Radiation- and Photo-Induced Oxidation Pathways of Methionine in Model Peptide Backbone under Anoxic Conditions

Within the reactive oxygen species (ROS) generated by cellular metabolisms, hydroxyl radicals (HO^•) play an important role, being the most aggressive towards biomolecules. The reactions of HO^• with methionine residues (Met) in peptides and proteins have been intensively studied, but some fundamental aspects remain unsolved. In the present study we examined the biomimetic model made of Ac-Met-OMe, as the simplest model peptide backbone, and of HO^• generated by ionizing radiation in aqueous solutions under anoxic conditions. We performed the identification and quantification of transient species by pulse radiolysis and of final products by LC-MS and high-resolution MS/MS after γ-radiolysis. By parallel photochemical experiments, using 3-carboxybenzophenone (CB) triplet with the model peptide, we compared the outcomes in terms of short-lived intermediates and stable product identification. The result is a detailed mechanistic scheme of Met oxidation by HO^•, and by CB triplets allowed for assigning transient species to the pathways of products formation.     

Mechanism of Anticancer Action of Novel Imidazole Platinum(II) Complex Conjugated with G2 PAMAM-OH Dendrimer in Breast Cancer Cells

Transition metal coordination compounds play an important role in the treatment of neoplastic diseases. However, due to their low selectivity and bioavailability, as well as the frequently occurring phenomenon of drug resistance, new chemical compounds that could overcome these phenomena are still being sought. The solution seems to be the synthesis of new metal complexes conjugated with drug carriers, e.g., dendrimers. Numerous literature data have shown that dendrimers improve the bioavailability of the obtained metal complexes, solving the problem of their poor solubility and stability in an aqueous environment and also breaking down inborn and acquired drug resistance. Therefore, the aim of this study was to synthesize a novel imidazole platinum(II) complex conjugated with and without the second-generation PAMAM dendrimer (PtMet2–PAMAM and PtMet2, respectively) and to evaluate its antitumor activity. Cell viability studies indicated that PtMet2–PAMAM exhibited higher cytotoxic activity than PtMet2 in MCF-7 and MDA-MB-231 breast cancer cells at relatively low concentrations. Moreover, our results indicated that PtMet2–PAMAM exerted antiproliferative effects in a zebrafish embryo model. Treatment with PtMet2–PAMAM substantially increased apoptosis in a dose-dependent manner via caspase-9 (intrinsic pathway) and caspase-8 (extrinsic pathway) activation along with pro-apoptotic protein expression modulation. Additionally, we showed that apoptosis can be induced by activating POX, which induces ROS production. Furthermore, our results also clearly showed that the tested compounds trigger autophagy through p38 pathway activation and increase Beclin-1, LC3, AMPK, and mTOR inhibition. The high pro-apoptotic activity and the ability to activate autophagy by the imidazole platinum(II) complex conjugated with a dendrimer may be due to its demonstrated ability to reverse multidrug resistance (MDR) and thereby increase cellular accumulation in breast cancer cells.     

Coralyne Radiosensitizes A549 Cells by Upregulation of CDKN1A Expression to Attenuate Radiation Induced G2/M Block of the Cell Cycle

Coralyne is a synthetic analog of berberine related to protoberberine-isoquinoline alkaloids. Isoquinoline derivatives and analogs are renowned as potent radiosensitizers with potential medical application. In the present study, we investigated the effect of coralyne on the cell death, cytoskeletal changes and cell cycle progression of irradiated A549 cells. A clonogenic assay revealed that coralyne pretreatment decreased the viability of A549 cells in a time- and dose-dependent manner. Moreover, exposure to coralyne and ionizing radiation (IR) markedly altered the filamentous actin cytoskeletal architecture and integrin-β binding sites of A549 cells. Treatment with 1–25 µM coralyne in combination with 2 Gy of IR significantly reduced the percentage of cells in G2/M phase compared with 2 Gy IR alone. These results indicate that coralyne is a potent radiosensitizing agent that may find an application in medicine.     

