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Tumor growth is influenced by a complex network of interactions between multiple cell types in the tumor microenvironment (TME). These constrained conditions trigger the endoplasmic reticulum (ER) stress response, which extensively reprograms mRNA translation. When uncontrolled over time, chronic ER stress impairs the antitumor effector function of CD8 T lymphocytes. How cells promote adaptation to chronic stress in the TME without the detrimental effects of the terminal unfolded protein response (UPR) is unknown. Here, we find that, in effector CD8 T lymphocytes, RNA-binding protein CPEB4 constitutes a new branch of the UPR that allows cells to adapt to sustained ER stress, yet remains decoupled from the terminal UPR. ER stress, induced during CD8 T-cell activation and effector function, triggers CPEB4 expression. CPEB4 then mediates chronic stress adaptation to maintain cellular fitness, allowing effector molecule production and cytotoxic activity. Accordingly, this branch of the UPR is required for the antitumor effector function of T lymphocytes, and its disruption in these cells exacerbates tumor growth.
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Estrés del Retículo Endoplásmico , Neoplasias , Humanos , Estrés del Retículo Endoplásmico/genética , Respuesta de Proteína Desplegada , Neoplasias/metabolismo , Linfocitos T CD8-positivos/metabolismo , Adaptación Fisiológica , Microambiente Tumoral , Proteínas de Unión al ARN/metabolismoRESUMEN
The circular economy and bioeconomy can contribute to transitioning towards more sustainable production and consumption in the olive oil sector. This article is the first to analyse multi-actor strategies and multi-level socio-economic conditions for olive oil waste and by-product valorisation in the Mediterranean area using circular bioeconomy principles. Government policies, the strategies of corporations and farmers and consumers' perceptions are discussed, and various methods are applied, such as desk reviews, case studies and quantitative and qualitative surveys. The findings show strong aspirations for improved sustainability in the olive industry. Furthermore, waste and by-product valorisation strategies foster the creation of innovative practices. However, a common regulatory framework, public financial measures, new circular business models using innovative technologies, multi-actor collaboration and increased consumer awareness of the circular economy and new olive oil waste-based products are necessary for more efficient and sustainable use of olive resources. The policy and management recommendations presented in this study may aid in improving and innovating frameworks and practices for better sustainable management of valuable olive resources.
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Olea , Residuos , Agricultores , Humanos , Industrias , Aceite de OlivaRESUMEN
The scholars comprising journal editorial boards play a critical role in defining the trajectory of knowledge in their field. Nevertheless, studies of editorial board composition remain rare, especially those focusing on journals publishing research in the increasingly globalized fields of science, technology, engineering, and math (STEM). Using metrics for quantifying the diversity of ecological communities, we quantified international representation on the 1985-2014 editorial boards of 24 environmental biology journals. Over the course of 3 decades, there were 3,827 unique scientists based in 70 countries who served as editors. The size of the editorial community increased over time-the number of editors serving in 2014 was 4-fold greater than in 1985-as did the number of countries in which editors were based. Nevertheless, editors based outside the "Global North" (the group of economically developed countries with high per capita gross domestic product [GDP] that collectively concentrate most global wealth) were extremely rare. Furthermore, 67.18% of all editors were based in either the United States or the United Kingdom. Consequently, geographic diversity-already low in 1985-remained unchanged through 2014. We argue that this limited geographic diversity can detrimentally affect the creativity of scholarship published in journals, the progress and direction of research, the composition of the STEM workforce, and the development of science in Latin America, Africa, the Middle East, and much of Asia (i.e., the "Global South").
