Saccharomyces Cerevisiae as a biotechnological tool for ageing research:studies on translation and metabolism

The yeast Saccharomyces cerevisiae is an important model organism for the study of cell biology. The similarity between yeast and human genes and the conservation of fundamental pathways means it can be used to investigate characteristics of healthy and diseased cells throughout the lifespan. Yeast is an equally important biotechnological tool that has long been the organism of choice for the production of alcoholic beverages, bread and a large variety of industrial products. For example, yeast is used to manufacture biofuels, lubricants, detergents, industrial enzymes, food additives and pharmaceuticals such as anti-parasitics, anti-cancer compounds, hormones (including insulin), vaccines and nutraceuticals. Its function as a cell factory is possible because of the speed with which it can be grown to high cell yields, the knowledge that it is generally recognized as safe (GRAS) and the ease with which metabolism and cellular pathways, such as translation can be manipulated. In this thesis, these two pathways are explored in the context of their biotechnological application to ageing research: (i) understanding translational processes during the high-yielding production of membrane protein drug targets and (ii) the manipulation of yeast metabolism to study the molecule, L-carnosine, which has been proposed to have anti-ageing properties. In the first of these themes, the yeast strains, spt3?, srb5?, gcn5? and yTHCBMS1, were examined since they have been previously demonstrated to dramatically increase the yields of a target membrane protein (the aquaporin, Fps1) compared to wild-type cells. The mechanisms underlying this discovery were therefore investigated. All high yielding strains were shown to have an altered translational state (mostly characterised by an initiation block) and constitutive phosphorylation of the translational initiation factor, eIF2a. The relevance of the initiation block was further supported by the finding that other strains, with known initiation blocks, are also high yielding for Fps1. A correlation in all strains between increased Fps1 yields and increased production of the transcriptional activator protein, Gcn4, suggested that yields are subject to translational control. Analysis of the 5´ untranslated region (UTR) of FPS1 revealed two upstream open reading frames (uORFs). Mutagenesis data suggest that high yielding strains may circumvent these control elements through either a leaky scanning or a re-initiation mechanism. In the second theme, the dipeptide L-carnosine (ß-alanyl-L-histidine) was investigated: it has previously been shown to inhibit the growth of cancer cells but delay senescence in cultured human fibroblasts and extend the lifespan of male fruit flies. To understand these apparently contradictory properties, the effects of L-carnosine on yeast were studied. S. cerevisiae can respire aerobically when grown on a non-fermentable carbon source as a substrate but has a respiro-fermentative metabolism when grown on a fermentable carbon source; these metabolisms mimic normal cell and cancerous cell metabolisms, respectively. When yeast were grown on fermentable carbon sources, in the presence of L-carnosine, a reduction in cell growth and viability was observed, which was not apparent for cells grown on a non-fermentable carbon source. The metabolism-dependent mechanism was confirmed in the respiratory yeast species Pichia pastoris. Further analysis of S. cerevisiae yeast strains with deletions in their nutrient-sensing pathway, which result in an increase in respiratory metabolism, confirmed the metabolism-dependent effects of L-carnosine.

Measuring social identity in interfunctional research in marketing

Management of social identities is important for optimizing intergroup relations in organizations, and for overall organizational performance. Research on marketing’s intergroup relations employs different social identity constructs. This leaves managers and academics confused as to what impact different social identity constructs have on organizational outcomes. We therefore tested the impact of competing social identity constructs (i.e., functional identity [FI], organizational identity [OI]) on important outcomes. We find different combinations of social identity constructs result in different levels of relationship quality and departmental performance, and that FI and OI measures provide more useful information than the accepted relative functional identity or OI measures in isolation. Academic and practical implications are advanced.

