Publications by authors named "Titov D"

Many prokaryotic and eukaryotic cells metabolize glucose to organism-specific by-products instead of fully oxidizing it to carbon dioxide and water-a phenomenon referred to as the Warburg Effect. The benefit to a cell is not fully understood, given that partial metabolism of glucose yields an order of magnitude less adenosine triphosphate (ATP) per molecule of glucose than complete oxidation. Here, we test a previously formulated hypothesis that the benefit of the Warburg Effect is to increase ATP production rate by switching from high-yielding respiration to faster glycolysis when excess glucose is available and respiration rate becomes limited by proteome occupancy.

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Mitochondrial membrane potential (ΔΨm) is one of the key parameters controlling cellular bioenergetics. Investigation of the role of ΔΨm in live cells is complicated by a lack of tools for its direct manipulation without off-target effects. Here, we adopted the uncoupling protein UCP1 from brown adipocytes as a genetically encoded tool for direct manipulation of ΔΨm.

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The use of a nanostructured graphene-zirconia composite will allow the development of new materials with improved performance properties and a high functionality. This work covers a stepwise study related to the creation of a nanostructured composite based on ZrO and graphene. A composite was prepared using two suspensions: nano-zirconia obtained by sol-gel synthesis and oxygen-free graphene obtained sonochemically.

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The directions of the transformation of benzene induced by low-voltage discharges at various energies of pulsed discharges were revealed. This paper shows the dependencies of the morphology and other characteristics of nanostructures obtained in the induced transformation of benzene on the energy of pulsed discharges. Nanostructures with different morphologies are formed when the energy of the low-voltage discharges changes during the induced transformation of benzene in the liquid phase.

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Over the past few years, we have seen an explosion of novel genetically encoded tools for measuring and manipulating metabolism in live cells and animals. Here, we will review the genetically encoded tools that are available, describe how these tools can be used and outline areas where future development is needed in this fast-paced field. We will focus on tools for direct measurement and manipulation of metabolites.

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Cellular respiration is essential for multiple bacterial pathogens and a validated antibiotic target. In addition to driving oxidative phosphorylation, bacterial respiration has a variety of ancillary functions that obscure its contribution to pathogenesis. We find here that the intracellular pathogen encodes two respiratory pathways which are partially functionally redundant and indispensable for pathogenesis.

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Article Synopsis
  • AIRR (Adaptive Immune Receptor Repertoires) are crucial for tracking immune responses, making them important in biomedical research.
  • Machine learning (ML) is useful for analyzing complex patterns in AIRR, but issues like reproducibility and transparency have slowed its adoption.
  • immuneML is a new open-source tool that simplifies the AIRR ML process and includes user-friendly interfaces, extensive documentation, and demonstrates its effectiveness through various applications in immune state prediction and antigen specificity.
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Many types of data from genomic analyses can be represented as genomic tracks, features linked to the genomic coordinates of a reference genome. Examples of such data are epigenetic DNA methylation data, ChIP-seq peaks, germline or somatic DNA variants, as well as RNA-seq expression levels. Researchers often face difficulties in locating, accessing and combining relevant tracks from external sources, as well as locating the raw data, reducing the value of the generated information.

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Cells are the basic units of all living matter which harness the flow of energy to drive the processes of life. While the biochemical networks involved in energy transduction are well-characterized, the energetic costs and constraints for specific cellular processes remain largely unknown. In particular, what are the energy budgets of cells? What are the constraints and limits energy flows impose on cellular processes? Do cells operate near these limits, and if so how do energetic constraints impact cellular functions? Physics has provided many tools to study nonequilibrium systems and to define physical limits, but applying these tools to cell biology remains a challenge.

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Article Synopsis
  • Metazoan organisms use conserved stress response pathways to protect against adverse conditions, especially in stem cells involved in tissue formation and repair.
  • The study identifies the E3 ligase CUL2 and its substrate FNIP1 as key components in managing reductive stress, which occurs during prolonged antioxidant signaling or mitochondrial inactivity.
  • The degradation of FNIP1 by CUL2 helps restore mitochondrial function, maintaining redox balance and stem cell integrity, highlighting the link between metabolic control and stress/developmental signaling.
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Nanocrystalline 3 mol% yttria-tetragonal zirconia polycrystal (3Y-TZP) ceramic powder containing 5 wt.% AlO with 64 m/g specific area was synthesized through precipitation method. Different amounts of Co (0-3 mol%) were introduced into synthesized powders, and ceramic materials were obtained by heat treatment in the air for 2 h at 1350-1550 °C.

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Mitochondrial dysfunction is associated with activation of the integrated stress response (ISR) but the underlying triggers remain unclear. We systematically combined acute mitochondrial inhibitors with genetic tools for compartment-specific NADH oxidation to trace mechanisms linking different forms of mitochondrial dysfunction to the ISR in proliferating mouse myoblasts and in differentiated myotubes. In myoblasts, we find that impaired NADH oxidation upon electron transport chain (ETC) inhibition depletes asparagine, activating the ISR via the eIF2α kinase GCN2.