Measurement of mechanical properties in a 316L stainless steel welded joint

The aim of this study was to measure the mechanical properties of weld material taken from a single weld bead laid down on a 316L steel plate. Due to the low available volume of weld material, microsamples with a total length of 5.5 mm were used. The Digital Image Correlation method (DIC), which enables measurement of mechanical properties of very small samples, was employed for the strain measurements in a uniaxial tensile test. Samples were cut out from three different zones of the specimen: plate, weld, and the heat affected zone. The material from heat affected zone showed the highest value of the Ultimate Tensile Strength (UTS) (580 ± 7 MPa) and yield strength (339 ± 6 MPa). Plate material had lower UTS (559 ± 5 MPa) and yield strength (304 ± 7 MPa). The lowest values of UTS (526 ± 6 MPa) and yield strength (291 ± 8 MPa) have been revealed for the weld. The values obtained for UTS, yield strength and elongation to failure for the plate material were compared with data obtained using standard test specimens. No significant differences between results obtained for the microsamples and standard samples have been found.     

Evaluation of the mechanical behavior of W7-X central support connections by means of semi-automated FE analysis

The stellarator Wendelstein 7-X is under construction at the Max-Planck-Institut für Plasmaphysik in Greifswald. Its superconducting coil system is fixed by a massive structure. During machine operation the coils exert high forces and moments against each other and the central support structure (CSS). Therefore, the detailed analysis of the coil to CSS connections, the so-called central support elements (CSE), is a critical item. The major details of the design have been frozen; nevertheless, there is still need for detailed analysis of the CSEs due to assembly issues, and later on for exploring operational limits of the machine. These analyses have to be performed quickly, reliably, and shall provide results in a standardized form to enable timely responses to the assembly team. Special numerical tools – finite element (FE) parametric models of CSEs – have been developed for the purpose of such analyses. In the models, the geometry, material properties, contact conditions, loads as well as results presentation are defined in a parametric way. The use of the developed models for the definition of the final weld parameters, bolt preloads, assessment of acceptable tolerances, and optimal positions of the CSE-wedges before welding is also discussed.     

XPS studies of perovskites surface instability caused by Ar+ ion and electron bombardment and metal deposition

X-ray Photoelectron Spectroscopy (XPS) was used to study the influence of low energy Ar⁺ ion bombardment, electron bombardment and Pt deposition on the SrTiO₃ (STO) single crystal electronic structure. Atomic composition changes were found and attributed to chemical reconstruction of the STO surface. A clear correlation between the presence of conducting, low Ti oxidation states in valence band and core level changes was detected. A strong effect caused by electron irradiation was ascribed to the electroreduction process. The influence of lanthanum doping on surface instability of STO was also discussed. The La doped sample (STO: 3,75% La) was found to be modified upon Pt metal deposition to a higher degree than pure STO crystal.     

Surface potential measurements of Langmuir films of azo dye/liquid crystal mixtures

Two-component films of a non-amphiphilic azo dye and a liquid crystal with strongly polar –CN group were studied at an air–water interface on the basis of the surface potential–mean molecular area dependence recorded simultaneously with the surface pressure–mean molecular area isotherm. Additionally, the morphology of the films was monitored with the aid of Brewster angle microscope. A conventional Langmuir technique was used to form dye/liquid crystal films during reduction and expansion of an area occupied by the molecules. From the surface potential value, the effective dipole moment in the first monolayer formed on the water was calculated. Moreover, the number of molecules with dipole moments directed from the water to the air with respect to those directed towards water was estimated. The influence of the two components' miscibilities upon the surface potential after addition of the dye to the liquid crystal was determined.     

Detection and identification of aqueous saccharides by using surface-enhanced Raman spectroscopy

The sensitive detection and characterization of carbohydrates by means of a strategy based on surface-enhanced Raman spectroscopy is demonstrated. Spectra are obtained after injecting a small amount of saccharide solution onto a roughened silver substrate, with subsequent deposition of silver colloid. The sensitivity achieved by this two-step approach enables high-quality Raman spectra to be obtained for small amounts of aqueous saccharides (5 microL of a 10(-2) M solution) utilizing minimal laser power and small signal acquisition times (a few seconds). Spectral "fingerprints" obtained for seven structurally similar monosaccharides demonstrate clearly an effective means by which each sugar can be identified. The application to more complex analyses is demonstrated for monosaccharide mixtures and a disaccharide, whereby the SERS fingerprints aid in the determination of components.