E-Skin Development and Prototyping via Soft Tooling and Composites with Silicone Rubber and Carbon Nanotubes

The strategy of embedding conductive materials on polymeric matrices has produced functional and wearable artificial electronic skin prototypes capable of transduction signals, such as pressure, force, humidity, or temperature. However, these prototypes are expensive and cover small areas. This study proposes a more affordable manufacturing strategy for manufacturing conductive layers with 6 × 6 matrix micropatterns of RTV-2 silicone rubber and Single-Walled Carbon Nanotubes (SWCNT). A novel mold with two cavities and two different micropatterns was designed and tested as a proof-of-concept using Low-Force Stereolithography-based additive manufacturing (AM). The effect SWCNT concentrations (3 wt.%, 4 wt.%, and 5 wt.%) on the mechanical properties were characterized by quasi-static axial deformation tests, which allowed them to stretch up to ~160%. The elastomeric soft material’s hysteresis energy (Mullin’s effect) was fitted using the Ogden–Roxburgh model and the Nelder–Mead algorithm. The assessment showed that the resulting multilayer material exhibits high flexibility and high conductivity (surface resistivity ~7.97 × 104 Ω/sq) and that robust soft tooling can be used for other devices.

Transcriptome Analysis Reveals Candidate Genes Regulating the Skin and Hair Diversity of Xinji Fine-Wool Sheep and Tan Sheep

The hair follicle is a complex mini-organ in the skin that undergoes organ induction, morphogenesis, and regeneration. However, the accurate molecular mechanism of skin and hair diversity regulation is still elusive. The sheep is an animal model that can be used to further explore the mechanisms of skin and hair diversity. In this study, we carried out a transcriptomic analysis of the mRNA expression in the skin of Xinji fine-wool sheep at different growth stages (3 and 12 months old) and 12-month-old Tan sheep and explored the transcripts’ relationship with hair follicle growth. A total of 1327 mRNAs and 67 transcription factors were identified to be differentially expressed in the different breeds and during different periods of skin development. The differentially expressed genes were enriched in GO terms represented by system development, multicellular organism development, animal organ development, and skin development, and three KEGG pathways typified those governing differences in skin structure. Combining protein–protein interaction networks of skin development (GO:0043588) and functional annotation, nine important candidate genes, namely, LAMA5, OVOL1, SRF, DHCR24, NGFR, SMO, CDSN, HOXC13, and KDF1, and many core genes with minor effects were confirmed to be associated with hair follicle development. Furthermore, members of the zf-C2H2 and homeobox transcription factor families, which were identified to play a crucial role in producing finer and denser wool, were mainly upregulated in 12-month-old Xinji fine-wool sheep when compared with expression in 12-month-old Tan sheep and 3-month-old Xinji fine-wool sheep. This study revealed the major–minor gene interactions in the developmental pathway and provided ideas for an in-depth understanding of the genetic structure and gene regulation in the skin/hair growth process.

NFAT5 Controls the Integrity of Epidermis

The skin protects the human body against dehydration and harmful challenges. Keratinocytes (KCs) are the most abundant epidermal cells, and it is anticipated that KC-mediated transport of Na+ ions creates a physiological barrier of high osmolality against the external environment. Here, we studied the role of NFAT5, a transcription factor whose activity is controlled by osmotic stress in KCs. Cultured KCs from adult mice were found to secrete more than 300 proteins, and upon NFAT5 ablation, the secretion of several matrix proteinases, including metalloproteinase-3 (Mmp3) and kallikrein-related peptidase 7 (Klk7), was markedly enhanced. An increase in Mmp3 and Klk7 RNA levels was also detected in transcriptomes of Nfat5-/- KCs, along with increases of numerous members of the ‘Epidermal Differentiation Complex’ (EDC), such as small proline-rich (Sprr) and S100 proteins. NFAT5 and Mmp3 as well as NFAT5 and Klk7 are co-expressed in the basal KCs of fetal and adult epidermis but not in basal KCs of newborn (NB) mice. The poor NFAT5 expression in NB KCs is correlated with a strong increase in Mmp3 and Klk7 expression in KCs of NB mice. These data suggests that, along with the fragile epidermis of adult Nfat5-/- mice, NFAT5 keeps in check the expression of matrix proteases in epidermis. The NFAT5-mediated control of matrix proteases in epidermis contributes to the manifold changes in skin development in embryos before and during birth, and to the integrity of epidermis in adults.

Time-Resolved Extracellular Matrix Atlas of the Developing Human Skin Dermis

Skin aging is a physiological issue that is still relatively poorly understood. Studies have demonstrated that the dermal extracellular matrix (ECM) plays important roles in skin aging. However, the roles of the changes in ECM characteristics and the molecules that are secreted to the extracellular space and are involved in the formation of the dermal matrix from birth to old age remain unclear. To explore the way in which the ECM microenvironment supports the functions of skin development across different age groups is also poorly understood, we used a decellularization method and matrisome analysis to compare the composition, expression, and function of the dermal ECM in toddler, teenager, adult, and elderly skin. We found that the collagens, glycoproteins, proteoglycans, and regulatory factors that support skin development and interact with these core ECM proteins were differentially expressed at different ages. ECM expression markers occurring during the process of skin development were identified. In addition, our results elucidated the characteristics of ECM synthesis, response to skin development, and the features of the ECM that support epidermal stem cell growth via the basement membrane during skin aging.

