myo-inositol pentakisphosphates. Structure, biological occurrence and phosphorylation to myo-inositol hexakisphosphate

1. Standard and high-performance anion-exchange-chromatographic techniques have been used to purify myo-[3H]inositol pentakisphosphates from various myo-[3H]inositol-prelabelled cells. Slime mould (Dictyostelium discoideum) contained 8 microM-myo-[3H]inositol 1,3,4,5,6-pentakisphosphate 16 microM-myo-[3H]inositol 1,2,3,4,6-pentakisphosphate and 36 microM-D-myo-[3H]inositol 1,2,4,5,6-pentakisphosphate [calculated intracellular concentrations; Stephens & Irvine (1990) Nature (London) 346 580-583]; germinating mung-bean (Phaseolus aureus) seedlings contained both D- and L-myo-[3H]inositol 1,2,4,5,6-pentakisphosphate (which was characterized by 31P and two-dimensional proton n.m.r.) and D- and/or L-myo-[3H]inositol 1,2,3,4,5-pentakisphosphate; HL60 cells contained myo-[3H]inositol 1,3,4,5,6-pentakisphosphate (in a 500-fold excess over the other species), myo-[3H]inositol 1,2,3,4,6-pentakisphosphate and D- and/or L-myo-[3H]inositol 1,2,4,5,6-pentakisphosphate; and NG-115-401L-C3 cells contained myo-[3H]inositol 1,3,4,5,6-pentakisphosphate (in a 100-fold excess over the other species), D- and/or L-myo-[3H]inositol 1,2,4,5,6-pentakisphosphate, myo-[3H]inositol 1,2,3,4,6-pentakisphosphate and D- and/or L-myo-[3H]inositol 1,2,3,4,5-pentakisphosphate. 2. Multiple soluble ATP-dependent myo-inositol pentakisphosphate kinase activities have been detected in slime mould, rat brain and germinating mung-bean seedling homogenates. In slime-mould cytosolic fractions, the three myo-inositol pentakisphosphates that were present in intact slime moulds could be phosphorylated to myo-[3H]inositol hexakisphosphate: the relative first-order rate constants for these reactions were, in the order listed above, 1:8:31 respectively (with first-order rate constants in the intact cell of 0.1, 0.8 and 3.1 s-1, assuming a cytosolic protein concentration of 50 mg/ml), and the Km values of the activities for their respective inositol phosphate substrates (in the presence of 5 mM-ATP) were 1.6 microM, 3.8 microM and 1.4 microM. At least two forms of myo-inositol pentakisphosphate kinase activity could be resolved from a slime-mould cytosolic fraction by both pharmacological and chromatographic criteria. Rat brain cytosol and a soluble fraction derived from germinating mung-bean seedlings could phosphorylate myo-inositol D/L-1,2,4,5,6-, D/L-1,2,3,4,5-, 1,2,3,4,6- and 1,3,4,5,6-pentakisphosphates to myo-inositol hexakisphosphate: the relative first-order rate constants were 57:27:77:1 respectively for brain cytosol (with first-order rate constants in the intact cell of 0.0041, 0.0019, 0.0056 and 0.000073 s-1 respectively, assuming a cytosolic protein concentration of 50 mg/ml) and 1:11:12:33 respectively for mung-bean cytosol (with first-order rate constants in a supernatant fraction with a protein concentration of 10 mg/ml of 0.0002, 0.0022, 0.0024 and 0.0066 s-1 respectively).

Transglutaminase 2 cross-linking of matrix proteins: biological significance and medical applications

This review summarises the functions of the enzyme tissue transglutaminase (TG2) in the extracellular matrix (ECM) both as a matrix stabiliser through its protein cross-linking activity and as an important cell adhesion protein involved in cell survival. The contribution of extracellular TG2 to the pathology of important diseases such as cancer and fibrosis are discussed with a view to the potential importance of TG2 as a therapeutic target. The medical applications of TG2 are further expanded by detailing the use of transglutaminase cross-linking in the development of novel biocompatible biomaterials for use in soft and hard tissue repair.

