bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneidad y homeóstasis en la vigencia de la muliza Falsía. Diferentes narrativas de la canción
Authors: Asto Carbajal Tatiana Valeria
Published: January 2024

Durante nuestra República Peruana, diversos compositores han enriquecido el imaginario musical popular al inmortalizar canciones que desde el pasado han hecho eco hasta nuestro presente. Una de estas piezas en cuestión es la inolvidable muliza Falsía de Emilio Alanya Carhuamaca y Pablo Pastor Díaz Reynoso. Si bien este trabajo parte de la disciplina literaria para enfrentarse a la canción, esta investigación sigue la línea de estudios interdisciplinarios entre la literatura y la música. La problemática principal que guiará este artículo será: ¿Qué elementos característicos de los estudios literarios intervienen dentro de la vigencia de la muliza Falsía? Estos elementos serán dos: la psicodinámica homeóstasis de la literatura de tradición oral y la heterogeneidad discursiva. Veremos, pues, cómo es que a través de estos se explica la actualización de nuevas intervenciones en el texto de la canción al posibilitar distintas reinterpretaciones de la muliza. Es decir, evidenciaremos sus diferentes narrativas. Por un lado, la homeóstasis se manifestará a través de una serie de cambios y alteraciones en las letras. También, en los códigos musicales que intervienen en la canción a través de los años en concordancia a su contexto social. Por el otro lado, la heterogeneidad visibilizará la presencia de tres sujetos sociales.
An Elite Analysis: Reimagining LDP’s Factions, 1955-1993
Authors: Akçevin Yalın
Published: January 2024

he factions of the Liberal Democratic Party of Japan have been studied from cultural and functional-structural viewpoints, and have been characterized as being integral to both the functioning and breakdown of the Japanese political system and the LDP. This study seeks to expand the discussion on the factions by moving beyond both these existing viewpoints by using elite and Weberian theory, as well as through a reconstruction of available data and discourse on the subject. The aim here is to reexamine the functions of the factions and their political significance, seeking to reconceptualize them as politically engaged elite organizations. The findings indicate that the factions of the LDP are competing elite organizations with discernible policy involvements and differentiations, both from a theoretical and evidential perspective.
Cognitive Linguistics and Japanese-Language Education: How to deal with cross-cultural conflict?
Authors: Moriya Michiyo
Published: January 2024

Japanese companies are increasingly expanding their employment quotas for international students and foreigners in recent years. On the other hand, this movement has exceeded expectations and is having a major impact on the field of Japanese language education. This paper examines the current situation and problems surrounding Japanese language education at Japanese universities, analyses the cases of cross-cultural conflicts from the perspective of cognitive linguistics, and based on that, proposes training of mentors equipped with knowledge of cognitive linguistics to cope with cross-cultural conflicts.
La importancia de la Economía de la Felicidad: análisis de la situación actual y perspectivas a futuro
Authors: Coll Agustin Julian , Maceri Sandra
Published: January 2024

El objetivo principal del presente trabajo fue analizar los distintos descubrimientos obtenidos por la Economía de la Felicidad en las últimas décadas con la finalidad de contextualizarlos en el contexto global pospandémico. En vista de este nuevo escenario global, se buscó dar las razones por las cuales la Economía de la Felicidad debe tener un rol aún más activo y preponderante, repensando el campo. Se examinó la situación actual de la Economía de la Felicidad y las perspectivas a futuro, así como qué medidas pueden ser llevadas a cabo para mejorar los índices de felicidad en la sociedad. La metodología utilizada fue de carácter analítico – conceptual. Se repasaron las distintas conclusiones obtenidas por la Economía de la Felicidad, tomando en cuenta los distintos resultados estadísticos y descriptivos de la disciplina. El trabajo fue dividido en tres partes, observando la necesidad de acción en la esfera estatal, empresarial y educativa, explicando la necesidad de que la felicidad posea un rol más preponderante en estas áreas y evaluando como podrían llevarlo a cabo, así como los beneficios que obtendrían estos sectores en particular y la sociedad en su conjunto. Los resultados obtenidos mostraron que, en este nuevo escenario, la Economía de la Felicidad tiene la oportunidad – y necesidad – de cobrar mayor importancia que nunca, algo que será beneficioso para todos los involucrados.
Principios rectores de los smart contracts en el ordenamiento jurídico ecuatoriano
Authors: Cuvi Santacruz Mario Francisco , Franco Cortázar Cristina , Carrillo Solís Heyddy Francis
Published: January 2024

La presente investigación científica aborda un tema muy poco conocido en el mercado nacional y guarda como finalidad introducir al lector a los contratos inteligentes, conocidos como smart contracts. Se utilizó una metodología analítica descriptiva y documental para analizar tanto su terminología y conceptos especializados, como las posibles ventajas y desventajas al momento de celebrarlos, para obtener una visión crítica frente al nuevo paradigma de la tecnología e innovación y la necesidad de un marco regulatorio mínimo que garantice el cumplimiento de los principios generales del Derecho Privado, en particular el principio de buena fe y la autonomía de la voluntad en observancia de las normas internacionales del Derecho Comercial.
Los resultados del estudio contribuyen a la democratización del conocimiento a efectos de despertar el interés en la utilización de esta nueva modalidad contractual. De esta manera, se busca promover el avance legal y el tráfico comercial como mecanismos de desarrollo de la economía del país.
Principio de contradicción en audiencias telemáticas
Authors: Orellana Batallas Fabian Ernesto
Published: January 2024

