bluuebunny/crossref_metadata_2025 huggingface dataset:
Janet Malcolm
Authors: Fakazis Elizabeth
Published: February 2006

In the 1980s, Janet Malcolm was sued for libel for allegedly fabricating direct quotations in a profile she wrote for the New Yorker. The suit lasted nine years and generated a wealth of legal documents as well as articles in newspapers, magazines and trade journals. In this article, I draw on work on the sociology of science to analyze how representations of journalism constructed in and around the Malcolm case were used to defend and challenge old boundary lines separating ‘subjective storytelling’ from ‘objective reporting’, and to affirm journalism’s authority.
‘Improper liberties’
Authors: Goddard Peter
Published: February 2006

This article draws on the archives of Granada Television and of the Independent Television Authority/Independent Broadcasting Authority to explore how and why the use of surreptitious recording equipment and hidden cameras by television investigative journalists was regulated, particularly within Independent Television in Britain. The first instances of regulatory intervention are identified and the substance and operation of the guidelines governing Independent Television journalism are examined, along with their implications for editorial and journalistic autonomy. The contemporary documents used here bring to light the substance of the ongoing debates between journalists and regulators over the purposes of journalism and appropriate forms for its regulation, revealing much about their authors’ own perceptions of their roles as well as the balance to be struck between serving the public interest and safeguarding individual privacy.
The mission of the j-blog
Authors: Robinson Susan
Published: February 2006

Drawing from normative journalism theory, this textual analysis argues that mainstream journalism weblogs are now occupying a role serving to reify traditional norms even as the j-bloggers shift those standard values. When journalists blog, they engage in postmodern reporting and writing even as they are attempting to reclaim journalism authority online. The j-blog has already begun to evolve traditional notions of the mainstream press. Readers and other non-journalists help craft the story. News format changes. Ultimately, this evolution will affect what we know as the ‘truth’ about our society and ourselves, what we mean by ‘community’, and how we understand reality.
Reporting more, informing less
Authors: Nord Lars W. , Strömbäck Jesper
Published: February 2006

The purpose of this study is to examine and compare how leading Swedish news media in television and the press covered and described the terrorist attacks in the USA on September 11 in 2001, the US attacks on Afghanistan later in 2001 and the war in Iraq in 2003. The article examines factors influencing news decisions and media ability to maintain fair news reporting. The study looks specifically at the sources that are used, the occurrence of speculations and whether the coverage was anti-American or anti-Muslim. The central questions are: what were the most frequently used sources?, how frequent were different types of speculation?, and how frequent were anti-American and anti-Muslim rhetorical figures respectively?
Savagery and Civilization
Authors: Buchan Bruce , Heath Mary
Published: February 2006

This article argues that the colonization of Australia was justified by denying that Indigenous peoples possessed recognizable societies, law, property rights or sovereignty. This denial, in turn, rests upon the supposition that Indigenous Australians were living in a ‘savage’, pre-civilized state: the state of nature of liberal theory. Such concepts, deeply embedded in western political thought, informed the view that Australia was a terra nullius or unowned land. Consequently, the contrast between ‘savagery’ and its counterpart, ‘civilization’ formed a critical element of colonial arguments that Australia could be colonized without either a war of ‘conquest’, or making a treaty. We argue here that more than 14 years after the rejection of terra nullius in Australian law, its legacy and the assumptions that underpinned it persist in the concepts more recent debates deploy as well as in the concept of terra nullius that some of these debates rehabilitate.
‘Struggling with Language’
Authors: Nichols Robert Lee
Published: February 2006

In this article, I explore the relationship between linguistic diversity and political power. Specifically, I outline some of the ways that linguistic diversity has served as a barrier to the centralization of power, thus constraining, for example, the political practice of empire-formation. A brief historical example of this dynamic is presented in the case of Spanish colonialism of the 16th-century. The article proceeds then to demonstrate how linguistic diversity remains tied to struggles against forms of domination. I argue that in contemporary indigenous movements for linguistic security, the languages themselves are not merely conceived of as the object of the political struggle, but also as the means to preserve a space for local action and deliberation - a ‘politics of local community’. I show that linguistic diversity and the devolution of political power to the local level are in a mutually reinforcing relationship. Finally, I consider the implications of this thesis for liberal theorizing on language rights, arguing that such theory cannot fully come to terms with this political-strategic dimension of language struggles.
Multiracial versus Collective Black Categories
Authors: Bailey Stanley R. , Telles Edward E.
Published: February 2006

Current census debates in Brazil surrounding Brazilian race categories center on two contrasting proposals: the adoption of the multiracial moreno term vs. the use of the collective black classification negro. Those proposing the former base their argument on the right to self-classify according to one’s own sense of identity. Proponents of the negro category contend that it would be most efficient for redressing racial discrimination. We examine the meaning and saliency of these categories and explore the possible consequences of their adoption. Using national survey data, we demonstrate how education, age, color, sex and local racial composition structure the choices of moreno and negro over official census terms. Findings include a negative correlation between education and the choice of moreno, while the opposite is true for negro. In addition, an age effect on both categories suggests a popular shift in racial labeling away from official census terms. We note that similar issues structure current census debates in the USA.
Principles, feelings and reality
Authors: Noddings Nel
Published: February 2006

