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排序方式: 共有102条查询结果,搜索用时 15 毫秒
1.
Chirag Nepal Yavor Hadzhiev Christopher Previti Vanja Haberle Nan Li Hazuki Takahashi Ana Maria M. Suzuki Ying Sheng Rehab F. Abdelhamid Santosh Anand Jochen Gehrig Altuna Akalin Christel E.M. Kockx Antoine A.J. van der Sloot Wilfred F.J. van IJcken Olivier Armant Sepand Rastegar Craig Watson Uwe Str?hle Elia Stupka Piero Carninci Boris Lenhard Ferenc Müller 《Genome research》2013,23(11):1938-1950
2.
P.M. Fischer N.Z. Zhelev S. Wang J.E. Melville R. Fhraeus D.P. Lane 《Chemical biology & drug design》2000,55(2):163-172
Abstract: Peptides derived from the third α‐helix of the homeodomain (residues 43–58; Penetratin) of Antennapedia, a Drosophila homeoprotein, were prepared by simultaneous multiple synthesis. Sets of N‐ and C‐terminally truncated peptides, as well as a series of alanine substitution analogues, were studied. Cell penetration assays using human cell cultures with these peptides revealed that the C‐terminal segment 52Arg‐Arg‐Met‐Lys‐Trp‐Lys‐Lys58 of the parent sequence was necessary and sufficient for efficient cell membrane translocation. Individual Ala substitutions of the peptide’s basic residues led to markedly decreased cell internalization ability, whereas replacement of hydrophobic residues was tolerated surprisingly well. Subcellular localization was seen to be affected by substitutions, with analogues being addressed preferentially to the cytosol or to the nucleus. Conformational constriction of the Penetratin sequence through placement and oxidation of flanking cysteine residues afforded a cyclic disulfide peptide which had lost most of its membrane translocation capacity. 相似文献
3.
Chemoattractant receptor-stimulated F-actin polymerization in the human neutrophil is signaled by 2 distinct pathways 总被引:3,自引:0,他引:3
We characterized the overall rate of F-actin polymerization in the pseudopod region by measuring the rate of extension of single pseudopods stimulated by f-Met-Leu-Phe. The rate of pseudopod extension was measured in the presence of inhibitors for signaling molecules that are known to be involved in motility. Our data show the existence of 2 distinct signaling pathways of actin polymerization in the pseudopod region: a phosphoinositide 3-kinase gamma (PI3Kgamma)-dependent and -independent pathway. The PI3Kgamma dependent signaling of F-actin polymerization also depends on protein kinase C zeta and protein kinase B (Akt/PKB). The PI3Kgamma-independent pathway depends on GTPase RhoA, the RhoA ROCK kinase, Src family tyrosine kinases, and NADPH, and is modulated by cAMP. 相似文献
4.
In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine) 总被引:4,自引:0,他引:4
McClue SJ Blake D Clarke R Cowan A Cummings L Fischer PM MacKenzie M Melville J Stewart K Wang S Zhelev N Zheleva D Lane DP 《International journal of cancer. Journal international du cancer》2002,102(5):463-468
CDK2 inhibitors have been proposed as effective anti-cancer therapeutics. We show here that CYC202 (R-roscovitine) is a potent inhibitor of recombinant CDK2/cyclin E kinase activity (IC(50) = 0.10 microM) with an average cytotoxic IC(50) of 15.2 microM in a panel of 19 human tumour cell lines, and we also demonstrate selectivity for rapidly proliferating cells over non-proliferating cells. A study of the cell cycle effects of CYC202 in Lovo colorectal carcinoma cells showed that the major effect was not the predicted arrest in one part of the cycle, but rather an induction of cell death from all compartments of the cell cycle. The maximum tolerated dose given intravenously to mice was in excess of 20 mg/kg. Doses up to 2,000 mg/kg were tolerated when administered orally in mice. Following repeated intraperitoneal administration (3 times daily for 5 days) of 100 mg/kg to nude mice bearing the Lovo human colorectal tumour, CYC202 induced a significant antitumour effect with a 45% reduction in tumour growth compared to controls. A second experiment using the human uterine xenograft MESSA-DX5 treated with orally administered CYC202 (500 mg/kg 3 times daily for 4 days) also exhibited a significant reduction in the rate of growth of the tumour (62%). These data, showing enzyme and cellular potency together with antitumour activity, confirm the potential of CDK2 inhibitors such as CYC202 as anticancer drugs. 相似文献
5.
