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121.
122.
Walensky LD Kung AL Escher I Malia TJ Barbuto S Wright RD Wagner G Verdine GL Korsmeyer SJ 《Science (New York, N.Y.)》2004,305(5689):1466-1470
BCL-2 family proteins constitute a critical control point for the regulation of apoptosis. Protein interaction between BCL-2 members is a prominent mechanism of control and is mediated through the amphipathic alpha-helical BH3 segment, an essential death domain. We used a chemical strategy, termed hydrocarbon stapling, to generate BH3 peptides with improved pharmacologic properties. The stapled peptides, called "stabilized alpha-helix of BCL-2 domains" (SAHBs), proved to be helical, protease-resistant, and cell-permeable molecules that bound with increased affinity to multidomain BCL-2 member pockets. A SAHB of the BH3 domain from the BID protein specifically activated the apoptotic pathway to kill leukemia cells. In addition, SAHB effectively inhibited the growth of human leukemia xenografts in vivo. Hydrocarbon stapling of native peptides may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in many signaling pathways. 相似文献
123.
Bartke A Wright JC Mattison JA Ingram DK Miller RA Roth GS 《Science (New York, N.Y.)》2002,296(5576):2141-2; author reply 2141-2
124.
PC Sereno DB Dutheil M Iarochene HCE Larsson GH Lyon PM Magwene CA Sidor DJ Varricchio JA Wilson 《Science (New York, N.Y.)》1996,272(5264):986-991
Late Cretaceous (Cenomanian) fossils discovered in the Kem Kem region of Morocco include large predatory dinosaurs that inhabited Africa as it drifted into geographic isolation. One, represented by a skull approximately 1.6 meters in length, is an advanced allosauroid referable to the African genus Carcharodontosaurus. Another, represented by a partial skeleton with slender proportions, is a new basal coelurosaur closely resembling the Egyptian genus Bahariasaurus. Comparisons with Cretaceous theropods from other continents reveal a previously unrecognized global radiation of carcharodontosaurid predators. Substantial geographic differentiation of dinosaurian faunas in response to continental drift appears to have arisen abruptly at the beginning of the Late Cretaceous. 相似文献
125.
Structural characterization of a partly folded apomyoglobin intermediate 总被引:41,自引:0,他引:41
To understand why proteins adopt particular three-dimensional structures, it is important to elucidate the hierarchy of interactions that stabilize the native state. Proteins in partly folded states can be used to dissect protein organizational hierarchies. A partly folded apomyoglobin intermediate has now been characterized structurally by trapping slowly exchanging peptide NH protons and analyzing them by two-dimensional 1H-NMR (nuclear magnetic resonance). Protons in the A, G, and H helix regions are protected from exchange, while protons in the B and E helix regions exchange freely. On the basis of these results and the three-dimensional structure of native myoglobin, a structural model is presented for the partly folded intermediate in which a compact subdomain retains structure while the remainder of the protein is essentially unfolded. 相似文献
126.
Alexander Bruckner John Wright Christian Kampichler Roswitha Bauer Ellen Kandeler 《Biology and Fertility of Soils》1995,19(2-3):257-262
Equipment and handling methods for the preparation of soil mesocosms were developed. The mesocosms were used to investigate the interrelationships between mesofauna and microflora in a coniferous forest soil. Soil monoliths were taken from the ground, defaunated by deep-freezing, wrapped in nets to control reimmigration of different faunal size-classes, and replanted in the field for 8 months. in a practical test the technique described here proved to be an inexpensive field method for producing a replicated series of mesocosm in a short time. Deep-freezing is appropriate for defaunating soil monoliths. The fine nets effectively exluded meso-and macrofauna. No significant differences were found in the abundance of Enchytraeids and Collembola between recolonized mesocosms and the undisturbed control at the end of the study period. In contrast, oribatid mite abundace was still greatly reduced in the recolonized esocosms. Dominance structure and species composition of the more dominant oribatid species in the different treatments were apparently similar. To compensate for the low colonization ability of oribatids, a reintroduction of selected animal size-classes to defaunated monoliths is recommended. 相似文献
127.
