Involvement of φ29 DNA polymerase thumb subdomain in the proper coordination of synthesis and degradation during DNA replication

φ29 DNA polymerase achieves a functional coupling between its 3′–5′ exonuclease and polymerization activities by means of important contacts with the DNA at both active sites. The placement and orientation of residues Lys538, Lys555, Lys557, Gln560, Thr571, Thr573 and Lys575 in a modelled φ29 DNA polymerase–DNA complex suggest a DNA-binding role. In addition, crystal structure of φ29 DNA polymerase–oligo (dT)(5) complex showed Leu567, placed at the tip of the thumb subdomain, lying between the two 3′-terminal bases at the exonuclease site. Single replacement of these φ29 DNA polymerase residues by alanine was made, and mutant derivatives were overproduced and purified to homogeneity. The results obtained in the assay of their synthetic and degradative activities, as well as their coordination, allow us to propose: (1) a primer-terminus stabilization role at the polymerase active site for residues Lys538, Thr573 and Lys575, (2) a primer-terminus stabilization role at the exonuclease active site for residues Leu567 and Lys555 and (3) a primer-terminus binding role in both editing and polymerization modes for residue Gln560. The results presented here lead us to propose φ29 DNA polymerase thumb as the main subdomain responsible for the coordination of polymerization and exonuclease activities

Role of the LEXE motif of protein-primed DNA polymerases in the interaction with the incoming nucleotide

The LEXE motif, conserved in eukaryotic type DNA polymerases, is placed close to the polymerization active site. Previous studies suggested that the second Glu was involved in binding a third noncatalytic ion in bacteriophage RB69 DNA polymerase. In the protein-primed DNA polymerase subgroup, the LEXE motif lacks the first Glu in most cases, but it has a conserved Phe/Trp and a Gly preceding that position. To ascertain the role of those residues, we have analyzed the behavior of mutants at the corresponding φ29 DNA polymerase residues Gly-481, Trp-483, Ala-484, and Glu-486. We show that mutations at Gly-481 and Trp-483 hamper insertion of the incoming dNTP in the presence of Mg2+ ions, a reaction highly improved when Mn2+ was used as metal activator. These results, together with previous crystallographic resolution of φ29 DNA polymerase ternary complex, allow us to infer that Gly-481 and Trp-483 could form a pocket that orients Val-250 to interact with the dNTP. Mutants at Glu-486 are also defective in polymerization and, as mutants at Gly-481 and Trp-483, in the pyrophosphorolytic activity with Mg2+. Recovery of both reactions with Mn2+ supports a role for Glu-486 in the interaction with the pyrophosphate moiety of the dNT

“Acute kidney injury in critically ill patients with COVID–19: The AKICOV multicenter study in Catalonia”

Acute kidney injury; COVID-19; CataloniaLesión renal aguda; COVID-19; CataluñaLesió renal aguda; COVID-19; CatalunyaThis study describes the incidence, evolution and prognosis of acute kidney injury (AKI) in critical COVID-19 during the first pandemic wave. We performed a prospective, observational, multicenter study of confirmed COVID-19 patients admitted to 19 intensive care units (ICUs) in Catalonia (Spain). Data regarding demographics, comorbidities, drug and medical treatment, physiological and laboratory results, AKI development, need for renal replacement therapy (RRT) and clinical outcomes were collected. Descriptive statistics and logistic regression analysis for AKI development and mortality were used. A total of 1,642 patients were enrolled (mean age 63 (15.95) years, 67.5% male). Mechanical ventilation (MV) was required for 80.8% and 64.4% of these patients, who were in prone position, while 67.7% received vasopressors. AKI at ICU admission was 28.4% and increased to 40.1% during ICU stay. A total of 172 (10.9%) patients required RRT, which represents 27.8% of the patients who developed AKI. AKI was more frequent in severe acute respiratory distress syndrome (ARDS) ARDS patients (68% vs 53.6%, p<0.001) and in MV patients (91.9% vs 77.7%, p<0.001), who required the prone position more frequently (74.8 vs 61%, p<0.001) and developed more infections. ICU and hospital mortality were increased in AKI patients (48.2% vs 17.7% and 51.1% vs 19%, p <0.001) respectively). AKI was an independent factor associated with mortality (IC 1.587–3.190). Mortality was higher in AKI patients who required RRT (55.8% vs 48.2%, p <0.04). Conclusions There is a high incidence of AKI in critically ill patients with COVID-19 disease and it is associated with higher mortality, increased organ failure, nosocomial infections and prolonged ICU stay

