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Search results for: phase ii enzymes
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Modulation of rat hepatic and kidney phase II enzymes by cabbage juices: comparison with the effects of indole-3-carbinol and phenethyl isothiocyanate
PublicationZbadano wpływ soków ze świeżej i kiszonej kapusty na ekspresję i aktywność takich enzymów II fazy jak transferazy S-glutationowe i oksydoreduktaza NQO1 w wątrobie i nerkach szczurów, którym podawano wspomniane soki doustnie. Uzyskane wyniki porównano z oznaczeniami uzyskanymi po doustnym podaniu wyizolowanych produktów degradacji glukozynolanów, indolo-3-karbinolu i izotiocyjanianu fenyloetylu. Wszystkie testowane czynniki powodowały...
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Detoxification of the tricyclic antidepressant opipramol and its analog – IS-noh by UGT enzymes before and after activation by phase I enzymes in rat liver microsomes
PublicationThe present studies were carried out to evaluate the simultaneous one-pot metabolism of opipramol (IS-opi) and analog (IS-noh) by phase I and phase II enzymes present in rat liver microsomes (RLM) as an alternative to separate testing with recombinant enzymes. This approach allows for more time-saving and cost-effective screening of the metabolism of newly discovered drugs. We also considered that the lack of results for phase...
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Thermodynamic properties and phase stability of wadsleyite II
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The II phase metabolism of endogenous and exogenous compounds, including antitumor chemotherapeutics
PublicationThe II phase metabolism, it is a set of metabolism and excretion pathways of endogenous as well as exogenous compounds including xenobiotics. UDP-glucuronyltransferases (UGTs; EC 2.4.1.17) are the most crucial representatives of II phase enzymes, which are responsible for the transformation of bilirubine and bile acids, steroids and thyroid hormones and lipids. Exogenous compounds, including drugs, carcinogens, environmental pollutants...
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Phase I and phase II metabolism simulation of antitumor-active 2-hydroxyacridinone with electrochemistry coupled on-line with mass spectrometry.
PublicationHere, we report the metabolic profile and the results of associated metabolic studies of 2-hydroxyacridinone (2-OH-AC), the reference compound for antitumor-active imidazo- and triazoloacridinones. Electrochemistry coupled with mass spectrometry was applied to simulate the general oxidative metabolism of 2-OH-AC for the first time. The reactivity of 2-OH-AC products to biomolecules was also examined. The usefulness of the electrochemistry...
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Development of a vortex-assisted switchable-hydrophilicity solvent-based liquid phase microextraction for fast and reliable extraction of Zn (II), Fe (II), Pb (II), and Cd (II) from various baby food products
PublicationThis manuscript describes the development of a novel liquid phase microextraction (LPME) method for the extraction and determination of Zn (II), Fe (II), Pb (II), and Cd (II) in various infant/baby food and supplements products. The method is based on vortex-assisted extraction combined with a switchable-hydrophilicity solvent (SHS) sample preparation. The SHS, which undergoes reversible phase changes triggered by pH change, enables...
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Venetoclax for Patients With Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase II Pivotal Trial
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Effective phospholipid removal from plasma samples by solid phase extraction with the use of copper (II) modified silica gel cartridges
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Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study
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Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma: Results From the Open-Label, Multicenter, Phase II DAWN Study
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Solid-phase extraction using octadecyl-bonded silica modified with photosynthetic pigments from Spinacia oleracea L. for the preconcentration of lead(II) ions from aqueous samples
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Blowing Kinetics, Pressure Resistance, Thermal Stability, and Relaxation of the Amorphous Phase of the PET Container in the SBM Process with Hot and Cold Mold. Part II: Statistical Analysis and Interpretation of Tests
PublicationThe technology of filling drinks without preservatives (such as fresh juices, iced tea drinks, and vitaminized drinks) is carried out using hot filling. Mainly due to the production costs and lower carbon footprint, polyethylene terephthalate (PET) bottles are increasingly used in this technology. In this paper, the main aim is to describe and interpret the results of statistical analysis of the influence of the temperature of...
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Chiral Pyrazolo[4,3-e][1,2,4]triazine Sulfonamides—Their Biological Activity, Lipophilicity, Protein Affinity, and Metabolic Transformations
PublicationReferring to our previous laboratory results related to the tyrosinase and urease inhibition by pyrazolo[4,3-e][1,2,4]triazine sulfonamides, we examined here in silico the mechanism of action at the molecular level of the investigated pyrazolotriazine sulfonamides by the molecular docking method. The studied compounds being evaluated for their cytotoxic effect against cancer cell lines (MCF-7, K-562) and for recombinant Abl and...
