bluuebunny/crossref_metadata_2025 huggingface dataset:
From Government to Governance: Polish Regional Development Agencies in a Changing Regional Context
Authors: Ferry Martin
Published: August 2007

This article charts the evolving role of Regional Development Agencies (RDAs) in Poland. It argues that changes to regional institutional and policy environments, linked to processes of regionalisation, EU accession, and the administration of European Union structural funds, have prompted increasing diversification of RDA activities. Moreover, questions of democratic accountability and economic efficiency are becoming increasingly pointed. Has regionalisation boosted the democratic accountability and regional orientation of agencies? Has administrative reform simplified agencies' delivery of development programmes? What influence has the administration of structural funds had on this? The article explores these issues, stressing generally that theoretical analyses of RDA activities must take increasing account of agency “positioning,” i.e., their role and purpose in an increasingly crowded and complex regional policy arena. Future scenarios for the evolution of RDAs in Poland are also outlined.
A Minority at the Border: EU Enlargement and the Ukrainian Minority in Poland
Authors: Vermeersch Peter
Published: August 2007

This article examines the impact of the eastward enlargement of the European Union (EU) on the position of the Ukrainian minority in Poland. The enlargement process has set two conflicting developments into motion that both may have a serious influence on patterns of minority activism in countries at the peripheral borders of the enlarged EU. On one hand, there is a development toward increased protection of the external borders of the EU. On the other hand, a new trend has become perceptible within the EU toward increased political, security, economic, and cultural cooperation with the new neighboring countries in the east. Applying concepts from research on social movements and using statements by Ukrainian minority activists as the basis for an empirical analysis, this article explores how these two opposite developments have affected Ukrainian minority activism in Poland.
An Update on Monoclonal Antibody Therapies in Multiple Sclerosis
Authors: Choudry Bilal A. , Chan Jane W.
Published: August 2007

Multiple sclerosis (MS) is a complex disease that causes a great deal of disability, especially in the young adult population. There have been several immunomodulatory agents that have been approved by the Food and Drug Administration for MS, including glatiramer acetate, interferon-β 1a and -β 1b, mitoxantrone, and corticosteroids. The effectiveness of these therapies has not been optimal, and drugs, such as monoclonal antibodies, that more selectively target the pathogenetic process of MS have been sought. These agents have their own intrinsic limitations such as systemic inflammatory reactions, induction of neutralizing antiantibodies, and even life-threatening infectious processes. The agent that has been in the forefront of the discussion is natalizumab, a monoclonal antibody (mAb) against α 4 integrin, which shows much promise in suppressing MS activity. However, 3 individuals treated with natalizumab developed a life-threatening infection, progressive multifocal leukoencephalopathy. This article reviews the role of mAbs in the treatment of MS, particularly their advantages over other drugs and their limitations, which have to be overcome for these agents to be at the forefront in the treatment of MS.
Phenomenology
Authors: Wojnar Danuta M. , Swanson Kristen M.
Published: August 2007

Investigators who use phenomenological approaches to understand experiences of human healing, caring, and wholeness need to consider the differences that exist between descriptive and hermeneutic phenomenology. In this article, these two approaches are compared and contrasted with respect to roots, similarities, and differences. Guidelines are offered to assist prospective investigators in selecting the approach most suitable to personal cognitive style and beliefs about the ways humans experience and find meanings during transitions through wellness and illness to advance nursing knowledge in a holistic view.
A Theoretical Framework for Using Health Realization to Reduce Stress and Improve Coping in Refugee Communities
Authors: Halcón Linda L. , Robertson Cheryl L. , Monsen Karen A. , Claypatch Cindi C.
Published: August 2007

Refugees have faced extraordinarily stressful situations in their past, and many continue to experience stress daily as they cope with the refugee adjustment experience. A strengths-based, community-focused intervention known as Health Realization (HR) is a promising strategy for nurses to promote positive psychological outcomes in these populations. Although similar in some ways to cognitive therapy, the HR intervention emphasizes the role of thought versus the content of thought. It does not promote actively changing intrusive or negative thoughts but rather promotes an understanding that allows a degree of detachment from thoughts—a shift in consciousness that can provide relief and facilitate healing. An adapted stress and coping model provides a theoretical framework to test the effectiveness of using HR with refugees, which in turn provides a solid foundation for research that can support or refute the existing substantial anecdotal evidence for the use of this intervention in holistic nursing practice.
The Silence of Suffering
Authors: Kazanowski Mary , Perrin Kathleen , Potter Mertie , Sheehan Caryn
Published: August 2007

Suffering is an inevitable reality that student nurses may be unprepared to witness. The 14-week college course, Understanding Suffering, was developed to help students better understand the suffering experience. Content for the course was drawn from nursing, sociological, and theological perspectives. Students scored significantly higher on a post-course evaluation of empathy and stated they felt better prepared to intervene in difficult clinical situations involving suffering. Course development, assignments, and evaluation are described in the article.
Emergency response: Elearning for paramedics and firefighters
Authors: Taber Nancy
Published: August 2007

