Diversity in warning coloration: selective paradox or the norm?

Aposematic theory has historically predicted that predators should select for warning signals to converge on a single form, as a result of frequency-dependent learning. However, widespread variation in warning signals is observed across closely related species, populations and, most problematically for evolutionary biologists, among individuals in the same population. Recent research has yielded an increased awareness of this diversity, challenging the paradigm of signal monomorphy in aposematic animals. Here we provide a comprehensive synthesis of these disparate lines of investigation, identifying within them three broad classes of explanation for variation in aposematic warning signals: genetic mechanisms, differences among predators and predator behaviour, and alternative selection pressures upon the signal. The mechanisms producing warning coloration are also important. Detailed studies of the genetic basis of warning signals in some species, most notably Heliconius butterflies, are beginning to shed light on the genetic architecture facilitating or limiting key processes such as the evolution and maintenance of polymorphisms, hybridisation, and speciation. Work on predator behaviour is changing our perception of the predator community as a single homogenous selective agent, emphasising the dynamic nature of predator-prey interactions. Predator variability in a range of factors (e.g. perceptual abilities, tolerance to chemical defences, and individual motivation), suggests that the role of predators is more complicated than previously appreciated. With complex selection regimes at work, polytypisms and polymorphisms may even occur in Mullerian mimicry systems. Meanwhile, phenotypes are often multifunctional, and thus subject to additional biotic and abiotic selection pressures. Some of these selective pressures, primarily sexual selection and thermoregulation, have received considerable attention, while others, such as disease risk and parental effects, offer promising avenues to explore. As well as reviewing the existing evidence from both empirical studies and theoretical modelling, we highlight hypotheses that could benefit from further investigation in aposematic species. Finally by collating known instances of variation in warning signals, we provide a valuable resource for understanding the taxonomic spread of diversity in aposematic signalling and with which to direct future research. A greater appreciation of the extent of variation in aposematic species, and of the selective pressures and constraints which contribute to this once-paradoxical phenomenon, yields a new perspective for the field of aposematic signalling.Peer reviewe

Current Status of Forecasting Toxic Harmful Algae for the North-East Atlantic Shellfish Aquaculture Industry

Across the European Atlantic Arc (Scotland, Ireland, England, France, Spain, and Portugal) the shellfish aquaculture industry is dominated by the production of mussels, followed by oysters and clams. A range of spatially and temporally variable harmful algal bloom species (HABs) impact the industry through their production of biotoxins that accumulate and concentrate in shellfish flesh, which negatively impact the health of consumers through consumption. Regulatory monitoring of harmful cells in the water column and toxin concentrations within shellfish flesh are currently the main means of warning of elevated toxin events in bivalves, with harvesting being suspended when toxicity is elevated above EU regulatory limits. However, while such an approach is generally successful in safeguarding human health, it does not provide the early warning that is needed to support business planning and harvesting by the aquaculture industry. To address this issue, a proliferation of web portals have been developed to make monitoring data widely accessible. These systems are now transitioning from “nowcasts” to operational Early Warning Systems (EWS) to better mitigate against HAB-generated harmful effects. To achieve this, EWS are incorporating a range of environmental data parameters and developing varied forecasting approaches. For example, EWS are increasingly utilizing satellite data and the results of oceanographic modeling to identify and predict the behavior of HABs. Modeling demonstrates that some HABs can be advected significant distances before impacting aquaculture sites. Traffic light indices are being developed to provide users with an easily interpreted assessment of HAB and biotoxin risk, and expert interpretation of these multiple data streams is being used to assess risk into the future. Proof-of-concept EWS are being developed to combine model information with in situ data, in some cases using machine learning-based approaches. This article: (1) reviews HAB and biotoxin issues relevant to shellfish aquaculture in the European Atlantic Arc (Scotland, Ireland, England, France, Spain, and Portugal; (2) evaluates the current status of HAB events and EWS in the region; and (3) evaluates the potential of further improving these EWS though multi-disciplinary approaches combining heterogeneous sources of information.Versión del edito

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making

Abstract: Background: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. Methods: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. Results: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5–60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0–25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. Discussion: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

The Presence of <i>Pseudo-nitzschia australis</i> in North Atlantic Aquaculture Sites, Implications for Monitoring Amnesic Shellfish Toxins

The farming of shellfish plays an important role in providing sustainable economic growth in coastal, rural communities in Scotland and acts as an anchor industry, supporting a range of ancillary jobs in the processing, distribution and exporting industries. The Scottish Government is encouraging shellfish farmers to double their economic contribution by 2030. These farmers face numerous challenges to reach this goal, among which is the problem caused by toxin-producing microplankton that can contaminate their shellfish, leading to harvesting site closure and the recall of product. Food Standards Scotland, a non-ministerial department of the Scottish Government, carries out a monitoring programme for both the toxin-producing microplankton and the toxins in shellfish flesh, with farms being closed when official thresholds for any toxin are breached. The farm remains closed until testing for the problematic toxin alone, often diarrhetic shellfish toxin (DST), shows the site to have dropped below the regulatory threshold. While this programme has proved to be robust, questions remain regarding the other toxins that may be present at a closed site. In this study, we tested archival material collected during site closures but only tested for DSTs as part of the official control monitoring. We found the presence of amnesic shellfish toxin (AST) in low concentrations in the majority of sites tested. In one case, the level of AST breached the official threshold. This finding has implications for AST monitoring programmes around Europe