Incentivos fiscales al emprendimiento y economía social

En este trabajo se analizan los incentivos fiscales creados en los últimos años por el legislador estatal con la finalidad de fomentar el emprendimiento y su aplicación a las empresas y entidades de la Economía Social. El objetivo de este análisis es evaluar si dichas medidas de carácter tributario cumplen adecuadamente el mandato dirigido a los poderes públicos por el artículo de 8 la Ley de Economía Social, tanto en relación con este sector en su conjunto como con el denominado ¿emprendimiento social¿.-------------------------------------------------------------------------------This work analyses the tax incentives included in the recent state acts oriented to the promotion of the entrepreneurship and his application to the companies and entities of the Social Economy. The aim of this analysis is to evaluate if those tax measures properly fulfil the mandate that article 8 of the Social Economy Act headed to the public powers, in relation with this sector as a whole and with the so called ¿social entrepreneurship¿.Artículo revisado por pare

Citizen science provides a reliable and scalable tool to track disease-carrying mosquitoes

Recent outbreaks of Zika, chikungunya and dengue highlight the importance of better understanding the spread of disease-carrying mosquitoes across multiple spatio-temporal scales. Traditional surveillance tools are limited by jurisdictional boundaries and cost constraints. Here we show how a scalable citizen science system can solve this problem by combining citizen scientists'' observations with expert validation and correcting for sampling effort. Our system provides accurate early warning information about the Asian tiger mosquito (Aedes albopictus) invasion in Spain, well beyond that available from traditional methods, and vital for public health services. It also provides estimates of tiger mosquito risk comparable to those from traditional methods but more directly related to the human-mosquito encounters that are relevant for epidemiological modelling and scalable enough to cover the entire country. These results illustrate how powerful public participation in science can be and suggest citizen science is positioned to revolutionize mosquito-borne disease surveillance worldwide

Sun exposure and PDZK1 genotype modulate PDZK1 gene expression in normal skin

Human skin pigmentation results from the enzymatically controlled synthesis of melanin pigments in specialized organelles (melano‐somes) produced within epidermal melanocytes, followed by their transfer to neighboring keratinocytes and their distribution through‐out the epidermis.1 Constitutive skin pigmentation seems to be mostly genetically determined,2 being altered by numerous intrinsic and extrinsic factors affecting the epidermal melanin uni

First detection of Aedes japonicus in Spain: An unexpected finding triggered by citizen science

Background: Aedes japonicus is an invasive vector mosquito from Southeast Asia which has been spreading across central Europe since the year 2000. Unlike the Asian Tiger mosquito (Aedes albopictus) present in Spain since 2004, there has been no record of Ae. japonicus in the country until now. Results: Here, we report the first detection of Ae. japonicus in Spain, at its southernmost location in Europe. This finding was triggered by the citizen science platform Mosquito Alert. In June 2018, a citizen sent a report via the Mosquito Alert app from the municipality of Siero in the Asturias region (NW Spain) containing pictures of a female mosquito compatible with Ae. japonicus. Further information was requested from the participant, who subsequently provided several larvae and adults that could be classified as Ae. japonicus. In July, a field mission confirmed its presence at the original site and in several locations up to 9 km away, suggesting a long-time establishment. The strong media impact in Asturias derived from the discovery raised local participation in the Mosquito Alert project, resulting in further evidence from surrounding areas. Conclusions: Whilst in the laboratory Ae. japonicus is a competent vector for several mosquito-borne pathogens, to date only West Nile virus is a concern based on field evidence. Nonetheless, this virus has yet not been detected in Asturias so the vectorial risk is currently considered low. The opportunity and effectiveness of combining citizen-sourced data to traditional surveillance methods are discussed

Sex-specific genetic effects associated with pigmentation, sensitivity to sunlight, and melanoma in a population of Spanish origin

