Dynamics of hyaluronan aqueous solutions as assessed by fast field cycling NMR relaxometry

Fast field cycling (FFC) NMR relaxometry has been used to study the conformational properties of aqueous solutions of hyaluronan (HYA) at three concentrations in the range 10 to 25 mg mL^–1. Results revealed that, irrespective of the solution concentration, three different hydration layers surround hyaluronan. The inner layer consists of water molecules strongly retained in the proximity of the HYA surface. Because of their strong interactions with HYA, water molecules in this inner hydration layer are subject to very slow dynamics and have the largest correlation times. The other two hydration layers are made of water molecules which are located progressively further from the HYA surface. As a result, decreasing correlation times caused by faster molecular motion were measured. The NMRD profiles obtained by FFC-NMR relaxometry also showed peaks attributable to ¹H–¹⁴N quadrupole interactions. Changes in intensity and position of the quadrupolar peaks in the NMRD profiles suggested that with increasing concentration the amido group is progressively involved in the formation of weak and transient intramolecular water bridging adjacent hyaluronan chains. In this work, FFC-NMR was used for the first time to obtain deeper insight into HYA–water interactions and proved itself a powerful and promising tool in hyaluronan chemistry.     

Amino Acid Functionalized Superparamagnetic Nanoparticles Inhibit Lysozyme Amyloid Fibrillization

Nanoparticles have great potential to be used in various biomedical applications, including therapy or diagnosis of amyloid-related diseases. The physical and chemical properties of iron oxide superparamagnetic nanoparticles (MNPs) functionalized with different amino acids (AAs), namely, with lysine (Lys), glycine (Gly), or tryptophan (Trp), have been characterized. The cytotoxicity of nanoparticles and their effect on amyloid fibrillization of lysozymes in vitro was also verified. The AA-MNPs under study are nontoxic to human SHSY5Y neuroblastoma cells. Moreover, the AA-MNPs were able to significantly inhibit lysozyme amyloid fibrillization and destroy amyloid fibrils. Kinetic studies revealed that the presence of AA-MNPs affected lysozyme fibrillization, namely, the lag phase and steady-state phase of the growth curves. The most effective activities were observed for Trp-MNPs, which revealed the importance of aromatic rings in the structure of AAs used as coating agents. The obtained results indicate the possible application of these AA-MNPs in the treatment of amyloid diseases associated with lysozyme or other amyloidogenic proteins.     

Aza-Michael reaction of 12-N-carboxamide of (–)-cytisine under high pressure conditions

The first example of aza-Michael reaction of 12-N-carboxamide of quinolizidine alkaloid (–)-cytisine with α,β-unsaturated ketones, dimethyl acetylenedicarboxylate and β-nitrostyrene under high pressure condition has been described. It has been shown that the [4+2]-cycloaddition takes place in the case with N-phenylmaleimide.     

Kinetics of the total hydrolysis of acetyl-β-methylcholine by acetylcholinesterase

Mechanism and kinetics of in vitro hydrolysis of acetyl-β-methylcholine by acetylcholinesterase from electric eel in a mixed batch reactor at 25 and 37°C, pH 8, ionic strength 0.11 M and catalytic activity of the enzyme preparat of 3.5 U mL⁻¹ were studied. The optimal kinetic parameters were determined.     

Mechanism of the antioxidant action of silybin and 2,3-dehydrosilybin flavonolignans: a joint experimental and theoretical study

Flavonolignans from silymarin, the standardized plant extract obtained from thistle, exhibit various antioxidant activities, which correlate with the other biological and therapeutic properties of that extract. To highlight the mode of action of flavonolignans as free radical scavengers and antioxidants, 10 flavonolignans, selectively methylated at different positions, were tested in vitro for their capacity to scavenge radicals (DPPH and superoxide) and to inhibit the lipid peroxidation induced on microsome membranes. The results are rationalized on the basis of (i) the oxidation potentials experimentally obtained by cyclic voltammetry and (ii) the theoretical redox properties obtained by quantum-chemical calculations (using a polarizable continuum model (PCM)-density functional theory (DFT) approach) of the ionization potentials and the O-H bond dissociation enthalpies (BDEs) of each OH group of the 10 compounds. We clearly establish the importance of the 3-OH and 20-OH groups as H donors, in the presence of the 2,3 double bond and the catechol moiety in the E-ring, respectively. For silybin derivatives (i.e., in the absence of the 2,3 double bond), secondary mechanisms (i.e., electron transfer (ET) mechanism and adduct formation with radicals) could become more important (or predominant) as the active sites for H atom transfer (HAT) mechanism are much less effective (high BDEs).     

Acclimation Response of Green Microalgae Chlorella Sorokiniana to 2,3′,4,4′,6-Pentachlorobiphenyl

The effect of the toxicant 2,3′,4,4′,6-pentachlorobiphenyl (PCB-119) on the growth, chlorophyll content, and PSII activity of C. sorokiniana cells was investigated. A strong negative effect of the toxicant was observed at PCB concentration of 0.05 μg mL⁻¹, when culture growth ceased, chlorophyll strongly bleached, and cell death occurred. The use of original highly sensitive fluorimeter to measure three types of high-resolution chlorophyll fluorescence kinetics allowed us to detect an initial dramatic decrease in the activity of primary photosynthetic reactions, followed by their almost complete recovery at the end of the incubation period when most cells were dead. The study of the distribution of individual cells in culture in terms of F_v/F_m parameter, which reflects the quantum yield of PSII photochemistry, revealed the existence of 2–3% of cells retaining high F_v/F_m (>0.7) in the presence of the toxicant. The treated cultures were able to resume growth after prolonged incubation in fresh medium. The high sensitivity fluorescence methods used made it possible to identify stress-resistant cells which maintain high photosynthetic activity in the presence of lethal doses of toxic substances; these cells provide recovery of the population after stress.     

Impact of wavelength and spot size on laser depth of focus: Considerations for mass spectrometry imaging of non-flat samples

Biospecimens with nearly flat surfaces on a flat stage are typically required for laser-based mass spectrometry imaging (MSI) techniques. However, sampling stages are rarely perfectly level, and accounting for this and the need to accommodate non-flat samples requires a deeper understanding of the laser beam depth of focus. In ablation-based MSI methods, a laser is focused on top of the sample surface, ensuring that the sample is at the focal point or remains within depth of focus. In general, the depth of focus of a given laser is related to the beam quality (M²) and the wavelength (λ). However, because laser is applied on a biological sample, other variables can also impact the depth of focus, which could affect the robustness of the MSI techniques for diverse sample types. When the height of a sample ranges outside of the depth of focus, ablated area and the corresponding ion abundances may vary as well, increasing the variability of results. In this tutorial, we examine the parameters and equations that describe the depth of focus of a Gaussian laser beam. Additionally, we describe several approaches that account for surface roughness exceeding the depth of focus of the laser.     

On variants of the Halton sequence

A generalisation of the classical Halton sequence \((\phi _{\beta }(n))_{n\in \mathbb {N}}\) has emerged in recent years based on \(\beta \)-adic expansions of elements of [0, 1). In the case where \(\beta \) is a natural number greater than 1, this reduces to the classical Halton sequence. In this paper, we use ergodic and analytic methods to prove the uniform distribution of a sequence \((\phi _{\beta }(k_j))_{j\in \mathbb {N}}\) for the sequence of integers \((k_j)_{j\ge 0}\), which is both Hartman uniformly distributed and good universal. This builds on earlier work of M. Hofer, M. R. Iaco and R. Tichy in the special case \(k_j =j \ (j=0,1, \ldots )\). Variants of this phenomenon are also studied.