En el año 2020 el mundo vivió una serie de contagios masivos provocados por el COVID 19. Se produjeron distintas restricciones en todos los campos de la vida social, como en el sistema judicial; por tal motivo, la Corte Nacional de Justicia del Ecuador estableció un protocolo para la realización de la audiencia telemática. No obstante, a pesar del avance, surge la preocupación al no tratarse asuntos que podrían afectar los principios procesales que giran en torno al principio de inocencia, como el de contradicción; razón por la cual, la procedencia investigativa descriptiva es evidenciar como la falta de normativa que regula las audiencias telemáticas en el Ecuador puede provocar una receptación de información poco clara al juzgador. Este tipo de análisis de enfoque cualitativo basados en los métodos teóricos y empíricos permite identificar en el estudio como se va desencadenando una percepción sesgada en cuanto a la información proporcionada por los intervinientes en una audiencia, puesto que en ella participan testigos, peritos y otros profesionales que aportan elementos para que el juzgador cree un sano juicio al momento de resolver, observándose como una solución al problema.
Reseña del libro “Guía para el desarrollo de las habilidades del pensamiento”
Authors: Pérez López Armenio
Published: January 2024

La sociedad se encuentra en el inicio de una nueva etapa pospandémica, donde la educación se encuentra desempeñando un rol esencial. La formación de las futuras generaciones nos demuestra que, si realizamos mal las cosas hoy, los ciudadanos mañana no será virtuosos. La pandemia dejó un escenario nuevo para muchas personas, donde la virtualidad ha ganado espacios, junto a ella, la necesidad de formar a un sujeto que se interese más por las maneras en que en nuestra aldea común el comportamiento de algunos puede afectar la vida de todos.
Vacunación contra el COVID-19: impacto en el mercado, DDHH, contagios y muertes en Perú
Authors: Lupaca Zurita Jesús David , Ortiz Merma Yudy Roxana , Quilca Flores Nataly Alexandra
Published: January 2024

El objetivo de la investigación fue determinar el impacto de vacunar contra el COVID-19 por parte del Gobierno de Perú en los derechos humanos, el mercado, la disminución de muertes y contagios, donde se aplicó la metodología aplicada cualitativa y cuantitativa, descriptivo, con un nivel correlacional; considerando la utilización del modelo econométrico de tipo dinámico, para los dos periodos de tiempo y su comparación, donde se determinó el impacto de las vacunas contra el COVID-19 en la cantidad de contagios y disminución de muertes. De igual manera, el impacto que tuvo la vacunación en la vulneración de los derechos fundamentales de las personas descritas en la Constitución, el Código Civil y Penal de Perú, donde también se generó el monopolio legal que afectó al mercado.
Saberes profesionales, desarrollo personal y práctica pedagógica de las docentes de educación inicial en la provincia de El Oro
Authors: Rivadeneira Rodríguez Elmina , Quintero Arjona Gisela Consolación
Published: January 2024

Los saberes profesionales están relacionados con los conocimientos necesarios que imparten las instituciones en la formación de docente para actuar con autonomía en el campo laboral. El artículo plantea la posibilidad de identificar los saberes profesionales y el desarrollo profesional que se aplican en las prácticas pedagógicas de las docentes de Educación Inicial de las instituciones fiscales y particulares, en la provincia de El Oro. Es una investigación con un enfoque cualitativo cuanto pretende interpretar la realidad desde las experiencias y vivencias de los docentes en la praxis pedagógica. La muestra está conformada por tres docentes, con un mínimo de tres años en ejercicio de la profesión en base al régimen del MINEDUC, con la aplicación del método inductivo. Para la obtención de la información se aplicaron tres instrumentos de corte cualitativo: entrevista oral con preguntas abiertas en respuesta de las competencias intrapersonales y competencias interpersonales en la categoría desarrollo personal; una entrevista escrita con preguntas abiertas para comprender sobre los saberes profesionales, y, finalmente, se aplicó una entrevista semiestructurada para conocer y comprender los procesos de los saberes, normas y sujetos de la práctica pedagógica. Con la información obtenida mediante la aplicación de los tres instrumentos se concluye que los saberes profesionales adquiridos por las tres docentes en ejercicio han fomentado la autonomía en el desarrollo profesional mediante la implantación de competencias como son: autoconocimiento, regulación emocional, responsabilidad, autoconfianza, resiliencia, liderazgo, empatía, trabajo en equipo, negociación y comunicación en el proceso de la práctica pedagógica.
El Telégrafo: orígenes de un diario guayaquileño
Authors: Tamayo Cruz Natalia Yolanda
Published: January 2024

