The Nucleocapsid (N) Proteins of Different Human Coronaviruses Demonstrate a Variable Capacity to Induce the Formation of Cytoplasmic Condensates.

To date, seven human coronaviruses (HCoVs) have been identified. Four of these viruses typically manifest as a mild respiratory disease, whereas the remaining three can cause severe conditions that often result in death. The reasons for these differences remain poorly understood, but they may be related to the properties of individual viral proteins.

Bifunctionalized Betulinic Acid Conjugates with C-3-Monodesmoside and C-28-Triphenylphosphonium Moieties with Increased Cancer Cell Targetability.

A convenient synthesis is presented for a new class of bioactive bifunctionalized conjugates of lupane-type triterpenoids with triphenylphosphonium (TPP) and glycopyranosyl targeting moieties. The main synthesis steps include glycosylation of haloalkyl esters of the triterpene acid at the C-3 position by the imidate derivatives of glycopyranose followed by the product modification at the C-28 position with triphenylphosphine. The conjugates of betulinic acid (BetA) with TPP and d-glucose, l-rhamnose, or d-mannose moieties were thus synthesized as potential next-generation BetA-derived anticancer compounds.

Ectopic expression of HIV-1 Tat modifies gene expression in cultured B cells: implications for the development of B-cell lymphomas in HIV-1-infected patients.

An increased frequency of B-cell lymphomas is observed in human immunodeficiency virus-1 (HIV-1)-infected patients, although HIV-1 does not infect B cells. Development of B-cell lymphomas may be potentially due to the action of the HIV-1 Tat protein, which is actively released from HIV-1-infected cells, on uninfected B cells. The exact mechanism of Tat-induced B-cell lymphomagenesis has not yet been precisely identified.

NEDD9 Restrains dsDNA Damage Response during Non-Small Cell Lung Cancer (NSCLC) Progression.

DNA damaging modalities are the backbone of treatments for non-small cell lung cancer (NSCLC). Alterations in DNA damage response (DDR) in tumor cells commonly contribute to emerging resistance to platinating agents, other targeted therapies, and radiation. The goal of this study is to identify the previously unreported role of NEDD9 scaffolding protein in controlling DDR processes and sensitivity to DNA damaging therapies.

Molecular Coevolution of Nuclear and Nucleolar Localization Signals inside the Basic Domain of HIV-1 Tat.

During evolution, viruses had to adapt to an increasingly complex environment of eukaryotic cells. Viral proteins that need to enter the cell nucleus or associate with nucleoli possess nuclear localization signals (NLSs) and nucleolar localization signals (NoLSs) for nuclear and nucleolar accumulation, respectively. As viral proteins are relatively small, acquisition of novel sequences seems to be a more complicated task for viruses than for eukaryotes.

Musashi 2 (MSI2) expression as an independent prognostic biomarker in non-small cell lung cancer (NSCLC).

Background: Musashi-2 (MSI2) is a member of RNA-binding protein family that regulates mRNA translation of numerous intracellular targets and influences maintenance of stem cell identity. This study assessed MSI2 as a potential clinical biomarker in non-small cell lung cancer (NSCLC).

Methods: The current study included 40 patients with NSCLC, of whom one presented with stage 1, 14 presented with stage II, 15 presented with stage III, and 10 patients had stage IV.

Calpain activity in plasma of patients with essential tremor and Parkinson's disease: a pilot study.

: Essential tremor (ET) and Parkinson's disease (PD) are the two most common movement disorders in adults with similar clinical symptoms, which is hinting towards existence of coincident pathogenesis steps.: The objective of this report is to characterize the relationship between ET and PD severity and the activity of calcium-dependent proteases calpain in plasma.: The study enrolled 12 volunteers for each condition: ET, PD, healthy.

m-Calpain is released from striatal synaptosomes.

We aimed to investigate whether m-calpain (a Ca2+-dependent neutral cysteine protease) is released from synaptosomes. This research was carry on Wistar male rats and isolated nerve endings - synaptosomes. The synaptosomal integrity was checked by the method of measuring LDH activity.

Glibenclamide as a neuroprotective antidementia drug.

In the view of progressively aging human population and increased occurrence of dysmetabolic disorders, such as diabetes mellitus, cognitive impairment becomes a major threat to the national health. To date, the molecular mechanisms of cognitive dysfunction are partially described for diabetes and diseases of different nature, such as Alzheimer disease or Parkinson disease. The emergence of data pointing towards pleotropic effects of hypoglycaemic medicines indicates involvement of their targets in pathogenesis of cognitive impairment.

The GAR domain integrates functions that are necessary for the proper localization of fibrillarin (FBL) inside eukaryotic cells.

Fibrillarin (FBL) is an essential nucleolar protein that participates in pre-rRNA methylation and processing. The methyltransferase domain of FBL is an example of an extremely well-conserved protein domain in which the amino acid sequence was not substantially modified during the evolution from to . An additional N-terminal glycine-arginine-rich (GAR) domain is present in the FBL of eukaryotes.

Synthetic biology-based cellular biomedical tattoo for detection of hypercalcemia associated with cancer.

Diagnosis marks the beginning of any successful therapy. Because many medical conditions progress asymptomatically over extended periods of time, their timely diagnosis remains difficult, and this adversely affects patient prognosis. Focusing on hypercalcemia associated with cancer, we aimed to develop a synthetic biology-inspired biomedical tattoo using engineered cells that would (i) monitor long-term blood calcium concentration, (ii) detect onset of mild hypercalcemia, and (iii) respond via subcutaneous accumulation of the black pigment melanin to form a visible tattoo.

