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Journal articleCanton APM, Tinano FR, Guasti L, et al., 2023,
Rare variants in the MECP2 gene in girls with central precocious puberty: a translational cohort study
, The Lancet Diabetes & Endocrinology, Vol: 11, Pages: 545-554, ISSN: 2213-8587BackgroundIdentification of genetic causes of central precocious puberty have revealed epigenetic mechanisms as regulators of human pubertal timing. MECP2, an X-linked gene, encodes a chromatin-associated protein with a role in gene transcription. MECP2 loss-of-function mutations usually cause Rett syndrome, a severe neurodevelopmental disorder. Early pubertal development has been shown in several patients with Rett syndrome. The aim of this study was to explore whether MECP2 variants are associated with an idiopathic central precocious puberty phenotype.MethodsIn this translational cohort study, participants were recruited from seven tertiary centres from five countries (Brazil, Spain, France, the USA, and the UK). Patients with idiopathic central precocious puberty were investigated for rare potentially damaging variants in the MECP2 gene, to assess whether MECP2 might contribute to the cause of central precocious puberty. Inclusion criteria were the development of progressive pubertal signs (Tanner stage 2) before the age of 8 years in girls and 9 years in boys and basal or GnRH-stimulated LH pubertal concentrations. Exclusion criteria were the diagnosis of peripheral precocious puberty and the presence of any recognised cause of central precocious puberty (CNS lesions, known monogenic causes, genetic syndromes, or early exposure to sex steroids). All patients included were followed up at the outpatient clinics of participating academic centres. We used high-throughput sequencing in 133 patients and Sanger sequencing of MECP2 in an additional 271 patients. Hypothalamic expression of Mecp2 and colocalisation with GnRH neurons were determined in mice to show expression of Mecp2 in key nuclei related to pubertal timing regulation.FindingsBetween Jun 15, 2020, and Jun 15, 2022, 404 patients with idiopathic central precocious puberty (383 [95%] girls and 21 [5%] boys; 261 [65%] sporadic cases and 143 [35%] familial cases from 134 unrelated families) were enrolled and
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Journal articleRuehr S, Keenan TF, Williams C, et al., 2023,
Evidence and attribution of the enhanced land carbon sink
, Nature Reviews Earth & Environment, Vol: 4, Pages: 518-534, ISSN: 2662-138XClimate change has been partially mitigated by an increasing net land carbon sink in the terrestrial biosphere; understanding the processes that drive the land carbon sink is thus essential for protecting, managing, and projecting this important ecosystem service. In this Review, we examine evidence for an enhanced land carbon sink and attribute the observed response to drivers and processes. The land carbon sink has doubled from 1.2 ± 0.5 PgC yr-1 in the 1960s to 3.1 ± 0.6 PgC yr-1 in the 2010s. This trend results largely from carbon dioxide (CO2) fertilization increasing photosynthesis (driving an increase in the annual land carbon sink of >2PgC globally since 1900), mainly in tropical forest regions, and elevated temperatures reducing cold-limitation, mainly at higher latitudes. Continued long term land carbon sequestration is possible through the end of this century under multiple emissions scenarios, especially if nature-based climate solutions and appropriate ecosystem management are deployed. A new generation of globally distributed field experiments are needed to improve understanding of future carbon sink potential by measuring belowground carbon release, the response to CO2 enrichment, and long-term shifts in carbon allocation and turnover .
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Journal articlePearse WD, Stemkovski M, Lee BRR, et al., 2023,
Consistent, linear phenological shifts across a century of observations in South Korea
, NEW PHYTOLOGIST, Vol: 239, Pages: 824-829, ISSN: 0028-646X -
Journal articleBeidler KV, Powers JS, Dupuy-Rada JM, et al., 2023,
Seasonality regulates the structure and biogeochemical impact of ectomycorrhizal fungal communities across environmentally divergent neotropical dry forestsPalabras clave
, JOURNAL OF ECOLOGY, Vol: 111, Pages: 1598-1613, ISSN: 0022-0477 -
Journal articleBellotto-Trigo FC, Uezu A, Hatfield JH, et al., 2023,
Intraspecific variation in sensitivity to habitat fragmentation is influenced by forest cover and distance to the range edge
, BIOLOGICAL CONSERVATION, Vol: 284, ISSN: 0006-3207 -
Journal articleMartÃnez-Riaño A, Wang S, Boeing S, et al., 2023,
Long-term retention of antigens in germinal centers is controlled by the spatial organization of the follicular dendritic cell network.
