Ligand Binding Promiscuity of Human Liver Fatty Acid Binding Protein: Structural and Dynamic Insights from an Interaction Study with Glycocholate and Oleate

Human liver fatty acid binding protein (hL‐FABP) has been reported to act as an intracellular shuttle of lipid molecules, thus playing a central role in systemic metabolic homeostasis. The involvement of hL‐FABP in the transport of bile salts has been postulated but scarcely investigated. Here we describe a thorough NMR investigation of glycocholate (GCA) binding to hL‐FABP. The protein molecule bound a single molecule of GCA, in contrast to the 1:2 stoichiometry observed with fatty acids. GCA was found to occupy the large internal cavity of hL‐FABP, without requiring major conformational rearrangement of the protein backbone; rather, this led to increased stability, similar to that estimated for the hL‐FABP:oleate complex. Fast‐timescale dynamics appeared not to be significantly perturbed in the presence of ligands. Slow motions (unlike for other proteins of the family) were retained or enhanced upon binding, consistent with a requirement for structural plasticity for promiscuous recognition.     

Trickle Bed Wetting Factors From Pressure Drop And Liquid Holdup Measurements

In this work, solid-liquid wetting factors were determined from liquid holdup and pressure drop measurements according to the model proposed by Pironti et al. for different air-liquid systems: distilled water and CMC solutions at viscosity values of 3, 6, 9, and 12 mPa.s. The experiments were carried out at atmospheric conditions in a column of 10.2 cm internal diameter and 2 m high, packed with a cylindrical material. The superficial mass velocities varied from 0.67 to 18.6 kg/m 2 s for liquid flow and from 0.024 to 0.31 kg/m 2 s for gas flow. Under these operating conditions, regime of continuous gas flow was observed. The wetting factors obtained were in agreement with those reported by other methods, which allow us to confirm that the model used in this work is applicable to fluids of different properties at low gas velocities.     

Internal structure of bitumen/polymer/wax ternary mixtures for warm mix asphalts

Polymer modified asphalts (PMA) and warm mix asphalts (WMA) are technologies widely adopted in the paving industry. The first one is well established, while the second one is relatively new, but rapidly growing since it guarantees economic and environmental advantages. Until now PMA and WMA have been used disjointedly, but it would be useful to combine them to keep the advantages of both. One of the adopted solutions to obtain a warm effect is the addition of waxes to the asphaltic binder. Therefore, a “warm mix polymer modified asphalt” may be potentially obtained with a ternary asphalt/polymer/wax system. However, the final warm effect and performances of the binder will depend on the interactions between the three components. A preliminary investigation was done by mixing asphalt, styrene‐butadiene‐styrene block copolymer and a wax chosen among the following three categories: paraffinic, partially oxidized and maleic anhydride functionalized. The morphological and calorimetric analyses and solubility tests allowed identifying different behaviors depending on the wax type, which may preferentially interact either with the asphalt or with the polymer, thus influencing the whole binder structure. With regard to the ternary mixes, it was found that: (i) the paraffinic wax preferentially resides in the polymer‐rich phase, and slightly enhances the asphalt‐polymer compatibility; (ii) the partially oxidized wax prefers the asphaltene‐rich phase and reduces the compatibility; (iii) it is not clear where the functionalized wax is located, but it has a considerable compatibilizing effect and strongly alters the colloidal equilibrium of the asphalt‐polymer blend. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Densification and properties of bulk nanocrystalline functional ceramics with grain size below 50 nm

The synthesis and functional characterization of dense bulk nanometric oxides are reviewed, with particular emphasis on the modifications that a grain size in the low nanometric range (10–50 nm) introduces in their physical properties. The preparation of ceramics with low porosity and extremely small grain size is particularly challenging and mostly relies on the sintering of extremely fine nanopowder. The most popular methods for the preparation of the starting nanopowders are introduced and briefly discussed as well as the most widely employed densification techniques. The role of nanostructure in controlling phase stability, electrical and thermal transport, optical and magnetic properties of nano-oxides is discussed in details. Several examples are given where bulk materials prepared with grain size equal or below 50 nm show characteristics that are either enhanced or, in some cases, completely different from those possessed by the same materials, but with larger grain sizes.     

Cobalt‐Catalysed Addition of Allylidene Dipivalate to Aldehydes. A Formal Homoaldol Condensation

A Co(I)‐catalysed condensation of allylidene dipivalate with aldehydes to give (Z)‐4‐hydroxybut‐1‐enyl pivalates in 62 to 87% isolated yields, is reported. Reactions are run in acetonitrile at 0 or 25 °C depending on the nature of the aldehyde, and exploiting the Co(II)/Zn(0) redox couple for the preparation of the catalytic Co(I) species.     

3D Bioprinting of Gelatin–Xanthan Gum Composite Hydrogels for Growth of Human Skin Cells

In recent years, bioprinting has attracted much attention as a potential tool for generating complex 3D biological constructs capable of mimicking the native tissue microenvironment and promoting physiologically relevant cell–cell and cell–matrix interactions. The aim of the present study was to develop a crosslinked 3D printable hydrogel based on biocompatible natural polymers, gelatin and xanthan gum at different percentages to be used both as a scaffold for cell growth and as a wound dressing. The CellInk Inkredible 3D printer was used for the 3D printing of hydrogels, and a glutaraldehyde solution was tested for the crosslinking process. We were able to obtain two kinds of printable hydrogels with different porosity, swelling and degradation time. Subsequently, the printed hydrogels were characterized from the point of view of biocompatibility. Our results showed that gelatin/xanthan-gum bioprinted hydrogels were biocompatible materials, as they allowed both human keratinocyte and fibroblast in vitro growth for 14 days. These two bioprintable hydrogels could be also used as a helpful dressing material.     

Effects of polymer modification on the fuel resistance of asphalt binders

Fuel resistance is an important characteristic of asphalt binders, especially when used in airport fields and filling stations. However, the relevant standards are presently lacking and the scientific literature on the development of suited formulations is sparse. In this paper, a simple procedure to assess the fuel resistance of asphalts (considered in a dynamic sense) is proposed. A number of polymer modified asphalts (PMAs), prepared from two bases and 4 or 6 wt% of several polymers, have been analyzed with this procedure and the relationships between fuel resistance and morphology of the PMAs, the chemical structure of the polymers and the composition of the asphalt bases have been investigated.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.