bluuebunny/crossref_metadata_2025 huggingface dataset:
Peri-Implant Tissue Response to Pathological Insults
Authors: Jovanovic Sascha A.
Published: January 2009

With the increased use of osseointegrated implants and with many implants functioning for long periods of time, the soft tissue barrier around implants has become more important. This paper reviews the soft tissue response around implants under healthy and diseased conditions and presents the etiology of peri-implant tissue breakdown. Diagnostic techniques such as probing pocket depth, radiographic evidence, and microbial sampling have been analyzed and modified from the periodontal field and used during the maintenance phase of the dental implant. The long-term goal of implant maintenance is to prevent or to arrest the progression of disease, and to achieve a maintainable implant site. Recent reports indicate that peri-implant tissues can be treated with either non-surgical or surgical techniques.
A Simple Model of Legislator and News Media Interaction
Authors: Fogarty Brian J.
Published: January 2009

This article examines the effect of a strategic news media on legislators' interactions with their constituencies. Specifically, legislators can only be constrained by constituency preferences over policies when voters have the information to hold legislators accountable for their actions. A strategic news media can provide such information in a constant and continuous manner unlike, say, challengers. This article addresses this scenario with several models. First, a signaling model is introduced with constituency preferences and a journalist's investigating and reporting strategies serving as constraints on a legislator's voting preferences. Results of the baseline model include a pooling equilibrium where legislators vote with the district and are always re-elected. Second, a basic ultimatum bargaining model is introduced to allow for collusion between journalists and legislators in the output of the news product. This extension highlights a pure strategy-separating equilibrium where an out-of-step legislator is able to secure silence from the journalist and win re-election. Finally, the role of multiple journalists covering a legislator is considered. Results illustrate that as the number of media outlets increases within a district, the quality of representation also increases.
Explaining the 1914 War in Europe
Authors: Zagare Frank C.
Published: January 2009

This essay constructs a theoretically rigorous explanation of the 1914 European war that involved Austria—Hungary, Germany, Russia, and France. It also serves to confirm Trachtenberg's contention that `one does not have to take a particularly dark view of German intentions' to explain the onset of war in 1914 and `question the ``inadvertent war'' theory'. A number of related questions about the Great War are also addressed within the context of a generic game-theoretic escalation model with incomplete information. The analysis suggests that general war broke out in Europe in 1914 because both Austria— Hungary and Germany believed that, when push came to shove, Russia would stand aside if Austria moved aggressively against Serbia. There is a sense in which the war can be said to be unintended but there is no sense in which it should be understood as accidental.
ESPAnet/JESP Doctoral Researcher Prize Essay
Authors: Jensen Carsten
Published: January 2009

Childcare services have experienced a sudden surge in the level of public provision since the late 1990s. There is a rising awareness of the benefits of childcare services, not least in terms of the human capital they generate. These recent changes — and especially the country variation therein — are vaguely covered by existing literature, which tends to focus on effects rather than the causes of policies. In this article, three competing hypotheses on the institutional conditions of change are derived and tested. The article shows that change is determined by curriculum traditions and not by the size of vested interests or ceiling effects. Countries belonging to the readiness-for-school-curriculum tradition have expanded their provision considerably more than countries belonging to the social-pedagogical-curriculum tradition; the reason is argued to be that the former conceptually matches the political preference for generation of human capital much better than the latter.
Towards productive welfare? A comparative analysis of 23 OECD countries
Authors: Hudson John , Kühner Stefan
Published: January 2009

Numerous analysts have suggested that globalization and the emergence of more knowledge-based economies have encouraged high-income nations to shift towards a model of productive welfare focused on social investment, yet typologies of welfare are still largely drawn on the basis of measures of social protection rather than social investment. Here we develop a classification of welfare state types that incorporates both productive and protective elements of social policy. Using fuzzy set ideal type analysis we explore data for a sample of 23 OECD countries in three time points: 1994, 1998 and 2003. Our findings provide no more than very modest support for claims that welfare states are shifting from protective to productive modes of provision and, in many cases, we identify a shift in the alternative direction. In addition, we identify some nations that are clearly productive in their focus and others that manage to combine productive and protective features.
Dealing with older workers in Europe: a comparative survey of employers' attitudes and actions
Authors: Van Dalen Hendrik P. , Henkens Kène , Schippers Joop
Published: January 2009

This article addresses employers' attitudes and actions regarding the position of older workers. A comparative survey among employers from four European countries — Greece, Spain, the Netherlands and the United Kingdom — is used to examine their expectations with respect to the ageing of the workforce, the productivity of older workers and their recruitment and retention behaviour regarding this cohort. The results show that in spite of the perceived challenges ahead (including the ageing workforce), employers take no substantial measures to retain and recruit older workers or improve their productivity. Only employers in the United Kingdom seem to recognize older workers as a valuable source of labour supply and act accordingly.
Changing East–West Division of Labour in the European Automotive Industry
Authors: Jürgens Ulrich , Krzywdzinski Martin
Published: January 2009

