Design of a novel globular protein fold with atomic-level accuracy     

Kuhlman B  Dantas G  Ireton GC  Varani G  Stoddard BL  Baker D 《Science (New York, N.Y.)》2003,302(5649):1364-1368

A major challenge of computational protein design is the creation of novel proteins with arbitrarily chosen three-dimensional structures. Here, we used a general computational strategy that iterates between sequence design and structure prediction to design a 93-residue alpha/beta protein called Top7 with a novel sequence and topology. Top7 was found experimentally to be folded and extremely stable, and the x-ray crystal structure of Top7 is similar (root mean square deviation equals 1.2 angstroms) to the design model. The ability to design a new protein fold makes possible the exploration of the large regions of the protein universe not yet observed in nature.  相似文献   

RECENT PROGRESS IN VERTEBRATE PALEONTOLOGY     

Eastman CR  Gregory WK  Matthew WD 《Science (New York, N.Y.)》1916,43(1099):103-110

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Spongiform degeneration in mahoganoid mutant mice     

He L  Lu XY  Jolly AF  Eldridge AG  Watson SJ  Jackson PK  Barsh GS  Gunn TM 《Science (New York, N.Y.)》2003,299(5607):710-712

mahoganoid is a mouse coat-color mutation whose pigmentary phenotype and genetic interactions resemble those of Attractin (Atrn). Atrn mutations also cause spongiform neurodegeneration. Here, we show that a null mutation for mahoganoid causes a similar age-dependent neuropathology that includes many features of prion diseases but without accumulation of protease-resistant prion protein. The gene mutated in mahoganoid encodes a RING-containing protein with E3 ubiquitin ligase activity in vitro. Similarities in phenotype, expression, and genetic interactions suggest that mahoganoid and Atrn genes are part of a conserved pathway for regulated protein turnover whose function is essential for neuronal viability.  相似文献   

Targeted genome editing across species using ZFNs and TALENs   总被引：2，自引：0，他引：2  

Wood AJ  Lo TW  Zeitler B  Pickle CS  Ralston EJ  Lee AH  Amora R  Miller JC  Leung E  Meng X  Zhang L  Rebar EJ  Gregory PD  Urnov FD  Meyer BJ 《Science (New York, N.Y.)》2011,333(6040):307

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Complete genome sequence of the apicomplexan, Cryptosporidium parvum     

Abrahamsen MS  Templeton TJ  Enomoto S  Abrahante JE  Zhu G  Lancto CA  Deng M  Liu C  Widmer G  Tzipori S  Buck GA  Xu P  Bankier AT  Dear PH  Konfortov BA  Spriggs HF  Iyer L  Anantharaman V  Aravind L  Kapur V 《Science (New York, N.Y.)》2004,304(5669):441-445

The apicomplexan Cryptosporidium parvum is an intestinal parasite that affects healthy humans and animals, and causes an unrelenting infection in immunocompromised individuals such as AIDS patients. We report the complete genome sequence of C. parvum, type II isolate. Genome analysis identifies extremely streamlined metabolic pathways and a reliance on the host for nutrients. In contrast to Plasmodium and Toxoplasma, the parasite lacks an apicoplast and its genome, and possesses a degenerate mitochondrion that has lost its genome. Several novel classes of cell-surface and secreted proteins with a potential role in host interactions and pathogenesis were also detected. Elucidation of the core metabolism, including enzymes with high similarities to bacterial and plant counterparts, opens new avenues for drug development.  相似文献   

Selective logging in the Brazilian Amazon   总被引：3，自引：0，他引：3  

Asner GP  Knapp DE  Broadbent EN  Oliveira PJ  Keller M  Silva JN 《Science (New York, N.Y.)》2005,310(5747):480-482

