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61.
Ptáková Michaela Pokorný Petr Šída Petr Novák Jan Horáček Ivan Juřičková Lucie Meduna Petr Bezděk Aleš Myšková Eva Walls Matthew Poschlod Peter 《Vegetation History and Archaeobotany》2021,30(2):269-286
Vegetation History and Archaeobotany - In a continuous, perfectly stratified sedimentary sequence which was discovered under a large sandstone overhang in northern Bohemia, Czech Republic, we... 相似文献
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Goncharov Alexey I. Levina Inna S. Shliapina Viktoriia L. Morozov Ivan A. Rubtsov Petr M. Zavarzin Igor V. Smirnova Olga V. Shchelkunova Tatiana A. 《Biochemistry. Biokhimii?a》2021,86(11):1446-1460
Biochemistry (Moscow) - Progesterone and its synthetic analogues act on cells through different types of receptors, affecting proliferation and apoptosis. These compounds exert their effect through... 相似文献
64.
Mohammad-Reza Ghovanloo Koushik Choudhury Tagore S. Bandaru Mohamed A. Fouda Kaveh Rayani Radda Rusinova Tejas Phaterpekar Karen Nelkenbrecher Abeline R. Watkins Damon Poburko Jenifer Thewalt Olaf S. Andersen Lucie Delemotte Samuel J. Goodchild Peter C. Ruben 《The Journal of general physiology》2021,153(5)
Cannabidiol (CBD) is the primary nonpsychotropic phytocannabinoid found in Cannabis sativa, which has been proposed to be therapeutic against many conditions, including muscle spasms. Among its putative targets are voltage-gated sodium channels (Navs), which have been implicated in many conditions. We investigated the effects of CBD on Nav1.4, the skeletal muscle Nav subtype. We explored direct effects, involving physical block of the Nav pore, as well as indirect effects, involving modulation of membrane elasticity that contributes to Nav inhibition. MD simulations revealed CBD’s localization inside the membrane and effects on bilayer properties. Nuclear magnetic resonance (NMR) confirmed these results, showing CBD localizing below membrane headgroups. To determine the functional implications of these findings, we used a gramicidin-based fluorescence assay to show that CBD alters membrane elasticity or thickness, which could alter Nav function through bilayer-mediated regulation. Site-directed mutagenesis in the vicinity of the Nav1.4 pore revealed that removing the local anesthetic binding site with F1586A reduces the block of INa by CBD. Altering the fenestrations in the bilayer-spanning domain with Nav1.4-WWWW blocked CBD access from the membrane into the Nav1.4 pore (as judged by MD). The stabilization of inactivation, however, persisted in WWWW, which we ascribe to CBD-induced changes in membrane elasticity. To investigate the potential therapeutic value of CBD against Nav1.4 channelopathies, we used a pathogenic Nav1.4 variant, P1158S, which causes myotonia and periodic paralysis. CBD reduces excitability in both wild-type and the P1158S variant. Our in vitro and in silico results suggest that CBD may have therapeutic value against Nav1.4 hyperexcitability. 相似文献
65.
Stéphane Guyot Laurence Pottier Lucie Bertheau Jennifer Dumont Eminence Dorelle Hondjuila Miokono Sébastien Dupont Mélanie Ragon Emmanuel Denimal Ambroise Marin John E. Hallsworth Laurent Beney Patrick Gervais 《Microbial biotechnology》2021,14(4):1445-1461
Although mechanisms involved in response of Saccharomyces cerevisiae to osmotic challenge are well described for low and sudden stresses, little is known about how cells respond to a gradual increase of the osmotic pressure (reduced water activity; aw) over several generations as it could encounter during drying in nature or in food processes. Using glycerol as a stressor, we propagated S. cerevisiae through a ramp of the osmotic pressure (up to high molar concentrations to achieve testing-to-destruction) at the rate of 1.5 MPa day-1 from 1.38 to 58.5 MPa (0.990–0.635 aw). Cultivability (measured at 1.38 MPa and at the harvest osmotic pressure) and glucose consumption compared with the corresponding sudden stress showed that yeasts were able to grow until about 10.5 MPa (0.926 aw) and to survive until about 58.5 MPa, whereas glucose consumption occurred until 13.5 MPa (about 0.915 aw). Nevertheless, the ramp conferred an advantage since yeasts harvested at 10.5 and 34.5 MPa (0.778 aw) showed a greater cultivability than glycerol-shocked cells after a subsequent shock at 200 MPa (0.234 aw) for 2 days. FTIR analysis revealed structural changes in wall and proteins in the range 1.38–10.5 MPa, which would be likely to be involved in the resistance at extreme osmotic pressure. 相似文献
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David Malinak Rafael Dolezal Vendula Hepnarova Miroslava Hozova Rudolf Andrys Petr Bzonek 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):478-488
Abstract The series of symmetrical and unsymmetrical isoquinolinium-5-carbaldoximes was designed and prepared for cholinesterase reactivation purposes. The novel compounds were evaluated for intrinsic acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) inhibition, when the majority of novel compounds resulted with high inhibition of both enzymes and only weak inhibitors were selected for reactivation experiments on human AChE or BChE inhibited by sarin, VX, or paraoxon. The AChE reactivation for all used organophosphates was found negligible if compared to the reactivation ability of obidoxime. Importantly, two compounds were found to reactivate BChE inhibited by sarin or VX better to obidoxime at human attainable concentration. One compound resulted as better reactivator of NEMP (VX surrogate)-inhibited BChE than obidoxime. The in vitro results were further rationalized by molecular docking studies showing future directions on designing potent BChE reactivators. 相似文献
68.
