Role of CPI-17 in restoring skin homoeostasis in cutaneous field of cancerization: effects of topical application of a film-forming medical device containing photolyase and UV filters

Cutaneous field of cancerization (CFC) is caused in part by the carcinogenic effect of the cyclobutane pyrimidine dimers CPD and 6‐4 photoproducts (6‐4PPs). Photoreactivation is carried out by photolyases which specifically recognize and repair both photoproducts. The study evaluates the molecular effects of topical application of a film‐forming medical device containing photolyase and UV filters on the precancerous field in AK from seven patients. Skin improvement after treatment was confirmed in all patients by histopathological and molecular assessment. A gene set analysis showed that skin recovery was associated with biological processes involved in tissue homoeostasis and cell maintenance. The CFC response was associated with over‐expression of the CPI‐17 gene, and a dependence on the initial expression level was observed (P = 0.001). Low CPI‐17 levels were directly associated with pro‐inflammatory genes such as TNF (P = 0.012) and IL‐1B (P = 0.07). Our results suggest a role for CPI‐17 in restoring skin homoeostasis in CFC lesions

La formación ético-cívica y el compromiso social de los estudiantes universitarios

Estamos siendo testigos en estas últimas décadas de una creciente preocupación internacional por el escaso compromiso social de los jóvenes, que se manifiesta en su baja participación social, el exiguo interés que muestran por la política formal y la insignificante participación electoral que ejercen. El esquema que seguimos es, en primer lugar, dibujar el marco internacional en que nos movemos. Después se indaga en la formación ético-cívica del alumnado universitario en el marco de la tercera misión de la universidad y del Espacio Europeo de Educación Superior. Posteriormente tratamos de una de las iniciativas más fructíferas en este ámbito: el service learning. Finalizamos haciendo una propuesta de algunas sugerencias para la educación superior. Está latente a lo largo del artículo la necesidad de la suscitación de una formación ético-cívica como clave para la promoción del compromiso social de los jóvenes

Differential Analysis of Proteins Involved in Ester Metabolism in two Saccharomyces cerevisiae Strains during the Second Fermentation in Sparkling Wine Elaboration

The aromatic metabolites derived from yeast metabolism determine the characteristics of aroma and taste in wines, so they are considered of great industrial interest. Volatile esters represent the most important group and therefore, their presence is extremely important for the flavor profile of the wine. In this work, we use and compare two Saccharomyces cerevisiae yeast strains: P29, typical of sparkling wines resulting of second fermentation in a closed bottle; G1, a flor yeast responsible for the biological aging of Sherry wines. We aimed to analyze and compare the effect of endogenous CO2 overpressure on esters metabolism with the proteins related in these yeast strains, to understand the yeast fermentation process in sparkling wines. For this purpose, protein identification was carried out using the OFFGEL fractionator and the LTQ Orbitrap, following the detection and quantification of esters with gas chromatograph coupled to flame ionization detector (GC-FID) and stir-bar sorptive extraction, followed by thermal desorption and gas chromatography-mass spectrometry (SBSE-TD-GC-MS). Six acetate esters, fourteen ethyl esters, and five proteins involved in esters metabolism were identified. Moreover, significant correlations were established between esters and proteins. Both strains showed similar behavior. According to these results, the use of this flor yeast may be proposed for the sparkling wine production and enhance the diversity and the typicity of sparkling wine yeasts

Fibroblasts activation and abnormal extracellular matrix remodelling as common hallmarks in three cancer-prone genodermatoses

Background. Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer-prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders. Objectives. To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC. Methods. We conducted RNA-Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies. Results. Interdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analyses validated the RNA-Seq data. In addition, enzyme-linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB. Conclusions. Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury-sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS.This study was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2013-43475R, SAF2017-88908-R and SAF2017-86810-R); from Instituto de Salud Carlos III and CIBERER, cofunded with European Regional Development Funds (ERDF) (PT13/0001/0007, PI14/00931, PI15/00716, PI15/00956, PT17/0009/0006 and PI17/01747); and from the European Union (HEALTH-F2-2011-261392 and H2020-INFRADEV-1-2015-1/ELIXIR-EXCELERATEref. 676559). Additional funding from Comunidad de Madrid (AvanCell-CM S2017/BMD-3692); Catalan Government (AGAUR 2014_SGR_603); ‘Fundacio' La Marató de TV3, 01331-30’; CERCA Programme/Generalitat de Catalunya; and ‘Fundación Científica de la Asociación Española Contra el Cáncer’, Spain

Monitoring treatment of field cancerisation with 3% diclofenac sodium 2.5% hyaluronic acid by reflectance confocal microscopy: a histologic correlation

