ATAC and SAGA co-activator complexes utilize co-translational assembly, but their cellular localization properties and functions are distinct.

To understand the function of multisubunit complexes, it is of key importance to uncover the precise mechanisms that guide their assembly. Nascent proteins can find and bind their interaction partners during their translation, leading to co-translational assembly. Here, we demonstrate that the core modules of ATAC (ADA-two-A-containing) and SAGA (Spt-Ada-Gcn5-acetyltransferase), two lysine acetyl transferase-containing transcription co-activator complexes, assemble co-translationally in the cytoplasm of mammalian cells. In addition, a SAGA complex containing all of its modules forms in the cytoplasm and acetylates non-histone proteins. In contrast, ATAC complex subunits cannot be detected in the cytoplasm of mammalian cells. However, an endogenous ATAC complex containing two functional modules forms and functions in the nucleus. Thus, the two related co-activators, ATAC and SAGA, assemble using co-translational pathways, but their subcellular localization, cytoplasmic abundance, and functions are distinct.

The ANTI-Vea-UGR Platform: A Free Online Resource to Measure Attentional Networks (Alertness, Orienting, and Executive Control) Functioning and Executive/Arousal Vigilance.

The Attentional Networks Test for Interactions and Vigilance-executive and arousal components (ANTI-Vea) is a computerized task of 32 min duration in the standard format. The task simultaneously assesses the main effects and interactions of the three attentional networks (i.e., phasic alertness, orienting, and executive control) and two dissociated components of vigilance with reasonable reliability (executive and arousal vigilance). We present this free and publicly accessible resource (ANTI-Vea-UGR; https://anti-vea.ugr.es/) developed to easily run, collect, and analyze data with the ANTI-Vea (or its subtasks measuring some attentional and/or vigilance components embedded in the ANTI-Vea). Available in six different languages, the platform allows for the adaptation of stimulus timing and procedure to facilitate data collection from different populations (e.g., clinical patients, children). Collected data can be freely downloaded and easily analyzed with the provided scripts and tools, including a Shiny app. We discuss previous evidence supporting that attention and vigilance components can be assessed in typical lab conditions as well as online and outside the laboratory. We hope this tutorial will help researchers interested in measuring attention and vigilance with a tool useful to collect data from large sample sizes and easy to use in applied contexts.

ATAC and SAGA coactivator complexes utilize co-translational assembly, but their cellular localization properties and functions are distinct.

To understand the function of multisubunit complexes it is of key importance to uncover the precise mechanisms that guide their assembly. Nascent proteins can find and bind their interaction partners during their translation, leading to co-translational assembly. Here we demonstrate that the core modules of ATAC (ADA-Two-A-Containing) and SAGA (Spt-Ada-Gcn5-acetyltransferase), two lysine acetyl transferase-containing transcription coactivator complexes, assemble co-translationally in the cytoplasm of mammalian cells. In addition, SAGA complex containing all of its modules forms in the cytoplasm and acetylates non-histones proteins. In contrast, fully assembled ATAC complex cannot be detected in the cytoplasm of mammalian cells. However, endogenous ATAC complex containing two functional modules forms and functions in the nucleus. Thus, the two related coactivators, ATAC and SAGA, assemble by using co-translational pathways, but their subcellular localization, cytoplasmic abundance and functions are distinct.

Hierarchical TAF1-dependent co-translational assembly of the basal transcription factor TFIID.

Large heteromeric multiprotein complexes play pivotal roles at every step of gene expression in eukaryotic cells. Among them, the 20-subunit basal transcription factor TFIID nucleates the RNA polymerase II preinitiation complex at gene promoters. Here, by combining systematic RNA-immunoprecipitation (RIP) experiments, single-molecule imaging, proteomics and structure-function analyses, we show that human TFIID biogenesis occurs co-translationally. We discovered that all protein heterodimerization steps happen during protein synthesis. We identify TAF1-the largest protein in the complex-as a critical factor for TFIID assembly. TAF1 acts as a flexible scaffold that drives the co-translational recruitment of TFIID submodules preassembled in the cytoplasm. Altogether, our data suggest a multistep hierarchical model for TFIID biogenesis that culminates with the co-translational assembly of the complex onto the nascent TAF1 polypeptide. We envision that this assembly strategy could be shared with other large heteromeric protein complexes.

