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Although the Na-K-Cl cotransporter (NKCC1) inhibitor bumetanide has prominent positive effects on the pathophysiology of many neurological disorders, the mechanism of action is obscure. Attention for elucidating the role of Nkcc1 has been mainly focused on neurons. Recent single cell mRNA sequencing analysis has demonstrated that the major cellular populations expressing NKCC1 in the cortex are non-neuronal. We used a combination of conditional transgenic animals, in vivo electrophysiology, two-photon imaging, cognitive behavioral tests and flow cytometry to investigate the role of Nkcc1 inhibition by bumetanide in a mouse model of controlled cortical impact (CCI). Here, we found that bumetanide rescues parvalbumin-positive interneurons by increasing interneuron-microglia contacts shortly after injury. The longitudinal phenotypic changes of microglia were significantly modified by bumetanide, including an increase in the expression of microglial-derived Bdnf. These effects were accompanied by the prevention of CCI-induced decrease in hippocampal neurogenesis. Treatment with bumetanide during the first week post-CCI resulted in significant recovery of working and episodic memory as well as changes in theta band oscillations one month later. These results disclose a novel mechanism for the neuroprotective action of bumetanide mediated by an acceleration of microglial activation dynamics that leads to an increase of parvalbumin interneuron survival following CCI, possibly resulting from increased microglial Bdnf expression and contact with interneurons. Salvage of interneurons may normalize ambient gamma-aminobutyric acid (GABA), resulting in the preservation of adult neurogenesis processes as well as contributing to bumetanide-mediated improvement of cognitive performance.

Quiescence is essential for the long-term maintenance of adult stem cells but how stem cells maintain quiescence is poorly understood. Here, we show that neural stem cells (NSCs) in the adult mouse hippocampus actively transcribe the pro-activation factor Ascl1 regardless of their activated or quiescent states. We found that the inhibitor of DNA binding protein Id4 is enriched in quiescent NSCs and that elimination of Id4 results in abnormal accumulation of Ascl1 protein and premature stem cell activation. Accordingly, Id4 and other Id proteins promote elimination of Ascl1 protein in NSC cultures. Id4 sequesters Ascl1 heterodimerization partner E47, promoting Ascl1 protein degradation and stem cell quiescence. Our results highlight the importance of non-transcriptional mechanisms for the maintenance of NSC quiescence and reveal a role for Id4 as a quiescence-inducing factor, in contrast with its role of promoting the proliferation of embryonic neural progenitors., eLife digest Stem cells in embryos give rise to all the tissues in the body. Adults also have stem cells, but they are fewer in number and they are usually dedicated to repairing and regenerating specific tissues. A region of the brain called the hippocampus, which is involved in learning, memory and mood, has a pool of neural stem cells. These cells can produce new brain cells long into adulthood, but maintaining their regenerative potential is a balancing act. Enough new brain cells need to be made to keep up with the brain’s demands, but if every stem cell matured into a brain cell, the brain’s capacity for repair would be lost. So, some neural stem cells hit a metaphorical snooze button to enter a resting state known as quiescence. Stem cells in the hippocampus make a protein called Ascl1 that interacts with DNA to switch on quiescent cells so they will divide and mature. Left unchecked, Ascl1 could deplete the stem cell supply, so resting stem cells must have a way to turn Ascl1 off, but it was previously unknown how. Clues point to the E proteins, which interact with Ascl1 to allow it to bind to DNA. If the E proteins are not present, Ascl1 cannot work as a genetic switch. E proteins can also interact with inhibitor of DNA binding/differentiation proteins, known as Id proteins for short. To find out whether Id proteins affect Ascl1 activity, Blomfield et al. looked at stem cells in the hippocampus of adult mice, and at quiescent stem cells grown in the laboratory. Blomfield et al. showed that all stem cells in the hippocampus make Ascl1, but its levels are much lower when stem cells are resting. This difference was down to an Id protein called Id4. In resting stem cells, Id4 interacted with E proteins, preventing them from binding to Ascl1, and stopping Ascl1 from ‘waking up’ the cells. This not only left Ascl1 unable to activate its target genes, it also made it vulnerable to destruction by the cell's protein recycling system. Mice with no Id4 in their hippocampus stem cells had higher levels of Ascl1, and their stem cells were more active. The number of stem cells in a resting state increases as we age, and in illnesses like depression, limiting brain cell replacement. Uncovering the signals that switch Id4 on or off could reveal why stem cells rest more with age and illness. This could help us find ways to kick-start the production of new brain cells in adulthood.