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Biología , Ecología , Políticas Editoriales , Internacionalidad , Edición , Estados UnidosRESUMEN
This study analyzed the use of fifteen groups of digital tools that 197 active teachers made during the sudden shift to remote instruction due to the COVID-19 quarantine orders placed by various health departments in Spain and the United States. The study also examined the impact that the use of digital tools had on teachers' perceived self-efficacy. A quantitative research design was used, supported by an exploratory descriptive approach that materializes in the application of an online questionnaire during the spring of 2020. The results indicate that perceived self-efficacy differs from country of origin and is conditioned by sociodemographic variables such as the training received and type of center. It is noted that teachers in Spain prefer the use of Moodle or Escholarium over that of teachers in the United States that opted for Google Classroom as a primary platform for teaching online, and the frequency of use of digital tools analyzed does not guarantee that their implementation is effective.
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Practically all animals are affected by humans, especially in urban areas. Although most species respond negatively to urbanization, some thrive in human-dominated settings. A central question in urban ecology is why some species adapt well to the presence of humans and others do not. We show that Northern Mockingbirds (Mimus polyglottos) nesting on the campus of a large university rapidly learn to assess the level of threat posed by different humans, and to respond accordingly. In a controlled experiment, we found that as the same human approached and threatened a nest on 4 successive days, mockingbirds flushed from their nest at increasingly greater distances from that human. A different human approaching and threatening the nest identically on the fifth day elicited the same response as the first human on the first day. Likewise, alarm calls and attack flights increased from days 1-4 with the first human, and decreased on day 5 with the second human. These results demonstrate a remarkable ability of a passerine bird to distinguish one human from thousands of others. Also, mockingbirds learned to identify individual humans extraordinarily quickly: after only 2 30-s exposures of the human at the nest. More generally, the varying responses of mockingbirds to intruders suggests behavioral flexibility and a keen awareness of different levels of threat posed by individuals of another species: traits that may predispose mockingbirds and other species of urban wildlife to successful exploitation of human-dominated environments.
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Conducta Animal , Aprendizaje , Passeriformes/fisiología , Animales , HumanosRESUMEN
To determine whether or not digital inequalities exist, the frequency, duration, satisfaction, importance, and perceived competence of eighteen groups of digital tools during the COVID-19 pandemic confinement were examined. An online survey was administered to 2882 Latin American university students (49% female; M = 21.3 years). The following items are checked: (1) increased digital inequalities during the pandemic; (2) adequate reliability and validity of the Digital Technology Survey (DTS) instrument; (3) patterns of digital inequalities to the detriment of men, lower strata and unemployed people; and (4) evidence that the importance of digital activities as a causal factor on satisfaction with such digital activities as an outcome is mediated by the purpose of use and communication recipients, but not by strata or employment status, nor moderated by gender. The results are discussed in the light of previous studies, the limitations of the study and future perspectives.
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COVID-19 , Brecha Digital , COVID-19/epidemiología , Tecnología Digital , Femenino , Humanos , América Latina/epidemiología , Masculino , Pandemias , Reproducibilidad de los Resultados , UniversidadesRESUMEN
Digital media play a fundamental role in the social, emotional, and cognitive development of adolescents, since they involve a very significant use and investment of time at this age. The objectives of this work are twofold: analyze the use of the Internet and digital devices by Spanish young people outside school, and the time they use them and their attitude towards the use of digital devices, as well as to identify the effects of the use of internet and digital devices on social and interpersonal relationships. The sample is composed of 35,943 students of Compulsory Secondary Education, from different Spanish high schools that participated in the PISA 2018 Report. The data provided by this study confirm the widespread consumption of digital devices. Identified as actions that they carry out every day were: the use of online chat, use of social networks to contact their friends, and surfing the internet for fun. Regarding the attitude towards digital devices, the participants say they feel comfortable using digital devices and discovering new applications or games. However, we also found as one of the most relevant results of this study the fact that participants say they feel bad if they do not have internet connection.
