Sub-Threshold Fabrication of Laser-Induced Periodic Surface Structures on Diamond-like Nanocomposite Films with IR Femtosecond Pulses

In the paper, we study the formation of laser-induced periodic surface structures (LIPSS) on diamond-like nanocomposite (DLN) a-C:H:Si:O films during nanoscale ablation processing at low fluences—below the single-pulse graphitization and spallation thresholds—using an IR fs-laser (wavelength 1030 nm, pulse duration 320 fs, pulse repetition rate 100 kHz, scanning beam velocity 0.04–0.08 m/s). The studies are focused on microscopic analysis of the nanostructured DLN film surface at different stages of LIPSS formation and numerical modeling of surface plasmon polaritons in a thin graphitized surface layer. Important findings are concerned with (i) sub-threshold fabrication of high spatial frequency LIPSS (HSFL) and low spatial frequency LIPSS (LSFL) under negligible surface graphitization of hard DLN films, (ii) transition from the HSFL (periods of 140 ± 30 and 230 ± 40 nm) to LSFL (period of 830–900 nm) within a narrow fluence range of 0.21–0.32 J/cm², (iii) visualization of equi-field lines by ablated nanoparticles at an initial stage of the LIPSS formation, providing proof of larger electric fields in the valleys and weaker fields at the ridges of a growing surface grating, (iv) influence of the thickness of a laser-excited glassy carbon (GC) layer on the period of surface plasmon polaritons excited in a three-layer system “air/GC layer/DLN film”.     

Marinobufagenin,an endogenous ligand of alpha-1 sodium pump,is a marker of congestive heart failure severity

BACKGROUND : A reduced cardiac output in chronic heart failure (CHF) evokes renal NaCl and water retention, and, therefore, activates mechanisms promoting natriuresis. Atrial natriuretic peptide (ANP) is one such factor. We hypothesized that another NaCl sensitive endogenous natriuretic factor, i.e., marinobufagenin (MBG), a specific ligand of the alpha-1 subunit of Na/K ATPase (the main kidney isoform) and also a vasoconstrictor and cardiotonic substance, would be elevated in CHF patients in a graded manner with the severity of CHF. METHODS AND RESULTS : We measured the plasma levels of MBG, alpha-hANP, ouabain-like compound (OLC) and left ventricular (LV) volumes and ejection fraction in 23 consecutive hypertensive male patients with CHF. Plasma MBG levels exhibited progressive increases (0.59 +/- 0.15, 1.08 +/- 0.20, 1.35 +/- 0.17 and 1.88 +/- 0.05 nmol/l NYHA 1-4, respectively) and paralleled the changes of alpha-hANP. Conversely, plasma OLC did not exhibit such increases. Plasma MBG correlated with alpha-hANP (r = 0.82; P < 0.0001). Both MBG and alpha-hANP correlated with LV systolic (r = 0.55 and r = 0.47; P < 0.01) diameter and inversely with ejection fraction (r = -0.73 and r = -0.60; P < 0.01). OLC did not exhibit correlations with alpha-hANP or LV volumes, but positively correlated with systolic brachial blood pressure and with pulse pressure. CONCLUSIONS : In CHF, MBG exhibits progressive increases similar to ANP, varies with CHF severity and correlates with LV systolic function. We hypothesize, that, in CHF, the concurrent production of these two natriuretic hormones, a vasorelaxant, ANP, and a vasoconstrictor, MBG, potentiate each other's natriuretic effects, but may offset their vasoactive actions.     

High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis

High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is a new and promising approach to the treatment of multiple sclerosis (MS) patients because currently there are no effective treatment methods for this disease. In this article, we present results of a prospective clinical study of efficacy of HDIT + auto-HSCT in MS patients. The following treatment strategies were employed in the study: "early," "conventional," and "salvage/late" transplantation. Fifty patients with various types of MS were included in this study. No toxic deaths were reported among 50 MS patients; transplantation procedure was well-tolerated by the patients. The efficacy analysis was performed in 45 patients. Twenty-eight patients achieved an objective improvement of neurological symptoms, defined as at least 0.5-point decrease in the Expanded Disability Status Scale (EDSS) score as compared to the baseline and confirmed during 6 months, and 17 patients had disease stabilization (steady EDSS level as compared to the baseline and confirmed during 6 months). The progression-free survival at 6 years after HDIT + auto-HSCT was 72%. Magnetic resonance imaging data were available in 37 patients before transplantation showing disease activity in 43.3%. No active, new, or enlarging lesions were registered in patients without disease progression. In conclusion, HDIT + auto-HSCT suggests positive results in management of patients with different types of MS. Identification of treatment strategies based on the level of disability, namely "early," "conventional," and "salvage/late" transplantation, appears to be feasible to improve treatment outcomes.     

