bluuebunny/crossref_metadata_2025 huggingface dataset:
Transferable and Negotiated Knowledge
Authors: Närhi Kati
Published: April 2009

• Summary: This article explores the knowledge of community-based social workers in the context of an action research project aimed at exploring the practitioners’ own descriptions of their knowledge and expertise on the theme of spatial marginalization.

• Findings: The knowledge of social workers seemed to be based on service users’ experiences and case examples, on value and moral constructions, and it was created from experience, by doing and in action. It was local and contextual, in some sense silent but shared through a discussion process. It was not based on empirically based scientific research understood in the traditional sense; rather, social workers resorted to practical knowledge in its various forms.

• Applications: The sharing of individuals’ social work knowledge, both ‘knowing that’ and ‘knowing how’, with other social workers and reflecting together on the knowledge and tradition that social workers carry serves to define, study and promote the transferability of common and shared knowledge.
Which side was Becker on? Questioning political and epistemological radicalism
Authors: Hammersley Martyn
Published: April 2009

Howard Becker’s article ‘Whose side are we on?’ has been widely cited, and widely misunderstood. It has frequently been interpreted as recommending partisan research, or as suggesting that social research cannot be objective. This article examines Becker’s position in detail, arguing that while there are some ambiguities within it, what it proposes is neither epistemologically nor politically radical in the way that is frequently assumed. What is true, though, is that Becker believes that systematic and rigorous sociological research inevitably tends to have radical political implications. In addition, he adopts a form of cultural relativism, whilst holding on to a notion of objectivity that is grounded in a commitment to pragmatism.
Computer-mediated focus group sessions: naturalistic inquiry in a networked environment
Authors: Franklin Kathy K. , Lowry Catherine
Published: April 2009

This article reports on a naturalistic research study exploring faculty attitudes about the use of technology in the college classroom. The data collection method consisted of a series of synchronous, computer-mediated focus group sessions using a group support system. Participants in the four focus group sessions were faculty employed at the University of Arkansas at Little Rock. The researchers found that the computer-mediated format for the focus group method of inquiry improved the objectivity of each session, reduced the influence of a sensitive topic on participation and enhanced the management of participant discussion. Furthermore, the electronic format improved the accuracy of the data collected by capturing every voice and every comment in ‘real time’. The primary disadvantage of the computer-mediated method was the reduced ability of the researcher to guide the discussion and request elaboration on any given topic.
Establishing research legitimacy in the contested political ground of contemporary Northern Ireland
Authors: Knox Colin
Published: April 2009

Despite the plethora of literature on the macro politics of Northern Ireland, there is a dearth of material on grassroots activity, in particular the dynamic between communities and paramilitary groups which enforce ‘law and order’ in working-class areas. Political progress in the form of the Belfast Agreement (1998) has overshadowed the ongoing level of violence at the micro level and the voice of victims remains unheard in the search to attain a greater goal - a long-term political and constitutional settlement. This article examines the methodological difficulties in establishing research legitimacy in the contested political arenas of Northern Ireland. It considers issues of access, establishing the researchers’ bona fides, openness and transparency, language and personal security, and offers some insights into research in sensitive topics.
Imagining possibilities with and for contemporary youth: (re)writing and (re)visioning education today
Authors: Dimitriadis Greg , Weis Lois
Published: April 2009

Over the years, each of the authors has explored the lives of young people in a range of sites and settings, from community centers to schools and beyond. They have seen senses of self and community that exceed the narrow and debilitating categories into which they are so readily cast. In this article, they join forces in highlighting two key (though clearly not exhaustive) examples from their recent research ideas: first, black history and generational identity expressed through popular culture at a local community center in the US; and second, the important work done by women in an abstinence-based sex education program in an urban magnet school. Honoring what Maxine Greene (2000) calls the work of the imagination, they focus on the ways in which young people engage in a re-writing of self and future in distinct and overlapping ways.
Data analysis and ‘theorizing as ideology’
Authors: Roulston Kathryn
Published: April 2009

In this article the author reviews a segment from a report of a research project that she undertook in 1991. In this initial entry into the research world, the research process used aimed to make audible one part of the ‘personal practical knowledge’ of a group of music teachers. By critiquing one segment of the report and contrasting this with a re-analysis of the original data upon which this segment relies, an alternative view of the research process and the research findings may be gained. The research process used in the first report aimed to allow teachers’ voices and knowledge to become explicit. In fact, it may be seen to gloss over underlying discourses and in doing so, romanticize those voices. Concomitantly, a re-analysis of the original data using methods drawn from conversation analysis reveals the ways in which the researcher’s voice is indelibly inscribed in the research process. The critique presented here elucidates the ways in which ‘theorizing as ideology’ may be accomplished by a novice researcher in the writing of a research report. Further, the utilization of conversation analysis to investigate interview transcripts of teacher talk demonstrates an approach to data analysis which might be further explored by researchers employing interviews as a method of data generation.
Group discussion and the importance of a shared perspective: learning from collaborative research
Authors: Corden Roy
Published: April 2009