The article deals with the impact of the emerging new division of labour between Western and Central and Eastern Europe (CEE) on work and employment, both in the Western and CEE countries. Major points of discussion will be the hypothesis of a `hollowingout' of the Western European auto industry, and the hypothesis of a `regime flight'; that is, the claim that companies use CEE locations to escape the collectively regulated work models of Western Europe. The article draws from our own empirical research, including company case-studies in Western and Eastern auto plants, and on statistical analysis. The main conclusions are: in CEE countries, an upgrading process of production sites can be observed, which challenges the view of an emerging `high end/low end' division of labour between the West and the East.While relocation has led to some losses of low-skill jobs in Western Europe, the overall effect of the expansion of the automotive industry to CEE on growth and employment in Western Europe was positive.The impact of low-cost component imports from CEE countries has increased the competitiveness of the German firms, which are by far the main investor in CEE countries. Our case-studies reveal no trend towards regime flight from Western European work models, but management threats of relocation have become commonplace and have led to a renegotiation of work models in Western European countries. In CEE countries, the work models of automobile companies more and more are oriented at a high-road path.This development is fostered by the companies' responses to the problems of migration and the increasing shortage of skilled labour.
Industrial Upgrading Through Foreign Direct Investment in Central European Automotive Manufacturing
Authors: Pavlínek Petr , Domański Bolesław , Guzik Robert
Published: January 2009

This article draws on the global value-chain approach to investigate industrial upgrading in the automotive industry of four Central European (CE) countries: Czech Republic, Hungary, Poland and Slovakia. We review post-1990 production trends and the associated changes in the geography of automobile production in Central and Eastern Europe (CEE) based on inflows of foreign direct investment (FDI).To evaluate industrial upgrading, we examine the changes in the international trade of CE countries with automotive products classified in three value-added classes between 1996 and 2006, and we consider the increasing location of automotive design in CE by foreign investors.We classify CE automobile assembly plants into four types based upon the role of local design, local content, and their links with domestic economies. Based on the results of the analysis, we consider the effects of FDI and industrial upgrading on the role of CE in the European automotive production system.
Managed Flexibility
Authors: Coe Neil M. , Johns Jennifer , Ward Kevin
Published: January 2009

This article provides an account of the temporary staffing industry outside its two largest markets, the UK and the US. It argues that there is greater national variation in industry characteristics than has generally been acknowledged, using the example of Sweden to illustrate the importance of understanding staffing industries in relation to the regulatory context in which they are embedded. Drawing on secondary materials and interviews with senior officials in transnational and domestic temporary staffing agencies, labour unions, industry trade bodies and government departments, the article asserts that the temporary staffing industry should be understood as an active agent of labour market restructuring. It provides a detailed analysis of the Swedish industry's distinct periods of expansion, charting its legalization and subsequent growth in the context of a highly regulated labour market. In conclusion, the article makes two key points. First, the Swedish temporary staffing market is the product of a particular social democratic welfare state regime and the roles played by the different social partners which lead to the production of a managed flexibility. Second, the particularities of the Swedish system, and the need for transnational staffing agencies to adapt their activities, underline how firms both shape, and are shaped by, the economic and social characteristics and dynamics that exist in the territories in which they invest.
One Less Barrier to Foreign Direct Investment in Turkey?
Authors: Özdemir Dilek , Darby James
Published: January 2009

Despite various reasons for the relatively low levels of foreign direct investment (FDI) inflow into Turkey throughout the postwar period, Istanbul has proved relatively successful in attracting inward FDI in services in recent years. Increased production by both foreign and domestic manufacturers in the wider Marmara region has also resulted in a concentration of service sector firms in the greater Istanbul metropolitan area. Examination of the profile of foreign investors and investment categories reveals that Germany and the Netherlands remain major sources of investment, and that investment from these two countries shows the most marked signs of functional linkage between manufacturing and service projects. This growth of functional linkage, exemplified by the increased importance of logistics operations, may represent the removal of one more factor inhibiting inward investment into Turkey on a scale appropriate to its size and growth potential.
Regulation of Calcium in Salivary Gland Secretion
Authors: Ambudkar I.S.
Published: January 2009