Amelioration of Neurosensory Structure and Function in Animal and Cellular Models of a Congenital Blindness

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Retinal ganglion cell topography and spatial resolution in the Japanese smelt Hypomesus nipponensis (McAllister, 1963)

Vision plays a crucial role in the life of the vast majority of vertebrate species. The spatial arrangement of retinal ganglion cells has been reported to be related to a species’ visual behavior. There are many studies focusing on the ganglion cell topography in bony fish species. However, there are still large gaps in our knowledge on the subject. We studied the topography of retinal ganglion cells (GCs) in the Japanese smelt Hypomesus nipponensis, a highly visual teleostean fish with a complex life cycle. DAPI labeling was used to visualize cell nuclei in the ganglion cell and inner plexiform layers. The ganglion cell layer was relatively thin (about 6-8 μm), even in areas of increased cell density (area retinae temporalis), and was normally composed of a single layer of cells. In all retinal regions, rare cells occurred in the inner plexiform layer. Nissl-stained retinae were used to estimate the proportion of displaced amacrine cells and glia in different retinal regions. In all retinal regions, about 84.5% of cells in the GC layer were found to be ganglion cells. The density of GCs varied across the retina in a regular way. It was minimum (3990 and 2380 cells/mm² in the smaller and larger fish, respectively) in the dorsal and ventral periphery. It gradually increased centripetally and reached a maximum of 14,275 and 10,960 cells/mm² (in the smaller and larger fish, respectively) in the temporal retina, where a pronounced area retinae temporalis was detected. The total number of GCs varied from 177 × 10³ (smaller fish) to 212 × 10³ cells (larger fish). The theoretical anatomical spatial resolution (the anatomical estimate of the upper limit of visual acuity calculated from the density of GCs and eye geometry and expressed in cycles per degree) was minimum in the ventral periphery (smaller fish, 1.46 cpd; larger fish, 1.26 cpd) and maximum in area retinae temporalis (smaller fish, 2.83 cpd; larger fish, 2.75 cpd). The relatively high density of GCs and the presence of area retinae temporalis in the Japanese smelt are consistent with its highly visual behavior. The present findings contribute to our understanding of the factors affecting the topography of retinal ganglion cells and visual acuity in fish.     

Malignant and benign thyroid nodule differentiation through the analysis of blood plasma with terahertz spectroscopy

The liquid and lyophilized blood plasma of patients with benign or malignant thyroid nodules and healthy individuals were studied by terahertz (THz) time-domain spectroscopy and machine learning. The blood plasma samples from malignant nodule patients were shown to have higher absorption. The glucose concentration and miRNA-146b level were correlated with the sample’s absorption at 1 THz. A two-stage ensemble algorithm was proposed for the THz spectra analysis. The first stage was based on the Support Vector Machine with a linear kernel to separate healthy and thyroid nodule participants. The second stage included additional data preprocessing by Ornstein-Uhlenbeck kernel Principal Component Analysis to separate benign and malignant thyroid nodule participants. Thus, the distinction of malignant and benign thyroid nodule patients through their lyophilized blood plasma analysis by terahertz time-domain spectroscopy and machine learning was demonstrated.     

The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport

Fast axonal transport is characterized by the bidirectional, microtubule-based movement of membranous organelles. Cytoplasmic dynein is necessary but not sufficient for retrograde transport directed from the synapse to the cell body. Dynactin is a heteromultimeric protein complex, enriched in neurons, that binds to both microtubules and cytoplasmic dynein. To determine whether dynactin is required for retrograde axonal transport, we examined the effects of anti-dynactin antibodies on organelle transport in extruded axoplasm. Treatment of axoplasm with antibodies to the p150^Glued subunit of dynactin resulted in a significant decrease in the velocity of microtubule-based organelle transport, with many organelles bound along microtubules. We examined the molecular mechanism of the observed inhibition of motility, and we demonstrated that antibodies to p150^Glued disrupted the binding of cytoplasmic dynein to dynactin and also inhibited the association of cytoplasmic dynein with organelles. In contrast, the anti-p150^Glued antibodies had no effect on the binding of dynactin to microtubules nor on cytoplasmic dynein-driven microtubule gliding. These results indicate that the interaction between cytoplasmic dynein and the dynactin complex is required for the axonal transport of membrane-bound vesicles and support the hypothesis that dynactin may function as a link between the organelle, the microtubule, and cytoplasmic dynein during vesicle transport.     

Normal vibrations of ternary DOPC/DPPC/cholesterol lipid bilayers by low-frequency Raman spectroscopy

A lipid bilayer containing a ternary mixture of low- and high-melting lipids and cholesterol (Chol) can give rise to domain formation, referred to as lipid rafts. Low-frequency Raman spectroscopy at reduced temperatures allows detection of normal membrane mechanical vibrations. In this work, Raman spectra were obtained in the spectral range between 5 and 90 cm⁻¹ for bilayers prepared from dioleoyl-glycero-phosphocholine (DOPC), dipalmitoyl-glycero-phosphocholine (DPPC) and Chol. A narrow peak detected between 13 and 16 cm⁻¹ was attributed to the vibrational eigenmode of a lipid monolayer (a leaflet). For the equimolar DOPC/DPPC ratio, the Chol concentration dependence for the peak position, width and amplitude may be divided into three distinct ranges: below 9 mol%, the intermediate range between 9 mol% and 38 mol%, and above 38 mol%. In the intermediate range the peak position attains its minimum, and the peak width drops approximately by a factor of two as compared with the Chol-free bilayers. Meanwhile, this range is known for raft formation in a fluid state. The obtained results may be interpreted as evidence that bilayer structures in the raft-containing fluid state may be frozen at low temperatures. The drop of peak width indicates that at the spatial scale of the experiment (∼2.5 nm) the intermolecular bilayer structure with raft formation becomes more homogeneous and more cohesive.

Upon lipid raft formation, the Raman peak corresponding to monolayer normal mechanical vibrations drops remarkably in position and width.