17 research outputs found

    Microplastic exposure increases predictability of predator avoidance strategies in hermit crabs

    Get PDF
    The contamination of natural systems with plastic debris has become one of the most pressing global environmental issues. Microplastics (MPs) are of particular concern because their ubiquity and small size make them available for ingestion by a range of aquatic biota. MP exposure studies are hence proliferating rapidly but are typically limited to the analyses of population-level responses in toxicity endpoints across treatments. Potential contaminant-induced alterations in behavioural patterns, however, could manifest on numerous levels of variation: at the population-level, between individuals and within individuals. Here, we used repeated measures on startle response durations – a risk-avoidance mechanism – in European hermit crabs, Pagurus bernhardus, to measure behavioural responses to MP exposure across multiple levels of variation. We found that MP exposure led to a significant decrease of startle duration at the population-level as well as a reduction of intra-individual variation. In other words, crabs became less risk averse on average and their behaviour became more predictable with increasing MP concentrations. Collectively, our findings indicate that MP pollution might increase susceptibility to predation in hermit crabs

    Modelling and mapping how common guillemots balance their energy budgets over a full annual cycle

    Get PDF
    The ability of individual animals to balance their energy budgets throughout the annual cycle is important for their survival, reproduction and population dynamics. However, the annual cycles of many wild, mobile animals are difficult to observe and our understanding of how individuals balance their energy budgets throughout the year therefore remains poor. We developed a hierarchical Bayesian state-space model to investigate how key components of animal energy budgets (namely individual energy gain and storage) varied in space and time. Our model used biologger-derived estimates of time-activity budgets, locations and energy expenditure to infer year-round time series of energy income and reserves. The model accounted for seasonality in environmental drivers such as sea surface temperature and daylength, allowing us to identify times and locations of high energy gain. Our study system was a population of common guillemots Uria aalge breeding at a western North Sea colony. These seabirds manage their energy budgets by adjusting their behaviour and accumulating fat reserves. However, typically during severe weather conditions, birds can experience an energy deficit over a sustained period, leading to starvation and large-scale mortality events. We show that guillemot energy gain varied in both time and space. Estimates of guillemot body mass varied throughout the annual cycle and birds periodically experienced losses in mass. Mass losses were likely to have either been adaptive, or due to energetic bottlenecks, the latter leading to increased susceptibility to mortality. Guillemots tended to be lighter towards the edge of their spatial distribution. We describe a framework that combines biologging data, time-activity budget analysis and Bayesian state-space modelling to identify times and locations of high energetic reward or potential energetic bottlenecks in a wild animal population. Our approach can be extended to address ecological and conservation-driven questions that were previously unanswerable due to logistical complexities in collecting data on wild, mobile animals across full annual cycles

    Impaired expression of metallothioneins contributes to allergen-induced inflammation in patients with atopic dermatitis

    Get PDF
    Regulation of cutaneous immunity is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance versus inflammation in atopic dermatitis, we utilise a human in vivo allergen challenge study, exposing atopic dermatitis patients to house dust mite. Here we analyse transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of cutaneous immunocytes revealed a distinct dichotomy in atopic dermatitis patient responsiveness to house dust mite challenge. Our study shows that reactivity to house dust mite was associated with high basal levels of TNF-expressing cutaneous Th17 T cells, and documents the presence of hub structures where Langerhans cells and T cells co-localised. Mechanistically, we identify expression of metallothioneins and transcriptional programmes encoding antioxidant defences across all skin cell types, that appear to protect against allergen-induced inflammation. Furthermore, single nucleotide polymorphisms in the MTIX gene are associated with patients who did not react to house dust mite, opening up possibilities for therapeutic interventions modulating metallothionein expression in atopic dermatitis

    Effect of priming interval on reactogenicity, peak immunological response, and waning after homologous and heterologous COVID-19 vaccine schedules: exploratory analyses of Com-COV, a randomised control trial

    Get PDF
    BackgroundPriming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca).MethodsCom-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020–005085–33).FindingsBetween Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77–89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2–ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second dose, with geometric mean ratios of 1·4 (95% CI 1·1–1·8) for homologous BNT162b2, 1·5 (1·2–1·9) for ChAdOx1 nCoV-19–BNT162b2, 1·6 (1·3–2·1) for BNT162b2–ChAdOx1 nCoV-19, and 2·4 (1·7–3·2) for homologous ChAdOx1 nCoV-19. At 6 months post-second dose, anti-spike IgG geometric mean concentrations fell to 0·17–0·24 of the 28-day post-second dose value across all eight study groups, with only homologous BNT162b2 showing a slightly slower decay for the 12-week versus 4-week interval in the adjusted analysis. The rank order of schedules by humoral response was unaffected by interval, with homologous BNT162b2 remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals compared with their 4-week counterparts. 12-week schedules for homologous BNT162b2 and ChAdOx1 nCoV-19–BNT162b2 were up to 80% less reactogenic than 4-week schedules.InterpretationThese data support flexibility in priming interval in all studied COVID-19 vaccine schedules. Longer priming intervals might result in lower reactogenicity in schedules with BNT162b2 as a second dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines using these novel platforms might benefit from schedules with long intervals

    Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial

    Get PDF
    Background: Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer–BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines. Methods: Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139. Findings: Between Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation. Interpretation: Despite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines. Funding: UK Vaccine Task Force and National Institute for Health Research

    Love thy neighbour or opposites attract? Patterns of spatial segregation and association among crested penguin populations during winter

    Get PDF
    Competition for food among populations of closely related species and conspecifics that occur in both sympatry and parapatry can be reduced by interspecific and intraspecific spatial segregation. According to predictions of niche partitioning, segregation is expected to occur at habitat boundaries among congeners and within habitats among conspecifics, while negative relationships in the density of species or populations will occur in areas of overlap. We tested these predictions by modelling the winter distributions of two crested penguin species from three colonies in the south-western Atlantic. Penguins were tracked from two large colonies on the Falkland Islands and one in South Georgia, from where they dispersed through the South Atlantic, Southern Ocean and south-eastern Pacific. Forty macaroni penguins (Eudyptes chrysolophus) from South Georgia and 82 southern rockhopper penguins (Eudyptes chrysocome chrysocome) from two colonies in the Falkland Islands were equipped with global location sensors which log time and light, allowing positions to be estimated twice-daily, from April to August in 2011. Positions were gridded and converted into maps of penguin density. Metrics of overlap were calculated and density was related to remote-sensed oceanographic variables and competitor density using generalized additive models. Macaroni penguins from western South Georgia and southern rockhopper penguins from Steeple Jason Island, Falkland Islands, were spatially segregated by differences in their habitat preferences thus supporting our first prediction regarding interspecific segregation. However, southern rockhopper penguins from Beauchêne Island showed a marked spatial overlap with macaroni penguins as the two had similar habitat preferences and strong mutual associations when controlling for habitat. Contrary to our predictions relating to intraspecific segregation, southern rockhopper penguins from Beauchêne Island and Steeple Jason Island were segregated by differences in habitat selection. Morphological differentiation probably allows macaroni penguins from South Georgia and southern rockhopper penguins from Beauchêne Island to coexist in areas of spatial overlap, whereas segregation of the two Falkland rockhopper penguin populations may have arisen from two distinct lineages retaining cultural fidelity to ancestral wintering areas

    The Spl Serine Proteases Modulate Staphylococcus aureus Protein Production and Virulence in a Rabbit Model of Pneumonia

    No full text
    ABSTRACT The Spl proteases are a group of six serine proteases that are encoded on the νSaβ pathogenicity island and are unique to Staphylococcus aureus. Despite their interesting biochemistry, their biological substrates and functions in virulence have been difficult to elucidate. We found that an spl operon mutant of the community-associated methicillin-resistant S. aureus USA300 strain LAC induced localized lung damage in a rabbit model of pneumonia, characterized by bronchopneumonia observed histologically. Disease in the mutant-infected rabbits was restricted in distribution compared to that in wild-type USA300-infected rabbits. We also found that SplA is able to cleave the mucin 16 glycoprotein from the surface of the CalU-3 lung cell line, suggesting a possible mechanism for wild-type USA300 spreading pneumonia to both lungs. Investigation of the secreted and surface proteomes of wild-type USA300 and the spl mutant revealed multiple alterations in metabolic proteins and virulence factors. This study demonstrates that the Spls modulate S. aureus physiology and virulence, identifies a human target of SplA, and suggests potential S. aureus targets of the Spl proteases. IMPORTANCE Staphylococcus aureus is a versatile human pathogen that produces an array of virulence factors, including several proteases. Of these, six proteases called the Spls are the least characterized. Previous evidence suggests that the Spls are expressed during human infection; however, their function is unknown. Our study shows that the Spls are required for S. aureus to cause disseminated lung damage during pneumonia. Further, we present the first example of a human protein cut by an Spl protease. Although the Spls were predicted not to cut staphylococcal proteins, we also show that an spl mutant has altered abundance of both secreted and surface-associated proteins. This work provides novel insight into the function of Spls during infection and their potential ability to degrade both staphylococcal and human proteins

    Modelling and mapping how common guillemots balance their energy budgets over a full annual cycle

