El control del entrenamiento de la resistencia: importancia de la frecuencia crítica de fusión ocular

La frecuencia crítica de fusión ocular (FCF) se define como la frecuencia de un estímulo luminoso, a partir de la cual se percibe como una sensación estable y continua. Su utilidad en el contexto del entrenamiento deportivo se centra con su probable relación con el nivel de activación y fatiga del sistema nervioso central (SNC). Si la FCF aumenta se considera que el nivel de activación es superior y si desciende, la activación es inferior. Valores inferiores al de la línea base se relacionan con una fatiga del SNC. Como es evidente cada disciplina deportiva requiere de un nivel óptimo de activación para obtener el máximo rendimiento. El trabajo que presentamos introduce la FCF en el control del entrenamiento. Su principal objetivo fue determinar si existe alguna relación entre la FCF y diferentes tipos de esfuerzo físico que implican diferentes manifestaciones de la resistencia aeróbica y anaeróbica láctica. Los resultados obtenidos indican diferencias estadísticamente significativas entre el nivel de activación de la FCF antes y después de los diferentes tipos de esfuerzos físicos que se han planteado. En todas las situaciones experimentales, los entrenamientos que se han aplicado han comportado un aumento de la FCF. Destacamos que no se han demostrado diferencias estadísticamente significativas en cuanto el nivel de activación de la FCF entre esfuerzos de carácter aeróbico intensivo y anaeróbicos lácticos

El control de l’entrenament de la resistència: importància de la freqüència crítica de fusió ocular

La freqüència crítica de fusió ocular (FCF) es defineix com la freqüència d’un estímul lluminós, a partir de la qual es percep com una sensació estable i contínua. La seva utilitat en el context de l’entrenament esportiu se centra en la seva probable relació amb el nivell d’activació i fatiga del sistema nerviós central (SNC). Si la FCF augmenta es considera que el nivell d’activació és superior i si baixa, l’activació és inferior. Valors inferiors al de la línia base es relacionen amb una fatiga del SNC. Com és evident cada disciplina esportiva requereix un nivell òptim d’activació per obtenir el màxim rendiment. El treball que presentem introdueix la FCF en el control de l’entrenament. El seu principal objectiu va ser determinar si hi ha alguna relació entre la FCF i diferents tipus d’esforç físic que impliquen diferents manifestacions de la resistència aeròbica i anaeròbica làctica. Els resultats obtinguts indiquen diferències estadísticament significatives entre el nivell d’activació de la FCF abans i després dels diferents tipus d’esforços físics que s’han plantejat. En totes les situacions experimentals, els entrenaments que s’han aplicat han comportat un augment de la FCF. Destaquem que no s’han demostrat diferències estadísticament significatives pel que fa al nivell d’activació de la FCF entre esforços de caràcter aeròbic intensiu i anaeròbics làctics

Planteamiento, desarrollo y explotación en datos científicos

En esta nota se reseñan tres informes de temática común. El primero (de Erway) identifica los stakeholders o personas implicadas en el escenario de los datos de investigación y plantea el rol líder que puede asumir la biblioteca; el segundo (de LERU) informa exhaustivamente sobre qué debe acometerse; y el tercero (de Filippov) es una muestra de cómo el análisis de datos con técnicas de minería pone en valor los datasets, única justificación de la extendida frase “los datos son el nuevo petróleo de la economía”

Bibliografía [Cuadernos del Instituto Antonio de Nebrija de estudios sobre la Universidad. 2002, nº 5]