Student-led discussion during small group work is now a familiar feature in many schools. However, simply organizing students in small groups does not mean they will automatically participate in collaborative discussion. In this article I report on a small-scale research project in the UK which examined the discourse patterns of year 8 (13-14-year-old students) as they worked in discussion groups during English lessons. Using a multi-case study approach, video recordings were made in four high schools over a one-year period and qualitative analysis was undertaken. For illustrative purposes I focus on two transcripts which are representative of discussions from a full range of 40 video recordings and illustrate common and recurrent patterns of discourse. The findings suggest that students’ interpretations of tasks are influenced by an orthodox perception of teaching and learning which emphasizes independent and individualized working practices in schools. The importance of explicit and unambiguous teacher guidance is highlighted, and the apparent paradox of encouraging critical and open discussion of texts within a structured framework is examined.
Men, sport, spinal cord injury and the construction of coherence: narrative practice in action
Authors: Smith Brett , Sparkes Andrew C.
Published: April 2009

Based on life history data, this article explores the manner in which coherence is constructed in the narratives told by two men who have acquired a spinal cord injury through playing sport. Drawing on the principles advocated by Gubrium and Holstein, and Holstein and Gubrium, along with a number of analytic concepts provided by others (e.g. Frank, Gerschick and Miller, Leder, van Manen and Yoshida), we illustrate how various narrative practices inform this process and how they are framed by both the local and cultural conventions of telling. It is suggested that coherence is not an inherent feature of narratives but is both artfully crafted in the telling and drawn from the available meanings, structures and linkages that comprise stories.
Focusing on focus groups: lessons from a research project involving a Bangladeshi community
Authors: Fallon Grahame , Brown Reva Berman
Published: April 2009

This article examines the main issues and challenges associated with the use of the focus group method in a research study involving small business and entrepreneurship. The project concerned the education and training needs of a Bangladeshi community in a West Midlands city, commissioned by the local Chamber of Commerce Training and Enterprise. The article considers the advice provided in the literature on the conduct of focus groups, describes the application of that advice to gather empirical data from an ethnic community, and discusses the insights gained from the use of focus groups in these circumstances. Both the positive and negative features of the research process and outcomes are covered, and the impact of the focus group method on the successes and failures of the project is discussed.
Studying the self: from the subjective and the social to personal and political dialogues
Authors: Saukko Paula
Published: April 2009

This article analyses and discusses the emotivist goal of capturing the subjective self as well as the poststructuralist quest to grasp the social self produced by discourses. It argues that both of these positions are predicated on the classical notion of a ‘subject’ that ‘knows’ the subjective self and its desires and/or its social ramifications. The downside of this understanding of the self is illustrated by the way in which the experience, research and treatment of eating disorders are all driven by a similar elusive, gendered ideal of a subject who knows itself and the world and how they both work. This article argues for a more ambivalent or ‘agonistically dialogic’ way of approaching the self that acknowledges that the subjective is always confounded by the social, and that the social can only be grasped from a subjective point of view. This mode of studying the self paves the way for a less judgemental and more conversational way of relating to our selves, others and the social world, leading to a more dialogic (inter)personal and political life.
Researching environmental resistance: working through Secondspace and Thirdspace approaches
Authors: Anderson Jon
Published: April 2009

During the last decade resistance against environmental destruction has spread throughout much of the developed world. Over this period Environmental Direct Action (EDA) has evolved into an inventive and dynamic movement that not only rallies against specific environmental damages, but also the broader political and economic systems that are perceived to facilitate them. With the growth of Environmental Direct Action there has been a concomitant increase in the number wishing to understand and explain the phenomenon. This expansion of academic interest raises two questions: (1) Are conventional academic epistemologies suitable to understand and explain the motivations of and challenges posed by EDA?, and (2) Do the power relations inherent within such approaches facilitate or preclude our opportunities to make sense of this resistance movement? This paper uses experience gained from my own empirical work on EDA in the UK to explore these issues. Beginning with what Soja terms the ‘Secondspace’ approach to social science research, it will focus on the problems posed by issues of positionality and power relations for the study of EDA. The paper will go on to illustrate that, although entailing a number of problems, a ‘Thirdspace’ approach offers some solutions that can secure important insights into this political practice.
Women researching their lives: exploring violence and identity in Belfast, the North of Ireland
Authors: Mcintyre Alice
Published: April 2009

As the newly elected members of the Northern Ireland Assembly work towards implementing mechanisms for protecting and furthering the economic, social, political, cultural, and civic rights of the people of the North of Ireland, many local people are simultaneously developing strategies for addressing the legacy of violence that has characterized life in that region of the world for over 30 years. In this article, I describe how one group of working-class women living in Belfast address their personal and collective experiences with the multiple forms of violence that structure their daily lives. I do so by describing an ongoing feminist participatory action research (PAR) project that provided the women with a culturally relevant lens through which to view the historical and political contexts in which they live and act.

