The metabolic changes in tumor-associated macrophages during cancer grow in mice with Ehrlich ascites carcinoma

In this work, we investigated the activity of the key NAD(P)-dependent dehydrogenases associated with macrophage tumors in mice with Ehrlich ascites carcinoma. It was shown that cancer grow is associated with the development of conditions in macrophages leading to a decrease in the substrate flow intensity in the tricarboxylic acid cycle, deceleration of oxidative deamination of L-glutamate, NADP regeneration, and a decrease in the antioxidant defense efficiency. There results are consistent with our recent concept on the nonspecific metabolic reaction of cells to extreme exposures.     

Ecdysteroids: isolation,chemical transformations,and biological activity

Phytochemistry Reviews - Ecdysteroids are polyhydroxylated sterols, and are widespread in the plant and animal world. To date, over 520 ecdysteroids have been isolated from natural sources. The...     

Species specificity of morphogenetic factors of Acetabularia, localized in the cytoplasmic zone adjacent to the cell membrane]

The species specificity of the factors controlling the cap development was established in the experiments with the transplantation of both the intact and centrifuged in the basal direction apical regions of Acetabularia meditteranea on nuclear basal regions of A. crenulata. These factors are found at the stage of 72 hrs of regeneration primarily in the cytoplasmic zone adjacent to the cell membrane which is not displaced during centrifugation. Using direct measurements and radiochemical method, we have shown that the accumulation of proteins proceeded in this zone due, mainly, to their transition from the cytoplasmic zone displaced during centrifugation.     

The CRISPR-associated Cas4 protein Pcal_0546 from Pyrobaculum calidifontis contains a [2Fe-2S] cluster: crystal structure and nuclease activity

Cas4 nucleases constitute a core family of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) associated proteins, but little is known about their structure and activity. Here we report the crystal structure of the Cas4 protein Pcal_0546 from Pyrobaculum calidifontis, which revealed a monomeric protein with a RecB-like fold and one [2Fe-2S] cluster coordinated by four conserved Cys residues. Pcal_0546 exhibits metal-dependent 5′ to 3′ exonuclease activity against ssDNA substrates, whereas the Cas4 protein SSO1391 from Sulfolobus solfataricus can cleave ssDNA in both the 5′ to 3′ and 3′ to 5′ directions. The active site of Pcal_0546 contains a bound metal ion coordinated by the side chains of Asp123, Glu136, His146, and the main chain carbonyl of Ile137. Site-directed mutagenesis of Pcal_0546 and SSO1391 revealed that the residues of RecB motifs II, III and QhXXY are critical for nuclease activity, whereas mutations of the conserved Cys residues resulted in a loss of the iron-sulfur cluster, but had no effect on DNA cleavage. Our results revealed the biochemical diversity of Cas4 nucleases, which can have different oligomeric states, contain [4Fe-4S] or [2Fe-2S] clusters, and cleave single stranded DNA in different directions producing single-stranded DNA overhangs, which are potential intermediates for the synthesis of new CRISPR spacers.     

Normalization of the adaptive avoidance reaction in rats using substances with nootropic activity

The system of double coaxial cylinders filled with water was used as a device for studying simple extrapolation behaviour of rats. The amount of rats which were able to dive under the lower edge of the inner cylinder, without reaching the bottom of the outer cylinder and the latency of this avoidance reaction were considered as a measure of extrapolation ability. This reaction was altered by the pretreatment of animals with cycloheximide, a protein synthesis inhibitor. Piracetam as a standard nootropic, sodium and lithium hydroxybutyrate as substances with a potential nootropic effect were shown to be able to antagonize the damaging effect of cycloheximide on the avoidance performance. Benzodiazepine tranquilizer, phenazepam, in contrast to nootropics, evokes additional worsening of extrapolation reaction. Normalization of avoidance disturbed by cycloheximide, can be used as an adequate and informative approach for screening of nootropics.