[Epithelial-stromal interactions in pancreatic adenocarcinoma: the role of stroma in disease progression]. / Epitelial'no-stromal'nye vzaimodeistviya v adenokartsinome podzheludochnoi zhelezy: rol' stromy v progressirovanii zabolevaniya.

Pancreatic ductal adenocarcinoma (PDAC) is the most common and difficult to treat form of pancreas cancer. PDAC and other solid cancers contain both tumor cells and normal connective tissue cells called stromal cells, which are responsible for the excess production of extracellular matrix. It is known that in more than 90% of PDAC tumors and in many other types of cancer, mutations of the KRAS gene are observed, the reciprocal signaling of which has been shown between tumor and stromal cells in vitro. Pancreatic stromal stellate cells are considered precursors of activated or tumor-associated fibroblasts (CAFs), which are an increasing population of cells that proliferate in situ or are recruited into the tumor. CAFs are a heterogeneous population of stromal fibroblasts with different molecular profiles that change during tumorigenesis. Both immunosuppressive and immunosuppressive subsets of CAFs can coexist in the stroma of a single tumor. Based on the heterogeneity of the intertumor stroma, attempts are being made to classify PDAC and predict the course of the disease.

The effect of energy-dependent electron scattering on thermoelectric transport in novel topological semimetal CoSi.

Cobalt monosilicide and its solid solutions with Fe or Ni crystallize in B20 cubic noncentrosymmetric structure. These compounds have long been known as promising thermoelectric materials. Recently it was revealed, that they also have unconventional electronic topology. This renewed interest to the investigation of their transport properties. In order to improve theoretical description of thermoelectric transport in these compounds, we take into account electron scattering beyond commonly used constant relaxation time approximation. Using first principle calculations, we investigate the scattering of charge carriers by phonons and point defects. The dependence of the scattering rate on the energy correlates with that for the total density of states. This implies that in this material not only the intraband, but also the interband scattering is important, especially for bands with low density of states. The Seebeck coefficient and the electrical resistivity of CoSi and of dilute solid solutions Co1-x M x Si (M = Fe or Ni, x < 0.1) are calculated as a function of temperature and the alloy composition. We show that the account of strong energy dependence of relaxation time is important for the description of experimentally observed rapid increase of the resistivity and qualitative change of its temperature dependence with the substitution of cobalt for iron, as well as for the description of the magnitude of the Seebeck coefficient, its temperature and composition dependence.

Band structure and unconventional electronic topology of CoSi.

Semimetals with certain crystal symmetries may possess unusual electronic structure topology, distinct from that of the conventional Weyl and Dirac semimetals. Characteristic property of these materials is the existence of band-touching points with multiple (higher than two-fold) degeneracy and nonzero Chern number. CoSi is a representative of this group of materials exhibiting the so-called 'new fermions'. We report on an ab initio calculation of the electronic structure of CoSi using density functional methods, taking into account the spin-orbit interactions. The linearized [Formula: see text] Hamiltonian, describing the anisotropic electronic structure of CoSi near the Γ point is derived. The topological features of band-touching nodes with four- and six-fold degeneracy located at the Γ and R points in the first Brillouin zone are analysed using the linearized Hamiltonians and first principle calculations. In particular, we show, using the non-Abelian Berry curvature, that these band-touching points carry topological charges of [Formula: see text], which change signs at certain values of parameters of the Hamiltonians. We describe the resulting Fermi arc surface states and their spin texture. We also discuss the influence of many body [Formula: see text] corrections on the electronic band structure and the topological properties of CoSi.

Ballistic thermoelectric transport in a Luttinger liquid.

The Seebeck and Peltier coefficients of a homogeneous Luttinger liquid are calculated in the ballistic regime. Nonlinearity of the electron spectrum is taken into account. It is shown that, in the framework of the defined approximations, the thermoelectric power of a Luttinger liquid is equal to zero, in agreement with the exponentially small thermopower of a one-dimensional degenerate Fermi gas. The Peltier coefficient is controlled by a nonequilibrium state of the system. It is finite and renormalized by the interaction in the case of a convective flow of a Luttinger liquid. The zero modes of bosonic excitations and the dispersion-induced contribution to the electric current operator are taken into account in calculations.

