The increasing ineffectiveness of traditional antibiotics and the rise of multidrug resistant (MDR) bacteria have necessitated the revival of bacteriophage (phage) therapy. However, bacteria might ...also evolve resistance against phages. Phages and their bacterial hosts coexist in nature, resulting in a continuous coevolutionary competition for survival. We have isolated several clinical strains of
and phages that infect them. Among these, the PIAS (Phage Induced Antibiotic Sensitivity) phage belonging to the
family can induce multistep genomic deletion in drug-resistant clinical strains of
, producing a compromised drug efflux system in the bacterial host. We identified two types of mutant lines in the process: green mutants with SNPs (single nucleotide polymorphisms) and smaller deletions and brown mutants with large (∼250 kbp) genomic deletion. We demonstrated that PIAS used the MexXY-OprM system to initiate the infection.
clogged PIAS phage infection by either modifying or deleting these receptors. The green mutant gaining phage resistance by SNPs could be overcome by evolved PIASs (E-PIASs) with a mutation in its tail-fiber protein. Characterization of the mutant phages will provide a deeper understanding of phage-host interaction. The coevolutionary process continued with large deletions in the same regions of the bacterial genomes to block the (E-)PIAS infection. These mutants gained phage resistance
either complete loss or substantial modifications of the phage receptor, MexXY-OprM, negating its essential role in antibiotic resistance.
and
studies indicated that combined use of PIAS and antibiotics could effectively inhibit
growth. The phage can either eradicate bacteria or induce antibiotic sensitivity in MDR-resistant clinical strains. We have explored the potential use of combination therapy as an alternative approach against MDR
infection.
Sigma-1 receptor (S1R) is detected in different cell types and can regulate intracellular signaling pathways. S1R plays a role in the pathomechanism of diseases and the regulation of ...neurotransmitters. Fluvoxamine can bind to S1R and reduce the serotonin uptake of neurons and platelets. We therefore hypothesized that platelets express S1R, which can modify platelet function. The expression of the SIGMAR1 gene in rat platelets was examined with a reverse transcription polymerase chain reaction and a quantitative polymerase chain reaction. The receptor was also visualized by immunostaining and confocal laser scanning microscopy. The effect of S1R agonist PRE-084 on the eicosanoid synthesis of isolated rat platelets and ADP- and AA-induced platelet aggregation was examined. S1R was detected in rat platelets both at gene and protein levels. Pretreatment with PRE-084 of resting platelets induced elevation of eicosanoid synthesis. The rate of elevation in thromboxane B
2
and prostaglandin D
2
synthesis was similar, but the production of prostaglandin E
2
was higher. The concentration-response curve showed a sigmoidal form. The most effective concentration of the agonist was 2 µM. PRE-084 increased the quantity of cyclooxygenase-1 as detected by ELISA. PRE-084 also elevated the ADP- and AA-induced platelet aggregation. S1R of platelets might regulate physiological or pathological functions.
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3.
Effects of kisspeptin on diabetic rat platelets Mezei, Zsófia; Váczi, Sándor; Török, Viktória ...
Canadian journal of physiology and pharmacology,
11/2017, Volume:
95, Issue:
11
Journal Article
Peer reviewed
Open access
Hyperglycemia, hyperlipidemia, and free radicals result in platelet activation and atherogenesis. Kisspeptin (KP) is able to regulate metabolism, hemostasis, and the development of atherosclerosis. ...We examined whether platelet aggregation of streptozotocin-induced diabetic rats depends on the inducer type and if KP-13 and RF-9 (a kisspeptin receptor modifier) can influence platelet function. We measured the speed and the maximum of aggregation, along with the area under the curve. Serum glucose and calcium levels and urine formation of diabetic animals increased, while the body mass and platelet count decreased. Collagen was the most effective inducer of platelet aggregation. The aggregability of nondiabetic platelets was elevated in the presence of 5 × 10
mol/L KP-13. This effect was less expressed in diabetic animals. The effectivity of RF-9 was stronger than that of KP-13 in nondiabetic platelets, however it was ineffective in diabetic animals. RF-9 pre-treatment did not change the effects of 5 × 10
mol/L KP-13 in either animal group. The in vivo activation of diabetic platelets, which may be due to elevated serum calcium, induces thrombocytopenia and may lead to reduced in vitro aggregability. We could not demonstrate the antagonistic effect of RF-9 against KP-13 in isolated platelets.
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The use of big data in urban mobility research is growing dynamically. However, relatively few studies have been devoted to systematically review the results in this field. Therefore, the aim of the ...present study is to explore the general characteristics of the application of the big data approach in urban mobility research. For this purpose, the systematic literature review method was applied and the scientific Scopus database was accessed to collect publications relevant to the predefined criteria. Then the papers included in the sample were analysed using quantitative and qualitative techniques, focusing on the trends emerging from the years of publications in the database, the distribution of the papers by journal, the geographical distribution of case-study areas, the methods and data types employed, and their policy implications. This literature review demonstrates the diversity of big datadriven urban mobility research and provides lessons for geography and urban policy in Hungary.
