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Solanum bulbocastanum nucleotide‐binding leucine‐rich repeat receptor evolution reveals functional variants and critical residues in Rpi‐blb1/RB
Get PDFFunding: This work was supported by the National Natural Science Foundation of China (32372558), National Natural Science Foundation of China‐The Royal Society (32061130211), the Rural and Environment Science and Analytical Services Di-vision of the Scottish Government through project JHI‐B1‐1,the Biotechnology and Biological Sciences Research Council (BBSRC) through award BB/S015663/1, and the Royal Society through award NAF\R1\201061.Host–pathogen co‐evolution shapes resistance (R) proteins and their recognition of pathogen avirulence factors. However, little attention has been paid to naturally occurring genetic diversity in R genes. In this study, 12 Solanum bulbocastanum accessions from the Commonwealth Potato Collection were screened for resistance to Phytophthora infestans, identifying 11 resistant and one susceptible accession. Targeted enrichment sequencing of nucleotide‐binding leucine‐rich repeat (NLR) genes using RenSeq, followed by diagnostic RenSeq (dRenSeq) analysis, revealed that all accessions except 7650 contained Rpi‐blb1/RB variants. Variants in accessions 7641 and 7648 were non‐functional, while three novel functional variants were identified. Cloning and functional analysis of Rpi‐blb1/RB variants assessed their recognition of the avirulence factor IPI‐O1. Three variants were functional, conferring resistance to P. infestans. Variants in accessions 7644 and 7647 also recognized IPI‐O4, confirmed in transgenic potatoes. Analysis of a non‐functional variant in S. bulbocastanum accession 7648 identified amino acid Ser347 in the nucleotide‐binding (NB‐ARC) domain as critical for cell‐death initiation following IPI‐O1 recognition. Predictions from the FunFOLD2 protein–ligand interaction model suggested that Ser347 is essential for ATP binding, suggesting potential inhibition on pentameric resistosome assembly. Western blot analysis revealed that the mutation of Ser347 to Asn markedly compromises the Rpi‐blb1/RB protein stability, and co‐immunoprecipitation assay further confirmed that this mutation severely disrupts the self‐association of CCNB, thereby preventing Rpi‐blb1/RB activation. Consistently, substituting Asn347 with serine restored function, underscoring its key role in Rpi‐blb1/RB activity. Cell biology experiments demonstrated that Rpi‐blb1/RB relocalize to the plasma membrane in response to IPI‐O1. This relocalization depends on Ser347, further supporting the idea that its mutation affects resistosome formation, impairing resistance. This study provides an in‐depth functional analysis of natural Rpi‐blb1/RB diversity, offering insights into NLR protein evolution and resistance mechanisms in potatoes.Peer reviewe
Scoping review of evidence-based practice guidelines for the evaluation and care of young children with developmental disabilities in LMIC settings : evidence for action
Get PDFIntroduction: Childhood disability is increasingly prevalent, particularly in low-income and middle-income countries, as more children survive worldwide. Global practice guidelines are essential to address the need for timely identification, evaluation and management of children with developmental disabilities, particularly in resource-limited settings. This scoping review aims to summarise recent evidence-based practice guidelines for the assessment and care of children aged 0–5 years at risk or with developmental disabilities and identify those practice guidelines that are suitable for use across both global and resource-limited settings. Methods: We searched PubMed, Scopus, CINAHL as well as websites for professional associations using Google to identify evidence-based practice guidelines for specific developmental disabilities with established global prevalence estimates. We identified additional literature through snowballing. Practice guidelines were included if they were published between September 2012 and June 2024, were in English, and demonstrated a systematic process of reviewing available evidence, which then provided information on the detection, diagnosis, treatment and management of children under five with developmental disabilities. Three reviewers independently screened results by title, abstract and full text. Study characteristics and outcome data were extracted, and results were narratively synthesised. Results: 43 practice guidelines met the eligibility search criteria. Few evidence-based practice guidelines were generated from resource-limited settings (n=3, 7.0%). Of these, two were published in Malaysia and one from Cameroon. Most of the practice guidelines focused on both assessment and management (n=20, 46.5%), with some addressing only assessment (n=9, 20.9%) or management of the conditions (n=14, 32.6%). Conclusions: Practice guidelines focusing on the identification and support of children with developmental disabilities, chiefly published within high-income settings, are available to be selectively adapted and utilised across similar localities globally. All young children with developmental disabilities worldwide have the right to access equitable, timely and quality health and developmental care services.Peer reviewe
Evolutionary ecophysiology in extreme environments under a global change scenario