Este trabajo se realizó en el marco del Proyecto de Investigación patrocinado por la Universidad de las Artes, La Biblioteca de las Artes, historia de un proceso adscrito al Grupo de Trabajo Arte y Memoria Social. Indaga en la historia de Diario El Telégrafo desde su fundación en 1884 hasta 1925 en consonancia con las relaciones sociales, políticas y económicas que influyeron para que se convierta en el medio de referencia de Guayaquil. La investigación toma como abordaje metodológico las consideraciones planteadas por la historia del tiempo presente respecto al análisis de la prensa y pone en relación las historias de vida de sus primeros propietarios con el fin de evidenciar las conexiones sociales, económicas y políticas que contribuyeron en el desarrollo de la empresa periodística. El relato que se presenta habla de la vida del diario y de sus fundadores. Espera develar las complejas relaciones de la prensa con el poder económico, empresarial y financiero del país, y contribuir con nuevos elementos que permitan reescribir la historia de la prensa escrita del país, como instituciones que intervienen
Reducing inequality in access to Higher Education in Denmark: Technical report for Nextstep 1.0 intervention and data collection
Authors: Reimer David , Olsen Astrid , Sortkær Bent , Thomsen Rie
Published: January 2024

The aim of the project Reducing Inequality in Access to Higher Education1 was to raise the university application rate for upper secondary students whose parents did not them-selves have a university degree. The project implemented an information intervention, and his technical report outlines the procedures involved in designing that the interven-tion called NextStep 1.0. It includes the selection and recruitment of schools, as well as the development of a survey for both students and counsellors and the creation of role model videos which was implemented in the intervention. The project Reducing Inequality in Access to Higher Education also included a NextStep 2.0 and a nudge experiment, which are not included in this technical report. To smoothen the readability of the report, we call the project NextStep throughout this report. The NextStep study is funded by Independent Research Fund Denmark, Grant No. 8019-00100B in a project running from 2019 to 2024. The target group for the intervention was upper secondary students in the spring of 2020, when they were just three-five month from graduation. In this report, we will address the following topics: • The design of the intervention • Randomization • Recruitment of schools • Data management including data to register data • Intervention videos and home page activity • Nudges • Appendix with transcripts of intervention material including the survey
Konflikten mellem diskurs og figur
Authors: Madsen Carsten
Published: January 2024

In this article, the author seeks to show how an ontologically conditioned conflict between discourse and figure defines a fundamental controversy over how an audience should and can view a rhetorical matter. Inspired by J.-F. Lyotard’s Discourse, figure (French 1971, English 2011), the author emphasizes that the figurality of an image in its primary appeal to the senses always already will have constituted the emotional disposition (pathos) with which an audience may feel called to identify. The author distinguishes sharply between the internal differences that constitute the ontology of an image and the external, dichotomously determined differences that a discourse produces between itself and an image. As an example of how this conflict between discourse and figure can manifest itself in the relationship between word and image in a political statement, the author analyzes a campaign poster published by The Danish People’s Party in 2009. The author further argues that the rhetorical critique of visual rhetoric in its prioritization of discourse typically overlooks the peculiar indeterminacy of images and its constitutive and thus unconscious influence on an audience.
Teorihistorisk skitsering af den nye protestcyklus
Authors: Bolt Mikkel
Published: January 2024

The article proposes a reading of the new cycle of protests that erupted in 2011 with the so-called Arab Spring and the square occupation movements in Souther Europe before moving on to the US with the Occupy movement. The years since 2011 have been marked by a significant rise in the numer of protests, riots and revolts across the world with the years 2011, 2014 and 2019 as preliminary high points. The pandemic and the repressive anti-rebellion measures put in place during the pandemic does not seem to have stopped protests from continuing to take place. The article challenges readings of the contemporary protests that fault them for being desperate, defensive and unpolitical proposing a reading using the notion of refusal put forth by Maurice Blanchot and Dionys Mascolo in 1958 as a prims for understanding the emergence of a new anti-political protest culture.
Den liberala demokratins konstkritiska protest
Authors: Svensk Fredrik
Published: January 2024

Claims that liberal democracy is in crisis need to reckon with the fact that it is a social system historically premised on crisis and criticality. Protest and protesting can, from this standpoint, be viewed as constitutive boundary phenomena of liberal democracy. By considering liberal democracy as a critical life form from a biopolitical perspective, the aim of the article is to suggest how liberal democracy itself can protest art-critically and that this indicates a crisis of its critical life form that is rarely acknowledged. The article argues that the crisis of liberal democracy in Sweden is made visible in the racial aspects of art-critical protests. The claim is also that these art-critical protests, in their turn, must be understood through an analysis of the relationship between, on the one hand, art criticism and citizenship and, on the other, the class relation and capital accumulation. In the article, this is demonstrated through an account of the biopolitical function of the aesthetic culture of the critical tradition, followed by two recent examples of the art-critical protest of liberal democracy. Whereas one of these examples represents a liberal critique of identity politics in art, the other demonstrates a transgression of the liberal principle of arm’s length distance in culture policy. The article concludes that the aesthetic culture of the critical tradition, strategically taken over by the Social Democrats at the dawn of liberal democracy, enabled a continuous reformation of how politics in liberal democracy is organically developed, and that the art-critical protest of liberal democracy today challenges this critical life form.
« Moi, je suis dans le froid »
Authors: Mothes Patricia
Published: January 2024

