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11.
Glutamatergic plasticity by synaptic delivery of GluR-B(long)-containing AMPA receptors 总被引:3,自引:0,他引:3
Kolleker A Zhu JJ Schupp BJ Qin Y Mack V Borchardt T Köhr G Malinow R Seeburg PH Osten P 《Neuron》2003,40(6):1199-1212
Activity-driven delivery of AMPA receptors is proposed to mediate glutamatergic synaptic plasticity, both during development and learning. In hippocampal CA1 principal neurons, such trafficking is primarily mediated by the abundant GluR-A subunit. We now report a study of GluR-B(long), a C-terminal splice variant of the GluR-B subunit. GluR-B(long) synaptic delivery is regulated by two forms of activity. Spontaneous synaptic activity-driven GluR-B(long) transport maintains one-third of the steady-state AMPA receptor-mediated responses, while GluR-B(long) delivery following the induction of LTP is responsible for approximately 50% of the resulting potentiation at the hippocampal CA3 to CA1 synapses at the time of GluR-B(long) peak expression-the second postnatal week. Trafficking of GluR-B(long)-containing receptors thus mediates a GluR-A-independent form of glutamatergic synaptic plasticity in the juvenile hippocampus. 相似文献
12.
Cul1 and Cul7 are cullin E3 ubiquitin ligase scaffold proteins. Cul1 is known to form a complex with the RING domain protein Rbx1 and one of approximately 70 different F-box proteins. F-box proteins function as substrate receptor subunits and recruit numerous substrates for poly-ubiquitination. Similarly to Cul1, Cul7 interacts with Rbx1, however, only one F-box protein, Fbxw8, has been shown to bind to Cul7. To date only few Cul7 E3 ubiquitin ligase substrates, including cyclin D1, IRS-1 and GRASP65, have been reported, and using Fbxw8 affinity purification, we were unable to identify additional substrate proteins. Here we provide evidence for a model in which Cul7-Rbx1 can promote the ubiquitination of Cul1 substrates by forming high order complexes with Cul1-Rbx1. Binding of Cul1-Rbx1 to Cul7-Rbx1 is mediated via heterodimerization of Fbxw8 with other F-box proteins which function to recruit substrates into the E3 ligase complex. The formation of this high order complex is likely to increase polyubiquitination efficiency. 相似文献
13.
Jana A. Eccard Antje Herde Andrea C. Schuster Thilo Liesenjohann Tatjana Knopp Gerald Heckel Melanie Dammhahn 《Ecology and evolution》2022,12(2)
Individuals of a population may vary along a pace‐of‐life syndrome from highly fecund, short‐lived, bold, dispersive “fast” types at one end of the spectrum to less fecund, long‐lived, shy, plastic “slow” types at the other end. Risk‐taking behavior might mediate the underlying life history trade‐off, but empirical evidence supporting this hypothesis is still ambiguous. Using experimentally created populations of common voles (Microtus arvalis)—a species with distinct seasonal life history trajectories—we aimed to test whether individual differences in boldness behavior covary with risk taking, space use, and fitness. We quantified risk taking, space use (via automated tracking), survival, and reproductive success (via genetic parentage analysis) in 8 to 14 experimental, mixed‐sex populations of 113 common voles of known boldness type in large grassland enclosures over a significant part of their adult life span and two reproductive events. Populations were assorted to contain extreme boldness types (bold or shy) of both sexes. Bolder individuals took more risks than shyer ones, which did not affect survival. Bolder males but not females produced more offspring than shy conspecifics. Daily home range and core area sizes, based on 95% and 50% Kernel density estimates (20 ± 10 per individual, n = 54 individuals), were highly repeatable over time. Individual space use unfolded differently for sex‐boldness type combinations over the course of the experiment. While day ranges decreased for shy females, they increased for bold females and all males. Space use trajectories may, hence, indicate differences in coping styles when confronted with a novel social and physical environment. Thus, interindividual differences in boldness predict risk taking under near‐natural conditions and have consequences for fitness in males, which have a higher reproductive potential than females. Given extreme inter‐ and intra‐annual fluctuations in population density in the study species and its short life span, density‐dependent fluctuating selection operating differently on the sexes might maintain (co)variation in boldness, risk taking, and pace‐of‐life. 相似文献
14.
