bluuebunny/crossref_metadata_2025 huggingface dataset:
Trust and Professionalism in Social Professions
Authors: Sáez Juan , Sánchez Mariano
Published: July 2006

This article aims at fostering reflection on trust and social professions through looking at a particular case: social education and its development and current status in Spain. The main argument presented has to do with the link between social professions and the permanent challenge faced by welfare states and democracies to provide answers to social problems and needs. Hence, social education is characterized as a means to fight social exclusion and grant wider access to social rights. Through educational programmes, projects and activities, social educators can struggle against exclusion and social injustice. Therefore, the authors sustain that exclusion is the hinge that articulates the connection between social practitioners and citizens' trust. Specific attention is paid to the capacity of Spanish social educators to be a depository of trust from their clients. The idea that excluded people actually have no choice but to trust someone else, such as for instance, social educators, is explored. According to this analysis, unless an effort is made in Spain to explain to lay citizens the role of social educators the development of trust will be more difficult. Therefore, a major challenge for Spanish social educators at the moment is to expand the knowledge and awareness about their practices in order to promote among citizens not only general confidence in the social system but trust in these social professionals.
Traces of Doubt and Sources of Trust
Authors: Kuhlmann Ellen
Published: July 2006

This article analyses the seemingly contradictory developments between seeking trust and demanding control in the field of health care. The author links the debates on trust to the concept of professionalism and changing health policy and practice. Analysis is based on empirical material from a study of modernization of ambulatory care in Germany. Results show that calls are increasing for ‘rational criteria’ and ‘visible markers’ of trust both on the provider and user side, and the new tools of bureaucratic regulation fulfil this function as signifiers of quality. These signifiers are not merely externally imposed rules but actively constructed and utilized by physicians to build trustful relations with colleagues and give ‘public proofs’ of quality of their services under conditions of tighter control and regulation. They are also taken up by patients and perceived as prerequisites for self-determined decisions and trustworthy relations. The traditional ‘embodied’ professionalism, represented by a (male) physician, is hereby transformed into a ‘disembodied’ professionalism, which is founded on information. The highly flexible nature of professionalism allows for transformations according to new demands in health care without necessarily weakening its power and appeal in building trust. Rather than a mere decline, we face new patterns of building trust.
Regaining Trust in Medicine
Authors: Allsop Judith
Published: July 2006

Recently, the system of medical regulation through which doctors are held to account has come under sustained criticism. A series of public inquiries have revealed incompetence, dishonesty, sexual misconduct by individual doctors and, in one case, serial killing, as well as weaknesses in systems that failed to detect deviant behaviour early and then to take action to protect patients. This article looks at the longer-term social and political changes that have brought a shift in the relationship between patients, doctors and the state and a greater concern for predictability in medical competence. It then assesses the evidence for a decline in public trust in doctors as individual practitioners and in the system of professional self-regulation. The concept of trust is discussed and, from the data available, it is suggested that members of the public continue to trust their doctor. However, data on complaints indicate an increasing propensity for people to make complaints about individual doctors and the doctors' regulatory body, the General Medical Council (GMC) has been seen by the public as self-interested. Various state-sponsored inquiries have questioned whether professional self-regulation in its present form can be sustained. The final section of the article looks at the reforms introduced by the GMC and government, and considers whether these are sufficient to restore trust. The discussions have implications for other professions as professional governance systems in the UK have been based on the medical model.
Professional Discourses under the Pressure of Economic Values
Authors: Champy Florent
Published: July 2006

More and more professionals are being put under intense pressure by markets and organizations to achieve ‘economization’ of their field of activity. The new discourse of professionalism and the managerial norms that characterize it illustrate these pressures. Despite this evolution, which jeopardizes the autonomy of professions as an alternative form of coordination of economic activities to that of markets and organizations, some professional groups still seek to achieve the status of a self-regulated profession or at least some of the advantages of it. The case of industrial designers and landscape designers, as shown in this article, however, bears testimony that these pressures for economization have had a strong effect on the evolution of the discourse of these professionals and of their representatives seeking recognition. The economic benefits of the professional work for both clients and employers as well as for society as a whole now constitute a key theme in this discourse. However, the case of architects, an old profession already quite well protected, shows how dangerous it can be to maintain a traditional discourse without adapting it to new requirements from the professionals’ partners in economic life.
Abusive supervision and subordinate problem drinking: Taking resistance, stress and subordinate personality into account
Authors: Bamberger Peter A. , Bacharach Samuel B.
Published: July 2006

We test hypotheses derived from two alternative perspectives regarding the association between supervisory abuse and subordinate problem drinking. Drawing from the employee resistance literature, we examine the degree to which such an association may be sensitive to variation in subordinate personality. Drawing from the stress literature, we examine the degree to which this association may be mediated by somatic stress. Multi-source data from 1473 blue-collar workers employed in 55 work units, indicates that while the main effect of abusive supervision on problem drinking is attenuated under conditions of high subordinate conscientiousness and agreeableness (consistent with a resistance-based explanation), the main effect is not mediated by somatic stress.
Aesthetics, performativity and resistance in the narratives of a computer programming community
Authors: Case Peter , Piñeiro Erik
Published: July 2006

