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Many restoring formulations for damaged hair keratin have been developed. Some patents claim that the hair repair occurs through the reconstruction of disulfide bridges of keratin, through α,β-unsaturated Michael acceptors, such as shikimic acid and bis-aminopropyl diglycol dimaleate. To gain more insights into the possible repairing mechanism, this study is aimed at assessing, by IR and Raman spectroscopies coupled to scanning electron microscopy (SEM), the structural changes induced in keratin from bleached hair by the treatment with commercial reconstructive agents as well as shikimic acid and dimethyl maleate, chosen as model compounds. Vibrational spectroscopy revealed that shikimic acid- and maleate-based restoring agents interacted with hair fibers modifying both their cortex and cuticle regions. None of the investigated treatments induced an increase in the SS disulfide bridges content of the hair cortex, although it cannot be excluded that this phenomenon could have occurred in the cuticle. SS rearrangements were found to occur. None of our results can be interpreted as direct evidence of the sulfa-Michael reaction/cross-linking. From a morphological point of view, beneficial effects of the restoring agents were observed by SEM analyses, in terms of a more regular hair surface and more imbricated scales., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study evaluated a quantitative method to predict the success of nuclear DNA (nuDNA) typing for head hair roots, using the minor-groove DNA binding dye, 4', 6-diamidino-2-phenylindole (DAPI). The procedure was successful in staining nuclear material in hair roots, regardless of soft tissue presence or growth phase. We found that the dye can even reveal an abundance of visible nuclei in hairs that were previously assumed to be unsuitable for nuDNA analysis (e.g., telogen hairs). The value of DAPI staining is particularly evident when considering the STR typing results for telogen hairs. Here, telogen hairs with greater than 100 visible nuclei frequently produced full or high-partial STR profiles, while telogen hairs with fewer than 100 visible nuclei rarely resulted in >20 % STR allele recovery. In addition, our findings indicated no interference by DAPI in the forensic examination of hair evidence, including preparation of hairs on microscopic slides, microscopic examination, DNA extraction, quantitative PCR, and short tandem repeat (STR) typing. Furthermore, the method remained steadfast for hairs washed by sonication as well as hairs retrieved from Permount™ mounting medium. When validated, this simple, quick, and quantitative screening method can be used in casework to select a hair for nuDNA analysis, especially for hairs that were previously sent directly for mitochondrial (mt) DNA analysis based on the lack of adhering soft tissue, regardless of growth phase. Conversely, nuDNA degradation may exist in hairs which exhibit microscopic characteristics typically associated with a potential to generate successful nuclear DNA profile including stretched roots with attached root sheath. DAPI staining of hairs gives forensic examiners the ability to have more information, other than growth phase, when selecting a hair or hairs for possible nuDNA analysis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Direct exploration to differences between normal hair (NH) and alopecic hair (AH) at different degeneration stages is still lacking. To reveal compositional and structural variation of AH with reference to NH internally and externally, infrared spectroscopic imaging combined with scanning electron microscopy was applied to investigate integral changes of hair chemical profiles and surface texture structures, and infrared macro-fingerprinting analysis revealed detailed chemical compositions of NH and AH. Results showed that AH had excessive irregular laminated structures compared to NH, leading to a lower weight bearing capacity. Spatial distributions of lipids, phosphates, lipoproteins and phospholipids in hair transverse sections showed that their infrared absorptions were intensified and gradually centralized to medulla with average variable-areas increasing upto 2.3 folds (lipoproteins area changed from 13% in NH to 30% in AH)as the alopecia progressed. Extracted pixel spectra from the chemical images showed different fingerprint characteristics in 1075-1120 cm -1 . Specifically, compared to NH, AH showed red shift of phosphate peaks, indicating the occurrence of phosphates transformation. In this study, in-situ visible and infrared chemical imaging directly revealed more irregular laminated scalps with decreasing weight bearing capacity and increasing distributive areas expanding to medulla of key components (phosphates, phospholipids, etc.) that were relevant to alopecia development from NH to AH, and offered a fast, eco-friendly and effective method for hair research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Calcium signaling plays a central role in bone development and homeostasis. Store operated calcium entry (SOCE) is an important calcium influx pathway mediated by calcium release activated calcium (CRAC) channels in the plasma membrane. Stromal interaction molecule 1 (STIM1) is an endoplasmic reticulum calcium sensing protein important for SOCE. We generated a mouse model expressing the STIM1 R304W mutation, causing Stormorken syndrome in humans. Stim1 R304W/R304W mice showed perinatal lethality, and the only three animals that survived into adulthood presented with reduced growth, low body weight, and thoracic kyphosis. Radiographs revealed a reduced number of ribs in the Stim1 R304W/R304W mice. Microcomputed tomography data revealed decreased cortical bone thickness and increased trabecular bone volume fraction in Stim1 R304W/R304W mice, which had thinner and more compact bone compared to wild type mice. The Stim1 R304W/+ mice showed an intermediate phenotype. Histological analyses showed that the Stim1 R304W/R304W mice had abnormal bone architecture, with markedly increased number of trabeculae and reduced bone marrow cavity. Homozygous mice showed STIM1 positive osteocytes and osteoblasts. These findings highlight the critical role of the gain-of-function (GoF) STIM1 R304W protein in skeletal development and homeostasis in mice. Furthermore, the novel feature of bilateral subgingival hair growth on the lower incisors in the Stim1 R304W/R304W mice and 25 % of the heterozygous mice indicate that the GoF STIM1 R304W protein also induces an abnormal epithelial cell fate., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The understanding of the mechanical behavior of hair under various conditions broadens our knowledge in biological materials science and contributes to the cosmetic industry. The hierarchical organization of hair is studied from the intermediate filament to the structural levels. The effects of strain rate, relative humidity, and temperature are evaluated. Hair exhibits a high tensile strength, 150-270MPa, which is significantly dependent on strain rate and humidity. The strain-rate sensitivity, approximately 0.06-0.1, is comparable to that of other keratinous materials and common synthetic polymers. The structures of the internal cortex and surface cuticle are affected by the large tensile extension. One distinguishing feature, the unwinding of the α-helix and the possible transformation to β-sheet structure of keratin under tension, which affects the ductility of hair, is analytically evaluated and incorporated into a constitutive equation. A good agreement with the experimental results is obtained. This model elucidates the tensile response of the α-keratin fibers. The contributions of elastic and plastic strains on reloading are evaluated and correlated to structural changes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A computational molecular model of a truncated keratin protofibril (8 chains of hair keratin, PDB provided in Supplementary material) was used, to run a series of steered molecular dynamics simulations obtaining strain-stress curves. These results were compared with experimental mechanical data on hair fibers. Our data demonstrate that the molecular dynamics simulations can model hair mechanical properties. Simulations done in vacuum showed a better agreement with experimental Young's Modulus (YM) values. The role of hydrogen bonds and the secondary structure of keratin on the mechanical properties was evaluated in detail. The incubation with a fragment of one surfactant protein, the SPD-2 peptide (QAAFSQ), showed the improvement of YM of the hair keratin either by simulations and experimental data. For the first, our research provides mechanistic insights on mechanical microscopic properties of keratin protofibrils through molecular dynamics simulations., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Keratin micro-tubes were obtained by heating medullated keratin fibres to temperatures above 230°C under nitrogen atmosphere, when, as documented by microscopy, the cortex (the core of the fibre) melts from the medulla outwards, followed by pyrolysis of the material through the remaining solid cuticle (shell) layer. The resulted hollow tubes from fibres void of cortical material keep the external cuticle structure, as shown by AFM investigation, and the moisture sorption properties of the initial keratin fibre. Despite similar amino-acid compositions of cuticle and cortex the two morphological components differ significantly in their thermal behaviour, which appears to be a "cortex-cuticle thermal stability paradox"., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Here we report the first ever studies on nanomechanical properties e.g., nanohardness and Young׳s modulus for human hair of Indian origin. Three types of hair samples e.g., virgin hair samples (VH), bleached hair samples (BH) and Fe-tannin complex colour treated hair samples (FT) with the treatment by a proprietary hair care product are used in the present work. The proprietary hair care product involves a Fe-salt based formulation. The hair samples are characterized by optical microscopy, atomic force microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy (EDAX) genesis line map, EDAX spot mapping, nanoindentation, tensile fracture, and X-ray diffraction techniques. The nanoindentation studies are conducted on the cross-sections of the VH, BH and FT hair samples. The results prove that the nanomechanical properties e.g., nanohardness and Young׳s modulus are sensitive to measurement location e.g., cortex or medulla and presence or absence of the chemical treatment. Additional results obtained from the tensile fracture experiments establish that the trends reflected from the evaluations of the nanomechanical properties are general enough to hold good. Based on these observations a schematic model is developed. The model explains the present results in a qualitative yet satisfactory manner., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Many animals use their mouthparts or tongue to feed themselves rapidly and efficiently. Honeybees have evolved specialized tongues to collect nectar from flowers. Nectar-intake movements consist of rapid protraction and retraction of glossa from a tube formed by the maxillae and labial palps. We establish a physical model to reveal the driving mechanism of hair erection. Results indicate that the glossa of honeybees is similar to a compression spring. Experimental results show that hair erection is generated by the tension of hyaline rod and the elasticity of segmental sheath. The retractor muscle of hyaline rod is contracted at first, which compresses the sheath of pigmented rings and flattens the hairs. While the retractor muscle of hyaline rod relaxes, the elastic energy storage in the compressed glossal sheath will release to change the equivalent stiffness of glossal sheath and erect glossal hairs. These results explain the erection mechanism of glossal hairs during honeybee feeding., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The appearance of an individual's hair is said to be reflective of internal health. Patients with hair shaft disorders commonly present with fragile, lusterless, sparse hair in addition to psychosocial distress. Hair shaft disorders may be hereditary or acquired and may present in children or adults. Due to the varied presentations, the differential diagnosis for hair is broad and often confusing. The authors present a question-by-question guide to help clinicians arrive at the correct diagnosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Human hair-based biocomposite nanofibers (NFs) have been fabricated by an electrospinning technique. Aqueous keratin extracted from human hair was successfully blended with poly(vinyl alcohol) (PVA). The focus here is on transforming into keratin/PVA nanofibrous membranes and insoluble property of electrospun NFs. The resulting hair-based NFs were characterized using Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning colorimetry (DSC), and thermogravimetric analysis (TGA). Toward the potential use of these NFs after cross-linking with various weight fractions of glyoxal, its physicochemical properties, such as morphology, mechanical strength, crystallinity, and chemical structure were investigated. Keratin/PVA ratio of 2/1 NFs with 6 wt%-glyoxal showed good uniformity in fiber morphology and suitable mechanical properties, and excellent antibacterial activity providing a potential application of hair-based NFs in biomedical field., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Although keratosis pilaris (KP) is common, its etiopathogenesis remains unknown. KP is associated clinically with ichthyosis vulgaris and atopic dermatitis and molecular genetically with filaggrin-null mutations. In 20 KP patients and 20 matched controls, we assessed the filaggrin and claudin 1 genotypes, the phenotypes by dermatoscopy, and the morphology by light and transmission electron microscopy. Thirty-five percent of KP patients displayed filaggrin mutations, demonstrating that filaggrin mutations only partially account for the KP phenotype. Major histologic and dermatoscopic findings of KP were hyperkeratosis, hypergranulosis, mild T helper cell type 1-dominant lymphocytic inflammation, plugging of follicular orifices, striking absence of sebaceous glands, and hair shaft abnormalities in KP lesions but not in unaffected skin sites. Changes in barrier function and abnormal paracellular permeability were found in both interfollicular and follicular stratum corneum of lesional KP, which correlated ultrastructurally with impaired extracellular lamellar bilayer maturation and organization. All these features were independent of filaggrin genotype. Moreover, ultrastructure of corneodesmosomes and tight junctions appeared normal, immunohistochemistry for claudin 1 showed no reduction in protein amounts, and molecular analysis of claudin 1 was unremarkable. Our findings suggest that absence of sebaceous glands is an early step in KP pathogenesis, resulting in downstream hair shaft and epithelial barrier abnormalities., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Shed hair from domestic animals readily adheres to clothing and other contact items, providing a source of transfer evidence for criminal investigations. Mitochondrial DNA is often the only option for DNA analysis of shed hair. Human mitochondrial DNA analysis has been accepted in the US court system since 1996. The murder trial of the State of Missouri versus Henry L. Polk, Jr. represents the first legal proceeding where cat mitochondrial DNA analysis was introduced into evidence. The mitochondrial DNA evidence was initially considered inadmissible due to concerns about the cat dataset and the scientific acceptance of the marker. Those concerns were subsequently addressed, and the evidence was deemed admissible. This report reviews the case in regards to the cat biological evidence and its ultimate admission as generally accepted and reliable. Expansion and saturation analysis of the cat mitochondrial DNA control region dataset supported the initial interpretation of the evidence., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The success rate of STR profiling of hairs found at a crime scene is quite low and negative results of hair analysis are frequently reported. To increase the success rate of DNA analysis of hairs in forensics, nuclei in hair roots can be counted after staining the hair root with DAPI. Two staining methods were tested: a longer method with two 1h incubations in respectively a DAPI- and a wash-solution, and a fast, direct staining of the hair root on microscope slides. The two staining methods were not significantly different. The results of the STR analysis for both procedures showed that 20 nuclei are necessary to obtain at least partial STR profiles. When more than 50 nuclei were counted, full STR profiles were always obtained. In 96% of the cases where no nuclei were detected, no STR profile could be obtained. However, 4% of the DAPI-negative hair roots resulted in at least partial STR profiles. Therefore, each forensic case has to be evaluated separately in function of the importance of the evidential value of the found hair. The fast staining method was applied in 36 forensic cases on 279 hairs in total. A fast screening method using DAPI can be used to increase the success rate of hair analysis in forensics., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

