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911.
Deák F Shin OH Tang J Hanson P Ubach J Jahn R Rizo J Kavalali ET Südhof TC 《The EMBO journal》2006,25(12):2856-2866
Synaptic vesicle fusion is catalyzed by assembly of synaptic SNARE complexes, and is regulated by the synaptic vesicle GTP-binding protein Rab3 that binds to RIM and to rabphilin. RIM is a known physiological regulator of fusion, but the role of rabphilin remains obscure. We now show that rabphilin regulates recovery of synaptic vesicles from use-dependent depression, probably by a direct interaction with the SNARE protein SNAP-25. Deletion of rabphilin dramatically accelerates recovery of depressed synaptic responses; this phenotype is rescued by viral expression of wild-type rabphilin, but not of mutant rabphilin lacking the second rabphilin C2 domain that binds to SNAP-25. Moreover, deletion of rabphilin also increases the size of synaptic responses in synapses lacking the vesicular SNARE protein synaptobrevin in which synaptic responses are severely depressed. Our data suggest that binding of rabphilin to SNAP-25 regulates exocytosis of synaptic vesicles after the readily releasable pool has either been physiologically exhausted by use-dependent depression, or has been artificially depleted by deletion of synaptobrevin. 相似文献
912.
Jung YY Oh MS Shin DW Kang SH Oh HS 《Biometrical journal. Biometrische Zeitschrift》2006,48(3):435-450
A Bayesian model-based clustering approach is proposed for identifying differentially expressed genes in meta-analysis. A Bayesian hierarchical model is used as a scientific tool for combining information from different studies, and a mixture prior is used to separate differentially expressed genes from non-differentially expressed genes. Posterior estimation of the parameters and missing observations are done by using a simple Markov chain Monte Carlo method. From the estimated mixture model, useful measure of significance of a test such as the Bayesian false discovery rate (FDR), the local FDR (Efron et al., 2001), and the integration-driven discovery rate (IDR; Choi et al., 2003) can be easily computed. The model-based approach is also compared with commonly used permutation methods, and it is shown that the model-based approach is superior to the permutation methods when there are excessive under-expressed genes compared to over-expressed genes or vice versa. The proposed method is applied to four publicly available prostate cancer gene expression data sets and simulated data sets. 相似文献
913.
Aust G Wandel E Boltze C Sittig D Schütz A Horn LC Wobus M 《Cell and tissue research》2006,324(1):139-147
CD97, an epidermal growth factor (EGF)-TM7 receptor, is not restricted to hematopoetic and carcinoma cells but is also found
on smooth muscle cells (SMC). We have examined its location and biochemical structure in various normal and tumorigenic SMC-containing
tissues. SMC of the urinary bladder, lung bronchi and bronchioles, myometrium, and gastrointestinal tract were immunohistologically
stained by using monoclonal antibodies (mabs) to the CD97 stalk region (CD97stalk). Mabs directed against an N-glycosylation-dependent epitope within the EGF-domains (CD97EGF) did not bind to normal SMC. Vascular SMC, which was also CD97EGF-negative, showed further CD97 heterogeneity. Only a few, if any, SMC from the aorta or elastic arteries of the systemic circulation
were positive for CD97 mRNA and therefore also for CD97stalk. CD97stalk-positive SMC were slightly more numerous in muscular and peripheral arteries. In contrast, most venous SMC expressed CD97stalk. A comparison with other SMC molecules revealed a similar but not identical staining pattern for CD97stalk and desmin. Further CD97 heterogeneity was observed during SMC transformation. All leiomyomas (n=5) and nine out of 21 leiomyosarcomas were positive for both CD97stalk and CD97EGF. As expected, CD97EGF-positive SMC tumors expressed partly N-glycosylated CD97. Seven out of 21 leiomyosarcomas were completely devoid of CD97.
Thus, CD97 showed variable expression in vascular and biochemical modification in tumorigenic SMC, suggesting that the function
of the molecule is specific for the SMC subtype.
This study was supported by a joint grant from the German Research Council (DFG; project AU 132/3-1) and by the Interdisziplinary
Center of Clinical Research (IZKF) Leipzig at the Faculty of Medicine, University of Leipzig (project D6). E. Wandel is a
fellow of the IZKF. 相似文献
914.
