Linoleic and oleic acids enhance cell migration by altering the dynamics of microtubules and the remodeling of the actin cytoskeleton at the leading edge

Fatty acids (FA) have a multitude of biological actions on living cells. A target of their action is cell motility, a process of critical importance during cancer cell dissemination. Here, we studied the effect of unsaturated FA on ovarian cancer cell migration in vitro and its role in regulating cytoskeleton structures that are essential for cell motility. Scratch wound assays on human ovary cancer SKOV-3 cell monolayers revealed that low doses (16 μM) of linoleic acid (LA, 18:2 ω6) and oleic acid (OA; 18:1 ω9) promoted migration, while α-linolenic acid (ALA, 18:3 ω3), showed a migration rate similar to that of the control group. Single cell tracking demonstrated that LA and OA-treated cells migrated faster and were more orientated towards the wound closure than control. In vitro addition of those FA resulted in an increased number, length and protrusion speed of filopodia and also in a prominent and dynamic lamellipodia at the cell leading edge. Using time-lapse video-microscopy and FRAP we observed an increase in both the speed and frequency of actin waves associated with more mobile actin and augmented Rac1 activity. We also observed that FA induced microtubule-organizing center (MTOC)-orientation towards the cell front and affected the dynamics of microtubules (MT) in the direction of cell migration. We propose that environmental cues such as OA and LA present in ascitic fluid, should be taken into account as key factors for the regulation of cell migration.Fil: Masner Moratorio, Martin. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Instituto de Investigación Médica Mercedes y Martín Ferreyra. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa; ArgentinaFil: Lujea, Noelia Carolina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Instituto de Investigación Médica Mercedes y Martín Ferreyra. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa; ArgentinaFil: Bisbal, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Acosta, Cristian Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Kunda, Patricia Elena. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Instituto de Investigación Médica Mercedes y Martín Ferreyra. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa; Argentin

La evaluación de competencias en los trabajos fin de estudios

En este artículo proponemos un procedimiento objetivo para la evaluación, basada en competencias, de los trabajos fin de grado (TFG) y de máster (TFM) en el contexto de las ingenierías. Dicho procedimiento se ha dividido en seis etapas: (1) definición de las competencias asociadas al TFG o al TFM y de indicadores objetivos; (2) definición de los momentos (hitos) de evaluación, las acciones concretas de evaluación y los agentes implicados; (3) asignación de indicadores objetivos a cada acción de evaluación; (4) definición de los niveles de cumplimiento de cada indicador; (5) elaboración de los informes de evaluación que los agentes evaluadores deberán cumplimentar y (6) definición del criterio de puntación para asignar la nota final a partir de los informes de evaluación. Para cada uno de estos puntos se ofrecen ayudas en forma de encuestas, fichas de competencias y/o ejemplos de aplicación.Peer Reviewe

Lectin-gated and glycan functionalized mesoporous silica nanocontainers for targeting cancer cells overexpressing Lewis X antigen

