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1.
Cheng X Mihindukulasuriya K Den Z Kowalczyk AP Calkins CC Ishiko A Shimizu A Koch PJ 《Molecular and cellular biology》2004,24(1):154-163
Desmocollin 1 (Dsc1) is part of a desmosomal cell adhesion receptor formed in terminally differentiating keratinocytes of stratified epithelia. The dsc1 gene encodes two proteins (Dsc1a and Dsc1b) that differ only with respect to their COOH-terminal cytoplasmic amino acid sequences. On the basis of in vitro experiments, it is thought that the Dsc1a variant is essential for assembly of the desmosomal plaque, a structure that connects desmosomes to the intermediate filament cytoskeleton of epithelial cells. We have generated mice that synthesize a truncated Dsc1 receptor that lacks both the Dsc1a- and Dsc1b-specific COOH-terminal domains. This mutant transmembrane receptor, which does not bind the common desmosomal plaque proteins plakoglobin and plakophilin 1, is integrated into functional desmosomes. Interestingly, our mutant mice did not show the epidermal fragility previously observed in dsc1-null mice. This suggests that neither the Dsc1a- nor the Dsc1b-specific COOH-terminal cytoplasmic domain is required for establishing and maintaining desmosomal adhesion. However, a comparison of our mutants with dsc1-null mice suggests that the Dsc1 extracellular domain is necessary to maintain structural integrity of the skin. 相似文献
2.
The Gene Ontology project (http://www.geneontology.org/) produces structured, controlled vocabularies and gene product annotations. Gene products are classified according to the cellular locations and biological process in which they act, and the molecular functions that they carry out. We annotate gene products from a broad range of model species and provide support for those groups that wish to contribute annotation of further model species. The Gene Ontology facilitates the exchange of information between groups of scientists studying similar processes in different model organisms, and so provides a broad range of opportunities for plant scientists. 相似文献
3.
Access to data is something that every molecular biologist takes for granted nowadays, but data alone is of little use unless it is made available in a useable form through the development and global uptake of data standards. The challenge of standards development has been taken up by grass-roots movements working within several different branches of the biomedical research community. Many of these initiatives are proving extremely successful; for example, the Gene Ontology, which provides a controlled vocabulary for describing the properties of gene products, the Microarray Gene Expression Data Society's standards for describing microarray experiments, and the emerging standards developed by the Proteomics Standards Initiative are gaining broad acceptance. Standards development now faces its greatest ever challenge--the integration of diverse data types to fulfill the goals of systems biology. Now is the time for the communities that are developing these standards, the funding bodies that have invested so heavily in high-throughput data generation, and the publishers of biomedical research papers to cooperate fully to make the goals of integrated data analysis a reality. 相似文献
4.
In rain forest, the large numbers of species of fleshy-fruited plants and frugivorous animals result in a large number of potential fruit–frugivore interactions, which are challenging to survey in the field. Yet, knowledge of these relationships is needed to predict consequences of changes in the frugivore assemblage for seed dispersal. In the absence of comprehensive dietary information, it may be possible to delineate between frugivores that disperse different plants using ‘functional traits,’ or morphological and behavioral attributes of frugivores that interact with differences in salient characteristics of plant species. Here we use data on the consumption of 244 Australian rain forest plant species by 38 bird species to test for associations between patterns of frugivory and birds': (1) degree of frugivory, (2) gape width, and (3) seed treatment (seed crushing or seed dispersing). Degree of frugivory and gape width explain 74 percent of the variation in the sizes of fruits consumed by frugivorous birds. Among birds that consume a substantial dietary proportion of fruit, birds with wider gapes consume larger fruits. In contrast, this relationship was not shown by birds for which fruit is only a minor dietary component. Degree of frugivory and gape width, together with seed treatment, also strongly predict the overall taxonomic composition and diversity of plants consumed by bird species. Functional classifications of frugivore species may prove useful in developing a predictive understanding of fruit–frugivore interactions in other rain forest regions where detailed dietary information is not available for most frugivores. 相似文献
5.
