Winter distribution and size structure of Antarctic krill \u3cem\u3eEuphausia superba\u3c/em\u3e populations in-shore along the West Antarctic Peninsula

Antarctic krill Euphausia superba are a key component of food webs in the maritime West Antarctic Peninsula, and their life history is tied to the seasonal cycles of sea ice and primary production in the region. Previous work has shown a general in-shore migration of krill in winter in this region; however, the very near-shore has not often been sampled as part of these surveys. We investigated distribution, abundance, and size structure of krill in 3 fjordic bays along the peninsula, and in the adjacent Gerlache Strait area using vertically stratified MOCNESS net tows and ADCP acoustic biomass estimates. Krill abundance was high within bays, with net estimated densities exceeding 60 krill m-3, while acoustic estimates were an order of magnitude higher. Krill within bays were larger than krill in the Gerlache Strait. Within bays, krill aggregations were observed near the seafloor during the day with aggregations extending to the sediment interface, and exhibited diel vertical migration higher into the water column at night. We suggest these high winter krill abundances within fjords are indicative of an active seasonal migration by krill in the peninsula region. Potential drivers for such a migration include reduced advective losses and costs, and availability of sediment food resources within fjords. Seasonally near-shore krill may also affect stock and recruitment assessments and may have implications for managing the krill fishery in this area

Image-based monitoring for early detection of fouling in crystallisation processes

Fouling or encrustation is a significant problem in continuous crystallisation processes where crystal deposits at surfaces impede heat transfer, increase flow resistance and reduce product quality. This paper proposes an automatic algorithm to detect early stages of fouling using images of vessel surfaces from commodity cameras. Statistical analysis of the pixel intensity variation offers the ability to distinguish appearance of crystals in the bulk solution and on the crystalliser walls. This information is used to develop a fouling metric indicator and determine separately induction times for appearance of first crystals at the surfaces and in the bulk. A method to detect process state changes using Bayesian online change point detection is also proposed, where the first change point is used to determine induction time either at the surface or in the bulk, based on real-time online measurements without using any predetermined threshold which usually varies between experiments and depends on data acquisition equipment. This approach can be used for in situ monitoring of early signs of encrustation to allow early warning for corrective actions to be taken when operating continuous crystallisation processes

Exome-wide association study of pancreatic cancer risk

We conducted a case-control exome-wide association study to discover germline variants in coding regions that affect risk for pancreatic cancer, combining data from 5 studies. We analyzed exome and genome sequencing data from 437 patients with pancreatic cancer (cases) and 1922 individuals not known to have cancer (controls). In the primary analysis, BRCA2 had the strongest enrichment for rare inactivating variants (17/437 cases vs 3/1922 controls) (P=3.27x10(-6); exome-wide statistical significance threshold P<2.5x10(-6)). Cases had more rare inactivating variants in DNA repair genes than controls, even after excluding 13 genes known to predispose to pancreatic cancer (adjusted odds ratio, 1.35, P=.045). At the suggestive threshold (P<.001), 6 genes were enriched for rare damaging variants (UHMK1, AP1G2, DNTA, CHST6, FGFR3, and EPHA1) and 7 genes had associations with pancreatic cancer risk, based on the sequence-kernel association test. We confirmed variants in BRCA2 as the most common high-penetrant genetic factor associated with pancreatic cancer and we also identified candidate pancreatic cancer genes. Large collaborations and novel approaches are needed to overcome the genetic heterogeneity of pancreatic cancer predisposition

Prey differences drive local genetic adaptation in Antarctic fur seals

Antarctic fur seal Arctocephalus gazella colonies are found on sub-Antarctic islands around the continent. These islands experience a range of conditions in terms of physical and biological habitat, creating a natural laboratory to investigate local genetic adaptation. One striking habitat difference is in the availability of Euphausia superba krill as prey, which has led to A. gazella exhibiting a range of diets. A. gazella in some colonies consume exclusively krill, while their conspecifics in other colonies feed mainly on fish and consume few to no krill. To investigate potential adaptations to these different prey fields, reduced representation genome sequencing was conducted on A. gazella from all 8 of the major colonies. Twenty-seven genomic regions exhibiting signatures of natural selection were identified. Two of these genomic regions were clearly associated with seals living in krill-dominated areas or those in fish-dominated areas. Twenty-two additional genomic regions under selection showed a pattern consistent with prey differences as the driver of selection, after historical migrations from krill-dominated habitats where lineages evolved to present krill-poor habitat areas were taken into account. Only 1 of the genomic regions identified appeared to be explained by any other environmental variable analysed (depth). Genomic regions under prey-driven selection included genes associated with regulation of gene expression, skeletal development, and lipid metabolism. Adaptation to local prey has implications for spatial management of this species and for the potential impacts of climate- or harvest-driven reductions in krill abundance on these seals.The Norwegian Antarctic Research Expeditions (NARE) programmehttp://www.int-res.com/journals/meps/meps-homehj2020Mammal Research Institut

Lung Megakaryocytes are Immune Modulatory Cells that Present Antigen to CD4+ T cells.

