There is increasing evidence for the generation of reactive oxygen species in skin upon ultraviolet exposure, but little is known about their pathophysiologic relevance in human skin in vivo. We hypothesized that chronic and acute photodamage is mediated by depleted antioxidant enzyme expression and increased oxidative protein modifications. Biopsies from patients with histologically confirmed solar elastosis, from non-ultraviolet-exposed sites of age-matched controls, and from young subjects were analyzed. To evaluate the influence of acute ultraviolet exposures, buttock skin of 12 healthy subjects was irradiated repetitively on 10 d with a solar simulator and compared intraindividually to non-ultraviolet-treated contralateral sites. The antioxidant enzymes catalase, copper-zinc superoxide dismutase, and manganese superoxide dismutase were investigated by immunohistochemistry. Protein carbonyls were analyzed by immunohistochemical and immunoblotting techniques in human skin and in cell models. Whereas overall expression of antioxidant enzymes was very high in the epidermis, low baseline levels were found in the dermis. In photoaged skin, a significant depletion of antioxidant enzyme expression was observed within the stratum corneum and in the epidermis. Importantly, an accumulation of oxidatively modified proteins was found specifically within the upper dermis of photoaged skin. Upon acute ultraviolet exposure of healthy subjects, depleted catalase expression and increased protein oxidation were detected. Exposures of keratinocytes and fibroblasts to ultraviolet B, ultraviolet A, and H2O2 led to dose-dependent protein oxidation and thus confirmed in vivo results. In conclusion, the correlation between photodamage and protein oxidation was demonstrated for the first time, which hence may be a relevant pathophysiologic factor in photoaging.

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Background: Multiple studies have compared the performance of artificial intelligence (AI)ebased models for automated skin cancer classification to human experts, thus setting the cornerstone for a successful translation of AI-based tools into clinicopathological practice.

Spontaneous melanoma phenotype switching is controlled by unknown environmental factors and may determine melanoma outcome and responsiveness to anticancer therapy. We show that Orai1 and STIM2 are highly expressed and control store-operated Ca(2+) entry in human melanoma. Lower extracellular Ca(2+) or silencing of Orai1/STIM2 caused a decrease in intracellular Ca(2+) , which correlated with enhanced proliferation and increased expression of microphthalmia-associated transcription factor, a marker for proliferative melanoma phenotype. In contrast, the invasive and migratory potential of melanoma cells was reduced upon silencing of Orai1 and/or STIM2. Accordingly, markers for a non-proliferative, tumor-maintaining phenotype such as JARID1B and Brn2 decreased. Immunohistochemical staining of primary melanomas and lymph node metastases revealed a heterogeneous distribution of Orai1 and STIM2 with elevated expression in the invasive rim of the tumor. In summary, our results support a dynamic model in which Orai1 and STIM2 inversely control melanoma growth and invasion. Pharmacological tuning of Orai1 and particularly STIM2 might thus prevent metastatic spread and render melanomas more susceptible to conventional therapy.

Polymetallic nodules (manganese nodules) have been formed on deep sea sediments over millions of years and are currently explored for their economic potential, particularly for cobalt, nickel, copper, and manganese. Here we explored microbial communities inside nodules from the northeastern equatorial Pacific. The nodules have a large connected pore space with a huge inner surface of 120 m(2)/g as analyzed by computer tomography and BET measurements. X-ray photoelectron spectroscopy (XPS) and electron microprobe analysis revealed a complex chemical fine structure. This consisted of layers with highly variable Mn/Fe ratios (<1 to >500) and mainly of turbostratic phyllomanganates such as 7 and 10 Å vernadites alternating with layers of Fe-bearing vernadite (δ-MnO2) epitaxially intergrown with amorphous feroxyhyte (δ-FeOOH). Using molecular 16S rRNA gene techniques (clone libraries, pyrosequencing, and real-time PCR), we show that polymetallic nodules provide a suitable habitat for prokaryotes with an abundant and diverse prokaryotic community dominated by nodule-specific Mn(IV)-reducing and Mn(II)-oxidizing bacteria. These bacteria were not detected in the nodule-surrounding sediment. The high abundance and dominance of Mn-cycling bacteria in the manganese nodules argue for a biologically driven closed manganese cycle inside the nodules relevant for their formation and potential degradation.