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Internet , Relaciones Interpersonales , Adolescente , Humanos , Instituciones Académicas , Red Social , Estudiantes/psicologíaRESUMEN
The impact of digital devices and the Internet has generated various changes at social, political, and economic levels, the repercussion of which is a great challenge characterized by the changing and globalized nature of today's society. This demands the development of new skills and new learning models in relation to information and communication technologies. Universities must respond to these social demands in the training of their future professionals. This paper aims to analyze the empirical evidence provided by international studies in the last eleven years, related to the digital literacy of university students, including those pursuing degrees related to the field of education. Our findings highlight the fact that the digital literacy that is offered in universities to graduate/postgraduate students, in addition to treating digital literacy as a central theme, also focuses on perceived and developed self-efficacy. This is done by strengthening competencies related to digital writing and reading, the use of databases, the digital design of content and materials, and the skills to edit, publish or share them on the web, or applications aimed at treating digital literacy as emerging pedagogies and educational innovation. Secondly, we found studies related to digital competencies and use of the Internet, social networks, web 2.0, or the treatment of digital risks and their relationship with digital literacy. Thirdly, we found works that, in addition to focusing on digital literacy, also focused on different psychological constructs such as motivation, commitment, attitudes, or satisfaction. Systematic review registration: https://www.scopus.com/home.uri; https://www.recursoscientificos.fecyt.es/.
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Chronic inflammation is a major cause of disease. Inflammation resolution is in part directed by the differential stability of mRNAs encoding pro-inflammatory and anti-inflammatory factors. In particular, tristetraprolin (TTP)-directed mRNA deadenylation destabilizes AU-rich element (ARE)-containing mRNAs. However, this mechanism alone cannot explain the variety of mRNA expression kinetics that are required to uncouple degradation of pro-inflammatory mRNAs from the sustained expression of anti-inflammatory mRNAs. Here, we show that the RNA-binding protein CPEB4 acts in an opposing manner to TTP in macrophages: it helps to stabilize anti-inflammatory transcripts harboring cytoplasmic polyadenylation elements (CPEs) and AREs in their 3'-UTRs, and it is required for the resolution of the lipopolysaccharide (LPS)-triggered inflammatory response. Coordination of CPEB4 and TTP activities is sequentially regulated through MAPK signaling. Accordingly, CPEB4 depletion in macrophages impairs inflammation resolution in an LPS-induced sepsis model. We propose that the counterbalancing actions of CPEB4 and TTP, as well as the distribution of CPEs and AREs in their target mRNAs, define transcript-specific decay patterns required for inflammation resolution. Thus, these two opposing mechanisms provide a fine-tuning control of inflammatory transcript destabilization while maintaining the expression of the negative feedback loops required for efficient inflammation resolution; disruption of this balance can lead to disease.
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Macrófagos , Estabilidad del ARN , Proteínas de Unión al ARN , Tristetraprolina , Regiones no Traducidas 3' , Humanos , Inflamación/metabolismo , Lipopolisacáridos , Macrófagos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Tristetraprolina/genética , Tristetraprolina/metabolismoRESUMEN
Upon tissue injury, cytokine expression reprogramming transiently remodels the inflammatory immune microenvironment to activate repair processes and subsequently return to homeostasis. However, chronic inflammation induces permanent changes in cytokine production which exacerbate tissue damage and may even favor tumor development. Here, we address the contribution of post-transcriptional regulation, by the RNA-binding protein CPEB4, to intestinal immune homeostasis and its role in inflammatory bowel diseases (IBD) and colorectal cancer (CRC) development. We found that intestinal damage induces CPEB4 expression in adaptive and innate immune cells, which is required for the translation of cytokine mRNA(s) such as the one encoding interleukin-22. Accordingly, CPEB4 is required for the development of gut-associated lymphoid tissues and to maintain intestinal immune homeostasis, mediating repair and remodeling after acute inflammatory tissue damage and promoting the resolution of intestinal inflammation. CPEB4 is chronically overexpressed in inflammatory cells in patients with IBD and in CRC, favoring tumor development.
