bluuebunny/crossref_metadata_2025 huggingface dataset:
A Taste of Honey Is Worse Than None at All?
Authors: Bale Tim , Bergman Torbjörn
Published: February 2006

Some parties support rather than join the executive, thereby operating in a grey area between opposition and office – in governance but not in government. Previous research on the New Zealand Greens’ experience as a support party has shown that this liminal position may prove a blessing or a curse – or, more likely, a mixture of both. This article compares the experience of the Swedish Greens. While the Swedish party gained more on policy, it suffered the same frustrations as its Kiwi counterpart with regard to consultation, to the media and to a government that could potentially find support elsewhere. It, too, avoided overwhelming internal tensions, but was likewise left wanting more. Neither party broke into government at the next election, but tried to put lessons learned into practice when supporting centre–left cabinets once again. That the challenges encountered were so similar suggests the possibility that they are common to support parties elsewhere.
Implementation of Political Party Gender Quotas
Authors: Davidson-Schmich Louise K.
Published: February 2006

The use of gender quotas to increase women's political representation in legislatures has expanded in recent years. Scholars have identified three main categories of gender quotas, including constitutional, election law and political party quotas. While considerable attention has been devoted to classifying types of quotas, to explaining why they were adopted and to investigating which quota provisions are most effective, little is known about the actual implementation of political party gender quotas. This article is a first step in explaining when parties live up to their promises to promote women's representation and when they fail to do so. Focusing on Germany, I examine four parties’ experiences in implementing quotas in 16 states over a decade. I argue that while structural factors such as the electoral and party systems as well as the supply and demand of female candidates are not unimportant, cultural variables best explain whether or not parties actually comply with their own quotas.
District Magnitude, Social Heterogeneity and Local Party System Fragmentation
Authors: Geys Benny
Published: February 2006

Scholars analysing party system structures have generally followed two approaches. The ‘institutional’ approach emphasizes the role of electoral laws, while the ‘sociological’ approach highlights the effect of socioeconomic heterogeneity. Recently, evidence based on cross-country data indicated that a high level of fragmentation requires both a permissive electoral system and substantial socio-economic heterogeneity. As electoral rules have their main impact at the level of the constituency, using country-level data may not be ideal, however. Moreover, previous results appear to be driven by the inclusion of single-member district states. Both these caveats are addressed in this article. Based on a sample of Belgian municipal elections over the period 1982–2000, I show that the model incorporating an interaction between heterogeneity and district magnitude significantly outperforms specifications that disregard the interaction effect (a) at the constituency level and (b) in (mediumsize) multi-member districts.
Ethics and power in community-campus partnerships for research
Authors: Boser Susan
Published: February 2006

The past 20 years have seen a strong emergence of participatory approaches in social research. Such efforts typically include the researched in defining the questions, in data collection and analysis, and in interpreting and taking action based on the research findings. The objective is co-generating knowledge and, potentially, sharing decision-making based on that knowledge. This movement toward participatory research brings new sets of social relations for research and, as such, presents a new set of ethical challenges. The current framework for understanding the ethical issues involved in research is predicated on post-positivist epistemological assumptions of a distanced objectivist research stance, and thus is ill-suited for examining the ethics of participatory research. This article shall address this gap, outlining the potential ethical implications and presenting a framework for considering the ethical questions involved in participatory research partnerships.
And they shall be known by their deeds
Authors: Hilsen Anne Inga
Published: February 2006

What makes something action research (AR) or someone an action researcher? In this article, I address several questions aimed at clarifying the ethical and methodological foundation of my action research practice: How can I define my research within the many AR traditions? How do I define the ethical foundation of my AR, and why is it important for me, as an action researcher, to discuss and acknowledge my ethical foundation? What is the grounding of my research practice? There are three pivots in my argument on which I will elaborate in this article: human interdependency; cogeneration of knowledge; and fairer power relations. I base my argument on the premise that human life is relational and thus human practice becomes the centre of attention for both scientific and ethical reasons. As the title implies, I argue that it is through our practice that human beings ‘live our ethics’. For me, as an action researcher, this means that it is through my scientific practice that I demonstrate my ethical foundation. To illustrate the empirical consequences of this position, I use the experiences from an ongoing three-years, national, organizational development project (2003–2005) in the National Insurance Service (NIS) in Norway.
The ethics of silence
Authors: Lundy Patricia , McGovern Mark
Published: February 2006

