Methyltransferase Set7/9 as a Multifaceted Regulator of ROS Response.

Reactive oxygen species (ROS) induce multiple signaling cascades in the cell and hence play an important role in the regulation of the cell's fate. ROS can cause irreversible damage to DNA and proteins resulting in cell death. Therefore, finely tuned regulatory mechanisms exist in evolutionarily diverse organisms that are aimed at the neutralization of ROS and its consequences with respect to cellular damage. The SET domain-containing lysine methyltransferase Set7/9 (KMT7, SETD7, SET7, SET9) post-translationally modifies several histones and non-histone proteins via monomethylation of the target lysines in a sequence-specific manner. In cellulo, the Set7/9-directed covalent modification of its substrates affects gene expression, cell cycle, energy metabolism, apoptosis, ROS, and DNA damage response. However, the in vivo role of Set7/9 remains enigmatic. In this review, we summarize the currently available information regarding the role of methyltransferase Set7/9 in the regulation of ROS-inducible molecular cascades in response to oxidative stress. We also highlight the in vivo importance of Set7/9 in ROS-related diseases

Influence of welding on aluminium alloy AW6082-T6 strength

Comparison of welding influence on structural strength of Al-Mg-Si alloy (AW6082-T6), supplied with 10 mm thick sheets, is made. Within the research tension and impact tests of welding joints, made with argon-arc and friction stir welding, were carried out. During the research we observed the following: strength and plasticity decrease for welding joint zones, impact strength increase of weld metal in friction stir welding, welding defects influence on joint strength

Phytochemicals Target Multiple Metabolic Pathways in Cancer.

Cancer metabolic reprogramming is a complex process that provides malignant cells with selective advantages to grow and propagate in the hostile environment created by the immune surveillance of the human organism. This process underpins cancer proliferation, invasion, antioxidant defense, and resistance to anticancer immunity and therapeutics. Perhaps not surprisingly, metabolic rewiring is considered to be one of the "Hallmarks of cancer". Notably, this process often comprises various complementary and overlapping pathways. Today, it is well known that highly selective inhibition of only one of the pathways in a tumor cell often leads to a limited response and, subsequently, to the emergence of resistance. Therefore, to increase the overall effectiveness of antitumor drugs, it is advisable to use multitarget agents that can simultaneously suppress several key processes in the tumor cell. This review is focused on a group of plant-derived natural compounds that simultaneously target different pathways of cancer-associated metabolism, including aerobic glycolysis, respiration, glutaminolysis, one-carbon metabolism, de novo lipogenesis, and β-oxidation of fatty acids. We discuss only those compounds that display inhibitory activity against several metabolic pathways as well as a number of important signaling pathways in cancer. Information about their pharmacokinetics in animals and humans is also presented. Taken together, a number of known plant-derived compounds may target multiple metabolic and signaling pathways in various malignancies, something that bears great potential for the further improvement of antineoplastic therapy

Femtosecond primary charge separation in Synechocystis sp. PCC 6803 photosystem I

AbstractThe ultrafast (<100fs) conversion of delocalized exciton into charge-separated state between the primary donor P700 (bleaching at 705nm) and the primary acceptor A0 (bleaching at 690nm) in photosystem I (PS I) complexes from Synechocystis sp. PCC 6803 was observed. The data were obtained by application of pump–probe technique with 20-fs low-energy pump pulses centered at 720nm. The earliest absorbance changes (close to zero delay) with a bleaching at 690nm are similar to the product of the absorption spectrum of PS I complex and the laser pulse spectrum, which represents the efficiency spectrum of the light absorption by PS I upon femtosecond excitation centered at 720nm. During the first ∼60fs the energy transfer from the chlorophyll (Chl) species bleaching at 690nm to the Chl bleaching at 705nm occurs, resulting in almost equal bleaching of the two forms with the formation of delocalized exciton between 690-nm and 705-nm Chls. Within the next ∼40fs the formation of a new broad band centered at ∼660nm (attributed to the appearance of Chl anion radical) is observed. This band decays with time constant simultaneously with an electron transfer to A1 (phylloquinone). The subtraction of kinetic difference absorption spectra of the closed (state P700+A0A1) PS I reaction center (RC) from that of the open (state P700A0A1) RC reveals the pure spectrum of the P700+A0− ion–radical pair. The experimental data were analyzed using a simple kinetic scheme: An* →k1 [(PA0)*A1→<100fs P+A0−A1] →k2P+A0A1−, and a global fitting procedure based on the singular value decomposition analysis. The calculated kinetics of transitions between intermediate states and their spectra were similar to the kinetics recorded at 694 and 705nm and the experimental spectra obtained by subtraction of the spectra of closed RCs from the spectra of open RCs. As a result, we found that the main events in RCs of PS I under our experimental conditions include very fast (<100fs) charge separation with the formation of the P700+A0−A1 state in approximately one half of the RCs, the ∼5-ps energy transfer from antenna Chl* to P700A0A1 in the remaining RCs, and ∼25-ps formation of the secondary radical pair P700+A0A1−