French linguistics research and teaching in UK and Irish HE institutions

Introduction: The research and teaching of French linguistics in UK higher education (HE) institutions have a venerable history; a number of universities have traditionally offered philology or history of the language courses, which complement literary study. A deeper understanding of the way that the phonology, syntax and semantics of the French language have evolved gives students linguistic insights that dovetail with their study of the Roman de Renart, Rabelais, Racine or the nouveau roman. There was, in the past, some coverage of contemporary French phonetics but little on sociolinguistic issues. More recently, new areas of research and teaching have been developed, with a particular focus on contemporary spoken French and on sociolinguistics. Well supported by funding councils, UK researchers are also making an important contribution in other areas: phonetics and phonology, syntax, pragmatics and second-language acquisition. A fair proportion of French linguistics research occurs outside French sections in psychology or applied linguistics departments. In addition, the UK plays a particular role in bringing together European and North American intellectual traditions and methodologies and in promoting the internationalisation of French linguistics research through the strength of its subject associations, and that of the Journal of French Language Studies. The following sections treat each of these areas in turn. History of the French Language There is a long and distinguished tradition in Britain of teaching and research on the history of the French language, particularly, but by no means exclusively, at the universities of Cambridge, Manchester and Oxford.

Directions for a troubled discipline:strategy research, teaching and practice introduction to the dialog

This Dialog responds to a growing debate about the relevance of business schools generally and the value of strategy theory and research for strategic management practice. The authors propose that academic theory and management practice can be better connected through management education. The academy researches practice, derives theory, and returns it to practice through the development of teaching materials and the teaching of current and future practitioners. The three articles in this Dialog examine how different approaches to strategy research inform strategy teaching and its application to practice. Joseph Bower explains the rise of business policy and the process research approach that informed that teaching tradition at Harvard Business School. Robert Grant responds by emphasizing the economic theory underpinnings of strategic management research and its impact on teaching. Paula Jarzabkowski and Richard Whittington conclude by proposing a strategyas-practice perspective and suggesting ways to better incorporate strategy-as-practice research into strategy teaching.

Person-oriented and process-oriented teachers : an investigation of the links between ESOL teachers' personal belief systems and approaches to teaching

This thesis looks to two traditions in research into language teaching, teacher beliefs and classroom interaction, in order to investigate the question: Do teachers of ESOL have an identifiable and coherent system of beliefs about teaching and learning that may account for different approaches to teaching? A qualitative approach to research is taken, following a case study tradition, in order to carry out an in-depth study into the beliefs of six ESOL teachers. Five teachers participated in an initial pilot study and two subsequently became the main case studies for the research. The beliefs of a sixth teacher were then investigated to verify the findings. Semi-structured interviews and classroom observations were carried out with all the teachers. The teachers in the study were found to have personal belief systems that cohere around two orientations to teaching and learning - a person orientation and a process orientation. Moreover, the findings suggest that underlying the orientations is the perception that teachers have of their teacher identity, in terms of whether this is seen as a separate identity or as part of their personality. It is suggested that the two orientations may offer a powerful tool for teacher education as it is increasingly recognised that, in order to be effective, teacher educators must take into account the beliefs that teachers bring with them to training and development programmes. An initial investigations into the teachers’ classroom behaviour suggests that while their methodologies approach may be very similar there are fundamental differences in their interactions patterns and these differences may be a result of their own orientation. However, while teachers’ personal belief systems undoubtedly underlie their approach to teaching, further research is needed to establish the extent and the nature of the relationship between orientation and classroom interaction.

Cellular uptake and biological activity of synthetic hammerhead ribozymes

Glioblastoma Multiforme (GBM) is a highly malignant form of brain cancer for which there is no effective cure. The over-expression of a number of genes, including the epidermal growth factor receptor (EGFr), has been implicated as a causative factor of tumourigenesis. Ribozymes are a class of ribonucleic acid that possess enzymatic properties. They can inhibit gene-expression in a highly sequence specific manner by catalysing the trans-cleavage of target RNA. The potential use of synthetic hammerhead ribozymes as novel anti-brain tumour agents was investigated in this study. The successful use of synthetic, exogenously administered ribozymes for such applications will require chemical modifications that improve biological stability and a fundamental understanding of cellular uptake mechanisms. Chimeric 2'-O-methylated hammerhead ribozymes proved to be significantly more stable (>4000-fold) in serum than unmodified RNA ribozymes and exhibited high in vitro catalytic activity. The cellular association of an internally [32P]-labelled 2'-O-methylated chimeric ribozyme in U87-MG human glioma cells was temperature-, energy- and pH-dependent and involved an active process that could be competed with a variety of polyanions. Indications are that the predominant mechanism of uptake is by adsorptive and / or receptor mediated endocytosis. Twenty 2'-O-methylated chimeric ribozymes were designed to cleave various sites along the EGFr mRNA. In vitro, 18 ribozymes exhibited high activity in cleaving a complementary short substrate. Using LipofectAMINETM as a delivery agent, the efficacy of these ribozymes was evaluated in the A431 cell line, which expresses amplified levels of EGFr. Studies revealed that although the ribozymes were taken up by the cells and remained stable over a period of 4 days, no significant reduction in either EGFr expression or cell proliferation was evident. The presence of telomerase, a ribonucleoprotein responsible for telomere elongation, has been strongly associated with tumour progression. The biological activity of a 2'-O-methylated ribozyme targeted against the RNA component of telomerase was determined. The ribozyme exhibited specific dose-dependent inhibition of telomerase activity in U87-MG cell lysates with an IC50 of –4μM. When 4μM ribozyme was delivered to intact U87-MG cells, complexed to LipofectAMINETM, telomerase activity was significantly reduced to 74.5±4.17% of the untreated control. Free ribozyme showed no significant inhibitory effect demonstrating the importance of an appropriate delivery system for optimum delivery of exogenously administered ribozymes.