Nous tentons de comprendre comment, mis par la Loi dans une situation de suspension identitaire relevant de « l’impossible à supporter », les mineurs non accompagnés (MNA) peuvent se construire entre une identité singulière dont il sait devoir faire le deuil pour pouvoir rester sur le territoire, et une identité projetée, construite aussi par et dans le fantasme de l’Autre. Dans ce cadre, nous nous demandons quel espace peut exister pour une relation au travailleur social ou au bénévole associatif, et comment la compréhension de la topologie du nouage borroméen peut être mise au service de la formation des travailleurs sociaux et bénévoles.
Une posture professionnelle pour l’accompagnement clinique des adolescents dans l’entre-deux : entre rigueur et souplesse
Authors: Kattar Antoine
Published: January 2024

Dans le cadre de cet article, en partant d’une compréhension progressive de sa propre subjectivité déterminante pour développer sa capacité d’entendre les adolescents, l’auteur avance l’hypothèse qu’une posture professionnelle qu’il qualifierait de « l’entre-deux » exige de la rigueur et de la souplesse permettant au professionnel de rester poreux aux mobilisations inconscientes des sujets-adolescents ainsi qu’aux siennes propres. Il s’appuiera sur les résultats d’une recherche longitudinale et partenariale qu’il a conduite auprès de dix adolescents, entre 2015 et 2020, avec une équipe d’éducateurs et d’éducatrices de prévention spécialisée. Plus particulièrement, l’auteur fera le choix d’analyser quelques passages rétrospectifs de sa rencontre avec l’une des adolescentes du groupe pour montrer ce que pourrait être la rigueur d’une posture de l’entre-deux pour un « professionnel du lien ».
Enseigner une langue étrangère dans une perspective d’entre-deux
Authors: Menouti Kanellina
Published: January 2024

Partant du fait qu’il y a une discontinuité entre les objectifs assignés par les politiques linguistiques en Grèce et leur mise en place dans les classes de français langue étrangère (FLE) à l’école publique, cet article se propose d’étudier, chez l’enseignant de français langue étrangère, la posture de l’entre-deux comme une possibilité de penser autrement la notion de différence et de favoriser l’apprentissage.
L’entre-deux de la transition professionnelle : quelle posture de l’accompagnement ?
Authors: Ciobanu-Gout Varvara
Published: January 2024

Dans un contexte de transformation du marché du travail, les transitions professionnelles se multiplient. Cette contribution explore le vécu du sujet pendant cette transition, considérée comme un « entre-deux ». Elle met en avant les besoins d’accompagnement de la transition. La posture professionnelle de l’accompagnateur qui utilise le récit biographique est présentée comme celle d’un artisan qui participe, au côté de la personne accompagnée, à la construction du sens de l’histoire de sa vie.
Did large foraging migrations favor the enormous body size of giant sauropods? The case of Turiasaurus
Authors: Agusti Jordi , Alcalá Luis , Santos-Cubedo Andrés
Published: January 2024

We propose that the huge sizes attained by many sauropod dinosaurs can be explained in the context of a climate characterized by pronounced seasonal changes. Under these conditions, the large herbivores would have become migratory, forced to move great distances during the drier times of year, in which case large body size becomes an adaptive advantage, since large home ranges and the ability to travel great distances increase with size. In this way, the need for a large foraging radius is a potent source of selection for larger size, and the capacity for sauropods to migrate and explore new territory was significantly higher than in extant herbivores. Examples discussed are Turiasaurus riodevensis and Camarasaurus lentus; some of their anatomical structures, such as vertebral neural extensions and crests associated with nasal cavities, can also be explained under this scenario, as adaptations to drought conditions.
La geografía del estómago / el estómago de la geografía: texturas, cuerpos y ofrendas de arrieros en los Andes argentinos
Authors: Pazzarelli Francisco , Lema Veronica S.
Published: January 2024

In this work, we delve into the intricate connections between the movement of people, especially muleteers, in the highlands of Jujuy (Argentina), and specific offerings of archaeological and ethnographic origin that shape the local landscape. These offerings, known as challas, are acullicos or chewed coca wads thrown fresh onto mountain walls, where they adhere and subsequently dry. The research focuses on Huachichocana, an indigenous community located between the valley and puna areas of the province of Jujuy, where there are several ancient natural passes historically used for human movement. Drawing on ethnographic data gathered from 2011 to 2019, we analyze the practices and contexts surrounding these offerings, exploring their sensory dimensions—textures, colors, and shapes. This study aligns with various academic precedents in the field. As our research progresses, we establish a connection between these coca offerings and pusno: processed plant matter retrieved from the carcasses of ruminant animals when they are butchered. Pusno, handled delicately and placed at specific points in space, serves as an offering to powerful locations. Inspired by Levi-Strauss’s culinary analyses, we posit that acullicos and pusno function as intermediary terms between fresh coca and decomposed guano, akin to the circulation of human and animal bodies through space. This exploration opens up novel avenues in Andean studies, prompting a reflection on the intertwined existence of body and geography, navigating transformations and intermediate stages—a contemplation on the possibility that they are fractal reflections of each other.
“¿Cuáles son los espacios que se deben abrir?”: Escenarios de comunicación entre pacientes mapuche y áreas biomédicas en la Patagonia norte
Authors: Santisteban Kaia
Published: January 2024

