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Référence électronique Sophie Hamon, Mathieu Amy et Jean-Claude Anscombre, « Présentation », Linx [En ligne], 54 | 2006, mis en ligne le 01 août 2007, consulté le 01 mars 2017. ... URL : http://linx.revues.org/490 Département de Sciences du langage, Université Paris Ouest Présentation Sophie Hamon, Université Paris X -Nanterre, UMR 7114, Mathieu Amy, Université Paris X -Nanterre, ... Sophie Hamon fournit une description globale de son expression : la cause prend une certaine forme langagière qui ne peut se réduire à la définition intuitive du concept puisqu'une cause « objective » ...doi:10.4000/linx.490 fatcat:g6i4ebqm7vhj7jwkktkidr5a6m
doi:10.3791/52476 pmid:25867540 pmcid:PMC4401155 fatcat:327rbltc2vajrlsgq6a5pycr2u
Supplementary Information Pseudomonas aeruginosa resistance of monosaccharide- Functionalized glass surfaces Mathieu Scalabrini a , Jonathan Hamon c , Isabelle Linossier a , Vincent Ferrières b and ...doi:10.1016/j.colsurfb.2019.110383 pmid:31450058 fatcat:xffhor7cubcm5gfvglrt4nkbz4
Monocytes are phagocytic effector cells in the blood and precursors of resident and inflammatory tissue macrophages. The aim of the current study was to analyse and compare their contribution to innate immune surveillance of the lung in the steady state with macrophage and dendritic cells (DC). ECFP and EGFP transgenic reporters based upon Csf1r and Cx3cr1 distinguish monocytes from resident mononuclear phagocytes. We used these transgenes to study the migratory properties of monocytes anddoi:10.7554/elife.07847 pmid:26167653 pmcid:PMC4521583 fatcat:37l5awf7pfe65ew47bcnxmybaq
more »... phages by functional imaging on explanted lungs. Migratory monocytes were found to be either patrolling within large vessels of the lung or locating at the interface between lung capillaries and alveoli. This spatial organisation gives to monocytes the property to capture fluorescent particles derived from both vascular and airway routes. We conclude that monocytes participate in steady-state surveillance of the lung, in a way that is complementary to resident macrophages and DC, without differentiating into macrophages.
The cells of the mononuclear phagocyte system are essential for the correct healing of adult skin wounds, but their specific functions remain ill-defined. The absence of granulation tissue immediately after skin injury makes it challenging to study the role of mononuclear phagocytes at the initiation of this inflammatory stage. To study their recruitment and migratory behavior within the wound bed, we developed a new model for real-time in vivo imaging of the wound, using transgenic mice thatdoi:10.1371/journal.pone.0108212 pmid:25272047 pmcid:PMC4182700 fatcat:psbtfjncqbaohhpshz74ozkxou
more »... press green and cyan fluorescent proteins and specifically target monocytes. Within hours after the scalp injury, monocytes invaded the wound bed. The complete abrogation of this infiltration in monocyte-deficient CCR2 2/2 mice argues for the involvement of classical monocytes in this process. Monocyte infiltration unexpectedly occurred as early as neutrophil recruitment did and resulted from active release from the bloodstream toward the matrix through microhemorrhages rather than transendothelial migration. Monocytes randomly scouted around the wound bed, progressively slowed down, and stopped. Our approach identified and characterized a rapid and earlier than expected wave of monocyte infiltration and provides a novel framework for investigating the role of these cells during early stages of wound healing.