Neurotransmitter-regulation of fluid secretion in the salivary glands is achieved by a coordinated sequence of intracellular signaling events, including the activation of membrane receptors, generation of the intracellular second messenger, inositol 1,4,5, trisphosphate, internal Ca2+release, and Ca2+influx. The resulting increase in cytosolic [Ca2+] ([Ca2+]i) regulates a number of ion transporters, e.g., Ca2+-activated K+ channel, Na+/K+/2Cl-co-transporter in the basolateral membrane, and the Ca2+-activated Cl-channel in the luminal membrane, which are intricately involved in fluid secretion. Thus, regulation of [Ca2+]iis central to the regulation of salivary acinar cell function and is achieved by the concerted activities of several ion channels and Ca2+-pumps localized in various cellular membranes. Ca2+ pumps, present in the endoplasmic reticulum and the plasma membrane, serve to remove Ca2+from the cytosol. Ca2+ channels present in the endoplasmic reticulum and the plasma membrane facilitate rapid influx of Ca2+into the cytosol from the internal Ca2+stores and from the external medium, respectively. It is well-established that prolonged fluid secretion is regulated via a sustained elevation in [Ca2+]ithat is primarily achieved by the influx of Ca2+into the cell from the external medium. This Ca2+influx occurs via a putative plasma-membrane-store-operated Ca2+channel which has not yet been identified in any non-excitable cell type. Understanding the molecular nature of this Ca2+ influx mechanism is critical to our understanding of Ca2+signaling in salivary gland cells. This review focuses on the various active and passive Ca2+transport mechanisms in salivary gland cells-their localization, regulation, and role in neurotransmitter-regulation of fluid secretion. In addition to a historical perspective of Ca2+signaling, recent findings and challenging problems facing this field are highlighted.
Acute and Chronic Craniofacial Pain: Brainstem Mechanisms of Nociceptive Transmission and Neuroplasticity, and Their Clinical Correlates
Authors: Sessle Barry J.
Published: January 2009

This paper reviews the recent advances in knowledge of brainstem mechanisms related to craniofacial pain. It also draws attention to their clinical implications, and concludes with a brief overview and suggestions for future research directions. It first describes the general organizational features of the trigeminal brainstem sensory nuclear complex (VBSNC), including its input and output properties and intrinsic characteristics that are commensurate with its strategic role as the major brainstem relay of many types of somatosensory information derived from the face and mouth. The VBSNC plays a crucial role in craniofacial nociceptive transmission, as evidenced by clinical, behavioral, morphological, and electrophysiological data that have been especially derived from studies of the relay of cutaneous nociceptive afferent inputs through the subnucleus caudalis of the VBSNC. The recent literature, however, indicates that some fundamental differences exist in the processing of cutaneous vs. other craniofacial nociceptive inputs to the VBSNC, and that rostral components of the VBSNC may also play important roles in some of these processes. Modulatory mechanisms are also highlighted, including the neuro-chemical substrate by which nociceptive transmission in the VBSNC can be modulated. In addition, the long-term consequences of peripheral injury and inflammation and, in particular, the neuroplastic changes that can be induced in the VBSNC are emphasized in view of the likely role that central sensitization, as well as peripheral sensitization, can play in acute and chronic pain. The recent findings also provide new insights into craniofacial pain behavior and are particularly relevant to many approaches currently in use for the management of pain and to the development of new diagnostic and therapeutic procedures aimed at manipulating peripheral inputs and central processes underlying nociceptive transmission and its control within the VBSNC.
Passive Immunization Against Dental Caries and Periodontal Disease: Development of Recombinant and Human Monoclonal Antibodies
Authors: Abiko Y.
Published: January 2009

Indigenous micro-organisms in the oral cavity can cause two major diseases, dental caries and periodontal diseases. There is neither agreement nor consensus as to the actual mechanisms of pathogenesis of the specific virulence factors of these micro-organisms. The complexity of the bacterial community in dental plaque has made it difficult for the single bacterial agent of dental caries to be determined. However, there is considerable evidence that Streptococcus mutans is implicated as the primary causative organism of dental caries, and the cell-surface protein antigen (SA I/II) as well as glucosyltransferases (GTFs) produced by S. mutans appear to be major colonization factors. Various forms of periodontal diseases are closely associated with specific subgingival bacteria. Porphyromonas gingivalis has been implicated as an important etiological agent of adult periodontitis. Adherence of bacteria to host tissues is a prerequisite for colonization and one of the important steps in the disease process. Bacterial coaggregation factors and hemagglutinins likely play major roles in colonization in the subgingival area. Emerging evidence suggests that inhibition of these virulence factors may protect the host against caries and periodontal disease. Active and passive immunization approaches have been developed for immunotherapy of these diseases. Recent advances in mucosal immunology and the introduction of novel strategies for inducing mucosal immune responses now raise the possibility that effective and safe vaccines can be constructed. In this regard, some successful results have been reported in animal experimental models. Nevertheless, since the public at large might be skeptical about the seriousness of oral diseases, immunotherapy must be carried out with absolute safety. For this goal to be achieved, the development of safe antibodies for passive immunization is significant and important. In this review, salient advances in passive immunization against caries and periodontal diseases are summarized, and the biotechnological approaches for developing recombinant and human-type antibodies are introduced. Furthermore, our own attempts to construct single-chain variable fragments (ScFv) and human-type antibodies capable of neutralizing virulence factors are discussed.
Oro-Facial Gangrene (Noma/Cancrum Oris): Pathogenetic Mechanisms
Authors: Enwonwu C.O. , Falkler W.A. , Idigbe E.O.
Published: January 2009

