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101.
In synaptosomal brain membranes, the addition of oleic acid (cis), elaidic acid (trans), and the cis and trans isomers of vaccenic acid, at a concentration of 0.87 mumol of lipid/mg of protein, strongly reduced the Bmax and, to a lesser degree, the binding affinity of the mu-selective opioid [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol ([3H]DAMGO). At comparable membrane content, the cis isomers of the fatty acids were more potent than their trans counterparts in inhibiting ligand binding and in decreasing membrane microviscosity, both at the membrane surface and in the core. However, trans-vacenic acid affected opioid receptor binding in spite of just marginally altering membrane microviscosity. If the receptors were uncoupled from guanine nucleotide regulatory protein, an altered inhibition profile was obtained: the impairment of KD by the fatty acids was enhanced and that of Bmax reduced. Receptor interaction of the delta-opioid [3H](D-Pen2,D-Pen5)enkephalin was modulated by lipids to a greater extent than that of [3H]DAMGO: saturable binding was abolished by both oleic and elaidic acids. The binding of [3H]naltrexone was less susceptible to inhibition by the fatty acids, particularly in the presence of sodium. In the absence of this cation, however, cis-vaccenic acid abolished the low-affinity binding component of [3H]naltrexone. These findings support the membrane model of opioid receptor sequestration depicting different ionic environments for the mu- and delta-binding sites. The results of this work show distinct modulation of different types and molecular states of opioid receptor by fatty acids through mechanisms involving membrane fluidity and specific interactions with membrane constituents. 相似文献
102.
The effect of transcranial magnetic stimulation (TMS) of the right and the left frontotemporal areas on the short- and long-term verbal memory was studied in healthy subjects and patients with Parkinson’s disease. TMS with a magnetic induction of more than 1.2 T at 10 Hz was found to affect the short-term memory when applied to the left frontotemporal area and to have no significant effect on this type of memory when applied to the right frontotemporal area. In healthy subjects, TMS applied to the left or the right hemisphere did not affect the long-term memory. However, in patients with Parkinson’s disease, significant changes in the long-term memory were observed upon TMS of either the left or the right hemisphere. The effect was more evident on TMS of the right hemisphere.__________Translated from Fiziologiya Cheloveka, Vol. 31, No. 4, 2005, pp. 33–36.Original Russian Text Copyright © 2005 by Gimranov, Mal’tseva. 相似文献
103.
104.
We describe the species Metschnikowia bowlesiae sp. nov. based on the recovery of six isolates from Hawaii and Belize. The species belongs to the Metschnikowia arizonensis subclade of the large-spored Metschnikowia clade. The isolates are haploid and heterothallic. Both Hawaiian strains had the mating type h + and the Belizean strains were h ?. Paraphyletic species structures observed in some ribosomal DNA sequence analyses suggest that M. bowlesiae sp. nov. might represent an intermediate stage in a succession of peripatric speciation events from Metschnikowia dekortorum to Metschnikowia similis and might even hybridize with these species. The type of M. bowlesiae sp. nov. is strain UWOPS 04-243x5 (CBS 12940T, NRRL Y-63671) and the allotype is strain UWOPS 12-619.1 (CBS 12939A, NRRL Y-63670). 相似文献
105.
CNS inflammation is a hallmark of neurodegenerative disease, and recent studies suggest that the inflammatory response may contribute to neuronal demise. In particular, increased tumor necrosis factor (TNF) signaling is implicated in the pathology of both Parkinson''s disease (PD) and Alzheimer''s disease (AD). We have previously shown that localized gene delivery of dominant negative TNF to the degenerating brain region can limit pathology in animal models of PD and AD. TNF is upregulated in Huntington''s disease (HD), like in PD and AD, but it is unknown whether TNF signaling contributes to neuronal degeneration in HD. We used in vivo gene delivery to test whether selective reduction of soluble TNF signaling could attenuate medium spiny neuron (MSN) degeneration in the YAC128 transgenic (TG) mouse model of Huntington''s disease (HD). AAV vectors encoding cDNA for dominant-negative tumor necrosis factor (DN-TNF) or GFP (control) were injected into the striatum of young adult wild type WT and YAC128 TG mice and achieved 30–50% target coverage. Expression of dominant negative TNF protein was confirmed immunohistologically and biochemically and was maintained as mice aged to one year, but declined significantly over time. However, the extent of striatal DN-TNF gene transfer achieved in our studies was not sufficient to achieve robust effects on neuroinflammation, rescue degenerating MSNs or improve motor function in treated mice. Our findings suggest that alternative drug delivery strategies should be explored to determine whether greater target coverage by DN-TNF protein might afford some level of neuroprotection against HD-like pathology and/or that soluble TNF signaling may not be the primary driver of striatal neuroinflammation and MSN loss in YAC128 TG mice. 相似文献
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107.