This article is based on an innovative research project with academics, software developers, and organizational pilot sites to design and develop elearning software for an emergency response simulation with supporting collaborative tools. In particular, this article focuses on the research that the author has conducted to provide the theoretical foundations for the project. After discussing the unique characteristics of the SIMergency project, the author provides a critical applied analysis of learning principles directly related to simulation and gaming; stresses the importance of balancing virtual methods with face-to-face interaction; and examines design principles that place learning before technology in an emergency response organizational context. This research, although concentrating on paramedics and firefighters, is transferable to other organizations, and it highlights the importance of collaborative learning. It also emphasizes the crucial use of simulations based on real life for preparing people to deal with stressful and challenging situations in their work.
Teaching Business Students About HIV and AIDS in the Workplace: Curriculum and Resources
Authors: Miller Alan N.
Published: August 2007

The significant and increasing number of people in the U.S. and global work-forces who are infected with HIV or who have AIDS must be managed differently from those who are not infected and those who have other life-threatening diseases. Business schools can prepare their MBA students to effectively, legally, and compassionately manage people with HIV infection or AIDS and to deal with all other workers who are affected by these conditions by offering a short, noncredit or one-credit, required course about how to do so. This article describes one such course that teaches students how to develop a workplace HIV/AIDS program, including policy development, manager and labor leader training, and employee and family education. Presentation options other than a stand-alone course for MBA students are considered as well.
Dissemination
Authors: Lawrenz Frances , Gullickson Arlen , Toal Stacie
Published: August 2007

Use of evaluation findings is a valued outcome for most evaluators. However, to optimize use, the findings need to be disseminated to potential users in formats that facilitate use of the information. This reflective case narrative uses a national evaluation of a multisite National Science Foundation (NSF) program as the setting for describing the evolution of, and strategic planning for, effectively disseminating evaluation findings and recommendations. The program being evaluated is NSF's Advanced Technological Education (ATE) program. The dissemination to more than 200 active ATE projects and other audiences forced the evaluation project to be creative in its approaches. The dissemination strategies are related to two very common types of evaluation information: surveys and site visits. Approaches used include Web postings of various reports, brochures, interactive data displays, guidebooks, and videoconferencing. Advantages and disadvantages in terms of use of the techniques by various audiences are discussed.
Youth Empowerment Evaluation: Learning Voice
Authors: Walker Kathrin
Published: August 2007

Including youth in the evaluation process can enhance the quality of the inquiry and be empowering for the participants, but it is not without challenges. In this article, several principles for youth-involved research and evaluation are outlined. These come from those who are pioneering this approach and from current research on the dilemmas of practice encountered by youth program leaders. These guidelines, along with the American Evaluation Association's Guiding Principles, are then applied to Dr. Luanda's case to explore how she might proceed and to consider how she might have avoided this ethical challenge.
Task-based research and language pedagogy
Authors: Ellis Rod
Published: August 2007

Two very different theoretical accounts of task-based language use and learning are critiqued and their relevance for language pedagogy discussed. One account, which will be referred to as the psycholinguistic perspective, draws on a computational model of second language (L2) acquisition (Lantolf, 1996). According to this perspective, tasks are viewed as devices that provide learners with the data they need for learning; the design of a task is seen as potentially determining the kind of language use and opportunities for learning that arise.Three different psycholinguistic models are discussed: Long’s Interaction Hypothesis, Skehan’s ‘cognitive approach’ and Yule’s framework of communicative efficiency. The second theoretical account of tasks is that provided by socio-cultural theory. This is premised on the claim that participants co-construct the ‘activity’ they engage in when performing a task, in accordance with their own socio-history and locally determined goals, and that, therefore, it is difficult to make reliable predictions regarding the kinds of language use and opportunities for learning that will arise. Socio-cultural theory emphasizes the dialogic processes (such as ‘scaffolding’) that arise in a task performance and how these shape language use and learning. Both theoretical approaches afford insights that are of value to task-based language pedagogy. The psycholinguistic approach provides information that is of importance for planning task-based teaching and learning. The socio-cultural approach illuminates the kinds of improvisation that teachers and learners need to engage in during task-based activity to promote communicative efficiency and L2 acquisition.
The role of individual and social variables in oral task performance
Authors: Dörnyei Zoltán , Kormos Judit
Published: August 2007

This paper reports on a data-based study in which we explored - as part of a larger-scale British-Hungarian research project - the effects of a number of affective and social variables on foreign language (L2) learners’ engagement in oral argumentative tasks. The assumption underlying the investigation was that students’ verbal behaviour in oral task situations is partly determined by a number of non-linguistic and non-cognitive factors whose examination may constitute a potentially fruitful extension of existing task-based research paradigms. The independent variables in the study included various aspects of L2 motivation and several factors characterizing the learner groups the participating students were members of (such as group cohesiveness and intermember relations), as well as the learners’ L2 proficiency and ‘willingness to communicate’ in their L1. The dependent variables involved objective measures of the students’ language output in two oral argumentative tasks (one in the learners’ L1, the other in their L2): the quantity of speech and the number of turns produced by the speakers. The results provide insights into the interrelationship of the multiple variables determining the learners’ task engagement, and suggest a multi-level construct whereby some independent variables only come into force when certain conditions have been met.
What task designers do
Authors: Johnson Keith
Published: August 2007