This work analyzes the tensions that arise when individuals from the Mapuche Tehuelche people, located in northern Patagonia, Argentina, navigate through biomedical spaces where indigenous belongings, concepts, knowledge, and practices of Mapuche medicine and biomedicine come into play. These itineraries unveil situations of inequality, racism, discrimination, and epistemological and ontological tensions when Mapuche medicine is questioned or silenced by biomedicine. For years, Mapuche Tehuelche organizations, communities, and members have been undertaking collective actions to defend and demand that the State recognize lawen (Mapuche medicine) in health-disease care processes. For this work, I focus on some experiences that occurred during 2022 in the town of San Carlos de Bariloche (Río Negro, Argentina), where I observed certain recurring tensions among those navigating diverse paths in Mapuche medicine and in spaces such as hospitals or primary health care centers. This article is part of a broader anthropological research in which I use a qualitative methodology with an ethnographic and narrative approach based on in-depth interviews, participant observations, and informal conversations conducted with activists, women from Mapuche communities, and health professionals who identify themselves as part of the network of relationships around health. Focusing on these stories and experiences, this study concludes that the lawen has not yet found a receptive audience in certain biomedical spaces based on the frameworks it proposes. The commitment is to continue reflecting on future challenges to co-produce knowledge and health spaces with critical reflection that values the demands of the Mapuche Tehuelche people.
Identidad cultural de los migrantes acorianos en Lima a través de la danza Los negritos de Acoria
Authors: Silvera La Torre Hernán , Fernández Fabián Liliana
Published: January 2024

Cultural identity in the context of migration is shaped by the gathering of migrants in so-called provincial clubs that have formed in Lima. In these spaces, Acorian migrants recreate festivities and expressions such as the dance Los negritos, which brings families together with the winning troupe from the celebration held in Acoria (Huancavelica, Peru). This festive moment is loaded with symbols that recognize the identity of Acorian residents in Lima, based on a sense of belonging that encompasses the community from the diaspora to the dance itself, sustaining the memory and identity of the Acorians. This qualitative, ethnographically designed article analyzes the relationship between these significant elements of Acorian identity among migrants in Lima. In-depth interviews were conducted with nine Acorians residing in the capital (during the months of September and October 2022), some involved in organizing the festival, others recurring participants in club activities. The research results are based on these interviews. It is concluded that social, familial networks generate the sense of identity in migratory processes, and cultural expressions such as dance contribute to the consolidation of cultural identity by recognizing its social and cultural value, making it representative of a people. In sum, this article captures the voices of Acorian migrants who value their origin and find in dance a symbol of unity between residents in Lima and those in Acoria. This supports the sense of belonging and strengthens the group that constructs its identity by recognizing itself as migrants. Thus, the article contributes to discussions on the reconstruction of identity in a context of migration.
Un archivo para repensar distintas formas de violencia: maternidades sospechadas, interrumpidas y acalladas en Argentina
Authors: Villalta Carla , Gesteira Soledad
Published: January 2024

Archives have attracted renewed attention since the late 1990s and have been examined from different disciplinary perspectives. Far from being merely an artifact of power and at the service of states or colonial states (Stoler 2010), archives have also served to demonstrate and contest various forms of violence and thus shed light on different violations marked by their opacity. They are also reservoirs of social memory and bearers of a high affective and emotional value. The purpose of this work is to analyze the potential of a unique archive that we propose to create, based on a collaborative ethnographic research, to collect the testimonies of women who currently denounce having had their children separated from them at birth without their consent. The purpose of this archive will be to safeguard and emphasize the value of these stories, which for a long time were silenced and which not only reveal the different violent practices generally exerted on very young women who were forced to give up their children for adoption or were directly deprived of them, but also the prejudices and stigmas that later weighed on them. In this article we will examine the potential of building a documentary reservoir of this type and some of the challenges involved in this task. To do so, we first analyze the narratives of the women we have already interviewed in the framework of our research work, which focuses on the 2012-2022 period, in Argentina, in order to account for the particular characteristics of their stories and claims. These are semi-directed and in-depth interviews that we have conducted in an ethnographic research and that have allowed us to learn about and analyze the practices of which these women were victims and also the meanings that they attribute to them. Next, we present a review of some of the most important contributions that different authors have made on “alternative archives” or “community” archives. Thus, we argue that establishing an archive with silenced voices can serve as a tool to shed light on various violations and contribute to understanding different ways of managing “out-of-place motherhoods,” (Fonseca 2012) while also being a tool to challenge diverse forms of violence and serve as a mechanism for reparation.
Coupling of Slack and NaV1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development
Authors: Yuan Tian , Wang Yifan , Jin Yuchen , Yang Hui , Xu Shuai , Zhang Heng , Chen Qian , Li Na , Ma Xinyue , Song Huifang , Peng Chao , Geng Ze , Dong Jie , Duan Guifang , Sun Qi , Yang Yang , Yang Fan , Huang Zhuo
Published: January 2024

