bluuebunny/crossref_metadata_2025 huggingface dataset:
Àrokò, Mmomomme Twe, Nsibidi, Ogede, and Tusona
Authors: Ogunleye Tolagbe M.
Published: December 2005

For approximately 150 years, Africans fled enslavement on Southern plantations and lived autonomously in Florida, using discrete African art forms, traditions, and sensibilities in their modes of communications, rituals, subsistence strategies, and battle plans to prosper and achieve and sustain their freedom and autonomy. This article reconstructs the ways cultural forms and practices, such as àrokò, nsibidi, tusona or sona (ideographic writing systems), and mmomomme twe and ogede (incantations), functioned in these self-emancipated Africans’ stratagems to escape from Spanish, British, and American plantations; thrive socially and economically in the autonomous settlements they established; elude recapture; and defeat their former enslavers and other foe militarily despite their adversaries’ incessant onslaughts, advanced artillery, manpower, and economic advantages.
Are HBCUs Up to Speed Technologically?
Authors: Snipes Vincent T. , Ellis Walter , Thomas Joy
Published: December 2005

In the United States, the digital divide exists, which is a gap between people with access to technology and those who do not have access. The African American community is far behind Whites in terms of computer and Internet usage. Many advocates of Historically Black Colleges and Universities (HBCUs) are concerned about the existence of a digital divide between predominantly White colleges and HBCUs. This study reports technology scores for the faculty of a small Southern HBCU on its familiarity and use of technology. Furthermore, the study focuses on how the college administrators addressed technology issues on the campus over a 3-year period following the initial faculty technology survey. Recommendations are shared to enable HBCUs to compete and thrive technologically.
Civil Rights in Twilight
Authors: Lehman Christopher Paul
Published: December 2005

Despite inattention given to the civil rights movement in 1973, it was very much alive then. The major groups of the movement still existed. In addition, anticivil rights groups funded by Mississippi and Alabama taxpayers continued to spy on movement participants. However, both the movement and its opposition did not effectively adjust to federally imposed desegregation under the Civil Rights Act and the Voting Rights Act. Their simultaneous disintegration in 1973 effectively ended the civil rights movement era.
The Development of a Counter-Epistemic Community: AIDS, South Africa, and International Regimes
Authors: Youde Jeremy
Published: December 2005

The South African government’s open challenging of the international AIDS control regime presents a paradox for the study of international regimes and epistemic communities: why would a state that would presumably benefit the most from a regime not only refuse to adhere to its precepts, but openly challenge its basic tenets? I argue that a fundamental disjuncture exists between the international AIDS control regime and the South African government, and that this disjuncture is rooted in the country’s negative past experiences with public health interventions and the attempts to forge a new, African Renaissance-inspired self-identity. This disjuncture finds its expression through the development of a counter-epistemic community which offers scientific expertise and policy recommendations to the South African government. The counter-epistemic community translates history and identity into policy outcomes that challenge the established discourse.
Health and Peacebuilding: Resuscitating the Failed State in Sierra Leone
Authors: Rushton Simon
Published: December 2005

In recent years it has increasingly been claimed that health-sector initiatives have the potential to make a meaningful contribution to post-conflict peacebuilding. This article examines two types of such claims - that health can act as a ‘bridge for peace’, and that health-sector reconstruction can assist in rebuilding the social contract and reestablishing the legitimacy of the government - and how they played out in the case of Sierra Leone. In this case there was an opportunity for health-sector assistance to go beyond mere humanitarian relief and for it to play an active role in promoting peace and stability. It is argued that the best chance of success may lie in a successful blending of Health as a Bridge for Peace-type approaches and ‘top-down’ government-centred interventions as the country moves from the immediate post-war relief phase to the longer-term process of securing future peace and stability.
Chinese Medicine and Medical Pluralism in Dar es Salaam: Globalisation or Glocalisation?
Authors: Jennings Michael
Published: December 2005

African healing systems have always been pluralistic in form and structure, capable of absorbing new traditions and practices. The spread of Chinese medicine in Tanzania over the past decade is a testament to the flexibility of pluralistic healing systems, as well as evidence of south-south processes of globalisation that are often ignored by the literature on globalisation. This article suggests, through a study of a Chinese medical clinic in Dar es Salaam, that its popularity highlights the strengths of local cultures despite increasing globalising forces, and that any consideration of globalisation must include south-south (or East-south) dynamics as well as the customary focus on the north-south track. The article also suggests that whilst the absorption of new traditions of healing speaks to the strength of the local, it also functions as an indication of the failure of alternative healing systems to address key current medical needs, and as such represents a crisis in health, as much as strength, in the healing sector.
Resource-based theories of competitive advantage: A ten-year retrospective on the resource-based view
Authors: Barney Jay B.
Published: December 2005

The resource-based view can be positioned relative to at least three theoretical traditions: SCP-based theories of industry determinants of firm performance, neo-classical microeconomics, and evolutionary economics. In the 1991 article, only the first of these ways of positioning the resourcebased view is explored. This article briefly discusses some of the implications of positioning the resource-based view relative to these other two literatures; it also discusses some of the empirical implications of each of these different resource-based theories.
A resource-based theory of sustainable rents
Authors: Mahoney Joseph T.
Published: December 2005