[EN] Gated mesoporous silica nanoparticles can deliver payload upon the application of a predefined stimulus, and therefore are promising drug delivery systems. Despite their important role, relatively low emphasis has been placed on the design of gating systems that actively target carbohydrate tumor cell membrane receptors. We describe herein a new Lewis X (Le(x)) antigen-targeted delivery system comprising mesoporous silica nanoparticles (MSNs) loaded with ATTO 430LS dye, functionalized with a Le(x) derivative (1) and capped with a fucose-specific carbohydrate-binding protein (Aleuria aurantia lectin (AAL)). This design takes advantage of the affinity of AAL for Le(x) overexpressed receptors in certain cancer cells. In the proximity of the cells, AAL is detached from MSNs to bind Le(x), and selectins in the cells bind Le(x) in the gated MSNs, thereby inducing cargo delivery. Gated MSNs are nontoxic to colon cancer DLD-1 cells, and ATTO 430LS dye delivered correlated with the amount of Le(x) antigen overexpressed at the DLD-1 cell surface. This is one of the few examples of MSNs using biologically relevant glycans for both capping (via interaction with AAL) and targeting (via interaction with overexpressed Le(x) at the cell membrane).The authors thank the Spanish Government (Projects MAT2015-64139-C4-1-R and MAT2013-46101-R (MINECO/ FEDER)), Fondo de Investigacion Sanitaria (PI15/00480) and Generalitat Valenciana (Project PROMETEOII/2014/047 and project GVA/2014/13) for support. R. B. is thankful to Svagata. Eu (Erasmus Mundus Action-II program) for his fellowship. The authors also thank the Electron Microscopy Service at the UPV for support.Bhat, R.; García, I.; Aznar, E.; Arnáiz, B.; Martínez-Bisbal, M.; Liz-Marzán, L.; Penadés, S.... (2018). Lectin-gated and glycan functionalized mesoporous silica nanocontainers for targeting cancer cells overexpressing Lewis X antigen. Nanoscale. 10(1):239-249. https://doi.org/10.1039/c7nr06415bS239249101Argyo, C., Weiss, V., Bräuchle, C., & Bein, T. (2013). Multifunctional Mesoporous Silica Nanoparticles as a Universal Platform for Drug Delivery. Chemistry of Materials, 26(1), 435-451. doi:10.1021/cm402592tAznar, E., Martínez-Máñez, R., & Sancenón, F. (2009). Controlled release using mesoporous materials containing gate-like scaffoldings. Expert Opinion on Drug Delivery, 6(6), 643-655. doi:10.1517/17425240902895980Aznar, E., Oroval, M., Pascual, L., Murguía, J. R., Martínez-Máñez, R., & Sancenón, F. (2016). Gated Materials for On-Command Release of Guest Molecules. Chemical Reviews, 116(2), 561-718. doi:10.1021/acs.chemrev.5b00456Wang, X., Tan, L.-L., Li, X., Song, N., Li, Z., Hu, J.-N., … Yang, Y.-W. (2016). Smart mesoporous silica nanoparticles gated by pillararene-modified gold nanoparticles for on-demand cargo release. Chemical Communications, 52(95), 13775-13778. doi:10.1039/c6cc08241fChen, X., Sun, H., Hu, J., Han, X., Liu, H., & Hu, Y. (2017). Transferrin gated mesoporous silica nanoparticles for redox-responsive and targeted drug delivery. Colloids and Surfaces B: Biointerfaces, 152, 77-84. doi:10.1016/j.colsurfb.2017.01.010Prasad, R., Aiyer, S., Chauhan, D. S., Srivastava, R., & Selvaraj, K. (2016). Bioresponsive carbon nano-gated multifunctional mesoporous silica for cancer theranostics. Nanoscale, 8(8), 4537-4546. doi:10.1039/c5nr06756aAgostini, A., Mondragón, L., Coll, C., Aznar, E., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2012). Dual Enzyme-Triggered Controlled Release on Capped Nanometric Silica Mesoporous Supports. ChemistryOpen, 1(1), 17-20. doi:10.1002/open.201200003García-Fernández, A., García-Laínez, G., Ferrándiz, M. L., Aznar, E., Sancenón, F., Alcaraz, M. J., … Orzáez, M. (2017). Targeting inflammasome by the inhibition of caspase-1 activity using capped mesoporous silica nanoparticles. Journal of Controlled Release, 248, 60-70. doi:10.1016/j.jconrel.2017.01.002Ultimo, A., Giménez, C., Bartovsky, P., Aznar, E., Sancenón, F., Marcos, M. D., … Murguía, J. R. (2016). Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells. Chemistry - A European Journal, 22(5), 1582-1586. doi:10.1002/chem.201504629Polo, L., Gómez-Cerezo, N., Aznar, E., Vivancos, J.-L., Sancenón, F., Arcos, D., … Martínez-Máñez, R. (2017). Molecular gates in mesoporous bioactive glasses for the treatment of bone tumors and infection. Acta Biomaterialia, 50, 114-126. doi:10.1016/j.actbio.2016.12.025Luo, Z., Ding, X., Hu, Y., Wu, S., Xiang, Y., Zeng, Y., … Zhao, Y. (2013). Engineering a Hollow Nanocontainer Platform with Multifunctional Molecular Machines for Tumor-Targeted Therapy in Vitro and in Vivo. ACS Nano, 7(11), 10271-10284. doi:10.1021/nn404676wZhang, Q., Neoh, K. G., Xu, L., Lu, S., Kang, E. T., Mahendran, R., & Chiong, E. (2014). Functionalized Mesoporous Silica Nanoparticles with Mucoadhesive and Sustained Drug Release Properties for Potential Bladder Cancer Therapy. Langmuir, 30(21), 6151-6161. doi:10.1021/la500746eGuillet-Nicolas, R., Popat, A., Bridot, J.-L., Monteith, G., Qiao, S. Z., & Kleitz, F. (2013). pH-Responsive Nutraceutical-Mesoporous Silica Nanoconjugates with Enhanced Colloidal Stability. Angewandte Chemie International Edition, 52(8), 2318-2322. doi:10.1002/anie.201208840Bringas, E., Köysüren, Ö., Quach, D. V., Mahmoudi, M., Aznar, E., Roehling, J. D., … Stroeve, P. (2012). Triggered release in lipid bilayer-capped mesoporous silica nanoparticles containing SPION using an alternating magnetic field. Chemical Communications, 48(45), 5647. doi:10.1039/c2cc31563gOroval, M., Climent, E., Coll, C., Eritja, R., Aviñó, A., Marcos, M. D., … Amorós, P. (2013). An aptamer-gated silica mesoporous material for thrombin detection. Chemical Communications, 49(48), 5480. doi:10.1039/c3cc42157kHe, D., He, X., Wang, K., Chen, M., Zhao, Y., & Zou, Z. (2013). Intracellular acid-triggered drug delivery system using mesoporous silica nanoparticles capped with T–Hg2+–T base pairs mediated duplex DNA. Journal of Materials Chemistry B, 1(11), 1552. doi:10.1039/c3tb00473bChen, L., Zhou, X., Nie, W., Zhang, Q., Wang, W., Zhang, Y., & He, C. (2016). Multifunctional Redox-Responsive Mesoporous Silica Nanoparticles for Efficient Targeting Drug Delivery and Magnetic Resonance Imaging. ACS Applied Materials & Interfaces, 8(49), 33829-33841. doi:10.1021/acsami.6b11802Croissant, J. G., Zhang, D., Alsaiari, S., Lu, J., Deng, L., Tamanoi, F., … Khashab, N. M. (2016). Protein-gold clusters-capped mesoporous silica nanoparticles for high drug loading, autonomous gemcitabine/doxorubicin co-delivery, and in-vivo tumor imaging. Journal of Controlled Release, 229, 183-191. doi:10.1016/j.jconrel.2016.03.030Oroval, M., Díez, P., Aznar, E., Coll, C., Marcos, M. D., Sancenón, F., … Martínez-Máñez, R. (2016). Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery. Chemistry - A European Journal, 23(6), 1353-1360. doi:10.1002/chem.201604104Chen, C., Geng, J., Pu, F., Yang, X., Ren, J., & Qu, X. (2010). Polyvalent Nucleic Acid/Mesoporous Silica Nanoparticle Conjugates: Dual Stimuli-Responsive Vehicles for Intracellular Drug Delivery. Angewandte Chemie International Edition, 50(4), 882-886. doi:10.1002/anie.201005471Yang, X., Liu, X., Liu, Z., Pu, F., Ren, J., & Qu, X. (2012). Near-Infrared Light-Triggered, Targeted Drug Delivery to Cancer Cells by Aptamer Gated Nanovehicles. Advanced Materials, 24(21), 2890-2895. doi:10.1002/adma.201104797Deng, Z., Zhen, Z., Hu, X., Wu, S., Xu, Z., & Chu, P. K. (2011). Hollow chitosan–silica nanospheres as pH-sensitive targeted delivery carriers in breast cancer therapy. Biomaterials, 32(21), 4976-4986. doi:10.1016/j.biomaterials.2011.03.050Palanikumar, L., Choi, E. S., Cheon, J. Y., Joo, S. H., & Ryu, J.