We report experiments in which positronium (Ps) atoms were created in thin, porous silica films containing isolated voids with diameters ranging from 5 to 75 nm. Ps lifetimes in the pore structures were measured directly via time-delayed laser excitation of ${1}^{3}{S}_{1}\ensuremath{\rightarrow}{2}^{3}{P}_{J}$ transitions. In a film containing 5-nm pores Ps was predominantly emitted into vacuum, with a small component of confined Ps with a lifetime of 75 ns also observed. In films with larger pores Ps atoms were not emitted into vacuum except from the film surface, and confined Ps lifetimes of $\ensuremath{\approx}90$ ns were measured with no dependence on the pore size. However, for such large pores, extended Tao-Eldrup (ETE)-type models predict Ps lifetimes close to the 142-ns vacuum value. Moreover, ${1}^{3}{S}_{1}\ensuremath{\rightarrow}{2}^{3}{P}_{J}$ excitation of Ps atoms inside the pores was found to result in annihilation and exhibited an extremely broad $(\ensuremath{\approx}10$ THz) linewidth. We attribute these observations to a process in which nonthermal Ps atoms in the isolated voids become temporarily trapped in a series of surface states that dissociate following excitation. The occurrence of this mechanism is not necessarily apparent from ground-state Ps decay rates without some prior knowledge of the sample structure, and it precludes the application of ETE-type models as they do not take into account surface interactions other than pickoff annihilation.

The wavelength used during photochemical grafting of alkene onto silicon related surfaces influences molecular surface coverage. Ultraviolet light leads to apparent highly dense layers on UV absorbing materials due to the side reaction between alkenes resulting in strongly physisorbed dimers whereas higher wavelengths lead to dense and well-controlled layers.

A transparent glass or ceramic or glass-ceramic substrate, coated with a functional layer or with a stack of at least two functional layers, the functional layer or at least one of the functional layers of the stack being porous and made of an inorganic material M1, wherein the or at least one of the porous functional layer(s) of inorganic material M1 has, at the surface of at least one portion of the pores thereof, at least one inorganic material M2 different from M1.

International audience; Proneural proteins, which include Ascl1, Atoh1 and Neurogenins e ´ piniè re in vertebrates and Achaete-Scute proteins and Atonal in Drosophila, are expressed in the developing nervous system throughout the animal kingdom and have an essential and well-characterised role in specifying the neural identity of progenitors. New properties and additional roles of these factors have emerged in recent years, including the regulation of stem cell proliferation and the capacity to reprogram many types of cells into neurons. This review will focus on these recent findings. The review will also discuss the mechanisms that allow proneural proteins to induce the transcription of their target genes in different chromatin contexts and the phosphorylation events and other post-transcriptional mechanisms that regulate the proneural proteins themselves.