Cancrum oris (Noma) is a devastating infectious disease which destroys the soft and hard tissues of the oral and para-oral structures. The dehumanizing oro-facial gangrenous lesion affects predominantly children ages 2 to 16 years, particularly in sub-Saharan Africa, where the estimated frequency in some communities varies from I to 7 cases per 1000 population. The risk factors are poverty, malnutrition, poor oral hygiene, residential proximity to livestock in unsanitary environments, and infectious diseases, particularly measles and those due to the herpesviridae. Infections and malnutrition impair the immune system, and this is the common denominator for the occurrence of noma. Acute necrotizing gingivitis (ANG) and oral herpetic ulcers are considered the antecedent lesions, and ongoing studies suggest that the rapid progression of these precursor lesions to noma requires infection by a consortium of micro-organisms, with F usobacterium necrophorum (Fn) and P revotella intermedia (Pi) as the suspected key players. Additional to production of a growth-stimulating factor for Pi, Fn displays a classic endotoxin, a dermonecrotic toxin, a cytoplasmic toxin, and a hemolysin. Without appropriate treatment, the mortality rate from noma is 70-90%. Survivors suffer the two-fold afflictions of oro-facial mutilation and functional impairment, which require a time-consuming, financially prohibitive surgical reconstruction.
Mouse Submandibular Gland Morphogenesis: a Paradigm for Embryonic Signal Processing
Authors: Molnick Michael , Jaskoll Tina
Published: January 2009

Signal processing is the sine qua non of embryogenesis. At its core, any single signal transduction pathway may be understood as classic Information Theory, adapted as an open system such that, because of networking, the "receiver" is presented with more information than was initially signaled by the "source". Over 40 years ago, Waddington presented his "Epigenetic Landscape" as a metaphor for the hierarchical nature of embryogenesis. Mathematically, Waddington's landscape may be modeled as a neural net. The "black box" of the neural net is an interacting network of signal transduction pathways (using hormones, growth factors, cytokines, neurotransmitters, and others) which inform the Boolean logic gates. An emerging theme in developmental biology is that defined sets of epigenetic circuits are used in multiple places, at multiple times, for similar and sometimes different purposes during organogenesis. As we show here, submandibular gland embryonic and fetal development is a splendid paradigm of these epigenetic circuits and their phenotypic outcomes, such as branching and lumen formation.
The Role of Serotonin and Neurotransmitters During Craniofacial Development
Authors: Moiseiwitsch Julian R.D.
Published: January 2009

Several neurotransmitters, in particular serotonin (5-HT), have demonstrated multiple functions during early development and mid-gestational craniofacial morphogenesis. Early studies indicated that 5-HT is present in the oocyte, where it appears to function as a regulator of cell cleavage. Later, it has a significant role during gastrulation, during which there are significant areas of 5-HT uptake in the primitive streak. Subsequently, in association with neurulation, 5-HT uptake is seen in the floor plate of the developing neural tube. During neural crest formation and branchial arch formation, 5-HT has been demonstrated to facilitate cell migration and stimulate cell differentiation. During morphogenesis of the craniofacial structures, 5-HT stimulates dental development and may aid in cusp formation. All of the most commonly prescribed anti-depressant drugs inhibit serotonin uptake, yet they do not appear to cause major craniofacial malformations in vivo. Given the wide spectrum of effects that 5-HT has during development, it is difficult to understand why these anti-depressants are not major teratogens. Redundancy within the system may allow receptor and uptake pathways to function normally even with lower than normal levels of circulating serotonin. Serotonin-binding proteins, that are expressed in most craniofacial regions at critical times during craniofacial development, may have a buffering capacity that maintains adequate 5-HT tissue concentrations over a wide range of 5-HT serum concentrations. Dental development appears to be particularly sensitive to even small fluctuations in concentrations of 5-HT. Therefore, it may be that children of patients who have received selective serotonergic re-uptake inhibitors (such as Prozac and Zoloft) or the less selective tricyclic anti-depressant drugs (such as Elavil) would be at a higher risk for developmental dental defects such as anodontia and hypodontia. In this review, the evidence supporting a role for 5-HT during mammalian craniofacial development is discussed. A series of models is proposed that may explain how the craniofacial effects of 5-HT are mediated.
PAF, a Putative Mediator of Oral Inflammation
Authors: McManus L.M. , Pinckard R.N.
Published: January 2009