, Nat Immunol, Vol: 24, Pages: 1281-1294Germinal centers (GCs) require sustained availability of antigens to promote antibody affinity maturation against pathogens and vaccines. A key source of antigens for GC B cells are immune complexes (ICs) displayed on follicular dendritic cells (FDCs). Here we show that FDC spatial organization regulates antigen dynamics in the GC. We identify heterogeneity within the FDC network. While the entire light zone (LZ) FDC network captures ICs initially, only the central cells of the network function as the antigen reservoir, where different antigens arriving from subsequent immunizations colocalize. Mechanistically, central LZ FDCs constitutively express subtly higher CR2 membrane densities than peripheral LZ FDCs, which strongly increases the IC retention half-life. Even though repeated immunizations gradually saturate central FDCs, B cell responses remain efficient because new antigens partially displace old ones. These results reveal the principles shaping antigen display on FDCs during the GC reaction.
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Journal articleHorrocks V, King OG, Yip AYG, et al., 2023,
Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization.
, Microbiology, Vol: 169, Pages: 1-13, ISSN: 1350-0872The human gut microbiota can restrict the growth of pathogens to prevent them from colonizing the intestine ('colonization resistance'). However, antibiotic treatment can kill members of the gut microbiota ('gut commensals') and reduce competition for nutrients, making these nutrients available to support the growth of pathogens. This disturbance can lead to the growth and expansion of pathogens within the intestine (including antibiotic-resistant pathogens), where these pathogens can exploit the absence of competitors and the nutrient-enriched gut environment. In this review, we discuss nutrient competition between the gut microbiota and pathogens. We also provide an overview of how nutrient competition can be harnessed to support the design of next-generation microbiome therapeutics to restrict the growth of pathogens and prevent the development of invasive infections.
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Journal articleSethi SS, Bick A, Ewers RM, et al., 2023,
Limits to the accurate and generalizable use of soundscapes to monitor biodiversity
, Nature Ecology and Evolution, Vol: 7, Pages: 1373-1378, ISSN: 2397-334XAlthough eco-acoustic monitoring has the potential to deliver biodiversity insight on vast scales, existing analytical approaches behave unpredictably across studies. We collated 8,023 audio recordings with paired manual avifaunal point counts to investigate whether soundscapes could be used to monitor biodiversity across diverse ecosystems. We found that neither univariate indices nor machine learning models were predictive of species richness across datasets but soundscape change was consistently indicative of community change. Our findings indicate that there are no common features of biodiverse soundscapes and that soundscape monitoring should be used cautiously and in conjunction with more reliable in-person ecological surveys.
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Journal articleDobson S, Dunning J, Burke T, et al., 2023,
Indirect genetic effects increase heritability estimates for male and female extra-pair reproduction
, EVOLUTION, Vol: 77, Pages: 1893-1901, ISSN: 0014-3820 -
Journal articleFadini A, Hutchison CDM, Morozov D, et al., 2023,
Serial femtosecond crystallography reveals that photoactivation in a fluorescent protein proceeds via the hula twist mechanism
, Journal of the American Chemical Society, Vol: 145, Pages: 15796-15808, ISSN: 0002-7863Chromophore cis/trans photoisomerization is a fundamental process in chemistry and in the activation of many photosensitive proteins. A major task is understanding the effect of the protein environment on the efficiency and direction of this reaction compared to what is observed in the gas and solution phases. In this study, we set out to visualize the hula twist (HT) mechanism in a fluorescent protein, which is hypothesized to be the preferred mechanism in a spatially constrained binding pocket. We use a chlorine substituent to break the twofold symmetry of the embedded phenolic group of the chromophore and unambiguously identify the HT primary photoproduct. Through serial femtosecond crystallography, we then track the photoreaction from femtoseconds to the microsecond regime. We observe signals for the photoisomerization of the chromophore as early as 300 fs, obtaining the first experimental structural evidence of the HT mechanism in a protein on its femtosecond-to-picosecond timescale. We are then able to follow how chromophore isomerization and twisting lead to secondary structure rearrangements of the protein β-barrel across the time window of our measurements.