Publicad

Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles

[EN] A new gated nanodevice design able to control cargo delivery using glucose as a trigger and cyclodextrin-modified glucose oxidase as a capping agent is reported.Financial support from the Spanish Government (projects MAT2012-38429-C04-01 and CTQ2011-24355), Generalitat Valenciana (project PROMETEO/2009/016), UPV (project SP20120795) and Ramon y Cajal Programme (to R. V.) is gratefully acknowledged.Aznar Gimeno, E.; Villalonga, R.; Giménez Morales, C.; Sancenón Galarza, F.; Marcos Martínez, MD.; Martínez Mañez, R.; Díez, P.... (2013). Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles. Chemical Communications. 49(57):6391-6393. https://doi.org/10.1039/c3cc42210kS639163934957Coll, C., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2012). Gated Silica Mesoporous Supports for Controlled Release and Signaling Applications. Accounts of Chemical Research, 46(2), 339-349. doi:10.1021/ar3001469Aznar, 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:10.1517/17425240902895980Cotí, K. K., Belowich, M. E., Liong, M., Ambrogio, M. W., Lau, Y. A., Khatib, H. A., … Stoddart, J. F. (2009). Mechanised nanoparticles for drug delivery. Nanoscale, 1(1), 16. doi:10.1039/b9nr00162jKresge, C. T., Leonowicz, M. E., Roth, W. J., Vartuli, J. C., & Beck, J. S. (1992). Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature, 359(6397), 710-712. doi:10.1038/359710a0Lai, C.-Y., Trewyn, B. G., Jeftinija, D. M., Jeftinija, K., Xu, S., Jeftinija, S., & Lin, V. S.-Y. (2003). A Mesoporous Silica Nanosphere-Based Carrier System with Chemically Removable CdS Nanoparticle Caps for Stimuli-Responsive Controlled Release of Neurotransmitters and Drug Molecules. Journal of the American Chemical Society, 125(15), 4451-4459. doi:10.1021/ja028650lPark, C., Oh, K., Lee, S. C., & Kim, C. (2007). Controlled Release of Guest Molecules from Mesoporous Silica Particles Based on a pH-Responsive Polypseudorotaxane Motif. Angewandte Chemie International Edition, 46(9), 1455-1457. doi:10.1002/anie.200603404Casasús, R., Climent, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Ruiz, E. (2008). Dual Aperture Control on pH- and Anion-Driven Supramolecular Nanoscopic Hybrid Gate-like Ensembles. Journal of the American Chemical Society, 130(6), 1903-1917. doi:10.1021/ja0756772Liu, R., Liao, P., Liu, J., & Feng, P. (2011). Responsive Polymer-Coated Mesoporous Silica as a pH-Sensitive Nanocarrier for Controlled Release. Langmuir, 27(6), 3095-3099. doi:10.1021/la104973jCliment, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., Maquieira, A., & Amorós, P. (2010). Controlled Delivery Using Oligonucleotide-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 49(40), 7281-7283. doi:10.1002/anie.201001847Mal, N. K., Fujiwara, M., & Tanaka, Y. (2003). Photocontrolled reversible release of guest molecules from coumarin-modified mesoporous silica. Nature, 421(6921), 350-353. doi:10.1038/nature01362Fu, Q., Rao, G. V. R., Ista, L. K., Wu, Y., Andrzejewski, B. P., Sklar, L. A., … López, G. P. (2003). Control of Molecular Transport Through Stimuli-Responsive Ordered Mesoporous Materials. Advanced Materials, 15(15), 1262-1266. doi:10.1002/adma.200305165Aznar, E., Mondragón, L., Ros-Lis, J. V., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2011). Finely Tuned Temperature-Controlled Cargo Release Using Paraffin-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 50(47), 11172-11175. doi:10.1002/anie.201102756Bringas, 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/c2cc31563gPatel, K., Angelos, S., Dichtel, W. R., Coskun, A., Yang, Y.-W., Zink, J. I., & Stoddart, J. F. (2008). Enzyme-Responsive Snap-Top Covered Silica Nanocontainers. Journal of the American Chemical Society, 130(8), 2382-2383. doi:10.1021/ja0772086Schlossbauer, A., Kecht, J., & Bein, T. (2009). Biotin-Avidin as a Protease-Responsive Cap System for Controlled Guest Release from Colloidal Mesoporous Silica. Angewandte Chemie International Edition, 48(17), 3092-3095. doi:10.1002/anie.200805818Park, C., Kim, H., Kim, S., & Kim, C. (2009). Enzyme Responsive Nanocontainers with Cyclodextrin Gatekeepers and Synergistic Effects in Release of Guests. Journal of the American Chemical Society, 131(46), 16614-16615. doi:10.1021/ja9061085Bernardos, A., Mondragón, L., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2010). Enzyme-Responsive Intracellular Controlled Release Using Nanometric Silica Mesoporous Supports Capped with «Saccharides». ACS Nano, 4(11), 6353-6368. doi:10.1021/nn101499dAgostini, A., Mondragón, L., Bernardos, A., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., … Murguía, J. R. (2012). Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 51(42), 10556-10560. doi:10.1002/anie.201204663Schlossbauer, A., Warncke, S., Gramlich, P. M. E., Kecht, J., Manetto, A., Carell, T., & Bein, T. (2010). A Programmable DNA-Based Molecular Valve for Colloidal Mesoporous Silica. Angewandte Chemie International Edition, 49(28), 4734-4737. doi:10.1002/anie.201000827Climent, E., Bernardos, A., Martínez-Máñez, R., Maquieira, A., Marcos, M. D., Pastor-Navarro, N., … Amorós, P. (2009). Controlled Delivery Systems Using Antibody-Capped Mesoporous Nanocontainers. Journal of the American Chemical Society, 131(39), 14075-14080. doi:10.1021/ja904456dZhao, Y., Trewyn, B. G., Slowing, I. I., & Lin, V. S.-Y. (2009). Mesoporous Silica Nanoparticle-Based Double Drug Delivery System for Glucose-Responsive Controlled Release of Insulin and Cyclic AMP. Journal of the American Chemical Society, 131(24), 8398-8400. doi:10.1021/ja901831uHolzinger, M., Bouffier, L., Villalonga, R., & Cosnier, S. (2009). Adamantane/β-cyclodextrin affinity biosensors based on single-walled carbon nanotubes. Biosensors and Bioelectronics, 24(5), 1128-1134. doi:10.1016/j.bios.2008.06.029Oliver, N. S., Toumazou, C., Cass, A. E. G., & Johnston, D. G. (2009). Glucose sensors: a review of current and emerging technology. Diabetic Medicine, 26(3), 197-210. doi:10.1111/j.1464-5491.2008.02642.xWu, Q., Wang, L., Yu, H., Wang, J., & Chen, Z. (2011). Organization of Glucose-Responsive Systems and Their Properties. 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The use of mixed collagen-Matrigel matrices of increasing complexity recapitulates the biphasic role of cell adhesion in cancer cell migration: ECM sensing, remodeling and forces at the leading edge of cancer invasion