PAF, or platelet-activating factor, is a family of structurally related phospholipids (1-O-alkyl/acyl/alkenyl-2-acetylsn-glycero-3-phosphocholine) which possesses a wide spectrum of potent pro-inflammatory actions. These phospholipids are synthesized by a diverse array of cells, including neutrophilic polymorphonuclear leukocytes (PMN), platelets, mast cells, monocytes/macrophages, vascular endothelial cells, and lymphocytes. PAF targets these and other cells via specific, G-protein-coupled receptors to initiate intracrine, autocrine, paracrine, and juxtacrine cell activation. Of importance, these unique acetylated phospholipids are frequently synthesized in concert with pro-inflammatory lipid mediators derived from arachidonic acid. Since PAF synergizes with these and other mediators to amplify the inflammatory response, it seems likely that PAF plays an integral, perhaps pivotal, role in acute and chronic inflammatory processes. PAF is present in the mixed saliva of dentate, but not edentulous, human subjects. The levels of PAF in mixed saliva or in gingival crevicular fluid and tissues are significantly increased during oral inflammatory conditions such as periodontitis and mucositis. Interestingly, the levels of salivary PAF correlate with the extent/severity of these oral diseases. These observations suggest that PAF may participate in pathophysiologic events during the course of oral inflammation. The availability of specific PAF receptor antagonists and human recombinant PAF-acetylhydrolase (PAF-AH), a plasma enzyme which rapidly destroys PAF, should provide clinical tools for the investigation of the role of PAF in these and other inflammatory disorders; and perhaps, ultimately, some of these reagents may prove to be therapeutically useful in the treatment and management of these conditions.
Biocompatibility of Resin-Modified Filling Materials
Authors: Geurtsen W.
Published: January 2009

Increasing numbers of resin-based dental restorations have been placed over the past decade. During this same period, the public interest in the local and especially systemic adverse effects caused by dental materials has increased significantly It has been found that each resin-based material releases several components into the oral environment. In particular, the comonomer triethyleneglycol di-methacrylate (TEGDMA), and the 'hydrophilic' monomer, 2-hydroxy-ethyl-methacrylate (HEMA), are leached out from various composite resins and 'adhesive' materials (e.g., resin-modified glass-ionomer cements [GICs] and dentin adhesives) in considerable amounts during the first 24 hours after polymerization. Numerous unbound resin components may leach into saliva during the initial phase after polymerization, and later, due to degradation or erosion of the resinous restoration. Those substances may be systemically distributed and could potentially cause adverse systemic effects in patients. In addition, absorption of organic substances from unpolymerized material, through unprotected skin due to manual contact may pose a special risk for dental personnel. This is borne out by the increasing numbers of dental nurses, technicians, and dentists who present with allergic reactions to one or more resin components like HEMA glutaraldehyde ethyleneglycol di-methacrylate (EGDMA), and dibenzoyl peroxide (DPO). However, it must be emphasized that except for conventional composite resins, data reported on the release of substances from resin-based materials are scarce. There is very little reliable information with respect to the biological interactions between resin components and various tissues. Those interactions may be either protective, like absorption to dentin, or detrimental, e.g., inflammatory reactions of soft tissues Microbial effects have also been observed which may contribute indirectly to caries and irritation of the pulp. Therefore, it is critical, both for our patients and for the profession, that the biological effects of resin-based filling materials be clarified in the near future
Smoking and Periodontal Disease
Authors: Kinane D.F. , Chestnutt I.G.
Published: January 2009

Numerous investigations of the relationship between smoking and periodontal disease have been performed over the last 15 years, and there now exists a substantial body of literature upon which this current review is based. From both cross-sectional and longitudinal studies, there appears to be strong epidemiological evidence that smoking confers a considerably increased risk of periodontal disease. This evidence is further supported by the data emanating from patients who stop smoking. These patients have levels of risk similar to those of non-smokers. Numerous studies of the potential mechanisms whereby smoking tobacco may predispose to periodontal disease have been conducted, and it appears that smoking may affect the vasculature, the humoral immune system, and the cellular immune and inflammatory systems, and have effects throughout the cytokine and adhesion molecule network. The aim of this review is to consider the evidence for the association between smoking and periodontal diseases and to highlight the biological mechanisms whereby smoking may affect the periodontium.
Epithelial Structural Proteins of the Skin and Oral Cavity: Function in Health and Disease
Authors: Presland Richard B. , Dale Beverly A.
Published: January 2009

Epithelial tissues function to protect the organism from physical, chemical, and microbial damage and are essential for survival. To perform this role, epithelial keratinocytes undergo a well-defined differentiation program that results in the expression of structural proteins which maintain the integrity of epithelial tissues and function as a protective barrier. This review focuses on structural proteins of the epidermis and oral mucosa. Keratin proteins comprise the predominant cytoskeletal component of these epithelia. Keratin filaments are attached to the plasma membrane via desmosomes, and together these structural components form a three-dimensional array within the cytoplasm of epithelial cells and tissues. Desmosomes contain two types of transmembrane proteins, the desmogleins and desmocollins, that are members of the cadherin family. The desmosomal cadherins are linked to the keratin cytoskeleton via several cytoplasmic plaque proteins, including desmoplakin and plakoglobin (γ-catenin). Epidermal and oral keratinocytes express additional differentiation markers, including filaggrin and trichohyalin, that associate with the keratin cytoskeleton during terminal differentiation, and proteins such as loricrin, small proline-rich proteins, and involucrin, that are cross-linked into the cornified envelope by transglutaminase enzymes. The importance of these cellular structures is highlighted by the large numbers of genetic and acquired (autoimmune) human disorders that involve mutations in, or autoantibodies to, keratins and desmosomal and cornified envelope proteins. While much progress has been made in the identification of the structural proteins and enzymes involved in epithelial differentiation, regulation of this process is less clear. Both calcium and retinoids influence epithelial differentiation by altering the transcription of target genes and by regulating activity of enzymes critical in epithelial differentiation, such as transglutaminases proteinases, and protein kinases. These studies have furthered our understanding of how epithelial tissue and cell integrity is maintained and provide a basis for the future treatment of skin and oral disorders by gene therapy and other novel therapeutics
Links Among Growth Factors, Hormones, and Nuclear Factors With Essential Roles in Bone Formation
Authors: McCarthy Thomas L. , Changhua Ji  , Centrella Michael
Published: January 2009

