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81.
Herrmann A Svangård E Claeson P Gullbo J Bohlin L Göransson U 《Cellular and molecular life sciences : CMLS》2006,63(2):235-245
Cyclotides are cyclic plant proteins with potent cytotoxic effects. Here we systematically probed the importance of surface-exposed
charged amino acid residues of the cyclotide cycloviolacin O2, using a strategy involving chemical modifications. We show
that the single glutamic acid plays a key role for the cytotoxicity: methylation of this residue produced a 48-fold decrease
in potency. Virtually no change in potency was observed when masking the single arginine residue using 1,2-cyclohexanedione,
while acetylation of the two lysine residues reduced the potency 3-fold. The derivative with modifications at both arginine
and lysine residues showed a 7-fold loss of potency. In addition, we show that the activity is dependent on an intact disulfide
network and that the short sequences between the six cysteine residues, that is, the backbone loops, are devoid of cytotoxic
activity.
Received 11 October 2005; received after revision 3 November 2005; accepted 15 November 2005 相似文献
82.
Serial translocation by means of circular intermediates underlies colour sidedness in cattle 总被引:1,自引:0,他引:1
Durkin K Coppieters W Drögemüller C Ahariz N Cambisano N Druet T Fasquelle C Haile A Horin P Huang L Kamatani Y Karim L Lathrop M Moser S Oldenbroek K Rieder S Sartelet A Sölkner J Stålhammar H Zelenika D Zhang Z Leeb T Georges M Charlier C 《Nature》2012,482(7383):81-84
Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips. It is also referred to as 'lineback' or 'witrik' (which means white back), as colour-sided animals typically display a white band along their spine. Colour sidedness is documented at least since the Middle Ages and is presently segregating in several cattle breeds around the globe, including in Belgian blue and brown Swiss. Here we report that colour sidedness is determined by a first allele on chromosome 29 (Cs(29)), which results from the translocation of a 492-kilobase chromosome 6 segment encompassing KIT to chromosome 29, and a second allele on chromosome 6 (Cs(6)), derived from the first by repatriation of fused 575-kilobase chromosome 6 and 29 sequences to the KIT locus. We provide evidence that both translocation events involved circular intermediates. This is the first example, to our knowledge, of a phenotype determined by homologous yet non-syntenic alleles that result from a novel copy-number-variant-generating mechanism. 相似文献
83.
Dissolved organic carbon trends resulting from changes in atmospheric deposition chemistry 总被引:6,自引:0,他引:6
Monteith DT Stoddard JL Evans CD de Wit HA Forsius M Høgåsen T Wilander A Skjelkvåle BL Jeffries DS Vuorenmaa J Keller B Kopácek J Vesely J 《Nature》2007,450(7169):537-540
Several hypotheses have been proposed to explain recent, widespread increases in concentrations of dissolved organic carbon (DOC) in the surface waters of glaciated landscapes across eastern North America and northern and central Europe. Some invoke anthropogenic forcing through mechanisms related to climate change, nitrogen deposition or changes in land use, and by implication suggest that current concentrations and fluxes are without precedent. All of these hypotheses imply that DOC levels will continue to rise, with unpredictable consequences for the global carbon cycle. Alternatively, it has been proposed that DOC concentrations are returning toward pre-industrial levels as a result of a gradual decline in the sulphate content of atmospheric deposition. Here we show, through the assessment of time series data from 522 remote lakes and streams in North America and northern Europe, that rising trends in DOC between 1990 and 2004 can be concisely explained by a simple model based solely on changes in deposition chemistry and catchment acid-sensitivity. We demonstrate that DOC concentrations have increased in proportion to the rates at which atmospherically deposited anthropogenic sulphur and sea salt have declined. We conclude that acid deposition to these ecosystems has been partially buffered by changes in organic acidity and that the rise in DOC is integral to recovery from acidification. Over recent decades, deposition-driven increases in organic matter solubility may have increased the export of DOC to the oceans, a potentially important component of regional carbon balances. The increase in DOC concentrations in these regions appears unrelated to other climatic factors. 相似文献
84.