A travers un exercice périlleux d’égo-histoire, cette contribution sur le groupe Bérurier Noir s’attache à présenter des aspects culturels et politiques de la genèse du groupe alternatif des années 1980. L’auteur a privilégié une perspective culturelle qui permet de mieux comprendre les sources d’inspiration des chansons et des thématiques portées par ce groupe musical entre 1983 et 1989. Au fil de quatre temps forts, les lecteurs sont plongés dans un tourbillon d’actions débutant au lycée Paul Valéry (Paris 12e), se poursuivant dans la rue sur le Parvis Beaubourg, les squatts et l’Usine Pali-Kao, pour investir le Zénith de Paris en mars 1988, le Québec et finalement l’Olympia les 9, 10 et 11 novembre 1989 alors que le mur de Berlin tombe. Sur le plan culturel, l’imaginaire élaboré par Bérurier Noir au fil de son existence est dévoilé : du cinéma d’avant-garde japonais aux films politiques européens, de la bande à Baader-Meinhof à l’association Actes Energie Perdue, de la boutique Harry Cover (aux Halles) aux dojos de Karaté, du « No future » au « Yes future », du noir & blanc à la couleur. En outre, l’Asie apparaît comme le fil conducteur invisible d’une expérience plus personnelle. Cette contribution peut se concevoir comme un essai d’interprétation d’une histoire culturelle en construction. Through a perilous exercise of ego-history, this contribution seeks to present cultural and political aspects of the genesis of Bérurier Noir, the famous French alternative musical band of the 1980s. In order to better understanding the sources of inspiration of songs and themes carried by this group between 1983 and 1989, the author have privileged a cultural perspective. By four highlights, readers are immersed in a whirlwind of actions debuting at lycée Paul Valéry (Paris 12th district), continuing in the streets of Paris in alternative and artistic places, in the Zenith in March 1988, in Quebec (Canada) and finally at the Olympia concert hall on the 9, 10 and 11 November 1989 when the Berlin Wall fell. Culturally, the imaginary developed by Bérurier Noir throughout its existence is unveiled: Japanese avant-garde cinema and European political films, the Baader-Meinhof group influence and the artistic association Actes Energie Perdue, from the Harry Cover shop (Les Halles in the centre of Paris) to Karate dojos, from "No future" to "future Yes", from black & white to color. In addition, Asia emerges as the invisible thread of a more personal experience. This contribution can be seen as a tentative interpretation of a cultural history in progress.

Summary The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program., Graphical Abstract, Highlights • Genome-wide binding of Ascl1 correlates with transcription activation • Ascl1 can bind to both open and closed chromatin in proliferating cells • Ascl1 promotes local chromatin accessibility at its target sites • Chromatin dynamics at Ascl1 sites regulates temporal progression of its program, The proneural transcription factor Ascl1 sequentially activates target genes in proliferating and differentiating progenitors during neurogenesis. Here Raposo et al. show that Ascl1 binds closed and open chromatin in proliferating cells. Binding to closed chromatin promotes accessibility and activation of differentiation specific genes. Thus, dynamics of chromatin landscape at Ascl1 target regions regulate the temporal onset of Ascl1 targets.

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International audience; BACKGROUND & AIMS: Albumin infusion improves renal function and survival in cirrhotic patients with spontaneous bacterial peritonitis (SBP) but its efficacy in other types of infections remains unknown. We investigated this issue through a multicenter randomized controlled trial.METHODS: A total of 193 cirrhotic patients with a Child-Pugh score greater than 8 and sepsis unrelated to SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kg on day 1 and 1g/kg on day 3; albumin group [ALB]: n=96) or antibiotics alone (control group [CG]: n=97). The primary endpoint was the 3-month renal failure rate (increase in creatinine ⩾50% to reach a final value ⩾133 μmol/L). The secondary endpoint was 3-month survival rate.RESULTS: Forty-seven (24.6%) patients died (ALB: n=27 vs. CG: n=20; 3-month survival: 70.2% vs. 78.3%; p=0.16). Albumin infusion delayed the occurrence of renal failure (mean time to onset, ALB: 29.0 ± 21.8 vs. 11.7 ± 9.1 days, p=0.018) but the 3-month renal failure rate was similar (ALB: 14.3% vs. CG: 13.5%; p=0.88). By multivariate analysis, MELD score (pCONCLUSIONS: In cirrhotic patients with infections other than SBP, albumin infusion delayed onset of renal failure but did not improve renal function or survival at 3 months. Infusion of large amounts of albumin should be cautiously administered in the sickest cirrhotic patients.

