The Scaffold Protein IscU Retains a Structured Conformation in the FeS Cluster Assembly Complex

IscU and IscS are two essential proteins in the machine responsible for the biogenesis of iron–sulfur clusters, prosthetic groups that are involved in several essential functions. The scaffold protein IscU is the temporary acceptor of the cluster that results when the protein forms a 110 kDa complex with the desulfurase IscS. In the absence of zinc, which stabilises the folded state, IscU is present in solution in equilibrium between a structured and an unstructured form. It has been suggested that IscS preferentially binds unstructured IscU, although crystal structures indicate otherwise. To learn more about the IscS–IscU complex, we have used advanced solution NMR techniques to observe directly the state of fold of IscS‐bound IscU. We present unambiguous evidence that IscU is folded in the complex and that the unstructured form does not bind to IscS. Our data correlate with several observations and explain an IscU‐related pathology.     

Chiral Resolution and Pharmacological Characterization of the Enantiomers of the Hsp90 Inhibitor 2‐Amino‐7‐[4‐fluoro‐2‐(3‐pyridyl)phenyl]‐4‐methyl‐7,8‐dihydro‐6H‐quinazolin‐5‐one Oxime

Heat‐shock protein 90 (Hsp90) is a molecular chaperone involved in the stabilization of key oncogenic signaling proteins, and therefore, inhibition of Hsp90 represents a new strategy in cancer therapy. 2‐Amino‐7‐[4‐fluoro‐2‐(3‐pyridyl)phenyl]‐4‐methyl‐7,8‐dihydro‐6H‐quinazolin‐5‐one oxime is a racemic Hsp90 inhibitor that targets the N‐terminal adenosine triphosphatase site. We developed a method to resolve the enantiomers and evaluated their inhibitory activity on Hsp90 and the consequent antitumor effects. The (S) stereoisomer emerged as a potent Hsp90 inhibitor in biochemical and cellular assays. In addition, this enantiomer exhibited high oral bioavailability in mice and excellent antitumor activity in two different human cancer xenograft models.     

Effect of the water sorption on the mechanical response of microcrystalline cellulose‐based composites for art protection and restoration

Thermoplastic composites based on a commercial acrylic matrix widely used in the field of art protection and restoration (Paraloid B72) and various concentrations (up to 30 wt %) of microcrystalline cellulose powder (MCC) were prepared by melt‐compounding and compression molding. The mechanical behavior of the resulting materials conditioned at a temperature of 23°C and a relative humidity level of 55% was compared to that of the corresponding dried materials. Even though the moisture absorption of the filler was lower than the neat matrix, the maximum moisture content increased with the MCC amount, probably due to the preferential water diffusion path through the microvoids and/or the filler‐matrix interface. Although the increase of moisture content for filled samples, DMTA analysis evidenced a stabilization upon MCC introduction, with an increase of the storage modulus and a decrease of the thermal expansion coefficient proportional to the filler loading. A similar trend was displayed by the corresponding dried materials. The tensile elastic modulus and the ultimate properties such as the stress at break and the tensile energy to break (TEB) of conditioned samples increased proportionally to the filler amount. On the contrary, the failure properties of dried composites were negatively affected by the presence of the microcellulose. It is worthwhile to report that a significant improvement of the creep stability was induced by MCC introduction both for dried and conditioned samples. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40741.     

Photorefractivity of poly-N-vinylindole-based materials as compared with that of poly-N-vinylcarbazole-based blends

The asymmetric two-beam coupling technique has been employed to measure the photorefractivity of thin films of polymer blends containing 2,5-dimethyl-4-(p-nitrophenylazo)anisole as the nonlinear optical component. Poly-(1-vinylindole) and poly-(2,3-dimethyl-1-vinylindole) were the photoconductive polymer counterparts. The values of the photorefractivity are reported. It appears that they are comparable with those of similar blends based on the well-known poly-(9-vinylcarbazole) (PVK), here considered as a reference standard. Careful differential scanning calorimetry analyses have been accomplished on the different blends taken into account to rationalize the significantly longer shelf lifetime of the indolyl-based films with respect to the PVK-based blends.     

Natural radionuclides in the rocks of the Valle del Cervo Pluton in Piedmont

Monitoring of the gamma radiation in Valle del Cervo Pluton was performed by determining U and Th contents in the main rock types cropping out over the entire area and pertaining to the granitic complex, syenitic complex and monzonitic complex. In particular, syenitic rocks were largely used as building and ornamental materials (e.g. Sienite della Balma). All the samples are fresh and do not present joints or fractures filled with U minerals. In the crushed samples the activity of uranium varies from 346 to 764 Bq/kg. Concentration of thorium varies from 202 to 478 Bq/kg. For all the analysed rocks uranium activity is higher than thorium one. The lowest value of radioactive concentration is referred to rocks of the granitic complex. The most active rocks are syenites. The data confirm the high activities of Valle del Cervo rock types, strongly connected with high K content of the source magma (geochemical signature); on the contrary, the activity seems to be not related to the location of the samples.     

Results of Measuring the Influence of Casimir Energy on Superconducting Phase Transitions

The ALADIN experiment aims at observing how the critical magnetic field of a superconducting aluminum film is modified, when it constitutes one of the reflecting surfaces of a Casimir cavity. If successful, such an observation would reveal the influence of vacuum energy on the superconducting phase transition. In this paper, a rigorous analysis of experimental data is reported, the results are discussed and compared with theoretical predictions based on Lifshitz theory of dispersion forces, and the BCS formula for the optical conductivity of superconductors. Thanks to this rigorous analysis, it can now be asserted that in the region of energy where it is expected that Casimir energy is comparable with condensation energy and the deviations of critical field from BCS formula to be not negligible, an anomalous behavior is found.     

Unfolding under Pressure: An NMR Perspective

This review aims to analyse the role of solution nuclear magnetic resonance spectroscopy in pressure-induced in vitro studies of protein unfolding. Although this transition has been neglected for many years because of technical difficulties, it provides important information about the forces that keep protein structure together. We first analyse what pressure unfolding is, then provide a critical overview of how NMR spectroscopy has contributed to the field and evaluate the observables used in these studies. Finally, we discuss the commonalities and differences between pressure-, cold- and heat-induced unfolding. We conclude that, despite specific peculiarities, in both cold and pressure denaturation the important contribution of the state of hydration of nonpolar side chains is a major factor that determines the pressure dependence of the conformational stability of proteins.     

Hyaluronan-coated poly(propylene imine) dendrimers as biomimetic nanocarriers of doxorubicin

A coating technology based on low molecular weight hyaluronic acid (HA) and ferulic acid (FA) was applied to the coating of low generation poly(propylene imine) dendrimers through a biocompatible hexa(ethylene glycol) spacer. The ensuing HA-FA-HEG-PPID dendrimeric materials showed interesting loading capability (between 7.65% and 9.08%) regarding anticancer agent doxorubicin, and their interactions with the drug appeared to hamper the drug release in the physiological environment. Thus, the stable nanostructured loaded delivery systems were able to internalize into cells expressing the HA receptor CD44 and to demonstrate high cytotoxicity comparable to that shown by equivalent amounts of free doxorubicin. Thus, HA-FA-HEG-PPID dendrimeric materials were proposed as biocompatible drug carriers capable of transporting anticancer doxorubicin to tumor cells.