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Journal articleTong Jia Ming S, Tan Yi Jun K, Carissimo G, 2024,
Pathogenicity and virulence of O’nyong-nyong virus: A less studied <i>Togaviridae</i> with pandemic potential
, Virulence, Vol: 15, ISSN: 2150-5594 -
Journal articleCheong B, Tang W, Kostrzewa M, et al., 2024,
Use of stable isotope combined with intact cell lipidomic by routine MALDI mass spectrometry analysis for rapid drug susceptibility assay in mycobacteria
, Rapid Communications in Mass Spectrometry, Vol: 38, ISSN: 0951-4198<jats:sec><jats:title>Rationale</jats:title><jats:p>Rapid, accurate, and easy‐to‐perform diagnostic assays are required to address the current need for the diagnosis of resistant pathogens. That is particularly the case for mycobacteria, such as the human pathogen <jats:styled-content style="fixed-case"><jats:italic>Mycobacterium tuberculosis</jats:italic></jats:styled-content>, which requires up to 2 weeks for the determination of the drug susceptibility profile using the conventional broth microdilution method. To address this challenge, we investigated the incorporation of deuterium, the stable isotope of hydrogen, into lipids as a read out of the drug susceptibility profile.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Deuterium is incorporated into newly synthesized proteins or lipids in place of hydrogen as bacterial cells grow, increasing the mass of the macromolecules, which can then be observed via matrix‐assisted laser desorption ionization time of flight mass spectrometry (MALDI‐TOF MS). As proof‐of‐concept, we used the non‐pathogenic <jats:styled-content style="fixed-case"><jats:italic>Mycobacterium smegmatis</jats:italic></jats:styled-content> mc<jats:sup>2</jats:sup>155 strain, which is susceptible to the aminoglycoside antibiotic kanamycin, and <jats:styled-content style="fixed-case"><jats:italic>M. smegmatis</jats:italic></jats:styled-content> mc<jats:sup>2</jats:sup>155 containing the empty vector pVV16, which is kanamycin‐resistant. Bacteria were incubated in a culture medium containing 50% of deuterium oxide (D<jats:sub>2</jats:sub>O) and either 1 or 2 times the minimal inhibitory concentration (MIC<jats:sub>50</jats:sub>) of kanamycin. Lipids were then analyzed using the MBT lipi
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Journal articleChen W, Park Y-K, Studená L, et al., 2024,
Synthetic, marine, light-driven, autotroph-heterotroph co-culture system for sustainable β-caryophyllene production
, Bioresource Technology, Vol: 410, ISSN: 0960-8524Applying low-cost substrate is critical for sustainable bioproduction. Co-culture of phototrophic and heterotrophic microorganisms can be a promising solution as they can use CO2 and light as feedstock. This study aimed to create a light-driven consortium using a marine cyanobacterium Synechococcus sp. PCC 7002 and an industrial yeast Yarrowia lipolytica. First, the cyanobacterium was engineered to accumulate and secrete sucrose by regulating the expression of genes involved in sucrose biosynthesis and transport, resulting in 4.0 g/L of sucrose secretion. Then, Yarrowia lipolytica was engineered to efficiently use sucrose and produce β-caryophyllene that has various industrial applications. Then, co- and sequential-culture were optimized with different induction conditions and media compositions. A maximum β-caryophyllene yield of 14.1 mg/L was obtained from the co-culture. This study successfully established an artificial light-driven consortium based on a marine cyanobacterium and Y. lipolytica, and provides a foundation for sustainable bioproduction from CO2 and light through co-culture systems.
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Book chapterGrob A, Enrico Bena C, Redwood-Sawyerr C, et al., 2024,
Simultaneous Plate-Reader Characterization of Promoter Activity and Cell Growth in Engineered Mammalian Cells
, Synthetic Promoters Methods and Protocols, Editors: Marchisio, Publisher: Humana, ISBN: 9781071640623Automated high-throughput methods that support tracking of mammalian cell growth are currently needed to advance cell line characterization and identification of desired genetic components required for cell engineering. Here, we describe a high-throughput noninvasive assay based on plate reader measurements. The assay relies on the change in absorbance of the pH indicator phenol red. We show that its basic and acidic absorbance profiles can be converted into a cell growth index consistent with cell count profiles, and that, by adopting a computational pipeline and calibration measurements, it is possible to identify a conversion that enables prediction of cell numbers from plate measurements alone. The assay is suitable for growth characterization of both suspension and adherent cell lines when these are grown under different environmental conditions and treated with chemotherapeutic drugs. The method also supports characterization of stably engineered cell lines and identification of desired promoters based on fluorescence output.
