Research in the Bioarchaeology Laboratory in the International Institute for Prehistoric Research (IIIPC) - University of Cantabria

RESUMEN: Cantabria se caracteriza por ser una región especialmente rica en yacimientos de época prehistórica. En ellos, se han podido recuperar múltiples evidencias que, con la aplicación de las técnicas metodológicas adecuadas, permiten reconstruir los modos de vida de los grupos humanos del pasado, la explotación que realizaban del medio, su tipo de dieta, su movilidad, así como el tipo de clima y medioambiente en que habitaron, entre otros aspectos. Una de las líneas de investigación más novedosas desarrollada en la región es la Bioarqueología, entendida como el estudio y análisis de restos biológicos procedentes de yacimientos arqueológicos. En este artículo se muestran las diferentes colecciones de referencia de materiales bioarqueológicos que alberga el Laboratorio de Bioarqueología del Instituto Internacional de Investigaciones Prehistóricas de Cantabria (Universidad de Cantabria), así como las investigaciones desarrolladas en dicha institución sobre esta temática en los últimos años.ABSTRACT: Cantabria is a region characterised as especially rich in prehistoric archaeological sites. These sites can be investigated using stateof- the art methodologies, making it possible to reconstruct the way of life of humans in the past, answering questions about diet and mobility, and what the climate and environment was like, amongst other things. One of these newly-developed lines of research in the region is bioarchaeology, which is the study and analysis of biological remains recovered from archaeological sites. This article introduces the different bioarchaeological reference collection materials housed in the Bioarchaeology Laboratory at the International Institute of Prehistoric Research in Cantabria (University of Cantabria), as well as the bioarchaeological research that has been carried out within the institution in the last few years.La investigación llevada a cabo por el grupo de investigadores del Laboratorio de Bioarqueología ha sido posible gracias a diversas fuentes de financiación españolas y europeas. En primer lugar, a título personal señalar las siguientes ayudas: Programa Ramon y Cajal a ABMA (RYC-2011-00695), Programa Juan de la Cierva a IGZ (JCI-2012-12094) y DCS (IJCI- 2014-20590), Marie Skłodowska-Curie Individual Fellowship a JJ (H2020-MSCA-IF-2014-Ref. 656122), Becas Predoctorales FPI a JMG (BES-2013-063309) y RSR (BES-2014-070075), AH (BES-2015-075176), Predoctorales UC a ILD y AGE y Técnicos de Apoyo I+D a LAP (PTA2013-8401-I). En segundo lugar, parte de estas investigaciones forma o ha formado parte de los siguientes proyectos de investigación financiados por la Comisión Europea (FP7-PEOPLE- 2012-CIG (322112), la British Academy y The Royal Society (Newton International Fellowship NF100413), y el Ministerio de Economía y Competitividad de España (HAR2008-06477-C03-00/HIST; HAR2010- 22115-C02-01; HAR2011-29907-C03-00; HAR2012- 33956; HAR2013-46802-P; HAR2014-51830-P). Por último, queremos agradecer el acceso a los fondos de museos como los depositados en el Museo de Prehistoria y Arqueología de Cantabria (MUPAC), el Museo de Altamira, Centro de Patrimonio Cultural Mueble de Gipuzkoa (Gordailua), Museo Arqueológico de Asturias, Grupo de Ingeniería Fotónica de la Universidad de Cantabria, Laboratorio de la División de Ciencia e Ingeniería de los Materiales de la Universidad de Cantabria (LADICIM) e Instituto de Biomedicina y Biotecnología de Cantabria