An analysis of research on the future of purchasing and supply management

Business organisations are going through rapid external environmental and internal organisational changes due to increasing globalisation, E-business, and outsourcing. As a result, the future of purchasing and supply management—as a function within organisations, as a process that spans organisation boundaries and as a profession—raises important concerns for both organisations and the purchasing professional. This paper considers a broad and rather fragmented body of empirical evidence and analyses 42 relevant empirical studies on the future of purchasing and supply management. The major findings are reported in terms of changes in business contexts, purchasing strategy, structure, role and responsibility, system development and skills. Cross-sectional comparative analyses were also conducted to examine variation by sector, firm type, people's roles in purchasing, and country. A number of major implications for the purchasing function, process and professional bodies are presented together with suggestions for future research to address significant gaps in the current body of knowledge.

Finding qualitative research: an evaluation of search strategies

Background Qualitative research makes an important contribution to our understanding of health and healthcare. However, qualitative evidence can be difficult to search for and identify, and the effectiveness of different types of search strategies is unknown. Methods Three search strategies for qualitative research in the example area of support for breast-feeding were evaluated using six electronic bibliographic databases. The strategies were based on using thesaurus terms, free-text terms and broad-based terms. These strategies were combined with recognised search terms for support for breast-feeding previously used in a Cochrane review. For each strategy, we evaluated the recall (potentially relevant records found) and precision (actually relevant records found). Results A total yield of 7420 potentially relevant records was retrieved by the three strategies combined. Of these, 262 were judged relevant. Using one strategy alone would miss relevant records. The broad-based strategy had the highest recall and the thesaurus strategy the highest precision. Precision was generally poor: 96% of records initially identified as potentially relevant were deemed irrelevant. Searching for qualitative research involves trade-offs between recall and precision. Conclusions These findings confirm that strategies that attempt to maximise the number of potentially relevant records found are likely to result in a large number of false positives. The findings also suggest that a range of search terms is required to optimise searching for qualitative evidence. This underlines the problems of current methods for indexing qualitative research in bibliographic databases and indicates where improvements need to be made.

Illness perceptions predict reassurance following a negative exercise stress testing result

Many patients are not reassured after receiving normal results following cardiac investigations. While previous studies have shown anxiety to be a contributing factor, little research has investigated the influence of patients’ illness perceptions on reassurance. In this study we investigated whether illness perceptions predicted patients’ reassurance following normal exercise stress test results. Sixty-two chest pain patients without prior diagnosed cardiac pathology completed questionnaires assessing anxiety and illness perceptions prior to exercise stress testing. Patients completed a reassurance questionnaire immediately following their appointment and again one month later. Illness perceptions (consequences, timeline, identity, illness concern, and emotional effect) but not anxiety, significantly predicted reassurance immediately following testing. We found both state anxiety and illness perceptions to predict reassurance one month later. After controlling for anxiety, longer timeline and lower treatment control beliefs predicted lower reassurance. The results suggest that an intervention targeting patients who have high anxiety and negative illness perceptions prior to testing may improve reassurance and decrease disability and the subsequent use of medical care.