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Journal articleHaslam S, 2024,
Glycomics of cervicovaginal fluid from women at risk of preterm birth reveals immuno-regulatory epitopes that are hallmarks of cancer and viral glycosylation
, Scientific Reports, ISSN: 2045-2322 -
Journal articleFlo V, Joshi J, Sabot M, et al., 2024,
Incorporating photosynthetic acclimation improves stomatal optimisation models
, Plant, Cell and Environment, Vol: 47, Pages: 3478-3493, ISSN: 0140-7791Stomatal opening in plant leaves is regulated through a balance of carbon and water exchange under different environmental conditions. Accurate estimation of stomatal regulation is crucial for understanding how plants respond to changing environmental conditions, particularly under climate change. A new generation of optimality-based modelling schemes determines instantaneous stomatal responses from a balance of trade-offs between carbon gains and hydraulic costs, but most such schemes do not account for biochemical acclimation in response to drought. Here, we compare the performance of six instantaneous stomatal optimisation models with and without accounting for photosynthetic acclimation. Using experimental data from 37 plant species, we found that accounting for photosynthetic acclimation improves the prediction of carbon assimilation in a majority of the tested models. Photosynthetic acclimation contributed significantly to the reduction of photosynthesis under drought conditions in all tested models. Drought effects on photosynthesis could not accurately be explained by the hydraulic impairment functions embedded in the stomatal models alone, indicating that photosynthetic acclimation must be considered to improve estimates of carbon assimilation during drought.
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Journal articleDechant B, Kattge J, Pavlick R, et al., 2024,
Intercomparison of global foliar trait maps reveals fundamental differences and limitations of upscaling approaches
, Remote Sensing of Environment, Vol: 311, ISSN: 0034-4257Foliar traits such as specific leaf area (SLA), leaf nitrogen (N), and phosphorus (P) concentrations play important roles in plant economic strategies and ecosystem functioning. Various global maps of these foliar traits have been generated using statistical upscaling approaches based on in-situ trait observations. Here, we intercompare such global upscaled foliar trait maps at 0.5° spatial resolution (six maps for SLA, five for N, three for P), categorize the upscaling approaches used to generate them, and evaluate the maps with trait estimates from a global database of vegetation plots (sPlotOpen). We disentangled the contributions from different plant functional types (PFTs) to the upscaled maps and quantified the impacts of using different plot-level trait metrics on the evaluation with sPlotOpen: community weighted mean (CWM) and top-of-canopy weighted mean (TWM). We found that the global foliar trait maps of SLA and N differ drastically and fall into two groups that are almost uncorrelated (for P only maps from one group were available). The primary factor explaining the differences between these groups is the use of PFT information combined with remote sensing-derived land cover products in one group while the other group mostly relied on environmental predictors alone. The maps that used PFT and corresponding land cover information exhibit considerable similarities in spatial patterns that are strongly driven by land cover. The maps not using PFTs show a lower level of similarity and tend to be strongly driven by individual environmental variables. Upscaled maps of both groups were moderately correlated to sPlotOpen data aggregated to the grid-cell level (R = 0.2–0.6) when processing sPlotOpen in a way that is consistent with the respective trait upscaling approaches, including the plot-level trait metric (CWM or TWM) and the scaling to the grid cells with or without accounting for fractional land cover. The impact of using TWM or CWM was relevant
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Journal articleJeong S, Ryu Y, Gentine P, et al., 2024,
Persistent global greening over the last four decades using novel long-term vegetation index data with enhanced temporal consistency
, Remote Sensing of Environment, Vol: 311, ISSN: 0034-4257Advanced Very High-Resolution Radiometer (AVHRR) satellite observations have provided the longest global daily records from 1980s, but the remaining temporal inconsistency in vegetation index datasets has hindered reliable assessment of vegetation greenness trends. To tackle this, we generated novel global long-term Normalized Difference Vegetation Index (NDVI) and Near-Infrared Reflectance of vegetation (NIRv) datasets derived from AVHRR and Moderate Resolution Imaging Spectroradiometer (MODIS). We addressed residual temporal inconsistency through three-step post processing including cross-sensor calibration among AVHRR sensors, orbital drifting correction for AVHRR sensors, and machine learning-based harmonization between AVHRR and MODIS. After applying each processing step, we confirmed the enhanced temporal consistency in terms of detrended anomaly, trend and interannual variability of NDVI and NIRv at calibration sites. Our refined NDVI and NIRv datasets showed a persistent global greening trend over the last four decades (NDVI: 0.0008 yr−1; NIRv: 0.0003 yr−1), contrasting with those without the three processing steps that showed rapid greening trends before 2000 (NDVI: 0.0017 yr−1; NIRv: 0.0008 yr−1) and weakened greening trends after 2000 (NDVI: 0.0004 yr−1; NIRv: 0.0001 yr−1). These findings highlight the importance of minimizing temporal inconsistency in long-term vegetation index datasets, which can support more reliable trend analysis in global vegetation response to climate changes.
