Modeling recent human evolution in mice by expression of a selected EDAR variant.

An adaptive variant of the human Ectodysplasin receptor, EDARV370A, is one of the strongest candidates of recent positive selection from genome-wide scans. We have modeled EDAR370A in mice and characterized its phenotype and evolutionary origins in humans. Our computational analysis suggests the allele arose in central China approximately 30,000 years ago. Although EDAR370A has been associated with increased scalp hair thickness and changed tooth morphology in humans, its direct biological significance and potential adaptive role remain unclear. We generated a knockin mouse model and find that, as in humans, hair thickness is increased in EDAR370A mice. We identify new biological targets affected by the mutation, including mammary and eccrine glands. Building on these results, we find that EDAR370A is associated with an increased number of active eccrine glands in the Han Chinese. This interdisciplinary approach yields unique insight into the generation of adaptive variation among modern humans.

Polydopamine Synergizes with Quercetin Nanosystem to Reshape the Perifollicular Microenvironment for Accelerating Hair Regrowth in Androgenetic Alopecia.

Accumulated reactive oxygen species (ROS) and their resultant vascular dysfunction in androgenic alopecia (AGA) hinder hair follicle survival and cause permanent hair loss. However, safe and effective strategies to rescue hair follicle viability to enhance AGA therapeutic efficiency remain challenging. Herein, we fabricated a quercetin-encapsulated (Que) and polydopamine-integrated (PDA@QLipo) nanosystem that can reshape the perifollicular microenvironment to initial hair follicle regeneration for AGA treatment. Both the ROS scavenging and angiogenesis promotion abilities of PDA@QLipo were demonstrated. In vivo assays revealed that PDA@QLipo administrated with roller-microneedles successfully rejuvenated the "poor" perifollicular microenvironment, thereby promoting cell proliferation, accelerating hair follicle renewal, and facilitating hair follicle recovery. Moreover, PDA@QLipo achieved a higher hair regeneration coverage of 92.5% in the AGA mouse model than minoxidil (87.8%), even when dosed less frequently. The nanosystem creates a regenerative microenvironment by scavenging ROS and augmenting neovascularity for hair regrowth, presenting a promising approach for AGA clinical treatment.

Keratose hydrogel for tissue regeneration and drug delivery.

Keratin (KRT), a natural fibrous structural protein, can be classified into two categories: "soft" cytosolic KRT that is primarily found in the epithelia tissues (e.g., skin, the inner lining of digestive tract) and "hard" KRT that is mainly found in the protective tissues (e.g., hair, horn). The latter is the predominant form of KRT widely used in biomedical research. The oxidized form of extracted KRT is exclusively denoted as keratose (KOS) while the reduced form of KRT is termed as kerateine (KRTN). KOS can be processed into various forms (e.g., hydrogel, films, fibers, and coatings) for different biomedical applications. KRT/KOS offers numerous advantages over other types of biomaterials, such as bioactivity, biocompatibility, degradability, immune/inflammatory privileges, mechanical resilience, chemical manipulability, and easy accessibility. As a result, KRT/KOS has attracted considerable attention and led to a large number of publications associated with this biomaterial over the past few decades; however, most (if not all) of the published review articles focus on KRT regarding its molecular structure, biochemical/biophysical properties, bioactivity, biocompatibility, drug/cell delivery, and in vivo transplantation, as well as its applications in biotechnical products and medical devices. Current progress that is directly associated with KOS applications in tissue regeneration and drug delivery appears an important topic that merits a commentary. To this end, the present review aims to summarize the current progress of KOS-associated biomedical applications, especially focusing on the in vitro and in vivo effects of KOS hydrogel on cultured cells and tissue regeneration following skin injury, skeletal muscle loss, peripheral nerve injury, and cardiac infarction.

Detection and Imaging of Exposure-Related Metabolites and Xenobiotics in Hard Tissues by Laser Sampling and Mass Spectrometry.

