Transcriptomic analysis of melanoma cells reveals an association of α-synuclein with regulation of the inflammatory response.

The Parkinson's disease protein, alpha-synuclein (α-syn/SNCA), is highly expressed in neurons and melanomas. The goal of this study was to reveal the mechanism(s) of α-syn's involvement in melanoma pathogenesis. To decipher the genes and pathways affected by α-syn, we conducted an RNA sequencing analysis of human SK-MEL-28 cells and several SK-MEL-28 SNCA-KO clones.

Clinical, Anamnestic, and Demographic Characteristics of Patients with Myocardial Infarction in Russian Federation According to the Russian Registry of Acute Myocardial Infarction - REGION-IM.

Aim: Based on data from the Russian REGION-MI registry, to characterize patients with myocardial infarction (MI) hospitalized in Russian hospitals, describe their historical, demographic, and clinical characteristics, and compare the results with the data of previous Russian and international registries of acute coronary syndrome.

Material And Methods: REGION-MI is a multicenter prospective observational study. The follow-up period was divided into three stages: during the hospital stay, at 6 and 12 months after the inclusion in the registry.

Distinct early role of PTEN regulation during HCMV infection of monocytes.

Human cytomegalovirus (HCMV) infection of monocytes is essential for viral dissemination and persistence. We previously identified that HCMV entry/internalization and subsequent productive infection of this clinically relevant cell type is distinct when compared to other infected cells. We showed that internalization and productive infection required activation of epidermal growth factor receptor (EGFR) and integrin/c-Src, via binding of viral glycoprotein B to EGFR, and the pentamer complex to β1/β3 integrins.

Human Cytomegalovirus Manipulates Syntaxin 6 for Successful Trafficking and Subsequent Infection of Monocytes.

Human cytomegalovirus (HCMV) exhibits a complex host-pathogen interaction with peripheral blood monocytes. We have identified a unique, cell-type specific retrograde-like intracellular trafficking pattern that HCMV utilizes to gain access to the monocyte nucleus and for productive infection. We show that infection of primary human monocytes, epithelial cells, and fibroblasts leads to an increase in the amount of the trafficking protein Syntaxin 6 (Stx6).

Registry of Acute Myocardial Infarction. REGION-MI - Russian Registry of Acute Myocardial Infarction.

Aim      To study features of diagnosis and treatment of acute myocardial infarction (AMI) in Russian hospitals, results of the treatment, and early and late outcomes (6 and 12 months after AMI diagnosis); to evaluate the consistence of the treatment with clinical guidelines; and to evaluate patients' compliance with the treatment.Material and methods  The program was designed for 3 years, including 24 months for recruitment of patients to the study. The study will include 10, 000 patients hospitalized with a confirmed diagnosis (I21 according to ICD-10) of ST segment elevation acute myocardial infarction (MI) (STEMI) or non-ST segment elevation MI (NSTEMI) based on criteria of the European Society of Cardiology Guidelines on Forth Universal Definition of Myocardial Infarction (2018).

Using a Phosphoproteomic Screen to Profile Early Changes During HCMV Infection of Human Monocytes.

During the binding and infection of monocytes, HCMV binds to at least two major cell surface receptors/receptor families: the epidermal growth factor receptor (EGFR) to initiate downstream signaling through the EGFR-PI3K pathway, and to β- and β-integrins to initiate downstream signaling through the integrin-c-Src pathway (Nogalski et al. PLoS Pathog 9:e1003463, 2013; Chan et al. Proc Natl Acad Sci U S A 106:22369-22374, 2009; Kim et al.

HCMV-induced signaling through gB-EGFR engagement is required for viral trafficking and nuclear translocation in primary human monocytes.

Previous analysis of postentry events revealed that human cytomegalovirus (HCMV) displays a unique, extended nuclear translocation pattern in monocytes. We determined that c-Src signaling through pentamer engagement of integrins is required upon HCMV entry to avoid sorting of the virus into late endosomes and subsequent degradation. To follow up on this previous study, we designed experiments to investigate how HCMV-induced signaling through the other major axis-the epidermal growth factor receptor (EGFR) kinase-regulates viral postentry events.

HCMV Infection and Apoptosis: How Do Monocytes Survive HCMV Infection?