International audience; The optimization of functional optical devices requires the appropriate control of light propagation, which can be achieved by using engineered dielectric structures. Innovative materials combination and fabrication strategies are required to achieve a robust gain in performance without impacting manufacturing complexity and cost. In the present work, a novel liquid-based approach is proposed for the simple and scalable fabrication of highly effi - cient and robust optical multilayer dielectric coatings. In particular, a sol-gel process is developed that enables the fabrication of large-area distributed Bragg refl ectors (DBR) integrating macroporous materials of controlled closed porosity. The DBRs have a very high index contrast, excellent and tunable optical properties, and high stability of performance and structural integrity with respect to crack formation and delamination, even against harsh ageing tests or solvent exposure. The potential of this approach to be integrated within existing optoelectronic architectures is demonstrated through the integration of a DBR structure as a back refl ector in an amorphous silicon solar cell (a-Si:H), resulting in a signifi cant increase in light absorption, photocurrent, and overall effi ciency. This opens the way towards simple dielectric engineering of robust photoactive devices based on the versatile use of liquid routes for the deposition of structured dielectric coatings.

International audience; Oligodendrocytes are the myelin-forming cells of the CNS. They differentiate from oligodendrocyte precursor cells (OPCs) that are produced from progenitors throughout life but more actively during the neonatal period and in response to demyelinating insults. An accurate regulation of oligodendrogenesis is required to generate oligodendrocytes during these developmental or repair processes. We hypothesized that this regulation implicates transcription factors, which are expressed by OPCs and/or their progenitors. Ascl1/Mash1 is a proneural transcription factor previously implicated in embryonic oligodendrogenesis and operating in genetic interaction with Olig2, an essential transcriptional regulator in oligodendrocyte development. Herein, we have investigated the contribution of Ascl1 to oligodendrocyte development and remyelination in the postnatal cortex. During the neonatal period, Ascl1 expression was detected in progenitors of the cortical subventricular zone and in cortical OPCs. Different genetic approaches to delete Ascl1 in cortical progenitors or OPCs reduced neonatal oligodendrogenesis, showing that Ascl1 positively regulated both OPC specification from subventricular zone progenitors as well as the balance between OPC differentiation and proliferation. Examination of remyelination processes, both in the mouse model for focal demyelination of the corpus callosum and in multiple sclerosis lesions in humans, indicated that Ascl1 activity was upregulated along with increased oligodendrogenesis observed in remyelinating lesions. Additional genetic evidence indicated that remyelinating oligodendrocytes derived from Ascl1(+) progenitors/OPCs and that Ascl1 was required for proper remyelination. Together, our results show that Ascl1 function modulates multiple steps of OPC development in the postnatal brain and in response to demyelinating insults.

International audience; We aimed to identify cis-regulatory elements that control gene expression in progenitors of the cerebral cortex. A list of 975 putative enhancers were retrieved from a ChIP-Seq experiment performed in NS5 mouse stem cells with antibodies to Sox2, Brn2/Pou3f2, or Brn1/Pou3f3. Through a selection pipeline including gene ontology and expression pattern, we reduced the number of candidate enhancer sequences to 20. Ex vivo electroporation of green fluorescent pProtein (GFP) reporter constructs in the telencephalon of mouse embryos showed that 35% of the 20 selected candidate sequences displayed enhancer activity in the developing cortex at E13.5. In silico transcription factor binding site (TFBS) searches and mutagenesis experiments showed that enhancer activity is related to the presence of Sox/Pou TFBS pairs in the sequence. Comparative genomic analyses showed that enhancer activity is not related to the evolutionary conservation of the sequence. Finally, the combination of in utero electroporation of GFP reporter constructs with immunostaining for Tbr2 (basal progenitor marker) and phospho-histoneH3 (mitotic activity marker) demonstrated that each enhancer is specifically active in precise subpopulations of progenitors in the cortical germinal zone, highlighting the heterogeneity of these progenitors in terms of cis-regulation.

SummaryHuntingtin is the protein mutated in Huntington's disease, a devastating neurodegenerative disorder. We demonstrate here that huntingtin is essential to control mitosis. Huntingtin is localized at spindle poles during mitosis. RNAi-mediated silencing of huntingtin in cells disrupts spindle orientation by mislocalizing the p150Glued subunit of dynactin, dynein, and the large nuclear mitotic apparatus NuMA protein. This leads to increased apoptosis following mitosis of adherent cells in vitro. In vivo inactivation of huntingtin by RNAi or by ablation of the Hdh gene affects spindle orientation and cell fate of cortical progenitors of the ventricular zone in mouse embryos. This function is conserved in Drosophila, the specific disruption of Drosophila huntingtin in neuroblast precursors leading to spindle misorientation. Moreover, Drosophila huntingtin restores spindle misorientation in mammalian cells. These findings reveal an unexpected role for huntingtin in dividing cells, with potential important implications in health and disease.