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

TRPC1 and ORAI1 channels in colon cancer

Colon cancer cells, like other types of cancer cells, undergo the remodeling of the intracellular Ca2+ homeostasis that contributes to cancer cell hallmarks including enhanced cell proliferation, migration, and survival. Colon cancer cells display enhanced store-operated Ca2+ entry (SOCE) compared with their non-cancer counterparts. Colon cancer cells display an abnormal expression of SOCE molecular players including Orai1 and TRPC1 channels, and the stromal interacting molecule (STIM) 1 and 2. Interestingly, upregulation of Orai1 and TRPC1 channels and their contribution to SOCE are associated with cancer malignancy in colon cancer cells. In a specific cellular model of colon cancer, whereas in non-cancer colon cells SOCE is composed of the Ca2+ release activated (CRAC) currents, in colon cancer cells SOCE is composed of CRAC- and cationic, non-selective store operated (SOC) currents. Former SOCs are mediated by TRPC1 channels. Moreover, colon cancer cells also display dysregulation of the expression of 1,4,5-triphosphate receptors (IP3R) that could contribute to the enhanced SOCE. Another important factor underlying the enhanced SOCE is the differential mitochondrial modulation of the CRAC and SOC currents in non-cancer and colon cancer cells. In colon cancer cells, mitochondria take up more Ca2+ that prevent the Ca2+-dependent inactivation of the SOCs, leading to sustained Ca2+ entry. Notably, the inhibition of SOCE in cancer colon cells abolishes their cancer hallmarks. Robust evidence has shown the efficiency of non-steroidal anti-inflammatory drugs (NSAIDs) and difluoromethylornithine (DFMO) to reverse the enhanced cell proliferation, migration, and apoptosis resistance of cancer cells. In colon cancer cells, both NSAIDs and DFMO decrease SOCE, but they target different molecular components of SOCE. NSAIDs decrease the Ca2+ uptake by mitochondria, limiting their ability to prevent the Ca2+-dependent inactivation of the SOCs that underlie SOCE. On the other hand, DFMO inhibits the expression of TRPC1 channels in colon cancer cells, eliminating their contribution to SOCE. The identification of players of SOCE in colon cancer cells may help to better understand the remodeling of the Ca2+ homeostasis in cancer. Importantly, the use of different pharmacological tools that target different SOCE molecular players in colon cancer cells may play a pivotal role in designing better chemoprevention strategies.We gratefully acknowledge support from the Spanish Ministry of Economy and Competitivity (grant BFU2015-70131R), Junta de Castilla y León, Spain (grant VA294P18), the Spanish Association Against Cancer (AECC), and a predoctoral fellowship of the University of Valladolid to LGG.Peer reviewe

Inhibition of Polyamine Biosynthesis Reverses Ca2+ Channel Remodeling in Colon Cancer Cells

Store-operated Ca2+ entry (SOCE) is the most important Ca2+ entry pathway in non-excitable cells. Colorectal cancer (CRC) shows decreased Ca2+ store content and enhanced SOCE that correlate with cancer hallmarks and are associated to remodeling of store-operated channels (SOCs). Normal colonic cells display small, Ca2+-selective currents driven by Orai1 channels. In contrast, CRC cells display larger, non-selective currents driven by Orai1 and transient receptor potential canonical type 1 channels (TRPC1). Difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase (ODC), the limiting step in polyamine biosynthesis, strongly prevents CRC, particularly when combined with sulindac. We asked whether DFMO may reverse SOC remodeling in CRC. We found that CRC cells overexpress ODC and treatment with DFMO decreases cancer hallmarks including enhanced cell proliferation and apoptosis resistance. Consistently, DFMO enhances Ca2+ store content and decreases SOCE in CRC cells. Moreover, DFMO abolish selectively the TRPC1-dependent component of SOCs characteristic of CRC cells and this effect is reversed by the polyamine putrescine. Combination of DFMO and sulindac inhibit both SOC components and abolish SOCE in CRC cells. Finally, DFMO treatment inhibits expression of TRPC1 and stromal interaction protein 1 (STIM1) in CRC cells. These results suggest that polyamines contribute to Ca2+ channel remodeling in CRC, and DFMO may prevent CRC by reversing channel remodeling

Mitochondrial control of store-operated Ca2+ channels in cancer: Pharmacological implications

Intracellular Ca2+ is a pleiotropic second messenger involved in control of different cell and physiological functions including long-term processes such as cell proliferation, migration and survival. Agonist-induced Ca2+ entry in most cells, especially in non-excitable cells including epithelial cells, is mediated by store-operated Ca2+ entry (SOCE), a Ca2+ entry pathway activated by agonist-induced release of Ca2+ from intracellular stores in the endoplasmic reticulum (ER). This pathway is modulated also by mitochondria which, acting as Ca2+ sinks, take up Ca2+, thus limiting Ca2+-dependent inactivation of Ca2+-release activated Ca2+ channels (CRAC). Compelling evidence shows that SOCE is upregulated in a large variety of cancer cells and this change contribute to cancer hallmarks. Mechanisms for enhanced SOCE include changes in expression of members of the Orai, Stromal interaction molecule (STIM) and canonical transient receptor potential channel (TRPc) gene families. Tumor cell mitochondria may contribute to SOCE upregulation in cancer as well. Molecular players involved in enhancing mitochondrial Ca2+ uptake are upregulated in tumor cells whereas negative modulators are repressed. Furthermore, mitochondrial potential, the driving force for mitochondrial Ca2+ uptake, is enhanced in tumor cells due to the Warburg effect. Finally, SOCE in tumor cells may be sustained further by the gain of function of non-selective TRPC channels permeable to Na+ that favour Ca2+ exit from mitochondria in exchange for Na+, thus limiting Ca2+-dependent inactivation of Orai1 channels. Therefore, tumor cell mitochondria may efficiently contribute to enhance and sustain SOCE in cancer. Interestingly, this effect could be counterbalanced by selected non-steroidal anti-inflammatory drugs (NSAIDs) reported to prevent colorectal cancer and other forms of cancer.This work has been supported by grant BFU2015-70131R to CV and LN from Ministry of Economy and Innovation, Spain.Peer reviewe