Although there were multiple dimensions of the women’s lives that were revealed in the project, in this article I focus specifically on the ‘frozen watchfulness’ that characterizes life on Monument Road - a watchfulness that is born out of years of living in and with chronic and unpredictable violence. First, I provide an overview of the overall project. Second, I provide a glimpse of how violence acts as an organizer in the women’s lives. Lastly, I discuss the importance of opening up spaces for women living in conflicted communities to speak about their lives and develop strategies for generating new contexts for the revitalization of everyday life.
Performing identities in illness narrative: masculinity and multiple sclerosis
Authors: Riessman Catherine Kohler
Published: April 2009

Case studies have a valuable place in health research, including the increasingly popular illness narrative. In a thrice-told tale, I analyze and compare the performance of identities in two illness narratives, men with multiple sclerosis whom I interviewed in the 1980s. I include myself as a figure in the construction of the narratives, as audience for their performance, and I reinterpret them drawing on contemporary concepts of gender, disability, and performativity. Initially inspired theoretically by Goffman, the re-analysis locates the men in social structural contexts, drawing on Bourdieu’s work on class and the body’s relationship to social space.
Crafting participation: designing ecologies, configuring experience
Authors: Heath Christian , Luff Paul , Lehn Dirk Vom , Hindmarsh Jon , Cleverly Jason
Published: April 2009

There is a growing interest amongst both artists and curators in designing art works which create new forms of visual communication and enhance interaction in museums and galleries. Despite extraordinary advances in the analysis of talk and discourse, there is relatively little research concerned with conduct and collaboration with and around aesthetic objects and artefacts, and to some extent, the social and cognitive sciences have paid less attention to the ways in which conduct - both visual and vocal - is inextricably embedded within the immediate ecology, the material realities at hand. In this article, we examine how people in and through interaction with others, explore, examine and experience a mixed-media installation. Whilst primarily concerned with interaction with and around an art work, the article is concerned with the ways in which people, in interaction with each other (both those they are with and others who happen to be in the same space), reflexively constitute the sense and significance of objects and artefacts, and the ways in which those material features reflexively inform the production and intelligibility of conduct and interaction.
Materiality in children’s meaning-making practices
Authors: Ormerod Fiona , Ivanič Roz
Published: April 2009

This article develops Kress and Van Leeuwen’s insight that material features combine with visual and linguistic features to convey meaning, showing how this is particularly true of the meaning-making practices of children. Taking examples from a corpus of project work by children aged 8-11 years, we identify the sorts of material resources they were drawing on and categorize the examples according to the types of meaning they carry, linking this categorization to Halliday’s three macro-functions of semiotic resources. We then provide examples of the ways in which physical characteristics provide traces of decision-making processes in the construction of a meaningful message, and of importation and adaptation of semiotic material from elsewhere. We end by suggesting that the practices we have observed represent a fast-changing period in the development of technologies of literacy and that awareness of the materiality of children’s meaning making may contribute to an understanding of the richness and complexity of literacy development.
Pockets Full of Memories: an interactive museum installation
Authors: Legrady George ,   TIMO HONKELA
Published: April 2009

Conceived as an installation on the topic of the archive and memory, Pockets Full of Memories was exhibited on the main floor of the Centre Pompidou National Museum of Modern Art, Paris from 10 April to 3 September 2001. During this time, approximately 20,000 visitors came to view the installation and contributed over 3300 objects in their possession, digitally scanning and describing them. This information was stored in a database and organized by the Kohonen Self-Organizing Map algorithm [http://www.cis.hut.fi/teuvo/] that positioned objects of similar descriptions near each other in a two-dimensional map. The map of objects was projected in the gallery space and was also accessible online at [www.pocketsfullofmemories.com] where individuals in the gallery and at home could review the objects and add comments and stories to any of them.
Goffman’s Gender Advertisements revisited: combining content analysis with semiotic analysis
Authors: Bell Philip , Milic Marko
Published: April 2009

An analysis of 827 advertisements from a representative sample of magazines demonstrates that an abstract framework from Systemic Functional Analysis can be used to identify the semiotic resources which are the basis for gender stereotypes. Resources such as perspectival angle, plane of composition and gaze are used to investigate stereotyped portrayals of males and females. Goffman’s work, Gender Advertisements, forms the basis for hypotheses about how male and female participants would be represented in terms of eight dimensions of visual structure, derived from Kress and Van Leeuwen’s system of analysis. Hypotheses were largely confirmed, indicating that gender stereotyping was still significant in the sample of Australian magazines analysed more than two decades after Goffman’s analysis was first published. However, several results did not confirm the hypotheses or were contrary to the direction of differences predicted. Three types of explanations for exceptions to the hypotheses are discussed: first, the need for some degree of supplementary macrocosmic or contextual analysis; second, the possibility of socially determined changes in some features of stereotyped portrayals; and third, limitations in the functional semiotic framework of analysis adopted in this study.
Who initiates a global flow? Japanese popular culture in Asia
Authors: Nakano Yoshiko
Published: April 2009

