Unbinding forces and energies between a siRNA molecule and a dendrimer measured by force spectroscopy

We have measured the intermolecular forces between small interference RNA (siRNA) and polyamidoamine dendrimers at the single molecular level. A single molecule force spectroscopy approach has been developed to measure the unbinding forces and energies between a siRNA molecule and polyamidoamine dendrimers deposited on a mica surface in a buffer solution. We report three types of unbinding events which are characterized by forces and free unbinding energies, respectively, of 28 pN, 0.709 eV; 38 pN, 0.722 eV; and 50 pN, 0.724 eV. These events reflect different possible electrostatic interactions between the positive charges of one or two dendrimers and the negatively charged phosphate groups of a single siRNA. We have evidence of a high binding affinity of siRNA towards polyamidoamine dendrimers that leads to a 45% probability of measuring specific unbinding eventsThis work was funded by the European Research Council ERC-AdG-340177 (3DNanoMech) grant to RG and by the Spanish Ministry of Economy (MINECO) through grants CSD2010-00024, MAT2013-44858-R to RG and BFU2011-30161- C02-01 and BFU2014-59009-P to VC.Peer reviewe

Valores sociales en los spots publicitarios de bebidas emitidos en España en el 2006

El objetivo principal de este artículo es señalar los valores sociales presentes en los spots de bebidas emitidos por televisión, en España, durante el año 2006. Se estudian los valores sociales que transmiten los anuncios al margen de su función comercial. En total, se han analizado 191 spots; para los que se detallan los valores atribuidos al producto y al consumidor. La salud, la juventud, la importancia de las relaciones sociales o de construirse una personalidad genuina son algunos de los principales valores e ideales transmitidos a través de los spots sometidos a estudio

Role of toxin activation on binding and pore formation activity of the Bacillus thuringiensis Cry3 toxins in membranes of Leptinotarsa decemlineata (Say)

AbstractBinding and pore formation constitute key steps in the mode of action of Bacillus thuringiensis δ-endotoxins.In this work, we present a comparative analysis of toxin-binding capacities of proteolytically processed Cry3A, Cry3B and Cry3C toxins to brush border membranes (BBMV) of the Colorado potato beetle Leptinotarsa decemlineata (CPB), a major potato coleopteran-insect pest. Competition experiments showed that the three Cry3 proteolytically activated toxins share a common binding site. Also heterologous competition experiments showed that Cry3Aa and Cry3Ca toxins have an extra binding site that is not shared with Cry3Ba toxin. The pore formation activity of the three different Cry3 toxins is analysed. High pore-formation activities were observed in Cry3 toxins obtained by proteolytical activation with CPB BBMV in contrast to toxins activated with either trypsin or chymotrypsin proteases. The pore-formation activity correlated with the formation of soluble oligomeric structures. Our data support that, similarly to the Cry1A toxins, the Cry3 oligomer is formed after receptor binding and before membrane insertion, forming a pre-pore structure that is insertion-competent

Transcriptional dissection of pancreatic tumors engrafted in mice.

BACKGROUND: Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice to generate patient-derived xenograft (PDX) models is a promising platform for biological and therapeutic studies in this disease. However, these models are still incompletely characterized. Here, we measured the impact of the murine tumor environment on the gene expression of the engrafted human tumoral cells. METHODS: We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published microarray data of 18 PDX models, 53 primary tumors and 41 cell lines from PDAC. The results obtained in the PDAC system were further compared with public available microarray data from 42 PDX models, 108 primary tumors and 32 cell lines from hepatocellular carcinoma (HCC). We developed a robust analysis protocol to explore the gene expression space. In addition, we completed the analysis with a functional characterization of PDX models, including if changes were caused by murine environment or by serial passing. RESULTS: Our results showed that PDX models derived from PDAC, or HCC, were clearly different to the cell lines derived from the same cancer tissues. Indeed, PDAC- and HCC-derived cell lines are indistinguishable from each other based on their gene expression profiles. In contrast, the transcriptomes of PDAC and HCC PDX models can be separated into two different groups that share some partial similarity with their corresponding original primary tumors. Our results point to the lack of human stromal involvement in PDXs as a major factor contributing to their differences from the original primary tumors. The main functional differences between pancreatic PDX models and human PDAC are the lower expression of genes involved in pathways related to extracellular matrix and hemostasis and the up- regulation of cell cycle genes. Importantly, most of these differences are detected in the first passages after the tumor engraftment. CONCLUSIONS: Our results suggest that PDX models of PDAC and HCC retain, to some extent, a gene expression memory of the original primary tumors, while this pattern is not detected in conventional cancer cell lines. Expression changes in PDXs are mainly related to pathways reflecting the lack of human infiltrating cells and the adaptation to a new environment. We also provide evidence of the stability of gene expression patterns over subsequent passages, indicating early phases of the adaptation process