Quinidine has been used as an anticonvulsant to treat patients with KCNT1-related epilepsy by targeting gain-of-function KCNT1 pathogenic mutant variants. However, the detailed mechanism underlying quinidine’s blockade against KCNT1 (Slack) remains elusive. Here, we report a functional and physical coupling of the voltage-gated sodium channel NaV1.6 and Slack. NaV1.6 binds to and highly sensitizes Slack to quinidine blockade. Homozygous knockout of NaV1.6 reduces the sensitivity of native sodium-activated potassium currents to quinidine blockade. NaV1.6-mediated sensitization requires the involvement of NaV1.6’s N- and C-termini binding to Slack’s C-terminus and is enhanced by transient sodium influx through NaV1.6. Moreover, disrupting the Slack-NaV1.6 interaction by viral expression of Slack’s C-terminus can protect against SlackG269S-induced seizures in mice. These insights about a Slack-NaV1.6 complex challenge the traditional view of ‘Slack as an isolated target’ for anti-epileptic drug discovery efforts and can guide the development of innovative therapeutic strategies for KCNT1-related epilepsy.
Behavioral entrainment to rhythmic auditory stimulation can be modulated by tACS depending on the electrical stimulation field properties
Authors: Cabral-Calderin Yuranny , van Hinsberg Daniela , Thielscher Axel , Henry Molly J
Published: January 2024

Synchronization between auditory stimuli and brain rhythms is beneficial for perception. In principle, auditory perception could be improved by facilitating neural entrainment to sounds via brain stimulation. However, high inter-individual variability of brain stimulation effects questions the usefulness of this approach. Here we aimed to modulate auditory perception by modulating neural entrainment to frequency modulated (FM) sounds using transcranial alternating current stimulation (tACS). In addition, we evaluated the advantage of using tACS montages spatially optimized for each individual’s anatomy and functional data compared to a standard montage applied to all participants. Across two different sessions, 2 Hz tACS was applied targeting auditory brain regions. Concurrent with tACS, participants listened to FM stimuli with modulation rate matching the tACS frequency but with different phase lags relative to the tACS, and detected silent gaps embedded in the FM sound. We observed that tACS modulated the strength of behavioral entrainment to the FM sound in a phase-lag specific manner. Both the optimal tACS lag and the magnitude of the tACS effect were variable across participants and sessions. Inter-individual variability of tACS effects was best explained by the strength of the inward electric field, depending on the field focality and proximity to the target brain region. Although additional evidence is necessary, our results also provided suggestive insights that spatially optimizing the electrode montage could be a promising tool to reduce inter-individual variability of tACS effects. This work demonstrates that tACS effectively modulates entrainment to sounds depending on the optimality of the electric field. However, the lack of reliability on optimal tACS lags calls for caution when planning tACS experiments based on separate sessions.
Aβ-driven nuclear pore complex dysfunction alters activation of necroptosis proteins in a mouse model of Alzheimer’s Disease
Authors: Bansal Vibhavari Aysha , Tan Jia Min , Soon Hui Rong , Zainolabidin Norliyana , Saito Takashi , Ch’ng Toh Hean
Published: January 2024

The emergence of Aβ pathology is one of the hallmarks of Alzheimer’s disease (AD), but the mechanisms and impact of Aβ in progression of the disease is unclear. The nuclear pore complex (NPC) is a multi-protein assembly in mammalian cells that regulates movement of macromolecules across the nuclear envelope and its function is shown to undergo age-dependent decline during normal aging and is also impaired in multiple neurodegenerative disorders. Yet not much is known about the impact of Aβ on NPC function in neurons. Here, we examined NPC and nucleoporin (NUP) distribution and nucleocytoplasmic transport using a mouse model of AD (

App
NL-G-F/NL-G-F

) that expresses Aβ in young animals. Our studies revealed that a time-dependent accumulation of intracellular Aβ corresponded with a reduction of NPCs and NUPs in the nuclear envelope which resulted in the degradation of the permeability barrier and inefficient segregation of nucleocytoplasmic proteins, and active transport. As a result of the NPC dysfunction
App
KI neurons become more vulnerable to inflammation-induced necroptosis – a programmed cell death pathway where the core components are activated via phosphorylation through nucleocytoplasmic shutting. Collectively, our data implicates Aβ in progressive impairment of nuclear pore function and further confirms that the protein complex is vulnerable to disruption in various neurodegenerative diseases and is a potential therapeutic target.
ProteasomeID: quantitative mapping of proteasome interactomes and substrates for in vitro and in vivo studies
Authors: Bartolome Aleksandar , Heiby Julia C. , Fraia Domenico Di , Heinze Ivonne , Knaudt Hannah , Späth Ellen , Omrani Omid , Minetti Alberto , Hofmann Maleen , Kirkpatrick Joanna M. , Dau Therese , Ori Alessandro
Published: January 2024

Proteasomes are essential molecular machines responsible for the degradation of proteins in eukaryotic cells. Altered proteasome activity has been linked to neurodegeneration, auto-immune disorders and cancer. Despite the relevance for human disease and drug development, no method currently exists to monitor proteasome composition and interactions
in vivo
in animal models. To fill this gap, we developed a strategy based on tagging of proteasomes with promiscuous biotin ligases and generated a new mouse model enabling the quantification of proteasome interactions by mass spectrometry. We show that biotin ligases can be incorporated in fully assembled proteasomes without negative impact on their activity. We demonstrate the utility of our method by identifying novel proteasome-interacting proteins, charting interactomes across mouse organs, and showing that proximity-labeling enables the identification of both endogenous and small molecule-induced proteasome substrates.
Control of T-shaped Bifurcation by Multiple Guidance Mechanisms during Dorsal Funiculus Development in the Spinal Cord
Authors: Curran Bridget M , Nickerson Kelsey R , Yung Andrea R , Goodrich Lisa V , Jaworski Alexander , Tessier-Lavigne Marc , Ma Le
Published: January 2024

