Non-human peptides revealed in blood reflect the composition of intestinal microbiota.

Background: The previously underestimated effects of commensal gut microbiota on the human body are increasingly being investigated using omics. The discovery of active molecules of interaction between the microbiota and the host may be an important step towards elucidating the mechanisms of symbiosis.

Results: Here, we show that in the bloodstream of healthy people, there are over 900 peptides that are fragments of proteins from microorganisms which naturally inhabit human biotopes, including the intestinal microbiota.

Russian Biodiversity Collections: A Professional Opinion Survey.

Biodiversity collections are important vehicles for protecting endangered wildlife in situations of adverse anthropogenic influence. In Russia, there are currently a number of institution- and museum-based biological collections, but there are no nation-wide centres of biodiversity collections. In this paper, we report on the results of our survey of 324 bioconservation, big-data, and ecology specialists from different regions of Russia in regard to the necessity to create several large national biodiversity centres of wildlife protection.

Physiological and Functional Effects of Dominant Active TCRα Expression in Transgenic Mice.

A T cell receptor (TCR) consists of α- and β-chains. Accumulating evidence suggests that some TCRs possess chain centricity, i.e.

Evolutionary Challenges to Humanity Caused by Uncontrolled Carbon Emissions: The Stockholm Paradigm.

This review paper discusses the Stockholm Paradigm (SP) as a theoretical framework and practical computational instrument for studying and assessing the risk of emerging infectious diseases (EIDs) as a result of climate change. The SP resolves the long-standing parasite paradox and explains how carbon emissions in the atmosphere increase parasites' generalization and intensify host switches from animals to humans. The SP argues that the growing rate of novel EID occurrence caused by mutated zoonotic pathogens is related to the following factors brought together as a unified issue of humanity: (a) carbon emissions and consequent climate change; (b) resettlement/migration of people with hyper-urbanization; (c) overpopulation; and (d) human-induced distortion of the biosphere.

Using Alternative Sources of Energy for Decarbonization: A Piece of Cake, but How to Cook This Cake?

Few analytical or research works claim that the negative impact of improper use of ASEs may be comparable with that of hydrocarbons and sometimes even greater. It has become a common view that "green" energy (ASE) is clean, safe and environmentally friendly (eco-friendly) in contrast with "black" energy (hydrocarbons). We analyzed 144 works on systemic and/or comparative research of the modern and prospective ASE: biofuels, hydrogen, hydropower, nuclear power, wind power, solar power, geothermal power, oceanic thermal power, tidal power, wind wave power and nuclear fusion power.

Public Policy Measures to Increase Anti-SARS-CoV-2 Vaccination Rate in Russia.

The total vaccination rate remains relatively low in Russia as of March 2022 (around 55%, with around 20% in some regions). In the paper, we study the reasons for it. We communicate the results of our survey aimed at detecting reasons for the relatively low anti-SARS-CoV-2 vaccination rate in Russia (47.

Proteasomes in Patient Rectal Cancer and Different Intestine Locations: Where Does Proteasome Pool Change?

A special problem in the surgery of rectal cancer is connected with a need for appropriate removal of intestine parts, along with the tumor, including the fragment close to the sphincter. To determine the length of fragments to remove, it is necessary to reveal areas without changes in molecule functioning, specific for tumor. The purpose of the present study was to investigate functioning the proteasomes, the main actors in protein hydrolysis, in patient rectal adenocarcinoma and different intestine locations.

Respiratory syncytial virus upregulates IL-33 expression in mouse model of virus-induced inflammation exacerbation in OVA-sensitized mice and in asthmatic subjects.

Background: Bronchial asthma (BA) is a chronic disease of the airways. The great majority of BA exacerbations are associated with respiratory viral infections. Recent findings point out a possible role of proinflammatory cytokine interleukin-33 (IL-33) in the development of atopic diseases.

Estrogen Receptors and Ubiquitin Proteasome System: Mutual Regulation.

This review provides information on the structure of estrogen receptors (ERs), their localization and functions in mammalian cells. Additionally, the structure of proteasomes and mechanisms of protein ubiquitination and cleavage are described. According to the modern concept, the ubiquitin proteasome system (UPS) is involved in the regulation of the activity of ERs in several ways.

HIV-1 Escape from Small-Molecule Antagonism of Vif.

The HIV-1 accessory protein Vif, which counteracts the antiviral action of the DNA-editing cytidine deaminase APOBEC3G (A3G), is an attractive and yet unexploited therapeutic target. Vif reduces the virion incorporation of A3G by targeting the restriction factor for proteasomal degradation in the virus-producing cell. Compounds that inhibit Vif-mediated degradation of A3G in cells targeted by HIV-1 would represent a novel antiviral therapeutic.

Changes in the Content of Mononuclear Liver Cells Expressing Immune Proteasomes after Transplantation of Ovarian Tissues Depending on Donor-Recipient Differences in Rats.

Implantation of ovarian tissue allografts in outbred Wistar rats and inbred August rats against the background of induction of donor-specific tolerance was accompanied by an increase in liver content of mononuclear cells expressing LMP2 immune of proteasome subunit by day 37 after transplantation in comparison with day 0. Graft rejection, on the contrary, was associated with a decrease in the number of LMP2 cells in the liver of rats of both lines during this period. The difference in the content of these cells and the graft take rate were higher in Wistar rats.

Combined Effect of Bortezomib and Menadione Sodium Bisulfite on Proteasomes of Tumor Cells: The Dramatic Decrease of Bortezomib Toxicity in a Preclinical Trial.