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Nanostructured composite particles of nano- and submicron sizes were synthesized by a combination of sol-gel and sonochemical techniques. Their graphene content was 0.8-0.

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A clinical case of apical hypertrophic cardiomyopathy (HCM) in 44‑years old man is presented. In this patient exercise ECG testing and 24‑hour ECG monitoring revealed exercise-induced ST depression in the angiographically confirmed absence of coronary atherosclerosis. The uncommonness of this observation was the combination of HCM with a rare anomaly of coronary arteries origin.

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This review considers one of the most clinically relevant representatives of the ABC transporters - multidrug resistance protein 1 (P-glycoprotein 1 or Pgp). Data on the primary, secondary, and tertiary structure of the protein, its synthesis and degradation, and roles of its fragments in transporter activity are presented. Particular attention is given to the mechanism of functioning of Pgp.

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Functional genomics assays produce sets of genomic regions as one of their main outputs. To biologically interpret such region-sets, researchers often use colocalization analysis, where the statistical significance of colocalization (overlap, spatial proximity) between two or more region-sets is tested. Existing colocalization analysis tools vary in the statistical methodology and analysis approaches, thus potentially providing different conclusions for the same research question.

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Environmental stress can induce adult reproductive diapause, a state of developmental arrest that temporarily suspends reproduction. Deficiency for C. elegans Piwi protein PRG-1 results in strains that reproduce for many generations but then become sterile.

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The state of palladium and copper on the surface of the PdCl₂-CuCl₂/γ-Al₂O₃ nanocatalyst for the low-temperature oxidation of CO by molecular oxygen was studied by various spectroscopic techniques. Using X-ray absorption spectroscopy (XAS), powder X-ray diffraction (XRD), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), freshly prepared samples of the catalyst were studied. The same samples were also evaluated after interaction with CO, O₂, and H₂O vapor in various combinations.

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Inflammaging plays an important role in most age-related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha-1 antitrypsin (hAAT) has immune-regulatory, anti-inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke.

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The redox coenzymes NADH and NADPH are broadly required for energy metabolism, biosynthesis and detoxification. Despite detailed knowledge of specific enzymes and pathways that utilize these coenzymes, a holistic understanding of the regulation and compartmentalization of NADH- and NADPH-dependent pathways is lacking, partly because of a lack of tools with which to investigate these processes in living cells. We have previously reported the use of the naturally occurring Lactobacillus brevis HO-forming NADH oxidase (LbNOX) as a genetic tool for manipulation of the NAD/NADH ratio in human cells.

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Article Synopsis
  • The decline in electron transport chain (ETC) activity is linked to various human diseases, primarily due to reduced ATP production and uncertain impacts on NAD(+)/NADH ratios.
  • Researchers employed a NADH oxidase from Lactobacillus brevis (LbNOX) to selectively boost the NAD(+)/NADH ratio in human cells, affecting key metabolic processes and signaling.
  • By expressing LbNOX in either the cytoplasm or mitochondria, they were able to improve growth and metabolism in cells with ETC impairments, highlighting the importance of redox balance in mitochondrial health.
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Objective: To define the mechanism responsible for fatigue, lethargy, and weakness in 2 cousins who had a normal muscle biopsy.

Methods: Exome sequencing, long-range PCR, and Sanger sequencing to identify the pathogenic mutation. Functional analysis in the patient fibroblasts included oxygen consumption measurements, extracellular acidification studies, Western blotting, and calcium imaging, followed by overexpression of the wild-type protein.

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Presently, visual and quantitative approaches for image-supported diagnosis of dementing disorders rely on regional intensity rather than on connectivity measurements. Here, we test metabolic connectivity for differentiation between Alzheimer's disease and frontotemporal lobar degeneration. Positron emission tomography with 18F-fluorodeoxyglucose was conducted in 47 patients with mild Alzheimer's disease, 52 patients with mild frontotemporal lobar degeneration, and 45 healthy elderly subjects.

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Cyclo-oligo-(1→6)-β-D-glucosamines functionalized with hydrophobic tails are reported as a new class of transmembrane ion-transport system. These macrocycles with hydrophilic cavities were introduced as an alternative to cyclodextrins, which are supramolecular systems with hydrophobic cavities. The transport activities of these glycoconjugates were manipulated by altering the oligomericity of the macrocycles, as well as the length and number of attached tails.

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Positron emission tomography (PET) data are commonly analyzed in terms of regional intensity, while covariant information is not taken into account. Here, we searched for network correlates of healthy cognitive function in resting state PET data. PET with [(18)F]-fluorodeoxyglucose and a test of verbal working memory (WM) were administered to 35 young healthy adults.

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