This paper summarizes and comments on Conner (1991) that contributes to the strategic management area by providing an historical comparison of resource-based theory and five schools of thought within industrial organization economics. Conner (1991) argues that the fundamental distinction between resource-based theory and transaction costs theory is that resource-based theory focuses on the deployment and combination of specific inputs while transaction costs theory focuses on the avoidance of opportunism. I offer three responses to this claim. First, Conner’s distinction was not central to the resource-based literature at the time the article was published. Second, I raise concerns about building a resource-based theory of the firm that assumes away the problems of opportunistic behavior. Third, I offer an alternative view of the fundamental similarities and differences between resource-based theory and transaction costs theory.
The managerial rents model: Theory and empirical analysis
Authors: Castanias Richard P. , Helfat Constance E.
Published: December 2005

Managerial resources, defined as the skills and abilities of managers, are important contributors to the entire bundle of firm resources that enable some firms to generate rents. Here we build on our original analysis (Castanias & Helfat, 1991) and present an expanded classification of managerial resources, elaborate on how this classification relates to the fundamental resource-based characteristics of value, scarcity, inimitability, and difficulty of substitution, and highlight the issue of appropriability of rents from managerial resources. We then move well beyond the original analysis to examine a large number of empirical implications of our model, including many contingency factors, and discuss recent empirical research. Finally, we suggest extensions of the model to include managerial cognition and social capital, and draw implications for resource-based theory more generally.
Resource complementarity in business combinations: Extending the logic to organizational alliances
Authors: Harrison Jeffrey S. , Hitt Michael A. , Hoskisson Robert E. , Ireland R. Duane
Published: December 2005

Organizations are combining resources through acquisitions and alliances in record numbers. Since publication of our original study in 1991, research has confirmed that resource complementarity creates the potential for greater synergy from acquisitions and alliances, leading to higher long-term firm performance as an end result. The valuable, unique, and inimitable synergy that can be realized by integrating complementary resources provides an opportunity for the firm to create competitive advantages that can be sustained for a period of time. In addition, complementary resources present opportunities for enhanced learning as well as the development of new capabilities. However, we also suggest that the existence of complementary resources is a necessary but insufficient condition to achieve synergy. The resources must be effectively integrated and managed to realize the synergy.
The entrepreneurship of resource-based theory
Authors: Alvarez Sharon A. , Busenitz Lowell W.
Published: December 2005

This paper examines the relationship between resource-based theory and entrepreneurship and develops insights that advance the boundaries of resource-based theory and begin to address important questions in entrepreneurship. We extend the boundaries of resource-based theory to include the cognitive ability of individual entrepreneurs. Entrepreneurs have individual-specific resources that facilitate the recognition of new opportunities and the assembling of resources for the venture. By focusing on resources, from opportunity recognition to the ability to organize these resources into a firm and then to the creation of heterogeneous outputs through the firm that are superior to the market, we help identify issues that begin to address the distinctive domain of entrepreneurship.
Freedom of Information in a Modern Society
Authors: Sejersted Francis
Published: December 2005

In 2004 the Norwegian Parliament adopted a new article on the freedom of expression in the Constitution. The problems confronting a liberal society as considered in this connection are discussed. Special attention is given to the conditions for the freedom of information in a modern society. The problems of the information policy of the public authorities are given special attention, as are also the problems and possibilities caused by the new technological development. The importance of the institutional setting and the need for diversity are emphasized.
Rising from the Wreckage: development of tsunami-affected libraries in Sri Lanka
Authors: Amarasiri Upali
Published: December 2005

Describes the devastation caused to public, school and other kinds of libraries and public records by the tsunami which hit the coasts of Sri Lanka and other Asian countries on 26 December 2004. Outlines the rebuilding efforts now under way, including the establishment of a national disaster management committee for library and information services and archives, the involvement of local communities and the response of the international community. Notes that the rebuilding of the village-based social fabric in the coastal zone of Sri Lanka is the principal challenge at present. Emphasizes the need to keep libraries on the reconstruction agenda and to establish an international rapid response team able to team up with local librarians, archivists, archaeologists and others in countries affected by similar disasters to identify vulnerable resources, assess the damage and take remedial action.
Public Libraries and the Millennium Development Goals
Authors: Forsyth Ellen
Published: December 2005

Public libraries can make a major contribution to the achievement of the eight United Nations Millennium Development Goals. This paper examines actual and potential uses highlighting the importance of libraries to community development, and provides some examples, such as mobile libraries in slums and reading tents, where libraries are already assisting with Millennium Development Goals being achieved.
Bioinformatics and the Library and Information Science Community
Authors: Kalra Harinder P.S.
Published: December 2005

