68 research outputs found

    Вимоги СОТ для державного регулювання регіонального ринку сільськогосподарської продукції України

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    Державне регулювання України, як країни з перехідною ринковою економікою, повинно базуватися на основних положеннях та вимогах СОТ (Світової організації торгівлі). Україна вибрала курс Європейської інтеграції, тому її економіка повинна відповідати та працювати по принципах світового ринку. Мета досліджень: проаналізувати основні положення та вимоги Світової організації торгівлі, основні моменти державного регулювання ринку сільськогосподарської продукції, що відповідають принципам світового ринку і які повинні працювати в умовах України

    Алгоритм проведення попередньої дегазації методом гравітаційного знещільнення вуглепородного масиву

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    Приводится алгоритм проведения предварительной дегазации при применении нового способа гравитационной разгрузки на угольных месторождениях Донбасса и Львовско-Волынского бассейнов. Среди главных эффектов, которые будут получены при внедрении способа – обеспечение безопасности работ на шахтах и промышленная добыча метана.The algorithm of realization of pre-degassing with using new way of gravitational unloading on coal fields of Donbas and Lviv-Volyn basins is given in this article. Guaranteeing of safety works in mines and industrial methane-mining are between main effects which will be got on conditions of application of this method

    Cryo-EM structure of a tetrameric photosystem I from Chroococcidiopsis TS-821, a thermophilic, unicellular, non-heterocyst-forming cyanobacterium

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    Photosystem I (PSI) is one of two photosystems involved in oxygenic photosynthesis. PSI of cyanobacteria exists in monomeric, trimeric, and tetrameric forms, in contrast to the strictly monomeric form of PSI in plants and algae. The tetrameric organization raises questions about its structural, physiological, and evolutionary significance. Here we report the ∼3.72 Å resolution cryo-electron microscopy structure of tetrameric PSI from the thermophilic, unicellular cyanobacterium Chroococcidiopsis sp. TS-821. The structure resolves 44 subunits and 448 cofactor molecules. We conclude that the tetramer is arranged via two different interfaces resulting from a dimer-of-dimers organization. The localization of chlorophyll molecules permits an excitation energy pathway within and between adjacent monomers. Bioinformatics analysis reveals conserved regions in the PsaL subunit that correlate with the oligomeric state. Tetrameric PSI may function as a key evolutionary step between the trimeric and monomeric forms of PSI organization in photosynthetic organisms

    Updates to the Integrated Protein–Protein Interaction Benchmarks: Docking Benchmark Version 5 and Affinity Benchmark Version 2

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    We present an updated and integrated version of our widely used protein–protein docking and binding affinity benchmarks. The benchmarks consist of non-redundant, high-quality structures of protein–protein complexes along with the unbound structures of their components. Fifty-five new complexes were added to the docking benchmark, 35 of which have experimentally measured binding affinities. These updated docking and affinity benchmarks now contain 230 and 179 entries, respectively. In particular, the number of antibody–antigen complexes has increased significantly, by 67% and 74% in the docking and affinity benchmarks, respectively. We tested previously developed docking and affinity prediction algorithms on the new cases. Considering only the top 10 docking predictions per benchmark case, a prediction accuracy of 38% is achieved on all 55 cases and up to 50% for the 32 rigid-body cases only. Predicted affinity scores are found to correlate with experimental binding energies up to r = 0.52 overall and r = 0.72 for the rigid complexes.Peer ReviewedPostprint (author's final draft

    Capturing protein communities by structural proteomics in a thermophilic eukaryote:Structural systems biology of lysates

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    The arrangement of proteins into complexes is a key organizational principle for many cellular functions. Although the topology of many complexes has been systematically analyzed in isolation, their molecular sociology in situ remains elusive. Here, we show that crude cellular extracts of a eukaryotic thermophile, Chaetomium thermophilum, retain basic principles of cellular organization. Using a structural proteomics approach, we simultaneously characterized the abundance, interactions, and structure of a third of the C. thermophilum proteome within these extracts. We identified 27 distinct protein communities that include 108 interconnected complexes, which dynamically associate with each other and functionally benefit from being in close proximity in the cell. Furthermore, we investigated the structure of fatty acid synthase within these extracts by cryoEM and this revealed multiple, flexible states of the enzyme in adaptation to its association with other complexes, thus exemplifying the need for in situ studies. As the components of the captured protein communities are known-at both the protein and complex levels-this study constitutes another step forward toward a molecular understanding of subcellular organization

    Antimicrobial and Efflux Pump Inhibitory Activity of Caffeoylquinic Acids from Artemisia absinthium against Gram-Positive Pathogenic Bacteria

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    Background: Traditional antibiotics are increasingly suffering from the emergence of multidrug resistance amongst pathogenic bacteria leading to a range of novel approaches to control microbial infections being investigated as potential alternative treatments. One plausible antimicrobial alternative could be the combination of conventional antimicrobial agents/antibiotics with small molecules which block multidrug efflux systems known as efflux pump inhibitors. Bioassay-driven purification and structural determination of compounds from plant sources have yielded a number of pump inhibitors which acted against gram positive bacteria. Methodology/Principal Findings: In this study we report the identification and characterization of 4′,5′-O-dicaffeoylquinic acid (4′,5′-ODCQA) from Artemisia absinthium as a pump inhibitor with a potential of targeting efflux systems in a wide panel of Gram-positive human pathogenic bacteria. Separation and identification of phenolic compounds (chlorogenic acid, 3′,5′-ODCQA, 4′,5′-ODCQA) was based on hyphenated chromatographic techniques such as liquid chromatography with post column solid-phase extraction coupled with nuclear magnetic resonance spectroscopy and mass spectroscopy. Microbial susceptibility testing and potentiation of well know pump substrates revealed at least two active compounds; chlorogenic acid with weak antimicrobial activity and 4′,5′-ODCQA with pump inhibitory activity whereas 3′,5′-ODCQA was ineffective. These intitial findings were further validated with checkerboard, berberine accumulation efflux assays using efflux-related phenotypes and clinical isolates as well as molecular modeling methodology. Conclusions/Significance: These techniques facilitated the direct analysis of the active components from plant extracts, as well as dramatically reduced the time needed to analyze the compounds, without the need for prior isolation. The calculated energetics of the docking poses supported the biological information for the inhibitory capabilities of 4′,5′-ODCQA and furthermore contributed evidence that CQAs show a preferential binding to Major Facilitator Super family efflux systems, a key multidrug resistance determinant in gram-positive bacteria.National Institutes of Health (U.S.) (grant R01GM59903)National Institutes of Health (U.S.) (grant R01AI050875)Netherlands Organization for Scientific Research (VICI grant 700.56.442)Massachusetts Technology Transfer Center (MTTC)National Institutes of Health (U.S.) (grant 5U54MH084690-02

    Cracking the code of cellular protein–protein interactions: Alphafold and whole‐cell crosslinking to the rescue

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    Integration of experimental and computational methods is crucial to better understanding protein–protein interactions (PPIs), ideally in their cellular context. In their recent work, Rappsilber and colleagues (O'Reilly et al, 2023) identified bacterial PPIs using an array of approaches. They combined whole‐cell crosslinking, co‐fractionation mass spectrometry, and open‐source data mining with artificial intelligence (AI)‐based structure prediction of PPIs in the well‐studied organism Bacillus subtilis. This innovative approach reveals architectural knowledge for in‐cell PPIs that are often lost upon cell lysis, making it applicable to genetically intractable organisms such as pathogenic bacteria
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