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141.
G. R. Pettit L. E. Houghton N. H. Rogers R. M. Coomes D. F. Berger P. R. Reucroft J. F. Day J. L. Hartwell H. B. Wood Jr. 《Cellular and molecular life sciences : CMLS》1972,28(4):381-382
Zusammenfassung Eine Voruntersuchung der Insektengruppe Lepidoptera auf anti-tumor-aktive Stoffe führte zu einer detaillierten chemischen Prüfung der aus Asien stammenden SchmetterlingeCatopsilia crocale Cramer (Pieridae) undPieris rapae cruavora. Ein bedeutender Teil der Anti-Tumor-Aktivität scheint ihren Ursprung in der chemischen Substanz Isoxanthopterin zu besitzen.
The present contribution represents Part XXVII of the series Antineoplastic Agents. For Part XXVI refer toG. R. Pettit, J. F. Day, J. L. Hartwell andH. B. Wood, Nature, Lond.227, 962 (1970).
This investigation was supported by Public Health Service Research Grants No. CA-10612-01 to No. CA-10612-04 from the National Cancer Institute, and was presented in part at the American Chemical Society Meeting, Washington, D.C., September 1971. We are also grateful to the National Science Foundation for financial assistance (Grant numbers GB-4939 and GB-6979) used in obtaining the Atlas CH-4B and SM-1B mass spectrometers employed in this study. 相似文献
The present contribution represents Part XXVII of the series Antineoplastic Agents. For Part XXVI refer toG. R. Pettit, J. F. Day, J. L. Hartwell andH. B. Wood, Nature, Lond.227, 962 (1970).
This investigation was supported by Public Health Service Research Grants No. CA-10612-01 to No. CA-10612-04 from the National Cancer Institute, and was presented in part at the American Chemical Society Meeting, Washington, D.C., September 1971. We are also grateful to the National Science Foundation for financial assistance (Grant numbers GB-4939 and GB-6979) used in obtaining the Atlas CH-4B and SM-1B mass spectrometers employed in this study. 相似文献
142.
143.
A chemical switch for inhibitor-sensitive alleles of any protein kinase 总被引:32,自引:0,他引:32
Bishop AC Ubersax JA Petsch DT Matheos DP Gray NS Blethrow J Shimizu E Tsien JZ Schultz PG Rose MD Wood JL Morgan DO Shokat KM 《Nature》2000,407(6802):395-401
Protein kinases have proved to be largely resistant to the design of highly specific inhibitors, even with the aid of combinatorial chemistry. The lack of these reagents has complicated efforts to assign specific signalling roles to individual kinases. Here we describe a chemical genetic strategy for sensitizing protein kinases to cell-permeable molecules that do not inhibit wild-type kinases. From two inhibitor scaffolds, we have identified potent and selective inhibitors for sensitized kinases from five distinct subfamilies. Tyrosine and serine/threonine kinases are equally amenable to this approach. We have analysed a budding yeast strain carrying an inhibitor-sensitive form of the cyclin-dependent kinase Cdc28 (CDK1) in place of the wild-type protein. Specific inhibition of Cdc28 in vivo caused a pre-mitotic cell-cycle arrest that is distinct from the G1 arrest typically observed in temperature-sensitive cdc28 mutants. The mutation that confers inhibitor-sensitivity is easily identifiable from primary sequence alignments. Thus, this approach can be used to systematically generate conditional alleles of protein kinases, allowing for rapid functional characterization of members of this important gene family. 相似文献
144.
A VEGF-A splice variant defective for heparan sulfate and neuropilin-1 binding shows attenuated signaling through VEGFR-2 总被引:1,自引:0,他引:1
Cébe Suarez S Pieren M Cariolato L Arn S Hoffmann U Bogucki A Manlius C Wood J Ballmer-Hofer K 《Cellular and molecular life sciences : CMLS》2006,63(17):2067-2077
The development of functional blood and lymphatic vessels requires spatio-temporal coordination of the production and release
of growth factors such as vascular endothelial growth factors (VEGFs). VEGF family proteins are produced in multiple isoforms
with distinct biological properties and bind to three types of VEGF receptors. A VEGF-A splice variant, VEGF-A165b, has recently been isolated from kidney epithelial cells. This variant is identical to VEGF-A165 except for the last six amino acids encoded by an alternative exon. VEGF-A165b and VEGF-A165 bind VEGF receptors 1 and 2 with similar affinity. VEGF-A165b elicits drastically reduced activity in angiogenesis assays and even counteracts signaling by VEGF-A165. VEGF-A165b weakly binds to heparan sulfate and does not interact with neuropilin-1, a coreceptor for VEGF receptor 2. To determine
the molecular basis for altered signaling by VEGF-A165b we measured VEGF receptor 2 and ERK kinase activity in endothelial cells in culture. VEGF-A165 induced strong and sustained activation of VEGF receptor 2 and ERK-1 and −2, while activation by VEGF-A165b was only weak and transient. Taken together these data show that VEGF-A165b has attenuated signaling potential through VEGF receptor 2 defining this new member of the VEGF family as a partial receptor
agonist.
