Efectos de las políticas de transporte sobre las áreas sensibles.

El Centro de Investigacion del Transporte de la Universidad Politecnica de Madrid - TRANSyT-UPM- forma parte del proyecto de investigacion ASSET (Assessing SEnsitiveness to Transport) financiado por la Comision Europea. Su objetivo principal es desarrollar las capacidades cientificas y metodologicas para poner en ejecucion politicas e instrumentos que tienen como fin el equilibrio entre la protection de las areas ambientalmente sensibles con la disposition de un sistema eficiente de transporte en el ambito europeo. En su primer estadio ASSET ha considerado "zonas ambientalmente sensibles al transporte" aquellas que por sus caracteristicas poseen un alto valor ecologico, son consideradas como de alta fragilidad ecologica y ademas estan afectadas de manera notable por las actividades del transporte. En esta ponencia se presentan las conclusiones obtenidas en la segunda fase de las investigaciones llevadas a cabo en TRANSyT-UPM. A partir de una biisqueda y analisis de casos reales, se han identificado ejemplos de buenas practicas en la aplicacion de politicas e instrumentos en zonas ambientalmente sensibles a los efectos del transporte. De esta forma se ha podido comparar, contrastar y determinar politicas potencialmente adecuadas para su aplicacion a casos concretos con el objetivo de reducir lo maximo posible los efectos negativos del transporte en el medio ambiente. Este analisis servira de base cientifica para una tercera fase, en la que se estudiaran los posibles efectos de la aplicacion de politicas e instrumentos adecuados en areas sensibles al transporte situadas en diferentes ambitos geograficos europeos, mediante diversos casos de estudio

Functional diversity of motoneurons in the oculomotor system

Extraocular muscles contain two types of muscle fibers according to their innervation pattern: singly innervated muscle fibers (SIFs), similar to most skeletal muscle fibers, and multiply innervated muscle fibers (MIFs). Morphological studies have revealed that SIF and MIF motoneurons are segregated anatomically and receive different proportions of certain afferents, suggesting that while SIF motoneurons would participate in the whole repertoire of eye movements, MIF motoneurons would contribute only to slow eye movements and fixations. We have tested that proposal by performing single-unit recordings, in alert behaving cats, of electrophysiologically identified MIF and SIF motoneurons in the abducens nucleus. Our results show that both types of motoneuron discharge in relation to eye position and velocity, displaying a tonic–phasic firing pattern for different types of eye movement (saccades, vestibulo-ocular reflex, vergence) and gaze-holding. However, MIF motoneurons presented an overall reduced firing rate compared with SIF motoneurons, and had significantly lower recruitment threshold and also lower eye position and velocity sensitivities. Accordingly, MIF motoneurons could control mainly gaze in the off-direction, when less force is needed, whereas SIF motoneurons would contribute to increase muscle tension progressively toward the on-direction as more force is required. Anatomically, MIF and SIF motoneurons distributed intermingled within the abducens nucleus, with MIF motoneurons being smaller and having a lesser somatic synaptic coverage. Our data demonstrate the functional participation of both MIF and SIF motoneurons in fixations and slow and phasic eye movements, although their discharge properties indicate a functional segregation.Ministerio de Ciencia, Innovación y Universidades – Fondo Europeo de Desarrollo Regional (BFU2015-64515-P)Junta de Andalucía (BIO-297

Nanostructured Lipid Carriers Made of Ω-3 Polyunsaturated Fatty Acids: In Vitro Evaluation of Emerging Nanocarriers to Treat Neurodegenerative Diseases