Acoso escolar y autoconcepto en personas trans

Introduction. Bullying is a phenomenon present in all schools and its consequences on the mental health of victims can be very important. Trans people often live with a social stigma that makes them more prone to discrimination. The objective of this study is to analyze the characteristics of bullying in trans people and its relationship with self-concept, as well as to establish a comparison with a cisgender control group. Method: The sample was made up of 68 participants. The experimental group was made up of 34 trans people. The control group was made up of 34 people with similar sociodemographic characteristics. Results: The prevalence of bullying is 20.1% in trans people. There are no significant differences in bullying compared to the control group. There were also no differences regarding self-concept or other sociodemographic variables. Conclusions: Our results do not support the idea, pointed out by other authors, that trans people experience more bullying or less self-concept. They have been found to receive more object-based assaults and physical abuse than harassed cisgender peopleIntroducción: El acoso escolar es un fenómeno presente en todos los centros escolares y sus consecuencias sobre la salud mental de las víctimas pueden ser muy importantes. Las personas trans viven muchas veces con un estigma social que las hace más proclives a sufrir discriminación. El objetivo de este estudio es analizar las características del acoso escolar en personas trans y su relación con el autoconcepto, así como establecer una comparación con un grupo control cisgénero. Método: La muestra estuvo compuesta por 68 participantes. El grupo experimental estuvo compuesto por 34 personas trans. El grupo control estuvo compuesto por 34 personas de características sociodemográficas similares. Resultados: La prevalencia del acoso escolar es del 20,1% en personas trans. No hay diferencias significativas en acoso escolar respecto al grupo control. Tampoco se encontraron diferencias respecto al autoconcepto ni otras variables sociodemográficas. Conclusiones: Nuestros resultados no apoyan la idea, señalada por otros autores, de que las personas trans experimentan mayor acoso escolar ni un menor autoconcepto. Se ha hallado que reciben más agresiones basadas en objetos y maltrato físico que las personas cisgénero acosadas

Effect of a dietary intervention based on the mediterranean diet on the quality of life of patients recovered from depression: analysis of the PREDIDEP randomized trial

Introduction: There is substantial evidence supporting that improving diet quality leads to improved healthrelated quality of life (HRQoL). Our major aim was to assess the effectiveness of a Mediterranean diet–based nutritional intervention to improve HRQoL in the context of a secondary prevention trial of depression. Secondarily to assess its effectiveness among adults aged 60 or more years. Methods: The PREDIDEP study is a 2-year multicentre, randomized, single-blinded nutritional trial. At baseline and at 1-year and 2-year follow-up, SF-36 health survey questionnaire was collected to evaluate participants' HRQoL (total and specific range for each of the 8 dimensions: 0 to 100 points). Mixed effect linear models were used to assess changes in HRQoL according to adherence to the Mediterranean diet. The trial was registered at ClinicalTrials.gov NCT03081065. Results: After 2 years of intervention, the Mediterranean Diet intervention group compared to control group (without nutritional intervention, only usual clinical care) showed an improvement in some dimensions of HRQoL such as Mental Health (7.22; 95 % CI = 2.22–12.22) (between-group difference: 6.79; 95 % CI − 0.14–13.73, p = 0.055); Vitality (9.51; 95 % CI = 4.00–15.03) (between-group difference: 9.00; 95 % CI 1.75–16.25, p = 0.020); Mental Summary Component (2.83; 95 % CI = 0.55–5.11) (between-group difference: 1.17; 95 % CI = − 1.96–4.30, p = 0.462); and General Health (10.70; 95 % CI = 5.58–15.81) (between-group difference: 6.20; 95 % CI = − 0.89–13.28, p = 0.086). Similar results were observed for participants aged 60 or more years. Conclusion: The intervention based on Mediterranean diet in patients with previous depression seems to be effective in improving HRQoL, especially the mental dimensions. This effect is also observed among participants aged 60 or more years.This study was externally funded by the Spanish Ministry of Science and Innovation (Carlos III National Health Institute-ISCIII), PI16/01274

Blockade of the Interaction of Calcineurin with FOXO in Astrocytes Protects Against Amyloid-beta-Induced Neuronal Death

Astrocytes actively participate in neuro-inflammatory processes associated to Alzheimer's disease (AD), and other brain pathologies. We recently showed that an astrocyte-specific intracellular signaling pathway involving an interaction of the phosphatase calcineurin with the transcription factor FOXO3 is a major driver in AD-associated pathological inflammation, suggesting a potential new druggable target for this devastating disease. We have now developed decoy molecules to interfere with calcineurin/FOXO3 interactions, and tested them in astrocytes and neuronal co-cultures exposed to amyloid-beta (A beta) toxicity. We observed that interference of calcineurin/FOXO3 interactions exerts a protective action against A beta-induced neuronal death and favors the production of a set of growth factors that we hypothesize form part of a cytoprotective pathway to resolve inflammation. Furthermore, interference of the A beta-induced interaction of calcineurin with FOXO3 by decoy compounds significantly decreased amyloid-beta protein precursor (A beta PP) synthesis, reduced the A beta PP amyloidogenic pathway, resulting in lower A beta levels, and blocked the expression of pro-inflammatory cytokines TNF alpha and IL-6 in astrocytes. Collectively, these data indicate that interrupting pro-inflammatory calcineurin/FOXO3 interactions in astrocytes triggered by A beta accumulation in brain may constitute an effective new therapeutic approach in AD. Future studies with intranasal delivery, or brain barrier permeable decoy compounds, are warranted.Peer ReviewedPostprint (author's final draft