Britta Spanier Mandy Starke Fabian Higel Siegfried Scherer Thilo M. Fuchs 《Applied and environmental microbiology》2010,76(18):6277-6285
Caenorhabditis elegans is a validated model to study bacterial pathogenicity. We report that Yersinia enterocolitica strains (biovar 2, serovar O:9) and WA314 (biovar 1B, serovar O:8) kill C. elegans when feeding on the pathogens for at least 15 min before transfer to the feeding strain Escherichia coli OP50. The killing by Yersinia enterocolitica requires viable bacteria and, in contrast to that by Yersinia pestis and Yersinia pseudotuberculosis strains, is biofilm independent. The deletion of tcaA encoding an insecticidal toxin resulted in an OP50-like life span of C. elegans, indicating an essential role of TcaA in the nematocidal activity of Y. enterocolitica. TcaA alone is not sufficient for nematocidal activity because E. coli DH5α overexpressing TcaA did not result in a reduced C. elegans life span. Spatial-temporal analysis of C. elegans infected with green fluorescent protein-labeled Y. enterocolitica strains showed that Y. enterocolitica colonizes the nematode intestine, leading to an extreme expansion of the intestinal lumen. By low-dose infection with W22703 or DH5α followed by transfer to E. coli OP50, proliferation of Y. enterocolitica, but not E. coli, in the intestinal lumen of the nematode was observed. The titer of W22703 cells within the worm increased to over 106 per worm 4 days after infection while a significantly lower number of a tcaA knockout mutant was recovered. A strong expression of tcaA was observed during the first 5 days of infection. Y. enterocolitica WA314 (biovar 1B, serovar O:8) mutant strains lacking the yadA, inv, yopE, and irp1 genes known to be important for virulence in mammals were not attenuated or only slightly attenuated in their toxicity toward the nematode, suggesting that these factors do not play a significant role in the colonization and persistence of this pathogen in nematodes. In summary, this study supports the hypothesis that C. elegans is a natural host and nutrient source of Y. enterocolitica.Yersinia enterocolitica belongs to the family of Enterobacteriaceae and is a psychrotolerant human pathogen that causes gastrointestinal syndromes ranging from acute enteritis to mesenteric lymphadenitis ( W227035). It infects a number of mammals, and swine was identified as a major source for human infection (6). A multiphasic life cycle, which comprises a free-living phase and several host-associated phases, including cold-blooded and warm-blooded hosts, appears to be characteristic for biovars 1B and 2 to 5 of Y. enterocolitica (7, 24).Nonmammalian host organisms including Dictyostelium discoideum, Drosophila melanogaster, or Caenorhabditis elegans are increasingly used to study host-pathogen interactions (16, 26). Due to the obvious parallels between the mammalian and invertebrate defense mechanisms, it has been suggested that the bacteria-invertebrate interaction has shaped the evolution of microbial pathogenicity (53). Several human pathogens including Gram-positive and Gram-negative bacteria infect and kill the soil nematode C. elegans when they are supplied as a nutrient source (42). For example, Streptococcus pneumoniae (4), Listeria monocytogenes (50), extraintestinal Escherichia coli (15), and Staphylococcus aureus (43) but not Bacillus subtilis have been shown to kill the nematode. Upon infection of C. elegans with Enterococcus faecalis, Gram-positive virulence-related factors as well as putative antimicrobials have been identified (20, 35). The extensive conservation in virulence mechanisms directed against invertebrates as well as mammals was demonstrated using a screen with Pseudomonas aeruginosa (30). In this study, 10 of 13 genes whose knockout attenuated the nematode killing were also required for full virulence in a mouse model, confirming the suitability of the C. elegans model to study bacterial pathogenicity. C. elegans is also colonized by Salmonella enterica serovar Typhimurium (S. Typhimurium). This process requires Salmonella virulence factors and was used to study the innate immune response of the nematode (1, 2, 49).The effect of pathogenic Yersinia spp. on C. elegans has also been investigated. It could be demonstrated that both Yersinia pestis and Yersinia pseudotuberculosis block food intake by creating a biofilm around the worm''s mouth (13, 27). This biofilm formation requires the hemin storage locus (hms) and has been suggested to be responsible for the blockage of the digestive tract following uptake by fleas, thus acting as a bacterial defense against predation by invertebrates. In a study with 40 Y. pseudotuberculosis strains, one-quarter of them caused an infection of C. elegans by biofilm formation on the worm head (27). In contrast, a similar effect was not observed following nematode infection with 15 Y. enterocolitica strains. Using a Y. pestis strain lacking the hms genes, it could be demonstrated that this mutant can infect and kill the nematode by a biofilm-independent mechanism that includes the accumulation of Y. pestis in the intestine of the worm (47). This pathogenesis model was applied to show that putative virulence factors such as YapH, OmpT, or a metalloprotease, Y3857, but not the virulence plasmids pCD1 and pPCP1, are required for Y. pestis virulence in C. elegans. Six yet unknown genes required for full virulence in C. elegans were also identified, and one of them appeared to be a virulence factor in the mouse infection model.C. elegans has not been used to study the pathogenicity properties of Y. enterocolitica, mainly due to the fact that many of its virulence factors are upregulated at 37°C in comparison to growth at lower temperatures while C. elegans cannot be cultivated at temperatures above 25°C. In this study, we examined for the first time the infection of C. elegans by Y. enterocolitica strains, demonstrating that this pathogen colonizes and kills C. elegans and that the insecticidal toxin TcaA, which is expressed only at ambient temperature, is required for full nematocidal activity. 相似文献
15.