This article reports on an empirical study of a computer programmer community, focusing on online exchanges in which participants discuss the aesthetics of coding. Naturalistic data were collected during a 12-month period of non-participant observation of the software community in question. The authors estimate that approximately 200 participants are represented in the main dataset. Narrative data are presented under two interpretative rubrics: ‘programmer performatives’ and ‘commercial performativity’. We seek to demonstrate that there is the online equivalent of a great deal of intricate ‘face work’ that programmers do in their narrative exchanges. In expressing and conforming to a ‘hacker ethic’, programmer narratives simultaneously evince technical, ethical and aesthetic motives. There is frequent articulation of resistance and subversive intent expressed toward representatives of employers and employing organizations. Software engineers are acutely aware of the facets of organizational control and demands for performativity that they feel compromise their artistic endeavours. Programmers make sense of their condition ideologically both through their practical pursuit of coding ideals and by espousing a hacker ethic that legitimates their passionate engagement with coding tasks.
Action research: Explaining the diversity
Authors: Cassell Catherine , Johnson Phil
Published: July 2006

For nearly 70 years scholars have been discussing the characteristics of action research and it is apparent that there is an increasingly wide range of forms that action research takes in practice. Here we argue that such diversity is not haphazard and that we must be cautious about developing all-embracing standards to differentiate the ‘good’ from the ‘bad’. Rather this diversity is inspired by different philosophical stances, which usually remain tacit in published accounts thereby fuelling ambiguity and controversy about what action research should entail in practice and as to its ‘scientific’ status. The aim of this article is to explain the apparent diversity of action research in the organization studies domain, by clarifying how variable philosophical assumptions systematically lead to the constitution of distinctive forms of action research with their attendant conceptions of social science. This diversity is illustrated, with examples from the relevant literature, in terms of variation in: the aims of action research; its conception of social science; the role of the action researcher and their relations with members; the validity criteria deployed and the internal tensions that arise.
Job referral in China: The advantages of strong ties
Authors: Cheung Chau-kiu , Gui Yong
Published: July 2006

There is evidence for the importance of strong ties in job referral among Chinese working people. The principle of reciprocity in exchange theory has been used as an explanation for this. According to the theory, a job seeker who has more resources is more appealing to a matchmaker, who is then more likely to refer the job seeker to a more rewarding job. A strong tie acts to enhance the expectation of reciprocity from the referred person. This study of Chinese working people in Shanghai seeks to identify the effect of strong ties on job referral. The results point to the advantages of having strong ties in job referral, which include not just earnings but also satisfaction from the referred job. Importantly, people with more resources benefit more from job referral through a matchmaker, particularly when the tie with the matchmaker is strong.
The Impact of 9/11 and Other Terrible Global Events on Tourism in the United States and Hawaii
Authors: Bonham Carl , Edmonds Christopher , Mak James
Published: July 2006

This article reviews recent trends in travel and tourism in the United States and Hawaii to ascertain how the terrorist attacks of 9/11 and subsequent terrible global events affected tourism flows. United States tourism has not recovered fully from 9/11 and other international shocks; indeed, recovery may be a long way off. By contrast, Hawaii tourism is enjoying robust growth in the aftermath of 9/11 as growth in tourist arrivals from the mainland has offset declines in international visitors. We suggest that Hawaii’s current tourism boom is explained in part by the diversion of United States travel from foreign travel. The article demonstrates the usefulness of vector error correction models to generate dynamic visitor forecasts, which we use to determine whether tourism in Hawaii has recovered fully from 9/11 and other terrible international events. The article considers policy options for facilitating the recovery of international tourism to the United States.
How Big, How Many? Enterprise Size Distributions in Tourism and Other Industries
Authors: Smith Stephen L. J.
Published: July 2006

Tourism often is characterized as being dominated by small- and medium-sized enterprises (SMEs), a characteristic that leads to certain challenges for the sector. This research article examines the degree of the assertion of dominance by SMEs and whether tourism is different than other industry sectors. The distribution of enterprise sizes within specific tourism industries also is examined. The results indicate that the percentage of small firms in tourism is lower than that in the overall business sector and that the percentage of medium-sized tourism firms is slightly higher than in the overall economy. Recreation and entertainment firms display the most uniform dispersal of enterprise sizes, whereas the travel trade shows a very high concentration of SMEs. Some implications of these findings are suggested.
Tourism Satellite Accounts: A Critical Assessment
Authors: Smeral Egon
Published: July 2006

Experts faced with the problems of measuring the size of tourism and its contribution to GDP have proposed tourism satellite accounts (TSAs), which focus on a regular stream of financial data that can be compared through time and with other economic activities at a regional, national, and international level. The article makes it clear that in measuring the TSA-based contribution made by the tourism industry to national or regional GDP, results must be adjusted for indirect effects and intermediate consumption (such as business trips of residents). Using the case of Austria and two of its Länder (states), the article demonstrates the sheer scope by which the tourism industry’s contribution to the national and regional GDP is underestimated. Even when business trips by residents are included and thus make for a greater contribution of tourism to GDP, this fails to compensate for the downward bias produced by ignoring the indirect effects of tourism demand.
Assessing the Economic Impacts of Events: A Computable General Equilibrium Approach
Authors: Dwyer Larry , Forsyth Peter , Spurr Ray
Published: July 2006