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New Chalcones Derivatives With Potent Antitumor Activity And Their Metabolism In Vitro
PublicationChalcone derivatives exhibit a broad range of biological activities, with antioxidant and cytotoxic properties among the most studied. Despite numerous reports on chalcones as cytotoxic, and potentially anticancer agents, very little is know on their actual mechanism of activity. Generally, chalcones are considered as antimitotic agents, which interfere with tubulin assembly.We have recently developed a new class of chalcones with...
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Metabolic Profiles of New Unsymmetrical Bisacridine Antitumor Agents in Electrochemical and Enzymatic Noncellular Systems and in Tumor Cells
PublicationNew unsymmetrical bisacridines (UAs) demonstrated high activity not only against a set of tumor cell lines but also against human tumor xenografts in nude mice. Representative UA compounds, named C-2028, C-2045 and C-2053, were characterized in respect to their physicochemical properties and the following studies aimed to elucidate the role of metabolic transformations in UAs action. We demonstrated with phase I and phase II enzymes...
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Human UDP-Glucuronosyltransferases: Effects of altered expression in breast and pancreatic cancer cell lines.
PublicationIncreased aerobic glycolysis and de novo lipid biosynthesis are common characteristics of invasive cancers. UDP-glucuronosyltransferases (UGTs) are phase II drug metabolizing enzymes that in normal cells possess the ability to glucuronidate these lipids and speed their excretion; however, de-regulation of these enzymes in cancer cells can lead to an accumulation of bioactive lipids, which further fuels cancer progression. We hypothesize...
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Targeting DNA Topoisomerase II in Antifungal Chemotherapy.
PublicationTopoisomerase inhibitors have been in use clinically for the treatment of several diseases for decades. Although those enzymes are significant molecular targets in antibacterial and anticancer chemotherapy very little is known about the possibilities to target fungal topoisomerase II (topo II). Raising concern for the fungal infections, lack of effective drugs and a phenomenon of multidrug resistance underlie a strong need to expand...
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Novel insights into conjugation of antitumor-active unsymmetrical bisacridine C-2028 with glutathione: characteristics of non-enzymatic and glutathione S-transferase-mediated reactions
PublicationUnsymmetrical bisacridines (UAs) are a novel potent class of antitumor-active therapeutics. A significant route of phase II drug metabolism is conjugation with glutathione (GSH), which can be non-enzymatic and/or catalyzed by GSH-dependent enzymes. The aim of this work was to investigate the GSH-mediated metabolic pathway of a representative UA, C 2028. GSH supplemented incubations of C-2028 with rat, but not with human, liver...
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Drug-drug interaction potential of antitumor acridine agent C-1748: The substrate of UDP-glucuronosyltransferases 2B7, 2B17 and the inhibitor of 1A9 and 2B7
PublicationBackground The compound 9-(2′-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748), the promising antitumor agent developed in our laboratory was determined to undergo phase I metabolic pathways. The present studies aimed to know its biotransformation with phase II enzymes – UDP-glucuronosyltransferases (UGTs) and its potential to be engaged in drug-drug interactions arising from the modulation of UGT activity. Methods UGT-mediated...
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Cold-adapted bacterial lipolytic enzymes and their applications
PublicationLipolytic enzymes, esterases and lipases catalyze the hydrolysis and transesterification of fatty acid esters. This class of enzymes is the most important group of biocatalysts for biotechnological applications. From this perspective, coldactive lipolytic enzymes from cold adapted bacteria display attractive properties for some industrial purposes, including high catalytic activity at low temperatures and low thermostability. To...
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The influence of selenium addition during seeds' germination on the biological properties of obtained sprouts
PublicationSelenium plays a vital role in human body, because in the form of aminoacids (Se-methionine, Se-cysteine) it is found in the active centres of over 25 enzymes, including those regarded as 'cytoprotective'. Unfortunatelly, its daily intake in Poland and other European countries is lower than predicted by dietary recommendations. The consequences of selenium deficiency in diet might be severe, including higher susceptibility to cardio-vascular...
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Extremophile Deinococcus geothermalis as potential source of proteolytic enzymes
PublicationAmong many extremozymes, thermophilic enzymes have attracted most attention during the past four decades. Such enzymes are of considerable industrial and biotechnological interest due to the fact that the enzymes are better suited for harsh industrial processes. There are many advantages of conducting industrial processes at high temperature, such as the increased solubility of many polymeric substrates, resulting in decreased...