Delva E Jennings JM Calkins CC Kottke MD Faundez V Kowalczyk AP 《The Journal of biological chemistry》2008,283(26):18303-18313
Pemphigus vulgaris (PV) is a life-threatening autoimmune disease characterized by oral mucosal erosions and epidermal blistering. The autoantibodies generated target the desmosomal cadherin desmoglein-3 (Dsg3). Previous studies demonstrate that upon PV IgG binding, Dsg3 is internalized and enters an endo-lysosomal pathway where it is degraded. To define the endocytic machinery involved in PV IgG-induced Dsg3 internalization, human keratinocytes were incubated with PV IgG, and various tools were used to perturb distinct endocytic pathways. The PV IgG.Dsg3 complex failed to colocalize with clathrin, and inhibitors of clathrin- and dynamin-dependent pathways had little or no effect on Dsg3 internalization. In contrast, cholesterol binding agents such as filipin and nystatin and the tyrosine kinase inhibitor genistein dramatically inhibited Dsg3 internalization. Furthermore, the Dsg3 cytoplasmic tail specified sensitivity to these inhibitors. Moreover, inhibition of Dsg3 endocytosis with genistein prevented disruption of desmosomes and loss of adhesion in the presence of PV IgG. Altogether, these results suggest that PV IgG-induced Dsg3 internalization is mediated through a clathrin- and dynamin-independent pathway and that Dsg3 endocytosis is tightly coupled to the pathogenic activity of PV IgG. 相似文献
6.
Graham J. Edgar Neville S. Barrett Cath R. Samson 《Journal of experimental marine biology and ecology》2004,312(1):67-87
Changes in assemblages of plants, macroinvertebrates and fishes on three eastern Tasmanian reefs were monitored over 12 months in replicated control blocks and adjacent 10×12-m blocks cleared of fucoid, laminarian and dictyotalean algae. Removal of canopy-forming plants produced less change to biotic assemblages than reported in studies elsewhere, with the magnitude of change for fish and invertebrate taxa lower than variation between sites and comparable to variation between months.The introduced annual kelp Undaria pinnatifida exhibited the only pronounced response to canopy removal amongst algal taxa, with a fivefold increase in cleared blocks compared to control blocks. Marine reserves are suggested to assist reef communities resist invasion by U. pinnatifida, through an indirect mechanism involving increased predation pressure on sea urchins and reduced formation of urchin barrens that are amenable to U. pinnatifida propagation.Large invertebrates were more associated with turfing algae or the reef substratum than the macroalgal canopy. The herbivorous sea urchin Heliocidaris erythrogramma and abalone Haliotis ruber showed the strongest response to clearing amongst common macroinvertebrate species, with a halving of population numbers. Observed densities of the common monacanthid fish Acanthaluteres vittiger also declined by about 50%. The relatively high level of resistance shown by eastern Tasmanian reef biota to patch disturbance was attributed largely to high diversity and biomass of turfing macroalgae damping effects of canopy clearance. 相似文献
7.
Barlaam B Acton DG Ballard P Bradbury RH Cross D Ducray R Germain H Hudson K Klinowska T Magnien F Ogilvie DJ Olivier A Ross HS Smith R Trigwell CB Vautier M Wright L 《Bioorganic & medicinal chemistry letters》2008,18(6):1799-1803
We have identified a new series of C-5 substituted indazolylaminoquinazolines as potent erbB2 kinase inhibitors. The lead compound 22 showed excellent in vitro potency, good physical properties, acceptable oral pharmacokinetics in rat and dog, and low human in vitro clearance. It showed at least equivalent activity dose for dose compared to lapatinib in various erbB2- or EGFR-driven xenograft models after chronic oral administration. 相似文献
8.