This paper describes part of a research project which is concerned with the design procedures followed by those engaged in designing pedagogic tasks for use in classrooms. The project as a whole is at first briefly described. The paper then focuses on that part of the project which involves actual observation of designers in the process of developing one specific task for class use. Two groups of designers are observed, specialist designers and non-specialists. Findings are presented under three headings. The first, ‘control procedures’, relates to the overall design patterns followed by the subjects. On this level, significant differences between specialists and non-specialists are identified. Second, the ‘design schemata’ of the subjects -the knowledge and belief systems they bring to the activity -are identified, particularly as they relate to the way design is undertaken. On this level, two broad designer types emerge, called language-oriented, and task-oriented. The main concern of the former is to develop tasks with valuable language content, while the latter are more concerned with providing what they regard as interesting and meaningful activities. The third heading, ‘heuristics’, deals with how specific and detailed design problems are tackled. On this level, a number of characteristics are identified, some though not all relating to the specialist/non-specialist distinction. The paper concludes with some observations regarding the production of a Task Design Guide, which the project undertook as part of its aim.
Exploring conversational shadowing
Authors: Murphey Tim
Published: August 2007

The background literature on the repeating of a conversation partner’s words, here called conversational shadowing, shows it to be naturally occurring in L1 acquisition and adult use. This study was motivated by the question ‘What happens when second language learners and native speakers actively shadow each other in conversation?’ I look closely at conversational shadowing through transcripts of recorded conversations between two Japanese learners of English talking with two English native speakers in mixed dyads in which they were instructed to shadow each other.

First, it was found that the different sets of data emerging from the two Japanese students reveal that there may be a variety of effective types of shadowing, from those which may lengthen auditory short-term memory to more interactive and naturally selective shadowing that includes commenting and questioning. Secondly, it was found that interactive conversational shadowing gives rise to the types of conversational adjustments and negotiations that are thought to positively affect language acquisition (Long, 1983) through their impact on negotiation, noticing, intake, and uptake. Thirdly, the data highlights different learning advantages for the non-native speakers (NNSs) when shadowing native speakers (NSs) and when being shadowed by NSs. Finally, I attempt to place shadowing developmentally within Vygotskian socio-cultural theory with reference to Bakhtin’s ventriloquation and to outline a generative action research agenda.
The research journal: a tool for promoting and understanding researcher development
Authors: Borg Simon
Published: August 2007

Forms of reflective writing such as diaries and journals are widely acknowledged as important tools in promoting both the development and the understanding of teachers. However, little attention has been awarded to the role these forms of writing can play in the development and understanding of researchers. In this paper I draw on my own experience of keeping a research journal during a study of language teaching to illustrate the significant contribution journal writing can make to deepening researchers’ understanding of all facets of the research processes. I also argue that such journals can provide other researchers with illuminating insight into the research process. Given these benefits to both writers and readers of research journals, I claim that the issue of reflective writing by researchers in language teaching merits much more discussion that it has been awarded to date.
Implicit knowledge, explicit knowledge and general language proficiency
Authors: Han Youngju , Ellis Rod
Published: August 2007

This paper explores ways of measuring implicit and explicit second language (L2) knowledge and examines the relationship between these measures and measures of general language proficiency. Scores were obtained from a timed oral production test, a timed grammaticality judgement test (administered twice), a delayed grammaticality judgement test and an interview designed to tap metalingual knowledge, all of which focused on learners’ knowledge of verb complementation in English. A factor analysis revealed a two-factor solution, reflecting a clear distinction between those measures that incorporated a time constraint (hypothesized to reflect implicit knowledge) and those that did not (hypothesized to tap explicit knowledge). Both factors were found to correlate with scores on the Secondary Level English Proficiency Test (SLEP). However, only one measure of explicit knowledge (the Delayed Grammaticality Judgement Test) was found to be significantly related to scores on the Test of English as a Foreign Language (TOEFL). The significance of these results for language teaching and testing is considered.
Investigating learners’ course diaries as explorations of language
Authors: Allison Desmond
Published: August 2007

Most recent accounts of work with diaries or journals on language courses have offered insights into learners’ attitudes towards course goals and activities and towards their own learning. The present study focuses more on the use of language course diaries as a means of language exploration by learners, looking specifically at diaries kept by 38 second-year undergraduate students in five tutorial groups during an English language course at the National University of Singapore. The investigation comprises a preliminary content analysis of the course diaries, a presentation of learners’ responses to a questionnaire, a fuller illustrative account of learners’ engagement with language issues in their diaries, and a commentary on teacher feedback and learner reactions. The discussion suggests implications for roles and responsibilities of learners and teachers, over a range of teaching circumstances, and points to other researchable issues to which course diary studies oriented towards language might contribute.
Girls being quiet: a problem for foreign language classrooms?
Authors: Sunderland Jane
Published: August 2007

