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The colon mucosa is lined with crypts of circa 300 cells, forming a continuous barrier whose roles include absorption of water, recovery of metabolic energy sources (notably short chain fatty acids), secretion of a protective mucus barrier, and physiological signalling. There is high turnover and replenishment of cells in the mucosa, disruption of this may lead to bowel pathologies including cancer and inflammatory bowel disease. Keratins have been implicated in the processes of cell death, epithelial integrity, response to inflammation and as a result are often described as guardians of the colonic epithelium. Keratin proteins carry extensive post-translational modifications, the cofactors for kinases, acetyl transferases and other modification-regulating enzymes are themselves products of metabolism. A cluster of studies has begun to reveal a bidirectional relationship between keratin form and function and metabolism. In this paper we hypothesise a mechanistic interaction between keratins and metabolism is governed through regulation of post-translational modifications and may contribute significantly to the normal functioning of the colon, placing keratins at the centre of a nutrition-metabolism-health triangle., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Mitochondria fulfill essential roles in ATP production, metabolic regulation, calcium signaling, generation of reactive oxygen species (ROS), and additional determinants of cellular health. Recent studies have highlighted a role for mitochondria during cell differentiation, including in skin epidermis. The observation of oxidative stress in keratinocytes from Krt16 null mouse skin, a model for pachyonychia congenita (PC)-associated palmoplantar keratoderma, prompted us to examine the role of Keratin (K) 16 protein and its partner K6 in regulating the structure and function of mitochondria. Electron microscopy revealed major anomalies in mitochondrial ultrastructure in late stage, E18.5, Krt6a/Krt6b null embryonic mouse skin. Follow-up studies utilizing biochemical, metabolic, and live imaging readouts showed that, relative to controls, skin keratinocytes null for Krt6a/Krt6b or Krt16 exhibit elevated ROS, reduced mitochondrial respiration, intracellular distribution differences, and altered movement of mitochondria within the cell. These findings highlight a novel role for K6 and K16 in regulating mitochondrial morphology, dynamics, and function and shed new light on the causes of oxidative stress observed in PC and related keratin-based skin disorders.

Background: Nowadays, nail care products are extremely important both in medical and cosmetic fields. Actually, there are only a very few "in vivo" methods to evaluate the safety and the efficacy of nail products., Methods: The new apparatus, based on a recently patented technology, is developed for the "in vivo" evaluation of nails in terms of thickness, structural firmness, flattening, and bending properties. The device analyzes nails by an "in vivo" non-invasive methodology in a timely way and with high accuracy. The assessment of the resistance to compression measures the cohesion of the nail matrix (nail firmness), while the evaluation of the resistance to transversal deformation detects the elasticity of the nail plate. Furthermore, the apparatus is able to assess the nail thickness and the flexibility of their distal edge., Results: The instrument provides nail thickness and several parameters reflecting mechanical properties of nail plate: Viscoelasticity expressed as viscoelasticity index (VI), structural strength/ firmness expressed as Firmness Index (FI), and viscoelasticity of the distal edge expressed as Bending Index (BI)., Conclusions: The instruments described in this work represent an innovative apparatus for the safety and efficacy evaluation of nail products in several fields: cosmetics, pharmaceuticals, and medical devices., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Natures and amounts of water retained at the surface of stratum corneum (SC) of human skins, affecting skin health and penetration of chemical components, remain unclear., Methods: A keratin film, a main component of human SC surface, was measured by IR micro-spectroscopy combined with a quartz crystal microbalance (QCM) and a relative humidity (RH) control system., Results: Water contents increased with RH up to about 19 wt% and were correlated linearly with the OH + NH band areas in IR spectra of the keratin film. The OH + NH band areas for the triple helix collagen film are about twice as large as those for the keratin film (double helix). The free water component increases with RH by keeping the bound water component minor for the keratin film. About twice of water retention capacity of the collagen film can be due to increasing adsorption of free water, interacting possibly with hydrophobic aliphatic CH surfaces., Conclusion: The present results suggest relatively low water contents less than about 19 wt% of outermost SC layers of human skin composed mostly of keratin exposed to ambient RH conditions. The triple helix collagen can be used as an effective moisturizing agent., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bone morphogenetic protein 6 (BMP6) has unique properties regarding structure and function in supporting bone formation during development and adult life. Despite its known role in various malignant tumors, the prognostic significance of BMP6 expression in oral squamous cell carcinoma (OSCC) remains unknown. The aim of the study was to investigate immunohistochemical expression of BMP6 in OSCC in correlation with clinical and pathological parameters, disease recurrence and survival. In addition, we investigated other parameters in order to identify prognosticators of neck metastases and final outcome. The study included 120 patients with clinically T1-3N0 OSCC who were primarily surgically treated between 2003 and 2008. There were 99 (82.5%) male and 21 (17.5%) female patients. The five-year disease-specific survival for the whole cohort was 79.7%. Tumors smaller than 2 cm in diameter showed higher incidence of strong BMP6 expression. No statistical correlation was observed between other clinico-pathological factors and BMP6 expression. Expression of BMP6 was not associated with disease recurrence and survival. BMP6 may not serve as prognosticator of final outcome or recurrence in clinically node-negative OSCC subjects. In multivariate analysis predictors of poorer survival were positive surgical margin, moderate tumor cell differentiation and pathological involvement of levels IV and/or V., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: This study aims to evaluate the use of the leukocyte- and platelet-rich fibrin (L-PRF) membranes in increasing the width of the keratinized mucosa (KM) around implants., Material and Methods: Eight patients in need for bilateral widening of the KM around implants in the lower jaw were recruited for a spit-mouth randomized controlled trial. At the control site, a free gingival graft (FGG) was used, whereas at the other side (test), L-PRF membranes were applied. The primary outcome was the increase in width of KM around the implants. As secondary outcomes, the postoperative pain and surgical time were assessed. The follow-up period was 6 weeks., Results: A significant increase in the total bucco-lingual width of KM in both groups was observed, with 1.3 mm ± 0.9 extra gain (P < .05) for the FGG sites. Shrinkage of the widened areas in this period was 32.1% at the test site and 23.6% at the control site. All values of the postoperative pain scores at the control site were higher than at the test site. The mean surgery time in the test and control group was 29.1 ± 4.8 and 48.1 ± 7.7 minutes, respectively., Conclusion: Within the limitations of this randomized controlled trial with split mouth design, it can be concluded that L-PRF can increase the width of KM around implants. Furthermore, the use of L-PRF results in a lower surgical time with less postoperative discomfort and pain for the patients in comparison to the FGG., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Mechanical stress is an ubiquitous challenge of human cells with fundamental impact on cell physiology. Previous studies have shown that stretching promotes signalling cascades involved in proliferation and tissue enlargement., Objective: The present study is dedicated to learn more about cellular structures contributing to perception and signal transmission of cell stretch. In particular, we hypothesized that desmosmal contacts and the adjacent keratin filament build an intercellular matrix providing information about the mechanical load., Methods: Epidermal cells with different keratin equipment were seeded on flexible silicon dishes and stretched. As read out parameter the activation of PKB/Akt and p44/42 was monitored by Western blotting. Likewise desomosomal contacts were manipulated by depletion or addition of calcium. Moreover, desmoglein 3 and desmocollin 3 were blocked by either specific antibodies or siRNA., Results: It was found that the omission of calcium from the medium, a necessary cofactor for desmosomal cadherins, inhibited stretch mediated activation of PKB/Akt and p44/42. The relevance of desmosomes in this context was further substantiated by experiments using a desmoglein 3 blocking antibody (AK23) and siRNA against desmocollin 3. Moreover, disruption of the keratin filament by sodium orthovanadate also abrogates PKB/Akt and p44/42 activation in response to stretch. Likewise, KEB-7 keratinocytes harbouring a mutation in the keratin 14 gene and genetically modified keratinocytes devoid of any keratin show an altered signalling after stretch indicating the relevance of the keratin filament in this context., Conclusion: Besides their important role in cell architecture our results identify desmosomes and keratins as mechanosensing structures., (Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Embryonic development of the mouse salivary glands begins with epithelial thickening and continues with sequential changes from the pre-bud to terminal bud stages. After birth, morphogenesis proceeds, and the glands develop into a highly branched epithelial structure that terminates with saliva-producing acinar cells at the adult stage. Acinar cells derived from the epithelium are differentiated into serous, mucous, and seromucous types. During differentiation, cytokeratins, intermediate filaments found in most epithelial cells, play vital roles. Although the localization patterns and developmental roles of cytokeratins in different epithelial organs, including the mammary glands, circumvallate papilla, and sweat glands, have been well studied, their stage-specific localization and morphogenetic roles during salivary gland development have yet to be elucidated. Therefore, the aim of this study was to determine the stage and acinar cell type-specific localization pattern of cytokeratins 4, 5, 7, 8, 13, 14, 18, and 19 in the major salivary glands (submandibular, sublingual, and parotid glands) of the mouse at the E15.5, PN0, PN10, and adult stages. In addition, cell physiology, including cell proliferation, was examined during development via immunostaining for Ki67 to understand the cellular mechanisms that govern acinar cell differentiation during salivary gland morphogenesis. The distinct localization patterns of cytokeratins in conjunction with cell physiology will reveal the roles of epithelial cells in salivary gland formation during the differentiation of serous, mucous or seromucous salivary glands.