Hierarchical TAF1-dependent co-translational assembly of the basal transcription factor TFIID.

Large heteromeric multiprotein complexes play pivotal roles at every step of gene expression in eukaryotic cells. Among them, the 20-subunit basal transcription factor TFIID nucleates RNA polymerase II preinitiation complex at gene promoters. Here, by combining systematic RNA-immunoprecipitation (RIP) experiments, single-molecule imaging, proteomics and structure-function analyses, we show that TFIID biogenesis occurs co-translationally. We discovered that all protein heterodimerization steps happen during protein synthesis. We identify TAF1 - the largest protein in the complex - as a critical factor for TFIID assembly. TAF1 acts as a flexible scaffold that drives the co-translational recruitment of TFIID submodules preassembled in the cytoplasm. Altogether, our data suggest a multistep hierarchical model for TFIID biogenesis that culminates with the co-translational assembly of the complex onto the nascent TAF1 polypeptide. We envision that this assembly strategy could be shared with other large heteromeric protein complexes.

The Kv10.1 Channel: A Promising Target in Cancer.

Carcinogenesis is a multistage process involving the dysregulation of multiple genes, proteins, and pathways that make any normal cell acquire a cancer cell phenotype. Therefore, it is no surprise that numerous ion channels could be involved in this process. Since their discovery and subsequent cloning, ion channels have been established as therapeutic targets in excitable cell pathologies (e.g., cardiac arrhythmias or epilepsy); however, their involvement in non-excitable cell pathologies is relatively recent. Among all ion channels, the voltage-gated potassium channels Kv10.1 have been established as a promising target in cancer treatment due to their high expression in tumoral tissues compared to low levels in healthy tissues.

Violencia de pareja en adolescentes chilenos: Influencia del abuso infantil en la victimización y perpetración / Association of adolescent dating violence as victim or perpetrator with childhood maltreatment

BACKGROUNDBackground: Childhood maltreatment extends beyond this stage of development, impacting adolescence and adulthood, and even adolescent dating violence. Adolescence is an essential transitional stage, so dating violence puts development at risk. In Chile, studies on adolescent dating violence are just emerging and still show a gap. Aim: To examine the relationship between abuse during childhood with victimization and perpetration experiences for adolescent dating violence. MATERIAL AND METHODS: The sample consisted of 242 adolescents between 14 and 19 years of age (59% females) who completed the Conflict in Adolescent Dating Relationship Inventory (CADRI) and the Childhood Trauma Questionnaire-Short Form (CQT-SF), both in their Spanish version. Multiple regression analysis was used to evaluate the degree of association between sexual, emotional, and physical abuse during childhood with adolescent dating violence. Results: Sexual and emotional abuse were predictors of dating victimization. In addition, sexual and physical abuse were found to be predictors of perpetration. CONCLUSIONS: Our study supports the evidence on differentiated outcomes between adolescent dating victimization and perpetration. Moreover, it highlights the role of childhood sexual abuse as a predictor of both.

[Association of adolescent dating violence as victim or perpetrator with childhood maltreatment]. / Violencia de pareja en adolescentes chilenos: Influencia del abuso infantil en la victimización y perpetración.