Diabetes mellitus is a chronic metabolic disorder which induces endothelial dysfunction and platelet activation. Eicosanoids produced from arachidonic acid regulate cellular and vascular functions. ...Sigma-1 receptors (S1R) are expressed in platelets and endothelial cells and S1R expression is protective in diabetes.
Our aim was to examine the influence of sub-chronic, in vivo administered S1R ligands PRE-084, (S)-L1 (a new compound) and NE-100 on the ex vivo arachidonic acid metabolism of platelets and aorta in streptozotocin-induced diabetic rats.
The serum level of the S1R ligands was detected by LC-MS/MS before the ex vivo analysis. Sigma-1 receptor and cyclooxygenase gene expression in platelets were determined by RT-qPCR. The eicosanoid synthesis was examined with a radiolabelled arachidonic acid substrate and ELISA.
One month after the onset of STZ-induced diabetes, in vehicle-treated, diabetic rat platelet TxB2 and aortic 6-k-PGF1α production dropped. Sub-chronic in vivo treatment of STZ-induced diabetes in rats for one week with PRE-084 enhanced vasoconstrictor and platelet aggregator and reduced vasodilator and anti-aggregator cyclooxygenase product formation. (S)-L1 reduced the synthesis of vasodilator and anti-aggregator cyclooxygenase metabolites and promoted the recovery of physiological platelet function in diabetic rats. The S1R antagonist NE-100 produced no significant changes in platelet arachidonic acid metabolism. (S)-L1 decreased the synthesis of vasoconstrictor and platelet aggregator cyclooxygenase metabolites, whereas NE-100 increased the quantity of aortic vasodilator and anti-aggregator cyclooxygenase products and promoted the recovery of diabetic endothelial dysfunction in the aorta. The novel S1R ligand, (S)-L1 had similar effects on eicosanoid synthesis in platelets as the agonist PRE-084 and in aortas as the antagonist NE-100.
S1R ligands regulate cellular functions and local blood circulation by influencing arachidonic acid metabolism. In diabetes mellitus, the cell-specific effects of S1R ligands have a compensatory role and aid in restoring physiological balance between the platelet and vessel.
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Platelets regulate cell-cell interactions and local circulation through eicosanoids from arachidonic acid. Sigma non-opioid intracellular receptor 1 (sigma-1 receptor) expressed in platelets and ...endothelial cells can regulate intracellular signalization. Our aim was to examine the influence of sub-chronic, in vivo-administered sigma-1 receptor ligands 2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate (PRE-084); N-benzyl-2-(1S)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-ylethan-1-amine; dihydrochloride, a new compound ((S)-L1); and N-2-4-methoxy-3-(2-phenylethoxy)phenylethyl-N-propylpropan-1-amine (NE-100) on the ex vivo arachidonic acid metabolism of the platelets and aorta of male rats. The serum level of sigma-1 receptor ligands was determined by liquid chromatography-mass spectrometry. Sigma-1 receptor and cyclooxygenase gene expression in the platelets were determined by a reverse transcription-coupled quantitative polymerase chain reaction. The eicosanoid synthesis was examined using a radiolabeled arachidonic acid substrate and enzyme-linked immunosorbent assay. We confirmed the absorption of sigma-1 receptor ligands and confirmed that the ligands were not present during the ex vivo studies, so their acute effect could be excluded. We detected no changes in either sigma-1 receptor or cyclooxygenase mRNA levels in the platelets. Nevertheless, (S)-L1 and NE-100 increased the quantity of cyclooxygenases there. Both platelet and aortic eicosanoid synthesis was modified by the ligands, although in different ways. The effect of the new sigma-1 receptor ligand, (S)-L1, was similar to that of PRE-084 in most of the parameters studied but was found to be more potent. Our results suggest that sigma-1 receptor ligands may act at multiple points in arachidonic acid metabolism and play an important role in the control of the microcirculation by modulating the eicosanoid synthesis of the platelets and vessels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hyperglycemia, hyperlipidemia, and free radicals result in platelet activation and atherogenesis. Kisspeptin (KP) is able to regulate metabolism, hemostasis, and the development of atherosclerosis. ...We examined whether platelet aggregation of streptozotocin-induced diabetic rats depends on the inducer type and if KP-13 and RF-9 (a kisspeptin receptor modifier) can influence platelet function. We measured the speed and the maximum of aggregation, along with the area under the curve. Serum glucose and calcium levels and urine formation of diabetic animals increased, while the body mass and platelet count decreased. Collagen was the most effective inducer of platelet aggregation. The aggregability of nondiabetic platelets was elevated in the presence of 5 × 10
−8
mol/L KP-13. This effect was less expressed in diabetic animals. The effectivity of RF-9 was stronger than that of KP-13 in nondiabetic platelets, however it was ineffective in diabetic animals. RF-9 pre-treatment did not change the effects of 5 × 10
−8
mol/L KP-13 in either animal group. The in vivo activation of diabetic platelets, which may be due to elevated serum calcium, induces thrombocytopenia and may lead to reduced in vitro aggregability. We could not demonstrate the antagonistic effect of RF-9 against KP-13 in isolated platelets.
