Development of the Bispecific Antibody in Fab-scFv Format Based on an Antibody to Human Interferon Beta-1 and Antibody to HER2 Receptor

Russian Journal of Bioorganic Chemistry - The development of new therapies for malignant tumors is an urgent task. Currently, the humanized antibody trastuzumab is considered the “gold...     

Conditioning adhesive contacts between the neutrophils and the endotheliocytes by Staphylococcus aureus

We have developed a model for evaluating the integral intercellular interactions in the “endotheliocyte‐neutrophil” system and have shown the high variability of adhesion contacts in different donors associated with different expression profiles of neutrophils. Two methods (forсe spectroscopy‐spectroscopy and scanning ion‐conductance microscopy) showed a decrease in the rigidity of the membrane‐cytoskeletal complex of neutrophils under the influence of Staphylococcus aureus 2879 M. Adding this strain to the “endotheliocyte‐neutrophil” system caused a statistically significant decrease in the adhesion force and adhesion work, which indicates a change in the expression profile and physicochemical properties of membranes of both types of interacting cells (neutrophils and endotheliocytes).     

Establishment of <i>Rhodiola quadrifida</i> Hairy Roots and Callus Culture to Produce Bioactive Compounds

Rhodiola quadrifida is a rare mountain medicinal plant whose root extracts are used in traditional Chinese medicine as a hemostatic, antitussive, and tonic in the treatment of gynecological diseases. The aim of the study was to obtain R. quadrifida cultures at different degrees of differentiation in vitro and compare their growth characteristics and the content of salidroside and rosavin. Hairy roots were obtained by incubating cotyledons and hypocotyls in a suspension of Agrobacterium rhizogenes strain A4. The presence of the rolB and rolC genes was proven by polymerase chain reaction. The obtained roots were cultivated in Murashige-Skoog medium (MS). Calluses were obtained from the hairy roots in MS medium with the addition of hormones: 3 mg/L 2,4 D and 0.5 mg/L BAP. The presence of the main secondary metabolites of R. quadrifida, salidroside and rosavin, in calluses and salidroside in hairy roots by HPLC/MS was confirmed. The content of salidroside in callus culture was significantly higher than in hairy roots, 0.158 and 0.047%, respectively. The content of rosavin in callus culture was 0.07%. The content of rosavin and salidroside in callus culture was close to the level of these substances in the rhizomes of R. quadrifida plants growing in vivo, making this culture promising for its possible biotechnological use.     

Lamin A as a Determinant of Mechanical Properties of the Cell Nucleus in Health and Disease

Biochemistry (Moscow) - One of the main factors associated with worse prognosis in oncology is metastasis, which is based on the ability of tumor cells to migrate from the primary source and to...     

Climatic Factors Influencing the Anthrax Outbreak of 2016 in Siberia,Russia

In 2016, an outbreak of anthrax killing thousands of reindeer and affecting dozens of humans occurred on the Yamal peninsula, Northwest Siberia, after 70 years of epidemiological situation without outbreaks. The trigger of the outbreak has been ascribed to the activation of spores due to permafrost thaw that was accelerated during the summer heat wave. The focus of our study is on the dynamics of local environmental factors in connection with the observed anthrax revival. We show that permafrost was thawing rapidly for already 6 years before the outbreak. During 2011–2016, relatively warm years were followed by cold years with a thick snow cover, preventing freezing of the soil. Furthermore, the spread of anthrax was likely intensified by an extremely dry summer of 2016. Concurrent with the long-term decreasing trend in the regional annual precipitation, the rainfall in July 2016 was less than 10% of its 30-year mean value. We conclude that epidemiological situation of anthrax in the previously contaminated Arctic regions requires monitoring of climatic factors such as warming and precipitation extremes.

     

Effect of selenolipoic acid on peroxynitrite-dependent inactivation of NADPH-cytochrome P450 reductase

Seleno-organic compounds are known as efficient “scavengers” of peroxynitrite (PN). Here we studied the protective effect of selenolipoic acid (SeLA), the seleno-containing analogue of lipoic acid, on peroxynitrite-dependent inactivation of NADPH-cytochrome P450 reductase. 3-Morpholinosydnonimine hydrochloride (SIN-1) was used as a source of peroxynitrite. The reductase was irreversibly inactivated by PN generated from SIN-1. The inactivation occurred with the rate constant of about 3 × 10⁴M^-1s^-1. The presence of SeLA at low concentration (0.5 μM) led to synergistic increase of the reductase inactivation by PN. Our results suggest the formation of a reactive derivative of SeLA in the reaction of SeLA with PN, probably selenolseleninate, that mediates the aggravation of reductase inactivation. In the presence of SeLA, the inactivation was reversible under the action of thiols, allowing us to conclude that the observed action of SeLA may be considered as protective.     

Synthesis of Non-Natural Pyrimidine Nucleosides

Abstract

Two new non-natural nucleosides bearing an amide (8) or an amidine (9) function have been synthesized. Their properties and the geometry of the exocyclic double bond have been studied.     

Abscisic acid and the herbicide safener cyprosulfamide cooperatively enhance abiotic stress tolerance in rice

Plants adapt to abiotic stress by undergoing diverse biochemical and physiological changes that involve hormone-dependent signaling pathways. The effects of plant hormones can be mimicked by exogenous chemical regulators such as herbicide safeners, which not only enhance stress tolerance but also confer hormetic benefits such as increased vigor and yield. In this study, rice plants growing in normal and saline soils were exposed to abscisic acid (ABA), the safener cyprosulfamide or both compounds together. We found that cyprosulfamide, either alone or in combination with ABA, protected the plants from salinity stress and induced vigorous growth, including the formation of new tillers and early flowering. Proteomic analysis identified several proteins that were induced by stress and/or the chemical treatments, including the late embryogenesis abundant protein OsLEA3, a putative mitochondrial translocase and a putative fumarylacetoacetate hydrolase. The corresponding genes were induced by stress and/or the individual chemical treatments, but expression dropped back when the stress was removed. However, the combination of ABA and cyprosulfamide prolonged the expression of all three genes beyond the stress period, and allowed the plants to maintain their enhanced growth characteristics. These data support a model involving cooperation between the cyprosulfamide and ABA signaling pathways. Accordingly, it was found that cyprosulfamide induces ABA synthesis more robustly than salinity stress, allowing the two regulators to converge on certain downstream target genes. We discuss the impact of our results on current models for the hormonal regulation of stress response pathways in rice and other plants.