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In the last decade, published data on the performance of Colombian students have concerned educators and researchers, making critical reading one of the priorities of Colombian education. That is why this article presents the results of a study carried out in a Latin American university in which the perceptions of students and professors are analyzed regarding the strategies and textual genres used to work and cross-evaluate the advanced reading comprehension (ARC). This study is materialized in the application of an ad hoc online questionnaire, in its two versions (students and teachers), designed through Survey Monkey. For this, it has the participation of 182 teachers and 2,775 students. There are several trends in the use of specific textual strategies and typologies to work and evaluate ARC, by both, depending on the department of assignment. The evidence found is provided and evaluated considering the implications for cross-curricular instruction and assessment in higher education in Latin America, including study limitations and prospects for overcoming them.
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RNA-binding proteins (RBPs) control critical aspects of cardiomyocyte function, but the repertoire of active RBPs in cardiomyocytes during the growth response is largely unknown. We define RBPs in healthy and diseased cardiomyocytes at a system-wide level by RNA interactome capture. This identifies 67 cardiomyocyte-specific RBPs, including several contractile proteins. Furthermore, we identify the cytoplasmic polyadenylation element-binding protein 4 (Cpeb4) as a dynamic RBP, regulating cardiac growth both in vitro and in vivo. We identify mRNAs bound to and regulated by Cpeb4 in cardiomyocytes. Cpeb4 regulates cardiac remodeling by differential expression of transcription factors. Among Cpeb4 target mRNAs, two zinc finger transcription factors (Zeb1 and Zbtb20) are discovered. We show that Cpeb4 regulates the expression of these mRNAs and that Cpeb4 depletion increases their expression. Thus, Cpeb4 emerges as a critical regulator of cardiomyocyte function by differential binding to specific mRNAs in response to pathological growth stimulation.
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Miocitos Cardíacos/metabolismo , Proteínas de Unión al ARN/metabolismo , Animales , Proliferación Celular , Humanos , RatonesRESUMEN
Organogenesis is directed by coordinated cell proliferation and differentiation programs. The hierarchical networks of transcription factors driving mammary gland development and function have been widely studied. However, the contribution of posttranscriptional gene expression reprogramming remains largely unexplored. The 3' untranslated regions of messenger RNAs (mRNAs) contain combinatorial ensembles of cis-regulatory elements that define transcript-specific regulation of protein synthesis through their cognate RNA binding proteins. We analyze the contribution of the RNA binding cytoplasmic polyadenylation element-binding (CPEB) protein family, which collectively regulate mRNA translation for about 30% of the genome. We find that CPEB2 is required for the integration of hormonal signaling by controlling the protein expression from a subset of ER/PR- regulated transcripts. Furthermore, CPEB2 is critical for the development of ER-positive breast tumors. This work uncovers a previously unknown gene expression regulation level in breast morphogenesis and tumorigenesis, coordinating sequential transcriptional and posttranscriptional layers of gene expression regulation.
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Neoplasias de la Mama , Glándulas Mamarias Humanas , Regiones no Traducidas 3' , Neoplasias de la Mama/genética , Femenino , Hormonas , Humanos , Glándulas Mamarias Humanas/metabolismo , Organogénesis , ARN Mensajero/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
Despite the enormous advances in genetics, links between phenotypes and genotypes have been made for only a few nonmodel organisms. However, such links can be essential to understand mechanisms of ecological speciation. The Costa Rican endemic Mangrove Warbler subspecies provides an excellent subject to study differentiation with gene flow, as it is distributed along a strong precipitation gradient on the Pacific coast with no strong geographic barriers to isolate populations. Mangrove Warbler populations could be subject to divergent selection driven by precipitation, which influences soil salinity levels, which in turn influences forest structure and food resources. We used single nucleotide polymorphisms (SNPs) and morphological traits to examine the balance between neutral genetic and phenotypic divergence to determine whether selection has acted on traits and genes with functions related to specific environmental variables. We present evidence showing: (a) associations between environmental variables and SNPs, identifying candidate genes related to bill morphology (BMP) and osmoregulation, (b) absence of population genetic structure in neutrally evolving markers, (c) divergence in bill size across the precipitation gradient, and (d) strong phenotypic differentiation (P ST) which largely exceeds neutral genetic differentiation (F ST) in bill size. Our results indicate an important role for salinity, forest structure, and resource availability in maintaining phenotypic divergence of Mangrove Warblers through natural selection. Our findings add to the growing body of literature identifying the processes involved in phenotypic differentiation along environmental gradients in the face of gene flow.