Discusses the emergence of bioinformatics in the last three decades as a result of the convergence of networks and genetics. Though a variety of definitions and descriptions of bioinformatics are available, a cross-disciplinary definition eludes. The paper emphasizes that the core activities of library and information science can be of immense value in advancing the theoretical foundations of this emerging subject, as well as developing the mechanisms and tools for quality biomedical information in a timely manner. The creation, management, and dissemination of biomedical knowledge and information for both specialists and for laymen is a challenge and an opportunity for library and information professionals to broaden their professional horizons and to generate new knowledge in the process.
The Continuing Myth of the Violent Female Offender
Authors: Pollock Joycelyn M. , Davis Sareta M.
Published: December 2005

There have been periodic “discoveries” of the violent female offender as well as dire predictions of an increase in violence committed by women. The authors examine the pattern of violent crime by women over a long period of time to determine whether or not the “problem” of increasing violence is a myth. The authors conclude that women’s contribution to violent crime has been and continues to make up a small percentage, except for crime categories that are highly vulnerable to changes in system responses.
Registers in the Academic Writing of African American College Students
Authors: Syrquin Anna F.
Published: December 2005

The study examines the development of the registers of academic writing by African American college-level students through style and grammar: indirection inherent in the oral culture of the African American community and the paratactic functions of because. Discourse analysis of 74 samples of academic writing by 20 African American undergraduate students and of 61 samples by a control group showed that first, only African American subjects used indirection; second, paratactic functions of because were significantly more prevalent among African American students than in the control group; and third, among African American students, those from low-income families showed statistically significant higher frequencies of the use of both indirection and paratactic because. A relationship of hierarchy in the uses of indirection and paratactic because was also evident in the data.
Why We Chose Rhetoric
Authors: Spigelman Candace , Grobman Laurie
Published: December 2005

This article examines the authors’ arduous struggle to develop a professional communication program that would not only meet their students’ professional and intellectual needs but also achieve an identity consistent with their goals as scholars and teachers of composition. Ultimately, the authors argue that a professional communication program that combines in its teaching the ethos of a liberal arts tradition along with the practical skills needed by writers in the workplace is both desirable and possible but that it must be flexible enough to allow for ongoing curricular and philosophical negotiations to meet changing contextual demands.
Technology Artifacts, Instrumentalism, and the Humanist Manifestos
Authors: Knievel Michael
Published: December 2005

Since the late 1970s, technical communication scholars and teachers have largely agreed that technical communication’s humanistic character can be found in the field’s rhetorical nature and the social nature of discourse. Building on Patrick Moore’s efforts to rehabilitate “instrumental discourse” in the face of such general consensus, this essay argues that such notions of technical communication’s humanistic character, although unquestionably groundbreaking and crucial to the field’s sense of self and mission, remain too deeply indebted to traditional academic humanities’ and English studies’ constructions of humanistic purview, which largely refuse to accommodate technology, especially physical technology artifacts. Considering alternatives that recast the technology-humanities relationship and situate technology within a humanistic framework can yield benefits for both technical communication and English studies broadly construed.
An Indirect Style in Business Communication
Authors: Ding Daniel D.
Published: December 2005

This article investigates how Confucianism inspires an indirect style in professional communication in China. Particularly, the author examines two major philosophical principles of Confucianism, Li (rituals/rules) and Ren (love/benevolence), and discusses how they encourage individuals to establish proper human relationships, to humble themselves, and to shun pure personal profits. Dictated by Confucianism, Chinese writers often focus on interpersonal relationships, humble themselves, and avoid personal profits before discussing pertinent business issues. As a result, Chinese writers are indirect in their style. They often employ the indirect style to accommodate two pragmatic acts: (a) establishing their ethos that helps create a strong bond between individuals at a more personal level and (b) building a harmonious social structure at a more societal level. Such a style is conducive to successful business transactions. So, it should not be explained as ineffective or as mere digressions.
Research Self-Efficacy Beliefs and Research Outcome Expectations: Implications for Developing Scientifically Minded Psychologists
Authors: Bieschke Kathleen J.
Published: December 2005

This article explores how and whether the empirical evidence pertaining to research self-efficacy beliefs and research outcome expectations can inform the training and development of scientifically minded psychologists. The competencies associated with a scientifically minded psychologist are described, and a summary and critique of the literature focused on research self-efficacy beliefs and research outcome expectations are presented. An assessment of whether these constructs are adequate for facilitating the development of scientifically minded psychologists is provided. Implications for future research directions are discussed.
The Form of the Firm
Authors: Baecker Dirk
Published: December 2005

This paper presents a sociological and constructivist model of the organization of a firm. It presents five suggestions, and one problem, on which the theory of the firm may be based. These are history, business, culture, management, systems references and context respectively. It goes on to introduce George Spencer Brown’s notion of form as an appropriate device with which to handle the problem. Niklas Luhmann’s theory of social systems is considered to be an important step in developing a theory of differentiation that combines closure with structure, or self-referentiality with coupling, in showing how dependent communication emerges from independent contingency. The model then focuses on the idea of a contingent co-variation of the variables product, technology, organization, economy, society and individuals. It is developed with respect to five levels of re-entry: work, business, corporate culture, communication and philosophy. The idea of the paper is that models of this kind may be able to contribute to an analytical understanding of the synthesis of a firm by enabling an observer, who may be an employee, a manager, an investor, a client, a partner, an analyst or a consultant, to interact selectively with that firm and thereby take part in its reproduction and variation.
Collaboration for School Improvement
Authors: Connolly Michael , James Chris
Published: December 2005

