Evaluating the suitability of close-kin mark-recapture as a demographic modelling tool for a critically endangered elasmobranch population

Estimating the demographic parameters of contemporary populations is essential to the success of elasmobranch conservation programmes, and to understanding their recent evolutionary history. For benthic elasmobranchs such as skates, traditional fisheries-independent approaches are often unsuitable as the data may be subject to various sources of bias, whilst low recapture rates can render mark-recapture programmes ineffectual. Close-kin mark-recapture (CKMR), a novel demographic modelling approach based on the genetic identification of close relatives within a sample, represents a promising alternative approach as it does not require physical recaptures. We evaluated the suitability of CKMR as a demographic modelling tool for the critically endangered blue skate (Dipturus batis) in the Celtic Sea using samples collected during fisheries-dependent trammel-net surveys that ran from 2011 to 2017. We identified three full-sibling and 16 half-sibling pairs among 662 skates, which were genotyped across 6291 genome-wide single nucleotide polymorphisms, 15 of which were cross-cohort half-sibling pairs that were included in a CKMR model. Despite limitations owing to a lack of validated life-history trait parameters for the species, we produced the first estimates of adult breeding abundance, population growth rate, and annual adult survival rate for D. batis in the Celtic Sea. The results were compared to estimates of genetic diversity, effective population size (Ne), and to catch per unit effort estimates from the trammel-net survey. Although each method was characterized by wide uncertainty bounds, together they suggested a stable population size across the time-series. Recommendations for the implementation of CKMR as a conservation tool for data-limited elasmobranchs are discussed. In addition, the spatio-temporal distribution of the 19 sibling pairs revealed a pattern of site fidelity in D. batis, and supported field observations suggesting an area of critical habitat that could qualify for protection might occur near the Isles of Scilly

Population and seascape genomics of a critically endangered benthic elasmobranch, the blue skate Dipturus batis

The blue skate (Dipturus batis) has a patchy distribution across the North-East Atlantic Ocean, largely restricted to occidental seas around the British Isles following fisheries-induced population declines and extirpations. The viability of remnant populations remains uncertain, and could be impacted by continued fishing and bycatch pressure and the projected impacts of climate change. We genotyped 503 samples of D. batis, obtained opportunistically from the widest available geographic range, across 6,350 single nucleotide polymorphisms (SNPs) using a reduced-representation sequencing approach. Genotypes were used to assess the species’ contemporary population structure, estimate effective population sizes, and identify putative signals of selection in relation to environmental variables using a seascape genomics approach. We identified genetic discontinuities between inshore (British Isles) and offshore (Rockall and Faroe Island) populations, with differentiation most pronounced across the deep waters of the Rockall Trough. Effective population sizes were largest in the Celtic Sea and Rockall, but low enough to be of potential conservation concern among Scottish and Faroese sites. Among the 21 candidate SNPs under positive selection was one significantly correlated with environmental variables predicted to be affected by climate change, including bottom temperature, salinity, and pH. The paucity of well annotated elasmobranch genomes precluded us from identifying a putative function for this SNP. Nevertheless, our findings suggest that climate change could inflict a strong selective force upon remnant populations of D. batis, further constraining its already restricted habitat. Furthermore, the results provide fundamental insights on the distribution, behaviour, and evolutionary biology of D. batis in the North-East Atlantic that will be useful for the establishment of conservation actions for this and other critically endangered elasmobranchs

Compound-specific stable isotope analysis of amino acids in pelagic shark vertebrae reveals baseline, trophic, and physiological effects on bulk protein isotope records