Two of Susan Moller Okin’s articles are discussed:‘Reason and feeling in thinking about justice’, Ethics 99(2), 1989: 229-49 and ‘Mistresses of their own destiny: group rights, gender, and realistic rights of exit’, Ethics 112(2), 2002: 205-30. Her argument on the foundation necessary for Rawls’s original position is accepted and extended. Her argument on the handling of illiberal groups in a liberal society is largely accepted, but a question is raised on how to address First Amendment precedents.
Religious freedom vs. sex equality
Authors: Song Sarah
Published: February 2006

This essay examines Susan Moller Okin’s writing on conflicts between religious freedom and sex equality, and her criticism of ‘political liberal’ approaches to these conflicts, which I take to be a part of her lifelong critique of the public-private distinction. I argue that, while Okin ultimately accepted a version of the distinction, she was much less hopeful than most liberal theorists that private actions could be made just without a great deal of public coercion. This comes through especially in her writing on religion. I suggest an approach to addressing these conflicts that seeks to respect religious liberty more than Okin’s prescriptions suggest she did but which, in my view, is more consistent with Okin’s own liberal commitments.
Educating for a just world without gender
Authors: Enslin Penny , Tjiattas Mary
Published: February 2006

In this article we examine Okin’s ideal of a ‘gender-free society’ and its relations to central educational values and practices. We suggest that this ideal pervades her work on the family, culture and, more recently, her focus on the developing world, and gives her liberal feminist stance its radical bite. We contrast this ideal with the more standard notion of gender-neutrality (non-discrimination) and argue that Okin’s more demanding concept (going beyond equal access to positions, benefits and opportunities as currently defined, to insist on the critical overhauling of the systems that determine them) far better accords with requirements of justice. We then go on to explore the contribution to a ‘gender-free society’ of construing women’s rights as human rights which Okin saw as crucial to countering threats against gender equality from competing claims of both multiculturalists and economic development theorists. We consider implications for education (including schooling) arising from the commitment to bring about a ‘gender-free society’.
Three models of education
Authors: Robeyns Ingrid
Published: February 2006

This article analyses three normative accounts that can underlie educational policies, with special attention to gender issues. These three models of education are human capital theory, rights discourses and the capability approach. I first outline five different roles that education can play. Then I analyse these three models of educational policies. The human capital approach is problematic because it is economistic, fragmentized and exclusively instrumentalistic. Rights and capabilities are in principle multi-dimensional and comprehensive models, and can therefore account for the intrinsic and non-economic roles that education plays. However, depending on how one fills out the specific details of the rights and capability frameworks, they also have some drawbacks. I conclude by arguing that the intrinsic aim of educational policy should be to expand people’s capabilities, whereas we should use the rights discourses strategically, that is, when they are likely to contribute to expanding people’s capabilities.
Does curriculum matter?
Authors: Yates Lyn
Published: February 2006

This article discusses the relevance of curriculum to current UN Millennium targets to extend access to education and equality in education for women. It argues, firstly, that it is contradictory to be concerned about women’s access to education but leave curriculum out of the discussion; secondly, that curriculum is not adequately seen as a choice between imposing new universal values or leaving cultural traditions untouched, but is about choices within a situation where cultural traditions are neither untouched nor monolithic; and, thirdly, that attention to who speaks and who is heard in developing and assessing new practices remains important in any initiatives to extend education rights for women.
Habituated reason
Authors: Kristjánsson Kristján
Published: February 2006

R.S. Peters coined the term ‘paradox of moral education’. In this article, the author identifies two subordinate paradoxes: how habituated reason is psychologically possible and how heteronomously formed autonomy is morally/politically possible and justifiable. He sketches possible Aristotelian solutions of those paradoxes and argues that for Aristotle it is essentially an empirical fact, to be further explained by natural scientists, that habituated reason develops within an individual through successful upbringing into critical reason, and a heteronomously formed self becomes capable of taking autonomous decisions. Moreover, the moral and political justification of heteronomously formed autonomy will, according to the Aristotelian model, be provided by the specifically human substantive good of eudaimonia.
‘One expertise among many’— working appreciatively to make miracles instead of finding problems
Authors: Carter Bernie
Published: February 2006

Serendipity plays a role in the articles we read and the ways that we chance upon new ideas, and serendipity brought me to appreciative inquiry (AI). AI, at its heart, is about studying, exploring, actively searching out the best and focusing on what is good, strong, already working and being achieved in organisations. It has been utilised and reported as being effective and transformative in many different aspects of organisational change and change management. AI is based on the 4-D cycle which consists of four phases — discovery (the best of what is or has been), dreaming (what might be), designing (what should be) and destiny (what will be). The cycle starts with the choice of an affirmative topic to study. We used AI successfully within a research study that looked at best practice within multi-agency working with children with complex needs (and their families). Whilst AI is reported, and we experienced it, as an interesting, stimulating and creative way of researching, it is not a panacea and will not provide a ‘cure all’ for all the ills of the health, social care, education and voluntary services. It does, however, provide one way forward. At its best AI's non-problem orientation means that researchers study what is already working well (is clinically effective). Acknowledging existing clinical effectiveness provides a platform for envisaging and developing even better nursing, health and social care practices.
In command of care: clinical nurse leadership explored
Authors: Stanley David
Published: February 2006