-H. (2014). Noncovalent Polymer-Gatekeeper in Mesoporous Silica Nanoparticles as a Targeted Drug Delivery Platform. Advanced Functional Materials, 25(6), 957-965. doi:10.1002/adfm.201402755Li, L.-L., Xie, M., Wang, J., Li, X., Wang, C., Yuan, Q., … Tan, W. (2013). A vitamin-responsive mesoporous nanocarrier with DNA aptamer-mediated cell targeting. Chemical Communications, 49(52), 5823. doi:10.1039/c3cc41072bHäuselmann, I., & Borsig, L. (2014). Altered Tumor-Cell Glycosylation Promotes Metastasis. Frontiers in Oncology, 4. doi:10.3389/fonc.2014.00028Haltiwanger, R. S., & Lowe, J. B. (2004). Role of Glycosylation in Development. Annual Review of Biochemistry, 73(1), 491-537. doi:10.1146/annurev.biochem.73.011303.074043A. Varki , R.Kannagi and B. P.Toole , Glycosylation Changes in Cancer , Cold Spring Harbor Laboratory Press , 2009A. Varki and J. B.Lowe , Biological Roles of Glycans , Cold Spring Harbor Laboratory Press , 2009Gary-Bobo, M., Hocine, O., Brevet, D., Maynadier, M., Raehm, L., Richeter, S., … Durand, J.-O. (2012). Cancer therapy improvement with mesoporous silica nanoparticles combining targeting, drug delivery and PDT. International Journal of Pharmaceutics, 423(2), 509-515. doi:10.1016/j.ijpharm.2011.11.045Brevet, D., Gary-Bobo, M., Raehm, L., Richeter, S., Hocine, O., Amro, K., … Durand, J.-O. (2009). Mannose-targeted mesoporous silica nanoparticles for photodynamic therapy. Chemical Communications, (12), 1475. doi:10.1039/b900427kHocine, O., Gary-Bobo, M., Brevet, D., Maynadier, M., Fontanel, S., Raehm, L., … Frochot, C. (2010). Silicalites and Mesoporous Silica Nanoparticles for photodynamic therapy. International Journal of Pharmaceutics, 402(1-2), 221-230. doi:10.1016/j.ijpharm.2010.10.004Park, I. Y., Kim, I. Y., Yoo, M. K., Choi, Y. J., Cho, M.-H., & Cho, C. S. (2008). Mannosylated polyethylenimine coupled mesoporous silica nanoparticles for receptor-mediated gene delivery. International Journal of Pharmaceutics, 359(1-2), 280-287. doi:10.1016/j.ijpharm.2008.04.010Luo, Z., Cai, K., Hu, Y., Zhao, L., Liu, P., Duan, L., & Yang, W. (2010). Mesoporous Silica Nanoparticles End-Capped with Collagen: Redox-Responsive Nanoreservoirs for Targeted Drug Delivery. Angewandte Chemie International Edition, 50(3), 640-643. doi:10.1002/anie.201005061PENG, J., WANG, K., TAN, W., HE, X., HE, C., WU, P., & LIU, F. (2007). Identification of live liver cancer cells in a mixed cell system using galactose-conjugated fluorescent nanoparticles. Talanta, 71(2), 833-840. doi:10.1016/j.talanta.2006.05.064Yu, M., Jambhrunkar, S., Thorn, P., Chen, J., Gu, W., & Yu, C. (2013). Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells. Nanoscale, 5(1), 178-183. doi:10.1039/c2nr32145aHe, Q., Ma, M., Wei, C., & Shi, J. (2012). Mesoporous carbon@silicon-silica nanotheranostics for synchronous delivery of insoluble drugs and luminescence imaging. Biomaterials, 33(17), 4392-4402. doi:10.1016/j.biomaterials.2012.02.056Wu, S., Huang, X., & Du, X. (2013). Glucose- and pH-Responsive Controlled Release of Cargo from Protein-Gated Carbohydrate-Functionalized Mesoporous Silica Nanocontainers. Angewandte Chemie International Edition, 52(21), 5580-5584. doi:10.1002/anie.201300958Li, J., Qu, X., Payne, G. F., Zhang, C., Zhang, Y., Li, J., … Liu, C. (2015). Biospecific Self-Assembly of a Nanoparticle Coating for Targeted and Stimuli-Responsive Drug Delivery. Advanced Functional Materials, 25(9), 1404-1417. doi:10.1002/adfm.201403636Burchell, J., Poulsom, R., Hanby, A., Whitehouse, C., Cooper, L., Clausen, H., … Taylor-Papadimitriou, J. (1999). An  2,3 sialyltransferase (ST3Gal I) is elevated in primary breast carcinomas. Glycobiology, 9(12), 1307-1311. doi:10.1093/glycob/9.12.1307Pinho, S. S., Reis, C. A., Paredes, J., Magalhaes, A. M., Ferreira, A. C., Figueiredo, J., … Seruca, R. (2009). The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional modifications of