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Magozzi, S., Thorrold, S. R., Houghton, L., Bendall, V. A., Hetherington, S., Mucientes, G., Natanson, L. J., Queiroz, N., Santos, M. N., & Trueman, C. N. Compound-specific stable isotope analysis of amino acids in pelagic shark vertebrae reveals baseline, trophic, and physiological effects on bulk protein isotope records. Frontiers in Marine Science, 8, (2021): 673016, https://doi.org/10.3389/fmars.2021.673016.Variations in stable carbon and nitrogen isotope compositions in incremental tissues of pelagic sharks can be used to infer aspects of their spatial and trophic ecology across life-histories. Interpretations from bulk tissue isotopic compositions are complicated, however, because multiple processes influence these values, including variations in primary producer isotope ratios and consumer diets and physiological processing of metabolites. Here we challenge inferences about shark tropho-spatial ecology drawn from bulk tissue isotope data using data for amino acids. Stable isotope compositions of individual amino acids can partition the isotopic variance in bulk tissue into components associated with primary production on the one hand, and diet and physiology on the other. The carbon framework of essential amino acids (EAAs) can be synthesised de novo only by plants, fungi and bacteria and must be acquired by consumers through the diet. Consequently, the carbon isotopic composition of EAAs in consumers reflects that of primary producers in the location of feeding, whereas that of non-essential amino acids (non-EAAs) is additionally influenced by trophic fractionation and isotope dynamics of metabolic processing. We determined isotope chronologies from vertebrae of individual blue sharks and porbeagles from the North Atlantic. We measured carbon and nitrogen isotope compositions in bulk collagen and carbon isotope compositions of amino acids. Despite variability among individuals, common ontogenetic patterns in bulk isotope compositions were seen in both species. However, while life-history movement inferences from bulk analyses for blue sharks were supported by carbon isotope data from essential amino acids, inferences for porbeagles were not, implying that the observed trends in bulk protein isotope compositions in porbeagles have a trophic or physiological explanation, or are suprious effects. We explored variations in carbon isotope compositions of non-essential amino acids, searching for systematic variations that might imply ontogenetic changes in physiological processing, but patterns were highly variable and did not explain variance in bulk protein δ13C values. Isotopic effects associated with metabolite processing may overwhelm spatial influences that are weak or inconsistently developed in bulk tissue isotope values, but interpreting mechanisms underpinning isotopic variation in patterns in non-essential amino acids remains challenging.The internship of SM at the Woods Hole Oceanographic Institution was funded by the School of Ocean and Earth Science at University of Southampton. Stable isotope analyses were paid by CT and ST research budgets and SM Ph.D. and placement funding

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

Data Availability Statement: The individual-level data from these studies is not publicly available to main confidentiality. Data generated by the ISARIC4C consortium is available for collaborative analysis projects through an independent data and materials access committee at isaric4c.net/sample_access. Data and samples from the COVID-Clinical Neuroscience Study are available through collaborative research by application through the NIHR bioresource at https://bioresource.nihr.ac.uk/using-our-bioresource/apply-for-bioresource-data-access/. Brain injury marker and immune mediator data are present in the paper and in the source data file. Source data are provided with this paper.To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.National Institute for Health and Care Research (NIHR) (CO-CIN-01) and jointly by NIHR and UK Research and Innovation (CV220-169, MC_PC_19059). B.D.M. is supported by the UKRI/MRC (MR/V03605X/1), the MRC/UKRI (MR/V007181/1), MRC (MR/T028750/1) and Wellcome (ISSF201902/3). C.D. is supported by MRC (MC_PC_19044). We would like to thank the University of Liverpool GCP laboratory facility team for Luminex assistance and the Liverpool University Biobank team for all their help, especially Dr. Victoria Shaw, Lara Lavelle-Langham, and Sue Holden. We would like to acknowledge the Liverpool Experimental Cancer Medicine Centre for providing infrastructure support for this research (Grant Reference: C18616/A25153). We acknowledge the Liverpool Centre for Cell Imaging (CCI) for provision of imaging equipment (Dragonfly confocal microscope) and excellent technical assistance (BBSRC grant number BB/R01390X/1). Tom Solomon is supported by The Pandemic Institute and the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool. D.K.M. and E.N. are supported by the NIHR Cambridge Biomedical Centre and by NIHR funding to the NIHR BioResource (RG94028 and RG85445), and by funding from Brain Research UK 201819-20. We thank NIHR BioResource volunteers for their participation, and gratefully acknowledge NIHR BioResource centres, NHS Trusts and staff for their contribution. We thank the National Institute for Health and Care Research, NHS Blood and Transplant, and Health Data Research UK as part of the Digital Innovation Hub Programme. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute. The authors would like to acknowledge the eDRIS team (Public Health Scotland) for their support in obtaining approvals, the provisioning and linking of data and facilitating access to the National Safe Haven. The views expressed are those of the author(s) and not necessarily those of the UKRI, NHS, the NIHR or the Department of Health and Social Care

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely