The free energy landscape of GABA binding to a pentameric ligand-gated ion channel and its disruption by mutations

Pentameric ligand-gated ion channels (pLGICs) of the Cys-loop superfamily are important neuroreceptors that mediate fast synaptic transmission. They are activated by the binding of a neurotransmitter, but the details of this process are still not fully understood. As a prototypical pLGIC, here we choose the insect resistance to dieldrin (RDL) receptor, involved in the resistance to insecticides, and investigate the binding of the neurotransmitter GABA to its extracellular domain at the atomistic level. We achieve this by means of $\mu$-sec funnel-metadynamics simulations, which efficiently enhance the sampling of bound and unbound states by using a funnel-shaped restraining potential to limit the exploration in the solvent. We reveal the sequence of events in the binding process, from the capture of GABA from the solvent to its pinning between the charged residues Arg111 and Glu204 in the binding pocket. We characterize the associated free energy landscapes in the wild-type RDL receptor and in two mutant forms, where the key residues Arg111 and Glu204 are mutated to Ala. Experimentally these mutations produce non-functional channels, which is reflected in the reduced ligand binding affinities, due to the loss of essential interactions. We also analyze the dynamical behaviour of the crucial loop C, whose opening allows the access of GABA to the binding site, while its closure locks the ligand into the protein. The RDL receptor shares structural and functional features with other pLGICs, hence our work outlines a valuable protocol to study the binding of ligands to pLGICs beyond conventional docking and molecular dynamics techniques.Comment: accepted (May 2016); 27 pages, 6 figures, Table of contents graphic, Journal of Chemical Theory and Computation (2016

The Impact of COVID-19 on Protected Areas : A Systematic Review

Esta investigación contribuye a la comprensión de los impactos de la pandemia de COVID-19 en áreas protegidas (PAs), terrestres y marinas. Por un lado, analizamos sus efectos sobre las dimensiones ecológicas, sociales y administrativas de las PAs. Comprender los impactos de la pandemia sobre las PAs es importante debido a que estos espacios son estratégicos para las políticas internacionales de conservación de la biodiversidad y el desarrollo sostenible. Para abordar esta problemática, realizamos una reseña sistemática de la literatura sobre los impactos de la pandemia en los espacios de conservación. Utilizamos las pautas de Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) que es una guía que establece criterios para realizar revisiones sistemáticas de la literatura de un tópico de interés. A partir de ella, revisamos cinco bases de datos y lleva a cabo a una búsqueda complementaria en Google Scholar. Tras identificar, examinar y seleccionar, incluimos 14 artículos, publicados entre febrero 2020 y mayo 2021. Por último, llevamos a cabo un análisis cualitativo de los artículos seleccionados, estudiando los cambios a corto plazo, los efectos positivos y negativos, así como los retos y oportunidades que emergieron. En las discusiones, explicamos que las áreas protegidas adquirieron relevancia social durante la pandemia al mismo tiempo que se incrementó la vulnerabilidad de ciertos actores y medios de financiación de los parques. Además, los espacios tuvieron problemáticas sociales distintivos en países desarrollados y en desarrollo. En suma, la sustentabilidad de las PAs se vio comprometida. Concluimos que la pandemia nos hizo ver todo a través de las lentes de la salud, y las áreas protegidas no fueron la excepción.Understanding the effects of COVID-19 on protected areas (PAs) is very important because these spaces are crucial for international policies for biodiversity conservation and sustainable development. Therefore, the aim of this paper was to fully understand the impacts of COVID-19 on terrestrial and marine protected areas (PAs). To address this concern, we conducted a systematic review on the literature of the impacts of the pandemic on PAs. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines which helps authors to follow certain specific criteria when they make a systematic review on a topic. Following it, we examined five databases, together with complementary search perform in Google Scholar. Lastly, we made a qualitative assessment of articles retrieved, studying short-term changes, and identifying positive and negative effects, as well as challenges and opportunities that arise. After identifying, screening, and selecting, we included 14 journal articles published between February 2020 and May 2021. In the results we showed how the new virus-related restrictions affected the ecological, social and management dimensions of PAs. We discuss how these conserved areas gained social relevance during the pandemic but, at the same time, the vulnerability of related actors increased. Also, we suggested that some social problems differed between develop and developing countries. Additionally, digital tendencies consolidated in PAs management, research, and engagement. Overall sustainability of these places was compromised. We concluded that COVID-19 made humans to see everything through the lenses of health and PAs were not the exception