The exoskeleton for gait rehabilitation ALICE: dynamic analysis and control system evaluation using Hamilton quaternions

[EN] A robotic exoskeleton is an electromechanical device that can be worn by a person to increase its physical capacity, to assist locomotion or for gait rehabilitation processes. In the case of rehabilitation exoskeletons, the control system is required to be smooth and capable to match accurately with the patients’ evolution in order to optimize the eciency of their recovery, this implies the design of robust and precise controllers. In this paper, kinematic analysis, dynamic analysis and control system evaluation for ALICE rehabilitation exoskeleton is presented. Among the control techniques used are: the PD controller, adaptive PD, and the sliding mode controller. In addition, a stability analysis using the Lyapunov criterion is performed. To test the performance of the controllers, gait data obtained by the ONCE School of  Physiotherapy in Madrid, which correspond to healthy people and people with multiple sclerosis, are used. MATLAB as simulation software and programming language is used.[ES] Un exoesqueleto robótico es un dispositivo electromecánico utilizado para aumentar la capacidad física de una persona, como ayuda a la locomoción o para procesos de rehabilitación de la marcha. En el caso de los exoesqueletos de rehabilitación se requiere que el sistema de control sea capaz de adaptarse adecuadamente a la evolución del paciente con el fin de optimizar su recuperación, esto implica el diseño de controladores robustos y precisos. En este trabajo se presenta el análisis cinemático, análisis dinámico y evaluación del sistema de control del exoesqueleto de rehabilitación ALICE. Dentro de las técnicas de control presentadas se encuentran: el controlador PD, PD adaptativo, y el controlador en modo deslizante. Además, se realiza un análisis de estabilidad utilizando el criterio de Lyapunov. Para probar el rendimiento de los reguladores, se utiliza un conjunto de datos de la Escuela de Fisioterapia de la ONCE de Madrid, correspondiente a personas sanas y personas con esclerosis múltiple. Se utiliza MATLAB como software de simulación y lenguaje de programación.Manuel Cardona agradece a la Fundación Carolina y a la Universidad Politécnica de Madrid, España, por el apoyo para la realización de esta investigación gracias a la beca de Doctorado otorgada en el marco del convenio con la Universidad Don Bosco, El Salvador.Cardona, M.; Serrano, F.; Martín, JA.; Rausell, E.; Saltaren, R.; García-Cena, C. (2020). El exoesqueleto de rehabilitación de la marcha ALICE: análisis dinámico y evaluación del sistema de control utilizando cuaternios de Hamilton. Revista Iberoamericana de Automática e Informática industrial. 18(1):48-57. https://doi.org/10.4995/riai.2020.12558OJS4857181Abolvafaei, M., Ganjefar, S., 2019. Maximum power extraction from a wind turbine using second-order fast terminal sliding mode control. Renewable Energy 139, 1437 - 1446. https://doi.org/10.1016/j.renene.2019.03.044Arnold, E. M., Ward, S. R., Lieber, R. L., Delp, S. L., 2010. A model of the lower limb for analysis of human movement.Cardona, M., Destarac, M. A., García, C. E., Nov 2017. Exoskeleton robots for rehabilitation: State of the art and future trends. In: 2017 IEEE 37th Central America and Panama Convention (CONCAPAN XXXVII). pp. 1-6. https://doi.org/10.1109/CONCAPAN.2017.8278480Cardona, M., García Cena, C. E., 2019a. Biomechanical analysis of the lower limb: A full-body musculoskeletal model for muscle-driven simulation. IEEE Access 7, 92709-92723. https://doi.org/10.1109/ACCESS.2019.2927515Cardona, M., García Cena, C. E., October 2019b. Musculoskeletal modeling as a tool for biomechanical analysis of normal and pathological