Who are the clinical nurse leaders? What are the qualities and characteristics of clinical nurse leaders? Why are they seen as clinical leaders and what might their experiences of clinical leadership be? This paper outlines a research project that sought to explore these questions. The research involved surveying registered/qualified nurses from D to H grade ( n= 830) who staffed 36 clinical areas in one acute NHS Trust in the English Midlands. Only 188 questionnaires were returned, but the data proved a rich source of information about clinical leadership, the attributes of clinical leaders and who might be recognised as a clinical leader. F-grade sisters were seen as strongly associated with the role. The questionnaire was followed by interviews with 42 qualified nurses from D to H grade on four clinical areas in the same NHS Trust, and these were followed by eight further interviews with nurses identified from the interviews as clinical nurse leaders. The results demonstrate that clinical leaders appeared to be present at all nursing levels and in considerable numbers, but they were often not the most senior nurses and their approach to clinical leadership was based upon a foundation of care that was fundamental to their values and beliefs or view of nursing and care. The study also indicated that the type of clinical area had an influence on who might be seen as a clinical leader. The attributes of clinical leaders appeared to be clinical competence, clinical knowledge, approachability, motivation, empowerment, decision-making, effective communication, being a role model and visibility.
Low threshold: a future model for drug service provision? An evaluation of the model used in South Islington Drug Services
Authors: Fernandez Jeff , McNeill Campbell , Haskew Michael , Orr Terry
Published: February 2006

This paper illustrates the key role the nurse can play in reshaping and streamlining a service for more effective treatment. This is demonstrated using the example at the Islington Drugs Service in London, where external pressures initiated a re-design of the part of the service and its aim and objectives.

This re-design was successful and it is noted that, while the team delivering the service was multi-disciplinary, nurses played a central role in the effective design and implementation that ultimately received positive feedback from the clients involved in the project.

Good clinical knowledge and an ability to think creatively and practically are important skills for nurses in today's healthcare system. This paper hopefully illustrates that nurses are well placed to play an active role in re-designing services and should definitely be playing a central role in strategic service delivery.
A critical realist rationale for using a combination of quantitative and qualitative methods
Authors: McEvoy Phil , Richards David
Published: February 2006

Although using a combination of quantitative and qualitative approaches is widely advocated, there is considerable scope for confusion due to the complex ontological and epistemological issues that need to be resolved. This paper examines some of the issues that may arise when the methods are combined. Three distinct standpoints with regard to using mixed method approaches are highlighted: a methodological purist position, a pragmatic standpoint and an anti-conflationist position. It is suggest that an anti-conflationist approach that is underpinned by the philosophy of critical realism is compatible with all three of the purposes of methodological triangulation identified by Risjord and his co-authors (Risjord et al., 2001, 2002) and that adopting a critical realist perspective may circumvent many of the problems that are associated with paradigm ‘switching’. The case for adopting a critical realist framework is illustrated by a case study, in which a combination of quantitative and qualitative methods was used to explore how and why gatekeeping decisions emerge at the interface between primary care and community mental health teams.
Evaluation of Anticyclin B1 Serum Antibody as a Diagnostic and Prognostic Biomarker for Lung Cancer
Authors: EGLOFF ANN MARIE , WEISSFELD JOEL , LAND STEPHANIE R. , FINN OLIVERA J.
Published: February 2006

Abstract: The primary aims of this study were to establish a high‐throughput assay and analytic procedures that would allow us to assess with accuracy and reproducibility the presence of anti‐cyclin B1 antibodies in a large cohort of subjects at‐risk for development of lung cancer. The overall goal is to identify factors significantly associated with immune responses against this lung tumor antigen and to evaluate the relationship between anticyclin B1 antibodies and lung cancer risk in a prospective cohort. Successful cancer treatment relies on early detection. The immune system could respond to tumor antigens arising from altered host factors and provide an early readout for cancer presence. This study examines immune responses to the tumor antigen cyclin B1. Lung cancer patients have antibodies against cyclin B1. Unscheduled overexpression of this cell cycle regulator occurs early in tumorigenesis and might be detected by the immune system long before clinical diagnosis of cancer. Antibodies recognizing cyclin B1 were measured using semiautomated ELISAs in sera samples from subjects without detectable lung cancer enrolled in the Pittsburgh Lung Screening Study (PLuSS), a longitudinal study of long‐term smokers over age 50. Factors significantly associated with antibody presence were identified using linear regression analysis. We have established a highly reproducible, semiautomated ELISA‐based assay for the high‐throughput assessment of serum antibody titers. Using this technology and a small subset of PluSS subjects, cyclin B1 antibody levels were found to be high in a small proportion of subjects tested. Regression analysis identified gender as well as age in women smokers to be significant determinants of cyclin B1 antibody levels, association not seen in male subjects. This work represents an important first step toward defining the importance of the presence of anticyclin B1 antibodies in an at‐risk population and assessing the predictive value of serum cyclin B1 antibody as relates to lung cancer risk.
T‐Cell Immunotherapy for Adenoviral Infections of Stem‐Cell Transplant Recipients
Authors: LEEN A. M. , MYERS G. D. , BOLLARD C. M. , HULS M. H. , SILI U. , GEE A. P. , HESLOP H. E. , ROONEY C. M.
Published: February 2006