This article examines the diffusion of Japanese television programs in Hong Kong and China. It demonstrates how dramas designed for the Japanese younger generation proliferated in the form of pirated video compact disks (VCDs), without being on the air and without marketing campaigns. Far from being cultural imperialism pushed from the economic center, the Chinese people have actively initiated the in-flow of these dramas. The complex combination of local demand, digital technology and the Chinese people’s highly developed literacy in regard to Japanese popular culture made this flow possible. Tokyo was not even participating in the diffusion when the dramas crossed the border into China. To better illustrate globalization processes, this article argues that we should not focus solely on the story of corporate-led cultural flow, but should also examine its twists and turns from the perspectives of unforeseen consumers and unauthorized intermediaries.
The Warlpiri alphabet and other colonial fantasies
Authors: Biddle Jennifer L.
Published: April 2009

This article is a critical interrogation of the alphabet as it has been used to write a so-called ‘pre-literate’ or ‘oral’ language, Warlpiri, an Aboriginal language of the Central Desert of Australia. The author compares a literacy-teaching chart called Warlpiri Letters with traditional Warlpiri inscriptive practices, and finds that both employ a culturally specific form of writing - a writing understood in terms of material ‘imprints’ or ‘traces’. In developing this notion of writing as material ‘trace’, the author argues that it is not the case that Warlpiri Aborigines are without writing. On the contrary, the fact that Warlpiri do indeed possess writing has been simultaneously acknowledged and yet disavowed by a colonial context where only one form of writing is allowed. This analysis shows that an effacement of Warlpiri writing, of Warlpiri culture - including the radical challenge(s) they pose - has occurred in the creation of alphabetically written Warlpiri.
Colour as a semiotic mode: notes for a grammar of colour
Authors: Kress Gunther , Van Leeuwen Theo
Published: April 2009

This article presents a brief review of several approaches of ‘grammar’, as the basis for a discussion of culturally produced regularities in the uses of colour; that is, the possibility of extending the use of ‘grammar’ to colour as a communicational resource. Colour is discussed as a semiotic resource - a mode, which, like other modes, is multifunctional in its uses in the culturally located making of signs. The authors make some use of the Jakobson/Halle theory of ‘distinctive features’, highlighting as signifier-resources those of differentiation, saturation, purity, modulation, value and hue. These are treated as features of a grammar of colour rather than as features of colour itself. The article demonstrates its theoretical points through the analysis of several examples and links notions of ‘colour schemes’ and ‘colour harmony’ into the social and cultural concept of grammar in the more traditional sense.
Utilization of Poly(N-vinyl-2-pyrrolidone) in Easy Care Finishing of Cotton Fabrics to Improve their Performance Properties and Antibacterial Activities
Authors: Fahmy H.M.
Published: April 2009

Poly(N-vinyl-2-pyrrolidone) (PVP) can be oxidized under the influence of the ammonium persulphate (APS) to yield a mixture of different products causing PVP crosslinking as well as pyrrolidone ring opening. Major factors affecting fixation of PVP onto cotton fabrics were studied. These include APS as well as PVP concentrations, time, and temperature. Furthermore, PVP was incorporated in the easy care finishing of cotton fabrics with DMDHEU utilizing APS to serve as catalyst in both the fixation of PVP as well as finishing of cotton fabrics. Results indicated that cotton fabrics treated with 6% PVP and 1.5% APS followed by heating at 90°C for 30 minutes were partially crosslinked with better performance properties and dyeability. Additionally, the post-treating of PVP-finished fabrics with silver nitrate aqueous solution imparts antibacterial activity. Increasing the PVP and/or resin concentrations enhance the antibacterial properties of the treated fabrics. Furthermore, characterization of crosslinked PVP was performed by investigating the infrared, thermal gravimetric analysis, and scanning electron microscope of treated cotton fabrics.
Enhancement of Wrinkle Free Properties of Carboxymethylated Cotton Fabric via Ionic Crosslinking with Poly(vinylpyrrolidone)
Authors: Hashem Mohamed , Refaie Rakia , Goli Kiral , Smith Brent , Hauser Peter
Published: April 2009