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The effect of convective heating and microwave heating on antioxidant enzymes in pooled mature human milk
PublicationThe effects of convective and microwave heating at constant temperature (62.5, 66 and 70 °C) on the activity of antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPx) in pooled mature human milk were compared. Activities of the enzymes were determined using spectrophotometric kits. Activity of GPx decreased significantly in the first stage of heating when milk samples were warmed to pasteurisation...
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New generation of analytical tests based on the assessment of enzymatic and nuclear receptor activity changes induced by environmental pollutants
PublicationAnalytical methods show great potential in biological tests. The analysis of biological response that results from environmental pollutant exposure allows: (i) prediction of the risk of toxic effects and (ii) provision of the background for the development of markers of the toxicants presence. Bioanalytical tests based on changes in enzymatic activity and nuclear receptor action provide extremely high specificity and sensitivity....
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Enzymes of the lysine biosynthetic pathway as targets for antifungals ?
PublicationSystemic infections caused by human pathogenic fungi in immunocompromized patients continue to be one of the important clinical problems. Limited availability of safe and efficacious antifungal chemotherapeutics and emerging resistance to existing drugs stimulates search for novel molecular targets for antifungals. The α-aminoadipate pathway (AAP) of L-lysine biosynthesis is unique in fungi and thus has been so far considered...
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Study of pH and temperature effect on lipophilicity of catechol-containing antioxidants by reversed phase liquid chromatography
PublicationLipophilicity of selected antioxidant phytochemicals, including flavonoids, phenolic acids and xanthonoids, was determined by reversed phase high performance liquid chromatography with UV detection (RP-HPLC-UV). The analyses run at different temperature and pH conditions in isocratic mode suggested that lipophilicity as distribution coefficient (logD) between aqueous and organic phase decreases with increasing temperature. For...
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N-Alkyl Derivatives of L-Glutamine As Inhibitors of Glutamine - Utilizing Enzymes
PublicationA general facile method to synthesize the N-gamma-alkyl and N-gamma,N-gamma-dialkyl derivatives of L-glutamine (1a-d) from L-glutamic acid as a starting substrate is presented. The obtained compounds are shown to inhibit three diferent glutamine-utilizing enzymes, namely: glutaminase, gamma-glutamyl transpeptidase, and glucosamine-6-phosphate synthase, with inhibitory constants within the milimolar range.
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Electrochemistry meets enzymes: Investigation of the biotransformation pathway of C-1311 based on electrochemical simulation in comparison to in vitro methods.
PublicationThe knowledge of the metabolic pathways and the biotransformation of new drugs is one of the major challenges in pharmaceutical research. It is crucial for elucidation of degradation routes of the new biologically active compounds, especially in the area of possible toxicity. Conventional in vitro drug metabolism studies are based on incubating drug candidate with e.g. hepatocytes or, most importantly, liver cell microsomes and...
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Microcapsules and their applications in pharmaceutical and food industry.
PublicationMicroencapsulation is a process in which tiny particles or droplets are surrounded by a coating or embedded in a homogeneous or heterogeneous matrix, to generate small capsules in size range from a few to few thousand micrometers. The material inside the microcapsule is referred to as the core, internal phase, or fill, whereas the wall is sometimes called shell, coating, wall material, or membrane. It has found application in...
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Enzyme immobilization on magnetic nanoparticles
PublicationImmobilized enzymes have been commonly used in many branches of industry, biotechnology, medicine and also in analytical chemistry. Their use provides many advantages in comparison with free enzymes including repeated, easy recovery of the enzyme and improvement in enzyme stability. Enzymes are strong and specific catalysts, but are also expensive and fragile. Their immobilization and stabilization may reduce reaction costs, which...
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Beta-galactosidases from a psychrotolerant Arthrobacter isolates and their potential use
PublicationEnzymes from extremophiles, especially psychrophiles and psychrotolerant microorganisms are currently intensively studied because of their unusual structural and functional properties. One of these enzymes is a cold-adapted - galactosidase (EC 3.2.1.23) which catalyzes the hydrolysis of - 1,4-glycosidic bonds in -galactosides. The most common - galactoside is lactose, a disaccharide which makes up 2-7% of milk. The majority of...
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Folding‐upon‐repair DNA nanoswitches for monitoring DNA repair enzymes activity
PublicationWe demonstrate here a new class of DNA‐based nanoswitches that, upon enzymatic repair, could undergo a conformational change mechanism leading to a change in fluorescent signal. Such folding‐upon‐repair DNA nanoswitches are synthetic DNA sequences containing O6‐methyl‐guanine (O6‐MeG) nucleobases and labelled with a fluorophore/quencher optical pair. The nanoswitches are rationally designed so that only upon enzymatic demethylation...
