Growth-induced mass flows in fungal networks

Cord-forming fungi form extensive networks that continuously adapt to maintain an efficient transport system. As osmotically driven water uptake is often distal from the tips, and aqueous fluids are incompressible, we propose that growth induces mass flows across the mycelium, whether or not there are intrahyphal concentration gradients. We imaged the temporal evolution of networks formed by Phanerochaete velutina, and at each stage calculated the unique set of currents that account for the observed changes in cord volume, while minimising the work required to overcome viscous drag. Predicted speeds were in reasonable agreement with experimental data, and the pressure gradients needed to produce these flows are small. Furthermore, cords that were predicted to carry fast-moving or large currents were significantly more likely to increase in size than cords with slow-moving or small currents. The incompressibility of the fluids within fungi means there is a rapid global response to local fluid movements. Hence velocity of fluid flow is a local signal that conveys quasi-global information about the role of a cord within the mycelium. We suggest that fluid incompressibility and the coupling of growth and mass flow are critical physical features that enable the development of efficient, adaptive, biological transport networks.Comment: To be published in PRSB. 20 pages, plus 8 pages of supplementary information, and 3 page bibliograph

Automated analysis of Physarum network structure and dynamics

We evaluate different ridge-enhancement and segmentation methods to automatically extract the network architecture from time-series of Physarum plasmodia withdrawing from an arena via a single exit. Whilst all methods gave reasonable results, judged by precision-recall analysis against a ground-truth skeleton, the mean phase angle (Feature Type) from intensity-independent, phase-congruency edge enhancement and watershed segmentation was the most robust to variation in threshold parameters. The resultant single pixel-wide segmented skeleton was converted to a graph representation as a set of weighted adjacency matrices containing the physical dimensions of each vein, and the inter-vein regions. We encapsulate the complete image processing and network analysis pipeline in a downloadable software package, and provide an extensive set of metrics that characterise the network structure, including hierarchical loop decomposition to analyse the nested structure of the developing network. In addition, the change in volume for each vein and intervening plasmodial sheet was used to predict the net flow across the network. The scaling relationships between predicted current, speed and shear force with vein radius were consistent with predictions from Murray's law. This work was presented at PhysNet 2015

Advection, diffusion and delivery over a network

Many biological, geophysical and technological systems involve the transport of resource over a network. In this paper we present an algorithm for calculating the exact concentration of resource at any point in space or time, given that the resource in the network is lost or delivered out of the network at a given rate, while being subject to advection and diffusion. We consider the implications of advection, diffusion and delivery for simple models of glucose delivery through a vascular network, and conclude that in certain circumstances, increasing the volume of blood and the number of glucose transporters can actually decrease the total rate of glucose delivery. We also consider the case of empirically determined fungal networks, and analyze the distribution of resource that emerges as such networks grow over time. Fungal growth involves the expansion of fluid filled vessels, which necessarily involves the movement of fluid. In three empirically determined fungal networks we found that the minimum currents consistent with the observed growth would effectively transport resource throughout the network over the time-scale of growth. This suggests that in foraging fungi, the active transport mechanisms observed in the growing tips may not be required for long range transport.Comment: 54 pages including appendix, 10 figure

First gene-edited calf with reduced susceptibility to a major viral pathogen

Bovine viral diarrhea virus (BVDV) is one of the most important viruses affecting the health and well-being of bovine species throughout the world. Here, we used CRISPR-mediated homology-directed repair and somatic cell nuclear transfer to produce a live calf with a six amino acid substitution in the BVDV binding domain of bovine CD46. The result was a gene-edited calf with dramatically reduced susceptibility to infection as measured by reduced clinical signs and the lack of viral infection in white blood cells. The edited calf has no off-target edits and appears normal and healthy at 20 months of age without obvious adverse effects from the on-target edit. This precision bred, proof-of-concept animal provides the first evidence that intentional genome alterations in the CD46 gene may reduce the burden of BVDV-associated diseases in cattle and is consistent with our stepwise, in vitro and ex vivo experiments with cell lines and matched fetal clones

Patient-derived precision cut tissue slices from primary liver cancer as a potential platform for preclinical drug testing