Received 31 May 2006; received after revision 26 June 2006; accepted 14 July 2006 相似文献
145.
Jaeger E Webb E Howarth K Carvajal-Carmona L Rowan A Broderick P Walther A Spain S Pittman A Kemp Z Sullivan K Heinimann K Lubbe S Domingo E Barclay E Martin L Gorman M Chandler I Vijayakrishnan J Wood W Papaemmanuil E Penegar S Qureshi M;CORGI Consortium Farrington S Tenesa A Cazier JB Kerr D Gray R Peto J Dunlop M Campbell H Thomas H Houlston R Tomlinson I 《Nature genetics》2008,40(1):26-28
We mapped a high-penetrance gene (CRAC1; also known as HMPS) associated with colorectal cancer (CRC) in the Ashkenazi population to a 0.6-Mb region on chromosome 15 containing SCG5 (also known as SGNE1), GREM1 and FMN1. We hypothesized that the CRAC1 locus harbored low-penetrance variants that increased CRC risk in the general population. In a large series of colorectal cancer cases and controls, SNPs near GREM1 and SCG5 were strongly associated with increased CRC risk (for rs4779584, P = 4.44 x 10(-14)). 相似文献
146.
Accretion of the Earth and segregation of its core 总被引:1,自引:0,他引:1
The Earth took 30-40 million years to accrete from smaller 'planetesimals'. Many of these planetesimals had metallic iron cores and during growth of the Earth this metal re-equilibrated with the Earth's silicate mantle, extracting siderophile ('iron-loving') elements into the Earth's iron-rich core. The current composition of the mantle indicates that much of the re-equilibration took place in a deep (> 400 km) molten silicate layer, or 'magma ocean', and that conditions became more oxidizing with time as the Earth grew. The high-pressure nature of the core-forming process led to the Earth's core being richer in low-atomic-number elements, notably silicon and possibly oxygen, than the cores of the smaller planetesimal building blocks. 相似文献
147.
Elachi C Wall S Janssen M Stofan E Lopes R Kirk R Lorenz R Lunine J Paganelli F Soderblom L Wood C Wye L Zebker H Anderson Y Ostro S Allison M Boehmer R Callahan P Encrenaz P Flamini E Francescetti G Gim Y Hamilton G Hensley S Johnson W Kelleher K Muhleman D Picardi G Posa F Roth L Seu R Shaffer S Stiles B Vetrella S West R 《Nature》2006,441(7094):709-713
Cassini's Titan Radar Mapper imaged the surface of Saturn's moon Titan on its February 2005 fly-by (denoted T3), collecting high-resolution synthetic-aperture radar and larger-scale radiometry and scatterometry data. These data provide the first definitive identification of impact craters on the surface of Titan, networks of fluvial channels and surficial dark streaks that may be longitudinal dunes. Here we describe this great diversity of landforms. We conclude that much of the surface thus far imaged by radar of the haze-shrouded Titan is very young, with persistent geologic activity. 相似文献
148.
Many botanists doubt the existence of plant species, viewing them as arbitrary constructs of the human mind, as opposed to discrete, objective entities that represent reproductively independent lineages or 'units of evolution'. However, the discreteness of plant species and their correspondence with reproductive communities have not been tested quantitatively, allowing zoologists to argue that botanists have been overly influenced by a few 'botanical horror stories', such as dandelions, blackberries and oaks. Here we analyse phenetic and/or crossing relationships in over 400 genera of plants and animals. We show that although discrete phenotypic clusters exist in most genera (> 80%), the correspondence of taxonomic species to these clusters is poor (< 60%) and no different between plants and animals. Lack of congruence is caused by polyploidy, asexual reproduction and over-differentiation by taxonomists, but not by contemporary hybridization. Nonetheless, crossability data indicate that 70% of taxonomic species and 75% of phenotypic clusters in plants correspond to reproductively independent lineages (as measured by postmating isolation), and thus represent biologically real entities. Contrary to conventional wisdom, plant species are more likely than animal species to represent reproductively independent lineages. 相似文献
149.
Cox JJ Reimann F Nicholas AK Thornton G Roberts E Springell K Karbani G Jafri H Mannan J Raashid Y Al-Gazali L Hamamy H Valente EM Gorman S Williams R McHale DP Wood JN Gribble FM Woods CG 《Nature》2006,444(7121):894-898
The complete inability to sense pain in an otherwise healthy individual is a very rare phenotype. In three consanguineous families from northern Pakistan, we mapped the condition as an autosomal-recessive trait to chromosome 2q24.3. This region contains the gene SCN9A, encoding the alpha-subunit of the voltage-gated sodium channel, Na(v)1.7, which is strongly expressed in nociceptive neurons. Sequence analysis of SCN9A in affected individuals revealed three distinct homozygous nonsense mutations (S459X, I767X and W897X). We show that these mutations cause loss of function of Na(v)1.7 by co-expression of wild-type or mutant human Na(v)1.7 with sodium channel beta(1) and beta(2) subunits in HEK293 cells. In cells expressing mutant Na(v)1.7, the currents were no greater than background. Our data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans. These findings should stimulate the search for novel analgesics that selectively target this sodium channel subunit. 相似文献
150.