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Journal articleCavan E, 2024,
Antarctic krill sequester similar amounts of carbon to key coastal blue carbon habitats
, Nature Communications, ISSN: 2041-1723 -
Journal articleLi J, Prentice IC, 2024,
Global patterns of plant functional traits and their relationships to climate
, Communications Biology, ISSN: 2399-3642 -
Journal articleCoathup M, Savolainen V, 2024,
Ecological speciation in sympatric palms: 5. Evidence for pleiotropic speciation genes using gene knockout and high-throughput phenotyping
, Evolutionary Journal of the Linnean SocietyTheoretical models predict that sympatric, ecological speciation may be facilitated more readily when so-called ‘magic traits’ are present, linking traits under divergent selection with assortative mating. Such traits might be encoded by pleiotropic genes, that is, genes that affect multiple, apparently unrelated, phenotypes. However, few convincing examples of sympatric speciation exist, and empirical evidence for the role of magic traits in driving such speciation is rare. One of the strongest cases of sympatric speciation is the Howea palms of Lord Howe Island, Australia, comprising the sister species H. belmoreana and H. forsteriana, which have diverged due to soil substrate preferences and flowering time displacement. By carrying out high-throughput phenotyping experiments using 1,830 Arabidopsis thaliana plants with knockouts of candidate Howea ‘speciation genes’, here we investigate the role that pleiotropy may have played in the speciation process. We identify several genes that show signatures of adaptive divergence between the Howea species and demonstrate pleiotropic roles in soil stress tolerance and flowering time, consistent with the Howea speciation scenario – notably, Howea orthologs of the A. thaliana loci At2-MMP, DCL1, RCD1, SAL1, and SIZ1. Empirical evidence is provided, therefore, for a range of pleiotropic genes with the potential to have driven sympatric speciation by generating magic traits which link divergent selection to non-random mating.
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Journal articleGeffen AJ, Nash RDM, Fox CJ, 2024,
How well do connectivity tools agree over the full life cycle? A case study of Irish Sea plaice Pleuronectes platessa Linnaeus, 1758.
, J Fish BiolAdult plaice in the Irish Sea have distinct traits that reflect the spawning locations that could suggest a number of different populations. However, do connectivity pathways support this concept? Different tools are directed at measuring exchange or connectivity between different life-history stages, and the challenge is to integrate the signals to obtain full life-cycle estimates. Collectively, the different methods reveal stable connectivity between known spawning and nursery grounds, with sufficient exchange to maintain a single population with weak genetic structure.
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Journal articleBoyle MJW, Sharp AC, Barclay MV, et al., 2024,
Tropical beetles more sensitive to impacts are less likely to be known to science
, Current Biology, Vol: 34, Pages: R770-R771, ISSN: 0960-9822Insects are posited to be declining globally. This is particularly pertinent in tropical forests, which exhibit both the highest levels of biodiversity and the highest rates of biodiversity loss. However, for the hyper-diverse tropical insects there are scant data available to evidence declines. Understanding tropical insect diversity and its response to environmental change has therefore become a challenge, but it is estimated that 80% of tropical insect species remain undescribed1. Insect biodiversity predictions are based mostly on well-studied taxa and extrapolated to other groups, but no one knows whether resilience to environmental change varies between undescribed and described species. Here, we collected staphylinid beetles from unlogged and logged tropical forests in Borneo and investigated their responses to environmental change. Out of 252 morphospecies collected, 76% were undescribed. Undescribed species showed higher community turnover, reduced abundance and decreased probability of occurrence in logged forests. Thus the unknown components of tropical insect biodiversity are likely more impacted by human-induced environmental change. If these patterns are widespread, how accurate will assessments of insect declines in the tropics be?