70-S ribosomes of Escherichia coli have an additional site for deacylated tRNA binding.

Escherichia coli 70-S ribosomes contain a third site for tRNA binding, additional to the A and P sites. This conclusion is based on several findings. Direct measurements showed that in the presence of poly(U), when both A and P sites are occupied by Ac[14C]Phe-tRNAPhe, ribosomes are capable of binding additionally deacylated non-cognate [3H]tRNA. If ribosomes in the preparation are active enough, the total binding of labeled ligands amounted to 2.5 mol/mol ribosomes. In the absence of poly(U), when the A site can not bind, the P site and the 'additional' site can be filled simultaneously with Ac[14C]Phe-tRNAPhe and deacylated [3H]tRNA, or with [3H]tRNA alone; the total binding exceeds in this case 1.5 mol/mol ribosomes. The binding at the 'additional' site is not sensitive to the template. [3H]tRNA bound there is able to exchange rapidly for unlabeled tRNA in solution. Deacylated tRNA is preferred to the aminoacylated one. The binding of AcPhe-tRNAPhe was not observed there at all. The 3'-end adenosine is essential for the affinity. The function of the 'additional' site is not known, but its existence has to be considered when tRNA . ribosome complexes are studied.

On the mechanism of interaction of N-acetylphenylalanyl-tRNAPhe with ribosomes of Escherichia coli: effect of antibiotics and Tp psi pCpGp.

The tetranucleotide Tp psi pCpGp acts as a specific inhibitor of the rate of AcPhe-tRNAPhe binding in the ribosomal P site. This effect is observed both in the presence and in the absence of poly(U). In the absence of poly(U) antibiotics tetracycline and puromycin also decrease the rate of AcPhe-tRNAPhe binding. Some inhibition by tetracycline is observed with poly(U). All these inhibitors are known to be ligands of the ribosomal A site, and their influence on the P site binding can be most naturally explained by the suggestion that AcPhe-tRNAPhe enters the ribosome via the A site, forms there an intermediate complex, and spontaneous translocation into the P site follows. In the presence of poly(U) arguments in favour of this hypothesis are much weaker, but the same sequence of events is possible.

Quantitative study of the interaction of formylmethionyl-tRNAfMet with ribosomes of Escherichia coli.

fMet-tRNAfMet binds reversibly to the donor site (P-site) of Escherichia coli ribosomes both in the absence of messenger and in the presence of ApUpGp and some other oligonucleotides or poly(U). Kinetics of interaction conforms the second-order law. The equilibrium constants and the rate constants of binding are estimated at 0 degrees C. Not only the cognate trinucleotide ApUpGp but also some other oligonucleotides and even poly(U) stimulate the binding. The presence of total deacylated tRNA considerably increases the selectivity of association.

Interaction of transfer RNA with 50S ribosomal subunits of Escherichia coli in absence of templates.

The equilibrium constant of a complex of tRNA with the 50S ribosomal subunit was measured in the absence of a template. It was shown that the stability of the complex increases with an increase in the concentration of Mg2+, it decreases with an increase in the concentration of univalent ions, and does not depend on the pH of the medium in the range of 7.0-8.2. Removal of the 3'-terminal nucleoside of tRNA weakens the association approximately 40-fold; the subsequent successive splitting off of another three nucleotides has little effect on the association constant. In 90% 2H2O the stability of the complex increases approximately four-fold, which points to the large contribution of the hydrogen bonds to the free energy of the interaction. The tetranucleotide TphiCG competes slightly with tRNA for sites on the 50S subparticles; this means that the TphiC segment of tRNA does not play an important role in the formation of the complex under investigation.