Antidepressants, prescribed as first line treatment of neuropathic pain, have a limited efficacy and poorly tolerated side effects. Because recent studies pointed out the implication of astroglial connexins (Cx) in both neuropathic pain and antidepressive treatment, we investigated whether their blockade by mefloquine could modulate the action of the tricyclic antidepressant amitriptyline. Using primary cultures, we found that both mefloquine and amitriptyline inhibited Cx43-containing gapdoi:10.1038/srep38766 pmid:27941941 pmcid:PMC5150232 fatcat:daspo4g2tbh3hiuc2bd37s6wou
more »... ions, and that the drug combination acted synergically. We then investigated whether mefloquine could enhance amitriptyline efficacy in a preclinical model of neuropathic pain. Sprague-Dawley rats that underwent chronic unilateral constriction injury (CCI) to the sciatic nerve (SN) were treated with either amitriptyline, mefloquine or the combination of both drugs. Whereas acute treatments were ineffective, chronic administration of amitriptyline reduced CCI-SN-induced hyperalgesia-like behavior, and this effect was markedly enhanced by co-administration of mefloquine, which was inactive on its own. No pharmacokinetic interactions between both drugs were observed and CCI-SN-induced neuroinflammatory and glial activation markers remained unaffected by these treatments in dorsal root ganglia and spinal cord. Mechanisms downstream of CCI-SN-induced neuroinflammation and glial activation might therefore be targeted. Connexin inhibition in astroglia could represent a promising approach towards improving neuropathic pain therapy by antidepressants. Neuropathic pain, caused by lesion or dysfunction of the peripheral or central nervous system 1 , substantially affects the quality of life and is associated with heavy individual and societal burden 2 . Available treatments with anticonvulsants, antidepressants, opioids, and lidocaine or capsaicin patches are only moderately effective and may induce poorly tolerated side effects that negatively impact compliance 1-5 . Numerous peripheral and central pathways have been suggested as new therapeutic avenues 6 ; this study focused on a recently proposed target, astroglial connexins (Cxs), since these "gap junction proteins" have been reported to be involved in neuropathic pain 7 and as a target for antidepressants 8 . Connexins are transmembrane proteins, assembled as hexamers, called hemichannels (HCs) that, when open, allow direct communication between the cytoplasm and the extracellular space 9-12 . Hemichannels of adjacent cells can join to form gap junctions channels (GJCs), through which direct cytoplasm-to-cytoplasm exchanges occur 9-11 . A large variety of ions and signaling molecules (< 1 kDa) can diffuse through GJCs, which play therefore a key role in extensive ionic and biochemical exchanges between cells 9-11 . In the brain, astrocytes' coupling through GJC channels contributes to ionic homeostasis maintenance and to various biochemical/metabolic processes 9 . On the other hand, HCs are involved in astrocyte release of gliotransmitters 12,13 , uptake of glucose 14 and efflux of glutathione 15 . In astrocytes, two major Cxs have been identified, Cx43 and Cx30, both contributing to GJC. However, so far only Cx43-containing HCs have been shown to operate in astrocytes 16 . Under peripheral and central neuropathic conditions, a marked increase in Cx43 levels was reported in both dorsal root ganglia (DRG) and spinal cord tissues, during pain induction phase and its maintenance 7,17 .
Satellite altimetry is one of the main sources of information used to constrain global ocean analysis and forecasting systems. In addition to in situ vertical temperature and salinity profiles and sea surface temperature (SST) data, sea level anomalies (SLA) from multiple altimeters are assimilated through the knowledge of a surface reference, the mean dynamic topography (MDT). The quality of analyses and forecasts mainly depends on the availability of SLA observations and on the accuracy ofdoi:10.1175/jtech-d-18-0236.1 fatcat:ltt2dwno3zcn7i4xeuwmjox6yu
more »... MDT. A series of observing system evaluations (OSEs) were conducted to assess the relative importance of the number of assimilated altimeters and the accuracy of the MDT in a Mercator Ocean global 1/48 ocean data assimilation system. Dedicated tools were used to quantify impacts on analyzed and forecast sea surface height and temperature/ salinity in deeper layers. The study shows that a constellation of four altimeters associated with a precise MDT is required to adequately describe and predict upper-ocean circulation in a global 1/48 ocean data assimilation system. Compared to a one-altimeter configuration, a four-altimeter configuration reduces the mean forecast error by about 30%, but the reduction can reach more than 80% in western boundary current (WBC) regions. The use of the most recent MDT updates improves the accuracy of analyses and forecasts to the same extent as assimilating a fourth altimeter.
The Golgi resident glycosyltransferases (GTs) are membrane-bound glycoproteins but are frequently found as soluble proteins in biological fluids where their function remains largely unknown. Previous studies have established that the release of these proteins involved Alzheimer disease-associated proteases such as β-secretases (BACE1 and BACE2) and the intramembrane-cleaving aspartyl proteases Presenilins 1 and 2. Recent studies have involved another intramembrane-cleaving enzyme, the signaldoi:10.1101/317214 fatcat:6a4epiqjybgkrjngkx2ht67qaq
more »... tide peptidese-like-3 (SPPL3). Except for the latter, the two former studies mostly addressed particular cases of GTs, namely ST6Gal-I (BACEs) or GnT-V (Presenilins). Therefore the question still remains as which of these secretases is truly responsible for the cleavage and secretion of GTs. We herein combined the 3 proteases in a single study with respect to their abilities to release 3 families of GTs encompassing three N-acetylglucosaminyltransferases, two fucosyltransferases and two sialyltransferases. Green fluorescent protein (gfp)-fused versions of these GTs were virally transduced in mouse embryonic fibroblasts devoid of BACEs, Presenilins or SPPL3. We found that neither BACE nor Presenilins are involved in the shedding of these glycosyltransferases, while SPPL3 was involved in the cleavage and release of some but not all GTs. Notably, the γ-secretase inhibitor DFK-167 was the only molecule capable of significantly decreasing glycosyltransferase secretion, suggesting the involvement of γ-secretase(s), yet different from Presenilins but comprising SPPL3 among other proteases still to be identified. Using confocal microscopy, we show that SPPL3 selectivity towards GTs relays not only on sequence specificity but also depends on how GTs distribute in the cell with respect SPPL3 during their cycling within and outside the Golgi.
