Fatty acids in veterinary medicine and research

Fatty acid regulation is an essential process for all animals. A number of studies have shown that diet affects the levels/availability of fatty acids in the body but increasingly evidence shows that disease states can alter the amounts within the body too. Fatty acid levels and availability have been altered by a number of diseases, disorders and reactions including inflammatory responses, heart disease and heart failure and wound repair. They are also essential during the growth and development stages of animals. The amount of research into the consequences of different fatty acid intake and levels in various disease states and during development has increased in both humans and animals. This review presents an overview of the research undertaken to date and highlights the importance, uses and benefits of understanding the roles of fatty acids in both the healthy animal and under differing disorders and diseases

Seeing the big PICTURE: A framework for improving the communication of requirements within the Business-IT relationship

The relationship between the business and IT departments in the context of the organisation has been characterised as highly divisive. Contributing problems appear to revolve around the failure to adequately communicate and understand the required information for the alignment of business and IT strategies and infrastructures. This study takes a communication-based view on the concept of alignment, in terms of the relationship between the retail business and IT within a major high street UK bank. A research framework (PICTURE) is used to provide insight into this relationship and guide the analysis of interviews with 29 individuals on mid-high management level for their thematic content. The paper highlights the lessons that can be derived from the study of the BIT relationship and how possible improvements could be made

Communication issues in requirements elicitation: A content analysis of stakeholder experiences

The gathering of stakeholder requirements comprises an early, but continuous and highly critical stage in system development. This phase in development is subject to a large degree of error, influenced by key factors rooted in communication problems. This pilot study builds upon an existing theory-based categorisation of these problems through presentation of a four-dimensional framework on communication. Its structure is validated through a content analysis of interview data, from which themes emerge, that can be assigned to the dimensional categories, highlighting any problematic areas. The paper concludes with a discussion on the utilisation of the framework for requirements elicitation exercises

HEADS OR TAILS: LIPID INHIBITORS OF THE GLYCINE TRANSPORTER, GLYT2

Membrane proteins are influenced by the dynamic lipid membrane environment, which can impart stability, mediate protein interactions, and provide highly selective contacts essential for function. Membrane proteins can also bind endogenous lipid ligands or are able to be allosterically modulated by lipids, many of which are thought to access their specific binding sites via the cell membrane. N-arachidonyl glycine (NAGly) is a bioactive lipid that is found in its highest concentrations within the spinal cord and may play an important role in endogenous regulation of glycinergic neurotransmission and pain perception through inhibition of the glycine transporter, GlyT2. In addition to NAGly, a number of lipid inhibitors of GlyT2 have been identified. These compounds are comprised of a long flexible unsaturated acyl tail conjugated to an amino acid or amino acid derivative head group. The aims of my study were two-fold; first to identify new, more potent, lipid inhibitors and develop a structure activity relationship for these compounds; and second, to elucidate the molecular mechanisms of inhibition. Wild type and mutant GlyT2 transporters were expressed in Xenopus laevis oocytes with glycine transport and the subsequent inhibition of transport measured using two-electrode voltage clamp electrophysiology, and radiolabelled uptake of glycine. A library of 55 N-acyl amino acids with varying head and tail groups were synthesised and tested at both GlyT2 and the closely related glycine transporter, GlyT1. Two distinct groups of compounds were tested: the first group maintaining a glycine head group and altering the lipid tail; and the second conjugating the [C18 ω9] oleoyl tail to amino acids with varying properties. I found the lipid constituent of the acyl-glycine analogues is essential for specific interactions and the mechanism of inhibition and is not merely a non-selective, sticky adjunct. There was an ideal chain length, with an order of potency C18 > C16 > C14, and stringently defined double bond conformation and position. Conservative differences between compounds are sufficient to impart or remove inhibitory activity which validates highly specific binding to a subtype specific, allosteric pocket. While changing the tail did not greatly alter potency, analogues where the head group was altered significantly influenced apparent affinity. Acyl amino acids containing an aromatic or positively charged side chain conferred the highest apparent affinity, with C16 ω3 L-Lys possessing the highest potency (10.7 nM). 12 compounds inhibited GlyT2 < 100nM, and one of these inhibitors, oleoyl D-Lys, is also metabolically stable and produces analgesia in a rat model of neuropathic pain. Mutagenesis of extracellular loop 4 (EL4), and transmembrane helices TM5 and TM8 suggest that the allosteric binding site is comprised of a cluster of aromatic residues which may strongly coordinate aromatic or positively charged head groups of the most potent analogues. Additionally, changing the properties of a membrane facing residue alters the otherwise slow washout of lipids. From these results, in addition to dynamic docking studies, it is proposed that acyl amino acids may first diffuse into the lipid bilayer and interact with regions of GlyT2 at the protein-membrane interface. Acyl amino acids then access their final binding site formed by aliphatic and aromatic residues from TM5, TM8, and EL4. It has previously been shown that EL4 undergoes important conformational changes in this family of transporters, where EL4 shifts into the outward facing vestibule to occlude the extracellular side and continue the transport cycle. Acyl amino acids may therefore inhibit GlyT2 by stabilising EL4 in a conformation that does not favour transport. The combination of structure-activity studies with molecular insights provides key information on the mechanism of inhibition which will drive further generation of GlyT2 inhibitors for the treatment of neuropathic pain

