Hyperresolution information and hyperresolution ignorance in modelling the hydrology of the land surface

There is a strong drive towards hyperresolution earth system models in order to resolve finer scales of motion in the atmosphere. The problem of obtaining more realistic representation of terrestrial fluxes of heat and water, however, is not just a problem of moving to hyperresolution grid scales. It is much more a question of a lack of knowledge about the parameterisation of processes at whatever grid scale is being used for a wider modelling problem. Hyperresolution grid scales cannot alone solve the problem of this hyperresolution ignorance. This paper discusses these issues in more detail with specific reference to land surface parameterisations and flood inundation models. The importance of making local hyperresolution model predictions available for evaluation by local stakeholders is stressed. It is expected that this will be a major driving force for improving model performance in the future. Keith BEVEN, Hannah CLOKE, Florian PAPPENBERGER, Rob LAMB, Neil HUNTE

MYCN mediates cysteine addiction and sensitizes neuroblastoma to ferroptosis

Aberrant expression of MYC transcription factor family members predicts poor clinical outcome in many human cancers. Oncogenic MYC profoundly alters metabolism and mediates an antioxidant response to maintain redox balance. Here we show that MYCN induces massive lipid peroxidation on depletion of cysteine, the rate-limiting amino acid for glutathione (GSH) biosynthesis, and sensitizes cells to ferroptosis, an oxidative, non-apoptotic and iron-dependent type of cell death. The high cysteine demand of MYCN-amplified childhood neuroblastoma is met by uptake and transsulfuration. When uptake is limited, cysteine usage for protein synthesis is maintained at the expense of GSH triggering ferroptosis and potentially contributing to spontaneous tumor regression in low-risk neuroblastomas. Pharmacological inhibition of both cystine uptake and transsulfuration combined with GPX4 inactivation resulted in tumor remission in an orthotopic MYCN-amplified neuroblastoma model. These findings provide a proof of concept of combining multiple ferroptosis targets as a promising therapeutic strategy for aggressive MYCN-amplified tumors

Sustainable water resources: A framework for assessing adaptation options in the rural sector.

Abstract.  This project developed a framework to assess how the irrigated agriculture and turf grass leisure sectors in England could adapt to climate change impacts on water resources. Two catchments (the Nar and Wensum) in East Anglia provided case studies for hydrological, crop yield and land-use modelling; farmer interviews were held across East Anglia, and the golf sector study covered England and Wales. Future climate scenarios were developed from the UKCIP02 dataset, using the high and low emission scenarios for the 2020s and 2050s. For all these scenarios, hydrological modelling showed, even by the 2020s, groundwater recharge is reduced, ground water levels are lower, and both summer and winter river flows fall despite higher winter rainfall. These changes imply major reductions in water available for abstraction and its reliability. It would be impossible to meet the current environmental river flow objectives even without abstraction. Crop yield and land use modelling suggested that farmers will still grow high value irrigated crops such as potatoes and field- scale vegetables. If water resources are limited, they will reduce irrigation of other crops and invest in farm reservoirs, using winter abstraction. However, the extra costs will reduce farm net margins, and make farm businesses more vulnerable. Farmer interviews confirmed that cropping changes and reservoirs are the preferred adaptations. A prototype knowledge elicitation tool was developed to improve understanding of farmer behaviour. A survey of golf course irrigation in England and Wales revealed courses are about equally split between using mains water and direct abstraction. If water is limited, many could adapt by restricting irrigation to greens and tees; others could use reservoirs, re-use and water harvesting. However, client/member pressure is for fully irrigated surfaces. Overall, the study revealed that adaptations options do exist, albeit with costs. Better information on the climate impacts and careful regulation would reduce the risks of users adopting individual adaptations that are not optimal overall and/or inappropriate