Those with an interest in public sector institutions increasingly recognize the necessity for those institutions to work collaboratively with each other and with other organizations. In part, this trend is based on the acceptance that many public policy problems are interconnected and can only be meaningfully tackled interorganizationally. One such policy area is school improvement, which constitutes the central concern of the article and is currently a dominant feature of education policy in Britain. The article conceptualizes the notion of educational collaboration by developing a framework through a review of the relevant literature. The analytical framework makes a paradigmatic distinction between resource dependency and institutional perspectives on collaboration. It recognizes that, although the perspectives interrelate in practice, the interests they serve are distinct and different. The framework acknowledges that individual actors, such as teachers, those in leadership positions in schools, and managers in local authorities may have different purposes for collaboration and disaggregates the antecedents, the process and the successful and unsuccessful outcomes of collaboration.
Closing the Gap
Authors: Mercer David , Ri Lai
Published: December 2005

This article explores the role of heads of department in a small sample of secondary schools in the People's Republic of China. The research which underpins the article consisted of data collected from school teachers and headteachers of the case study schools. The outcome was that there is a large gap between how middle managers perceive their actual responsibilities and what they wish those responsibilities might be. The situation revealed by the research was contrasted with the situation common in Western schools as we move towards a situation of distributed leadership as a means of developing effective schools. While it is recognized that cultural differences exist and that such differences must be taken into account in any comparative exercise, the research concludes that there is a need for schools in China to review their thinking with regard to the role of the head of department.
Developing a Model for Strategic Leadership in Schools
Authors: Davies Barbara J. , Davies Brent
Published: December 2005

Strategic leadership is a critical component in the effective development of schools. Currently the educational debate is shifting to focus on how short-term improvements can become strategically sustainable. This article will put forward the view that renewed attention needs to be paid to the strategic dimension of leadership to ensure this sustainability. Much of the orthodox perspective of leadership development suggests that new leaders tend to .rst address current administrative and managerial issues to build con.dence and organizational ability before moving to a strategic and futures activities. The article argues that schools need a concurrent or parallel view of leadership development in which leaders focus not only on the ‘now’ of school improvement but concurrently build strategic capability within the school.
The Notch ligand delta-1 is a hematopoietic development cofactor for plasmacytoid dendritic cells
Authors: Olivier Aurélie , Lauret Evelyne , Gonin Patrick , Galy Anne
Published: December 2005

Plasmacytoid dendritic cells (pDCs) play an important role in innate and adaptive immunity, prompting interest in mechanisms controlling the production of this lineage of cells. Notch signaling via one of the Notch ligands, delta-like 1 (delta-1), influences the hematopoietic development of several lymphoid and myeloid lineages, but whether or not delta-1 affects the formation of pDCs is unknown and was tested here. Human CD34+ progenitor cells were cultured onto delta-1–expressing OP9 stroma in the presence of flt-3 ligand and IL-7, and this efficiently generated BDCA-2+ CD123+ CD4+ CD11c– cells with the characteristic morphology of pDCs, expressing toll-like receptor-9 (TLR9), pre-Tα mRNAs, and secreting CpG-induced IFN-α. Delta-1 augmented the numbers of BDCA-2+ cells produced without affecting their proliferation, and the effect was blocked by γ-secretase inhibition. The development of pDCs was stroma-, delta-1–, and cytokine-dependent and could be induced from committed lymphoid progenitor cells, which responded to delta-1 by opposite changes in pDC- and B-cell production. Our results identify delta-1 as a novel factor enhancing pDC hematopoiesis and delineate a new role for Notch signaling in lymphopoiesis by showing its opposite effect on pDC and B lineage determination.
Human mast cells express multiple EP receptors for prostaglandin E2 that differentially modulate activation responses
Authors: Feng Chunli , Beller Elizabeth M. , Bagga Savita , Boyce Joshua A.
Published: December 2005

Prostaglandin E2 (PGE2) blocks mast-cell (MC)-dependent allergic responses in humans but activates MCs in vitro. We assessed the functions of the EP receptors for PGE2 on cultured human MCs (hMCs). hMCs expressed the EP3, EP2, and EP4 receptors. PGE2 stimulated the accumulation of cyclic adenosine monophosphate (cAMP), and suppressed both FcϵRI-mediated eicosanoid production and tumor necrosis factor-α (TNF-α) generation. PGE2 also caused phosphorylation of extracellular signal-regulated kinase (ERK), exocytosis, and production of prostaglandin D2 (PGD2), as well as leukotriene C4 (LTC4) when protein kinase A (PKA) was inhibited. An EP3 receptor-selective agonist, AE-248, mimicked PGE2-mediated ERK phosphorylation, exocytosis, and eicosanoid formation. Selective agonists of both EP2 and EP4 receptors (AE1-259-01 and AE-329, respectively) stimulated cAMP accumulation. No selective agonist, alone or in combination, was as effective as PGE2. AE-248, AE1-259-01, and AE-329 all inhibited FcϵRI-mediated TNF-α generation, while AE1-259-01 blocked eicosanoid production. PGE2 caused the expression of inducible cAMP early repressor (ICER) by a pathway involving PKA and ERK. Thus, while PGE2 activates MCs through EP3 receptors, it also counteracts FcϵRI-mediated eicosanoid production through EP2 receptors and PKA, and blocks cytokine transcription. These functions explain the potency of PGE2 as a suppressor of early- and late-phase allergic responses.
Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated in alternatively activated macrophages and secreted via lysosomal pathway
Authors: Kzhyshkowska Julia , Mamidi Srinivas , Gratchev Alexei , Kremmer Elisabeth , Schmuttermaier Christina , Krusell Liis , Haus Georg , Utikal Jochen , Schledzewski Kai , Scholtze Joachim , Goerdt Sergij
Published: December 2005