Abstract: Human adenoviruses are ubiquitous lytic DNA viruses that can be divided into 51 different serotypes, grouped from A to F on the basis of genome size, composition, homology, and organization. Adenovirus infections, although frequent, are rarely fatal in immunocompetent individuals, due to potent innate and adaptive immune responses. By contrast, adenoviruses are a significant cause of morbidity and mortality in immunosuppressed individuals, for whom there are limited treatment options. Since antiviral drugs have variable efficacy in the treatment of severe adenovirus disease, iatrogenic reconstitution with in vitro expanded virus‐specific cytotoxic T lymphocytes (CTLs) is an attractive option for prophylaxis and treatment, particularly because the endogenous recovery of adenovirus‐specific T cells has proved important in controlling infection in vivo. Thus, we have characterized human T‐cell responses to adenovirus in vitro and explored the potential of adoptive T‐cell immunotherapy as a prophylactic or therapeutic strategy for adenovirus infections posttransplant.
Fat and Wingless signaling oppositely regulate epithelial cell-cell adhesion and distal wing development inDrosophila
Authors: Jaiswal Manish , Agrawal Namita , Sinha Pradip
Published: February 2006

Development of organ-specific size and shape demands tight coordination between tissue growth and cell-cell adhesion. Dynamic regulation of cell adhesion proteins thus plays an important role during organogenesis. In Drosophila, the homophilic cell adhesion protein DE-Cadherin (DE-Cad)regulates epithelial cell-cell adhesion at adherens junctions (AJs). Here, we show that along the proximodistal (PD) axis of the developing wing epithelium,apical cell shapes and expression of DE-Cad are graded in response to Wingless (Wg), a morphogen secreted from the dorsoventral (DV) organizer in distal wing, suggesting a PD gradient of cell-cell adhesion. The Fat (Ft)tumor suppressor, by contrast, represses DE-Cad expression. In genetic tests, ft behaves as a suppressor of Wg signaling. Cytoplasmic pool of β-catenin/Arm, the intracellular transducer of Wg signaling, is negatively correlated with the activity of Ft. Moreover, unlike that of Wg, signaling by Ft negatively regulates the expression of Distalless(Dll) and Vestigial (Vg). Finally, we show that Ft intersects Wnt/Wg signaling, downstream of the Wg ligand. Fat and Wg signaling thus exert opposing regulation to coordinate cell-cell adhesion and patterning along the PD axis of Drosophila wing.
Notch 1 inhibits photoreceptor production in the developing mammalian retina
Authors: Jadhav Ashutosh P. , Mason Heather A. , Cepko Constance L.
Published: February 2006

The transmembrane receptor Notch1 plays a role in development and homeostasis in vertebrates and invertebrates. The mammalian retina is an excellent tissue in which to dissect the precise role of Notch signaling in regulating cell fate and proliferation. However, a systematic analysis has been limited by the early embryonic lethality of Notch1-null mice. Here, Notch1 was conditionally removed from the murine retina either early or late in development. Removal of Notch1 early led to a reduction in the size of the retina as well as aberrant morphology. A decrease in the number of progenitor cells and premature neurogenesis accounted for the reduction in size. Unexpectedly, ablation of Notch1 in early progenitor cells led to enhanced cone photoreceptor production, and ablation of Notch1 at later points led to an almost exclusive production of rod photoreceptor cells. These data suggest that Notch1 not only maintains the progenitor state, but is required to inhibit the photoreceptor fate. These cone enriched mutant mice should prove to be a valuable resource for the study of this relatively rare mammalian photoreceptor cell type.
Hedgehog signalling from the zona limitans intrathalamica orchestrates patterning of the zebrafish diencephalon
Authors: Scholpp Steffen , Wolf Olivia , Brand Michael , Lumsden Andrew
Published: February 2006

Midway between the anterior neural border and the midbrain-hindbrain boundary, two well-known local signalling centres in the early developing brain, is a further transverse boundary with putative signalling properties– the zona limitans intrathalamica (ZLI). Here, we describe formation of the ZLI in zebrafish in relation to expression of sonic hedgehog(shh) and tiggy-winkle hedgehog (twhh), and to development of the forebrain regions that flank the ZLI: the prethalamus and thalamus. We find that enhanced Hh signalling increases the size of prethalamic and thalamic gene expression domains, whereas lack of Hh signalling leads to absence of these domains. In addition, we show that shh and twhh display both unique and redundant functions during diencephalic patterning. Genetic ablation of the basal plate shows that Hh expression in the ZLI alone is sufficient for diencephalic differentiation. Furthermore, acquisition of correct prethalamic and thalamic gene expression is dependent on direct Hh signalling. We conclude that proper maturation of the diencephalon requires ZLI-derived Hh signalling.
Signal dynamics in Sonic hedgehog tissue patterning
Authors: Saha Krishanu , Schaffer David V.
Published: February 2006