Using a case study of the Ardoyne Commemoration Project (ACP), a community-based ‘truth-telling’ project in the North of Ireland, this article explores the role that action research can play in researching sensitive topics in violently divided societies. The article focuses on the ethics of carrying out research that could be potentially harmful for participants and researchers. The principles that underpinned the work of the ACP, including participation, local ownership and control, and the role of ‘insiders’ are critically examined. The article argues that in situations where political violence has occurred and marginalized groups have experienced social injustice, it is ethically impossible and morally reprehensible for social researchers to remain detached and silent. Action research methodologies are framed by a commitment to social justice, giving voice to those who are usually silenced, challenging structures of oppression and acting withordinary people to bring about social change –therefore they offer appropriate research models for engaging in community-based ‘truth-telling’ in post-conflict situations.
Between a rock and a (very) hard place
Authors: Judah Mary-Lee , Richardson George H.
Published: February 2006

Conversations with teachers and professional development leaders enable us, as researchers, to highlight the ambiguous promise of action research within the context of mandated teacher professional development in the province of Alberta, Canada. From this departure, we investigate how educators believe action research projects influence their professional practices and we explore the question of the validity of using state-mandated action research projects as a means of bringing about authentic teacher professional development. Using conversations, we recount the experiences of three teachers who took part in two separate action research projects. As the conversations we present underscore, many teachers involved in state-mandated school-based projects found themselves caught between competing discourses of personal empowerment and individual autonomy on the one hand and externally driven measures of accountability and excellence on the other. In this complex and ambiguous location and within the context of their involvement in action research projects, the three teachers in this study negotiated their own understandings of professional development.
Intellectual property and action research
Authors: Greenwood Davydd J. , Brydon-Miller Mary , Shafer Carla
Published: February 2006

This brief article offers an overview of the issue of intellectual property and the ways in which this intersects with the practice and dissemination of action research. Particular attention is paid to various forms of co-authorship and to the impact of developing forms of information and communication technologies on the question of intellectual property.
A re-examination of the relationship between action research and human subjects review processes
Authors: Brydon-Miller Mary , Greenwood Davydd
Published: February 2006

In this brief article, we review the history of the human subjects review process and identify key aspects of that review as they relate to action research. In particular, we examine the issues of coercion, predictability, confidentiality, and risk –concerns central to the criteria used in current review processes but reflecting fundamental differences in the basic conceptualization of ethical practice as this is understood in action research.
Reflexivity
Authors: Arber Anne
Published: February 2006

In this article I focus on what it means to have a dual identity as a practitioner and a researcher within an ethnographic research study in the context of a hospice. I discuss moments when I experienced the tension between the roles of researcher and practitioner during fieldwork. I discuss some of the difficulties of managing the boundary between closeness and distance in terms of the observer and participant roles adopted. I explore the challenges for the researcher with a dual identity and how methods of reflexive accounting enhance the credibility of such a study. Thus I document the lived experience of my fieldwork; my thoughts and feelings when the insider and outsider identities collide; and how the identity crisis that resulted was resolved.
In command of care: Toward the theory of congruent leadership
Authors: Stanley David
Published: February 2006

This is the second of two papers that discuss clinical leadership in the light of a research study which explored who the clinical nurse leaders are, what the characteristics and qualities of clinical leaders might be, why some nurses are seen as clinical leaders and what their experiences might be (Part 1 (Stanley, 2006)). Outlined are contemporary views about leadership and nursing, with emphasis on transformational leadership. Also explored is the new theory of congruent leadership. It is proposed that congruent leadership is a theory best suited for understanding clinical leadership because it is defines leadership in terms of a match (congruence) between the activities, actions and deeds of the leader and the leader's values, principles and beliefs.
The politics of the evidencebased practice movements
Authors: Rycroft-Malone Jo
Published: February 2006

In the United Kingdom the election of the Labour government in 1997 signalled the arrival of evidence-based policy making based on a philosophy of ‘what counts is what works’. Mirroring the emphasis on evidence-based policy-making has been a concern about encouraging the use of evidence in practice. As an ideology it has penetrated the consciousness, discourse and working practices of professionals. However, despite the apparent engagement with evidence-based approaches to care, there remain a number of key areas that stimulate discussion and warrant debate. This discussion paper highlights some of these issues and considers their implications. Specifically, the political context of the evidence-based movements is considered and the resulting consequences outlined. These include issues about how nursing has signed up to evidence-based practice, the way in which evidence is conceptualised and the continuing gap between evidence and practice. Finally, a number of issues are presented that need to be tackled if there is a genuine desire to improve the evidence base and increase its influence on policy and practice.
A study of quality of life in Internet health chat room users
Authors: Holmes Susan
Published: February 2006

Maintenance of quality of life (QoL) is central to healthcare and an increasingly important outcome of care provision reflecting enhanced awareness of the need to consider the effects of a disease or treatment on a patient's life. However, while its assessment has intuitive appeal it is predicated on the belief that QoL can be effectively defined, assessed and quantified. Achieving this is, however, difficult as individuals value different things and, it is claimed, often define QoL differently; there are no ‘generally agreed referents' and no ‘gold standard’ through which it can be measured. This may significantly affect the value and the uses to which such data can be put.