Mammalian Glyco_18-domain–containing proteins include catalytically active chitinases and chitinase-like proteins with cytokine activity involved in host defense and Th2-type inflammatory reactions. Here, we describe a novel human Glyco_18-domain–containing protein, SI-CLP, as an interacting partner of the endocytic/sorting receptor stabilin-1. Similarly to the chitinase-like cytokines YKL-39, YKL-40, and YM1/2, SI-CLP lacks a chitin-binding domain and catalytic amino acids. Using a novel mAb 1C11, we demonstrated that SI-CLP is sorted into late endosomes and secretory lysosomes in human alternatively activated macrophages. The direct interaction of SI-CLP with stabilin-1, their colocalization in the trans-Golgi network, and the reduced sorting of SI-CLP into lysosomes in macrophages treated with stabilin-1 siRNA suggest that stabilin-1 is involved in intracellular sorting of SI-CLP. Expression of SI-CLP in macrophages was strongly up-regulated by the Th2 cytokine IL-4 and by dexamethasone. This effect was suppressed by IFNγ but not affected by IL-10. In contrast, expression of YKL-40 was induced by IFNγ and suppressed by dexamethasone. Macrophages treated with IL-4 secreted SI-CLP, while costimulation with dexamethasone blocked secretion and resulted in intracellular accumulation of SI-CLP. The 1C11 mAb detected SI-CLP in human bronchoalveolar lavage and peripheral-blood leukocytes (PBLs), and can be used to analyze the role of SI-CLP in human disorders.
The small GTPase Rap1b regulates the cross talk between platelet integrin α2β1 and integrin αIIbβ3
Authors: Bernardi Bruno , Guidetti Gianni F. , Campus Francesca , Crittenden Jill R. , Graybiel Ann M. , Balduini Cesare , Torti Mauro
Published: December 2005

The involvement of the small GTPase Rap1b in platelet integrin α2β1-dependent outside-in signaling was investigated. Platelet adhesion to 4 different specific ligands for integrin α2β1, monomeric collagen, decorin, and collagen-derived peptides CB8(II) and CB11(II), induced a robust and rapid activation of Rap1b. This process did not require secreted ADP or thromboxane A2 production but was critically regulated by phospholipase C (PLC)–derived second messengers. Both Ca2+ and protein kinase C were found to organize independent but additive pathways for Rap1b activation downstream of integrin-α2β1, which were completely blocked by inhibition of PLC with U73122. Moreover, integrin α2β1 engagement failed to trigger Rap1b activation in murine platelets lacking CalDAG-GEFI, a guanine nucleotide exchange factor regulated by Ca2+ and diacylglycerol, despite normal phosphorylation and activation of PLCγ2. In addition, CalDAG-GEFI–deficient platelets showed defective integrin α2β1-dependent adhesion and spreading. We found that outside-in signaling through integrin α2β1 triggered inside-out activation of integrin αIIbβ3 and promoted fibrinogen binding. Similarly to Rap1b stimulation, this process occurred downstream of PLC activation and was dramatically impaired in murine platelets lacking the Rap1 exchange factor CalDAG-GEFI. These results demonstrate that Rap1b is an important element in integrin-dependent outside-in signaling during platelet adhesion and regulates the cross talk between adhesive receptors.
Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?
Authors: D'hulst An I , Maes Tania , Bracke Ken R , Demedts Ingel K , Tournoy Kurt G , Joos Guy F , Brusselle Guy G
Published: December 2005

Background

Chronic obstructive pulmonary disease is associated with a chronic inflammatory response of the host to chronic exposure to inhaled toxic gases and particles. Although inflammatory cells of both the innate and adaptive immune system infiltrate the lungs in pulmonary emphysema and form lymphoid follicles around the small airways, the exact role of the acquired immune system in the pathogenesis of emphysema is not known.

Methods

In this study, wild typeBalb/cmice and immunodeficientscidmice – which lack functional B- and T-cells – were exposed to mainstream cigarette smoke (CS) for 5 weeks or 6 months.