During development, secreted signaling factors, called morphogens, instruct cells to adopt specific mature phenotypes. However, the mechanisms that morphogen systems employ to establish a precise concentration gradient for patterning tissue architecture are highly complex and are typically analyzed only at long times after secretion (i.e. steady state). We have developed a theoretical model that analyzes dynamically how the intricate transport and signal transduction mechanisms of a model morphogen, Sonic hedgehog (Shh),cooperate in modular fashion to regulate tissue patterning in the neural tube. Consistent with numerous recent studies, the model elucidates how the dynamics of gradient formation can be a key determinant of cell response. In addition,this work yields several novel insights into how different transport mechanisms or `modules' control pattern formation. The model predicts that slowing the transport of a morphogen, such as by lipid modification of the ligand Shh, by ligand binding to proteoglycans, or by the moderate upregulation of dedicated transport molecules like Dispatched, can actually increase the signaling range of the morphogen by concentrating it near the secretion source. Furthermore, several transcriptional targets of Shh, such as Patched and Hedgehog-interacting protein, significantly limit its signaling range by slowing transport and promoting ligand degradation. This modeling approach elucidates how individual modular elements that operate dynamically at various times during patterning can shape a tissue pattern.
Retinoids signal directly to zebrafish endoderm to specifyinsulin-expressing β-cells
Authors: Stafford David , White Richard J. , Kinkel Mary D. , Linville Angela , Schilling Thomas F. , Prince Victoria E.
Published: February 2006

During vertebrate development, the endodermal germ layer becomes regionalized along its anteroposterior axis to give rise to a variety of organs, including the pancreas. Genetic studies in zebrafish and mice have established that the signaling molecule retinoic acid (RA) plays a crucial role in endoderm patterning and promotes pancreas development. To identify how RA signals to pancreatic progenitors in the endoderm, we have developed a novel cell transplantation technique, using the ability of the SOX32 transcription factor to confer endodermal identity, to selectively target reagents to (or exclude them from) the endodermal germ layer of the zebrafish. We show that RA synthesized in the anterior paraxial mesoderm adjacent to the foregut is necessary for the development of insulin-expressingβ-cells. Conversely, RA receptor function is required in the foregut endoderm for insulin expression, but not in mesoderm or ectoderm. We further show that activation of RA signal transduction in endoderm alone is sufficient to induce insulin expression. Our results reveal that RA is an instructive signal from the mesoderm that directly induces precursors of the endocrine pancreas. These findings suggest that RA will have important applications in the quest to induce islets from stem cells for therapeutic uses.
An ancient Wnt-Dickkopf antagonism inHydra
Authors: Guder Corina , Pinho Sonia , Nacak Tanju G. , Schmidt Heiko A. , Hobmayer Bert , Niehrs Christof , Holstein Thomas W.
Published: February 2006

The dickkopf (dkk) gene family encodes secreted antagonists of Wnt signalling proteins, which have important functions in the control of cell fate, proliferation, and cell polarity during development. Here, we report the isolation, from a regeneration-specific signal peptide screen, of a novel dickkopf gene from the fresh water cnidarian Hydra. Comparative sequence analysis demonstrates that the Wnt antagonistic subfamily Dkk1/Dkk2/Dkk4 and the non-modulating subfamily Dkk3 separated prior to the divergence of cnidarians and bilaterians. In steady-state Hydra, hydkk1/2/4-expression is inversely related to that of hywnt3a. hydkk1/2/4 is an early injury and regeneration responsive gene, and hydkk1/2/4-expressing gland cells are essential for head regeneration in Hydra, although once the head has regenerated they are excluded from it. Activation of Wnt/β-Catenin signalling leads to the complete downregulation of hydkk1/2/4transcripts. When overexpressed in Xenopus, HyDkk1/2/4 has similar Wnt-antagonizing activity to the Xenopus gene Dkk1. Based on the corresponding expression patterns of hydkk1/2/4 and neuronal genes,we suggest that the body column of Hydra is a neurogenic environment suppressing Wnt signalling and facilitating neurogenesis.
Competence of cranial ectoderm to respond to Fgf signaling suggests a two-step model of otic placode induction
Authors: Martin Kareen , Groves Andrew K.
Published: February 2006

Vertebrate craniofacial sensory organs derive from ectodermal placodes early in development. It has been suggested that all craniofacial placodes arise from a common ectodermal domain adjacent to the anterior neural plate,and a number of genes have been recently identified that mark such a`pre-placodal' domain. However, the functional significance of this pre-placodal domain is still unclear. In the present study, we show that Fgf signaling is necessary and sufficient to directly induce some, but not all,markers of the otic placode in ectoderm taken from the pre-placodal domain. By contrast, ectoderm from outside this domain is not competent to express otic markers in response to Fgfs. Grafting naïve ectoderm into the pre-placodal domain causes upregulation of pre-placodal markers within 8 hours, together with the acquisition of competence to respond to Fgf signaling. This suggests a two-step model of craniofacial placode induction in which ectoderm first acquires pre-placodal region identity, and subsequently differentiates into particular craniofacial placodes under the influence of local inducing signals.
Sema3a1 guides spinal motor axons in a cell- and stage-specific manner in zebrafish
Authors: Sato-Maeda Mika , Tawarayama Hiroshi , Obinata Masuo , Kuwada John Y. , Shoji Wataru
Published: February 2006