Shin HW Schwindt CD Aledia AS Rose-Gottron CM Larson JK Newcomb RL Cooper DM George SC 《American journal of physiology. Regulatory, integrative and comparative physiology》2006,291(6):R1741-R1748
Exhaled nitric oxide (NO) is altered in asthmatic subjects with exercise-induced bronchoconstriction (EIB). However, the physiological interpretation of exhaled NO is limited because of its dependence on exhalation flow and the inability to distinguish completely proximal (large airway) from peripheral (small airway and alveolar) contributions. We estimated flow-independent NO exchange parameters that partition exhaled NO into proximal and peripheral contributions at baseline, postexercise challenge, and postbronchodilator administration in steroid-naive mild-intermittent asthmatic subjects with EIB (24-43 yr old, n = 9) and healthy controls (20-31 yr old, n = 9). The mean +/- SD maximum airway wall flux and airway diffusing capacity were elevated and forced expiratory flow, midexpiratory phase (FEF(25-75)), forced expiratory volume in 1 s (FEV(1)), and FEV(1)/forced vital capacity (FVC) were reduced at baseline in subjects with EIB compared with healthy controls, whereas the steady-state alveolar concentration of NO and FVC were not different. Compared with the response of healthy controls, exercise challenge significantly reduced FEV(1) (-23 +/- 15%), FEF(25-75) (-37 +/- 18%), FVC (-12 +/- 12%), FEV(1)/FVC (-13 +/- 8%), and maximum airway wall flux (-35 +/- 11%) relative to baseline in subjects with EIB, whereas bronchodilator administration only increased FEV(1) (+20 +/- 21%), FEF(25-75) (+56 +/- 41%), and FEV(1)/FVC (+13 +/- 9%). We conclude that mild-intermittent steroid-naive asthmatic subjects with EIB have altered airway NO exchange dynamics at baseline and after exercise challenge but that these changes occur by distinct mechanisms and are not correlated with alterations in spirometry. 相似文献
915.
Marine reserves demonstrate trophic interactions across habitats 总被引:1,自引:0,他引:1
Several infaunal bivalve taxa show patterns of decreased biomass in areas with higher densities of adjacent reef-associated
predators (the snapper, Pagrus auratus and rock lobster, Jasus edwardsii). A caging experiment was used to test the hypothesis that patterns observed were caused by predation, using plots seeded
with a known initial density of the bivalve Dosinia subrosea to estimate survivorship. The caging experiment was replicated at several sites inside and outside two highly protected marine
reserves: predators are significantly more abundant inside these reserves. Survivorship in fully caged, partially caged and
open plots were then compared at sites having either low (non reserve) or high (reserve) predator density. The highest rates
of survivorship of the bivalve were found in caged plots inside reserves and in all treatments outside reserves. However,
inside reserves, open and partially caged treatments exhibited low survivorship. It was possible to specifically attribute
much of this mortality to predation by large rock lobsters, due to distinctive marks on the valves of dead D. subrosea. This suggests that predation by large rock lobster could indeed account for the distributional patterns previously documented
for certain bivalve populations. Our results illustrate that protection afforded by marine reserves is necessary to investigate
how depletion through fishing pressure can change the role of upper-level predators and trophic processes between habitats.
Electronic Supplementary Material Supplementary material is available for this article at
An erratum to this article can be found at 相似文献
916.
Genetic mapping of the Isaac-CACTA transposon in maize 总被引:1,自引:0,他引:1
Lee JK Park JY Kim JH Kwon SJ Shin JH Hong SK Min HK Kim NS 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2006,113(1):16-22
We constructed a genetic linkage map with Isaac-TD, SSR, and SNAP markers in a RIL population which had been derived from a cross of waxy corn (KW7) and dent corn (Mo17). A total of 368 markers, including 241 Isaac-TD, 121 SSR, and 6 SNAP markers, were assigned to 10 linkage groups, encompassing 1687.0 cM, with an average genetic distance of 4.6 cM between markers. SSR markers were utilized as chromosome anchors, in order to assign the Isaac-TD markers to the chromosomes, and the number of markers in each of the linkage groups ranged between 22 and 49. The majority of the Isaac-TD markers were determined to have been distributed throughout the ten maize chromosomes. In linkage analysis of the Isaac-TD markers with genes of agronomic interest, six genes related with maize kernel starch biosynthesis, ae1, bt2, sh1, sh2, su1, and wx1, were analyzed and shown that they were closely linked with either the Isaac-TD or SSR markers on chromosomes of 3, 4, 5, and 9. We observed and mapped segregation-distorted markers on chromosomes 1, 5, 6, 7, 8, and 10, where these markers were clustered. The Isaac-TD or SSR markers which were closely linked with starch synthesis genes may prove useful in marker-assisted breeding programs. 相似文献
917.
