Nonlinear optical properties of interconnected gold nanoparticles on silicon

International audienceWe report second harmonic generation (SHG) measurements in reflectivity from chains of gold nanoparticles interconnected with metallic bridges. We measured more than 30 times a SHG enhancement when a surface plasmon resonance was excited in the chains of nanoparticles, which was influenced by coupling due to the electrical connectivity of the bridges. This enhancement was confirmed by rigorous coupled wave method calculations and came from high localization of the electric field at the bridge. The introduction of 10% random defects into the chains of nanoparticles dropped the SHG by a factor of 2 and was shown to be very sensitive to the fundamental wavelengt

The impact of transposable element activity on therapeutically relevant human stem cells

Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use, including genomic instability and tumorigenesis concerns. Thus, a deeper understanding of the factors and molecular mechanisms contributing to stem cell genome stability are a prerequisite to harnessing their therapeutic potential for degenerative diseases. Chemical and physical factors are known to influence the stability of stem cell genomes, together with random mutations and Copy Number Variants (CNVs) that accumulated in cultured human stem cells. Here we review the activity of endogenous transposable elements (TEs) in human multipotent and pluripotent stem cells, and the consequences of their mobility for genomic integrity and host gene expression. We describe transcriptional and post-transcriptional mechanisms antagonizing the spread of TEs in the human genome, and highlight those that are more prevalent in multipotent and pluripotent stem cells. Notably, TEs do not only represent a source of mutations/CNVs in genomes, but are also often harnessed as tools to engineer the stem cell genome; thus, we also describe and discuss the most widely applied transposon-based tools and highlight the most relevant areas of their biomedical applications in stem cells. Taken together, this review will contribute to the assessment of the risk that endogenous TE activity and the application of genetically engineered TEs constitute for the biosafety of stem cells to be used for substitutive and regenerative cell therapiesS.R.H. and P.T.R. are funded by the Government of Spain (MINECO, RYC-2016- 21395 and SAF2015–71589-P [S.R.H.]; PEJ-2014-A-31985 and SAF2015–71589- P [P.T.R.]). GGS is supported by a grant from the Ministry of Health of the Federal Republic of Germany (FKZ2518FSB403)

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

MECANISMES DE RENVERSEMENT DE L'AIMANTATION DANS DES COUCHES COUPLEES PAR ECHANGE DIRECT AVEC DU NIO ET DANS DES JONCTIONS TUNNEL

ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Photonique et plasmonique appliquées à la détection biomoléculaire

ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Near- and Far-Field Effects on the Plasmon Coupling in Gold Nanoparticle Arrays

International audienceUnderstanding the plasmon coupling between metal nanoparticles under light irradiation remains a challenging issue for optimizing plasmonic devices for chemical and biological sensing. Here, the optical properties of dense spatially ordered two-dimensional arrays of 50 nm gold nanoparticles are investigated in this aim. Microspectrophotometry experiments are carried out on square arrays and parallel chains, elaborated by electron beam lithography, having different periodicities ranging from 80 to 170 nm. The wavelength, width, and amplitude of the localized surface plasmon resonance (SPR) are quantitatively monitored as a function of both the incident light polarization and the interparticle distance. The experimental findings are then compared with calculations based on the discrete dipole approximation. They match remarkably well these numerical results, not only for the spectral location and the width of the SPR but also for the absolute value of the extinction cross section of the nanoparticles that is linked with the local field enhancement. The variation of the SPR band characteristics as a function of the periodicity of the arrays is investigated in terms of near field and far field coupling effects by discussing the topography of the field amplitude and phase in the arrays Moreover, in order to highlight the influence of phase retardation and radiative effects on the plasmon coupling, the optical properties of equivalent arrays scaled by 1/10, which can be qualitatively described by electrostatic dipolar interactions, are also studied by numerical calculations The discrepancies then observed between the two scales are interpreted. The contributions of the radiative and nonradiative dampings to the width and magnitude of the plasmon resonance are also investigated

Metallic nanoparticle chains on dielectric waveguides: coupled and uncoupled situations compared

International audienceWe investigate the optical behaviors of metallic nanoparticle (MNP) chains supporting localized surface plasmon (LSP) for different distances between particles. MNPs are excited through the fundamental TE mode of a silicon waveguide. Finite difference time domain (FDTD) calculations and optical power transmission measurements reveal three different behaviors. For short distances between particles, dipolar coupling occurs, and the MNP chain behaves as a waveguide. For the longest distances, nanoparticles are uncoupled, and the MNP chain acts as a LSP Bragg grating. Finally, for intermediate distances, we observe one behavior at a time, i.e. dipolar coupling or LSP Bragg reflection. There is only a small range of wavelengths within which both behaviors can coexist

Two-dimensional filtering in the Fourier domain of transient grating coherent artifacts in time-resolved spectroscopy

Removal of coherent artifacts is important in the analysis of time and wavelength resolved spectroscopy data. By taking advantage of the strong correlation between spectra acquired sequentially in time, artifact removal can be formulated as a 2D problem for improved effectiveness. This paper proposes a 2D method to remove transient grating coherent artifacts from femtosecond time-resolved spectroscopy data based on filtering in the Fourier domain, leading to better estimation of the material parameters from the measured data. The method is simple, intuitive, and light on computation resources. The effectiveness of the method is demonstrated with experimental data acquired from a bare gold film with and without coherent artifacts using mutually parallel and perpendicular pump/probe polarizations, as well as with more complex samples (nanostructured gold film on a glass substrate and rhodamine fluorophores in solution). The proposed method is expected to be applicable to coherent artifact removal in other types of time and wavelength-resolved spectroscopy data

Comparison between conventional and next generation lithography for bimodal SPRI-SERS biosensors

International audienc