The majority of quantitative and arguably of qualitative studies of gendered classroom discourse have produced depressing findings in terms of the quality and quantity of teacher attention female students attract/receive and the amount of talk they produce. In the language classroom, considered by many teachers to be a ‘girls’ world’, findings may be rather different.
A community of learners: Cambodians in an adult ESL classroom
Authors: Hardman Joel C.
Published: August 2007

This article focuses on the English literacy development of Cambodian adults living in the United States. Using an adult ESL classroom as a context, the researcher describes: how the Cambodian adults, literate in Khmer, participate in each other’s English literacy development; how Cambodian children, fluent though not typically literate in Khmer, participate in their parents’ development of English literacy; and how a Cambodian teacher participates in his students’ development of English literacy. To answer these questions it examines how the participants draw on multiple linguistic competencies to help each other accomplish classroom tasks. In contrast to traditional home-school discontinuity studies, it is argued that people have multiple ways for sharing knowledge and creating environments for learning, especially in the case of immigrant communities that are in the process of cultural change and adaptation.
Does aid increase growth?
Authors: Morrissey Oliver
Published: August 2007

Is aid effective in increasing growth rates of recipient countries? This is the burning question in any economic evaluation of aid effectiveness, yet there is no consensus on the answer. Recent advances in growth theory help us to identify the various mechanisms by which aid can increase growth, notably through increasing investment in physical and human capital. The empirical evidence has tended to focus on aid effectiveness by examining its impact as (physical) investment and, more recently, by considering the relationship between aid and government economic policy. There is an increasing body of evidence that aid does work, conditional on other variables in the growth regression.
Postcolonialism, feminism and development: intersections and dilemmas
Authors: McEwan Cheryl
Published: August 2007

In recent years, postcolonial and feminist theories have had enormous consequences for how development is conceptualized. In light of this, the present paper explores the intersections between postcolonialism, feminism and development. It does so by, first, reviewing the primary issues underpinning postcolonial approaches to development. Secondly, the paper reviews the emergence of postcolonial feminisms and explores the key areas of debate generated by these approaches within development studies. Thirdly, the paper examines some of the dilemmas and criticisms provoked by these approaches, and concludes by exploring the ways in which postcolonial feminist approaches might continue to make significant advancement in rethinking development.
Commodity futures markets in LDCs: a review and prospects
Authors: Morgan C. W.
Published: August 2007

Recent moves by the World Bank to devise market-based approaches for dealing with commodity price risk provide a fresh impetus for research in the area of commodity futures markets as a policy option. Since the collapse of the International Commodity Agreements there has been little progress in finding a solution to the perennial problem of price risk arising from price volatility. This paper aims to provide a background to the more general issue of development and growth in less developed countries (LDCs) by examining past and current policy attempts to reduce the effects of price volatility in primary commodity markets.
Social capital formation and development in marginal communities, with reference to post-Soviet societies
Authors: Osgood Maggie , Ong Bie Nio
Published: August 2007

This paper re-assesses the relevant literature on social capital formation and its development role in marginal communities, using the case example of the Crimean Tatars. In order to review the current literature, a modified systematic review procedure has been adopted, leading to the formulation of a more thoroughly grounded conceptual framework. The concept of social capital was originally developed as a tool for explaining different developmental outcomes in societies with otherwise similar resources. By integrating various theoretical strands, a complex understanding of the various forms and levels of social capital emerges. The value of the concept of social capital is examined, and attention is paid to both its positive and negative meanings. Of particular interest for development studies is the analysis of the impact of external intervention on social capital formation. This is then tested in terms of its relevance for marginal communities, and specifically when thinking through alternative policy effects.
Convergence: myths and realities
Authors: Rapley John
Published: August 2007

Although economists have become increasingly agnostic about convergence, neo-liberal policies tend to presume it. Such policies assume that economic liberalization, open markets and minimalist states will encourage the globalization of capital, thereby spreading economic growth from the First World to the Third World. In this, they resemble orthodox Marxist theories of the internationalization of capital. However, divergence rather than convergence continues to prevail in the global economy, and neo-liberal policies may be intensifying these trends. It appears the flaw common to both neo-liberal and Marxist thinking on convergence is a supply-sided approach that neglects the important role demand plays in attracting investment.
The North-South terms of trade debate: a re-examination
Authors: Sarkar Prabirjit
Published: August 2007

