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.     

pH-Dependent Spectroscopy of Tetracycline and Its Analogs

Tetracyclines (TCs), broad spectrum antibiotics widely used in the prevention and treatment of infectious diseases, are amphoteric molecules containing several ionizable functional groups that exist predominantly as zwitterions at a given pH value. TCs are reported to undergo a wide variety of reactions at different pH values i.e. TCs form to anhydrotetracyclines at low pH, 4-epitetracyclines at pH 3–5 and isotetracyclines at high pH values. The pH-dependent absorbance and emission properties of tetracycline and its 10 analogs (4-epitetracycline, doxycyline, oxytetracycline, chlortetracycline, 4-epichlortetracycline, isochlortetracycline, methacycline, rolitetracycline, minocycline, and demeclocycline) were investigated and reported in this paper. The main focus of the study was on the pH dependent transformation of epichlortetracycline, chlortetracycline and isotetracycline at basic pH. Absorption, emission and time resolved spectroscopy were used to determine the behavior of the three TC derivatives at this condition. Increasing the buffer’s ionic concentration leads to faster transformation to iCTC. A pH dependent transformation of CTC to iCTC was observed and the lifetimes of CTC and iCTC were determined to be 3.0 and 5.89 ns respectively. The distribution factor of CTC to iCTC at basic pH was also reported for the first time.     

Stability of silicon and titanium carbide suspensions in electrolyte, poly(ethylene oxide), and PEO-surfactant solutions

It has been shown that the coagulation values of counterions for SiC and TiC suspensions with particle radius from 0.5 to 5 microm obey a z(2.5-3.5) law and there is an insufficient change in the critical concentration of 1-1 electrolytes (CCE) when the surface potential of particles increases more than two times. Also, the CCE values hardly depend on the position of counterions in the lyotropic sequence. This is explained by aggregation of SiC and TiC particles at a secondary minimum, which is proved by calculations of the potential curves of interparticle interactions using the DLVO theory. The adsorption of poly(ethylene oxide) on the surfaces studied does not cause--in contradiction to dispersions with smaller particles--an unlimited growth in the stability of suspensions. This is due to the aggregation of large particles with adsorbed PEO, as in polymer-free dispersions, under barrierless conditions in which the coordinates of the secondary minimum are determined by superposition of molecular attractive forces and steric repulsive forces of adsorbed polymeric chains, without a contribution from the electric repulsion term. PEO-anionic surfactant complexes possess higher stabilizing capacity compared to the individual components of the mixture. Our results show that the adsorbed polymer layers may hinder the aggregation both in the primary and in the secondary minimum for not very large particles only, the critical size of which depends on the dispersed phase nature and the molecular mass of the polymer.