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Journal articleSavolainen V, Bezeng BS, 2024,
An African perspective to biodiversity conservation in the 21st century
, Philosophical Transactions of the Royal Society B: Biological Sciences, ISSN: 0962-8436Africa boasts high biodiversity while also being home to some of the largest and fastest-growing human populations. Although the current environmental footprint of Africa is low compared to other continents, the population of Africa is estimated at around 1.5 billion inhabitants, representing nearly 18% of the world's total population. Consequently, Africa’s rich biodiversity is under threat, yet only 19% of the landscape and 17% of the seascape are under any form of protection. To effectively address this issue and align with the Convention on Biological Diversity's ambitious ‘30 by 30’ goal, which seeks to protect 30% of the world's land and oceans by 2030, substantial funding and conservation measures are urgently required. In response to this critical challenge, as scientists and conservationists working in Africa, we propose five recommendations for future directions aimed at enhancing biodiversity conservation for the betterment of African society: (i) accelerate data collection, data sharing and analytics for informed policy and decision making; (ii) innovate education and capacity building for future generations; (iii) enhance and expand protected areas, ecological networks, and foundational legal frameworks; (iv) unlock creative funding channels for cutting-edge conservation initiatives; and (v) integrate indigenous and local knowledge into forward-thinking conservation strategies. By implementing these recommendations, we believe Africa can make significant strides towards preserving its unique biodiversity, while fostering a healthier society, and contributing to global conservation efforts.
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Journal articleMills MB, Both S, Jotan P, et al., 2024,
From tree to plot: investigating stem CO2 efflux and its drivers along a logging gradient in Sabah, Malaysian Borneo.
, New PhytolStem respiration constitutes a substantial proportion of autotrophic respiration in forested ecosystems, but its drivers across different spatial scales and land-use gradients remain poorly understood. This study quantifies and examines the impact of logging disturbance on stem CO2 efflux (EA) in Malaysian Borneo. EA was quantified at tree- and stand-level in nine 1-ha plots over a logging gradient from heavily logged to old-growth using the static chamber method. Tree-level results showed higher EA per unit stem area in logged vs old-growth plots (37.0 ± 1.1 vs 26.92 ± 1.14 g C m-2 month-1). However, at stand-level, there was no difference in EA between logged and old-growth plots (6.7 ± 1.1 vs 6.0 ± 0.7 Mg C ha-1 yr-1) due to greater stem surface area in old-growth plots. Allocation to growth respiration and carbon use efficiency was significantly higher in logged plots. Variation in EA at both tree- and stand-level was driven by tree size, growth and differences in investment strategies between the forest types. These results reflect different resource allocation strategies and priorities, with a priority for growth in response to increased light availability in logged plots, while old-growth plots prioritise maintenance and cell structure.
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Journal articleMajumdar A, Upadhyay MK, Ojha M, et al., 2024,
A critical review on the organo-metal(loid)s pollution in the environment: Distribution, remediation and risk assessment.
, Sci Total Environ, Vol: 951Toxic metal(loid)s, e.g., mercury, arsenic, lead, and cadmium are known for several environmental disturbances creating toxicity to humans if accumulated in high quantities. Although not discussed critically, the organo-forms of these inorganic metal(loid)s are considered a greater risk to humans than their elemental forms possibly due to physico-chemical modulation triggering redox alterations or by the involvement of biological metabolism. This extensive review describes the chemical and physical causes of organometals and organometal(loid)s distribution in the environment with ecotoxicity assessment and potential remediation strategies. Organo forms of various metal(loid)s, such as mercury (Hg), arsenic (As), lead (Pb), tin (Sn), antimony (Sb), selenium (Se), and cadmium (Cd) have been discussed in the context of their ecotoxicity. In addition, we elaborated on the transformation, speciation and transformation pathways of these toxic metal(loid)s in soil-water-plant-microbial systems. The present review has pointed out the status of toxic organometal(loid)s, which is required to make the scientific community aware of this pressing condition of organometal(loid)s distribution in the environment. The gradual disposal and piling of organometal(loid)s in the environment demand a thorough revision of the past-present status with possible remediation strategies prescribed as reflected in this review.
