ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

Semirigid inclusions in elastic bodies: Mechanical interplay and optimal control

The paper concerns an analysis of an equilibrium problem for 2D elastic body with two semirigid inclusions. It is assumed that inclusions have a joint point, and we investigate a junction problem for these inclusions. The existence of solutions is proved, and different equivalent formulations of the problem are proposed. We investigate a convergence to infinity of a rigidity parameter of the semirigid inclusion. It is proved that in the limit, we obtain an equilibrium problem for the elastic body with a rigid inclusion and a semirigid one. A parameter identification problem is investigated. In particular, the existence of a solution to a suitable optimal control problem is proved.     

Synergistic antimicrobial effect of lactocin AL705 and nisin combined with organic acid salts against Listeria innocua 7 in broth and a hard cheese

The effectiveness of antimicrobial mixtures against Listeria innocua 7, used as a L. monocytogenes surrogate, was investigated in broth and a food system. Synergistic effects were found for nisin (Nis), potassium sorbate (PS), calcium propionate (CP) and sodium lactate (SL), Nis + PS being the most effective binary mixture that exhibited listericidal activity in broth. To assess the effect of adding lactocin AL705 (AL705) to Nis + organic acid salt combinations, tridimensional isobolograms were generated. Sub-MIC combinations of the antimicrobials exerted bactericidal activity against L. innocua 7 after AL705 addition to the binary mixtures. However, when applied on Sardo cheese contaminated with L. innocua 7 (initial inoculum 4.45 ± 0.06 CFU g⁻¹), only Nis + PS + AL705 produced count reductions respect to the control, reaching 3.04 ± 0.35 CFU g⁻¹ counts after 15 days at 15 °C. Ternary combinations containing AL705 showed potential to reduce antimicrobial usages for L. innocua 7 inhibition.     

Dynamic Effects of Submillimeter Wave Radiation on Biological Objects of Various Levels of Organization

We have presented an overview of the literature and of our experimental data on the influence of electromagnetic radiation in the submillimeter spectral region on biological objects of molecular, cellular, and organism levels. Possible physical mechanisms involved and the reasons for limited development of the research in this spectral range are discussed.     

Waveguide probe structures for a multilayer magnetodielectric: An inverse problem

Direct and inverse problems are considered for diffraction by an open end of a rectangular waveguide (RW) with a flange that adjoins a piecewise inhomogeneous planar layered lossy medium. Also considered are similar diffraction problems for a junction of an RW and a rectangular resonator filled with a multilayer medium and a junction of two RWs, one of which contains a multilayer plate. Such open and shielded waveguide probe structures (WPSs) are used for determination and nondestructive testing of parameters of multilayer samples. The direct problem is formulated on the basis of admittance and impedance algorithms with consideration for losses existing in the medium, flange, and screens. In this case, the approximation of the given aperture field allows obtainment of explicit solutions for open and shielded WPSs in the form of integrals. Solution of the inverse problem that lies in determining thicknesses, permittivities, and permeabilities of the layers from measured values of the magnitude of the reflection coefficient is obtained by minimizing the corresponding least-squares error and by constructing artificial neural networks. In order to increase the accuracy, it is proposed to use a two-port of errors and perform measurements for several positions of the sample with respect to the flange and different impedance conditions behind the sample.     

Structure and composition of guanidine acrylate, guanidine methacrylate, their homopolymers, and copolymers with diallyldimethylammonium chloride

Structures and compositions of the monomers guanidine acrylate and guanidine methacrylate, their homopolymers, and copolymers with diallyldimethylammonium chloride enriched in acrylate comonomer units were determined. It was shown that ampholytic copolymers, owing to their ionic nature, contained comonomeric guanidine acrylate or methacrylate units and diallyldimethylammonium chloride units, as well as the acrylate comonomer with the diallyl counterion and polymeric acrylate and diallyl ion pairs. It follows from IR and ¹H NMR data that guanidine methacrylate has the same structure (with two hydrogen bonds) in the solid state and in solutions. Guanidine acrylate structures in the solid state and in dimethylsulfoxide are identical and analogous to guanidine methacrylate structure in this solvent. In water, the guanidine acrylate structure has another type of hydrogen bonding (with one hydrogen bond, where the proton is shifted toward the guanidine group). These features of hydrogen bonding of guanidine acrylate and guanidine methacrylate are also retained in their homopolymers and copolymers with diallyldimethylammonium chloride. It was shown that the thermal stability of the copolymers was higher than that of their homopolymers, confirming the formation of intramolecular ion pairs of oppositely charged units of ampholytic copolymers. Moreover, the thermal stability of guanidine methacrylate-diallyldimethylammonium chloride copolymers is higher than that of guanidine acrylate-diallyldimethylammonium chloride copolymers.     

Influence of Cu<Superscript>2+</Superscript> ions on structural and magnetic properties of NiZn ferrites

The paper is devoted to the preparation of NiZn ferrite with small substitutions of copper by means of ceramic technology. The influence of small Cu substitution on the microstructural and magnetic properties of NiZn ferrites have been analysed by means of various experimental methods and interpreted from the point of view of preparation technology optimisation and possible applications of such materials. A strong correlation between the substituent content and resulting properties has been observed, thus allowing preparation of material with the properties tailored for any particular application.     

Control of locomotion in the marine mollusc Clione limacina. XI. Effects of serotonin

The locomotor activity in the marine mollusc Clione limacina has been found to be strongly excited by serotonergic mechanisms. In the present study putative serotonergic cerebropedal neurons were recorded simultaneously with pedal locomotor motoneurons and interneurons. Stimulation of serotonergic neurons produced acceleration of the locomotor rhythm and strengthening of motoneuron discharges. These effects were accompanied by depolarization of motoneurons, while depolarization of the generator interneurons was considerably lower (if it occurred at all). Effects of serotonin application on isolated locomotor and non-locomotor pedal neurons were studied. Serotonin (5 x 10(-7) to 1 x 10(-6) M) affected most pedal neurons. All locomotor neurons were excited by serotonin. This suggests that serotonergic command neurons exert direct influence on locomotor neurons. Effects of serotonin on nonlocomotor neurons were diverse, most neurons being inhibited by serotonin. Some effects of serotonin on locomotor neurons could not be reproduced by neuron depolarization. This suggests that, along with depolarization, serotonin modulates voltage-sensitive membrane properties of the neurons. As a result, serotonin promotes the endogenous rhythmical activity in neurons of the C. limacina locomotor central pattern generator.