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《Bioorganic & medicinal chemistry》2016,24(5):1014-1022
Amino derivatives of NCI8642 were synthesized and evaluated as inhibitors of DKK1/LRP6 interactions. The new inhibitors were able to activate the Wnt signaling pathway as indicated by the increased levels of β-catenin, and decrease the DKK1-induced Tau phosphorylation at serine 396. 相似文献
134.
Reuben S.E. Young Andrew P. Bowman Kaylyn D. Tousignant Berwyck L.J. Poad Jennifer H. Gunter Lisa K. Philp Colleen C. Nelson Shane R. Ellis Ron M.A. Heeren Martin C. Sadowski Stephen J. Blanksby 《Journal of lipid research》2022,63(6):100223
The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics. 相似文献
135.
136.
I. N. Konareva 《Neurophysiology》2006,38(3):201-208
Modifications of different EEG rhythms induced by a single neurofeedback session (by the EEG characteristics) directed toward
an increase in the ratio of the spectral powers (SPs) of the α vs θ oscillations were compared with the psychological characteristics of the tested subjects (the group included 30 persons).
A generally accepted neurofeedback technique was used; the intensity of acoustic white noise served as the feedback signal.
EEG potentials were recorded from the C3 and C4 leads. Psychological testing was carried out using Eysenck’s (EPQ), Rusalov’s
(OST), and (16 PF) questionnaires. The directions of changes in the SPs of EEG frequency components were found to significantly
correlate with some individuality-related peculiarities of the tested subjects. The SP of the δ rhythm correlated with the
EPQ scale “neuroticism,” OST scale “social plasticity,” and 16 PF factors H (“parmia”), I (“premsia”), and Q3 (“self-control of behavior”). The SP of the θ component demonstrated correlations with the OST scales “ergisity,” “plasticity,”
and “social temp” and with 16 PF factors M (“autia”), Q4 (“frustration”), and Q1 (“exvia”). The SP of the α rhythm correlated with 16 PF factors Q3 (“self-control of behavior”), G (“strength of superEgo”), O (“hypothymia”), L (“protension”), and N (“shrewdness”). The SP
of the β rhythm correlated with the OST scale “emotionality,” while that of the γ rhythm showed correlations with the 16 PF
indices L (“protension”) and M (“autia”). Changes in the ratio of the α vs θ SPs correlated with the EPQ scale “neuroticism.” Thus, our data confirm the statement that a high individual variability
of the results of a single (first in the series) neurofeedback session is to a great extent related to peculiarities of the
individual psychological pattern of the subject.
Neirofiziologiya/Neurophysiology, Vol. 38, No. 3, pp. 239–247, May–June, 2006. 相似文献
137.
贝壳历来是生物工程和材料学研究的重要对象。贝壳中的贝壳基质蛋白质在贝壳的形成与发育过程中具有重要的调控作用。Whirlin类蛋白质(Whirlin-like protein,WLP)是一种从厚壳贻贝(Mytilus coruscus)中鉴定的新型贝壳基质蛋白质。序列分析结果显示,该蛋白质含有PDZ(postsynaptic density/Discs large/Zonula occludens)结构域,而该结构域对贝壳生物矿化的影响目前尚无报道。为深入了解WLP在贝壳形成中对碳酸钙晶体的影响,在序列分析基础上,采用密码子优化结合原核重组表达,获得其重组表达产物后,开展了重组WLP对碳酸钙晶体形貌及晶型的影响研究,结晶速度抑制以及碳酸钙晶体结合分析。分析结果表明,重组WLP能诱导文石型碳酸钙晶体的形貌和方解石型碳酸钙晶体的晶型发生改变;同时重组WLP对碳酸钙晶体具有结合作用,且能抑制碳酸钙晶体的结晶速度。上述结果表明,WLP对贝壳的形成及发育具有重要影响,并可能在贝壳肌棱柱层的形成中发挥了重要作用。 相似文献
138.
D. F. Roberts 《International Journal of Anthropology》1996,11(2-4):185-191
As a conclusion, this paper reviews briefly the content of the volume. The wealth of demographic data has not been adequately
exploited in anthropology; this is why this publication is valuable in showing attempts to apply demographic data in a variety
of anthropological problems. This symposium has explored many interesting points which we recall here. Yet it has also opened
up a whole range of further questions on the material presented as well as in this broad field. Several directions of research
could be developed, for instance, testing among human populations, over long periods, the ecological thoughts of ecosystems
evolving as a cascade of instabilities, rather than a succession of equilibrium states. Let us also recall the pervasive nature
of demographic facts in topics such as the energy cycle or the genetic structure and evolution of human populations. 相似文献
139.
Nina Boiko Volodymyr Kucher Benjamin A. Eaton James D. Stockand 《The Journal of biological chemistry》2013,288(13):9418-9427
The voltage-gated K+ (Kv) channel blocker 4-aminopyridine (4-AP) is used to target symptoms of the neuroinflammatory disease multiple sclerosis (MS). By blocking Kv channels, 4-AP facilitates action potential conduction and neurotransmitter release in presynaptic neurons, lessening the effects of demyelination. Because they conduct inward Na+ and Ca2+ currents that contribute to axonal degeneration in response to inflammatory conditions, acid-sensing ion channels (ASICs) contribute to the pathology of MS. Consequently, ASICs are emerging as disease-modifying targets in MS. Surprisingly, as first demonstrated here, 4-AP inhibits neuronal degenerin/epithelial Na+ (Deg/ENaC) channels, including ASIC and BLINaC. This effect is specific for 4-AP compared with its heterocyclic base, pyridine, and the related derivative, 4-methylpyridine; and akin to the actions of 4-AP on the structurally unrelated Kv channels, dose- and voltage-dependent. 4-AP has differential actions on distinct ASICs, strongly inhibiting ASIC1a channels expressed in central neurons but being without effect on ASIC3, which is enriched in peripheral sensory neurons. The voltage dependence of the 4-AP block and the single binding site for this inhibitor are consistent with 4-AP binding in the pore of Deg/ENaC channels as it does Kv channels, suggesting a similar mechanism of inhibition in these two classes of channels. These findings argue that effects on both Kv and Deg/ENaC channels should be considered when evaluating the actions of 4-AP. Importantly, the current results are consistent with 4-AP influencing the symptoms of MS as well as the course of the disease because of inhibitory actions on Kv and ASIC channels, respectively. 相似文献
140.