International audience; Porous sol−gel silica films are prepared using different PMMA latex nanoparticles, 30−80 nm in diameter, as sacrificial templates. By changing the size and the content of the latex particles in the deposited silica sol, it was possible for the first time to tailor the porosity of the sol−gel films (uniform pore size and porous fraction from 0.10 to 0.74) independently of their thickness. This is the consequence of a low microporosity in the silica walls as shown by the correspondence between the measured porous fraction after calcination and the starting latex volume fraction. No ethanol capillary condensation occurs in these films before high partial pressure (above 0.9), leading to a stable refractive index that can be tuned in a large range (from 1.15 to 1.40 at 600 nm). A porosity percolation transition with the opening of the extrinsic pore interconnection was observed at a pore fraction threshold of about 0.40 for different sizes of the initial template. Below the threshold, the films showed a closed porosity structure with a low stable refractive index (down to 1.29 at 600 nm), opening the way to their use for antireflective applications.

Thin films with low-refractive index are of great interest to adjust the optical properties of optical components, e.g. reflectivity. In this respect, sol-gel coatings are very efficient for flat glass functionalisation because of ease of application, low cost and versatility. Mesoporous silica films prepared by surfactant self-assembly have been extensively studied but show poor refractive index stability as capillary condensation of atmospheric water can occur in the pores. One way to tackle this issue is to prepare films with larger pores for which capillary condensation is impossible at ambient humidity. Starting from custom made latex nanoparticles, we successfully prepared sol-gel porous silica film with pore size above 30nm and no microporosity in the silica walls. We are then able to independently and accurately tailor pore size, pore volume fraction and pore surface chemistry, leading to a stable refractive index that can be tuned in a large range (from 1.15 to 1.40 at 600 nm). Pore accessibility as a function of pore size and porous fraction was investigated through ellipsometry-porosimetry for ethanol adsorption, and a transition between open and closed pore structure at decreasing volume fraction was shown. Below the threshold, the films showed a closed porosity structure with a low stable refractive index (down to 1.29 at 600 nm), opening the way to their use for antireflective applications.

International audience; La mémoire et l’histoire font du Viêt Nam un terrain d’observation particulièrement complexe. Traversé par la révolution indépendantiste, les guerres (civile et internationale) et les exils, le pays a retrouvé la paix au prix d’un sacrifice humain profondément inscrit dans l’histoire mondiale. Le séminaire Mémoires d’Indochine dispensé à l’Institut d’Asie Orientale (IAO) s’est attaché depuis dix ans à élaborer une histoire d’en bas, à l’aune du vécu des populations locales. Pour clore cette recherche collective, cette projection/débat propose deux trajectoires d’exils vietnamiens en France. Celui d’une femme, Jeanne Dang, restituée par les images animées allégoriques de Bach-Hông, et celui d’un homme, l’Oncle Liêm puis de son fils, interviewés, par Juliette Galli. Ces deux récits interrogent tout à la fois passé et le présent, les brûlures de l’histoire et les souvenirs personnels.

This dissertation presents an exploratory and pluridiscplinary study about domestic violence in Vietnam, in order to rethink the Vietnamese society after the social and economic Renovation. This study, through a focus on gender and Vietnamese feminities and masculinities, aims for reinterpreting the theory and a culturalist reading, by underlining the stakes of a phenomenon and bringing up some responses to the issue.; Le présent travail est une étude exploratoire et pluridisciplinaire sur les violences conjugales au Vietnam, permettant de repenser le fonctionnement de la société vietnamienne en pleine transformation après le Renouveau social et économique. Cette étude, à travers un focus sur le genre ainsi que sur les féminités et masculinités vietnamiennes, a pour but de réinterpréter la théorie ainsi qu’une lecture culturaliste, en éclairant les enjeux d’un phénomène et en apportant des éléments de réponses au problème.