Identification of Novel Molecules that Bind and Regulate AMP-activated Protein Kinase (AMPK)

AMPK is a structurally complex energy sensor allosterically regulated by AMP and ADP. In the presence of energetic stress, AMPK up- and down-regulates catabolic and anabolic pathways, respectively, by phosphorylating targets that mediate cytoplasmic signaling and proteins that help regulate gene expression. For years, researchers specializing in cancer and type II diabetes have advocated for the discovery of selective AMPK drugs. To date, however, there are no direct AMPK modulators available for patients. To identify selective AMPK drugs, we first published a high-throughput, fluorescence-based assay biased toward the detection of molecules that bind the regulatory region of AMPK. This assay design was based on the premise that molecules that bind the AMPK regulatory region may be less likely to bind the conserved kinase active site found throughout the kinome. One of the primary hits identified by this assay became the parent molecule for a panel of structural analogs that dose-dependently inhibit binding of a fluorescent probe to the AMPK regulatory region. These analogs have now been characterized in orthogonal protein-based and cell-based assays.Doctor of Philosoph

Global green infrastructure: How is green infrastructure research translated into practice outside the UK?

The Centre for Sustainable Planning and Environments at the University of the West of England, Bristol have been commissioned by the Natural Environment Research Council(NERC) to conduct a review of how the evidence base for Green Infrastructure (GI) is being translated into practice across the international community. This builds on previous work that focussed on the grey literature targeted to a UK audience (Sinnett et al., 2016). This review will inform the future investment in GI from Innovation Programme and Partnershipswithin NERC.We reviewed 26 pieces of grey literature aimed at an international audience. These include those from government departments (e.g. US Department of Agriculture) and globalinstitutions (e.g. World Bank). Differences in the definition of GI internationally meant that some documents focussed almost exclusively on water management. Others included comprehensive reviews of the health and well-being outcomes associated with the use and presence of GI as well as broader evidence summaries.The review examined the extent to which academic evidence is cited in the grey literature and which ecosystem services are prioritised in these documents

National benchmark for green infrastructure: A feasibility study

This research examines whether a market exists for a national benchmark for green infrastructure (GI) in England. It is funded through a Natural Environment Research Council Innovation Fund (Grant Reference: NE/N016971/1). This builds on a Knowledge Transfer Partnership between the University of the West of England (UWE) and Gloucestershire Wildlife Trust, a project which includes the development of a local benchmark for Gloucestershire and the West of England and which focusses, naturally, on local priorities.This project sought to answer three main questions:•What is the demand for a GI benchmark in the built environment sector?•What types of GI and corresponding ecosystem services should the benchmark include?•What is the most appropriate model to ensure the long-term success of the benchmark?First, a desktop review of relevant assessment systems was conducted to examine a) if, and how, GI is incorporated into such systems and b) their overall operation to understand current practice within the built environment sector. The desktop review included 22 assessment systems, including benchmarks for green developments (building and community-scale) and other infrastructure, and audits, awards, guidance and tool kits that related more specifically to GI, green space or biodiversity.Second, five Expert Symposia were held to test the findings of the review as well as the initial work completed in the KTP on experts from the built environment and GI professions. Thus, the five symposia were co-hosted by the Royal Institution of Chartered Surveyors (RICS), Landscape Institute, Royal Town Planning Institute (RTPI), The Royal Society of Wildlife Trusts (RSWT), and Town and Country Planning Association (TCPA). Whilst the first three of these were quite profession specific, the latter two included participants from a broader range of backgrounds. A total of 55 experts participated in the symposia

Raising the standard: Developing a benchmark for green infrastructure

© 2018 WIT Press Green infrastructure (GI) is globally recognised as an essential component of liveable and sustainable places. It is valued for its multifunctionality and the connectedness of the individual features to each other, the surrounding countryside and urban populations. It brings together many land uses (e.g. parks, gardens, cemeteries, allotments, nature reserves, surface water), urban design (e.g. street trees, landscaping) and functional features (e.g. sustainable urban drainage systems, green roofs) operating at differing spatial scales. It is widely acknowledged that GI is the primary mechanism for delivering ecosystem services in towns and cities, and there is a substantial body of research demonstrating the multiple benefits of GI to urban populations. Despite this evidence base, there is still considerable uncertainty about the best way to design, deliver and maintain GI. This paper presents an emerging benchmark that has been developed through a combination of literature review and engagement with key stakeholders. It provides a suite of standards that are flexible enough to be used across different spatial scales depending on the specific needs of the location, covering the form and function of GI including nature conservation, water management, health and well-being, environmental and design quality. It allows an assessment of GI policy, and the planning, design, delivery and long-term management of GI in new and existing places, ensuring that current good practice is adopted at all stages. The development of the benchmark to date is summarised along with the outcome of preliminary testing using the outline planning applications for two contrasting mixed-use developments. This found that the benchmark performed well, with standards set at a level to ensure that high-quality GI is rewarded but without requiring a level of GI provision and quality that would only be expected on truly exemplary developments. Plans for the future development and testing of the benchmark are provided