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Journal articleSethi S, Bick IA, Chen M-Y, et al., 2024,
Large-scale avian vocalization detection delivers reliable global biodiversity insights
, Proceedings of the National Academy of Sciences of USA, Vol: 121, ISSN: 0027-8424Tracking biodiversity and its dynamics at scale is essential if we are to solve global environmental challenges. Detecting animal vocalizations in passively recorded audio data offers an automatable, inexpensive, and taxonomically broad way to monitor biodiversity. However, the labor and expertise required to label new data and fine-tune algorithms for each deployment is a major barrier. In this study, we applied a pretrained bird vocalization detection model, BirdNET, to 152,376 h of audio comprising datasets from Norway, Taiwan, Costa Rica, and Brazil. We manually listened to a subset of detections for each species in each dataset, calibrated classification thresholds, and found precisions of over 90% for 109 of 136 species. While some species were reliably detected across multiple datasets, the performance of others was dataset specific. By filtering out unreliable detections, we could extract species and community-level insight into diel (Brazil) and seasonal (Taiwan) temporal scales, as well as landscape (Costa Rica) and national (Norway) spatial scales. Our findings demonstrate that, with relatively fast but essential local calibration, a single vocalization detection model can deliver multifaceted community and species-level insight across highly diverse datasets; unlocking the scale at which acoustic monitoring can deliver immediate applied impact.
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Journal articleOgwang R, Osoti V, Wamae K, et al., 2024,
A retrospective analysis of P. falciparum drug resistance markers detects an early (2016/17) high prevalence of the k13 C469Y mutation in asymptomatic infections in Northern Uganda.
, Antimicrob Agents ChemotherThe emergence of drug-resistant Plasmodium falciparum parasites in sub-Saharan Africa will substantially challenge malaria control. Here, we evaluated the frequency of common drug resistance markers among adolescents from Northern Uganda with asymptomatic infections. We used an established amplicon deep sequencing strategy to screen dried blood spot samples collected from 2016 to 2017 during a reported malaria epidemic within the districts of Kitgum and Pader in Northern Uganda. We screened single-nucleotide polymorphisms within: kelch13 (Pfk13), dihydropteroate synthase (Pfdhps), multidrug resistance-1 (Pfmdr1), dihydrofolate reductase (Pfdhfr), and apical membrane antigen (Pfama1) genes. Within the study population, the median age was 15 years (14.3-15.0, 95% CI), and 54.9% (78/142) were Plasmodium positive by 18S rRNA qPCR, which were subsequently targeted for sequencing analysis. We observed a high frequency of resistance markers particularly for sulfadoxine-pyrimethamine (SP), with no wild-type-only parasites observed for Pfdhfr (N51I, C59R, and S108N) and Pfdhps (A437G and K540E) mutations. Within Pfmdr1, mixed infections were common for NF/NY (98.5%). While for artemisinin resistance, in kelch13, there was a high frequency of C469Y (34%). Using the pattern for Pfama1, we found a high level of polygenomic infections with all individuals presenting with complexity of infection greater than 2 with a median of 6.9. The high frequency of the quintuple SP drug-resistant parasites and the C469Y artemisinin resistance-associated mutation in asymptomatic individuals suggests an earlier high prevalence than previously reported from symptomatic malaria surveillance studies (in 2016/2017). Our data demonstrate the urgency for routine genomic surveillance programs throughout Africa and the value of deep sequencing.
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Journal articlePatin EC, Nenclares P, Chan Wah Hak C, et al., 2024,
Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy.
, Nat Commun, Vol: 15The combination of radiotherapy/chemoradiotherapy and immune checkpoint blockade can result in poor outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Here, we show that combining ATR inhibition (ATRi) with radiotherapy (RT) increases the frequency of activated NKG2A+PD-1+ T cells in animal models of HNSCC. Compared with the ATRi/RT treatment regimen alone, the addition of simultaneous NKG2A and PD-L1 blockade to ATRi/RT, in the adjuvant, post-radiotherapy setting induces a robust antitumour response driven by higher infiltration and activation of cytotoxic T cells in the tumour microenvironment. The efficacy of this combination relies on CD40/CD40L costimulation and infiltration of activated, proliferating memory CD8+ and CD4+ T cells with persistent or new T cell receptor (TCR) signalling, respectively. We also observe increased richness in the TCR repertoire and emergence of numerous and large TCR clonotypes that cluster based on antigen specificity in response to NKG2A/PD-L1/ATRi/RT. Collectively, our data point towards potential combination approaches for the treatment of HNSCC.
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Journal articleWayman JP, Sadler JP, Martin TE, et al., 2024,
Unravelling the complexities of biotic homogenization and heterogenization in the British avifauna.