The Effects of COVID-19 Pandemic on Spanish Protected Areas: the Case of Picos de Europa National Park

Protected areas are complex social-ecological systems; thus, they were unavoidably impacted by COVID-19. Spain is one of the most diverse countries in terms of biodiversity in the European Union and the second most visited country in 2019 and third touristic destination worldwide. Understanding the effects of the pandemic in Spanish protected areas is very important to discuss new possibilities on how to drive sustainable development on these conserved spaces and how to manage them in the event of external shocks and uncertain scenarios. Therefore, the aim of this study is to have a better understanding of the effects and opportunities of the pandemic on Spanish protected areas. To address this concern, a qualitative analysis is conducted based on an assessment of secondary literature and relevant interviews. Picos de Europa national park was chosen as case study because of its unique features. This study shows the drawbacks of the pandemic in Picos de Europa in terms of management operations, drastic fluctuation of visitors, loss of tourism revenues, vulnerability of neighboring communities, missed opportunities in conservation and education and pressure on nature. On the other hand, it poses opportunities in terms of technology, innovation, fundings, lessons learned, rise in educational and conservation activities and more awareness on the environment and rural surroundings. This study suggests that is difficult to find a win-win solution that includes the targets of nature conservation, viability of local economies and tourism activities in Picos de Europa. Ideas for management options that focus on dealing with the negative outcomes of the pandemic are suggested.Las áreas protegidas son sistemas socioecológicos complejos y se vieron inevitablemente afectadas por la pandemia de COVID-19. España es uno de los países más diversos en biodiversidad de Europa y el tercer destino turístico mundial. Comprender los efectos de la pandemia en las áreas protegidas españolas es muy importante para discutir nuevas posibilidades sobre cómo impulsar el desarrollo sostenible en estos espacios conservados y cómo gestionarlos bajo impactos externos y escenarios inciertos. Por tanto, el objetivo de este estudio es conocer mejor los efectos y oportunidades de la pandemia en los espacios protegidos españoles. Para abordar esta preocupación, se lleva a cabo un análisis cualitativo basado en una evaluación de literatura secundaria y entrevistas oportunistas. El parque nacional de los Picos de Europa es el caso de estudio analizado debido a sus características únicas. Este estudio muestra los inconvenientes de la pandemia en Picos de Europa en términos de operación de gestión, fluctuación drástica de visitantes, pérdida de ingresos por turismo, vulnerabilidad de las comunidades vecinas, pérdida de oportunidades en conservación y educación y presión sobre la naturaleza. Por otro lado, presenta las oportunidades en términos de tecnología, innovación, ampliación de fondos, lecciones aprendidas, aumento de actividades educativas y de conservación y mayor conciencia sobre el medio ambiente y el entorno rural. Este estudio sugiere que es difícil encontrar una solución beneficiosa para todos que incluya los objetivos de conservación de la naturaleza, viabilidad de las economías locales y actividades turísticas en Picos de Europa. Se sugieren ideas para las opciones de gestión sobre cómo abordar los resultados negativos de la pandemia

In-plane structure and ordering at liquid sodium surfaces and interfaces from ab initio molecular dynamics

