SciCombinator

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Concept: Hair

509

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10(-8) to 3 × 10(-119)), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair.

Concepts: Protein, United States, Spanish language, Facial features, Hair, Hair follicle, Facial hair, Moustache

204

The idea that low surface densities of hairs could be a heat loss mechanism is understood in engineering and has been postulated in some thermal studies of animals. However, its biological implications, both for thermoregulation as well as for the evolution of epidermal structures, have not yet been noted. Since early epidermal structures are poorly preserved in the fossil record, we study modern elephants to infer not only the heat transfer effect of present-day sparse hair, but also its potential evolutionary origins. Here we use a combination of theoretical and empirical approaches, and a range of hair densities determined from photographs, to test whether sparse hairs increase convective heat loss from elephant skin, thus serving an intentional evolutionary purpose. Our conclusion is that elephants are covered with hair that significantly enhances their thermoregulation ability by over 5% under all scenarios considered, and by up to 23% at low wind speeds where their thermoregulation needs are greatest. The broader biological significance of this finding suggests that maintaining a low-density hair cover can be evolutionary purposeful and beneficial, which is consistent with the fact that elephants have the greatest need for heat loss of any modern terrestrial animal because of their high body-volume to skin-surface ratio. Elephant hair is the first documented example in nature where increasing heat transfer due to a low hair density covering may be a desirable effect, and therefore raises the possibility of such a covering for similarly sized animals in the past. This elephant example dispels the widely-held assumption that in modern endotherms body hair functions exclusively as an insulator and could therefore be a first step to resolving the prior paradox of why hair was able to evolve in a world much warmer than our own.

Concepts: Evolution, Temperature, Heat, Convection, Heat transfer, Hair, Elephant, Paleontology

172

Body hair shafts from the beard, trunk, and extremities can be used to treat baldness when patients have inadequate amounts of scalp donor hair, but reports in the literature concerning use of body hair to treat baldness are confined to case reports.

Concepts: Human body, Hair, Hair transplantation, Scalp, Facial hair, Follicular unit transplantation, Follicular Unit Extraction, Beard

170

BACKGROUND: Thuja orientalis has been traditionally used to treat patients who suffer from baldness and hair loss in East Asia. The present study sought to investigate the hair growth-promoting activity of T. orientalis hot water extract and the underlying mechanism of action. METHODS: After T. orientalis extract was topically applied to the shaved dorsal skin of telogenic C57BL/6 N mice, the histomorphometric analysis was employed to study induction of the hair follicle cycle. To determine the effect of T. orientalis extract on the telogen to anagen transition, the protein expression levels of beta-catenin and Sonic hedgehog (Shh) in hair follicles were determined by immunohistochemistry. RESULTS: We observed that T. orientalis extract promoted hair growth by inducing the anagen phase in telogenic C57BL/6 N mice. Specifically, the histomorphometric analysis data indicates that topical application of T. orientalis extract induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to either the control or 1% minoxidil-treated group. We also observed increases in both the number and size of hair follicles of the T. orientalis extract-treated group. Moreover, the immunohistochemical analysis reveals earlier induction of beta-catenin and Shh proteins in hair follicles of the T. orientalis extract-treated group, compared to the control or 1% minoxidil-treated group. CONCLUSION: These results suggest that T. orientalis extract promotes hair growth by inducing the anagen phase in resting hair follicles and might therefore be a potential hair growth-promoting agent.

Concepts: Chemotherapy, Skin, Immunohistochemistry, Topical, Hair, Hair follicle, Sonic hedgehog, Sebaceous gland

170

Human multipotent skin derived precursor cells (SKPs) are traditionally sourced from dissociated dermal tissues; therefore, donor availability may become limiting. Here we demonstrate that both normal and diseased adult human dermal fibroblasts (DF) pre-cultured in conventional monolayers are capable of forming SKPs (termed m-SKPs). Moreover, we show that these m-SKPs can be passaged and that cryopreservation of original fibroblast monolayer cultures does not reduce m-SKP yield; however, extensive monolayer passaging does. Like SKPs generated from dissociated dermis, these m-SKPs expressed nestin, fibronectin and versican at the protein level. At the transcriptional level, m-SKPs derived from normal adult human DF, expressed neural crest stem cell markers such as p75NTR, embryonic stem cell markers such as Nanog and the mesenchymal stem cell marker Dermo-1. Furthermore, appropriate stimuli induced m-SKPs to differentiate down either mesenchymal or neural lineages resulting in lipid accumulation, calcification and S100β or β-III tubulin expression (with multiple processes). m-SKP yield was greater from neonatal foreskin cultures compared to those from adult DF cultures; however, the former showed a greater decrease in m-SKP forming capacity after extensive monolayer passaging. m-SKP yield was greater from adult DF cultures expressing more alpha-smooth muscle actin (αSMA). In turn, elevated αSMA expression correlated with cells originating from specimens isolated from biopsies containing more terminal hair follicles; however, αSMA expression was lost upon m-SKP formation. Others have shown that dissociated human hair follicle dermal papilla (DP) are a highly enriched source of SKPs. However, conversely and unexpectedly, monolayer cultured human hair follicle DP cells failed to form m-SKPs whereas those from the murine vibrissae follicles did. Collectively, these findings reveal the potential for using expanded DF cultures to produce SKPs, the heterogeneity of SKP forming potential of skin from distinct anatomical locations and ages, and question the progenitor status of human hair follicle DP cells.