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Journal articleMurooka Y, Bryan W, Clarke J, et al., 2023,
The Design of Relativistic Ultrafast Electron Diffraction and Imaging (RUEDI) Facility for Materials in Extremes.
, Microsc Microanal, Vol: 29, Pages: 1487-1488 -
Journal articleMathews DH, Casadio R, Sternberg MJE, 2023,
Computational Resources for Molecular Biology 2023.
, J Mol Biol, Vol: 435 -
Journal articlePennica C, Sternberg M, Islam S, et al., 2023,
Missense3D-PPI: a web resource to predict the impact of missense variants at protein interfaces using 3D structural data
, Journal of Molecular Biology, Vol: 435, Pages: 1-9, ISSN: 0022-2836In 2019, we released Missense3D which identifies stereochemical features that are disrupted by a missense variant, such as introducing a buried charge. Missense3D analyses the effect of a missense variant on a single structure and thus may fail to identify as damaging surface variants disrupting a protein interface i.e., a protein–protein interaction (PPI) site. Here we present Missense3D-PPI designed to predict missense variants at PPI interfaces.Our development dataset comprised of 1,279 missense variants (pathogenic n = 733, benign n = 546) in 434 proteins and 545 experimental structures of PPI complexes. Benchmarking of Missense3D-PPI was performed after dividing the dataset in training (320 benign and 320 pathogenic variants) and testing (226 benign and 413 pathogenic). Structural features affecting PPI, such as disruption of interchain bonds and introduction of unbalanced charged interface residues, were analysed to assess the impact of the variant at PPI.The performance of Missense3D-PPI was superior to that of Missense3D: sensitivity 44 % versus 8% and accuracy 58% versus 40%, p = 4.23 × 10−16. However, the specificity of Missense3D-PPI was lower compared to Missense3D (84% versus 98%). On our dataset, Missense3D-PPI’s accuracy was superior to BeAtMuSiC (p = 3.4 × 10−5), mCSM-PPI2 (p = 1.5 × 10−12) and MutaBind2 (p = 0.0025).Missense3D-PPI represents a valuable tool for predicting the structural effect of missense variants on biological protein networks and is available at the Missense3D web portal (http://missense3d.bc.ic.ac.uk).
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Journal articleWaring B, Gurgel A, Koberle A, et al., 2023,
Natural Climate Solutions must embrace multiple perspectives to ensure synergy with sustainable development
, Frontiers in Climate, Vol: 5, Pages: 1-7, ISSN: 2624-9553To limit global warming to well below 2°C, immediate emissions reductions must be coupled with active removal of greenhouse gases from the atmosphere. 'Natural Climate Solutions' (NCS) achieve atmospheric CO2 reduction through the conservation, restoration, or altered management of natural ecosystems, 1,2 with enormous potential to deliver 'win-win-win' outcomes for climate, nature and society.Yet the supply of high-quality NCS projects does not meet market demand, and projects already underway often fail to deliver their promised benefits, due to a complex set of interacting ecological, social, and financial constraints. How can these cross-sectoral challenges be surmounted? Here we draw from expert elicitation surveys and workshops with professionals across the ecological, sociological, and economic sciences, evaluating differing perspectives on NCS, and suggesting how these might be integrated to address urgent environmental challenges. We demonstrate that funders' perceptions of operational, political, and regulatory risk strongly shape the kinds of NCS projects that are implemented, and the locations where they occur. Because of this, greenhouse gas removal through NCS may fall far short of technical potential.Moreover, socioecological co-benefits of NCS are unlikely to be realized unless the local communities engaged with these projects are granted ownership over implementation and outcomes.