, J Anim EcolBiotic homogenization is a process whereby species assemblages become more similar through time. The standard way of identifying the process of biotic homogenization is to look for decreases in spatial beta-diversity. However, using a single assemblage-level metric to assess homogenization can mask important changes in the occupancy patterns of individual species. Here, we analysed changes in the spatial beta-diversity patterns (i.e. biotic heterogenization or homogenization) of British bird assemblages within 30 km × 30 km regions between two periods (1988-1991 and 2008-2011). We partitioned the change in spatial beta-diversity into extirpation and colonization-resultant change (i.e. change in spatial beta-diversity within each region resulting from both extirpation and colonization). We used measures of abiotic change in combination with Bayesian modelling to disentangle the drivers of biotic heterogenization and homogenization. We detected both heterogenization and homogenization across the two time periods and three measures of diversity (taxonomic, phylogenetic, and functional). In addition, both extirpation and colonization contributed to the observed changes, with heterogenization mainly driven by extirpation and homogenization by colonization. These assemblage-level changes were primarily due to shifting occupancy patterns of generalist species. Compared to habitat generalists, habitat specialists had significantly (i) higher average contributions to colonization-resultant change (indicating heterogenization within a region due to colonization) and (ii) lower average contributions to extirpation-resultant change (indicating homogenization from extirpation). Generalists showed the opposite pattern. Increased extirpation-resultant homogenization within regions was associated with increased urban land cover and decreased habitat diversity, precipitation, and temperature. Changes in extirpation-resultant heterogenization and col
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Journal articleSellés J, Alric J, Rutherford AW, et al., 2024,
In vivo ElectroChromic Shift measurements of photosynthetic activity in far-red absorbing cyanobacteria.
, Biochim Biophys Acta Bioenerg, Vol: 1865Some cyanobacteria can do photosynthesis using not only visible but also far-red light that is unused by most other oxygenic photoautotrophs because of its lower energy content. These species have a modified photosynthetic apparatus containing red-shifted pigments. The incorporation of red-shifted pigments decreases the photochemical efficiency of photosystem I and, especially, photosystem II, and it might affect the distribution of excitation energy between the two photosystems with possible consequences on the activity of the entire electron transport chain. To investigate the in vivo effects on photosynthetic activity of these pigment changes, we present here the adaptation of a spectroscopic method, based on a physical phenomenon called ElectroChromic Shift (ECS), to the far-red absorbing cyanobacteria Acaryochloris marina and Chroococcidiopsis thermalis PCC7203. ECS measures the electric field component of the trans-thylakoid proton motive force generated by photosynthetic electron transfer. We show that ECS can be used in these cyanobacteria to investigate in vivo the stoichiometry of photosystem I and photosystem II and their absorption cross-section, as well as the overall efficiency of light energy conversion into electron transport. Our results indicate that both species use visible and far-red light with similar efficiency, despite significant differences in their light absorption characteristics. ECS thus represents a new non-invasive tool to study the performance of naturally occurring far-red photosynthesis.
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Journal articleEwers RM, 2024,
An audacious approach to conservation.
, Trends Ecol EvolNew digital and sensor technology provides a huge opportunity to revolutionise conservation, but we lack a plan for deploying the technologies effectively. I argue that environmental research should be concentrated at a small number of 'super-sites' and that the concentrated knowledge from super-sites should be used to develop holistic ecosystem models. These, in turn, should be morphed into digital twin ecosystems by live connecting them with automated environmental monitoring programmes. Data-driven simulations can then help select pathways to achieve locally determined conservation goals, and digital twins could revise and adapt those decisions in real-time. This technology-heavy vision for 'smart conservation' provides a map toward a future defined by more flexible, more responsive, and more efficient management of natural environments.
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Journal articleCasadio R, Mathews DH, Sternberg MJE, 2024,
Computational Resources for Molecular Biology 2024.
, J Mol Biol -
Journal articleRogers J, Bajur AT, Salaita K, et al., 2024,
Mechanical control of antigen detection and discrimination by T and B cell receptors.
