Participation in the Development of UK Regulatory Policy for Pesticides

This thesis explores possible constraints on effective participation and the scope of alternatives considered by central policy makers, in a debate on the content of regulations to control pesticides. These aspects of the policy process were examined in a case study of the Food and Environment Protection Act (1985) and the Control of Pesticides Regulations (1986). Four issues affecting manufacture, marketing and use were examined in each of three chronological phases: pre-parliamentary, parliamentary and administrative. Interview data, interest group responses to two Government consultative documents and Hansard material were analysed. Key constraining factors framing the current debate were seen to encompass "situational" factors, which were historical (existing structures, past debates and views of long-standing central participants in the control system) or current (present procedures, time available and views of newer central participants), substantive or procedural. The operation and effects of such framing in the contemporary debate on the chosen issues are discussed

Indigenous, Settler, Animal; a Triadic Approach

In his Indigenous critique of the field of animal studies, Billy-Ray Belcourt (Driftpile Cree Nation) describes it as having an analytic blind spot when it comes to settler-colonialism, a blind spot that manifests through universalising claims and clumsy arguments about ‘shared’ oppressions, through assumptions that settler colonial political institutions can be a neutral part of the solution, and through a failure to engage with ‘Indigenous studies of other than human life’ (20). In the same article, he calls on decolonial projects to do more to include animality within their purview, to include critiques of animal agriculture and to incorporate critiques of anthropocentrism as ‘a key logic of white supremacy’. Belcourt’s critique of both Animal studies and decolonial projects on the basis of an unequal but mutual marginalisation is an important starting point for research projects like ours that hope to bring Animal studies and Indigenous studies approaches into dialogue about the cultural impacts of introduced animals. Our approach sets out to be ‘triadic’, always involving at least three sides; Settler- Coloniser, Indigene and Animal

AMP-activated protein kinase can be allosterically activated by ADP but AMP remains the key activating ligand

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. When activated by increases in ADP:ATP and/or AMP:ATP ratios (signalling energy deficit), AMPK acts to restore energy balance. Binding of AMP to one or more of three CBS repeats (CBS1, CBS3, CBS4) on the AMPK-γ subunit activates the kinase complex by three complementary mechanisms: (i) promoting α-subunit Thr172 phosphorylation by the upstream kinase LKB1; (ii) protecting against Thr172 dephosphorylation; (iii) allosteric activation. Surprisingly, binding of ADP has been reported to mimic the first two effects, but not the third. We now show that at physiologically relevant concentrations of Mg.ATP2- (above those used in the standard assay) ADP binding does cause allosteric activation. However, ADP causes only a modest activation because (unlike AMP), at concentrations just above those where activation becomes evident, ADP starts to cause competitive inhibition at the catalytic site. Our results cast doubt on the physiological relevance of the effects of ADP and suggest that AMP is the primary activator in vivo. We have also made mutations to hydrophobic residues involved in binding adenine nucleotides at each of the three γ subunit CBS repeats of the human α2β2γ1 complex and examined their effects on regulation by AMP and ADP. Mutation of the CBS3 site has the largest effects on all three mechanisms of AMP activation, especially at lower ATP concentrations, while mutation of CBS4 reduces the sensitivity to AMP. All three sites appear to be required for allosteric activation by ADP.<br/

AMP-Activated Protein Kinase:Do We Need Activators or Inhibitors to Treat or Prevent Cancer?

AMP-activated protein kinase (AMPK) is a key regulator of cellular energy balance. In response to metabolic stress, it acts to redress energy imbalance through promotion of ATP-generating catabolic processes and inhibition of ATP-consuming processes, including cell growth and proliferation. While findings that AMPK was a downstream effector of the tumour suppressor LKB1 indicated that it might act to repress tumourigenesis, more recent evidence suggests that AMPK can either suppress or promote cancer, depending on the context. Prior to tumourigenesis AMPK may indeed restrain aberrant growth, but once a cancer has arisen, AMPK may instead support survival of the cancer cells by adjusting their rate of growth to match their energy supply, as well as promoting genome stability. The two isoforms of the AMPK catalytic subunit may have distinct functions in human cancers, with the AMPK-&alpha;1 gene often being amplified, while the AMPK-&alpha;2 gene is more often mutated. The prevalence of metabolic disorders, such as obesity and Type 2 diabetes, has led to the development of a wide range of AMPK-activating drugs. While these might be useful as preventative therapeutics in individuals predisposed to cancer, it seems more likely that AMPK inhibitors, whose development has lagged behind that of activators, would be efficacious for the treatment of pre-existing cancers

AMP-activated protein kinase can be allosterically activated by ADP but AMP remains the key activating ligand

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. When activated by increases in ADP:ATP and/or AMP:ATP ratios (signalling energy deficit), AMPK acts to restore energy balance. Binding of AMP to one or more of three CBS repeats (CBS1, CBS3, CBS4) on the AMPK-γ subunit activates the kinase complex by three complementary mechanisms: (i) promoting α-subunit Thr172 phosphorylation by the upstream kinase LKB1; (ii) protecting against Thr172 dephosphorylation; (iii) allosteric activation. Surprisingly, binding of ADP has been reported to mimic the first two effects, but not the third. We now show that at physiologically relevant concentrations of Mg.ATP2- (above those used in the standard assay) ADP binding does cause allosteric activation. However, ADP causes only a modest activation because (unlike AMP), at concentrations just above those where activation becomes evident, ADP starts to cause competitive inhibition at the catalytic site. Our results cast doubt on the physiological relevance of the effects of ADP and suggest that AMP is the primary activator in vivo. We have also made mutations to hydrophobic residues involved in binding adenine nucleotides at each of the three γ subunit CBS repeats of the human α2β2γ1 complex and examined their effects on regulation by AMP and ADP. Mutation of the CBS3 site has the largest effects on all three mechanisms of AMP activation, especially at lower ATP concentrations, while mutation of CBS4 reduces the sensitivity to AMP. All three sites appear to be required for allosteric activation by ADP.<br/

University libraries and digital learning environments

University libraries around the world have embraced the possibilities of the digital learning environment, facilitating its use and proactively seeking to develop the provision of electronic resources and services. The digital environment offers opportunities and challenges for librarians in all aspects of their work – in information literacy, virtual reference, institutional repositories, e-learning, managing digital resources and social media. The authors in this timely book are leading experts in the field of library and information management, and are at the forefront of change in their respective institutions. University Libraries and Digital Learning Environments will be invaluable for all those involved in managing libraries or learning services, whether acquiring electronic resources or developing and delivering services in digital environments