The study described here represents the first stage of a programme of work focusing upon defining QoL as it is currently perceived in the UK; it relied upon a qualitative, descriptive survey involving a sample of Internet health chat room users. It attempts to define QoL and to identify the factors contributing to life quality in these respondents. A subsidiary aim was to evaluate the use of email as a recruitment tool in such research.

A common definition was difficult to find but, in general terms, is taken to represent ‘what you think of your life’. Within this a range of factors are seen to contribute to individual perceptions and it was possible to identify those appearing to determine perceptions of QoL in this study population. Email was an effective route for recruiting subjects in this work.
Developing a best practice framework to benchmark research and development activity in nursing and midwifery
Authors: Mccance Tanya V. , Fitzsimons Donna , Armstrong Nicola C.
Published: February 2006

Clinical and social care governance provides a strategic climate in which research and development (R&D) is a key component. Within this context, nurses and midwives have the opportunity and responsibility to make a difference to the quality of patient care by raising the profile of their R&D activity. The R&D Best Practice Framework advanced in this paper has been developed as a mechanism to identify good practice and to help build a more positive culture within which nursing and midwifery research and development can flourish. The aim of the Framework was to identify explicit criteria for developing the nursing and midwifery R&D agenda, against which organisations can benchmark activity. The R&D Best Practice Framework was developed using a systematic approach, and resulted in the formulation of best practice statements relating to key stakeholder groups including health and care providers, education providers and R&D funders. Statements were themed under six headings: strategy development; building capacity; infrastructure; partnership working; research in practice; and outcome assessment. The potential exists for the Framework to be translated across a range of settings, to be used by organisations as a benchmark for current activity, and as a tool which can facilitate future planning.
Up-regulation of asparagine synthetase expression is not linked to the clinical response l-asparaginase in pediatric acute lymphoblastic leukemia
Authors: Appel Inge M. , den Boer Monique L. , Meijerink Jules P. P. , Veerman Anjo J. P. , Reniers Nathalie C. M. , Pieters Rob
Published: February 2006

l-asparaginase (l-Asp) is an effective drug for treatment of children with acute lymphoblastic leukemia (ALL). The effectiveness is generally thought to result from a rapid depletion of asparagine in serum and cells. Asparagine synthetase (AS) opposes the action of l-Asp by resynthesis of asparagine. In vitro, resistance to l-Asp has been associated with up-regulation of AS mRNA expression. We monitored AS mRNA levels in leukemic cells before and during 5 days after intravenous administration of 1000 IU/m2 pegylated l-asparaginase (PEG-Asp) in a therapeutic window in children with ALL at initial diagnosis. Within 24 hours, AS mRNA levels increased by 3.5-fold and remained stable in the following 4 days. Baseline and l-Asp–induced expression levels of AS did not differ between clinically good, intermediate, and poor responders to PEG-Asp. No significant difference of AS mRNA up-regulation was found between precursor B- and T-ALL or between hyperdiploids, TEL/AML1 rearranged ALL or absence of genetic abnormalities. In 3 of 12 patients with T-ALL even a slight down-regulation of AS mRNA expression upon l-Asp exposure was found. In conclusion, although l-Asp exposure induces the expression of AS mRNA, the up-regulated gene expression does not correlate with an early clinical poor response to this drug in children with ALL.
Constitutive NF-κB and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas
Authors: Fu Lingchen , Lin-Lee Yen-Chiu , Pham Lan V. , Tamayo Archito , Yoshimura Linda , Ford Richard J.
Published: February 2006

B-lymphocyte stimulator (BLyS), a relatively recently recognized member of the tumor necrosis factor ligand family (TNF), is a potent cell-survival factor expressed in many hematopoietic cells. BLyS binds to 3 TNF-R receptors, TACI, BCMA, BAFF-R, to regulate B-cell survival, differentiation, and proliferation. The mechanisms involved in BLYS gene expression and regulation are still incompletely understood. In this study, we examined BLYS gene expression, function, and regulation in B-cell non-Hodgkin lymphoma (NHL-B) cells. Our studies indicate that BLyS is constitutively expressed in aggressive NHL-B cells, including large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL), playing an important role in the survival and proliferation of malignant B cells. We found that 2 important transcription factors, NF-κB and NFAT, are involved in regulating BLyS expression through at least one NF-κB and 2 NFAT binding sites in the BLYS promoter. We also provide evidence suggesting that the constitutive activation of NF-κB and BLyS in NHL-B cells forms a positive feedback loop associated with lymphoma cell survival and proliferation. Our findings indicate that constitutive NF-κB and NFAT activations are crucial transcriptional regulators of the BLyS survival pathway in malignant B cells that could be therapeutic targets in aggressive NHL-B.
Antimicrobial proteins and polypeptides in pulmonary innate defence
Authors: Rogan Mark P , Geraghty Patrick , Greene Catherine M , O'Neill Shane J , Taggart Clifford C , McElvaney Noel G
Published: February 2006

