NADPH oxidase derived ROS promote arterial contraction in early postnatal rats by activation of L-type voltage-gated Ca channels.

Reactive oxygen species (ROS) produced by NADPH oxidase promote contraction of peripheral arteries, which is especially pronounced in early postnatal period in comparison to adulthood, but the mechanisms of such vasomotor influence are poorly understood. We tested the hypothesis that Rho-kinase and protein kinase C (PKC) mediate procontractile influence of NADPH oxidase derived ROS in peripheral artery of early postnatal rats. In addition, we evaluated the involvement Src-kinase and L-type voltage-gated Ca channels (LTCC) into procontractile influence of ROS, produced by NADPH oxidase, because of their known interplay with Rho-kinase and PKC pathways.

Extracting information on virus-human interactions and on antiviral compounds based on automated analysis of large text collections.

The development of effective antivirals is of great importance due to the threat associated with the rapid spread of viral infections. The accumulation of data in scientific publications and in databases of biologically active compounds provides an opportunity to extract specific information about interactions between chemicals and their viral and host targets. This information can be used for elucidation of knowledge about potential antiviral activity of chemical compounds, their side effects and toxicities.

Hibernation enhances contractile responses of basilar artery in ground squirrels: The role of Rho-kinase and NO.

Hibernation is accompanied by dramatic decrease of blood flow in many organs due to the increase of their vascular resistances. We compared the responses of mesenteric, renal, and cerebral proximal resistance arteries in summer active (SA) and winter hibernating (WH) ground squirrels and studied the signaling pathways of Rho-kinase and NO. Wire myography and Western blotting were used to assess the arterial responses and protein abundances.

Viral Factors in Modulation of Host Immune Response: A Route to Novel Antiviral Agents and New Therapeutic Approaches.

Viruses utilize host cells at all stages of their life cycle, from the transcription of genes and translation of viral proteins to the release of viral copies. The human immune system counteracts viruses through a variety of complex mechanisms, including both innate and adaptive components. Viruses have an ability to evade different components of the immune system and affect them, leading to disruption.

Quantitative Prediction of Human Immunodeficiency Virus Drug Resistance.

Drug resistance of pathogens, including viruses, is one of the reasons for decreased efficacy of therapy. Considering the impact of HIV type 1 (HIV-1) on the development of progressive immune dysfunction and the rapid development of drug resistance, the analysis of HIV-1 resistance is of high significance. Currently, a substantial amount of data has been accumulated on HIV-1 drug resistance that can be used to build both qualitative and quantitative models of HIV-1 drug resistance.

SAnDReS 2.0: Development of machine-learning models to explore the scoring function space.

Classical scoring functions may exhibit low accuracy in determining ligand binding affinity for proteins. The availability of both protein-ligand structures and affinity data make it possible to develop machine-learning models focused on specific protein systems with superior predictive performance. Here, we report a new methodology named SAnDReS that combines AutoDock Vina 1.

Reactive oxygen species augment contractile responses of saphenous artery in 10-15-day-old but not adult rats: Substantial role of NADPH oxidases.

Reactive oxygen species (ROS) produced by NADPH oxidases (NOX, a key source of ROS in vascular cells) are involved in the regulation of vascular tone, but this has been explored mainly for adult organisms. Importantly, the mechanisms of vascular tone regulation differ significantly in early postnatal ontogenesis and adulthood, while the vasomotor role of ROS in immature systemic arteries is poorly understood. We tested the hypothesis that the functional contribution of NADPH oxidase-derived ROS to the regulation of peripheral arterial tone is higher in the early postnatal period than in adulthood.

Self-Assembly of 4,4'-Linked Dipyrromethanes from Unconventional Reactants─Propargylamines, 2-(Vinyloxy)ethyl Isothiocyanate, and Alkylating Agents under Basic Conditions.

