates, and relative brain size following the K-Pg extinction event, supporting the hypothesis that emerging ecological opportunities catalyzed the diversification of modern birds. The resulting phylogenetic estimate offers novel insights into the rapid radiation of modern birds and provides a taxon-rich backbone tree for future comparative studies.
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Journal articleKabasakal BV, Cotton CAR, Murray JW, 2024,
Dynamic lid domain of Chloroflexus aurantiacus Malonyl-CoA reductase controls the reaction.
, Biochimie, Vol: 219, Pages: 12-20, ISSN: 0300-9084Malonyl-Coenzyme A Reductase (MCR) in Chloroflexus aurantiacus, a characteristic enzyme of the 3-hydroxypropionate (3-HP) cycle, catalyses the reduction of malonyl-CoA to 3-HP. MCR is a bi-functional enzyme; in the first step, malonyl-CoA is reduced to the free intermediate malonate semialdehyde by the C-terminal region of MCR, and this is further reduced to 3-HP by the N-terminal region of MCR. Here we present the crystal structures of both N-terminal and C-terminal regions of the MCR from C. aurantiacus. A catalytic mechanism is suggested by ligand and substrate bound structures, and structural and kinetic studies of MCR variants. Both MCR structures reveal one catalytic, and one non-catalytic SDR (short chain dehydrogenase/reductase) domain. C-terminal MCR has a lid domain which undergoes a conformational change and controls the reaction. In the proposed mechanism of the C-terminal MCR, the conversion of malonyl-CoA to malonate semialdehyde is based on the reduction of malonyl-CoA by NADPH, followed by the decomposition of the hemithioacetal to produce malonate semialdehyde and coenzyme A. Conserved arginines, Arg734 and Arg773 are proposed to play key roles in the mechanism and conserved Ser719, and Tyr737 are other essential residues forming an oxyanion hole for the substrate intermediates.
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Journal articleSalvalaio M, Sena G, 2024,
Long-term root electrotropism reveals habituation and hysteresis
, Plant Physiology, Vol: 194, Pages: 2697-2708, ISSN: 0032-0889Plant roots sense many physical and chemical cues in soil, such as gravity, humidity, light, and chemical gradients, and respond by redirecting their growth toward or away from the source of the stimulus. This process is called tropism. While gravitropism is the tendency to follow the gravitational field downwards, electrotropism is the alignment of growth with external electric fields and the induced ionic currents. Although root tropisms are at the core of their ability to explore large volumes of soil in search of water and nutrients, the molecular and physical mechanisms underlying most of them remain poorly understood. We have previously provided a quantitative characterization of root electrotropism in Arabidopsis (Arabidopsis thaliana) primary roots exposed for 5 h to weak electric fields, showing that auxin asymmetric distribution is not necessary for root electrotropism but that cytokinin biosynthesis is. Here, we extend that study showing that long-term electrotropism is characterized by a complex behavior. We describe overshoot and habituation as key traits of long-term root electrotropism in Arabidopsis and provide quantitative data about the role of past exposures in the response to electric fields (hysteresis). On the molecular side, we show that cytokinin, although necessary for root electrotropism, is not asymmetrically distributed during the bending. Overall, the data presented here represent a step forward toward a better understanding of the complexity of root behavior and provide a quantitative platform for future studies on the molecular mechanisms of electrotropism.
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Journal articleSmith TP, Clegg T, Ransome E, et al., 2024,
High-throughput characterization of bacterial responses to complex mixtures of chemical pollutants.
, Nat Microbiol, Vol: 9, Pages: 938-948Our understanding of how microbes respond to micropollutants, such as pesticides, is almost wholly based on single-species responses to individual chemicals. However, in natural environments, microbes experience multiple pollutants simultaneously. Here we perform a matrix of multi-stressor experiments by assaying the growth of model and non-model strains of bacteria in all 255 combinations of 8 chemical stressors (antibiotics, herbicides, fungicides and pesticides). We found that bacterial strains responded in different ways to stressor mixtures, which could not be predicted simply from their phylogenetic relatedness. Increasingly complex chemical mixtures were both more likely to negatively impact bacterial growth in monoculture and more likely to reveal net interactive effects. A mixed co-culture of strains proved more resilient to increasingly complex mixtures and revealed fewer interactions in the growth response. These results show predictability in microbial population responses to chemical stressors and could increase the utility of next-generation eco-toxicological assays.
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Journal articleWang X, Slater A, Lee SC, et al., 2024,
Purification and characterisation of the platelet-activating GPVI/FcRγ complex in SMALPs.