Visual inspection may fail to accurately evaluate field cancerisation (subclinical actinic keratoses [AKs]). We aimed to describe field cancerisation by confocal reflectance microscopy and changes induced by the application of 3% diclofenac sodium gel in 2.5% hyaluronic acid. Fourteen male patients, > 50 years old, with AKs on the bald scalp were included. Clinical examination, confocal microscopy and histological study of clinically visible lesions and 'normal appearing' adjacent skin before and after treatment was completed. Reflectance confocal microscopy showed a decrease in scaling (p = 0.001) and atypia of the honeycomb pattern (p = 0.001) at 2 weeks of treatment. Changes in parakeratosis, inflammation and dermal collagen remodelling were also observed. Histology correlated with confocal features in AK and subclinical AK. Reflectance confocal microscopy was useful in the evaluation of field cancerisation and monitoring of treatment response. A rapid improvement in epidermal atypia was observed

Correction: Porous monoliths synthesized via polymerization of styrene and divinyl benzene in nonaqueous deep-eutectic solvent-based HIPEs (RSC Advances (2015) 5 (23255-23260) DOI: 10.1039/C5RA02374B)

© 2018 The Royal Society of Chemistry. The authors regret that there was an error in the results and discussion section of the original article. On page 23257, the text read, The surfactant employed here was sorbitan monooleate . This should have read, The surfactant employed here was sorbitan stearate . The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers

Machine Learning-Based Rockfalls Detection with 3D Point Clouds, Example in the Montserrat Massif (Spain)

Rock slope monitoring using 3D point cloud data allows the creation of rockfall inventories, provided that an efficient methodology is available to quantify the activity. However, monitoring with high temporal and spatial resolution entails the processing of a great volume of data, which can become a problem for the processing system. The standard methodology for monitoring includes the steps of data capture, point cloud alignment, the measure of differences, clustering differences, and identification of rockfalls. In this article, we propose a new methodology adapted from existing algorithms (multiscale model to model cloud comparison and density-based spatial clustering of applications with noise algorithm) and machine learning techniques to facilitate the identification of rockfalls from compared temporary 3D point clouds, possibly the step with most user interpretation. Point clouds are processed to generate 33 new features related to the rock cliff differences, predominant differences, or orientation for classification with 11 machine learning models, combined with 2 undersampling and 13 oversampling methods. The proposed methodology is divided into two software packages: point cloud monitoring and cluster classification. The prediction model applied in two study cases in the Montserrat conglomeratic massif (Barcelona, Spain) reveal that a reduction of 98% in the initial number of clusters is sufficient to identify the totality of rockfalls in the first case study. The second case study requires a 96% reduction to identify 90% of the rockfalls, suggesting that the homogeneity of the rockfall characteristics is a key factor for the correct prediction of the machine learning models

All chemical YBa2Cu3O7 superconducting multilayers: Critical role of CeO2 cap layer flatness

New advances toward microstructural improvement of epitaxial Ce0 2 films grown by chemical solution deposition and their use as buffer layers for YBa2Cu3O7 (YBCO) films are presented. We demonstrate that the degree of epitaxy and the fraction of (001) atomically flat surface area are controlled by the incorporation of tetravalent (Zr4+) or trivalent (Gd3+) cations into the ceria lattice. The degree of epitaxy has been investigated by means of Rutherford backscattering spectroscopy-channeling and reflection high-energy electron diffraction. In addition, we use a new methodology to quantify the fraction of (001) atomically flat area from atomic force microscopy images. Results are further correlated with the superconducting properties, microstructure, and texture of YBCO films grown by the trifluoroacetate route. A comparison with pulsed laser deposition and YBCO films grown on the same ceria layers is also presented. This growth procedure has allowed us to obtain all chemical multilayer films with controlled microstructure and critical current densities above 4 MA cm-2 at 77 K. © 2009 Materials Research Society.We acknowledge the financial support from MEC (MAT2005-02047, and CONSOLIDER NANOSELECT), Generalitat de Catalunya (Catalan Pla de Recerca SGR-0029 and CeRMAE), EU (HIPERCHEM, NMP4-CT2005-516858). J. Gàzquez, M. Coll, and A. Pomar are grateful to Spanish Ministery of Educacion y Ciencia (MEC) for financial support through Formacion de Personal Investigador (FPI), Formacion de Profesorado Universitario (FPU), and “Ramón y Cajal” programs.Peer Reviewe

Development of cutaneous toxicities during selective anti-BRAF therapies: preventive role of combination with MEK inhibitors

Activated BRAF mutations affecting the mitogen-activated protein kinases (MAPK) pathway are present in 50% of metastatic melanomas. Targeted therapies have been developed to block such mutations (1, 2). There is a risk of other components of the MAPK signalling pathway, such as MEK, being reactivated after the use of BRAF inhibitors (3-5). Given the evidence of drug resistance and side-effects of BRAF inhibitors, combined treatments with BRAF and MEK inhibitors are being tested in clinical trials for metastatic melanoma. Trametinib is one of these MEK inhibitors. Skin toxicities from BRAF inhibitors, such as photosensitivity, palmoplantar keratoderma (PPK) and keratosis pilaris (KP), have been reported (4, 6-11). Also, non-melanoma skin cancers (NMSC) are considered one of the most significant sideeffects (3, 11). We report here the profile of skin toxicities from vemurafenib, dabrafenib alone, or dabrafenib and trametinib combined treatment