BACKGROUND: Childhood maltreatment extends beyond this stage of development, impacting adolescence and adulthood, and even adolescent dating violence. Adolescence is an essential transitional stage, so dating violence puts development at risk. In Chile, studies on adolescent dating violence are just emerging and still show a gap. AIM: To examine the relationship between abuse during childhood with victimization and perpetration experiences for adolescent dating violence. MATERIAL AND METHODS: The sample consisted of 242 adolescents between 14 and 19 years of age (59% females) who completed the Conflict in Adolescent Dating Relationship Inventory (CADRI) and the Childhood Trauma Questionnaire-Short Form (CQT-SF), both in their Spanish version. Multiple regression analysis was used to evaluate the degree of association between sexual, emotional, and physical abuse during childhood with adolescent dating violence. RESULTS: Sexual and emotional abuse were predictors of dating victimization. In addition, sexual and physical abuse were found to be predictors of perpetration. CONCLUSIONS: Our study supports the evidence on differentiated outcomes between adolescent dating victimization and perpetration. Moreover, it highlights the role of childhood sexual abuse as a predictor of both.

LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes.

The lactate dehydrogenase isoform A (LDHA) is a key metabolic enzyme that preferentially catalyzes the conversion of pyruvate to lactate. Whereas LDHA is highly expressed in many tissues, its expression is turned off in the differentiated adult ß-cell within the pancreatic islets. The repression of LDHA under normal physiological condition and its inappropriate upregulation under a diabetogenic environment is well-documented in rodent islets/ß-cells but little is known about LDHA expression in human islet cells and whether its abundance is altered under diabetic conditions. Analysis of public single-cell RNA-seq (sc-RNA seq) data as well as cell type-specific immunolabeling of human pancreatic islets showed that LDHA was mainly localized in human α-cells while it is expressed at a very low level in ß-cells. Furthermore, LDHA, both at mRNA and protein, as well as lactate production is upregulated in human pancreatic islets exposed to chronic high glucose treatment. Microscopic analysis of stressed human islets and autopsy pancreases from individuals with type 2 diabetes (T2D) showed LDHA upregulation mainly in human α-cells. Pharmacological inhibition of LDHA in isolated human islets enhanced insulin secretion under physiological conditions but did not significantly correct the deregulated secretion of insulin or glucagon under diabetic conditions.

Effectiveness of Telerehabilitation in Physical Therapy: A Rapid Overview.

OBJECTIVE: The purpose of this article was to summarize the available evidence from systematic reviews on telerehabilitation in physical therapy. METHODS: We searched Medline/PubMed, EMBASE, and Cochrane Library databases. In addition, the records in PROSPERO and Epistemonikos and PEDro were consulted. Systematic reviews of different conditions, populations, and contexts-where the intervention to be evaluated is telerehabilitation by physical therapy-were included. The outcomes were clinical effectiveness depending on specific condition, functionality, quality of life, satisfaction, adherence, and safety. Data extraction and risk of bias assessment were carried out by a reviewer with non-independent verification by a second reviewer. The findings are reported qualitatively in the tables and figures. RESULTS: Fifty-three systematic reviews were included, of which 17 were assessed as having low risk of bias. Fifteen reviews were on cardiorespiratory rehabilitation, 14 on musculoskeletal conditions, and 13 on neurorehabilitation. The other 11 reviews addressed other types of conditions and rehabilitation. Thirteen reviews evaluated with low risk of bias showed results in favor of telerehabilitation versus in-person rehabilitation or no rehabilitation, while 17 reported no differences between the groups. Thirty-five reviews with unclear or high risk of bias showed mixed results. CONCLUSIONS: Despite the contradictory results, telerehabilitation in physical therapy could be comparable with in-person rehabilitation or better than no rehabilitation for conditions such as osteoarthritis, low-back pain, hip and knee replacement, and multiple sclerosis and also in the context of cardiac and pulmonary rehabilitation. It is imperative to conduct better quality clinical trials and systematic reviews. IMPACT: Providing the best available evidence on the effectiveness of telerehabilitation to professionals, mainly physical therapists, will impact the decision-making process and therefore yield better clinical outcomes for patients, both in these times of the COVID-19 pandemic and in the future. The identification of research gaps will also contribute to the generation of relevant and novel research questions.

