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排序方式: 共有295条查询结果,搜索用时 62 毫秒
91.
Amino-acid composition of soluble and membranous lipoproteins 总被引:3,自引:0,他引:3
92.
93.
Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice 总被引:56,自引:0,他引:56
Zhu S Stavrovskaya IG Drozda M Kim BY Ona V Li M Sarang S Liu AS Hartley DM Wu DC Gullans S Ferrante RJ Przedborski S Kristal BS Friedlander RM 《Nature》2002,417(6884):74-78
Minocycline mediates neuroprotection in experimental models of neurodegeneration. It inhibits the activity of caspase-1, caspase-3, inducible form of nitric oxide synthetase (iNOS) and p38 mitogen-activated protein kinase (MAPK). Although minocycline does not directly inhibit these enzymes, the effects may result from interference with upstream mechanisms resulting in their secondary activation. Because the above-mentioned factors are important in amyotrophic lateral sclerosis (ALS), we tested minocycline in mice with ALS. Here we report that minocycline delays disease onset and extends survival in ALS mice. Given the broad efficacy of minocycline, understanding its mechanisms of action is of great importance. We find that minocycline inhibits mitochondrial permeability-transition-mediated cytochrome c release. Minocycline-mediated inhibition of cytochrome c release is demonstrated in vivo, in cells, and in isolated mitochondria. Understanding the mechanism of action of minocycline will assist in the development and testing of more powerful and effective analogues. Because of the safety record of minocycline, and its ability to penetrate the blood-brain barrier, this drug may be a novel therapy for ALS. 相似文献
94.
IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity 总被引:51,自引:0,他引:51
Shankaran V Ikeda H Bruce AT White JM Swanson PE Old LJ Schreiber RD 《Nature》2001,410(6832):1107-1111
Lymphocytes were originally thought to form the basis of a 'cancer immunosurveillance' process that protects immunocompetent hosts against primary tumour development, but this idea was largely abandoned when no differences in primary tumour development were found between athymic nude mice and syngeneic wild-type mice. However, subsequent observations that nude mice do not completely lack functional T cells and that two components of the immune system-IFNgamma and perforin-help to prevent tumour formation in mice have led to renewed interest in a tumour-suppressor role for the immune response. Here we show that lymphocytes and IFNgamma collaborate to protect against development of carcinogen-induced sarcomas and spontaneous epithelial carcinomas and also to select for tumour cells with reduced immunogenicity. The immune response thus functions as an effective extrinsic tumour-suppressor system. However, this process also leads to the immunoselection of tumour cells that are more capable of surviving in an immunocompetent host, which explains the apparent paradox of tumour formation in immunologically intact individuals. 相似文献
95.
The second nesting record for the Great - tailed Grackle ( Quiscalus mexicanus ) in Nevada is reported from the central part of the state approximately 240 km north of the previous record. Since 1912 this species has undergone a dramatic northward extension of its previous range in the United States, presumably as a result of increased agricultural irrigation in areas that were previously desert or short - grass prairie. 相似文献
96.
When removed from the field and maintained under laboratory conditions, meadow voles exhibited significant change in body composition. Voles increased body mass due primarily to large gains in lipid mass combined with small losses in fat-free mass. Lipid deposition amounts increased as dietary fat was increased, and animals demonstrated a leveling of body mass instead of continuous unregulated obesity. When dietary fat content was changed, lipid deposition or utilization responded directly. Thus, meadow voles regulate overall body mass and body composition (lipid and fat-free mass) at levels that correspond to dietary quality (fat) and abundance in the laboratory, and they deposit considerably more lipid than do animals in the field. Our experiments demonstrate that food quality has a substantial effect on the body composition of wild-caught animals maintained in the laboratory. 相似文献
97.
To determine the role of the California red-backed vole ( Clethrionomys califonicus ), the northern flying squirrel ( Glaucomys sabrinus ), and the deer mouse ( Peromyscus maniculatus ) in the nitrogen cycle of forest stands in western Oregon, bacterial colonies were isolated and purified from feces, and their nitrogen-fixing ability measured by acetylene-reduction assay. The ability of the bacterial species Azospirillum sp. to withstand freezing was also tested. Fecal extracts were used to test whether fecal pellets can provide the nutrients necessary for growth of the bacteria. All the feces tested contained viable nitrogen-fixing bacteria, and both species can survive drying and one can survive freezing. Azospirillum colonies grew well on liquid medium but required yeast extract for growth and nitrogenase activity. Fecal extracts from flying squirrels and chickarees ( Tamiasciurus douglasi ) were as effective as the yeast. The results suggest another link in the chain of mutualism that unites small mammals, mycorrhizal fungi, and forest trees. 相似文献
98.
99.
Luther S Fenton FH Kornreich BG Squires A Bittihn P Hornung D Zabel M Flanders J Gladuli A Campoy L Cherry EM Luther G Hasenfuss G Krinsky VI Pumir A Gilmour RF Bodenschatz E 《Nature》2011,475(7355):235-239
Controlling the complex spatio-temporal dynamics underlying life-threatening cardiac arrhythmias such as fibrillation is extremely difficult, because of the nonlinear interaction of excitation waves in a heterogeneous anatomical substrate. In the absence of a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for cardiac fibrillation. Here we establish the relationship between the response of the tissue to an electric field and the spatial distribution of heterogeneities in the scale-free coronary vascular structure. We show that in response to a pulsed electric field, E, these heterogeneities serve as nucleation sites for the generation of intramural electrical waves with a source density ρ(E) and a characteristic time, τ, for tissue depolarization that obeys the power law τ?∝?E(α). These intramural wave sources permit targeting of electrical turbulence near the cores of the vortices of electrical activity that drive complex fibrillatory dynamics. We show in vitro that simultaneous and direct access to multiple vortex cores results in rapid synchronization of cardiac tissue and therefore, efficient termination of fibrillation. Using this control strategy, we demonstrate low-energy termination of fibrillation in vivo. Our results give new insights into the mechanisms and dynamics underlying the control of spatio-temporal chaos in heterogeneous excitable media and provide new research perspectives towards alternative, life-saving low-energy defibrillation techniques. 相似文献
100.
Chapman HN Fromme P Barty A White TA Kirian RA Aquila A Hunter MS Schulz J DePonte DP Weierstall U Doak RB Maia FR Martin AV Schlichting I Lomb L Coppola N Shoeman RL Epp SW Hartmann R Rolles D Rudenko A Foucar L Kimmel N Weidenspointner G Holl P Liang M Barthelmess M Caleman C Boutet S Bogan MJ Krzywinski J Bostedt C Bajt S Gumprecht L Rudek B Erk B Schmidt C Hömke A Reich C Pietschner D Strüder L Hauser G Gorke H Ullrich J Herrmann S Schaller G Schopper F Soltau H Kühnel KU Messerschmidt M 《Nature》2011,470(7332):73-77
X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (~200?nm to 2?μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage. 相似文献