Publications

Deliverables

Body weight and social dominance in anticoagulant-resistant rats

Bayesian calibration as a tool for initialising the carbon pools of dynamic soil models

Carbon Mitigation Options in Agriculture: Improving our Estimates for Kyoto

Abstract C26: Development of selective MELK kinase inhibitors for breast cancer treatment

Abstract Breast cancer is the second most common cancer in the world and the most frequent cancer among women. Despite the progress in developing breast cancer therapies, approximately, 15% of all breast cancers are diagnosed as triple negative breast cancer (TNBC) and due to the lack of estrogen and progesterone receptors this subgroup of patients remains difficult to treat with hormonal therapies. Additionally, therapies targeting HER2, such as Herceptin, are also inefficient against TNBC. In recent years, maternal embryonic leucine zipper kinase (MELK) has been identified as a novel oncogenic target that is highly expressed in several types of solid cancers: breast (especially triple negative breast cancer), colon, ovary, lung, and brain and present at low levels in normal tissues. MELK overexpression in patient tumors strongly correlates with poor prognosis in glioblastoma and breast cancer. siRNA mediated knockdown of MELK kinase significantly inhibits growth of tumor cell lines both in vitro and in vivo. Therefore, MELK kinase is emerging as a novel and interesting target with significant potential for therapeutic intervention in cancer. MELK is an atypical member of the AMPK family of serine-threonine kinases that been implicated has been implicated in stem cell renewal, cell cycle progression, cytokinesis, mRNA splicing and apoptosis. Its activity is correlated with its phosphorylation level, is cell cycle dependent, and maximal during mitosis although direct upstream regulators of MELK kinase activity are unknown. Despite the fact that the exact function is currently under investigation, selective targeting of MELK may be an effective cancer treatment strategy in a wide range of solid tumors. In this study, we are reporting development of a series of selective MELK kinase inhibitors. Synthesized compounds exert excellent selectivity and potency in MELK inhibition in a low nanomolar range. Therapeutic effect of the compounds was investigated in the panel of breast cancer cell lines with different genetic background as well as with different MELK kinase levels; it was shown that for some cell lines compounds induced cell death with nanomolar ED50 values. The compound's effect on the proliferation and in the colony formation assay was also investigated. Taken altogether, the presented data supports our rationale of using MELK kinase inhibitors as a novel approach for the cancer therapy. Citation Format: Piotr Kowalczyk, Paulina Węgrzyn, Monika Prokopowicz, Martyna Knop, Karolina Mazur, Katarzyna Dziedzic, Karolina Gluza, Martyna Knop, Katarzyna Dziedzic, Karolina Mazur, Adam Radzimierski, Claude Commandeur, Magdalena Zawadzka, Kristjan Bloudoff, Fred Vaillancourt, Nick Larsen, John Wang, Dom Reynolds, Daisuke Ito, Jian Zou, Michelle Aicher, Pete Smith, Ping Zhu, Krzysztof Brzózka. Development of selective MELK kinase inhibitors for breast cancer treatment. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C26.

How can we possibly resolve the planet's nitrogen dilemma?

Abstract Nitrogen is the most crucial element in the production of nutritious feeds and foods. The production of reactive nitrogen by means of fossil fuel has thus far been able to guarantee the protein supply for the world population. Yet, the production and massive use of fertilizer nitrogen constitute a major threat in terms of environmental health and sustainability. It is crucial to promote consumer acceptance and awareness towards proteins produced by highly effective microorganisms, and their potential to replace proteins obtained with poor nitrogen efficiencies from plants and animals. The fact that reactive fertilizer nitrogen, produced by the Haber Bosch process, consumes a significant amount of fossil fuel worldwide is of concern. Moreover, recently, the prices of fossil fuels have increased the cost of reactive nitrogen by a factor of 3 to 5 times, while international policies are fostering the transition towards a more sustainable agro‐ecology by reducing mineral fertilizers inputs and increasing organic farming. The combination of these pressures and challenges opens opportunities to use the reactive nitrogen nutrient more carefully. Time has come to effectively recover used nitrogen from secondary resources and to upgrade it to a legal status of fertilizer. Organic nitrogen is a slow‐release fertilizer, it has a factor of 2.5 or higher economic value per unit nitrogen as fertilizer and thus adequate technologies to produce it, for instance by implementing photobiological processes, are promising. Finally, it appears wise to start the integration in our overall feed and food supply chains of the exceptional potential of biological nitrogen fixation. Nitrogen produced by the nitrogenase enzyme, either in the soil or in novel biotechnology reactor systems, deserves to have a ‘renaissance’ in the context of planetary governance in general and the increasing number of people who desire to be fed in a sustainable way in particular.