Christian Feißt Carlo Pergola Marija Rakonjac Antonietta Rossi Andreas Koeberle Gabriele Dodt Marika Hoffmann Christina Hoernig Lutz Fischer Dieter Steinhilber Lutz Franke Gisbert Schneider Olof Rådmark Lidia Sautebin Oliver Werz 《Cellular and molecular life sciences : CMLS》2009,66(16):2759-2771
We previously showed that, in vitro, hyperforin from St. John’s wort (Hypericum perforatum) inhibits 5-lipoxygenase (5-LO), the key enzyme in leukotriene biosynthesis. Here, we demonstrate that hyperforin possesses
a novel and unique molecular pharmacological profile as a 5-LO inhibitor with remarkable efficacy in vivo. Hyperforin (4 mg/kg, i.p.) significantly suppressed leukotriene B4 formation in pleural exudates of carrageenan-treated rats associated with potent anti-inflammatory effectiveness. Inhibition
of 5-LO by hyperforin, but not by the iron-ligand type 5-LO inhibitor BWA4C or the nonredox-type inhibitor ZM230487, was abolished
in the presence of phosphatidylcholine and strongly reduced by mutation (W13A-W75A-W102A) of the 5-LO C2-like domain. Moreover,
hyperforin impaired the interaction of 5-LO with coactosin-like protein and abrogated 5-LO nuclear membrane translocation
in ionomycin-stimulated neutrophils, processes that are typically mediated via the regulatory 5-LO C2-like domain. Together,
hyperforin is a novel type of 5-LO inhibitor apparently acting by interference with the C2-like domain, with high effectiveness
in vivo. 相似文献
85.
Gudmundsson J Sulem P Rafnar T Bergthorsson JT Manolescu A Gudbjartsson D Agnarsson BA Sigurdsson A Benediktsdottir KR Blondal T Jakobsdottir M Stacey SN Kostic J Kristinsson KT Birgisdottir B Ghosh S Magnusdottir DN Thorlacius S Thorleifsson G Zheng SL Sun J Chang BL Elmore JB Breyer JP McReynolds KM Bradley KM Yaspan BL Wiklund F Stattin P Lindström S Adami HO McDonnell SK Schaid DJ Cunningham JM Wang L Cerhan JR St Sauver JL Isaacs SD Wiley KE Partin AW Walsh PC Polo S Ruiz-Echarri M 《Nature genetics》2008,40(3):281-283
We conducted a genome-wide SNP association study on prostate cancer on over 23,000 Icelanders, followed by a replication study including over 15,500 individuals from Europe and the United States. Two newly identified variants were shown to be associated with prostate cancer: rs5945572 on Xp11.22 and rs721048 on 2p15 (odds ratios (OR) = 1.23 and 1.15; P = 3.9 x 10(-13) and 7.7 x 10(-9), respectively). The 2p15 variant shows a significantly stronger association with more aggressive, rather than less aggressive, forms of the disease. 相似文献
86.
A. Björklund R. Håkanson A. Nobin N. -O. Sjöberg 《Cellular and molecular life sciences : CMLS》1972,28(10):1232-1233
Zusammenfassung Die Histidin-Decarboxylase-(HD)-Aktivität im Hypothalamus des Kaninchens wurde nach Oophorectomie und Thyroidectomie gemessen. Die Resultate zeigten, dass die HD-Aktivität sich 20 Tage nach der Oophorectomie und der Thyroidectomie verdoppelt. 20 Tage nach kombinierter Oophorectomie und Thyroidectomie stieg die HD-Aktivität ungefär 4mal, verglichen mit der Aktivität des Kontrollmatrials. Sham-operierte Kontrollen zeigten keine Veränderungen der HD-Aktivität im Hypothalamus. 相似文献
87.
Niels Henrik Abel and solvable equations 总被引:1,自引:0,他引:1
Communicated by J. Lützen 相似文献
88.
G. Bynke R. Håkanson J. Hörig K. Folkers 《Cellular and molecular life sciences : CMLS》1984,40(4):368-369
Summary The long-term effect of ocular administration of a substance P (SP) antagonist, (D-Pro2, D-Trp7,9)-SP, was studied in the rabbit. After 2–3 months of topical administration of the antagonist twice daily, a mild trauma was applied in the form of infrared irradiation of the iris. The control eye responded with disruption of the blood-aqueous barrier, the eye treated with the antagonist did not. Two days after termination of treatment, the response to ocular injury was still reduced. Another 2 days later, ocular injury evoked a normal response, which shows that the protection was reversible. No adverse reaction to the SP antagonist was noted. 相似文献
89.
Zusammenfassung Durch fluoreszenzmikroskopische Untersuchung und nachfolgende Silberfärbung an ein und demselben Schnitt konnte gezeigt werden, dass das System argyrophiler, nicht argentaffiner Zellen in der Magenschleimhaut der Ratte mit demjenigen histaminspeichernder Epithelzellen identisch ist. Die histaminspeichernden Zellen, die argyrophil (aber nicht argentaffin) sind, bilden ein Zellsystem, das von dem der enterochromaffinen, serotoninhaltigen Zellen getrennt ist. Diese enterochromaffinen Epithelzellen sind im Gegensatz zu den histaminhaltigen Zellen sowohl argyrophil als auch argentaffin. 相似文献
90.