Review of doctoral research in second-language teaching and learning in Australia (2003–2006)

This article reviews recent doctoral research in Australian universities in the area of language teaching and learning. Doctoral work in three main areas of research concentration is described: language teaching, language learning, and writing. The authors whose studies are reviewed are graduates of the Australian National University, Griffith University, Macquarie University, the University of Technology, Sydney, the University of Sydney, the University of New South Wales, the University of Melbourne, Monash University, La Trobe University, Deakin University and Murdoch University.

Supporting learners’ agentic engagement with feedback:a systematic review and a taxonomy of recipience processes

Much has been written in the educational psychology literature about effective feedback and how to deliver it. However, it is equally important to understand how learners actively receive, engage with, and implement feedback. This article reports a systematic review of the research evidence pertaining to this issue. Through an analysis of 195 outputs published between 1985 and early 2014, we identified various factors that have been proposed to influence the likelihood of feedback being used. Furthermore, we identified diverse interventions with the common aim of supporting and promoting learners' agentic engagement with feedback processes. We outline the various components used in these interventions, and the reports of their successes and limitations. Moreover we propose a novel taxonomy of four recipience processes targeted by these interventions. This review and taxonomy provide a theoretical basis for conceptualizing learners' responsibility within feedback dialogues and for guiding the strategic design and evaluation of interventions. Receiving feedback on one's skills and understanding is an invaluable part of the learning process, benefiting learners far more than does simply receiving praise or punishment (Black & Wiliam, 1998 Black, P., & Wiliam, D. (1998). Assessment and classroom learning. Assessment in Education: Principles, Policy & Practice, 5, 7–74. doi:10.1080/0969595980050102[Taylor & Francis Online]; Hattie & Timperley, 2007 Hattie, J., & Timperley, H. (2007). The power of feedback. Review of Educational Research, 77, 81–112. doi:10.3102/003465430298487[CrossRef], [Web of Science ®]). Inevitably, the benefits of receiving feedback are not uniform across all circumstances, and so it is imperative to understand how these gains can be maximized. There is increasing consensus that a critical determinant of feedback effectiveness is the quality of learners' engagement with, and use of, the feedback they receive. However, studies investigating this engagement are underrepresented in academic research (Bounds et al., 2013 Bounds, R., Bush, C., Aghera, A., Rodriguez, N., Stansfield, R. B., & Santeen, S. A. (2013). Emergency medicine residents' self-assessments play a critical role when receiving feedback. Academic Emergency Medicine, 20, 1055–1061. doi:10.1111/acem.12231[CrossRef], [PubMed], [Web of Science ®]), which leaves a “blind spot” in our understanding (Burke, 2009 Burke, D. (2009). Strategies for using feedback students bring to higher education. Assessment & Evaluation in Higher Education, 34, 41–50. doi:10.1080/02602930801895711[Taylor & Francis Online], [Web of Science ®]). With this blind spot in mind, the present work sets out to systematically map the research literature concerning learners' proactive recipience of feedback. We use the term “proactive recipience” here to connote a state or activity of engaging actively with feedback processes, thus emphasizing the fundamental contribution and responsibility of the learner (Winstone, Nash, Rowntree, & Parker, in press Winstone, N. E., Nash, R. A., Rowntree, J., & Parker, M. (in press). ‘It'd be useful, but I wouldn't use it’: Barriers to university students' feedback seeking and recipience. Studies in Higher Education. doi: 10.1080/03075079.2015.1130032[Taylor & Francis Online]). In other words, just as Reeve and Tseng (2011 Reeve, J., & Tseng, M. (2011). Agency as a fourth aspect of student engagement during learning activities. Contemporary Educational Psychology, 36, 257–267. doi:10.1016/j.cedpsych.2011.05.002[CrossRef], [Web of Science ®]) defined “agentic engagement” as a “student's constructive contribution into the flow of the instruction they receive” (p. 258), likewise proactive recipience is a form of agentic engagement that involves the learner sharing responsibility for making feedback processes effective.