Complex organization of the Streptomyces avermitilis genes encoding the avermectin polyketide synthase

The avermectin (Av) polyketide synthase (PKS) and erythromycin (Er) PKS are encoded by modular repeats of DNA, but the genetic organization of the modules encoding Av PKS is more complex than Er PKS. Sequencing of several related DNA fragments from Streptomyces avermitilis that are part of the Av biosynthetic gene cluster, revealed that they encode parts of large multifunctional PKS proteins. The Av PKS proteins show strong similarity to each other, as well as similarity to Er PKS proteins [Donadio et al., Science 252 (1991) 675–679] and fatty acid synthases. Partial DNA sequencing of the 65-kb region containing all the related sequence elements in the avr genes provides evidence for twelve modular repeats encoding FAS-like domains. The genes encoding the Av PKS are organized as two sets of six modular repeats which are convergently transcribed.

timng of the last glacial maximum from observed sea level minima

During the Last Glacial Maximum, ice sheets covered large areas in northern latitudes, and global temperatures were significantly lower than today. But few direct estimates exist of the volume of the ice sheets, or the timing and rates of change during their advance and retreat. Here we analyze four distinct sediment facies in the shallow, tectonically stable Bonaparte Gulf, Australia - each of which is characteristic of a distinct range in sea level - to estimate the maximum volume of land-based ice during the last glaciation and the timing of the initial melting phase. We use faunal assemblages and preservation status of the sediments to distinguish open marine, shallow marine, marginal marine and brackish conditions, and estimate the timing and the mass of the ice sheets using radiocarbon dating and glacio-hydroisostatic modelling. Our results indicate that from at least 22,000 to 19,000 (calendar) years before present, land-based ice volume was at its maximum, exceeding today's grounded ice sheets by 52.5 x 10 exp 6 cu km. A rapid decrease in ice volume by about 10 percent within a few hundred years terminated the Last Glacial Maximum at 19,000 +/- 250 years.

Expression of C-reactive protein in human lung epithelial cells and up-regulation by cytokines and carbon particles.

C-reactive protein (CRP) is the prototypic human acute-phase protein and is found at increased levels in the blood during episodes of inflammation. CRP was generally thought to be produced only by hepatocytes; however, several studies have shown extrahepatic synthesis of CRP. A previous study showed that PM10 and ultrafine carbon black (ufCB) were able to induce CRP expression in A549 cells. This study aims to examine the factors that lead to the production of CRP in A549 cells. A549 human lung epithelial cells were treated with cytokines (interleukin 6, tumor necrosis factor , interferon , or interleukin 1) or carbon particles (CB and ufCB) for 18 h. It was found that CRP could be expressed within the cells and that CRP was secreted from the cells particularly with tumor necrosis factor , CB and ufCB treatments. It was also found that this expression of CRP with CB and ufCB treatments was dependent on nuclear factor kappa B (NFB). The expression of CRP in A549 cells may indicate an important role for CRP expression and secretion from lung epithelial cells in response to inflammatory stimuli.

Learning from patterns during information technology configuration.

This paper asks how people can be assisted in learning from practice, as a basis for informing future action, when configuring information technology (IT) in organizations. It discusses the use of Alexanderian Patterns as a means of aiding such learning. Three patterns are presented that have been derived from a longitudinal empirical study that has focused on practices surrounding IT configuration. The paper goes on to argue that Alexanderian Patterns offer a valuable means of learning from past experience. It is argued that learning from experience is an important dimension of deciding “what needs to be done” in configuring IT with organizational context. The three patterns outlined are described in some detail, and the implications of each discussed. Although it is argued that patterns, per se, provide a valuable tool for learning from experience, some potential dangers in seeking to codify experience with a patterns approach are also discussed.

Innovation and hybrid genres: disturbing social rhythm in legal practice.

This paper explores the non-adoption of an innovation via the concept of hybrid genres, that is digital genres that emerge from a non-digital material precedent. As instances of innovation these are often resisted because they disturb the order of activity and balance of power relations in a given situation, or require users to make conceptual and physical adaptation efforts that they consider too costly. The authors investigate such issues with a case study of the introduction of a hybrid digital genre, ODR or online dispute resolution, in legal practice

Traversing digital learning landscapes: an Institutional and faculty case study.

Within the UK, there is a growing awareness to better understand what online educational technologies can offer in relation to learning and teaching, and how social technologies are changing communication and collaboration out with formal education. The concept of the ‘digital university’ is being widely debated within the UK Higher education sector (McCluskey and Winter, 2012), becoming embedded in educational policy, and beginning to be explored within many institutions. This session will report on one such institutional initiative, undertaken at Edinburgh Napier University in Scotland. A Digital Futures Working Group was established to: benchmark best practice in key areas including digitally enhanced education and digital literacies development; identify areas for short term action; and to produce a robust ‘digital agenda’ to inform the future direction of the university. Pivotal to this was the recognition to evolve staff digital pedagogical practices and to harness emerging digital opportunities, meet learner expectations, and meet wider expectations for contemporary able citizens. This session will be delivered in two parts. Firstly we will provide an insight into the focus of the project and the rich picture methodology used to consult with staff and students. Secondly we will specify the outcomes produced, and provide a case study of how the Faculty of Health, Life and Social Sciences engaged with the process and the progression of their digitally enabled educational practices.

