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101.
Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines 总被引:5,自引:0,他引:5
Xie Z Srivastava DP Photowala H Kai L Cahill ME Woolfrey KM Shum CY Surmeier DJ Penzes P 《Neuron》2007,56(4):640-656
Activity-dependent rapid structural and functional modifications of central excitatory synapses contribute to synapse maturation, experience-dependent plasticity, and learning and memory and are associated with neurodevelopmental and psychiatric disorders. However, the signal transduction mechanisms that link glutamate receptor activation to intracellular effectors that accomplish structural and functional plasticity are not well understood. Here we report that NMDA receptor activation in pyramidal neurons causes CaMKII-dependent phosphorylation of the guanine-nucleotide exchange factor (GEF) kalirin-7 at residue threonine 95, regulating its GEF activity, leading to activation of small GTPase Rac1 and rapid enlargement of existing spines. Kalirin-7 also interacts with AMPA receptors and controls their synaptic expression. By demonstrating that kalirin expression and spine localization are required for activity-dependent spine enlargement and enhancement of AMPAR-mediated synaptic transmission, our study identifies a signaling pathway that controls structural and functional spine plasticity. 相似文献
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103.
Background
To infer homology and subsequently gene function, the Smith-Waterman (SW) algorithm is used to find the optimal local alignment between two sequences. When searching sequence databases that may contain hundreds of millions of sequences, this algorithm becomes computationally expensive. 相似文献104.
105.
Abstract The synthesis and 19F NMR spectra of dTMP and TpT analogues in which the phosphate group is replaced by a difluoromethylphosphonate group are described. 相似文献
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108.
Monika Killer Adam Arthur Abdul Rahman Al-Schameri John Barr Donald Elbert Gunther Ladurner Julie Shum Gregory Cruise 《Neurochemical research》2010,35(10):1652-1658
To better understand the development of hydrocephalus of different origins, we evaluated cytokine and growth factor concentration in cerebrospinal fluid from patients with hydrocephalus. CSF was collected from patients developing hydrocephalus following hemorrhage (n = 15), patients with normal pressure hydrocephalus (n = 10), and following the embolization of unruptured intracranial aneurysms (n = 9). Myelography patients (n = 15) served as controls. Quantification of 11 molecules relating angiogenesis, inflammation, and wound healing in the CSF was performed using ELISA. All three hydrocephalus groups had decreased concentration of TIMP-4 compared to the normal group. The hemorrhage group showed increased concentration of IL-6, IL-8, MCP-1, MMP-9, and TIMP-1 compared to the control group. The unruptured aneurysm group had increased concentration of IL-6 and decreased concentration of TIMP-2 compared to the control group. Compared to the normal patients, increased concentrations of wound healing molecules were evident in all three groups. Increased inflammation was evident in the hemorrhage and unruptured aneurysm groups. 相似文献
109.
Guyan Liang Yong Mi Choi-Sledeski Gregory Poli Xin Chen Patrick Shum Anne Minnich Qingping Wang Joseph Tsay Keith Sides Jennifer Cairns Gregory Stoklosa Thaddeus Nieduzak Zhicheng Zhao Jie Wang Roy J. Vaz 《Bioorganic & medicinal chemistry letters》2010,20(22):6721-6724
A novel β-tryptase inhibitor with a basic benzylamine P1 group, a piperidine-amide linker, and a substituted indole P4 group was discovered. A substitution at 4-indole position was introduced to constrain the conformational flexibility of the inhibitor to the bioactive conformation exhibited by X-ray structures so that entropic penalty was decreased. More importantly, this constrained conformation limited the accessibility of this molecule to anti-targets, especially SSAO, so that an enhanced metabolic profile was achieved. 相似文献
110.
Rolph MS Young TR Shum BO Gorgun CZ Schmitz-Peiffer C Ramshaw IA Hotamisligil GS Mackay CR 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(11):7794-7801
The fatty acid-binding protein (FABP) family consists of a number of conserved cytoplasmic proteins with roles in intracellular lipid transport, storage, and metabolism. Examination of a comprehensive leukocyte gene expression database revealed strong expression of the adipocyte FABP aP2 in human monocyte-derived dendritic cells (DCs). We isolated bone marrow-derived DC from aP2-deficient mice, and showed that expression of DC cytokines including IL-12 and TNF was significantly impaired in these cells. Degradation of IkappaBalpha was also impaired in aP2-deficient DCs, indicative of reduced signaling through the IkappaB kinase-NF-kappaB pathway. The cytokine defect was selective because there was no effect on Ag uptake or expression of MHC class II, CD40, CD80, or CD86. In an MLR, aP2-deficient DCs stimulated markedly lower T cell proliferation and cytokine production than did wild-type DCs. Moreover, aP2-deficient mice immunized with keyhole limpet hemocyanin/CFA showed reduced production of IFN-gamma by restimulated draining lymph node cells, suggesting a similar defect in DC function in vivo. Similarly, infection of aP2-deficient mice with the natural mouse pathogen ectromelia virus resulted in substantially lower production of IFN-gamma by CD8+ T cells. Thus, FABP aP2 plays an important role in DC function and T cell priming, and provides an additional link between metabolic processes and the regulation of immune responses. 相似文献