This article explores the use of computable general equilibrium (CGE) analysis in evaluating the economic impacts of special events. It is argued that CGE analysis is preferred to input-output (I-O) approaches for assessing other than local economic impacts. The article illustrates several differences between the alternative forms of analysis in event assessment. These include assessing the differential effects of events on the host region, other regions, and nationally and the ability to estimate interindustry effects. The article then shows how CGE models can be adapted to estimate the displacement effects of events, their fiscal impacts, intraregional effects, event subsidies, and multistate effects. The article also discusses how event impacts will vary depending on the extent of integration between regional and national resource markets and regional and national product and services markets and how labor markets are modeled.
The Effects of a Community-Based Exercise Program on Function and Health in Older Adults: The EnhanceFitness Program
Authors: Belza Basia , Shumway-Cook Anne , Phelan Elizabeth A. , Williams Barbara , Snyder Susan J. , LoGerfo James P.
Published: July 2006

This study examined the effectiveness of participation in EnhanceFitness (EF) (formerly the Lifetime Fitness Program), an established community-based group exercise program for older adults. EF incorporated performance and health status measure testing in year 2000. Initial performance was compared to age and gender-based norms to classify participants as within or at or above normal limits (WNL) or below (BNL). In 2,889 participants who participated in outcomes testing, improvements were observed at 4 and 8 months on performance tests for both subgroups. Participants’ self-rating of health improved at 8 months. All participants improved on performance tests. Implementation of performance-based measures in community studies is possible. Challenges included selecting measures, staff training, collecting performance measures, and deciding on time points for data collection. Older adults can maintain and/or improve physical function through participation in EnhanceFitness.
Ethnic media, community media and participatory culture
Authors: Deuze Mark
Published: July 2006

Several recent studies document the rapid growth and success of ethnic or minority media in, for example, North America and Western Europe. Scholars in the field tend to attribute this trend as an expression of increasing worldwide migration patterns. In this article this explanation is challenged by locating the proliferation of these (news) media in a wider social trend: the worldwide emergence of all kinds of community, alternative, oppositional, participatory and collaborative media practices, in part amplified by the internet. A critical awareness of an increasingly participatory global media culture in multicultural societies is developed as a necessary tool to explain the success and impact of ethnic or minority media, as well as to embrace the changing ways in which people ‘use’ their media.
Reaching at risk groups
Authors: Wilkin Holley A. , Ball-Rokeach Sandra J.
Published: July 2006

Latinos are at high risk for many health problems, but are often missed by traditional health communication campaigns aired through general audience channels. This article explores Latinos’ connections to communication channels for health goals - both mediated and interpersonal and media that is general audience and geo-ethnic (targeted toward a specific ethnicity and/or community). Data from a random digit dial telephone survey of Latinos in two Los Angeles communities are analyzed. The results indicate that Latinos have strong connections to media that target their ethnic group or community, to interpersonal networks of friends and family, and to health professionals. The implications of these findings are discussed and recommendations made for increased health storytelling about the dominant health risks facing Latino communities.
The role of Native American print and online media in the ‘era of big stories’
Authors: Daniels George L.
Published: July 2006

In the face of continuing fragmentation of media audiences and an obsession by most news outlets with the ‘big story’, this article examined the coverage of one such ‘big story’ by four Native American media outlets. An analysis of the news reporting of the shootings of 10 students in Red Lake, Minnesota, on 21 March 2005 showed that while the Internet has changed the role of these outlets, both the printed and electronic Native American media maintain their relevance by providing news by and for Native Americans. Even as some of the Native American media utilized a ‘filtering’ strategy to showcase stories of particular interest to their audiences, these particular ethnic media outlets have begun to realize the advantages and flexibility of the web as a news medium. Construction of meaning theory was used to better understand the role of the Native American media in the so-called ‘era of big stories’.
Is changing the language enough? The Spanish-language ‘alternative’ in the USA
Authors: Moran Kristin C.
Published: July 2006

Alternative voices in the USA have been found in ethnic media outlets that provide information in languages other than English and focus on issues often ignored by the mainstream news. One such example is the Spanish-language media, which have had a long history in the USA. A content analysis was performed to analyze broadcast news in San Diego County to assess the similarities and differences between an ethnic news channel, KBNT (Univisión affiliate), and a mainstream station, KGTV (ABC affiliate). The data from the content analysis show some diversity in the stories covered, but the overall frequency of story type was fairly consistent among the stations. The corporate structure of Spanish-language media is looking more like its English-language counterparts and this oligopoly structure may make it more likely to follow trends such as displacing public discourse with entertainment and reducing the availability of diverse voices.
HIV/AIDS in the Middle East: a guide to a proactive response
Authors: Cheemeh Parvaneh Ehsanzadeh , Montoya Isaac D , Essien E James , Ogungbade Gbadebo O
Published: July 2006

