How allosteric control of Staphylococcus aureus penicillin binding protein 2a enables methicillin resistance and physiological function

6 pags, 4 figs, 1 tabThe expression of penicillin binding protein 2a (PBP2a) is the basis for the broad clinical resistance to the β-lactam antibiotics by methicillin-resistant Staphylococcus aureus (MRSA). The highmolecular mass penicillin binding proteins of bacteria catalyze in separate domains the transglycosylase and transpeptidase activities required for the biosynthesis of the peptidoglycan polymer that comprises the bacterial cell wall. In bacteria susceptible to β-lactam antibiotics, the transpeptidase activity of their penicillin binding proteins (PBPs) is lost as a result of irreversible acylation of an active site serine by the β-lactam antibiotics. In contrast, the PBP2a of MRSA is resistant to β-lactam acylation and successfully catalyzes the DD-transpeptidation reaction necessary to complete the cell wall. The inability to contain MRSA infection with β-lactam antibiotics is a continuing public health concern. We report herein the identification of an allosteric binding domain - a remarkable 60 Å distant from the DD-transpeptidase active site - discovered by crystallographic analysis of a soluble construct of PBP2a. When this allosteric site is occupied, a multiresidue conformational change culminates in the opening of the active site to permit substrate entry. This same crystallographic analysis also reveals the identity of three allosteric ligands: muramic acid (a saccharide component of the peptidoglycan), the cell wall peptidoglycan, and ceftaroline, a recently approved anti-MRSA β-lactam antibiotic. The ability of an anti-MRSA β-lactam antibiotic to stimulate allosteric opening of the active site, thus predisposing PBP2a to inactivation by a second β-lactam molecule, opens an unprecedented realm for β-lactam antibiotic structure-based design.Work in the United States was supported by National Institutes of Health Grants AI090818 and AI104987, and work in Spain was supported by Grants BFU2011-25326 (from the Spanish Ministry of Economy and Competitiveness) and S2010/BMD-2457 (from the Autonomous Government of Madrid)

Study of the operation features of CHP cooling tower in conditions of forced air supply

Abstract In our country, at thermal and nuclear power plants, tower cooling towers built in 1960-1975 are still in operation. At the same time, the construction of new facilities and the modernization of existing installations requires a high-quality mathematical study of technical solutions. As part of the work, it is proposed to simulate the operation of a tower cooling tower, subject to additional forced air supply. Using the equations of heat and material balance for the cooling tower, a mathematical model of the operation of the cooling tower was developed in Microsoft Excel. The modelling of the operation of the cooling tower in the design conditions of the city of Yoshkar-Ola, as well as when installing additional fans of various capacities, has been carried out.</jats:p

Study of the biogas plant with catalytic heating

Abstract Nowadays improving the methods of anaerobic processing of organic waste is an important topic in the development of biogas technologies. Different articles suggest different options to increase the efficiency of biogas plants. The use of catalytic heaters in biogas plants makes it possible to increase the efficiency of their operation. To study the features of using catalytic heaters, a scheme for the functioning of a biogas plant with catalytic heating was developed. The experimental studies with the use of the designed biogas plant with catalytic heating was carried out. Experimental studies of the designed biogas plant with catalytic heating showed the applicability of the proposed technical solutions for the catalytic heating system.</jats:p

Mathematical modeling of a PV installation for rural electrification

Abstract Since a new Federal Law of the Russian Federation “On Electric Power Industry” has been adopted consumers with microgeneration systems can now sell excess electric energy. Consequently, more agricultural consumers got interested in using renewable energy installations. In this context, the study focuses on mathematical modeling of electricity output by a microgeneration system, in particular with PV panels, to assess the conceivable amount of electric energy that can be eventually sold. The authors built a model of the system tied to a grid for three options: fixed-tilt PV panels, PV panels with a solar tracking system, and concentrator PV systems. The findings analysis confirms that in order to maximize the electricity transmitted to the electric grid, it is rational to use solar energy concentrators with a Sun-tracking system.</jats:p

Influence of cultivation factors on morphogenesis in vitro Salix acutifolia Willd

AbstractSalix contains salicylates in their leaves, bark, and buds. That is why there is a necessity in elaborating microcloning propagation technologies of same genotypes which are high productive in salicin in order to create industrial plantations. The study examined the effect of 25 different combinations of BAP and NAA concentrations on the growth and development of S. acutifolia. The best results were observed on MS supplemented with 1.0 mg/l BAP and 0.01 or 0.1 mg/l NAA, and rhizogenesis on MS medium supplemented with 0.1 and 0.2 mg/l NAA. In order to study the effect of the mineral composition of basic media on the morphogenesis of S. acutifolia in an in vitro culture, DKW, GD, MS, and WPM were tested. Kn, BAP, and 2iP were compared to study the effect of cytokinins on the morphogenetic ability of S. acutifolia explants. The influence of the mineral composition of the medium on the rhizogenesis of S. acutifolia explants in vitro was evaluated on four studied media DKW, GD, WPM, and MS. Each medium contained 3% sucrose, 0.6% agar-agar, and 0.2 mg/l NAA. As a control, MS medium supplemented with 0.2 mg/l NAA was selected.</jats:p