The Effect of Mice Adaptation Process on the Pathogenicity of Influenza A/South Africa/3626/2013 (H1N1)pdm09 Model Strain.

Influenza virus strain A/South Africa/3626/2013 (H1N1)pdm09 (SA-WT) is a non-mouse-adapted model strain that has naturally high pathogenic properties in mice. It has been suggested that the high pathogenicity of this strain for mice could be due to the three strain-specific substitutions in the polymerase complex (Q687R in PB1, N102T in PB2, and E358E/K heterogeneity in PB2). To evaluate the role of these replacements, SA-WT was passaged five times in mouse lungs, and the genome of the mouse-adapted version of the SA-WT strain (SA-M5) was sequenced.

A new Caenorhabditis elegans model to study copper toxicity in Wilson disease.

Wilson disease (WD) is caused by mutations in the ATP7B gene that encodes a copper (Cu) transporting ATPase whose trafficking from the Golgi to endo-lysosomal compartments drives sequestration of excess Cu and its further excretion from hepatocytes into the bile. Loss of ATP7B function leads to toxic Cu overload in the liver and subsequently in the brain, causing fatal hepatic and neurological abnormalities. The limitations of existing WD therapies call for the development of new therapeutic approaches, which require an amenable animal model system for screening and validation of drugs and molecular targets.

Abnormalities in Copper Status Associated with an Elevated Risk of Parkinson's Phenotype Development.

In the last 15 years, among the many reasons given for the development of idiopathic forms of Parkinson's disease (PD), copper imbalance has been identified as a factor, and PD is often referred to as a copper-mediated disorder. More than 640 papers have been devoted to the relationship between PD and copper status in the blood, which include the following markers: total copper concentration, enzymatic ceruloplasmin (Cp) concentration, Cp protein level, and non-ceruloplasmin copper level. Most studies measure only one of these markers.

Influence of Silver Nanoparticles on the Growth of Ascitic and Solid Ehrlich Adenocarcinoma: Focus on Copper Metabolism.

The link between copper metabolism and tumor progression motivated us to use copper chelators for suppression of tumor growth. We assume that silver nanoparticles (AgNPs) can be used for lowering bioavailable copper. Our assumption is based on the ability of Ag(I) ions released by AgNPs in biological media and interfere with Cu(I) transport.

Chemical background of silver nanoparticles interfering with mammalian copper metabolism.

The rapidly increasing application of silver nanoparticles (AgNPs) boosts their release into the environment, which raises a reasonable alarm for ecologists and health specialists. This is manifested as increased research devoted to the influence of AgNPs on physiological and cellular processes in various model systems, including mammals. The topic of the present paper is the ability of silver to interfere with copper metabolism, the potential health effects of this interference, and the danger of low silver concentrations to humans.

Properties of recombinant extracellular N-terminal domain of human high-affinity copper transporter 1 (hNdCTR1) and its interactions with Cu(II) and Ag(I) ions.

High-affinity copper transporter 1 (CTR1) is a key link in the transfer of copper (Cu) from the extracellular environment to the cell. Violation in the control system of its expression, or mutations in this gene, cause a global copper imbalance. However, the mechanism of copper transfer CTR1 remains unclear.

Understanding the Variability of Certain Biological Properties of H1N1pdm09 Influenza Viruses.

The influenza virus continually evolves because of the high mutation rate, resulting in dramatic changes in its pathogenicity and other biological properties. This study aimed to evaluate the evolution of certain essential properties, understand the connections between them, and find the molecular basis for the manifestation of these properties. To that end, 21 A(H1N1)pdm09 influenza viruses were tested for their pathogenicity and toxicity in a mouse model with a phenotype manifestation and HA thermal stability.

The Crossroads between Host Copper Metabolism and Influenza Infection.

Three main approaches are used to combat severe viral respiratory infections. The first is preemptive vaccination that blocks infection. Weakened or dead viral particles, as well as genetic constructs carrying viral proteins or information about them, are used as an antigen.

Size-Dependent Bioactivity of Silver Nanoparticles: Antibacterial Properties, Influence on Copper Status in Mice, and Whole-Body Turnover.

Purpose: The ability of silver nanoparticles (AgNPs) of different sizes to influence copper metabolism in mice is assessed.