Research performed during the last several years implicates important roles for a variety of growth factors that affect osteoblasts or their precursors during bone development, remodeling, or repair. Of these, three families of growth factors in particular-the transforming growth factor betas (TGF-βs), insulin-like growth factors (IGFs), and bone morphogenetic proteins (BMPs)-are considered to be principal local regulators of osteogenesis, although none is specific for cells of the osteoblast lineage. Therefore, mechanisms to induce skeletal tissue specificity might occur through interactions among these growth factors, with circulating hormones, or through specific intracellular mediators. In the latter case, even more recent studies point to two nuclear transcription factors, termed Core Binding Factor al (CBFal) and CCAAT/Enhancer Binding Protein 8 (C/EBP8), as significant regulators of the expression or activity of specific bone growth factors or their receptors. Perhaps more importantly, events that link these growth factors to nuclear proteins occur in response to glucocorticoids, sex steroids, parathyroid hormone (PTH), or prostaglandin E2 (PGE2), which themselves have well-known effects on bone biology. in this review, we discuss the situations and processes that initially suggested growth-factor- and hormone-specific interactions on cells within the osteoblast lineage, and present evidence for roles that CBFa I and C/EBP8 have on osteoblast function. Finally, we offer examples for how these factors integrate events that are associated with various aspects of bone formation.
Primary Mineralization At the Surfaces of Implants
Authors: Sela J. , Gross U.M. , Kohavi D. , Shani J. , Dean D.D. , Boyan B.D. , Schwartz Z.
Published: January 2009

Osteogenesis around implants is affected by the physical and chemical characteristics of the biomaterials used. The osteoprogenitor cells must migrate to the implant site and synthesize and secrete a mineralizable extracellular matrix. Because this is neo-bone formation, the mechanism by which the cells calcify their matrix involves extracellular organelles called matrix vesicles in a process termed "primary mineralization". Two different methods for assessing the effects of implant materials on primary mineralization are presented in this report. In the first approach, different implant materials used in dentistry and orthopedic surgery were placed in rat tibial bones after marrow ablation. Two groups of implants were used, bone-bonding and non-bonding materials. We examined the effects of the materials on calcification morphometrically by quantitating changes in matrix vesicle morphology and distribution in endosteal tissue around implants as compared with normal endosteal bone healing. In addition, matrix vesicles were isolated from the endosteal tissue around the implant as well as from the contralateral limb and were examined biochemically. The results demonstrated that bone-bonding materials induced a greater increase in matrix vesicle enzyme activity than did non-bonding materials. However, all materials caused changes in matrix vesicles that were different from those seen in normal endosteal bone formation following injury. The effects of implant materials on biochemical markers of mineralization, including specific activities of matrix vesicle alkaline phosphatase and phospholipase A2 and phosphatidylserine content, demonstrated a high correlation with the morphometric observations with regard to enhancement and/or delay of primary mineralization. In the other approach, we used a radioisotopic method to evaluate the effects of implant materials on primary mineralization. This analysis revealed that implants alter bone healing, as shown by the differential uptake of 99mTc and 32P in different bone compartments. Decreased 32P uptake by the organic phase in the presence of bone-bonding implants suggests that cleavage of 99mTcMD32P into its technetium and methylene diphosphonate moieties was inhioited by the presence of the implants. In summary, these approaches to evaluating the effects of materials on primary mineralization demonstrate that the marrow ablation model can easily distinguish between bone-bonding and non-bonding materials. The use of this model can be valuable in the development of new materials.
The Chemistry of Enamel Caries
Authors: Robinson C. , Shore R.C. , Brookes S.J. , Strafford S. , Wood S.R. , Kirkham J.
Published: January 2009