The cuticular hairs and sensory bristles that decorate the adult Drosophila epidermis and the denticles found on the embryo have been used in studies on planar cell polarity and as models for the cytoskeletal mediated morphogenesis of cellular extensions. ZP domain proteins have recently been found to be important for the morphogenesis of both denticles and bristles. Here we show that the ZP domain protein Dusky-like is a key player in hair morphogenesis. As is the case in bristles, in hairs dyl mutants display a dramatic phenotype that is the consequence of a failure to maintain the integrity of the extension after outgrowth. Hairs lacking dyl function are split, thinned, multipled and often very short. dyl is required for normal chitin deposition in hairs, but chitin is not required for the normal accumulation of Dyl, hence dyl acts upstream of chitin. A lack of chitin however, does not mimic the dyl hair phenotype, thus Dyl must have other targets in hair morphogenesis. One of these appears to be the actin cytoskeleton. Interestingly, dyl mutants also display a unique planar cell polarity phenotype that is distinct from that seen with mutations in the frizzled/starry night or dachsous/fat pathway genes. Rab11 was previously found to be essential for Dyl plasma membrane localization in bristles. Here we found that the expression of a dominant negative Rab11 can mimic the dyl hair morphology phenotype consistent with Rab11 also being required for Dyl function in hairs. We carried out a small directed screen to identify genes that might function with dyl and identified Chitinase 6 (Cht6) as a strong candidate, as knocking down Cht6 function led to weak versions of all of the dyl hair phenotypes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The characterisation of nanoscale surface properties of textile and hair fibres is key to developing new effective laundry and hair care products. Here, we develop nanomechanical methods to characterise fibres using an atomic force microscope (AFM) to give their nanoscale modulus. Good mounting methods for the fibre that are chemically inert, clean and give strong mechanical coupling to a substrate are important and here we detail two methods to do this. We show, for elastic nanoindentation measurements, the situation when the tip radius significantly affects the result via a function of the ratio of the radii of the tip and fibre and indicate the importance of using an AFM for such work. A valid method to measure the nanoscale modulus of fibres using AFM is thus detailed and exampled on hair to show that bleaching changes the nanoscale reduced modulus at the outer surface., (Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.)