Contrary to the classical proposition, the works of Prebisch and Singer launched the controversial hypothesis of long-term decline in the terms of trade of primary products vis-à-vis manufactures and a corresponding decline in the terms of trade of the South vis-à-vis the North. The present study traces the origin and evolution of the hypothesis and reviews the related statistical debate. It concludes that the empirical base of the Prebisch-Singer hypothesis is much stronger than it appeared in earlier decades. Reviewing some of the North-South models, the study also finds theoretical support for the Prebisch-Singer hypothesis.
Cooperation of the proapoptotic receptor agonist rhApo2L/TRAIL with the CD20 antibody rituximab against non-Hodgkin lymphoma xenografts
Authors: Daniel Dylan , Yang Becky , Lawrence David A. , Totpal Klara , Balter Inessa , Lee Wyne P. , Gogineni Alvin , Cole Mary J. , Yee Sharon Fong , Ross Sarajane , Ashkenazi Avi
Published: August 2007

Recombinant human rhApo2L/TRAIL selectively stimulates apoptosis in various cancer cells through its receptors DR4 and DR5, and is currently in clinical trials. Preclinical studies have established antitumor activity of rhApo2L/TRAIL in models of epithelial cancers; however, efficacy in non-Hodgkin lymphoma (NHL) models is not well studied. Of 7 NHL cell lines tested in vitro, rhApo2L/TRAIL stimulated apoptosis in BJAB, Ramos RA1, and DoHH-2 cells. Rituximab, a CD20 antibody used to treat certain types of NHL, augmented rhApo2L/TRAIL-induced caspase activation in Ramos RA1 and DoHH2 but not BJAB or SC-1 cells, through modulation of intrinsic rather than extrinsic apoptosis signaling. In vivo, rhApo2L/TRAIL and rituximab cooperated to attenuate or reverse growth of tumor xenografts of all 4 of these cell lines. Depletion of natural killer (NK) cells or serum complement substantially reduced combined efficacy against Ramos RA1 tumors, suggesting involvement of antibodydependent cell- and complement-mediated cytotoxicity. Both agents exhibited greater activity against disseminated than subcutaneous BJAB xenografts, and worked together to inhibit or abolish disseminated tumors and increase survival. Moreover, rhApo2L/TRAIL helped circumvent acquired rituximab resistance of a Ramos variant. These findings provide a strong rationale for clinical investigation of rhApo2L/TRAIL in combination with rituximab as a novel strategy for NHL therapy.
Extracellular calcium sensing promotes human B-cell activation and function
Authors: Hammond Caitlin M. , White Dionne , Tomic Jelena , Shi Yonghong , Spaner David E.
Published: August 2007

Calcium is a second messenger for many signaling pathways in B cells, but its role as a receptor ligand has not been well characterized. However, pulses of free calcium were found to cause the rapid release of internal calcium stores in normal human B cells. This response appeared to be mediated by a cell surface protein with receptor properties as it could be blocked by pretreatment with trypsin and with kinase and phospholipase Cγ inhibitors. The calcium receptor on B cells was not the conventional calcium-sensing receptor (CaSR) since B cells did not express CaSR and calcium-induced responses could not be blocked by specific CaSR inhibitors. B-cell responses to extracellular calcium activated phosphoinositide-3 kinase/AKT, calcineurin, extracellular signal regulated kinase, p38 mitogen-activated protein kinase, protein kinase C, Ca2+/calmodulin kinase II, and nuclear factor-κB signaling pathways, and resulted in transcription of the early response gene, CD83. This extracellular calcium sensor enhanced B-cell responses to Toll-like receptor, B-cell receptor, and cytokine receptor agonists. These findings suggest a means by which B cells prepare to engage in immune responses by responding to calcium fluctuations in their environment.
T cell–depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin
Authors: Jakubowski Ann A. , Small Trudy N. , Young James W. , Kernan Nancy A. , Castro-Malaspina Hugo , Hsu Katherine C. , Perales Miguel-Angel , Collins Nancy , Cisek Christine , Chiu Michelle , van den Brink Marcel R. M. , O'Reilly Richard J. , Papadopoulos Esperanza B.
Published: August 2007

Antithymocyte globulin (ATG) has been used in allogeneic stem-cell transplantation to prevent graft rejection and graft-versus-host disease (GvHD). Its use, however, has been associated with delayed T-cell reconstitution and prolonged susceptibility to opportunistic infections (OIs) especially in patients undergoing T cell–depleted (TCD) transplantation. Recently, a prospective trial was conducted in 52 adult patients (median age, 47 years) with various hematologic malignancies undergoing TCD transplantation from HLA-matched related donors without the use of ATG. The cytoreductive regimen consisted of hyperfractionated total body irradiation (HFTBI), thiotepa, and fludarabine. The preferred source of the graft was peripheral blood stem cells (PBSCs). No additional graft rejection or GvHD prophylaxis was given. All evaluable patients engrafted without any immune-mediated graft rejections. Disease-free survival (DFS) at 3 years was 61% in all patients, and 70% in patients with standard-risk disease. Acute GvHD was limited to grade 2 in 8% and chronic GvHD in 9% of patients. Life-threatening OIs occurred in 3 of 52 patients and was fatal in 1. This study demonstrates durable engraftment with a low incidence of GvHD despite the lack of ATG, as well as the curative potential of this regimen.
Analysis of the role of retrotransposition in gene evolution in vertebrates
Authors: Yu Zhan , Morais David , Ivanga Mahine , Harrison Paul M
Published: August 2007

Background

The dynamics of gene evolution are influenced by several genomic processes. One such process is retrotransposition, where an mRNA transcript is reverse-transcribed and reintegrated into the genomic DNA.