, Biophys J, Vol: 123, Pages: 2234-2255The adaptive immune response is orchestrated by just two cell types, T cells and B cells. Both cells possess the remarkable ability to recognize virtually any antigen through their respective antigen receptors-the T cell receptor (TCR) and B cell receptor (BCR). Despite extensive investigations into the biochemical signaling events triggered by antigen recognition in these cells, our ability to predict or control the outcome of T and B cell activation remains elusive. This challenge is compounded by the sensitivity of T and B cells to the biophysical properties of antigens and the cells presenting them-a phenomenon we are just beginning to understand. Recent insights underscore the central role of mechanical forces in this process, governing the conformation, signaling activity, and spatial organization of TCRs and BCRs within the cell membrane, ultimately eliciting distinct cellular responses. Traditionally, T cells and B cells have been studied independently, with researchers working in parallel to decipher the mechanisms of activation. While these investigations have unveiled many overlaps in how these cell types sense and respond to antigens, notable differences exist. To fully grasp their biology and harness it for therapeutic purposes, these distinctions must be considered. This review compares and contrasts the TCR and BCR, placing emphasis on the role of mechanical force in regulating the activity of both receptors to shape cellular and humoral adaptive immune responses.
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Journal articleIliopoulou M, Bajur AT, McArthur HCW, et al., 2024,
Extracellular matrix rigidity modulates physical properties of subcapsular sinus macrophage-B cell immune synapses.
, Biophys J, Vol: 123, Pages: 2282-2300Subcapsular sinus macrophages (SSMs) play a key role in immune defense by forming immunological barriers that control the transport of antigens from lymph into lymph node follicles. SSMs participate in antibody responses by presenting antigens directly to naive B cells and by supplying antigens to follicular dendritic cells to propagate germinal center reactions. Despite the prominent roles that SSMs play during immune responses, little is known about their cell biology because they are technically challenging to isolate and study in vitro. Here, we used multicolor fluorescence microscopy to identify lymph node-derived SSMs in culture. We focused on the role of SSMs as antigen-presenting cells, and found that their actin cytoskeleton regulates the spatial organization and mobility of multivalent antigens (immune complexes [ICs]) displayed on the cell surface. Moreover, we determined that SSMs are mechanosensitive cells that respond to changes in extracellular matrix rigidity by altering the architecture of the actin cytoskeleton, leading to changes in cell morphology, membrane topography, and IC mobility. Changes to extracellular matrix rigidity also modulate actin remodeling by both SSMs and B cells when they form an immune synapse. This alters synapse duration but not IC internalization nor NF-κB activation in the B cell. Taken together, our data reveal that the mechanical microenvironment may influence B cell responses by modulating physical characteristics of antigen presentation by SSMs.
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Journal articleHeath BE, Suzuki R, LePenru NP, et al., 2024,
Spatial ecosystem monitoring with a Multichannel Acoustic Autonomous Recording Unit (MAARU)
, Methods in Ecology and Evolution, ISSN: 2041-210X1. Multi-microphone recording adds spatial information to recorded audio with emerging applications in ecosystem monitoring. Specifically placing sounds in space can improve animal count accuracy, locate illegal activity like logging and poaching, track animals to monitor behaviour and habitat use and allow for ‘beamforming’ to amplify sounds from target directions for downstream classification. Studies have shown many advantages of spatial acoustics, but uptake remains limited as the equipment is often expensive, complicated, inaccessible or only suitable for short-term deployments.2. With an emphasis on enhanced uptake and usability, we present a low-cost, open-source, six-channel recorder built entirely from commercially available components which can be integrated into a solar-powered, online system. The MAARU (Multichannel Acoustic Autonomous Recording Unit) works as an independent node in long-term autonomous, passive and/or short-term deployments. Here, we introduce MAARU's hardware and software and present the results of lab and field tests investigating the device's durability and usability.3. MAARU records multichannel audio with similar costs and power demands to equivalent omnidirectional recorders. MAARU devices have been deployed in the United Kingdom and Brazil, where we have shown MAARUs can accurately localise pure tones up to 6 kHz and bird calls as far as 8 m away (±10° range, 100% and >60% of signals, respectively). Louder calls may have even further detection radii. We also show how beamforming can be used with MAARUs to improve species ID confidence scores.4. MAARU is an accessible, low-cost option for those looking to explore spatial acoustics accurately and easily with a single device, and without the formidable expenses and processing complications associated with establishing arrays. Ultimately, the added directional element of the multichannel recording provided by MAARU allows for enhanced recording
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Journal articleConnolly JB, Burt A, Christophides G, et al., 2024,
Publisher Correction: Considerations for first field trials of low-threshold gene drive for malaria vector control
, Malaria Journal, Vol: 23, ISSN: 1475-2875 -
Journal articleBa W, Nollet M, Yin C, et al., 2024,
A REM-active basal ganglia circuit that regulates anxiety
, Current Biology, Vol: 34, Pages: 3301-2214.E4, ISSN: 0960-9822REM sleep has been hypothesized to promote emotional resilience, but any neuronal circuits mediating this have not been identified. We find that in mice, somatostatin (Som)neurons in the entopeduncular nucleus (EP Som )/internal globus pallidus are predominantly active during REM sleep. This unique REM activity is necessary and sufficient formaintaining normal REM sleep. Inhibiting or exciting EPSom neurons reduced or increased REM sleep duration, respectively. Activation of the sole downstream target of EPSom neurons, Vglut2 cells in the lateral habenula (LHb), increased sleep via the ventral tegmental area (VTA). A simple chemogenetic scheme to periodically inhibit the LHb over 4 days selectively removed a significant amount of cumulative REM sleep. Chronic, but not acute, REM reduction correlated with mice becoming anxious and more sensitive to aversive stimuli. Therefore, we suggest that cumulative REM sleep, in part generated by the EP→LHb→VTA circuit identified here, could contribute to stabilizing reactions to habitual aversive stimuli.