Human hair is principally composed of hair keratins and keratin-associated proteins (KAPs) that form a complex network giving the hair its rigidity and mechanical properties. However, during their growth, hairs are subject to various treatments that can induce irreversible damage. For a better understanding of the human hair protein structures, proteomic mass spectrometry (MS)-based strategies could assist in characterizing numerous isoforms and posttranslational modifications of human hair fiber proteins. However, due to their physicochemical properties, characterization of human hair proteins using classical proteomic approaches is still a challenge. To address this issue, we have used two complementary approaches to analyze proteins from the human hair cortex. The multidimensional protein identification technology (MudPit) approach allowed identifying all keratins and the major KAPs present in the hair as well as posttranslational modifications in keratins such as cysteine trioxidation, lysine, and histidine methylation. Then two-dimensional gel electrophoresis coupled with MS (2-DE gel MS) allowed us to obtain the most complete 2-DE gel pattern of human hair proteins, revealing an unexpected heterogeneity of keratin structures. Analyses of these structures by differential peptide mapping have brought evidence of cleaved species in hair keratins and suggest a preferential breaking zone in α-helical segments., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Patients expressing mutations in the gene encoding the gap junction protein Cx43 suffer from a disease called oculodentodigital dysplasia (ODDD). Patients with ODDD are often reported to develop hair that is dry, dull, sparse, and slow growing. To evaluate the linkage between Cx43 and hair growth, structure, and follicle density we employed a mouse model of ODDD that harbors a Cx43 G60S point mutant. Regionally sparse and overall dull hair were observed in mutant mice compared with their wild-type (WT) littermates. However, histological analysis of overall hair follicle density in mutant and WT mice did not reveal any significant differences. After epilation, mutant mouse hair grew back slower, and hair growth was asynchronous. In addition, ultrastructural scanning electron microscopic imaging of hair fibers taken from mutant mice and two patients harboring the G143S mutation revealed severe cuticle weathering. Nodule formation was also observed in the proximal region of hair fibers taken from mutant mice. These results suggest that the G60S mutant mouse model mimics the hair phenotype found in at least some ODDD patients and suggests an important role for Cx43 in hair regeneration, growth, and cuticle formation.