Hybrid speciation is rare in vertebrates, and reproductive isolation arising from hybridization is infrequently demonstrated. Here, we present evidence supporting a hybrid-speciation event involving the genetic admixture of the snow-capped ( Lepidothrix nattereri ) and opal-crowned ( Lepidothrix iris ) manakins of the Amazon basin, leading to the formation of the hybrid species, the golden-crowned manakin ( Lepidothrix vilasboasi ). We used a genome-wide SNP dataset together with analysis of admixture, population structure, and coalescent modeling to demonstrate that the golden-crowned manakin is genetically an admixture of these species and does not represent a hybrid zone but instead formed through ancient genetic admixture. We used spectrophotometry to quantify the coloration of the species-specific male crown patches. Crown patches are highly reflective white (snow-capped manakin) or iridescent whitish-blue to pink (opal-crowned manakin) in parental species but are a much less reflective yellow in the hybrid species. The brilliant coloration of the parental species results from nanostructural organization of the keratin matrix feather barbs of the crown. However, using electron microscopy, we demonstrate that the structural organization of this matrix is different in the two parental species and that the hybrid species is intermediate. The intermediate nature of the crown barbs, resulting from past admixture appears to have rendered a duller structural coloration. To compensate for reduced brightness, selection apparently resulted in extensive thickening of the carotenoid-laden barb cortex, producing the yellow crown coloration. The evolution of this unique crown-color signal likely culminated in premating isolation of the hybrid species from both parental species., Competing Interests: The authors declare no conflict of interest.

The coordination of individual cell behaviors is a crucial step in the assembly and morphogenesis of tissues. Xenopus mesendoderm cells migrate collectively along a fibronectin (FN) substrate at gastrulation, but how the adhesive and mechanical forces required for these movements are generated and transmitted is unclear. Traction force microscopy (TFM) was used to establish that traction stresses are limited primarily to leading edge cells in mesendoderm explants, and that these forces are balanced by intercellular stresses in follower rows. This is further reflected in the morphology of these cells, with broad lamellipodial protrusions, mature focal adhesions and a gradient of activated Rac1 evident at the leading edge, while small protrusions, rapid turnover of immature focal adhesions and lack of a Rac1 activity gradient characterize cells in following rows. Depletion of keratin (krt8) with antisense morpholinos results in high traction stresses in follower row cells, misdirected protrusions and the formation of actin stress fibers anchored in streak-like focal adhesions. We propose that maintenance of mechanical integrity in the mesendoderm by keratin intermediate filaments is required to balance stresses within the tissue to regulate collective cell movements., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

SUMMARYThe establishment and continuous cell type-specific adaptation of cytoplasmic intermediate filament (IF) networks are linked to various types of IF motility. Motor protein-driven active transport, linkage to other cellular structures, diffusion of small soluble subunits, and intrinsic network elasticity all contribute to the motile behavior of IFs. These processes are subject to regulation by multiple signaling pathways. IF motility is thereby connected to and involved in many basic cellular processes guarding the maintenance of cell and tissue integrity. Disturbances of IF motility are linked to diseases that are characterized by cytoplasmic aggregates containing IF proteins together with other cellular components., (Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.)

The aim of this overview was to assess the methods, quality, and outcomes of systematic reviews conducted to evaluate the importance of keratinized mucosa (KM) for the maintenance of peri-implant tissue health in humans. An electronic search was conducted without date or language restriction using the MEDLINE/PubMed, Cochrane Library, Web of Science, and Embase databases up to December 2015. The eligibility criteria included systematic reviews with/without meta-analysis and with a focus on the influence of KM on peri-implant health around implants. Two independent authors performed the quality analysis of the reviews with the AMSTAR guidelines and another checklist proposed in 2003. After screening, four systematic reviews were selected. The present study demonstrated the existence of structural and methodological variability among the systematic reviews with/without meta-analysis. None of the systematic reviews that were included in the study obtained the maximum score in the two quality analyses performed. All systematic reviews included reported a positive association between an adequate KM width (≥2mm) and peri-implant health. There is still insufficient data on the long-term survival and success rates of dental implants. Prospective studies evaluating the importance of KM for the long-term maintenance of dental implants are needed., (Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

We present a case of a patient with long-standing hyperpigmented macules and erythematous papules over his chest, abdomen, back and arms, suggestive of Dowling-Degos disease (DDD). In addition, there were hyperkeratotic papules, alternating red and white nail-bed discolouration, and V-shaped nail notching consistent with Darier disease (DD). Histology showed findings consistent with DDD and DD on separate specimens. The lack of acantholysis in areas of filiform hyperpigmented rete ridges ruled out Galli-Galli disease (GGD). DDD results from mutations in the genes encoding keratin 5 (KRT5), protein O-glucosyltransferase 1 (POGLUT1) or protein O-fucosyltransferase 1 (POFUT1), while DD results from mutations in the ATP2A2 gene. Both genes are present on chromosome 12. In this case, the patient presented with features of both DDD and DD, which suggests that either a cooperating mutation or a mutation in an unrelated gene locus may underlie the findings in this patient., (© 2015 British Association of Dermatologists.)

