Molecular Requirements for Ethanol Differential Allosteric Modulation of Ligand-Gated Ion Channels Based on Selective G Beta Gamma Modulation

It is now believed that the allosteric modulation produced by ethanol in glycine receptors (GlyRs) depends on alcohol binding to discrete sites within the protein structure. Thus, the differential ethanol sensitivity of diverse GlyR isoforms and mutants was explained by the presence of specific residues in putative alcohol pockets. Here, we demonstrate that ethanol sensitivity in two LGIC members, the GlyR adult alpha1 and embryonic alpha2 subunits, can be modified through selective mutations that rescued or impaired Gbetagamma modulation. Even though that both isoforms were able to physically interact with Gbetagamma, only the alpha1 GlyR was functionally modulated by Gbetagamma and pharmacological ethanol concentrations. Remarkably, the simultaneous switching of two transmembrane and a single extracellular residue in alpha2 GlyRs was enough to generate GlyRs modulated by Gbetagamma and low ethanol concentrations. Interestingly, while we found that these TM residues were different to those in the alcohol binding site, the extracellular residue was recently implicated in conformational changes important to generate a pre-open activated state that precedes ion channel gating. Thus, these results support the idea that the differential ethanol sensitivity of these two GlyR isoforms rests on conformational changes in transmembrane and extracellular residues within the ion channel structure rather than in differences in alcohol binding pockets. Our results describe the molecular basis for the differential ethanol sensitivity of two LGIC members based on selective Gbetagamma modulation and provide a new mechanistic framework for allosteric modulations of abuse drugs

Relationship between Dyslipidemia and Physical Activity in Mexican Children

Purpose: The purpose of this research was to determine the relationship between physical activity and lipid levels in children 10 to 13 years of age living in Durango, Mexico. Method: Cross-sectional study performed in 823 children (n=428, 52% boys; n=395, 48% girls) enrolled in nine elementary schools. Physical activity was monitored in two ways: a) a questionnaire was used to obtain information about physical activity done in the previous week, and b) steps were counted for 24 hours with a Yamax SW-200 pedometer. A subsample of 425 children provided serum samples to determine total-cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and triglycerides (TG). Results: Over half (52.9%) participated in a sports team inside or outside of school; most (90.9%) reported one sport, with few (9.1%) reporting 2-3 sports. The most commonly reported vigorous PA was: soccer (33%), basketball (24%), jogging (8-12 km/h) (23%), volleyball (17%) and others (3%). Those who participated in a sports team had higher levels of HDL-C and lower TG. Participation in 2 or 3 sports reduced TG levels just over 20%. Boys who reported 30 minutes or more per day of vigorous activity had lower triglyceride levels than those who reported less (p = 0.020). Boys accumulated significantly more steps per day (m=17,030 ± 6444) than girls (m=12,991± 5316; p \u3c 0.001). The prevalence of lipid abnormalities was higher in children with fewer steps. Hypercholesterolemia was lower in boys with the highest number of steps (p = 0.044), in girls the differences were not statistically significant. Hypertriglyceridemia in both sexes was lower in the group with the highest number of steps (

Nueva benzoil lactona y otros costituyentes de pilocarpus alvaradoii (rutaceae)

Del extracto etanólico de hojas de Pilocarpus alvaradoii fue aislada e identificada la nueva lactona α-Benzoil-γ-valerolactona (1), junto con los triterpenos pentacíclicos conocidos lupeol (2), epibetulina (3); y las furanocumarinas bergapteno (4), psoraleno (5), y xantotoxina (6).  El aislamiento y la purificación fueron realizados por técnicas cromatográficas convencionales.   La elucidación estructural de estos compuestos se determinó mediante técnicas espectroscópicas (IR, RMN 1H, 13C, EM)

Approach and management of diaphragmatic paralysis in adults

3 years ago, 38-year-old male, with no relevant personal pathological history, began to present exertional dyspnea, gastroesophageal reflux, retrosternal pyrosis, dyspepsia and postprandial abdominal distension after a traffic accident. A study protocol was initiated, where cabinet studies documented elevation of the left hemidiaphragm was documented. A minimally invasive approach was performed with the finding of elevation of the left hemidiaphragm of approximately 8 cm in relation to the contralateral diaphragm without evidence of paraesophageal hernia. Mayo type left diaphragmatic plication was performed with non-absorbable suture (polypropylene 1) without complications. With favorable evolution, he started the oral route 8 hours postoperatively, and was discharged 48 hours after surgery due to clinical improvement and without gastroesophageal reflux. Surgical plication of the affected hemidiaphragm is successful in carefully selected patients with severe symptoms thought to be due to unilateral diaphragmatic paralysis. Studies demonstrate improvement in several parameters, including lung and respiratory muscle function, exercise endurance, blood gas exchange, and possibly dyspnea

Perspectivas literarias: traducción e intertextualidad

En este libro hemos reunido un conjunto de trabajos que exploran temas relacionados con la traducción literaria y con los estudios literarios desde una perspectiva múltiple y comparada, pues creemos que, en estos tiempos, es valioso detenerse a analizar experiencias complejas con respecto a las prácticas literarias que permiten la comunicación intercultural, ya que ésta es una vía para cuestionar visiones nacionalistas que, en ocasiones, tienden a achatar el panorama en lugar de reconocer la hibridez y la heterogeneidad de los discursos literarios. Se trata de analizar estos temas desde distintos ángulos, tales como la traducción, las intertextualidades temáticas, la formación de traductores, la perspectiva de los lectores, la construcción del canon por distintas instancias culturales y los estudios comparados

