Metal ion mediated transition from random coil to β-sheet and aggregation of Bri2-23, a natural inhibitor of Aβ aggregation

Furin-dependent maturation of the BRI2 protein generates the Bri2-23 fragment that is able to arrest the aggregation of amyloidβ, the peptide implicated in Alzheimer's disease (AD). Bri2-23 contains cysteines at positions 5 and 22, which are likely to bind to metal ions such as Cu(i). Metal ions may play a role in the etiology of neurodegenerative disorders such as AD, and in this work we explore the metal ion induced folding and aggregation of Bri2-23 using Hg(ii) and Ag(i) as spectroscopic probes with structural and ligand preferences similar to those of Cu(i), while not displaying redox activity under the experimental conditions. In general, interaction of Bri2-23 with soft metal ions changes the structural properties and solution behavior of the peptide that tune to increasing metal to peptide stoichiometry. Potentiometric, (199m)Hg PAC and ESI-MS data indicate that addition of up to 0.5 equivalents of Hg(ii) to Bri2-23 yields a two-coordinated HgS2 structure at the metal site. While the free peptide is inherently unstructured, the presence of Ag(i) and Hg(ii) gives rise to β-sheet formation. NMR spectroscopy supports the formation of β-sheet structure in the presence of 0.5 equivalents of Hg(ii), and displays an interesting and marked change in the TOCSY spectra when increasing the Hg(ii) to peptide stoichiometry from 0.5 to 0.7 equivalents, indicating the equilibrium between two structural analogues of the complex. Addition of more than 0.7 equivalents of Hg(ii) gives rise to line broadening, presumably reflecting aggregation. This is further supported by ThT fluorescence studies showing that the Bri2-23 peptide does not aggregate over 24 hours, while addition of over 0.7 equivalents of Ag(i) or Hg(ii) leads to increase of fluorescence, indicating that these metal ions induce aggregation. Thus, a model integrating all data into a coherent picture is that the metal ion binding to the two thiolates gives rise to folding of the peptide into a structure that is prone to aggregation, forming aggregates with a considerable amount of β-sheets. Molecular dynamics simulations initiated with structures that agree with NMR data additionally support this model

The catechin flavonoid reduces proliferation and induces apoptosis of murine lymphoma cells LB02 through modulation of antiapoptotic proteins

AbstractFlavonoids are products of secondary metabolism of plants. They are present in herbs and trees and also act as natural chemopreventives and anticancer agents. Ligaria cuneifolia (Ruiz & Pav.) Tiegh., Loranthaceae, is a hemiparasite species that belongs to Argentine flora. Phytochemical studies have disclosed the presence of quercetin, catechin-4β-ol and pro-anthocyanidine as polyphenolic compounds in the active extracts. We previously demonstrated that ethyl acetate extract was capable of reducing cell proliferation and inducing apoptotic death of lymphoid tumor cells. The aim of the current study is to determine whether or not catechin, isolated from L. cuneifolia extracts can induce leukemia cell death and to determine its effect on the cytoplasmatic proteins that modulate cell survival. Our results show that catechin can reduce proliferation of murine lymphoma cell line LB02. The effect is mediated by apoptosis at concentrations upper to 100μg/mL. Cell death is related to the loss of mitochondrial membrane potential (ΔΨm) and a down regulation of survivin and Bcl-2 together with the increase of pro-apoptotic protein Bax. In summary, the current study indicates that catechin present in the extract of L. cuneifolia is in part, responsible for the anti-proliferative activity of whole extracts by induction of ΔΨm disruption and modulation of the anti-apoptotic proteins over expressed in tumor cells. These results give new findings into the potential anticancer and chemopreventive activities of L. cuneifolia

Review and Recommendations for Experimentations in Earth Orbit and Beyond

The space environment is regularly used for experiments addressing astrobiology research goals. The specific conditions prevailing in Earth orbit and beyond, notably the radiative environment (photons and energetic particles) and the possibility to conduct long-duration measurements, have been the main motivations for developing experimental concepts to expose chemical or biological samples to outer space, or to use the reentry of a spacecraft on Earth to simulate the fall of a meteorite. This paper represents an overview of past and current research in astrobiology conducted in Earth orbit and beyond, with a special focus on ESA missions such as Biopan, STONE (on Russian FOTON capsules) and EXPOSE facilities (outside the International Space Station). The future of exposure platforms is discussed, notably how they can be improved for better science return, and how to incorporate the use of small satellites such as those built in cubesat format

Ontologías en disputa: Diálogos entre la antropología y la arqueología para la problematización de paisajes regionals