Aim: To fabricate a keratin hydrogel, characterize its functionality as a biomaterial and investigate the effects of keratin on growth and differentiation of odontoblast-like cells., Methodology: Keratins were extracted from sheep wool using a well-established technique. The extracted proteins were purified by dialysis, quantified by gel electrophoresis, mass spectrometry, amino acid analysis and inductively coupled mass spectrometry. The microstructure of the fabricated keratin hydrogels was studied by scanning electron microscopy, flow characteristics by rheometer, hydrolytic stability and cytocompatibility by Live/Dead(®) cell assay. Furthermore, the influence of keratin on odontoblast-like cells (MDPC-23) was assessed to confirm their bioactivity at different dilutions. Cell proliferation was studied using alamarBlue(®) assay and differentiation by alkaline phosphatase enzyme activity, alizarin red staining and calcium quantification, reverse transcription polymerase chain reaction (rt-PCR) and immunocytochemical staining for dentine matrix protein- 1 (DMP-1) expression. anova with Tukey's tests was performed for statistical comparison., Results: The characterized hydrogel was injectable with a highly porous architecture that underwent slow degradation, and its cytocompatibility was statistically equivalent to collagen hydrogel (P > 0.05). Cell proliferation and differentiation were enhanced at the optimal keratin concentration of 0.1 mg mL(-1) . At this concentration, the influence of keratin on cell differentiation was demonstrated by marked elevation in alkaline phosphatase activity (P < 0.05), calcium deposition (P < 0.01), gene expression (P < 0.01) and positive immunostaining for DMP-1., Conclusion: The presence of keratin enhanced odontoblast cell behaviour. Keratin hydrogels may be a potential scaffold for pulp-dentine regen-eration., (© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Epiplakin is a large member (>700 kDa) of the plakin protein family and exclusively expressed in epithelial cell types. Compared to other plakin proteins epiplakin exhibits an unusual structure as it consists entirely of a variable number of consecutive plakin repeat domains (13 in humans, 16 in mice). The only binding partners of epiplakin identified so far are keratins of simple as well as of stratified epithelia. Epiplakin-deficient mice show no obvious spontaneous phenotype. However, ex vivo studies using epiplakin-deficient primary cells indicated protective functions of epiplakin in response to stress. Recent studies using stress models for organs of the gastrointestinal tract revealed that epiplakin-deficient mice develop more pronounced pancreas and liver injuries than their wild-type littermates. In addition, impaired stress-induced keratin network reorganization was observed in the affected organs, and primary epiplakin-deficient hepatocytes showed reduced tolerance for forced keratin overexpression which could be rescued by a chemical chaperone. These findings indicate protective functions of epiplakin in chaperoning disease-induced keratin reorganization. In this review, we describe some of the methods we used to analyze epiplakin's function with the focus on biochemical and ex vivo techniques., (© 2016 Elsevier Inc. All rights reserved.)

Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease (EDED) and dysfunction is widely thought to mechanistically involve ductal hyperkeratinization, plugging and obstruction. This review re-evaluates the role of hyperkeratinization in MGD based on more recent findings from mouse models. In these studies, eyelids from normal young and old mice or mice exposed to desiccating stress were evaluated by immunofluorescent tomography and 3-dimensional reconstruction to evaluate gland volume, expression of hyperkeratinization markers and cell proliferation or stimulated Raman scattering (SRS) microscopy to assess lipid quality. Results indicate that aging mice show dropout of meibomian glands with loss of gland volume and a forward migration of the mucocutaneous junction anterior to the gland orifice; similar age-related changes that are detected in human subjects. Atrophic glands also showed evidence of epithelial plugging of the orifice without the presence of hyperkeratinization. Mice exposed to desiccating stress showed hyperproliferation of the meibomian gland and ductal dilation suggesting a marked increase in lipid synthesis. Lipid quality was also affected in EDED mice with an increase in the protein content of lipid within the duct of the gland. Overall, age-related changes in the mouse show similar structural and functional correlates with that observed in clinical MGD without evidence of hyperkeratinization suggesting that gland atrophy may be a major cause of EDED. The response of the meibomian gland to desiccating stress also suggest that environmental conditions may accelerate or potentiate age-related changes.

Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Mysticetes have evolved a novel filter feeding apparatus-baleen-an epidermal keratinous tissue composed of keratin that grows as a serial arrangement of transverse cornified laminae from the right and left sides of the palate. The structure and function of baleen varies among extant mysticete clades and this variation likely can be viewed as adaptations related to different filter feeding strategies. In one of the first morphometric studies of the full baleen apparatus, we describe the morphology of complete baleen racks in neonate, yearling and adult gray whales (Eschrichtius robustus), and note morphometric variations between age groups as well as within individual racks. Morphometric data and detailed descriptions were collected from the full baleen apparatus of three frozen specimens of E. robustus using previously derived ecologically significant and broad scale measurements of baleen. Additionally, characters of the baleen apparatus were described based on visible patterns of baleen laminae and plates on the dorsal root of the rack. Results indicate that the longest, widest, and thickest plates and laminae are found toward the posterior half of the rack, resulting in the greatest surface area for filtration of prey occurring in this region. Ontogenetic changes were also documented that reveal a progressive increase in the filter surface area of the developing baleen apparatus as baleen laminae and main plates grow in length and width. Also noted was a progressive posterior shift in the position of greatest filtration area. Histological examination of the epithelial base (Zwischensubstanz) and laminae showed basic epidermal layers, as well as gapping between layers and vacuoles., (© 2015 Wiley Periodicals, Inc.)

Keratin are among the most abundant proteins in epithelial cells. Functions of the keratin network in cells are shaped by their dynamical organization. Using a collection of experimentally-driven mathematical models, different hypotheses for the turnover and transport of the keratin material in epithelial cells are tested. The interplay between turnover and transport and their effects on the keratin organization in cells are hence investigated by combining mathematical modeling and experimental data. Amongst the collection of mathematical models considered, a best model strongly supported by experimental data is identified. Fundamental to this approach is the fact that optimal parameter values associated with the best fit for each model are established. The best candidate among the best fits is characterized by the disassembly of the assembled keratin material in the perinuclear region and an active transport of the assembled keratin. Our study shows that an active transport of the assembled keratin is required to explain the experimentally observed keratin organization.