Results

Subacute CS-exposure for 5 weeks significantly increased innate inflammatory cells (neutrophils, macrophages and dendritic cells) in the bronchoalveolar lavage (BAL) fluid of wild type mice andscidmice, which correlated with the CS-induced upregulation of the chemokines Monocyte Chemotactic Protein-1, Macrophage Inflammatory Protein-3α and KC (= mouse Interleukin-8). Chronic CS-exposure for 6 months significantly increased the number of neutrophils, macrophages, dendritic cells, CD4+and CD8+T-lymphocytes in BAL fluid and lungs of wild type mice compared to air-exposed littermates, and augmented the size and number of peribronchial lymphoid follicles. In contrast, neither B-lymphocytes, nor T-lymphocytes, nor lymphoid follicles could be discerned in the lungs of air- or CS-exposedscidmice. Importantly, chronic CS-exposure induced pulmonary emphysema in both wild type animals andscidmice, as evidenced by a significant increase in the mean linear intercept and the destructive index of CS-exposed versus air-exposed animals. The CS-induced emphysema was associated with increased mRNA expression of matrix metalloproteinase-12 in the lungs and increased protein levels of Tumor Necrosis Factor-α in the BAL fluid of CS-exposedBalb/candscidmice compared to air-exposed littermates.

Conclusion

This study suggests that the adaptive immune system is not required per se to develop pulmonary emphysema in response to chronic CS-exposure, since emphysema can be induced inscidmice, which lack lymphoid follicles as well as functional B- and T-cells.
Dimerization and enzymatic activity of fungal 17β-hydroxysteroid dehydrogenase from the short-chain dehydrogenase/reductase superfamily
Authors: Kristan Katja , Deluca Dominga , Adamski Jerzy , Stojan Jure , Rižner Tea Lanišnik
Published: December 2005

Background

17β-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17β-HSDcl) is a member of the short-chain dehydrogenase/reductase (SDR) superfamily. SDR proteins usually function as dimers or tetramers and 17β-HSDcl is also a homodimer under native conditions.

Results

We have investigated here which secondary structure elements are involved in the dimerization of 17β-HSDcl and examined the importance of dimerization for the enzyme activity. Sequence similarity with trihydroxynaphthalene reductase from Magnaporthe grisea indicated that Arg129 and His111 from the αE-helices interact with the Asp121, Glu117 and Asp187 residues from the αE and αF-helices of the neighbouring subunit. The Arg129Asp and His111Leu mutations both rendered 17β-HSDcl monomeric, while the mutant 17β-HSDcl-His111Ala was dimeric. Circular dichroism spectroscopy analysis confirmed the conservation of the secondary structure in both monomers. The three mutant proteins all bound coenzyme, as shown by fluorescence quenching in the presence of NADP+, but both monomers showed no enzymatic activity.

Conclusion

We have shown by site-directed mutagenesis and structure/function analysis that 17β-HSDcl dimerization involves the αE and αF helices of both subunits. Neighbouring subunits are connected through hydrophobic interactions, H-bonds and salt bridges involving amino acid residues His111 and Arg129. Since the substitutions of these two amino acid residues lead to inactive monomers with conserved secondary structure, we suggest dimerization is a prerequisite for catalysis. A detailed understanding of this dimerization could lead to the development of compounds that will specifically prevent dimerization, thereby serving as a new type of inhibitor.
Introduction of in vitro transcribed ENO1 mRNA into neuroblastoma cells induces cell death
Authors: Ejeskär Katarina , Krona Cecilia , Carén Helena , Zaibak Faten , Li Lingli , Martinsson Tommy , Ioannou Panayiotis A
Published: December 2005

Background

Neuroblastoma is a solid tumour of childhood often with an unfavourable outcome. One common genetic feature in aggressive tumours is 1p-deletion.

The α-enolase (ENO1) gene is located in chromosome region 1p36.2, within the common region of deletion in neuroblastoma. One alternative translated product of the ENO1 gene, known as MBP-1, acts as a negative regulator of the c-myc oncogene, making the ENO1 gene a candidate as a tumour suppressor gene.

Methods

Methods used in this study are transfection of cDNA-vectors and in vitro transcribed mRNA, cell growth assay, TUNEL-assay, real-time RT-PCR (TaqMan) for expression studies, genomic sequencing and DHPLC for mutation detection.

Results

Here we demonstrate that transfection of ENO1 cDNA into 1p-deleted neuroblastoma cell lines causes' reduced number of viable cells over time compared to a negative control and that it induces apoptosis. Interestingly, a similar but much stronger dose-dependent reduction of cell growth was observed by transfection of in vitro transcribed ENO1 mRNA into neuroblastoma cells. These effects could also be shown in non-neuroblastoma cells (293-cells), indicating ENO1 to have general tumour suppressor activity.

Expression of ENO1 is detectable in primary neuroblastomas of all different stages and no difference in the level of expression can be detected between 1p-deleted and 1p-intact tumour samples. Although small numbers (11 primary neuroblastomas), there is some evidence that Stage 4 tumours has a lower level of ENO1-mRNA than Stage 2 tumours (p = 0.01). However, mutation screening of 44 primary neuroblastomas of all different stages, failed to detect any mutations.