Sarek J Klinot J Dzubák P Klinotová E Nosková V Krecek V Korínková G Thomson JO Janost'áková A Wang S Parsons S Fischer PM Zhelev NZ Hajdúch M 《Journal of medicinal chemistry》2003,46(25):5402-5415
Cellular screening of various synthetic triterpenoid compounds formally derived from lupane has identified a number of analogues as potential anticancer drug candidates. Here we describe the synthesis and structure-activity relationships of betulin and betulinic acid derivatives containing an E-ring modified with different oxygen functions. Thus compounds containing the lup-18-en-21-one, lup-18-ene-21,22-dione, 18,19-secolupane, and the highly oxygenated 18,19-secolupane systems, as well as des-E-lupane derivatives, were prepared from the readily available natural pentacyclic triterpene betulin using oxidative procedures. These compounds were named betulinines. We demonstrate that only selected compounds, particularly those containing a lupane E-ring-derived unsaturated ketone or diketone function, possessed in vitro cytotoxic activity against tumor cell lines, suggesting a structure-activity relationship. 相似文献
6.
Segmental duplications: organization and impact within the current human genome project assembly 总被引:38,自引:13,他引:25 下载免费PDF全文
Segmental duplications play fundamental roles in both genomic disease and gene evolution. To understand their organization within the human genome, we have developed the computational tools and methods necessary to detect identity between long stretches of genomic sequence despite the presence of high copy repeats and large insertion-deletions. Here we present our analysis of the most recent genome assembly (January 2001) in which we focus on the global organization of these segments and the role they play in the whole-genome assembly process. Initially, we considered only large recent duplication events that fell well-below levels of draft sequencing error (alignments 90%-98% similar and > or =1 kb in length). Duplications (90%-98%; > or =1 kb) comprise 3.6% of all human sequence. These duplications show clustering and up to 10-fold enrichment within pericentromeric and subtelomeric regions. In terms of assembly, duplicated sequences were found to be over-represented in unordered and unassigned contigs indicating that duplicated sequences are difficult to assign to their proper position. To assess coverage of these regions within the genome, we selected BACs containing interchromosomal duplications and characterized their duplication pattern by FISH. Only 47% (106/224) of chromosomes positive by FISH had a corresponding chromosomal position by comparison. We present data that indicate that this is attributable to misassembly, misassignment, and/or decreased sequencing coverage within duplicated regions. Surprisingly, if we consider putative duplications >98% identity, we identify 10.6% (286 Mb) of the current assembly as paralogous. The majority of these alignments, we believe, represent unmerged overlaps within unique regions. Taken together the above data indicate that segmental duplications represent a significant impediment to accurate human genome assembly, requiring the development of specialized techniques to finish these exceptional regions of the genome. The identification and characterization of these highly duplicated regions represents an important step in the complete sequencing of a human reference genome. 相似文献
7.
Karlberg M Halmagyi GM Büttner U Yavor RA 《Archives of otolaryngology--head & neck surgery》2000,126(8):1024-1029
We describe 4 patients who all simultaneously developed a sudden total or partial unilateral sensorineural hearing loss and an unusual acute peripheral vestibulopathy in the same ear characterized by posterior semicircular canal benign paroxysmal positional vertigo with intact lateral semicircular canal function. Two patients also had ipsilateral loss of otolith function. The vertigo resolved in all 4 patients after particle-repositioning maneuvers. The findings of audiometry and vestibular tests indicated that the lesion responsible for this syndrome was probably located within the labyrinth itself rather than within the vestibulocochlear nerve and that it was more likely a viral vestibulocochlear neurolabyrinthitis than a labyrinthine infarction. 相似文献
8.
The acquired immunodefficiency syndrome (AIDS) is characterized by a gross defect in the cell-mediated immune response. However, infection with human immunodeficiency virus (HIV), which is the generally accepted etiological factor of AIDS, cannot explain by itself the following problems: why do not some of the seropositive subjects develop AIDS or AIDS-related complex; why are some of the patients with AIDS seronegative for HIV and its corresponding antibodies; what is the reason why some of the healthy seronegative subjects from groups at a high risk for AIDS (homosexuals, hemophiliacs and drug abusers) have low T-helper to T-suppressor ratios. We suggest that some additional factor is necessary for the development of AIDS. We propose that the factor needed is a 'partial functional thymectomy'. We suspect that slow fungal infections, producing thymotoxic metabolites, may be a major cause for the latter. 相似文献
9.
Pure beta-amanitin was isolated by combined adsorption chromatography of a crude methanol extract from Amanita phalloides on Sephasorb HP Ultrafine and Sephadex LH-20. The beta-amanitin was coupled to concanavalin A by the carbodiimide method. The conjugate was purified by fractionation on a column of Sephadex G-75. The molar ratio beta-amanitin to concanavalin A in this conjugate was 4.14. The purified conjugate was tested by thin-layer chromatography and showed characteristic (for amatoxins) bright purple staining but different mobility. The ultraviolet spectrum of the conjugate was different from the spectra of the native beta-amanitin and the native concanavalin A. The toxicity of the conjugate was determined by in vivo toxicological studies and was four-fold lower than that of the native beta-amanitin. These results suggest that this conjugate may be used for immunization procedures and for the production of amatoxin-specific antibodies. 相似文献
10.