Background: Necessity of keratinized tissues (KTs) for maintaining health around dental implants (DIs) remains as a controversial issue., Purpose: The aim of this study was to investigate the effects of KT width (KTW) on peri-implant tissues by evaluating peri-implant clinical and inflammatory parameters., Materials and Methods: Sixty DIs were included in this 6-month longitudinal study. After classifying DI based on the presence of KTs at the buccal aspect as with adequate/inadequate KTW, DIs were randomly assigned into three study groups. In the first group, while free gingival graft (FGG) was performed, DIs in maintenance (M) group were followed up by standardized maintenance procedures at baseline, first, third, and sixth months as with DI with adequate KTW (Control). Clinical parameters, peri-implant sulcular fluid (PISF) volume, PISF Interleukin 1β concentration, and bone loss were analyzed., Results: Significant improvements in clinical and immunological parameters were noted only for FGG for the whole study period. Statistical differences detected between the treatment groups (FGG vs M) were for gingival index at all time points and for PISF volume at sixth month. For the other parameters evaluated, while lower values were observed for FGG, statistically no differences were noted between the groups., Conclusions: Based on the results of this study, it can be suggested that FGG performed around DIs lacking KT is a reliable method, leading to significant improvements in clinical and inflammatory parameters. Further long-term studies including more DIs are needed to clarify the role of KT on maintenance of DIs., (© 2013 Wiley Periodicals, Inc.)

The significance of keratinized mucosa (KM) around dental implants is still not well explained and has been controversial. The aim of this systematic review was to evaluate the importance of KM around dental implants. The electronic databases Cochrane library, MEDLINE, EMBASE, and Virtual Health Library (VHL) databases were utilized to search original articles from 2006 to March 2013. The inclusion and exclusion criteria used to select the articles were: (1) Human studies published in the English language; (2) Study published in international peer-viewed journals; (3) Studies evaluated the association between KM width and the peri-implant tissue health; (4) Studies that have follow up of greater than 12 months; (5) Publication of studies not older than 10 years. The searches retrieved 285 citations. Seven articles fulfilled all of the inclusion criteria. Out of these, three studies were ranked as presenting high methodological quality, and four were judged to be of moderate quality. This systematic review concludes that the presence of an adequate zone of keratinized tissue may be necessary because it was shown to be related to better peri-implant tissue health. Further randomized controlled trials are necessary to support this statement., (Copyright © 2013 Wiley Periodicals, Inc.)

Epithelial reorganization involves coordinated changes in cell shapes and movements. This restructuring occurs during formation of placodes, ectodermal thickenings that initiate the morphogenesis of epithelial organs including hair, mammary gland, and tooth. Signaling pathways in ectodermal placode formation are well known, but the cellular mechanisms have remained ill defined. We established imaging methodology for live visualization of embryonic skin explants during the first wave of hair placode formation. We found that the vast majority of placodal cells were nonproliferative throughout morphogenesis. We show that cell compaction and centripetal migration are the main cellular mechanisms associated with hair placode morphogenesis and that inhibition of actin remodeling suppresses placode formation. Stimulation of both ectodysplasin/NF-κB and Wnt/β-catenin signaling increased cell motility and the number of cells committed to placodal fate. Thus, cell fate choices and morphogenetic events are controlled by the same molecular pathways, providing the framework for coordination of these two processes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The skin of squamates consists of a keratinized epidermis divided into thick scale and thinner, folded interscale regions underlain by a dermis containing a complex array of fibrous connective tissues. We examined the skin of the lower jaw of watersnakes (Nerodia sipedon) to determine how skin morphology changes when highly stretched during ingestion of large prey. Video records of skin behavior in the lower jaws of watersnakes feeding on fish or anesthetized watersnakes being stretched on an Instron machine showed that most skin extension involves the interscale skin. The largest intermandibular separation recorded during feeding was 7.7× resting distance, but intermandibular separation reached 10× without tissue failure during mechanical testing. Histological and anatomical analyses of lower jaws fixed in resting, moderately or highly stretched conditions showed that stretching had little effect on scale regions of the epidermis. However, stretching flattened folds of interscale regions at both gross and cellular levels and imposed changes in epidermal cell shape. Stretching of the dermis is primarily limited to realignment of collagen and stretching of elastin in the deep dermis. The configuration of dermal elastin suggests a model for passive recovery of epidermal folding following release of tension., (© 2013 Wiley Periodicals, Inc.)

Maintenance of epithelial cell adhesion is crucial for epidermal morphogenesis and homeostasis and relies predominantly on the interaction of keratins with desmosomes. Although the importance of desmosomes to epidermal coherence and keratin organization is well established, the significance of keratins in desmosome organization has not been fully resolved. Here, we report that keratinocytes lacking all keratins show elevated, PKC-α-mediated desmoplakin phosphorylation and subsequent destabilization of desmosomes. We find that PKC-α activity is regulated by Rack1-keratin interaction. Without keratins, desmosomes assemble but are endocytosed at accelerated rates, rendering epithelial sheets highly susceptible to mechanical stress. Re-expression of the keratin pair K5/14, inhibition of PKC-α activity, or blocking of endocytosis reconstituted both desmosome localization at the plasma membrane and epithelial adhesion. Our findings identify a hitherto unknown mechanism by which keratins control intercellular adhesion, with potential implications for tumor invasion and keratinopathies, settings in which diminished cell adhesion facilitates tissue fragility and neoplastic growth.

Despite its vital function in a highly dynamic environment, baleen is typically assumed to be a static material. Its biomechanical and material properties have not previously been explored. Thus I tested sections of baleen from bowhead whales, Balaena mysticetus, and humpback whales, Megaptera novaeangliae, alone or in groups representing miniature 'racks', in a flow tank through which water and buoyant particles circulated with variable flow velocity. Kinematic sequences were recorded through an endoscopic camera or viewing window. One set of experiments investigated particle capture; another series analyzed biomechanical behavior, including fringe spacing, movement and interaction. Baleen fringe porosity directly correlates, in a mostly linear fashion, with velocity of incident water flow. However, undulation and interaction of fringes (especially of bowheads) at higher flow velocities can decrease porosity. Fringe porosity depends on distance from the baleen plate. Porosity also varies, with fringe length, by position along the length of an individual plate. Plate orientation, which varied from 0 to 90 deg relative to water flow, is crucial in fringe spacing and particle capture. At all flow velocities, porosity is lowest with plates aligned parallel to water flow. Turbulence introduced when plates rotate perpendicular to flow (as in cross-flow filtration) increases fringe interaction, so that particles more easily strike fringes yet more readily dislodge. Baleen of bowhead whales, which feed by continuous ram filtration, differs biomechanically from that of humpbacks, which use intermittent lunge filtration. The longer, finer fringes of bowhead baleen readily form a mesh-like mat, especially at higher flow velocities, to trap tiny particles.