The utility of two novel laser-based methods, laser ablation electrospray ionization (LAESI) and laser desorption ionization (LDI) from silicon nanopost array (NAPA), is explored via local analysis and mass spectrometry imaging (MSI) of hard tissues (tooth and hair) for the detection and mapping of organic components. Complex mass spectra are recorded in local analysis mode from tooth dentin and scalp hair samples. Nicotine and its metabolites (cotinine, hydroxycotinine, norcotinine, and nicotine) are detected by LAESI-MS in the teeth of rats exposed to tobacco smoke. The intensities of the detected metabolite peaks are proportional to the degree of exposure. Incorporating ion mobility separation in the LAESI-MS analysis of scalp hair enables the detection of cotinine in smoker hair along with other common molecular species, including endogenous steroid hormones and some lipids. Single hair strands are imaged by MALDI-MSI and NAPA-LDI-MSI to explore longitudinal variations in the level of small molecules. Comparing spectra integrated from NAPA-LDI-MSI and MALDI-MSI images reveals that the two techniques provide complementary information. There were 105 and 82 sample-related peaks for MALDI and NAPA, respectively, with an overlap of only 16 peaks, indicating a high degree of complementarity. Enhanced molecular coverage and spatial resolution offered by LAESI-MS and NAPA-LDI-MSI can reveal the distributions of known and potential biomarkers in hard tissues, facilitating exposome research.

Concurrent and prospective associations between family socioeconomic status, social support and salivary diurnal and hair cortisol in adolescence.

BACKGROUND: Exposure to socioeconomic adversity is hypothesized to impact hypothalamic-pituitary-adrenal (HPA) axis activity and cortisol secretion, but existing evidence is inconsistent. Yet, few studies have investigated this association using a developmental approach that considers potential protective contextual factors. This study examined the role of stability and changes in family socioeconomic status (SES) in the prediction of multiple cortisol indicators and tested whether social support moderated these associations. METHODS: Participants were part of a population-based sample of twin pairs recruited at birth. Family SES was assessed in early childhood (ages 0-5) and mid-adolescence (age 14). Social support was assessed at ages 14 and 19. Diurnal cortisol (n = 569) was measured at age 14 at awakening, 30 min later, in the afternoon and evening over four non-consecutive days. Hair cortisol concentration (HCC, n = 704) was measured at age 19. All data were collected before the pandemic and multilevel regression models were conducted to account for the nested data structure. RESULTS: Youth exposed to lower family SES levels in childhood and mid-adolescence had a flatter diurnal slope and higher HCC compared with those who experienced upward socioeconomic mobility in mid-adolescence. Contrastingly, mid-adolescence SES showed no association with the diurnal slope or HCC for youth from higher-SES households in early childhood. Moreover, youth raised in higher-SES families in early childhood had a higher CAR in mid-adolescence if they reported greater social support in mid-adolescence. Social support also moderated the SES-cortisol association in mid-adolescence, with higher-SES youth showing higher awakening cortisol secretion when reporting more social support. CONCLUSIONS: Our findings support the hypothesis that early socioeconomic adversity sensitizes HPA axis activity to later socioeconomic disadvantage, which may bear consequences for socioemotional and behavioral functioning.

Sr-Pb isotope differences in pre- and post-burial human bone, teeth, and hair keratin: implications for isotope forensics.

The isotopic signatures of human tissues can provide valuable information on geographic origin for medicolegal investigations involving unidentified persons. It is important to understand the impact of diagenetic processes on isotopic signatures, as alterations could result in incorrect estimation of geographic origin. This study examines alterations in isotope signatures of different tissues of five human body donors studied throughout decomposition at the Forensic Anthropology Research Facility (FARF), San Marcos, TX. Two body donors were buried, two were placed in open pits, and one was first allowed to naturally mummify and then buried. Remains were recovered after a period of 7-34 months. The preplacement and post-recovery Sr-Pb isotope data of scalp hair, bone (iliac and tibia), and tooth enamel and dentine were compared. The hair samples record significant shifts in Sr-Pb isotope compositions, with hair keratin Pb isotope composition shifting towards the Pb signature of local soil samples. Hair keratin Sr isotope compositions were altered by the burial environment and possibly also by the lab sample cleaning method. The spongy iliac bone samples show inconsistencies in the recoverability of the preplacement Sr-Pb isotope signatures. The post-placement signatures of the buried donors show slight elevation over preplacement signatures. The post-placement signatures of donors placed in open pits are significantly elevated. The tibia and dental samples record the most consistent isotopic data with the least alteration. These more densely mineralised elements show good recoverability of the preplacement isotope signatures in burials and open pits and are thus deemed better targets for forensic investigative purposes.