State of the production and consumption of pesticides in Mexico

Es un articulo publicado en la revista indexada "Tropical and Subtropical Agroecosystems" cuyo titulo es "Estado de la producción y consumo de plaguicidas en México" donde mediante un análisis profundo se puede identificar al panorama del consumo de plaguicidas en MEXICO

Imagen multimodal en la endocarditis infecciosa: el dilema del huevo o la gallina

In medicine the clinical context is essential to carry out a differential diagnosis, and thus it is important for the interpretation of the findings in the imaging techniques to be aware of the clinical history of the patient we are evaluating. We present a case of a patient derived to our hospital for the suspicious of endocarditis on the native mitral valve. However, in our hospital we found no compatible images with endocarditis, but a dissection in the ascending aorta with no signs of infection. Due to the chronology of the clinical case we concluded that the most likely diagnosis was a pseudoaneurysm secondary of an endocarditis.En medicina el contexto clínico es esencial para llevar a cabo un diagnóstico diferencial, y por este motivo es importante que los hallazgos de las pruebas de imagen vayan acompañados de la historia clínica del paciente para poderse interpretar. A continuación, se presenta el caso de una sospecha de endocarditis sobre válvula mitral que se remitió a nuestro centro; sin embargo, el equipo no encontró signos compatibles con endocarditis, más bien una disección en la aorta ascendente. Debido a la cronología de la historia clínica se concluyó que el diagnóstico más plausible era un pseudoaneurisma secundario a endocarditis

Riesgos psicosociales y la seguridad industrial en las lavanderías textiles del Cantón Pelileo / Psychosocial Risks and Industrial Safety in the Textile Laundries of Pelileo Canton

This piece of research was focused on identifying, evaluating and controlling the psychosocial risks in the Industrial Safety of textile laundries,  the level of impact was identified, which contributed to the physical, psychological and emotional well-being of workers, improving their quality of life, increasing productivity and complying with the organizational goals; the population was made up of men and women amounting to sixty-one workers, the age ranged from fifteen to sixty-five years, from different ethnic groups, the standardized Istas 21 Questionnaire of the Union Institute of Labor, Environment and Health Of Spain was used as a methodology. It consists of six sections related to psychosocial risks, at the research levels the descriptive and explanatory levels stand out, we got levels and reference values that allow us to compare with other studies about psychosocial factors. Later, a Guide to Prevent Psychosocial Factors  to improve Industrial Safety in textile laundries was designed, which served as a tool for the training of workers regarding this area, next, the retest with the Standardized Istas 21 Questionnaire was applied, which gave us   different results from those obtained initially; however, it is possible to identify that the sections with the greatest impact on the staff are insecurity about the future and double presence, which maintain considerable values; on the other hand, the sections that responded best to training were Social support and quality of leadership.La investigación se enfocó en identificar, evaluar y controlar los riesgos psicosociales en la Seguridad Industrial de las lavanderías textiles, evidenciando el nivel de impacto, lo cual sirvió de aporte al bienestar físico, psicológico y emocional de los trabajadores, mejorando su calidad de vida, incrementando la productividad y el cumplimiento de los objetivos organizacionales. La población estuvo conformada por hombres y mujeres correspondientes a sesenta y un trabajadores, con un rango de edad entre quince y sesenta y cinco años, de diferentes etnias y se utilizó como metodología el Cuestionario Estandarizado Istas 21 del Instituto Sindical de Trabajo, Ambiente y Salud de España. Consta de seis apartados relacionados a los riesgos psicosociales. En los niveles investigativos se destaca el descriptivo y el explicativo, obteniendo niveles y valores de referencia que permiten comparar con otros estudios sobre factores psicosociales. Posteriormente, se diseñó una Guía de Prevención de Factores Psicosociales para el mejoramiento de la Seguridad Industrial en las lavanderías textiles la cual sirvió como herramienta para la capacitación de los trabajadores en relación a esta temática, a continuación se realizó el retest con el Cuestionario Estandarizado Istas 21 el cual arrojó resultados diferentes a los obtenidos inicialmente, sin embargo es posible apreciar que los apartados con mayor impacto sobre el personal son inseguridad sobre el futuro y Doble presencia los cuales mantienen valores considerables, por otra parte, el apartado que respondió de mejor manera a la capacitación fue apoyo social y calidad de liderazgo

Producción de pitahaya en Costa Rica

Informe final de proyecto de investigación "Producción de pitahaya en Costa Rica"Universidad de Costa Rica/[736-B7-035]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Estación Experimental Agrícola Fabio Baudrit Moreno (EEAFBM