Neurodegenerative diseases (ND) are one of the main problems of public health systems in the 21st century. The rise of nanotechnology-based drug delivery systems (DDS) has become in an emerging approach to target and treat these disorders related to the central nervous system (CNS). Among others, the use of nanostructured lipid carriers (NLCs) has increased in the last few years. Up to today, most of the developed NLCs have been made of a mixture of solid and liquid lipids without any active role in preventing or treating diseases. In this study, we successfully developed NLCs made of a functional lipid, such as the hydroxylated derivate of docohexaenoic acid (DHAH), named DHAH-NLCs. The newly developed nanocarriers were around 100 nm in size, with a polydispersity index (PDI) value of <0.3, and they exhibited positive zeta potential due to the successful chitosan (CS) and TAT coating. DHAH-NLCs were shown to be safe in both dopaminergic and microglia primary cell cultures. Moreover, they exhibited neuroprotective effects in dopaminergic neuron cell cultures after exposition to 6-hydroxydopamine hydrochloride (6-OHDA) neurotoxin and decreased the proinflammatory cytokine levels in microglia primary cell cultures after lipopolysaccharide (LPS) stimuli. The levels of the three tested cytokines, IL-6, IL-1β and TNF-α were decreased almost to control levels after the treatment with DHAH-NLCs. Taken together, these data suggest the suitability of DHAH-NLCs to attaining enhanced and synergistic effects for the treatment of NDs.This project was partially supported by the Spanish Ministry of Economy and Competitiveness (RTC-2015-3542-1) and the Basque Government (Consolidated Groups, IT 907-16)

Tumour-derived extracellular vesicle based vaccines for melanoma treatment

The interest of extracellular vesicles (EVs) in cancer immunotherapy is increasing every day. EVs are lipid bilayer vesicles released by most cells, which contain the molecular signature of their parent cell. Melanoma-derived EVs present antigens specific to this aggressive type of cancer, but they also exert immunomodulatory and pro- metastatic activity. Until now, most reviews focus on the immunoevasive characteristics of tumour-derived EVs, but do not help to overcome the issues related to them. In this review, we describe isolation methods of EVs from melanoma patients and most interesting markers to oversee their effect if they are used as antigen carriers. We also discuss the methods developed so far to overcome the lack of immunogenicity of melanoma-derived EVs, which includes EV modification or adjuvant co-administration. In summary, we conclude that EVs can be an interesting antigen source for immunotherapy development once EV obtaining is optimised and the understanding of the mechanisms behind their multiple effects is further understood.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the Basque Government (ELKARTEK project ONKOtools (KK20/00069), ONKOVAC (2021111042), and Consolidated Groups, IT1448-22). Lorena Gonzalez-Melero thanks the University of the Basque Country (UPV/EHU) for the PhD grant (PIF18-295)

High resolution and fidelity 3D printing of Laponite and alginate ink hydrogels for tunable biomedical applications

The formulation of hydrogels that meet the necessary flow characteristics for their extrusion-based 3D printing while providing good printability, resolution, accuracy and stability, requires long development processes. This work presents the technological development of a hydrogel-based ink of Laponite and alginate and evaluates its printing capacity. As a novelty, this article reports a standardizable protocol to quantitatively define the best printing parameters for the development of novel inks, providing new printability evaluation parameters such as the Printing Accuracy Escalation Index. As a result, this research develops a printable Laponite-Alginate hydrogel that presents printability characteristics. This ink is employed for the reproducible manufacture of 3D printed scaffolds with versatile and complex straight or curved printing patterns for a better adaptation to different final applications. Obtained constructs prove to be stable over time thanks to the optimization of a curing process. In addition, the study of the swelling and degradation behavior of the Laponite and alginate 3D printed scaffolds in different culture media allows the prediction of their behavior in future in vitro or in vivo developments. Finally, this study demonstrates the absence of cytotoxicity of the printed formulations, hence, setting the stage for their use in the field of biomedicine.This project has been partially supported by Spanish government Ministerio de Ciencia e Innovación Grant PID2021-122577OB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe”. Grant IT1448-22 funded by Basque Government and Fundación Vital Fundazioa (vital21/28). Elena Munoz-Perez thanks the Basque Government for the predoctoral grant (PRE_2022_2_0115). Arantza Perez-Valle thanks the Spanish Government for the postdoctoral grant (MARSA55/21)