The chemical changes which occur during the process of carious destruction of enamel are complex due to a number of factors. First, substituted hydroxyapatite, the main component of dental enamel, can behave in a very complex manner during dissolution. This is due not only to its ability to accept substituent ions but also to the wide range of calcium phosphate species which can form following dissolution. In addition, the composition, i.e., the extent of substitution, changes throughout enamel in the direction of carious attack, i.e., from surface to interior. Both surface and positively birefringent zones of the lesion clearly illustrate that carious destruction is not simple dissolution. Selective dissolution of soluble minerals occurs, and there is the probability of reprecipitation. The role of fluoride here is crucial in that not only does it protect enamel per se but also its presence in solution means that rather insoluble fluoridated species can form very easily, encouraging redeposition. The role of organic material clearly needs further investigation, but there is the real possibility of both inhibition of repair and facilitation of redeposition. For the future, delivering fluoride deep into the lesion would appear to offer the prospect of improved repair. This would entail a delivery vehicle which solved the problem of fluoride uptake by apatite at the tooth surface. Elucidation of the role of organic material may also reveal putative mechanisms for encouraging repair and/or protecting the enamel mineral
Neural Control of Tongue Movement With Respect To Respiration and Swallowing
Authors: Sawczuk A. , Mosier K.M.
Published: January 2009

The tongue must move with remarkable speed and precision between multiple orofacial motor behaviors that are executed virtually simultaneously. Our present understanding of these highly integrated relationships has been limited by their complexity. Recent research indicates that the tongue's contribution to complex orofacial movements is much greater than previously thought. The purpose of this paper is to review the neural control of tongue movement and relate it to complex orofacial behaviors. Particular attention will be given to the interaction of tongue movement with respiration and swallowing, because the morbidity and mortality associated with these relationships make this a primary focus of many current investigations. This review will begin with a discussion of peripheral tongue muscle and nerve physiology that will include new data on tongue contractile properties. Other relevant peripheral oral cavity and oropharyngeal neurophysiology will also be discussed. Much of the review will focus on brainstem control of tongue movement and modulation by neurons that control swallowing and respiration, because it is in the brainstem that orofacial motor behaviors sort themselves out from their common peripheral structures. There is abundant evidence indicating that the neural control of protrusive tongue movement by motoneurons in the ventral hypoglossal nucleus is modulated by respiratory neurons that control inspiratory drive. Yet, little is known of hypoglossal motoneuron modulation by neurons controlling swallowing or other complex movements. There is evidence, however, suggesting that functional segregation of respiration and swallowing within the brainstem is reflected in somatotopy within the hypoglossal nucleus. Also, subtle changes in the neural control of tongue movement may signal the transition between respiration and swallowing. The final section of this review will focus on the cortical integration of tongue movement with complex orofacial movements. This section will conclude with a discussion of the functional and clinical significance of cortical control with respect to recent advances in our understanding of the peripheral and brainstem physiology of tongue movement.
Molecular Regulation of Tongue and Craniofacial Muscle Differentiation
Authors: Shuler C.F. , Dalrymple K.R.
Published: January 2009

The molecular regulation of muscle development is tightly controlled at three distinct stages of the process: determination, differentiation, and maturation. Developmentally, specific populations of myoblasts exhibit distinct molecular phenotypes that begin to limit the ultimate characteristics of the muscle fibers. The expression of the myogenic regulatory factor family of the transcription process plays a key role in muscle development and, ultimately, in the subset of contractile genes expressed in a specific muscle. Craniofacial muscles have distinct functional requirements and associated molecular phenotypes that distinguish them from other skeletal muscles. The general principles of muscle molecular differentiation with specific reference to craniofacial muscles, such as the tongue, are discussed in this review.
Conversion of Normal To Malignant Phenotype: Telomere Shortening, Telomerase Activation, and Genomic Instability During Immortalization of Human Oral Keratinocytes
Authors: Kang M.K. , Park M.-H.
Published: January 2009

Normal somatic cells terminate their replicative life span through a pathway leading to cellular senescence, which is triggered by activation of p53 and/or pRb in response to critically shortened telomere DNA. Potentially neoplastic cells must first overcome the senescence checkpoint mechanisms and subsequently activate telomerase to propagate indefinitely. Although telomerase activation is closely associated with cellular immortality, telomerase alone is not sufficient to warrant tumorigenicity. Environmental factors, including chemical carcinogens and viral infection, often contribute to aberrant changes leading to tumorigenic conversion of normal cells. Of particular importance in oral cancer development are tobacco-related chemical carcinogens and human papillomavirus (HPV) infection. To describe the molecular mechanisms by which these environmental factors facilitate the genesis of oral cancer, we first established an in vitro multistep oral carcinogenesis model by sequential exposure of normal human oral keratinocytes (NHOK) to "high risk" HPV and chemical carcinogens. Upon introduction of the HPV genome, the cells bypassed the senescence checkpoint and entered into an extended, but not immortal, life span during which telomere DNA continued to shorten. In a few immortal clones surviving beyond the crisis, we found a marked elevation of telomerase activity and stabilization of telomere length. Furthermore, the E6 and E7 oncoproteins of "high risk" HPV disrupted the cell cycle control and DNA repair in immortalized HOK, and enhanced mutation frequency resulting from genomic instability. However, HPV infection alone failed to give rise to a tumorigenic cell population, which required further exposure to chemical carcinogens in addition to HPV infection. Analysis of the data presented suggests that oral carcinogenesis is a series of discrete genetic alterations that result from a continued genotoxic challenge by environmental risk factors. Our in vitro model may be useful for investigators with interest in furthering our understanding of oral carcinogenesis.
Craniofacial Tissue Engineering
Authors: Alsberg E. , Hill E.E. , Mooney D.J.
Published: January 2009