, Arch Biochem Biophys, Vol: 754The collagen/fibrin(ogen) receptor, glycoprotein VI (GPVI), is a platelet activating receptor and a promising anti-thrombotic drug target. However, while agonist-induced GPVI clustering on platelet membranes has been shown to be essential for its activation, it is unknown if GPVI dimerisation represents a unique conformation for ligand binding. Current GPVI structures all contain only the two immunoglobulin superfamily (IgSF) domains in the GPVI extracellular region, so lacking the mucin-like stalk, transmembrane, cytoplasmic tail of GPVI and its associated Fc receptor γ (FcRγ) homodimer signalling chain, and provide contradictory insights into the mechanisms of GPVI dimerisation. Here, we utilised styrene maleic-acid lipid particles (SMALPs) to extract GPVI in complex with its two associated FcRγ chains from transfected HEK-293T cells, together with the adjacent lipid bilayer, then purified and characterised the GPVI/FcRγ-containing SMALPs, to enable structural insights into the full-length GPVI/FcRγ complex. Using size exclusion chromatography followed by a native polyacrylamide gel electrophoresis (PAGE) method, SMA-PAGE, we revealed multiple sizes of the purified GPVI/FcRγ SMALPs, suggesting the potential existence of GPVI oligomers. Importantly, GPVI/FcRγ SMALPs were functional as they could bind collagen. Mono-dispersed GPVI/FcRγ SMALPs could be observed under negative stain electron microscopy. These results pave the way for the future investigation of GPVI stoichiometry and structure, while also validating SMALPs as a promising tool for the investigation of human membrane protein interactions, stoichiometry and structure.
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Journal articleSandoval Calle D, Prentice IC, Nobrega R, 2024,
Simple process-led algorithms for simulating habitats (SPLASH v 2.0): robust calculations of water and energy fluxes.
, Geoscientific Model Development, ISSN: 1991-959X -
Journal articleCai JA, Christophides GK, 2024,
Immune interactions between mosquitoes and microbes during midgut colonization.
, Curr Opin Insect Sci, Vol: 63Mosquitoes encounter diverse microbes during their lifetime, including symbiotic bacteria, shaping their midgut ecosystem. The organization of the midgut supports microbiota persistence while defending against potential pathogens. The influx of nutrients during blood feeding triggers bacterial proliferation, challenging host homeostasis. Immune responses, aimed at controlling bacterial overgrowth, impact blood-borne pathogens such as malaria parasites. However, parasites deploy evasion strategies against mosquito immunity. Leveraging these mechanisms could help engineer malaria-resistant mosquitoes, offering a transformative tool for malaria elimination.
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Journal articleGuder F, Collins ASP, Kurt H, et al., 2024,
Parallel, Continuous Monitoring and Quantification of Programmed Cell Death in Plant Tissue
, Advanced Science, ISSN: 2198-3844 -
Journal articlePerkins R, Barron L, Glauser G, et al., 2024,
Down-the-drain pathways for fipronil and imidacloprid applied as spot-on parasiticides to dogs: Estimating aquatic pollution.
, Sci Total Environ, Vol: 917Fipronil and imidacloprid have been widely detected in UK surface waters in recent years, often at concentrations that ecotoxicological studies have shown can harm aquatic life. Down-the-drain (DTD) passage of pet flea and tick treatments are being implicated as an important source, with many of the UK's 22 million cats and dogs receiving routine, year-round preventative doses containing these parasiticides. The UK Water Industry's 3rd Chemical Investigation Programme (UKWIR CIP3) has confirmed wastewater as a major entry pathway for these chemicals into surface waters, but the routes by which they enter the wastewater system remain unclear. We addressed this knowledge gap by conducting the first quantification of DTD emissions from 98 dogs treated with spot-on ectoparasiticides containing fipronil or imidacloprid, through bathing, bed washing and washing of owners' hands. Both chemicals were detected in 100 % of washoff samples, with bathing accounting for the largest emissions per event (up to 16.8 % of applied imidacloprid and 24.5 % of applied fipronil). Modelled to account for the frequency of emitting activities, owner handwashing was identified as the largest source of DTD emissions from the population overall, with handwash emissions occurring for at least 28 days following product application and an estimated 4.9 % of imidacloprid and 3.1 % of fipronil applied in dog spot-ons passing down-the-drain via this route. The normalised daily per capita emissions for all routes combined were 8.7 μg/person/day for imidacloprid and 2.1 μg/person/day for fipronil, equivalent to 20-40 % of the daily per capita load in wastewater, as estimated from UKWIR CIP3 data. Within the current international regulatory framework adhered to by the UK, the environmental exposure of veterinary medicines intended for use in small companion animals is assumed to be low, and DTD pathways are not considered. We recommend a systematic rev
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Journal articleReda O, Monde K, Sugata K, et al., 2024,
HIV-Tocky system to visualize proviral expression dynamics.