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The cytoplasmic polyadenylation element-binding (CPEB) proteins regulate pre-mRNA processing and translation of CPE-containing mRNAs in early embryonic development and synaptic activity. However, specific functions in adult organisms are poorly understood. Here we show that CPEB4 is required for adaptation to high-fat-diet- and ageing-induced endoplasmic reticulum (ER) stress, and subsequent hepatosteatosis. Stress-activated liver CPEB4 expression is dual-mode regulated. First, Cpeb4 mRNA transcription is controlled by the circadian clock, and then its translation is regulated by the unfolded protein response (UPR) through upstream open reading frames within the 5'UTR. Thus, the CPEB4 protein is synthesized only following ER stress but the induction amplitude is circadian. In turn, CPEB4 activates a second wave of UPR translation required to maintain ER and mitochondrial homeostasis. Our results suggest that combined transcriptional and translational Cpeb4 regulation generates a 'circadian mediator', which coordinates hepatic UPR activity with periods of high ER-protein-folding demand. Accordingly, CPEB4 deficiency results in non-alcoholic fatty liver disease.
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Estrés del Retículo Endoplásmico/fisiología , Retículo Endoplásmico/metabolismo , Hígado Graso/genética , Regulación de la Expresión Génica/genética , Proteínas de Unión al ARN/genética , Animales , Estrés del Retículo Endoplásmico/genética , Homeostasis/fisiología , Ratones , Biosíntesis de Proteínas , Precursores del ARN/metabolismo , Transcripción Genética/genética , Respuesta de Proteína Desplegada/fisiologíaRESUMEN
Evidence is accumulating that individuals in poor physiologic condition may accumulate mutational damage faster than individuals in good condition. If poor condition results from pre-existing deleterious mutations, the result is "fitness-dependent mutation rate," which has interesting theoretical implications. Here we report a study in which 10 mutation accumulation (MA) lines of the nematode Caenorhabditis elegans that had previously accumulated mutations for 250 generations under relaxed selection were expanded into sets of "second-order" MA lines and allowed to accumulate mutations for an additional 150 generations. The 10 lines were chosen on the basis of the relative change in fitness over the first 250 generations of MA, five high-fitness lines and five low-fitness lines. On average, the mutational properties (per-generation change in mean relative fitness, mutational variance, and Bateman-Mukai estimates of genomic mutation rate and average mutational effect) of the high-fitness and low-fitness did not differ significantly, and averaged over all lines, the point estimates were extremely close to those of the first-order MA experiment after 200 generations of MA. However, several nonsignificant trends indicate that low-fitness lines may in fact be more likely to suffer mutational damage than high-fitness lines.
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Caenorhabditis elegans/genética , Mutación , Animales , Modelos Genéticos , Modelos Estadísticos , Selección GenéticaRESUMEN
Red colobus monkeys, due to their sensitivity to environmental change, are indicator species of the overall health of their tropical rainforest habitats. As a result of habitat loss and overhunting, they are among the most endangered primates in the world, with very few viable populations remaining. Traditionally, extant indicator species have been used to signify the conditions of their current habitats, but they have also been employed to track past environmental conditions by detecting previous population fluctuations. Kibale National Park (KNP) in Uganda harbors the only remaining unthreatened large population of red colobus. We used microsatellite DNA to evaluate the historical demography of these red colobus and, therefore, the long-term stability of their habitat. We find that the red colobus population throughout KNP has been stable for at least â¼40,000 years. We interpret this result as evidence of long-term forest stability because a change in the available habitat or population movement would have elicited a corresponding change in population size. We conclude that the forest of what is now Kibale National Park may have served as a Late Pleistocene refuge for many East African species.