16 research outputs found
nuevos datos a partir de la arqueometria
UID/HIS/04666/2013publishersversionpublishe
GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model
Cancer is a phenomenon broadly related to ageing in various ways such as cell cycle deregulation, metabolic defects or telomerases dysfunction as principal processes. Although the tumor cell is the main actor in cancer progression, it is not the only element of the disease. Cells and the matrix surrounding the tumor, called the tumor microenvironment (TME), play key roles in cancer progression. Phenotypic changes of the TME are indispensable for disease progression and a few of these transformations are produced by epigenetic changes including miRNA dysregulation. In this study, we found that a specific group of miRNAs in the liver TME produced by colon cancer called geromiRs, which are miRNAs related to the ageing process, are significantly downregulated. The three principal cell types involved in the liver TME, namely, liver sinusoidal endothelial cells, hepatic stellate (Ito) cells and Kupffer cells, were isolated from a murine hepatic metastasis model, and the miRNA and gene expression profiles were studied. From the 115 geromiRs and their associated hallmarks of aging, which we compiled from the literature, 75 were represented in the used microarrays, 26 out of them were downregulated in the TME cells during colon cancer colonization of the liver, and none of them were upregulated. The histone modification hallmark of the downregulated geromiRs is significantly enriched with the geromiRs miR-15a, miR-16, miR-26a, miR-29a, miR-29b and miR-29c. We built a network of all of the geromiRs downregulated in the TME cells and their gene targets from the MirTarBase database, and we analyzed the expression of these geromiR gene targets in the TME. We found that Cercam and Spsb4, identified as prognostic markers in a few cancer types, are associated with downregulated geromiRs and are upregulated in the TME cells.This work was supported by grants from Instituto de Salud Carlos III (AC17/00012), cofounded by the European Union projects (European Regional Development Fund/European Science Foundation, Investing in your future), (ERA-Net program EracoSysMed, JTC-2 2017) and (H2020-FETOPEN, Circular Vision, Project 899417); DiputaciĂłn Foral de Gipuzkoa and the Department of Economic Development and Infrastructures of the Basque Government (DFG109/20) and the Department of Economic Development and Infrastructures of the Basque Government (DFG109/Grants Health Department of the Basque Government (Spain), RIS3 call, Exp. No. 2020333039 and 2020333001. 20)
An Integrative Omics Approach Reveals Involvement of BRCA1 in Hepatic Metastatic Progression of Colorectal Cancer
(1) Background & Aims: The roles of different cells in the tumor microenvironment (TME) are critical to the metastatic process. The phenotypic transformation of the liver cells is one of the most important stages of the hepatic metastasis progression of colorectal cancer (CRC). Our aim was to identify the major molecules (i.e., genes, miRNAs and proteins) involved in this process. (2) Methods: We isolated and performed whole-genome analysis of gene, miRNA, and protein expression in three types of liver cells (Ito cells, Kupffer cells, and liver sinusoidal endothelial cells) from the TME of a murine model of CRC liver metastasis. We selected the statistically significant differentially expressed molecules using the Student’s t-test with Benjamini-Hochberg correction and performed functional statistically-significant enrichment analysis of differentially expressed molecules with hypergeometric distribution using the curated collection of molecular signatures, MSigDB. To build a gene-miRNA-protein network centered in Brca1, we developed a software package (miRDiana) that collects miRNA targets from the union of the TargetScan, MicroCosm, mirTarBase, and miRWalk databases. This was used to search for miRNAs targeting Brca1. We validated the most relevant miRNAs with real-time quantitative PCR. To investigate BRCA1 protein expression, we built tissue microarrays (TMAs) from hepatic metastases of 34 CRC patients. (3) Results: Using integrated omics analyses, we observed that the Brca1 gene is among the twenty transcripts simultaneously up-regulated in all three types of TME liver cells during metastasis. Further analysis revealed that Brca1 is the last BRCA1-associated genome surveillance complex (BASC) gene activated in the TME. We confirmed