Empowerment of Community Members

Soil inorganic carbon sequestration through alkalinity regeneration using biologically induced weathering of rock powder and biochar

Compounded iron supplement used to address hurdles and needs in the field

Climate change and drinking water from Scottish peatlands: Where increasing DOC is an issue?

Advances in biorenewables-resource-waste systems and modelling

The potential for bioenergy crops to contribute to meeting GB heat and electricity demands

Abstract The paper presents a model system, which consists of a partial equilibrium model and process‐based terrestrial biogeochemistry models, to determine the optimal distributions of both Miscanthus ( Miscanthus × giganteus ) and short rotation coppice willow ( SRC ) ( Salix. viminalis L. x S. viminalis var Joruun) in Great Britain ( GB ), as well as their potential contribution to meet heat and electricity demand in GB . Results show that the potential contribution of Miscanthus and SRC to heat and electricity demand is significant. Without considering farm‐scale economic constraints, Miscanthus and SRC could generate, in an economically competitive way compared with other energy generation costs, 224 800 GWh yr −1 heat and 112 500 GWh yr −1 electricity, with 8 Mha of available land under Miscanthus and SRC , accounting for 66% of total heat demand and 62% of total electricity demand respectively. Given the pattern of heat and electricity demand, and the relative yields of Miscanthus and SRC in different parts of GB , Miscanthus is mainly favoured in the Midlands and areas in the South of GB , whereas SRC is favoured in Scotland, the Midlands and areas in the South of GB .

Modelling energy systems: How much bioenergy feedstock can be grown sustainably in the UK?

This report presents the outcome of the wholeSEM UK Land Energy NexuS (LENS) workshop held at the Department of Engineering at the University of Cambridge on the 30th of September and 1st of October, 2014. The workshop brought together 40 stakeholders involved in bioenergy and natural resource management from research, academia, industry, agriculture, civil society groups and government agencies.

Simulation of Soil Organic Carbon Effects on Long-Term Winter Wheat (Triticum aestivum) Production Under Varying Fertilizer Inputs

Soil organic carbon (SOC) has a vital role to enhance agricultural productivity and for mitigation of climate change. To quantify SOC effects on productivity, process models serve as a robust tool to keep track of multiple plant and soil factors and their interactions affecting SOC dynamics. We used soil-plant-atmospheric model viz. DAISY, to assess effects of SOC on nitrogen (N) supply and plant available water (PAW) under varying N fertilizer rates in winter wheat (<i>Triticum aestivum</i>) in Denmark. The study objective was assessment of SOC effects on winter wheat grain and aboveground biomass accumulation at three SOC levels (low: 0.7% SOC; reference: 1.3% SOC; and high: 2% SOC) with five nitrogen rates (0-200 kg N ha^-1) and PAW at low, reference, and high SOC levels. The three SOC levels had significant effects on grain yields and aboveground biomass accumulation at only 0-100 kg N ha^-1 and the SOC effects decreased with increasing N rates until no effects at 150-200 kg N ha^-1. PAW had significant positive correlation with SOC content, with high SOC retaining higher PAW compared to low and reference SOC. The mean PAW and SOC correlation was given by PAW% = 1.0073 × SOC% + 15.641. For the 0.7-2% SOC range, the PAW increase was small with no significant effects on grain yields and aboveground biomass accumulation. The higher winter wheat grain and aboveground biomass was attributed to higher N supply in N deficient wheat production system. Our study suggested that building SOC enhances agronomic productivity at only 0-100 kg N ha^-1. Maintenance of SOC stock will require regular replenishment of SOC, to compensate for the mineralization process degrading SOC over time. Hence, management can maximize realization of SOC benefits by building up SOC and maintaining N rates in the range 0-100 kg N ha^-1, to reduce the off-farm N losses depending on the environmental zones, land use and the production system.