The unfolded protein response (UPR) is a signaling pathway from the endoplasmic reticulum (ER) to the nucleus that protects cells from stress caused by misfolded or unfolded proteins. As such, ER stress is an ongoing challenge for all cells, given the central biologic importance of secretion as part of normal physiologic functions. Mild UPR is activated by mild ER stress, which occurs under normal conditions. Abnormal UPR is activated by severe ER stress, which occurs under pathological conditions. Abnormal UPR activation is associated with a number of diseases, including diabetes mellitus and Alzheimer's disease. Within skin tissues, keratinocytes in the epidermis are especially dependent upon a mild UPR for normal differentiation in the course of their differentiation into secretory cells in the uppermost granular layers. Association between abnormal UPR activation and hereditary keratoses, including Darier's disease, keratosis linearis with ichthyosis congenita and keratoderma syndrome, erythrokeratoderma variabilis, and ichthyosis follicularis with atrichia and photophobia syndrome, have been elucidated recently. This review describes the UPR in normal and abnormal keratinization and discusses the regulation of abnormal UPR activation by chemical chaperones as a potential treatment for one of the hereditary keratoses., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Inherited keratinizing disorders are caused by mutations in the genes encoding cornified cell envelope proteins, enzymes and their inhibitors, adhesion molecules, cytoskeletal proteins and others in the epidermis. These molecules are known to regulate differentiation, proliferation and cell adhesions. Intriguingly, some keratinizing disorders show blistering skin lesions, while some inherited blistering disorders show abnormal keratinization. Therefore, hereditary keratinizing and blistering diseases are closely related and show overlapping genetic backgrounds. In this review, we overviewed keratinizing and blistering disorders in terms of overlapping of the two disease groups. Gene mutations in desmosomal components cause striate keratoderma, Naxos disease, epidermolytic palmoplantar keratoderma and plakophilin deficiency, which first show skin fragility and blisters and later hyperkeratosis. Gene mutations in hemidesmosomal components cause various forms of epidermolysis bullosa, some of which show hyperkeratosis on the nails, palms and soles, in addition to blister formation. Diseases with gene mutations in calcium pump proteins are Darier disease and Hailey-Hailey disease, which show clinicopathological overlaps and develop both keratinizing and blistering skin lesions. Finally, gene mutations in epidermal keratins cause epidermolysis bullosa simplex, epidermolytic ichthyosis, superficial epidermolytic ichthyosis, epidermolytic palmoplantar keratoderma and pachyonychia congenita/focal palmoplantar keratoderma, which show thickening of the palms and soles with underlying blister formation. In general, responsible proteins for diseases developing both keratinizing and blistering conditions are adhesion molecules, calcium pump proteins and keratins, but not connexins, cornified cell envelop proteins, enzymes or inhibitors. It is still unknown how particular keratinizing diseases develop blisters and vice versa., (© 2012 John Wiley & Sons A/S.)

The keratin (K)-hemidesmosome (HD) interaction is crucial for cell-matrix adhesion and migration in several epithelia, including the epidermis. Mutations in constituent proteins cause severe blistering skin disorders by disrupting the adhesion complex. Despite extensive studies, the role of keratins in HD assembly and maintenance is only partially understood. Here we address this issue in keratinocytes in which all keratins are depleted by genome engineering. Unexpectedly, such keratinocytes maintain many characteristics of their normal counterparts. However, the absence of the entire keratin cytoskeleton leads to loss of plectin from the hemidesmosomal plaque and scattering of the HD transmembrane core along the basement membrane zone. To investigate the functional consequences, we performed migration and adhesion assays. These revealed that, in the absence of keratins, keratinocytes adhere much faster to extracellular matrix substrates and migrate approximately two times faster compared with wild-type cells. Reexpression of the single keratin pair K5 and K14 fully reversed the above phenotype. Our data uncover a role of keratins, which to our knowledge is previously unreported, in the maintenance of HDs upstream of plectin, with implications for epidermal homeostasis and pathogenesis. They support the view that the downregulation of keratins observed during epithelial-mesenchymal transition supports the migratory and invasive behavior of tumor cells.

The objective of this field study was to compare the udder health status as well as the clinical mastitis rate during the first 100 d of lactation in cows that received long-acting dry cow antibiotic alone (group AB) or in combination with an internal teat sealant (group AB + OS). The study was conducted during a 9-month period and included 136 Holstein cows from 12 dairy farms in Hessia, Germany. Between days 1 and 5 after calving a California mastitis test (CMT) was performed. Milk-samples were collected for bacteriological culture before drying off, between days 6 and 14 and days 35 and 56 of lactation. Additionally the cows were monitored for the occurrence of clinical mastitis events until 100 d post partum. Within the 12 herds cow-pairs were formed on the basis of age, milk yield and SCC. A cow-pair consisted of one cow from group AB and one cow from group AB + OS. For statistical analysis within every cow-pair one quarter that has been dried off with internal teat sealant and dry cow antibiotic (group AB + OS) was compared with one quarter that has been dried off with dry cow antibiotic (group AB) alone. As criterion for the matching process of udder quarters the cytobacteriological udder health status before drying off was used. A total of 544 quarters (136 cows) were used in this analysis. In the first 5 d after calving, group AB had significantly more quarters with a positive CMT reaction than group AB + OS (85 vs. 57; P <0·001), and in the first 100 d of lactation, group AB had more quarters with clinical mastitis than group AB + OS (25 vs. 15; P = 0·03). In the time periods 6-14 and 35-56 d of lactation, there were fewer quarters in group AB + OS populated with Corynebacterium spp. (days 6-14, P = 0·05; days 35-56, P = 0·02) and aesculin-positive streptococci (days 35-56, P = 0·02). The internal teat sealant was a promising tool for the prevention of new intramammary infections (IMI) of dry cows with environmental udder pathogens as expressed during early lactation.

Hair evolution contributed to the biological success of mammals. Hair origin from synapsid scales is speculative and requires extensive modifications of the morphogenetic process transforming lens-shaped dermis of scales into small dermal papillae in hair. Hair evolution from glands is hypothetical but is supported from studies on the signaling control of hair vs. glandular morphogenesis. Based on immunocytochemical and comparative studies, it is hypothesized that the onion-like organization of hair derived from glandular pegs which central part produced lipids and some keratin. In a following stage, involucrin, trichohyalin, and keratins were produced in the central cells of the gland and formed a solid medulla surrounded by keratinocytes of the inner root sheath. The origin of this protohair was possibly related to increased concentration of beta-catenin and other signaling molecules in epithelial cells following the evolution of a dermal papilla. The latter activated the keratogenic genes, already utilized in cells of the claws, in concentric layers of cells of the glandular peg. Lipidogenic genes were depressed. As new genes evolved in the genome of synapsids, new circular layers of keratinocytes containing specialized hard keratins and keratin-associated proteins were formed around medullary cells. The new keratinocytes probably originated the cortex separating medulla from the external cells that became the inner root sheath. The hypothesis indicates that in a following stage, the medulla was obliterated or replaced by cortical cells while the external part of the cortex formed a cuticular surface due to the different growth rate with inner root sheath cells., (© 2012 WILEY PERIODICALS, INC.)