Concepts: Protein, Stem cell, Stem cells, Embryonic stem cell, Skin, Hair, Hair follicle, Stem cell marker

167

Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal.

Concepts: In vivo, In vitro, Hair, Hair care, Hair follicle, Ginger, Facial hair, Long hair

166

In most mammals, each hair follicle undergoes a cyclic process of growing, regressing and resting phases (anagen, catagen, telogen, respectively) called the hair cycle. Various biological factors have been reported to regulate or to synchronize with the hair cycle. Some factors involved in the extracellular matrix, which is a major component of skin tissue, are also thought to regulate the hair cycle. We have focused on an enzyme that degrades elastin, which is associated with skin elasticity. Since our previous study identified skin fibroblast elastase as neprilysin (NEP), we examined the fluctuation of NEP enzyme activity and its expression during the synchronized hair cycle of rats. NEP activity in the skin was elevated at early anagen, and decreased during catagen to telogen. The expression of NEP mRNA and protein levels was modulated similarly. Immunostaining showed changes in NEP localization throughout the hair cycle, from the follicular epithelium during early anagen to the dermal papilla during catagen. To determine whether NEP plays an important role in regulating the hair cycle, we used a specific inhibitor of NEP (NPLT). NPLT was applied topically daily to the dorsal skin of C3H mice, which had been depilated in advance. Mice treated with NPLT had significantly suppressed hair growth. These data suggest that NEP plays an important role in regulating the hair cycle by its increased expression and activity in the follicular epithelium during early anagen.

Concepts: Protein, Extracellular matrix, Skin, Hair, Hair follicle, Sebaceous gland, Goose bumps

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

37

Dun is a wild-type coat color in horses characterized by pigment dilution with a striking pattern of dark areas termed primitive markings. Here we show that pigment dilution in Dun horses is due to radially asymmetric deposition of pigment in the growing hair caused by localized expression of the T-box 3 (TBX3) transcription factor in hair follicles, which in turn determines the distribution of hair follicle melanocytes. Most domestic horses are non-dun, a more intensely pigmented phenotype caused by regulatory mutations impairing TBX3 expression in the hair follicle, resulting in a more circumferential distribution of melanocytes and pigment granules in individual hairs. We identified two different alleles (non-dun1 and non-dun2) causing non-dun color. non-dun2 is a recently derived allele, whereas the Dun and non-dun1 alleles are found in ancient horse DNA, demonstrating that this polymorphism predates horse domestication. These findings uncover a new developmental role for T-box genes and new aspects of hair follicle biology and pigmentation.

Concepts: DNA, Gene, Genetics, Allele, Evolution, Horse, Hair, Domestication of the horse

31

Propolis is a natural honeybee hive product with the potential for use in the treatment of dermatological conditions, such as cutaneous abrasions, burns, and acne. In this study, we investigated whether propolis stimulates hair growth in mice. Ethanol-extracted propolis, which contains various physiologically active substances such as caffeic acid and kaempferol, stimulated anagen induction in the shaved back skin. Anagen induction occurred without any detectable abnormalities in the shape of the hair follicles (HFs), hair stem cells in the bulge, proliferating hair matrix keratinocytes in the hair bulb, or in the localization of versican in the dermal papilla. Propolis treatment also stimulated migration of hair matrix keratinocytes into the hair shaft in HFs during late anagen in the depilated back skin. Organotypic culture of skin containing anagen stage HFs revealed significant stimulation of hair matrix keratinocyte proliferation by propolis. Furthermore, propolis facilitated the proliferation of epidermal keratinocytes. These results indicate that propolis stimulates hair growth by inducing hair keratinocyte proliferation.

Concepts: Skin, Epidermis, Caffeic acid, Hair, Hair follicle, Facial hair, Sebaceous gland, Propolis