Mesenchymal Stromal Cell Secretome for the Treatment of Immune-Mediated Inflammatory Diseases: Latest Trends in Isolation, Content Optimization and Delivery Avenues

Considering the high prevalence and the complex pharmacological management of immune-mediated inflammatory diseases (IMIDs), the search for new therapeutic approaches for their treatment is vital. Although the immunomodulatory and anti-inflammatory effects of mesenchymal stromal cells (MSCs) have been extensively studied as a potential therapy in this field, direct MSC implantation presents some limitations that could slow down the clinical translation. Since the beneficial effects of MSCs have been mainly attributed to their ability to secrete a plethora of bioactive factors, their secretome has been proposed as a new and promising pathway for the treatment of IMIDs. Formed from soluble factors and extracellular vesicles (EVs), the MSC-derived secretome has been proven to elicit immunomodulatory effects that control the inflammatory processes that occur in IMIDs. This article aims to review the available knowledge on the MSC secretome, evaluating the advances in this field in terms of its composition, production and application, as well as analyzing the pending challenges in the field. Moreover, the latest research involving secretome administration in IMIDs is discussed to provide an updated state-of-the-art for this field. Finally, novel secretome delivery alternatives are reviewed, paying special attention to hydrogel encapsulation as one of the most convenient and promising strategies.This research was funded by the projects SAF2017-82292-R (MINECO), AEI/FEDER, UE, ICTS “NANBIOSIS” Drug Formulation Unit (U10) and the Basque Country Government (Grupos Consolidados, No ref: IT907-16). Elena Munoz-Perez thanks the Basque Government for the predoctoral grant (PRE_2020_1_0279). A. Gonzalez-Pujana thanks the University of the Basque Country (UPV/EHU) for the postdoctoral grant (ESPDOC20/119)

La permacultura, una alternativa en la producción de alimentos desde la escuela y la comunidad

One of the performances high-priority collections in the Calendar 21 are the reorientation of the education toward a sustainable development; he/she intends, in this sense that is helped to the schools to design plans related with the environment very integrated in their study plans. These directive ones serve as mark for contextualizar the present project in the one that, observing the thematic axes of the permacultura and using as central axis that of the production of foods that can be implemented and maintained with minimum resources, and in coordination with the group Ecomujer of Germany, is sought to link the primary school of group with the community to actions of use of the water rain for the production of foods in a school orchard of vegetables, medicinal plants, as well as an area of fruit-bearing in the primary school Eberto Polanco of the Popular Council of New Town of the municipality of Consolation of the South and this way to contribute to the population's alimentary education from the school and the community, being achieved the reorientation of the education toward the sustainable development, by means of the design and execution of plans of actions related with the environment and the alimentary culture and integrated to the effective study plans.Una de las actuaciones prioritarias recogidas en la Agenda 21 es la reorientación de la educación hacia un desarrollo sostenible; se propone, en este sentido, que se ayude a las escuelas a diseñar planes relacionados con el medio ambiente bien integrado en sus planes de estudio. Estas directivas sirven de marco para contextualizar el presente proyecto en el que, observando los ejes temáticos de la permacultura y utilizando como eje central el de la producción de alimentos que pueda ser implementado y mantenido con mínimos recursos, y en coordinación con el grupo Ecomujer de Alemania, se pretende vincular la escuela primaria de conjunto con la comunidad a acciones de aprovechamiento del agua lluvia para la producción de alimentos en un huerto escolar de verduras, plantas medicinales, así como un área de frutales en la escuela primaria Eberto Polanco del Consejo Popular de Pueblo Nuevo del municipio de Consolación del Sur y de esta manera contribuir a la educación alimentaria de la población desde la escuela y la comunidad, lográndose la reorientación de la educación hacia el desarrollo sostenible, mediante el diseño y ejecución de planes de acciones relacionados con el medio ambiente y la cultura alimentaria e integrada a los planes de estudio vigentes

3D Bioprinting of Functional Skin Substitutes: From Current Achievements to Future Goals

