Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing     

Wu X  Zhou T  Zhu J  Zhang B  Georgiev I  Wang C  Chen X  Longo NS  Louder M  McKee K  O'Dell S  Perfetto S  Schmidt SD  Shi W  Wu L  Yang Y  Yang ZY  Yang Z  Zhang Z  Bonsignori M  Crump JA  Kapiga SH  Sam NE  Haynes BF  Simek M  Burton DR  Koff WC  Doria-Rose NA  Connors M;NISC Comparative Sequencing Program  Mullikin JC  Nabel GJ  Roederer M  Shapiro L  Kwong PD  Mascola JR 《Science (New York, N.Y.)》2011,333(6049):1593-1602

Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.  相似文献   

A melanocortin 1 receptor allele suggests varying pigmentation among Neanderthals     

Lalueza-Fox C  Römpler H  Caramelli D  Stäubert C  Catalano G  Hughes D  Rohland N  Pilli E  Longo L  Condemi S  de la Rasilla M  Fortea J  Rosas A  Stoneking M  Schöneberg T  Bertranpetit J  Hofreiter M 《Science (New York, N.Y.)》2007,318(5855):1453-1455

The melanocortin 1 receptor (MC1R) regulates pigmentation in humans and other vertebrates. Variants of MC1R with reduced function are associated with pale skin color and red hair in humans of primarily European origin. We amplified and sequenced a fragment of the MC1R gene (mc1r) from two Neanderthal remains. Both specimens have a mutation that was not found in approximately 3700 modern humans analyzed. Functional analyses show that this variant reduces MC1R activity to a level that alters hair and/or skin pigmentation in humans. The impaired activity of this variant suggests that Neanderthals varied in pigmentation levels, potentially on the scale observed in modern humans. Our data suggest that inactive MC1R variants evolved independently in both modern humans and Neanderthals.  相似文献   

奶花芸豆种植密度与施肥量优化组合模式的研究   总被引：1，自引：0，他引：1  

刘建国  李俊华  翟孟茹  帕尼古丽 《西北农业学报》2005,14(4):57-60,80

采用正交回归旋转组合设计，研究了密度、氮（N）、磷（P2O5）、钾（K2O）施用量对奶花芸豆产量的影响，通过田间试验测定参数，利用计算机技术对试验数据进行处理，建立了产量函数模型，经计算机模拟寻优，筛选出了产量的最佳农艺措施组合方案。在试验条件下，当奶花芸豆栽培密度为150000株／hm^2，施氮量300kg／hm^2，施磷量200kg／hm^2，施钾量45kg／hm^2组合时，产量可达到3833．4kg／hm^2。  相似文献   

T-cell tumor elimination as a result of T-cell receptor-mediated activation   总被引：5，自引：0，他引：5  

J D Ashwell  D L Longo  S H Bridges 《Science (New York, N.Y.)》1987,237(4810):61-64

It has recently been shown that activation of murine T-cell hybridomas with antigen inhibits their growth in vitro. The "suicide" of these neoplastic T cells upon stimulation with antigen suggested the possibility that activation via the antigen-specific receptor could also inhibit the growth of neoplastic T cells in vivo. To test this, mice were subcutaneously inoculated with antigen-specific T-cell hybridomas and then treated intraperitoneally with antigen. Administration of the appropriate antigen immediately after inoculation with the T-cell hybridoma abrogated tumor formation; antigen administered after tumors had become established decreased the tumor burden and, in a substantial fraction of animals, led to long-term survival. The efficacy of antigen therapy was due to both a direct inhibitory effect on tumor growth and the induction of host immunity. These studies demonstrate the utility of cellular activation as a means of inhibiting neoplastic T-cell growth in vivo and provide a rationale for studying the use of less selective reagents that can mimic the activating properties of antigen, such as monoclonal antibodies, in the treatment of T-cell neoplasms of unknown antigen specificity.  相似文献   

Bacterial diversity of terra preta and pristine forest soil from the Western Amazon     

Jong-Shik Kim  Regina M. Longo  David Crowley 《Soil biology & biochemistry》2007,39(2):684-690

The survey presented here describes the bacterial diversity and community structures of a pristine forest soil and an anthropogenic terra preta from the Western Amazon forest using molecular methods to identify the predominant phylogenetic groups. Bacterial community similarities and species diversity in the two soils were compared using oligonucleotide fingerprint grouping of 16S rRNA gene sequences for 1500 clones (OFRG) and by DNA sequencing. The results showed that both soils had similar bacterial community compositions over a range of phylogenetic distances, among which Acidobacteria were predominant, but that terra preta supported approximately 25% greater species richness. The survey provides the first detailed analysis of the composition and structure of bacterial communities from terra preta anthrosols using noncultured-based molecular methods.  相似文献   

Surgical management and long-term outcome of dogs with cervical spondylomyelopathy with an anchored intervertebral titanium device     

JC King  GS Corfield  JG Mouatt  CY Kan  PA Moses 《Australian veterinary journal》2020,98(4):156-163

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Computed tomographic localization of the deepest portion of the femoral trochlear groove in healthy dogs     

Tommaso Nicetto DVM  PhD  Federico Longo DVM  PhD  Barbara Contiero MsS  Maurizio Isola DVM  PhD  Massimo Petazzoni DVM 《Veterinary surgery : VS》2020,49(6):1246-1254

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Ulcerative dermatitis associate with Uronema sp infection of farmed sand whiting Sillago ciliata     

PA GILL  RB 《Australian veterinary journal》1997,75(5):357-357

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The effects of antigenic competition on the efficacy of multivalent footrot vaccines     

CL SCHWARTZKOFF  JR EGERTON†  DJ STEWART‡  PR LEHRBACH§  TC ELLEMAN¶  PA HOYNE¶ 《Australian veterinary journal》1993,70(4):123-126

SUMMARY A multivalent footrot vaccine has been developed, containing pilus antigens produced in recombinant Pseudomonas aeruginosa and representing all nine serogroups of Dichelobacter (Bacteroides) nodosus commonly recognised in the field. The responses of sheep to the multivalent vaccine have been compared with those to monovalent vaccines representing only a single serogroup. Antigenie competition between serogroups occurred in sheep immunised with the multivalent formulation, but high levels of protection were still achieved. The study showed that in multivalent footrot vaccines, antigenic competition is predominantly due to the presence of a family of immunologically-related pilus antigens rather than to interference by extraneous proteins.  相似文献   

Bovine abortion caused by Listeria ivanovii     

PA GILL  JG BOULTON  GC FRASER  AE STEVENSON  LA REDDACLIFF 《Australian veterinary journal》1997,75(3):214-214

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