Astrocytes are glial cells organized in dynamic and structured networks in the brain. These plastic networks, involving key proteins such as connexin 43 (Cx43), are engaged in fine neuronal tuning and have recently been considered as emerging therapeutic targets in central nervous system disorders. We developed and validated a new application of the manganese-enhanced magnetic resonance imaging (MEMRI) technique allowing in vivo investigations of astrocyte-neuron interactions throughdoi:10.1038/s41598-019-54858-9 pmid:31797899 pmcid:PMC6892890 fatcat:twzs5l5vqnbmbkwr7ht4nvareu
more »... ion of brain Cx43 functional activity. The proof of concept has been achieved by quantification of MEMRI signals in brain after either local astrocyte-specific Cx43 knockdown with shRNA or systemic administration of Cx43 blockers. Unilateral hippocampal Cx43 genetical silencing was associated with an ipsilateral local increase of MEMRI signal. Furthermore, Cx43 blockers also enhanced MEMRI signal responses in hippocampus. Altogether, these data reveal the MEMRI technique as a tool for quantitative imaging of in vivo Cx43-dependent function in astrocytes under physiological and pathological conditions.
Donepezil is a potent acetylcholinesterase inhibitor, largely used worldwide to alleviate cognitive symptoms in Alzheimer's disease (AD). Beyond the widely described neuronal impact of donepezil, it was recently shown that targeting connexins, the proteins involved in astrocyte network organization, potentiates donepezil efficacy profile using behavioral tests in AD rodent models. We herein present data demonstrating the potential of functional ultrasound imaging to monitor cerebral activitydoi:10.3389/fnins.2020.00835 pmid:32903470 pmcid:PMC7437134 fatcat:o7lonnqdr5bcjdbveo3ppuhpkm
more »... nges after pharmacological challenge in mice. As an example, we showed that although administration of donepezil or mefloquine alone at low dose had only very limited effects on the signal compared to the baseline, their combination produced marked hemodynamic effects in the hippocampus, in line with previously published behavioral data demonstrating a synergic interaction between both drugs. Thus, the present study provides new perspectives, (i) through the use of pharmaco-fUS, a new non-clinical imaging modality, to move forward drug discovery in AD and (ii) by the profiling of two drug treatments on brain dynamics, one used in AD: donepezil, and the other in development: donepezil combined with mefloquine (THN201) as a modulator of astrocyte network.
Whispering gallery mode resonators (WGMRs) trap light over many optical periods using total internal reflection. Thereby, they host multiple narrowband circulating modes that find applications in quantum electrodynamics, optomechanics, sensing and lasing. The spherical symmetry and low field leakage of dielectric microspheres make it difficult to probe their high-quality optical modes using far-field radiation. However, local field enhancement from metallic nanoparticles (MNPs) placed at thearXiv:2110.02119v1 fatcat:6v5ejkwlufhu3lb7mwjzhpfauu
more »... e of the resonators can interface the optical far-field and the bounded cavity modes. In this work, we study the interaction between whispering gallery modes and the MNP surface plasmons with nanometric spatial resolution by using electron-beam spectroscopies in a scanning transmission electron microscope. We show that gallery modes are induced over the spectral range of the dipolar plasmons of the nanoparticle. Additionally, we explore the dependence of the transverse electric and transverse magnetic polarization of the induced gallery mode on the induced dipole moment of the MNP. Our study demonstrates a viable mechanism to effectively excite high-quality-factor whispering gallery modes and holds potential for applications in optical sensing and light manipulation.
Mathieu Hamon: Methodology. Simon Van Gennip: Writing -review & editing. Jean-Michel Lellouche: Methodology, Writing -review & editing. ... ., 2015; Hamon et al., 2019) and significant improvements of ocean monitoring systems have been attributed to a more accurate MDT Guiavarc'h et al., 2019) . ...doi:10.1016/j.ocemod.2021.101768 fatcat:pjqxm5pjmvgebb5le66fbdfbnu
Donepezil (DPZ) is an acetylcholinesterase inhibitor used in Alzheimer's disease to restore cognitive functions but is endowed with limited efficacy. Recent studies pointed out the implication of astroglial networks in cognitive processes, notably via astrocyte connexins (Cxs), proteins involved in gap junction intercellular communications. Hence, we investigated the impact on cognition of pharmacological or genetic modulations of those astrocyte Cxs during DPZ challenge in two rodent models ofdoi:10.3389/fnins.2020.00563 pmid:32612499 pmcid:PMC7309601 fatcat:kklbbxvq2ffrnnz35ew5zzk67i
more »... Alzheimer's disease-like memory deficits. We demonstrated that the Cx modulator mefloquine (MEF) significantly enhanced the procognitive effect of DPZ in both models. In parallel, we determined that MEF potentiated DPZ-induced release of acetylcholine in hippocampus. Finally, local genetic silencing of astrocyte Cxs in the hippocampus was also found to enhance the procognitive effect of DPZ, pointing out the importance of Cx-dependent astrocyte networks in memory processes.
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