, Commun Biol, Vol: 7Determinants of HIV-1 latency establishment are yet to be elucidated. HIV reservoir comprises a rare fraction of infected cells that can survive host and virus-mediated killing. In vitro reporter models so far offered a feasible means to inspect this population, but with limited capabilities to dissect provirus silencing dynamics. Here, we describe a new HIV reporter model, HIV-Timer of cell kinetics and activity (HIV-Tocky) with dual fluorescence spontaneous shifting to reveal provirus silencing and reactivation dynamics. This unique feature allows, for the first time, identifying two latent populations: a directly latent, and a recently silenced subset, with the latter having integration features suggestive of stable latency. Our proposed model can help address the heterogeneous nature of HIV reservoirs and offers new possibilities for evaluating eradication strategies.
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Journal articleBaquero F, Beis K, Craik DJ, et al., 2024,
The pearl jubilee of microcin J25: thirty years of research on an exceptional lasso peptide.
, Nat Prod Rep, Vol: 41, Pages: 469-511Covering: 1992 up to 2023Since their discovery, lasso peptides went from peculiarities to be recognized as a major family of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products that were shown to be spread throughout the bacterial kingdom. Microcin J25 was first described in 1992, making it one of the earliest known lasso peptides. No other lasso peptide has since then been studied to such an extent as microcin J25, yet, previous review articles merely skimmed over all the research done on this exceptional lasso peptide. Therefore, to commemorate the 30th anniversary of its first report, we give a comprehensive overview of all literature related to microcin J25. This review article spans the early work towards the discovery of microcin J25, its biosynthetic gene cluster, and the elucidation of its three-dimensional, threaded lasso structure. Furthermore, the current knowledge about the biosynthesis of microcin J25 and lasso peptides in general is summarized and a detailed overview is given on the biological activities associated with microcin J25, including means of self-immunity, uptake into target bacteria, inhibition of the Gram-negative RNA polymerase, and the effects of microcin J25 on mitochondria. The in vitro and in vivo models used to study the potential utility of microcin J25 in a (veterinary) medicine context are discussed and the efforts that went into employing the microcin J25 scaffold in bioengineering contexts are summed up.
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Journal articlevan Haaren C, Byrne B, Kazarian SG, 2024,
Study of monoclonal antibody aggregation at the air-liquid interface under flow by ATR-FTIR spectroscopic imaging
, Langmuir: the ACS journal of surfaces and colloids, Vol: 40, Pages: 5858-5868, ISSN: 0743-7463Throughout bioprocessing, transportation, and storage, therapeutic monoclonal antibodies (mAbs) experience stress conditions that may cause protein unfolding and/or chemical modifications. Such structural changes may lead to the formation of aggregates, which reduce mAb potency and may cause harmful immunogenic responses in patients. Therefore, aggregates need to be detected and removed or ideally prevented from forming. Air-liquid interfaces, which arise during various stages of bioprocessing, are one of the stress factors causing mAb aggregation. In this study, the behavior of an immunoglobulin G (IgG) at the air-liquid interface was investigated under flow using macro attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopic imaging. This chemically specific imaging technique allows observation of adsorption of IgG to the air-liquid interface and detection of associated secondary structural changes. Chemical images revealed that IgG rapidly accumulated around an injected air bubble under flow at 45 °C; however, no such increase was observed at 25 °C. Analysis of the second derivative spectra of IgG at the air-liquid interface revealed changes in the protein secondary structure associated with increased intermolecular β-sheet content, indicative of aggregated IgG. The addition of 0.01% w/v polysorbate 80 (PS80) reduced the amount of IgG at the air-liquid interface in a static setup at 30 °C; however, this protective effect was lost at 45 °C. These results suggest that the presence of air-liquid interfaces under flow may be detrimental to mAb stability at elevated temperatures and demonstrate the power of ATR-FTIR spectroscopic imaging for studying the structural integrity of mAbs under bioprocessing conditions.
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Journal articlePosse-Sarmiento V, Banks-Leite C, 2024,
The effects of edge influence on the microhabitat, diversity and life-history traits of amphibians in western Ecuador
, Journal of Tropical Ecology, Vol: 40, ISSN: 0266-4674Edge effects change biodiversity patterns and ecological processes, particularly in tropical forests. To understand the synergistic impact of multiple edges, this study examines how edge influence (EI) is associated with life-history traits (snout-vent length and body temperature), diversity and microhabitat of amphibians as well as habitat characteristics in a tropical forest in Ecuador. We used EI, a metric that calculates cumulative effects across all nearby edges, in combination with five environmental variables that are part of the amphibians' microhabitat (temperature, humidity, slope, canopy cover and leaf litter depth) to understand how their biodiversity patterns are impacted. Our results show that most amphibian species tend to be habitat specialists, and many had an affinity for forest edges and warmer habitats. We do not find significant correlations between EI and amphibian life-history traits and diversity. Our findings corroborate previous results that many amphibian species tend to be positively associated with habitat fragmentation and show that this association is likely driven by thermal regulation.