Interactions between hairs and other natural fibers are of broad interest for both applications and fundamental understanding of biological interfaces. We present a novel method, that allows force measurements between individual hair strands. Hair fragments can be laser-cut without altering their surface chemistry. Subsequently, they are glued onto Atomic force microscopy (AFM) cantilevers. This allows carrying out measurements between the hair fragment and surface immobilized hair in a well-defined crossed-cylinder geometry. Both force-distance and friction measurements are feasible. Measurements in air with controlled humidity and in aqueous environment show clear differences which can be explained by the dominating role of capillary interactions in air. Friction is found to be anisotropic, reflecting the fine structure of hair cuticula. While the investigations are focused on the particular example of human hair, we expect that the approach can be extended to other animal/plant fibers and thus offers perspectives for broad spectrum systems., ((c) 2010 Elsevier B.V. All rights reserved.)

We have investigated the expression of 52 of the 54 keratins in beard hair medulla. We found that not only 12 hair keratins but, unexpectedly, also 12 epithelial keratins are potentially expressed in medulla cells. The latter comprise keratins also present in outer- and inner-root sheaths and in the companion layer. Keratins K5, K14, K17, K25, K27, K28, and K75 define a "pre-medulla," composed of cells apposed to the upper dermal papilla. Besides K6, K16, K7, K19, and K80, all pre-medullary epithelial keratins continue to be expressed in the medulla proper, along with the 12 hair keratins. Besides this unique feature of cellular keratin co-expression, the keratin pattern itself is highly variable in individual medulla cells. Remarkably, both epithelial and hair keratins behave highly promiscuously with regard to heterodimer- and IF formation, which also includes keratin chain interactions in IF bundles. We also identified cortex cells within the medullary column. These exhibit all the properties of genuine cortex cells, including a particular type of keratin heterogeneity of their compact IF bundles. In both keratin expression profile and keratin number, medulla cells are distinct from all other cells of the hair follicle or from any other epithelium.

India is home to seven species of mongoose (Herpestes sp). Mongooses are being poached primarily for their hair, which is used in the production of painting and shaving brushes. Prior to September 2002, mongooses were listed under Schedule-IV of the Wildlife (Protection) Act 1972 (India). Indiscriminate poaching of the mongoose created an immediate threat to their survival and hence mongooses have now been placed under Schedule-II of the Wildlife (Protection) Act-1972 (India). In order to convict a person under this legislation, species identification of case related samples is necessary. Four species of mongoose i.e. H. edwardsii, H. smithii, H. palustris and H. urva were characterised by performing discriminate functional analysis (DFA) on measurements of their dorsal guard hair banding pattern and by microscopic hair characteristics (Cuticular, medullar and cross section). It was possible to distinguish between the four species studied, based on both these methods.

AKR/J mice display a hair interior defect (hid) phenotype for which the molecular basis is unknown. To investigate the application of hair-shaft proteomics to the study of such diseases, pelage from AKR/J and two other mouse strains without this defect was analyzed by shotgun proteomics. The results permitted the identification of 111 proteins from tryptic digests of total hair from AKR/J-hid/hid mice, which were predominantly keratins (Krts) and Krt-associated proteins (Krtaps). From the non-solubilizable (crosslinked) fraction of the hair remaining after extensive detergent extraction, 58 proteins were identified. The majority were Krts and Krtaps, but junctional and other membrane proteins, cytoplasmic proteins, and histones were also identified. The results indicate the incorporation of a multitude of proteins into highly crosslinked material. Comparison of unique peptides generated among hair samples from AKR/J-hid/hid, FVB/NJ+/+, and LP/J+/+ mice indicated that these inbred strains could be distinguished by their proteomic patterns. Transmission electron microscopy after mild treatment in detergent and reducing agent permitted the visualization of projections of cortex cells, with characteristic filament patterns, into adjoining medulla cells. Hair shafts from AKR/J mice were deficient in these projections and also exhibited relatively low levels of trichohyalin, a possible contributor to or marker for the hid phenotype.

Leukonychia is an ungueal discoloration or dyschromia. The hereditary form is rare. In the observations reported in the literature, leukonychia was total or sub-total, and was sometimes associated to other various symptoms. We report an original observation of hereditary leukonychia totalis in a father and two of his children, associated with acanthosis-nigricans-like lesions and hair dysplasia. These symptoms were also present in eight other members of the same family.

The diffusion behavior of a commercial permanent liquid hair dye in human hair has been investigated using positron annihilation lifetime spectroscopy (PALS) and gravimetric sorption method. The positron technique makes it possible to non-invasively characterize the angstrom sized free volume holes in hair, which are supposed to be express pathways for diffusion of small molecules. The o-Ps lifetime parameters tau3 and I3 decrease rapidly during the first 60 min of sorption time. The overall decrease in o-Ps lifetime (tau3) was well over 200 ps and o-Ps intensity (I3) drops by 3.5%. These positron results are explained in terms of dye molecules filling the free volume holes and hair morphology. The dye penetrates the cuticle rapidly, but slowly in cortex. The first hour of dyeing appears to be the most effective period of deposition of dye molecules within hair. These results are well corroborated by the sorption results which suggest that the dye diffusion is essentially a diffusion controlled (i.e. Fickian) process, with no observable relaxation effects. In the latter part of the sorption, where positron parameters remain almost constant, mass increase might be due to surface adhesion. These two stages of sorption are well separated by the positron technique. The sorption curve also yielded an average value of apparent diffusivity of the dye in hair. From this study, we conclude that the free volume theory and positron technique, widely used in polymer research, may expediently be used to understand hair properties, more importantly diffusion of dye molecules.

Hair is a complex "cornified" multicellular tissue composed of cuticle and cortex cells mechanically acting as a whole. The cuticle cells overlap and cortex cells interdigitate, all cells being composed of different morphological elements and separated by the cell membrane complex (CMC). The CMC and the morphological elements of the cortex cells, the macrofibrils, composed of microfibrils or intermediate filaments (IFs), and the intermacrofibrillar and intermicrofibrillar cement or the amorphous matrix material determine the mechanical properties of hair. The IFs consist of alpha-keratin molecules being arranged in a sophisticated way of two parallel monomers and antiparallel and shifted dimers rationalized by the amino acid composition and sequence. The mechanical properties of hair result from mechanical interlocking effects, hydrophobic effects, hydrogen bridges, Coulombic interactions, and (covalent) isodipeptide and, in particular, disulfide bridges on a molecular level. The mechanical models applied to hair are based on a simple two-component system, the microfibril/matrix structure. An important regime of the stress-strain curve is the transition of the molecules of the microfibrils from the alpha-helical to the beta-sheet structure. Due to the longitudinal orientation of the IF molecules the longitudinal swelling of the fibers in water is negligible, the radial swelling, however, is substantial.