The dorsal funiculus in the spinal cord relays somatosensory information to the brain. It is made of T-shaped bifurcation of dorsal root ganglion (DRG) sensory axons. Our previous study has shown that Slit signaling is required for proper guidance during bifurcation, but loss of Slit does not affect all DRG axons. Here, we examined the role of the extracellular molecule Netrin-1 (Ntn1). Using wholemount staining with tissue clearing, we showed that mice lacking Ntn1 have axons escaping from the dorsal funiculus at the time of bifurcation. Genetic labeling confirmed that these misprojecting axons come from DRG neurons. Single axon analysis showed that the defect does not affect bifurcation but rather alters turning angles. To distinguish their guidance functions, we examined mice with triple deletion of Ntn1, Slit2, and Slit2 and found a completely disorganized dorsal funiculus. Comparing mice with different genotypes using immunolabeling and single axon tracing revealed additive guidance defects, demonstrating the independent roles of Ntn1 and Slit. Moreover, the same defects were observed in embryos lacking their cognate receptors. These
in vivo
studies thus demonstrate the presence of multi-factorial guidance mechanisms that ensure proper formation of a common branched axonal structure during spinal cord development.
Prolonged Cell Cycle Arrest in Response to DNA damage in Yeast Requires the Maintenance of DNA Damage Signaling and the Spindle Assembly Checkpoint
Authors: Zhou Felix Y. , Waterman David P. , Caban-Penix Suhaily , Memisoglu Gonen , Eapen Vinay V. , Haber James E.
Published: January 2024

Cells evoke the DNA damage checkpoint (DDC) to inhibit mitosis in the presence of DNA double-strand breaks (DSBs) to allow more time for DNA repair. In budding yeast, a single irreparable DSB is sufficient to activate the DDC and induce cell cycle arrest prior to anaphase for about 12 to 15 hours, after which cells “adapt” to the damage by extinguishing the DDC and resuming the cell cycle. While activation of the DNA damage-dependent cell cycle arrest is well-understood, how it is maintained remains unclear. To address this, we conditionally depleted key DDC proteins after the DDC was fully activated and monitored changes in the maintenance of cell cycle arrest. Degradation of Ddc2
ATRIP
, Rad9, Rad24, or Rad53
CHK2
results in premature resumption of the cell cycle, indicating that these DDC factors are required both to establish and to maintain the arrest. Dun1 is required for establishment, but not maintenance of arrest, whereas Chk1 is required for prolonged maintenance but not for initial establishment of the mitotic arrest. When the cells are challenged with 2 persistent DSBs, they remain permanently arrested. This permanent arrest is initially dependent on the continuous presence of Ddc2 and Rad53; however, after 15 hours both proteins become dispensable. Instead, the continued mitotic arrest is sustained by spindle-assembly checkpoint (SAC) proteins Mad1, Mad2, and Bub2 but not by Bub2’s binding partner Bfa1. These data suggest that prolonged cell cycle arrest in response to 2 DSBs is achieved by a handoff from the DDC to specific components of the SAC. Furthermore, the establishment and maintenance of DNA damage-induced cell cycle arrest requires overlapping but different sets of factors.
SRF-deficient astrocytes provide neuroprotection in mouse models of excitotoxicity and neurodegeneration
Authors: Thumu Surya Chandra Rao , Jain Monika , Soman Sumitha , Das Soumen , Verma Vijaya , Nandi Arnab , Gutmann David H , Jayaprakash Balaji , Nair Deepak , Clement James P , Marathe Swananda , Ramanan Narendrakumar
Published: January 2024

Reactive astrogliosis is a common pathological hallmark of CNS injury, infection, and neurodegeneration, where reactive astrocytes can be protective or detrimental to normal brain functions. Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. These SrfGFAP-ERCKO astrocytes do not affect neuron survival, synapse numbers, synaptic plasticity or learning and memory. However, the brains of Srf knockout mice exhibited neuroprotection against kainic-acid induced excitotoxic cell death. Relevant to human neurodegenerative diseases, SrfGFAP-ERCKO astrocytes abrogate nigral dopaminergic neuron death and reduce β-amyloid plaques in mouse models of Parkinson’s and Alzheimer’s disease, respectively. Taken together, these findings establish SRF as a key molecular switch for the generation of reactive astrocytes with neuroprotective functions that attenuate neuronal injury in the setting of neurodegenerative diseases.
The application of the propensity score matching method in stock prediction among stocks within the same industry
Authors: Li Shengnan , Xue Lei
Published: January 2024