Background: The exploitation of anti-tumour immunity, harnessed through immunomodulatory therapies, has fundamentally changed the treatment of primary liver cancer (PLC). However, this has posed significant challenges in preclinical research. Novel immunologically relevant models for PLC are urgently required to improve the translation from bench to bedside and back, explore and predict effective combinatorial therapies, aid novel drug discovery and develop personalised treatment modalities. / Methods: We used human precision-cut tissue slices (PCTS) derived from resected tumours to create a patient-specific immunocompetent disease model that captures the multifaceted and intricate heterogeneity of the tumour and the tumour microenvironment. Tissue architecture, tumour viability and treatment response to single agent and combination therapies were assessed longitudinally over 8 days of ex vivo culture by histological analysis, detection of proliferation/cell death markers, ATP content via HPLC. Immune cell infiltrate was assessed using PCR and immunofluorescence. Checkpoint receptor expression was quantified via Quantigene RNA assay. / Findings: After optimising the culture conditions, PCTS maintained the original tissue architecture, including tumour morphology, stroma and tumour-infiltrated leukocytes. Moreover, PCTS retained the tumour-specific immunophenotype over time, suggesting the utility of PCTS to investigate immunotherapeutic drug efficacy and identify non-responsiveness. / Interpretation: Here we have characterised the PCTS model and demonstrated its effectiveness as a robust preclinical tool that will significantly support the development of successful (immuno)therapeutic strategies for PLC. / Funding: Foundation for Liver Research, London

Marine20—the marine radiocarbon age calibration curve (0 – 55,000 cal BP)

T.J. Heaton is supported by a Leverhulme Trust Fellowship RF-2019-140\9, “Improving the Measurement of Time Using Radiocarbon”. M Butzin is supported by the German Federal Ministry of Education and Research (BMBF), as Research for Sustainability initiative (FONA); www.fona.de through the PalMod project (grant numbers: 01LP1505B, 01LP1919A). E. Bard is supported by EQUIPEX ASTER-CEREGE and ANR CARBOTRYDH. Meetings of the IntCal Marine Focus group have been supported by Collège de France.The concentration of radiocarbon (14C) differs between ocean and atmosphere. Radiocarbon determinations from samples which obtained their 14C in the marine environment therefore need a marine-specific calibration curve and cannot be calibrated directly against the atmospheric-based IntCal20 curve. This paper presents Marine20, an update to the internationally agreed marine radiocarbon age calibration curve that provides a non-polar global-average marine record of radiocarbon from 0–55 cal kBP and serves as a baseline for regional oceanic variation. Marine20 is intended for calibration of marine radiocarbon samples from non-polar regions; it is not suitable for calibration in polar regions where variability in sea ice extent, ocean upwelling and air-sea gas exchange may have caused larger changes to concentrations of marine radiocarbon. The Marine20 curve is based upon 500 simulations with an ocean/atmosphere/biosphere box-model of the global carbon cycle that has been forced by posterior realizations of our Northern Hemispheric atmospheric IntCal20 14C curve and reconstructed changes in CO2 obtained from ice core data. These forcings enable us to incorporate carbon cycle dynamics and temporal changes in the atmospheric 14C level. The box-model simulations of the global-average marine radiocarbon reservoir age are similar to those of a more complex three-dimensional ocean general circulation model. However, simplicity and speed of the box model allow us to use a Monte Carlo approach to rigorously propagate the uncertainty in both the historic concentration of atmospheric 14C and other key parameters of the carbon cycle through to our final Marine20 calibration curve. This robust propagation of uncertainty is fundamental to providing reliable precision for the radiocarbon age calibration of marine based samples. We make a first step towards deconvolving the contributions of different processes to the total uncertainty; discuss the main differences of Marine20 from the previous age calibration curve Marine13; and identify the limitations of our approach together with key areas for further work. The updated values for ΔR, the regional marine radiocarbon reservoir age corrections required to calibrate against Marine20, can be found at the data base http://calib.org/marine/.Publisher PDFPeer reviewe

Randomised controlled trial of a web-based programme in sustaining best practice alcohol management practices at community sports clubs: a study protocol