Hepatocyte growth factor activator inhibitor type 1 (HAI-1)/serine protease inhibitor, Kunitz type 1 (SPINT1) is a membrane-bound, serine proteinase inhibitor initially identified as an inhibitor of hepatocyte growth factor activator. It also inhibits matriptase and prostasin, both of which are membrane-bound serine proteinases that have critical roles in epidermal differentiation and function. In this study, skin and hair phenotypes of mice lacking the Hai-1/Spint1 gene were characterized. Previously, we reported that the homozygous deletion of Hai-1/Spint1 in mice resulted in embryonic lethality attributable to impaired placental development. To test the role of Hai-1/Spint1 in mice, the placental function of Hai-1/Spint1-mutant mice was rescued. Injection of Hai-1/Spint1(+/+) blastocysts with Hai-1/Spint1(-/-) embryonic stem cells successfully generated high-chimeric Hai-1/Spint1(-/-) embryos (B6Hai-1(-/-High)) with normal placentas. These embryos were delivered without apparent developmental abnormalities, confirming that embryonic lethality of Hai-1/Spint1(-/-) mice was caused by placental dysfunction. However, newborn B6Hai-1(-/-High) mice showed growth retardation and died by 16 days. These mice developed scaly skin because of hyperkeratinization, reminiscent of ichthyosis, and abnormal hair shafts that showed loss of regular cuticular septation. The interfollicular epidermis showed acanthosis with enhanced Akt phosphorylation. Immunoblot analysis revealed altered proteolytic processing of profilaggrin in Hai-1/Spint1-deleted skin with impaired generation of filaggrin monomers. These findings indicate that Hai-1/Spint1 has critical roles in the regulated keratinization of the epidermis and hair development.

Epithelial appendages, such as mammary glands and hair, arise as a result of epithelial-mesenchymal interactions. Bone morphogenetic proteins (BMPs) are important for hair follicle morphogenesis and cycling and are known to regulate a wide variety of developmental processes. For example, overexpression of BMPs inhibits hair follicle formation. We hypothesized that the down-regulation of the BMP signaling pathway in the basal epidermis expands regions that are competent to form hair follicles and could alter the fate of the epithelium in the mouse nipple to a hair-covered epidermal phenotype. To test our hypothesis, we used a transgenic mouse model in which keratin 14 (KRT14) promoter-mediated overexpression of Noggin, a BMP antagonist, modulates BMP activity. We observed the conversion of nipple epithelium into pilosebaceous units. During normal mammary gland organogenesis, BMPs are likely used by the nipple epithelium to suppress keratinocyte differentiation, thus preventing the formation of pilosebaceous units. In this report, we characterize the morphology and processes that influence the development of hairs within the nipple of the KRT14-Noggin mouse. We demonstrate that Noggin acts, in part, by reducing the BMP signal in the epithelium. Reduction of the BMP signal in turn leads to a reduction in the levels of parathyroid hormone-related protein. We propose that during evolution of the nipple, the BMP pathway was co-opted to suppress hair follicle formation and create a more functional milk delivery apparatus.

Uncombable hair syndrome, also named "pili trianguli et canaliculi" or "cheveux incoiffables", is a rare structural anomaly of the hair shaft first reported in 1973. Both inherited and sporadic forms have been described, characterized by dry and frizzy scalp hair that is impossible to comb. Diagnosis is suspected clinically and confirmed by scanning electron microscopy. The condition is usually isolated, however, several physical abnormalities can be associated. We report the case of a 2(1/2) year old-girl presenting isolated uncombable hair syndrome suspected clinically and confirmed by scanning electron microscopy.

We examined hair from 15 patients with trichothiodystrophy (TTD), a rare inherited disorder with brittle, cystine-deficient hair. They had a wide variety of phenotypes, from brittle hair only to severe intellectual impairment and developmental delay. Polarizing light microscopic examination showed alternating light and dark (tiger tail) bands under polarizing microscopy. Confocal microscopy captured structural features of breaks in intact TTD hairs. The autofluorescent appearance was regular and smooth in normal donors and markedly irregular in sections of TTD hairs possibly reflecting abnormalities in melanin distribution. Scanning electron microscopy revealed numerous surface irregularities. All TTD hair samples had reduced sulfur content. We observed an inverse correlation (R(val)=0.9) between sulfur content and percent of hairs with shaft abnormalities (trichoschisis, trichorrhexis nodosa, or ribbon/twist). There was no association between clinical disease severity and percent of abnormal hairs. Raman spectra of hairs from TTD patients and normal donors revealed a larger contribution of energetically less favored disulfide conformers in TTD hairs. Our data indicate that the brittleness of the TTD hair is dependent upon abnormalities at several levels of organization. These changes make TTD hairs excessively prone to breakage and weathering.

We employed a cantilever modified with a self-assembled monolayer (SAM) as a "hair-model-probe" for friction force microscopy (FFM) to measure friction acting between hair and hair-like surfaces. The "hair-model-probe" was prepared by forming a SAM of octadecanethiol on a gold-coated cantilever. We investigated frictional properties of human hair at both root and tip, and the dependency on applied load, influence of scanning direction, and local frictional distribution. The friction coefficient of the hair tip was greater than that of the hair root. Load dependency of friction at the hair tip was clearly observed, while friction at the hair root was less dependent on applied load. At the hair root, an anisotropic frictional property was observed: friction force along the long axis of the hair fiber was about 1.5-2 times larger than that along the short axis. Atomic force microscopy (AFM) images showed striations on the cuticle cells that have about 6 nm depth and their long axis oriented in the direction of the hair fiber. The frictional distribution images revealed that the local areas showing strong shear corresponded to striations. Since such distribution of friction was not observed at the hair tip, it is suggested that the anisotropic frictional property at the hair root was caused mainly by the striations. The frictional distribution in regions that excluded the striations also showed the anisotropic frictional property that friction parallel to the long axis of the hair fiber is greater than that along the short axis. This result suggests that the orientation of fatty acid molecules comprising the fat layer (F-layer) may also contribute to the anisotropic frictional property. We have concluded that loss of the F-layer is a dominant cause of strong friction detected at the hair tip, and at the striations of the hair root.