Objetivo/contexto: Hacia finales del siglo XX, el dualismo ontológico con el que antropólogos y arqueólogos nos hemos formado teórica y metodológicamente ha sido cuestionado y puesto en debate. En este contexto, nuestro objetivo es exponer críticamente los trabajos que se están realizando y que contribuyen a problematizar los paisajes enredados de existencias, materialidades, saberes, sentidos o prejuicios pasados y presentes, y con ello a restablecer el diálogo entre la antropología social y la arqueología. Metodología: Exponemos el estado actual de la apertura ontológica en clave latinoamericana. Problematizamos la noción de paisaje como concepto que permite diálogos teórico-metodológicos entre la antropología y la arqueología, así como con otras disciplinas. También presentamos ejes de comunicación y diálogo entre los artículos que forman parte del presente dossier para finalizar con los desafíos por delante en cuanto a traspasar fronteras disciplinarias, temporales y espaciales. Conclusiones: En contextos de históricas relaciones de poder, de profundas crisis socio-ambientales, los principales desafíos de la apertura ontológica serían: 1) generar referentes teóricos permeables a diversas disciplinas y saberes; 2) consolidar metodologías que integren lo etnográfico con lo arqueológico; 3) alentar diálogos constructivos hacia y con otras disciplinas y saberes, y 4) propiciar la comprensión del entramado político actual y la generación de políticas públicas que permitan diversas formas de relacionamiento con el entorno. Originalidad: El restablecimiento de diálogos entre la arqueología y la antropología social desde las aperturas ontológicas tiene el potencial de discutir cómo en determinados contextos se concretan y/o disputan paisajes y modos hegemónicos de habitar en el mundo, así como se problematizan los usos políticos del pasado y las políticas de uso del espacio y el ambiente.Objective/context: Towards the end of the 20th century, the ontological dualism with which anthropologists and archaeologists have trained us theoretically and methodologically has been questioned and debated. In this context, our objective is to critically expose the works that are being carried out and that contribute to problematizing the landscapes entangled with past and present existences, materialities, knowledge, senses or prejudices, and, with it, to re-establish the dialogue between social anthropology and archaeology. Methodology: We expose the current state of the ontological opening in Latin American code. We problematize the notion of landscape as a concept that allows theoretical-methodological dialogues between anthropology and archaeology, as well as with other disciplines. We also present axes of communication and dialogue between the articles that are part of this dossier, to end with the challenges ahead in terms of crossing disciplinary, temporal and spatial borders. Conclusions: In contexts of historical power relations, of deep socio-environmental crises, the main challenges for an ontological opening would be: 1) to generate theoretical referents permeable to various disciplines and fields of knowledge; 2) to consolidate methodologies that integrate the ethnographic with the archaeological; 3) to encourage constructive dialogues towards and with other disciplines and fields of knowledge; and 4) to propitiate the understanding of the current political framework and the generation of public policies that allow for diverse forms of relation with the environment. Originality: The re-establishment of dialogues between archaeology and social anthropology from ontological openings has the potential to discuss how, in certain contexts, landscapes and hegemonic ways of living are concretized and/or disputed, as well as the political uses of the past and the policies of use of space and the environment.Objetivo/contexto: No final do século XX, o dualismo ontológico com o qual antropólogos e arqueólogos se formaram teórica e metodologicamente vem sendo questionado e colocado em debate. Nesse contexto, nosso objetivo é expor criticamente os trabalhos que estão sendo realizados e que contribuem para problematizar as paisagens permeadas de existências, materialidades, saberes, sentidos ou preconceitos passados e presentes, e, com isso, reestabelecer o diálogo entre a antropologia social e a arqueologia. Metodologia: Expomos o estado atual da abertura ontológica no âmbito latino-americano. Problematizamos a noção de paisagem como conceito que permite diálogos teórico-metodológicos entre a antropologia e a arqueologia, assim como outras disciplinas. Também apresentamos eixos de comunicação e diálogo entre os artigos que fazem parte do presente dossiê para finalizar com os desafios que temos adiante sobre ultrapassar fronteiras disciplinares, temporais e espaciais. Conclusões: Em contextos de históricas relações de poder, de profundas crises socioambientais, os principais desafios para uma abertura ontológica seriam: 1) gerar referentes teóricos permeáveis a diversas disciplinas e saberes; 2) consolidar metodologias que integrem o etnográfico com o arqueológico; 3) promover diálogos construtivos com outras disciplinas e saberes; e 4) propiciar a compreensão da estrutura política atual e a geração de políticas públicas que permitam as diversas formas de relacionamentos com o ambiente. Originalidade: O reestabelecimento de diálogos entre a arqueologia e a antropologia social a partir das aberturas ontológicas tem o potencial de discutir como, em determinados contextos, se concretizam e/ou disputam paisagens e modos hegemônicos de habitar, bem como se problematizam os usos políticos do passado e as políticas de uso do espaço e do ambiente.Fil: Saldi, Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Mafferra, Luis Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Barrientos Salinas, J. Alejandro. Universidad Mayor de San Andrés; Bolivi

Isolamento e identificação de agentes bacterianos envolvidos nas míases cutâneas causadas pelas larvas de Dermatobia hominis em bovinos de leite

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Isolamento e identificação de agentes bacterianos envolvidos nas míases cutâneas causadas pelas larvas de Dermatobia hominis em bovinos de leite

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Habilito: Debt For Life

The documentary film Habilito: Debt for Life provides a case study of the conflicts and tensions that arise at the point of contact between highland migrants and Mosetenes, members of an indigenous community in the Bolivian Amazon

Immersive Learning. From Basic Design for Communication Design: A Theoretical Framework

In this paper we discuss the two changes that basic design education faced: one is the teaching need of transformation from visual to multisensory and synaesthetic communication; the other is the use of virtual environments to teach design. As an answer to the trend of constructivist learning, also in order to fulfil the need for multisensory training, the discussion of an innovative learning environment for basic design education has become essential. The problems remain, as virtual technology has limitations regarding visualizing abstract concepts. This research aims to build an immersive virtual environment to teach basic design, along with the value of subjective immersive experience for design learning in general. The study presented in this paper proposes a theoretical framework, starting with the redefinition of the concepts of “immersion” and “presence” from a cognitive perspective (Scuri, 2017). The main research method is based on two groups of case studies; through literature review and secondary research, this work categorizes the factors of presence into a three-dimensional framework, also defining the four typologies of immersion and two in-class educational models. The paper presents the results of the research at the first phase, aimed at bridging the gap between design learning and virtual spaces. Through the framework addressed, we are able to frame an actual design tool with the help of online platforms and tools