Identification of an alternative triglyceride biosynthesis pathway.

Triacylglycerols (TAGs) are the main source of stored energy in the body, providing an important substrate pool for mitochondrial beta-oxidation. Imbalances in the amount of TAGs are associated with obesity, cardiac disease and various other pathologies1,2. In humans, TAGs are synthesized from excess, coenzyme A-conjugated fatty acids by diacylglycerol O-acyltransferases (DGAT1 and DGAT2)3. In other organisms, this activity is complemented by additional enzymes4, but whether such alternative pathways exist in humans remains unknown. Here we disrupt the DGAT pathway in haploid human cells and use iterative genetics to reveal an unrelated TAG-synthesizing system composed of a protein we called DIESL (also known as TMEM68, an acyltransferase of previously unknown function) and its regulator TMX1. Mechanistically, TMX1 binds to and controls DIESL at the endoplasmic reticulum, and loss of TMX1 leads to the unconstrained formation of DIESL-dependent lipid droplets. DIESL is an autonomous TAG synthase, and expression of human DIESL in Escherichia coli endows this organism with the ability to synthesize TAG. Although both DIESL and the DGATs function as diacylglycerol acyltransferases, they contribute to the cellular TAG pool under specific conditions. Functionally, DIESL synthesizes TAG at the expense of membrane phospholipids and maintains mitochondrial function during periods of extracellular lipid starvation. In mice, DIESL deficiency impedes rapid postnatal growth and affects energy homeostasis during changes in nutrient availability. We have therefore identified an alternative TAG biosynthetic pathway driven by DIESL under potent control by TMX1.

Synthetic Peptides: Promising Modalities for the Targeting of Disease-Related Nucleic Acids.

DNA and RNA play pivotal roles in life processes by storing and transferring genetic information, modulating gene expression, and contributing to essential cellular machinery such as ribosomes. Dysregulation and mutations in nucleic acid-related processes are implicated in numerous diseases. Despite the critical impact on health of nucleic acid mutations or dysregulation, therapeutic compounds addressing these biomolecules remain limited. Peptides have emerged as a promising class of molecules for biomedical research, offering potential solutions for challenging drug targets. This review focuses on the use of synthetic peptides to target disease-related nucleic acids. We discuss examples of peptides targeting double-stranded DNA, including the clinical candidate Omomyc, and compounds designed for regulatory G-quadruplexes. Further, we provide insights into both library-based screenings and the rational design of peptides to target regulatory human RNA scaffolds and viral RNAs, emphasizing the potential of peptides in addressing nucleic acid-related diseases.

Contradicting perceptions of nursing teachers on the neoliberal context of labor.

OBJECTIVES: To identify and analyze the perceptions of nursing teachers on the new configurations of the job world and the repercussions for their labor activities. METHODS: Qualitative, descriptive, exploratory research, carried out at two federal nursing colleges in Rio de Janeiro. Data collection occurred with 27 nursing teachers, between May and June 2016, through semi-structured interviews. The data were treated using the thematic content analysis technique. RESULTS: The results showed contradictions in the teachers' perceptions about the job world, which has been guided by neoliberal precepts. Such contradictions are characterized by manifestations in favor of incorporating these precepts, highlighting their negative effects on nursing teaching work. FINAL CONSIDERATIONS: There are incongruities in the way of perceiving the current configuration of the job world, proposing more and profound reflections on such a work scenario.

Stereoselective Synthesis of Fused Vinylcyclopropanes by Intramolecular Tsuji-Trost Cascade Cyclization.

A stereoselective intramolecular Tsuji-Trost cascade cyclization of (homo)allylic vicinal diacetates with a pendant ß-ketoamide or related carbon nucleophile to give γ-lactam-fused vinylcyclopropanes is reported. In addition to two new rings, the products contain three new C-C stereocenters (two of which are quaternary) with a 9:1 dr. Moreover, the reaction proceeds in >94% enantiospecificity with optically enriched starting materials, using an inexpensive carbohydrate as the source of chirality.

Contradicting perceptions of nursing teachers on the neoliberal context of labor / Percepciones contradictorias de docentes de enfermería acerca del contexto neoliberal de trabajo / Percepções contraditórias de docentes de enfermagem sobre o contexto neoliberal do trabalho

ABSTRACT Objectives: To identify and analyze the perceptions of nursing teachers on the new configurations of the job world and the repercussions for their labor activities. Methods: Qualitative, descriptive, exploratory research, carried out at two federal nursing colleges in Rio de Janeiro. Data collection occurred with 27 nursing teachers, between May and June 2016, through semi-structured interviews. The data were treated using the thematic content analysis technique. Results: The results showed contradictions in the teachers' perceptions about the job world, which has been guided by neoliberal precepts. Such contradictions are characterized by manifestations in favor of incorporating these precepts, highlighting their negative effects on nursing teaching work. Final considerations: There are incongruities in the way of perceiving the current configuration of the job world, proposing more and profound reflections on such a work scenario.