Refining models of archaic admixture in Eurasia with ArchaicSeeker 2.0

We developed a method, ArchaicSeeker 2.0, to identify introgressed hominin sequences and model multiple-wave admixture. The new method enabled us to discern two waves of introgression from both Denisovan-like and Neanderthal-like hominins in present-day Eurasian populations and an ancient Siberian individual. We estimated that an early Denisovan-like introgression occurred in Eurasia around 118.8–94.0 thousand years ago (kya). In contrast, we detected only one single episode of Denisovan-like admixture in indigenous peoples eastern to the Wallace-Line. Modeling ancient admixtures suggested an early dispersal of modern humans throughout Asia before the Toba volcanic super-eruption 74 kya, predating the initial peopling of Asia as proposed by the traditional Out-of-Africa model. Survived archaic sequences are involved in various phenotypes including immune and body mass (e.g., ZNF169), cardiovascular and lung function (e.g., HHAT), UV response and carbohydrate metabolism (e.g., HYAL1/HYAL2/HYAL3), while “archaic deserts” are enriched with genes associated with skin development and keratinization.

What Do We Know about Pruritus in Very Young Infants? A Literature Review

In infants, pruritus is frequently considered as absent because they do not scratch themselves. Because pruritus could induce severe adverse effects in this vulnerable population, we aimed to review existing evidence on the ability of young infants to experience itch and on how to assess itch-related discomfort in this population. A literature review was performed (Pubmed, Google Scholar). Neurological itch pathways are well described. Skin development starts early during gestation. At 34 weeks of gestation, skin is almost complete while skin adaptations occur after birth. Newborn skin is neurologically functional, including the ability for young infants to feel pain. Similarities and interactions between pain and pruritus support the hypothesis that infants could feel pruritus. However, the existence of pruritus in infants has never been evidenced. Many itchy conditions can affect them, suggesting non-negligible prevalence of infant pruritus among which atopic dermatitis (AD) is the most studied disease. Studies reported a negative impact of AD on children and their families. There is no existing validated method to assess pruritus in infants, although they may feel pruritus and chronic pruritus can lead to serious adverse effects. To appropriately diagnose pruritus appears of great interest among young infants. Development of a method is required to this aim.

Comprehensive transcriptome and methylome analysis delineates the biological basis of hair follicle development and wool-related traits in Merino sheep

Background Characterization of the molecular mechanisms underlying hair follicle development is of paramount importance in the genetic improvement of wool-related traits in sheep and skin-related traits in humans. The Merino is the most important breed of fine-wooled sheep in the world. In this study, we systematically investigated the complexity of sheep hair follicle development by integrating transcriptome and methylome datasets from Merino sheep skin. Results We analysed 72 sequence datasets, including DNA methylome and the whole transcriptome of four gene types, i.e. protein-coding genes (PCGs), lncRNAs, circRNAs, and miRNAs, across four embryonic days (E65, E85, E105, and E135) and two postnatal days (P7 and P30) from the skin tissue of 18 Merino sheep. We revealed distinct expression profiles of these four gene types across six hair follicle developmental stages, and demonstrated their complex interactions with DNA methylation. PCGs with stage-specific expression or regulated by stage-specific lncRNAs, circRNAs, and miRNAs were significantly enriched in epithelial differentiation and hair follicle morphogenesis. Regulatory network and gene co-expression analyses identified key transcripts controlling hair follicle development. We further predicted transcriptional factors (e.g. KLF4, LEF1, HOXC13, RBPJ, VDR, RARA, and STAT3) with stage-specific involvement in hair follicle morphogenesis. Through integrating these stage-specific genomic features with results from genome-wide association studies (GWAS) of five wool-related traits in 7135 Merino sheep, we detected developmental stages and genes that were relevant with wool-related traits in sheep. For instance, genes that were specifically upregulated at E105 were significantly associated with most of wool-related traits. A phenome-wide association study (PheWAS) demonstrated that candidate genes of wool-related traits (e.g. SPHK1, GHR, PPP1R27, CSRP2, EEF1A2, and PTPN1) in sheep were also significantly associated with dermatological, metabolic, and immune traits in humans. Conclusions Our study provides novel insights into the molecular basis of hair follicle morphogenesis and will serve as a foundation to improve breeding for wool traits in sheep. It also indicates the importance of studying gene expression in the normal development of organs in understanding the genetic architecture of economically important traits in livestock. The datasets generated here are useful resources for functionally annotating the sheep genome, and for elucidating early skin development in mammals, including humans.

Metabolic Alterations in Preneoplastic Development Revealed by Untargeted Metabolomic Analysis

Metabolic rewiring is a critical hallmark of tumorigenesis and is essential for the development of cancer. Although many key features of metabolic alteration that are crucial for tumor cell survival, proliferation and progression have been identified, these are obtained from studies with established tumors and cancer cell lines. However, information on the essential metabolic changes that occur during pre-neoplastic cell (PNC) development that enables its progression to full blown tumor is still lacking. Here, we present an untargeted metabolomics analysis of human oncogene HRASG12V induced PNC development, using a transgenic inducible zebrafish larval skin development model. By comparison with normal sibling controls, we identified six metabolic pathways that are significantly altered during PNC development in the skin. Amongst these altered pathways are pyrimidine, purine and amino acid metabolism that are common to the cancer metabolic changes that support rapid cell proliferation and growth. Our data also suggest alterations in post transcriptional modification of RNAs that might play a role in PNC development. Our study provides a proof of principle work flow for identifying metabolic alterations during PNC development driven by an oncogenic mutation. In the future, this approach could be combined with transcriptomic or proteomic approaches to establish the detailed interaction between signaling networks and cellular metabolic pathways that occur at the onset of tumor progression.