Human cytomegalovirus (HCMV) infection of peripheral blood monocytes plays a key role in the hematogenous dissemination of the virus to multiple organ systems following primary infection or reactivation of latent virus in the bone marrow. Monocytes have a short life span of 1⁻3 days in circulation; thus, HCMV must alter their survival and differentiation to utilize these cells and their differentiated counterparts-macrophages-for dissemination and long term viral persistence. Because monocytes are not initially permissive for viral gene expression and replication, HCMV must control host-derived factors early during infection to prevent apoptosis or programmed cell death prior to viral induced differentiation into naturally long-lived macrophages.

The BDLF3 gene product of Epstein-Barr virus, gp150, mediates non-productive binding to heparan sulfate on epithelial cells and only the binding domain of CD21 is required for infection.

The cell surface molecules used by Epstein-Barr virus (EBV) to attach to epithelial cells are not well-defined, although when CD21, the B cell receptor for EBV is expressed epithelial cell infection increases disproportionately to the increase in virus bound. Many herpesviruses use low affinity charge interactions with molecules such as heparan sulfate to attach to cells. We report here that the EBV glycoprotein gp150 binds to heparan sulfate proteoglycans, but that attachment via this glycoprotein is not productive of infection.

Reactivation of Aggregated Proteins by the ClpB/DnaK Bi-Chaperone System.

Protein aggregation is a common problem in protein biochemistry and is linked to many cellular pathologies and human diseases. The molecular chaperone ClpB can resolubilize and reactivate aggregated proteins. This unit describes the procedure for following reactivation of an aggregated enzyme glucose-6-phosphate dehydrogenase mediated by ClpB from Escherichia coli in cooperation with another molecular chaperone, DnaK.

[Experimental evaluation of the impact of low doses of the herbicide 2,4-D in drinking water on some indices of lipid and immune status].

There were studied features of the manifestation of incoming with potable water nontoxic doses of the herbicide 2,4-D on the body mass index, some indices of lipid metabolism and immune system in different types of diets in the experiment in rats. There was shown a significant gain in body weight of animals, and MDA and leptin level in the serum under the action of a herbicide in conjunction with a high-calorie diet. In all experimental groups there was noted the increased level of total cholesterol, tendency to the increase of LDL cholesterol.

Viral Entry.

Epstein-Barr virus primarily, though not exclusively, infects B cells and epithelial cells. Many of the virus and cell proteins that are involved in entry into these two cell types in vitro have been identified, and their roles in attachment and fusion are being explored. This chapter discusses what is known about entry at the cellular level in vitro and describes what little is known about the process in vivo.

Epstein-Barr virus infection mechanisms.

Epstein-Barr virus (EBV) infection occurs by distinct mechanisms across different cell types. EBV infection of B cells in vitro minimally requires 5 viral glycoproteins and 2 cellular proteins. By contrast, infection of epithelial cells requires a minimum of 3 viral glycoproteins, which are capable of interacting with one or more of 3 different cellular proteins.

[Some indices of trace elements and antioxidant status in rats under chromic intoxication].

There was investigated the effect of chronic Cr (VI) on the content of chromium, iron, copper; zinc, nickel in the blood of rats and activity of antioxidant enzymes of erythrocytes in Wistar rats. The chromium concentration has been shown to increase multifold while the level of other metal is more or less declining. Also it was found a decrease in the activity of such antioxidant enzymes as superoxide dismutase, catalase, and the activation of the processes of free radical oxidation.

Epstein-Barr virus glycoprotein gB and gHgL can mediate fusion and entry in trans, and heat can act as a partial surrogate for gHgL and trigger a conformational change in gB.

Unlabelled: Epstein-Barr virus (EBV) fusion with an epithelial cell requires virus glycoproteins gHgL and gB and is triggered by an interaction between gHgL and integrin αvβ5, αvβ6, or αvβ8. Fusion with a B cell requires gHgL, gp42, and gB and is triggered by an interaction between gp42 and human leukocyte antigen class II. We report here that, like alpha- and betaherpesviruses, EBV, a gammaherpesvirus, can mediate cell fusion if gB and gHgL are expressed in trans.

αvβ6- and αvβ8-integrins serve as interchangeable receptors for HSV gH/gL to promote endocytosis and activation of membrane fusion.

Herpes simplex virus (HSV)--and herpesviruses in general--encode for a multipartite entry/fusion apparatus. In HSV it consists of the HSV-specific glycoprotein D (gD), and three additional glycoproteins, gH/gL and gB, conserved across the Herpesviridae family and responsible for the execution of fusion. According to the current model, upon receptor binding, gD propagates the activation to gH/gL and to gB in a cascade fashion.

