Basis of the hyperexcitability of nociceptive neurons induced by activation of protease- activated receptor-2

Tesis (Doctorado en Ciencias en Biología Molecular)Proteases released during inflammation cleave a portion of the external segment of the Protease-Activated Receptors-2 (PAR2) and the distal portion of the receptor can then activate itself. The neuronal fibers of dorsal root ganglia (DRG) that innervate the intestine express PAR2 and its activation has been related with visceral hyperalgesia. In the first set of experiments, we analized some mechanisms underlying PAR2-evoked hyperexcitability of mouse colonic DRG neurons. To identify DRG neurons that inervate the colon we injected Fast Blue and DiI retrograde tracers into the mouse colon. We later used epi-fluorescence, to identify DiI-labelled neurons. Whole-cell current-clamp recordings of acutely dissociated neurons demonstrated that PAR2 activation with a brief application (2 min) of PAR2 agonists (SLIGRL-NH2 and trypsin) evoked sustained membrane depolarizations, which occurred concomitantly to an increased in input membrane resistance and a marked reduction in rheobase. In voltage clamp, SLIGRL-NH2 markedly suppressed delayed rectifier IK currents, but had no effect on the transient IA current or TTX-resistant sodium currents. The hyperexcitability induced by PAR2 activation was blocked with Calphostin C (a PKC inhibitor), and PD98059 (a ERK1/2 inhibitor). Our conclusion is that activation of PAR2 receptors on colonic nociceptive neurons causes hyperexcitability that is mediated by suppression of delayed rectifier IK currents. Both PKC and ERK1/2 mediate this hyperexcitability. These studies describe a novel mechanism of sensitization of colonic nociceptive neurons that may be implicated in conditions of visceral hyperalgesia such as irritable bowel syndrome. In a second set of experiments, carried out in HEK cells, activation of PAR2 sensitizes TRPV1 currents by a PKC and PKA-dependent mechanism. Activation of these receptors also potentiates TRPV4-mediated currents, effect that appears to require PKC and PKA activity

Oxidation of Micro-Sized Aluminium Particles: Hollow Alumina Spheres

Oxidized aluminium microparticles have recently been proposed for manufacturing new, environmentally-friendly, protective coatings on stainless-steels and Ni-base alloys. The oxidation mechanisms of spherical aluminium microparticles of an average particle size of 3.5 mu m were studied. Accordingly, simultaneous differential thermal analysis-thermogravimetry tests were carried out in air at different temperatures, always above aluminium melting temperature. Scanning electron microscopy and XRD were also used for the interpretation of results. Weight gain and energy results were explained in terms of the different structural changes taking place in aluminium particles. Dehydroxylation process was identified. The transformation of amorphous alumina to gamma-Al2O3 was numerically evaluated and the alumina phase transformation (gamma-Al2O3 -> I +/--Al2O3) was also studied. The temperature ranges revealed the appearance of metastable phases (theta-Al2O3). Complete oxidation of particles can be obtained at 1,300 A degrees C in < 1 h, although this also takes place at lower temperatures if enough oxidation time is used. Activation energy of oxidation process at high temperature was also estimated, taking a value of 334 kJ/mol. High temperature oxidation causes the formation of hollow alumina spheres, without any aluminium left inside them.This study was supported under the Project PARTICOAT (FP7-NMP-LARGE- 11329) funded by the European Union.Publicad

Hand features extractor using hand contour – a case study

Hand gesture recognition is an important topic in natural user interfaces (NUI). Hand features extraction is the first step for hand gesture recognition. This work proposes a novel real time method for hand features recognition. In our framework we use three cameras and the hand region is extracted with the background subtraction method. Features like arm angle and fingers positions are calculated using Y variations in the vertical contour image. Wrist detection is obtained by calculating the bigger distance from a base line and the hand contour, giving the main features for the hand gesture recognition. Experiments on our own data-set of about 1800 images show that our method performs well and is highly efficient

CRF Mediates Stress-Induced Pathophysiological High-Frequency Oscillations in Traumatic Brain Injury

Copyright © 2019 Narla et al. It is not known why there is increased risk to have seizures with increased anxiety and stress after traumatic brain injury (TBI). Stressors cause the release of corticotropin-releasing factor (CRF) both from the hypothalamic pituitary adrenal (HPA) axis and from CNS neurons located in the central amygdala and GABAergic interneurons. We have previously shown that CRF signaling is plastic, becoming excitatory instead of inhibitory after the kindling model of epilepsy. Here, using Sprague Dawley rats we have found that CRF signaling increased excitability after TBI. Following TBI, CRF type 1 receptor (CRFR1)-mediated activity caused abnormally large electrical responses in the amygdala, including fast ripples, which are considered to be epileptogenic. After TBI, we also found the ripple (120-250 Hz) and fast ripple activity (\u3e250 Hz) was cross-frequency coupled with θ (3-8 Hz) oscillations. CRFR1 antagonists reduced the incidence of phase coupling between ripples and fast ripples. Our observations indicate that pathophysiological signaling of the CRFR1 increases the incidence of epileptiform activity after TBI. The use for CRFR1 antagonist may be useful to reduce the severity and frequency of TBI associated epileptic seizures

Responsabilidad del Estado Salvadoreño respecto a la Propaganda Electoral Anticipada.