The aim of this review is to present 3D bioprinting of skin substitutes as an efficient approach of managing skin injuries. From a clinical point of view, classic treatments only provide physical protection from the environment, and existing engineered scaffolds, albeit acting as a physical support for cells, fail to overcome needs, such as neovascularisation. In the present work, the basic principles of bioprinting, together with the most popular approaches and choices of biomaterials for 3D-printed skin construct production, are explained, as well as the main advantages over other production methods. Moreover, the development of this technology is described in a chronological manner through examples of relevant experimental work in the last two decades: from the pioneers Lee et al. to the latest advances and different innovative strategies carried out lately to overcome the well-known challenges in tissue engineering of skin. In general, this technology has a huge potential to offer, although a multidisciplinary effort is required to optimise designs, biomaterials and production processes.This research was funded by the Spanish Ministry of Economy and Competitiveness through the “RETOS” Program (NANOGROW project, RTC-2017-6696-1) and by the Basque Government (Grupos Consolidados, IT 907-16) and through the PhD grant conceded to Paula Gabriela Maniţă (PRE_2020_2_0261)

Malaria Vaccine Adjuvants: Latest Update and Challenges in Preclinical and Clinical Research

There is no malaria vaccine currently available, and the most advanced candidate has recently reported a modest 30% efficacy against clinical malaria. Although many efforts have been dedicated to achieve this goal, the research was mainly directed to identify antigenic targets. Nevertheless, the latest progresses on understanding how immune system works and the data recovered from vaccination studies have conferred to the vaccine formulation its deserved relevance. Additionally to the antigen nature, the manner in which it is presented (delivery adjuvants) as well as the immunostimulatory effect of the formulation components (immunostimulants) modulates the immune response elicited. Protective immunity against malaria requires the induction of humoral, antibody-dependent cellular inhibition (ADCI) and effector and memory cell responses. This review summarizes the status of adjuvants that have been or are being employed in the malaria vaccine development, focusing on the pharmaceutical and immunological aspects, as well as on their immunization outcomings at clinical and preclinical stages.This project was partially supported by the "Ministerio de Ciencia e Innovacion" (SAF2007-66115), the University of the Basque Country (UPV/EHU) (UFI 11/32), and FEDER funds. E. Mata thanks the Basque Government for a fellowship grant

Role of Vascular Endothelial Growth Factor as a Critical Neurotrophic Factor for the Survival and Physiology of Motoneurons

Vascular endothelial growth factor (VEGF) was discovered by its angiogenic activity. However, during evolution, it appeared earlier as a neurotrophic factor required for the development of the nervous system in invertebrates lacking a circulatory system. We aimed at reviewing recent evidence indicating that VEGF has neuroprotective effects in neurons exposed to a variety of insults. Of particular interest is the link established between VEGF and motoneurons, especially after the design of the VEGFδ/δ mutant mice. These mice are characterized by low levels of VEGF and develop muscle weakness and motoneuron degeneration resembling amyotrophic lateral sclerosis. The administration of VEGF through several routes to animal models of amyotrophic lateral sclerosis delays motor impairment and motoneuron degeneration and increases life expectancy. There are new recent advances in the role of VEGF in the physiology of motoneurons. Our experimental aims use the extraocular (abducens) motoneurons lesioned by axotomy as a model for studying VEGF actions. Axotomized abducens motoneurons exhibit severe alterations in their discharge activity and a loss of synaptic boutons. The exogenous administration of VEGF to axotomized abducens motoneurons, either from the transected nerve or intraventricularly, fully restores the synaptic and discharge properties of abducens motoneurons, despite being axotomized. In addition, when an anti-VEGF neutralizing antibody is delivered from the muscle to intact, uninjured abducens motoneurons, these cells display alterations in their discharge pattern and a loss of synaptic boutons that resemble the state of axotomy. All these data indicate that VEGF is an essential neurotrophic factor for motoneurons.Junta de Andalucía P20_00529Ministerio de Ciencia e Innovación PGC2018-094654-B-100, PID2021-124300NB-I00Gobierno de España BES-2016-07791