[Proinflammatory cytokine levels depending on the stage of hepatic fibrosis in patients with metabolic syndrome and non-alcoholic fatty liver disease].

Aim: To study levels of systemic inflammation markers and plasminogen activator inhibitor-1 (PAL-1) in patients with metabolic syndrome (MS) and establish their relationship with the progress of selected stages of non-alcoholic fatty liver disease (NAFLD).

Materials And Methods: 129 patients aged 18-59 yr with abdominal obesity and MS underwent elastometry for the assessment of the degree of fibrosis depending on concomitant metabolic disorders and measurement of proinflammatory cytokine levels.

Results: Disorders of carbohydrate metabolism in MS patients are associated with the high levels of systemic inflammation markers (CRP, TNF-α, IL-6) and a two-fold rise in the PAI-1 level.

αvβ3-integrin is a major sensor and activator of innate immunity to herpes simplex virus-1.

Pathogens are sensed by Toll-like receptors (TLRs) and a growing number of non-TLR receptors. Integrins constitute a family of signaling receptors exploited by viruses and bacteria to access cells. By gain- and loss-of-function approaches we found that αvβ3-integrin is a sensor of and plays a crucial role in the innate defense against herpes simplex virus (HSV).

[Monitoring the quality of drinking water and air in the industrial center].

The quality of potable water at the exit point for distribution networks and a network for three zones (central, east and northern) where the Orenburg population lived compactly were studied which showed its difference. The complex anthropogenic and total oxidative loads created by aqueous and air environments were calculated; the maximum values for inhabitants of the east part of the city were established, which correspond to the higher levels of nitrates, chlorides, and sulfates in the water and its general mineralization and general rigidity.

Fusion of Epstein-Barr virus with epithelial cells can be triggered by αvβ5 in addition to αvβ6 and αvβ8, and integrin binding triggers a conformational change in glycoproteins gHgL.

Fusion of herpesviruses with their target cells requires a minimum of three glycoproteins, namely, gB and a complex of gH and gL. Epstein-Barr virus (EBV) fusion with an epithelial cell requires no additional virus glycoproteins, and we have shown previously that it can be initiated by an interaction between integrin αvβ6 or αvβ8 and gHgL. We now report that integrin αvβ5 can also bind to gHgL and trigger fusion.

Integrins as triggers of Epstein-Barr virus fusion and epithelial cell infection.

Epstein-Barr virus is a ubiquitous orally-transmitted human herpesvirus that is carried by most of the adult population. It establishes latent infections in B lymphocytes, reactivates periodically from latency and can be amplified in epithelial cells where it is thought more commonly to undergo lytic replication. Entry into either cell involves fusion of the virus envelope with a cell membrane.

Fusion of epithelial cells by Epstein-Barr virus proteins is triggered by binding of viral glycoproteins gHgL to integrins alphavbeta6 or alphavbeta8.

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is causally implicated in the development of lymphoid and epithelial tumors. Entry of virus requires fusion of virus envelopes and cell membranes. Fusion with B lymphocytes requires virus glycoprotein gB and a 3-part complex of glycoproteins, gHgLgp42.

[The chemical and trace element composition of water sources in the Orenburg Region].

The chemical composition of drinking water was studied by some indices: total mineralization, oxidability, harshness by different regional economic areas of an angoindustrial region. The content of trace elements, imbalance of which had been found by earlier studies, was determined. Higher water mineralization was ascertained in the central area, higher water harshness and oxidability were in the eastern area.

[The content of toxic trace elements in the conjugate media].

The purpose of this study was to make a qualitative and quantitative analysis of the content of toxic trace element (Pb, Co, Ni, Cd, Ni, Cd, Sr, and Cr) in the deposited media (snow cover, soil) and drinking water and to define the relationship of the levels of elements in the snow-soil and soil-water systems. The analysis was made in the economic (eastern, western, and central) areas of the region. The higher levels of metals were recorded in the snow cover and soil of the eastern area, which was caused by a high man-made load.

Antibodies to gp350/220 enhance the ability of Epstein-Barr virus to infect epithelial cells.

Epstein-Barr virus (EBV) is a persistent, orally transmitted herpesvirus that replicates in B cells and epithelial cells and is associated with lymphoid and epithelial malignancies. The virus binds to CD21 on B cells via glycoprotein gp350/220 and infects efficiently. Infection of cultured epithelial cells has not typically been efficient but can occur in the absence of gp350/220 and CD21 and in vivo is thought to be important to the development of nasopharyngeal carcinoma.