After 24 years of being declared an epidemic, the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) has found its way to the remote parts of the Middle East. There are no fastidious HIV/AIDS epidemiological data available specific for the Middle East and insufficient surveys have been conducted in a larger area including the Middle East and North Africa. Currently the total number of people living with HIV in the Middle East and North Africa is 540,000.1-3 About 92,000 individuals were newly infected in 2004 and 28,000 people have died of AIDS during the same time period.2 With increasing spread of sexually transmitted infections (STIs), injection drug users (IDUs), numbers of unemployed youth, a conservative culture and low awareness of HIV4 the region is especially vulnerable to a large-scale epidemic. In this age of globalization the rapid spread of HIV along with highly virulent and multi-drug-resistant HIV strains that progress rapidly to AIDS, the more difficult and expensive prevention efforts and treatment regimes become. Complicating the issue there are many unresolved socio-economic conflicts in the Middle East.5,6 Valid and reliable HIV/AIDS epidemiological data, to facilitate policy formulation and to effect urgent prevention intervention is inadequate. This article identifies numerous gaps and shortfalls in the existing programs, elucidates the reasons behind the lack of information, and provides suggestions for taking actions.7,8
Sex, lives and videotape
Authors: Meldrum Julie , Pringle Alan
Published: July 2006

Various areas of the healthcare system are under pressure to find solutions to what are seen as the ‘problems’ of teenage pregnancy and the behaviours displayed by young people around sexual health issues. In many cases this has seen organizations such as Primary Care Trusts (PCTs) and Hospital Trusts charged with producing strategies and policies to influence the sexual behaviour of young people and to impact on the prominence of teenage pregnancy. It becomes clear, however, that any attempt to create policies or delivery systems to intervene in these areas will have a much greater chance of success if attempts are made to maximize the involvement of the young people in the process of constructing the delivery and content of health promotion approaches and service provision. This article outlines a process developed in Ashfield in Nottinghamshire whereby video interviews with community members, healthcare professionals and local young people formed the structure for focus groups. These were used to involve the community, and teenagers in particular, in the design of the service delivery. Videotaped interviews were conducted with local community members, local healthcare professionals and young people from the locality. The same interview schedule was used for each group but the responses showed marked differences of viewpoint between groups. Excerpts from the video interviews were used at externally facilitated focus groups firstly for young people, then for community members and then for healthcare professionals. A final large meeting brought the three groups together to discuss the important elements that a strategy should contain. The information gathered from the project influenced the development of the policy adopted by the PCT to engage with young people in the areas of teenage pregnancy and sexual health
Open Moral Communities and the Myth of the Armchair Theorist
Authors: Verma Niraj
Published: July 2006

How can planning theory be simultaneously expansive and manageable? By adapting Mandelbaum’s Open Moral Communities, this article argues that myths like the armchair theorist help to enlarge the scope of planning by connecting diverse communities of scholars. The moral imperative ensures that myths remain myths.
Italian Juvenile Justice: Tolerance, Leniency or Indulgence?
Authors: Nelken David
Published: July 2006

This paper offers a critique and further development of points made in Scalia’s account of Italian juvenile justice as a ‘lesson in tolerance’, published in an earlier issue of the journal. It discusses tolerance as a value and as a fact, the supposed sources of tolerance, and the stages at which tolerance can be displayed. It then re-examines quantitative and qualitative evidence of tolerance in Italy, paying special attention to comparing like with like, and considers the relevance of the wider conditions that may help shape Italian patterns of tolerance. It concludes with some brief cautions about how far lessons can be drawn from Italian practice.
The Mahatma didn’t like the movies and why it matters
Authors: Jeffrey Robin
Published: July 2006

This article examines the ideological and structural foundations of Indian broadcasting policy as it developed from the 1920s to the 1990s. The article argues that the failure of Indian governments to make the most of radio and television for economic and social development stemmed from three sources: (i) the restrictive policies inherited from a colonial state; (ii) the puritanism of the Gandhian national movement; and (iii) the fear, made vivid by the 1947 partition, of inflaming social conflict. The policies and institutions established in the 1940s and 1950s shaped Indian broadcasting for the next 40 years and have been significantly subverted only since 1992 as a result of the transformation effected by satellite television.
‘An Insider’s Game’
Authors: Davidson Roei
Published: July 2006

The article examines the way in which media mergers in France and the US are framed. This is done in order to ascertain whether media mergers, which are symptomatic of the growing concentration in the global media industries, are presented as purely commercial events or as events with sociopolitical repercussions. Content analysis of articles in the French press covering the Vivendi Universal merger in France and in the American press covering the AOL Time Warner merger in the US was conducted. Results suggest that in both countries the respective mergers are mostly framed as economic events, thereby removing the event from the realm of political contention.
‘Non’ Mediated Images
Authors: Khattab Umi
Published: July 2006