In order for axons to reach their proper targets, both spatiotemporal regulation of guidance molecules and stepwise control of growth cone sensitivity to guidance molecules is required. Here, we show that, in zebrafish, Sema3a1, a secreted class 3 semaphorin, plays an essential role in guiding the caudal primary (CaP) motor axon that pioneers the initial region of the motor pathway. The expression pattern of Sema3a1 suggests that it delimits the pioneer CaP axons to the initial, common pathway via a repulsive action, but then CaP axons become insensitive to Sema3a1 beyond the common pathway. Indeed, nrp1a, which probably encodes a component of the Sema3a1 receptor, is specifically expressed by CaP during the early part of its outgrowth but not during later stages when extending into sema3a1-expressing muscle cells. To examine this hypothesis directly,expression of sema3a1 and/or nrp1a was manipulated in several ways. First, antisense knockdown of Sema3a1 induced CaP axons to branch excessively, stall and/or follow aberrant pathways. Furthermore,dynamic analysis showed they extended more lateral filopodia and often failed to pause at the horizontal myoseptal choice point. Second, antisense knockdown of Nrp1a and double knockdown of Nrp1a/Sema3a1 induced similar outgrowth defects in CaP. Third, CaP axons were inhibited by focally misexpressed sema3a1 along the initial common pathway but not along their pathway beyond the common pathway. Thus, as predicted, Sema3a1 is repulsive to CaP axons in the common region of the pathway, but not beyond the common pathway. Fourth, induced ubiquitous overexpression of sema3a1 caused the CaP axons but not the other primary motor axons to follow aberrant pathways. These results suggest that the repulsive response to Sema3a1 of the primary motor axons along the common pathway is both cell-type specific and dynamically regulated, perhaps via regulation of nrp1a.
Transgenic isolation of skeletal muscle and kidney defects in lamininβ2 mutant mice: implications for Pierson syndrome
Authors: Miner Jeffrey H. , Go Gloriosa , Cunningham Jeanette , Patton Bruce L. , Jarad George
Published: February 2006

Pierson syndrome is a recently defined disease usually lethal within the first postnatal months and caused by mutations in the gene encoding lamininβ2 (LAMB2). The hallmarks of Pierson syndrome are congenital nephrotic syndrome accompanied by ocular abnormalities, including microcoria(small pupils), with muscular and neurological developmental defects also present. Lamb2-/- mice are a model for Pierson syndrome;they exhibit defects in the kidney glomerular barrier, in the development and organization of the neuromuscular junction, and in the retina. Lamb2-/- mice fail to thrive and die very small at 3 weeks of age, but to what extent the kidney and neuromuscular defects each contribute to this severe phenotype has been obscure, though highly relevant to understanding Pierson syndrome. To investigate this, we generated transgenic mouse lines expressing rat laminin β2 either in muscle or in glomerular epithelial cells (podocytes) and crossed them onto the Lamb2-/- background. Rat β2 was confined in skeletal muscle to synapses and myotendinous junctions, and in kidney to the glomerular basement membrane. In transgenic Lamb2-/- mice, β2 deposition in only glomeruli prevented proteinuria but did not ameliorate the severe phenotype. By contrast, β2 expression in only muscle restored synaptic architecture and led to greatly improved health, but the mice died from kidney disease at 1 month. Rescue of both glomeruli and synapses was associated with normal weight gain, fertility and lifespan. We conclude that muscle defects in Lamb2-/- mice are responsible for the severe failure to thrive phenotype, and that renal replacement therapy alone will be an inadequate treatment for Pierson syndrome.
Wnt signals mediate a fate decision between otic placode and epidermis
Authors: Ohyama Takahiro , Mohamed Othman A. , Taketo Makoto M. , Dufort Daniel , Groves Andrew K.
Published: February 2006

The otic placode, the anlagen of the inner ear, develops from an ectodermal field characterized by expression of the transcription factor Pax2. Previous fate mapping studies suggest that these Pax2+cells will give rise to both otic placode tissue and epidermis, but the signals that divide the Pax2+ field into placodal and epidermal territories are unknown. We report that Wnt signaling is normally activated in a subset of Pax2+ cells, and that conditional inactivation of β-catenin in these cells causes an expansion of epidermal markers at the expense of the otic placode. Conversely, conditional activation of β-catenin in Pax2+ cells causes an expansion of the otic placode at the expense of epidermis, and the resulting otic tissue expresses exclusively dorsal otocyst markers. Together, these results suggest that Wnt signaling acts instructively to direct Pax2+cells to an otic placodal, rather than an epidermal, fate and promotes dorsal cell identities in the otocyst.
In situ Polymerization of Liquid Crystalline Monomers within Photoaligned Mesoporous Silica Thin Film
Authors: Fukumoto Haruhiko , Nagano Shusaku , Seki Takahiro
Published: February 2006