MAGNA CARTA AND ACCESS TO JUSTICE IN FAMILY PROCEEDINGS

We had a surprise in January 2012 when a practising QC was parachuted straight into the Supreme Court (as the Judicial Committee of the House of Lords became in 2009). But if there were expressions of discontent they were definitely sub rosa since the man in question, Jonathan Sumption QC, was then, and has since proved himself to be, pre-eminently qualified for the position. He is one of our foremost medieval historians, a Fellow of Magdalen College who taught History, before leaving to pursue a career at the Bar, where he rose to dizzy heights. His as yet uncompleted history of the Hundred Years’ War has received the highest praise. So it perhaps was not surprising that in this octocentenial year he should have been asked by the Friends of the British Library (an audience I warrant as challenging as this) to speak to them about Magna Carta on 9 March 2015. If I may say so, his address ‘Magna Carta then and now’ is a masterpiece. It completes the destruction of the hermeneutical myth originated by Sir Edward Coke which had been commenced by William McKechnie in his landmark essay published in 1905.

Ligand isotope vibrational studies of metal(II) complexes with particular reference to heterocyclic N-oxides

Includes bibliographical references.A critical examination of the characteristic N-O vibrational frequencies of aromatic N-oxides questions the widely held assignment of αN-O (840cm⁻¹) and YN-O (47oon- 1). The present investigation supports the assignments of αN-O (470cm⁻¹) and γN-O (280cm⁻¹), with the assignment of the band at 840cm⁻¹ as being vring coupled with νN-O

Taxonomy and pathogenicity of rusts from Allium species in the U.K

Comparison of seven isolates of rust from leek (Allium porrum), three from chives (Allium schoenoprasum), one from A. scorodoprasum and one from A. babingtonii on the basis of telial and uredinial morphology showed there to be three morphologically distinct species. Application of these criteria to herbarium material confirmed these findings and showed the rust on leeks in the U.K. to be the same species found on European leeks, garlic and certain wild Allium spp. from the Mediterranean. It is suggested that the following names be adopted, viz. Puccinia allii (DC.) Rud. for the rust on leeks, Puccinia mixta Fuck. for the rust on chives and Uromyces ambiguus (DC) Lev. for the rust on A. babingtonii. Infection studies on isolates of each rust supported the morphological evidence, and showed the three species to have different, extensive but overlapping host ranges within the genus Allium. In the ampeloprasum complex, A. kurrat accessions were highly susceptible to leek rust whereas some accessions of A. ampeloprasum and A. babingtonii had high levels of quantitative resistance. There was no evidence of 'hypersensitive-type' resistance in the complex. Tests within one leek cultivar (Musselburgh) showed older plants to be more resistant than seedlings in at least two quantitative components. However leaf tissue appeared to become more susceptible to infection with age, except in the leaf tips, which did not change in susceptibility over time. Inoculation of 16 leek cultivars with leek rust isolates from different geographical areas, and subsequent analysis during the disease cycle of several components of resistance (viz; latent period, pustule density and pustule length) showed that some cultivars performed consistently better against all isolates. However, in most cases there was a considerable and complex cultivar-isolate-component interaction. There was no evidence of physiologic specialisation in the isolates, but low levels of specialisation could have been hidden by the high level of variation in the experiments. Comparison of field cultivars of garlic with equivalent virus-free material using an isolate of leek rust gave inconclusive results, and further study of the rust-garlic-virus interaction is recommended. Major trends in the infection/resistance studies included a high level of environmentally-dependent variation and a lack of 'hypersensitive-type' resistance, even in host species quite distantly related to the normal host

A Decision Model for Choosing among Photovoltaic Technologies to Generate Electricity at Grid-Connected Air Force Facilities: A Value-Focused Approach

The United States is currently consuming fossil fuels faster than natural processes can replace them. Our nation\u27s leaders recognize that a diverse energy portfolio including renewable energy is the key to maintaining our economy, security, and the environment. The federal government is by far the greatest energy consumer; thus, our nation\u27s leaders have directed federal agencies to strive to increase the use of renewable energy at federal facilities. Solar electricity technologies, in the form of photovoltaics, have great potential in the renewable energy mix. Although a major strategy should be integrating photovoltaics into the design of new facilities, an important early consideration should be the installation of photovoltaic modules in open areas and/or module retrofits onto existing structures. This research developed a model based on decision makers\u27 value systems to quantify and rank several photovoltaic technologies. The goal of the model was to determine what alternatives would most align with Air Force energy and environmental objectives. After working with subject matter experts at three bases, a comprehensive hierarchy was developed. This hierarchy was then used to find the best alternatives at one base. It was found that photovoltaic technologies may indeed successfully compete with grid-supplied electricity when utilizing a value-focused approach