Get PDFFunding: This work was supported by the Spanish Ministry of Science and Innovation (Ramón y Cajal Program RyC2023-044964-I to P.B. and Ramón y Cajal Program RYC-2016-20656 to G.O.), the Biotechnology and Biosciences Research Council UK (to L.H.), the Agence Nationale de la Recherche (ANR project VITIBIRD ANR-20-CE34-0008 to F.A.), the Region Nouvelle-Aquitaine (MULTISTRESS project to F.A.), the Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (ANSES project BiodiTox #2019/1/031 to F.A.), the Contrat Plan-État Region (CPER ECONAT to F.A.), the Centre National de la Recherche Scientifique (to F.A.), and the Research Foundation Flanders (FWO, post-doctoral fellow 1222123N to K.I.B.).As wildlife increasingly has to face levels of environmental conditions that go far beyond normal ranges, understanding the ecological and evolutionary dynamics behind such extreme scenarios becomes essential for animal conservation. Here, we discuss the eco-physiological singularities of wildlife coping with extreme conditions. We first discuss the conditions under which scenarios can be considered ‘extreme’. This includes distinguishing the nature of natural and anthropogenic disturbances, considering aspects such as their intensities, as well as the understanding of species biology and evolutionary history. To exemplify the diversity of wildlife responses to extreme conditions, we highlight five different representative study cases (two with natural causes, three of anthropogenic origin): birds at high altitude, fish in geothermal habitats, birds in pesticide-laden farmlands, invertebrates in urban ponds, and amphibians in radioactive zones. These examples illustrate the diverse physiological and ecological responses to extreme factors, emphasizing the complexity of wildlife adaptation under different scenarios. However, they also reveal significant knowledge gaps regarding long-term effects of responses to extreme environments, and the mechanistic basis behind these processes. Future research should ideally include long-term approaches making use of validated physiological markers of individual, population or species health or fitness. This information could be then incorporated into mechanistic models like Species Distribution Models (SDMs) to predict species geographic occurrence and the impact of future extreme scenarios. Such holistic and integrative physiological approaches will enhance our understanding of species and population resilience, and will facilitate the identification of vulnerable populations, ultimately improving management strategies. By prioritizing these research efforts, we will better anticipate the impacts of environmental changes on wildlife health, and thus improve biodiversity conservation strategies.Peer reviewe
Applying a psychological lens to educators’ professional identity : the case of English for Academic Purposes educators
Get PDFThis paper advances the social identity approach as a valuable theoretical lens for interrogating teaching-related professional identities, illustrating its analytical utility through a case study of English for Academic Purposes educators in higher education. Despite their pivotal role in supporting internationalisation agendas and student success, English for Academic Purposes educators often occupy structurally marginal and ambiguously defined positions, situated between academic and professional domains. Drawing on the two core components of the social identity approach—social identity theory and self-categorisation theory—this paper offers a social-psychological framework for examining how status, belonging and legitimacy are negotiated by English for Academic Purposes educators in roles historically undervalued within higher education academic hierarchies. The analysis carried out within this paper foregrounds key social identity processes, such as in-group identification (how individuals locate themselves within communities), perceptions of boundary permeability (the perceived openness of group boundaries and opportunities for movement between communities), and the ideological positioning of teaching (how teaching is framed and valued within institutional hierarchies). In doing so, the paper demonstrates the utility of the social identity approach in theorising the structural and psychological dynamics that influence teaching identities in higher education, offering new insight into the identity struggles and strategies of this group of educators.Peer reviewe
On synthetic interval data with predetermined subject partitioning and partial control of the variables’ marginal correlation structure
Get PDF(Publication fee waved)A standard approach for assessing the performance of partition models is to create synthetic datasets with a prespecified clustering structure and assess how well the model reveals this structure. A common format involves subjects being assigned to different clusters, with observations simulated so that subjects within the same cluster have similar profiles, allowing for some variability. In this manuscript, we consider observations from interval variables. Interval data are commonly observed in cohort and Genome-Wide Association studies, and our focus is on Single-Nucleotide Polymorphisms. Theoretical and empirical results are utilized to explore the dependence structure between the variables in relation to the clustering structure for the subjects. A novel algorithm is proposed that allows control over the marginal stratified correlation structure of the variables, specifying exact correlation values within groups of variables. Practical examples are shown, and a synthetic dataset is compared to a real one, to demonstrate similarities and differences.Peer reviewe
Radial diffusion driven by spatially localized ULF waves in the Earth's magnetosphere
Get PDFFunding: Support for AO was provided by the University of Helsinki and the Research Council of Finland profiling action Matter and Materials (Grant 318913). OA would like to acknowledge financial support from the University of Birmingham, the University of Exeter, and also from the United Kingdom Research and Innovation (UKRI) Natural Environment Research Council (NERC) Independent Research Fellowship NE/V013963/1 and NE/V013963/2. The work of LT is funded by the European Union (ERC grant WAVESTORMS - 101124500). LT also acknowledges support from the Research Council of Finland (Grant 322544).Ultra-Low Frequency (ULF) waves are critical drivers of particle acceleration and loss in the Earth's magnetosphere. While statistical models of ULF-induced radial transport have traditionally assumed that the waves are uniformly distributed across magnetic local time (MLT), decades of observational evidence show significant MLT localization of ULF waves in the Earth's magnetosphere. This study presents, for the first time, a quasi-linear radial diffusion coefficient accounting for localized ULF waves. Our results reveal that when ULF waves cover more than 30% of the MLT, the radial diffusion efficiency is comparable to that of uniform wave distributions. However, when ULF waves are confined within 10% of the drift orbit, the transport coefficient is enhanced by 10%–25%, indicating that narrowly localized ULF waves are efficient drivers of radial diffusion.Peer reviewe