Amazon deforestation has been measured by remote sensing for three decades. In comparison, selective logging has been mostly invisible to satellites. We developed a large-scale, high-resolution, automated remote-sensing analysis of selective logging in the top five timber-producing states of the Brazilian Amazon. Logged areas ranged from 12,075 to 19,823 square kilometers per year (+/-14%) between 1999 and 2002, equivalent to 60 to 123% of previously reported deforestation area. Up to 1200 square kilometers per year of logging were observed on conservation lands. Each year, 27 million to 50 million cubic meters of wood were extracted, and a gross flux of approximately 0.1 billion metric tons of carbon was destined for release to the atmosphere by logging.  相似文献   

Microbiology. Rapid insect evolution by symbiont transfer     

Jiggins FM  Hurst GD 《Science (New York, N.Y.)》2011,332(6026):185-186

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Protection from genital herpes simplex virus type 2 infection by vaccination with cloned type 1 glycoprotein D   总被引：22，自引：0，他引：22  

P W Berman  T Gregory  D Crase  L A Lasky 《Science (New York, N.Y.)》1985,227(4693):1490-1492

Guinea pigs were vaccinated with truncated herpes simplex virus type-1 (HSV-1) glycoprotein D produced in the genetically engineered mammalian cell line gD10.2. Vaccinated animals formed antibodies that neutralized both HSV-1 and herpes simplex virus type 2 (HSV-2) in an in vitro neutralization assay. Vaccinated animals were challenged with HSV-2 by intravaginal infection. Animals that received the immunogen in Freund's complete adjuvant were completely protected from the clinical manifestations of genital HSV-2 infection. Animals that received the immunogen incorporated in alum adjuvants were partly protected from clinical disease; the infections that did develop were significantly less severe than those that occurred in control animals injected with adjuvant alone. The results demonstrate that immunization with a purified viral protein can provide significant protection against primary genital infection by HSV-2 in guinea pigs.  相似文献   

Melatonin suppresses nighttime memory formation in zebrafish     

Rawashdeh O  de Borsetti NH  Roman G  Cahill GM 《Science (New York, N.Y.)》2007,318(5853):1144-1146

Memory processes are modulated by the biological clock, although the mechanisms are unknown. Here, we report that in the diurnal zebrafish both learning and memory formation of an operant conditioning paradigm occur better during the day than during the night. Melatonin treatment during the day mimics the nighttime suppression of memory formation. Training in constant light improves nighttime memory formation while reducing endogenous melatonin concentrations. Treatment with melatonin receptor antagonists at night dramatically improves memory. Pinealectomy also significantly improves nighttime memory formation. We adduce that melatonin is both sufficient and necessary for poor memory formation during the night.  相似文献   

Effect of lipopolysaccharide on sickness behaviour in hens kept in cage and free range environments     

N.G. Gregory  S.R. Payne  C.J. Cook 《Research in veterinary science》2009,87(1):167-170

The aim of this study was to assess whether environmental enrichment and environmental conditions can influence the expression of sickness behaviour. The behaviour in response to injection of lipopolysaccharide or saline was examined in a total of 96 62-weeks old hatchmate hens kept in a free range or cage environment. There were eight experimental treatments, each with 12 birds. Half the birds were sourced from a commercial cage layer unit (C/-) and half from a commercial free range unit (FR/-). After intraperitoneal injection with either lipopolysaccharide or saline (as a control), the hens were placed in either a cage (-/C) or free range (-/FR) environment. Lipopolysaccharide caused greater suppression of activity in free range (FR/FR) than in caged hens, including less walking (53% reduction), roosting (−86%) and preening (−60%) (p < 0.05). Those responses were not observed in caged birds released into free range, nor in free range birds introduced to cages, suggesting that both the presence of and the familiarity with an environment affected sickness behaviour patterns. Increased sleeping was the most consistent response (+147%; p < 0.001), and it was least influenced by environment. It was concluded that free range layer hens can express a greater range of sickness behaviours than caged hens, and this may make it more difficult to recognise disease expression in the caged environment.  相似文献