Influence of 1D and 2D carbon fillers and their functionalisation on crystallisation and thermomechanical properties of injection moulded nylon 6,6 nanocomposites

Carbon nanotubes (CNTs) and graphene were used as reinforcing fillers in nylon 6,6 in order to obtain nanocomposites by using an injection moulding process. The two differently structured nanofillers were used in their pristine or reduced form, after oxidation treatment and after amino functionalisation.Three low nanofiller contents were employed. Crystallisation behaviour and perfection of nylon 6,6 crystals were determined by differential scanning calorimetry and wide angle X-ray diffraction, respectively. Crystallinity was slightly enhanced in most samples as the content of the nanofillers was increased. The dimensionality of the materials was found to provide different interfaces and therefore different features in the nylon 6,6 crystal growth resulting in improved crystal perfection. Dynamical, mechanical analysis showed the maximum increases provided by the two nanostructures correspond to the addition of 0.1 wt.% amino functionalised CNTs, enhancing in 30% the storage modulus and the incorporation of 0.5 wt.% of graphene oxide caused an increase of 44% in this property. The latter also provided better thermal stability when compared to pure nylon 6,6 under inert conditions. The superior properties of graphene nanocomposites were attributed to the larger surface area of the two-dimensional graphene compared to the one-dimensional CNTs

The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis

A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major determinant of virulence. Elimination of SARS-CoV E protein PBM by using reverse genetics caused a reduction in the deleterious exacerbation of the immune response triggered during infection with the parental virus and virus attenuation. Cellular protein syntenin was identified to bind the E protein PBM during SARS-CoV infection by using three complementary strategies, yeast two-hybrid, reciprocal coimmunoprecipitation and confocal microscopy assays. Syntenin redistributed from the nucleus to the cell cytoplasm during infection with viruses containing the E protein PBM, activating p38 MAPK and leading to the overexpression of inflammatory cytokines. Silencing of syntenin using siRNAs led to a decrease in p38 MAPK activation in SARS-CoV infected cells, further reinforcing their functional relationship. Active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM as compared with the parental virus, leading to a decreased expression of inflammatory cytokines and to virus attenuation. Interestingly, administration of a p38 MAPK inhibitor led to an increase in mice survival after infection with SARS-CoV, confirming the relevance of this pathway in SARS-CoV virulence. Therefore, the E protein PBM is a virulence domain that activates immunopathology most likely by using syntenin as a mediator of p38 MAPK induced inflammation

Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis

Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+/K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence

Can reducing the incoming energy flux over the Southern Ocean in a CGCM improve its simulation of tropical climate?

Atmosphere-ocean general circulation models (CGCMs) show important systematic errors. Simulated precipitation in the tropics is generally overestimated over the oceans south of the equator, and stratocumulus (SCu) clouds are underestimated above too warm sea surface temperatures (SSTs). In the extratropics, SSTs are also too warm over the Southern Ocean. We argue that ameliorating these extratropical errors in a CGCM can result in an improved model's performance in the tropics depending upon the success in simulating the sensitivity of SCu to underlying SST. Our arguments are supported by the very different response obtained with two CGCMs to an idealized reduction of solar radiation flux incident at the top of the atmosphere over the Southern Ocean. It is shown that local perturbation impacts are very similar in the two models but that SST reductions in the SCu regions of the southern subtropics are stronger in the model with the stronger SCu-SST feedbacks.NOAA's Climate Program Office, Climate Variability and Predictability Program Award. Grant Number: NA14OAR4310278. European Union Seventh Framework Programme. Grant Numbers: FP7/2007–2013, 60352Peer reviewe

Maternal serum angiopoietin-like 3 levels in healthy and mild preeclamptic pregnant women

