Nutrients are essential for living organisms because they fuel biological processes in cells. Cells monitor nutrient abundance and coordinate a ratio of anabolic and catabolic reactions. Mechanistic target of rapamycin (mTOR) signaling is the essential nutrient-sensing pathway that controls anabolic processes in cells. The central component of this pathway is mTOR, a highly conserved and essential protein kinase that exists in two distinct functional complexes. The nutrient-sensitive mTOR complex 1 (mTORC1) controls cell growth and cell size by phosphorylation of the regulators of protein synthesis S6K1 and 4EBP1, whereas its second complex, mTORC2, regulates cell proliferation by functioning as the regulatory kinase of Akt and other members of the AGC kinase family. The regulation of mTORC2 remains poorly characterized. Our study shows that the cellular ATP balance controls a basal kinase activity of mTORC2 that maintains the integrity of mTORC2 and phosphorylation of Akt on the turn motif Thr-450 site. We found that mTOR stabilizes SIN1 by phosphorylation of its hydrophobic and conserved Ser-260 site to maintain the integrity of mTORC2. The optimal kinase activity of mTORC2 requires a concentration of ATP above 1.2 mm and makes this kinase complex highly sensitive to ATP depletion. We found that not amino acid but glucose deprivation of cells or acute ATP depletion prevented the mTOR-dependent phosphorylation of SIN1 on Ser-260 and Akt on Thr-450. In a low glucose medium, the cells carrying a substitution of SIN1 with its phosphomimetic mutant show an increased rate of cell proliferation related to a higher abundance of mTORC2 and phosphorylation of Akt. Thus, the homeostatic ATP sensor mTOR controls the integrity of mTORC2 and phosphorylation of Akt on the turn motif site.

The nuclear import of ribosomal proteins is regulated by mTOR The nuclear import of ribosomal proteins is regulated by mTOR

Aim of the present study was to provide presence of opisthorchiid metacercariae in cyprinid fish Leuciscus idus in Nura-Sarysu river, Kazakhstan. Infection rate of the ides by the metacercariae was 42%. The metacercariae, similar morphologically to those of the liver flukes, were found: elliptical in shape, 0.19-0.25×0.15-0.22 mm, oral and ventral suckers nearly equal size, and excretory bladder O-shape with black content, occupying posterior part of the body. The metacercariae were divided into 2 groups with differences in size and thickness of cyst wall. Adult flukes were recovered from the Syrian hamsters infected with the opisthorch metacercariae and identified with morphological characters to Opisthorchis felineus and Metorchis bilis. DNA sequences of ITS1, ITS2, and cox1 supported the taxonomic assignment.

In eukaryotes, ribosome assembly is a rate-limiting step in ribosomal biogenesis that takes place in a distinctive subnuclear organelle, the nucleolus. How ribosomes get assembled at the nucleolar site by forming initial preribosomal complexes remains poorly characterized. In this study, using several human and murine cell lines, we developed a method for isolation of native mammalian preribosomal complexes by lysing cell nuclei through mild sonication. A sucrose gradient fractionation of the nuclear lysate resolved several ribonucleoprotein (RNP) complexes containing rRNAs and ribosomal proteins. Characterization of the RNP complexes with MS-based protein identification and Northern blotting–based rRNA detection approaches identified two types of preribosomes we named here as intermediate preribosomes (IPRibs) and composed preribosome (CPRib). IPRib complexes comprised large preribosomes (105S to 125S in size) containing the rRNA modification factors and premature rRNAs. We further observed that a distinctive CPRib complex consists of an 85S preribosome assembled with mature rRNAs and a ribosomal biogenesis factor, Ly1 antibody–reactive (LYAR), that does not associate with premature rRNAs and rRNA modification factors. rRNA-labeling experiments uncovered that IPRib assembly precedes CPRib complex formation. We also found that formation of the preribosomal complexes is nutrient-dependent because the abundances of IPRib and CPRib decreased substantially when cells were either deprived of amino acids or exposed to an mTOR kinase inhibitor. These findings indicate that preribosomes form via dynamic and nutrient-dependent processing events and progress from an intermediate to a composed state during ribosome maturation.

Background and Aim: The study of Echinococcus infection among farm animals in Kazakhstan was carried out to monitor the invasion among livestock and map the data obtained. Unfortunately, there are only partial data on the study of echinococcosis among wild carnivores in Kazakhstan, which makes it difficult to conduct a comparative analysis of the epidemiological situation among wild animals. The present study aimed to estimate the genetic diversity of Echinococcus spp. (Leuckart, 1863) in Kazakhstan based on sequence analysis of cytochrome c oxidase subunit 1 (cox1) and dehydrogenase subunit 1 (nad1) of worms isolated from wild carnivorous animals wolf (Canis lupus), red fox (Vulpes vulpes) and corsac (Vulpes corsac). Materials and Methods: DNA from parasite tissue was used as a template for the amplification of the two mitochondrial genes cox1 and nad1. Sequencing was performed according to the manual for the Seq Studio Genetic Analyzer. The multiple alignments of obtained sequences were performed using the ClustalW algorithm in Mega (v.11) software. Alignments were exported as a Nexus extension and used as input for TCS v1.21 for the identification of haplotypes. The phylogenetic analysis was constructed according to the neighbor-joining method using Mega (v.11) software. Results: Analysis of the extensiveness of echinococcosis invasion showed that 6.3% were wolves, 18.2% were corsacs, and 85% were foxes. In total, 159 adults of Echinococcus spp. from the three species of animals in different parts of Kazakhstan were analyzed, and 17 individual biological samples were successfully sequenced. Sequence analysis of cox1 and nad1 genes revealed two types of echinococcosis – Echinococcus granulosus in red foxes and wolves, and Echinococcus multilocularis in corsacs. Sequencing of a portion of the mitochondrial genome made it possible to determine seven haplotypes of the pathogen in the studied samples of E. granulosus. Molecular analysis of cox1 and nad1 genes of E. multilocularis revealed three new haplotypes, which have significant variability compared with other studied Asian haplotypes. Conclusion: This study made it possible to fill the gaps in understanding the localization of the foci of the spread of the echinococcosis pathogen among the main wild carnivores and to determine the species reservoir of the pathogen in the greater territory of Kazakhstan.

We report a rare case of non-dermatophytic onychomycosis of the toenail caused by Phoma macrostoma. Was studied the biological properties of the strain isolated in Kazakhstan. P. macrostoma forms pink colonies, the reverzum is pink-orange. The mycelium is colorless, septate. The appearance of growth tubes from pycnidospores occurs within 12 hours, mycelial growth and branching after 18 hours, the appearance of pycnids is 48 hours. The saccharolytic and urease activity of the strain is low.