Television has been a state privilege in Malaysia since independence from British rule in 1957 and instrumental in Malaysia’s attempt to fashion and display public culture. RTM (Radio Television Malaysia) has functioned as a state mouthpiece, since 1963, most often representing deep differences between ethnic groups, and in the process manufacturing sacred and non-sacred circuits of cultures. Under a one-party, Malay-dominated, national coalition rule since independence, state television tends to reflect Malay culture in hegemonic and monolithic terms, failing to represent diverse differences within and between various ethnic and indigenous groups in Malaysia. The article explores how the state strategizes public and private television in manufacturing a public culture, arguing that the Vision 2020 desire to create a public Malay(sian) culture for polyethnic and multireligious Malaysia seems a myth mediated through polarized spheres. If state television is public service broadcasting (PSB), then it is clear that it is a utopia yet to arrive in postcolonial nations such as Malaysia.
Integrated risk modelling
Authors: Dimakos Xeni K , Aas Kjersti
Published: July 2006

In this article, we present a new approach to modelling the total economic capital required to protect a financial institution against possible losses. The approach takes into account the correlation between risk types, and in this respect, it improves upon the conventional practice that assumes perfectly correlated risks. A statistical model is built, and Monte Carlo simulation is used to estimate the total loss distribution. The methodology has been implemented in the Norwegian financial group DnB’s system for risk management. Incorporating current expert knowledge of relationships between risks, rather than taking the most conservative stand, gives a 20% reduction in the total economic capital for a one year time horizon.
Smoothing and forecasting mortality rates
Authors: Currie Iain D , Durban Maria , Eilers Paul HC
Published: July 2006

The prediction of future mortality rates is a problem of fundamental importance for the insurance and pensions industry. We show how the method of P-splines can be extended to the smoothing and forecasting of two-dimensional mortality tables. We use a penalized generalized linear model with Poisson errors and show how to construct regression and penalty matrices appropriate for two-dimensional modelling. An important feature of our method is that forecasting is a natural consequence of the smoothing process. We illustrate our methods with two data sets provided by the Continuous Mortality Investigation Bureau, a central body for the collection and processing of UK insurance and pensions data.
Stem Cells and Tissue Engineering: Past, Present, and Future
Authors: POLAK JULIA M. , BISHOP ANNE E.
Published: July 2006

Abstract: Tissue engineering is an interdisciplinary field that brings together the principles of the life sciences and medicine with those of engineering. The increase in its development over the past decade has resulted from a variety of factors; advances in genomics and proteomics, the advent of new biomaterials as potential templates for tissue growth, improvements in bioreactor design, and increased understanding of healing processes. Possibly the greatest contribution has come from our increased knowledge and understanding of stem cell biology, which is paving the way for the generation of unlimited cells of specific phenotypes for incorporation into engineered tissue constructs. Thus, tissue engineering approaches for expanding and engrafting the differentiated progeny of embryonic, fetal, or adult stem cells have major potential for tissue repair and will make a major contribution to medicine in the 21st century.
PTHrP and Skeletal Development
Authors: KRONENBERG HENRY M.
Published: July 2006

Abstract:  Parathyroid hormone‐related protein (PTHrP) participates in the regulation of endochondral bone development. After the cartilage mold is established in fetal life, perichondrial cells and chondrocytes at the ends of the mold synthesize PTHrP. This ligand then acts on PTH/PTHrP receptors on chondrocytes. As chondrocytes go through a program of proliferation and then further differentiation into post‐mitotic, hypertrophic chondrocytes, PTHrP action keeps chondrocytes proliferating and delays their further differentiation. Indian hedgehog (Ihh) is synthesized by chondrocytes that have just stopped proliferating and is required for synthesis of PTHrP. The feedback loop between PTHrP and Ihh serves to regulate the pace of chondrocyte differentiation and the sites at which perichondrial cells first differentiate into osteoblasts. Activation of the PTH/PTHrP receptor leads to stimulation of both Gs and Gq family heterotrimeric G proteins. Genetic analyses demonstrate that Gs activation mediates the action of PTHrP to keep chondrocytes proliferating, while Gq activation opposes this action. Downstream from Gs activation, synthesis of the cyclin‐cdk inhibitor, p57, is suppressed, thereby increasing the pool of proliferating chondrocytes. PTHrP's actions to delay chondrocyte differentiation are mediated by the phosphorylation of the transcription factor, SOX9, and by suppression of synthesis of mRNA encoding the transcription factor, Runx2. These pathways and undoubtedly others cooperate to regulate the pace of differentiation of growth plate chondrocytes in response to PTHrP.
BMP Signaling and Skeletogenesis
Authors: LI XUELIN , CAO XU
Published: July 2006

