Repression of glucocorticoid-stimulated angiopoietin-like 4 gene transcription by insulin.

Angiopoietin-like 4 (Angptl4) is a glucocorticoid receptor (GR) primary target gene in hepatocytes and adipocytes. It encodes a secreted protein that inhibits extracellular LPL and promotes adipocyte lipolysis. In Angptl4 null mice, glucocorticoid-induced adipocyte lipolysis and hepatic steatosis are compromised. Markedly, insulin suppressed glucocorticoid-induced Angptl4 transcription. To unravel the mechanism, we utilized small molecules to inhibit insulin signaling components and found that phosphatidylinositol 3-kinase and Akt were vital for the suppression in H4IIE cells. A forkhead box transcription factor response element (FRE) was found near the 15 bp Angptl4 glucocorticoid response element (GRE). Mutating the Angptl4 FRE significantly reduced glucocorticoid-induced reporter gene expression in cells. Moreover, chromatin immunoprecipitation revealed that GR and FoxO1 were recruited to Angptl4 GRE and FRE in a glucocorticoid-dependent manner, and cotreatment with insulin abolished both recruitments. Furthermore, in 24 h fasted mice, significant occupancy of GR and FoxO1 at the Angptl4 GRE and FRE was found in the liver. In contrast, both occupancies were diminished after 24 h refeeding. Finally, overexpression of dominant negative FoxO1 mutant abolished glucocorticoid-induced Angptl4 expression, mimicking the insulin suppression. Overall, we demonstrate that both GR and FoxO1 are required for Angptl4 transcription activation, and that FoxO1 negatively mediates the suppressive effect of insulin

An empirical study of the impact of internet financial reporting on stock prices

This study examines the economic consequences of internet financial reporting (IFR) in Taiwan. The results show that the stock prices of IFR firms change more quickly than those of the non-FR firms using Akaike’s (1969) Final Prediction Error (FPE) methodology. Second, the results from the event study methodology show that the cumulative abnormal returns of the firms with IFR are significantly higher than those of the firms without IFR. Lastly, the results indicate that firms with a higher degree of information transparency yield a higher abnormal return on theirstock prices

Trabajo post experiencia laboral realizado en base a la práctica clínica en el tratamiento de los disturbios en la comunicación durante los años 2006 al 2009 en tres instituciones privadas de Lima Metropolitana

This article summarizes the descriptive memory of work experience carried out through three years of work in the treatment of communication disorder in children, adolescents, and adults.Este artículo sintetiza la memoria descriptiva de la experiencia laboral realizada a lo largo de tres años en el tratamiento de los disturbios en la comunicación en niños, adolescentes yadultos

Advance Care Planning in China

Objectives • Describe the interprofessional components of this project. • Describe the attitude of advance care planning among Chinese healthcare professionals

Casa Ecológica, una opción de viviendas adecuadas sostenibles y de bajo costo

Las cuarentenas impuestas como parte de las medidas sanitarias ante la pandemia del SARS-COV-2 (Covid 19) han expuesto la relevancia de contar con una vivienda adecuada, esto es, que tenga los estándares mínimos necesarios para el desarrollo de los integrantes de la familia. Sin embargo, en el Perú, existe un déficit de viviendas que afecta sobre todo a las familias de los sectores socioeconómicos más desfavorecidos. En este sentido, el problema está enmarcado en la falta de alternativas de vivienda social para los sectores socioeconómicos D y E. Como solución, se ha propuesto la implementación de un sistema de viviendas sociales con un método constructivo innovador a base de ladrillo fabricados 100% con plástico reciclado (Ladrillo PET). Así, el modelo de negocio incluye la comercialización de casas en el marco del programa Techo Propio modalidad Construcción en Sitio Propio administrado por el Fondo MiVivienda, así como la venta directa de Ladrillos PET a través de canales de venta directa e indirecta. De esta manera, con una inversión de S/ 804,372.00, este modelo de negocio generará un VAN de S/ 4’117,936.67 a un horizonte de cinco años. Mientras que, por el lado social, se impactará positivamente en la vida de más de 4 000 mil familias y se promoverá la concientización sobre la necesidad de reciclaje y la aplicación de la economía circula. Así, este modelo de negocio en cinco años generará un VANS de S/ 9’844,645.98, teniendo un índice de relevancia en los ODS 11 y 12.The quarantines imposed as part of the sanitary measures in response to the SARS-COV-2 pandemic (Covid 19) have exposed the importance of having adequate housing, that has the minimum standards necessary for the development of the members of the family. However, in Peru, there is a housing deficit that mainly affects families from the most disadvantaged socio-economic sectors. In this sense, the problem is related to the lack of social housing alternatives for the D and E socio-economic sectors. As a solution, it has been proposed the implementation of social housing. system with an innovative construction method based on bricks made of 100% recycled plastic (PET Brick). Thus, the business model includes the commercialization of houses within the framework of the Techo Propio program, which is administered by the Fondo MiVivienda, as well as the direct sale of PET Bricks through direct and indirect sales channels. Thus, with an investment of S/ 804,372.00, this business model will generate an NPV of S/ 4'117,936.67 over a five-year horizon. Meanwhile, on the social side, it will have a positive impact on the lives of more than 4,000,000 families and will promote awareness of the need for recycling and the application of the circular economy. Accordingly, this business model in five years will generate a Social NPV of S/ 9’844,645.98, having a relevance index in SDGs 11 and 12

Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation

10.1371/journal.ppat.1004649PLoS Pathogens11

Polymer membrane-based ion-, gas- and bio-selective potentiometric sensors

Recent progress in the design of new polymer membrane-based potentiometric ion-, gas- and bio-selective electrodes in chemistry laboratories at the University of Michigan (Ann Arbor) is reviewed. Emphasis is placed on describing the performance of devices for measuring anions (e.g., salicylate, thiocyanate, chloride and heparin) and gases (e.g., ammonia, carbon dioxide and oxygen) in biological samples, both in vitro and in vivo. Beyond direct measurement of key ions and gases in complex matrices, some of the new membrane electrode systems reported can serve as base transducers for the development of biosensors containing integrated biological reagents, including enzymes and antibodies. New approaches for mass fabricating solid-state ion and biosensor devices as well as future directions for research in the entire field of polymer membrane sensors are also described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31010/1/0000685.pd

The homozygous K280N troponin T mutation alters cross-bridge kinetics and energetics in human HCM

Hypertrophic cardiomyopathy (HCM) is a genetic form of left ventricular hypertrophy, primarily caused by mutations in sarcomere proteins. The cardiac remodeling that occurs as the disease develops can mask the pathogenic impact of the mutation. Here, to discriminate between mutation-induced and disease-related changes in myofilament function, we investigate the pathogenic mechanisms underlying HCM in a patient carrying a homozygous mutation (K280N) in the cardiac troponin T gene (TNNT2), which results in 100% mutant cardiac troponin T. We examine sarcomere mechanics and energetics in K280N-isolated myofibrils and demembranated muscle strips, before and after replacement of the endogenous troponin. We also compare these data to those of control preparations from donor hearts, aortic stenosis patients (LVHao), and HCM patients negative for sarcomeric protein mutations (HCMsmn). The rate constant of tension generation following maximal Ca2+ activation (k ACT) and the rate constant of isometric relaxation (slow k REL) are markedly faster in K280N myofibrils than in all control groups. Simultaneous measurements of maximal isometric ATPase activity and Ca2+-activated tension in demembranated muscle strips also demonstrate that the energy cost of tension generation is higher in the K280N than in all controls. Replacement of mutant protein by exchange with wild-type troponin in the K280N preparations reduces k ACT, slow k REL, and tension cost close to control values. In donor myofibrils and HCMsmn demembranated strips, replacement of endogenous troponin with troponin containing the K280N mutant increases k ACT, slow k REL, and tension cost. The K280N TNNT2 mutation directly alters the apparent cross-bridge kinetics and impairs sarcomere energetics. This result supports the hypothesis that inefficient ATP utilization by myofilaments plays a central role in the pathogenesis of the disease

Elevated circulating monocytes and monocyte activation in COVID-19 convalescent individuals

BackgroundMonocytes and macrophages play a pivotal role in inflammation during acute SARS-CoV-2 infection. However, their contribution to the development of post-acute sequelae of SARS-CoV-2 infection (PASC) are not fully elucidated.MethodsA cross-sectional study was conducted comparing plasma cytokine and monocyte levels among three groups: participants with pulmonary PASC (PPASC) with a reduced predicted diffusing capacity for carbon monoxide [DLCOc, <80%; (PG)]; fully recovered from SARS-CoV-2 with no residual symptoms (recovered group, RG); and negative for SARS-CoV-2 (negative group, NG). The expressions of cytokines were measured in plasma of study cohort by Luminex assay. The percentages and numbers of monocyte subsets (classical, intermediate, and non-classical monocytes) and monocyte activation (defined by CD169 expression) were analyzed using flow cytometry analysis of peripheral blood mononuclear cells.ResultsPlasma IL-1Ra levels were elevated but FGF levels were reduced in PG compared to NG. Circulating monocytes and three subsets were significantly higher in PG and RG compared to NG. PG and RG exhibited higher levels of CD169+ monocyte counts and higher CD169 expression was detected in intermediate and non-classical monocytes from RG and PG than that found in NG. Further correlation analysis with CD169+ monocyte subsets revealed that CD169+ intermediate monocytes negatively correlated with DLCOc%, and CD169+ non-classical monocytes positively correlated with IL-1α, IL-1β, MIP-1α, Eotaxin, and IFN-γ.ConclusionThis study present evidence that COVID convalescents exhibit monocyte alteration beyond the acute COVID-19 infection period even in convalescents with no residual symptoms. Further, the results suggest that monocyte alteration and increased activated monocyte subsets may impact pulmonary function in COVID-19 convalescents. This observation will aid in understanding the immunopathologic feature of pulmonary PASC development, resolution, and subsequent therapeutic interventions