Human breast milk exosomes accelerate mouse wound healing

P543 The healing of cutaneous wounds is a very efficient process despite being very complex. Under certain pathological conditions healing may be impaired, prolonging the healing process and eventually leading to medical intervention and the chronicity of the wound. Exosomes are secreted extracellular vesicles present in biological fluids where they play a key role in intercellular communication at the tissue, organ and organismal levels. Given that human breast milk contains abundant maternal extracellular vesicles (MEVs) with pro-regenerative and immunomodulatory properties, the aim of the present study was to evaluate if topical application ofMEVs into open wounds would be beneficial for healing. Full-thickness excision wounds of 4-mm diameter were created in the dorsal skin of C57BL/6 mice and topical application of 20 micrograms of human MEV isolated at weeks 9, 11, 12 and 15 postpartum of breastfeeding were placed onto the open wounds. Control wounds were vehicle-treated. Macroscopic measurements up to 7 days postwounding revealed that the area of the wound treated with MEV significantly decreased compared with controls. Histological analyses at day 7 post-wounding showed no differences in the granulation tissue area between groups. ..

Soluble interleukin-2 receptor, intercellular adhesion molecule-1 and interleukin-10 serum levels in patients withelanoma

Serum soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (sICAM-1) and interleukin-10 (IL-10) have each been reported as useful markers for melanoma progression. To evaluate the clinical relevance of these three markers, we simultaneously analysed their serum levels in patients with melanoma. A longitudinal study with a 3-year follow-up was performed and different stages of the disease were considered. Mean values of sIL-2R were significantly higher than in normal controls in all stages and correlated with the disease progression. The prognosis of patients with levels > 529 U/ml of sIL-2R was significantly poorer than in patients with sIL-2R levels < 529 U/ml. Levels of sICAM-1 were also elevated in melanoma patients, specially at the time of the metastatic disease. Serum IL-10 levels were more frequently detectable in the patients that developed metastasis during follow-up, and the prognosis of patients with detectable IL-10 levels was significantly poorer than in those patients with IL-10 undetected levels. Statistical analysis based on Logistic and Cox regression models showed that only sex, stage and sIL-2R value are factors significantly associated with metastatic progression. Moreover, high levels of sIL-2R could be a risk factor for malignant progression in melanoma. © 2000 Cancer Research Campaig

AgroTutor: A Mobile Phone Application Supporting Agricultural Sustainable Intensification

Traditional agricultural extension services rely on extension workers, especially in countries with large agricultural areas. In order to increase adoption of sustainable agriculture, the recommendations given by such services must be adapted to local conditions and be provided in a timely manner. The AgroTutor mobile application was built to provide highly specific and timely agricultural recommendations to farmers across Mexico and complement the work of extension agents. At the same time, AgroTutor provides direct contributions to the United Nations Sustainable Development Goals, either by advancing their implementation or providing local data systems to measure and monitor specific indicators such as the proportion of agricultural area under productive and sustainable agriculture. The application is freely available and allows farmers to geo-locate and register plots and the crops grown there, using the phone’s in-built GPS, or alternatively, on top of very high-resolution imagery. Once a crop and some basic data such as planting date and cultivar type have been registered, the app provides targeted information such as weather, potential and historical yield, financial benchmarking information, data-driven recommendations as well as commodity price forecasts. Farmers are also encouraged to contribute in-situ information, e.g., soils, management, and yield data. The information can then be used by crop models, which, in turn, would send tailored results back to the farmers. Initial feedback from farmers and extension agents has already improved some of the app’s characteristics. More enhancements are planned for inclusion in the future to increase the app’s function as a decision support tool

AgroTutor: A Mobile Phone Application Supporting Sustainable Agricultural Intensification

Traditional agricultural extension services rely on extension workers, especially in countries with large agricultural areas. In order to increase adoption of sustainable agriculture, the recommendations given by such services must be adapted to local conditions and be provided in a timely manner. The AgroTutor mobile application was built to provide highly specific and timely agricultural recommendations to farmers across Mexico and complement the work of extension agents. At the same time, AgroTutor provides direct contributions to the United Nations Sustainable Development Goals, either by advancing their implementation or providing local data systems to measure and monitor specific indicators such as the proportion of agricultural area under productive and sustainable agriculture. The application is freely available and allows farmers to geo-locate and register plots and the crops grown there, using the phone&rsquo;s built-in GPS, or alternatively, on top of very high-resolution imagery. Once a crop and some basic data such as planting date and cultivar type have been registered, the application provides targeted information such as weather, potential and historical yield, financial benchmarking information, data-driven recommendations, and commodity price forecasts. Farmers are also encouraged to contribute in-situ information, e.g., soils, management, and yield data. The information can then be used by crop models, which, in turn, send tailored results back to the farmers. Initial feedback from farmers and extension agents has already improved some of the application&rsquo;s characteristics. More enhancements are planned for inclusion in the future to increase the application&rsquo;s function as a decision support tool