Materials And Methods: AgNPs with diameters of 10, 20, and 75 nm were fabricated through a chemical reduction of silver nitrate and characterized by UV/Vis spectrometry, transmission and scanning electronic microscopy, and laser diffractometry. To test their bioactivity, cells, cultured A549 cells, and C57Bl/6 mice were used.

Anti-Influenza Effect of Nanosilver in a Mouse Model.

The present study assesses copper metabolism of the host organism as a target of antiviral strategy, basing on the "virocell" concept. Silver nanoparticles (AgNPs) were used as a specific active agent because they reduce the level of holo-ceruloplasmin, the main extracellular cuproenzyme. The mouse model of influenza virus A infection was used with two doses: 1 LD and 10 LD.

Evaluation of the Effectiveness of Metabolites of Bacterial Strains Bacillus thuringiensis against Human Influenza Virus A/Aichi/2/68 (H3N2) In Vitro and In Vivo.

The morphological and physiological characteristics of Bacillus thuringiensis strains were analyzed and conditions for obtaining culture fluid with maximum yield of secreted RNases were determined. Zymographic analysis showed that culture fluid of B. thuringiensis strains along with low-molecular-weight (15-20 kDa) RNases contained enzymes with a molecular weight ~55 kDa and their content depended on the duration and conditions of culturing.

Non-Mouse-Adapted H1N1pdm09 Virus as a Model for Influenza Research.

The number of lung-adapted influenza viruses is limited. Most of them are not antigenically related to current circulating viruses. Viruses similar to recent strains are required for screening modern antiviral compounds and studying new vaccine candidates against novel influenza viruses.

Synthetic Lethality Screening Identifies FDA-Approved Drugs that Overcome ATP7B-Mediated Tolerance of Tumor Cells to Cisplatin.

Tumor resistance to chemotherapy represents an important challenge in modern oncology. Although platinum (Pt)-based drugs have demonstrated excellent therapeutic potential, their effectiveness in a wide range of tumors is limited by the development of resistance mechanisms. One of these mechanisms includes increased cisplatin sequestration/efflux by the copper-transporting ATPase, ATP7B.

Study of Antiviral Activity of Metabolites of a New Serratia species K-57 Strain.

The results of studies of a newly isolated Serratia species K-57 strain are presented. The strain is characterized by antiviral activity towards human influenza A/Aichi/2/68/H3N2, vaccinia, mouse smallpox, and herpes simplex-2 viruses. The detected characteristics of the strain, including the data on activities on nucleolytic enzymes, recommend it for the development of therapeutic and preventive antiviral drugs.

How Has the Hazard to Humans of Microorganisms Found in Atmospheric Aerosol in the South of Western Siberia Changed over 10 Years?

One of the most important components of atmospheric aerosols are microorganisms. Therefore, it is necessary to assess the hazard to humans, both from individual microorganisms which are present in atmospheric bioaerosols as well as from their pool. An approach for determining the hazard of bacteria and yeasts found in atmospheric bioaerosols for humans has previously been proposed.

Case of Early-Onset Parkinson's Disease in a Heterozygous Mutation Carrier of the Gene.

In this paper, we report a clinically proven case of Parkinson's disease (PD) with early onset in a patient who is a heterozygous mutation carrier of (the Wilson's disease gene). The patient was observed from 2011 to 2018 in the Center for Neurodegenerative Diseases, Institute of Experimental Medicine (St. Petersburg, Russia).

Silver Ions as a Tool for Understanding Different Aspects of Copper Metabolism.

In humans, copper is an important micronutrient because it is a cofactor of ubiquitous and brain-specific cuproenzymes, as well as a secondary messenger. Failure of the mechanisms supporting copper balance leads to the development of neurodegenerative, oncological, and other severe disorders, whose treatment requires a detailed understanding of copper metabolism. In the body, bioavailable copper exists in two stable oxidation states, Cu(I) and Cu(II), both of which are highly toxic.

CRISP-R/Cas9 Mediated Deletion of Copper Transport Genes CTR1 and DMT1 in NSCLC Cell Line H1299. Biological and Pharmacological Consequences.

Copper, the highly toxic micronutrient, plays two essential roles: it is a catalytic and structural cofactor for Cu-dependent enzymes, and it acts as a secondary messenger. In the cells, copper is imported by CTR1 (high-affinity copper transporter 1), a transmembrane high-affinity copper importer, and DMT1 (divalent metal transporter). In cytosol, enzyme-specific chaperones receive copper from CTR1 C-terminus and deliver it to their apoenzymes.