E-cadherin. Human Molecular Genetics, 18(14), 2599-2608. doi:10.1093/hmg/ddp194Takahashi, M., Kuroki, Y., Ohtsubo, K., & Taniguchi, N. (2009). Core fucose and bisecting GlcNAc, the direct modifiers of the N-glycan core: their functions and target proteins. Carbohydrate Research, 344(12), 1387-1390. doi:10.1016/j.carres.2009.04.031Li, M., Song, L., & Qin, X. (2010). Glycan changes: cancer metastasis and anti-cancer vaccines. Journal of Biosciences, 35(4), 665-673. doi:10.1007/s12038-010-0073-8Nagao, K., Itoh, Y., Fujita, K., & Fujime, M. (2007). Evaluation of urinary CA19-9 levels in bladder cancer patients classified according to the combinations of Lewis and Secretor blood group genotypes. International Journal of Urology, 14(9), 795-799. doi:10.1111/j.1442-2042.2007.01840.xGao, W., Liang, J., & Liang, Y. (2016). Clinicopathological and prognostic significance of sialyl Lewis X overexpression in patients with cancer: a meta-analysis. OncoTargets and Therapy, 3113. doi:10.2147/ott.s102389Sozzani, P., Arisio, R., Porpiglia, M., & Benedetto, C. (2008). Is Sialyl Lewis x Antigen Expression a Prognostic Factor in Patients With Breast Cancer? International Journal of Surgical Pathology, 16(4), 365-374. doi:10.1177/1066896908324668Yusa, A., Miyazaki, K., Kimura, N., Izawa, M., & Kannagi, R. (2010). Epigenetic Silencing of the Sulfate Transporter Gene DTDST Induces Sialyl Lewisx Expression and Accelerates Proliferation of Colon Cancer Cells. Cancer Research, 70(10), 4064-4073. doi:10.1158/0008-5472.can-09-2383Golijanin, D., Sherman, Y., Shapiro, A., & Pode, D. (1995). Detection of bladder tumors by immunostaininc of the lewis x antigen in cells from voided urine. Urology, 46(2), 173-177. doi:10.1016/s0090-4295(99)80189-7Hittelet, A., Camby, I., Nagy, N., Legendre, H., Bronckart, Y., Decaestecker, C., … Yeaton, P. (2003). Binding Sites for Lewis Antigens Are Expressed by Human Colon Cancer Cells and Negatively Affect Their Migration. Laboratory Investigation, 83(6), 777-787. doi:10.1097/01.lab.0000073129.62433.39De la Torre, C., Casanova, I., Acosta, G., Coll, C., Moreno, M. J., Albericio, F., … Martínez-Máñez, R. (2014). Gated Mesoporous Silica Nanoparticles Using a Double-Role Circular Peptide for the Controlled and Target-Preferential Release of Doxorubicin in CXCR4-Expresing Lymphoma Cells. Advanced Functional Materials, 25(5), 687-695. doi:10.1002/adfm.201403822De la Fuente, J. M., & Penadés, S. (2002). Synthesis of Lex-neoglycoconjugate to study carbohydrate–carbohydrate associations and its intramolecular interaction. Tetrahedron: Asymmetry, 13(17), 1879-1888. doi:10.1016/s0957-4166(02)00480-9Zhu, T., & Boons, G.-J. (2000). A Novel and Efficient Synthesis of a Dimeric LexOligosaccharide on Polymeric Support. Journal of the American Chemical Society, 122(41), 10222-10223. doi:10.1021/ja001930lMartínez-Ávila, O., Hijazi, K., Marradi, M., Clavel, C., Campion, C., Kelly, C., & Penadés, S. (2009). GoldManno-Glyconanoparticles: Multivalent Systems to Block HIV-1 gp120 Binding to the Lectin DC-SIGN. Chemistry - A European Journal, 15(38), 9874-9888. doi:10.1002/chem.200900923Cory, A. H., Owen, T. C., Barltrop, J. A., & Cory, J. G. (1991). Use of an Aqueous Soluble Tetrazolium/Formazan Assay for Cell Growth Assays in Culture. Cancer Communications, 3(7), 207-212. doi:10.3727/095535491820873191Malich, G., Markovic, B., & Winder, C. (1997). The sensitivity and specificity of the MTS tetrazolium assay for detecting the in vitro cytotoxicity of 20 chemicals using human cell lines. Toxicology, 124(3), 179-192. doi:10.1016/s0300-483x(97)00151-0Sakuma, K., Aoki, M., & Kannagi, R. (2012). Transcription factors c-Myc and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/bFGF-induced epithelial-mesenchymal transition. Proceedings of the National Academy of Sciences, 109(20), 7776-7781. doi:10.1073/pnas.111113510

