Structural studies of PrPSc

Elucidation of the structure of PrPSc continues to be one major challenge in prion research. Molecular basis of the biology of prion protein, such as the molecular mechanism of prion replication and aggregation, the species barrier and the pathogenesis of neurodegeneration will not be understood until the structure is solved. Given that high-resolution techniques such as NMR or X-ray crystallography cannot be used, a number of lower resolution analytical approaches have been attempted

La evaluación de las competencias básicas. Última fase del proceso de operativización

Desde la Unión Europea se ha optado por un modelo competencial que los distintos Estados miembros han asumido en la configuración de sus correspondientes currículos. España no es una excepción. A partir de la Ley Orgánica 2/2006 de Educación, de 3 de mayo, las competencias básicas se han convertido en un elemento curricular prescriptivo más y, por ende, en objeto de análisis y estudio desde diferentes ámbitos y perspectivas. Sin embargo, no se ha ofrecido un modelo de operativización que las aborde desde la planificación docente diferentes autores han apuntado algunas soluciones, pero los docentes han de desarrollar y evaluar las competencias básicas en el aula, en ocasiones, sin tener claro cómo hacerlo. El objetivo de este trabajo es aportar algunas orientaciones al profesorado para la evaluación de las competencias básicas partiendo de la operativización de las mismas a través de siete fases que concluyen en la elaboración de rúbricas que posibilitan dicha evaluación.The European Union has decided in favour of a competence-based model that the Member states have assumed in the configuration of his corresponding curricula. Spain is not an exception. From the Organic Law 2/2006 of Education of May 3, the based competences have turned into an element curricular prescriptive more and, for it, into object of analysis and study from different contexts and perspectives. Nevertheless, nobody has offered a model of coperativización that tackles them from the teaching planning. Different authors have aimed at somee solutions, but the teachers have to develop and evaluate the based competences in the classroom, sometimes, without knowing how to do it. The aim of this paper is to contribute a series of orientations to the professorship for the evaluation of the basic competences that begin on having made them operative across seven phases that they conclude in the making of rubrics that make possible the above mentioned evaluatio

A novel hydrogel-based connection mechanism for soft modular robots

Connection mechanisms are crucial in reconfigurable robots. In this work, we present a novel approach, based on the self-healing property of a hydrogel synthesized by our group, which allows us to easily attach and detach robotic modules using water as the only trigger element. Our connection mechanism does not need external energy to work and it is reversible and soft, being useful for soft modular robots. Tensile, fatigue and adhesion tests are presented to demonstrate the mechanical performance of our mechanism. Two modular soft robots, manipulator and snake, are featured to show the functionality of our approach.Los mecanismos de conexión son cruciales en los robots reconfigurables. En este trabajo, presentamos un enfoque novedoso, basado en la propiedad de autocuración de un hidrogel sintetizado por nuestro grupo, que nos permite acoplar y desacoplar fácilmente módulos robóticos utilizando el agua como como único elemento activador. Nuestro mecanismo de conexión no necesita energía externa para funcionar y es reversible y suave, siendo útil para los robots modulares blandos. Se presentan ensayos de tracción ensayos de tracción, fatiga y adherencia para demostrar el rendimiento mecánico de nuestro mecanismo. Se presentan dos robots modulares blandos, un manipulador y una serpiente, para para mostrar la funcionalidad de nuestro enfoque

Sublethal exposure of small few-layer graphene promotes metabolic alterations in human skin cells

Small few-layer graphene (sFLG), a novel small-sized graphene-related material (GRM), can be considered as an intermediate degradation product of graphene. GRMs have a promising present and future in the field of biomedicine. However, safety issues must be carefully addressed to facilitate their implementation. In the work described here, the effect of sub-lethal doses of sFLG on the biology of human HaCaT keratinocytes was examined. A one-week treatment of HaCaTs with sub-lethal doses of sFLG resulted in metabolome remodeling, dampening of the mitochondrial function and a shift in the redox state to pro-oxidant conditions. sFLG raises reactive oxygen species and calcium from 24 hours to one week after the treatment and this involves the activation of NADPH oxidase 1. Likewise, sFLG seems to induce a shift from oxidative phosphorylation to glycolysis and promotes the use of glutamine as an alternative source of energy. When sub-toxic sFLG exposure was sustained for 30 days, an increase in cell proliferation and mitochondrial damage were observed. Further research is required to unveil the safety of GRMs and degradation-derived products before their use in the workplace and in practical applications

Hydrogel-based soft pneumatic bending actuator with self-healing and proprioception capabilities

Proprioception is a necessary skill in robots and especially complicated in soft robots. It is commonly achieved by adding an external complement to the robotic structure that acts as a sensor. In this work, we present an approach in which the material itself (a cationic network hydrogel) serves as a structure and as a curvature sensor in a soft pneumatic bending actuator. The experiments carried out validate the use of the resistive strain capacity of our hydrogel as a proprioceptive sensor. We believe that this sensing capacity, together with the high stretchability and self-healing capability of our material makes our approach an interesting alternative for the development of soft actuators.La propiocepción es una habilidad necesaria en los robots y especialmente complicada en los robots blandos. Se suele conseguir añadiendo un complemento externo a la estructura robótica que actúa como sensor. En este trabajo, presentamos un enfoque en el que el propio material (un hidrogel de red catiónico) sirve como estructura y como sensor de curvatura en un actuador neumático blando de flexión. de flexión. Los experimentos realizados validan el uso de la capacidad resistiva resistiva de nuestro hidrogel como sensor propioceptivo. Creemos que creemos que esta capacidad de detección, junto con la alta capacidad de estiramiento y autocuración capacidad de autocuración de nuestro material hace que nuestro enfoque sea una alternativa interesante para el desarrollo de actuadores blandos