Open-source high-resolution exoplanet atmosphere retrievals with POSEIDON
Get PDFFunding: R.J.M. is supported by NASA through the NASA Hubble Fellowship grant HST-HF2-51513.001, awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS 5-26555.High-resolution spectroscopy (R > 25,000) has opened new opportunities to characterize exoplanet atmospheres from the ground. By resolving individual lines in planetary emission and transmission spectra, one can sensitively probe the chemical inventory and temperature structure of exoplanets. However, a significant challenge to reliable and reproducible atmospheric inferences from high-resolution data sets has been the lack of open-source codes for high-resolution retrievals. Here, we present a unified high-resolution retrieval framework, for both emission and transmission spectroscopy, made publicly available within the open-source POSEIDON retrieval code. Our high-resolution retrieval framework is fast, accessible (no GPUs required), and well documented via Python notebooks. We validate our framework by reproducing previous emission retrievals of the hot Jupiter WASP-77Ab and transmission retrievals of the ultrahot Jupiter WASP-121b. Our results are broadly consistent with those of published works when making the same data detrending assumptions, but we demonstrate that user choices can subtly propagate into retrieved chemical abundances.Peer reviewe
The impact of mild cognitive impairment on healthcare utilization and costs : AUK Biobank study
Get PDFFunding: Novo Nordisk.INTRODUCTION: Mild cognitive impairment (MCI) is common in older adults, but the burden on patients and health systems is not well understood. We aimed to estimate the impact of MCI on healthcare utilization and costs. METHODS: This was a matched cohort study in UK Biobank comparing healthcare costs and Alzheimer's disease (AD) dementia incidence rates in participants with MCI to propensity score-matched participants without MCI. RESULTS: Of 164,508 eligible participants, 6605(4%) had cognitive testing scores consistent with MCI. Ten-year inpatient costs were 7.6% higher in MCI versus matched no-MCI participants, while 6-year primary care costs were 9.1% higher. Among MCI participants, AD dementia incidence rates were substantially higher than in non-MCI participants (7.2 5-year incidence rate ratio 95% CI: 3.3 to 15.7), and eventual AD dementia accrued higher additional inpatient costs (mean £20,199) over 10 years. DISCUSSION: MCI is characterized by modestly higher healthcare utilization and costs. Subsequent AD dementia diagnosis was strongly associated with costs.Peer reviewe
Faster adaptation but slower divergence of X chromosomes under paternal genome elimination
Get PDFFunding: This work was funded by a European Research Council starting grant (PGErepro, to LR), the RIKEN Special Postdoctoral Researchers Program (to TJH), a RIKEN Incentive Grant (to TJH), and a European Research Council Consolidator Grant (no. 771387, to AG).Differences in transmission and ploidy between sex chromosomes and autosomes drive divergent evolutionary trajectories, with sex chromosomes generally evolving faster. Because sex-linked genes are transmitted less frequently, they are under less efficient selection. Conversely, exposure of recessive mutations on haploid sex chromosomes creates more efficient selection. In most systems, these effects occur simultaneously and are confounded. The fly families Sciaridae (fungus gnats) and Cecidomyiidae (gall midges) have X0 sex determination, but males transmit only maternally inherited chromosomes. This phenomenon results in equal transmission of the X and autosomes, allowing the effect of haploid selection to be studied in isolation. We discover that, unlike well-studied systems, X chromosomes diverge more slowly than autosomes in these flies. Using population genomic and expression data, we show that despite the X evolving more adaptively, stronger purifying selection explains slower divergence. Our findings demonstrate the utility of non-Mendelian inheritance systems for understanding fundamental evolutionary processes.Peer reviewe
A dataset for expert reviewer recommendation with large language models as zero-shot rankers
Get PDFFunding: This work was partially supported by the UK EP-SRC via the projects Sodestream (EP/S033564/1, EP/S036075/1), AP4L (EP/W032473/1), ARCIDUCA (EP/W001632/1) and AdSoLve (Responsible AI UK, EP/Y009800/1, project KP0016); and by the Slovenian Research Agency via research core funding for the programme Knowledge Technologies (P2-0103) and the project EMMA (L2-50070).The task of reviewer recommendation is increasingly important, with main techniques utilizing general models of text relevance. However, state of the art (SotA) systems still have relatively high error rates. Two possible reasons for this are: a lack of large datasets and the fact that large language models (LLMs) have not yet been applied. To fill these gaps, we first create a substantial new dataset, in the domain of Internet specification documents; then we introduce the use of LLMs and evaluate their performance. We find that LLMs with prompting can improve on SotA in some cases, but that they are not a cure-all: this task provides a challenging setting for prompt-based methods
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