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Obstructive sleep apnea (OSA), a breathing disorder featured by chronic intermittent hypoxia (CIH) is associated with pulmonary hypertension (PH). Rodents exposed to CIH develop pulmonary vascular remodeling and PH, but the pathogenic mechanisms are not well known. Overexpression of Stim-activated Transient Receptor Potential Channels (TRPC) and Calcium Release-Activated Calcium Channel Protein (ORAI) TRPC-ORAI Ca 2+ channels (STOC) has been involved in pulmonary vascular remodeling and PH in sustained hypoxia. However, it is not known if CIH may change STOC levels. Accordingly, we studied the effects of CIH on the expression of STOC subunits in the lung and if these changes paralleled the progression of the vascular pulmonary remodeling and PH in a preclinical model of OSA. Male Sprague-Dawley rats (∼200 g) were exposed to CIH (5%O 2 , 12 times/h for 8 h) for 14, 21, and 28 days. We measured right ventricular systolic pressure (RVSP), cardiac morphometry with MRI, pulmonary vascular remodeling, and wire-myographic arterial responses to KCl and endothelin-1 (ET-1). Pulmonary RNA and protein STOC levels of TRPC1, TRPC4, TRPC6, ORAI 1, ORAI 2, and STIM1 subunits were measured by qPCR and western blot, and results were compared with age-matched controls. CIH elicited a progressive increase of RVSP and vascular contractile responses to KCl and ET-1, leading to vascular remodeling and augmented right ventricular ejection fraction, which was significant at 28 days of CIH. The levels of TRPC1, TRPC4, TRPC 6, ORAI 1, and STIM 1 channels increased following CIH, and some of them paralleled morphologic and functional changes. Our findings show that CIH increased pulmonary STOC expression, paralleling vascular remodeling and PH.

[ES] El presente documento describe el desarrollo de un sistema integral para la optimización del proceso de entrega de los productos de una farmacia, a través de la reducción de los tiempos de búsqueda de estos. Partiendo de un mobiliario de almacenaje adecuado para farmacias, y de una instalación electroneumática que opera el mobiliario ya diseñados, se procede a diseñar un sistema de control basado en Arduino para gobernar dicha instalación electroneumática, todo ello comandado desde un software programado que se ejecuta desde el ordenador del farmacéutico de la farmacia, y desde donde se puede gestionar el stock de los productos, [EN] This document describes the development of an integral system for the optimization of the delivery process of the products of a pharmacy, through the reduction of the time it takes to find them. Starting from a storage furniture suitable for pharmacies, and an electro-pneumatic installation that operates the furniture already designed, we proceed to design a control system based on Arduino to govern this electro-pneumatic installation, all commanded from a programmed software that runs from the computer of the pharmacist of the pharmacy, and from where the stock of products can be managed, [CA] El present document descriu el desenvolupament d'un sistema integral per a l'optimització del procés de lliurament dels productes d'una farmàcia, a través de la reducció dels temps de cerca d'aquests. Partint d'un mobiliari de magatzematge adequat per a farmàcies, i d'una instal·lació electropneumàtica que opera el mobiliari ja dissenyats, es procedeix a dissenyar un sistema de control basat en Arduino per a governar aquesta instal·lació electropneumàtica, tot això comandat des d'un software programat que s'executa des de l'ordinador del farmacèutic de la farmàcia, i des d'on es pot gestionar l'estoc dels productes

Slides and abstract from the BCC2020 talk "Producing biodiversity indicators from citizen science projects: update of birds and bats monitoring schemes on Galaxy-E" Video capture of the talk is available here: https://vimeo.com/437705490, Video capture of the talk is available here: https://vimeo.com/437705490

International audience; Capsule A first-time observer effect in the new French breeding bird survey (BBS) was found to result from new observers learning how to use the point count method on randomly selected sites. Aims To estimate the first-year effect in a newly started BBS, to look for correlates and test for a temporal trend in learning. Methods Trends of 105 species were estimated using data from 2001-2007 obtained by 1100 observers conducting point counts over 1535 randomly selected squares. I estimated the average increase in detected numbers between the first and all subsequent years of survey at a site. Results Observers counted 4.3% more birds in subsequent years than during the initial year of survey. This first-year effect decreased from 2001 to 2007 (by an average of 2% per year). It was not related to most variables known to influence species detection probability. Only species with songs of lower sound frequencies (ranging from 0.5 to 8 kHz here) displayed a greater increase in locally detected numbers. Conclusion The detected first-year effect was the result of method learning by new observers who had not previously conducted point counts or visited randomly selected sites. The learning effect was larger for species with songs of lower sound frequency which are harder to hear during the dawn chorus.; Pour la première fois l'effet observateur dans la nouvelle enquête de relevé d'oiseaux nicheurs (BBS) français a été trouvé et résultait des nouveaux observateurs qui apprennent à utiliser la méthode de point de comptage sur des sites choisis au hasard. Objectifs : estimer l'effet première année dans un BBS nouvellement ouvert, pour trouver des corrélations et pour tester une temporelle tendance lors de l'apprentissage. Méthodes : Les tendances de 105 espèces ont été estimées en utilisant les données de 2001-2007 obtenues par des observateurs qui procèdent aux dénombrements 1100 points par rapport à 1535 places choisies au hasard. J'ai estimé que l'augmentation moyenne du nombre détectés entre le premier et toutes les années suivantes de l'enquête sur un site. Résultats : Les observateurs comptent 4,3% d'oiseaux en plus les années suivantes que durant la première année de l'enquête. Cet effet première année a diminué de 2001 à 2007 (en moyenne de 2% par an). Il n'était pas lié à la plupart des variables connues pour influencer la probabilité de détection des espèces. Seules les espèces avec des chants de faibles fréquences (de 0,5 à 8 kHz ici) affichent une plus grande augmentation du nombre détecté localement. Conclusion L'effet première année détecté était le résultat de la méthode d'apprentissage des nouveaux observateurs qui n'avaient pas précédemment menées de comptage ponctuels ou visité des sites choisis au hasard. L'effet d'apprentissage a été plus important pour les espèces avec des chants de fréquence faible qui sont plus difficiles à entendre durant le chant des oiseaux à l'aube