Objective: Angiopoietin-like protein 3(ANGPTL3) is an important regulator of lipoprotein metabolism in the fed state by inhibiting the enzyme lipoprotein lipase in oxidative tissues. However, the possible role of ANGPTL3 throughout gestation and its relationship with hormonal and biochemical variables are still unknown. The aim of this study was to determinate serum ANGPTL3 level in healthy non-pregnant women, during healthy and preeclamptic pregnancy and postpartum. Methods: Serum ANGPTL3 was analyzed by enzyme-linked immunosorbent assay (ELISA), in a prospective cohort of healthy pregnant women (n = 52) and women with mild preeclampsia (n = 21), and women at three months postpartum (n = 20) and healthy non-pregnant women (n = 20). The results obtained were correlated with biochemical, hormonal and anthropometric variables and insulin resistance indices. Results: Levels of ANGPTL3 were not different between the follicular and the luteal phases of the cycle in healthy non-pregnant women. There was a significant reduction in serum ANGPTL3 levels from the first to the third trimester in healthy pregnant women compared with healthy non-pregnant and postpartum women (p 0.05) Conclusions: We describe for the first time the profile of ANGPTL3 throughout pregnancy and postpartum as well as and discussed about explore their potential contribution interactions with lipoprotein metabolism throughout pregnancy and postpartum. Thus, low levels of ANGPTL3 during pregnancy might favor lipid uptake in oxidative tissues as the main maternal energy source, while may helping to preserve glucose for use by the fetus and placenta.Fil: Garces, María Fernanda. Universidad Nacional de Colombia; ColombiaFil: Rodriguez Navarro, Haiver Antonio. Universidad Nacional de Colombia; ColombiaFil: Buell Acosta, Julieth Daniela. Universidad Nacional de Colombia; ColombiaFil: Burgos Cardenas, Alvaro Javier. Universidad Nacional de Colombia; ColombiaFil: Franco Vega, Roberto. Universidad Nacional de Colombia; ColombiaFil: Maldonado Acosta, Luis Miguel. Universidad Nacional de Colombia; ColombiaFil: Eslava Schmalbach, Javier. Universidad Nacional de Colombia; ColombiaFil: Parada Baños, Arturo José. Universidad Nacional de Colombia; ColombiaFil: Castro Pinzon, Andres. Universidad Nacional de Colombia; ColombiaFil: Sanchez, Elizabeth. Universidad Nacional de Colombia; ColombiaFil: Angel Muller, Edith. Universidad Nacional de Colombia; ColombiaFil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Castaño, Justo P.. Universidad de Córdoba; EspañaFil: Dieguez, Carlos. Universidad de Santiago de Compostela; EspañaFil: Nogueiras, Rubén. Universidad de Santiago de Compostela; EspañaFil: Ruiz Parra, Ariel Ivan. Universidad Nacional de Colombia; ColombiaFil: Caminos, Jorge Eduardo. Universidad Nacional de Colombia; Colombi

Therapeutic implications of selecting the SCORE (European) versus the D'AGOSTINO (American) risk charts for cardiovascular risk assessment in hypertensive patients

Background: No comparisons have been made of scales estimating cardiovascular mortality and overall cardiovascular morbidity and mortality. The study objectives were to assess the agreement between the Framingham-D'Agostino cardiovascular risk (CVR) scale and the chart currently recommended in Europe (SCORE) with regard to identification of patients with high CVR, and to describe the discrepancies between them and the attendant implications for the treatment of hypertension and hyperlipidaemia. Methods: A total of 474 hypertensive patients aged 40-65 years monitored in primary care were enrolled into the study. CVR was assessed using the Framingham-D'Agostino scale, which estimates the overall cardiovascular morbidity and mortality risk, and the SCORE chart, which estimates the cardiovascular mortality risk. Cardiovascular risk was considered to be high for values ≥ 20% and ≥ 5% according to the Framingham-D'Agostino and SCORE charts respectively. Kappa statistics was estimated for agreement in classification of patients with high CVR. The therapeutic recommendations in the 2007 European Guidelines on Cardiovascular Disease Prevention were followed. Results

SARS-CoV-2-Mediated Lung Edema and Replication Are Diminished by Cystic Fibrosis Transmembrane Conductance Regulator Modulators

20 Pág.Coronaviruses (CoVs) of genera α, β, γ, and δ encode proteins that have a PDZ-binding motif (PBM) consisting of the last four residues of the envelope (E) protein (PBM core). PBMs may bind over 400 cellular proteins containing PDZ domains (an acronym formed by the combination of the first letter of the names of the three first proteins where this domain was identified), making them relevant for the control of cell function. Three highly pathogenic human CoVs have been identified to date: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. The PBMs of the three CoVs were virulence factors. SARS-CoV mutants in which the E protein PBM core was replaced by the E protein PBM core from virulent or attenuated CoVs were constructed. These mutants showed a gradient of virulence, depending on whether the alternative PBM core introduced was derived from a virulent or an attenuated CoV. Gene expression patterns in the lungs of mice infected with SARS-CoVs encoding each of the different PBMs were analyzed by RNA sequencing of infected lung tissues. E protein PBM of SARS-CoV and SARS-CoV-2 dysregulated gene expression related to ion transport and cell homeostasis. Decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA, essential for alveolar edema resolution, was shown. Reduced CFTR mRNA levels were associated with edema accumulation in the alveoli of mice infected with SARS-CoV and SARS-CoV-2. Compounds that increased CFTR expression and activity, significantly reduced SARS-CoV-2 growth in cultured cells and protected against mouse infection, suggesting that E protein virulence is mediated by a decreased CFTR expression. IMPORTANCE Three highly pathogenic human CoVs have been identified: SARS-CoV, MERS-CoV, and SARS-CoV-2. The E protein PBMs of these three CoVs were virulence factors. Gene expression patterns associated with the different PBM motifs in the lungs of infected mice were analyzed by deep sequencing. E protein PBM motif of SARS-CoV and SARS-CoV-2 dysregulated the expression of genes related to ion transport and cell homeostasis. A decrease in the mRNA expression of the cystic fibrosis transmembrane conductance regulator (CFTR), which is essential for edema resolution, was observed. The reduction of CFTR mRNA levels was associated with edema accumulation in the lungs of mice infected with SARS-CoV-2. Compounds that increased the expression and activity of CFTR drastically reduced the production of SARS-CoV-2 and protected against its infection in a mice model. These results allowed the identification of cellular targets for the selection of antivirals.This work was supported by grants from the Government of Spain (BIO2016-75549-R; PID2019-107001RB-I00 AEI/FEDER, UE; SEV 2017-0712 and PIE_INTRAMURAL_LINEA 1- 202020E079), CSIC (PIE_INTRAMURAL-202020E043), the European Zoonotic Anticipation and Preparedness Initiative (ZAPI) (IMI_JU_115760), the European Commission (H2020-SC1- 2019, ISOLDA Project No. 848166-2), and the U.S. National Institutes of Health (NIH) (2P01AI060699). J.M.H. received a contract from Comunidad de Madrid (Y2020/BIO-6576, COVID-PREclinical-MODels-CM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. In vivo experiments were performed at INIA-CISA (Madrid, Spain)Peer reviewe