Historia de la Propaganda Electoral – Actividad de la Propaganda Electoral – La Propaganda Electoral en la Legislación Salvadoreña – Régimen Sancionatorio

Accumulation of target gene mutations confers multiple resistance to ALS, ACCase and EPSPS inhibitors in Lolium species in Chile

Different Lolium species, common weeds in cereal fields and fruit orchards in Chile, were reported showing isolated resistance to the acetyl CoA carboxylase (ACCase), acetolactate synthase (ALS) and 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) inhibiting herbicides in the late 1990s. The first case of multiple resistance to these herbicides was Lolium multiflorum found in spring barley in 2007. We hypothesized that other Lolium species may have evolved multiple resistance. In this study, we characterised the multiple resistance to glyphosate, diclofop-methyl and iodosulfuron-methyl-sodium in Lolium rigidum, Lolium perenne and Lolium multiflorum resistant (R) populations from Chile collected in cereal fields. Lolium spp. populations were confirmed by AFLP analysis to be L. rigidum, L. perenne and L. multiflorum. Dose-response assays confirmed multiple resistance to glyphosate, diclofop-methyl and iodosulfuron methyl-sodium in the three species. Enzyme activity assays (ACCase, ALS and EPSPS) suggested that the multiple resistance of the three Lolium spp. was caused by target site mechanisms, except the resistance to iodosulfuron in the R L. perenne population. The target site genes sequencing revealed that the R L. multiflorum population presented the Pro-106-Ser/Ala (EPSPS), Ile-2041-Asn+Asp-2078-Gly (ACCase), and Trp-574-Leu (ALS) mutations; and the R L. rigidum population had the Pro-106-Ser (EPSPS), Ile-1781-Leu+Asp-2078-Gly (ACCase) and Pro-197-Ser/Gln+Trp-574-Leu (ALS) mutations. Alternatively, the R L. perenne population showed only the Asp-2078-Gly (ACCase) mutation, while glyphosate resistance could be due to EPSPS gene amplification (no mutations but high basal enzyme activity), whereas iodosulfuron resistance presumably could involve non-target site resistance (NTSR) mechanisms. These results support that the accumulation of target site mutations confers multiple resistance to the ACCase, ALS and EPSPS inhibitors in L. multiflorum and L. rigidum from Chile, while in L. perenne, both target and NTSR could be present. Multiple resistance to three herbicide groups in three different species of the genus Lolium in South America represents a significant management challenge.This work was funded by the Asociación de Agroquímicos y Medioambiente. The Spanish Ministry of Science and Innovation (Project PID2019-110847RB-I00) and the European Regional Development Fund (FEDER) supported this research. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI). JT acknowledges support from the Spanish Ministry of Science, Innovation and Universities (grant Ramon y Cajal RYC2018-023866-I) and RA thanks support to the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2018/15910-6)

Novel genes and sex differences in COVID-19 severity

Here, we describe the results of a genome-wide study conducted in 11939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P= 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.Instituto de Salud Carlos III European Commission COV20_00622 COV20/00792 COV20_00181 COV20_1144 PI20/00876European Union (ERDF) 'A way of making Europe'Fundacion Amancio Ortega, Banco de SantanderEstrella de Levante S.A.Colabora Mujer AssociationLa Caixa FoundationAgencia Estatal de Investigacion RTC-2017-6471-1Cabildo Insular de Tenerife (Apuestas cientificas del ITER para colaborar en la lucha contra la COVID-19) CGIEU0000219140Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias PIFIISC20/5

Caracterización geométrica y cinemática de un chorro pulverizado empleando la técnica óptica PTV