Both acid deposition and changes in the global atmosphere and climate affect terrestrial and aquatic ecosystems. In the atmosphere sulphate aerosols tend to increase haze, altering the global radiation balance. Increased nitrogen deposition to N-limited systems such as boreal forests results in increased growth and increased sequestration of atmospheric CO2, slowing the increase in CO2 levels in the atmosphere. Future reduction in S and N emissions may result in a trade-off -- better with respect to some effects of acid deposition and greenhouse warming, but worse with respect to others. Global warming may cause the incidence and severity of drought to increase. Mineralisation of N and oxidation of organic S compounds release pulses of SO4, acid and Al to surface waters. Effects in lakes may include reduced deep water refugia for cold stenotherms, lower nutrient concentrations, and greater penetration of harmful UV radiation. Longer water renewal times cause declines in SO4 and NO3, due to increased in situ removal, but increases in base cations. The net result is increased internal alkalinity production. In areas characterised by cold winters, global warming may result in a major shift in hydrologic cycle, with snowmelt episodes occurring during the winter rather than the typical pattern of accumulation in the winter and melting in the spring. Increased storm frequency predicted for the future will cause increased frequency and severity of sea salt episodes in coastal regions. Predicting the interactions of regional and global environmental factors in the coming decades poses new challenges to scientists, managers and policy-makers. 相似文献
128.
M. Brown H. Dyke S. M. Wright R. A. Wadsworth K. R. Bull A. Farmer S. Bareham S. E. Metcalfe D. Whyatt C. Powlesland 《Water, air, and soil pollution》1995,85(4):2589-2594
Concern about the environmental effect of air pollution on areas of high conservation value in the UK has prompted the statutory agencies to initiate an investigation on these areas. For this, critical loads maps have been used together with predicted air pollution data, monitored air pollution data and remotely sensed land cover information within a geographic information system (GIS). Additional information on designated Sites of Special Scientific Interest (SSSI) for England and Wales have also been incorporated. This provides the framework for examining potential impacts to these sites under various current and future scenarios. The approach allows for the investigation of the impacts of individual point sources as well as complete national scenarios. Preliminary results are provided from analysis of a single pollutant (sulphur). These indicate that nationally up to 52% of the area of SSSI's (5000 km2) are at risk from soil acidification. Using this approach it has been possible to apportion the load on any SSSI, thereby enabling the ecological impacts of each point source to be identified. This information can then be used to assess priorities for regulatory controls. 相似文献
129.
R. Siddaramappa G. W. McCarty R. J. Wright F. E. Codling 《Biology and Fertility of Soils》1994,18(4):279-284
There is an increasing need to find a suitable means for disposal of coal combustion byproducts because of the increasing world-wide production of these byproducts. This need has prompted interest in the use of land disposal, but there are concerns that this use may degrade the quality of soil. To determine the influence of coal combustion byproducts on the transformation and fate of soil N and assess the potential impact of land disposal on soil quality, we studied the effects of two combustion byproducts (fly ash and bed ash) applied at rates of 22.5, 45, 90, and 180 Mg ha-1 on mineralization and volatile loss of N from soil. Studies comparing the influence of the byproducts on these processes showed that whereas fly ash had little influence on the fate of soil N, bed ash caused substantial mineralization of organic soil N and volatile loss of this N as NH3. Studies monitoring the pH of soils treated with bed ash showed that soil pH increased immediately after this treatment, with values reaching as high as 12.8. These studies indicated that such extreme alkaline conditions caused chemical degradation and volatile loss of as much as 10% of the organic N in soil, and they provide strong evidence that the improper disposal of bed ash on land can have a substantial negative impact on soil quality. 相似文献
130.
Wright AJ McGauley SE Narine SS Willis WM Lencki RW Marangoni AG 《Journal of agricultural and food chemistry》2000,48(4):1033-1040
The high- and medium-melting fractions of milk fat (HMF and MMF, respectively) were crystallized in the presence of various solvents, including the low-melting fraction of milk fat (LMF), canola oil (CO), hexane, and ethyl acetate. Choice of solvent was shown to have a strong influence on phase behavior and crystallization kinetics. Dilution and solubilization effects were observed for all the blends. More solids were formed in the HMF and MMF blends with LMF than with CO, and complexes were formed between the milk fat fractions possibly because of molecular complementarity. Solids were slightly higher for the more polar ethyl acetate than for hexane. Crystallization proceeded more rapidly in the presence of LMF and ethyl acetate than in the presence of CO and hexane, respectively. According to the Hildebrand equation, HMF and MMF were ideally soluble in LMF and CO. X-ray diffraction spectroscopy (XRD) revealed the existence of liquid-state structure in mixtures of HMF/CO, HMF/LMF, MMF/CO, and MMF/LMF. The observed liquid-state structure was reminiscent of liquid crystals. No differences were observed in the structure of the liquid phase between LMF- and CO-containing mixtures. 相似文献