    Get PDF
    Abstract: The ability of individual animals to balance their energy budgets throughout the annual cycle is important for their survival, reproduction and population dynamics. However, the annual cycles of many wild, mobile animals are difficult to observe and our understanding of how individuals balance their energy budgets throughout the year therefore remains poor. We developed a hierarchical Bayesian state‐space model to investigate how key components of animal energy budgets (namely individual energy gain and storage) varied in space and time. Our model used biologger‐derived estimates of time‐activity budgets, locations and energy expenditure to infer year‐round time series of energy income and reserves. The model accounted for seasonality in environmental drivers such as sea surface temperature and daylength, allowing us to identify times and locations of high energy gain. Our study system was a population of common guillemots Uria aalge breeding at a western North Sea colony. These seabirds manage their energy budgets by adjusting their behaviour and accumulating fat reserves. However, typically during severe weather conditions, birds can experience an energy deficit over a sustained period, leading to starvation and large‐scale mortality events. We show that guillemot energy gain varied in both time and space. Estimates of guillemot body mass varied throughout the annual cycle and birds periodically experienced losses in mass. Mass losses were likely to have either been adaptive, or due to energetic bottlenecks, the latter leading to increased susceptibility to mortality. Guillemots tended to be lighter towards the edge of their spatial distribution. We describe a framework that combines biologging data, time‐activity budget analysis and Bayesian state‐space modelling to identify times and locations of high energetic reward or potential energetic bottlenecks in a wild animal population. Our approach can be extended to address ecological and conservation‐driven questions that were previously unanswerable due to logistical complexities in collecting data on wild, mobile animals across full annual cycles. Read the free Plain Language Summary for this article on the Journal blog

    Cryptic population decrease due to invasive species predation in a long‐lived seabird supports need for eradication

    Get PDF
    SUMMARY 1. Invasive species are one of the greatest drivers of biodiversity loss worldwide, but the eradication of invasive species from islands is a highly efficient management strategy. Because eradication operations require large financial investments, uncertainty over the magnitude of impacts of both invasive species and their removal can impede the willingness of decision makers to invest in eradication. Such uncertainty is prevalent for long-lived species that display an inherent lag between life stages affected by invasive species and those used for population status assessments. 2. Albatrosses are among the longest-living bird species and are threatened on land by invasive species and at sea by industrial fisheries. As in many seabird species, usually only a segment of the population (breeding adults) is used for status assessments, making it difficult to assess their population trends and the potential benefit of conservation action, such as the management of predatory invasive species. 3. We used population monitoring and mark-recapture data to estimate the past population trajectory of the Critically Endangered Tristan Albatross (Diomedea dabbenena) by accounting for unobservable birds at sea in an integrated population model. We then projected the future population trajectory for scenarios with or without predation by invasive house mice (Mus musculus) on their main site, Gough Island. 4. The adult breeding population remained stable between 2004 and 2021, but breeding success was low (31%) and our model indicated that the total population (including unobservable immature birds) decreased from a median estimate of 9795 to 7752 birds. Eradicating invasive mice leading to a two-fold increase in breeding success would result in a 1.8–7.6 times higher albatross population by 2050 (median estimate 10 352 individuals) than without this intervention. 5. Low reproductive output for long-lived species may lead to a cryptic population decrease, which can be obscured from readily available counts of breeding pairs by changes in the breeding population. Mouse eradication is necessary to revert the ongoing population decrease, even if this decrease is not yet apparent in the breeding population size.Copyright: © 2022 The Authors. This document is the author’s submitted version of the journal article. You are advised to consult the published version if you wish to cite from it

    Cryptic population decrease due to invasive species predation in a long‐lived seabird supports need for eradication

    Get PDF
    Invasive species are one of the greatest drivers of biodiversity loss worldwide, and the eradication of invasive species from islands is a highly efficient management strategy. Because eradication operations require large financial investments, uncertainty over the magnitude of impacts of both invasive species and their removal can impede the willingness of decision makers to invest in eradication. Such uncertainty is prevalent for long-lived species that display an inherent lag between life stages affected by invasive species and those used for population status assessments. Albatrosses are amongst the longest-living bird species and are threatened on land by invasive species and at sea by industrial fisheries. As in many seabird species, usually only a segment of the population (breeding adults) is used for status assessments, making it difficult to assess albatross population trends and the potential benefit of conservation action, such as the management of predatory invasive species. We used population monitoring and mark-recapture data to estimate the past population trajectory of the critically endangered Tristan albatross Diomedea dabbenena by accounting for unobservable birds at sea in an integrated population model. We then projected the future population trajectory of Tristan albatrosses for scenarios with or without predation by invasive house mice Mus musculus on their main breeding site, Gough Island. The adult breeding population remained stable between 2004 and 2021, but breeding success was low (31%) and our model indicated that the total population (including unobservable immature birds) decreased from a median estimate of 9,795 to 7,752 birds. Eradicating invasive mice leading to a two-fold increase in breeding success would result in a 1.8–7.6 times higher albatross population by 2050 (median estimate 10,352 individuals) than without this intervention. Low reproductive output for long-lived species may lead to a cryptic population decrease, which can be obscured from readily available counts of breeding pairs by changes in the population structure. Mouse eradication is necessary to halt the ongoing population decrease of the Tristan albatross, even if this decrease is not yet apparent in the breeding population size
    corecore