Abstract:  Bone morphogenetic proteins (BMPs) are members of the transforming growth factor (TGF)‐β superfamily of signal molecules that mediate many diverse biological processes ranging from early embryonic tissue patterning to postnatal tissue homeostasis. BMPs trigger cell responses mainly through the canonical signaling pathway where intracellular Smads play central roles in delivering the extracellular signals to the nucleus. While the same Smads are used by BMPs in all types of cells, different transcription factors account in part for the functional diversity of BMPs. These transcription factors are recruited by Smads to regulate the expression of specific subsets of target genes depending on the cell types. Among the transcription factors are Hox proteins. Experimental gain and loss‐of‐function studies as well as naturally occurring mutations in Hox genes demonstrate their central roles in embryonic skeletal patterning. In addition to the interactions with Smads observed for several Hox proteins, there is also evidence that the expression of a number of Hox genes is regulated by BMPs. It is suggested that Hox proteins play an important role in the BMP pathway.
Function of BMPs and BMP Antagonists in Adult Bone
Authors: ABE ETSUKO
Published: July 2006

Abstract:  The expression and function of BMPs and BMPs in bone tissues have been studied for a long time because of their remarkable activities. However, their biological functions in normal bone remodeling in adults were not fully understood until recently. Advanced technologies using gene manipulation were used to study their roles in adulthood. In addition, findings of new BMP antagonists and the effect of Wnt‐canonical pathways on bone features also provided new insights in bone studies.
The Pericellular Matrix as a Transducer of Biomechanical and Biochemical Signals in Articular Cartilage
Authors: GUILAK FARSHID , ALEXOPOULOS LEONIDAS G. , UPTON MAUREEN L. , YOUN INCHAN , CHOI JAE BONG , CAO LI , SETTON LORI A. , HAIDER MANSOOR A.
Published: July 2006

Abstract:  The pericellular matrix (PCM) is a narrow tissue region surrounding chondrocytes in articular cartilage, which together with the enclosed cell(s) has been termed the “chondron.” While the function of this region is not fully understood, it is hypothesized to have important biological and biomechanical functions. In this article, we review a number of studies that have investigated the structure, composition, mechanical properties, and biomechanical role of the chondrocyte PCM. This region has been shown to be rich in proteoglycans (e.g., aggrecan, hyaluronan, and decorin), collagen (types II, VI, and IX), and fibronectin, but is defined primarily by the presence of type VI collagen as compared to the extracellular matrix (ECM). Direct measures of PCM properties via micropipette aspiration of isolated chondrons have shown that the PCM has distinct mechanical properties as compared to the cell or ECM. A number of theoretical and experimental studies suggest that the PCM plays an important role in regulating the microenvironment of the chondrocyte. Parametric studies of cell–matrix interactions suggest that the presence of the PCM significantly affects the micromechanical environment of the chondrocyte in a zone‐dependent manner. These findings provide support for a potential biomechanical function of the chondrocyte PCM, and furthermore, suggest that changes in the PCM and ECM properties that occur with osteoarthritis may significantly alter the stress‐strain and fluid environments of the chondrocytes. An improved understanding of the structure and function of the PCM may provide new insights into the mechanisms that regulate chondrocyte physiology in health and disease.
Regulation of Osteoclast Differentiation
Authors: ROODMAN G. DAVID
Published: July 2006

Abstract:  The osteoclast (OCL) is derived from the cells in monocyte‐macrophage lineage. The earliest identifiable OCL precursor is the granulocyte‐macrophage colony‐forming unit (CFU‐GM), which gives rise to granulocytes, monocytes, and OCL. CFU‐GM–derived cells then differentiate to committed OCL precursors, which are post‐mitotic cells, and fuse to form multinucleated OCL. A variety of factors both positively and negatively regulate OCL formation and activity. These include growth factors, such as macrophage colony‐simulating factor, which simulates the proliferation and prevents apoptosis of early OCL precursors, and RANK ligand (RANKL), which is the primary mediator of OCL formation. Most factors that induce OCL differentiation, such as PTHrP, IL‐11, and prostaglandins, do so by inducing expression of RANKL on the surface of immature osteoblasts. Osteoprotegerin is a decoy receptor that blocks RANKL activity. In addition, OCL produce autocrine‐paracrine factors that regulate OCL formation, such as IL‐6, which is produced at high levels by OCL in Paget's disease and increases OCL formation. We screened human and murine OCL cDNA libraries to identify autocrine‐paracrine factors that regulate OCL activity. We identified annexin‐II, MIP‐1α, ADAM8, eosinophil chemotactic factor, and OCL inhibitor factors 1 and 2 as factors involved in OCL formation. Most recently, we have identified the receptor for ADAM8, α9β1 integrin, which appears to be critical for normal OCL activity. OCL differentiation is controlled by exogenous hormones and cytokines as well as autocrine‐paracrine factors that positively or negatively regulate OCL proliferation and differentiation.
M‐CSF, c‐Fms, and Signaling in Osteoclasts and their Precursors
Authors: ROSS F. PATRICK
Published: July 2006

Abstract:  Prevention of conditions, such as osteoporosis, requires an understanding of the molecular mechanisms of bone resorption. The understanding that cells of the myeloid lineage are osteoclast precursors suggests that macrophage colony‐stimulating factor (M‐CSF) plays an important role in osteoclast biology. Signals generated by the binding of M‐CSF to the cell‐surface receptor c‐Fms appear to trigger events leading to osteoclast differentiation. We have created a chimeric variant of the c‐Fms receptor, which has allowed study of downstream events activated by M‐CSF in a model more relevant to normal physiology than prior studies, which have relied on myeloid tissues. Our studies suggest novel regulatory signaling pathways initiated via the c‐Fms receptor.
Direct and Indirect Estrogen Actions on Osteoblasts and Osteoclasts
Authors: ZALLONE ALBERTA
Published: July 2006