gait. VIII Latin American Conference on Biomedical Engineering and XLII National Conference on Biomedical Engineering. CLAIB 2019. IFMBE Proceedings, Springer 75, 955-963. https://doi.org/10.1007/978-3-030-30648-9_124Chong, L., Jianfeng, S., Linhong, J., 2013. Lower limb rehabilitation robots: A review. In: World Congress on Medical Physics and Biomedical Engineering. IFMBE Proceedings. Vol. 39. p. 2042-2045. https://doi.org/10.1007/978-3-642-29305-4_536Eker, I., 2010. Second-order sliding mode control with experimental application. ISA Transactions 49 (3), 394 - 405. https://doi.org/10.1016/j.isatra.2010.03.010He, W., Li, Z., Dong, Y., Zhao, T., Jan 2019. Design and adaptive control for an upper limb robotic exoskeleton in presence of input saturation. IEEE Transactions on Neural Networks and Learning Systems 30 (1), 97-108. DOI: 10.1109/TNNLS.2018.2828813 https://doi.org/10.1109/TNNLS.2018.2828813Kapandji, A., 2010. Fisiología Articular, 6th Edition. Vol. 2. Editorial Panamericana, France.Maciejasz, P., Eschweiler, J., Gerlach-Hahn, K., et.al., 2014. "A survey on robotic devices for upper limb rehabilitation". https://doi.org/10.1186/1743-0003-11-3Proietti, T., Jarrasse, N., Roby-Brami, A., Morel, G., April 2015. Adaptive control of a robotic exoskeleton for neurorehabilitation. In: 2015 7th International IEEE/EMBS Conference on Neural Engineering (NER). pp. 803-806. https://doi.org/10.1109/NER.2015.7146745Reinkensmeyer, D. J., 2003. How to retrain movement after neurologic injury: a computational rationale for incorporating robot (or therapist) assistance. In: Proceedings of the 25th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE Cat. No.03CH37439). Vol. 2. pp. 1479-1482 Vol.2.Reinkensmeyer, D. J., Aoyagi, D., Emken, J., Galvez, J., Ichinose W, W., etal, Aug-Sep 2006. Tools for understanding and optimizing robotic gait training. J Rehabil Res Dev 43 (5), 657-70. https://doi.org/10.1682/JRRD.2005.04.0073Riener, R., Guidali, M., Keller, U., Duschau-Wicke, A., et.al., 2014. "a survey on robotic devices for upper limb rehabilitation".Serrano, F. E., Rossell, J. M., 2015. Complete kinematic analysis of the stewartgough platform by unit quaternions. Mechanics and Control (Vol, 34, no. 4), 59-69.Spong, M., Hutchinson, S., Vidyasagar, M., 2006. Robot Modeling and Control. John Wiley and Sons.Wang, J.-Y., Liang, H.-Z., Sun, Z.-W., Wu, S.-N., Zhang, S.-J., 2013. Relative motion coupled control based on dual quaternion. Aerospace Science and Technology 25 (1), 102 - 113. https://doi.org/10.1016/j.ast.2011.12.013Wu, Q., Chen, B., Wu, H., 2019. Rbfn-based adaptive backstepping sliding mode control of an upper-limb exoskeleton with dynamic uncertainties. IEEE Access 7, 134635-134646. https://doi.org/10.1109/ACCESS.2019.2941973Yakub, F., Khudzari, A., Mori, Y., March 2014. "recent trends for practical rehabilitation robotics, current challenges and the future". https://doi.org/10.1097/MRR.0000000000000035Yang, Z., Zhu, Y., Yang, X., Zhang, Y., Aug 2009. Impedance control of exoskeleton suit based on adaptive rbf neural network. In: 2009 International Conference on Intelligent Human-Machine Systems and Cybernetics. Vol. 1. pp. 182-187. https://doi.org/10.1109/IHMSC.2009.54Zhou, W., Chen, W., Liu, H., Li, X., 2015. A new forward kinematic algorithm for a general stewart platform. Mechanism and Machine Theory 87, 177 - 190. https://doi.org/10.1016/j.mechmachtheory.2015.01.002Özgur, E., Mezouar, Y., 2016. Kinematic modeling and control of a robot arm ¨ using unit dual quaternions. Robotics and Autonomous Systems 77, 66 - 73. https://doi.org/10.1016/j.robot.2015.12.005Ilyas Eker, 2010. Second-order sliding mode control with experimental application. ISA Transactions 49 (3), 394 - 405. https://doi.org/10.1016/j.isatra.2010.03.01