Relationships among Cortisol, Perceived Stress, and Dental Caries Experience in Adolescents and Young Adults.

INTRODUCTION: Stress can impact mental and physical health, especially during adolescence and young adulthood, but the extent of its contribution to dental caries is poorly understood. The present study assessed the association between perceived stress, cortisol levels (in hair and saliva), and overall caries experience of adolescents and young adults aged 15-25 years. METHODS: Hair and saliva samples were obtained from 93 participants free of periodontal disease. Cortisol in hair and saliva was determined using a competitive enzyme-linked immunosorbent assay. Participants completed a perceived stress questionnaire and underwent full-mouth oral examination by a calibrated examiner. Dental caries experience was based on the decayed, missing, and filled teeth (DMFT) index. Sociodemographic variables were also recorded. RESULTS: There were significantly higher hair cortisol levels and perceived stress scale (PSS) scores in individuals with dental caries experience (DMFT≥1) than in those without (DMFT = 0). However, there was no significant difference in salivary cortisol concentration. A binary logistic regression revealed that higher hair cortisol levels and greater scores on the perceived stress scale were associated with increased odds of having experienced dental caries. In contrast, no significant association was found between salivary cortisol concentration and dental caries. Using multivariable regression models, caries experience was found to be significantly associated with both hair cortisol levels and PSS scores. These associations remained statistically significant even after adjusting for sociodemographic variables. CONCLUSION: Hair cortisol levels and perceived stress have a significant association with dental caries experience, whereas salivary cortisol concentrations do not.

Complications with Follicular Unit Excision.

Hair restoration surgery (HRS) is typically a safe outpatient or office-based procedure when physicians follow high ethical standards and uphold community practice standards. Patients' clinical outcomes are mostly operator dependent, and temporary and permanent complications rarely occur. Follicular unit excision (FUE) donor harvesting, in particular, is a challenging harvesting technique requiring a long learning curve, physical stamina, higher than average hand-eye coordination and manual dexterity. The types of complications associated with FUE are comparable to linear strip excision (LSE). Similar to LSE donor harvesting, FUE complications may occur irrespective if standard precautions are followed by the physician. As in any skin and scalp procedure, injuries and poor cosmetic outcomes occur despite appropriate preoperative precautions and intraoperative technique. In increasing and greater instances, however, FUE complications are observed when the physician fails to follow hair restoration practice standards and routine surgical precautions. Physician induced, or iatrogenic complications occur more often when untrained licensed surgeons perform HRS, and who fail to meet practice standards and best practices. In the last decade, physician-influenced FUE complications, or iatrogenic cause of FUE injuries are increasingly observed which results in poor aesthetic outcomes. Higher than average FUE complication rates occur in cases involving inadequately trained physicians, as well as in cases where improper delegation of the FUE hair transplant procedure is performed by unlicensed and untrained individuals. In this chapter, we described commonly encountered HRS complications, as well as physician influenced, or iatrogenic causes of FUE complications.

Transparent silicone-free shampoo containing proteins with strong hair conditioning properties.

OBJECTIVE: With the constant upgrading of healthcare concepts, silicone-free hair products have attracted more attention among consumers. In the present study, transparent silicone-free shampoo containing proteins was successfully fabricated by mixing mild non-sulphate surfactants, compound cationic conditioners, natural silicone oil substitutes, protein conditioners, thickeners, and other auxiliary ingredients. The effects of the type of surfactants, hair conditioners and thickeners, the type and content of proteins, and the mass ratio of compound proteins on the hair foaming performance, hair grooming performance, and penetration performance were investigated. METHODS: The basic formulation framework for transparent silicone-free shampoo was established at first. Then, various hydrolyzed proteins were further added to the basic formulation in the form of single use or compound use to prepare transparent silicone-free shampoo containing different proteins. The morphology of hair samples and penetration of protein in hair were evaluated with a scanning electron microscope and laser confocal fluorescence microscopy, respectively. And the hair grooming performance was also determined by a dynamic combing tester. RESULTS: The compound proteins of Croquat WKP PE-LQ-WD and Gluadin® Kera-PLM with mass ratios of 1:9 and 1:1 at 2 wt% total protein content added to the silicone-free shampoo brought a higher contact angle and a lower frictional coefficient than commercial silicone-free shampoo without proteins. In addition, the compound proteins also have the dual effect of adsorbing the hair surface and penetrating deep into the interior of the hair. CONCLUSION: The combination of cationic modified hydrolyzed protein (e.g., Croquat WKP PE-LQ-WD) and hydrolyzed protein with low molecular weight (e.g., Gluadin® Kera-P LM) at an appropriate mass ratio exhibited a strong synergistic effect on hair conditioning properties. It could provide a significant reference for developing silicone-free hair products with more benefits.