La evaluación de competencias en los Trabajos Fin de Estudios

En este artículo proponemos un procedimiento objetivo para la evaluación, basada en competencias, de los trabajos fin de grado (TFG) y de máster (TFM) en el contexto de las ingenierías. Dicho procedimiento se ha dividido en seis etapas: (1) definición de las competencias asociadas al TFG o al TFM y de indicadores objetivos; (2) definición de los momentos (hitos) de evaluación, las acciones concretas de evaluación y los agentes implicados; (3) asignación de indicadores objetivos a cada acción de evaluación; (4) definición de los niveles de cumplimiento de cada indicador; (5) elaboración de los informes de evaluación que los agentes evaluadores deberán cumplimentar y (6) definición del criterio de puntación para asignar la nota final a partir de los informes de evaluación. Para cada uno de estos puntos se ofrecen ayudas en forma de encuestas, fichas de competencias y/o ejemplos de aplicación

Gated Mesoporous Silica Nanocarriers for a "two-Step" Targeted System to Colonic Tissue

[EN] Colon targeted drug delivery is highly relevant not only to treat colonic local diseases but also for systemic therapies. Mesoporous silica nanoparticles (MSNs) have been demonstrated as useful systems for controlled drug release given their biocompatibility and the possibility of designing gated systems able to release cargo only upon the presence of certain stimuli. We report herein the preparation of three gated MSNs able to deliver their cargo triggered by different stimuli (redox ambient (S1), enzymatic hydrolysis (S2), and a surfactant or being in contact with cell membrane (S3)) and their performance in solution and in vitro with Caco-2 cells. Safranin O dye was used as a model drug to track cargo fate. Studies of cargo permeability in Caco-2 monolayers demonstrated that intracellular safranin O levels were significantly higher in Caco-2 monolayers when using MSNs compared to those of free dye. Internalization assays indicated that S2 nanoparticles were taken up by cells via endocytosis. S2 nanoparticles were selected for in vivo tests in rats. For in vivo assays, capsules were filled with S2 nanoparticles and coated with Eudragit FS 30 D to target colon. The enteric coated capsule containing the MSNs was able to deliver S2 nanoparticles in colon tissue (first step), and then nanoparticles were able to deliver safranin O inside the colonic cells after the enzymatic stimuli (second step). This resulted in high levels of safranin O in colonic tissue combined with low dye levels in plasma and body tissues. The results suggested that this combination of enzyme-responsive gated MSNs and enteric coated capsules may improve the absorption of drugs in colon to treat local diseases with a reduction of systemic effects.The authors acknowledge the financial support from the Spanish Government (Projects MAT2015-64139-C4-1-R, SAF2016-78756 and AGL2015-70235-C2-2-R) and the Generalitat Valenciana (Project GVA/2014/13).Gonzalez-Alvarez, M.; Coll Merino, MC.; Gonzalez-Alvarez, I.; Giménez Morales, C.; Aznar, E.; Martínez-Bisbal, M.; Lozoya Agulló, I.... (2017). Gated Mesoporous Silica Nanocarriers for a "two-Step" Targeted System to Colonic Tissue. Molecular Pharmaceutics. 14(12):4442-4453. https://doi.org/10.1021/acs.molpharmaceut.7b00565S44424453141

Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens

Background: Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation. Methods: Nested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models. Results: We analyzed 619 plasma samples from 148 patients (3DR, N=90; 2DR, N=58), the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, hs-CRP, sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-CRP quartile increase (aOR 3.3, 95%CI 1.1-10) and D-dimer quartile increase (aOR 3.7, 95%CI 1.1-13). The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI vs DTG). Conclusions: In this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation.The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by Instituto de Salud Carlos III, Spanish Health Ministry (Grant n° proyectos RD06/0006/0035, RD12/0017/0037 and RD16/0025/0019) as part of the Plan Nacional R + D + I and co-financed by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF). The RIS Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA (RIS C03/173, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional R+D+I and cofinanced by ISCIII-Subdirección General de Evaluacion and Fondo Europeo de Desarrollo Regional (FEDER)”. This work was supported by the Instituto de Salud Carlos III projects AC17/00019, PI18/00154, ICI20/00058, CIBER de Enfermedades Infecciosas, and Gilead Sciences (Investigator Sponsored Research ISR-17-10192). The funders had no role in the study design, data analysis, or in the interpretation of the results.S

Benefit of left atrial roof linear ablation in paroxysmal atrial fibrillation: a prospective, randomized study

Background Isolation of the pulmonary veins (PVs) for the treatment of atrial fibrillation (AF) is often supplemented with linear lesions within the left atrium (LA). However, there are conflicting data on the effects of creating a roof line (RL) joining the superior PVs in paroxysmal atrial fibrillation (PAF). Methods and Results A cohort of 120 patients with drug-refractory PAF referred for ablation were prospectively randomized into 2 strategies: (1) PV isolation in combination with RL ablation (LA roof ablation [LARA]-1: 59 patients) or (2) PV isolation (LARA-2: 61 patients). Follow-up was performed at 1, 3, and 6 months after the procedure and every 6 months thereafter. After a 3-month blanking period, recurrence was defined as the ocurrence of any atrial tachyarrhythmia lasting ≥30 seconds. PV isolation was achieved in 89% and complete RL block in 81%. RF duration, fluoroscopy, and procedural times were slightly, but not significantly, longer in the LARA-1 group. After 15±10 months, there was no difference in the arrhythmia-free survival after a single AF ablation procedure (LARA-1: 59% vs. LARA-2: 56% at 12 months; log rank P=0.77). The achievement of complete RL block did not influence the results. The incidence of LA macroreentrant tachycardias was 5.1% in the LARA-1 group (n=3) versus 8.2% in the LARA-2 (n=5) (P=ns). Univariate analysis only identified AF duration as a covariate associated with arrhythmia recurrence (hazard ratio, 1.01 [95% confidence interval, 1.002 to 1.012]; P<0.01). Conclusion The linear block at the LA roof is not associated with an improved clinical outcome compared with PV isolation alone

MAP1B Regulates Axonal Development by Modulating Rho-GTPase Rac1 Activity

This article shows a novel function for the MAP1B protein, related to the control of actin dynamics through interaction with Tiam1

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics