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111.
112.
The functional effect of mutations near the intracellular mouth of the short viral Kcv potassium channel was studied by molecular dynamics simulations. As a model system we used the analogously mutated and truncated KirBac1.1, a channel with known crystal structure that shares genuine local sequence motifs with Kcv. By a novel simulated annealing methodology for structural averaging, information about the structure and dynamics of the intracellular mouth was extracted and complemented by Poisson-Boltzmann and 3D-RISM (reference interaction site model) integral equation theory for the determination of the K+ free energy surface. Besides the wild-type analogue of Kcv with its experimental reference activity (truncated KirBac1.1), two variants were studied: a deletion mutant where the N-terminus is further truncated by eight amino acids, showing inactivity in the Kcv reference system, and a point mutant where the kink-forming proline at position 13 is substituted by alanine, resulting in hyperactivity. The computations reveal that the change of activity is closely related to a hydrophilic intracellular constriction formed by the C-terminal residues of the monomers. Hyperactivity of the point mutant is correlated with both sterical and electrostatic factors, while inactivity of the deletion mutant is related to a loss of specific salt bridge patterns between the C- and N-terminus at the constriction and to the consequences for ion passage barriers, as revealed by integral equation theory. The cytosolic gate, however, is probably formed by the N-terminal segment up to the proline kink and not by the constriction. The results are compared with design principles found for other channels. 相似文献
113.
114.
Flohé SB Agrawal H Flohé S Rani M Bangen JM Schade FU 《Molecular medicine (Cambridge, Mass.)》2008,14(5-6):247-256
The development of immunosuppression during polymicrobial sepsis is associated with the failure of dendritic cells (DC) to promote the polarization of T helper (Th) cells toward a protective Th1 type. The aim of the study was to test potential immunomodulatory approaches to restore the capacity of splenic DC to secrete interleukin (IL) 12 that represents the key cytokine in Th1 cell polarization. Murine polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Splenic DC were isolated at different time points after CLP or sham operation, and stimulated with bacterial components in the presence or absence of neutralizing anti-IL-10 antibodies, murine interferon (IFN) gamma, and/or granulocyte macrophage colony-stimulating factor (GM-CSF). DC from septic mice showed an impaired capacity to release the pro-inflammatory and Th1-promoting cytokines tumor necrosis factor alpha, IFN-gamma, and IL-12 in response to bacterial stimuli, but secreted IL-10. Endogenous IL-10 was not responsible for the impaired IL-12 secretion. Up to 6 h after CLP, the combined treatment of DC from septic mice with IFN-gamma and GM-CSF increased the secretion of IL-12. Later, DC from septic mice responded to IFN-gamma and GM-CSF with increased expression of the co-stimulatory molecule CD86, while IL-12 secretion was no more enhanced. In contrast, splenic macrophages from septic mice during late sepsis responded to GM-CSF with increased cytokine release. Thus, therapy of sepsis with IFN-gamma/GM-CSF might be sufficient to restore the activity of macrophages, but fails to restore DC function adequate for the development of a protective Th1-like immune response. 相似文献
115.
Siddique M Gernhard S von Koskull-Döring P Vierling E Scharf KD 《Cell stress & chaperones》2008,13(2):183-197
The small heat shock proteins (sHsps), which are ubiquitous stress proteins proposed to act as chaperones, are encoded by
an unusually complex gene family in plants. Plant sHsps are classified into different subfamilies according to amino acid
sequence similarity and localization to distinct subcellular compartments. In the whole Arabidopsis thaliana genome, 19 genes were annotated to encode sHsps, of which 14 belong to previously defined plant sHsp families. In this paper,
we report studies of the five additional sHsp genes in A. thaliana, which can now be shown to represent evolutionarily distinct sHsp subfamilies also found in other plant species. While two
of these five sHsps show expression patterns typical of the other 14 genes, three have unusual tissue specific and developmental
profiles and do not respond to heat induction. Analysis of intracellular targeting indicates that one sHsp represents a new
class of mitochondrion-targeted sHsps, while the others are cytosolic/nuclear, some of which may cooperate with other sHsps
in formation of heat stress granules. Three of the five new proteins were purified and tested for chaperone activity in vitro.
Altogether, these studies complete our basic understanding of the sHsp chaperone family in plants.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
116.