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A Duna Dunaújváros fölötti teljes szakaszán felszín közelben megjelenő pleisztocén hordalékában a változatos összetételű kavicsanyagba ágyazottan szabálytalan elrendeződésben, kis mennyiségben akár ...több mint 1 méteres átmérőjű, változatos összetételű, különböző mértékben koptatott kőzettömböket is lehet találni. Legfőbb előfordulásaik a Kisalföld és a Dél-pesti-síkság, legismertebb lelőhelyei a Dunavarsány-Délegyháza környéki kavicsbányák. Eredetüket régóta kutatják, de forrásuk pontos helyének meghatározása eddig még nem történt meg, így ide kerülésük módja máig vitatott. A kérdés megoldását a tömbök között talált ritka ásványtartalmú exotikus metamorf kőzetek petrográfiai vizsgálata tette lehetővé. A Dunavarsányi Aqua kft. kavicsbányájában talált diagnosztikus, dumortieritet tartalmazó cordierit-turmalin-sillimanit gneisz, a klinohumitot tartalmazó olivin-spinell-apatit-tremolit-klorit-flogopit dolomárvány és a szkapolitot tartalmazó prehnit-aktinolit-diopszid amfibolit szálfeltárásai a Cseh-masszívum ausztriai részén, egymáshoz közeli meredek Duna parti lelőhelyeken megtalálhatók. A terepi megfigyelések, az összehasonlító polarizációs és pásztázó elektronmikroszkópos elemzés, a fázisanalízist segítő Raman-spektroszkópia, valamint az irodalmi analógiák alapján a jellegzetes ásványokkal bíró kőzettömbök forrásterülete jól behatárolható. A tömbök összetétele, mérete és alakja alapján a szállítást leginkább meghatározó tényező a pleisztocén folyóvízi jég lehetett.
Tourmaline-rich pegmatitic orthogneisses, tourmalinites, kyanite-chlorite-muscovite schists and quartzites crosscut by subordinate quartz-tourmaline veins and layers were newly described from the ...Sopron area, Western Hungary. The orthogneisses mainly consist of quartz, plagioclase, tourmaline, garnet and white mica. In smaller amounts K-feldspar, beryl, Mg-rich chlorite, kyanite, lazulite, florencite, monazite and apatite also are present. Magmatic cores and two generations of metamorphic tourmaline (Fe-rich and Mg-rich) were distinguished. Tourmaline in tourmalinites is generally large (several cm), deformed, contains chlorite inclusions and shows oscillatory zoning or polygonal fabric. Large tourmaline crystals often contain dark brown mica-shaped relic areas with higher amount of Ti and Fe than the adjacent parts, interpreted as relics of micas from the protolith. Besides tourmaline, quartz, white mica, plagioclase, apatite, garnet, rutile, ilmenite, scheelite, zircon and monazite are also present in the tourmalinites. Deformed tourmaline-quartz bands and veins occur in kyanite-chlorite-muscovite schists and quartzites. Euhedral, zoned and deformed schorl-dravite is accompanied with kyanite, Mg-chlorite (leuchtenbergite), rutile muscovite and sillimanite. Narrow colorless tourmaline rims enriched exclusively in Mg (FeO < 1 wt. %) can be identified. Coarse-grained orthogneisses with a significant amount of primary tourmaline-beryl assemblage indicates a fluid-rich, B-Be-bearing environment during the final crystallization of the Variscan peraluminous leucogranite. The formation of tourmalinites can be explained by the related boron metasomatism. Phengitic white mica rims and calcic garnet rims in orthogneisses and tourmalinites indicate high-pressure Alpine metamorphic overprint. The presence of REE-rich phosphate mineralisation and leuchtenbergite in the orthogneisses imply that high salinity fluids metasomatized the orthogneisses along the pre-existing shear zones after the Alpine metamorphic peak. Tourmaline grains in kyanite-bearing quartzites and schists may have originated from a micaschist that underwent a strong Mg-metasomatism during the formation of leucophyllites described from the area.
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