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Journal articleJohansson J, Arce A, Gill R, 2023,
How competition between overlapping generations can influence optimal egg-laying strategies in annual social insects
, Oecologia, Vol: 202, Pages: 535-547, ISSN: 0029-8549Annual social insects are an integral functional group of organisms, particularly in temperate environments. An emblematic part of their annual cycle is the social phase, during which the colony-founding queen rears workers that later assist her in rearing sexual progeny (gynes and drones). In many annual social insects, such as species of bees, wasps, and other groups, developing larvae are provisioned gradually as they develop (progressive provisioning) leading to multiple larval generations being reared simultaneously. We present a model for how the queen in such cases should optimize her egg-laying rate throughout the social phase depending on number-size trade-offs, colony age-structure, and energy balance. Complementing previous theory on optimal allocation between workers vs. sexuals in annual social insects and on temporal egg-laying patterns in solitary insects, we elucidate how resource competition among overlapping larval generations can influence optimal egg-laying strategies. With model parameters informed by knowledge of a common bumblebee species, the optimal egg-laying schedule consists of two temporally separated early broods followed by a more continuous rearing phase, matching empirical observations. However, eggs should initially be laid continuously at a gradually increasing rate when resources are scarce or mortality risks high and in cases where larvae are fully supplied with resources at the egg-laying stage (mass-provisioning). These factors, alongside sexual:worker body size ratios, further determine the overall trend in egg-laying rates over the colony cycle. Our analysis provides an inroad to study and mechanistically understand variation in colony development strategies within and across species of annual social insects.
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Journal articleClive J, Flintham E, Savolainen V, 2023,
Same-sex sociosexual behaviour is widespread and heritable in male rhesus macaques
, Nature Ecology and Evolution, Vol: 7, Pages: 1287-1301, ISSN: 2397-334XNumerous reports have documented the occurrence of same-sex sociosexual behaviour (SSB) across animal species. However, the distribution of the behaviour within a species is needed to test the theories describing its evolution and maintenance, in particular whether the behaviour is heritable and can therefore evolve by natural selection. Here, we collected detailed observations across three years of social and mounting behaviour of 236 male semi-wild rhesus macaques, which we combined with a pedigree dating back to 1938, to show that SSB was both repeatable (19.35%) and heritable (6.4%). Demographic factors (age and group structure) explained SSB variation only marginally. Furthermore, we found a positive genetic correlation between same-sex mounter and mountee activities, indicating a common basis to different forms of SSB. Finally, we found no evidence of fitness costs to SSB, but show instead that the behaviour mediated coalitionary partnerships that have been linked with improved reproductive success. Together, our results demonstrate that SSB is frequent in rhesus macaques, can evolve, and is not costly, indicating that SSB may be a common feature of primate reproductive ecology.
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Journal articleHui L, Ippolito K, Sarsfield M, et al., 2023,
Using a self-reflective ePortfolio and feedback dialogue to understand and address problematic feedback expectations
, ASSESSMENT & EVALUATION IN HIGHER EDUCATION, ISSN: 0260-2938- Author Web Link
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- Citations: 1
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Journal articleGranville NR, Banks-Leite C, 2023,
Mangrove propagules are limited in their capacity to disperse across long distances
, JOURNAL OF TROPICAL ECOLOGY, Vol: 39, ISSN: 0266-4674 -
Journal articlede Lorm TA, Horswill C, Rabaiotti D, et al., 2023,
Optimizing the automated recognition of individual animals to support population monitoring