Inspired air contains a myriad of potential pathogens, pollutants and inflammatory stimuli. In the normal lung, these pathogens are rarely problematic. This is because the epithelial lining fluid in the lung is rich in many innate immunity proteins and peptides that provide a powerful anti-microbial screen. These defensive proteins have anti-bacterial, anti- viral and in some cases, even anti-fungal properties. Their antimicrobial effects are as diverse as inhibition of biofilm formation and prevention of viral replication. The innate immunity proteins and peptides also play key immunomodulatory roles. They are involved in many key processes such as opsonisation facilitating phagocytosis of bacteria and viruses by macrophages and monocytes. They act as important mediators in inflammatory pathways and are capable of binding bacterial endotoxins and CPG motifs. They can also influence expression of adhesion molecules as well as acting as powerful anti-oxidants and anti-proteases. Exciting new antimicrobial and immunomodulatory functions are being elucidated for existing proteins that were previously thought to be of lesser importance. The potential therapeutic applications of these proteins and peptides in combating infection and preventing inflammation are the subject of ongoing research that holds much promise for the future.
Quantitative comparison of EST libraries requires compensation for systematic biases in cDNA generation
Authors: Liu Donglin , Graber Joel H
Published: February 2006

Background

Publicly accessible EST libraries contain valuable information that can be utilized for studies of tissue-specific gene expression and processing of individual genes. This information is, however, confounded by multiple systematic effects arising from the procedures used to generate these libraries.

Results

We used alignment of ESTs against a reference set of transcripts to estimate the size distributions of the cDNA inserts and sampled mRNA transcripts in individual EST libraries and show how these measurements can be used to inform quantitative comparisons of libraries. While significant attention has been paid to the effects of normalization and substraction, we also find significant biases in transcript sampling introduced by the combined procedures of reverse transcription and selection of cDNA clones for sequencing. Using examples drawn from studies of mRNA 3'-processing (cleavage and polyadenylation), we demonstrate effects of the transcript sampling bias, and provide a method for identifying libraries that can be safely compared without bias. All data sets, supplemental data, and software are available at our supplemental web site [1].

Conclusion

The biases we characterize in the transcript sampling of EST libraries represent a significant and heretofore under-appreciated source of false positive candidates for tissue-, cell type-, or developmental stage-specific activity or processing of genes. Uncorrected, quantitative comparison of dissimilar EST libraries will likely result in the identification of statistically significant, but biologically meaningless changes.
Transcriptomic response to differentiation induction
Authors: Patton GW , Stephens R , Sidorov IA , Xiao X , Lempicki RA , Dimitrov DS , Shoemaker RH , Tudor G
Published: February 2006

Background

Microarrays used for gene expression studies yield large amounts of data. The processing of such data typically leads to lists of differentially-regulated genes. A common terminal data analysis step is to map pathways of potentially interrelated genes.

Methods

We applied a transcriptomics analysis tool to elucidate the underlying pathways of leukocyte maturation at the genomic level in an established cellular model of leukemia by examining time-course data in two subclones of U-937 cells. Leukemias such as Acute Promyelocytic Leukemia (APL) are characterized by a block in the hematopoietic stem cell maturation program at a point when expansion of clones which should be destined to mature into terminally-differentiated effector cells get locked into endless proliferation with few cells reaching maturation. Treatment with retinoic acid, depending on the precise genomic abnormality, often releases the responsible promyelocytes from this blockade but clinically can yield adverse sequellae in terms of potentially lethal side effects, referred to as retinoic acid syndrome.

Results

Briefly, the list of genes for temporal patterns of expression was pasted into the ABCC GRID Promoter TFSite Comparison Page website tool and the outputs for each pattern were examined for possible coordinated regulation by shared regelems (regulatory elements). We found it informative to use this novel web tool for identifying, on a genomic scale, genes regulated by drug treatment.

Conclusion

Improvement is needed in understanding the nature of the mutations responsible for controlling the maturation process and how these genes regulate downstream effects if there is to be better targeting of chemical interventions. Expanded implementation of the techniques and results reported here may better direct future efforts to improve treatment for diseases not restricted to APL.
The PowerAtlas: a power and sample size atlas for microarray experimental design and research
Authors: Page Grier P , Edwards Jode W , Gadbury Gary L , Yelisetti Prashanth , Wang Jelai , Trivedi Prinal , Allison David B
Published: February 2006

Background

Microarrays permit biologists to simultaneously measure the mRNA abundance of thousands of genes. An important issue facing investigators planning microarray experiments is how to estimate the sample size required for good statistical power. What is the projected sample size or number of replicate chips needed to address the multiple hypotheses with acceptable accuracy? Statistical methods exist for calculating power based upon a single hypothesis, using estimates of the variability in data from pilot studies. There is, however, a need for methods to estimate power and/or required sample sizes in situations where multiple hypotheses are being tested, such as in microarray experiments. In addition, investigators frequently do not have pilot data to estimate the sample sizes required for microarray studies.