Analysis of the authors’ rights collection frontier using PCA-MDEA: an application to the Valencia region

The aim of this paper is to estimate the authors’ rights collection frontier within the collection zones into which the Valencia Region (Spain) has been divided. To be more exact, a nonparametric frontier technique (Modified Data Envelopment Analysis, MDEA) and the Principal Components Analysis (PCA) are jointly employed to map out an initial approach to the potential authors’ rights collection within this region (as divided into collection zones). The analysis has been carried out both jointly and by majority sectors (performing, musical, and audio-visual arts).Publicaciones Econcult: Área de Investigación en Economía de la Cultura y Turismo. Universitat de Valènci

Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses.

BACKGROUND: Known antiretroviral restriction factors are encoded by genes that are under positive selection pressure, induced during HIV-1 infection, up-regulated by interferons, and/or interact with viral proteins. To identify potential novel restriction factors, we performed genome-wide scans for human genes sharing molecular and evolutionary signatures of known restriction factors and tested the anti-HIV-1 activity of the most promising candidates. RESULTS: Our analyses identified 30 human genes that share characteristics of known restriction factors. Functional analyses of 27 of these candidates showed that over-expression of a strikingly high proportion of them significantly inhibited HIV-1 without causing cytotoxic effects. Five factors (APOL1, APOL6, CD164, TNFRSF10A, TNFRSF10D) suppressed infectious HIV-1 production in transfected 293T cells by >90% and six additional candidates (FCGR3A, CD3E, OAS1, GBP5, SPN, IFI16) achieved this when the virus was lacking intact accessory vpr, vpu and nef genes. Unexpectedly, over-expression of two factors (IL1A, SP110) significantly increased infectious HIV-1 production. Mechanistic studies suggest that the newly identified potential restriction factors act at different steps of the viral replication cycle, including proviral transcription and production of viral proteins. Finally, we confirmed that mRNA expression of most of these candidate restriction factors in primary CD4+ T cells is significantly increased by type I interferons. CONCLUSIONS: A limited number of human genes share multiple characteristics of genes encoding for known restriction factors. Most of them display anti-retroviral activity in transient transfection assays and are expressed in primary CD4+ T cells

Single-cell analysis identifies cellular markers of the HIV permissive cell.

Cellular permissiveness to HIV infection is highly heterogeneous across individuals. Heterogeneity is also found across CD4+ T cells from the same individual, where only a fraction of cells gets infected. To explore the basis of permissiveness, we performed single-cell RNA-seq analysis of non-infected CD4+ T cells from high and low permissive individuals. Transcriptional heterogeneity translated in a continuum of cell states, driven by T-cell receptor-mediated cell activation and was strongly linked to permissiveness. Proteins expressed at the cell surface and displaying the highest correlation with T cell activation were tested as biomarkers of cellular permissiveness to HIV. FACS sorting using antibodies against several biomarkers of permissiveness led to an increase of HIV cellular infection rates. Top candidate biomarkers included CD25, a canonical activation marker. The combination of CD25 high expression with other candidate biomarkers led to the identification of CD298, CD63 and CD317 as the best biomarkers for permissiveness. CD25highCD298highCD63highCD317high cell population showed an enrichment of HIV-infection of up to 28 fold as compared to the unsorted cell population. The purified hyper-permissive cell subpopulation was characterized by a downregulation of interferon-induced genes and several known restriction factors. Single-cell RNA-seq analysis coupled with functional characterization of cell biomarkers provides signatures of the "HIV-permissive cell"