Although platelets are the cellular mediators of thrombosis, they are also immune cells. Platelets interact both directly and indirectly with immune cells, impacting their activation and differentiation, as well as all phases of the immune response. Megakaryocytes (Mks) are the cell source of circulating platelets, and until recently Mks were typically only considered bone marrow–resident (BM-resident) cells. However, platelet-producing Mks also reside in the lung, and lung Mks express greater levels of immune molecules compared with BM Mks. We therefore sought to define the immune functions of lung Mks. Using single-cell RNA sequencing of BM and lung myeloid-enriched cells, we found that lung Mks, which we term MkL, had gene expression patterns that are similar to antigen-presenting cells. This was confirmed using imaging and conventional flow cytometry. The immune phenotype of Mks was plastic and driven by the tissue immune environment, as evidenced by BM Mks having an MkL-like phenotype under the influence of pathogen receptor challenge and lung-associated immune molecules, such as IL-33. Our in vitro and in vivo assays demonstrated that MkL internalized and processed both antigenic proteins and bacterial pathogens. Furthermore, MkL induced CD4+ T cell activation in an MHC II–dependent manner both in vitro and in vivo. These data indicated that MkL had key immune regulatory roles dictated in part by the tissue environment.pre-print236 K

The hospital microbiome project: meeting report for the UK science and innovation network UK-USA workshop ‘beating the superbugs: hospital microbiome studies for tackling antimicrobial resistance’, October 14th 2013

The UK Science and Innovation Network UK-USA workshop ‘Beating the Superbugs: Hospital Microbiome Studies for tackling Antimicrobial Resistance’ was held on October 14th 2013 at the UK Department of Health, London. The workshop was designed to promote US-UK collaboration on hospital microbiome studies to add a new facet to our collective understanding of antimicrobial resistance. The assembled researchers debated the importance of the hospital microbial community in transmission of disease and as a reservoir for antimicrobial resistance genes, and discussed methodologies, hypotheses, and priorities. A number of complementary approaches were explored, although the importance of the built environment microbiome in disease transmission was not universally accepted. Current whole genome epidemiological methods are being pioneered in the UK and the benefits of moving to community analysis are not necessarily obvious to the pioneers; however, rapid progress in other areas of microbiology suggest to some researchers that hospital microbiome studies will be exceptionally fruitful even in the short term. Collaborative studies will recombine different strengths to tackle the international problems of antimicrobial resistance and hospital and healthcare associated infections

Observing change in pelagic animals as sampling methods shift: the case of Antarctic krill

Understanding and managing the response of marine ecosystems to human pressures including climate change requires reliable large-scale and multi-decadal information on the state of key populations. These populations include the pelagic animals that support ecosystem services including carbon export and fisheries. The use of research vessels to collect information using scientific nets and acoustics is being replaced with technologies such as autonomous moorings, gliders, and meta-genetics. Paradoxically, these newer methods sample pelagic populations at ever-smaller spatial scales, and ecological change might go undetected in the time needed to build up large-scale, long time series. These global-scale issues are epitomised by Antarctic krill (Euphausia superba), which is concentrated in rapidly warming areas, exports substantial quantities of carbon and supports an expanding fishery, but opinion is divided on how resilient their stocks are to climatic change. Based on a workshop of 137 krill experts we identify the challenges of observing climate change impacts with shifting sampling methods and suggest three tractable solutions. These are to: improve overlap and calibration of new with traditional methods; improve communication to harmonise, link and scale up the capacity of new but localised sampling programs; and expand opportunities from other research platforms and data sources, including the fishing industry. Contrasting evidence for both change and stability in krill stocks illustrates how the risks of false negative and false positive diagnoses of change are related to the temporal and spatial scale of sampling. Given the uncertainty about how krill are responding to rapid warming we recommend a shift towards a fishery management approach that prioritises monitoring of stock status and can adapt to variability and change

Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer

Background Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. Results We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P Conclusion Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.Peer reviewe

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene

Observing change in pelagic animals as sampling methods shift: the case of Antarctic krill

Understanding and managing the response of marine ecosystems to human pressures including climate change requires reliable large-scale and multi-decadal information on the state of key populations. These populations include the pelagic animals that support ecosystem services including carbon export and fisheries. The use of research vessels to collect information using scientific nets and acoustics is being replaced with technologies such as autonomous moorings, gliders, and meta-genetics. Paradoxically, these newer methods sample pelagic populations at ever-smaller spatial scales, and ecological change might go undetected in the time needed to build up large-scale, long time series. These global-scale issues are epitomised by Antarctic krill (Euphausia superba), which is concentrated in rapidly warming areas, exports substantial quantities of carbon and supports an expanding fishery, but opinion is divided on how resilient their stocks are to climatic change. Based on a workshop of 137 krill experts we identify the challenges of observing climate change impacts with shifting sampling methods and suggest three tractable solutions. These are to: improve overlap and calibration of new with traditional methods; improve communication to harmonise, link and scale up the capacity of new but localised sampling programs; and expand opportunities from other research platforms and data sources, including the fishing industry. Contrasting evidence for both change and stability in krill stocks illustrates how the risks of false negative and false positive diagnoses of change are related to the temporal and spatial scale of sampling. Given the uncertainty about how krill are responding to rapid warming we recommend a shift towards a fishery management approach that prioritises monitoring of stock status and can adapt to variability and change