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101.
Bhabhra R Richie DL Kim HS Nierman WC Fortwendel J Aris JP Rhodes JC Askew DS 《Eukaryotic cell》2008,7(4):575-583
Aspergillus fumigatus is an important opportunistic fungal pathogen that is responsible for high mortality rates in the immunosuppressed population. CgrA, the A. fumigatus ortholog of a Saccharomyces cerevisiae nucleolar protein involved in ribosome biogenesis, contributes to the virulence of this fungus by supporting rapid growth at 37 degrees C. To determine how CgrA affects ribosome biogenesis in A. fumigatus, polysome profile and ribosomal subunit analyses were performed on both wild-type A. fumigatus and a DeltacgrA mutant. The loss of CgrA was associated with a reduction in the level of 80S monosomes as well as an imbalance in the 60S:40S subunit ratio and the appearance of half-mer ribosomes. The gene expression profile in the DeltacgrA mutant revealed increased abundance of a subset of translational machinery mRNAs relative to the wild type, suggesting a potential compensatory response to CgrA deficiency. Although DeltacgrA conidia germinated normally at 22 degrees C, they swelled excessively when incubated at 37 degrees C and accumulated abnormally high numbers of nuclei. This hypernucleated phenotype could be replicated pharmacologically by germinating wild-type conidia under conditions of reductive stress. These findings indicate that the germination process is particularly vulnerable to global disruption of protein synthesis and suggest that CgrA is involved in both ribosome biogenesis and polarized cell growth in A. fumigatus. 相似文献
102.
Research ethics recommendations for whole-genome research: consensus statement 总被引:1,自引:1,他引:0 下载免费PDF全文
103.
Beswick P Charrier N Clarke B Demont E Dingwall C Dunsdon R Faller A Gleave R Hawkins J Hussain I Johnson CN MacPherson D Maile G Matico R Milner P Mosley J Naylor A O'Brien A Redshaw S Riddell D Rowland P Skidmore J Soleil V Smith KJ Stanway S Stemp G Stuart A Sweitzer S Theobald P Vesey D Walter DS Ward J Wayne G 《Bioorganic & medicinal chemistry letters》2008,18(3):1022-1026
This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays. 相似文献
104.
The roles of MAPKs in disease 总被引:2,自引:0,他引:2
Lawrence MC Jivan A Shao C Duan L Goad D Zaganjor E Osborne J McGlynn K Stippec S Earnest S Chen W Cobb MH 《Cell research》2008,18(4):436-442
105.
Intra- and interchromosomal interactions have been implicated in a number of genetic phenomena in diverse organisms, suggesting that the higher-order structural organization of chromosomes in the nucleus can have a profound impact on gene regulation. In Drosophila, homologous chromosomes remain paired in somatic tissues, allowing for trans interactions between genes and regulatory elements on the two homologs. One consequence of homolog pairing is the phenomenon of transvection, in which regulatory elements on one homolog can affect the expression of a gene in trans. We report a new instance of transvection at the Drosophila apterous (ap) locus. Two different insertions of boundary elements in the ap regulatory region were identified. The boundaries are inserted between the ap wing enhancer and the ap promoter and have highly penetrant wing defects typical of mutants in ap. When crossed to an ap promoter deletion, both boundary inserts exhibit the interallelic complementation characteristic of transvection. To confirm that transvection occurs at ap, we generated a deletion of the ap wing enhancer by FRT-mediated recombination. When the wing-enhancer deletion is crossed to the ap promoter deletion, strong transvection is observed. Interestingly, the two boundary elements, which are inserted ~10 kb apart, fail to block enhancer action when they are present in trans to one another. We demonstrate that this is unlikely to be due to insulator bypass. The transvection effects described here may provide insight into the role that boundary element pairing plays in enhancer blocking both in cis and in trans. 相似文献
106.
Adam J. Matich Marian J. McKenzie David A. Brummell Daryl D. Rowan 《Phytochemistry》2009,70(9):1098-1106
Nicotiana tabacum L. (tobacco) plants were transformed to overexpress a selenocysteine methyltransferase gene from the selenium hyperaccumulator Astragalus bisulcatus (Hook.) A. Gray (two-grooved milkvetch), and an ATP-sulfurylase gene from Brassica oleracea L. var. italica (broccoli). Solvent extraction of leaves harvested from plants treated with selenate revealed five selenium-containing compounds, of which four were identified by chemical synthesis as 2-(methylseleno)acetaldehyde, 2,2-bis(methylseleno)acetaldehyde, 4-(methylseleno)-(2E)-nonenal, and 4-(methylseleno)-(2E,6Z)-nonadienal. These four compounds have not previously been reported in nature. 相似文献
107.
108.
Robertson BC Frauenfelder N Eason DK Elliott G Moorhouse R 《Molecular ecology resources》2009,9(2):664-666
Thirty polymorphic microsatellite loci were developed from the critically endangered kakapo (Strigops habroptilus), using an enriched genomic library. Characterization of loci using 90 kakapo revealed an average of 3.3 alleles per locus (range: 2–5) and an average expected heterozygosity of 0.47 (range: 0.17–0.70). The probability of identity (7.2 × 10?15) and probability of exclusion (0.999999) demonstrate that these loci are a highly informative marker set that can aid the genetic management of the kakapo. 相似文献
109.
110.
Geneste H Amberg W Backfisch G Beyerbach A Braje WM Delzer J Haupt A Hutchins CW King LL Sauer DR Unger L Wernet W 《Bioorganic & medicinal chemistry letters》2006,16(7):1934-1937
In our efforts to further pursue one of the most selective dopamine D(3)-receptor antagonists reported to date, we now describe the synthesis and SAR of novel and highly selective dopamine D(3) antagonists based on a 1H-pyridin-2-one or on a urea scaffold. The most potent compounds exhibited K(i) values toward the D(3) receptor in the nano- to subnanomolar range and high selectivity versus the related D(2) dopamine receptor. Thus, 1H-pyridin-2-one 7b displays oral bioavailability (F=37%) as well as brain penetration (brain plasma ratio 3.7) in rat. Within the urea series, an excellent D(3) versus D(2) selectivity (>100-fold) could be achieved by removal of one NH group (compound 6), although bioavailability (rat) was suboptimal (F<10%). These data significantly enhance our understanding of the D(3) pharmacophore and are expected to lead to novel approaches for the treatment of schizophrenia. 相似文献