Neutrophils in advanced non-small cell lung cancer

Lung cancer is the third most common cancer in the UK; 87% are histologically nonsmall cell lung cancer (NSCLC). At the time of diagnosis, patients frequently have advanced disease, with poor one-year survival due to metastatic burden. The immune system should act as a key line of defence; recognising, killing and clearing malignant cells. However, ineffective immune responses contribute to cancer progression. Neutrophils are active players in the metastatic environment, but there is limited data regarding human neutrophil populations in advanced lung cancer. Greater understanding of the interplay between extrinsic cell signals and intrinsic cell features in determining neutrophil roles, is also needed. In this study, to investigate how the extrinsic metastatic NSCLC pleural environment influences the function of neutrophils, it was modelled in vitro by culturing healthy donor neutrophils in conditions emulating the pleural space. Tumour necrosis factor alpha (TNFa) and hypoxia acted as pro-survival signals leading to neutrophil persistence and NSCLC pleural fluid conditioned neutrophils to suppress CD8+ T cells through mechanisms including programmed death-ligand 1 (PD-L1) expression. To establish the phenotype of neutrophil populations in advanced NSCLC, neutrophils were extracted from the pleural fluid (metastatic site) and blood of patients. Cellular morphology, surface marker expression and functional assays were utilised. There was an expanded population of low-density blood neutrophils in advanced NSCLC, that were not present in health, and a proportion of which were immature with banded nuclei. Similar immature neutrophils were seen in NSCLC pleural fluid. NSCLC pleural fluid neutrophils expressed PD-L1 and were long-lived. To understand how cell-intrinsic features of neutrophil populations in advanced NSCLC may determine their role in cancer, the populations were defined by their transcriptomic and proteomic signatures. This provided evidence that implied NSCLC low-density blood neutrophils represent immature cells that have been recruited from the bone marrow; they may retain proliferative capacity, have reduced neutrophil granules, and are pro-survival. In summary, the data favours a phenotype of sustained neutrophilic inflammation that is immunosuppressive at the NSCLC metastatic site, with a subpopulation of immature cells that may be ineffective/ detrimental. This is likely to permit tumour progression, leading to adverse patient outcomes

Quantifying variation in δ13C and δ15N isotopes within and between feathers and individuals : is one sample enough?

This study represents a contribution to the ecosystems component of the British Antarctic Survey Polar Science for Planet Earth Programme, funded by The Natural Environment Research Council and through a NERC standard grant NE/I02237X/1.Studies of avian migration increasingly use stable isotope analysis to provide vital trophic and spatial markers. However, when interpreting differences in stable isotope values of feathers, many studies are forced to make assumptions about the timing of moult. A fundamental question remains about the consistency of these values within and between feathers from the same individual. In this study, we examine variation in carbon and nitrogen isotopes by sub-sampling feathers collected from the wings of adults of two small congeneric petrel species, the broad-billed Pachyptila vittata and Antarctic prion P. desolata. Broad-billed prion feather vane material was enriched in 15N compared to feather rachis material, but there was no detectable difference in δ13C. Comparison of multiple samples taken from Antarctic prion feathers indicated subtle difference in isotopes; rachis material was enriched in 13C compared to vane material, and there were differences along the length of the feather, with samples from the middle and tip of the feather depleted in 15N compared to those from the base. While the greatest proportion of model variance was explained by differences between feathers and individuals, the magnitude of these within-feather differences was up to 0.5 ‰ in δ15N and 0.8 ‰ in δ13C. We discuss the potential drivers of these differences, linking isotopic variation to individual-level dietary differences, movement patterns and temporal dietary shifts. A novel result is that within-feather differences in δ13C may be attributed to differences in keratin structure within feathers, suggesting further work is required to understand the role of different amino acids. Our results highlight the importance of multiple sampling regimes that consider both within- and between-feather variation in studies using stable isotopes.Publisher PDFPeer reviewe

Hypoxia drives murine neutrophil protein scavenging to maintain central carbon metabolism

Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic machinery to shape neutrophil phenotypes in response to hypoxia. Through the tracing of labeled amino acids into metabolic enzymes, proinflammatory mediators, and granule proteins, we demonstrated that ongoing protein synthesis shapes the neutrophil proteome. To maintain energy supplies in the tissues, neutrophils consumed extracellular proteins to fuel central carbon metabolism. The physiological stresses of hypoxia and hypoglycemia, characteristic of inflamed tissues, promoted this extracellular protein scavenging with activation of the lysosomal compartment, further driving exploitation of the protein-rich inflammatory milieu. This study provides a comprehensive map of neutrophil proteomes, analysis of which has led to the identification of active catabolic and anabolic pathways that enable neutrophils to sustain synthetic and effector functions in the tissues

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world's oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species.B.L.C., C.H., and A.M. were funded by the Cambridge Conservation Initiative’s Collaborative Fund sponsored by the Prince Albert II of Monaco Foundation. E.J.P. was supported by the Natural Environment Research Council C-CLEAR doctoral training programme (Grant no. NE/S007164/1). We are grateful to all those who assisted with the collection and curation of tracking data. Further details are provided in the Supplementary Acknowledgements. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government.Peer reviewe

Global assessment of marine plastic exposure risk for oceanic birds

Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species

Quantifying variation in delta C-13 and delta N-15 isotopes within and between feathers and individuals: Is one sample enough?

Studies of avian migration increasingly use stable isotope analysis to provide vital trophic and spatial markers. However, when interpreting differences in stable isotope values of feathers, many studies are forced to make assumptions about the timing of moult. A fundamental question remains about the consistency of these values within and between feathers from the same individual. In this study, we examine variation in carbon and nitrogen isotopes by sub-sampling feathers collected from the wings of adults of two small congeneric petrel species, the broad-billed Pachyptila vittata and Antarctic prion P. desolata. Broad-billed prion feather vane material was enriched in 15N compared to feather rachis material, but there was no detectable difference in δ 13C. Comparison of multiple samples taken from Antarctic prion feathers indicated subtle difference in isotopes; rachis material was enriched in 13C compared to vane material, and there were differences along the length of the feather, with samples from the middle and tip of the feather depleted in 15N compared to those from the base. While the greatest proportion of model variance was explained by differences between feathers and individuals, the magnitude of these within-feather differences was up to 0.5 ‰ in δ 15N and 0.8 ‰ in δ 13C. We discuss the potential drivers of these differences, linking isotopic variation to individual-level dietary differences, movement patterns and temporal dietary shifts. A novel result is that within-feather differences in δ 13C may be attributed to differences in keratin structure within feathers, suggesting further work is required to understand the role of different amino acids. Our results highlight the importance of multiple sampling regimes that consider both within- and between-feather variation in studies using stable isotopes

aniMotum, an R package for animal movement data: Rapid quality control, behavioural estimation and simulation

Animal tracking data are indispensable for understanding the ecology, behaviour and physiology of mobile or cryptic species. Meaningful signals in these data can be obscured by noise due to imperfect measurement technologies, requiring rigorous quality control as part of any comprehensive analysis. State–space models are powerful tools that separate signal from noise. These tools are ideal for quality control of error-prone location data and for inferring where animals are and what they are doing when they record or transmit other information. However, these statistical models can be challenging and time-consuming to fit to diverse animal tracking data sets. The R package aniMotum eases the tasks of conducting quality control on and inference of changes in movement from animal tracking data. This is achieved via: (1) a simple but extensible workflow that accommodates both novice and experienced users; (2) automated processes that alleviate complexity from data processing and model specification/fitting steps; (3) simple movement models coupled with a powerful numerical optimization approach for rapid and reliable model fitting. We highlight aniMotum's capabilities through three applications to real animal tracking data. Full R code for these and additional applications is included as Supporting Information, so users can gain a deeper understanding of how to use aniMotum for their own analyses