Tumor growth is associated with elevated proteasome expression and activity. This makes proteasomes a promising target for antitumor drugs. Current antitumor drugs such as bortezomib that inhibit proteasome activity have significant side effects.

Functioning of Proteasomes in Lymphogenic Metastasizing of Non-Small-Cell Lung Cancer.

Chymotrypsin- and caspase-like activities and expression of the total proteasome pool subunits (α1α2α3α5α6α7) were studied in patients with non-small-cell lung cancer. Proteasome activities were higher in the primary tumors and lymphogenic metastases than in corresponding adjacent lung tissue. The content of α1α2α3α5α6α7 subunits decreased in metastases and remained unchanged in primary tumor tissue.

Changes in the Expression of Immune Proteasomes in the Liver after the Induction of Portal Tolerance Depending on Donor-Recipient Differences in Rats.

Induction of donor-specific tolerance in outbred Wistar rats (RT1) and inbred August rats (RT1) increased the expression of immune proteasome subunits in liver with a peak on day 7 after beginning of the induction. The increase in the level of immune subunits LMP2 and LMP7 was more pronounced in the liver of August rats in comparison with Wistar rats (by 2 and 6 times, respectively), which was associated with higher concentrations of monoamines in the CNS of August rats. After induction of donor-specific tolerance in August and Wistar rats, the immune subunits were in cells of sinusoidal lining and in cells located in sinusoid lumens.

Effect of Neoadjuvant Chemoradiation Therapy on Proteasome Pool in Rectal Cancer.

In untreated rectal cancer patients, the chymotrypsin-like activity of proteasomes in tumor tissue was 3-fold higher than that in conventionally normal tissue, which is explained by up-regulation of expression of immunoproteasomes and total pool of proteasomes. After neoadjuvant chemoradiation therapy, expressions of the total pool of proteasomes and immunoproteasomes in the tumor as well as the relative ratios of these indices to those in conventionally normal tissue were smaller by 1.4-3.

Change in the Content of Immunoproteasomes and Macrophages in Rat Liver At the Induction of Donor-Specific Tolerance.

Induction of donor specific tolerance (DST) by the introduction of donor cells into a recipient's portal vein is one of the approaches used to solve the problem of transplant engraftment. However, the mechanism of DST development remains unclear to this moment. In the present work, we first studied the change in the content of immunoproteasomes and macrophages of the liver at early stages of the development of allospecific portal tolerance in rats by Western blotting and flow cytofluorimetry.

Amyloid-β Increases Activity of Proteasomes Capped with 19S and 11S Regulators.

Accumulation of amyloid-β (Aβ) in neurons accompanies Alzheimer's disease progression. In the cytoplasm Aβ influences activity of proteasomes, the multisubunit protein complexes that hydrolyze the majority of intracellular proteins. However, the manner in which Aβ affects the proteolytic activity of proteasomes has not been established.

1,2,3-Triazoles as Amide Bioisosteres: Discovery of a New Class of Potent HIV-1 Vif Antagonists.

RN-18 based viral infectivity factor (Vif), Vif antagonists reduce viral infectivity by rescuing APOBEC3G (A3G) expression and enhancing A3G-dependent Vif degradation. Replacement of amide functionality in RN-18 (IC50 = 6 μM) by isosteric heterocycles resulted in the discovery of a 1,2,3-trizole, 1d (IC50 = 1.2 μM).

Native structure of rat liver immune proteasomes.

Native structure of active forms of rat liver immune proteasomes has been studied by two-dimensional electrophoresis method modified for analysis of unpurified protein fractions. The developed method allowed revealing the proteasome immune subunits LMP7 and LMP2 in 20S subparticles and in the structures bound to one or two PA28αβ activators, but not to the PA700 activator, which is involved in the hydrolysis of ubiquitinated proteins. The results obtained indicate the participation of the immune proteasomes in delicate regulatory mechanisms based on the production of biologically active peptides and exclude their participation in processes of crude degradation of "rotated" ubiquitinated proteins.

Occludin controls HIV transcription in brain pericytes via regulation of SIRT-1 activation.

HIV invades the brain early after infection; however, its interactions with the cells of the blood-brain barrier (BBB) remain poorly understood. Our goal was to evaluate the role of occludin, one of the tight junction proteins that regulate BBB functions in HIV infection of BBB pericytes. We provide evidence that occludin levels largely control the metabolic responses of human pericytes to HIV.

The role of lysosomal proteinases and estradiol in neurodegeneration induced by beta-amyloid.

Activation of lysosomal degradation process in nervous tissue may be neuroprotective. One of the factors that may influence on expression of lysosomal proteinases is the sex hormone, estradiol (E2). In this regard the expression of lysosomal proteinases after intracerebral injection of beta-amyloid peptide (Aβ) was investigated as well as the neuroprotective effect of E2 in Aβ-induced neurodegeneration.

Association Between Local Pediatric Vaccination Rates and Patterns of Pneumococcal Disease in Adults.

Background: Pneumococcal conjugate vaccine (PCV) is now recommended for use in adults in the United States. Because vaccination of children with PCVs protects adults from the targeted serotypes, local variations in PCV uptake among children could influence disease patterns in adults.

Methods: We obtained ZIP code-level data on invasive pneumococcal disease (IPD) from an active population-based surveillance system in Connecticut (study interval, 1998-2009) and ZIP code-level data on immunization with at least 3 or at least 4 doses of 7-valent PCV (PCV7) from the state immunization registry.