Engineering education research - the UK perspective at a time of change

Engineering education in the United Kingdom is at the point of embarking upon an interesting journey into uncharted waters. At no point in the past have there been so many drivers for change and so many opportunities for the development of engineering pedagogy. This paper will look at how Engineering Education Research (EER) has developed within the UK and what differentiates it from the many small scale practitioner interventions, perhaps without a clear research question or with little evaluation, which are presented at numerous staff development sessions, workshops and conferences. From this position some examples of current projects will be described, outcomes of funding opportunities will be summarised and the benefits of collaboration with other disciplines illustrated. In this study, I will account for how the design of task structure according to variation theory, as well as the probe-ware technology, make the laws of force and motion visible and learnable and, especially, in the lab studied make Newton's third law visible and learnable. I will also, as a comparison, include data from a mechanics lab that use the same probe-ware technology and deal with the same topics in mechanics, but uses a differently designed task structure. I will argue that the lower achievements on the FMCE-test in this latter case can be attributed to these differences in task structure in the lab instructions. According to my analysis, the necessary pattern of variation is not included in the design. I will also present a microanalysis of 15 hours collected from engineering students' activities in a lab about impulse and collisions based on video recordings of student's activities in a lab about impulse and collisions. The important object of learning in this lab is the development of an understanding of Newton's third law. The approach analysing students interaction using video data is inspired by ethnomethodology and conversation analysis, i.e. I will focus on students practical, contingent and embodied inquiry in the setting of the lab. I argue that my result corroborates variation theory and show this theory can be used as a 'tool' for designing labs as well as for analysing labs and lab instructions. Thus my results have implications outside the domain of this study and have implications for understanding critical features for student learning in labs. Engineering higher education is well used to change. As technology develops the abilities expected by employers of graduates expand, yet our understanding of how to make informed decisions about learning and teaching strategies does not without a conscious effort to do so. With the numerous demands of academic life, we often fail to acknowledge our incomplete understanding of how our students learn within our discipline. The journey facing engineering education in the UK is being driven by two classes of driver. Firstly there are those which we have been working to expand our understanding of, such as retention and employability, and secondly the new challenges such as substantial changes to funding systems allied with an increase in student expectations. Only through continued research can priorities be identified, addressed and a coherent and strong voice for informed change be heard within the wider engineering education community. This new position makes it even more important that through EER we acquire the knowledge and understanding needed to make informed decisions regarding approaches to teaching, curriculum design and measures to promote effective student learning. This then raises the question 'how does EER function within a diverse academic community?' Within an existing community of academics interested in taking meaningful steps towards understanding the ongoing challenges of engineering education a Special Interest Group (SIG) has formed in the UK. The formation of this group has itself been part of the rapidly changing environment through its facilitation by the Higher Education Academy's Engineering Subject Centre, an entity which through the Academy's current restructuring will no longer exist as a discrete Centre dedicated to supporting engineering academics. The aims of this group, the activities it is currently undertaking and how it expects to network and collaborate with the global EER community will be reported in this paper. This will include explanation of how the group has identified barriers to the progress of EER and how it is seeking, through a series of activities, to facilitate recognition and growth of EER both within the UK and with our valued international colleagues.

Servitization:revisiting the state-of-the-art and research priorities

Purpose – This paper consolidates the servitization knowledge base from an organisational change perspective, identifying developed, developing and undeveloped topics to provide a platform that directs future research. Design/methodology/approach – This paper addresses three objectives : a) it comprehensively examines organisational change management literature for selection of a theoretical framework, b) it classifies extant studies within the framework through a systemic literature review, and (c) it analyses 232 selected papers and proposes a research agenda. Findings – Analysis suggests increasing global awareness of the importance of services to manufacturers. However, some topics, especially related to servitization transformation, remain undeveloped. Research limitations/implications – Although the authors tried to include all publications relevant to servitization, some might not have been captured. Evaluation and interpretation relied on the research team and subsequent research workshops. Practical implications - One of the most significant challenges for practitioners of servitization is how to transform a manufacturing organisation to exploit the opportunity. This paper consolidates literature regarding servitization, identifying progress concerning key research topics and contributing a platform for future research. The goal is to inform research to result eventually in a roadmap for practitioners seeking to servitize. Originality/value - Although extant reviews of servitization identify themes that are examined well, they struggle to identify unanswered questions. This paper addresses this gap by focusing on servitization as a process of organisational change.

The regulatory environment of the section of the non-standardized goods market - The findings of an interview research on Hungarian construction industry small enterprises

In this paper the behavior of economic actors shown in the uncertain quality goods markets is examined from the perspective of the sociology of markets. The analysis uses the findings of in-depth interviews conducted in 2011 and 2012 respectively amongst small and medium size entrepreneurs working in construction industry. In the Hungarian construction industry neither formal rules, nor vocational chambers, are able to create a safe environment for entrepreneurs. Nevertheless, networks created as a result of micro-selection steps might be able to enforce the quality of services, observe deadlines and what is more, ensure payment discipline. In this market, the typical high risk can be reduced by relationships. Networks reduce also the cost of transactions, since the important part of the services in this field could only be standardized at significant costs.

