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排序方式: 共有591条查询结果,搜索用时 156 毫秒
41.
McConville MJ Ilgoutz SC Teasdale RD Foth BJ Matthews A Mullin KA Gleeson PA 《European journal of cell biology》2002,81(9):485-495
The GRIP domain, found in a family of coiled-coil peripheral membrane Golgi proteins, is a specific targeting sequence for the trans-Golgi network of animal cells. In this study we show that a coiled-coil protein with a GRIP domain occurs in the primitive eukaryote, Trypanosoma brucei, and that reporter proteins containing this domain can be used as a marker for the poorly characterized trans Golgi/trans-Golgi network of trypanosomatid parasites. The T. brucei GRIP domain, when fused to the carboxyl terminus of the green fluorescent protein (GFP-TbGRIP), was efficiently localized to the Golgi apparatus of transfected COS cells. Overexpression of GFP-TbGRIP in COS cells displaced the endogenous GRIP protein, GCC1p, from the Golgi apparatus indicating that the trypanosomatid and mammalian GRIP sequences interact with similar membrane determinants. GFP fusion proteins containing either the T. brucei GRIP domain or the human p230 GRIP (p230GRIP) domain were also expressed in the trypanosomatid parasite, Leishmania mexicana, and localized by fluorescence and immuno-electron microscopy to the trans face of the single Golgi apparatus and a short tubule that extended from the Golgi apparatus. Binding of GFP-p230GRIP to Golgi membranes in L. mexicana was abrogated by mutation of a critical tyrosine residue in the p230 GRIP domain. The levels of GFP-GRIP fusion proteins were dramatically reduced in stationary-phase L. mexicana promastigotes, suggesting that specific Golgi trafficking steps may be down-regulated as the promastigotes cease dividing. This study provides a protein marker for the trans-Golgi network of trypanosomatid parasites and suggests that the GRIP domain binds to a membrane component that has been highly conserved in eukaryotic evolution. 相似文献
42.
Honghua?Zhao Max?F.?Rothschild Rohan?L.?Fernando Jack?C. M.?DekkersEmail author 《Mammalian genome》2003,14(7):472-482
In recent years, several F2 crosses between outbred lines of livestock have been developed to identify quantitative trait loci (QTL). These populations are valuable for further genetic analysis, including positional candidate gene loci (CGL). Analysis of CGL in F2 populations is, however, hindered by extensive between-breed linkage disequilibrium (LD). The objectives here were to develop and evaluate three tests for CGL in simulated F2 breed-cross populations. 1) A standard association test, based on the fixed effect of CGL genotype. This test was significant for CGL at considerable distances from the QTL. 2) A marker-assisted association test, based on a test at the CGL of the fixed effect of CGL genotype in a breed-cross QTL interval mapping model. This removed the impact of between-breed LD, but was not powerful in detecting CGL closely linked to the QTL, unless the CGL was the QTL. 3) An F-drop test, comparing F ratios for a QTL at the CGL with and without the CGL included as fixed effect. It had low power to distinguish close from distant CGL. Power to distinguish two CGL within 10 cM from the QTL was limited and little improved by including QTL effects associated with markers to remove between-breed LD, although the power was greater when one of the CGL was the causative mutation. Therefore, while we conclude that candidate gene tests in QTL mapping populations must be interpreted with caution, we now have a clearer picture of the value of candidate gene tests in these populations. 相似文献
43.
