Characterization of Tight Junctions and Their Disruption by UVB in Human Epidermis and Cultured Keratinocytes

It has not been confirmed whether tight junctions (TJs) function as a paracellular permeability barrier in adult human skin. To clarify this issue, we performed a TJ permeability assay using human skin obtained from abdominal plastic surgery. Occludin, a marker protein of TJs, was expressed in the granular layer, in which a subcutaneously injected paracellular tracer, Sulfo-NHS-LC-Biotin (556.59Da), was halted. Incubation with ochratoxin A decreased the expression of claudin-4, an integral membrane protein of TJs, and the diffusion of paracellular tracer was no longer prevented at the TJs. These results demonstrate that human epidermis possesses TJs that function as an intercellular permeability barrier at least against small molecules (∼550Da). UVB irradiation of human skin xenografts and human skin equivalents (HSEs) resulted in functional deterioration of TJs. Immunocytochemical staining of cultured keratinocytes showed that occludin was localized into dot-like shapes and formed a discontinuous network when exposed to UVB irradiation. Furthermore, UVB irradiation downregulated the active forms of Rac1 and atypical protein kinase C, suggesting that their inactivation caused functional deterioration of TJs. In conclusion, TJs function as a paracellular barrier against small molecules (∼550Da) in human epidermis and are functionally deteriorated by UVB irradiation

Scientific rationale for Uranus and Neptune <i>in situ</i> explorations

The ice giants Uranus and Neptune are the least understood class of planets in our solar system but the most frequently observed type of exoplanets. Presumed to have a small rocky core, a deep interior comprising ∼70% heavy elements surrounded by a more dilute outer envelope of H2 and He, Uranus and Neptune are fundamentally different from the better-explored gas giants Jupiter and Saturn. Because of the lack of dedicated exploration missions, our knowledge of the composition and atmospheric processes of these distant worlds is primarily derived from remote sensing from Earth-based observatories and space telescopes. As a result, Uranus's and Neptune's physical and atmospheric properties remain poorly constrained and their roles in the evolution of the Solar System not well understood. Exploration of an ice giant system is therefore a high-priority science objective as these systems (including the magnetosphere, satellites, rings, atmosphere, and interior) challenge our understanding of planetary formation and evolution. Here we describe the main scientific goals to be addressed by a future in situ exploration of an ice giant. An atmospheric entry probe targeting the 10-bar level, about 5 scale heights beneath the tropopause, would yield insight into two broad themes: i) the formation history of the ice giants and, in a broader extent, that of the Solar System, and ii) the processes at play in planetary atmospheres. The probe would descend under parachute to measure composition, structure, and dynamics, with data returned to Earth using a Carrier Relay Spacecraft as a relay station. In addition, possible mission concepts and partnerships are presented, and a strawman ice-giant probe payload is described. An ice-giant atmospheric probe could represent a significant ESA contribution to a future NASA ice-giant flagship mission

Neonatal Skin Maturation-Vernix Caseosa and Free Amino Acids

Abstract: Neonatal skin hydration decreases rapidly postnatally and then increases, indicating adaptive changes in stratum corneum water handling properties. Transition from high to low humidity at birth may initiate filaggrin proteolysis to free amino acids. Neonatal skin with vernix caseosa retained is more hydrated than skin with vernix removed. This study examines the potential roles of free amino acids and vernix in postnatal adaptation of infant stratum corneum in vivo. Specifically, the ontogeny of free amino acid generation in neonatal stratum corneum and the role of vernix caseosa in postnatal adaptation were examined using high performance liquid chromatography. Free amino acids were quantified for infant skin samples collected at (i) birth and 1 month and (ii) birth and 24 hours after vernix caseosa retention or removal and compared to neonatal foreskin, vernix caseosa, and adult stratum corneum using t-tests, analysis of variance, or univariate procedures. Free amino acids were extremely low at birth, significantly higher 1 month later but lower than in adults. Vernix caseosa retention led to significantly higher free amino acids 24 hours after birth compared to infants with vernix caseosa removed, and it paralleled the higher stratum corneum hydration of vernix caseosa-retained skin. Vernix caseosa contained free amino acids, with glutamic acid and histidine levels higher than in infants. Free amino acids in vernix caseosa-retained skin appear to originate from vernix caseosa. Free amino acids were lower in neonatal foreskin than adult forearm stratum corneum. Arginine was higher than citrulline at birth, but levels were comparable in older infants. The free amino acid increase at 1 month may be initiated by the humidity transition at birth and supports results in animals. The findings have implications for infant skin care practices