, Ecology and Evolution, Vol: 13, ISSN: 2045-7758Reliable estimates of population size and demographic rates are central to assessing the status of threatened species. However, obtaining individual-based demographic rates requires long-term data, which is often costly and difficult to collect. Photographic data offer an inexpensive, noninvasive method for individual-based monitoring of species with unique markings, and could therefore increase available demographic data for many species. However, selecting suitable images and identifying individuals from photographic catalogs is prohibitively time-consuming. Automated identification software can significantly speed up this process. Nevertheless, automated methods for selecting suitable images are lacking, as are studies comparing the performance of the most prominent identification software packages. In this study, we develop a framework that automatically selects images suitable for individual identification, and compare the performance of three commonly used identification software packages; Hotspotter, I3S-Pattern, and WildID. As a case study, we consider the African wild dog, Lycaon pictus, a species whose conservation is limited by a lack of cost-effective large-scale monitoring. To evaluate intraspecific variation in the performance of software packages, we compare identification accuracy between two populations (in Kenya and Zimbabwe) that have markedly different coat coloration patterns. The process of selecting suitable images was automated using convolutional neural networks that crop individuals from images, filter out unsuitable images, separate left and right flanks, and remove image backgrounds. Hotspotter had the highest image-matching accuracy for both populations. However, the accuracy was significantly lower for the Kenyan population (62%), compared to the Zimbabwean population (88%). Our automated image preprocessing has immediate application for expanding monitoring based on image matching. However, the difference in accuracy between population
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Journal articleVoisin TB, Couves EC, Tate EW, et al., 2023,
Dynamics and molecular interactions of GPI-anchored CD59
, Toxins, Vol: 15, ISSN: 2072-6651CD59 is a GPI-anchored cell surface receptor that serves as a gatekeeper to controlling pore formation. It is the only membrane-bound inhibitor of the complement membrane attack complex (MAC), an immune pore that can damage human cells. While CD59 blocks MAC pores, the receptor is co-opted by bacterial pore-forming proteins to target human cells. Recent structures of CD59 in complexes with binding partners showed dramatic differences in the orientation of its ectodomain relative to the membrane. Here, we show how GPI-anchored CD59 can satisfy this diversity in binding modes. We present a PyLipID analysis of coarse-grain molecular dynamics simulations of a CD59-inhibited MAC to reveal residues of complement proteins (C6:Y285, C6:R407 C6:K412, C7:F224, C8β:F202, C8β:K326) that likely interact with lipids. Using modules of the MDAnalysis package to investigate atomistic simulations of GPI-anchored CD59, we discover properties of CD59 that encode the flexibility necessary to bind both complement proteins and bacterial virulence factors.
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Journal articleMorissette O, Trueman CN, Sturrock AM, et al., 2023,
Limited evidence for species-specific sensitivity of temperature-dependent fractionation of oxygen stable isotope in biominerals: A meta-analysis
, METHODS IN ECOLOGY AND EVOLUTION, Vol: 14, Pages: 1719-1731, ISSN: 2041-210X- Author Web Link
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- Citations: 1
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Journal articleDong N, Dechant B, Wang H, et al., 2023,
Global leaf-trait mapping based on optimality theory
, Global Ecology and Biogeography, Vol: 32, Pages: 1152-1162, ISSN: 1466-822XAimLeaf traits are central to plant function, and key variables in ecosystem models. However recently published global trait maps, made by applying statistical or machine-learning techniques to large compilations of trait and environmental data, differ substantially from one another. This paper aims to demonstrate the potential of an alternative approach, based on eco-evolutionary optimality theory, to yield predictions of spatio-temporal patterns in leaf traits that can be independently evaluated.InnovationGlobal patterns of community-mean specific leaf area (SLA) and photosynthetic capacity (Vcmax) are predicted from climate via existing optimality models. Then leaf nitrogen per unit area (Narea) and mass (Nmass) are inferred using their (previously derived) empirical relationships to SLA and Vcmax. Trait data are thus reserved for testing model predictions across sites. Temporal trends can also be predicted, as consequences of environmental change, and compared to those inferred from leaf-level measurements and/or remote-sensing methods, which are an increasingly important source of information on spatio-temporal variation in plant traits.Main conclusionsModel predictions evaluated against site-mean trait data from > 2,000 sites in the Plant Trait database yielded R2 = 73% for SLA, 38% for Nmass and 28% for Narea. Declining species-level Nmass, and increasing community-level SLA, have both been recently reported and were both correctly predicted. Leaf-trait mapping via optimality theory holds promise for macroecological applications, including an improved understanding of community leaf-trait responses to environmental change.