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Journal articleHutchison CDM, Perrett S, van Thor JJ, 2024,
XFEL beamline optical instrumentation for ultrafast science
, The Journal of Physical Chemistry B, ISSN: 1520-6106Free electron lasers operating in the soft and hard X-ray regime provide capabilities for ultrafast science in many areas, including X-ray spectroscopy, diffractive imaging, solution and material scattering, and X-ray crystallography. Ultrafast time-resolved applications in the picosecond, femtosecond, and attosecond regimes are often possible using single-shot experimental configurations. Aside from X-ray pump and X-ray probe measurements, all other types of ultrafast experiments require the synchronized operation of pulsed laser excitation for resonant or nonresonant pumping. This Perspective focuses on the opportunities for the optical control of structural dynamics by applying techniques from nonlinear spectroscopy to ultrafast X-ray experiments. This typically requires the synthesis of two or more optical pulses with full control of pulse and interpulse parameters. To this end, full characterization of the femtosecond optical pulses is also highly desirable. It has recently been shown that two-color and two-pulse femtosecond excitation of fluorescent protein crystals allowed a Tannor-Rice coherent control experiment, performed under characterized conditions. Pulse shaping and the ability to synthesize multicolor and multipulse conditions are highly desirable and would enable XFEL facilities to offer capabilities for structural dynamics. This Perspective will give a summary of examples of the types of experiments that could be achieved, and it will additionally summarize the laser, pulse shaping, and characterization that would be recommended as standard equipment for time-resolved XFEL beamlines, with an emphasis on ultrafast time-resolved serial femtosecond crystallography.
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Journal articleKabasakal BV, McFarlane CR, Cotton CAR, et al., 2024,
The crystal structure of Shethna protein II (FeSII) from Azotobacter vinelandii suggests a domain swap.
, Acta Crystallogr D Struct Biol, Vol: 80, Pages: 599-604The Azotobacter vinelandii FeSII protein forms an oxygen-resistant complex with the nitrogenase MoFe and Fe proteins. FeSII is an adrenodoxin-type ferredoxin that forms a dimer in solution. Previously, the crystal structure was solved [Schlesier et al. (2016), J. Am. Chem. Soc. 138, 239-247] with five copies in the asymmetric unit. One copy is a normal adrenodoxin domain that forms a dimer with its crystallographic symmetry mate. The other four copies are in an `open' conformation with a loop flipped out exposing the 2Fe-2S cluster. The open and closed conformations were interpreted as oxidized and reduced, respectively, and the large conformational change in the open configuration allowed binding to nitrogenase. Here, the structure of FeSII was independently solved in the same crystal form. The positioning of the atoms in the unit cell is similar to the earlier report. However, the interpretation of the structure is different. The `open' conformation is interpreted as the product of a crystallization-induced domain swap. The 2Fe-2S cluster is not exposed to solvent, but in the crystal its interacting helix is replaced by the same helix residues from a crystal symmetry mate. The domain swap is complicated, as it is unusual in being in the middle of the protein rather than at a terminus, and it creates arrangements of molecules that can be interpreted in multiple ways. It is also cautioned that crystal structures should be interpreted in terms of the contents of the entire crystal rather than of one asymmetric unit.
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