Insulin Resistance and Obesity in Mexican Youth

Purpose: Although research shows that prevalence rates of insulin resistance (IR) is increasing in children, little is known about the impact of obesity in IR in Mexican youth. This study investigated the association between overweight, obesity, and insulin resistance in Mexican adolescents. Methods: Data were collected from 448 adolescents aged 12 to 18 years from a random sample of a high school student population in Durango, Mexico. After fasting overnight, blood samples were obtained from participants. Glucose, insulin, lipid profile, leptin, insulin growth factor, growth hormone, cortisol, TNF-alpha, and C-reactive protein were determined in serum. Body Mass Index (BMI) was calculated using CDC parameters. Fat mass was determined using a bioelectrical impedance analyzer. THE HOMA index was used to calculate IR and a Keskin diagnosis value of 3.1 was considered. Statistical analyses were conducted. Results: The mean age of the sample was 15.44 years and a majority was female (61.4%). Prevalence of overweight and obesity was 31.9%. The BMI mean was slightly higher in females (65.5) than in males (61.1) (p \u3e0.05). Females had a greater mean of body fat percentage (31.9) than males (20.2) (p\u3c 0.05). Prevalence of resistance to insulin by HOMA-IR was 14.4% with no statistically significant gender differences. The IR mean was higher in adolescents with greater BMI (≥85th percentile) than those with low and normal BMI (\u3c85th percentile) (p \u3c0.05). Adolescents with high IR levels (≥3.1) had higher mean values of corporal fat (37.69%) and BMI (89.76) than those with lower IR levels (\u3c3.1) and lower corporal fat and BMI values (26.4%3 and 61.67, respectively). Conclusions: The significant association found between obesity and insulin resistance in Mexican adolescents suggests a greater risk for the development of degenerative disease in this young population during adulthood. Public health programs among Mexican adolescents are essential to prevent obesity and IR related consequences

Induction of TIMP-1 expression in rat hepatic stellate cells and hepatocytes: a new role for homocysteine in liver fibrosis

Elevated plasma levels of homocysteine have been shown to interfere with normal cell function in a variety of tissues and organs, such as the vascular wall and the liver. However, the molecular mechanisms behind homocysteine effects are not completely understood. In order to better characterize the cellular effects of homocysteine, we have searched for changes in gene expression induced by this amino acid. Our results show that homocysteine is able to induce the expression and synthesis of the tissue inhibitor of metalloproteinases-1 (TIMP-1) in a variety of cell types ranging from vascular smooth muscle cells to hepatocytes, HepG2 cells and hepatic stellate cells. In this latter cell type, homocysteine also stimulated alpha 1(I) procollagen mRNA expression. TIMP-1 induction by homocysteine appears to be mediated by its thiol group. Additionally, we demonstrate that homocysteine is able to promote activating protein-1 (AP-1) binding activity, which has been shown to be critical for TIMP-1 induction. Our findings suggest that homocysteine may alter extracellular matrix homeostasis on diverse tissular backgrounds besides the vascular wall. The liver could be considered as another target for such action of homocysteine. Consequently, the elevated plasma levels of this amino acid found in different pathological or nutritional circumstances may cooperate with other agents, such as ethanol, in the onset of liver fibrosis

Using a Floating-Gate MOS Transistor as a Transducer in a MEMS Gas Sensing System

Floating-gate MOS transistors have been widely used in diverse analog and digital applications. One of these is as a charge sensitive device in sensors for pH measurement in solutions or using gates with metals like Pd or Pt for hydrogen sensing. Efforts are being made to monolithically integrate sensors together with controlling and signal processing electronics using standard technologies. This can be achieved with the demonstrated compatibility between available CMOS technology and MEMS technology. In this paper an in-depth analysis is done regarding the reliability of floating-gate MOS transistors when charge produced by a chemical reaction between metallic oxide thin films with either reducing or oxidizing gases is present. These chemical reactions need temperatures around 200 °C or higher to take place, so thermal insulation of the sensing area must be assured for appropriate operation of the electronics at room temperature. The operation principle of the proposal here presented is confirmed by connecting the gate of a conventional MOS transistor in series with a Fe2O3 layer. It is shown that an electrochemical potential is present on the ferrite layer when reacting with propane

Transformed but not normal hepatocytes express UCP2

Uncoupling protein 2 (UCP2) expression in liver is restricted to non-parenchymal cells. By means of differential display screening between normal rat liver and H4IIE hepatoma cells we have isolated a cDNA clone encompassing part of UCP2 cDNA. Northern blot analysis revealed that UCP2 is expressed in some hepatocarcinoma cell lines, while it is absent in adult hepatocytes. UCP2 mRNA in H4IIE cells was downregulated when cells were cultured for 36 h in 0.1% serum and its expression was restored upon addition of 10% serum or phorbol esters. Hypomethylation of UCP2 was observed in transformed UCP2 expressing cells. Our results indicate that UCP2 is expressed in some hepatocarcinoma cell lines and that serum components may participate in maintaining elevated UCP2 levels

Design Of A Minicomputer Separator Of Urban Solid Waste (RSU)

In Mexico, the society in general lacks the habit and ethics of properly disposing garbage or in taking care of the environment. This paper focuses on analyzing and disposing garbage in an automated way. The present study also seeks to create and promote care for the planet. The minicomputer (GreenScanProcess) is an automated system whose process is based on an algorithm that stands out for its functionality. GreenScanProcess has sensors that allow the analysis and scanning of garbage. It also measures the weight and humidity of the garbage. The minicomputer also examines the garbage to know its composition. Likewise, GreenScanProcess takes the garbage to the container according to the garbage. The benefits obtained when conducting the research were: environmental, economic, technological, and educational