Ca(2+) sparks are highly localized cytosolic Ca(2+) transients caused by a release of Ca(2+) from the sarcoplasmic reticulum via ryanodine receptors (RyRs); they are the elementary events underlying global changes in Ca(2+) in skeletal and cardiac muscle. In smooth muscle and some neurons, Ca(2+) sparks activate large conductance Ca(2+)-activated K(+) channels (BK channels) in the spark microdomain, causing spontaneous transient outward currents (STOCs) that regulate membrane potential and, hence, voltage-gated channels. Using the fluorescent Ca(2+) indicator fluo-3 and a high speed widefield digital imaging system, it was possible to capture the total increase in fluorescence (i.e., the signal mass) during a spark in smooth muscle cells, which is the first time such a direct approach has been used in any system. The signal mass is proportional to the total quantity of Ca(2+) released into the cytosol, and its rate of rise is proportional to the Ca(2+) current flowing through the RyRs during a spark (I(Ca(spark))). Thus, Ca(2+) currents through RyRs can be monitored inside the cell under physiological conditions. Since the magnitude of I(Ca(spark)) in different sparks varies more than fivefold, Ca(2+) sparks appear to be caused by the concerted opening of a number of RyRs. Sparks with the same underlying Ca(2+) current cause STOCs, whose amplitudes vary more than threefold, a finding that is best explained by variability in coupling ratio (i.e., the ratio of RyRs to BK channels in the spark microdomain). The time course of STOC decay is approximated by a single exponential that is independent of the magnitude of signal mass and has a time constant close to the value of the mean open time of the BK channels, suggesting that STOC decay reflects BK channel kinetics, rather than the time course of [Ca(2+)] decline at the membrane. Computer simulations were carried out to determine the spatiotemporal distribution of the Ca(2+) concentration resulting from the measured range of I(Ca(spark)). At the onset of a spark, the Ca(2+) concentration within 200 nm of the release site reaches a plateau or exceeds the [Ca(2+)](EC50) for the BK channels rapidly in comparison to the rate of rise of STOCs. These findings suggest a model in which the BK channels lie close to the release site and are exposed to a saturating [Ca(2+)] with the rise and fall of the STOCs determined by BK channel kinetics. The mechanism of signaling between RyRs and BK channels may provide a model for Ca(2+) action on a variety of molecular targets within cellular microdomains.

Because of its reversibility and adaptability, deep brain stimulation (DBS) has recently gained interest in psychiatric disorders, such as obsessive-compulsive disorders (OCD) and depression. In OCD, DBS is now an alternative procedure to lesions of fascicles such as the anterior capsule, which links the orbitofrontal cortex, the cingulum, and the thalamus, and has been applied to new target such as the nucleus accumbens, with promising results. However, a recent interest has been developed toward the subthalamic nucleus (STN), a key structure of the basal ganglia that connects the motor, limbic, and associative systems. It is known from patients with Parkinson disease that STN-DBS can have significant effects on mood and cognition. Those transient effects are usually seen as "side effects" in Parkinson disease, but are clues to the underappreciated role that STN plays in the limbic circuitry, a role whose precise details are as yet unknown and under active investigation. We present the rationale supporting the use of nonmotor STN as a therapeutic target to treat OCD. In particular, we discuss the recent experience and preliminary results of our group after 6 months of nonmotor STN-DBS in patients with severe OCD.

Ca(2+) sparks are small, localized cytosolic Ca(2+) transients due to Ca(2+) release from sarcoplasmic reticulum through ryanodine receptors. In smooth muscle, Ca(2+) sparks activate large conductance Ca(2+)-activated K(+) channels (BK channels) in the spark microdomain, thus generating spontaneous transient outward currents (STOCs). The purpose of the present study is to determine experimentally the level of Ca(2+) to which the BK channels are exposed during a spark. Using tight seal, whole-cell recording, we have analyzed the voltage-dependence of the STOC conductance (g((STOC))), and compared it to the voltage-dependence of BK channel activation in excised patches in the presence of different [Ca(2+)]s. The Ca(2+) sparks did not change in amplitude over the range of potentials of interest. In contrast, the magnitude of g((STOC)) remained roughly constant from 20 to -40 mV and then declined steeply at more negative potentials. From this and the voltage dependence of BK channel activation, we conclude that the BK channels underlying STOCs are exposed to a mean [Ca(2+)] on the order of 10 microM during a Ca(2+) spark. The membrane area over which a concentration > or =10 microM is reached has an estimated radius of 150-300 nm, corresponding to an area which is a fraction of one square micron. Moreover, given the constraints imposed by the estimated channel density and the Ca(2+) current during a spark, the BK channels do not appear to be uniformly distributed over the membrane but instead are found at higher density at the spark site.