Thilo Waag Christoph Gelhaus Jennifer Rath August Stich Matthias Leippe Tanja Schirmeister 《Bioorganic & medicinal chemistry letters》2010,20(18):5541-5543
Allicin and derivatives thereof inhibit the CAC1 cysteine proteases falcipain 2, rhodesain, cathepsin B and L in the low micromolar range. The structure–activity relationship revealed that only derivatives with primary carbon atom in vicinity to the thiosulfinate sulfur atom attacked by the active-site Cys residue are active against the target enzymes. Some compounds also show potent antiparasitic activity against Plasmodium falciparum and Trypanosoma brucei brucei. 相似文献
16.
Henryk Flachowsky Iris Szankowski Thilo C. Fischer Klaus Richter Andreas Peil Monika Höfer Claudia Dörschel Sylvia Schmoock Achim E. Gau Heidrun Halbwirth Magda-Viola Hanke 《Planta》2010,231(3):623-635
Transgenic apple plants (Malus × domestica cv. ‘Holsteiner Cox’) overexpressing the Leaf Colour (Lc) gene from maize (Zea mays) exhibit strongly increased production of anthocyanins and flavan-3-ols (catechins, proanthocyanidins). Greenhouse plants investigated in this study exhibit altered phenotypes with regard to growth habit and resistance traits. Lc-transgenic plants show reduced size, transversal gravitropism of lateral shoots, reduced trichome development, and frequently reduced shoot diameter and abnormal leaf development with fused leaves. Such phenotypes seem to be in accordance with a direct or an indirect effect on polar-auxin-transport in the transgenic plants. Furthermore, leaves often develop necrotic lesions resembling hypersensitive response lesions. In tests, higher resistance against fire blight (caused by the bacterium Erwinia amylovora) and against scab (caused by the fungus Venturia inaequalis) is observed. These phenotypes are discussed with respect to the underlying altered physiology of the Lc-transgenic plants. The results are expected to be considered in apple breeding strategies. 相似文献
17.
Jan Plue Pieter De Frenne Kamal Acharya Jrg Brunet Olivier Chabrerie Guillaume Decocq Martin Diekmann Bente J. Graae Thilo Heinken Martin Hermy Annette Kolb Isgard Lemke Jaan Liira Tobias Naaf Anna Shevtsova Kris Verheyen Monika Wulf Sara A. O. Cousins 《Global Ecology and Biogeography》2013,22(10):1106-1117
18.
19.
Lutz Thilo 《生物化学与生物物理学报:生物膜》1977,469(3):326-334
In an accompanying publication by Duckwitz-Peterlein, Eilenberger and Overath ((1977) Biochim. Biophys. Acta 469, 311–325) it is shown that the exchange of lipid molecules between negatively charged vesicles consisting of total phospholipid extracts from Escherichia coli occurs by the transfer of single lipid monomers or small micelles through the water. Here a kinetic interpretation is presented in terms of a rate constant, , for the escape of lipid molecules from the vesicle bilayer into the water. The evaluated rate constants are and for phospholipid molecules with and , respectively, as the predominant acyl chain component. The rate constants are discussed in terms of the acyl chain and polar head group composition of the lipids. 相似文献
20.
Sabine Favre-Bonté Eric Chamot Thilo Köhler Jacques-A Romand Christian van Delden 《BMC microbiology》2007,7(1):33