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Concept: Keratin

188

Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either self-implanted by patients or accidentally adhering to lesions, and conclude that patients with this disease have delusions of infestation. We present histological observations and electron microscopic imaging from representative Morgellons disease samples revealing that dermal filaments in these cases are keratin and collagen in composition and result from proliferation and activation of keratinocytes and fibroblasts in the epidermis. Spirochetes were detected in the dermatological specimens from our study patients, providing evidence that Morgellons disease is associated with an infectious process.

Concepts: Medicine, Infectious disease, Medical terms, Collagen, Hospital, Skin, Epidermis, Keratin

168

Studies on bimatoprost were performed with two objectives: (i) to determine whether bimatoprost possesses hair growth-stimulating properties beyond eyelash hypertrichosis and (ii) to investigate the biodisposition of bimatoprost in skin for the first time. Bimatoprost, at the dose used clinically for eyelash growth (0.03%) and given once daily for 14 days, increased pelage hair growth in C57/black 6 mice. This occurred as a much earlier onset of new hair growth in shaved mice and the time taken to achieve complete hair regrowth, according to photographic documentation and visual assessment. Bimatoprost biodisposition in the skin was determined at three concentrations: 0.01%, 0.03% and 0.06%. Dose-dependent C(max) values were obtained (3.41, 6.74, 12.3 μg/g tissue), and cutaneous bimatoprost was well maintained for 24 h following a single dose. Bimatoprost was recovered from the skin only as the intact molecule, with no detectable levels of metabolites. Thus, bimatoprost produces hypertrichosis as the intact molecule.

Concepts: Skin, Tissue, According to Jim, Mouse, Hair follicle, Keratin, Facial hair, Hair removal

167

The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.

Concepts: Colloid, Skin, Topical, Dermis, Epidermis, Keratin, Stratum corneum, Topical steroid

162

Case study A boy aged 6 years was referred to our clinic for evaluation of the presence of fair, thin hair on both of his elbows. This condition had first been observed when he was 2 years of age and the hair had subsequently increased in length and thickness (Figure 1). He had a history of asthma and was being treated by a paediatrician. His family medical record was otherwise unremarkable. This unusual hairiness was symmetrically distributed on the extensor surfaces of both proximal forearms and distal arms. The underlying skin showed no abnormalities. No hypertrichosis was found elsewhere and examination of teeth, skeleton and fingernails was also normal. No other morphological changes were noted. In addition, his height was appropriate for his age. No developmental, mental or physical impairment was observed. The blood cell count and general biochemistry, as well as thyroid and sexual hormonal profiles were all normal. Radiological examination, which was performed on the parents' request, was normal. The boy was diagnosed with hypertrichosis cubiti (HC), and shaving of the areas was recommended.

Concepts: Scientific method, Protein, Height, Hair, Hair follicle, Keratin, Facial hair, Long hair

59

The holotype (MHM-K2) of the Eocene cheloniine Tasbacka danica is arguably one of the best preserved juvenile fossil sea turtles on record. Notwithstanding compactional flattening, the specimen is virtually intact, comprising a fully articulated skeleton exposed in dorsal view. MHM-K2 also preserves, with great fidelity, soft tissue traces visible as a sharply delineated carbon film around the bones and marginal scutes along the edge of the carapace. Here we show that the extraordinary preservation of the type of T. danica goes beyond gross morphology to include ultrastructural details and labile molecular components of the once-living animal. Haemoglobin-derived compounds, eumelanic pigments and proteinaceous materials retaining the immunological characteristics of sauropsid-specific β-keratin and tropomyosin were detected in tissues containing remnant melanosomes and decayed keratin plates. The preserved organics represent condensed remains of the cornified epidermis and, likely also, deeper anatomical features, and provide direct chemical evidence that adaptive melanism - a biological means used by extant sea turtle hatchlings to elevate metabolic and growth rates - had evolved 54 million years ago.

Concepts: Evolution, Tissues, Turtle, Reptile, Anatomy, Keratin, Sea turtle, Sea turtles

36

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2(-/-) mice compared with irhom2(+/+)mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this ‘stress’ keratin is regulated.

