Soil health metrics reflect yields in long-term cropping system experiments

Soil health metrics with strong links to ecological function and agricultural productivity are needed to ensure that future management of agricultural systems meets sustainability goals. While ecological metrics and crop yields are often considered separately from one another, our work sought to assess the links between the two in an agricultural context where productivity is a key consideration. Here, we investigated the value of soil health tests in terms of their relevance to agricultural management practices and crop yields at contrasting long term cropping systems experiments. One site was on a sandy loam Leptic Podzol and the other on a sandy clay loam Endostagnic Luvisol. Furthermore, the experiments had different management systems. One contained legume-supported rotations with different grass-clover ley durations and organic amendment usage, while the other compared a range of nutrient input options through fertiliser and organic amendments on the same rotation without ley periods. Metrics included field tests (earthworm counts and visual evaluation of soil structure scores) with laboratory analysis of soil structure, chemistry and biology. This analysis included bulk density, macroporosity, pH, available phosphorus, exchangeable potassium, soil organic matter and potentially mineralizable nitrogen. Using a novel combination of long-term experiments, management systems and distinctive soil types, we demonstrated that as well as providing nutrients, agricultural management which resulted in better soil organic matter, pH, potassium and bulk density was correlated with higher crop yields. The importance of ley duration and potentially mineralizable nitrogen to yield in legume-supported systems showed the impact of agricultural management on soil biology. In systems with applications of synthetic fertiliser, earthworm counts and visual evaluation of soil structure scores were correlated with higher yields. We concluded that agricultural management altered yields not just through direct supply of nutrients to crops, but also through the changes in soil health measured by simple metrics

New approach combining food value with nutrient budgeting provides insights into the value of alternative farming systems

Sustainable farming systems provide food for humans while balancing nutrient management. Inclusion or exclusion of livestock has nutrient management implications, as livestock produce food from otherwise inedible crops and their manure is a valuable soil conditioner. However, plant-based diets are becoming more widespread due to perceived environmental benefits. We measure both food production in terms of nourishment to humans (in this study measured by protein, fat, starch and sugar production) and nutrient sustainability in terms of fertiliser use of six rotational farming systems with differences in nutrient management approaches. The arable practices included were the application of synthetic fertilisers, a range of organic amendments, incorporation of crop residues and legume cultivation. Livestock and associated products were included in some systems but excluded in others. The production of protein, fat, starch and sugar was combined with the balance of nitrogen (N), phosphorus (P) and potassium (K) into an overall measure of nutrient use efficiency of human macronutrient production. Across all systems considered, N use efficiency (5-13 kg protein/kg applied N) was lower than P (84-772 kg protein/kg applied P) or K (63-2060 kg protein/kg applied K), and combining synthetic fertiliser use with organic amendment applications raised production significantly while balancing P and K management, regardless of which organic amendment was used. Legume-supported rotations without livestock produced more protein, starch and sugar per unit area than those with livestock. Nutrient balances and nutrient use efficiencies were more sensitive to management changes than purely food production. Using this approach allowed us to identify areas for improvement in food production based on the specific nutritional value of offtakes as opposed to yield overall

New approach combining food value with nutrient budgeting provides insights into the value of alternative farming systems

Sustainable farming systems provide food for humans while balancing nutrient management. Inclusion or exclusion of livestock has nutrient management implications, as livestock produce food from otherwise inedible crops and their manure is a valuable soil conditioner. However, plant-based diets are becoming more widespread due to perceived environmental benefits. We measure both food production in terms of nourishment to humans (in this study measured by protein, fat, starch and sugar production) and nutrient sustainability in terms of fertiliser use of six rotational farming systems with differences in nutrient management approaches. The arable practices included were the application of synthetic fertilisers, a range of organic amendments, incorporation of crop residues and legume cultivation. Livestock and associated products were included in some systems but excluded in others. The production of protein, fat, starch and sugar was combined with the balance of nitrogen (N), phosphorus (P) and potassium (K) into an overall measure of nutrient use efficiency of human macronutrient production. Across all systems considered, N use efficiency (5-13 kg protein/kg applied N) was lower than P (84-772 kg protein/kg applied P) or K (63-2060 kg protein/kg applied K), and combining synthetic fertiliser use with organic amendment applications raised production significantly while balancing P and K management, regardless of which organic amendment was used. Legume-supported rotations without livestock produced more protein, starch and sugar per unit area than those with livestock. Nutrient balances and nutrient use efficiencies were more sensitive to management changes than purely food production. Using this approach allowed us to identify areas for improvement in food production based on the specific nutritional value of offtakes as opposed to yield overall.Peer reviewe

Soil health metrics reflect yields in long-term cropping system experiments

Acknowledgements We would like to acknowledge the technical staff and field teams at SRUC and NIAB who have been integral to the maintenance and continued function of the long-term field experiments. Funding Catriona Willoughby was supported by a PhD studentship co-funded by NIAB and SRUC. The long-term experiments at SRUC were financially supported by the Scottish Government RESAS Strategic Research programme (JHI-D3-1 Healthy Soils for a Green Recovery). The long-term experiments at NIAB are supported by a charitable grant from The Morley Agriculture Foundation.Peer reviewedPublisher PD

