Impaired Expression of Cytoplasmic Actins Leads to Chromosomal Instability of MDA-MB-231 Basal-Like Mammary Gland Cancer Cell Line

We have shown previously that two cytoplasmic actin isoforms play different roles in neoplastic cell transformation. Namely, β-cytoplasmic actin acts as a tumor suppressor, whereas γ-cytoplasmic actin enhances malignant features of tumor cells. The distinct participation of each cytoplasmic actin in the cell cycle driving was also observed. The goal of this study was to describe the diverse roles of cytoplasmic actins in the progression of chromosomal instability of MDA-MB-231 basal-like human carcinoma cell line. We performed traditional methods of chromosome visualization, as well as 3D-IF microscopy and western blotting for CENP-A detection/quantification, to investigate chromosome morphology. Downregulation of cytoplasmic actin isoforms alters the phenotype and karyotype of MDA-MB-231 breast cancer cells. Moreover, β-actin depletion leads to the progression of chromosomal instability with endoreduplication and aneuploidy increase. On the contrary, γ-actin downregulation results not only in reduced percentage of mitotic carcinoma cells, but leads to chromosome stability, reduced polyploidy, and aneuploidy.     

Synthesis and electronic spectra of new low-molecular weight compounds with possible application in electroluminescent layers

Two new low-molecular weight compounds — (Z)-4-(4-(dimethylamino)benzylidene)-1-(9-ethyl-9H-carbazol-3-yl)-2-phenyl-1H-imidazol-5(4H)-one and 2-(6-hydroxyhexyl)-6-(pyrrolidin-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione) — with possible application in organic light-emitting devices were synthesized. Their photophysical properties in solution and in polymer films were investigated. The determined relative fluorescence quantum yields in solution for both compounds were 0.003 and 0.51, while those in poly(methyl methacrylate) films were around 0.10 and 1.0, respectively. For 1H-imidazol-5(4H)-one derivative, single-layer organic displays with one emitting layer were prepared by spin-coating technology. The applied voltage was 40 V (AC) with 1–3 KHz frequency. The emission maximum of the experimental AC display structures was at 600–630 nm. For displays with 2-(6-hydroxyhexyl)-6-(pyrrolidin-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione) the applied voltage was 60 V (AC) with 6-9 KHz frequency, but its future success will require more appropriate binding polymers. Based on the obtained experimental results, it is concluded that the investigated compounds could be applied for preparation of color electroluminescent structures.      

Trialkyl borate assisted amination of fluorinated 1,3-diketones for synthesis of N,N′-1,2-phenylen-bis(β-aminoenones) and their Ni(II), Cu(II) and Pd(II) complexes

An effecient synthetic method for fluorinated tridentate β-aminoenones and tetradentate bis(β-aminoenones) via amination of fluorinated 1,3-diketones with o-phenylenediamine in the presence of trialkyl borates was developed. Ni(II), Cu(II) and Pd(II) complexes with tetradentate bis(β-aminoenones) were obtained. Their gaschromatographic behaviour and main fragmentation paths in the electron ionization mass spectra were described.     

Synthesis, crystal and electronic structure, and physical properties of the new lanthanum copper telluride La3Cu5Te7

The new lanthanum copper telluride La₃Cu_5−xTe₇ has been obtained by annealing the elements at 1073 K. Single-crystal X-ray diffraction studies revealed that the title compound crystallizes in a new structure type, space group Pnma (no. 62) with lattice dimensions of a=8.2326(3) Å, b=25.9466(9) Å, c=7.3402(3) Å, V=1567.9(1) Å³, Z=4 for La₃Cu_4.86(4)Te₇. The structure of La₃Cu_5−xTe₇ is remarkably complex. The Cu and Te atoms build up a three-dimensional covalent network. The coordination polyhedra include trigonal LaTe₆ prisms, capped trigonal LaTe₇ prisms, CuTe₄ tetrahedra, and CuTe₃ pyramids. All Cu sites exhibit deficiencies of various extents. Electrical property measurements on a sintered pellet of La₃Cu_4.86Te₇ indicate that it is a p-type semiconductor in accordance with the electronic structure calculations.     

New sorafenib derivatives: synthesis, antiproliferative activity against tumour cell lines and antimetabolic evaluation

Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a-e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1), 4-chloro-pyridine-2-carboxamides 2a-e, 4-(4-aminophenoxy)-pyridine-2-carboxamides 3a-e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a-e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a-e (IC(50) = 1-4.3 μmol·L-1). Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity.     

Conformational Flexibility of Cytokine-Like C-Module of Tyrosyl-tRNA Synthetase Monitored by Trp144 Intrinsic Fluorescence

The non-catalytic COOH-terminal module formed after proteolytic cleavage of full-length mammalian tyrosyl-tRNA synthetase displays dual function: tRNA binding ability and cytokine activity. With the aim to explore the intramolecular dynamics of C-module in solution we used fluorescence spectroscopy to study conformational changes of isolated protein. We used information from fluorescence spectra and computational model for characterization of a microenvironment of a single tryptophan residue (Trp144). Its fluorescence parameters and protection from quenching by Cs⁺ ions indicate the internal localization—buried into protein globule. The fluorescence quenching of Trp144 by acrylamide suggests rapid conformation dynamics of the C-module in nanosecond time scale. The temperature-induced conformational changes in the C-module were monitored by the fluorescence measurements of Trp144 emission and by red-edge excitation shift. An emission maximum shift up to ∼349 nm and significant decrease of the red-edge shift effect at 37–52 °C indicated a major conformational transition of Trp144 from buried native state into highly relaxing polar solvent environment.     