Cathérine Pauline Herter Erhard Ebmeyer Sonja Kollers Viktor Korzun Willmar Lukas Leiser Tobias Würschum Thomas Miedaner 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2018,131(6):1263-1272
Key message
The dwarfing gene Rht24 on chromosome 6A acts in the wheat population ‘Solitär × Bussard’, considerably reducing plant height without increasing Fusarium head blight severity and delaying heading stage.Abstract
The introduction of the Reduced height (Rht)-B1 and Rht-D1 semi-dwarfing genes led to remarkable increases in wheat yields during the Green Revolution. However, their utilization also brings about some unwanted characteristics, including the increased susceptibility to Fusarium head blight. Thus, Rht loci that hold the potential to reduce plant height in wheat without concomitantly increasing Fusarium head blight (FHB) susceptibility are urgently required. The biparental population ‘Solitär × Bussard’ fixed for the Rht-1 wild-type alleles, but segregating for the recently described gibberellic acid (GA)-sensitive Rht24 gene, was analyzed to identify quantitative trait loci (QTL) for FHB severity, plant height, and heading date and to evaluate the effect of the Rht24 locus on these traits. The most prominent QTL was Rht24 on chromosome 6A explaining 51% of genotypic variation for plant height and exerting an additive effect of ? 4.80 cm. For FHB severity three QTL were detected, whereas five and six QTL were found for plant height and heading date, respectively. No FHB resistance QTL was co-localized with QTL for plant height. Unlike the Rht-1 semi-dwarfing alleles, Rht24b did not significantly affect FHB severity. This demonstrates that the choice of semi-dwarfing genes used in plant breeding programs is of utmost consideration where resistance to FHB is an important breeding target.9.
Calkins CC Setzer SV Jennings JM Summers S Tsunoda K Amagai M Kowalczyk AP 《The Journal of biological chemistry》2006,281(11):7623-7634
Desmosomes are adhesive intercellular junctions prominent in the skin and heart. Loss of desmosome function is associated with severe congenital and acquired disorders characterized by tissue fragility. Pemphigus vulgaris (PV) is an autoimmune disorder in which antibodies are directed against the desmosomal adhesion molecule Dsg3, resulting in severe mucosal erosions and epidermal blistering. To define the mechanisms by which Dsg3 autoantibodies disrupt keratinocyte adhesion, the fate of PV IgG and various desmosomal components was monitored in primary human keratinocytes exposed to PV patient IgG. PV IgG initially bound to keratinocyte cell surfaces and colocalized with desmosomal markers. Within 6 h after PV IgG binding to Dsg3, electron microscopy revealed that desmosomes were dramatically disrupted and keratinocyte adhesion was severely compromised. Immunofluorescence analysis indicated that PV IgG and Dsg3 were rapidly internalized from the cell surface in a complex with plakoglobin but not desmoplakin. Dsg3 internalization was associated with retraction of keratin filaments from cell-cell borders. Furthermore, the internalized PV IgG-Dsg3 complex colocalized with markers for both endosomes and lysosomes, suggesting that Dsg3 was targeted for degradation. Consistent with this possibility, biotinylation experiments demonstrated that soluble Dsg3 cell surface pools were rapidly depleted followed by loss of detergent-insoluble Dsg3. These findings demonstrate that Dsg3 endocytosis, keratin filament retraction, and the loss of keratinocyte cell-cell adhesion are coordinated responses to PV IgG. 相似文献
10.
Cath Oberholtzer 《American anthropologist》2000,102(1):139-147
First Peoples, First Contacts: Tangible Records. Chase Manhattan Gallery of North America and First Peoples, First Contacts, British Museum, London, permanent installation.
First Peoples, First Contacts: Native Peoples of North America. J. C. H. King. Cambridge, MA: Harvard University Press, 1999.288 pp. 相似文献
First Peoples, First Contacts: Native Peoples of North America. J. C. H. King. Cambridge, MA: Harvard University Press, 1999.288 pp. 相似文献