Incorporation of poly(vinylpyrrolidone) (PVP) in the structure of cotton, carboxymethylated cotton (CMC) or ionically crosslinked cotton fabric induces besides ether crosslinking of cotton cellulose, strong columbic forces and weaker forces such as dipole—dipole, hydrogen bonds, van der Waals, or hydrophobic interactions. The ether bonds are formed in the dry state (i.e., un-swelled state), whereas, the other interactions are formed in wet state (i.e., swelled state) of cotton fabrics. Both interactions greatly enhance wet and dry wrinkle recovery angle of cotton fabric without strength loss. Fixation of PVP onto cotton or CMC fabric was achieved thermally by curing the treated fabric at 140°C for 5 minutes. Higher wet and dry wrinkle recovery angles (WRA and DRA) were obtained with lower molecular weight PVP (3000 Da) compared with higher molecular weight one (8000 Da). The results obtained also show that a balance between WRA, DRA as high as 228° and 225°, respectively, could be obtained without loss in tensile strength and elongation at break by treatment CMC fabric having carboxyl content 115 meq/100 g fabric with 4% PVP then cured at 140°C for 5 minutes. Additionally, treatment of the ionically crosslinked fabric (having 115 meq/100 g fabric carboxyl content and 0.22% nitrogen content) with 4% aqueous PVP enhances the DRA and WRA to reach a value of 289° and 286°, respectively, without any loss in the strength properties of the fabrics. These values of WRA and DRA are much higher than those obtained with cotton fabric (blank) or carboxymethylated cotton. The existence of ionic interaction and ether bonds as well as functional groups introduced into cotton fabrics were confirmed by FTIR spectroscopy.
The Six-Point Dial of Treatment
Authors: Witte Tracy K. , Gordon Kathryn H. , Joiner Thomas E.
Published: April 2009

The 6-point dial of treatment described in this case report is developed to guide graduate student psychological trainees through treatment and includes the following components: assessment of dangerousness, diagnosis, diagnosis-based treatment, ongoing evaluation of treatment response, obstacles to treatment, and motivation. The article describes the dial of treatment and present a case study of a client with paranoid schizophrenia (John) who presented at a graduate student training clinic to illustrate how this framework can be successfully applied. John exhibits marked improvement, based on both objective measures and clinician judgment of global functioning.
Liberalism in a Romantic State
Authors: Maya Stolzenberg Nomi
Published: April 2009

This article explores the connections between liberalism and romanticism, and argues that there is a split within liberal thought between a rationalist conception of liberalism, which relies on traditional moral psychology, and romanticist versions of liberalism, which adopt the romantic critique of reason and attach a positive value to the supposedly “irrational” faculties of the human psyche, such as passion, emotion, and love. Attending to this split within liberal theory provides us with a deeper understanding of what motivates religious fundamentalism and the more general movement of “return to traditional values” in religious and socially conservative quarters. Fundamentalists and other socially and religiously conservative critics of liberalism perceive that the embrace of a romantic picture of human psychology, and the implementation of doctrines of individual freedom and choice in the realm of marital and sexual relations (in the realm of love) undermines the premises of traditional moral psychology, which insists that “the passions” be subordinated to the faculty of human reason. Paradoxically, religion (a religious conservatism in particular) appears in this face-off between romantic and rationalist conceptions of human psychology and freedom on the side of reason. Religious conservatives attack (romantic) liberalism precisely because they perceive liberalism to constitute an assault on reason and morality. Liberalism has responded to this conservative attack by entering even further into a romantic state, in particular, the romantic state of war. War, love, and religion are the three domains of human experience in which the contrast between romantic and rationalist conceptions of human psychology and freedom is sharpest. Liberalism at war, liberalism in love, and liberalism on faith are the subjects of this Commentary.
Shouting at the Hebrews: Imperial Liberalism v Liberal Pluralism and the Practice of Male Circumcision
Authors: Shweder Richard A.
Published: April 2009

The aim of this essay is to distinguish between two types of liberals: imperial liberals versus liberal pluralists. The two types I have in mind are those who assume that liberal ways of life are objectively more valuable than illiberal ways of life and should replace them (for the sake of making the world a better place), and those (such as myself) who don't make that universalizing assumption and believe instead that you can't live by liberalism alone. As a thought experiment I am going to examine the proposed distinction with regard to one small aspect of family life, albeit one that affects 20—30 percent of all males in the world in a very intimate way, namely the practice of male circumcision. This is a practice which at least in some of its varieties (for example, Jewish neonatal circumcision) and in the eyes of some of its critics (those who are unimpressed by claims and arguments about health benefits), seems patently illiberal (and even barbaric). Given the characteristic features of Jewish circumcision — a customary practice which originated as part of an imagined everlasting pact between Jews and their God and by means of which adult members of that community surgically mark the body of all male infants born to members of the group — it is not hard to see how in the eyes of an imperial liberal who assumes the universal pre-eminence of liberal ways of life over illiberal ways of life, this particular familial and communal tradition might be viewed as “the despotism of custom.” On the other hand it is also not hard to imagine how in the eyes of a liberal pluralist who makes no assumption about the universal progressive replacement value of liberal over illiberal ways of life, the practice of neonatal male circumcision, even in absence of health benefits, might merely be viewed as an alternative and legitimate way of life “expressive of genuine human needs and embodying authentic varieties of human flourishing” (here quoting John Gray),1 whose illiberality is not a measure of its lack of moral value. Examined are those two sets of eyes and their view of the practice of male circumcision.
Valuing All Families
Authors: Bell Melina Constantine
Published: April 2009

