Accurate energies of hydrogen bonded nucleic acid base pairs and triplets in tRNA tertiary interactions

Tertiary interactions are crucial in maintaining the tRNA structure and functionality. We used a combined sequence analysis and quantum mechanics approach to calculate accurate energies of the most frequent tRNA tertiary base pairing interactions. Our analysis indicates that six out of the nine classical tertiary interactions are held in place mainly by H-bonds between the bases. In the remaining three cases other effects have to be considered. Tertiary base pairing interaction energies range from −8 to −38 kcal/mol in yeast tRNA(Phe) and are estimated to contribute roughly 25% of the overall tRNA base pairing interaction energy. Six analyzed posttranslational chemical modifications were shown to have minor effect on the geometry of the tertiary interactions. Modifications that introduce a positive charge strongly stabilize the corresponding tertiary interactions. Non-additive effects contribute to the stability of base triplets

Haitianas migradas desafiando contextos de alienación ocupacional: prácticas cotidianas de resistencia de mujeres haitianas en Santiago de Chile

Tesis (Terapeuta Ocupacional)En los últimos años, Chile ha sido un lugar predilecto para migrar, aumentando día a día el número de población migrante. Actualmente, la comunidad haitiana ha dado cuenta de la diversidad de naciones que han arribado al país, llamando particularmente la atención el incremento de la población femenina haitiana en las calles de Santiago, permitiéndonos identificar que existe escasa información proporcionada por fuentes oficiales respecto de la población actual que habita el país, desconociendo además los motivos por los que migran desde Centroamérica. La Ley de migración que rige actualmente en nuestro país, data del año 1975 bajo periodo de dictadura militar, por lo cual nos surgen diversas interrogantes respecto de qué tan preparado está Chile para recibir e integrar a nuevas poblaciones migrantes, quienes traen consigo riquezas culturales y ocupacionales, las cuales, a primera impresión, no han sido valoradas ni respetadas en su totalidad, debiendo limitarse a la aceptación de la sociedad chilena a través del aporte laboral, situación por la que nos interesa conocer y analizar las diversas dificultades que enfrentan diariamente las mujeres, desde que migran de su país de origen, hasta su llegada al país de destino, poniendo énfasis en todos aquellos cambios ocupacionales subyacentes al fenómeno de la migración que además están sujetos a condiciones por el sólo hecho de ser mujeres, teniendo por objetivo analizar su noción de ocupación y las prácticas cotidianas de resistencia que ejercen frente a contextos de alienación ocupacional vivenciados durante el proceso de migración, otorgando relevancia social dado que permite cuestionar lo que significa para Chile que se implementen nuevas políticas, capaces de explicitar las necesidades que las mujeres refirieron durante la misma; además, se espera que la información recopilada a continuación, se transforme en un aporte teórico relevante para posibilitar nuevas orientaciones desde el quehacer de Terapia Ocupacional respecto de las implicancias de este fenómeno social llamado migración. Cabe mencionar, que la metodología cualitativa nos permitió experimentar diferentes dimensiones de la sensibilidad investigadora expuestas por Íñiguez (histórica, cultural, política y contextual), utilizando como técnicas de producción de información la entrevista semiestructurada y el grupo de discusión, mientras que la técnica y procedimientos de análisis de información fue el análisis de contenido a través de la operacionalización de información a través de ejes temáticos y conceptos claves. A través de la presente investigación, fue posible indagar en las prácticas que emergen a partir del proceso de migración de cada mujer entrevistada y cómo estas prácticas, a pesar de que se ejecutan de manera individual, se configuran, construyen y significan en la comunidad haitiana migrante. La finalidad, por tanto, fue construir y develar cuáles son las concepciones que nacen en esta comunidad de manera que esta fue, dentro de lo posible, una aproximación a las percepciones de conceptos tales como ocupación, prácticas de resistencia y motivaciones para buscar más oportunidades de surgimiento

Structural Basis for the Recognition in an Idiotype-Anti-Idiotype Antibody Complex Related to Celiac Disease

Anti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interaction between the two antibodies, a 3D model of the MB2.8-AIM2 complex has been obtained by molecular docking. Analysis and selection of the different obtained docking solutions was based on the conservation within them of the inter-residue contacts. The selected model is very well representative of the different solutions found and its stability is confirmed by molecular dynamics simulations. Furthermore, the binding mode it adopts is very similar to that observed in most of the experimental structures available for idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is directed against the MB2.8 CDR region, especially on its variable light chain. This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8-TG2 complex incompatible, thus explaining the experimentally observed inhibitory effect on the MB2.8 binding to TG2

Wearable Health Technology for Preoperative Risk Assessment in Elderly Patients: The WELCOME Study