Calcium remodeling in colorectal cancer

Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC. SOCE and store-operated currents (SOCs) are dramatically enhanced in CRC while Ca stores are partially empty in CRC cells. These features may contribute to CRC hallmarks including enhanced cell proliferation, migration, invasion and survival. At the molecular level, enhanced SOCE and depleted stores are mediated by overexpression of Orai1, Stromal interaction protein 1 (STIM1) and Transient receptor protein channel 1 (TRPC1) and downregulation of STIM2. In normal colonic cells, SOCE is mediated by Ca-release activated Ca channels made of STIM1, STIM2 and Orai1. In CRC cells, SOCE is mediated by different store-operated currents (SOCs) driven by STIM1, Orai1 and TRPC1. Loss of STIM2 contributes to depletion of Ca stores and enhanced resistance to cell death in CRC cells. Thus, SOCE is a novel key player in CRC and inhibition by salicylate and other NSAIDs may contribute to explain chemoprevention activity. Summary Colorectal cancer (CRC) is the third most frequent form of cancer worldwide. Recent evidence suggests that intracellular Ca remodeling may contribute to cancer hallmarks. In addition, aspirin and other NSAIDs might prevent CRC acting on remodeled Ca entry pathways. In this review, we will briefly describe 1) the players involved in intracellular Ca homeostasis with a particular emphasis on the mechanisms involved in SOCE activation and inactivation, 2) the evidence that aspirin metabolite salicylate and other NSAIDs inhibits tumor cell growth acting on SOCE, 3) evidences on the remodeling of intracellular Ca in cancer with a particular emphasis in SOCE, 4) the remodeling of SOCE and Ca store content in CRC and, finally, 5) the molecular basis of Ca remodeling in CRC. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.This work has been funded by a grant from Ministerio de Economía y competitividad, Spain (BFU2015-70131R) and Junta de Castilla y León, Spain [BIO/VA46/14].Peer Reviewe

A reciprocal shift in transient receptor potential channel 1 (TRPC1) and stromal interaction molecule 2 (STIM2) contributes to Ca2+remodeling and cancer hallmarks in colorectal carcinoma cells

Producción CientíficaWe have investigated the molecular basis of intracellular Ca2+ handling in human colon carcinoma cells (HT29) versus normal human mucosa cells (NCM460) and its contribution to cancer features. We found that Ca2+ stores in colon carcinoma cells are partially depleted relative to normal cells. However, resting Ca2+ levels, agonist-induced Ca2+ increases, store-operated Ca2+ entry (SOCE), and store-operated currents (ISOC) are largely enhanced in tumor cells. Enhanced SOCE and depleted Ca2+ stores correlate with increased cell proliferation, invasion, and survival characteristic of tumor cells. Normal mucosa cells displayed small, inward Ca2+ release-activated Ca2+ currents (ICRAC) mediated by ORAI1. In contrast, colon carcinoma cells showed mixed currents composed of enhanced ICRAC plus a nonselective ISOC mediated by TRPC1. Tumor cells display increased expression of TRPC1, ORAI1, ORAI2, ORAI3, and STIM1. In contrast, STIM2 protein was nearly depleted in tumor cells. Silencing data suggest that enhanced ORAI1 and TRPC1 contribute to enhanced SOCE and differential store-operated currents in tumor cells, whereas ORAI2 and -3 are seemingly less important. In addition, STIM2 knockdown decreases SOCE and Ca2+ store content in normal cells while promoting apoptosis resistance. These data suggest that loss of STIM2 may underlie Ca2+ store depletion and apoptosis resistance in tumor cells. We conclude that a reciprocal shift in TRPC1 and STIM2 contributes to Ca2+ remodeling and tumor features in colon cancer.Ministerio de Economía, Industria y Competitividad (grants BFU2009-08967 and BFU2012-37)Junta de Castilla y León (grant VA145U13

Evaluación de la función pulmonar y ocurrencia de EPOC en mujeres palmeadoras de tortillas, mayores de 40 años expuestas ocupacionalmente a humo de leña y carbón en 6 Barrios urbanos de Managua, 2008

La enfermedad pulmonar obstructgiva crónica (EPOC) fue definida por la global initiative for chronic obstructive lung disease (GOLD) como un cuadro parológico caracterizado por una limitación del flujo de aire que no es totalmentee reversible (http://wwwgoldcopd.com/). La EPOC incluye el enfisema, un cuadro anatómicamente definido y que se caracteriza por destrucción y ensanchamiento de los avélolos pulmonares; la bronquitis crónica, un cuadro definido clínicamente por tos crónic