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Expression of a GDSL esterase from Pseudomonas sp. S9 in Pichiapastoris
PublicationCold active lipolytic enzymes are promising to replace the conventional enzymes processes of biotechnological industries. One of the most important feature of the cold-active lipases and esterases is that they offer economic benefits through energy saving. In general, they exhibit high activity at low temperatures and low thermostability at moderate temperatures. Lipolytic enzyme EstS9 was isolated from Pseudomonas sp. S9. A multiple...
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Changes in enzymatic activity of fish and slaughter animals meat after high pressure treatment at subzero temperatures
PublicationThe aim of this study was to determine changes in the activity of proteolytic enzymes and transglutaminase of fish and mammal meat after pressurization at subzero temperatures. The activity was measured at the optimal pHs determined for enzymes from particular types of tested meat. It was found that increasing the pressure in the range of 60–193 MPa, did not change significantly the activity of acidic proteases of cod flesh, while...
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The Role of Electrostatics in Enzymes: Do Biomolecular Force Fields Reflect Protein Electric Fields?
PublicationPreorganization of large, directionally oriented, electric fields inside protein active sites has been proposed as a crucial contributor to catalytic mechanism in many enzymes, and it may be efficiently investigated at the atomistic level with molecular dynamics simulations. Here, we evaluate the ability of the AMOEBA polarizable force field, as well as the additive Amber ff14SB and Charmm C36m models, to describe the electric...
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Properties and applications of thermostable proteases sourced from Deinococcus geothermalis.
PublicationThe growing interest of extremophiles results from the fact that their enzymes arestable and active under harsh environment conditions. These type of biocatalysts are attractivedue to the fact that can be used in industrial processes that were previously regarded asincompatible with biological materials. Among extremozymes the largest group constitutethermozymes. Currently it is estimated that approximately 40% of enzymes used...
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Inhibitors of amino acids biosynthesis as antifungal agents
PublicationFungal microorganisms, including the human pathogenic yeast and filamentous fungi, are able to synthesize all proteinogenic amino acids, including nine that are essential for humans. A number of enzymes catalyzing particular steps of human-essential amino acid biosynthesis are fungi specific. Numerous studies have shown that auxotrophic mutants of human pathogenic fungi impaired in biosynthesis of particular amino acids exhibit...
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Investigation of interaction between xanthene dye rhodamine B and metagenomic-derivated methylthioadenosine phosphorylase RSFP
PublicationIn the previous study we found that the expression of the metagenomic - derived methylthioadenosine phosphorylase gene (rsfp) in E. coli cells and the presence of rhodamine B in the growth medium were crucial for the pink fluorescence of one E. coli colony from Antarctic soil metagenomic library (Cieśliński et al., 2009). In this study, rsfp gene expression was induced by an arabinose promoter in an LMG194 E. coli strain and the...
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Characteristic and specificity of protease activity of thermophilic bacteria Meiothermus ruber
PublicationThe primary purpose of research was to establish the possibility of using thermophilic bacteria Meiothermus ruber as a source of proteolytic enzymes. The main reason of searching new proteases is their commercial value especially in production of detergents, food, pharmaceuticals, leather, diagnostics or waste management. The development of this type processes will be possible by utilization of enzymes which have unique characteristics...
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Enzymatic cross-linking of β-lactoglobulin in solution and at air–water interface: Structural constraints
PublicationEffective and controlled use of cross-linking enzymes in structure engineering of food systems depends on characterization of the favorable conditions for enzyme-substrate complex and the limiting factors for the desired modification. In this respect, we analyzed the susceptibility of bovine β-lactoglobulin (BLG) to enzymatic cross-linking by Trichoderma reesei tyrosinase (TrTyr) and transglutaminase (TG). Changes in BLG molecular...
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Meiothermus ruber cells as β-galactosidase activity biocatalyst
PublicationThe current study allowed to establish the possibility of using whole cells of thermophilic bacteria Meiothermus ruber as a biocatalyst with β-galactosidase activity. β-galactosidases are used for hydrolysis of lactose as well as for oligosaccharides synthesis. The advantages of using whole bacterial cells catalysis is not only elimination of tedious, expensive protein isolation and/or purification but also stabilization of enzymes...