Preoperative identification of high-risk groups has been extensively studied to improve patients’ outcomes. Wearable devices, which can track heart rate and physical activity data, are starting to be evaluated for patients’ management. We hypothesized that commercial wearable devices (WD) may provide data associated with preoperative evaluation scales and tests, to identify patients with poor functional capacity at increased risk for complications. We conducted a prospective observational study including seventy-year-old patients undergoing two-hour surgeries under general anesthesia. Patients were asked to wear a WD for 7 days before surgery. WD data were compared to preoperatory clinical evaluation scales and with a 6-min walking test (6MWT). We enrolled 31 patients, with a mean age of 76.1 (SD ± 4.9) years. There were 11 (35%) ASA 3–4 patients. 6MWT results averaged 328.9 (SD ± 99.5) m. Daily steps and 2 as recorded using WD and were associated with 6MWT performance (R = 0.56, p = 0.001 and r = 0.58, p = 0.006, respectively) and clinical evaluation scales. This is the first study to evaluate WD as preoperative evaluation tools; we found a strong association between 6MWT, preoperative scales, and WD data. Low-cost wearable devices are a promising tool for the evaluation of cardiopulmonary fitness. Further research is needed to validate WD in this setting

Estudio comparativo del tiempo de tránsito intestinal con marcadores radiopacos en pacientes seropositivos y seronegativos para la enfermedad de Chagas

La enfermedad de Chagas afecta el sistema digestivo en un 10 a 15% de los casos. En el período crónico, dentro de los megasíndromes digestivos, el megacolon es más frecuente en Argentina. Este estudio intentó determinar el tiempo de tránsito colorrectal en pacientes seropositivos y seronegativos para la enfermedad de Chagas y así efectuar una comparación entre los mismos y evaluar si existen diferencias significativas. Fueron incluidos pacientes seropositivos y seronegativos para la Enfermedad de Chagas, a los cuales se les realizó examen físico, electrocardiograma, ecocardiograma, RX de tórax y extracción de sangre para realizar diagnóstico serológico actual con Hemaglutinación indirecta, ELISA e Inmunofluorescencia. Para la determinación del tiempo de tránsito colónico se emplearon 24 marcadores radiopacos Sitzmarks administrados y al 5to. día se realizó RX simple de abdomen de pié. Se consideró anormal al encontrarse 5 o más radiomarcadores en la RX

Targeting CD34(+) cells of the inflamed synovial endothelium by guided nanoparticles for the treatment of rheumatoid arthritis

Despite the advances in the treatment of rheumatoid arthritis (RA) achieved in the last few years, several patients are diagnosed late, do not respond to or have to stop therapy because of inefficacy and/or toxicity, leaving still a huge unmet need. Tissue-specific strategies have the potential to address some of these issues. The aim of the study is the development of a safe nanotechnology approach for tissue-specific delivery of drugs and diagnostic probes. CD34 + endothelial precursors were addressed in inflamed synovium using targeted biodegradable nanoparticles (tBNPs). These nanostructures were made of poly-lactic acid, poly-caprolactone, and PEG and then coated with a synovial homing peptide. Immunofluorescence analysis clearly demonstrated their capacity to selectively address CD34 + endothelial cells in synovial tissue obtained from human, mouse, and rat. Biodistribution studies in two different animal models of rheumatoid arthritis (antigen-induced arthritis/AIA and collagen-induced arthritis/CIA) confirmed the selective accumulation in inflamed joints but also evidenced the capacity of tBNP to detect early phases of the disease and the preferential liver elimination. The therapeutic effect of methotrexate (MTX)-loaded tBNPs were studied in comparison with conventional MTX doses. MTX-loaded tBNPs prevented and treated CIA and AIA at a lower dose and reduced administration frequency than MTX. Moreover, MTX-loaded tBNP showed a novel mechanism of action, in which the particles target and kill CD34 + endothelial progenitors, preventing neo-angiogenesis and, consequently, synovial inflammation. tBNPs represent a stable and safe platform to develop highly-sensitive imaging and therapeutic approaches in RA targeting specifically synovial neo-angiogenesis to reduce local inflammation

Inflammatory bowel disease nurse specialists for patients on biological therapies: a nationwide Italian survey

Background Management of inflammatory bowel disease (IBD) patients requires a multidisciplinary approach. Among the working team, the role of IBD nurse is expected to be particularly relevant when managing patients receiving biological therapies. We performed a survey to assess the presence of IBD nurse in centers where patients were receiving biologics. Methods For this Italian nationwide survey a specific questionnaire was prepared. IBD nurse was defined as a nurse directly involved in all phases of biological therapy, from pre-therapy screening, administration and monitoring during therapy, to follow up performed by a dedicated helpline, completed a specific training on biological therapy therapy, and observed international guidelines. Results A total of 53 Italian IBD centers participated in the survey, and 91 valid questionnaires were collected. Overall, 34 (37.4%) nurses could be classified as IBD specialists. IBD nurses had a significantly higher educational level than other nurses, they were more frequently operating in Central or Southern than in Northern Italy, they were working in an Academic center rather than in a General hospital, and in IBD centers with >25 patients on biological therapy. On the contrary, mean age, gender distribution, years of nursing, and years working in the IBD unit did not significantly differ between IBD and other nurses. Conclusions Our nationwide survey showed that the presence of an IBD nurse is still lacking in the majority of Italian IBD centers where patients receive biological therapies, suggesting a prompt implementation