Beyond the mean gender wage gap : decomposition of differences in wage distributions using quantile regression

Using linked employer-employee data, this study measures and decomposes the differences in the earnings distribution between male and female employees in Germany. I extend the traditional decomposition to disentangle the effect of human capital characteristics and the effect of firm characteristics in explaining the gender wage gap. Furthermore, I implement the decomposition across the whole wage distribution with the method proposed by Machado and Mata (2005). Thereby, I take into account the dependence between the human capital endowment of individuals and workplace characteristics. The selection of women into less successful and productive firms explains a sizeable part of the gap. This selection is more pronounced in the lower part of the wage distribution than in the upper tail. In addition, women also benefit from the success of firms by rent-sharing to a lesser extent than their male colleagues. This is the source of the largest part of the pay gap. Gender differences in human capital endowment as well s differences in returns to human capital are less responsible for the wage differential

Terfenadine induces apoptosis and autophagy in melanoma cells through ROS-dependent and -independent mechanisms

Previously we found that terfenadine, an H1 histamine receptor antagonist, acts as a potent apoptosis inducer in melanoma cells through modulation of Ca2+ homeostasis. In this report, focusing our attention on the apoptotic mechanisms activated by terfenadine, we show that this drug can potentially activate distinct intrinsic signaling pathways depending on culture conditions. Serum-deprived conditions enhance the cytotoxic effect of terfenadine and caspase-4 and -2 are activated upstream of caspase-9. Moreover, although we found an increase in ROS levels, the apoptosis was ROS independent. Conversely, terfenadine treatment in complete medium induced ROS-dependent apoptosis. Caspase-4, -2, and -9 were simultaneously activated and p73 and Noxa induction were involved. ROS inhibition prevented p73 and Noxa expression but not p53 and p21 expression, suggesting a role for Noxa in p53-independent apoptosis in melanoma cells. Finally, we found that terfenadine induced autophagy, that can promote apoptosis. These findings demonstrate the great potential of terfenadine to kill melanoma cells through different cellular signaling pathways and could contribute to define new therapeutic strategies in melanoma

Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing

BACKGROUND: Deficient nucleotide excision repair (NER) activity causes a variety of autosomal recessive diseases including xeroderma pigmentosum (XP) a disorder which pre-disposes to skin cancer, and the severe multisystem condition known as Cockayne syndrome (CS). In view of the clinical overlap between NER-related disorders, as well as the existence of multiple phenotypes and the numerous genes involved, we developed a new diagnostic approach based on the enrichment of 16 NER-related genes by multiplex amplification coupled with next-generation sequencing (NGS). METHODS: Our test cohort consisted of 11 DNA samples, all with known mutations and/or non pathogenic SNPs in two of the tested genes. We then used the same technique to analyse samples from a prospective cohort of 40 patients. Multiplex amplification and sequencing were performed using AmpliSeq protocol on the Ion Torrent PGM (Life Technologies). RESULTS: We identified causative mutations in 17 out of the 40 patients (43 %). Four patients showed biallelic mutations in the ERCC6(CSB) gene, five in the ERCC8(CSA) gene: most of them had classical CS features but some had very mild and incomplete phenotypes. A small cohort of 4 unrelated classic XP patients from the Basque country (Northern Spain) revealed a common splicing mutation in POLH (XP-variant), demonstrating a new founder effect in this population. Interestingly, our results also found ERCC2(XPD), ERCC3(XPB) or ERCC5(XPG) mutations in two cases of UV-sensitive syndrome and in two cases with mixed XP/CS phenotypes. CONCLUSIONS: Our study confirms that NGS is an efficient technique for the analysis of NER-related disorders on a molecular level. It is particularly useful for phenotypes with combined features or unusually mild symptoms. Targeted NGS used in conjunction with DNA repair functional tests and precise clinical evaluation permits rapid and cost-effective diagnosis in patients with NER-defects