Jenny Chan Haruka Yamazaki Noboru Ishiyama Min-Duk Seo Tapas K. Mal Takayuki Michikawa Katsuhiko Mikoshiba Mitsuhiko Ikura 《The Journal of biological chemistry》2010,285(46):36092-36099
The three isoforms of the inositol 1,4,5-trisphosphate receptor (IP3R) exhibit distinct IP3 sensitivities and cooperativities in calcium (Ca2+) channel function. The determinants underlying this isoform-specific channel gating mechanism have been localized to the N-terminal suppressor region of IP3R. We determined the 1.9 Å crystal structure of the suppressor domain from type 3 IP3R (IP3R3SUP, amino acids 1–224) and revealed structural features contributing to isoform-specific functionality of IP3R by comparing it with our previously determined structure of the type 1 suppressor domain (IP3R1SUP). The molecular surface known to associate with the ligand binding domain (amino acids 224–604) showed marked differences between IP3R3SUP and IP3R1SUP. Our NMR and biochemical studies showed that three spatially clustered residues (Glu-20, Tyr-167, and Ser-217 in IP3R1 and Glu-19, Trp-168, and Ser-218 in IP3R3) within the N-terminal suppressor domains of IP3R1SUP and IP3R3SUP interact directly with their respective C-terminal fragments. Together with the accompanying paper (Yamazaki, H., Chan, J., Ikura, M., Michikawa, T., and Mikoshiba, K. (2010) J. Biol. Chem. 285, 36081–36091), we demonstrate that the single aromatic residue in this region (Tyr-167 in IP3R1 and Trp-168 in IP3R3) plays a critical role in the coupling between ligand binding and channel gating. 相似文献
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109.
Igor M. Raspopov Inna N. Andronikova Oksana N. Dotsenko Eugene A. Kurashov Galina I. Letanskaya Vadim E. Panov Margarita A. Rychkova Irena V. Telesh Olga A. Tchernykh Fedor F. Vorontsov 《Hydrobiologia》1996,322(1-3):39-47
The littoral zone of a lake is an important ecotone between terrestrial and aquatic systems. From the point of view of the lake ecosystem, much of the mineral, organic and toxic substances entering the lake from the drainage basin are transformed in the littoral zone by physical processes and biochemical pathways. The littoral zone of Lake Ladoga can be divided into three main regions: the shallow southern region, the fairly steep western and eastern shorelines, and the northern archipelago. In these regions, the communities of aquatic macrophytes, periphyton, phyto- and zooplankton and meio- and macrobenthos have been extensively studied. This paper presents numerical data on these communities, with special reference to comparisons between areas subjected to different degrees of anthropogenic loading. Most of the communities are characterized by high species diversity and spatial heterogeneity, especially among the macrophyte associations in which intensive production and decomposition takes place. Water dynamics and water exchange rate are the main abiotic factors in the formation of littoral communities. The characteristics of plant associations and bottom substrate, rather than pollution, appear as the most important factors structuring meio- and macrobenthic invertebrate communities in the littoral. 相似文献
110.
Cyclin-dependent kinases phosphorylate the adenovirus E1A protein, enhancing its ability to bind pRb and disrupt pRb-E2F complexes. 总被引:2,自引:2,他引:0
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The adenovirus E1A protein of 243 amino acids has been shown to affect a variety of cellular functions, most notably the immortalization of primary cells and the promotion of quiescent cells into S phase. The activity of E1A is derived, in part, from its association with various cellular proteins, many of which play important roles in regulating cell cycle progression. E1A is known to have multiple sites of phosphorylation. It has been suggested that cell cycle-dependent phosphorylation may also control some of E1A's functions. We find now that immune complexes of cyclin-dependent kinases such as cdk4, cdk2, and cdc2 are all capable of phosphorylating E1A in vitro. Additionally, the sites on E1A phosphorylated by these kinases in vitro are similar to the E1A sites phosphorylated in vivo. We have also found that a phosphorylated E1A is far more efficient than an unphosphorylated E1A in associating with pRB and in disrupting E2F/DP-pRB complexes as well. On the basis of our findings and the differences in timing and expression levels of the various cyclins regulating cdks, we suggest that E1A functions at different control points in the cell cycle and that phosphorylation controls, to some extent, its biological functions. 相似文献