Abstract:  Cells of osteoblast and osteoclast lineage are provided with the receptor for sex steroids, but discrepancies concerning mechanism of action still exist. Skeletal estrogen (ER) agonists induce osteoblastic osteoprotegerin (OPG) production through ER receptor‐α activation in vitro, while immune cells appear to overexpress RANKL in ER deficiency in vivo, not reproduced in in vitro study. It has also been evident that the effects of ER on bone to a large extent are mediated via its action on immune cells. We know now that ER regulates the expression of cytokines that target cell types involved in modulating bone turnover, as IL‐1 and IL‐6, and the latest findings confirm and expand the concept that T cells are key mediators of bone loss following gonadal failure. Although early work demonstrated that tumor necrosis factor‐α plays an important role in regulating bone mass, recent studies also implicate the lymphopoietic molecule IL‐7: it suppresses the bone‐forming osteoblasts, while stimulating formation and function of osteoclasts. More recent in vitro studies, however, indicate a stimulating effect of ER on osteoclastogenesis, which could have a positive effect on maintaining a high level of bone cell activity.
Molecular Mechanism of the Life and Death of the Osteoclast
Authors: TANAKA SAKAE , MIYAZAKI TSUYOSHI , FUKUDA AKIRA , AKIYAMA TORU , KADONO YUHO , WAKEYAMA HIDETOSHI , KONO SHINJIRO , HOSHIKAWA SHINYA , NAKAMURA MASAKI , OHSHIMA YASUSHI , HIKITA ATSUHIKO , NAKAMURA ICHIRO , NAKAMURA KOZO
Published: July 2006

Abstract:  The life span of osteoclasts is critically regulated by various cytokines, and therapeutics such as bisphosphonates act directly on osteoclasts and induce apoptosis of the cells. This article will focus on the molecular mechanism of osteoclast apoptosis and summarize the recent advances in this field with an emphasis on the role of intracellular signaling pathways.
Osteoblastic Activation in the Hematopoietic Stem Cell Niche
Authors: CALVI LAURA M.
Published: July 2006

Abstract:  Hematopoietic stem cells (HSC) are rare primitive cells capable of reconstituting all blood cell lineages throughout the life of an individual. The microenvironment in which stem cells reside is essential for their survival, self‐renewal, and differentiation. This microenvironment, or HSC niche, has been difficult to define in bone and bone marrow, but recent studies from our laboratory and others have shown that osteoblasts, the bone‐forming cells, are an essential regulatory component of this complex cellular network. We established that parathyroid hormone (PTH), through activation of the PTH/PTHrP receptor (PTH1R) in osteoblastic cells, could alter the HSC niche resulting in HSC expansion in vivo and in vitro and improving dramatically the survival of mice receiving bone marrow transplants. These findings are of great clinical appeal, because they suggest that a strategy aimed at modifying supportive cells in a stem cell niche can expand HSC. While a number of molecules have been found to be important for hematopoietic/osteoblastic interactions, we have focused on the Jagged1/Notch signaling pathway, which was necessary for the PTH‐dependent HSC expansion. Since the Jagged1/Notch signaling pathway has been implicated in the microenvironmental control of stem cell self‐renewal in several organ systems, definition of Jagged1 modulation, which is currently poorly understood, should provide additional molecular targets for stem cell regulation and advance the understanding of stem cell‐microenvironmental interactions.
Role of Connexin43 in Osteoblast Response to Physical Load
Authors: GRIMSTON SUSAN K. , SCREEN JOANNE , HASKELL JENNIFER H. , CHUNG DONG JIN , BRODT MICHAEL D. , SILVA MATTHEW J. , CIVITELLI ROBERTO
Published: July 2006

Abstract:  Gap junctions are hexameric transmembrane channels formed by connexins, and are responsible for direct cell‐to‐cell communication. The most abundant gap junction protein in bone is connexin43 (Cx43), although connexin45 (Cx45) is also expressed. In the present study, we tested the hypothesis that bone cell responses to mechanical stimulation are dependent on the type of gap junction communication provided by Cx43 in vitro and in an in vivo model of physical load. Application of cyclic stretch to calvaria osteoblasts results in a modest but detectable increase in PGE2 levels, and the amount of PGE2 produced was lower in cells isolated from Cx43 null mice. Mice with an osteoblast‐specific deletion of the Cx43 gene were subjected to an in vivo four‐point bending protocol on the tibia. This resulted in fast and exuberant formation of woven bone at the region directly below the loading fulcrum in both osteoblast Cx43‐deleted and wild‐type mice. However, indirect measurement of endosteal bone apposition suggested a less pronounced effect of physical load in Cx43‐deficient than in wild‐type mice. Taken together, these results indicate that deficiency of Cx43 in osteoblasts attenuates but does not abolish anabolic responses to mechanical strain.
Mechanism of Vitamin D Receptor Action
Authors: DEMAY MARIE B.
Published: July 2006

