936 research outputs found

    Cyclooxygenase 2: understanding the pathophysiological role through genetically altered mouse models

    Get PDF
    El pdf del artículo es la versión post-print.Cyclooxygenase (COX) -1 and –2 catalyze the first step in the biosynthesis of prostanoids. COX-1 is constitutively expressed in many tissues and seems to be involved in the house keeping function of prostanoids. COX-2, the inducible isoform, accounts for the elevated production of prostaglandins in response to various inflammatory stimuli, hormones and growth factors. COX-2 expression has been also associated with cell growth regulation, tissue remodelling and carcinogenesis. More of these characteristics have been elucidate through using COX selective inhibitors. Recent advances in transgenic and gene-targeting approaches allow a sophisticated manipulation of the mouse genome by gene addition, gene deletion or gene modifications. The development of COX-2 genetically altered mice has provided models to elucidate the physiological and pathophysiological roles of this enzyme.This work was supported by grants from Instituto de Salud Carlos III (Red de Centros C03/01), Generalitat Valenciana (GRUPOS03/072), Ministerio de Educación y Ciencia (SAF2004-00957) and Comunidad de Madrid (CAM2004-GR/SAL/0388).Peer reviewe

    Формирование профилированных импульсов напряжения для время пролетного спектрометра

    Get PDF
    В работе рассматривается возможность создания время пролетного спектрометра (ВПР) с высокой разрешающей способностью. Работа прибора основана на использовании временной группировки ионов с монотонно растущей энергией, задаваемой в анализирующим элементе ВПР спектрометра. Основная задача получения профилированных импульсов ускоряющего ионы напряжения решается с использованием оригинального формирователя, с включенной параллельно нагрузке предварительно заряженной емкости задающей уровень коррекции напряжения. Проведено моделирование различных модификаций генераторов импульсов. Разработан формирователь с частичным разрядом накопительной емкости и полупроводниковым коммутаторомThe paper considers the possibility of creating a time-of-flight spectrometer with high resolution. The operation of the device is based on the use of a time grouping of ions with a monotonically increasing energy, set in the analyzing element of the spectrometer. The main task of obtaining profiled pulses of ion-accelerating voltage is solved using an original shaper, with a pre-charged capacitance connected in parallel to the load, which sets the level of voltage correction. Various modifications of pulse generators are modeled. A shaper with a partial discharge of the storage capacity and a semiconductor switch has been develope

    Significance of beta-band oscillations in Autism Spectrum Disorders during motor response inhibition tasks: a MEG study

    Get PDF
    In Autism Spectrum Disorders (ASD), impaired response inhibition and lack of adaptation are hypothesized to underlie core ASD symptoms, such as social communication and repetitive, stereotyped behavior. Thus, the aim of the present study was to compare neural correlates of inhibition, post-error adaptation, and reaction time variability in ASD and neuro-typical control (NTC) participants by investigating possible differences in error-related changes of oscillatory MEG activity. Twelve male NTC (mean age 20.3 ± 3.7) and fourteen male patients with ASD (mean age 17.8 ± 2.9) were included in the analysis. Subjects with ASD showed increased error-related reaction time variability. MEG analysis revealed decreased beta power in the ASD group in comparison to the NTC group over the centro-parietal channels in both, the pre-stimulus and post-response interval. In the ASD group, mean centro-parietal beta power negatively correlated with dimensional autism symptoms. In both groups, false alarms were followed by an early increase in temporo-frontal theta to alpha power; and by a later decrease in alpha to beta power at central and posterior sensors. Single trial correlations were additionally studied in the ASD group, who showed a positive correlation of pre-stimulus beta power with post-response theta, alpha, and beta power, particularly after hit trials. On a broader scale, the results deliver important insights into top-down control deficits that may relate to core symptoms observed in ASD

    The role of GDNF family ligand signalling in the differentiation of sympathetic and dorsal root ganglion neurons

    Get PDF
    The diversity of neurons in sympathetic ganglia and dorsal root ganglia (DRG) provides intriguing systems for the analysis of neuronal differentiation. Cell surface receptors for the GDNF family ligands (GFLs) glial cell-line-derived neurotrophic factor (GDNF), neurturin and artemin, are expressed in subpopulations of these neurons prompting the question regarding their involvement in neuronal subtype specification. Mutational analysis in mice has demonstrated the requirement for GFL signalling during embryonic development of cholinergic sympathetic neurons as shown by the loss of expression from the cholinergic gene locus in ganglia from mice deficient for ret, the signal transducing subunit of the GFL receptor complex. Analysis in mutant animals and transgenic mice overexpressing GFLs demonstrates an effect on sensitivity to thermal and mechanical stimuli in DRG neurons correlating at least partially with the altered expression of transient receptor potential ion channels and acid-sensitive cation channels. Persistence of targeted cells in mutant ganglia suggests that the alterations are caused by differentiation effects and not by cell loss. Because of the massive effect of GFLs on neurite outgrowth, it remains to be determined whether GFL signalling acts directly on neuronal specification or indirectly via altered target innervation and access to other growth factors. The data show that GFL signalling is required for the specification of subpopulations of sensory and autonomic neurons. In order to comprehend this process fully, the role of individual GFLs, the transduction of the GFL signals, and the interplay of GFL signalling with other regulatory pathways need to be deciphered

    Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

    Get PDF
    The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

    Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an