The evolution of novel subgroups of feline leukaemia virus

Feline leukaemia virus is a significant pathogen of domestic cats which causes a range of proliferative and non-proliferative haematopoietic disorders. This virus has been extensively studied in the past, however advancements in molecular techniques now allow long-standing controversial topics to be revisited and reanalysed. Although FeLV-A is the only transmittable form of the virus, FeLV-B and –C may arise in infected cats if the initial virus escapes immune clearance and establishes a chronic infection. These studies aimed to investigate previously-unanswered questions regarding FeLV pathogenesis, specifically pertaining to the ability of FeLV-A to evolve into the novel subgroups B and C. These results indicate that strains of FeLV-A possessing residues D83 and D91 in their envelope glycoprotein display increased rates of viral replication, mediated by an enhanced interaction with their cognate receptor, THTR1. Evidence is provided that these viral proteins are also able to bind efficiently to the FeLV-C receptor, FLVCR1, and that these mutations represent the first in a step-wise accumulation of mutations which eventually result in a FeLV-C viral variant emerging within the host. Subsequent studies aimed to elucidate the respective roles of the acquired immune response (neutralising antibodies) and receptor availability in driving this evolutionary process; however a definitive conclusion regarding FeLV-C selection pressures was not reached due to limitations of the model. These studies also describe the first isolation of novel FeLV-B field isolates which present without a FeLV-A co-infection. Characterisation of these strains revealed they possessed recombinant genomes, composed of exogenous LTRs and mostly endogenously-derived env genes. Further investigations into the potential functionality of endogenous FeLV elements within the domestic cat genome revealed numerous intact env genes, the proviruses of which may be restricted from exogenous transmission by their inability to form homodimeric RNA genomes with functional secondary structures. Although this suggestion requires experimental validation, this represents a novel mechanism of endogenous retroviral restriction

Building Future Research Capacity In Student Healthcare Practitioners Through Research-Informed-Teaching

The Research-Informed-Teaching (RIT) agenda aims to broaden the scope of learning and teaching within higher education (Jenkins, Healey and Zetter, 2007). This may encompass raising students’ awareness of the research environment and knowledge base relevant to their discipline, developing advanced skills in critical appraisal of published research, engaging active researchers in the delivery of teaching, plus facilitating students’ direct experience of research processes and conduct. It may be anticipated that that RIT is already intrinsic to the nature of professional education in healthcare, where Evidence-Based Practice (EBP) is a now a fundamental requirement of professional regulation (Health and Care Professions’ Council (2014). However frameworks of RIT are not necessarily sufficiently defined to promote the required depth of critical reflection on clinical practice (Dey, Downe, Milston, Roddam and Hart, 2009)

NADPH as a potential intrinsic probe for tumour margin estimation

The fluorescent properties of the reduced coenzyme NADH and its phosphorylated derivative (NADPH) have been explored in order to assess their potential as an intrinsic probe for cancer surgery. NADPH production is increased in cancer cells to quench reactive oxygen species and meet higher demands for biosynthesis, and has attractive fluorescent properties such as emission towards the visible part of the spectrum and a relatively long fluorescence lifetime upon binding to enzymes (~ 1 – 6.5 ns) that helps discriminate against other endogenous species. Different environmental effects on NAD(P)H fluorescence are reported here, including an increase in lifetime upon oxygen removal, an ability to retain its fluorescent properties in a complex medium (a silica phantom) and its fluorescence lifetime also being distinguishable in a cell environment. In addition, the development of a miniaturized liquid light guide filter-based timecorrelated single photon counting fluorescence lifetime system is reported as a step towards time-resolved visual imaging in cancer surgery. This system has been demonstrated as being capable of accurately measuring NAD(P)H fluorescence lifetimes in both simple solvent and cellular environments

Characteristics of High School Girls which May Lead to Early Marriage

The problem of this study was to isolate some of the characteristics of tenth-grade girls which may lead to early marriage. The characteristics studied were: sibling rank, influence of a broken home, parents* education and occupations, mental ability, aptitude, scholastic achievement, study habits and attitudes, and personal problems identified by the subjects. A further problem of the study was the effectiveness of each of the characteristics in predicting the marriage of high school girls

Behavioral and other phenotypes in a cytoplasmic Dynein light intermediate chain 1 mutant mouse

The cytoplasmic dynein complex is fundamentally important to all eukaryotic cells for transporting a variety of essential cargoes along microtubules within the cell. This complex also plays more specialized roles in neurons. The complex consists of 11 types of protein that interact with each other and with external adaptors, regulators and cargoes. Despite the importance of the cytoplasmic dynein complex, we know comparatively little of the roles of each component protein, and in mammals few mutants exist that allow us to explore the effects of defects in dynein-controlled processes in the context of the whole organism. Here we have taken a genotype-driven approach in mouse (Mus musculus) to analyze the role of one subunit, the dynein light intermediate chain 1 (Dync1li1). We find that, surprisingly, an N235Y point mutation in this protein results in altered neuronal development, as shown from in vivo studies in the developing cortex, and analyses of electrophysiological function. Moreover, mutant mice display increased anxiety, thus linking dynein functions to a behavioral phenotype in mammals for the first time. These results demonstrate the important role that dynein-controlled processes play in the correct development and function of the mammalian nervous system