INTRODUCTION: Community-based interventions have been found to effectively increase the implementation of alcohol management practices and reduce excessive alcohol use and alcohol-related harm at sports clubs. However, once implementation support ceases there may be a reduction in such intervention effects. Thus, ongoing contribution to improving the health of the community is diminished; sustaining practice implementation is a key determinant to address this. One possible solution to the strategic and logistical challenges of sustainability involves the use of the web. The primary aim of this study is to assess the effectiveness of a web-based programme in sustaining the implementation of alcohol management practices by community football clubs. The secondary aim is to assess the effectiveness of the programme in preventing excessive alcohol consumption and alcohol-related harm among members of community football clubs. METHODS AND ANALYSIS: The study will employ a repeat randomised controlled trial design and be conducted in regional and metropolitan areas within two states of Australia. Community level football clubs who are currently accredited with an existing alcohol management programme (\u27Good Sports\u27) and implementing at least 10 of the 13 core alcohol management practices (eg, not serving alcohol to <18-year-olds) required by the programme will be recruited and randomised to either a web-based sustainability programme or a \u27minimal contact\u27 programme. The primary outcome measures are the proportion of football clubs implementing ≥10 of the 13 required alcohol management practices and the mean number of those practices being implemented at 3-year follow-up. Secondary outcomes include: the proportion of club members who report risky drinking at their club, the Alcohol Use Disorder Identification Test (AUDIT) score and mean AUDIT score of club members. Outcome data will be collected via observation at the club during a 1-day visit to a home game, conducted by trained research assistants at baseline and follow-up. ETHICS AND DISSEMINATION: The study was approved by The University of Newcastle Human Research Ethics Committee (reference: H-2013-0429). Study findings will be disseminated widely through peer-reviewed publications and conference presentations

Marine20—The Marine Radiocarbon Age Calibration Curve (0–55,000 cal BP)

The concentration of radiocarbon (14C) differs between ocean and atmosphere. Radiocarbon determinations from samples which obtained their 14C in the marine environment therefore need a marine-specific calibration curve and cannot be calibrated directly against the atmospheric-based IntCal20 curve. This paper presents Marine20, an update to the internationally agreed marine radiocarbon age calibration curve that provides a non-polar global-average marine record of radiocarbon from 0–55 cal kBP and serves as a baseline for regional oceanic variation. Marine20 is intended for calibration of marine radiocarbon samples from non-polar regions; it is not suitable for calibration in polar regions where variability in sea ice extent, ocean upwelling and air-sea gas exchange may have caused larger changes to concentrations of marine radiocarbon. The Marine20 curve is based upon 500 simulations with an ocean/atmosphere/biosphere box-model of the global carbon cycle that has been forced by posterior realizations of our Northern Hemispheric atmospheric IntCal20 14C curve and reconstructed changes in CO2 obtained from ice core data. These forcings enable us to incorporate carbon cycle dynamics and temporal changes in the atmospheric 14C level. The box-model simulations of the global-average marine radiocarbon reservoir age are similar to those of a more complex three-dimensional ocean general circulation model. However, simplicity and speed of the box model allow us to use a Monte Carlo approach to rigorously propagate the uncertainty in both the historic concentration of atmospheric 14C and other key parameters of the carbon cycle through to our final Marine20 calibration curve. This robust propagation of uncertainty is fundamental to providing reliable precision for the radiocarbon age calibration of marine based samples. We make a first step towards deconvolving the contributions of different processes to the total uncertainty; discuss the main differences of Marine20 from the previous age calibration curve Marine13; and identify the limitations of our approach together with key areas for further work. The updated values for ΔR, the regional marine radiocarbon reservoir age corrections required to calibrate against Marine20, can be found at the data bas

Deep-water circulation changes lead North Atlantic climate during deglaciation.

Constraining the response time of the climate system to changes in North Atlantic Deep Water (NADW) formation is fundamental to improving climate and Atlantic Meridional Overturning Circulation predictability. Here we report a new synchronization of terrestrial, marine, and ice-core records, which allows the first quantitative determination of the response time of North Atlantic climate to changes in high-latitude NADW formation rate during the last deglaciation. Using a continuous record of deep water ventilation from the Nordic Seas, we identify a ∼400-year lead of changes in high-latitude NADW formation ahead of abrupt climate changes recorded in Greenland ice cores at the onset and end of the Younger Dryas stadial, which likely occurred in response to gradual changes in temperature- and wind-driven freshwater transport. We suggest that variations in Nordic Seas deep-water circulation are precursors to abrupt climate changes and that future model studies should address this phasing

Deep-water circulation changes lead North Atlantic climate during deglaciation

Constraining the response time of the climate system to changes in North Atlantic Deep Water (NADW) formation is fundamental to improving climate and Atlantic Meridional Overturning Circulation predictability. Here we report a new synchronization of terrestrial, marine, and ice-core records, which allows the first quantitative determination of the response time of North Atlantic climate to changes in high-latitude NADW formation rate during the last deglaciation. Using a continuous record of deep water ventilation from the Nordic Seas, we identify a ∼400-year lead of changes in high-latitude NADW formation ahead of abrupt climate changes recorded in Greenland ice cores at the onset and end of the Younger Dryas stadial, which likely occurred in response to gradual changes in temperature- and wind-driven freshwater transport. We suggest that variations in Nordic Seas deep-water circulation are precursors to abrupt climate changes and that future model studies should address this phasing