There is substantial need for the replacement of tissues in the craniofacial complex due to congenital defects, disease, and injury. The field of tissue engineering, through the application of engineering and biological principles, has the potential to create functional replacements for damaged or pathologic tissues. Three main approaches to tissue engineering have been pursued: conduction, induction by bioactive factors, and cell transplantation. These approaches will be reviewed as they have been applied to key tissues in the craniofacial region. While many obstacles must still be overcome prior to the successful clinical restoration of tissues such as skeletal muscle and the salivary glands, significant progress has been achieved in the development of several tissue equivalents, including skin, bone, and cartilage. The combined technologies of gene therapy and drug delivery with cell transplantation will continue to increase treatment options for craniofacial cosmetic and functional restoration.
Molecular Strategies for Fimbrial Expression and Assembly
Authors: Hui Wu  , Fives-Taylor Paula M.
Published: January 2009

Fimbriae or pili are long, filamentous, multimeric macromolecules found on the bacterial cell surface. Bacteria express a diverse array of fimbriae or pili that are involved in bacterial adherence and invasion. Fimbriae can be categorized based on their modes of expression and assembly. Type I fimbriae and P pili are distributed peritrichously and translocated to the cell surface by a chaperone/usher pathway. Type 4 pili are located at the pole of the cell and assembled via the type II secretion system. Curli fimbriae are coiled surface structures assembled by an extracellular nucleation/precipitation pathway. Fimbriae of oral Gram-negative and Gram-positive bacteria have not been well-studied as compared with the fimbriae of enteric pathogens. Oral pathogens, such as Eikenella corrodens, Actinobacillus actinomycetemcomitans, and Porphyromonas gingivalis, possess fimbriae that have been implicated in bacterial adhesion and invasion. These fimbriae are potential virulence factors in oral infectious processes. A. actinomycetemcomitans and E. corrodens have Type 4-like fimbriae, whereas P. gingivalis displays a unique type of fimbriae. To date, fimbriae of the oral primary colonizers, Actinomyces naeslundii and Streptococcus parasanguis, represent the only fimbriae characterized for any Gram-positive bacteria. The putative major fimbrial subunits, FimA and FimP of A. naeslundii and Fapl of S. parasanguis, contain a signal sequence and cell-wall-sorting signal. The presence of extensive dipeptide repeats in Fapl makes it unique among fimbrial molecules. Based on experimental data, a nucleation/precipitation pathway is proposed for fimbrial biogenesis of both S. parasanguis and A. naeslundii, although we cannot rule out an alternative covalent linkage model. The model systems described in this review served as a framework for hypotheses for how the known molecular factors of fimbriae on oral bacteria may be expressed and assembled.
Involvement of T-Lymphocytes in Periodontal Disease and in Direct and Indirect Induction of Bone Resorption
Authors: Taubman M.A. , Kawai T.
Published: January 2009

Periodontal disease is a peripheral infection involving species of Gram-negative organisms. T-lymphocytes can be found in the dense inflammatory infiltrate in this disease. CD4+ and CD8+ T-cells are present in periodontal lesions, as are memory/activated T-lymphocytes. In addition, Th1- and Th2-type T-lymphocytes and their associated cytokines with a subtle polarization to Th 1 may be present. Th1-type T-cells up-regulate the production of pro-inflammatory cytokines IL-1 and TNF-α, which can induce bone resorption indirectly by promoting differentiation of osteoclast precursors and subsequently by activating osteoclasts. Such osteoclast differentiation is dependent on stimulation of osteoprotegerin ligand (OPG-L) production by osteoblastic cells. By contrast, activated T-cells, by virtue of direct production and expression of OPG-L, can directly promote osteoclast differentiation. OPG-L appears to be predominantly expressed on Th1-type cells. The direct and indirect T-cell involvement in periodontal bone resorption appears to be dependent on the degree of Th 1-type T-cell recruitment into inflamed gingival tissues. This T-cell recruitment is regulated by adhesion molecules and chemokines/chemokine receptors. The adhesion molecules involved include a4 and a6 integrins, LFA-1, and ICAM-1. The Th1-type T-cells preferentially express CCR5 and CXCR3, which are found prominently in diseased gingivae. By contrast, little CCR4, expressed by Th2-type T-cells, can be detected. Also, the chemokine ligands RANTES, MIP1-α (both CCR5), and IP-10 (CXCR3 ligand) were elevated in inflamed periodontal tissues. The T-cell features in diseased periodontal tissues can be compared with those in rheumatoid arthritis, wherein bone resorption often attributed to Th1-type T-cell involvement has also been demonstrated.