this finding in human reanalyzing transcriptomics datasets from 184 patients from non-tumor colorectal tissue, primary colorectal tumor and colorectal liver metastasis of the GEO database. We found that the most probable sequence of cell activation during metastasis is Endothelial→Ito→Kupffer. Immunohistochemical analysis of human liver metastases showed the BRCA1 protein was co-localized in Ito, Kupffer, and endothelial cells in 81.8% of early or synchronous metastases. However, in the greater part of the metachronous liver metastases, this protein was not expressed in any of these TME cells. (4) Conclusions: These results suggest a possible role of the co-expression of BRCA1 in Ito, Kupffer, and sinusoidal endothelial cells in the early occurrence of CRC liver metastases, and point to BRCA1 as a potential TME biomarker.D.G. and M.J.A.-B. have been supported by Grants DFG113/18 from Diputación Foral de Gipuzkoa (DFG), Spain, Ministry of Economy and Competitiveness, Spain, MINECO Grant BFU2016-77987-P and Instituto de Salud Carlos III (AC17/00012) Grant co-funded by the European Union (Eracosysmed/H2020 Grant Agreement No. 643271) and European Union (H2020-FETOPEN, Project 899417). D.G., M.J.A.-B. and I.B. have been supported by Grants Health Department of the Basque Government (Spain), RIS3 call, Exp. No. 2020333039 and 2020333001
Lexical and Sublexical Skills in Children's Literacy
Letter knowledge and word identification are key skills for reading and spelling. Letter knowledge facilitates the application of sublexical letter-sound mappings to decode words. With reading experience, word identification becomes a key lexical skill to support decoding. In transparent orthographies, however, letter knowledge might be an enduring predictor of decoding and spelling, even in children with some reading experience. This study investigated the association of children's sublexical (letter knowledge) and lexical skills (word identification and vocabulary) with word decoding and spelling accuracy in Spanish, which is a transparent orthography. The sample consisted of 117 Spanish-speaking children, aged 8 to 10. Results revealed that (1) letter knowledge and word identification were independently associated with children's word spelling; (2) word identification was uniquely associated with word decoding; and (3) children's vocabulary level was associated with word identification. The implications of these findings were examined within the framework of reading models and the characteristics of a transparent orthography.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grant number PID2020-116740 GB-I00 (funded by the MCIN/AEI/10.13039/501100011033) from the Spanish Ministry of Science and Innovation and grant CIAICO/2021/172 from the Valencian Government
The supply of ceramics to Portuguese north African strongholds in the 15th and 16th centuries: new archaeometric data from Ksar Seghir and Ceuta
The present study aims to present new archaeometric data from a wide typological rank of ceramics collected in Ksar Seghir (Morocco) and Ceuta (Spain), two different archaeological sites in the south bank of the Strait of Gibraltar occupied by the Portuguese from the 15th to the middle of the 16th centuries. We characterise and illustrate the most common ceramic fabrics and shapes found in these settlements, only possible by the intensive excavation of these two sites. Its mineralogical and chemical analyses confirm the idea that Seville and Lisbon were the most significant production centres in the Iberian Peninsula to supply the two Portuguese North African strongholds. These results reinforce the idea that Seville and Lisbon, besides being two great pottery workshops, played a complementary role as key cities in the logistics of the Iberian overseas expansion since its early beginning. The combination of the typological and archaeometrical studies will allow to better identify the centres of production of these ceramics, which were widely disseminated in the Mediterranean Sea and the Atlantic Ocean during this period.Ministerio de EconomĂa, Industria y Competitividad (HAR2017-84219-P)
European Regional Development Fund (MINECO/AEI/ERDF, UE)
Ramon y Cajal contract (RYC-2014-16835)
University of the Basque Country (UPV/EHU) for doctoral grant Hiring for Research Training (PIF2017/153)
Dokberri postdoctoral fellowship (DOCREC19/39
Los materiales arqueolĂłgicos de Ă©pocas marinĂ y portuguesa de la Puerta Califal de Ceuta
UIDB/04666/2020
UIDP/04666/2020publishersversionpublishe