Mars’ plasma system. Scientific potential of coordinated multipoint missions: “The next generation”

The objective of this White Paper, submitted to ESA’s Voyage 2050 call, is to get a more holistic knowledge of the dynamics of the Martian plasma system, from its surface up to the undisturbed solar wind outside of the induced magnetosphere. This can only be achieved with coordinated multi-point observations with high temporal resolution as they have the scientific potential to track the whole dynamics of the system (from small to large scales), and they constitute the next generation of the exploration of Mars analogous to what happened at Earth a few decades ago. This White Paper discusses the key science questions that are still open at Mars and how they could be addressed with coordinated multipoint missions. The main science questions are: (i) How does solar wind driving impact the dynamics of the magnetosphere and ionosphere? (ii) What is the structure and nature of the tail of Mars’ magnetosphere at all scales? (iii) How does the lower atmosphere couple to the upper atmosphere? (iv) Why should we have a permanent in-situ Space Weather monitor at Mars? Each science question is devoted to a specific plasma region, and includes several specific scientific objectives to study in the coming decades. In addition, two mission concepts are also proposed based on coordinated multi-point science from a constellation of orbiting and ground-based platforms, which focus on understanding and solving the current science gaps

Regularities of plastic deformation development in the crack tip vicinity

When determining the service life of cyclically loaded metal structures at the stage of fatigue crack development, an important role is played by the accuracy of assessing the plastic deformation zone size at the crack tip formed by the tensile overload. Within this zone, after reducing the load to the initial level, the fatigue crack development slows down. Despite the large number of studies in this area, none of the proposed dependencies is currently fully confirmed by experimental results in determining the plasticity zone size. The aim of the work is to assess the size of the plastic deformation zone formed by a single tensile overload. In the work of the finite element method for central-notch specimens and compact tension specimens, an analysis of the stress-strain state in the crack top vicinity is performed. As a calculation, a flat and three-dimensional model was used. Calculations are performed in the Ansys 14.0. Data on the mechanical properties of steels were used: St20, VSt3sp, 09G2S, 15G2SF. With increasing load, the plastic zone size in front of the crack tip was estimated, in the process of reduction, the distribution and length of the fields of residual compressive stresses and the size of the cyclic plastic zone were recorded, the length of which was also determined experimentally using strain gauges with a base of 0.5 mm. To assess the plastic zone size formed by a single tensile overload, a dependence is proposed that takes into account the patterns of plastic deformation development in the vicinity of the fatigue crack tip, and the results of the calculation agree well with the experimental data given in the literature. The obtained expression makes it possible to predict with greater reliability the development of fatigue cracks at variable load amplitudes

The informative nature of the tests for evaluating the processability of a steel product

The reasons for the appearance of cracks in the mounting connection, which is an unequal angle obtained by a plate at a right angle of 8x210x100, are investigated. The limited information received at the standard scope of material tests is shown to assess the processability of the product. Investigation of the composition, structure and viscosity of the material made it possible to establish that in order to obtain a quality product from rolled steel of St3sp, it is necessary to make changes in the technological operations of cutting and bending the production of the part. When performing the cutting operation of sheet metal, the long side of the plate (210 mm) should be placed along the direction of the fibers of the structure. During bending, the edge of the folding of the sheet must be made across the rolled fiber. For steels that are prone to splitting along the fibers of the structure, correct cutting of the sheet will prevent the formation of cracks along the stretched bending surface and fatigue failure during welding and operation of the assembly line