Background Human pigmentation is a polygenic quantitative trait with high heritability. In addition to genetic factors, it has been shown that pigmentation can be modulated by oestrogens and androgens via up- or down-regulation of melanin synthesis. Our aim was to identify possible sex differences in pigmentation phenotype as well as in melanoma association in a melanoma case-control population of Spanish origin. Methods Five hundred and ninety-nine females (316 melanoma cases and 283 controls) and 458 males (234 melanoma cases and 224 controls) were analysed. We genotyped 363 polymorphisms (single nucleotide polymorphisms (SNPs)) from 65 pigmentation gene regions. Results When samples were stratified by sex, we observed more SNPs associated with dark pigmentation and good sun tolerance in females than in males (107 versus 75; P = 2.32 × 10−6), who were instead associated with light pigmentation and poor sun tolerance. Furthermore, six SNPs in TYR, SILV/CDK2, GPR143, and F2RL1 showed strong differences in melanoma risk by sex (P < 0.01). Conclusions We demonstrate that these genetic variants are important for pigmentation as well as for melanoma risk, and also provide suggestive evidence for potential differences in genetic effects by sex.We thank the Madrid College of Lawyers and all patients from the different contributing Hospitals. We would like to thank Tais Moreno, M. Rosario Alonso, and Guillermo Pita for their expert technical assistance with Illumina genotyping, performed at the Spanish National Genotyping Centre (CeGen, Madrid). MI-V is funded by the “Ministry of Health Carlos III” under a Sara Borrell contract (CD15/00153). ML-C is funded by a Prometeo contract (2015/005). SSO is funded by the “ Ministry of Education, Culture and Sport” under a FPU fellowship (FPU13/04976). GR is funded by the “Ministry of Health Carlos III” under a Miquel Servet II contract (CPII14-00013). This work has also been partly funded by a research project from the Spanish Ministry of Economy and Competitiveness (CGL2014-58526-P), whose principal investigator is S

Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression

Endometrial cancer; Clonal evolution; MutationCáncer endometrial; Evolución clonal; MutaciónCàncer d'endometri; Evolució clonal; MutacióAnalyzing different tumor regions by next generation sequencing allows the assessment of intratumor genetic heterogeneity (ITGH), a phenomenon that has been studied widely in some tumor types but has been less well explored in endometrial carcinoma (EC). In this study, we sought to characterize the spatial and temporal heterogeneity of 9 different ECs using whole-exome sequencing, and by performing targeted sequencing validation of the 42 primary tumor regions and 30 metastatic samples analyzed. In addition, copy number alterations of serous carcinomas were assessed by comparative genomic hybridization arrays. From the somatic mutations, identified by whole-exome sequencing, 532 were validated by targeted sequencing. Based on these data, the phylogenetic tree reconstructed for each case allowed us to establish the tumors’ evolution and correlate this to tumor progression, prognosis, and the presence of recurrent disease. Moreover, we studied the genetic landscape of an ambiguous EC and the molecular profile obtained was used to guide the selection of a potential personalized therapy for this patient, which was subsequently validated by preclinical testing in patient-derived xenograft models. Overall, our study reveals the impact of analyzing different tumor regions to decipher the ITGH in ECs, which could help make the best treatment decision.We thank all those at the Translational Research Laboratory of the MD Anderson Cancer Center Madrid for their invaluable help with this study. Tissue samples were obtained with the support of the MD Anderson Foundation Biobank (record number B.0000745, ISCIII National Biobank Record), the “Xarxa Catalana de Bancs de Tumors” and “Plataforma de Biobancos” ISCIII (PT13/0010/0014, B.000609). This study has been supported by the Spanish Ministry of Economy and Innovation (PID2019-104644RB-I00 (GMB), the Instituto de Salud Carlos III (ISCIII, CIBERONC, CB16/12/00295 - GMB-, CB16/12/00328 -EC, AGM- and CB16/12/00231 -XMG- [all partly supported by FEDER funds]) and by the AECC Scientific Foundation (FC_AECC PROYE19036MOR -GMB- and Coordinated groups 2018 -XMG, AGM, GMB-). SO is funded by an AECC-postdoctoral grant (2020). JSR-F and BW are funded in part by the Breast Cancer Research Foundation and in part by the NIH/NCI P50 CA247749 01 grant. Research reported in this publication was supported in part by a Cancer Center Support Grant of the NIH/NCI (Grant No. P30CA008748; MSK). We thank the Eurofins Megalab laboratory for helping us to perform the analysis of DNA HPV detection

