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81.
Robbins EM Krupp AJ Perez de Arce K Ghosh AK Fogel AI Boucard A Südhof TC Stein V Biederer T 《Neuron》2010,68(5):894-906
Synaptogenesis is required for wiring neuronal circuits in the developing brain and continues to remodel adult networks. However, the molecules organizing synapse development and maintenance in?vivo remain incompletely understood. We now demonstrate that the immunoglobulin adhesion molecule SynCAM 1 dynamically alters synapse number and plasticity. Overexpression of SynCAM 1 in transgenic mice promotes excitatory synapse number, while loss of SynCAM 1 results in fewer excitatory synapses. By turning off SynCAM 1 overexpression in transgenic brains, we show that it maintains the newly induced synapses. SynCAM 1 also functions at mature synapses to alter their plasticity by regulating long-term depression. Consistent with these effects on neuronal connectivity, SynCAM 1 expression affects spatial learning, with knock-out mice learning better. The reciprocal effects of increased SynCAM 1 expression and loss reveal that this adhesion molecule contributes to the regulation of synapse number and plasticity, and impacts how neuronal networks undergo activity-dependent changes. 相似文献
82.
Mariana D. Argirova Iliyana D. Stefanova Athanas D. Krustev Valentin I. Turiiski 《Amino acids》2010,38(3):797-803
Water-soluble Maillard reaction products obtained from five different model systems were investigated for their effects upon
the mechanical activity of rat gastric smooth muscle. Most of the total Maillard reaction products applied at concentration
of 1.5 mg/ml evoked contractions; among them the product obtained from arginine and glucose (Arg-Glc) produced the most powerful
contractions. The product obtained from glycine and ascorbic acid (Gly-AsA) was the only one that brought about relaxation
response. The high molecular weight fractions (>3,500 Da) isolated from the reaction systems Arg-Glc and Gly-AsA demonstrated
effects similar in type and amplitude to those evoked by non-fractioned reaction products. The results obtained suggest that
moieties of molecules acting upon the muscle tonus originate mainly from lysine and arginine residues; that these structures
are available in both low and high molecular pools in similar concentrations, and most likely these fragments act upon membrane-located
cellular structures involved in calcium transport. 相似文献
83.
Artificial metalloenzymes result from the introduction of a catalytically competent non-native metal cofactor within a protein environment. In the present contribution, we summarize the recent achievements in the design and the optimization of such protein-based hybrid catalysts, with an emphasis on enantioselective transformations. The second part outlines the milestones required to achieve en masse production, screening and directed evolution of artificial metalloenzymes. In the spirit of Darwinian evolution, this will allow the full potential of such protein-based hybrid catalysts to be fully unraveled, thus complementing both homogeneous and enzymatic catalysis. 相似文献
84.
Tomasz Borowski Valentin Georgiev Per E. M. Siegbahn 《Journal of molecular modeling》2010,16(11):1673-1677
Catalytic cycle intermediates of a representative extradiol dioxygenase, homoprotocatechuate 2,3-dioxygenase (HPCD), have
recently been characterized in crystallo by Kovaleva and Lipscomb. The structures of the identified species indicate that
the process of inserting oxygen into the catechol ring occurs stepwise, and involves an Fe(II)-alkylperoxo intermediate and
its O–O cleavage product: a gem diol species. In general, these findings corroborate the results of our previous computational
studies; however, the fact that the gem diol species is stable enough to be observed in the crystal form seems to be at odds
with the computational mechanistic data, which suggest that this intermediate should very readily and spontaneously convert
to the epoxide species. The key question then becomes what is actually observed in the X-ray experiments. Here we report additional
computational studies undertaken with the hope of clarifying this issue. The results obtained for active site models hosting
both the native and the alternative (4-sulfonylcatechol) substrate indicate that the stability of the gem diol species is
substantially increased if an electron and a proton are added. If this occurs somehow, the lifetime of the intermediate should
be sufficient to observe it. 相似文献
85.
Philippe Latour Christel Thauvin-Robinet Pierre Soichot Laurence Faivre Martine Mayençon Emmanuel Broussolle William Camu Robert Rousson 《American journal of human genetics》2010,86(1):77-82
Charcot-Marie-Tooth disease (CMT) is the most common cause of inherited peripheral neuropathy, with an estimated frequency of 1/2500. We studied a large family with 17 patients affected by the axonal form of CMT (CMT2). Analysis of the 15 genes or loci known to date was negative. Genome-wide genotyping identified a CMT2 locus in 16q21-q23 between D16S3050 and D16S3106. The maximum two-point LOD score was 4.77 at θ = 0 for marker D16S3050. Sequencing of candidate genes identified a unique mutation, c.986G>A (p.Arg329His), affecting a totally conserved amino acid in the helical domain of cytoplasmic alanyl-tRNA synthetase (AlaRS). A second family with the same mutation and a different founder was then identified in a cohort of 91 CMT2 families. Although mislocation of mutant Arg329His-AlaRS in axons remains to be evaluated, experimental data point mostly to a quantitative reduction in tRNAAla aminoacylation. Aminoacylation and editing functions closely cooperate in AlaRS, and Arg329His mutation could also lead to qualitative errors participating in neurodegeneration. Our report documents in 18 patients the deleterious impact of a mutation in human cytoplasmic AlaRS and broadens the spectrum of defects found in tRNA synthetases. Patients present with sensory-motor distal degeneration secondary to predominant axonal neuropathy, slight demyelination, and no atypical or additional CNS features. 相似文献
86.
