CCR5 deficiency predisposes to fatal outcome in influenza virus infection

Influenza epidemics affect all age groups, although children, the elderly and those with underlying medical conditions are the most severely affected. Whereas co-morbidities are present in 50% of fatal cases, 25-50% of deaths are in apparently healthy individuals. This suggests underlying genetic determinants that govern infection severity. Although some viral factors that contribute to influenza disease are known, the role of host genetic factors remains undetermined. Data for small cohorts of influenza-infected patients are contradictory regarding the potential role of chemokine receptor 5 deficiency (CCR5-Δ32 mutation, a 32 bp deletion in the CCR5 gene) in the outcome of influenza virus infection. We tested 171 respiratory samples from influenza patients (2009 pandemic) for CCR5-Δ32 and evaluated its correlation with patient mortality. CCR5-Δ32 patients (17.4%) showed a higher mortality rate than WT individuals (4.7%; P = 0.021), which indicates that CCR5-Δ32 patients are at higher risk than the normal population of a fatal outcome in influenza infection.This work was supported by the Instituto de Salud Carlos III (Programa especial de investigación sobre la gripe pandémica GR09/0040 and GR09/0023), Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES) and the Spanish Ministry of Science and Innovation (BFU 2011-26175)S

Membrane shape as a reporter for applied forces

Recent advances have enabled 3-dimensional reconstructions of biological structures in vivo, ranging in size and complexity from single proteins to multicellular structures. In particular, tomography and confocal microscopy have been exploited to capture detailed 3-dimensional conformations of membranes in cellular processes ranging from viral budding and organelle maintenance to phagocytosis. Despite the wealth of membrane structures available, there is as yet no generic, quantitative method for their interpretation. We propose that by modeling these observed biomembrane shapes as fluid lipid bilayers in mechanical equilibrium, the externally applied forces as well as the pressure, tension, and spontaneous curvature can be computed directly from the shape alone. To illustrate the potential power of this technique, we apply an axial force with optical tweezers to vesicles and explicitly demonstrate that the applied force is equal to the force computed from the membrane conformation

Adherence Evaluation of a MacPherson Suspension under EuSAMA Norm in a Mathematical Model and one Multibody

En este trabajo se realiza una simulación computacional, para dar respuesta a un problema de dinámica asociado a la evaluación de la adhesión en sistemas de suspensión. El proceso inicia con el levantamiento de las geometrías más representativas de un sistema MacPherson de un Nissan Sentra B13, donde cada uno de los dispositivos se crea y ensambla en un software CAD para dar solución dinámica en un paquete CAE multicuerpo. Posteriormente se crea un modelo matemático cuyas ecuaciones diferenciales se generan fundamentadas en la segunda ley de Newton y se resuelven en Simulink de Matlab®. Finalizado el proceso de elaboración de los modelos se alimentan las variables con la información precisa del vehículo de estudio para obtener las gráficas que dan respuesta al protocolo de la prueba EuSAMA (European Shock Absorber Manufaturers Association) para el análisis de la adhesión. Los resultados obtenidos evidencian que los modelos desarrollados son confiables cuando se comparan con la prueba experimental; además, se observa que la disminución del coeficiente de amortiguamiento compromete la adhesión del vehículo en la vía, afectando la estabilidad y maniobrabilidad.A computational simulation is Implemented, in order to response to a problem of dynamics associated With The assessment of adherence in suspension systems. The process begins with the lifting of the most representative geometries of a MacPherson system of a Nissan Sentra B13, where each of the devices is created and assembled into a CAD software to give a dynamic solution on a CAE multibody package. Afterwards a mathematical model was created whose differential equations are generated substantiated on Newton's second law and this are resolved using Matlab-Simulink applications. Once the model developing process is over, the variables are fed with accurate information of the studied vehicle to obtain the graphs that give an answer to EuSAMA (European Shock Absorber Manufacturers Association) test protocol for the adherence analysis. The results presented show the reliability of the developed models when compared with the experimental test; furthermore, it demonstrates that the decrease of the damping coefficient compromises the vehicle´s adherence on the track, affecting its stability and maneuverability

RETRACTED ARTICLE: Age-dependent Increase in Desmosterol Restores DRM Formation and Membrane-related Functions in Cholesterol-free DHCR24−/− Mice

Cholesterol is a prominent modulator of the integrity and functional activity of physiological membranes and the most abundant sterol in the mammalian brain. DHCR24-knock-out mice lack cholesterol and accumulate desmosterol with age. Here we demonstrate that brain cholesterol deficiency in 3-week-old DHCR24−/− mice was associated with altered membrane composition including disrupted detergent-resistant membrane domain (DRM) structure. Furthermore, membrane-related functions differed extensively in the brains of these mice, resulting in lower plasmin activity, decreased β-secretase activity and diminished Aβ generation. Age-dependent accumulation and integration of desmosterol in brain membranes of 16-week-old DHCR24−/− mice led to the formation of desmosterol-containing DRMs and rescued the observed membrane-related functional deficits. Our data provide evidence that an alternate sterol, desmosterol, can facilitate processes that are normally cholesterol-dependent including formation of DRMs from mouse brain extracts, membrane receptor ligand binding and activation, and regulation of membrane protein proteolytic activity. These data indicate that desmosterol can replace cholesterol in membrane-related functions in the DHCR24−/− mouse

LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery

Neurotransmitter receptor trafficking during synaptic plasticity requires the concerted action of multiple signaling pathways and the protein transport machinery. However, little is known about the contribution of lipid metabolism during these processes. In this paper, we addressed the question of the role of cholesterol in synaptic changes during long-term potentiation (LTP). We found that N-methyl-d-aspartate-type glutamate receptor (NMDAR) activation during LTP induction leads to a rapid and sustained loss or redistribution of intracellular cholesterol in the neuron. A reduction in cholesterol, in turn, leads to the activation of Cdc42 and the mobilization of GluA1-containing α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) from Rab11-recycling endosomes into the synaptic membrane, leading to synaptic potentiation. This process is accompanied by an increase of NMDAR function and an enhancement of LTP. These results imply that cholesterol acts as a sensor of NMDAR activation and as a trigger of downstream signaling to engage small GTPase (guanosine triphosphatase) activation and AMPAR synaptic delivery during LTP.Peer Reviewe

Real-time incidence of travel-related symptoms through a smartphone-based app remote monitoring system: a pilot study

Trip Doctor(R), a Smartphone-based app monitoring system, was developed to detect infections among travelers in real-time. For testing, 106 participants were recruited (62.2% male, mean age 36 years (SD = 11)). Majority of trips were for tourism and main destinations were in South East Asia. Mean travel duration was 14 days (SD = 10). Diarrhea was the most frequently reported symptom (15.5%). The system demonstrated adequate usability and is ready to be used on a larger scale

Evaluating psychometric properties of the Emotional Eating Scale Adapted for Children and Adolescents (EES-C) in a clinical sample of children seeking treatment for obesity: a case for the unidimensional model.

BackgroundThe Emotional Eating Scale - Adapted for Children and Adolescents (EES-C) assesses children's urge to eat in response to experiences of negative affect. Prior psychometric studies have demonstrated the high reliability, concurrent validity, and test-retest reliability of theoretically defined subconstructs among non-clinical samples of children and adolescents who were primarily healthy weight; however, no psychometric studies exist investigating the EES-C among clinical samples of children with overweight/obesity (OW/OB). Furthermore, studies conducted in different contexts have suggested a discordant number of subconstructs of emotions related to eating. The purpose of this study was to evaluate the validity of the EES-C in a clinical sample of children seeking weight-loss treatment.MethodUsing a hierarchical bi-factor approach, we evaluated the validity of the EES-C to measure a single general construct, a set of two separate correlated subconstructs, or a hierarchical arrangement of two constructs, and determined reliability in a clinical sample of treatment-seeking children with OW/OB aged 8-12 years (N = 147, mean age = 10.4 years.; mean BMI z = 2.0; female = 66%; Hispanic = 32%, White and other = 68%).ResultsComparison of factor-extraction methods suggested a single primary construct underlying EES-C in this clinical sample. The bi-factor indices provided clear evidence that most of the reliable variance in the total score (90.8 for bi-factor model with three grouping factors and 95.2 for bi-factor model with five grouping factors) was attributed to the general construct. After adjusting for relationships with the primary construct, remaining correlations among sets of items did not suggest additional reliable constructs.ConclusionResults suggest that the primary interpretive emphasis of the EES-C among treatment-seeking children with overweight or obesity should be placed on a single general construct, not on the 3- or 5- subconstructs as was previously suggested

Effective Synthesis Procedure Based on Microwave Heating of the PdCo Aerogel Electrocatalyst for Its Use in Microfluidic Devices

Unsupported PdCo aerogels were successfully synthesized by means of microwave heating. The use of this heating methodology provides some advantages compared to conventional heating in terms of saving synthesis time and improved physicochemical properties (i.e., greater surface area and mesoporosity). The combination of palladium with cobalt reduces the dependence of the noble metal and increases the electrocatalytic performance in the ethanol oxidation reaction due to a higher percentage of Pd0 in the PdCo aerogel, confirmed using the X-ray photoelectron spectroscopy (XPS) technique. For the application in energy conversion electrochemical systems, the catalytic activity of aerogels was evaluated in a microfluidic fuel cell that uses ethanol as fuel, where the PdCo aerogel synthesized by microwave heating exhibited great performance with 330 mA cm-2 current density, tripling the value of the palladium-based aerogel.The authors thank Consejo Nacional de Humanidades, Ciencias y Tecnologías (CONAHCYT) for funding through the Ciencia de Frontera 2020-845132.Peer reviewe

An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin

The catechin, epigallocatechin gallate (eGCG), found in green tea, has inhibitory activity against a number of protein toxins and was investigated in relation to its impact upon ricin toxin (RT) in vitro. The IC50 for RT was 0.08 ± 0.004 ng/mL whereas the IC50 for RT + 100 μM eGCG was 3.02 ± 0.572 ng/mL, indicating that eGCG mediated a significant (p < 0.0001) reduction in ricin toxicity. This experiment was repeated in the human macrophage cell line THP-1 and IC50 values were obtained for RT (0.54 ± 0.024 ng/mL) and RT + 100 μM eGCG (0.68 ± 0.235 ng/mL) again using 100 μM eGCG and was significant (p = 0.0013). The documented reduction in ricin toxicity mediated by eGCG was found to be eGCG concentration dependent, with 80 and 100 μg/mL (i.e. 178 and 223 μM respectively) of eGCG mediating a significant (p = 0.0472 and 0.0232) reduction in ricin toxicity at 20 and 4 ng/ml of RT in Vero and THP-1 cells (respectively). When viability was measured in THP-1 cells by propidium iodide exclusion (as opposed to the MTT assays used previously) 10 ng/mL and 5 ng/mL of RT was used. The addition of 1000 μM and 100 μM eGCG mediated a significant (p = 0.0015 and < 0.0001 respectively) reduction in ricin toxicity relative to an identical concentration of ricin with 1 μg eGCG. Further, eGCG (100 μM) was found to reduce the binding of RT B chain to lactose-conjugated Sepharose as well as significantly (p = 0.0039) reduce the uptake of RT B chain in Vero cells. This data suggests that eGCG may provide a starting point to refine biocompatible substances that can reduce the lethality of ricin