Structure-based study of antiamyloidogenic cyclic d,l-α-peptides

Protein misfolding and aggregation are the hallmarks of many devastating diseases. We have previously shown that cyclic d,l-α-peptide CP-2 reacts and stabilizes less toxic forms of amyloid β (Aβ), and protects the cells from Aβ-induced toxicity. Here, we performed extensive structure-based studies on CP-2 to elucidate the contribution of each residue to the total antiamyloidogenic activity and determine the interactions that are involved between CP-2 and Aβ. We showed that the hydrophobicity of CP-2 analogs correlates with their antiamyloidogenic potency, however, aromatic interactions are even more important for this activity. The antiamyloidogenic activity of CP-2 analogs also correlates with their ability to self-assemble, as shown by the critical micelle concentration measurements. The cell survival studies performed on rat pheochromocytoma PC-12 cells suggest that incorporation of an additional aromatic residue to the CP-2's sequence increases its protective effect against Aβ42-induced toxicity.     

Polyaspartamide–Polylactide Graft Copolymers with Tunable Properties for the Realization of Fluorescent Nanoparticles for Imaging

Here, the synthesis and the characterization of novel amphiphilic graft copolymers with tunable properties, useful in obtaining polymeric fluorescent nanoparticles for application in imaging, are described. These copolymers are obtained by chemical conjugation of rhodamine B (RhB) moieties, polylactic acid (PLA), and O‐(2‐aminoethyl)‐O′‐methyl poly(ethylene glycol) (PEG) on α,β‐poly(N‐2‐hydroxyethyl)‐d,l ‐aspartamide (PHEA). In particular, PHEA is first functionalized with RhB to obtain PHEA–RhB with a derivatization degree in RhB (DD_RhB) equal to 0.55 mol%. By varying the reaction conditions, different amounts of PLA are grafted on PHEA–RhB to obtain PHEA‐RhB‐PLA with DD_PLA equal to 1.9, 4.0, and 6.2 mol%. Then, PEG chains are grafted on PHEA‐RhB‐PLA derivatives to obtain PHEA‐RhB‐PLA‐PEG graft copolymers. The preparation of polymeric fluorescent nanoparticles with tunable properties and spherical shape is described by using PHEA‐RhB‐PLA‐PEG with DD in PLA and PEG equal to 4.0 and 4.9 mol%, by following easily scaling up processes, such as emulsion‐solvent evaporation and high pressure homogenization (HPH)‐solvent evaporation techniques.

     

The Effect of Olive Fruit Fly Bactrocera oleae (Rossi) Infestation on Certain Chemical Parameters of Produced Olive Oils

Olives affected by active and damaging infestation (olive fruit fly Bactrocera oleae (Rossi)) were assayed for their chemical composition. Biophenols were determined by HPLC, sterols, triterpenic dialcohols, and fatty acids by gas chromatography analysis. The acquired data were statistically analyzed. Oils produced from “Istrska belica” fruit affected by active infestation compared to the oils made from fruit affected by damaging infestation showed higher amounts of total oleuropein biofenols (377.3 versus (vs.) 106.6 mg/kg), total biophenols (755 vs. 377 mg/kg), lignans (85.3 vs. 32.9 mg/kg), the dialdehydic form of decarboxymethyl oleuropein aglycone (DMO-Agl-dA) (148.3 vs. 49.0 mg/kg), its oxidized form (DMO-Agl-dA)ox (35.2 vs. 8.5 mg/kg), the dialdehydic form of oleuropein aglycone (O-Agl-dA) (61.1 vs. 8.0 mg/kg), the dialdehydic form of ligstroside aglycone (L-Agl-dA) (63.5 vs. 28.0 mg/kg), the aldehydic form of oleuropein aglycone (O-Agl-A) (40.6 vs. 8.4 mg/kg), and lower amounts of tyrosol (Tyr) (6.0 vs. 13. 9 mg/kg) and the aldehydic form of ligstroside aglycone (L-Agl-A) (13.8 vs. 40.3 mg/kg). Higher values of stigmasterol (2.99%) and lower values of campesterol (2.25%) were determined in oils affected by damaging infestation; an increase in triterpenic dialcohols was also observed (3.04% for damaging and 1.62% for active infestation). Oils affected by damaging infestation, compared to active infestation, showed lower amounts of oleic acid (73.89 vs. 75.15%) and higher amounts of myristic (0.013 vs. 0.011%), linoleic (7.27 vs. 6.48%), and linolenic (0.74 vs. 0.61%) acids.     

