1,298 publications from this institution
Agriculture’s global environmental impacts are widely expected to continue expanding, driven by population and economic growth and dietary changes. This Review highlights climate change as an additional amplifier of agriculture’s environmental impacts, by reducing agricultural productivity, reducing the efficacy of agrochemicals, increasing soil erosion, accelerating the growth and expanding the range of crop diseases and pests, and increasing land clearing. We identify multiple pathways through which climate change intensifies agricultural greenhouse gas emissions, creating a potentially powerful climate change–reinforcing feedback loop. The challenges raised by climate change underscore the urgent need to transition to sustainable, climate-resilient agricultural systems. This requires investments that both accelerate adoption of proven solutions that provide multiple benefits, and that discover and scale new beneficial processes and food products.
Environmental Research 2021 takes place at a critical time as the world tries to find global solutions to issues aligned with the UN’s Sustainable Development Goals. It will be one of the first major international scientific events taking place after COP26, providing the perfect platform to discuss key aspects from the world leaders’ talks. You can join live-streamed presentations from diverse voices, topical panel discussions, poster sessions and interactive networking opportunities. Environmental Research 2021 will unite a broad cross-section of communities – environmental and social scientists, engineers and policy influencers – at all career stages. The scientific programme has been designed around five core themes of: 1. Climate science 2. Energy 3. Infrastructure and sustainability 4. Environmental and global health 5. Ecology and biodiversity
B280 Nedd8-Activating Enzyme (NAE) initiates the conjugation of the ubiquitin-like protein nedd8 to its cellular targets, members of the cullin protein family. Nedd8 conjugation to cullins is known to be essential for the ubiquitination activity of cullin-dependent ubiquitin ligases (CDLs). These CDLs control the timely ubiquitination and subsequent degradation of many proteins with important roles in cell cycle progression and signal transduction. These cellular processes are relevant to tumor growth and survival providing a rationale for inhibiting NAE as an anti-cancer strategy. Targeting NAE for the therapeutic intervention of human cancers is unprecedented. Here we describe MLN4924, the first small molecule inhibitor of NAE. MLN4924 potently inhibits the growth of a variety of human tumor-derived cell lines in vitro and growth inhibition correlates with NAE inhibition. We demonstrate that MLN4924 inhibits the nedd8 conjugation pathway in cells, resulting in stabilization of numerous CDL substrates and disruption of protein homeostasis. In most of the cell lines studied, the mechanism of cell growth inhibition appears to be a consequence of uncontrolled DNA synthesis in the S-phase of the cell cycle followed by induction of a DNA damage response and apoptosis. This phenotype is consistent with DNA re-replication. In vivo administration of a single dose of MLN4924 to mice harboring human subcutaneous HCT-116 and Calu-6 xenografts results in a pharmacodynamic response of nedd8-pathway inhibition in the tumor. MLN4924 results in time and dose-dependent inhibition of the formation of total neddylated cullins and stabilization of CDL substrates as illustrated by the increased levels of the CDL3Keap1 substrate, Nrf-2. Inhibition of the nedd8 pathway in these tumors following repeated daily or intermittent dosing of MLN4924 translates into significant tumor growth inhibition at doses that are well tolerated. MLN4924 is the first small molecule inhibitor of NAE with a demonstrated pharmacodynamic response and anti-tumor activity and is expected to enter Phase I clinical trials in 2008.
Abstract Maximising resource‐use efficiency, productivity and environmental sustainability are all fundamental requirements to raise global food production by ~70 per cent in order to feed a world population of ~9.7 billion people by 2050. Perhaps the most vital resource within our capacity to achieve this goal is our soil. Broadly, the fundamental question concerns whether or not satisfying this production demand will accelerate soil degradation, climate change, and the loss of soil carbon stocks. This paper builds upon the outputs of the UK Charity ‘Food & Farming Futures’ (chaired by Lord Curry of Kirkharle) virtual workshop held on 23 March 2021, entitled ‘Capturing the Potential of Soil’. The event focussed on the link between soil health, primarily soil organic carbon (SOC), and agricultural productivity. Supported with commentaries by Professor Pete Smith (University of Aberdeen and Science Director of the Scottish Climate Change Centre of Expertise) and Professor Steve McGrath (Head of Sustainable Agricultural Sciences at Rothamsted Research), specific focus will be given to the research challenges within the UK’s ability to improve soil health and functionality, the implementation priorities that must be held in order to improve soil management by 2050 and what the potential co‐benefits could be. These co‐benefits were scattered across environmental, economic, social and political issues, yet they may be summarised into six primary co‐benefits: developing natural capital, climate change mitigation, carbon trading, improvements in crop yield, animal performance and human health (nutrition). Additionally, the main barriers to improved soil management practices are centred on knowledge exchange‐regarding agri‐environmental techniques—whilst the most impactful solutions rely on soil monitoring, reporting and verification.