Phoenixine-20-amide does not bind heterologously expressed GPR173

GPR173 (SREB3) is an orphan GPCR of the ‘Superconserved Receptors Expressed in the Brain’ family with high mRNA levels expressed in the hypothalamus, cortex and cerebellum. Phoenixin-20-amide (P20A), an endogenous hypothalamic ligand regulating ovarian cyclicity (Ullah et al., 2017; Stein et al., 2016), has been suggested to activate GPR173. In vitro studies on gonadotrophs showed that P20A stimulates GPR173, thereby increasing cAMP production, resulting in an elevated hypothalamic ‘Gonadotrophin Releasing Hormone Receptor’ (GnRHR) and kisspeptine expression, eventually increasing luteinizing hormone (LH) secretion (Treen et al., 2016; Stein et al., 2016). However, using the Promega GloSensor™ Technology, we failed to observe GPR173 mediated changes of cyclic AMP concentrations in HEK293 cellular models upon stimulation with P20A. Furthermore, it has been suggested that GPR173 could be stimulated by GnRH1_5 to trigger the recruitment of arrestin-3 in neurons co-expressing GnRHR, thereby inhibiting developmental neuronal migration (Larco et al., 2013). In our hands, with an arrestin-3-based firefly luciferase complementation assay in heterologously tranfected HEK293 cells, GPR173 was not able to recruit arrestin-3 upon stimulation with neither P20A nor GnRH1_5. Finally, GPR173 did neither bind any promiscuous g-proteins upon stimulation with P20A nor show any constitutive activity. Whether P20A influences the secretion of LH has not been studied, but P20A did not directly activate GPR173 in none of our assays. Nevertheless, transfected cellular models should be distinguished from native systems. Further studies are therefore necessary to determine if an endogenous partner is missing in our models and might be responsible for the previously reported results

The AT(1)/AT(2) Receptor Equilibrium Is a Cornerstone of the Regulation of the Renin Angiotensin System beyond the Cardiovascular System

The AT(1) receptor has mainly been associated with the pathological effects of the renin-angiotensin system (RAS) (e.g., hypertension, heart and kidney diseases), and constitutes a major therapeutic target. In contrast, the AT(2) receptor is presented as the protective arm of this RAS, and its targeting via specific agonists is mainly used to counteract the effects of the AT(1) receptor. The discovery of a local RAS has highlighted the importance of the balance between AT(1)/AT(2) receptors at the tissue level. Disruption of this balance is suggested to be detrimental. The fine tuning of this balance is not limited to the regulation of the level of expression of these two receptors. Other mechanisms still largely unexplored, such as S-nitrosation of the AT(1) receptor, homo- and heterodimerization, and the use of AT(1) receptor-biased agonists, may significantly contribute to and/or interfere with the settings of this AT(1)/AT(2) equilibrium. This review will detail, through several examples (the brain, wound healing, and the cellular cycle), the importance of the functional balance between AT(1) and AT(2) receptors, and how new molecular pharmacological approaches may act on its regulation to open up new therapeutic perspectives

Oriented Gold Nanorods and Gold Nanorod Chains within Smectic Liquid Crystal Topological Defects

International audienceWe show that the use of oriented linear arrays of smectic A defects, the so-called smectic oily streaks, enables the orientation of gold nanorods (GNRs) for a large range of GNR diameters, ranging from 7 to 48 nm, and for various ligands. For the small GNRs it enables oriented end-to-end small chains of GNRs when the density is increased from around 2 GNRs/μm2 to around 6 GNRs/μm2. We have characterized the orientation of single GNRs by spectrophotometry and two-photon luminescence (TPL). A strongly anisotropic absorption of the composites and an on–off switching of GNR luminescence, both controlled by incident light polarization, are observed, revealing an orientation of the GNRs mostly parallel to the oily streaks. A more favorable trapping of GNRs by smectic dislocations with respect to ribbon-like defects is thus demonstrated. The dislocations appear to be localized at a specific localization, namely, the summit of rotating grain boundaries. Combining plasmonic absorption measurements, TPL measurements, and simulation of the plasmonic absorption, we show that the end-to-end GNR chains are both dimers and trimers, all parallel to each other, with a small gap between the coupled GNRs, on the order of 1.5 nm, thus associated with a large red-shift of 110 nm of the longitudinal plasmonic mode. A motion of the GNRs along the dislocations appears as a necessary ingredient for the formation of end-to-end GNR chains, the gap value being driven by the balance between the attracting van der Waals interactions and the steric repulsion between the GNRs and leading to interdigitation of the neighboring ligands. We thus obtain electromagnetic coupling of nanorods controlled by light polarization

Virtual reality-based sensorimotor adaptation shapes subsequent spontaneous and naturalistic stimulus-driven brain activity

