“Chimie douce”: A land of opportunities for the designed construction of functional inorganic and hybrid organic-inorganic nanomaterials

Abstract“Chimie douce” based strategies allow, through the deep knowledge of materials chemistry and processing, the birth of the molecular engineering of nanomaterials. This feature article will highlight some of the main research accomplishments we have performed during the last years. We describe successively the design and properties of: sol–gel derived hybrids, Nano Building Blocks (NBBs) based hybrid materials, nanostructured porous materials proceeds as thin films and ultra-thin films, aerosol processed mesoporous powders and finally hierarchically structured materials. The importance of the control of the hybrid interfaces via the use of modern tools as DOSY NMR, SAXS, WAXS, Ellipsometry that are very useful to evaluate in situ the hybrid interfaces and the self-assembly processes is emphasized. Some examples of the optical, photocatalytic, electrochemical and mechanical properties of the resulting inorganic or hybrid nanomaterials are also presented

Processing of functional fine scale ceramic structures by ink-jet printing

International audienceThis review illustrates the potentiality of ink-jet printing for the fabrication of functional fine scale ceramic structures corresponding to two different kinds of micro-pillar arrays i.e. (i) PZT skeletons, etc..

Axion searches with the EDELWEISS-II experiment

We present new constraints on the couplings of axions and more generic axion-like particles using data from the EDELWEISS-II experiment. The EDELWEISS experiment, located at the Underground Laboratory of Modane, primarily aims at the direct detection of WIMPs using germanium bolometers. It is also sensitive to the low-energy electron recoils that would be induced by solar or dark matter axions. Using a total exposure of up to 448 kg.d, we searched for axion-induced electron recoils down to 2.5 keV within four scenarios involving different hypotheses on the origin and couplings of axions. We set a 95% CL limit on the coupling to photons $g_{A\gamma}<2.13\times 10^{-9}$ GeV$^{-1}$ in a mass range not fully covered by axion helioscopes. We also constrain the coupling to electrons, $g_{Ae} < 2.56\times 10^{-11}$, similar to the more indirect solar neutrino bound. Finally we place a limit on $g_{Ae}\times g_{AN}^{\rm eff}<4.70 \times 10^{-17}$, where $g_{AN}^{\rm eff}$ is the effective axion-nucleon coupling for $^{57}$Fe. Combining these results we fully exclude the mass range $0.91\,{\rm eV}<m_A<80$ keV for DFSZ axions and $5.73\,{\rm eV}<m_A<40$ keV for KSVZ axions

Mapping Neural Circuits with Activity-Dependent Nuclear Import of a Transcription Factor

Nuclear factor of activated T cells (NFAT) is a calcium-responsive transcription factor. We describe here an NFAT-based neural tracing method—CaLexA (calcium-dependent nuclear import of Lex A)—for labeling active neurons in behaving animals. In this system, sustained neural activity induces nuclear import of the chimeric transcription factor LexA-VP16-NFAT, which in turn drives green fluorescent protein (GFP) reporter expression only in active neurons. We tested this system in Drosophila and found that volatile sex pheromones excite specific neurons in the olfactory circuit. Furthermore, complex courtship behavior associated with multi-modal sensory inputs activated neurons in the ventral nerve cord. This method harnessing the mechanism of activity-dependent nuclear import of a transcription factor can be used to identify active neurons in specific neuronal population in behaving animals

Author Correction: Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Denotative and Connotative Semantics in Hypermedia: Proposal for a Semiotic-Aware Architecture

In this article we claim that the linguistic-centered view within hypermedia systems needs refinement through a semiotic-based approach before real interoperation between media can be achieved. We discuss the problems of visual signification for images and video in dynamic systems, in which users can access visual material in a non-linear fashion. We describe how semiotics can help overcome such problems, by allowing descriptions of the material on both denotative and connotative levels. Finally we propose an architecture for a dynamic semiotic-aware hypermedia system

DYNC2H1 hypomorphic or retina-predominant variants cause nonsyndromic retinal degeneration