OBJECTIF: Avec l'amélioration constante des concepts de soins de santé, les produits capillaires sans silicone ont attiré l'attention des consommateurs. Dans la présente étude, un shampooing transparent sans silicone contenant des protéines a été fabriqué avec succès en mélangeant des tensioactifs doux sans sulfate, des conditionneurs cationiques composés, des substituts naturels de l'huile de silicone, des conditionneurs protéiques, des épaississants et d'autres ingrédients auxiliaires. On a étudié les effets du type de tensioactifs, de conditionneurs pour les cheveux et d'épaississants, du type et de la teneur en protéines et du rapport massique des protéines composées sur les performances de moussage des cheveux, du nettoyage des cheveux et de la pénétration. MÉTHODES: le cadre de formulation de base pour le shampooing transparent sans silicone a d'abord été établi. Ensuite, diverses protéines hydrolysées ont été ajoutées à la formulation de base sous forme d'utilisation unique ou d'utilisation de composés pour préparer un shampooing transparent sans silicone contenant différentes protéines. La morphologie des échantillons de cheveux et la pénétration des protéines dans les cheveux ont été évaluées à l'aide d'un microscope électronique a balayage et d'une microscopie confocale laser à fluorescence, respectivement. Les performances de nettoyage des cheveux ont également été déterminées par un testeur de peignage dynamique. RÉSULTATS: les protéines composées de Croquat WKP PE-LQ-WD et de GluadinR Kera-PLM avec des rapports massiques de 1:9 et 1:1 à 2 % en poids de teneur en protéines totales ajoutées au shampooing sans silicone ont un angle de contact plus élevé et un coefficient de frottement plus faible que le shampooing sans silicone commercial sans protéines. En outre, les protéines composées ont également doublé l'effet d'adsorption à la surface des cheveux et de pénétration à l'intérieur des cheveux. CONCLUSION: la combinaison de protéines hydrolysées modifiées cationiques (par exemple, Croquat WKP PE-LQ-WD) et de protéines hydrolysées de faible poids moléculaire (par exemple, GluadinR Kera-P LM) avec un rapport massique approprié a montré un fort effet synergique sur les propriétés de conditionnement des cheveux. Il pourrait fournir une référence significative pour le développement de produits capillaires sans silicone avec plus d'avantages.

Foxi3GFP and Foxi3CreER mice allow identification and lineage labeling of pharyngeal arch ectoderm and endoderm, and tooth and hair placodes.

BACKGROUND: FOXI3 is a forkhead family transcription factor that is expressed in the progenitors of craniofacial placodes, epidermal placodes, and the ectoderm and endoderm of the pharyngeal arch region. Loss of Foxi3 in mice and pathogenic Foxi3 variants in dogs and humans cause a variety of craniofacial defects including absence of the inner ear, severe truncations of the jaw, loss or reduction in external and middle ear structures, and defects in teeth and hair. RESULTS: To allow for the identification, isolation, and lineage tracing of Foxi3-expressing cells in developing mice, we targeted the Foxi3 locus to create Foxi3GFP and Foxi3CreER mice. We show that Foxi3GFP mice faithfully recapitulate the expression pattern of Foxi3 mRNA at all ages examined, and Foxi3CreER mice can trace the derivatives of pharyngeal arch ectoderm and endoderm, the pharyngeal pouches and clefts that separate each arch, and the derivatives of hair and tooth placodes. CONCLUSIONS: Foxi3GFP and Foxi3CreER mice are new tools that will be of use in identifying and manipulating pharyngeal arch ectoderm and endoderm and hair and tooth placodes.

Minoxidil nanoliposomes as a hair growth stimulator and a scalp disinfectant.