Our everyday life summons numerous novel sensorimotor experiences, to which our brain needs to adapt in order to function properly. However, tracking plasticity of naturalistic behavior and associated brain modulations is challenging. Here, we tackled this question implementing a prism adaptation-like training in virtual reality (VRPA) in combination with functional neuroimaging. Three groups of healthy participants (N = 45) underwent VRPA (with a shift either to the left/right side, or with no shift), and performed functional magnetic resonance imaging (fMRI) sessions before and after training. To capture modulations in free-flowing, task-free brain activity, the fMRI sessions included resting-state and free-viewing of naturalistic videos. We found significant decreases in spontaneous functional connectivity between attentional and default mode (DMN)/fronto-parietal networks, only for the adaptation groups, more pronouncedly in the hemisphere contralateral to the induced shift. In addition, VRPA was found to bias visual responses to naturalistic videos: Following rightward adaptation, we found upregulation of visual response in an area in the parieto-occipital sulcus (POS) only in the right hemisphere. Notably, the extent of POS upregulation correlated with the size of the VRPA-induced after-effect measured in behavioral tests. This study demonstrates that a brief VRPA exposure can change large-scale cortical connectivity and correspondingly bias visual responses to naturalistic sensory inputs

Le port et la ville : les espaces de transition entre la ville et les 5 ports de Lorient

Available at INIST (FR), Document Supply Service, under shelf-number : RP 12993 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Primary and secondary emissions of pellets and logwood residential heating appliances: emissions factors, secondary aerosol formation potential and chemical characterization

International audienceTo decrease the dependence on fossil fuels and to limitglobal warming, the use of renewable energy hassignificantly increased over the last decade in Europe.Biomass energy has been largely promoted forresidential heating due to its (almost) neutralityconcerning CO2 emissions. However, residential woodcombustion accounts for an important source of airpollution as it emits large quantities of fine particulatematter (PM2.5), black carbon (BC) and volatile and semivolatileorganic compounds (VOCs and SVOCs) that areprecursors of secondary organic aerosol (SOA). Thequantity and composition of the emissions vary largelyaccording to the appliance, the fuel used and theoperating conditions. In particular, pellets appliancesare an interesting alternative to logwood ones due totheir lower primary emissions of PM2.5 and organicgaseous compounds (Olsen et al., 2020). To date, onlylimited information is available on the secondaryaerosol formation from pellets residential heatingappliances while several studies have shown the highSOA formation potential from logwood stoves emissions(Bertrand et al., 2017; Heringa et al., 2012). It istherefore urgent to evaluate the secondary emissions ofpellet devices as well as primary PM and BC emissions inorder to assess their impact on air quality. The aims ofthis study are to determine the emission factors ofprimary pollutants and secondary aerosol formationpotential of pellets and logwood appliances with adetailed chemical characterization of both gaseous andparticulate phases.Experiments have been carried out underdifferent output conditions (nominal and reduced) usingthree modern pellet boilers and stoves and one modernlogwood boiler and stove. In addition, two types ofpellets (soft and hard wood) have been tested. Afterdilution (20-40 times), biomass burning emissions wereaged through a potential aerosol mass-oxidation flowreactor (PAM-OFR) (Kang et al., 2007) at ambienttemperature and environmentally relevant relativehumidity (40-70%). Both daytime (with OH radical) andnight-time (with NO3 radical, only for the logwoodstove) chemistry have been investigated. Furthermore,“pure” secondary particles, formed by filtering (HEPAfilter) the entering emissions into the PAM-OFR, werealso studied. Primary and secondary emissions weremonitored using a high resolution-time of flight-aerosolmass spectrometer (HR-ToF-AMS), a scanning mobilityparticle sizer (SMPS), a condensation particle counter(CPC), a multi wavelength aethalometer, a TEOM-50(non-volatile PM fraction), a proton transfer reactiontime-of-flight mass spectrometer (PTR-ToF-MS) and gasanalyzers (CO2, O2, CO, NOx, total VOCs) providinginformation on the particulate and gaseous chemicalcomposition, particulate size distribution and numberconcentration. Moreover, effective particle density atdifferent aerosol size ranges have been investigated bycombining a differential mobility analyzer (DMA) and acentrifugal particle mass analyzer (CPMA). Finally,samples (filters and adsorbents) have been manuallycollected at the emission and after dilution forgravimetry and offline chemical analysis purposes.Primary (notably PM and BC) and secondaryemissions measured will be compared and discussed interms of wood appliances, output conditions and fuelused. Insights on the chemical composition of bothgaseous and particulate phases will be presented.This work was supported by ADEME (Agency forecological transition) under grant 206C0004 and theFrench Ministry of Environment

Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease

Germline mutations in CYBB, the human gene encoding the gp91(phox) subunit of the phagocyte NADPH oxidase, impair the respiratory burst of all types of phagocytes and result in X-linked chronic granulomatous disease (CGD). We report here two kindreds in which otherwise healthy male adults developed X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD) syndromes. These patients had previously unknown mutations in CYBB that resulted in an impaired respiratory burst in monocyte-derived macrophages but not in monocytes or granulocytes. The macrophage-specific functional consequences of the germline mutation resulted from cell-specific impairment in the assembly of the NADPH oxidase. This \u27experiment of nature\u27 indicates that CYBB is associated with MSMD and demonstrates that the respiratory burst in human macrophages is a crucial mechanism for protective immunity to tuberculous mycobacteria