Structural organization of mammalian prions as probed by limited proteolysis

Elucidation of the structure of PrP(Sc) continues to be one major challenge in prion research. The mechanism of propagation of these infectious agents will not be understood until their structure is solved. Given that high resolution techniques such as NMR or X-ray crystallography cannot be used, a number of lower resolution analytical approaches have been attempted. Thus, limited proteolysis has been successfully used to pinpoint flexible regions within prion multimers (PrP(Sc)). However, the presence of covalently attached sugar antennae and glycosylphosphatidylinositol (GPI) moieties makes mass spectrometry-based analysis impractical. In order to surmount these difficulties we analyzed PrP(Sc) from transgenic mice expressing prion protein (PrP) lacking the GPI membrane anchor. Such animals produce prions that are devoid of the GPI anchor and sugar antennae, and, thereby, permit the detection and location of flexible, proteinase K (PK) susceptible regions by Western blot and mass spectrometry-based analysis. GPI-less PrP(Sc) samples were digested with PK. PK-resistant peptides were identified, and found to correspond to molecules cleaved at positions 81, 85, 89, 116, 118, 133, 134, 141, 152, 153, 162, 169 and 179. The first 10 peptides (to position 153), match very well with PK cleavage sites we previously identified in wild type PrP(Sc). These results reinforce the hypothesis that the structure of PrP(Sc) consists of a series of highly PK-resistant β-sheet strands connected by short flexible PK-sensitive loops and turns. A sizeable C-terminal stretch of PrP(Sc) is highly resistant to PK and therefore perhaps also contains β-sheet secondary structure

Autonomous self-healing pneumatic McKibben muscle based on a new hydrogel material

In this paper we present a hydrogel with self-healing capabilities and its application for the development of a Pneumatic Artificial Muscle (PAM). Unlike other hydrogels, our material can be used outside of aqueous environments and does not need any external stimulus to self-heal, which makes it an interesting alternative for the manufacturing of soft robots. First, the mechanical properties of the hydrogel and its self-healing ability are analyzed. Second, we present the development of a pneumatic muscle based on the classic McKibben design but including our material. Finally, we analyze the capabilities of our self-repairing muscles before and after being punctured. The results show a good performance of our actuators even after low healing periods (10 minutes).En este trabajo presentamos un hidrogel con capacidad de autocuración y su aplicación para el desarrollo de un músculo artificial neumático (PAM). A diferencia de otros hidrogeles, nuestro material puede utilizarse fuera de entornos acuosos y no necesita ningún estímulo externo para autocurarse, lo que hace que sea una alternativa interesante para la fabricación de robots blandos. En primer lugar, se analizan las propiedades mecánicas del hidrogel y su capacidad de autocuración de autocuración. En segundo lugar, se presenta el desarrollo de un músculo neumático basado en el diseño clásico de McKibben pero incluyendo nuestro material. Por último analizamos las capacidades de nuestros músculos autorreparadores antes y después de de ser pinchados. Los resultados muestran un buen rendimiento de nuestros actuadores incluso después de periodos de curación bajos (10 minutos)

Stochastic vs. deterministic magnetic coding in designed cylindrical nanowires for 3D magnetic networks

[EN] Advances in cylindrical nanowires for 3D information technologies profit from intrinsic curvature that introduces significant differences with regards to planar systems. A model is proposed to control the stochastic and deterministic coding of remanent 3D complex vortex configurations in designed multilayered (magnetic/non-magnetic) cylindrical nanowires. This concept, introduced by micromagnetic simulations, is experimentally confirmed by magnetic imaging in FeCo/Cu multilayered nanowires. The control over the random/deterministic vortex states configurations is achieved by a suitable geometrical interface tilting of almost non-interacting FeCo segments with respect to the nanowire axis, together with the relative orientation of the perpendicular magnetic field. The proper design of the segments' geometry (e.g. tilting) in cylindrical nanowires opens multiple opportunities for advanced nanotechnologies in 3D magnetic networks.Spanish Ministry of Science and Innovation under Projects MAT2016-76824-C3-1-R, PID2019-108075RB-C31/ AEI / 10.13039/501100011033 and PGC2018-097789-B-I00 and the Regional Government of Madrid under Project S2018/NMT-4321 NANOMAGCOST-CM. LA and MF acknowledge project RTI2018-095303-B-C53.Peer reviewe

Malformations of the craniocervical junction (chiari type I and syringomyelia: classification, diagnosis and treatment)

Chiari disease (or malformation) is in general a congenital condition characterized by an anatomic defect of the base of the skull, in which the cerebellum and brain stem herniate through the foramen magnum into the cervical spinal canal. The onset of Chiari syndrome symptoms usually occurs in the second or third decade (age 25 to 45 years). Symptoms may vary between periods of exacerbation and remission. The diagnosis of Chiari type I malformation in patients with or without symptoms is established with neuroimaging techniques. The most effective therapy for patients with Chiari type I malformation/syringomyelia is surgical decompression of the foramen magnum, however there are non-surgical therapy to relieve neurophatic pain: either pharmacological and non-pharmacological. Pharmacological therapy use drugs that act on different components of pain. Non-pharmacological therapies are primarly based on spinal or peripheral electrical stimulation

Cannabinoid receptor CB2 drives HER2 pro-oncogenic signaling in breast cancer

Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different models of cancer. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen and Freiburg between 1997 and 2010. CB2 mRNA expression was also analyzed in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the HER2 rat ortholog (neu) and lacks CB2, and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by co-localization, coimmunoprecipitation and proximity ligation assays. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis. We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade, and that an increased CB2 expression activates the HER2 prooncogenic signaling machinery at the level of the tyrosine kinase c-SRC. Finally, HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and suggest that CB2 may be a biomarker with prognostic value in these tumors