RESUMEN Objetivos: Identificar y analizar las percepciones de docentes de Enfermería acerca de las nuevas configuraciones del mundo laboral y las repercusiones para sus actividades laborales. Métodos: Investigación cualitativa, descriptiva, exploratoria, realizada en dos facultades de Enfermería federales, en Rio de Janeiro. La recogida de datos ocurrió con 27 docentes de Enfermería, entre mayo y junio de 2016, por medio de entrevista semiestructurada. Los datos tratados por técnica de análisis temático de contenido. Resultados: Apuntaron contradicciones en las percepciones de los docentes acerca del mundo laboral, lo cual ha se pautado por preceptos neoliberales. Tales contradicciones se caracterizan por manifestaciones a favor de incorporación de eses preceptos, evidenciando sus efectos negativos acerca del trabajo docente de Enfermería. Consideraciones finales: Hay disonancias en la manera de percibir la actual configuración del mundo laboral, proponiéndose más y profundas reflexiones acerca de tal escenario laboral.

RESUMO Objetivos: Identificar e analisar as percepções de docentes de Enfermagem acerca das novas configurações do mundo do trabalho e as repercussões para suas atividades laborais. Métodos: Pesquisa qualitativa, descritiva, exploratória, realizada em duas faculdades de enfermagem federais, no Rio de Janeiro. A coleta de dados ocorreu com 27 docentes de Enfermagem, entre maio e junho de 2016, por meio de entrevista semiestruturada. Os dados foram tratados pela técnica de análise temática de conteúdo. Resultados: Os resultados apontaram contradições nas percepções dos docentes sobre o mundo do trabalho, o qual tem se pautado por preceitos neoliberais. Tais contradições se caracterizam por manifestações a favor da incorporação desses preceitos, evidenciando seus efeitos negativos sobre o trabalho docente de Enfermagem. Considerações finais: Há dissonâncias na maneira de perceber a atual configuração do mundo do trabalho, propondo-se mais e profundas reflexões sobre tal cenário laboral.

The effects of current-concern- and nonconcern-related waking suggestions on nocturnal dream content.

In previous research, presleep suggestions influenced nocturnal dream content. It was hypothesized that suggesting topics associated with participants' current concerns would influence dream content more than suggesting other topics. Ten students spent 4 nights in a sleep laboratory: an adaptation night, a baseline night, and 2 nights under suggestions to dream about a concern-related or other topic. Concern-related suggestions influenced dream content--largely its central imagery--more than did other suggestions, which did not differ from nonsuggestion. Number of transformations within dreams was uncorrelated with dream vividness, contrary to extended activation-synthesis theory. Thus, the concern-related status of suggestions moderates their effectiveness and, inconsistent with extended activation-synthesis theory but consistent with current-concerns and distributed-activation theories, motivational and volitional processes actively influence dream content.

Measurement of sulfamethizole clearance rate by nonthrombogenic constant blood-withdrawal system.

A method for the measurement of the total body clearance rate (CR) of drugs is described. It involves a single intravenous injection of a known quantity of the drug (D) and automatic integration of the plasma concentration curve, using a portable, nonthrombogenic, constant blood-withdrawal system. When blood withdrawal is carried out until the concentration of the drug in the plasma approaches zero, the concentration of the drug in the collected pool, the integrated concentration (ICT) multiplied by the time of collection (T) yields the integral of the concentration curve: (see article). The method was tested by measuring the clearance rate of sulfamethizole in five dogs by the established constant infusion method. At three plasma levels (25, 75, and 200 mg/liter), the plasma concentration had no significant effect on the clearance rate. The clearance rate of sulfamethizole was subsequently measured in the same dogs by the new single-injection constant withdrawal method. Multiple blood samples were collected at 15-min intervals simultaneously with the constant withdrawal of blood. There was no significant difference between the clearance rate of sulfamethizole measured by the two methods. The initial peak mean concentration of the drug from the time of injection (t = 0) to the time of the first blood sampling (t = 15 min) was calculated from the difference between (see article) obtained by the constant withdrawal method and that obtained from the results of the multiple blood withdrawals by the trapezoidal rule. The integrated concentration IC15 was significantly higher than its estimation by the semilogarithmic linear regression method.