A tudományterületi sajátosságok következményei a kutatásban, az oktatásban és a felsőoktatási intézmények vezetésében (The consequences of disciplinary difference on teaching, research and institutional management of higher education)

A szerző tanulmányában vizsgálja a tudományterületek különbségeinek következményeit az oktatásban, a kutatásban és a felsőoktatási intézmények irányításában. A tanulmány első felében a tudományterületek episztemológiai és közösségi különbségeit tárgyalja Becher és Trowler (2001) népszerű kategorizálása alapján. A tanulmány második felében a tudományszerveződésre, a publikációs gyakorlatra, a doktori képzésre, az oktatás céljára és formáira, a diákok tudásképére, valamint a menedzsmentfelfogásra gyakorolt hatást mutatja be. A konklúzióban egyrészt a minőség- és teljesítményértékelési rendszerek differenciált megközelítésének szükségességére hívja fel a figyelmet, másrészt arra, hogy a Bologna-rendszer és az élethosszig tartó tanulás erősödésének következményeként egy-egy mesterszakon nemcsak a hallgatóság háttere, előismerete lesz sokszínű, hanem a tudásról alkotott képe is. Ez újfajta oktatói szerepeket és oktatási megközelítéseket tesz szükségessé. ________ In the article the consequences of disciplinary difference on teaching, research and institutional management is examined. In the first part of the paper the epistemological and sociological differences of scientific disciplines are summarized based on the popular typology of Becher and Trowler (2001). In the second part the influence of differences on organisation of sciences, publication practices, PhD studies, the goal and form of teaching, students’ conception of knowledge as well as on the understanding on management and leadership are discussed. In the conclusions, attention is drawn on the necessity of differentiation in quality and performance management processes. Another conclusion is that new roles for teachers and approaches for teaching is required if students’ conception of knowledge become more heterogeneous which is the result of result of life long learning and Bologna-reform.

The impact of CEO compensation and CEO horizon on a firm's discretionary research and development expenditures

Agency costs are said to arise as a result of the separation of ownership from control inherent in the corporate form of ownership. One such agency problem concerns the potential variance between the time horizons of principal shareholders and agent managers. Agency theory suggests that these costs can be alleviated or controlled through performance-based Chief Executive Officer (CEO) contracting. However, components of a CEO's compensation contract can exacerbate or mitigate agency-related problems (Antle and Smith, 1985). According to the horizon hypothesis, a self-serving CEO reduces discretionary research and development (R&D) expenditures to increase earnings and earnings-based bonus compensation. Agency theorists contend that a CEO's market-based compensation component can mitigate horizon problems. This study seeks to determine whether there is a relationship between CEO earnings- and market-based compensation components and R&D expenditures in the largest United States industrial firms from 1987 to 1993.^ Consistent with the horizon hypothesis, results provide evidence of a negative and statistically significant relationship between CEO cash compensation (i.e., salary and bonus) and the firm's R&D expenditures. Consistent with the expectations of agency theory, results provide evidence of a positive and statistically significant relationship between market-based CEO compensation and R&D.^ Further results of this study provide evidence of a positive and statistically significant relationship between CEO tenure and the firm's R&D expenditures. Although there is a negative relationship between CEO age and the firm's R&D, it was not statistically significant at the 0.5 level. ^

The impact of pre -training interventions on cognitive, skill, and affective learning outcomes: A meta -analytic examination of four decades of research