Los fenómenos naturales o inducidos que involucran el movimiento de gotas motivan análisis para determinar aspectos como la pérdida de suelo por erosión o los cambios que pudieran ocurrir en la tasa de infiltración debido a la energía con la que impactan sobre la superficie del suelo. El diámetro y la velocidad definen la magnitud del efecto. Para caracterizar estas variables se han aplicando diversas técnicas (papel sensible al agua, harina, inmersiones en aceite, ópticas y fotografía). En este sentido, la presente investigación emplea velocimetría por rastreo de partículas (PTV) en la caracterización de gotas emitidas por un pulverizador de flujo. PTV ha encaminado parte de su desarrollo al análisis de la velocidad de sedimentación en flujos bifásicos donde se requiere del sembrado de partículas trazadoras para evaluar el fenómeno; sin embargo, las características experimentales del trabajo obligaron a omitir el uso de estos elementos, por lo que fue indispensable hacer adecuaciones al esquema propuesto por Salinas et al. (2006). Las gotas se originaron a una presión hidráulica constante de 175 kPa, las fotografías se capturaron a una distancia de 4.5 m con tres alturas diferentes del pulverizador. La información recolectada (diámetros y velocidades) posibilitó la construcción de campos vectoriales de velocidad. Los resultados presentados derivan del análisis de 1 582 gotas, con las que se obtuvieron valores medios de 0.39, 0.55 y 0.34 mm en diámetro, y 4.02, 3.70 y 3.63 ms-1 en velocidad, para alturas de 0.5, 1.0 y 1.5 m, respectivamente

Total and high molecular weight adiponectin have similar utility for the identification of insulin resistance

<p>Abstract</p> <p>Background</p> <p>Insulin resistance (IR) and related metabolic disturbances are characterized by low levels of adiponectin. High molecular weight adiponectin (HMWA) is considered the active form of adiponectin and a better marker of IR than total adiponectin. The objective of this study is to compare the utility of total adiponectin, HMWA and the HMWA/total adiponectin index (S_Aindex) for the identification of IR and related metabolic conditions.</p> <p>Methods</p> <p>A cross-sectional analysis was performed in a group of ambulatory subjects, aged 20 to 70 years, in Mexico City. Areas under the receiver operator characteristic (ROC) curve for total, HMWA and the S_Aindex were plotted for the identification of metabolic disturbances. Sensitivity and specificity, positive and negative predictive values, and accuracy for the identification of IR were calculated.</p> <p>Results</p> <p>The study included 101 men and 168 women. The areas under the ROC curve for total and HMWA for the identification of IR (0.664 <it>vs</it>. 0.669, <it>P </it>= 0.74), obesity (0.592 <it>vs</it>. 0.610, <it>P </it>= 0.32), hypertriglyceridemia (0.661 <it>vs</it>. 0.671, <it>P </it>= 0.50) and hypoalphalipoproteinemia (0.624 <it>vs</it>. 0.633, <it>P </it>= 0.58) were similar. A total adiponectin level of 8.03 μg/ml was associated with a sensitivity of 57.6%, a specificity of 65.9%, a positive predictive value of 50.0%, a negative predictive value of 72.4%, and an accuracy of 62.7% for the diagnosis of IR. The corresponding figures for a HMWA value of 4.25 μg/dl were 59.6%, 67.1%, 51.8%, 73.7% and 64.2%.</p> <p>The area under the ROC curve of the S_Aindex for the identification of IR was 0.622 [95% CI 0.554-0.691], obesity 0.613 [95% CI 0.536-0.689], hypertriglyceridemia 0.616 [95% CI 0.549-0.683], and hypoalphalipoproteinemia 0.606 [95% CI 0.535-0.677].</p> <p>Conclusions</p> <p>Total adiponectin, HMWA and the S_Aindex had similar utility for the identification of IR and metabolic disturbances.</p

Estimation of the Evapotranspiration and Crop Coefficients of Bell Pepper Using a Removable Weighing Lysimeter: A Case Study in the Southeast of Spain

Water use efficiency is essential in semiarid regions of Spain, and it can be achieved through a precise knowledge of the real crop water requirements (CWR). The Food and Agriculture Organization of the United Nations (FAO) offers standardized crop coefficients to establish the CWR. However, these coefficients can change due to different conditions, such as climatic variations and cultivation practices. In this work, the evapotranspiration (ETClys) and crop coefficients (KClys) of bell pepper were obtained with a compact removable weighing lysimeter between February and August for two crop seasons (2019 and 2020). ETClys was determined from the water balance, and the KClys values were determined as the ratio of the crop evapotranspiration, measured on the removable weighing lysimeter, and the reference evapotranspiration. The KClys average values for the bell pepper in the initial, middle, and final stages were 0.57, 1.06, and 0.80, respectively. KC regression models were obtained as a function of the fraction thermal units, achieving a maximum correlation of 0.67 (R2). In general, the KC values obtained in this research work were lower in the initial and in the final stages and larger in the middle stage in comparison with the FAO-56 values and other research works values in semiarid conditions. The bell pepper yield increased by 7.72% in 2019 and by 3.49% in 2020 compared to the yield reported by the Ministry of the Environment and Rural and Marine Areas of the Spanish Government in 2019 and with a minimum water loss through drainage. The results in this work can help farmers to determine the crop water requirements and to improve the system efficiency in semiarid locations with similar conditions to those in the study