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Journal articlePal D, Patel M, Boulet F, et al., 2023,
H4K16ac activates the transcription of transposable elements and contributes to their <i>cis</i>-regulatory function
, NATURE STRUCTURAL & MOLECULAR BIOLOGY, Vol: 30, Pages: 935-+, ISSN: 1545-9993 -
Journal articleHunt ESE, Felice RN, Tobias JA, et al., 2023,
Ecological and life-history drivers of avian skull evolution
, EVOLUTION, Vol: 77, Pages: 1720-1729, ISSN: 0014-3820 -
OtherMengoli G, Harrison SP, Prentice IC, 2023,
Supplementary material to "A global function of climatic aridity accounts for soil moisture stress on carbon assimilation"
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Journal articleTan C, Trew J, Peacock T, et al., 2023,
Genomic screening of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential
, Nature Communications, Vol: 14, Pages: 1-13, ISSN: 2041-1723There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses in 48 faecal samples from 16 of the 17 bat species breeding in the UK, collected through a bat rehabilitation and conservationist network. We recovered nine (two novel) complete genomes across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk is unknown and warrants closer surveillance.
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Journal articleLiu Y, Kaffah N, Pandor S, et al., 2023,
Ion mobility mass spectrometry for the study of mycobacterial mycolic acids
, Scientific Reports, Vol: 13, Pages: 1-8, ISSN: 2045-2322Lipids are highly structurally diverse molecules involved in a wide variety of biological processes. The involvement of lipids is even more pronounced in mycobacteria, including the human pathogen Mycobacterium tuberculosis, which produces a highly complex and diverse set of lipids in the cell envelope. These lipids include mycolic acids, which are among the longest fatty acids in nature and can contain up to 90 carbon atoms. Mycolic acids are ubiquitously found in mycobacteria and are alpha branched and beta hydroxylated lipids. Discrete modifications, such as alpha, alpha’, epoxy, methoxy, keto, and carboxy, characterize mycolic acids at the species level. Here, we used high precision ion mobility-mass spectrometry to build a database including 206 mass-resolved collision cross sections (CCSs) of mycolic acids originating from the strict human pathogen M. tuberculosis, the opportunistic strains M. abscessus, M. marinum and M. avium, and the nonpathogenic strain M. smegmatis. Primary differences between the mycolic acid profiles could be observed between mycobacterial species. Acyl tail length and modifications were the primary structural descriptors determining CCS magnitude. As a resource for researchers, this work provides a detailed catalogue of the mass-resolved collision cross sections for mycolic acids along with a workflow to generate and analyse the dataset generated.
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Journal articleSharma S, Roy T, Kashyap Y, et al., 2023,
Characterizing and demonstrating the role of <i>Klebsiella</i> SSN1 exopolysaccharide in osmotic stress tolerance using neutron radiography
, SCIENTIFIC REPORTS, Vol: 13, ISSN: 2045-2322 -
Journal articleOtero-Muras I, Perez-Carrasco R, Banga JR, et al., 2023,
Automated design of gene circuits with optimal mushroom-bifurcation behaviour
, iScience, Vol: 26, Pages: 1-15, ISSN: 2589-0042Recent advances in synthetic biology are enabling exciting technologies, including the next generation of biosensors, the rational design of cell memory, modulated synthetic cell differentiation and generic multifunctional biocircuits. These novel applications require the design of gene circuits leading to sophisticated behaviours and functionalities. At the same time, designs need to be kept minimal to avoid compromising cell viability. Bifurcation theory addresses such challenges by associating circuit dynamical properties with molecular details of its design. Nevertheless, incorporating bifurcation analysis into automated design processes has not been accomplished yet. This work presents an optimization-based method for the automated design of synthetic gene circuits with specified bifurcation diagrams that employ minimal network topologies. Using this approach, we designed circuits exhibiting the mushroom bifurcation, distilled the most robust topologies and explored its multi-functional behavior. We then outline potential applications in biosensors, memory devices, and synthetic cell differentiation.
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Journal articleGutierrez GV, Perez-Aviles D, Raczka N, et al., 2023,
Throughfall exclusion and fertilization effects on tropical dry forest tree plantations, a large-scale experiment
, BIOGEOSCIENCES, Vol: 20, Pages: 2143-2160, ISSN: 1726-4170
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