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Journal articleOgwang R, Murugu L, Nailain I, et al., 2024,
Bi-isotype immunoglobulins enhance antibody-mediated neutrophil activity against Plasmodium falciparum parasites
, Frontiers in Immunology-Vaccines and Molecular Therapeutics -
Journal articleMajumdar A, Upadhyay MK, Giri B, et al., 2024,
Sustainable water management in rice cultivation reduces arsenic contamination, increases productivity, microbial molecular response, and profitability.
, J Hazard Mater, Vol: 466Arsenic (As) and silicon (Si) are two structurally competitive natural elements where Si minimises As accumulation in rice plants, and based on this two-year field trial, the study proposes adopting alternating wetting and drying (AWD) irrigation as a sustainable water management strategy allowing greater Si availability. This field-based project is the first report on AWD's impact on As-Si distribution in fluvio-alluvial soils of the entire Ganga valley (24 study sites, six divisions), seasonal variance (pre-monsoon and monsoon), rice plant anatomy and productivity, soil microbial diversity, microbial gene ontology profiling and associated metabolic pathways. Under AWD to flooded and pre-monsoon to monsoon cultivations, respectively, greater Si availability was achieved and As-bioavailability was reduced by 8.7 ± 0.01-9.2 ± 0.02% and 25.7 ± 0.09-26.1 ± 0.01%. In the pre-monsoon and monsoon seasons, the physiological betterment of rice plants led to the high rice grain yield under AWD improved by 8.4 ± 0.07% and 10.0 ± 0.07%, proving the economic profitability. Compared to waterlogging, AWD evidences as an optimal soil condition for supporting soil microbial communities in rice fields, allowing diverse metabolic activities, including As-resistance, and active expression of As-responsive genes and gene products. Greater expressions of gene ontological terms and complex biochemical networking related to As metabolism under AWD proved better cellular, genetic and environmental responsiveness in microbial communities. Finally, by implementing AWD, groundwater usage can be reduced, lowering the cost of pumping and field management and generating an economic profit for farmers. These combined assessments prove the acceptability of AWD for the establishment of multiple sustainable development goals (SDGs).
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Journal articleKomenda J, Sobotka R, Nixon PJ, 2024,
The biogenesis and maintenance of photosystem II: recent advances and current challenges
, The Plant Cell, ISSN: 1040-4651 -
Journal articlePerrett S, Chatrchyan V, Buckup T, et al., 2024,
Application of density matrix Wigner transforms for ultrafast macromolecular and chemical x-ray crystallography.
, J Chem Phys, Vol: 160Time-Resolved Serial Femtosecond Crystallography (TR-SFX) conducted at X-ray Free Electron Lasers (XFELs) has become a powerful tool for capturing macromolecular structural movies of light-initiated processes. As the capabilities of XFELs advance, we anticipate that a new range of coherent control and structural Raman measurements will become achievable. Shorter optical and x-ray pulse durations and increasingly more exotic pulse regimes are becoming available at free electron lasers. Moreover, with high repetition enabled by the superconducting technology of European XFEL (EuXFEL) and Linac Coherent Light Source (LCLS-II) , it will be possible to improve the signal-to-noise ratio of the light-induced differences, allowing for the observation of vibronic motion on the sub-Angstrom level. To predict and assign this coherent motion, which is measurable with a structural technique, new theoretical approaches must be developed. In this paper, we present a theoretical density matrix approach to model the various population and coherent dynamics of a system, which considers molecular system parameters and excitation conditions. We emphasize the use of the Wigner transform of the time-dependent density matrix, which provides a phase space representation that can be directly compared to the experimental positional displacements measured in a TR-SFX experiment. Here, we extend the results from simple models to include more realistic schemes that include large relaxation terms. We explore a variety of pulse schemes using multiple model systems using realistic parameters. An open-source software package is provided to perform the density matrix simulation and Wigner transformations. The open-source software allows us to define any arbitrary level schemes as well as any arbitrary electric field in the interaction Hamiltonian.
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Journal articleKourelis J, Malik S, Mattinson O, et al., 2024,
Publisher Correction: Evolution of a guarded decoy protease and its receptor in solanaceous plants.
, Nat Commun, Vol: 15
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