Macroscale testing of human hair tribological properties has been widely used to aid in the development of better shampoos and conditioners. Recently, literature has focused on using the atomic force microscope (AFM) to study surface roughness, coefficient of friction, adhesive force, and wear (tribological properties) on the nanoscale in order to increase understanding about how shampoos and conditioners interact with the hair cuticle. Since there are both similarities and differences when comparing the tribological trends at both scales, it is thus recognized that scale effects are an important aspect of studying the tribology of hair. However, no microscale tribological data for hair exists in literature. This is unfortunate because many interactions between hair-skin, hair-comb, and hair-hair contact takes place at microasperities ranging from a few mum to hundreds of mum. Thus, to bridge the gap between the macro- and nanoscale data, as well as to gain a full understanding of the mechanisms behind the trends, it is now worthwhile to look at hair tribology on the microscale. Presented in this paper are coefficient of friction and adhesive force data on various scales for virgin and chemically damaged hair, both with and without conditioner treatment. Macroscale coefficient of friction was determined using a traditional friction test apparatus. Microscale and nanoscale tribological characterization was performed with AFM tips of various radii. The nano-, micro-, and macroscale trends are compared and the mechanisms behind the scale effects are discussed. Since the coefficient of friction changes drastically (on any scale) depending on whether the direction of motion is along or against the cuticle scales, the directionality dependence and responsible mechanisms are discussed.

Human hair ( approximately 50-100 microm in diameter) is a nanocomposite biological fiber with well-characterized microstructures, and is of great interest for both cosmetic science and materials science. Characterization of nanotribological and nanomechanical properties of human hair including the coefficient of friction and scratch resistance is essential to develop better shampoo and conditioner products and advance biological and cosmetic science. In this paper, the coefficient of friction and scratch resistance of Caucasian and Asian hair at virgin, chemo-mechanically damaged, and conditioner-treated conditions are measured using a nanoscratch technique with a Nano Indenter II system. The scratch tests were performed on both the single cuticle cell and multiple cuticle cells of each hair sample, and the scratch wear tracks were studied using scanning electron microscopy (SEM) after the scratch tests. The effect of soaking on the coefficient of friction, scratch resistance, hardness and Young's modulus of hair surface were also studied by performing experiments on hair samples which had been soaked in de-ionized water for 5 min. The nanotribological and nanomechanical properties of human hair as a function of hair structure (hair of different ethnicity), damage, treatment and soaking are discussed.

The gene encoding human desmoglein 4 (DSG4) was recently cloned, and a mutation in this gene has been reported in several consanguineous Pakistani families affected with localized autosomal recessive hypotrichosis (LAH). In addition, various mutations in the Dsg4 gene have been identified in animal models of hypotrichosis that share a characteristic phenotype called "lanceolate hair". To date, the features of the hair-shaft anomaly in patients with LAH have not been well described. We report a Japanese patient affected with congenital hypotrichosis that was originally diagnosed as monilethrix because she had a hair-shaft abnormality that resembled moniliform hair. However, no mutations were found in the type II hair keratin genes, hHb1, hHb3, and hHb6, whose mutations cause monilethrix. Instead, we identified novel compound heterozygous mutations in the DSG4 gene of our patient. On the maternal allele is a novel S192P transition within the extracellular cadherin II domain of DSG4; on the paternal allele is a novel 2039insT mutation leading to the generation of unstable transcripts. Here we present the observation that mutations in the DSG4 gene can cause monilethrix-like congenital hypotrichosis. Based on our findings, we propose that LAH and monilethrix could overlap.

Characterization of cellular structure and physical and mechanical properties of hair are essential to develop better cosmetic products and advance biological and cosmetic science. Although the morphology of the cellular structure of human hair has been traditionally investigated using scanning electron microscopy and transmission electron microscopy, these techniques provide limited capability to in situ study of the physical and mechanical properties of human hair in various environments. Atomic force microscopy (AFM) overcomes these problems and can be used for characterization in ambient conditions without requiring specific sample preparations and surface treatment. In this study, film thickness, adhesive forces and effective Young's modulus of various hair surfaces were measured at different environments (humidity and temperature) using force calibration plot technique with an AFM. Torsional resonance mode phase contrast images were also taken in order to characterize the morphology and cellular structure changes of human hair at different humidity. The correlation between the nanomechanical properties and the cellular structure of hair is discussed.

With semiconductor structures reaching the nanometer scale, heat conductivity measurements on the mesoscopic range of some tens of nanometers become an increasingly important aspect for the further improvement in digital processing and storage. Also the attempt to use atomic-force microscopy (AFM) technology for high-density data storage by writing information bits as nanometer-sized indentations into a polymer substrate with a heated cantilever tip asks for a careful investigation of the nano-scale heat-conductivity properties of polymers. Furthermore, in many AFM imaging applications, heat conductivity can provide additional information about the material the imaged structures consist of. In this respect, heat conductivity can also become very interesting in studies of usually quite heterogeneous biological samples, if the resolution can attain the nanometer range. In standard scanning thermal microscopy application, the tip forms a thermocouple, which precludes high-resolution imaging, as thermocouples cannot be made sufficiently small. In this paper, which focuses on biological applications, we demonstrate that by using an ultra sharp AFM cantilever with a Joule heating element above the tip structure different molecular components can be distinguished thanks to their different heat-conductivity properties. In this case, the resolution is determined by the actual tip size, and it can reach 10nm.