La vid silvestre en México. Actualidades y potencial

En ocho capítulos se aborda el estado del arte de la vid silvestre en MéxicoEl estudio de las especies vegetales nativas de México representa un reto que cada día más investigadores mexicanos asumen. Durante muchos años, el apoyo a la investigación pública ha sido mínimo; desde el punto de vista agronómico es insuficiente para avanzar a la velocidad que requiere nuestro país para afrontar problemas de producción y distribución de alimentos. Por esa razón, entre otras, me es grato presentar esta obra que compila parte de los trabajos de la Red de Vid Silvestre patrocinada por el Sistema Nacional de Recursos Fitogenéticos (sinarefi) dependiente de la sagarpa; trabajos apuntalados por investigadores que sin pertenecer a la red han colaborado en el estudio de las plantas del género Vitis. En este libro se muestra el potencial del país para aprovechar el recurso vid, empleado desde antes de la conquista española por nativos mexicanos que conocían sus bondades. Es necesario continuar el avance en el conocimiento de este recurso, por ello el presente libro pretende invitar a toda persona interesada en contribuir con el rescate y conservación de las vides mexicanas. Los autores y editores, así como las instituciones en donde laboramos y aquellas que patrocinan estas investigaciones, esperamos se cumpla este objetivo y que el lector, alumno, profesor, investigador, público en general, disfrute esta lectura y, sobre todo, se interese en el recurso VitisSEP, SINAREFI, UAEME

Serum angiopoietin-like 3 levels are elevated in obese non diabetic men but are unaffected during an oral glucose tolerance test

This study aimed to determine ANGPTL3 serum levels in healthy young lean and obese non-diabetic men during an oral glucose tolerance test (OGTT) and correlate them with anthropometric, biochemical and hormonal parameters. A case–control study was carried out and 30 young obese non-diabetic (23.90 ± 3.84 years and BMI 37.92 ± 4.85 kg/m2) and 28 age-matched healthy lean (24.56 ± 3.50 years and BMI of 22.10 ± 1.72 kg/m2) men were included in this study. The primary outcome measures were serum basal ANGPTL3 and ANGPTL3–area under the curve (AUC) levels. The percentage of body fat was measured by dual-energy X-ray absorptiometry and biochemical, hormonal and insulin resistance indices were determined. Basal ANGPTL3 and ANGPTL3–AUC levels were significantly elevated (p < 0.05) in young obese subjects compared with lean subjects and were positively and significantly associated with different anthropometric measurements. Fasting ANGPTL3 serum levels were positively correlated with fasting insulin, leptin, Leptin/Adiponectin index and triglyceride—glucose index. Moreover, ANGPTL3–AUC was negatively correlated with Matsuda index. In this regard, chronically high ANGPTL3 levels in young obese subjects might favor triglyceride-rich lipoprotein clearance to replenish triglyceride stores by white adipose tissue rather than oxidative tissues.Centro de Investigaciones Inmunológicas Básicas y Aplicada

First Colombian Multicentric Newborn Screening for Congenital Toxoplasmosis

Congenital toxoplasmosis can result in permanent sequel as blindness or neurological damage in children and it seems to be more severe in South America than in other continents. There is a lack of information about this frequency in Colombia, where no control program is established, although it is a recognized cause of potentially preventable congenital blindness. We propose the first Colombian multicentric study to determine the frequency and impact of congenital toxoplasmosis. More than 15,000 newborns in seven cities were studied. Newborns were tested at birth by doing a cord blood test for toxoplasmosis. Additionally, children from mothers with history of toxoplasmosis acquired during pregnancy were recalled for a follow-up. The program identified fifteen children otherwise undiagnosed; three of these children died as consequence of congenital toxoplasmosis. The frequency of the congenital infection varied significantly between cities, being higher in Armenia and Florencia, intermediate in Bogota, Bucaramanga and Barranquilla and very low in western cities such as Cucuta and Riohacha. For the first time a significant correlation was found between mean rainfall at the city and the incidence of this congenital infection