La cátedra Diseño Industrial 2 B trabajó sobre dispositivos domésticos para desinfección en contexto de la pandemia del COVID-19

TRABAJOS: PROYECTO: Pul.sa / AUTORES: Pilar Peralta y Bautista Mugnaini PROYECTO: Numo / AUTORES: Tamara Toledo y Ramiro Ríos PROYECTO: Zenely / AUTORES: Sergio Olmedo y Manuel Reartes PROYECTO: Torretas de Ozono / AUTORES: Pedro Juan Delgado Bratti y Daniel Shen PROYECTO: ANCO / AUTORES: Belén Sol Quinteros y Bruno Mediavilla PROYECTO: Fructífero / AUTORES: Romina Escudero y Santiago Bognano PROYECTO: Acom / AUTORES: Ariadna Cevasco y M. Laura Gonzalez PROYECTO: NOZ / AUTORES: Camila Rapaline & Tomás Rodriguez BravoLa cátedra Diseño Industrial 2 B trabajó sobre dispositivos domésticos para desinfección en contexto de la pandemia del COVID-19 Compartimos los proyectos realizados por estudiantes de la cátedra Diseño Industrial 2B, que durante la primera parte del año, trabajaron sobre dispositivos domésticos para desinfección en contexto de la pandemia del COVID-19. Desde la Facultad de Arquitectura, Urbanismo y Diseño (Universidad Nacional de Córdoba) se iniciaron diferentes acciones para adaptar los contenidos de las carreras y atender a las diferentes necesidades sociales en el contexto de emergencia sanitaria. En ese sentido, la cátedra Diseño Industrial 2B se propuso situar la problemática de trabajo en las condiciones generadas por la pandemia del COVID-19, a partir de las cuales se generan cambios en la vida cotidiana, que afectan las actividades y llevan a incorporar nuevos hábitos y formas de relacionarse. La cátedra propuso a sus estudiantes pensar sistemas portátiles para el ámbito doméstico que permitieran la desinfección de elementos y pertenencias en el ingreso al domicilio. El trabajo práctico propuesto, abordó la complejidad de un producto-máquina desde su comprensión como sistema, con piezas intercambiables y/o combinables que posibilitan diferentes instancias de funcionamiento, abarcando la variablidad de escalas, tanto de relación manual como corporal, en cuanto a la observación de actividades, posturas y situaciones de uso.Fil: Oliva, Silvia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño. Cátedra Diseño Industrial; Argentina.Fil: de la Fuente, Federico. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño. Cátedra Diseño Industrial; Argentina.Fil: Speroni, Diego. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño. Cátedra Diseño Industrial; Argentina.Fil: Franco, Belén. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño. Cátedra Diseño Industrial; Argentina.Fil: Cagliero, Leonardo. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño. Cátedra Diseño Industrial; Argentina.Fil: Parra, Javier. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño. Cátedra Diseño Industrial; Argentina.Fil: Talmon, Gaspar. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño. Cátedra Diseño Industrial; Argentina.Fil: Gili, Agustina. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño. Cátedra Diseño Industrial; Argentina.Fil: Costamagna, Camila. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño. Cátedra Diseño Industrial; Argentina.Fil: Vélez, Simón. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño. Cátedra Diseño Industrial; Argentina.Fil: Giménez, Lucas. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño. Cátedra Diseño Industrial; Argentina

Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70–75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70–80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands.Cancer Research UK, Grant/Award Number: FC001003; Changzhou Science and Technology Bureau, Grant/Award Number: CE20200503; Department of Energy and Climate Change, Grant/Award Numbers: DE-AR001213, DE-SC0020400, DE-SC0021303; H2020 European Institute of Innovation and Technology, Grant/Award Numbers: 675728, 777536, 823830; Institut national de recherche en informatique et en automatique (INRIA), Grant/Award Number: Cordi-S; Lietuvos Mokslo Taryba, Grant/Award Numbers: S-MIP-17-60, S-MIP-21-35; Medical Research Council, Grant/Award Number: FC001003; Japan Society for the Promotion of Science KAKENHI, Grant/Award Number: JP19J00950; Ministerio de Ciencia e Innovación, Grant/Award Number: PID2019-110167RB-I00; Narodowe Centrum Nauki, Grant/Award Numbers: UMO-2017/25/B/ST4/01026, UMO-2017/26/M/ST4/00044, UMO-2017/27/B/ST4/00926; National Institute of General Medical Sciences, Grant/Award Numbers: R21GM127952, R35GM118078, RM1135136, T32GM132024; National Institutes of Health, Grant/Award Numbers: R01GM074255, R01GM078221, R01GM093123, R01GM109980, R01GM133840, R01GN123055, R01HL142301, R35GM124952, R35GM136409; National Natural Science Foundation of China, Grant/Award Number: 81603152; National Science Foundation, Grant/Award Numbers: AF1645512, CCF1943008, CMMI1825941, DBI1759277, DBI1759934, DBI1917263, DBI20036350, IIS1763246, MCB1925643; NWO, Grant/Award Number: TOP-PUNT 718.015.001; Wellcome Trust, Grant/Award Number: FC00100

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support