Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold     

Azoitei ML  Correia BE  Ban YE  Carrico C  Kalyuzhniy O  Chen L  Schroeter A  Huang PS  McLellan JS  Kwong PD  Baker D  Strong RK  Schief WR 《Science (New York, N.Y.)》2011,334(6054):373-376

The manipulation of protein backbone structure to control interaction and function is a challenge for protein engineering. We integrated computational design with experimental selection for grafting the backbone and side chains of a two-segment HIV gp120 epitope, targeted by the cross-neutralizing antibody b12, onto an unrelated scaffold protein. The final scaffolds bound b12 with high specificity and with affinity similar to that of gp120, and crystallographic analysis of a scaffold bound to b12 revealed high structural mimicry of the gp120-b12 complex structure. The method can be generalized to design other functional proteins through backbone grafting.  相似文献   

Cell biology. Double membrane fusion     

Pfanner N  Wiedemann N  Meisinger C 《Science (New York, N.Y.)》2004,305(5691):1723-1724

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Geochemistry. Tiny tracers tell tall tales     

Ballentine CJ 《Science (New York, N.Y.)》2002,296(5571):1247-1248

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Relative impact of nucleotide and copy number variation on gene expression phenotypes     

Stranger BE  Forrest MS  Dunning M  Ingle CE  Beazley C  Thorne N  Redon R  Bird CP  de Grassi A  Lee C  Tyler-Smith C  Carter N  Scherer SW  Tavaré S  Deloukas P  Hurles ME  Dermitzakis ET 《Science (New York, N.Y.)》2007,315(5813):848-853

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Supernova shock breakout from a red supergiant     

Schawinski K  Justham S  Wolf C  Podsiadlowski P  Sullivan M  Steenbrugge KC  Bell T  Röser HJ  Walker ES  Astier P  Balam D  Balland C  Carlberg R  Conley A  Fouchez D  Guy J  Hardin D  Hook I  Howell DA  Pain R  Perrett K  Pritchet C  Regnault N  Yi SK 《Science (New York, N.Y.)》2008,321(5886):223-226

Massive stars undergo a violent death when the supply of nuclear fuel in their cores is exhausted, resulting in a catastrophic "core-collapse" supernova. Such events are usually only detected at least a few days after the star has exploded. Observations of the supernova SNLS-04D2dc with the Galaxy Evolution Explorer space telescope reveal a radiative precursor from the supernova shock before the shock reached the surface of the star and show the initial expansion of the star at the beginning of the explosion. Theoretical models of the ultraviolet light curve confirm that the progenitor was a red supergiant, as expected for this type of supernova. These observations provide a way to probe the physics of core-collapse supernovae and the internal structures of their progenitor stars.  相似文献   

Fiber-optical analog of the event horizon     

Philbin TG  Kuklewicz C  Robertson S  Hill S  König F  Leonhardt U 《Science (New York, N.Y.)》2008,319(5868):1367-1370

The physics at the event horizon resembles the behavior of waves in moving media. Horizons are formed where the local speed of the medium exceeds the wave velocity. We used ultrashort pulses in microstructured optical fibers to demonstrate the formation of an artificial event horizon in optics. We observed a classical optical effect: the blue-shifting of light at a white-hole horizon. We also showed by theoretical calculations that such a system is capable of probing the quantum effects of horizons, in particular Hawking radiation.  相似文献   

The calicheamicin gene cluster and its iterative type I enediyne PKS     

Ahlert J  Shepard E  Lomovskaya N  Zazopoulos E  Staffa A  Bachmann BO  Huang K  Fonstein L  Czisny A  Whitwam RE  Farnet CM  Thorson JS 《Science (New York, N.Y.)》2002,297(5584):1173-1176

The enediynes exemplify nature's ingenuity. We have cloned and characterized the biosynthetic locus coding for perhaps the most notorious member of the nonchromoprotein enediyne family, calicheamicin. This gene cluster contains an unusual polyketide synthase (PKS) that is demonstrated to be essential for enediyne biosynthesis. Comparison of the calicheamicin locus with the locus encoding the chromoprotein enediyne C-1027 reveals that the enediyne PKS is highly conserved among these distinct enediyne families. Contrary to previous hypotheses, this suggests that the chromoprotein and nonchromoprotein enediynes are generated by similar biosynthetic pathways.  相似文献   

Assessing the feasibility of biological control of locusts and grasshoppers in West Africa: Incorporating the farmers' perspective     

Hugo De Groote  Orou-Kobi Douro-Kpindou  Zakaria Ouambama  Comlan Gbongboui  Dieter Müller  Serge Attignon  Chris Lomer 《Agriculture and Human Values》2001,18(4):413-428

A participatory rural appraisal inthree West African countries examined thepossibility for replacing chemical pesticidesto control locusts and grasshoppers with abiological control method based on anindigenous fungal pathogen. The fungus iscurrently being tested at different sites inthe Sahel and in the humid tropics of WestAfrica. Structured group interviews, individualdiscussions, and field visits, were used toobtain farmers' perceptions of locust andgrasshoppers as crop pests, their quantitativeestimation of crop losses, and theirwillingness to pay for locust control. Farmersas well as plant protection officers generallyperceived locusts and grasshoppers as importantpests that cause significant damage. Farmerswere aware of some of the risks of the use ofchemical pesticides, but not of the potentialalternatives. The use of the fungus in anoil-formulation and standard Ultra Low Volume(ULV) equipment was demonstrated, and theresults discussed with farmers. Theirimpressions of biological control werefavorable, and they expressed an interest inusing the technology. Farmers' expressedwillingness to pay for locust control is small,but not negligible. Locusts and grasshoppersare very visible pests and thus amenable topressure from farmers to local administrators,as well as by farmers' relatives in the city onthe national government. Therefore, politicalpressure for locust control is strong, althoughnational governments spend little on it,depending mostly on foreign donors. Donors areincreasingly worried about the environmentaleffect of the large amounts of chemicalpesticides used on locust control, and arepushing for more benign alternatives. Theresults of the present survey indicate thatthere may be a potential market for abiopesticide against grasshoppers and locustson cash crops in the humid areas. The potentialmarket in the Sahel depends on a reduction ofcosts or a subsidy of its price. This subsidycould be justified by the expected reduction inenvironmental and health costs when replacingchemical pesticides. Since donors are thecurrent purchasers of chemical pesticides forthe Sahel, they would also be expected to beinvolved in the purchase of the biologicalproduct.  相似文献   

Epidermal viral immunity induced by CD8alpha+ dendritic cells but not by Langerhans cells     

Allan RS  Smith CM  Belz GT  van Lint AL  Wakim LM  Heath WR  Carbone FR 《Science (New York, N.Y.)》2003,301(5641):1925-1928

The classical paradigm for dendritic cell function derives from the study of Langerhans cells, which predominate within skin epidermis. After an encounter with foreign agents, Langerhans cells are thought to migrate to draining lymph nodes, where they initiate T cell priming. Contrary to this, we show here that infection of murine epidermis by herpes simplex virus did not result in the priming of virus-specific cytotoxic T lymphocytes by Langerhans cells. Rather, the priming response required a distinct CD8alpha+ dendritic cell subset. Thus, the traditional view of Langerhans cells in epidermal immunity needs to be revisited to accommodate a requirement for other dendritic cells in this response.  相似文献   

Donald Maitland Turner     

Graeme Allan  Chris Bellenger  Phil Davis  David Fraser  Rolfe Howlett  Richard Malik  Vera Pickering  Katrin Swindells  Malcolm Turner  Ashley Chadwick 《Australian veterinary journal》2009,87(7):279-279

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