The leopard cat (Prionailurus bengalensis), a member of the felidae family, is currently listed as threatened by the Ministry of Environment in South Korea. In exotic or endangered species, the lack of oocytes and recipients precludes the use of traditional somatic cell nuclear transfer, and an approach such as inter-genus nuclear transfer may be the only alternative for producing embryos and offspring. In the present study, we used the leopard cat as a somatic cell donor to evaluate the in vivo developmental competence, after transfer into domestic cat recipients, of cloned embryos produced by the fusion of leopard cat fibroblast cell nuclei with domestic cat cytoplasts. A total of 412 enucleated domestic cat oocytes were reconstructed with either male (Group A) or female (Group B) adult leopard cat fibroblasts. There was no significant difference in fusion rate (60.4% versus 56.9%) between Groups A and B. Of the cultured embryos, the cleavage and blastocyst developmental rate were not significantly different between Groups A and B (69.5% versus 60.8%; 7.2% versus 7.8%, P > 0.05). In Group A, in vivo developmental studies at 30-45 days postimplantation demonstrated 4.8% (21/435) of reconstructed embryos (n = 435) had entered into the uterine lining of recipients, while 1.4% (6/435) formed fetuses. However, all of the reconstructed embryos failed to develop to term (65 days). Microsatellite analyses confirmed that the nuclear genome of the cloned fetus were leopard cat in origin. 相似文献
918.
Ca(2+) binding to synaptotagmin 1 triggers fast exocytosis of synaptic vesicles that have been primed for release by SNARE-complex assembly. Besides synaptotagmin 1, fast Ca(2+)-triggered exocytosis requires complexins. Synaptotagmin 1 and complexins both bind to assembled SNARE complexes, but it is unclear how their functions are coupled. Here we propose that complexin binding activates SNARE complexes into a metastable state and that Ca(2+) binding to synaptotagmin 1 triggers fast exocytosis by displacing complexin from metastable SNARE complexes. Specifically, we demonstrate that, biochemically, synaptotagmin 1 competes with complexin for SNARE-complex binding, thereby dislodging complexin from SNARE complexes in a Ca(2+)-dependent manner. Physiologically, increasing the local concentration of complexin selectively impairs fast Ca(2+)-triggered exocytosis but retains other forms of SNARE-dependent fusion. The hypothesis that Ca(2+)-induced displacement of complexins from SNARE complexes triggers fast exocytosis accounts for the loss-of-function and gain-of-function phenotypes of complexins and provides a molecular explanation for the high speed and synchronicity of fast Ca(2+)-triggered neurotransmitter release. 相似文献
919.
Calpe S Erdos E Liao G Wang N Rietdijk S Simarro M Scholtz B Mooney J Lee CH Shin MS Rajnavölgyi E Schatzle J Morse HC Terhorst C Lanyi A 《Immunogenetics》2006,58(1):15-25
Human EAT-2 (SH2D1B) and SLAM-associated protein (SAP) (SH2D1A) are single SH2-domain adapters, which bind to specific tyrosine
residues in the cytoplasmic tail of six signaling lymphocytic activation molecule (SLAM) (SLAMF1)-related receptors. Here
we report that, unlike in humans, the mouse and rat Eat2 genes are duplicated with an identical genomic organization. The coding regions of the mouse Eat2a and Eat2b genes share 91% identity at the nucleotide level and 84% at the protein level; similarly, segments of introns are highly
conserved. Whereas expression of mouse Eat2a mRNA was detected in multiple tissues, Eat2b was only detectable in mouse natural killer cells, CD8+ T cells, and ovaries, suggesting a very restricted tissue expression of the latter. Both the EAT-2A and EAT-2B coimmunoprecipitated
with mouse SLAM in transfected cells and augmented tyrosine phosphorylation of the cytoplasmic tail of SLAM. Both EAT-2A and
EAT-2B bind to the Src-like kinases Fyn, Hck, Lyn, Lck, and Fgr, as determined by a yeast two-hybrid assay. However, unlike
SAP, the EAT-2 proteins bind to their kinase domains and not to the SH3 domain of these kinases. Taken together, the data
suggest that both EAT-2A and EAT-2B are adapters that recruit Src kinases to SLAM family receptors using a mechanism that
is distinct from that of SAP.
Electronic supplementary material Supplementary material is available for this article at and accessible for authorised users.
S. Calpe and E. Erdős contributed equally to this work 相似文献
920.
Kim YG Lee CS Chung WJ Kim EM Shin DS Kim JH Lee YS Chung J Kim BG 《Biotechnology letters》2006,28(2):79-84
Lipopolysaccharide (LPS)-binding peptides were enriched by using epoxy beads as a novel support to immobilize LPS for a phage
displayed peptide library screening. The sequence of Phe-Ala-Pro-Trp (FAPW) was the most significant consensus motif of 10
selected clones, and Pro-Phe (PF) was the key dipeptide for binding at the apex of the loop to form a characteristic structure
of CXXPFXXXC. Moreover, AWLPWAK, one of the highly conserved heptamer peptides, could detect specifically Gram-negative bacteria
via a whole cell binding test at 106 cells ml−1.
Received 12 July 2005; Revisions requested 1 August 2005 and 26 September 2005; Revisions received 12 September 2005 and 25
October 2005; Accepted 1 November 2005 相似文献