Mikhail Krasavin Raivis Žalubovskis Aiga Grandāne Ilona Domračeva Petr Zhmurov 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):506-510
Abstract The hypothesis that sulfocoumarin acting as inhibitors of human carbonic anhydrase (CA, EC 4.2.1.1) cancer-associated isoforms hCA IX and – hCA XII is being able to also inhibit thioredoxin reductase was verified and confirmed. The dual targeting of two cancer cell defence mechanisms, i.e. hypoxia and oxidative stress, may both contribute to the observed antiproliferative profile of these compounds against many cancer cell lines. This unprecedented dual anticancer mechanism may lead to a new approach for designing innovative therapeutic agents. 相似文献
69.
Ivan Literák Petr Heneberg Jiljí Sitko Eric J. Wetzel Jorge Manuel Cardenas Callirgos Miroslav Čapek Daniel Valle Basto Ivo Papoušek 《Parasitology international》2013,62(4):390-396
Until now, four species of eye trematodes have been found in South America. Of them, Philophthalmus lucipetus (synonymized with Philophthalmus gralli) displays a broad host spectrum, with at least 30 bird species (prevalently large water birds), five mammal species and humans serving as definitive hosts, and with snails Fagotia (Microcolpia) acicularis, Amphimelania holandri, Melanopsis praemorsa and Melanoides tuberculata serving as intermediate hosts. When examining a total of 50 birds of ten species in the wetland of Pantanos de Villa, Lima, Peru in July 2011, eye trematodes were identified visually in the edematous conjunctival sac of 11 (48%) out of 23 resident many-colored rush tyrants Tachuris rubrigastra. Based on morphometric characteristics, the trematodes were identified as P. lucipetus. ITS2 and CO1 gene of the examined specimens combined showed a 99% similarity to an Iranian isolate of Philophthalmus sp. from the intermediate host Melanoides tuberculata, an invasive freshwater snail, suggesting that these two isolates represent the same species with a wide geographical range. Moreover, the prevalence of infection with the philophthalmid cercariae was 31% in 744 Melanoides tuberculata examined in Pantanos de Villa in 2010. It is evident that P. lucipetus occurs throughout the world as well as locally, including Eurasia and South America. Here we report this trematode for the first time in Peru, and we were the first to sequence any of the South American eye trematodes. Low host specificity of P. lucipetus and the invasive character of Melanoides tuberculata as a competent intermediate host suggest that eye trematodosis caused by P. lucipetus may emerge frequently in various parts of the world, especially in the tropics. Increase of the zoonotic potential of the P. lucipetus associated with this invasive snail spreading across the world is predictable and should be of interest for further research. 相似文献
70.
The parasitism (Hymenoptera, Braconidae, Aphidiinae) of alfalfa aphids (Hemiptera, Aphididae) was determined during three crop growing seasons. The highest rates of parasitism of Acyrthosiphon pisum Harris and of Therioaphis trifolii Monell occurred during the first-second and the fourth alfalfa intercuts, respectively. The landscape surrounding the fields affected only parasitism rates of A. pisum. During the second intercut the forest area had a negative influence on parasitism rates, whereas the bordering surfaces of alfalfa and winter cereals had a positive influence. Positive correlations were found between the rates of parasitism of A. pisum and the rate of aphid population increase in the first intercut. By contrast, negative correlations were found in the second intercut, when the aphid population peaked, suggesting that parasitoids contribute to the regulation of the aphid. This study stresses that regulation of alfalfa aphids cannot be explained solely on the basis of one functional group of natural enemies. 相似文献