Stock price prediction is crucial in stock market research, yet existing models often overlook interdependencies among stocks in the same industry, treating them as independent entities. Recognizing and accounting for these interdependencies is essential for precise predictions. Propensity score matching (PSM), a statistical method for balancing individuals between groups and improving causal inferences, has not been extensively applied in stock interdependence investigations. Our study addresses this gap by introducing PSM to examine interdependence among pharmaceutical industry stocks for stock price prediction. Additionally, our research integrates Improved particle swarm optimization (IPSO) with long short-term memory (LSTM) networks to enhance parameter selection, improving overall predictive accuracy. The dataset includes price data for all pharmaceutical industry stocks in 2022, categorized into chemical pharmaceuticals, biopharmaceuticals, and traditional Chinese medicine. Using Stata, we identify significantly correlated stocks within each sub-industry through average treatment effect on the treated (ATT) values. Incorporating PSM, we match five target stocks per sub-industry with all stocks in their respective categories, merging target stock data with weighted data from non-target stocks for validation in the IPSO-LSTM model. Our findings demonstrate that including non-target stock data from the same sub-industry through PSM significantly improves predictive accuracy, highlighting its positive impact on stock price prediction. This study pioneers PSM’s use in studying stock interdependence, conducts an in-depth exploration of effects within the pharmaceutical industry, and applies the IPSO optimization algorithm to enhance LSTM network performance, providing a fresh perspective on stock price prediction research.
Characterizing transcriptomic responses to sediment stress across location and morphology in reef-building corals
Authors: Ashey Jill , McKelvie Hailey , Freeman John , Shpilker Polina , Zane Lauren H. , Becker Danielle M. , Cowen Lenore , Richmond Robert H. , Paul Valerie J. , Seneca Francois O. , Putnam Hollie M.
Published: January 2024

Anthropogenic activities increase sediment suspended in the water column and deposition on reefs can be largely dependent on colony morphology. Massive and plating corals have a high capacity to trap sediments, and active removal mechanisms can be energetically costly. Branching corals trap less sediment but are more susceptible to light limitation caused by suspended sediment. Despite deleterious effects of sediments on corals, few studies have examined the molecular response of corals with different morphological characteristics to sediment stress. To address this knowledge gap, this study assessed the transcriptomic responses of branching and massive corals in Florida and Hawai‘i to varying levels of sediment exposure. Gene expression analysis revealed a molecular responsiveness to sediments across species and sites. Differential Gene Expression followed by Gene Ontology (GO) enrichment analysis identified that branching corals had the largest transcriptomic response to sediments, in developmental processes and metabolism, while significantly enriched GO terms were highly variable between massive corals, despite similar morphologies. Comparison of DEGs within orthogroups revealed that while all corals had DEGs in response to sediment, there was not a concerted gene set response by morphology or location. These findings illuminate the species specificity and genetic basis underlying coral susceptibility to sediments.
Sleep and memory complaints in long COVID: an insight into clustered psychological phenotypes
Authors: Titze-de-Almeida Ricardo , Araújo Lacerda Pedro Henrique , Oliveira Edson Pereira de , Oliveira Mariah Eduarda Ferreira de , Vianna Yngrid Sallaberry Silva , Costa Amanda Machado , Pereira dos Santos Eloísa , Guérard Louise Marie Coelho , Ferreira Matheus Augusto de Miranda , Rodrigues dos Santos Isabel Cristina , Gonçalves Jéssica Daniele da Silva , Ginani Ferreira Gabriel , Souza Titze-de-Almeida Simoneide , Brandão Pedro Renato de Paula , Eri Shimizu Helena , Silva Andrezza Paula Brito , Delgado-Rodrigues Raimundo Nonato ,   Research Center for Major Themes–COVID-19 group
Published: January 2024

This study evaluated clinical features of individuals with long COVID (5–8 months after diagnosis) who reported sleep and memory problems (62 cases) compared to those without (52 controls). Both groups had a similar mean age (41 vs. 39 years). Around 86% of the participants were non-hospitalized at the time of infection, and none of them were vaccinated at that point. Subsequently, both cases and controls received the vaccine; however, the vaccination rates differed significantly between the groups (30.7% vs. 51.0%). Cases and controls had similar rates of symptoms at acute COVID phase. However, cases were more likely to experience coryza, dyspnea, headache, and nausea/vomiting during long COVID. Regarding new-onset symptoms in long COVID, 12.9% of cases had dyspnea, and 14.5% experienced nausea/vomiting, whereas in the control group there were only 1.9% and 0.0%, respectively. Cases also had a significantly higher prevalence of persistent headache (22.6% vs. 7.7%), and dyspnea (12.9% vs. 0.0). In addition, cases also showed an increased rate of mental health complaints: disability in daily activities (45.2% vs. 9.6%; P < 0.001); concentration/sustained attention difficulties (74.2% vs. 9.6%; P < 0.001); anxiety–Generalized Anxiety Disorder 2-item scale (GAD-2) ≥ 3 (66.1% vs. 34.6%; P = 0.0013); and “post-COVID sadness” (82.3% vs. 40.4%; P < 0.001). We observed a significant correlation between sadness and anxiety in cases, which was not observed in controls (P=0.0212; Spearman correlation test). Furthermore, the frequency of concomitant sadness and anxiety was markedly higher in cases compared to controls (59.7% vs. 19.2%) (P < 0.0001; Mann-Whitney test). These findings highlight a noteworthy association between sadness and anxiety specifically in cases. In conclusion, our data identified concurrent psychological phenotypes in individuals experiencing sleep and memory disturbances during long COVID. This strengthens the existing evidence that SARS-CoV-2 causes widespread brain pathology with interconnected phenotypic clusters. This finding highlights the need for comprehensive medical attention to address these complex issues, as well as major investments in testing strategies capable of preventing the development of long COVID sequelae, such as vaccination.