1-Thio-beta-D-galactofuranosides: synthesis and evaluation as beta-D- galactofuranosidase inhibitors
Marino C; Marino K; Miletti L; Manso Alves MJ; Colli W; de Lederkremer RM 《Glycobiology》1998,8(9):901-904
Beta-D-galactofuranosidase is a good chemotherapeutic target for the design
of inhibitors, since beta-D-galactofuranose is a constituent of important
parasite glycoconjugates but is not present in the host mammals. With this
aim, we have synthesized for the first time alkyl, benzyl and aryl
1-thio-beta-D-galactofuranosides by condensation of
penta-O-benzoyl-alpha,beta-D-galactofuranose with the corresponding thiols,
in the presence of SnCl4as catalyst. The complete chemical and
spectroscopical characterization of these compounds showed that the
reaction was stereoselective. Debenzoylation with sodium methoxide afforded
the beta-S-galactofuranosides in high yield. The thioglycosides were tested
as inhibitors of the beta-D- galactofuranosidase of Penicillium fellutanum,
using for the first time 4-nitrophenyl-beta-D-galactofuranoside as
chromogenic substrate. The 4- aminophenyl-1-thio-beta-D-galactofuranoside,
obtained by catalytic hydrogenation of the nitrophenyl derivative, was the
best inhibitor being then an adequate ligand for the preparation of an
affinity phase aimed at the isolation of beta-d-galactofuranosidases from
different sources. Also the inhibitory activity of d-galactono-1, 4-lactone
was shown.
相似文献
44.
45.
Rebecca Vicente-Steijn Roderick W. C. Scherptong Boudewijn P. T. Kruithof Sjoerd N. Duim Marie Jose T. H. Goumans Lambertus J. Wisse Bin Zhou William T. Pu Robert E. Poelmann Martin J. Schalij Michelle D. Tallquist Adriana C. Gittenberger-de Groot Monique RM Jongbloed 《PloS one》2015,10(9)
Background
Morphological and functional differences of the right and left ventricle are apparent in the adult human heart. A differential contribution of cardiac fibroblasts and smooth muscle cells (populations of epicardium-derived cells) to each ventricle may account for part of the morphological-functional disparity. Here we studied the relation between epicardial derivatives and the development of compact ventricular myocardium.Results
Wildtype and Wt1CreERT2/+ reporter mice were used to study WT-1 expressing cells, and Tcf21lacZ/+ reporter mice and PDGFRα-/-;Tcf21LacZ/+ mice to study the formation of the cardiac fibroblast population. After covering the heart, intramyocardial WT-1+ cells were first observed at the inner curvature, the right ventricular postero-lateral wall and left ventricular apical wall. Later, WT-1+ cells were present in the walls of both ventricles, but significantly more pronounced in the left ventricle. Tcf21-LacZ + cells followed the same distribution pattern as WT-1+ cells but at later stages, indicating a timing difference between these cell populations. Within the right ventricle, WT-1+ and Tcf21-lacZ+ cell distribution was more pronounced in the posterior inlet part. A gradual increase in myocardial wall thickness was observed early in the left ventricle and at later stages in the right ventricle. PDGFRα-/-;Tcf21LacZ/+ mice showed deficient epicardium, diminished number of Tcf21-LacZ + cells and reduced ventricular compaction.Conclusions
During normal heart development, spatio-temporal differences in contribution of WT-1 and Tcf21-LacZ + cells to right versus left ventricular myocardium occur parallel to myocardial thickening. These findings may relate to lateralized differences in ventricular (patho)morphology in humans. 相似文献46.
Herds of dugong, a largely tropical marine megaherbivore, are known to undertake long-distance movements, sequentially overgrazing seagrass meadows in their path. Given their drastic declines in many regions, it is unclear whether at lower densities, their grazing is less intense, reducing their need to travel between meadows. We studied the effect of the feeding behaviour of a small dugong population in the Andaman and Nicobar archipelago, India to understand how small isolated populations graze seagrasses. In the seven years of our observation, all recorded dugongs travelled either solitarily or in pairs, and their use of seagrasses was limited to 8 meadows, some of which were persistently grazed. These meadows were relatively large, contiguous and dominated by short-lived seagrasses species. Dugongs consumed approximately 15% of meadow primary production, but there was a large variation (3–40% of total meadow production) in consumption patterns between meadows. The impact of herbivory was relatively high, with shoot densities c. 50% higher inside herbivore exclosures than in areas exposed to repeated grazing. Our results indicate that dugongs in the study area repeatedly graze the same meadows probably because the proportion of primary production consumed reduces shoot density to levels that are still above values that can trigger meadow abandonment. This ability of seagrasses to cope perhaps explains the long-term site fidelity shown by individual dugongs in these meadows. The fact that seagrass meadows in the archipelago are able to support dugong foraging requirements allows us to clearly identify locations where this remnant population persists, and where urgent management efforts can be directed. 相似文献
47.