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Facilitated transport of Zn(II), Cd(II) and Pb(II) across polymer inclusion membranes doped with imidazole azocrown ethers
PublicationZbadano transport jonów Pb(II), Cd(II) i Zn(II) przez polimerowe membrany inkluzyjne (PIM) przy użyciu imidazolowych azokoron. Badanie prowadzono dla wodnych roztworów azotanów metali o c(Me)=0,001M i pH=5,0. Polimerowe membrany inkluzyjne otrzymywano z trójoctanu celulozy (nośnik), plastyfikatora i jonoforu (jeden z imidazolowych eterów koronowych z ugrupowaniem azowym). Badane azokorony różniły sięmiejscem podstawienia imidazolu...
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Biological Activity of Tea-Chokeberry and Chokeberry Fermented Beverages
PublicationFermented beverages, such as kombucha are gaining more and more popularity due to their beneficial effects on human health. These products are obtained by the fermentation of tea infusion using so called tea fungus. This microbial consortium can also be used to prepare fermented fruit beverages. Therefore, the aim of this study was to determine the changes in the antioxidant profile of tea-chokeberry and chokeberry beverages...
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Molecular targets for antifungals in amino acid and protein biosynthetic pathways
PublicationFungi cause death of over 1.5 million people every year, while cutaneous mycoses are among the most common infections in the world. Mycoses vary greatly in severity, there are long-term skin (ringworm), nail or hair infections (tinea capitis), recurrent like vaginal candidiasis or severe, life-threatening systemic, multiorgan infections. In the last few years, increasing importance is attached to the health and economic problems...
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Investigation of the Effect of the Rocket's Suborbital Flight on Biofilm, Enzymes and Biosynthesis on Autonomous, Modular and Scalable Platforms For Conducting Experiments of an Astrobiotechnological Nature
PublicationWith new incentives for human space exploration, biotechnological experiments in orbit became imperative. Answering this need, we build an autonomous, modular, and scalable platform that enables those experiments on rockets. We called it AMBER. The aim of the payload of the R6 suborbital rocket is to perform an experiment to study the influence of rocket flights on biofilm, molecular biology enzymes and biosynthesis using our platform....
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The influence of pre- and postharvest treatments on selected biological and epigenetic activities of Brassica sprouts
PublicationIntroduction The Brassica vegetables are rich in glucosinolates (GLs), which are enzymatically hydrolysed to bioactive isothiocynates (ITC) and indoles, regarded as the most promising chemopreventing agents. However, in the majority of brassica sprouts the GL conversion into these beneficial derivatives occurs at the level of about 1 %, while in cabbage leaves exceeds 70%. Since sprouts represent plant material, which is frequently...
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Facilitated transport of Zn(II), Cd(II) and Pb(II) ions trough polymer inclusion membranes with calix[4]-crown-6 derivaties
PublicationBadano transport mieszaniny równomolowych ilości jonów Zn(II), Cd(II) i Pb(II)z wodnej fazy azotanowej (cMe=0,001M) przez polimerowe membrany inkluzyjne(PIM) zawierające pochodne kaliks[4]korony-6 jako nośniki jonów. Badany był wpływ różnych podstawników na wydajność procesu. Selektywność transportu przez membrany zawierające jonofory 4 i 5 malała w kolejności Pb(II), Zn(II), Cd(II), natomiast z jonoforem 3 Pb(II), Zn(II)Cd(II)....
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Example of utilization of permeabilized microbial cells
PublicationThe benefits of using whole bacterial cells not only exclude expensive, laborious protein isolation and purification but also stabilize enzymes by cytosol components. Increase in activity of the cells can be achieved by cells permeabilization.
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INVESTIGATION OF THE EFFECT OF THE ROCKET'S SUBORBITAL FLIGHT ON BIOFILM, ENZYMES AND BIOSYNTHESIS ON AUTONOMOUS, MODULAR AND SCALABLE PLATFORM FOR CONDUCTING EXPERIMENTS OF AN ASTROBIOTECHNOLOGICAL NATURE
PublicationWith new incentives for human space exploration, biotechnological experiments in orbit became imperative.Answering this need, we build an autonomous, modular, and scalable platform that enables those experiments onrockets. We called it AMBER. The aim of the payload of the R6 suborbital rocket is to perform an experiment tostudy the influence of rocket flights on biofilm, molecular...
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Crystal structures of aminotransferases Aro8 and Aro9 from Candida albicans and structural insights into their properties
PublicationAminotransferases catalyze reversibly the transamination reaction by a ping-pong bi-bi mechanism with pyridoxal 5′-phosphate (PLP) as a cofactor. Various aminotransferases acting on a range of substrates have been reported. Aromatic transaminases are able to catalyze the transamination reaction with both aromatic and acidic substrates. Two aminotransferases from C. albicans, Aro8p and Aro9p, have been identified recently, exhibiting...