Allochthonous and autochthonous mire deposits, slope instability and palaeoenvironmental investigations in the Borve Valley, Barra, Outer Hebrides, Scotland

Ashmore, P. Brayshay, B.A Edwards, K.J Gilbertson, D. Grattan, J. Kent, M. Pratt, K. Weaver, R. 'Allochthonous and autochthonous mire deposits, slope instability and palaeoenvironmental investigations in the Borve Valley, Barra, Outer Hebrides, Scotland' The Holocene 2000 10, 1 pp.97-108

Dictionary of Continental Celtic Place-Names: A Celtic Companion to the Barrington Atlas of the Greek and Roman World

Falileyev, Alexander, in collaboration with Ashwin E. Gohil and Naomi Ward, Dictionary of Continental Celtic Place-Names: A Celtic Companion to the Barrington Atlas of the Greek and Roman World (CMCS Publications: Aberystwyth, 2010) Editor: Falileyev, Alexander in collaboration with Ashwin E. Gohil and Naomi Ward

The impact of short duration, high intensity exercise on cardiac troponin release

The aim of this study was to assess the appearance of cardiac troponins (cTnI and/or cTnT) after a short bout (30 s) of ‘all-out’ intense exercise and to determine the stability of any exercise-related cTnI release in response to repeated bouts of high intensity exercise separated by 7 days recovery. Eighteen apparently healthy, physically active, male university students completed two all-out 30 s cycle sprint, separated by 7 days. cTnI, blood lactate and catecholamine concentrations were measured before, immediately after and 24 h after each bout. Cycle performance, heart rate and blood pressure responses to exercise were also recorded. Cycle performance was modestly elevated in the second trial [6·5% increase in peak power output (PPO)]; there was no difference in the cardiovascular, lactate or catecholamine response to the two cycle trials. cTnI was not significantly elevated from baseline through recovery (Trial 1: 0·06 ± 0·04 ng ml−1, 0·05 ± 0·04 ng ml−1, 0·03 ± 0·02 ng ml−1; Trial 2: 0·02 ± 0·04 ng ml−1, 0·04 ± 0·03 ng ml−1, 0·05 ± 0·06 ng ml−1) in either trial. Very small within subject changes were not significantly correlated between the two trials (r = 0·06; P>0·05). Subsequently, short duration, high intensity exercise does not elicit a clinically relevant response in cTnI and any small alterations likely reflect the underlying biological variability of cTnI measurement within the participants.

Construction of a Festuca pratensis BAC library for map-based cloning in IFestulolium substitution lines

Iain S. Donnison, Donal M. O Sullivan, Ann Thomas, Peter Canter, Beverley Moore, Ian Armstead, Howard Thomas, Keith J. Edwards and Ian P. King (2005). Construction of a Festuca pratensis BAC library for map-based cloning in Festulolium substitution lines. Theoretical and Applied Genetics, 110 (5) pp.846-851 Sponsorship: BBSRC;BBSRC RAE2008

Modification of nitrogen remobilisation, grain fill and leaf senescence in maize (Zea mays L.) by transposon insertional mutagenensis in a protease gene

Donnison, I. S., Gay, A. P., Thomas, Howard, Edwards, K. J., Edwards, D., James, C. L., Thomas, A. M., Ougham, H. J. (2007). Modification of nitrogen remobilization, grain fill and leaf senescence in maize (Zea mays) by transposon insertional mutagenensis in a protease gene. New Phytologist, 173 (3), 481-494. Sponsorship: BBSRC RAE2008

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized.

Optimisation of the food dairy coop supply chain

In the European Union under the Common Agricultural Policy (CAP) milk production was restricted by milk quotas since 1984. However, due to recent changes in the Common Agricultural Policy (CAP), milk quotas will be abolished by 2015. Therefore, the European dairy sector will soon face an opportunity, for the first time in a generation, to expand. Numerous studies have shown that milk production in Ireland will increase significantly post quotas (Laepple and Hennessy (2010), Donnellan and Hennessy (2007) and Lips and Reider (2005)). The research in this thesis explored milk transport and dairy product processing in the Irish dairy processing sector in the context of milk quota removal and expansion by 2020. In this study a national milk transport model was developed for the Irish dairy industry, the model was used to examine different efficiency factors in milk transport and to estimate milk transport costs post milk quota abolition. Secondly, the impact of different milk supply profiles on milk transport costs was investigated using the milk transport model. Current processing capacity in Ireland was compared against future supply, it was concluded that additional milk processing capacity would not be sufficient to process the additional milk. Thirdly, the milk transport model was used to identify the least cost locations (based on transport costs) to process the additional milk supply in 2020. Finally, an optimisation model was developed to identify the optimum configuration for the Irish dairy processing sector in 2020 taking cognisance of increasing transport costs and decreasing processing costs.

Investment funds: What next?

Investment funds provide a low cost method of sharing in the rewards from capitalism. Recently “alternative investments” such as hedge funds have grown rapidly and the trading strategies open to hedge funds are now becoming available to mutual funds and even to ordinary retail investors. In this paper we analyze problems in assessing fund performance and the prospects for investment fund sectors. Choosing genuine outperformers among top funds requires a careful assessment of non-normality, order statistics and the possibility of false discoveries. The risk adjusted performance of the average hedge fund over the last 10-15 is actually not that impressive, although the “top” funds do appear to have statistically significant positive alphas.