The migration of cancer cells is highly regulated by the biomechanical properties of their local microenvironment. Using 3D scaffolds of simple composition, several aspects of cancer cell mechanosensing (signal transduction, EMC remodeling, traction forces) have been separately analyzed in the context of cell migration. However, a combined study of these factors in 3D scaffolds that more closely resemble the complex microenvironment of the cancer ECM is still missing. Here, we present a comprehensive, quantitative analysis of the role of cell-ECM interactions in cancer cell migration within a highly physiological environment consisting of mixed Matrigel-collagen hydrogel scaffolds of increasing complexity that mimic the tumor microenvironment at the leading edge of cancer invasion. We quantitatively show that the presence of Matrigel increases hydrogel stiffness, which promotes ß1 integrin expression and metalloproteinase activity in H1299 lung cancer cells. Then, we show that ECM remodeling activity causes matrix alignment and compaction that favors higher tractions exerted by the cells. However, these traction forces do not linearly translate into increased motility due to a biphasic role of cell adhesions in cell migration: at low concentration Matrigel promotes migration-effective tractions exerted through a high number of small sized focal adhesions. However, at high Matrigel concentration, traction forces are exerted through fewer, but larger focal adhesions that favor attachment yielding lower cell motility

Human-carnivore relations: conflicts, tolerance and coexistence in the American West

Carnivore and humans live in proximity due to carnivore recovery efforts and ongoing human encroachment into carnivore habitats globally. The American West is a region that uniquely exemplifies these human-carnivore dynamics, however, it is unclear how the research community here integrates social and ecological factors to examine human-carnivore relations. Therefore, strategies promoting human-carnivore coexistence are urgently needed. We conducted a systematic review on human-carnivore relations in the American West covering studies between 2000 and 2018. We first characterized human-carnivore relations across states of the American West. Second, we analyzed similarities and dissimilarities across states in terms of coexistence, tolerance, number of ecosystem services and conflicts mentioned in literature. Third, we used Bayesian modeling to quantify the effect of social and ecological factors influencing the scientific interest on coexistence, tolerance, ecosystem services and conflicts. Results revealed some underlying biases in humancarnivore relations research. Colorado and Montana were the states where the highest proportion of studies were conducted with bears and wolves the most studied species. Non-lethal management was the most common strategy to mitigate conflicts. Overall, conflicts with carnivores were much more frequently mentioned than benefits. We found similarities among Arizona, California, Utah, and New Mexico according to how coexistence, tolerance, services and conflicts are addressed in literature. We identified percentage of federal/private land, carnivore family, social actors, and management actions, as factors explaining how coexistence, tolerance, conflicts and services are addressed in literature. We provide a roadmap to foster tolerance towards carnivores and successful coexistence strategies in the American West based on four main domains, (1)the dual role of carnivores as providers of both beneficial and detrimental contributions to people, (2)social-ecological factors underpinning the provision of beneficial and detrimental contributions, (3)the inclusion of diverse actors, and (4) cross-state collaborative management

Characterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysis

Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions. Our results show the plasticity of lung cancer cell migration, which turns from mesenchymal in collagen only matrices, to lobopodial in collagen-Matrigel matrices that approximate the interface between a disrupted basement membrane and the underlying connective tissue. Our quantification of migration speed confirms a biphasic role of Matrigel. At low concentration, Matrigel facilitates migration, most probably by providing a supportive and growth factor retaining environment. At high concentration, Matrigel slows down migration, possibly due excessive attachment. Finally, we show that antibody-based integrin blockade promotes a change in migration phenotype from mesenchymal or lobopodial to amoeboid and analyze the effect of this change in migration dynamics, in regards to the structure of the matrix. In summary, we describe and characterize a robust microfluidic platform and a set of software tools that can be used to study lung cancer cell migration under different microenvironments and experimental conditions. This platform could be used in future studies, thus benefitting from the advantages introduced by microfluidic devices: precise control of the environment, excellent optical properties, parallelization for high throughput studies and efficient use of therapeutic drugs.We would like to acknowledge the support of the Spanish Ministry of Economy and Competitiveness, under grants number DPI2012-38090-C03-02 and DPI2015-64221-C2-2-R (COS), TEC2013-48552-C2-1-R, TEC2016-78052-R, TEC2015-73064-EXP (AMB) and the Torres Quevedo program PTQ-11-04778 (RP); the Spanish Ministry of Health (FIS PI13/02313) (AR); the Czech Science Foundation, under grant number 302/12/G157 (MK, MMaška); and the European Research Council (ERC) through project ERC-2012-StG 306751 (JMGA)

Cancer immunotherapy with immunomodulatory anti-CD137 and anti-PD-1 monoclonal antibodies requires Batf3-dependent dendritic cells

Weak and ineffective antitumor cytotoxic T lymphocyte (CTL) responses can be rescued by immunomodulatory mAbs targeting PD-1 or CD137. Using Batf3−/− mice, which are defective for cross-presentation of cell-associated antigens, we show that BATF3-dependent dendritic cells (DC) are essential for the response to therapy with anti-CD137 or anti–PD-1 mAbs. Batf3−/− mice failed to prime an endogenous CTL-mediated immune response toward tumor-associated antigens, including neoantigens. As a result, the immunomodulatory mAbs could not amplify any therapeutically functional immune response in these mice. Moreover, administration of systemic sFLT3L and local poly-ICLC enhanced DC-mediated cross-priming and synergized with anti–CD137- and anti–PD-1–mediated immunostimulation in tumor therapy against B16-ovalbumin–derived melanomas, whereas this function was lost in Batf3−/− mice. These experiments show that cross-priming of tumor antigens by FLT3L- and BATF3-dependent DCs is crucial to the efficacy of immunostimulatory mAbs and represents a very attractive point of intervention to enhance their clinical antitumor effects

Multiplex Real-Time PCR Assay Using TaqMan Probes for the Identification of Trypanosoma cruzi DTUs in Biological and Clinical Samples

Background: Trypanosoma cruzi has been classified into six Discrete Typing Units (DTUs), designated as TcI–TcVI. In order to effectively use this standardized nomenclature, a reproducible genotyping strategy is imperative. Several typing schemes have been developed with variable levels of complexity, selectivity and analytical sensitivity. Most of them can be only applied to cultured stocks. In this context, we aimed to develop a multiplex Real-Time PCR method to identify the six T. cruzi DTUs using TaqMan probes (MTq-PCR).Methods/Principal Findings: The MTq-PCR has been evaluated in 39 cultured stocks and 307 biological samples from vectors, reservoirs and patients from different geographical regions and transmission cycles in comparison with a multi-locus conventional PCR algorithm. The MTq-PCR was inclusive for laboratory stocks and natural isolates and sensitive for direct typing of different biological samples from vectors, reservoirs and patients with acute, congenital infection or Chagas reactivation. The first round SL-IR MTq-PCR detected 1 fg DNA/reaction tube of TcI, TcII and TcIII and 1 pg DNA/reaction tube of TcIV, TcV and TcVI reference strains. The MTq-PCR was able to characterize DTUs in 83% of triatomine and 96% of reservoir samples that had been typed by conventional PCR methods. Regarding clinical samples, 100% of those derived from acute infected patients, 62.5% from congenitally infected children and 50% from patients with clinical reactivation could be genotyped. Sensitivity for direct typing of blood samples from chronic Chagas disease patients (32.8% from asymptomatic and 22.2% from symptomatic patients) and mixed infections was lower than that of the conventional PCR algorithm.Conclusions/Significance: Typing is resolved after a single or a second round of Real-Time PCR, depending on the DTU. This format reduces carryover contamination and is amenable to quantification, automation and kit production.This work received financial support from the Ministry of Science and Technology of Argentina [PICT 2011-0207 to AGS] and the National Scientific and Technical Research Council in Argentina (CONICET) [PIP 112 2011-010-0974 to AGS]. Work related to evaluation of biological samples was partially sponsored by the Pan-American Health Organization (PAHO) [Small Grants Program PAHO-TDR]; the Drugs and Neglected Diseases Initiative (DNDi, Geneva, Switzerland), Wellcome Trust (London, United Kingdom), SANOFI-AVENTIS (Buenos Aires, Argentina) and the National Council for Science and Technology in Mexico (CONACYT) [FONSEC 161405 to JMR]