Results

To address this challenge, we have developed a Microrarray PowerAtlas [1]. The atlas enables estimation of statistical power by allowing investigators to appropriately plan studies by building upon previous studies that have similar experimental characteristics. Currently, there are sample sizes and power estimates based on 632 experiments from Gene Expression Omnibus (GEO). The PowerAtlas also permits investigators to upload their own pilot data and derive power and sample size estimates from these data. This resource will be updated regularly with new datasets from GEO and other databases such as The Nottingham Arabidopsis Stock Center (NASC).

Conclusion

This resource provides a valuable tool for investigators who are planning efficient microarray studies and estimating required sample sizes.
Phase analysis of circadian-related genes in two tissues
Authors: Liu Delong , Peddada Shyamal D , Li Leping , Weinberg Clarice R
Published: February 2006

Background

Recent circadian clock studies using gene expression microarray in two different tissues of mouse have revealed not all circadian-related genes are synchronized in phase or peak expression times across tissues in vivo. Instead, some circadian-related genes may be delayed by 4–8 hrs in peak expression in one tissue relative to the other. These interesting biological observations prompt a statistical question regarding how to distinguish the synchronized genes from genes that are systematically lagged in phase/peak expression time across two tissues.

Results

We propose a set of techniques from circular statistics to analyze phase angles of circadian-related genes in two tissues. We first estimate the phases of a cycling gene separately in each tissue, which are then used to estimate the paired angular difference of the phase angles of the gene in the two tissues. These differences are modeled as a mixture of two von Mises distributions which enables us to cluster genes into two groups; one group having synchronized transcripts with the same phase in the two tissues, the other containing transcripts with a discrepancy in phase between the two tissues. For each cluster of genes we assess the association of phases across the tissue types using circular-circular regression. We also develop a bootstrap methodology based on a circular-circular regression model to evaluate the improvement in fit provided by allowing two components versus a one-component von-Mises model.

Conclusion

We applied our proposed methodologies to the circadian-related genes common to heart and liver tissues in Storch et al. [2], and found that an estimated 80% of circadian-related transcripts common to heart and liver tissues were synchronized in phase, and the other 20% of transcripts were lagged about 8 hours in liver relative to heart. The bootstrap p-value for being one cluster is 0.063, which suggests the possibility of two clusters. Our methodologies can be extended to analyze peak expression times of circadian-related genes across more than two tissues, for example, kidney, heart, liver, and the suprachiasmatic nuclei (SCN) of the hypothalamus.
A graphical model approach to automated classification of protein subcellular location patterns in multi-cell images
Authors: Chen Shann-Ching , Murphy Robert F
Published: February 2006

Background

Knowledge of the subcellular location of a protein is critical to understanding how that protein works in a cell. This location is frequently determined by the interpretation of fluorescence microscope images. In recent years, automated systems have been developed for consistent and objective interpretation of such images so that the protein pattern in a single cell can be assigned to a known location category. While these systems perform with nearly perfect accuracy for single cell images of all major subcellular structures, their ability to distinguish subpatterns of an organelle (such as two Golgi proteins) is not perfect. Our goal in the work described here was to improve the ability of an automated system to decide which of two similar patterns is present in a field of cells by considering more than one cell at a time. Since cells displaying the same location pattern are often clustered together, considering multiple cells may be expected to improve discrimination between similar patterns.

Results

We describe how to take advantage of information on experimental conditions to construct a graphical representation for multiple cells in a field. Assuming that a field is composed of a small number of classes, the classification accuracy can be improved by allowing the computed probability of each pattern for each cell to be influenced by the probabilities of its neighboring cells in the model. We describe a novel way to allow this influence to occur, in which we adjust the prior probabilities of each class to reflect the patterns that are present. When this graphical model approach is used on synthetic multi-cell images in which the true class of each cell is known, we observe that the ability to distinguish similar classes is improved without suffering any degradation in ability to distinguish dissimilar classes. The computational complexity of the method is sufficiently low that improved assignments of classes can be obtained for fields of twelve cells in under 0.04 second on a 1600 megahertz processor.