Healthy hair and skin is highly desired. Characterization of their morphological, frictional, and adhesive properties (tribological properties) is essential to enhance understanding of hair and skin and to advance the science. Literature on the tribological characterization of hair and skin is scarce to date. The paper presents nanotribological data and analysis on hair (Caucasian, Asian, and African hair at virgin, chemo-mechanically damaged, and treated conditions) and synthetic hair and skin, as well as roughness data of human skin replica. Roughness statistics are presented to characterize the vertical and spatial surface parameters. Average coefficient of friction values were determined for each ethnicity and hair type, and are discussed. The directionality dependence of friction is also discussed. Magnitude and spatial distribution of adhesive force are used to estimate thickness and distribution of the conditioner film.

Human hair is a nanocomposite biological fiber with well-characterized microstructures. Nanomechanical characterization of human hair can help to evaluate the effect of cosmetic products on hair surface, can provide a better understanding of the physicochemical properties of a wide variety of composite biological systems, and can provide the dermatologists with some useful markers for the diagnosis of hair disorders. The paper presents systematic studies of nanomechanical properties of human hair including hardness, elastic modulus and creep, using the nanoindentation technique. The samples include Caucasian, Asian and African hair at virgin, chemo-mechanically damaged and treated conditions. Hair morphology was studied using scanning electron microscopy (SEM). Indentation experiments were performed on both the surface and cross-section of the hair, and the indents were studied using SEM. The nanomechanical properties of hair as a function of hair composition, microstructure, ethnicity, damage and treatment are discussed.

The effect of sodium dodecyl sulfate (SDS) on protein loss was studied. Three kinds of human hair were tested by rubbing or immersion in water or immersion in SDS solution, at 25, 40 and 70 degrees C. Under friction, hair treated with SDS solution loses seven times more protein than in water, while by immersion, protein loss is roughly two times higher in SDS than in water. Protein loss increases at higher temperatures. Estimated activation energy values for protein loss by immersion are 69+/-22 kJ mol(-1) for blended brown hair; 40+/-12 kJ mol(-1) for blond hair (tip-end region) and 61+/-4 kJ mol(-1) for blond hair (root-end region) for samples treated in water, while 53+/-8, 7+/-5 and 32+/-8 kJ mol(-1) were the corresponding activation energy values for samples treated in 5% SDS solution. These values indicate that protein loss is mainly a diffusion-controlled process. The more damaged the hair, the lower the activation energy and the higher the protein loss. From these data, it can be estimated that daily care shampooing at room temperature will cause opacity and combing difficulties in 1 year and split ends after 3 years by removal of all cuticle layers.

The existence of holes in the endocuticle, in the inter-macrofibrilar matrix and in the cell membrane complex of hair fibers is described. In this paper, we show that these holes are absent in the hair follicle. However, cell remnants found in young hair inside the follicle are located in the same regions and are of the same dimensions as the holes observed in mature fibers. Since holes in the endocuticle have been described to appear as a result of daily care actions, it is probable that the development of holes in the inter-macrofibrilar matrix and in the cell membrane complex is related to the removal of extractable substances. We discuss hole formation in terms of the nature of the extractable substances and the presence of cell remnants in the young fibers.

The elemental composition of melanin granules and other components of the hair shaft was determined by multi-isotope imaging mass spectrometry, a method with unique advantages for the visualization and quantification of stable isotopes and the elemental composition in study of the fine structure of biologic samples. We mapped and quantified the chemical composition of hair cross-sections using secondary ions generated from naturally occurring 16O, 12C14N, 32S, and 34S with a maximum lateral resolution of 35 nm. Based on these elemental maps of unprecedented resolution we obtained simultaneously the chemical fingerprints and the structural features, such as cuticle, melanin granules, the macro fibrils of the cortex, and small sulfur-rich domains in the medulla, in the hair cross-section. We found an intriguing distribution of 16O, 12C14N, and 32S in melanin granules that we interpret as a highly anisotropic pattern of oxidation.

We investigated 21 affected individuals in two unrelated monilethrix families of Indian origin and identified point mutation (g.4624G>A) in the HTM motif (exon-7) of the KRTHB6 gene in all the affected members leading to E413K change in this basic keratin. The HTM motif of KRTHB1, however, showed previously unreported two allelic variants, one with three novel variations (SNPs) in cis: g.4421insT (intronic); g.4461T>C (exonic); g.4485A>G (exonic) and second with only intronic variation (SNP) (g.4421insT). Interestingly, the two distinct phenotypes of: localized severe hair defect with beaded appearance confined to the scalp of all the affected members of Family 1 and of generalized unbeaded hair defect of moderate severity in Family 2, segregated in the two families, respectively, correlating with the two separate genotypes for the functionally critical HTM region of KRTHB1 gene in the background of E413K mutation in the KRTHB6 gene. Presence of E413K mutation in the HTM of KRTHB6 gene was not observed in the background of the allelic variant with three SNPs in KRTHB1 gene in homozygous condition in all the affected members of Family 1, affected with a localized but severe form of the disease. However, the same (E413K) mutation existed in the KRTHB6 gene in the background of the allelic variant with three SNPs in the KRTHB1 gene in homozygous condition, consistently in all the affected members of Family 2, where all its affected members showed the segregation of a milder form of the disease. Presence of both E413K mutation in the KRTHB6 and the variations in the KRTHB1 genes were not observed together in randomly selected 150 unaffected controls outside the two affected families. This is also the first report of HTM mutation of KRTHB6 gene in monilethrix cases of Indian origin and the first report of SNPs in the KRTHB1 gene in literature to our knowledge.

The hair growth cycle is generally recognized to comprise phases of growth (anagen), regression (catagen), and rest (telogen). Whereas, heretofore, the hair shedding function has been assumed to be part of the telogen phase, using a laboratory mouse model and newly developed techniques for quantitative collection and spectroscopic determination of shed hair, we found that shedding actually occurs as a distinct phase. Although some shedding occurs throughout the growth cycle, the largest peak is coupled to anagen. Using hair dye and rhodamine labeling we established that the shafts that shed arise during the previous hair cycle. We found that over the cycle the ratio of shed overfur to shed underfur hair shafts varies with the cycle phase and that the shed shaft base is unique morphologically, having a cylindrical shape with scalloped or "nibbled" edges. By electron microscopy the mooring cells of the exogen root show intercellular separation suggesting a proteolytic process in the final shedding step. This is the first report describing a distinct shedding, or exogen, phase of the hair cycle. This study supports the notion that this phase is uniquely controlled and that the final step in the shedding process involves a specific proteolytic step.