Photopolymerization of liquid crystalline monomers was achieved within photoaligned mesoporous silica film. After resolving the template of silica networks, bundles of nanofibers containing polymer chains with a narrow molecular weight distribution were obtained.
One-pot Synthesis of 3-Bromoimidazo[1,2-a]pyridine Derivatives Accompanied by Dimethyl Sulfoxide Oxidation
Authors: Kawano Tomikazu , Kato Nobuo
Published: February 2006

3-Bromoimidazo[1,2-a]pyridine derivatives have been directly synthesized from reaction of 2-aminopyridine derivative with α-haloketone derivatives in DMSO at room temperature, accompanied by DMSO oxidation.
Reproduction and ovarian ageing
Authors: Swanton Alexander , Child Tim
Published: February 2006

Female fertility rates are inherently linked to a woman's age, which is in turn related to ovarian function. Reproductive potential declines gradually until 37–38 years of age, from when the rate of decline hastens. Approximately 1% of women suffer from premature ovarian ageing, and many may not have completed their families. This paper reviews the physiology and fertility consequences of ovarian ageing, premature ovarian failure, measures of ovarian reserve and methods of fertility preservation.
The investigation and management of interstitial cystitis
Authors: Parsons Matthew , Toozs-Hobson Philip
Published: February 2006

Interstitial cystitis (IC) is a chronic inflammatory disorder of the bladder that is notoriously difficult to manage and can result in considerable morbidity. It very likely overlaps with painful bladder syndrome, but they are different conditions. The aetiology remains obscure, and the definition and diagnostic criteria are debated. The diagnosis of IC is one of exclusion, frequently based on symptoms and cystoscopy findings. Typical symptoms include frequency, urgency, dysuria and lower abdominal, bladder, vaginal, urethral or perineal pain, in the absence of bacterial cystitis. Voiding often relieves the suprapubic discomfort, and drinking alcohol- and caffeine-containing drinks frequently exacerbates it. Many treatments have been tried, with little sustained success. Proposed systemic treatments include anti-histamines, heparin, amitriptyline and pentosan polysulfate (a synthetic analogue of glycosaminoglycan which augments the mucous protective layer of the bladder). In many patients symptoms are improved following cysto-distension but the benefits are short-lived. Instillations of dimethyl sulfoxide, hyaluronic acid or chondroitin also show promise. Where treatments have failed and symptom severity is such that the patient's quality of life is poor, a urological opinion should be sought and reconstructive surgery considered. Available options include partial cystectomy, augmentation cystoplasty, and urinary diversion with or without cystectomy.
Hormone replacement therapy and colorectal cancer: an update
Authors: La Vecchia Carlo , Gallus Silvano , Fernandez Esteve
Published: February 2006

Observational studies and randomized clinical trials that have looked at the effect of hormone replacement therapy (HRT) on the risk of colorectal cancer are reviewed. Nine cohort studies in this area have included a total of over 2700 cases of colorectal cancer. Most of these studies found a relative risk (RR) of around or below unity. Of 15 case–control studies, with a total of over 7300 cases, six reported a 20–40% risk reduction among women who had ever used HRT. With reference to randomized clinical trials, in the Women's Health Initiative (WHI) study, after seven years of follow-up, 45 cases of colorectal cancer were observed in the combined HRT group versus 67 in the placebo group, corresponding to a RR of 0.63. A combined reanalysis of data from both the WHI and the Heart and Estrogen Progestin Replacement Study (HERS) included 56 cases in the com bined HRT group and 83 cases in the placebo group (pooled RR = 0.64). However, in the WHI study cancers diagnosed in the HRT group were more advanced and there were more positive lymph nodes. Furthermore, among women in the WHI who had had a hysterectomy, there was no difference at the eight-year follow-up in the incidence of colorectal cancer between those in the estrogen-only arm of the trial ( n = 61) and those in the control group ( n = 68).
Is there a role for hormone replacement therapy after breast cancer?
Authors: Kwan Kenny , Ward Charlotte , Marsden Jo
Published: February 2006

Breast cancer is the most common female malignancy in the UK, with an overall lifetime risk of 1 in 9. Despite the high incidence, breast cancer mortality is decreasing. Approximately 40,000 women were diagnosed with breast cancer in England and Wales in 2000 but the majority will have normal or near-normal life expectancy. One of the main contributory factors to this marked improvement in survival over the last 20 years in women of all ages has been the more widespread use of systemic therapy in early-stage disease. For women with hormone-sensitive cancer, this involves adjuvant endocrine therapy that reduces estrogen synthesis (i.e. ovarian suppression in premenopausal women or aromatase inhibitors in postmenopausal women) or estrogen activity (the anti-estrogen tamoxifen, irrespective of menopausal status). Many women experience health and quality-of-life problems related to estrogen deficiency as a result, the commonest being vasomotor symptoms and vaginal dryness. This article summarizes and interprets key recent papers on the use of hormone replacement therapy (HRT) and selective serotonin reuptake inhibitors in breast cancer survivors. HRT may be safe in women with receptor-negative disease or receptor-positive cancers in the presence of tamoxifen. However, there is a dearth of useful alternatives.
Diet and healthy ageing
Authors: McKevith Brigid
Published: February 2006

