Identification of PTPN22, ST6GAL1 and JAZF1 as Psoriasis Risk Genes Demonstrates Shared Pathogenesis between Psoriasis and Diabetes

Abstract

The biological connections between psoriasis and diabetes have been suggested by epidemiological, immunological and genetic studies. To identify additional shared susceptibility loci and investigate shared pathogenesis between these two diseases, we genotyped 89 reported diabetes susceptibility loci in 4,456 psoriasis cases and 6,027 controls of Chinese population using the MassARRAY system from Sequenom. We discovered three significant associations at rs6679677 on 1p13.2 (P = 6.15 × 10^-5, OR = 5.07), rs16861329 on 3q27.3 (P = 2.02 × 10^-4, OR = 0.87), and rs849135 on 7p15.1 (P = 6.59 × 10^-9, OR = 1.78), which suggested PTPN22, ST6GAL1 and JAZF1 as novel susceptibility genes for psoriasis in Chinese population. Our findings implicated the involvement of T-cell receptor signaling pathway in the pathogenesis of psoriasis and further confirmed the shared genetic susceptibility between psoriasis and diabetes.

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Mutation in IL36RN impairs the processing and regulatory function of the interleukin-36 receptor antagonist and is associated with DITRA syndrome

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Getting to the root of scales, feather and hair: as deep as odontodes?

Abstract

While every jawed vertebrate, or its recent ancestor, possesses teeth, skin appendages are characteristic of the living clades: skin denticles (odontodes) in chondrichthyians, dermal scales in teleosts, ducted multicellular glands in amphibians, epidermal scales in squamates, feathers in birds, and hair-gland complexes in mammals, all of them showing a dense periodic patterning. While the odontode origin of teleost scales is generally accepted, the origin of both feather and hair is still debated. They appear long before mammals and birds, at least in Jurassic in mammaliaforms and in ornithodires (pterosaurs and dinosaurs), and are contemporary to scales of early squamates. Epidermal scales might have appeared several times in evolution, and basal amniotes could not have developed a scaled-dry integument, as the function of hair follicle requires its association with glands. In areas such as amnion, cornea or plantar pads, the formation of feather and hair is prevented early in embryogenesis, but can be easily reverted by playing with the Wnt/BMP/Shh pathways, which both imply the plasticity and the default competence of ectoderm. Conserved ectodermal/mesenchymal signaling pathways lead to placode formation, while later the crosstalk differs, as well as the final performing tissue(s): both epidermis and dermis for teeth and odontodes, mostly dermis for teleosts scales, only epidermis for squamate scale, glands, feather and hair. We therefore suggest that tooth, dermal scale, epidermal scale, feather and hair evolved in parallel from a shared placode/dermal cells unit, which was present in a common ancestor, an early vertebrate gnathostome, c.a. 420 million years ago.

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A 3D in vitro model of the re-epithelialization phase in the wound healing process

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Atopic skin: In vivo Raman identification of global molecular signature, a comparative study with healthy skin

Abstract

Atopic dermatitis (AD) is the most common skin inflammatory disease, affecting up to 3% of adults and 20% of children. Skin barrier impairment is thought to be the primary factor in this disease. Currently, there is no method proposed to monitor non-invasively the different molecular disorders involved in the upper layer of AD skin. Raman microspectroscopy has proved to be a powerful tool to characterize some AD molecular descriptors such as lipid content, global hydration level, filaggrin and its derivatives. Our investigations aimed to extend the use of in vivo Raman microspectroscopy as a rapid and non-invasive diagnostic technique for lipid conformation and organisation, protein secondary structure and bound water content analysis in atopic skin. Our approach was based on the analysis of Raman data collected on the stratum corneum (SC) of 11 healthy and 10 mild to moderate atopic patients. Atopic skin revealed a modification of lipid organisation and conformation in addition to the decrease of the lipid to protein ratio. This study also highlighted a reduction of the bound water and an increase of protein organized secondary structure in atopic skin. All these descriptors worsen the barrier function, state and appearance of the skin in AD. These precise and relevant information will allow an in vivo follow-up of the pathology and a better evaluation of the pharmacological activity of therapeutic molecules for the treatment of AD.

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Reliability of the NICMAN Scale: An Instrument to Assess the Quality of Acupuncture Administered in Clinical Trials

Background. The aim of this study was to examine the reliability of a scale to assess the methodological quality of acupuncture administered in clinical research. Methods. We invited 36 acupuncture researchers and postgraduate students to participate in the study. Firstly, participants rated two articles using the scale. Following this initial stage, modifications were made to scale items and the exercise was repeated. Interrater reliability was assessed for individual items using the Fleiss kappa statistic, whilst the overall scale used the intraclass correlation coefficient statistic. A threshold agreement of ≥0.61 was acceptable. Results. We received 26 responses and a 72% response rate. The first phase of testing found moderate reliability with intraclass correlation coefficients of 0.46 and 0.55 for the articles. The interrater reliability of the scales varied between and within the researchers (0.35, 0.60) and was more consistent with the postgraduate students (0.54, 0.54). Five items on the scale scored below the threshold and were revised for further testing. In this phase the intraclass correlation coefficient demonstrated variability between articles but improved to achieve reliability above the agreed threshold. Conclusion. This study provides evidence of the reliability of the NICMAN scale although improvements to a small number of items remain.

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Flexible Zinc–Tin Oxide Thin Film Transistors Operating at 1 kV for Integrated Switching of Dielectric Elastomer Actuators Arrays

Flexible high-voltage thin-film transistors (HVTFTs) operating at more than 1 kV are integrated with compliant dielectric elastomer actuators (DEA) to create a flexible array of 16 independent actuators. To allow for high-voltage operation, the HVTFT implements a zinc–tin oxide channel, a thick dielectric stack, and an offset gate. At a source–drain bias of 1 kV, the HVTFT has a 20 µA on-current at a gate voltage bias of 30 V. Their electrical characteristics enable the switching of DEAs which require drive voltages of over 1 kV, making control of an array simpler in comparison to the use of external high-voltage switching. These HVTFTs are integrated in a flexible haptic display consisting of a 4 × 4 matrix of DEAs and HVTFTs. Using a single 1.4 kV supply, each DEA is independently switched by its associated HVTFT, requiring only a 30 V gate voltage for full DEA deflection. The 4 × 4 display operates well even when bent to a 5 mm radius of curvature. By enabling DEA switching at low voltages, flexible metal-oxide HVTFTs enable complex flexible systems with dozens to hundreds of independent DEAs for applications in haptics, Braille displays, and soft robotics.

High-voltage flexible thin-film transistors (HVTFTs) that can operate at an unprecedented 1 kV voltage are developed to drive dielectric elastomer actuators (DEAs). 16 HVTFTs are integrated with 16 DEAs, each operating at 1 kV, but individually switched using a 30 V gate voltage. Combining flexible HVTFTs with DEAs will lead to compact, complex, and compliant haptics and soft robotics.

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