Mikhail P. Moshkin Eugene A. Novikov Sergey E. Tkachev Valentin V. Vlasov 《BioEssays : news and reviews in molecular, cellular and developmental biology》2009,31(6):620-628
The morbidity of tick‐borne encephalitis (TBE) varies yearly by as much as 10‐fold among the people of Western Siberia. This long‐term variation is dependent on many factors such as the density of the tick populations, the prevalence of TBE virus (TBEV) among sub‐adult ticks, the yearly virulence of the TBEV, and prophylactic measures. Here we highlight the role of small mammal hosts in the circulation of TBEV through the ecosystem. Refining classical models of non‐viremic horizontal transmission, we emphasize the recently understood fact that the physiological and immunological status of the small mammal hosts affects the tick and virus‐host interactions. In addition to its theoretical interest, our approach may lead to some practical improvements in the precision of epidemiological forecasts and perhaps in forestalling the severity of outbreaks of TBE, or, at least, in forewarning medical authorities and the general public of impending TBE outbreaks. 相似文献
87.
Portet B Fabre N Roumy V Gornitzka H Bourdy G Chevalley S Sauvain M Valentin A Moulis C 《Phytochemistry》2007,68(9):1312-1320
The bioassay-guided purification of an n-hexane extract from the leaves of Piper hostmannianum var. berbicense led to the isolation of four monoterpene or prenyl-substituted dihydrochalcones (1a, 1b, 2, 3) as well as the known compounds 2',6'-dihydroxy-4'-methoxydihydrochalcone (4), linderatone (5), strobopinin (6), adunctin E (7) and (-)-methyllinderatin (8). Their structures were established on the basis of NMR and X-ray analysis. (-)-Methyllinderatin, linderatone and 2',6'-dihydroxy-4'-methoxydihydrochalcone exhibited the most potent antiplasmodial activity with IC50 values of 5.64, 10.33 and 12.69 microM, respectively against both chloroquine-sensitive and resistant strains of Plasmodium falciparum (F32,FcB1). The activity of (-)-methyllinderatin was confirmed in vivo against Plasmodium vinckei petteri in mice (80% of reduction of parasitemia) at a dose of 20 mg/kg/day. 相似文献
88.
The overproduction of TNF and other cytokines is associated with the pathophysiology of numerous diseases. Controlling cytokine synthesis and release is critical for preventing unrestrained inflammation and maintaining health. Recent studies identified an efferent vagus nerve-based mechanism termed "the cholinergic anti-inflammatory pathway" that controls cytokine production and inflammation. Here we review current advances related to the role of this pathway in neuro-immune interactions that prevent excessive inflammation. Experimental evidence indicates that vagus nerve cholinergic anti-inflammatory signaling requires alpha7 nicotinic acetylcholine receptors expressed on non-neuronal cytokine-producing cells. Alpha7 nicotinic acetylcholine receptor agonists inhibit cytokine release and protect animals in a variety of experimental lethal inflammatory models. Knowledge related to the cholinergic anti-inflammatory pathway can be exploited in therapeutic approaches directed towards counteracting abnormal chronic and hyper-activated inflammatory responses. 相似文献
89.
Edupuganti OP Antoci V King SB Jose B Adams CS Parvizi J Shapiro IM Zeiger AR Hickok NJ Wickstrom E 《Bioorganic & medicinal chemistry letters》2007,17(10):2692-2696
Self-protecting Ti6Al4V alloy pins were prepared by covalent bonding of bis(ethylene glycol) linkers, then vancomycin to the oxidized, aminopropylated Ti6Al4V alloy surface. Fluorescence modification-enabled estimation of yields of free amines on the metallic surface monolayer at each reaction step. The vancomycin-protected Ti6Al4V pins were not colonized by Staphylococcus aureus, even after 44days storage in physiological buffer. These results provide a basis for testing self-protection against S. aureus colonization in animal models. 相似文献
90.
Dourlat J Valentin B Liu WQ Garbay C 《Bioorganic & medicinal chemistry letters》2007,17(14):3943-3946
Investigation within the pTyr-binding pocket of the STAT3 SH2 domain led us to develop a novel synthesis of two pTyr mimetics, l-tetrazolylmethylphenylalanine (l-Tmp) and l-O-malonyltyrosine (l-OMT), that were next incorporated in a high affinity ligand of STAT3 SH2 domain. Biological evaluation of peptidomimetics on STAT3 dimerization identified l-OMT as the first non-phosphorus pTyr mimetic so far reported against STAT3 SH2 domain, harboring an activity similar to that of the Pmp-containing reference peptidomimetic. 相似文献