In the future there will be more people aged 65 years and over ('older adults'). Although the exact mechanisms underlying normal ageing are not fully understood, ageing is generally associated with an increase in chronic diseases, such as cardiovascular disease, diabetes, cancer and osteoporosis. It is becoming clear that it is possible to prevent, slow or reverse the onset of many these by modifying lifestyle factors such as diet. Studies of older adults in a range of countries have highlighted a number of areas in which dietary quality could be improved. It is important to identify dietary patterns in addition to specific dietary components that offer protection against chronic disease. The challenge in the area of diet and healthy ageing is twofold: first, there is a need to improve the diet of older adults; and second, as most chronic diseases begin earlier in life, there is a need to encourage other age groups to adapt their diet so they can enter old age in better health.
Managing the menopause: British Menopause Society Council consensus statement on hormone replacement therapy
Authors: Pitkin Joan , Rees Margaret C P , Gray Sarah , Lumsden Mary Ann , Marsden Jo , Stevenson John , Williamson Jennifer
Published: February 2006

The British Menopause Society Council aims to help health professionals inform and advise women about the menopause. This guidance regarding estrogen-based hormone replacement therapy (HRT), including tibolone, which is classified in the British National Formulary as HRT, responds to the results and analysis of the randomized Women's Health Initiative studies and the observational Million Women Study. Treatment choice should be based on up-to-date information and targeted to individual women's needs. HRT still offers the potential for benefit to outweigh harm, providing the appropriate regimen has been instigated in terms of dose, route and combination.
Recent advances in the use of aromatase inhibitors for women postmenopausal breast cancer
Authors: Chowdhury Simon , Ellis Paul A
Published: February 2006

The aromatase enzyme catalyses the last step in estrogen biosynthesis. There are two classes of third-generation aromatase inhibitors: irreversible steroidal inhibitors (e.g. exemestane) and reversible non-steroidal inhibitors (e.g. anastrozole, letrozole). All three agents have been found to be equivalent or superior to megestrol acetate as second-line therapy for metastatic breast cancer. In the first-line setting, large phase III trials have shown that all three are equivalent or superior to tamoxifen in women with metastatic disease. Several large trials with varying study designs have been launched to analyse their role in the adjuvant setting. The four that have reported found longer average disease-free survival for women who received an aromatase inhibitor than for those who did not. In addition, one trial, MA.17, has shown a survival advantage associated with the use of an aromatase inhibitor in node-positive patients. Guidelines produced by the American Society of Clinical Oncology suggest that adjuvant therapy for postmenopausal women with hormone-receptor-positive breast cancer should include an aromatase inhibitor. However, the long-term consequences of estrogen deprivation in postmenopausal women remain uncertain, particularly with regard to bone and cardiovascular health. The advantages and disadvantages of different hormonal strategies should therefore be carefully considered in each individual case.
The Internet and the menopause consultation: menopause management in the third millennium
Authors: Cumming Grant P , Currie Heather
Published: February 2006

The Internet was born in 1969; it was originally developed so that computers could share information on research and development in the scientific and military fields. The original Internet consisted of four university computers networked in the United States. Email became available two years later. The infant Internet initially required complex computing knowledge to be used. However, this was all to change with the development of the World Wide Web in the early 1990s, which made the Internet much more widely accessible. The Internet has since grown at a phenomenal rate and has evolved into a global communications tool. It is by nature anarchic, in that it is an unrestricted broadcast medium. Although this lack of censorship is a strength, it is also a weakness. The quality of information available on the Web is variable and discernment is required. With the growth of e-health, medicine and its allied specialties are faced with the challenges of providing their services in a novel way while maintaining the first principle of medicine, primum non nocere (first, do no harm). This provision of e-health care is in its infancy and this review explores issues arising from the use of the Internet as a medium for organizing menopausal health care in the third millennium.
Good practice for publishing the results of clinical trials
Authors: Wager Elizabeth
Published: February 2006

Publication is an important stage in the research process, yet until recently few guidelines existed about how trials should be published. This article reviews recent developments such as Good Publication Practice for pharmaceutical companies and recommendations from medical editors, medical writers and the pharmaceutical industry which encourage responsible practices and greater transparency.
Surgical treatment of bleeding problems in perimenopausal women
Authors: Dighe Sonal V , Bain Christine , Parkin David E
Published: February 2006

Bleeding problems are common in perimenopausal women. They affect quality of life. Traditionally, hysterectomy was the definitive 'cure'; however, the past two decades have seen the emergence of less invasive and safer alternatives, in the form of endometrial ablation. Like hysterectomy, these treatments have a high satisfaction rate. Endometrial ablation employing resection techniques may be the procedure of choice in perimenopausal women because the majority of the endometrial cavity is sampled, which may reduce the risk of undetected endometrial cancer. Since no operation is without risk, women should be appropriately selected and counselled.