Hair loss (alopecia) continues to be an issue for both sexes. There are multiple ways to reduce the effects of alopecia, one of which is topical minoxidil (MXD). This study aimed to test the effects of minoxidil nanoliposomes (MXD-NLs) on the hair of mice, compared with free MXD and to examine the disinfectant ability of MXD-NLs toward scalp bacteria. To test the study hypothesis, MXD-NLs and free MXD were prepared. Mouse hair was shaved prior to the experiment. MXD-NLs, free MXD and their vehicles were applied for 15 days. In addition, dermal swabs were used to isolate scalp bacteria and test the inhibitory effect of pretreated media with the two formulations and their vehicles. The results revealed that hair growth in the MXD-NLs -treated group (0.65±0.1cm) was higher than that in the free MXD -treated group (0.53±0.2cm). In addition, MXD-NLs treated media reduced the number of scalp bacteria (p=0.0456) compared with free MXD. These results reveal a novel formulation of MXD with faster hair growth properties and a better disinfectant effect than free MXD. This study can help future researchers to expand and develop MXD-NLs.

Pseudogenization of the Hair-Related Genes PADI3 and S100A3 in Cetaceans and Hippopotamus amphibius.

Hair-related genes in mammals play important roles in the development and maintenance of hair and other keratinous structures in mammals. The peptidyl arginine deiminase 3 (PADI3) gene encodes an enzyme that catalyzes the conversion of arginine residues to citrulline. The S100 calcium binding protein A3 (S100A3) gene encodes a protein that is highly expressed in the hair cuticle and contains arginine residues that are converted to citrullines by PADI enzymes. In this study, we investigated the pseudogenization events of PADI3 and S100A3 in cetaceans and Hippopotamus amphibius. We found that PADI3 underwent three independent pseudogenization events during cetacean evolution, in baleen whales, toothed cetaceans other than Physeter catodon, and P. catodon. Notably, the entire PADI3 gene is absent in the baleen whales. Pseudogenization of S100A3 occurred independently in cetaceans and H. amphibius. Interestingly, we found that in cetaceans S100A3 underwent pseudogenization before PADI3, suggesting that differential selection pressures were acting on the two genes. Our findings provide valuable insights into the molecular evolution of these genes in cetaceans and hippopotamuses, highlighting their importance for understanding the evolution of hair-related genes.

Rare diseases of ectoderm: Translating discovery to therapy.

Heritable conditions known as ectodermal dysplasias are rare and can be associated with marked morbidity, mortality, and a reduced quality of life. The diagnosis and care of individuals affected by one of the many ectodermal dysplasias presents myriad challenges due to their rarity and the diverse phenotypes. These conditions are caused by abnormalities in multiple genes and signaling pathways that are essential for the development and function of ectodermal derivatives. During a 2021 international conference focused on translating discovery to therapy, researchers and clinicians gathered with the goal of advancing the diagnosis and treatment of conditions affecting ectodermal tissues with an emphasis on skin, hair, tooth, and eye phenotypes. Conference participants presented a variety of promising treatment strategies including gene or protein replacement, gene editing, cell therapy, and the identification of druggable targets. Further, barriers that negatively influence the current development of novel therapeutics were identified. These barriers include a lack of accurate prevalence data for rare conditions, absence of an inclusive patient registry with deep phenotyping data, and insufficient animal models and cell lines. Overcoming these barriers will need to be prioritized in order to facilitate the development of novel treatments for genetic disorders of the ectoderm.

The Ectodermal Dysplasias-Burden of Disease Score: Development and Validation of an Ectodermal Dysplasia Family/Parental Burden Score.

Ectodermal dysplasias are genetic conditions affecting the development and/or homeostasis of 2 or more ectodermal derivatives, including hair, teeth, nails, and certain glands. No tool is available to assess the burden of ectodermal dysplasias and its multidimensional impact on patients and their families. This study developed and validated a familial/parental 19-item burden questionnaire designed specifically for ectodermal dysplasias. Each group of questions was linked to 1 of the following dimensions: (i) Impact of the disease on social life and hobbies; (ii) Future prospects; (iii) Restraint of the disease on outdoor activities; (iv) Financial burden of the disease; (v) Acceptance of the disease. Cronbach's alpha was 0.91 for the entire Ectodermal Dysplasias-Burden of Disease (ED-BD) scale, confirming excellent internal coherence. Intradimensional coherences all demonstrated excellent reliability (α > 0.76). The ED-BD questionnaire was highly correlated with the Short Form-12 and Psychological General Well Being Index validated questionnaires. Cultural and linguistic validation in US English was conducted. Development and validation of the questionnaire was based on data from patients with the 2 main ectodermal dysplasias subtypes. This ED-BD questionnaire represents the first specific assessment tool for evaluating the familial/parental burden of ectodermal dysplasias.