Conclusion

Our studies indicate that ENO1 has tumour suppressor activity and that high level of ENO1 expression has growth inhibitory effects.
Subacute Sclerosing Panencephalitis: Results of the Canadian Paediatric Surveillance Program and review of the literature
Authors: Campbell Craig , Levin Simon , Humphreys Peter , Walop Wikke , Brannan Renee
Published: December 2005

Background

Subacute Sclerosing Panencephalitis (SSPE) is so rare in developed countries with measles immunization programs that national active surveillance is now needed to capture sufficient number of cases for meaningful analysis of data. Through the Canadian Paediatric Surveillance Program (CPSP), the SSPE study was able to document a national incidence and determine the epidemiology of affected Canadian children.

Methods

Between 1997 and 2000, the CPSP surveyed monthly 1978 to 2294 Canadian pediatricians and sub-specialists for SSPE cases. The response rate varied from 82–86% over those years.

Results

Altogether, four SSPE cases were reported to the CPSP: one case before, two during and one after the study period. The incidence of SSPE in Canadian children was 0.06/million children/year. Of the four cases, diagnosed between ages four and 17 years, three children had measles infection in infancy. All children showed a progressive course of dementia, loss of motor skills and epilepsy. Two children were treated with isoprinosine and intraventricular interferon but died in less than three years from disease onset. One child did not have any treatment and died after seven years of illness. One child received intraventricular ribavirin and remains alive, but markedly impaired, nine years following diagnosis.

Conclusion

The CPSP has demonstrated that Canadian paediatricians and paediatric neurologists may encounter cases of SSPE. This report highlights the clinical course of affected Canadian children and provides a review of the disease and its management.
The effect of cartilage and bone density of mushroom-shaped, photooxidized, osteochondral transplants: an experimental study on graft performance in sheep using transplants originating from different species
Authors: Waselau Anja C , Nadler Daniel , Müller Jessika MV , Zlinszky Katalin , Hilbe Monika , Auer Jörg A , von Rechenberg Brigitte
Published: December 2005

Background

Differences in overall performance of osteochondral photooxidized grafts were studied in accordance of their species origin and a new, more rigorous cleansing procedure using alcohol during preparation.

Methods

Photooxidized mushroom-shaped grafts of bovine, ovine, human and equine origin were implanted in the femoral condyles of 32 sheep (condyles: n = 64). No viable chondrocytes were present at the time of implantation. Grafts were evaluated at 6 months using plastic embedded sections of non-decalcified bone and cartilage specimens. Graft incorporation, the formation of cyst-like lesions at the base of the cartilage junction as well as cartilage morphology was studied qualitatively, semi-quantitatively using a score system and quantitatively by performing histomorphometrical measurements of percentage of bone and fibrous tissue of the original defects. For statistical analysis a factorial analysis of variance (ANOVA- test) was applied.

Results

Differences of graft performance were found according to species origin and cleansing process during graft preparation. According to the score system cartilage surface integrity was best for equine grafts, as well as dislocation or mechanical stability. The equine grafts showed the highest percentage for bone and lowest for fibrous tissue, resp. cystic lesions. The new, more rigorous cleansing process decreased cartilage persistence and overall graft performance.

Conclusion

Performance of grafts from equine origin was better compared to bovine, ovine and human grafts. The exact reason for this difference was not proven in the current study, but could be related to differences in density of cartilage and subchondral bone between species.
Tango's maximized excess events test with different weights
Authors: Song Changhong , Kulldorff Martin
Published: December 2005

Background

Tango's maximized excess events test (MEET) has been shown to have very good statistical power in detecting global disease clustering. A nice feature of this test is that it considers a range of spatial scale parameters, adjusting for the multiple testing. This means that it has good power to detect a wide range of clustering processes. The test depends on the functional form of a weight function, and it is unknown how sensitive the test is to the choice of this weight function and what function provides optimal power for different clustering processes. In this study, we evaluate the performance of the test for a wide range of weight functions.

Results

The power varies greatly with different choice of weight. Tango's original choice for the weight function works very well. There are also other weight functions that provide good power.

Conclusion

We recommend the use of Tango's MEET to test global disease clustering, either with the original weight or one of the alternate weights that have good power.
Effects of psycho-educational intervention on health-related quality of life (QOL) of patients with chronic liver disease referring to Shiraz University of Medical Sciences
Authors: Sharif Farkhondeh , Mohebbi Sadrollah , Tabatabaee Hamid-Reza , Saberi-Firoozi Mehdi , Gholamzadeh Sakineh
Published: December 2005

Background

Chronic liver diseases (CLDs) are progressive disorder which has a significant impact on the well-being of patients and leads to significant morbidity. CLDs are characterized by disturbances in physical, psychological and social aspects of well-being. It causes significant health-related quality of life (QOL) impairment. Psycho-educational interventions targeting to functional factors could be beneficial for patients with CLDs.