Hair keratin-associated proteins (KRTAPs) are one of the major structural components of the hair shaft. Approximately 100 KRTAP genes have been identified in humans to date, with each of the genes classified into a number of families based on their sequence homology and the nature of the repeat structures. The biophysical features of KRTAPs, however, have remained largely unknown. In this study, we investigated the characteristics of the human KRTAP2 family members at the DNA, RNA, and protein levels. We initially found that these genes had various size polymorphisms that were mainly due to differences in the length of the 3'-noncoding sequences. Reverse transcriptase-PCR experiments further detected the presence of KRTAP2 transcripts in plucked human hairs. Using indirect immunofluorescence with an anti-KRTAP2 antibody, we found that there was a predominant expression of the KRTAP2 proteins in the keratinizing zone of the human hair shaft cortex. In addition, we showed that the KRTAP2 proteins interacted with each other and preferentially bound to hair keratins, but not to epithelial keratins. Finally, we determined that the head domain of the hair keratins was essential for the affinity to KRTAP2 proteins. Our results further enhance the crucial roles of KRTAPs in hair shaft keratinization in humans.

In recent years, there has been a surge in the development of finite-element (FE) models aimed at testing biological hypotheses. For example, recent modelling efforts suggested that the beak in Darwin's finches probably evolved in response to fracture avoidance. However, knowledge of the material properties of the structures involved is crucial for any model. For many biological structures, these data are not available and may be difficult to obtain experimentally given the complex nature of biological structures. Beaks are interesting as they appear to be highly optimized in some cases. In order to understand the biomechanics of this small and complex structure, we have been developing FE models that take into account the bilayered structure of the beak consisting of bone and keratin. Here, we present the results of efforts related to the determination and validation of the elastic modulus of bone and keratin in bird beaks. The elastic moduli of fresh and dried samples were obtained using a novel double-indentation technique and through an inverse analysis. A bending experiment is used for the inverse analysis and the validation of the measurements. The out-of-plane displacements during loading are measured using digital speckle pattern interferometry.

Injury to the epidermis triggers an elaborate homeostatic response resulting in tissue repair and recovery of the vital barrier function. The type II keratins 6a and 6b (K6a and K6b) are among the genes induced early on in wound-proximal keratinocytes and maintained during reepithelialization. Paradoxically, genetic ablation of K6a and K6b results in enhanced keratinocyte migration. In this paper, we show that this trait results from activation of Src kinase and key Src substrates that promote cell migration. Endogenous Src physically associated with keratin proteins in keratinocytes in a K6-dependent fashion. Purified Src bound K6-containing filaments via its SH2 domain in a novel phosphorylation-independent manner, resulting in kinase inhibition. K6 protein was enriched in the detergent-resistant membrane (DRM), a key site of Src inhibition, and DRMs from K6-null keratinocytes were depleted of both keratin and Src. We conclude that K6 negatively regulates Src kinase activity and the migratory potential of skin keratinocytes during wound repair. Our findings may also be important in related contexts such as cancer.

Keratins are intermediate filament family proteins which are predominantly expressed in the epithelial cells. Most of the studies which evaluate the status of keratins in clinical samples of the oral cavity are based on the identification of their presence and localization by immunohistochemistry using monoclonal antibodies. It is very well known that many monoclonal/polyclonal antibodies show cross-reactivity with the other closely related or non-related proteins. This cross-reactivity might be the result of epitope similarity, but it is not always necessary. Therefore studies done with only antibody based techniques can mislead interpretation unless they are validated with additional techniques like mass-spectrometry. In this investigation we have evaluated the status of keratin 18 in cancer of buccal mucosa using 1DE, 2DE and western blotting with monoclonal antibody to keratin 18. The patterns emerging showed aberrant as well as differential expression of K18 in adjacent normal versus tumor tissue samples of buccal mucosa. Mass spectrometry analysis of the immunodetected spots however revealed that it is keratin 13. Thus this study emphasizes the necessity of validation of antibody based findings when dealing with proteins of a large family having similarity/homology in amino acid sequence., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To evaluate the role of keratinized mucosa around dental implants, correlating with other clinical parameters related to the success of dental implants., Design: Cross-section., Setting: Institutional tertiary referral hospital., Patients: A total of 202 dental implants fixed in the cleft area of 109 patients with cleft lip and/or palate were evaluated. Interventions: The evaluated clinical parameters were probing depth and gingival and plaque indexes on the buccal surface (three sites)., Main Outcome Measures: All clinical parameters were correlated with the width of keratinized mucosa around the implants., Results: The largest probing depths were detected when the width of keratinized mucosa was 2 mm or more, with a statistically significant difference between the means of the probing depth and keratinized mucosa width., Conclusion: Even though the present results suggest that peri-implant health can be observed in areas with keratinized mucosa width under 2 mm provided an adequate oral hygiene control is performed, longitudinal randomized studies are necessary to analyze the relationship between the width of keratinized mucosa and the health of peri-implant tissues.

Flight feathers of birds interact with the flow field during flight. They bend and twist under aerodynamic loads. Two parameters are mainly responsible for flexibility in feathers: the elastic modulus (Young's modulus, E) of the material (keratin) and the geometry of the rachises, more precisely the second moment of area (I). Two independent methods were employed to determine Young's modulus of feather rachis keratin. Moreover, the second moment of area and the bending stiffness of feather shafts from fifth primaries of barn owls (Tyto alba) and pigeons (Columba livia) were calculated. These species of birds are of comparable body mass but differ in wing size and flight style. Whether their feather material (keratin) underwent an adaptation in stiffness was previously unknown. This study shows that no significant variation in Young's modulus between the two species exists. However, differences in Young's modulus between proximal and distal feather regions were found in both species. Cross-sections of pigeon rachises were particularly well developed and rich in structural elements, exemplified by dorsal ridges and a well-pronounced transversal septum. In contrast, cross-sections of barn owl rachises were less profiled but had a higher second moment of area. Consequently, the calculated bending stiffness (EI) was higher in barn owls as well. The results show that flexural stiffness is predominantly influenced by the geometry of the feathers rather than by local material properties.

Orthokeratinized odontogenic cysts (OOCs) are relatively uncommon developmental cysts lined with orthokeratinized epithelium consisting of a prominent granular layer and a basal layer of low cuboidal flattened cells that show no tendency for nuclear palisading. These cysts have been considered a distinct entity from odontogenic keratocysts since they exhibit a less aggressive behavior and a very low rate of recurrence. Developmental odontogenic cysts can become infected but serious complications, such as potentially life-threatening cellulitis, are rare. This report describes a rare case of facial cellulitis secondary to an infected OOC located in the mandible of a 27-year-old man. The relevant literature about the clinical-pathological features of OOC is reviewed.