Development of a three-point cantilever bending technique to study the mechanical properties of hair styling ingredients.

BACKGROUND: The mechanical properties of hair treated with styling ingredients is an important aspect to determine if products will be efficacious when used by the consumer. Measurement techniques have been proposed in earlier work; however, these are mostly aimed at hairspray systems and not the myriad of styling products available to the modern-day consumer. AIM: In this article, experimental and data analysis guidelines are proposed for the evaluation of styling ingredients using a three-point cantilever bending technique. Most of the experiments were carried out on polysaccharide-based ingredients-guar hydroxypropyltrimonium chloride (Guar HPTC) and cassia hydroxypropyltrimonium chloride (Cassia HPTC)-to establish basic characterization concepts of the polymer-fiber assemblies. METHODS: A three-point cantilever bending technique was developed using a texture analyzer housed in a temperature and humidity-controlled chamber. Scanning electron microscopy (SEM) studies were conducted to monitor the fracture mechanics of polymer-fiber assemblies. RESULTS: Fundamental studies were carried out to determine the effect of concentration, molecular weight (MW), and chemistry of the polysaccharides on the calculated indices, which characterize the stiffness, flexibility, elasticity, and plasticity of the treated hair. Experiments were conducted in a controlled temperature and humidity environment, which allowed us to monitor the behavior of the polymer-treated hair from 40-90% RH. Studies were also conducted on polymer blends and conventional styling polymers to provide guidance of the performance of naturally-derived polymers to their synthetic counterparts. CONCLUSIONS: A detailed description is provided for a user-friendly, quick method to measure the mechanical properties of styling ingredients on hair. We provide guidelines for three-point cantilever bending tests of straight hair tresses treated with conventional and naturally-derived styling polymers. Indices were developed to characterize the force-distance curves and were designated as E1, F1, position of F1, post-fracture gradient, toughness, E10/E1, and F10/F1. These indices provide an overall characterization of the stiffness, flexibility, elasticity, and plasticity of polymer-treated hair.

Hair-Bearing Expanded Scalp Flap for Total Beard Reconstruction in Patients With Chin and Submental Postburn Scars.

BACKGROUND: Loss of beard in adult male caused by severe burn may cause cosmetic and psychological problems for these patients. Reconstruction of the beard with hair-bearing skin flaps in similar color and texture of the surrounding tissues remains a challenge. METHODS: Eight male patients suffered from submental postburn scar and beard loss were treated by using the hair-bearing expanded scalp flap. A 1000 mL nephroid tissue expander was first implanted under the frontal and mid scalp. After a 3 to 4-month tissue expansion, the expanded hair-bearing scalp flap based on bilateral superficial temporal vessels were raised and transferred for beard reconstruction, and the cutaneous pedicles were curled into tubes. Delay and division of the pedicles were performed 3 to 4 weeks after flap transfer. RESULTS: Eight male patients with postburn scar and beard loss were successfully treated with no major complication. One patient suffered from edge necrosis at distal end of the flap and healed after daily dressing change. Chin and submental areas were repaired by expanded scalp flap and total beard was reconstructed at the same time. All donor sites were closed directly without skin grafting. CONCLUSIONS: The modified expanded bipedicled scalp flap provides an easy and reliable way for total beard reconstruction and large-scale submental scars repairment.

A Causal Treatment for X-Linked Hypohidrotic Ectodermal Dysplasia: Long-Term Results of Short-Term Perinatal Ectodysplasin A1 Replacement.