To establish a model for studying human scalp hair, individually isolated hair follicles were grafted onto back skin of severe combined immunodeficient mice. Histologic changes and cell kinetics in the hair loss and subsequent recovery process were investigated. In the dystrophic stage (from day 7 to 30), all the hair shafts became dystrophic and were shed. Thickening and corrugation of vitreous membrane, apoptosis, and regression of the lower part were observed in the grafted hair follicles. 5-bromo-2'-deoxy-uridine-labeled cells were not detected in the lower end of the follicles, and keratin 19-positive cells appeared there. At the end of this stage their lower part was maximally retracted, secondary germ remained beneath the bulge, and the vitreous membrane disappeared. In the regeneration stage (from day 30 to 50), the same histologic findings as those at the end of the dystrophic stage were observed. The keratin 19-positive cells in the secondary germ, however, were replaced with keratin 19-negative and 5-bromo-2'-deoxy-uridine-labeled cells. Then, differentiation into an inner root sheath and a hair shaft began, and apoptosis was terminated. In the stable growth stage (from day 40 to at least 150), the grafted follicles were immunohistochemically and light microscopically identical with the normal anagen hair follicles except for the presence of melanin incontinence. These findings suggest that the grafted hair follicles entered into dystrophic catagen, subsequently dystrophic telogen, then returned to normal anagen follicles, and that stem cells or their close progeny in the secondary germ play an important part in the recovery process.

The potential of genetic engineering gives current importance to the need to clarify the relations between structure, properties and performance of wool. There are at present three different models to explain the tensile stress-strain properties of alpha-keratin fibres: a development by Wortmann and Zahn (W/Z) of Feughelman's series-zone model based on the structure of intermediate filaments and a gel-->sol matrix; a new model by Feughelman (F94) based on a matrix of protein globules surrounded by water; and Chapman's model based on the composite mechanics of microfibrils, characterised by critical and equilibrium stresses for the alpha<-->beta transition, in an elastomeric matrix. This paper examines the arguments related to these theories, with additional attention to the Chapman/Hearle (C/H) treatment. The main area of uncertainty, on which more information is much needed, concerns the chemical and physical structure and properties of the matrix, which is composed of keratin-associated proteins. The conclusion is that the C/H model, which is based on reasonable values of input parameters and gives good agreement with a wide range of experimental results, is most likely to be valid, though it needs some additional refinement and incorporation in a total model, which includes larger-scale structural features.

Marie Unna congenital hypotrichosis (MUCH) is a rare autosomal dominant condition in which abnormalities are confined to hair shaft structure and hair density. We report a six-generation pedigree consisting of 59 members of whom 16 are affected; nine identified affected individuals are living. Affected individuals are born with adequate, normal to coarse hair. During early infancy the scalp hair becomes more coarse and wiry and stands out from the head. All affected individuals have sparse to absent eyebrows, eyelashes and body hair including secondary sexual hair. In some individuals, scalp hair is progressively lost beginning at puberty or beyond, until only a sparse fringe in the tonsorial distribution remains. The hair shafts are uniformly increased in diameter, measuring up to 0.12 mm. Individual hair shafts are deeply pigmented, variable in diameter, twisted, and bent at odd angles; some have a longitudinal groove visible on scanning electron microscopy. Cross-sectional shapes are variable and irregular, exhibiting oval, angular to reniform shapes. Multiple anagen hairs are extractable on gentle hair pull. Other ectodermal structures are unaffected except for exceptionally widely spaced upper incisor teeth seen in 50% of affected individuals. Histologically, there are dramatically reduced numbers of follicles per unit area, averaging nine total hairs per 4 mm cross-section as compared with a normal of 40. A mild to moderate inflammatory infiltrate is present, but little fibrosis and no scarring. The mechanism of progressive hair loss is unknown.

A technique using pure gallium metal as a replication material is reported for biological surface scanning electron microscopy (SEM). The technique first directly enables aquatic organisms in water to be replicated due to gallium's low melting point and, second, reproduces surface structures and images of the two-dimensional (2D) distribution of substances transferred from the original surface to the gallium surface due to gallium's high surface tension. An aquatic protozoan in water was directly replicated to show its typical surface structures. The technique was then used to visualize human hair surface structures and 2D transferred substance distribution using X-ray microanalysis.

Characterization of the molecular pathways controlling differentiation and proliferation in mammalian hair follicles is central to our understanding of the regulation of normal hair growth, the basis of hereditary hair loss diseases, and the origin of follicle-based tumors. We demonstrate that the proto-oncogene Wnt3, which encodes a secreted paracrine signaling molecule, is expressed in developing and mature hair follicles and that its overexpression in transgenic mouse skin causes a short-hair phenotype due to altered differentiation of hair shaft precursor cells, and cyclical balding resulting from hair shaft structural defects and associated with an abnormal profile of protein expression in the hair shaft. A putative effector molecule for WNT3 signaling, the cytoplasmic protein Dishevelled 2 (DVL2), is normally present at high levels in a subset of cells in the outer root sheath and in precursor cells of the hair shaft cortex and cuticle which lie immediately adjacent to Wnt3-expressing cells. Overexpression of Dvl2 in the outer root sheath mimics the short-hair phenotype produced by overexpression of Wnt3, supporting the hypothesis that Wnt3 and Dvl2 have the potential to act in the same pathway in the regulation of hair growth. These experiments demonstrate a previously unrecognized role for WNT signaling in the control of hair growth and structure, as well as presenting the first example of a mammalian phenotype resulting from overexpression of a Dvl gene and providing an accessible in vivo system for analysis of mammalian WNT signaling pathways., (Copyright 1999 Academic Press.)

The occurrence of hairs in the median sulcus of the tongue in two dogs, a 7-year-old Rottweiler and a 10-year-old Cocker spaniel, is reported as an incidental observation at necropsy. The gross pathology of both cases and the histological and scanning electron microscopical findings in one case indicated a heterotopic development of the hairs, with secondary inflammation. The term pili heterotopici mediani linguae is suggested.