A novel technique to generate three-dimensional Euclidean weavings, composed of close-packed, periodic arrays of one-dimensional fibres, is described. Some of these weavings are shown to dilate by simple shape changes of the constituent fibres (such as fibre straightening). The free volume within a chiral cubic example of a dilatant weaving, the ideal conformation of the G(129) weaving related to the Σ(+) rod packing, expands more than fivefold on filament straightening. This remarkable three-dimensional weaving, therefore, allows an unprecedented variation of packing density without loss of structural rigidity and is an attractive design target for materials. We propose that the G(129) weaving (ideal Σ(+) weaving) is formed by keratin fibres in the outermost layer of mammalian skin, probably templated by a folded membrane.

Trichomonas vaginalis and Tritrichomonas foetus are human and bovine parasites, respectively, that provoke the sexually transmitted disease trichomoniasis. These extracellular parasites adhere to the host epithelial cell surface. Although mucinases and proteases have been described as important proteins for parasite adhesion to epithelial cells, no studies have examined the role of the keratin molecules that cornify the vaginal epithelium. Here, we investigated the interaction of T. vaginalis and T. foetus with human keratin in vitro; additionally, adherence assays were performed in cattle with T. foetus to elucidate whether trichomonads were able to interact with keratin in vivo. We demonstrated that both T. vaginalisand T. foetusinteracted directly with keratin. Additionally, the trichomonads ingested and digested keratin, shedding new light on the Trichomonas infection process.

Dynamic changes in integumentary color occur in cases as diverse as the neurologically controlled iridiphores of cephalopod skin and the humidity-responsive cuticles of longhorn beetles. By contrast, feather colors are generally assumed to be relatively static, changing by small amounts only over periods of months. However, this assumption has rarely been tested even though structural colors of feathers are produced by ordered nanostructures that are analogous to those in the aforementioned dynamic systems. Feathers are neither innervated nor vascularized and therefore any color change must be caused by external stimuli. Thus, we here explore how feathers of iridescent mourning doves Zenaida macroura respond to a simple stimulus: addition and evaporation of water. After three rounds of experimental wetting and subsequent evaporation, iridescent feather color changed hue, became more chromatic and increased in overall reflectance by almost 50%. To understand the mechanistic basis of this change, we used electron microscopy to examine macro- and nanostructures before and after treatment. Transmission electron microscopy and transfer matrix thin-film models revealed that color is produced by thin-film interference from a single (∼ 35 nm layer of keratin around the edge of feather barbules, beneath which lies a layer of air and melanosomes. After treatment, the most striking morphological difference was a twisting of colored barbules that exposed more of their surface area for reflection, explaining the observed increase in brightness. These results suggest that some plumage colors may be more malleable than previously thought, leading to new avenues for research on dynamic plumage color., (Published by Elsevier GmbH.)

This monograph introduces innate immunity as a second force in the ovary in addition to the endocrine system. Innate immunity appears to orchestrate follicular atresia, follicle rupture, and follicle transformation into a corpus luteum (CL) and CL regression through sterile inflammation and tissue repair. The concept is new. It centers on cytokeratin-positive (CK+) cells being recognized as a potential non lymphoid dendritic cell (DC) type. Part I describes morphological aspects of immune privilege starting with hamster ovary implants into the chicken chorioallantoic membrane with a non reactive mesenchyme. Follicular atresia and follicle rupture correspond to mild and moderate tissue damage in ovaries of small rodents and rabbits. Superovulations cause severe tissue damage through intra-ovarian oocyte release with follicle wall remnants in oedema, rupture of vessel walls and thrombosis. The complement system and neuropeptides might play regulatory roles. Part IIa analyzes intact ovaries (cows, human) for the appearance of CK+ cells. In the fetal ovary, sex cords give rise to CK+ cells in primordial follicles. In the adult ovary, CK+ cells are absent in preantral follicles and reappear in mature and regressing follicles. In the CL of early development, steroidogenic CK+ cells build a peripheral zone in the previous granulosa cell layer, and are uniformly distributed in the following stages. A microvascular CK+ cell type is seldom found. Part IIb characterizes the morphology and function of CK+ cells in vitro. Isolated from human preovulatory follicles, the epithelioid CK+ granulosa cell subtype regulates TLR4 and CD14 at 36 h of treatment with oxidized lipoprotein (oxLDL, 150 microg/ml); non-apoptotic cell death and the increase of reactive oxygen species occur. In contrast, the CK-negative (CK) granulosa cell type regulates the lectin-like oxLDL receptor 1 (LOX-1) and survival autophagy under oxLDL stimulation. Isolated from bovine CL, the epitheliold CK+ cell type 1 is disclosed as a microvascular cell type with a single nonmotile cilium. The microvascular CK+ type strongly upregulates intercellular contacts under treatment with interferon-gamma (IFN-gamma). In the CK- cell type 5 of granulosa cell-like appearance, IFN-gamma treatment supports cell proliferation, N-cadherin upregulation, and the dramatic increase in major histocompatibility complex II peptides (MHC II) by 80-fold compared to basal levels. Type 5 could have been converted from the steroidogenic CK+ cell type. We summarize and conclude: CK+ granulosa cells express functionally active TLR4, which sense danger signals, such as oxidative stress in preovulatory follicles, and trigger inflammatory and immunoregulatory pathways. The final outcome regulates follicle rupture and transformation into CL. Luteolysis could start by danger-sensing through the microvascular CK+ type 1 cells and the DC-like type 5 cells, both sensitive to IFN-gamma. The future will witness a novel strategy in the therapy of ovarian disorders such as anovulations, luteal phase insufficiency and autoimmune failures.