Self-assembly of 4,4'-linked dipyrromethanes from 2-(vinyloxy)ethyl isothiocyanate, tertiary propargylamines, and alkylating agents has been discovered. The plausible reaction mechanism, the major stages of which have been confirmed experimentally, includes (1) the lithiation of propargylamine (with -BuLi); (2) the formation of lithium -[2-(vinyloxy)ethyl]but-2-ynimidothioate (product of the addition of monolithiated propargylamine to isothiocyanate); (3) isomerization of the latter in the corresponding allenylimidothioate (under the action of the -BuOK/-BuOH system); (4) low-temperature (<15 °C) intramolecular cyclization of the latter into potassium -(5-amino-2-thienyl)--[2-(vinyloxy)ethyl]amide; (5) the base-induced cleavage of the C-O bond of the -[2-(vinyloxy)ethyl] group and removal of vinyloxide-anion leading to acetaldehyde; (6) interaction of acetaldehyde with two molecules of -(5-amino-2-thienyl)--[2-(vinyloxy)ethyl]amide-anion resulting in dithienomethane N-anionic intermediate; (7) recyclization of the latter into dipyrromethane S-anionic intermediate. Final S-alkylation affords synthetically challenging 4,4'-dipyrromethanes in a yield of 22-51%.

Monitoring and Prediction of Siberian Silk Moth Tschetv. (Lepidoptera: Lasiocampidae) Outbreaks Using Remote Sensing Techniques.

The feasibility of risk assessment of a Siberian silk moth ( Tschetv.) outbreak was analyzed by means of landscape and weather characteristics and tree condition parameters. Difficulties in detecting forest pest outbreaks (especially in Siberian conditions) are associated with the inability to conduct regular ground surveillance in taiga territories, which generally occupy more than 2 million km.

Web Service for HIV Drug Resistance Prediction Based on Analysis of Amino Acid Substitutions in Main Drug Targets.

Predicting viral drug resistance is a significant medical concern. The importance of this problem stimulates the continuous development of experimental and new computational approaches. The use of computational approaches allows researchers to increase therapy effectiveness and reduce the time and expenses involved when the prescribed antiretroviral therapy is ineffective in the treatment of infection caused by the human immunodeficiency virus type 1 (HIV-1).

Current Perspectives in Antiviral Research.

Studies on virus-host interactions are of high significance for a number of reasons [...

Transcriptome-based analysis of human peripheral blood reveals regulators of immune response in different viral infections.

Introduction: There are difficulties in creating direct antiviral drugs for all viruses, including new, suddenly arising infections, such as COVID-19. Therefore, pathogenesis-directed therapy is often necessary to treat severe viral infections and comorbidities associated with them. Despite significant differences in the etiopathogenesis of viral diseases, in general, they are associated with significant dysfunction of the immune system.

Myography of isolated blood vessels: Considerations for experimental design and combination with supplementary techniques.

The study of the mechanisms of regulation of vascular tone is an urgent task of modern science, since diseases of the cardiovascular system remain the main cause of reduction in the quality of life and mortality of the population. Myography (isometric and isobaric) of isolated blood vessels is one of the most physiologically relevant approaches to study the function of cells in the vessel wall. On the one hand, cell-cell interactions as well as mechanical stretch of the vessel wall remain preserved in myography studies, in contrast to studies on isolated cells, e.

Development of an anatomical breast phantom from polyvinyl chloride plastisol with lesions of various shape, elasticity and echogenicity for teaching ultrasound examination.

Purpose: The WHO reported an increasing trend in the number of new cases of breast cancer, making it the most prevalent cancer in the world. This fact necessitates the availability of highly qualified ultrasonographers, which can be achieved by the widespread implementation of training phantoms. The goal of the present work is to develop and test an inexpensive, accessible, and reproducible technology for creating an anatomical breast phantom for practicing ultrasound diagnostic skills in grayscale and elastography imaging, as well as ultrasound-guided biopsy sampling.

Exploring Scoring Function Space: Developing Computational Models for Drug Discovery.

Background: The idea of scoring function space established a systems-level approach to address the development of models to predict the affinity of drug molecules by those interested in drug discovery.

Objective: Our goal here is to review the concept of scoring function space and how to explore it to develop machine learning models to address protein-ligand binding affinity.

Methods: We searched the articles available in PubMed related to the scoring function space.

A family of CuI-based 1D polymers showing colorful short-lived TADF and phosphorescence induced by photo- and X-ray irradiation.

Exploiting 2-(alkylsulfonyl)pyridines as 1,3-N,S-ligands, herein we have constructed 1D CuI-based coordination polymers (CPs) bearing unprecedented (CuI) chains and possessing remarkable photophysical properties. At room temperature, these CPs show efficient TADF, phosphorescence or dual emission in the deep-blue to red range with outstandingly short decay times of 0.4-2.