Atoms at liquid metal surfaces are known to form layers parallel to the surface. We analyze the two-dimensional arrangement of atoms within such layers at the surface of liquid sodium, using ab initio molecular dynamics (MD) simulations based on density functional theory. Nearest neighbor distributions at the surface indicate mostly 5-fold coordination, though there are noticeable fractions of 4-fold and 6-fold coordinated atoms. Bond angle distributions suggest a movement toward the angles corresponding to a six-fold coordinated hexagonal arrangement of the atoms as the temperature is decreased towards the solidification point. We rationalize these results with a distorted hexagonal order at the surface, showing a mixture of regions of five and six-fold coordination. The liquid surface results are compared with classical MD simulations of the liquid surface, with similar effects appearing, and with ab initio MD simulations for a model solid-liquid interface, where a pronounced shift towards hexagonal ordering is observed as the temperature is lowered

Las políticas de desarme y desmovilización tras el asedio de la ciudad de Buenos Aires (1853)

Hilario Lagos\u27 siege of the city of Buenos Aires demonstrated the existence of a politicized rural society, of federal adherence, with the ability to mobilize and arm itself. In this article we inquire about the restitution of order in the campaign and the city in the most immediate post-war period. For this, we analyze the measures of demobilization and disarmament of the armies, the eventual fate of the rebel officers and the material consequences of the pacification policies. We show that a combination of coercion and persuasion from Buenos Aires leaders´ allowed re-establishing order in the campaign.El asedio de Hilario Lagos a la ciudad de Buenos Aires demostró la existencia de sociedad rural politizada, de signo federal, con capacidad de movilizarse y armarse. En este artículo indagamos sobre la restitución del orden en la campaña y la ciudad en el periodo posbélico más inmediato. Para ello, analizamos las medidas de desmovilización y desarme de los ejércitos, el destino de la oficialidad rebelde y las consecuencias materiales de las políticas de la pacificación. Mostramos que una combinación de coacción y persuasión por parte de la dirigencia porteña permitió reestablecer el orden en la campaña

Between “mazorqueros” and “pillos”: Fights between neighbors and sociopolitical tensions in rural Buenos Aires after Caseros (1854-1858)

El artículo indaga acerca de la tensión sociopolítica abierta tras la batalla de Caseros en los pueblos de la campaña bonaerense. Para abordar esta problemática, en este artículo se investigan casos de disputas vecinales en tres partidos: Quilmes, San Nicolás y Patagones, y se profundiza en las causas y desarrollo de aquellas rencillas. Más allá de las especificidades propias de cada episodio, el conjunto de ellos demuestra que los intereses personales y locales se entremezclaron con problemáticas de alcance provincial e ideologías de los bandos en pugna, generando altos niveles de conflicto y violencia. Reflejan, también, el gradual resquebrajamiento de la unanimidad política, la feroz competencia electoral y el estallido de tensiones acumuladas durante el anterior régimen rosista. Esta investigación contribuye a comprender más cabalmente el desarrollo de la dinámica política y la sociabilidad rural en el periodo entre 1852 y 1860 en el Estado de Buenos Aires.This article research about the sociopolitical tension opened after the battle of Caseros in Buenos Aires hinterland. To address this problem, this article analyses cases of conflict in three villages: Quilmes, San Nicolás and Patagones, and delves into the causes and development of those disputes. Beyond the specificities of each episode, they show that personal and local interests were intermingled with provincial factors and the ideologies of the opposing sides, generating high levels of conflict and violence. They also reflect the breakdown of political unanimity, the fierce electoral competition and the outbreak of tensions accumulated during the Rosista regime. This research contributes to a more complete understanding of the development of political dynamics and rural sociability in the period between 1852 and 1860 in the State of Buenos Aires.Fil: Zubizarreta, Ignacio. Universidad Nacional de la Pampa. Facultad de Ciencias Humanas. Instituto de Estudios Historicos y Sociales de la Pampa. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Patagonia Confluencia. Instituto de Estudios Historicos y Sociales de la Pampa.; ArgentinaFil: Molteni, Carla. Magyar Agrár- És Élettudományi Egyetem Kaposvári; Hungrí