Technological advancements and the ever-evolving demands of a global marketplace may have changed the way in which training is designed, implemented, and even managed, but the ultimate goal of organizational training programs remains the same: to facilitate learning of a knowledge, skill, or other outcome that will yield improvement in employee performance on the job and within the organization (Colquitt, LePine, & Noe, 2000; Tannenbaum & Yukl, 1992). Studies of organizational training have suggested medium to large effect sizes for the impact of training on employee learning (e.g., Arthur, Bennett, Edens, & Bell, 2003; Burke & Day, 1986). However, learning may be differentially affected by such factors as the (1) level and type of preparation provided prior to training, (2) targeted learning outcome, (3) training methods employed, and (4) content and goals of training (e.g., Baldwin & Ford, 1988). A variety of pre-training interventions have been identified as having the potential to enhance learning from training and practice (Cannon-Bowers, Rhodenizer, Salas, & Bowers, 1998). Numerous individual studies have been conducted examining the impact of one or more of these pre-training interventions on learning. ^ I conducted a meta-analytic examination of the effect of these pre-training interventions on cognitive, skill, and affective learning. Results compiled from 359 independent studies (total N = 37,038) reveal consistent positive effects for the role of pre-training interventions in enhancing learning. In most cases, the provision of a pre-training intervention explained approximately 5–10% of the variance in learning, and in some cases, explained up to 40–50% of variance in learning. Overall attentional advice and meta-cognitive strategies (as compared with advance organizers, goal orientation, and preparatory information) seem to result in the most consistent learning gains. Discussion focuses on the most beneficial match between an intervention and the learning outcome of interest, the most effective format of these interventions, and the most appropriate circumstances under which these interventions should be utilized. Also highlighted are the implications of these results for practice, as well as propositions for important avenues for future research. ^

The self-perceived effects on faculty that result from the experience of serving in a residential college

The purpose of this phenomenological study was to examine the effects that faculty who live in residence with college students perceive result from their experience. This study examined the perspectives from current and recent residential faculty members. Data were gathered through structured interviews with current and former residential faculty who gave firsthand accounts of how they felt that experience impacted them. A pilot study had been previously conducted that enabled the researcher to modify and adjust the dissertation methodology accordingly, based upon the findings of the pilot study. The pilot study, in short, found that residential faculty members felt they gained from the experience in terms of relationships with students and other faculty while facing a few small challenges. Literature consistently showed that faculty-student interaction is very important to the development and success of students (Astin, 1993). Research has clearly demonstrated positive outcomes that result for students; the literature review revealed this information is plentiful. There is a dearth of research, however, regarding this impact on the faculty members themselves. Given the importance of faculty-student interaction outside of the classroom, it is crucial to recruit faculty for these communities. Thus, more information regarding this experience will be valuable. The study was conducted at a mid-sized private university in the Southeastern United States. The reason for this choice was the fact that this school has a 25-year history as a residential college system and utilizes 12–15 residential faculty members yearly. The researcher conducted interviews with 13 faculty members and coded and analyzed the data, then prepared the findings of the study based on the results. The data resulting from the study indicated that faculty perceived great benefits from serving as residential college faculty members. Perceived benefits as described by the participants included increased skill in teaching, feeling a sense of community, stronger relationships with other faculty members and students, and an increased affinity toward the university. While there were some challenges such as lack of training, politics, and loss of privacy all participants in the study felt they gained from the opportunity and would do it again in the same situation. This study enhanced the limited formal knowledge available regarding how faculty experience living in residential colleges with students.

The French Canadian founder population : lessons and insights for genetic epidemiological research