Loxl3 Promotes Melanoma Progression and Dissemination Influencing Cell Plasticity and Survival

Malignant melanoma is the most lethal skin cancer due to its aggressive clinical behavior and therapeutic resistance. A comprehensive knowledge of the molecular mechanisms underlying melanoma progression is urgently needed to improve the survival of melanoma patients. Phenotypic plasticity of melanoma cells has emerged as a key process in melanomagenesis and therapy resistance. This phenotypic plasticity is sustained by an epithelial-to-mesenchymal (EMT)-like program that favors multiple intermediate states and allows adaptation to changing microenvironments along melanoma progression. Given the essential role of lysyl oxidase-like 3 (LOXL3) in human melanoma cell survival and its contribution to EMT, we generated mice with conditional melanocyte-specific targeting of Loxl3, concomitant to Braf activation and Pten deletion. Our results supported a key role of Loxl3 for melanoma progression, metastatic dissemination, and genomic stability, and supported its contribution to melanoma phenotypic plasticity by modulating the expression of several EMT transcription factors (EMT-TFs). Malignant melanoma is a highly aggressive tumor causing most skin cancer-related deaths. Understanding the fundamental mechanisms responsible for melanoma progression and therapeutic evasion is still an unmet need for melanoma patients. Progression of skin melanoma and its dissemination to local or distant organs relies on phenotypic plasticity of melanoma cells, orchestrated by EMT-TFs and microphthalmia-associated TF (MITF). Recently, melanoma phenotypic switching has been proposed to uphold context-dependent intermediate cell states benefitting malignancy. LOXL3 (lysyl oxidase-like 3) promotes EMT and has a key role in human melanoma cell survival and maintenance of genomic integrity. To further understand the role of Loxl3 in melanoma, we generated a conditional Loxl3-knockout (KO) melanoma mouse model in the context of BrafV600E-activating mutation and Pten loss. Melanocyte-Loxl3 deletion increased melanoma latency, decreased tumor growth, and reduced lymph node metastatic dissemination. Complementary in vitro and in vivo studies in mouse melanoma cells confirmed Loxl3's contribution to melanoma progression and metastasis, in part by modulating phenotypic switching through Snail1 and Prrx1 EMT-TFs. Importantly, a novel LOXL3-SNAIL1-PRRX1 axis was identified in human melanoma, plausibly relevant to melanoma cellular plasticity. These data reinforced the value of LOXL3 as a therapeutic target in melanoma

A highly porous interpenetrated MOF-5-type network based on bipyrazolate linkers

A novel cobalt(II) metal organic framework containing two interpenetrated nets with the cubic pcu-a topology of MOF-5 has been synthesized and characterized. In spite of being interpenetrated, this material exhibits a highly accessible porous structure

Fixed point results for generalized cyclic contraction mappings in partial metric spaces