Anti-gay marriage amendments proliferate, and current welfare legislation includes coercive marriage promotion programs. This article argues that government sponsorship and promotion of the traditional institution of heterosexual marriage-based family are antithetical to the liberal democratic values that most Americans would claim are foundational principles of their society: liberty and individuality. I suggest that, in order to make the social and legal institution of family consistent with professed public values, it should be transformed from the traditional structure into a new structure that is (1) flexible and customizable, and (2) eligible for direct public support for its role in social reproduction.
How I treat paroxysmal nocturnal hemoglobinuria
Authors: Brodsky Robert A.
Published: April 2009

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal blood disorder that manifests with hemolytic anemia, bone marrow failure, and thrombosis. Many of the clinical manifestations of the disease result from complement-mediated intravascular hemolysis. Allogeneic bone marrow transplantation is the only curative therapy for PNH. Eculizumab, a monoclonal antibody that blocks terminal complement activation, is highly effective in reducing hemolysis, improving quality of life, and reducing the risk for thrombosis in PNH patients. Insights into the relevance of detecting PNH cells in PNH and other bone marrow failure disorders are highlighted, and indications for treating PNH patients with bone marrow transplantation and eculizumab are explored.
Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9
Authors: Peng Tie-Li , Chen Jie , Mao Wei , Song Xin , Chen Min-Hu
Published: April 2009

Background

Abberant aryl hydrocarbon receptor (AhR) expression and AhR pathway activation are involved in gastric carcinogenesis. However, the relationship between AhR pathway activation and gastric cancer progression is still unclear. In present study, we used 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD), a classic and most potent ligand of AhR, to activate AhR pathway and investigated the effect of AhR pathway activation on human gastric cancer AGS cell invasion and explored the corresponding mechanism.

Results

To determine whether AhR pathway can be activated in AGS cells, we examined the expression of CYP1A1, a classic target gene of AhR pathway, following TCDD exposure. RT-PCR and western blot analysis showed that both CYP1A1 mRNA and protein expression were increased in a dose-dependent manner following TCDD treatment and AhR antagonist resveratrol (RSV) could reverse this TCDD-induced CYP1A1 expression. To determine whether TCDD treatment of AGS cells results in an induction of MMP-9 expression, we detected MMP-9 mRNA using RT-PCR and detected MMP-9 enzymatic activity using gelatin zymography. The results showed that both MMP-9 mRNA expression and enzymatic activity were gradually increased with the concentration increase of TCDD in media and these changes could be reversed by RSV treatment in a dose-dependent manner. To examine whether AhR activation-induced MMP-9 expression and activity in AGS cells results in increased migration and invasion, we performed wound healing migration assay and transwell migration and invasion assay. After TCDD treatment, the migration distance and the migration and invasion abilities of AGS cells were increased with a dose-dependent manner. To demonstrate AhR activation-induced MMP-9 expression is mediated by c-Jun, siRNA transfection was performed to silence c-Jun mRNA in AGS cells. The results showed that MMP-9 mRNA expression and activity in untreated control AGS cells were very weak; After TCDD (10 nmol/L) treatment, MMP-9 mRNA expression and activity were significant increased; This TCDD-induced MMP-9 expression and activity increase could be abolished by c-Jun siRNA transfection.

Conclusion

AhR pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of MMP-9. Our results provide insight into the mechanism and function of the AhR pathway and its impact on gastric cancer progression.
Requirements for E1A dependent transcription in the yeast Saccharomyces cerevisiae
Authors: Yousef Ahmed F , Brandl Christopher J , Mymryk Joe S
Published: April 2009

Background

The human adenovirus type 5 early region 1A (E1A) gene encodes proteins that are potent regulators of transcription. E1A does not bind DNA directly, but is recruited to target promoters by the interaction with sequence specific DNA binding proteins. In mammalian systems, E1A has been shown to contain two regions that can independently induce transcription when fused to a heterologous DNA binding domain. When expressed in Saccharomyces cerevisiae, each of these regions of E1A also acts as a strong transcriptional activator. This allows yeast to be used as a model system to study mechanisms by which E1A stimulates transcription.

Results

Using 81 mutant yeast strains, we have evaluated the effect of deleting components of the ADA, COMPASS, CSR, INO80, ISW1, NuA3, NuA4, Mediator, PAF, RSC, SAGA, SAS, SLIK, SWI/SNF and SWR1 transcriptional regulatory complexes on E1A dependent transcription. In addition, we examined the role of histone H2B ubiquitylation by Rad6/Bre1 on transcriptional activation.