Pancreatic ductal adenocarcinomas from Mexican patients present a distinct genomic mutational pattern.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in humans, with less than 5% 5-year survival rate. PDAC is characterized by a small number of recurrent mutations, including KRAS, CDKN2A, TP53, and SMAD4 and a long "tail" of infrequent mutated genes. Most of the studies have been performed in US and European populations, so new studies are needed to describe the mutational landscape of these tumors in other cohorts. The present study analyzed the exome and transcriptome of four PDAC tumors from Mexican patients. We found a paucity of the previously described recurrent mutations, with mutations in only three genes (HERC2, CNTNAP2 and HMCN1) previously reported in PDAC with a frequency > 1%. In addition, we discovered several recurrent putative copy number aberrations in SKP2, BRAF, CSSF1R, FOXE1, JAK2 and MET genes and in genes previously reported as putative drivers in PDAC, including KRAS, SF3B1, BRAF, MYC and MET. Although a larger cohort is needed to validate these findings, our results could be pointing toward potential differences in contributing factors for PDAC in Latin-American populations.

[Prevalence of domestic violence in pregnant women from 20 to 35 years in a family medicine unit]. / Prevalencia de violencia intrafamiliar en embarazadas de 20 a 35 años de una unidad de medicina familiar.

BACKGROUND: Violence against women is one of the most important health problems in recent times. In Mexico, it is reported a prevalence of 21.5% during pregnancy; however, it seems to be underdiagnosed. The objective is to determine the prevalence of domestic violence in pregnant women from 20 to 35 years at the Unidad de Medicina Familiar (UMF) 171 of the Instituto Mexicano del Seguro Social (IMSS). METHODS: It was performed a cross-sectional descriptive study with a sample of 102 pregnant women to which we applied a sociodemographic questionnaire and the Severity of Violence Against Women Scale (ISVP). RESULTS: 19 women (18.6%) suffered violence; of these, 10.8% (n=11) experienced physical violence, 5.9% (n=6) psychological violence, and 4% (n=4) sexual violence. We used chi squared between the variable violence and each of the sociodemographic factors: 52.6% women (n=10) were married (p=0.005), 26.3% (n=5) had a bachelor's degree (p=0.074), 57.8% (n=11) had planned their pregnancy, 47.3% (n=9) were in the third trimester of pregnancy, and 78.95% (n=15) worked as laborers, shop-keepers or professionals (p=0.016). CONCLUSIONS: Among pregnant women belonging in UMF 171 of IMSS, domestic violence is a problem with a prevalence of 18.6%.

Introducción: la violencia contra la mujer es uno de los problemas sanitarios de mayor relevancia en los últimos tiempos. Durante el embarazo se reporta un 21.5 % de prevalencia en nuestro país y se cree que esta está subdiagnosticada. El objetivo fue conocer la prevalencia de violencia intrafamiliar en embarazadas de 20 a 35 años de la Unidad de Medicina Familiar 171 (UMF 171) del Instituto Mexicano del Seguro Social. Métodos: estudio transversal-descriptivo con pacientes embarazadas de 20 a 35 años con una muestra de 102 embarazadas a las cuales se les aplicó un cuestionario sociodemográfico y el instrumento índice de severidad de violencia de pareja (ISVP). Se utilizó media, porcentajes y chi cuadrada para los resultados. Resultados: el 18.6 % de las participantes (n = 19) padeció violencia. De estas la violencia física se presentó en el 10.8 % (n = 11), seguida de la violencia psicológica en un 5.9 % (n = 6) y la violencia sexual en 4 % (n = 4). Se empleó chi cuadrada entre la variable violencia y cada uno de los factores sociodemográficos: 52.6 % (n = 10) eran casadas (p 0.005), 26.3 % (n = 5) tenían licenciatura (p 0.074), 57.8 % (n = 11) habían planeado su embarazo, 47.3 % (n = 9) cursaban el tercer trimestre de embarazo y 78.95 % (n = 15) tenían un trabajo entre obreras, comerciantes o profesionistas (p 0.016). Conclusiones: la violencia intrafamiliar es un problema presente en las embarazadas de la UMF 171, con una prevalencia de 18.6 %.