Concepts: DNA, Protein, Gene expression, Mutation, Wound healing, Skin, Epidermis, Keratin

30

Solvents are commonly used in pharmaceutical and cosmetic formulations and sanitary products and cleansers. The uptake of solvent into the skin may change the molecular organization of skin lipids and proteins, which may in turn alter the protective skin barrier function. We herein examine the molecular effects of 10 different solvents on the outermost layer of skin, the stratum corneum (SC), using polarization transfer solid-state NMR on natural abundance (13)C in intact SC. With this approach it is possible to characterize the molecular dynamics of solvent molecules when present inside intact SC and to simultaneously monitor the effects caused by the added solvent on SC lipids and protein components. All solvents investigated cause an increased fluidity of SC lipids, with the most prominent effects shown for the apolar hydrocarbon solvents and 2-propanol. However, no solvent other than water shows the ability to fluidize amino acids in the keratin filaments. The solvent molecules themselves show reduced molecular mobility when incorporated in the SC matrix. Changes in the molecular properties of the SC, and in particular alternation in the balance between solid and fluid SC components, may have significant influences on the macroscopic SC barrier properties as well as mechanical properties of the skin. Deepened understanding of molecular effects of foreign compounds in SC fluidity can therefore have strong impact on the development of skin products in pharmaceutical, cosmetic, and sanitary applications.

Concepts: Protein, Oxygen, Amino acid, Ethanol, Chemistry, Atom, Skin, Keratin

29

BACKGROUND: Recent advances in sequencing technologies have enabled metagenomic analyses of many human body sites. Several studies have catalogued the composition of bacterial communities of the surface of human skin, mostly under static conditions in healthy volunteers. Skin injury will disturb the cutaneous homeostasis of the host tissue and its commensal microbiota, but the dynamics of this process have not been studied before. Here we analyzed the microbiota of the surface layer and the deeper layers of the stratum corneum of normal skin, and we investigated the dynamics of recolonization of skin microbiota following skin barrier disruption by tape stripping as a model of superficial injury. RESULTS: We observed gender differences in microbiota composition and showed that bacteria are not uniformly distributed in the stratum corneum. Phylogenetic distance analysis was employed to follow microbiota development during recolonization of injured skin. Surprisingly, the developing neo-microbiome at day 14 was more similar to that of the deeper stratum corneum layers than to the initial surface microbiome. In addition, we also observed variation in the host response towards superficial injury as assessed by the induction of antimicrobial protein expression in epidermal keratinocytes. CONCLUSIONS: We suggest that the microbiome of the deeper layers, rather than that of the superficial skin layer may be regarded as the host indigenous microbiome. Characterization of the skin microbiome under dynamic conditions, and the ensuing response of the microbial community and host tissue will shed further light on the complex interaction between resident bacteria and epidermis.

Concepts: Archaea, Bacteria, Microbiology, Skin, Epidermis, Keratin, Keratinocyte, Stratum corneum

28

Turtle shells are a form of armor that provides varying degrees of protection against predation. Although this function of the shell as armor is widely appreciated, the mechanical limits of protection and the modes of failure when subjected to breaking stresses have not been well explored. We studied the mechanical properties of whole shells and of isolated bony tissues and sutures in four species of turtles (Trachemys scripta, Malaclemys terrapin, Chrysemys picta, and Terrapene carolina) using a combination of structural and mechanical tests. Structural properties were evaluated by subjecting whole shells to compressive and point loads in order to quantify maximum load, work to failure, and relative shell deformations. The mechanical properties of bone and sutures from the plastral region of the shell were evaluated using three-point bending experiments. Analysis of whole shell structural properties suggests that small shells undergo relatively greater deformations before failure than do large shells and similar amounts of energy are required to induce failure under both point and compressive loads. Location of failures occurred far more often at sulci than at sutures (representing the margins of the epidermal scutes and the underlying bones, respectively), suggesting that the small grooves in the bone created by the sulci introduce zones of weakness in the shell. Values for bending strength, ultimate bending strain, Young’s modulus, and energy absorption, calculated from the three-point bending data, indicate that sutures are relatively weaker than the surrounding bone, but are able to absorb similar amounts of energy due to higher ultimate strain values. J. Exp. Zool. 9999A:1-13, 2012. © 2012 Wiley Periodicals, Inc.

Concepts: Turtle, Biomechanics, Failure, Turtles, Keratin, Diamondback terrapin, Reptiles of the United States, Emydidae

27

The hairs of the skin not only function to prevent heat loss but also have important sensory functions. Recent work has now established that each hair of the skin is innervated by one or more of three types of mechanoreceptor ending. Each of these three mechanoreceptor types possesses distinct molecular features and detects distinctive information about skin touch, which is relayed to specific brain locations in a somatotopic fashion.

Concepts: Heat, Sensory system, Skin, Hair, Hair follicle, Keratin, Sensory receptor, Long hair