Management effects on net ecosystem carbon and GHG budgets at European crop sites

Weakened growth of cropland‐N₂O emissions in China associated with nationwide policy interventions

Abstract China has experienced rapid agricultural development over recent decades, accompanied by increased fertilizer consumption in croplands; yet, the trend and drivers of the associated nitrous oxide (N 2 O) emissions remain uncertain. The primary sources of this uncertainty are the coarse spatial variation of activity data and the incomplete model representation of N 2 O emissions in response to agricultural management. Here, we provide new data‐driven estimates of cropland‐N 2 O emissions across China in 1990–2014, compiled using a global cropland‐N 2 O flux observation dataset, nationwide survey‐based reconstruction of N‐fertilization and irrigation, and an updated nonlinear model. In addition, we have evaluated the drivers behind changing cropland‐N 2 O patterns using an index decomposition analysis approach. We find that China's annual cropland‐N 2 O emissions increased on average by 11.2 Gg N/year 2 ( p &lt; .001) from 1990 to 2003, after which emissions plateaued until 2014 (2.8 Gg N/year 2 , p = .02), consistent with the output from an ensemble of process‐based terrestrial biosphere models. The slowdown of the increase in cropland‐N 2 O emissions after 2003 was pervasive across two thirds of China's sowing areas. This change was mainly driven by the nationwide reduction in N‐fertilizer applied per area, partially due to the prevalence of nationwide technological adoptions. This reduction has almost offset the N 2 O emissions induced by policy‐driven expansion of sowing areas, particularly in the Northeast Plain and the lower Yangtze River Basin. Our results underline the importance of high‐resolution activity data and adoption of nonlinear model of N 2 O emission for capturing cropland‐N 2 O emission changes. Improving the representation of policy interventions is also recommended for future projections.

The consolidated European synthesis of CH4 and N2O emissions for EU27 and UK: 1990-2019

&lt;p&gt;This repository contains the data files used for figures, and five updated figures&nbsp;from&lt;/p&gt; &lt;p&gt;essd-2022-287&lt;/p&gt; &lt;p&gt;Title: The consolidated European synthesis of CH4 and N2O emissions for EU27 and UK: 1990-2019&lt;/p&gt; &lt;p&gt;Author(s): Ana Maria Roxana Petrescu, Chunjing Qiu, Matthew J. McGrath, Philippe Peylin, Glen P. Peters, Philippe Ciais, Rona L. Thompson, Aki Tsuruta, Dominik Brunner, Matthias Kuhnert, Bradley Matthews, Paul I. Palmer, Oksana Tarasova, Pierre Regnier, Ronny Lauerwald, David Bastviken, Lena H&ouml;glund-Isaksson, Wilfried Winiwarter, Giuseppe Etiope, Tuula Aalto, Gianpaolo Balsamo, Vladislav Bastrikov, Antoine Berchet, Patrick Brockmann, Giancarlo Ciotoli, Giulia Conchedda, Monica Crippa, Frank Dentener, Christine D. Groot Zwaaftink, Diego Guizzardi, Dirk G&uuml;nther, Jean-Matthieu Haussaire, Sander Houweling, Greet Janssens-Maenhout, Massaer Kouyate, Adrian Leip, Antti Lepp&auml;nen, Emanuele Lugato, Manon Maisonnier, Alistair J. Manning, Tiina Markkanen, Joe McNorton, Marilena Muntean, Gabriel D. Oreggioni, Prabir K. Patra, Lucia Perugini, Isabelle Pison, Maarit T. Raivonen, Marielle Saunois, Arjo J. Segers, Pete Smith, Efisio Solazzo, Hanqin Tian, Francesco N. Tubiello, Timo Vesala, Chris W&nbsp; ilson, and S&ouml;nke Zaehle MS type: Review article&lt;/p&gt; &lt;p&gt;The data and the DOI number&nbsp;refers to the updated version which include the two review comments&lt;/p&gt;