Results

We have surveyed eight vertebrate genomes (human, chimp, dog, cow, rat, mouse, chicken and the puffer-fish T. nigriviridis), for putatively retrotransposed copies of genes. To gain a complete picture of the role of retrotransposition, a robust strategy to identify putative retrogenes (PRs) was derived, in tandem with an adaptation of previous procedures to annotate processed pseudogenes, also called retropseudogenes (RψGs). Mammalian genomes are estimated to contain 400–800 PRs (corresponding to ~3% of genes), with fewer PRs and RψGs in the non-mammalian vertebrates. Focussing on human and mouse, we aged the PRs, analysed for evidence of transcription and selection pressures, and assigned functional categories. The PRs have significantly less transcription evidence mappable to them, are significantly less likely to arise from alternatively-spliced genes, and are statistically overrepresented for ribosomal-protein genes, when compared to the proteome in general. We find evidence for spurts of gene retrotransposition in human and mouse, since the lineage of either species split from the dog lineage, with >200 PRs formed in mouse since its divergence from rat. To examine for selection, we calculated: (i) Ka/Ks values (ratios of non-synonymous and synonymous substitutions in codons), and (ii) the significance of conservation of reading frames in PRs. We found >50 PRs in both human and mouse formed since divergence from dog, that are under pressure to maintain the integrity of their coding sequences. For different subsets of PRs formed at different stages of mammalian evolution, we find some evidence for non-neutral evolution, despite significantly less expression evidence for these sequences.

Conclusion

These results indicate that retrotranspositions are a significant source of novel coding sequences in mammalian gene evolution.
Integrated network reconstruction, visualization and analysis using YANAsquare
Authors: Schwarz Roland , Liang Chunguang , Kaleta Christoph , Kühnel Mark , Hoffmann Eik , Kuznetsov Sergei , Hecker Michael , Griffiths Gareth , Schuster Stefan , Dandekar Thomas
Published: August 2007

Background

Modeling of metabolic networks includes tasks such as network assembly, network overview, calculation of metabolic fluxes and testing the robustness of the network.

Results

YANAsquare provides a software framework for rapid network assembly (flexible pathway browser with local or remote operation mode), network overview (visualization routine and YANAsquare editor) and network performance analysis (calculation of flux modes as well as target and robustness tests). YANAsquare comes as an easy-to-setup program package in Java. It is fully compatible and integrates the programs YANA (translation of gene expression values into flux distributions, metabolite network dissection) and Metatool (elementary mode calculation). As application examples we set-up and model the phospholipid network in the phagosome and genome-scale metabolic maps of S.aureus, S.epidermidis and S.saprophyticus as well as test their robustness against enzyme impairment.

Conclusion

YANAsquare is an application software for rapid setup, visualization and analysis of small, larger and genome-scale metabolic networks.
Translational machinery of the chaetognath Spadella cephaloptera: a transcriptomic approach to the analysis of cytosolic ribosomal protein genes and their expression
Authors: Barthélémy Roxane M , Chenuil Anne , Blanquart Samuel , Casanova Jean-Paul , Faure Eric
Published: August 2007

Background

Chaetognaths, or arrow worms, are small marine, bilaterally symmetrical metazoans. The objective of this study was to analyse ribosomal protein (RP) coding sequences from a published collection of expressed sequence tags (ESTs) from a chaetognath (Spadella cephaloptera) and to use them in phylogenetic studies.

Results

This analysis has allowed us to determine the complete primary structures of 23 out of 32 RPs from the small ribosomal subunit (SSU) and 32 out of 47 RPs from the large ribosomal subunit (LSU). Ten proteins are partially determined and 14 proteins are missing. Phylogenetic analyses of concatenated RPs from six animals (chaetognath, echinoderm, mammalian, insect, mollusc and sponge) and one fungal taxa do not resolve the chaetognath phylogenetic position, although each mega-sequence comprises approximately 5,000 amino acid residues. This is probably due to the extremely biased base composition and to the high evolutionary rates in chaetognaths. However, the analysis of chaetognath RP genes revealed three unique features in the animal Kingdom. First, whereas generally in animals one RP appeared to have a single type of mRNA, two or more genes are generally transcribed for one RP type in chaetognath. Second, cDNAs with complete 5'-ends encoding a given protein sequence can be divided in two sub-groups according to a short region in their 5'-ends: two novel and highly conserved elements have been identified (5'-TAATTGAGTAGTTT-3' and 5'-TATTAAGTACTAC-3') which could correspond to different transcription factor binding sites on paralog RP genes. And, third, the overall number of deduced paralogous RPs is very high compared to those published for other animals.