Rus (Approx. Convexity 3:171–178, 2005) introduced the concept of cyclic contraction mapping. P˘acurar and Rus (Nonlinear Anal. 72:1181–1187, 2010) proved some fixed point results for cyclic φ-contraction mappings on a metric space. Karapinar (Appl. Math. Lett. 24:822–825, 2011) obtained a unique fixed point of cyclic weak φ- contraction mappings and studied well-posedness problem for such mappings. On the other hand, Matthews (Ann. New York Acad. Sci. 728:183–197, 1994) introduced the concept of a partial metric as a part of the study of denotational semantics of dataflow networks. He gave a modified version of the Banach contraction principle, more suitable in this context. In this paper, we initiate the study of fixed points of generalized cyclic contraction in the framework of partial metric spaces. We also present some examples to validate our results.S. Romaguera acknowledges the support of the Ministry of Science and Innovation of Spain, grant MTM2009-12872-C02-01.Abbas, M.; Nazir, T.; Romaguera Bonilla, S. (2012). Fixed point results for generalized cyclic contraction mappings in partial metric spaces. Revista- Real Academia de Ciencias Exactas Fisicas Y Naturales Serie a Matematicas. 106(2):287-297. https://doi.org/10.1007/s13398-011-0051-5S2872971062Abdeljawad T., Karapinar E., Tas K.: Existence and uniqueness of a common fixed point on partial metric spaces. Appl. Math. Lett. 24(11), 1894–1899 (2011). doi: 10.1016/j.aml.2011.5.014Altun, I., Erduran A.: Fixed point theorems for monotone mappings on partial metric spaces. Fixed Point Theory Appl. article ID 508730 (2011). doi: 10.1155/2011/508730Altun I., Sadarangani K.: Corrigendum to “Generalized contractions on partial metric spaces” [Topology Appl. 157 (2010), 2778–2785]. Topol. 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MicroRNA profile in very young women with breast cancer

BACKGROUND: Breast cancer is rarely diagnosed in very young women (35 years old or younger), and it often presents with distinct clinical-pathological features related to a more aggressive phenotype and worse prognosis when diagnosed at this early age. A pending question is whether breast cancer in very young women arises from the deregulation of different underlying mechanisms, something that will make this disease an entity differentiated from breast cancer diagnosed in older patients. METHODS: We performed a comprehensive study of miRNA expression using miRNA Affymetrix2.0 array on paraffin-embedded tumour tissue of 42 breast cancer patients 35 years old or younger, 17 patients between 45 and 65 years old and 29 older than 65 years. Data were statistically analyzed by t-test and a hierarchical clustering via average linkage method was conducted. Results were validated by qRT-PCR. Putative targeted pathways were obtained using DIANA miRPath online software. RESULTS: The results show a differential and unique miRNA expression profile of 121 miRNAs (p-value <0.05), 96 of those with a FDR-value <0.05. Hierarchical clustering grouped the samples according to their age, but not by subtype nor by tumour characteristics. We were able to validate by qRT-PCR differences in the expression of 6 miRNAs: miR-1228*, miR-3196, miR-1275, miR-92b, miR-139 and miR-1207. Moreover, all of the miRNAs maintained the expression trend. The validated miRNAs pointed out pathways related to cell motility, invasion and proliferation. CONCLUSIONS: The study suggests that breast cancer in very young women appears as a distinct molecular signature. To our knowledge, this is the first time that a validated microRNA profile, distinctive to breast cancer in very young women, has been presented. The miRNA signature may be relevant to open an important field of research in order to elucidate the underlying mechanism in this particular disease, which in a more clinical setting, could potentially help to identify therapeutic targets in this particular set of patients.MPC is funded by the Generalitat Valenciana VALi + d, ACIF/2011/270. MTM is funded by”Rio Hortega Project” (CM12/00264). GR is a FIS “Miquel Servet” Researcher. AB holds a Translational Research Grant awarded by the Spanish Society of Medical Oncology (SEOM). This project was carried out thanks to Fundación LeCadó – proyecto Flor de Vida and co-funded by FIS project PI13/00606 and FEDER. We would like to give thanks to all the patients and volunteers for their participation and also to the INCLIVA Biobank, integrated into the Spanish Hospital Biobanks Network (ReTBioH) and supported by the Instituto de Salud Carlos III/FEDER (grant number: RD09/0076/00132). We also wish to thank several private Breast cancer associations that funded this study and the Unit for Multigenic Analysis from the Central Unit for Medical Research (UCIM/INCLIVA) for the performance of the Affymetrix microRNA profiles.S