Conclusion

Our analysis indicates that the two activation domains of E1A function via distinct mechanisms, identify new factors regulating E1A dependent transcription and suggest that yeast can serve as a valid model system for at least some aspects of E1A function.
Pegylated derivatives of recombinant human arginase (rhArg1) for sustained in vivo activity in cancer therapy: preparation, characterization and analysis of their pharmacodynamics in vivo and in vitro and action upon hepatocellular carcinoma cell (HCC)
Authors: Tsui Sam-Mui , Lam Wai-Man , Lam Tin-Lun , Chong Hiu-Chi , So Pui-Kin , Kwok Sui-Yi , Arnold Simon , Cheng Paul Ning-Man , Wheatley Denys N , Lo Wai-Hung , Leung Yun-Chung
Published: April 2009

Background

Protein used in medicine, e.g. interferon, are immunogenic and quickly broken down by the body. Pegylation is a recognized way of preserving their integrity and reducing immune reactions, and works well with enzymes used to degrade amino acids, a recent focus of attention in controlling cancer growth. Of the two arginine-degrading enzymes being explored clinically, arginine deiminase is a decidedly foreign mycoplasm-derived enzyme, whereas human arginase 1 is a native liver enzyme. Both have been pegylated, the former with adjuncts of 20 kD, the latter with 5 kD PEG. Pegylation is done by several different methods, not all of which are satisfactory or desirable.

Methods

The preparation of novel polyethylene glycol (PEG) derivatives for modifying proteins is described, but directed specifically at pegylation of recombinant human arginase 1 (rhArg1). rhArg1 expressed in Escherichia coli was purified and coupled in various ways with 5 different PEG molecules to compare their protective properties and the residual enzyme activity, using hepatocellular cell lines both in vitro and in vivo.

Results

Methoxypolyethylene glycol-succinimidyl propionate (mPEG-SPA 5,000) coupled with very high affinity under mild conditions. The resulting pegylated enzyme (rhArg1-peg5,000 mw) had up to 6 PEG chains of 5K length which not only protected it from degradation and any residual immunogenicity, but most importantly let it retain >90% of its native catalytic activity. It remained efficacious in depleting arginine in rats after a single ip injection of 1,500 U of the conjugate as the native enzyme, plasma arginine falling to >0.05 μM from ~170 μM within 20 min and lasting 6 days. The conjugate had almost the same efficacy as unpegylated rhArg1 on 2 cultured human liver cancer (HCC) cell lines. It was considerably more effective than 4 other pegylated conjugates prepared.

Conclusion

Valuable data on the optimization of the pegylation procedure and choice of ligand that best stabilizes the enzyme arginase 1 are presented, a protocol that should equally fit many other enzymes and proteins. It is a long lasting arginine-depleting enzyme in vivo which will greatly improve its use in anti-cancer therapy.
Environmentally persistent free radicals amplify ultrafine particle mediated cellular oxidative stress and cytotoxicity
Authors: Balakrishna Shrilatha , Lomnicki Slawo , McAvey Kevin M , Cole Richard B , Dellinger Barry , Cormier Stephania A
Published: April 2009

Background

Combustion generated particulate matter is deposited in the respiratory tract and pose a hazard to the lungs through their potential to cause oxidative stress and inflammation. We have previously shown that combustion of fuels and chlorinated hydrocarbons produce semiquinone-type radicals that are stabilized on particle surfaces (i.e. environmentally persistent free radicals; EPFRs). Because the composition and properties of actual combustion-generated particles are complex, heterogeneous in origin, and vary from day-to-day, we have chosen to use surrogate particle systems. In particular, we have chosen to use the radical of 2-monochlorophenol (MCP230) as the EPFR because we have previously shown that it forms a EPFR on Cu(II)O surfaces and catalyzes formation of PCDD/F. To understand the physicochemical properties responsible for the adverse pulmonary effects of combustion by-products, we have exposed human bronchial epithelial cells (BEAS-2B) to MCP230 or the CuO/silica substrate. Our general hypothesis was that the EPFR-containing particle would have greater toxicity than the substrate species.

Results

Exposure of BEAS-2B cells to our combustion generated particle systems significantly increased reactive oxygen species (ROS) generation and decreased cellular antioxidants resulting in cell death. Resveratrol treatment reversed the decline in cellular glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels for both types of combustion-generated particle systems.