Purpose: Determining the role of DYNC2H1 variants in nonsyndromic inherited retinal disease (IRD). Methods: Genome and exome sequencing were performed for five unrelated cases of IRD with no identified variant. In vitro assays were developed to validate the variants identified (fibroblast assay, induced pluripotent stem cell [iPSC] derived retinal organoids, and a dynein motility assay). Results: Four novel DYNC2H1 variants (V1, g.103327020_103327021dup; V2, g.103055779A>T; V3, g.103112272C>G; V4, g.103070104A>C) and one previously reported variant (V5, g.103339363T>G) were identified. In proband 1 (V1/V2), V1 was predicted to introduce a premature termination codon (PTC), whereas V2 disrupted the exon 41 splice donor site causing incomplete skipping of exon 41. V1 and V2 impaired dynein-2 motility in vitro and perturbed IFT88 distribution within cilia. V3, homozygous in probands 2–4, is predicted to cause a PTC in a retina-predominant transcript. Analysis of retinal organoids showed that this new transcript expression increased with organoid differentiation. V4, a novel missense variant, was in trans with V5, previously associated with Jeune asphyxiating thoracic dystrophy (JATD). Conclusion: The DYNC2H1 variants discussed herein were either hypomorphic or affecting a retina-predominant transcript and caused nonsyndromic IRD. Dynein variants, specifically DYNC2H1 variants are reported as a cause of non syndromic IRD

Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension

Background: Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats. Methods: Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed. Results: The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling. Conclusion: The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension

Identification of 4 novel human ocular coloboma genes ANK3, BMPR1B, PDGFRA, and CDH4 through evolutionary conserved vertebrate gene analysis

Purpose: Ocular coloboma arises from genetic or environmental perturbations that inhibit optic fissure (OF) fusion during early eye development. Despite high genetic heterogeneity, 70% to 85% of patients remain molecularly undiagnosed. In this study, we have identified new potential causative genes using cross-species comparative meta-analysis. Methods: Evolutionarily conserved differentially expressed genes were identified through in silico analysis, with in situ hybridization, gene knockdown, and rescue performed to confirm spatiotemporal gene expression and phenotype. Interrogation of the 100,000 Genomes Project for putative pathogenic variants was performed. Results: Nine conserved differentially expressed genes between zebrafish and mouse were identified. Expression of zebrafish ank3a, bmpr1ba/b, cdh4, and pdgfaa was localized to the OF, periocular mesenchyme cells, or ciliary marginal zone, regions traversed by the OF. Knockdown of ank3, bmpr1b, and pdgfaa revealed a coloboma and/or microphthalmia phenotype. Novel pathogenic variants in ANK3, BMPR1B, PDGFRA, and CDH4 were identified in 8 unrelated coloboma families. We showed BMPR1B rescued the knockdown phenotype but variant messenger RNAs failed, providing evidence of pathogenicity. Conclusion: We show the utility of cross-species meta-analysis to identify several novel coloboma disease-causing genes. There is a potential to increase the diagnostic yield for new and unsolved patients while adding to our understanding of the genetic basis of OF morphogenesis

Transient Reversal of Episome Silencing Precedes VP16-Dependent Transcription during Reactivation of Latent HSV-1 in Neurons

Herpes simplex virus type-1 (HSV-1) establishes latency in peripheral neurons, creating a permanent source of recurrent infections. The latent genome is assembled into chromatin and lytic cycle genes are silenced. Processes that orchestrate reentry into productive replication (reactivation) remain poorly understood. We have used latently infected cultures of primary superior cervical ganglion (SCG) sympathetic neurons to profile viral gene expression following a defined reactivation stimulus. Lytic genes are transcribed in two distinct phases, differing in their reliance on protein synthesis, viral DNA replication and the essential initiator protein VP16. The first phase does not require viral proteins and has the appearance of a transient, widespread de-repression of the previously silent lytic genes. This allows synthesis of viral regulatory proteins including VP16, which accumulate in the cytoplasm of the host neuron. During the second phase, VP16 and its cellular cofactor HCF-1, which is also predominantly cytoplasmic, concentrate in the nucleus where they assemble an activator complex on viral promoters. The transactivation function supplied by VP16 promotes increased viral lytic gene transcription leading to the onset of genome amplification and the production of infectious viral particles. Thus regulated localization of de novo synthesized VP16 is likely to be a critical determinant of HSV-1 reactivation in sympathetic neurons