Epitranscriptomic regulation of HIV-1 full-length RNA packaging.

During retroviral replication, the full-length RNA serves both as mRNA and genomic RNA. However, the mechanisms by which the HIV-1 Gag protein selects the two RNA molecules that will be packaged into nascent virions remain poorly understood. Here, we demonstrate that deposition of N6-methyladenosine (m6A) regulates full-length RNA packaging. While m6A deposition by METTL3/METTL14 onto the full-length RNA was associated with increased Gag synthesis and reduced packaging, FTO-mediated demethylation promoted the incorporation of the full-length RNA into viral particles. Interestingly, HIV-1 Gag associates with the RNA demethylase FTO in the nucleus and contributes to full-length RNA demethylation. We further identified two highly conserved adenosines within the 5'-UTR that have a crucial functional role in m6A methylation and packaging of the full-length RNA. Together, our data propose a novel epitranscriptomic mechanism allowing the selection of the HIV-1 full-length RNA molecules that will be used as viral genomes.

Development and implementation of guidelines for the management of depression: a systematic review.

OBJECTIVE: To evaluate the development and implementation of clinical practice guidelines for the management of depression globally. METHODS: We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries. FINDINGS: We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence. CONCLUSION: Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes.

Journal club experience in a postgraduate psychiatry program in Chile.

OBJECTIVE: Literature about journal clubs in postgraduate psychiatry programs is scarce, and there is no reference to residents' preferences. METHODS: Residents were asked to respond to a survey about their general satisfaction with the current journal club format and paper preferences, according to subject, scope, and type. RESULTS: Residents' general satisfaction was high. Residents preferred clinically relevant meta-analyses and randomized controlled trials about mood and psychotic disorders, neuroscience, and biological therapies. CONCLUSION: There is a trend to prefer articles related to biological aspects of psychiatry, centered in evidence-based medicine methodology. An effort should be made to broaden the scope of selection of papers, incorporating, for instance, humanistic views, psychotherapy, and other methodologies.

3-Hydr-oxy-3a,6,8c-trimethyl-perhydro-oxireno[2',3':7,8]naphtho[1,2-b]furan-7(2H)-one.

The title compound, C(15)H(22)O(4), consists of two trans-fused six-membered rings and a trans-fused five-membered γ-lactone. The ep-oxy and hydroxyl groups are α-oriented. The cyclo-hexane rings adopt half-chair and chair conformations and the lactone ring is in an envelope conformation. The mol-ecular structure is stabilized by one O-H⋯O and three C-H⋯O intra-molecular hydrogen bonds.

Valoración por los docentes de telesimulación en el grado de Odontología durante la COVID-19 / Assessment by telesimulation teachers in the Dentistry degree during COVID-19

Introducción: Debido a la pandemia por COVID-19, en la educación se implementaron diversas estrategias innovadoras de aprendizaje. El objetivo es conocer la experiencia de los docentes de la carrera de Odontología de la Universidad Autónoma de Chile, sede de Temuco, que utilizaron telesimulación como metodología de enseñanza en el contexto de pandemia. Sujetos y métodos: Se realizó una investigación cualitativa mediante un estudio intrínseco de casos. La muestra de 12 participantes fue no probabilística, intencionada de casos por criterios y por conveniencia. La recolección de datos fue a través de grupos focales. El análisis se realizó por reducción progresiva de la información. El estudio fue autorizado por el comité de ética de la Universidad Autónoma de Chile, sede de Temuco. Resultados: Se develaron 181 unidades de significado relevantes para el estudio agrupadas en cuatro categorías: ‘Significado de haber vivido la experiencia de telesimulación', ‘Factores que facilitan la telesimulación como estrategia metodológica', ‘Factores que dificultan la telesimulación como estrategia metodológica' y ‘Sugerencias para la implementación de la telesimulación en el futuro'. Finalmente, emergen dos dominios cualitativos: ‘Componentes asociados a factores que inciden en la telesimulación' y ‘Aportes de los docentes como resultado de haber vivido la experiencia'. Conclusiones: Docentes destacan, según su experiencia, que la telesimulación fue demandante y agotadora por los tiempos de dedicación para su desarrollo. Reconocieron el desconocimiento de la didáctica y los problemas de conectividad de los estudiantes.(AU)

Introduction: Due to the COVID-19 pandemic, various innovative learning strategies were implemented in education. The objective is to know the experience of the teachers of the Dentistry Career of the Autonomous University of Chile, Temuco campus, who used telesimulation as a teaching methodology in the context of a pandemic. Subjects and methods: A qualitative investigation was carried out through an intrinsic case study. The sample of 12 participants, was non-probabilistic, intentional of cases by criteria and for convenience. Data collection was through focus groups. The analysis was carried out by progressive reduction of the information. Study authorized by the Ethics Committee of the Autonomous University of Chile, Temuco headquarters. Results: One hundred eighty-one units of meaning relevant to the study were revealed, grouped into 4 categories: ‘Meaning of having lived the experience of Telesimulation', ‘Factors that facilitate telesimulation as a methodological strategy', ‘Factors that hinder telesimulation as a methodological strategy' and ‘Suggestions for the implementation of remote simulation in the future'. Finally, two qualitative domains emerge: Components associated with factors that affect telesimulation and Contributions from teachers as a result of having lived the experience. Conclusions: Teachers highlight based on their experience. That telesimulation it was demanding and exhausting, due to the dedication times for its development. They recognized lack of knowledge of the didactics and connectivity problems of the students.(AU)

Ion and diuretic specificity of chimeric proteins between apical Na(+)-K(+)-2Cl(-) and Na(+)-Cl(-) cotransporters.

The mammalian kidney bumetanide-sensitive Na(+)-K(+)-2Cl(-) and thiazide-sensitive Na(+)-Cl(-) cotransporters are the major pathways for salt reabsorption in the thick ascending limb of Henle's loop and distal convoluted tubule, respectively. These cotransporters serve as receptors for the loop- and thiazide-type diuretics, and inactivating mutations of corresponding genes are associated with development of Bartter's syndrome type I and Gitleman's disease, respectively. Structural requirements for ion translocation and diuretic binding specificity are unknown. As an initial approach for analyzing structural determinants conferring ion or diuretic preferences in these cotransporters, we exploited functional differences and structural similarities between Na(+)-K(+)-2Cl(-) and Na(+)-Cl(-) cotransporters to design and study chimeric proteins in which the NH(2)-terminal and/or COOH-terminal domains were switched between each other. Thus six chimeric proteins were produced. Using the heterologous expression system of Xenopus laevis oocytes, we observed that four chimeras exhibited functional activity. Our results revealed that, in the Na(+)-K(+)-2Cl(-) cotransporter, ion translocation and diuretic binding specificity are determined by the central hydrophobic domain. Thus NH(2)-terminal and COOH-terminal domains do not play a role in defining these properties. A similar conclusion can be suggested for the Na(+)-Cl(-) cotransporter.