Universality for 1d Random Band Matrices: Sigma-Model Approximation

The paper continues the development of the rigorous supersymmetric transfer matrix approach to the random band matrices started in (J Stat Phys 164:1233–1260, 2016; Commun Math Phys 351:1009–1044, 2017). We consider random Hermitian block band matrices consisting of \(W\times W\) random Gaussian blocks (parametrized by \(j,k \in \Lambda =[1,n]^d\cap \mathbb {Z}^d\)) with a fixed entry’s variance \(J_{jk}=\delta _{j,k}W^{-1}+\beta \Delta _{j,k}W^{-2}\), \(\beta >0\) in each block. Taking the limit \(W\rightarrow \infty \) with fixed n and \(\beta \), we derive the sigma-model approximation of the second correlation function similar to Efetov’s one. Then, considering the limit \(\beta , n\rightarrow \infty \), we prove that in the dimension \(d=1\) the behaviour of the sigma-model approximation in the bulk of the spectrum, as \(\beta \gg n\), is determined by the classical Wigner–Dyson statistics.     

Effect of detonation nanodiamond surface composition on physiological indicators of mitochondrial functions

For the first time, an effect of detonation nanodiamonds (NDs) with different surface compositions on the main functional characteristics of isolated rat liver mitochondria was studied. The response of membrane potential, calcium retention capacity, and redox state of pyridine nucleotides have been monitored upon the administration of NDs functionalized with carboxyl, hydroxyl, amine, hydrogen, and chlorine surface groups. Hydrogenated and chlorinated NDs caused reduction of the membrane potential and calcium retention capacity of mitochondria. An aminated ND caused an even greater decrease in calcium retention capacity (at a concentration of 0.75 mg/ml), reducing it to 65% of the control. The use of cyclosporine A prevented a decrease in membrane potential and calcium retention capacity indicating the induction of non-specific mitochondrial membrane pores during the NDs incubation with mitochondria. Hydrogenated and chlorinated NDs had no significant effect on the redox state of mitochondrial pyridine nucleotides. Other NDs studied had no effects on functional characteristics of mitochondria, even at high concentrations (up to 1.5 mg/ml). High activity of chlorinated and hydrogenated NDs may be due to the greater hydrophobicity of their surface and its interaction with mitochondrial pores components. Thus, isolated rat liver mitochondria can be used as a biomodel for initial testing of ND samples to assess the possibility of their use in drug delivery systems.     

MnFeNi-Based Composite as a Case Study of a Bifunctional Oxygen Electrocatalyst under Dynamically Changing Electrode Potentials

High-performance bifunctional electrocatalysts for the oxygen reduction (ORR) and oxygen evolution reaction (OER) are essential components in energy conversion and storage technologies. Yet, their poor reversibility hinders their applicability. A highly active ORR/OER catalyst, consisting of multiwalled carbon nanotubes-supported MnFeNiOx nanoparticles, was subjected to sequences of chronoamperometric steps alternating between the ORR, the OER and highly cathodic potentials (E_c). Rotating ring disk electrode methods revealed that applying E_c leads to a small increase in the current and peroxide species yield during the ORR while enhancing substantially the OER. X-ray absorption spectroscopy showed irreversible changes in the chemical state of MnFeNiOx correlating with its catalytic properties. The complexity of changes that a composite catalyst may undergo under varying potentials, the importance of monitoring product formation, and the convenience of using dynamic electrochemical sequences for the assessment of catalyst reversibility, as well as for the activation and/or restoration of their catalytic properties, are highlighted.     

Spherical Sampler Probes Enhance the Robustness of Ambient Ionization Mass Spectrometry for Rapid Drugs Screening

Ambient ionization mass spectrometry has become one of the most promising approaches for rapid and high-throughput screening of small molecules in complex biological matrices for emergency medicine, forensics, and food and agriculture applications. The simple procedures for sample collection and ionization without additional pretreatment are vital in these fields. Many efforts have been devoted to modifying various ambient ionization techniques to simplify the procedures and improve the robustness and sensitivity of the methods. Here, we demonstrate the implementation of rigid spherical sampler probes to improve the robustness of touch spray ionization mass spectrometry. The sphericity of the probes increases the stability of the cone-jet mode of electrospray, reduces the requirements for fine positioning of a sampler in the ion source, and decreases the possibility of corona discharge occurrence. The utilization of spherical sampler probes allows fast, non-invasive sampling, followed by rapid analysis for various drugs of different chemical classes in complex biological matrices, such as the whole blood or sebum collected from the skin surface. The linearity of the analytical signal response from drug concentration confirms the possibility of creating a simple semiquantitative method for small molecules monitoring using spherical sampler probes.