The translation and use of green infrastructure evidence

The success of green infrastructure (GI) depends on the sharing of good practice and research between disciplines and sectors. This paper presents findings from a study to examine how GI research is shared with non-academic audiences. GI has been an active research area in recent years, with a wealth of evidence coming from the academic community. This has been mirrored by a body of grey literature aimed at different disciplines and sectors. But it is important to understand which evidence is being used in this grey literature and what the gaps are either in research or in its translation. In this study, 25 pieces of grey literature were reviewed to identify what research is represented; presented as the benefits or ecosystem services provided by different types of GI. This review was presented to around 70 academics, policy makers and practitioners working in GI through two workshops. Attendees were asked questions in order to further understanding of how research is translated and used, and the mechanisms by which it can be more effectively shared. The paper provides insights into how those working in GI can work collaboratively to ensure research findings are relevant and usable

A framework for assessing the quality of green infrastructure in the built environment in the UK

The advocacy argument for green infrastructure has largely been won. Policy and statutory guidance for green infrastructure planning and development exists at international, national and regional/local levels and the functions and benefits of green infrastructure interventions are well evidenced in academic literature. To support this, professional bodies and experts from the built and natural environment have produced a multitude of practice guidance on the delivery of individual green infrastructure features. And yet, examples of high quality green infrastructure in new development schemes remain difficult to find, and the success of statutory guidance to accelerate this phenomenon surprisingly ineffective to manage change within the development sector. This paper presents a new framework for the delivery of high quality green infrastructure. Consultation with stakeholders in the UK suggested that a key factor affecting the translation of green infrastructure evidence, and policy and practice guidance, into delivery through planning and development is a lack of confidence amongst practitioners regarding the qualities and characteristics of high quality green infrastructure in the built environment. The key characteristics of high quality green infrastructure, based on a review of both academic and grey literature, and extensive work with stakeholders are grouped into principles that underpin high quality green infrastructure (including the presence of a multifunctional network, and provision for long-term management), and principles related to health and wellbeing, water management and nature conservation. The resulting framework is presented as twenty three principles for delivering green infrastructure. This can be used internationally as a set of standards to assess the quality of green infrastructure to ensure that it contributes to quality of life, health and wellbeing of individuals and communities, flood resilient towns and cities, and places where nature can flourish and be more viable as a result of development

Building with nature - a new benchmark for green infrastructure

This paper outlines the aims, development and proposed operation of Building with Nature, a new benchmark for appraising the quality of green infrastructur

Past strategies and future directions for identifying AMP-activated protein kinase (AMPK) modulators

AMP-activated protein kinase (AMPK) is a promising therapeutic target for cancer, type II diabetes, and other illnesses characterized by abnormal energy utilization. During the last decade, numerous labs have published a range of methods for identifying novel AMPK modulators. The current understanding of AMPK structure and regulation, however, has propelled a paradigm shift in which many researchers now consider ADP to be an additional regulatory nucleotide of AMPK. How can the AMPK community apply this new understanding of AMPK signaling to translational research? Recent insights into AMPK structure, regulation, and holoenzyme-sensitive signaling may provide the hindsight needed to clearly evaluate the strengths and weaknesses of past AMPK drug discovery efforts. Improving future strategies for AMPK drug discovery will require pairing the current understanding of AMPK signaling with improved experimental designs

Setting the Standard for Green Infrastructure: The Need for, and Features of, a Benchmark in England

© 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Green infrastructure is an essential component of health and sustainable places. The quality of green infrastructure often represents a missed opportunity to achieve this. This paper presents a review examining how built environment assessment systems evaluate the quality of green infrastructure. This was used to develop proposals for a new benchmark, which were examined by experts in terms of the demand, scope and operation. The findings suggest that current systems are not providing a robust assessment of green infrastructure and that a benchmark for green infrastructure would overcome some of the challenges associated with its planning, design and delivery

Green infrastructure: Research into practice

The Centre for Sustainable Planning and Environments at the University of the West of England, Bristol have been commissioned by the Natural Environment Research Council (NERC) to conduct a review of how the evidence base for Green Infrastructure (GI) is being translated into practice. This review will inform the future investment in GI from Innovation Programme and Partnerships within NERC.First, a review of grey literature identified the evidence related to the benefits of GI to biodiversity, ecosystem services and where these have been monetised.Second, in order to gain further insight into GI practices and their relationship with academic research there were two events bringing together the GI community of research, policy and practice