Subcellular Duplex DNA and G‐Quadruplex Interaction Profiling of a Hexagonal PtII Metallacycle

Metal‐driven self‐assembly afforded a multitude of fascinating supramolecular coordination complexes (SCCs) with applications as catalysts, host–guest, and stimuli‐responsive systems. However, the interest in the biological applications of SCCs is only starting to emerge and thorough characterization of their behavior in biological milieus is still lacking. Herein, we report on the synthesis and detailed in‐cell tracking of a Pt₂L₂ metallacycle. We show that our hexagonal supramolecule accumulates in cancer cell nuclei, exerting a distinctive blue fluorescence staining of chromatin resistant to UV photobleaching selectively in nucleolar G4‐rich regions. SCC co‐localizes with epitopes of the quadruplex‐specific antibody BG4 and replaces other well‐known G4 stabilizers. Moreover, the photophysical changes accompanying the metallacycle binding to G4s in solution (fluorescence quenching, absorption enhancement) also take place intracellularly, allowing its subcellular interaction tracking.     

Turbulent Drag Reduction by a Near Wall Surface Tension Active Interface

In this work we study the turbulence modulation in a viscosity-stratified two-phase flow using Direct Numerical Simulation (DNS) of turbulence and the Phase Field Method (PFM) to simulate the interfacial phenomena. Specifically we consider the case of two immiscible fluid layers driven in a closed rectangular channel by an imposed mean pressure gradient. The present problem, which may mimic the behaviour of an oil flowing under a thin layer of different oil, thickness ratio h₂/h₁ =?9, is described by three main flow parameters: the shear Reynolds number Re _τ (which quantifies the importance of inertia compared to viscous effects), the Weber number We (which quantifies surface tension effects) and the viscosity ratio λ = ν₁/ν₂ between the two fluids. For this first study, the density ratio of the two fluid layers is the same (ρ₂ = ρ₁), we keep Re _τ and We constant, but we consider three different values for the viscosity ratio: λ =?1, λ =?0.875 and λ =?0.75. Compared to a single phase flow at the same shear Reynolds number (Re _τ =?100), in the two phase flow case we observe a decrease of the wall-shear stress and a strong turbulence modulation in particular in the proximity of the interface. Interestingly, we observe that the modulation of turbulence by the liquid-liquid interface extends up to the top wall (i.e. the closest to the interface) and produces local shear stress inversions and flow recirculation regions. The observed results depend primarily on the interface deformability and on the viscosity ratio between the two fluids (λ).     

Quality of twelve clarithromycin dry syrup formulations-bitterness, grittiness and uniformity of drug loading

The objective of the study was to evaluate the bitterness, grittiness and uniformity of drug loading as measures of the quality of 12 formulations of clarithromycin dry syrup (CAMDS), comprising one branded and 11 generic products. Some of the generic CAMDS formulations were more bitter than the branded product while others had similar bitterness when tested as aqueous suspensions. Only one generic product was less bitter than the branded product when tested as a suspension in acidic sports drink. The usual dissolution test described in JP XV could not be used to evaluate the bitterness of the products. A brief dissolution test using only 12.5 ml of water was used to evaluate the bitterness of the products in aqueous suspensions. There were considerable variances in the grittiness of the various products, which were independent of particle size. Changes in grittiness level seemed to be correlated with changes in the intensity of bitterness due to the disintegration of the formulation. Finally, there was less variation in the uniformity of drug loading for the branded product than for the generic products. These data may be useful when selecting which CAMDS formulation to prescribe.     

Speeding up biomolecular interactions by molecular sledding

Numerous biological processes involve association of a protein with its binding partner, an event that is preceded by a diffusion-mediated search bringing the two partners together. Often hindered by crowding in biologically relevant environments, three-dimensional diffusion can be slow and result in long bimolecular association times. Similarly, the initial association step between two binding partners often represents a rate-limiting step in biotechnologically relevant reactions. We demonstrate the practical use of an 11-a.a. DNA-interacting peptide derived from adenovirus to reduce the dimensionality of diffusional search processes and speed up associations between biological macromolecules. We functionalize binding partners with the peptide and demonstrate that the ability of the peptide to one-dimensionally diffuse along DNA results in a 20-fold reduction in reaction time. We also show that modifying PCR primers with the peptide sled enables significant acceleration of standard PCR reactions.     

Theoretical elastic moduli for disordered packings of interconnected spheres

A theoretical model has been developed which provides analytical expressions for the elastic moduli of disordered isotropic ensembles of spheres interconnected by physical bonds. Young's and shear moduli have been derived assuming an ideal random isotropic network and the radial distribution function for disordered packings of spheres. The interparticle interactions are accounted for in terms of surface forces for the two distinct cases of perfectly rigid spheres and spheres deformable at contact. A theoretical expression is also derived in a similar way for the bulk or compressibility modulus. In this case, an atomistic approach has been followed based on the analogy with noble gas solids and colloidal crystals. Also in this case, disordered spatial distribution of the spheres is described statistically. For the case of colloidal aggregates, a total two-body mean-field interaction potential is used which includes the Born repulsion energy. This latter contribution plays an essential role in determining the compression behavior of systems of particles aggregated in the primary minimum of the potential well and, therefore, must not be neglected. Both the expression of the Young's modulus and that of the compressibility modulus derived in this work are found to be consistent with two distinct sets of experimental data which recently appeared in the literature.     

Production and extraction of astaxanthin from Phaffia rhodozyma and its biological effect on alcohol-induced renal hypoxia in Carassius auratus

The effect of astaxanthin (3,3′-dihydroxy-s-carotene-4,4′-dione) on alcohol-induced morphological changes in Carassius auratus, as an experimental model, was determined. The yeast Phaffia rhodozyma was used as a source of astaxanthin. The animals were divided into three groups for 30 days: one group was treated with ethanol at a dose of 1.5% mixed in water, the second one with EtOH 1.5% and food enriched with astaxanthin from P. rhodozyma, and the third was a control group. After a sufficient experimental period, the samples were processed using light microscopy and evaluated by histomorphological and histochemical staining, and the data were supported by immunohistochemical analysis, using a wide range of antibodies, such as calbindin, vimentin and alpha-smooth muscle actin. The results show that the alcoholic damage in the kidney led to hypoxia. In contrast, the group fed with astaxanthin from P. rhodozyma showed a normal morphological picture, with better glomeruli organisation and the presence of the area of filtration. Furthermore, the immunohistochemistry has confirmed these results.     

Magnetic couplings vs. stress and strain in epitaxial (La, Sr)MnO3

Based on ab initio calculations, we quantify the magnetic couplings and the stress tensor in ferromagnetic Sr-doped LaMnO₃ upon combined application of built-in epitaxial and external uniaxial strains. We suggest YAlO₃ as a substrate suited to change magnetic order in manganite film with practicable external strains. The effect could lead to strain-activated switches based on piezoelectric-piezomagnetic heterojunctions.