Pseudoislets as primary islet replacements for research : report on a symposium at King's College London, London UK

Laboratory-based research aimed at understanding processes regulating insulin secretion and mechanisms underlying beta-cell dysfunction and loss in diabetes often makes use of rodents, as these processes are in many respects similar between rats/mice and humans. Indeed, a rough calculation suggests that islets have been isolated from as many as 150,000 rodents to generate the data contained within papers published in 2009 and the first four months of 2010. Rodent use for islet isolation has been mitigated, to a certain extent, by the availability of a variety of insulin-secreting cell lines that are used by researchers world-wide. However, when maintained as monolayers the cell lines do not replicate the robust, sustained secretory responses of primary islets which limits their usefulness as islet surrogates. On the other hand, there have been several reports that configuration of MIN6 beta-cells, derived from a mouse insulinoma, as three-dimensional cell clusters termed 'pseudoislets' largely recapitulates the function of primary islet beta-cells. The Diabetes Research Group at King's College London has been using the MIN6 pseudoislet model for over a decade and they hosted a symposium on "Pseudoislets as primary islet replacements for research", which was funded by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), in London on 15(th) and 16(th) April 2010. This small, focused meeting was conceived as an opportunity to consolidate information on experiences of working with pseudoislets between different UK labs, and to introduce the theory and practice of pseudoislet culture to laboratories working with islets and/or beta-cell lines but who do not currently use pseudoislets. This short review summarizes the background to the development of the cell line-derived pseudoislet model, the key messages arising from the symposium and emerging themes for future pseudoislet research

Oxidized LDL activates blood platelets through CD36/NOX2–mediated inhibition of the cGMP/protein kinase G signaling cascade

Oxidized low-density lipoprotein (oxLDL) promotes unregulated platelet activation in dyslipidemic disorders. Although oxLDL stimulates activatory signaling, it is unclear how these events drive accelerated thrombosis. Here, we describe a mechanism for oxLDL- mediated platelet hyperactivity that requires generation of reactive oxygen species (ROS). Under arterial flow, oxLDL triggered sustained generation of platelet intracellular ROS, which was blocked by CD36 inhibitors, mimicked by CD36-specific oxidized phospholipids, and ablated in CD362/2 murine platelets. oxLDL-induced ROS generation was blocked by the reduced NAD phosphate oxidase 2 (NOX2) inhibitor, gp91ds-tat, and absent in NOX22/2 mice. The synthesis of ROS by oxLDL/CD36 required Src-family kinases and protein kinase C (PKC)-dependent phosphorylation and activation of NOX2. In functional assays, oxLDL abolished guanosine 39,59-cyclic monophosphate (cGMP)- mediated signaling and inhibited platelet aggregation and arrest under flow. This was prevented by either pharmacologic inhibition of NOX2 in human platelets or genetic ablation of NOX2 in murine platelets. Platelets from hyperlipidemic mice were also found to have a diminished sensitivity to cGMP when tested ex vivo, a phenotype that was corrected by infusion of gp91ds-tat into the mice. This study demonstrates that oxLDL and hyperlipidemia stimulate the generation of NOX2-derived ROS through a CD36-PKC pathway and may promote platelet hyperactivity through modulation of cGMP signaling

CXCR2 inhibition enables NASH-HCC immunotherapy

Objective: Hepatocellular carcinoma (HCC) is increasingly associated with non-alcoholic steatohepatitis (NASH). HCC immunotherapy offers great promise; however, recent data suggests NASH-HCC may be less sensitive to conventional immune checkpoint inhibition (ICI). We hypothesised that targeting neutrophils using a CXCR2 small molecule inhibitor may sensitise NASH-HCC to ICI therapy. Design: Neutrophil infiltration was characterised in human HCC and mouse models of HCC. Late-stage intervention with anti-PD1 and/or a CXCR2 inhibitor was performed in murine models of NASH-HCC. The tumour immune microenvironment was characterised by imaging mass cytometry, RNA-seq and flow cytometry. Results: Neutrophils expressing CXCR2, a receptor crucial to neutrophil recruitment in acute-injury, are highly represented in human NASH-HCC. In models of NASH-HCC lacking response to ICI, the combination of a CXCR2 antagonist with anti-PD1 suppressed tumour burden and extended survival. Combination therapy increased intratumoural XCR1+ dendritic cell activation and CD8+ T cell numbers which are associated with anti-tumoural immunity, this was confirmed by loss of therapeutic effect on genetic impairment of myeloid cell recruitment, neutralisation of the XCR1-ligand XCL1 or depletion of CD8+ T cells. Therapeutic benefit was accompanied by an unexpected increase in tumour-associated neutrophils (TANs) which switched from a protumour to anti-tumour progenitor-like neutrophil phenotype. Reprogrammed TANs were found in direct contact with CD8+ T cells in clusters that were enriched for the cytotoxic anti-tumoural protease granzyme B. Neutrophil reprogramming was not observed in the circulation indicative of the combination therapy selectively influencing TANs. Conclusion: CXCR2-inhibition induces reprogramming of the tumour immune microenvironment that promotes ICI in NASH-HCC