X-linked hypohidrotic ectodermal dysplasia (XLHED), caused by a genetic deficiency of ectodysplasin A1 (EDA1), is a rare developmental disorder of ectodermal derivatives such as hair, sweat glands, and teeth. The absence of sweat glands and perspiration can evoke life-threatening hyperthermia. As molecular genetic findings are not always conclusive, the concentrations of circulating EDA1 may help to distinguish between total and partial EDA1 deficiencies. We previously treated nine male patients with obvious signs of XLHED with a recombinant EDA1 replacement protein, Fc-EDA, either shortly after birth (n = 3) or by prenatal administration in gestational week 26 and beyond (n = 6). Here, we present the long-term follow-up for up to six years. In patients who had received Fc-EDA after birth, neither sweat glands nor sweating ability were detected at the age of 12-60 months. In contrast, prenatal EDA1 replacement resulted in ample sweat gland development and pilocarpine-inducible sweating in all treated subjects, who also attained more permanent teeth than their untreated affected relatives. Normal perspiration has persisted for six years in the two oldest boys treated repeatedly with Fc-EDA in utero. When they had a sauna, adequate thermoregulation was evidenced. Lower sweat production after single prenatal dosing may indicate a dose-response relationship. The absence of circulating EDA1 in five prenatally treated subjects proved that these children would have been unable to perspire if they had been left untreated. The sixth infant was shown to produce an EDA1 molecule that, albeit interacting with its cognate receptor, cannot activate EDA1 signaling. In conclusion, a causal treatment of XLHED before birth is feasible.

Hair surface interactions against different chemical functional groups as a function of environment and hair condition.

OBJECTIVE: The nature and magnitude of molecular interactions on hair surfaces underpin the design of formulated products, of which the application involves a competitive adsorption process between cationic surfactants, fatty alcohols and surface actives such as silicone. The knowledge of molecular interaction with hair surface will not only provide insight on the surface binding affinity but also offer an effective methodology in characterizing surface deposits. METHODS: Untreated and chemically treated hair samples were treated with either conditioner chassis alone (gel network) or conditioner chassis plus silicone (chassis/TAS). Hair surface interactions against four different chemical functional groups, namely methyl (-CH3 ), acid (-COOH), amine (-NH2 ) and hydroxyl (-OH), were quantified in both ambient and aqueous environment using Chemical Force Microscopy, a method based on atomic force microscopy (AFM). RESULTS: Surface adhesion on hair in ambient is dominated by capillary force that is determined by both the wettability of hair fibre (hydrophobic vs. hydrophilic), presence of any deposits and the chemical functionality of the AFM cantilever. Capillary force is diminished and replaced by electrostatic interaction when polar groups are present on both hair and AFM cantilever. A distinctively different force, hydrophobic interaction, plays a major role when virgin hair and hydrophobic functionalized AFM cantilever make contact in water. CONCLUSION: Results acquired by AFM cantilevers of different functional groups show that hydrophobic interaction is a key driver for deposition on virgin hair, whilst electrostatic interaction is the most important one for bleached hair. Interfacial conformation of chassis components upon deposition is determined by the hair surface properties. Our study highlights the possibility of a range of polar groups, not necessarily negatively charged, on the damaged hair. Unlike conventional surface chemical analysis method, it is possible to quantitatively evaluate the interfacial conformation of deposited surface actives on hair, which identifies the target moieties for conditioning products on different types of hair.