Abstract:  Studies in humans and in animal models have demonstrated that the receptor‐dependent actions of 1,25‐dihydroxyvitamin D are required for normal skeletal growth and maturation. Investigations were undertaken to address which consequences of vitamin D receptor deficiency are a direct result of impaired receptor‐dependent hormone actions versus being due to metabolic changes. Vitamin D receptor (VDR) knockout mice were therefore generated. Investigations were performed in mice with abnormal mineral ion homeostasis, as well as in mice in which the development of abnormal mineral ion homeostasis was prevented by dietary means. VDR null mice had hypocalcemia, hyperparathyroidism, and hypophosphatemia in the first month of life. Rickets and osteomalacia are observed as well. Institution of a high‐calcium, high‐phosphorus, lactose‐supplemented diet by the third week of life prevents abnormalities in mineral ion homeostasis. The bones of the VDR null mice with normal mineral ion homeostasis are indistinguishable from those of their wild‐type littermates. The rachitic changes in the growth plates are also prevented by maintenance of normal mineral ion homeostasis. Investigations into the pathophysiological basis for the growth plate abnormalities in the VDR null mice with abnormal mineral ion homeostasis demonstrated that impaired apoptosis of hypertrophic chondrocytes due to hypophosphatemia was the cause of rachitic changes. Studies investigating the cause of the alopecia demonstrate novel ligand‐independent VDR actions in the keratinocyte. The skeletal effects of VDR ablation are therefore indirect and reflect absence of ligand‐dependent receptor actions in the intestine. In contrast, the cutaneous phenotype of VDR ablation is a direct consequence of absence of ligand‐independent VDR actions in epidermal keratinocytes.
Inhibition of ATF4 Transcriptional Activity by FIAT/γ‐Taxilin Modulates Bone Mass Accrual
Authors: YU VIONNIE W.C. , GAUTHIER CLAUDE , ST‐ARNAUD RENÉ
Published: July 2006

Abstract:  The basic domain‐leucine zipper protein, activating transcription factor 4 (ATF4), was recently shown to control key aspects of osteoblast biology. ATF4 regulates the timely onset of osteoblast differentiation, the synthesis of type I collagen, and the transcription of the osteocalcin and RANKL (receptor activator of NFκ‐B ligand) genes. Accordingly, the levels and activity of ATF4 are under tight control through mechanisms that include protein stability and phosphorylation. We have uncovered yet another mode of inhibition of ATF4 through its interaction with the leucine zipper protein FIAT (Factor Inhibiting ATF4‐mediated Transcription, also described as γ‐taxilin). FIAT/γ‐taxilin localizes to the nucleus in osteoblasts and dimerizes with ATF4 to form inactive dimers, because it does not contain a DNA‐binding basic domain moiety. The interaction of FIAT/γ‐taxilin with ATF4 thus inhibits ATF4‐mediated transcription. Transgenic mice overexpressing FIAT/γ‐taxilin show osteopenia and reduced expression of the ATF4 target gene, osteocalcin. Interestingly, FIAT/γ‐taxilin also interacts with the transcriptional co‐activator αNAC (Nascent polypeptide associated complex And Coactivator alpha), suggesting alternative, non‐mutually exclusive mechanisms contributing to the inhibition of ATF4‐dependent osteocalcin gene transcription by FIAT/γ‐taxilin.
Autosomal‐Dominant Pseudohypoparathyroidism Type Ib is Caused by Different Microdeletions Within or Upstream of the GNAS Locus
Authors: JÜPPNER HARALD , LINGLART AGNÈS , FRÖHLICH LEOPOLD F. , BASTEPE MURAT
Published: July 2006

Abstract:  The term pseudohypoparathyroidism (PHP) refers to the different disorders that are caused by mutations within GNAS or upstream of this complex genetic locus. GNAS gives rise to several different transcripts, including Gsα (α‐subunit of heterotrimeric stimulatory G protein), XLαs (extra‐large variant of Gsα), and several additional sense and antisense transcripts. The complexity of the GNAS locus is furthermore reflected by a parent‐specific methylation pattern of most of its different promotors. PHP can be divided into two major groups, PHP type Ia (PHP‐Ia) and PHP type Ib (PHP‐Ib). PHP‐Ia is caused by heterozygous mutations affecting one of the 13 GNAS exons encoding Gsα or by large intragenic deletions. In contrast, PHP‐Ib is caused by heterozygous deletions within STX16, the gene‐encoding syntaxin 16, which is located more than 220 kb upstream of GNAS, or by deletions within GNAS involving exon NESP55 and two of the antisense exons. In either form of PHP, hormonal resistance develops only after maternal inheritance of the mutation, while paternal inheritance of the same molecular defect is not associated with endocrine abnormalities. In most familial cases of PHP‐Ib, there is a loss of exon A/B methylation combined with active A/B transcription from both parental alleles, which leads to suppression of Gsα transcription in the proximal renal tubules and, therefore, PTH resistance.