Methods

An interventional study was conducted on 110 patients with CLDs in Shiraz Liver Transplantation Center (SLTC). Subjects with the required CLDs criteria were selected and randomly divided into experimental (55) and control (55) groups. A two part questionnaire with 25 items concerning demographic and general information and 29 items regarding QOL was used. The psycho-educational needs of the experimental group were assessed in a session before the intervention, then the experimental group took part in 3 sessions individually and one session in groups. The questionnaires were filled in again for both groups but the control group did not receive the intervention program. The questionnaires were filled in again for both groups one day and three months after the intervention.

Results

Findings revealed no significant differences between the two groups from the view point of demographic characteristics such as marital status, gender, etc... (p > 0.05) and from the point of clinical variables no statistically significant differences were found (p > 0.05).

Findings revealed statistically significant differences in all domain of QOL in the experimental group three months after the intervention (p = 0.001), while there was no statistically significant differences in the control group.

Conclusion

The results of this study revealed that psycho-educational intervention had a significant effect on QOL of patients with CLDs.
It's the virus, stupid – part 2
Authors: Berkhout Ben
Published: December 2005

This editorial presents Retrovirology's choice for the best basic science "retrovirus paper of the year 2005".
Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis
Authors: Jongbloed Sarah L , Lebre M Cristina , Fraser Alasdair R , Gracie J Alastair , Sturrock Roger D , Tak Paul P , McInnes Iain B
Published: December 2005

Dendritic cells (DCs) comprise heterogeneous subsets of professional antigen-presenting cells, linking innate and adaptive immunity. Analysis of DC subsets has been hampered by a lack of specific DC markers and reliable quantitation assays. We characterised the immunophenotype and functional characteristics of psoriatic arthritis (PsA)-derived and rheumatoid arthritis (RA)-derived myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) to evaluate their potential role in arthritis. Circulating peripheral blood (PB) pDC numbers were significantly reduced in PsA patients (P = 0.0098) and RA patients (P = 0.0194), and mDCs were significantly reduced in RA patients (P = 0.0086) compared with healthy controls. The number of circulating mDCs in RA PB was significantly inversely correlated to C-reactive protein (P = 0.021). The phenotype of both DC subsets in PsA PB and RA PB was immature as compared with healthy controls. Moreover, CD62L expression was significantly decreased on both mDCs (PsA, P = 0.0122; RA, P = 0.0371) and pDCs (PsA, P = 0.0373; RA, P = 0.0367) in PB. Both mDCs and pDCs were present in PsA synovial fluid (SF) and RA SF, with the mDC:pDC ratio significantly exceeding that in matched PB (PsA SF, P = 0.0453; RA SF, P = 0.0082). pDCs isolated from RA SF and PsA SF displayed an immature phenotype comparable with PB pDCs. RA and PsA SF mDCs, however, displayed a more mature phenotype (increased expression of CD80, CD83 and CD86) compared with PB mDCs. Functional analysis revealed that both SF DC subsets matured following toll-like receptor stimulation. pDCs from PB and SF produced interferon alpha and tumour necrosis factor alpha on TLR9 stimulation, but only SF pDCs produced IL-10. Similarly, mDCs from PB and SF produced similar tumour necrosis factor alpha levels to TLR2 agonism, whereas SF mDCs produced more IL-10 than PB controls. Circulating DC subset numbers are reduced in RA PB and PsA PB with reduced CD62L expression. Maturation is incomplete in the inflamed synovial compartment. Immature DCs in SF may contribute to the perpetuation of inflammation via sampling of the inflamed synovial environment, and in situ presentation of arthritogenic antigen.
Intra-articular injection of recombinant TRAIL induces synovial apoptosis and reduces inflammation in a rabbit knee model of arthritis
Authors: Yao Qingping , Seol Dai-Wu , Mi Zhibao , Robbins Paul D
Published: December 2005

We demonstrated previously that local, intra-articular injection of an adenoviral vector expressing human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a rabbit knee model of inflammatory arthritis stimulated synovial apoptosis and reduced inflammation. To examine whether intra-articular injection of recombinant chimeric human TRAIL protein (rTRAIL) also induces apoptosis of proliferating rabbit synovium and reduces inflammation, we used an experimental rabbit arthritis model of rheumatoid arthritis, induced by intra-articular introduction of allogeneic fibroblasts genetically engineered to secrete human IL-1β. Analysis of synovium isolated from the rabbits treated with intra-articular injection of rTRAIL, relative to saline control, showed areas of extensive acellular debris and large fibrous regions devoid of intact cells, similar to adenoviral mediated TRAIL gene transfer. Extensive apoptosis of the synovial lining was demonstrated using TUNEL analysis of the sections, corresponding to the microscopic findings in hematoxylin and eosin staining. In addition, leukocyte infiltration into the synovial fluid of the inflamed knee joints following rTRAIL treatment was reduced more than 50% compared with the saline control. Analysis of the glycosaminoglycan synthetic rate by cultured cartilage using radiolabeled sulfur and cartilage histology demonstrated that rTRAIL did not adversely affect cartilage metabolism and structure. Analysis of serum alanine aminotransferase showed that intra-articular injection of rTRAIL did not have adverse effects on hepatic function. These results demonstrate that intra-articular injection of rTRAIL could be therapeutic for treating pathologies associated with rheumatoid arthritis.