[The changes of copper metabolism in rats fed with low- or high-calorie ration].

Unlabelled: Copper is an essential micronutrient, because it is a catalytic and structural cofactor of enzymes that control the basic processes in all cells, and moreover it is a participant in signaling pathways. The toxic properties of copper ions, due to their chemical nature, are manifested when the cellular and/or organism systems for copper homeostasis are disturbed. Aim of the work was to study the relationships between the diet caloric and the copper status in the blood serum, the copper metabolism in the liver and white adipose tissue (WAT) of rats.

Activation of Autophagy, Observed in Liver Tissues From Patients With Wilson Disease and From ATP7B-Deficient Animals, Protects Hepatocytes From Copper-Induced Apoptosis.

Background & Aims: Wilson disease (WD) is an inherited disorder of copper metabolism that leads to copper accumulation and toxicity in the liver and brain. It is caused by mutations in the adenosine triphosphatase copper transporting β gene (ATP7B), which encodes a protein that transports copper from hepatocytes into the bile. We studied ATP7B-deficient cells and animals to identify strategies to decrease copper toxicity in patients with WD.

Copper Metabolism of Newborns Is Adapted to Milk Ceruloplasmin as a Nutritive Source of Copper: Overview of the Current Data.

Copper, which can potentially be a highly toxic agent, is an essential nutrient due to its role as a cofactor for cuproenzymes and its participation in signaling pathways. In mammals, the liver is a central organ that controls copper turnover throughout the body, including copper absorption, distribution, and excretion. In ontogenesis, there are two types of copper metabolism, embryonic and adult, which maintain the balance of copper in each of these periods of life, respectively.

Role of Copper Dyshomeostasis in the Pathogenesis of Parkinson's Disease.

Serum concentration of copper, immunoreactive polypeptides of ceruloplasmin and its oxidase activity, and the number of copper atoms per ceruloplasmin molecule were decreased in patients with Parkinson's disease in comparison with the corresponding parameters in age-matched healthy individuals, but the ratio of apoceruloplasmin to holoceruloplasmin in patients with Parkinson's disease was similar in both groups. Treatment of blood serum with Helex 100, a high-affinity copper chelator, revealed reduced content of labile copper atoms per ceruloplasmin molecule in patients with Parkinson's disease in comparison with that in healthy controls. The mechanism underlying impaired metabolic incorporation of labile copper atoms into CP molecule is discussed as a possible cause of copper dyshomeostasis associated with Parkinson's disease.

A low blood copper concentration is a co-morbidity burden factor in Parkinson's disease development.

Parkinson's disease (PD) patients are often characterized by copper dyshomeostasis, which is responsible for ROS formation and fibrillogenesis. However, the relationships between copper metabolism and PD development are unclear. In this study in 50 patients with PD (pPD) and 50 age-matched healthy individuals, the serum total copper concentration, oxidase activity, ceruloplasmin and SOD3 protein concentrations were measured; and amount of copper atoms per ceruloplasmin molecule was calculated.

The Extracellular Domain of Human High Affinity Copper Transporter (hNdCTR1), Synthesized by E. coli Cells, Chelates Silver and Copper Ions In Vivo.

There is much interest in effective copper chelators to correct copper dyshomeostasis in neurodegenerative and oncological diseases. In this study, a recombinant fusion protein for expression in cells was constructed from glutathione-S-transferase (GST) and the N-terminal domain (ectodomain) of human high affinity copper transporter CTR1 (hNdCTR1), which has three metal-bound motifs. Several biological properties of the GST-hNdCTR1 fusion protein were assessed.

The role of subcutaneous adipose tissue in supporting the copper balance in rats with a chronic deficiency in holo-ceruloplasmin.

We have previously shown that (1) an acute deficiency in blood serum holo-ceruloplasmin (Cp) developed in rats that were fed fodder containing silver ions (Ag-fodder) for one month and (2) the deficiency in holo-Cp was compensated by non-hepatic holo-Cp synthesis in rats that were chronically fed Ag-fodder for 6 months (Ag-rats). The purpose of the present study is to identify the organ(s) that compensate for the hepatic holo-Cp deficiency in the circulation. This study was performed on rats that were fed Ag-fodder (40 mg Ag·kg-1 body mass daily) for 6 months.