Conclusion

We demonstrate that graphical models can be used to improve the accuracy of classification of subcellular patterns in multi-cell fluorescence microscope images. We also describe a novel algorithm for inferring classes from a graphical model. The performance and speed suggest that the method will be particularly valuable for analysis of images from high-throughput microscopy. We also anticipate that it will be useful for analyzing the mixtures of cell types typically present in images of tissues. Lastly, we anticipate that the method can be generalized to other problems.
Various criteria in the evaluation of biomedical named entity recognition
Authors: Tsai Richard Tzong-Han , Wu Shih-Hung , Chou Wen-Chi , Lin Yu-Chun , He Ding , Hsiang Jieh , Sung Ting-Yi , Hsu Wen-Lian
Published: February 2006

Background

Text mining in the biomedical domain is receiving increasing attention. A key component of this process is named entity recognition (NER). Generally speaking, two annotated corpora, GENIA and GENETAG, are most frequently used for training and testing biomedical named entity recognition (Bio-NER) systems. JNLPBA and BioCreAtIvE are two major Bio-NER tasks using these corpora. Both tasks take different approaches to corpus annotation and use different matching criteria to evaluate system performance. This paper details these differences and describes alternative criteria. We then examine the impact of different criteria and annotation schemes on system performance by retesting systems participated in the above two tasks.

Results

To analyze the difference between JNLPBA's and BioCreAtIvE's evaluation, we conduct Experiment 1 to evaluate the top four JNLPBA systems using BioCreAtIvE's classification scheme. We then compare them with the top four BioCreAtIvE systems. Among them, three systems participated in both tasks, and each has an F-score lower on JNLPBA than on BioCreAtIvE. In Experiment 2, we apply hypothesis testing and correlation coefficient to find alternatives to BioCreAtIvE's evaluation scheme. It shows that right-match and left-match criteria have no significant difference with BioCreAtIvE. In Experiment 3, we propose a customized relaxed-match criterion that uses right match and merges JNLPBA's five NE classes into two, which achieves an F-score of 81.5%. In Experiment 4, we evaluate a range of five matching criteria from loose to strict on the top JNLPBA system and examine the percentage of false negatives. Our experiment gives the relative change in precision, recall and F-score as matching criteria are relaxed.

Conclusion

In many applications, biomedical NEs could have several acceptable tags, which might just differ in their left or right boundaries. However, most corpora annotate only one of them. In our experiment, we found that right match and left match can be appropriate alternatives to JNLPBA and BioCreAtIvE's matching criteria. In addition, our relaxed-match criterion demonstrates that users can define their own relaxed criteria that correspond more realistically to their application requirements.
Dexamethasone protection from TNF-alpha-induced cell death in MCF-7 cells requires NF-kappaB and is independent from AKT
Authors: Machuca Catalina , Mendoza-Milla Criselda , Córdova Emilio , Mejía Salvador , Covarrubias Luis , Ventura José , Zentella Alejandro
Published: February 2006

Background

The biochemical bases for hormone dependence in breast cancer have been recognized as an important element in tumor resistance, proliferation and metastasis. On this respect, dexamethasone (Dex) dependent protection against TNF-alpha-mediated cell death in the MCF-7 cell line has been demonstrated to be a useful model for the study of this type of cancer. Recently, cytoplasmic signaling induced by steroid receptors has been described, such as the activation of the PI3K/Akt and NF-kappaB pathways. We evaluated their possible participation in the Dex-dependent protection against TNF-alpha-mediated cell death.

Results

Cellular cultures of the MCF-7 cell line were exposed to either, TNF-alpha or TNF-alpha and Dex, and cell viability was evaluated. Next, negative dominants of PI3K and IkappaB-alpha, designed to block the PI3K/Akt and NF-kappaB pathways, respectively, were transfected and selection and evaluation of several clones overexpressing the mutants were examined. Also, correlation with inhibitor of apoptosis proteins (IAPs) expression was examined. Independent inhibition of these two pathways allowed us to test their participation in Dex-dependent protection against TNF-alpha-cytotoxicity in MCF-7 cells. Expression of the PI3K dominant negative mutant did not alter the protection conferred by Dex against TNF-alpha mediated cell death. Contrariwise, clones expressing the IkappaB-alpha dominant negative mutant lost the Dex-conferred protection against TNF-alpha. In these clones degradation of c-IAP was accelerated, while that of XIAP was remained unaffected.

Conclusion

NF-kappaB, but not PI3K/Akt activation, is required for the Dex protective effect against TNF-alpha-mediated cell death, and correlates with lack of degradation of the anti-apoptotic protein c-IAP1.
FGF9 can induce endochondral ossification in cranial mesenchyme
Authors: Govindarajan Venkatesh , Overbeek Paul A
Published: February 2006

Background

The flat bones of the skull (i.e., the frontal and parietal bones) normally form through intramembranous ossification. At these sites cranial mesenchymal cells directly differentiate into osteoblasts without the formation of a cartilage intermediate. This type of ossification is distinct from endochondral ossification, a process that involves initial formation of cartilage and later replacement by bone.