[GAP-43 and its proteolytic fragment in spinal cord cells of rats with experimental autoimmune encephalomyelitis].

The regenerative capacity of the Central Nervous System (CNS) is a key factor implicated in the pathogenesis of neurodegenerative diseases. In the present study, the regenerative capacity of the CNS is considered using one of the markers of regeneration, Growth Associated Protein-43 (GAP-43) and its proteolytic fragment GAP-43-3 in the Experimental Autoimmune Encephalomyelitis (EAE) animal model of multiple sclerosis. The EAE on Wistar rats was characterized as an adequate model of multiple sclerosis, with typical clinical (pares and paralysis) and morphological (infiltration of spinal cord and deformation of motoneurons) disorders.

Directional R-Loop Formation by the CRISPR-Cas Surveillance Complex Cascade Provides Efficient Off-Target Site Rejection.

CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against foreign nucleic acids. In type I CRISPR-Cas systems, invading DNA is detected by a large ribonucleoprotein surveillance complex called Cascade. The crRNA component of Cascade is used to recognize target sites in foreign DNA (protospacers) by formation of an R-loop driven by base-pairing complementarity.

[The role of calpains in the regulation of synaptic function].

Calpains are calcium-activated neutral cysteine proteases, involved in the regulation of a number of physiological functions. Substrates of calpains include receptors, kinases, phosphatases, cytoskeleton and synaptosomal proteins. Some of them undergo complete degradation, though most of the substrates are subjected to limited proteolysis, which results in proteins having new properties.

Direct observation of R-loop formation by single RNA-guided Cas9 and Cascade effector complexes.

Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems protect bacteria and archaea from infection by viruses and plasmids. Central to this defense is a ribonucleoprotein complex that produces RNA-guided cleavage of foreign nucleic acids. In DNA-targeting CRISPR-Cas systems, the RNA component of the complex encodes target recognition by forming a site-specific hybrid (R-loop) with its complement (protospacer) on an invading DNA while displacing the noncomplementary strand.

[Development of thermotolerance in Drosophila melanogaster line l(1) ts403 with a defect in heat shock protein synthesis].

To elucidate the role of heat shock proteins (HSP) in the formation of resistance to extreme factors and in the development of organismic and cell response to these factors, thermotolerance in a Drosophila melanogaster line with defective HSP synthesis was studied with regard to several criteria: (1) survival of adult-females; (2) damage to egg chambers in ovarioles; (3) dynamics of oviposition; (4) frequency of loss and nondisjunction of sex chromosomes in meiosis of females exposed to a heat shock (HS). According to all these criteria, the l(l)ts403 females were more sensitive to a HS 37 degrees C, the exposure at 37 degrees C for 1 h (HS37) than the females of the wild-type line Canton S. Only the data on the first three aforementioned parameters were indicative of thermotolerance development.

[Mechanisms ensuring the resistance of the genetic material of the cell to stress exposures].

A brief review of studies performed in the Department of Genetics of St. Petersburg University by M.E.

[Temperature modification of the mutation process and heat shock proteins].

Heat shock protein synthesis and mutagenesis (X-chromosome losses induced by radiation and high temperature) were studied in different. Drosophila melanogaster strains. Two models (strain l(1)ts403 with the defect in heat shock protein synthesis and the heat-resistant T strain with a specific reaction to the extreme temperature differing from the wild type strains) were used.

[Formation of heat-sensitivity in the ontogenesis of a heat-resistant Drosophila strain and the relation between this property and the mutation process].

In the experiments with a heat-resistant line of Drosophila melanogaster, it has been shown that organismal heat-resistance is formed during ontogenesis, prior to hatching, though it can be changed, in accordance with the temperature conditions after hatching (acclimation). Heat-resistance of germ cells is formed during the pupal stage; it depends on the development temperature and remains unchanged thereafter. The mutation rate (the frequency of dominant lethals) in oocytes depends on the development temperature and not on the temperature life conditions of imago.

[DNA repair in Drosophila oogenesis].

In experiments with females of lines with an impaired DNA repair systems mei-9 (impaired excision repair) and mei-41 (impaired postreplicative repair), a method of successive irradiation by X-rays (1000 R) and hyperthermia (+37 degrees C) action was used for the purpose of defining a moment when DNA repair takes place in oogenesis. Repair in mature mei-41 oocytes judged of by synergism effect of the both factors acting was ascertained to take place right after X-raying (prior to DNA replication) and being absent at the fertilization period (at the time of or after DNA replication). DNA repair in mei-9 females was not registered in both cases.

[Radiation-protective effectiveness of ATP and adenosine against high-energy protons].

The radioprotective effect of ATP and adenosine was investigated on CBA and C57Bl mice hybrids F1 irradiated with 9 GeV protons. The prophylactic treatment of the animals with ATP at a dose of 350-700 mg/kg increased their survival to 63-80% for LD78-83/30 (7.5-8.

[X-ray-induced breaks in the X chromosomes in Drosophila lines of various radiosensitivities].

The frequency of X-ray induced X-chromosome breaks has been studied in females of the line rad (2) 201G1 hypersensitive to radiation and in females of the control line selected from the same population. The frequency of X-chromosome breaks was judged based on the frequency of X0 males occurrence. Synergism of the effects of X-rays (at doses 0.