The main goal of this study is to consider SLC34A2 as a potential prognostic marker of oncological diseases using the mutational, expression, and survival data of cancer studies which are publicly available online. We collected data from four databases (cBioPortal, The Cancer Genome Atlas; cBioPortal, Genie; International Cancer Genome Consortium; ArrayExpress). In total, 111,283 samples were categorized according to 27 tumor locations. Ninety-nine functionally significant missense mutations and twelve functionally significant indel mutations in SLC34A2 were found. The most frequent mutations were SLC34A2-ROS1, p.T154A, p.P506S/R/L, p.G257A/E/R, p.S318W, p.A396T, p.P410L/S/H, p.S461C, p.A473T/V, and p.Y503H/C/F. The upregulation of SLC34A2 was found in samples of myeloid, bowel, ovarian, and uterine tumors; downregulation was found in tumor samples of breast, liver, lung, and skin cancer tumors. It was found that the life expectancy of breast and thymus cancer patients with an SLC34A2 mutation is lower, and it was revealed that SLC34A2 overexpression reduced the life span of patients with brain, ovarian, and pancreatic tumors. Thereby, for these types of oncological diseases, the mutational profile of SLC34A2 can be a potential prognostic marker for breast and thymus cancers, and the upregulation of SLC34A2 can be a potential prognostic marker for brain, ovarian, and pancreatic cancers.

DNA-protein interactions, including DNA-antibody complexes, have both fundamental and practical significance. In particular, antibodies against double-stranded DNA play an important role in the pathogenesis of autoimmune diseases. Elucidation of structural mechanisms of an antigen recognition and interaction of anti-DNA antibodies provides a basis for understanding the role of DNA-containing immune complexes in human pathologies and for new treatments. Here we used Molecular Dynamic simulations of bimolecular complexes of a segment of dsDNA with a monoclonal anti-DNA antibody's Fab-fragment to obtain detailed structural and physical characteristics of the dynamic intermolecular interactions. Using a computationally modified crystal structure of a Fab-DNA complex (PDB: 3VW3), we studied in silico equilibrium Molecular Dynamics of the Fab-fragment associated with two homologous dsDNA fragments, containing or not containing dimerized thymine, a product of DNA photodamage. The Fab-fragment interactions with the thymine dimer-containing DNA was thermodynamically more stable than with the native DNA. The amino acid residues constituting a paratope and the complementary nucleotide epitopes for both Fab-DNA constructs were identified. Stacking and electrostatic interactions were shown to play the main role in the antibody-dsDNA contacts, while hydrogen bonds were less significant. The aggregate of data show that the chemically modified dsDNA (containing a covalent thymine dimer) has a higher affinity toward the antibody and forms a stronger immune complex. These findings provide a mechanistic insight into formation and properties of the pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus, associated with skin photosensibilization and DNA photodamage.

The use of precisely applied mechanical forces to induce site-specific chemical transformations is called positional mechanosynthesis, and diamond is an important early target for achieving mechanosynthesis experimentally. The next major experimental milestone may be the mechanosynthetic fabrication of atomically precise 3D structures, creating readily accessible diamond-based nanomechanical components engineered to form desired architectures possessing superlative mechanical strength, stiffness, and strength-to-weight ratio. To help motivate this future experimental work, the present paper addresses the basic stability of the simplest nanoscale diamond structures-cubes and octahedra-possessing clean, hydrogenated, or partially hydrogenated surfaces. Computational studies using Density Functional Theory (DFT) with the Car-Parrinello Molecular Dynamics (CPMD) code, consuming ∼1,466,852.53 CPU-hours of runtime on the IBM Blue Gene/P supercomputer (23 TFlops), confirmed that fully hydrogenated nanodiamonds up to 2 nm (∼900-1800 atoms) in size having only C(111) faces (octahedrons) or only C(110) and C(100) faces (cuboids) maintain stable sp 3 hybridization. Fully dehydrogenated cuboid nanodiamonds above 1 nm retain the diamond lattice pattern, but smaller dehydrogenated cuboids and dehydrogenated octahedron nanodiamonds up to 2 nm reconstruct to bucky-diamond or onion-like carbon (OLC). At least three adjacent passivating H atoms may be removed, even from the most graphitization-prone C(111) face, without reconstruction of the underlying diamond lattice.

The use of precisely applied mechanical forces to induce site-specific chemical transformations is called positional mechanosynthesis, and diamond is an important early target for achieving mechanosynthesis experimentally. A key step in diamond mechanosynthesis (DMS) may employ a Ge-substituted adamantane-based hydrogen donation tool (HDon) for the site-specific mechanical hydrogenation of depassivated diamond surfaces. This paper presents the first theoretical study of DMS tool-workpiece operating envelopes and optimal tool approach trajectories for a positionally controlled hydrogen donation tool during scanning-probe based UHV diamond mechanosynthesis. Trajectories were analyzed using Density Functional Theory (DFT) in PC-GAMESS at the B3LYP/6-311G(d, p)//B3LYP/3-21G(2d, p) level of theory. The results of this study help to define equipment and tooltip motion requirements that may be needed to execute the proposed reaction sequence experimentally and provide support for early developmental targets as part of a comprehensive near-term DMS implementation program.

Статья посвящена изучению содержания основных белков апоптоза (каспазы-3, Bcl-2) и аутофагии (LC3-II, Rubicon, UVRAG) в Т-клетках больных легкой и тяжелой формами атопической бронхиальной астмы. Анализ проводился на свежевыделенных и культивированных клетках в течение 3 и 6 сут. Результаты исследования содержания апоптотических белков показали, что культивирование клеток сопровождается снижением содержания активной формы каспазы-3 и повышением белка Bcl-2 в группах больных астмой, причем выявленные изменения возрастают с увеличением тяжести заболевания. Анализ белков аутофагии показал наличие II формы LC3-белка в группе с тяжелой формой заболевания и повышение содержания Rubicon и UVRAG по сравнению с контрольной группой. Полученные результаты позволяют сделать вывод, что для обеих исследованных групп больных астмой характерно торможение апоптоза Т-лимфоцитов. Наиболее выраженная устойчивость установлена в группе с тяжелой формой заболевания. Снижение апоптотической активности сопровождается повышением аутофагического процесса, который, по-видимому, служит альтернативным путем гибели клеток.