Conclusion

These results suggest that in chaetognaths the deleterious effects of the presence of paralogous RPs, such as apoptosis or cancer are avoided, and also that in each protein family, some of the members could have tissue-specific and extra-ribosomal functions. These results are congruent with the hypotheses of an allopolyploid origin of this phylum and of a ribosome heterogeneity.
Thioredoxin reductase is a key factor in the oxidative stress response of Lactobacillus plantarum WCFS1
Authors: Serrano L Mariela , Molenaar Douwe , Wels Michiel , Teusink Bas , Bron Peter A , de Vos Willem M , Smid Eddy J
Published: August 2007

Background

Thioredoxin (TRX) is a powerful disulfide oxido-reductase that catalyzes a wide spectrum of redox reactions in the cell. The aim of this study is to elucidate the role of the TRX system in the oxidative stress response in Lactobacillus plantarum WCFS1.

Results

We have identified the trxB1-encoded thioredoxin reductase (TR) as a key enzyme in the oxidative stress response of Lactobacillus plantarum WCFS1.

Overexpression of the trxB1 gene resulted in a 3-fold higher TR activity in comparison to the wild-type strain. Subsequently, higher TR activity was associated with an increased resistance towards oxidative stress. We further determined the global transcriptional response to hydrogen peroxide stress in the trxB1-overexpression and wild-type strains grown in continuous cultures. Hydrogen peroxide stress and overproduction of TR collectively resulted in the up-regulation of 267 genes. Additionally, gene expression profiling showed significant differential expression of 27 genes in the trxB1-overexpression strain. Over expression of trxB1 was found to activate genes associated with DNA repair and stress mechanisms as well as genes associated with the activity of biosynthetic pathways for purine and sulfur-containing amino acids. A total of 16 genes showed a response to both TR overproduction and hydrogen peroxide stress. These genes are involved in the purine metabolism, energy metabolism (gapB) as well as in stress-response (groEL, npr2), and manganese transport (mntH2).

Conclusion

Based on our findings we propose that overproduction of the trxB1-encoded TR in L. plantarum improves tolerance towards oxidative stress. This response coincides with simultaneous induction of a group of 16 transcripts of genes. Within this group of genes, most are associated with oxidative stress response. The obtained crossover between datasets may explain the phenotype of the trxB1-overexpression strain, which appears to be prepared for encountering oxidative stress. This latter property can be used for engineering robustness towards oxidative stress in industrial strains of L. plantarum.
Microglial activation in the hippocampus of hypercholesterolemic rabbits occurs independent of increased amyloid production
Authors: Xue Qing-Shan , Sparks D Larry , Streit Wolfgang J
Published: August 2007

Background

Rabbits maintained on high-cholesterol diets are known to show increased immunoreactivity for amyloid beta protein in cortex and hippocampus, an effect that is amplified by presence of copper in the drinking water. Hypercholesterolemic rabbits also develop sporadic neuroinflammatory changes. The purpose of this study was to survey microglial activation in rabbits fed cholesterol in the presence or absence of copper or other metal ions, such as zinc and aluminum.

Methods

Vibratome sections of the rabbit hippocampus and overlying cerebral cortex were examined for microglial activation using histochemistry with isolectin B4fromGriffonia simplicifolia. Animals were scored as showing either focal or diffuse microglial activation with or without presence of rod cells.

Results

Approximately one quarter of all rabbits fed high-cholesterol diets showed evidence of microglial activation, which was always present in the hippocampus and not in the cortex. Microglial activation was not correlated spatially with increased amyloid immunoreactivity or with neurodegenerative changes and was most pronounced in hypercholesterolemic animals whose drinking water had been supplemented with either copper or zinc. Controls maintained on normal chow were largely devoid of neuroinflammatory changes, but revealed minimal microglial activation in one case.

Conclusion

Because the increase in intraneuronal amyloid immunoreactivity that results from administration of cholesterol occurs in both cerebral cortex and hippocampus, we deduce that the microglial activation reported here, which is limited to the hippocampus, occurs independent of amyloid accumulation. Furthermore, since neuroinflammation occurred in the absence of detectable neurodegenerative changes, and was also not accompanied by increased astrogliosis, we conclude that microglial activation occurs because of metabolic or biochemical derangements that are influenced by dietary factors.
Fez1/Lzts1 a new mitotic regulator implicated in cancer development
Authors: Vecchione Andrea , Croce Carlo M , Baldassarre Gustavo
Published: August 2007

