Development of Naphthalene-Derivative Bis-QACs as Potent Antimicrobials: Unraveling Structure-Activity Relationship and Microbiological Properties.

While the pandemic is behind us, the world community faces a global threat of bacterial resistance outbreak. One of the key ways to combat the spread of multi-resistant bacteria is infection prevention and control tactics using modern antiseptic and disinfectant compositions. Herein, we continue the path to unravel the structure-activity relationship (SAR) of potent pyridine-derived biocide class bis-quaternary ammonium compounds (QACs).

Characterization of the C6D7-RBD Human Monoclonal Antibody Specific to the SARS-CoV-2 S Protein Receptor-Binding Domain.

The new coronavirus infection COVID-19 is an acute viral disease that affects primarily the upper respiratory tract. The etiological agent of COVID-19 is the SARS-CoV-2 RNA virus (Coronaviridae family, Betacoronavirus genus, Sarbecovirus subgenus). We have developed a high-affinity human monoclonal antibody, called C6D7-RBD, which is specific to the S protein receptor-binding domain (RBD) from the SARS-CoV-2 Wuhan-Hu-1 strain and exhibits virus-neutralizing activity in a test with recombinant antigens: angiotensin-converting enzyme 2 (ACE2) and RBD.

Mechanism of Action of Monoclonal Antibodies That Block the Activity of the Lethal Toxin of Bacillus Anthracis.

Neutralization of the lethal toxin of Bacillus anthracis is an important topic of both fundamental medicine and practical health care, regarding the fight against highly dangerous infections. We have generated a neutralizing monoclonal antibody 1E10 against the lethal toxin of Bacillus anthracis and described the stages of receptor interaction between the protective antigen (PA) and the surface of eukaryotic cells, the formation of PA oligomers, assembly of the lethal toxin (LT), and its translocation by endocytosis into the eukaryotic cell, followed by the formation of a true pore and the release of LT into the cell cytosol. The antibody was shown to act selectively at the stage of interaction between Bacillus anthracis and the eukaryotic cell, and the mechanism of toxin-neutralizing activity of the 1E10 antibody was revealed.

Comparison of locations and peptide content of postganglionic neurons innervating veins and arteries of the rat hindlimb.

The ganglionic location of hindlimb vasoconstrictor sympathetic neurons in several species is known but the locations of neurons innervating limb arteries or veins, specifically, have not been compared and neurochemical differences between them have not been examined in detail. This study was designed to determine whether neurons innervating arteries and veins are organized as distinct populations and whether neurons innervating arteries, veins or footpads contain the same peptides. Retrograde transport of fluorescent dyes was used to identify, separately, paravertebral postganglionic neurons in the 13th thoracic to 6th lumbar (T13-L6) chain ganglia that innervate the femoral arteries, femoral veins and footpads of the rat hindlimb.

[The role of neurons of the caudal ventrolateral region of the medulla oblongata of cats in the mechanism of realization of the cardio-hemodynamic reaction].

Glycine injection to the identified area of the RVLM leads to the development of a characteristic depressor reaction, due to a decrease of the total peripheral vascular resistance (TRP). Glycine injection to the identified area of CVLM results in the developing pressor reaction also due to the changes of TRP. Glycine injection to CVLM under preliminary functional switch-off the RVLM neuronal activity is not accompanied by the development of pressor reaction.

[The participation of the neurons of the caudal ventrolateral area of the medulla oblongata in the cat in regulating vascular tonus].

Inhibition of the separate neuronal groups located in the caudal ventrolateral part of the cat medulla at different depths from the brain surface is followed by the development of unidirectional cardiohemodynamic reactions. Microinjection of 30 nl of 0.1 M solution of glycine in the chemosensitive area "L" at a depth not more than 700 microns is followed by an increase of the arterial pressure to 160-225%, presumably, due to enhancement of the total peripheral vascular resistance, the cardiac output and heart rate change insignificantly.

Intracentral connections of the brain structures participating in the regulation of blood flow.

In this study, we conducted an investigation into the characteristics of hemodynamic reactions during electrical stimulation of the structures of the hypothalamus and during simultaneous stimulation of the sinus nerve and the hypothalamus in anesthetized cats. We also investigated the monosynaptic connections of the hypothalamus with the structures of the brain stem and spinal cord. The possible influence of the hypothalamus, following the activation of various descending pathways (both through the bulbar level of regulation and by-passing it), upon the efferent component of the regulation of blood circulation is discussed; a scheme of intracentral connections of the brain structures participating in the regulation of blood circulation is presented.

[Intracentral relationships of brain structures participating in blood circulation regulation].

Hemodynamic responses to stimulation of different hypothalamic sites, to simultaneous stimulation of the sinus nerve and a hypothalamic site as well as monosynaptic hypothalamic projections to brain stem structures and spinal cord as studied in anesthetized vagotomized cats revealed that hypothalamic influences to efferent link of cardiovascular control involved different efferent projections with activation of various groups of brain structures. A scheme showing intracentral monosynaptic projections participating in cardiovascular control was drawn.

[Distribution of horseradish peroxidase-labeled neurons, sources of descending fiber systems, in subcortical brain structures and the hypothalamus of cats].

Location of neurons which initiate different descending fibre systems from amygdaloid nuclei, basal ganglia and hypothalamus to brain stem was studied using the method of horse-radish peroxidase retrograde axonal transport. It was shown that neurons from magnocellular part of the basal amygdaloid nucleus and medial part of central amygdaloid nucleus send their axons to the dorsal hypothalamus, substantia nigra, lateral area of the mesencephalic central grey and midbrain reticular formation at the level of inferior olives. The central amygdaloid nucleus is the main source of projections to the hypothalamus and brain stem structures.