An altered lipid metabolism characterizes Charcot-Marie-Tooth type 2B peripheral neuropathy

Charcot-Marie Tooth type 2B (CMT2B) is a rare inherited peripheral neuropathy caused by five missense mutations in the RAB7A gene, which encodes a small GTPase of the RAB family. Currently, no cure is available for this disease. In this study, we approached the disease by comparing the lipid metabolism of CMT2B-derived fibroblasts to that of healthy controls. We found that CMT2B cells showed increased monounsaturated fatty acid level and increased expression of key enzymes of monounsaturated and polyunsaturated fatty acid synthesis. Moreover, in CMT2B cells a higher expression of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), key enzymes of de novo fatty acid synthesis, with a concomitantly increased [1-14C]acetate incorporation into fatty acids, was observed. The expression of diacylglycerol acyltransferase 2, a rate-limiting enzyme in triacylglycerol synthesis, as well as triacylglycerol levels were increased in CMT2B compared to control cells. In addition, as RAB7A controls lipid droplet breakdown and lipid droplet dynamics have been linked to diseases, we analyzed these organelles and showed that in CMT2B cells there is a strong accumulation of lipid droplets compared to control cells, thus reinforcing our data on abnormal lipid metabolism in CMT2B. Furthermore, we demonstrated that ACC and FAS expression levels changed upon RAB7 silencing or overexpression in HeLa cells, thus suggesting that metabolic modifications observed in CMT2B-derived fibroblasts can be, at least in part, related to RAB7 mutations

3D time-domain beam mapping for studying nonlinear dynamics in multimode optical fibers

The characterization of the complex spatiotemporal dynamics of optical beam propagation in nonlinear multimode fibers requires the development of advanced measurement methods, capable of capturing the real-time evolution of beam images. We present a new space-time mapping technique, permitting the direct detection, with picosecond temporal resolution, of the intensity from repetitive laser pulses over a grid of spatial samples from a magnified image of the output beam. By using this time-resolved mapping, we provide the first unambiguous experimental observation of instantaneous intrapulse nonlinear coupling processes among the modes of a graded index fiber.Comment: 4 pages, 6 figure

A Bio-Conjugated Fullerene as a Subcellular-Targeted and Multifaceted Phototheranostic Agent

Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C70@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C70@lysozyme are confirmed using UV-visible and 2D 1H, 15N NMR spectroscopy. The excellent imaging contrast of C70@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C70@lysozyme and its ability to initiate cell death by means of singlet oxygen (1O2) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C70@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications

3D time-domain beam mapping for studying nonlinear dynamics in multimode optical fibers

Characterization of the complex spatiotemporal dynamics of optical beam propagation in nonlinear multimode fibers requires the development of advanced measurement methods, capable of capturing the real-time evolution of beam images. We present a new space–time mapping technique, permitting the direct detection, with picosecond temporal resolution, of the intensity from repetitive laser pulses over a grid of spatial samples from a magnified image of the output beam. By using this time-resolved mapping, we provide, to the best of our knowledge, the first unambiguous experimental observation of instantaneous intrapulse nonlinear coupling processes among the modes of a graded index fiber

Robust three-dimensional high-order solitons and breathers in driven dissipative systems: a Kerr cavity realization

We present a general approach to excite robust dissipative three-dimensional and high-order solitons and breathers in passively driven nonlinear cavities. Our findings are illustrated in the paradigmatic example provided by an optical Kerr cavity with diffraction and anomalous dispersion, with the addition of an attractive three-dimensional parabolic potential. The potential breaks the translational symmetry along all directions, and impacts the system in a qualitatively unexpected manner: three-dimensional solitons, or light-bullets, are the only existing and stable states for a given set of parameters. This property is extremely rare, if not unknown, in passive nonlinear physical systems. As a result, the excitation of the cavity with any input field leads to the deterministic formation of a target soliton or breather, with a spatiotemporal profile that unambiguously corresponds to the given cavity and pumping conditions. In addition, the tuning of the potential width along the temporal direction results in the existence of a plethora of stable asymmetric solitons. Our results may provide a solid route towards the observation of dissipative light bullets and three-dimensional breathers

Mode decomposition method for investigating the nonlinear dynamics of a multimode beam

We overview our recent experimental studies on the nonlinear spatial reshaping of multimode beams at the output of multimode optical fibers. We use a holographic mode decomposition technique, which permits to reveal the variation of the spatial mode composition at the fiber output, as determined by either conservative (the Kerr effect) or dissipative (Raman scattering) nonlinear processes. For the first case, we consider the effect of spatial beam self-cleaning, and we compare experimental mode decompositions with predictions based on the thermodynamic theory, including the case of beams carrying nozero orbital angular momentum. For the second case, we analyze the beam mode content at the output of a Raman laser based on a graded index multimode fiber

Label-free biomechanical nanosensor based on LSPR for biological applications

A label-free localized surface plasmon resonance (LSPR)-based biosensor exploiting gold nanorods (ONRs) is proposed and demonstrated. For this aim, 35 +/- 5 nm long and 20 +/- 4 thick GNRs spaced by a few nanometers thick polyelectrolytes (PE) from a gold thin film was analyzed and synthesized. The morphology of the GNRs, the plasmon properties of GNRs, swelling of PE layers and the wettability of the surfaces were characterized by transmission and scanning electron microscopy, spectroscopic reflectivity and contact angle measurements, respectively. Indeed, when immersed in a phosphate buffer saline solution, the GNRs-PE-gold system shows an optical shift of the LSPR wavelength. This shift was found to correspond to a vertical swelling of about 2 nm, demonstrating the extreme sensitivity of the biosensor. Finally, we show that LSPR measurements can be used to detect dynamic resonance changes in response to both thickness and buffer solution, while the hydrophobic behavior of the surface can be exploited for reducing the number of liquid analytes in clinical biosensing application. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen

Nonlinear multimode fiber optics: recent advances

We start by providing an overview of the emerging field of nonlinear optics in multimode optical fibers [1]. These fibers provide a simple testbed for observing complex wave propagation dynamics, in analogy with other fields of physics ranging from two-dimensional hydrodynamic turbulence and Bose-Einstein condensation. In addition, nonlinear multimode optical fibers enable new methods for achieving the ultrafast, light-activated control of temporal, spatial and spectral degrees of freedom of intense, pulsed light beams, for a range of different technological applications

Spatial Division Multiplexing for Multiplex Coherent Anti-Stokes Raman Scattering

We demonstrate how a narrowband pump and a broadband spectrum can be spatially multiplexed by selective coupling them in two distinct modes of a few-mode microstructure fiber. The first mode carries most of the input pump energy, and experiences spectral broadening. Whereas the second mode preserves the narrow bandwidth of the remaining part of the pump. Bimodal propagation, with a power unbalance strongly in favor of the fundamental mode, is naturally obtained by maximizing coupling into the fundamental mode of the fiber. At the fiber output, the nearly monochromatic beam and the supercontinuum carried by the two different modes are combined by a microscope objective, and used as a pump and a Stokes wave for self-referenced multiplex coherent anti-Stokes Raman scattering micro-spectroscopy. The spectral resolution, the signal-to-noise-ratio, and the possible amplification of the remaining pump beam are discussed.Comment: 10 pages, 9 figure