La population canadienne-française a une histoire démographique unique faisant d’elle une population d’intérêt pour l’épidémiologie et la génétique. Cette thèse vise à mettre en valeur les caractéristiques de la population québécoise qui peuvent être utilisées afin d’améliorer la conception et l’analyse d’études d’épidémiologie génétique. Dans un premier temps, nous profitons de la présence d’information généalogique détaillée concernant les Canadiens français pour estimer leur degré d’apparentement et le comparer au degré d’apparentement génétique. L’apparentement génétique calculé à partir du partage génétique identique par ascendance est corrélé à l’apparentement généalogique, ce qui démontre l'utilité de la détection des segments identiques par ascendance pour capturer l’apparentement complexe, impliquant entre autres de la consanguinité. Les conclusions de cette première étude pourront guider l'interprétation des résultats dans d’autres populations ne disposant pas d’information généalogique. Dans un deuxième temps, afin de tirer profit pleinement du potentiel des généalogies canadienne-françaises profondes, bien conservées et quasi complètes, nous présentons le package R GENLIB, développé pour étudier de grands ensembles de données généalogiques. Nous étudions également le partage identique par ascendance à l’aide de simulations et nous mettons en évidence le fait que la structure des populations régionales peut faciliter l'identification de fondateurs importants, qui auraient pu introduire des mutations pathologiques, ce qui ouvre la porte à la prévention et au dépistage de maladies héréditaires liées à certains fondateurs. Finalement, puisque nous savons que les Canadiens français ont accumulé des segments homozygotes, à cause de la présence de consanguinité lointaine, nous estimons la consanguinité chez les individus canadiens-français et nous étudions son impact sur plusieurs traits de santé. Nous montrons comment la dépression endogamique influence des traits complexes tels que la grandeur et des traits hématologiques. Nos résultats ne sont que quelques exemples de ce que nous pouvons apprendre de la population canadienne-française. Ils nous aideront à mieux comprendre les caractéristiques des autres populations de même qu’ils pourront aider la recherche en épidémiologie génétique au sein de la population canadienne-française.

The French Canadian founder population : lessons and insights for genetic epidemiological research

La population canadienne-française a une histoire démographique unique faisant d’elle une population d’intérêt pour l’épidémiologie et la génétique. Cette thèse vise à mettre en valeur les caractéristiques de la population québécoise qui peuvent être utilisées afin d’améliorer la conception et l’analyse d’études d’épidémiologie génétique. Dans un premier temps, nous profitons de la présence d’information généalogique détaillée concernant les Canadiens français pour estimer leur degré d’apparentement et le comparer au degré d’apparentement génétique. L’apparentement génétique calculé à partir du partage génétique identique par ascendance est corrélé à l’apparentement généalogique, ce qui démontre l'utilité de la détection des segments identiques par ascendance pour capturer l’apparentement complexe, impliquant entre autres de la consanguinité. Les conclusions de cette première étude pourront guider l'interprétation des résultats dans d’autres populations ne disposant pas d’information généalogique. Dans un deuxième temps, afin de tirer profit pleinement du potentiel des généalogies canadienne-françaises profondes, bien conservées et quasi complètes, nous présentons le package R GENLIB, développé pour étudier de grands ensembles de données généalogiques. Nous étudions également le partage identique par ascendance à l’aide de simulations et nous mettons en évidence le fait que la structure des populations régionales peut faciliter l'identification de fondateurs importants, qui auraient pu introduire des mutations pathologiques, ce qui ouvre la porte à la prévention et au dépistage de maladies héréditaires liées à certains fondateurs. Finalement, puisque nous savons que les Canadiens français ont accumulé des segments homozygotes, à cause de la présence de consanguinité lointaine, nous estimons la consanguinité chez les individus canadiens-français et nous étudions son impact sur plusieurs traits de santé. Nous montrons comment la dépression endogamique influence des traits complexes tels que la grandeur et des traits hématologiques. Nos résultats ne sont que quelques exemples de ce que nous pouvons apprendre de la population canadienne-française. Ils nous aideront à mieux comprendre les caractéristiques des autres populations de même qu’ils pourront aider la recherche en épidémiologie génétique au sein de la population canadienne-française.

Tagged tree broken as result of Hurricane Wilma, Shark River Slough

This material is based upon work supported by the National Science Foundation through the Florida Coastal Everglades Long-Term Ecological Research program under Cooperative Agreements #DBI-0620409 and #DEB-9910514. This image is made available for non-commercial or educational use only.