Creencias de los escolares de educación primaria sobre los efectos del consumo de tabaco / Beliefs of primary school children about the effects of tobacco consumption

Resumen:

Introducción: el consumo de tabaco es considerado como un problema de salud pública, representa la segunda causa principal de muerte a nivel mundial. Se advierte una creciente tendencia en el inicio de consumo de tabaco a una edad cada vez más temprana.

Objetivo: describir las creencias de los escolares de sexto grado de educación primaria sobre los efectos del tabaco.

Metodología: estudio descriptivo en una muestra aleatoria de 155 estudiantes de sexto grado del total de escuelas primarias del municipio de San José de Gracia, Aguascalientes. Los datos se recabaron mediante un cuestionario autoadministrado para explorar las Creencias sobre los efectos del tabaco. Resultados: del total de estudiantes el 40 % refiere convivir en su hogar con fumadores, más de la mitad de los estudiantes (60.6 %) expresaron aspectos positivos respecto al tabaco, como que "fumar no quita el sueño". El 36.1 % y 31 % respectivamente, creen que "ayuda a las personas a distraerse de los problemas", y que "hace sentir bien a las personas". Es relevante que el 12.9 % de los estudiantes exprese que el consumo de tabaco no produce adicción y el 9 % crea que no es causa de cáncer. Conclusiones: los escolares comparten características personales, familiares, económicas, sociales y laborales, como la convivencia con fumadores activos en el hogar y en el trabajo, y tienen la creencia que el consumo del tabaco ayuda a las personas a distraerse de los problemas y que los hace sentir bien.

Abstract:

Introduction: Tobacco consumption is considered as a public health problem, is the second leading cause of death worldwide. A growing trend is seen in the first use of tobacco at an increasingly consumption at earlier ages.

Objective: To describe the beliefs of students of sixth grade of primary education on the effects of tobacco.

Methodology: Descriptive study in a random sample of 155 sixth grade students of all elementary schools in the municipality of San Jose de Gracia, Aguascalientes. Data were collected through a self-administered questionnaire to explore the "Beliefs about the effects of snuff." Results: The total number of students 40 % reported living at home with smokers, more than half of the students in 60.6 % expressed positive aspects about that "smoking is not related with losing sleep". In 36.1 % and 31 % respectively believe that "if it helps people to be distracted from the problems"; and "it makes people feel good." It is significant that 12.9 % of students expressed that consumption of snuff is not addictive and 9 % believe that it does not cause cancer. Conclusions: Students share personal characteristics, family, economic, social and labor, such as coexistence with active smokers at home and at work and have the belief that the consumption of tobacco helps people to get distracted from the problems and that it feels good.

Complexation of morin with three kinds of cyclodextrin. A thermodynamic and reactivity study.

Properties of inclusion complexes between morin (M) and beta-cyclodextrin (betaCD), 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and Heptakis (2,6-O-di methyl) beta-cyclodextrin (DMbetaCD) such as aqueous solubility and the association constants of this complex have been determined. The water solubility of morin was increased by inclusion with cyclodextrins. The phase-solubility diagrams drawn from UV spectral measurements are of the A(L)-type. Also ORAC(FL) studies were done. An increase in the antioxidant reactivity is observed when morin form inclusion complex with the three cyclodextrin studied. Finally, thermodynamics studies of cyclodextrin complexes indicated that for DMbetaCD the inclusion is primarily enthalpy-driven process meanwhile betaCD and HPbetaCD are entropy-driven processes. This is corroborated by the different inclusion geometries obtained by 2D-NMR.