Conclusion

The enhanced cytotoxicity upon exposure to MCP230 correlated with its ability to generate more cellular oxidative stress and concurrently reduce the antioxidant defenses of the epithelial cells (i.e. reduced GSH, SOD activity, and GPx). The EPFRs in MCP230 also seem to be of greater biological concern due to their ability to induce lipid peroxidation. These results are consistent with the oxidizing nature of the CuO/silica ultrafine particles and the reducing nature and prolonged environmental and biological lifetimes of the EPFRs in MCP230.
Short Photoperiod-Induced Decrease of Histamine H3 Receptors Facilitates Activation of Hypothalamic Neurons in the Siberian Hamster
Authors: Barrett P. , van den Top M. , Wilson D. , Mercer J. G. , Song C. K. , Bartness T. J. , Morgan P. J. , Spanswick D.
Published: April 2009

Nonhibernating seasonal mammals have adapted to temporal changes in food availability through behavioral and physiological mechanisms to store food and energy during times of predictable plenty and conserve energy during predicted shortage. Little is known, however, of the hypothalamic neuronal events that lead to a change in behavior or physiology. Here we show for the first time that a shift from long summer-like to short winter-like photoperiod, which induces physiological adaptation to winter in the Siberian hamster, including a body weight decrease of up to 30%, increases neuronal activity in the dorsomedial region of the arcuate nucleus (dmpARC) assessed by electrophysiological patch-clamping recording. Increased neuronal activity in short days is dependent on a photoperiod-driven down-regulation of H3 receptor expression and can be mimicked in long-day dmpARC neurons by the application of the H3 receptor antagonist, clobenproprit. Short-day activation of dmpARC neurons results in increased c-Fos expression. Tract tracing with the trans-synaptic retrograde tracer, pseudorabies virus, delivered into adipose tissue reveals a multisynaptic neuronal sympathetic outflow from dmpARC to white adipose tissue. These data strongly suggest that increased activity of dmpARC neurons, as a consequence of down-regulation of the histamine H3 receptor, contributes to the physiological adaptation of body weight regulation in seasonal photoperiod.
Gut Peptides: Targets for Antiobesity Drug Development?
Authors: Moran Timothy H. , Dailey Megan J.
Published: April 2009

Gut peptides play multiple roles in the controls of gastrointestinal function and in the initiation and termination of meals. Plasma levels of these peptides are differentially affected by the presence of nutrients in the digestive tract, and the patterns of peptide release are consistent with both their feeding stimulatory and inhibitory actions. A number of these peptide systems have been investigated as potential targets for antiobesity drug development. Progress has been made in developing long-acting peptide analogs and, in some cases, nonpeptide agonists and antagonists. Whether any individual approach will have significant long-term efficacy remains to be demonstrated. Approaches that target multiple systems may hold the most promise.
Obesity and Breast Cancer: The Estrogen Connection
Authors: Cleary Margot P. , Grossmann Michael E.
Published: April 2009

There is now substantial evidence that overweight and/or obesity and/or weight gain are risk factors for the development of postmenopausal breast cancer. In addition, obesity and/or elevated body mass index at breast cancer diagnosis has a negative impact on prognosis for both premenopausal and postmenopausal women. Therefore, understanding the mechanism of how obesity affects the mammary tumorigenesis process is an important health issue. Elevated serum estrogen levels as well as enhanced local production of estrogen have been considered primary mediators of how increased body weight promotes breast cancer development in postmenopausal women. Here, we provide an overview of estrogen’s relationship with both obesity and breast cancer as separate entities. Human and relevant preclinical studies are cited. In addition, other growth factors that may be involved in this relationship are considered.
Brain-Derived Neurotrophic Factor Promotes Implantation and Subsequent Placental Development by Stimulating Trophoblast Cell Growth and Survival
Authors: Kawamura Kazuhiro , Kawamura Nanami , Sato Wataru , Fukuda Jun , Kumagai Jin , Tanaka Toshinobu
Published: April 2009

Successful implantation of the blastocyst and subsequent placental development is essential for reproduction. Expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5, together with their receptor, tyrosine kinase B (TrkB), in trophectoderm cells of blastocyst suggests their potential roles in implantation and placental development. Here we demonstrated that treatment with BDNF promoted blastocyst outgrowth, but not adhesion, in vitro and increased levels of the cell invasion marker matrix metalloproteinase-9 in cultured blastocysts through the phosphatidylinositol 3-kinase pathway. After implantation, BDNF and neurotrophin-4/5 proteins as well as TrkB were expressed in trophoblast cells and placentas during different stages of pregnancy. Both TrkB and its ligands were also expressed in decidual cells. Treatment of cultured trophoblast cells with the TrkB ectodomain, or a Trk receptor inhibitor K252a, suppressed cell growth as reflected by decreased proliferation and increased apoptosis, whereas an inactive plasma membrane nonpermeable K252b was ineffective. Studies using the specific inhibitors also indicated the importance of the phosphatidylinositol 3-kinase/Akt pathway in mediating the action of TrkB ligands. In vivo studies in pregnant mice further demonstrated that treatment with K252a, but not K252b, suppressed placental development accompanied by increases in trophoblast cell apoptosis and decreases in placental labyrinth zone at midgestation. In vivo K252a treatment also decreased fetal weight at late gestational stages. Our findings suggested important autocrine/paracrine roles of the BDNF/TrkB signaling system during implantation, subsequent placental development, and fetal growth by increasing trophoblast cell growth and survival.