Background: Epiplakin (EPPK) belongs to the plakin family of cytolinker proteins and, resembling other members of the plakin family such as BPAG1 (an autoantigen of bullous pemphigoid) and plectin, EPPK has plakin repeat domains (PRDs) that bind to intermediate filaments. Elimination of EPPK by gene targeting in mice resulted in the acceleration of keratinocyte migration during wound healing. EPPK is expressed in proliferating keratinocytes at wound edges and, in view of its putative function in binding to keratin, we postulated that the keratin network in EPPK-null (EPPK(-/-)) mice might be disrupted during wound healing., Objective: To examine this hypothesis and to determine the precise localization of EPPK in relation to keratin filaments, we compared the non-wounded and wounded epidermis of wild-type and EPPK(-/-) mice., Methods: Non-wounded epidermis and wounded epidermis from wild-type and EPPK(-/-) mice were examined by immunofluorescence staining and electron microscopy before and after double immunostaining., Results: EPPK was colocalized with keratin 17 (K17) more extensively than with other keratins examined in wounded epidermis. The expression of K5, K10, K6, and K17 was the same in EPPK(-/-) mice after wounding as in normal mice, but diameters of keratin filaments were reduced in EPPK(-/-) keratinocytes. Electron microscopy after immunostaining revealed that EPPK colocalized with K5, K10 and K6 after wounding in wild-type mice., Conclusion: Our data indicate that EPPK accelerates keratin bundling in proliferating keratinocytes during wound healing and suggest that EPPK might contribute to reinforcement of keratin networks under mechanical stress., (Copyright © 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Basaloid skin tumors, including basal cell carcinoma (BCC) and basaloid follicular hamartoma, are associated with aberrant Hedgehog (Hh) signaling and, in the case of BCC, an expanding set of genetic variants including keratin 5 (encoded by KRT5), an intermediate filament-forming protein. We here show that genetic ablation of keratin 17 (Krt17) protein, which is induced in basaloid skin tumors and co-polymerizes with Krt5 in vivo, delays basaloid follicular hamartoma tumor initiation and growth in mice with constitutive Hh signaling in epidermis. This delay is preceded by a reduced inflammation and a polarization of inflammatory cytokines from a Th1- and Th17-dominated profile to a Th2-dominated profile. Absence of Krt17 also attenuates hyperplasia and inflammation in models of acute dermatitis. Re-expression of Krt17 in Gli2(tg); Krt17(-/-) keratinocytes induces select Th1 chemokines that have established roles in BCC. Our findings establish an immunomodulatory role for Krt17 in Hh driven basaloid skin tumors that could impact additional tumor settings, psoriasis and wound repair.

Using light and scanning electron microscopy, the morphological adaptations of the yak (Bos grunniens) tongue to its foraging environment in the Qinghai-Tibetan Plateau were studied. The tongue of the yak was compared with that of cattle (Bos taurus). Compared with cattle, yak tongues are on average 4 cm shorter (P < 0.001), and yak consume forages using the labia oris, rather than by extending the tongue into the harsh environment. The lingual prominence of yak is greater (P < 0.001) and more developed than in cattle. The conical papillae on the prominence surface of yak are slightly larger (diameter: P = 0.068 and height: P = 0.761) and more numerous (P < 0.001) than in cattle. The lenticular papillae on the prominence surface of yak are larger (diameter: P = 0.002 and height: P = 0.115) and more numerous (P = 0.007) than in cattle. Such characteristics may improve the digestibility of forage by the grinding of food between the tongue and the upper palate. Filiform, conical, lenticular, fungiform, and vallate papillae were observed on the dorsal surface of the tongues studied; no foliate papillae were observed. The papillae were covered by keratinized epithelium, which was thicker (P < 0.001) in the yak than in cattle. It is suggested that the development of characteristic filiform papillae, and more numerous lingual gland ducts and mucus-secreting pores in the lenticular, fungiform and vallate papillae, fungiform papillae, probably having mechanical functions, are all morphological adaptations by yak to diets with greater fiber and DM content as provided by the plants within the Qinghai-Tibetan Plateau environment. On average, yak has 26 vallate papillae and cattle have 28. In the vallate papillae of the yak, the taste buds are arranged in a monolayer within the epithelium, whereas they are multilayered (2 to 4) in those papillae in cattle. The number of taste buds in each vallate papillae was less (P < 0.001) in the yak than in cattle. Therefore, the gustatory function of the yak was weaker than in cattle. Yaks graze throughout the year on diverse natural grasslands and have evolved morphological characteristics enabling them to consume a wide variety of plant species, thereby better adapting them to the typically harsh characteristics of their pastures.

Background: The question of the importance of keratinized mucosa around dental implants for the prevention of peri-implant disease could not be answered in the relevant literature so far., Objective: To investigate the influence of peri-implant keratinized mucosa on long-term peri-implant soft-tissue health and stability over a period of 5 years., Material and Methods: A total of 386 mandibular dental implants were placed in 73 completely edentulous patients, and subsequently restored with fixed full-arch prostheses. At prosthesis delivery (baseline) and after 3, 6, 12, 18, 24, 36, 48 and 60 months, modified plaque index (mPlI), modified sulcus bleeding index (mBI), distance between implant shoulder and mucosal margin (DIM) and width of peri-implant keratinized mucosa (KM) were recorded. Statistical analysis included multivariate logistic regression, multivariate ordinal logistic regression, generalized estimating equations and Bonferroni's correction., Results: Fifty-eight patients with 307 implants completed the 5-year study. Statistically significantly higher plaque accumulation on lingual sites (mean mPlI 0.67, SD 0.85), bleeding tendencies on lingual sites (mean mBI 0.22, SD 0.53) and larger soft-tissue recession on buccal sites (mean DIM -0.69 mm, SD 1.11 mm) were found when the width of KM was <2 mm, compared to sites with>or=2 mm of KM (mean mPlI 0.40, SD 0.68, P=0.001; mean mBI 0.13, SD 0.41, P<0.01; mean DIM -0.08 mm, SD 0.86 mm, P<0.001). The width of keratinized mucosa had no effect on bleeding tendency or plaque accumulation on buccal sites (P>0.05)., Conclusion: In patients exercising good oral hygiene and receiving regular implant maintenance therapy, implants with a reduced width of <2 mm of peri-implant keratinized mucosa were more prone to lingual plaque accumulation and bleeding as well as buccal soft-tissue recession over a period of 5 years.

Simple epithelial keratins (SEKs) are found primarily in single-layered simple epithelia and include keratin 7 (K7), K8, K18-K20, and K23. Genetically engineered mice that lack SEKs or overexpress mutant SEKs have helped illuminate several keratin functions and served as important disease models. Insight into the contribution of SEKs to human disease has indicated that K8 and K18 are the major constituents of Mallory-Denk bodies, hepatic inclusions associated with several liver diseases, and are essential for inclusion formation. Furthermore, mutations in the genes encoding K8, K18, and K19 predispose individuals to a variety of liver diseases. Hence, as we discuss here, the SEK cytoskeleton is involved in the orchestration of several important cellular functions and contributes to the pathogenesis of human liver disease.

The structure, chemistry and physical properties of the cell membrane complex (CMC) of keratin fibers are reviewed, highlighting differences in the three types of CMC. Starting with Rogers' initial description of the CMC in animal hairs, several important developments have occurred that will be described, adding new details to this important structure in mammalian hair fibers. These developments show that essentially all of the covalently bound fatty acids of the beta layers are in the cuticle and exist as monolayers. The beta layers of the cortex are bilayers that are not covalently bonded but are attached by ionic and polar linkages on one side to the cortical cell membranes and on the other side to the delta layer. The delta layer between cortical cells consists of five sublayers; its proteins are clearly different from the delta layer that exists between cuticle cells. The cell membranes of cuticle cells are also markedly different from the cell membranes of cortical cells. Models with supporting evidence are presented for the three different types of cell membrane complex: cuticle-cuticle CMC, cuticle-cortex CMC, and cortex-cortex CMC.