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441.
Dorota Łażewska Szczepan Mogilski Stefanie Hagenow Kamil Kuder Monika Głuch-Lutwin Agata Siwek Małgorzata Więcek Maria Kaleta Ulla Seibel Armin Buschauer Barbara Filipek Holger Stark Katarzyna Kieć-Kononowicz 《Bioorganic & medicinal chemistry》2019,27(7):1254-1262
This study focuses on the design, synthesis, molecular modeling and biological evaluation of a novel group of alkyl-1,3,5-triazinyl-methylpiperazines. New compounds were synthesized and their affinities for human histamine H4 receptor (hH4R) were evaluated. Among them, 4-(cyclohexylmethyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (14) exhibited hH4R affinity with a Ki of 160?nM and behaved as antagonist in functional assays: the cellular aequorin-based assay (IC50?=?32?nM) and [35S]GTPγS binding assay (pKb?=?6.67). In addition, antinociceptive activity of 14 in vivo was observed in Formalin test (in mice) and in Carrageenan-induced acute inflammation test (in rats). 相似文献
442.
Najberek Kamil Solarz Wojciech Gąsienica-Staszeczek Magdalena Olejniczak Paweł 《Journal of plant research》2022,135(5):637-646
Journal of Plant Research - Comparative studies with taxonomically and geographically paired alien species that exhibit different degrees of success in their invasions may help to identify the... 相似文献
443.
Bajgar J Hajek P Slizova D Krs O Fusek J Kuca K Jun D Bartosova L Blaha V 《Chemico-biological interactions》2007,165(1):14-21
Acetylcholinesterase activity in defined brain regions was determined using biochemical and histochemical methods 30 min after treating rats with sarin, soman or VX (0.5 x LD(50)). Enzyme inhibition was high in the pontomedullar area and frontal cortex, but was low in the basal ganglia. Histochemical and biochemical results correlated well. Determination of the activity in defined brain structures was a more sensitive parameter than determination in whole brain homogenate where the activity was a "mean" of the activities in different structures. The pontomedullar area controls respiration, so that the special sensitivity of acetylcholinesterase to inhibition by nerve agents in this area is important for understanding the mechanism of death caused by nerve agents. Thus, acetylcholinesterase activity is the main parameter investigated in studies searching for target sites following nerve agent poisoning. 相似文献
444.
Pallová P Hercík K Sasková L Nováková L Branny P 《Biochemical and biophysical research communications》2007,355(2):526-530
Streptococcus pneumoniae carries a single Ser/Thr protein kinase gene stkP in its genome. Biochemical studies performed with recombinant StkP have revealed that this protein is a functional membrane-linked eukaryotic-type Ser/Thr protein kinase. Here, we demonstrate that the deletion of its extracellular domain negatively affects the stability of a core kinase domain. In contrast, the membrane anchored kinase domain and the full-length form of StkP were stable and capable of autophosphorylation. Furthermore, evidence is presented that StkP forms dimers through its transmembrane and extracellular domains. 相似文献
445.
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447.
Lyric A. Jorgenson William T. Newsome David J. Anderson Cornelia I. Bargmann Emery N. Brown Karl Deisseroth John P. Donoghue Kathy L. Hudson Geoffrey S. F. Ling Peter R. MacLeish Eve Marder Richard A. Normann Joshua R. Sanes Mark J. Schnitzer Terrence J. Sejnowski David W. Tank Roger Y. Tsien Kamil Ugurbil John C. Wingfield 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2015,370(1668)
The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions. 相似文献
448.
Kamil Wolanin Diana Fontinha Margarida Sanches‐Vaz Britta Nyboer Kirsten Heiss Ann‐Kristin Mueller Miguel Prudêncio 《Cellular microbiology》2019,21(10)
Intracellular Plasmodium parasites develop inside a parasitophorous vacuole (PV), a specialised compartment enclosed by a membrane (PVM) that contains proteins of both host and parasite origin. Although exported protein 1 (EXP1) is one of the earliest described parasitic PVM proteins, its function throughout the Plasmodium life cycle remains insufficiently understood. Here, we show that whereas the N‐terminus of Plasmodium berghei EXP1 (PbEXP1) is essential for parasite survival in the blood, parasites lacking PbEXP1's entire C‐terminal (CT) domain replicate normally in the blood but cause less severe pathology than their wild‐type counterparts. Moreover, truncation of PbEXP1's CT domain not only impairs parasite development in the mosquito but also abrogates PbEXP1 localization to the PVM of intrahepatic parasites, severely limiting their replication and preventing their egress into the blood. Our findings highlight the importance of EXP1 during the Plasmodium life cycle and identify this protein as a promising target for antiplasmodial intervention. 相似文献
449.
Suzana Berend Ana Luci Vrdoljak Boica Radi Kamil Ku
a 《Chemico-biological interactions》2008,175(1-3):413
Improving the efficacy of antidotal treatment of poisonings with nerve agents is still a challenge for the scientific community. This study investigated the interactions of four bispyridinium oximes with human erythrocyte acetylcholinesterase (AChE) and their effects on soman- and tabun-poisoned mice. Oximes HI-6 and TMB-4 were used for comparison. These oximes inhibited AchE with inhibitory potency (IC50) ranging from 0.02 to 1.0 mM. The best reactivating potency (%R) was obtained with K074, when AChE was inhibited by tabun. The protective potency (P50) of all oximes in human erythrocyte AChE inhibited by soman and tabun could not be determined. In tabun-poisoned mice very good antidotal efficacy was obtained with K027, K048, and K074, which makes them interesting for future investigation. The combination of HI-6 and atropine is the therapy of choice for soman poisoning. 相似文献
450.
To fully understand brain function, one must look beyond the level of a single neuron. By elucidating the spatial properties of the columnar and laminar functional architectures, information regarding the neural processing in the brain can be gained. To map these fine functional structures noninvasively and repeatedly, functional magnetic resonance imaging (fMRI) can be employed. In this article the basic principles of fMRI are introduced, including specific hardware requirements and the equipment necessary for animal magnetic resonance research. Since fMRI measures a change in secondary hemodynamic responses induced by neural activity, it is critical to understand the principles and potential pitfalls of fMRI techniques. Thus, the underlying physics of conventional blood oxygenation, cerebral blood flow, and cerebral blood volume-based fMRI techniques are extensively discussed. Tissue-specific signal change is close to the site of neural activity, while signals from large vessels can be distant from the actual active site. Thus, methods to minimize large vessel contributions and to maximize tissue signals are described. The fundamental limitation of fMRI spatial resolution is the intrinsic hemodynamic response. Based on our high-resolution fMRI studies, the hemodynamic response is regulated at submillimeter functional domains and thus spatial resolution can be achieved to an order of 100 microm. Since hemodynamic responses are sluggish, it is difficult to obtain very high temporal resolution. By using an approach with multiple experiments with different stimulus conditions, temporal resolution can be improved on the order of 100 ms. With current fMRI technologies, submillimeter columnar- and laminar-specific specific functional images can be obtained from animal brains. 相似文献