OBJECTIF: La nature et l'intensité des interactions moléculaires mesurables à la surface d'un cheveu, caractérisent l'effet de la formulation du produit initialement appliqué sur le cheveu. L'application du produit et son effet sur le cheveu repose sur un mécanisme d'adsorption complexe combinant l'effet de différents éléments tels que des surfactants cationiques, des alcools gras et des agents de surface tel que le silicone. L'étude et l'analyse des interactions moléculaires à la surface du cheveu permettent non seulement de déterminer l'affinité adhésive de surface, mais aussi d'offrir une méthode efficace pour caractériser les dépôts de surface. MÉTHODE: Des cheveux initialement traités et non-traités chimiquement, ont été analysés après l'application d'un après-shampoing chassis (structure en gel) ou d'un après-shampoing chassis avec du silicone (chassis/TAS). Les interactions entre la surface du cheveu et quatre groupes fonctionnels chimiques - méthyle (-CH3 ), acide (-COOH), amine (-NH2) et hydroxy (-OH) ont été quantifiées à l'air et en milieu aqueux par microscopie à force chimique, une méthode basée sur la microscopie à force atomique (AFM). RÉSULTATS: L'adhésion de surface sur cheveu à l'air est dominée par la force capillaire qui est déterminée par la mouillabilité de la fibre capillaire (hydrophobe vs. hydrophile), la présence de dépôts, et la fonction chimique du cantilever. La force capillaire diminue et est remplacée par des interactions électrostatiques quand des groupes polaires sont présents à la fois sur le cheveu et le cantilever. Une autre force - l'interaction hydrophobe, joue un rôle majeur quand un cheveu non-traité / vierge et un cantilever de fonction hydrophobe se rencontrent en milieu aqueux. CONCLUSIONS: Les résultats obtenus à partir de cantilevers de différentes fonctions chimiques, montrent que l'interaction hydrophobe joue un rôle clé dans l'application de produit capillaire sur cheveux non-traité tandis que les interactions électrostatiques sont prédominantes dans le cas de cheveux traités chimiquement. La conformation interfaciale des composés chassis avant déposition est déterminée par les propriétés de surface du cheveu. Notre étude souligne la présence potentielle de différents groupes polaires, pas nécessairement chargés négativement, sur la surface de cheveux endommagés. A l'inverse des méthodes conventionnelles d'analyse chimique de surface, il est possible d'évaluer quantitativement la conformation interfaciale de dépôts d'agents actifs présents à la surface du cheveu, ce qui permet d'identifier les zones cibles pour l'application d'après-shampoing sur différents types de cheveux.

CRISPR/Cas9-mediated deletion of Fam83h induces defective tooth mineralization and hair development in rabbits.

Family with sequence similarity 83 members H (Fam83h) is essential for dental enamel formation. Fam83h mutations cause human amelogenesis imperfecta (AI), an inherited disorder characterized by severe hardness defects in dental enamel. Nevertheless, previous studies showed no enamel defects in Fam83h-knockout/lacZ-knockin mice. In this study, a large deletion of the Fam83h gene (900 bp) was generated via a dual sgRNA-directed CRISPR/Cas9 system in rabbits. Abnormal tooth mineralization and loose dentine were found in homozygous Fam83h knockout (Fam83h-/- ) rabbits compared with WT rabbits. In addition, reduced hair follicle counts in dorsal skin, hair cycling dysfunction and hair shaft differentiation deficiency were observed in Fam83h-/- rabbits. Moreover, X-rays and staining of bone sections showed abnormal bending of the ulna and radius and an ulnar articular surface with insufficient trabecular bone in Fam83h-/- rabbits. Taken together, these data are the first report of defective hair cycling, hair shaft differentiation and abnormal bending of the ulna and radius in Fam83h-/- rabbits. This novel Fam83h-/- rabbit model may facilitate understanding the function of Fam83h and the pathogenic mechanism of the Fam83h mutation.

Biomarkers of environmental manganese exposure.

We conducted a critical review on biomarkers of environmental manganese (Mn) exposure to answer the following questions: 1) are there reliable biomarkers of internal Mn exposure (Mn in biological matrices) associated with external metrics of Mn exposure (Mn in environmental media)? and 2) are there accurate reference values (RVs) for Mn in biological matrices? Three bibliographic databases were searched for relevant references and identified references were screened by two independent reviewers. Of the 6342 unique references identified, 86 articles were retained for data abstraction. Our analysis of currently available evidence suggests that Mn levels in blood and urine are not useful biomarkers of Mn exposure in non-occupational settings. The strength of the association between Mn in environmental media and saliva was variable. Findings regarding the utility of hair Mn as a biomarker of environmental Mn exposure are inconsistent. Measurements of Mn in teeth are technically challenging and findings on Mn in tooth components are scarce. In non-occupationally exposed individuals, bone Mn measurements using in vivo neutron activation analysis (IVNAA) are associated with large uncertainties. Findings suggest that Mn in nails may reflect Mn in environmental media and discriminate between groups of individuals exposed to different environmental Mn levels, although more research is needed. Currently, there is no strong evidence for any biological matrix as a valid biomarker of Mn exposure in non-occupational settings. Because of methodological limitations in studies aimed at derivation of RVs for Mn in biological materials, accurate RVs are scarce.