Results

We have analyzed a line of transgenic mice that expresses FGF9, a member of the fibroblast growth factor family (FGF), in cranial mesenchymal cells. The parietal bones in these mice show a switch from intramembranous to endochondral ossification. Cranial cartilage precursors are induced to proliferate, then hypertrophy and are later replaced by bone. These changes are accompanied by upregulation of Sox9, Ihh, Col2a1, Col10a1 and downregulation of CbfaI and Osteocalcin. Fate mapping studies show that the cranial mesenchymal cells in the parietal region that show a switch in cell fate are likely to be derived from the mesoderm.

Conclusion

These results demonstrate that FGF9 expression is sufficient to convert the differentiation program of (at least a subset of) mesoderm-derived cranial mesenchyme cells from intramembranous to endochondral ossification.
Development and application of three-tiered nuclear genetic markers for basal Hexapods using single-stranded conformation polymorphism coupled with targeted DNA sequencing
Authors: Garrick Ryan C , Sunnucks Paul
Published: February 2006

Background

Molecular genetic approaches have much to offer population biology. Despite recent advances, convenient techniques to develop and screen highly-resolving markers can be limiting for some applications and taxa. We describe an improved PCR-based, cloning-free, nuclear marker development procedure, in which single-stranded conformation polymorphism (SSCP) plays a central role. Sequence-variable alleles at putative nuclear loci are simultaneously identified and isolated from diploid tissues. Based on a multiple allele alignment, locus-specific primers are designed in conserved regions, minimizing 'null' alleles. Using two undescribed endemic Australian Collembola as exemplars, we outline a comprehensive approach to generating and validating suites of codominant, sequence-yielding nuclear loci for previously unstudied invertebrates.

Results

Six markers per species were developed without any baseline genetic information. After evaluating the characteristics of each new locus via SSCP pre-screening, population samples were genotyped on the basis of either DNA sequence, restriction site, or insertion/deletion variation, depending on which assay was deemed most appropriate. Polymorphism was generally high (mean of nine alleles per locus), and the markers were capable of resolving population structuring over very fine spatial scales (<100 km). SSCP coupled with targeted DNA sequencing was used to obtain genotypic, genic and genealogical information from six loci (three per species). Phylogeographic analysis identified introns as being most informative.

Conclusion

The comprehensive approach presented here feasibly overcomes technical hurdles of (i) developing suitably polymorphic nuclear loci for non-model organisms, (ii) physically isolating nuclear allele haplotypes from diploid tissues without cloning, and (iii) genotyping population samples on the basis of nuclear DNA sequence variation.
The systematic functional characterisation of Xq28 genes prioritises candidate disease genes
Authors: Kolb-Kokocinski Anja , Mehrle Alexander , Bechtel Stephanie , Simpson Jeremy C , Kioschis Petra , Wiemann Stefan , Wellenreuther Ruth , Poustka Annemarie
Published: February 2006

Background

Well known for its gene density and the large number of mapped diseases, the human sub-chromosomal region Xq28 has long been a focus of genome research. Over 40 of approximately 300 X-linked diseases map to this region, and systematic mapping, transcript identification, and mutation analysis has led to the identification of causative genes for 26 of these diseases, leaving another 17 diseases mapped to Xq28, where the causative gene is still unknown. To expedite disease gene identification, we have initiated the functional characterisation of all known Xq28 genes.

Results

By using a systematic approach, we describe the Xq28 genes by RNA in situ hybridisation and Northern blotting of the mouse orthologs, as well as subcellular localisation and data mining of the human genes. We have developed a relational web-accessible database with comprehensive query options integrating all experimental data. Using this database, we matched gene expression patterns with affected tissues for 16 of the 17 remaining Xq28 linked diseases, where the causative gene is unknown.

Conclusion

By using this systematic approach, we have prioritised genes in linkage regions of Xq28-mapped diseases to an amenable number for mutational screens. Our database can be queried by any researcher performing highly specified searches including diseases not listed in OMIM or diseases that might be linked to Xq28 in the future.
Common features and interesting differences in transcriptional responses to secretion stress in the fungi Trichoderma reesei and Saccharomyces cerevisiae
Authors: Arvas Mikko , Pakula Tiina , Lanthaler Karin , Saloheimo Markku , Valkonen Mari , Suortti Tapani , Robson Geoff , Penttilä Merja
Published: February 2006

Background

Secretion stress is caused by compromised folding, modification or transport of proteins in the secretory pathway. In fungi, induction of genes in response to secretion stress is mediated mainly by the unfolded protein response (UPR) pathway. This study aims at uncovering transcriptional responses occurring in the filamentous fungi Trichoderma reesei exposed to secretion stress and comparing these to those found in the yeast Saccharomyces cerevisiae.

Results

Chemostat cultures of T. reesei expressing human tissue plasminogen activator (tPA) and batch bioreactor cultures treated with dithiothreitol (DTT) to prevent correct protein folding were analysed with cDNA subtraction and cDNA-amplified fragment length polymorphism (AFLP) experiments. ESTs corresponding to 457 unique genes putatively induced under secretion stress were isolated and the expression pattern of 60 genes was confirmed by Northern analysis. Expression of these genes was also studied in a strain over-expressing inositol-requiring enzyme 1 (IREI) protein, a sensor for the UPR pathway. To compare the data with that of S. cerevisiae, published transcriptome profiling data on various stress responses in S. cerevisiae was reanalysed. The genes up-regulated in response to secretion stress included a large number of secretion related genes in both organisms. In addition, analysis of T. reesei revealed up regulation of the cpc1 transcription factor gene and nucleosomal genes. The induction of the cpcA and histone gene H4 were shown to be induced also in cultures of Aspergillus nidulans treated with DTT.

Conclusion

Analysis of the genes induced under secretion stress has revealed novel features in the stress response in T. reesei and in filamentous fungi. We have demonstrated that in addition to the previously rather well characterised induction of genes for many ER proteins or secretion related proteins also other types of responses exist.
Evaluation of low density array technology for quantitative parallel measurement of multiple genes in human tissue
Authors: Goulter Andrew B , Harmer Daniel W , Clark Kenneth L
Published: February 2006

Background

Low density arrays (LDAs) have recently been introduced as a novel approach to gene expression profiling. Based on real time quantitative RT-PCR (QRT-PCR), these arrays enable a more focused and sensitive approach to the study of gene expression than gene chips, while offering higher throughput than more established approaches to QRT-PCR. We have now evaluated LDAs as a means of determining the expression of multiple genes simultaneously in human tissues and cells.

Results

Comparisons between LDAs reveal low variability, with correlation coefficients close to 1. By performing 2-fold and 10-fold serial dilutions of cDNA samples in the LDAs we determined a clear linear relationship between the gene expression data points over 5 orders of magnitude. We also showed that it is possible to use LDAs to accurately and quantitatively detect 2-fold changes in target copy number as well as measuring genes that are expressed with low and high copy numbers in the range of 1 × 102– 1 × 106copies. Furthermore, the data generated by the LDA from a cell based pharmacological study were comparable to data generated by conventional QRT-PCR.

Conclusion

LDAs represent a valuable new approach for sensitive and quantitative gene expression profiling.
Sca 1, a previously undescribed paralog from autotransporter protein-encoding genes in Rickettsia species
Authors: Ngwamidiba Maxime , Blanc Guillaume , Raoult Didier , Fournier Pierre-Edouard
Published: February 2006

Background

Among the 17 genes encoding autotransporter proteins of the "surface cell antigen" (sca) family in the currently sequenced Rickettsia genomes, ompA, sca 5 (ompB) and sca 4 (gene D), have been extensively used for identification and phylogenetic purposes for Rickettsia species. However, none of these genes is present in all 20 currently validated Rickettsia species. Of the remaining 14 sca genes, sca 1 is the only gene to be present in all nine sequenced Rickettsia genomes. To estimate whether the sca 1 gene is present in all Rickettsia species and its usefulness as an identification and phylogenetic tool, we searched for sca 1genes in the four published Rickettsia genomes and amplified and sequenced this gene in the remaining 16 validated Rickettsia species.

Results

Sca 1 is the only one of the 17 rickettsial sca genes present in all 20 Rickettsia species. R. prowazekii and R. canadensis exhibit a split sca 1 gene whereas the remaining species have a complete gene. Within the sca 1 gene, we identified a 488-bp variable sequence fragment that can be amplified using a pair of conserved primers. Sequences of this fragment are specific for each Rickettsia species. The phylogenetic organization of Rickettsia species inferred from the comparison of sca 1 sequences strengthens the classification based on the housekeeping gene gltA and is similar to those obtained from the analyses of ompA, sca 5 and sca4, thus suggesting similar evolutionary constraints. We also observed that Sca1 protein sequences have evolved under a dual selection pressure: with the exception of typhus group rickettsiae, the amino-terminal part of the protein that encompasses the predicted passenger domain, has evolved under positive selection in rickettsiae. This suggests that the Sca1 protein interacts with the host. In contrast, the C-terminal portion containing the autotransporter domain has evolved under purifying selection. In addition, sca 1 is transcribed in R. conorii, and might therefore be functional in this species.

Conclusion

The sca 1 gene, encoding an autotransporter protein that evolves under dual evolution pressure, is the only sca- family gene to be conserved by all Rickettsia species. As such, it is a valuable identification target for these bacteria, especially because rickettsial isolates can be identified by amplification and sequencing of a discriminatory gene fragment using a single primer pair. It may also be used as a phylogenetic tool. However, its current functional status remains to be determined although it was found expressed in R. conorii.