Ruthenium (II) Catalyzed C(sp2)−H Bond Alkenylation of 2-Arylbenzo[d]oxazole and 2-Arylbenzo[d]thiazole with Unactivated Olefins

Functionalization of the bio-relevant heterocycles 2-arylbenzo[d]oxazole and 2-arylbenzo[d]thiazole has been achieved through Ru(II)-catalyzed alkenylation with unactivated olefins leading to selective formation of the mono-alkenylated products. This approach has a broad substrate scope with respect to the coupling partners, affords high yields, and works for gram scale synthesis using a readily available Ru-based catalyst. Mechanistic studies reveal a C−H activation pathway for the dehydrogenative coupling leading to the alkenylation. However, the results of the ESI-MS-guided deuterium kinetic isotope effect studies indicate that the C−H activation stage may not be the rate-determining step of the reaction. The use of a radical scavenging agent such as TEMPO did not show any detrimental effect on the reaction outcome, eliminating the possibility of the involvement of a free-radical pathway.     

Influence of surface heterogeneity in electroosmotic flows—Implications in chromatography, fluid mixing, and chemical reactions in microdevices

We analyze the influence of surface heterogeneity, inducing a random ζ-potential at the walls in electroosmotic incompressible flows. Specifically, we focus on how surface heterogeneity modifies the physico-chemical processes (transport, chemical reaction, mixing) occurring in microchannel and microreactors. While the macroscopic short-time features associated with solute transport (e.g. chromatographic patterns) do not depend significantly on ζ-potential heterogeneity, spatial randomness in the surface ζ-potential modifies the spectral properties of the advection-diffusion operator, determining different long-term properties of transport/reaction phenomena compared to the homogeneous case. Examples of physical relevance (chromatography, infinitely fast reactions) are addressed.     

Visual investigation of the intermediate state in the region of metamagnetic phase transition in ErFeO3

We carried out the first observation of the intermediate state (IS) in the region of metamagnetic phase transition (MPT) in ErFeO₃: an external magnetic field H∥c (H=0–4 kOe), the temperature range 2.15–1.6 K. The ranges of the IS existence and the domain structure (DS) features were determined. Likely mechanisms of the IS thermodynamic stabilization and conditions for its visualization in ErFeO₃-plates with various crystallographic orientations were analyzed. The thermodynamic model of IS was offered: the intermediate state was stabilized by the mechanical stress that accompanies MPT. Excellent agreement with experiment was achieved.     

Shocks and cold fronts in galaxy clusters

The currently operating X-ray imaging observatories provide us with an exquisitely detailed view of the Megaparsec-scale plasma atmospheres in nearby galaxy clusters. At z<0.05$z<0.05$, the Chandra  's 1^″$1^{″}$ angular resolution corresponds to linear resolution of less than a kiloparsec, which is smaller than some interesting linear scales in the intracluster plasma. This enables us to study the previously unseen hydrodynamic phenomena in clusters: classic bow shocks driven by the infalling subclusters, and the unanticipated “cold fronts,” or sharp contact discontinuities between regions of gas with different entropies. The ubiquitous cold fronts are found in mergers as well as around the central density peaks in “relaxed” clusters. They are caused by motion of cool, dense gas clouds in the ambient higher-entropy gas. These clouds are either remnants of the infalling subclusters, or the displaced gas from the cluster's own cool cores.