CLC-Pred 2.0: A Freely Available Web Application for In Silico Prediction of Human Cell Line Cytotoxicity and Molecular Mechanisms of Action for Druglike Compounds.

In vitro cell-line cytotoxicity is widely used in the experimental studies of potential antineoplastic agents and evaluation of safety in drug discovery. In silico estimation of cytotoxicity against hundreds of tumor cell lines and dozens of normal cell lines considerably reduces the time and costs of drug development and the assessment of new pharmaceutical agent perspectives. In 2018, we developed the first freely available web application (CLC-Pred) for the qualitative prediction of cytotoxicity against 278 tumor and 27 normal cell lines based on structural formulas of 59,882 compounds.

Identification of Molecular Mechanisms Involved in Viral Infection Progression Based on Text Mining: Case Study for HIV Infection.

Viruses cause various infections that may affect human lifestyle for durations ranging from several days to for many years. Although preventative and therapeutic remedies are available for many viruses, they may still have a profound impact on human life. The human immunodeficiency virus type 1 is the most common cause of HIV infection, which represents one of the most dangerous and complex diseases since it affects the immune system and causes its disruption, leading to secondary complications and negatively influencing health-related quality of life.

[The practice of stapes surgury in Russia].

The aim of this study - to investigate the practice of stapes surgery in Russia using a special questionnaire (Appendix 1). Thirty-three questionnaires were sent to specialists dealing with stapes surgery in various Russian medical institutions. Responses were received from all ENT specialists, of whom 75.

Voluntary wheel exercise training affects locomotor muscle, but not the diaphragm in the rat.

Functional tests and training regimens intensity-controlled by an individual are used in sport practice, clinical rehabilitation, and space medicine. The model of voluntary wheel running in rats can be used to explore molecular mechanisms of such training regimens in humans. Respiratory and locomotor muscles demonstrate diverse adaptations to treadmill exercise, but the effects of voluntary exercise training on these muscle types have not been compared yet.

Chemical named entity recognition in the texts of scientific publications using the naïve Bayes classifier approach.

Motivation: Application of chemical named entity recognition (CNER) algorithms allows retrieval of information from texts about chemical compound identifiers and creates associations with physical-chemical properties and biological activities. Scientific texts represent low-formalized sources of information. Most methods aimed at CNER are based on machine learning approaches, including conditional random fields and deep neural networks.

The Effects of Acidosis on eNOS in the Systemic Vasculature: A Focus on Early Postnatal Ontogenesis.

The activity of many vasomotor signaling pathways strongly depends on extracellular/intracellular pH. Nitric oxide (NO) is one of the most important vasodilators produced by the endothelium. In this review, we present evidence that in most vascular beds of mature mammalian organisms metabolic or respiratory acidosis increases functional endothelial NO-synthase (eNOS) activity, despite the observation that direct effects of low pH on eNOS enzymatic activity are inhibitory.

TWIK-Related Acid-Sensitive Potassium Channels (TASK-1) Emerge as Contributors to Tone Regulation in Renal Arteries at Alkaline pH.

TASK-1 channels are established regulators of pulmonary artery tone but their contribution to the regulation of vascular tone in systemic arteries is poorly understood. We tested the hypothesis that TASK-1 channel functional impact differs among systemic vascular beds, that this is associated with differences in their expression and may increase with alkalization of the extracellular environment. Therefore, we evaluated the expression level of TASK-1 channels and their vasomotor role in mesenteric and renal arteries.

Spectrum of Atazanavir-Selected Protease Inhibitor-Resistance Mutations.

Ritonavir-boosted atazanavir is an option for second-line therapy in low- and middle-income countries (LMICs). We analyzed publicly available HIV-1 protease sequences from previously PI-naïve patients with virological failure (VF) following treatment with atazanavir. Overall, 1497 patient sequences were identified, including 740 reported in 27 published studies and 757 from datasets assembled for this analysis.

HIV-1 drug resistance profiling using amino acid sequence space cartography.

Motivation: Human immunodeficiency virus (HIV) drug resistance is a global healthcare issue. The emergence of drug resistance influenced the efficacy of treatment regimens, thus stressing the importance of treatment adaptation. Computational methods predicting the drug resistance profile from genomic data of HIV isolates are advantageous for monitoring drug resistance in patients.