Considerable evidence has accumulated suggesting that cancer has genetic origin, based on the development of genomic alterations, such as deletions, mutations, and/or methylations in critical genes for homeostasis of cellular functions, including cell survival, DNA replication and cell cycle control. Mechanism controlling the precise timing and sequence of cell cycle events as well as checkpoints insuring fidelity of those events are key targets that when disrupted could result in tumorigenesis. Mitosis is the process by which a cell duplicates its genetic information (DNA), in order to generate two, identical, daughter cells. In addition each daughter cell must receive one centrosome and the appropriate complements of cytoplasm and organelles. This process is conventionally divided in to five distinct stages: prophase, prometaphase, metaphase, anaphase and telophase that correspond to a different morphology of the cell. The entry into mitosis (M) is under the control of the cyclin dependent kinase Cdk1. During G2, the kinases Wee1 and Myt1 phosphorylate Cdk1 at T14/Y15 residues, rendering it inactive. The transition from G2 to M is promoted by the activation of Cdk1 via dephosphorylation by the Cdk1 phosphatase Cdc25C. Activated Cdk1 complexes translocate into the nucleus during prophase where phosphorylate numerous substrates in order to enhance their activation as the cells progresses trough prophase, prometaphase, and metaphase.

Recently we identified a new player: FEZ1/LZTS1 that contributes to the fine-tuning of the molecular events that determine progression through mitosis, and here will review its role in cancer development and in M phase regulation.
Insulin Secretion Is Increased in Pancreatic Islets of Neuropeptide Y-Deficient Mice
Authors: Imai Yumi , Patel Hiral R. , Hawkins Evan J. , Doliba Nicolai M. , Matschinsky Franz M. , Ahima Rexford S.
Published: August 2007

Neuropeptide Y (NPY), whose role in appetite regulation is well known, is also expressed in pancreatic islets. Although previous studies indicated that application of NPY to pancreatic islets inhibits insulin secretion, its physiological role in the regulation of insulin secretion is not fully understood. We hypothesized that NPY in islets tonically suppresses insulin secretion and the reduction of islet NPY increases insulin secretion. To address the hypothesis, islet function of NPY-deficient mice was analyzed. Although there was little change in glucose homeostasis in vivo, pancreatic islets from NPY-deficient mice had higher basal insulin secretion (1.5 times), glucose-stimulated insulin secretion (1.5 times), and islet mass (1.7 times), compared with wild-type mouse. Next we sought to determine whether the expression of NPY and Y1 receptor in islets was altered in hyperinsulinemia associated with obesity. Islets from C57BL/6J mice on a high-fat diet had 1.9 times higher basal insulin secretion and 2.4 times higher glucose-stimulated insulin secretion than control mice, indicating islet adaptation to obesity. Expression of NPY and Y1 receptor mRNA levels was decreased by 70 and 64%, respectively, in high-fat diet islets, compared with controls. NPY and Y1 receptor in islets were also reduced by 91 and 80%, respectively, in leptin-deficient ob/ob mice that showed marked hyperinsulinemia. Together these results suggest that endogenous NPY tonically inhibits insulin secretion from islets and a reduction of islet NPY may serve as one of the mechanisms to increase insulin secretion when islets compensate for insulin resistance associated with obesity.
Changes in Adiponectin and Inflammatory Genes in Response to Hormonal Imbalances in Female Mice and Exacerbation of Depot Selective Visceral Adiposity by High-Fat Diet: Implications for Insulin Resistance
Authors: Zhang Hui , Chen Xinlei , Aravindakshan Jayaprakash , Sairam M. Ram
Published: August 2007

Early obesity and late onset of insulin resistance associated with hormonal imbalances occur in FSH receptor-deficient follitropin receptor knockout female mice. This study tests the hypothesis that chronic high-fat diet aggravates obesogenic changes in a depot-specific manner and explores some molecular links of hormone imbalances with insulin resistance. In SV 129 mice, hormonal imbalances seem obligatory for exacerbation of diet-induced obesity. Visceral adiposity, glucose intolerance, and lipid disturbances in 9-month follitropin receptor knockout females were associated with decrease in adiponectin signaling. High-molecular-weight plasma adiponectin and adipose tissue adiponectin mRNA were decreased. Adiponectin receptors R1 and R2 mRNA was selectively altered in mesenteric fat but not periuterine fat. R2 decreased in the liver and R1 was higher in muscle. Whereas hepatic adenosine monophosphate T-activated protein kinase activity was down-regulated, both phosphoenolpyruvate carboxykinase and glucose-6-phosphatase enzymes were up-regulated. Longitudinally, diminishing sex hormone signaling in adipose tissue was associated with progressive down-regulation of adiponectin activity and gradual impaired glucose tolerance. Chronic high-fat diet in SV129 wild-type mice did not produce overt obesity but induced visceral fat depot changes accompanied by liver lipid accumulation, high cholesterol, and up-regulation of inflammation gene mRNAs. Thus, TNF-α, C-C motif chemokine receptor-2, and C-C motif chemokine ligand-2 were selectively elevated in mesenteric fat without altering glucose tolerance and adiponectin signaling. Our study highlights adiponectin signaling and regulation to be involved in hormone imbalance-induced insulin resistance and demonstrates selective visceral adipose depot alterations by chronic high-fat diet and induction of inflammatory genes.