Jasmin Kirchner Emese Vissi Sascha Gross Balazs Szoor Andrey Rudenko Luke Alphey Helen White-Cooper 《BMC molecular biology》2008,9(1):36
Background
Protein phosphatase 1 (PP1) is involved in diverse cellular processes, and is targeted to substrates via interaction with many different protein binding partners. PP1 catalytic subunits (PP1c) fall into PP1α and PP1β subfamilies based on sequence analysis, however very few PP1c binding proteins have been demonstrated to discriminate between PP1α and PP1β. 相似文献117.
Díaz-Carballo D Malak S Bardenheuer W Freistuehler M Peter Reusch H 《Bioorganic & medicinal chemistry》2008,16(22):9635-9643
Increasing efforts are directed toward finding applications for natural products and their derivatives in the treatment of human diseases. Among such products, propolis, a resinous substance produced by honey bees from various plant sources, has been found to be a promising source of potential therapeutics. In the present work, we aimed at studying the perspective of Cuban propolis as a source of possible anti-cancer agents. We found an anti-metastatic effect in mice and considerable cytotoxicity without cross-resistance in both wild-type and chemoresistant human tumor cell lines. Plukenetione A--identified for the first time in Cuban propolis--induced G0/G1 arrest and DNA fragmentation in colon carcinoma cells. Furthermore, the activities of both topoisomerase I and DNA polymerase were inhibited, while the expression of topoisomerase II-beta, EGF receptor, and multidrug resistance-related protein genes was found repressed. We assume that plukenetione A contributes to the anti-tumoral effect of Cuban propolis mainly by targeting topoisomerase I as well as DNA polymerase. 相似文献
118.
Myxozoan parasitism in waterfowl 总被引:2,自引:0,他引:2
Bartholomew JL Atkinson SD Hallett SL Lowenstine LJ Garner MM Gardiner CH Rideout BA Keel MK Brown JD 《International journal for parasitology》2008,38(10):1199-1207
Myxozoans are spore-forming, metazoan parasites common in cold-blooded aquatic vertebrates, especially fishes, with alternate life cycle stages developing in invertebrates. We report nine cases of infection in free-flying native and captive exotic ducks (Anseriformes: Anatidae) from locations across the United States and describe the first myxozoan in birds, Myxidium anatidum n. sp. We found developmental stages and mature spores in the bile ducts of a Pekin duck (domesticated Anas platyrhynchos). Spores are lens-shaped in sutural view, slightly sigmoidal in valvular view, with two polar capsules, and each valve cell has 14-16 longitudinal surface ridges. Spore dimensions are 23.1 microm x 10.8 microm x 11.2 microm. Phylogenetic analysis of the ssrRNA gene revealed closest affinity with Myxidium species described from chelonids (tortoises). Our novel finding broadens the definition of the Myxozoa to include birds as hosts and has implications for understanding myxozoan evolution, and mechanisms of geographical and host range extension. The number of infection records indicates this is not an incidental occurrence, and the detection of such widely dispersed cases suggests more myxozoans in birds will be encountered with increased surveillance of these hosts for pathogens. 相似文献
119.
120.
Birgit Ziegenhagen Silke Gneuss Georg Rathmacher Ilona Leyer Ronald Bialozyt Berthold Heinze Sascha Liepelt 《Conservation Genetics》2008,9(2):373-379
It is known that various poplar species and cultivated poplar hybrids have the potential to interbreed and produce fertile
offspring. Conservation strategies for the genetic resources of the endangered Eurasian black poplar (Populus nigra L.) thus rely on a monitoring which enables the identification and verification of the pure species status. At the same time,
the risk of hybrid dispersal and introgressive gene flow has to be estimated. In the present study a combination of two molecular
markers, one from chloroplast DNA and the other from nuclear DNA, was applied to evaluate a large P. nigra population on the Elbe River. Hybrid clones of P. × canadensis are scattered within this population and also occur as plantations in the surrounding landscape. By means of the DNA markers
the taxonomic status of 208 adult trees in the population and 140 young poplars along the riverbank was monitored. From the
analysed young poplars, almost 20 percent were found to exhibit at least one of the two P.
deltoides or P. × canadensis diagnostic alleles or genotypes, respectively. Possible vegetative spreads of F1 hybrids and precedent mating scenarios are
discussed. Most interestingly we found clear evidence for a small number of backcross hybrids where P. × canadensis acted as pollen donor. This case had long been debated and thought to be less probable, so far. 相似文献