48.
Background
Elucidation of the communal behavior of microbes in mixed species biofilms may have a major impact on understanding infectious diseases and for the therapeutics. Although, the structure and the properties of monospecies biofilms and their role in disease have been extensively studied during the last decade, the interactions within mixed biofilms consisting of bacteria and fungi such as Candida spp. have not been illustrated in depth. Hence, the aim of this study was to evaluate the interspecies interactions of Pseudomonas aeruginosa and six different species of Candida comprising C. albicans, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis, and C. dubliniensis in dual species biofilm development. 相似文献49.
The ubiquitin-conjugating enzyme Cdc34 (cell division cycle 34) plays an essential role in promoting the G1-S-phase transition of the eukaryotic cell cycle and is phosphorylated in vivo. In the present study, we investigated if phosphorylation regulates Cdc34 function. We mapped the in vivo phosphorylation sites on budding yeast Cdc34 (yCdc34; Ser207 and Ser216) and human Cdc34 (hCdc34 Ser203, Ser222 and Ser231) to serine residues in the acidic tail domain, a region that is critical for Cdc34's cell cycle function. CK2 (protein kinase CK2) phosphorylates both yCdc34 and hCdc34 on these sites in vitro. CK2-mediated phosphorylation increased yCdc34 ubiquitination activity towards the yeast Saccharomyces cerevisiae Sic1 in vitro, when assayed in the presence of its cognate SCFCdc4 E3 ligase [where SCF is Skp1 (S-phase kinase-associated protein 1)/cullin/F-box]. Similarly, mutation of the yCdc34 phosphorylation sites to alanine, aspartate or glutamate residues altered Cdc34-SCFCdc4-mediated Sic1 ubiquitination activity. Similar results were obtained when yCdc34's ubiquitination activity was assayed in the absence of SCFCdc4, indicating that phosphorylation regulates the intrinsic catalytic activity of Cdc34. To evaluate the in vivo consequences of altered Cdc34 activity, wild-type yCdc34 and the phosphosite mutants were introduced into an S. cerevisiae cdc34 deletion strain and, following synchronization in G1-phase, progression through the cell cycle was monitored. Consistent with the increased ubiquitination activity in vitro, cells expressing the phosphosite mutants with higher catalytic activity exhibited accelerated cell cycle progression and Sic1 degradation. These studies demonstrate that CK2-mediated phosphorylation of Cdc34 on the acidic tail domain stimulates Cdc34-SCFCdc4 ubiquitination activity and cell cycle progression. 相似文献
50.
Loveena Rishi Rohan DhimanManoj Raje Sekhar Majumdar 《Biochimica et Biophysica Acta (BBA)/General Subjects》2007
Constitutive active NF-κB have been shown to protect cutaneous T cell lymphoma (CTCL) cells from apoptosis. In the present study, we have studied the cytotoxic potential of nitric oxide generating compound, sodium nitroprusside (SNP) on CTCL cell line, HuT-78. Treatment of cells with SNP resulted in decrease in mitochondrial membrane potential, cytochrome c release, activation of caspase-3 and poly (ADP ribose) polymerase cleavage. SNP treatment inhibited activation of NF-κB in a concentration dependent manner. SNP increased the expression of IκBα without affecting the phosphorylation of IκBα. Downregulation of NF-κB by SNP decreased p65 nuclear translocation as evident by confocal fluorescence microscopy. Further it was found that SNP treatment caused downregulation of Bcl-2 family member (Bcl-xl) in HuT-78 cells. Thus, we have provided evidence that SNP induces apoptosis in CTCL cell line, HuT-78 by downregulating constitutive NF-κB and thereby Bcl-xl expression. 相似文献