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61.
Kuris AM Hechinger RF Shaw JC Whitney KL Aguirre-Macedo L Boch CA Dobson AP Dunham EJ Fredensborg BL Huspeni TC Lorda J Mababa L Mancini FT Mora AB Pickering M Talhouk NL Torchin ME Lafferty KD 《Nature》2008,454(7203):515-518
Parasites can have strong impacts but are thought to contribute little biomass to ecosystems. We quantified the biomass of free-living and parasitic species in three estuaries on the Pacific coast of California and Baja California. Here we show that parasites have substantial biomass in these ecosystems. We found that parasite biomass exceeded that of top predators. The biomass of trematodes was particularly high, being comparable to that of the abundant birds, fishes, burrowing shrimps and polychaetes. Trophically transmitted parasites and parasitic castrators subsumed more biomass than did other parasitic functional groups. The extended phenotype biomass controlled by parasitic castrators sometimes exceeded that of their uninfected hosts. The annual production of free-swimming trematode transmission stages was greater than the combined biomass of all quantified parasites and was also greater than bird biomass. This biomass and productivity of parasites implies a profound role for infectious processes in these estuaries. 相似文献
62.
Kukar TL Ladd TB Bann MA Fraering PC Narlawar R Maharvi GM Healy B Chapman R Welzel AT Price RW Moore B Rangachari V Cusack B Eriksen J Jansen-West K Verbeeck C Yager D Eckman C Ye W Sagi S Cottrell BA Torpey J Rosenberry TL Fauq A Wolfe MS Schmidt B Walsh DM Koo EH Golde TE 《Nature》2008,453(7197):925-929
Selective lowering of Abeta42 levels (the 42-residue isoform of the amyloid-beta peptide) with small-molecule gamma-secretase modulators (GSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer's disease. To identify the target of these agents we developed biotinylated photoactivatable GSMs. GSM photoprobes did not label the core proteins of the gamma-secretase complex, but instead labelled the beta-amyloid precursor protein (APP), APP carboxy-terminal fragments and amyloid-beta peptide in human neuroglioma H4 cells. Substrate labelling was competed by other GSMs, and labelling of an APP gamma-secretase substrate was more efficient than a Notch substrate. GSM interaction was localized to residues 28-36 of amyloid-beta, a region critical for aggregation. We also demonstrate that compounds known to interact with this region of amyloid-beta act as GSMs, and some GSMs alter the production of cell-derived amyloid-beta oligomers. Furthermore, mutation of the GSM binding site in the APP alters the sensitivity of the substrate to GSMs. These findings indicate that substrate targeting by GSMs mechanistically links two therapeutic actions: alteration in Abeta42 production and inhibition of amyloid-beta aggregation, which may synergistically reduce amyloid-beta deposition in Alzheimer's disease. These data also demonstrate the existence and feasibility of 'substrate targeting' by small-molecule effectors of proteolytic enzymes, which if generally applicable may significantly broaden the current notion of 'druggable' targets. 相似文献
63.
King N Westbrook MJ Young SL Kuo A Abedin M Chapman J Fairclough S Hellsten U Isogai Y Letunic I Marr M Pincus D Putnam N Rokas A Wright KJ Zuzow R Dirks W Good M Goodstein D Lemons D Li W Lyons JB Morris A Nichols S Richter DJ Salamov A Sequencing JG Bork P Lim WA Manning G Miller WT McGinnis W Shapiro H Tjian R Grigoriev IV Rokhsar D 《Nature》2008,451(7180):783-788
Choanoflagellates are the closest known relatives of metazoans. To discover potential molecular mechanisms underlying the evolution of metazoan multicellularity, we sequenced and analysed the genome of the unicellular choanoflagellate Monosiga brevicollis. The genome contains approximately 9,200 intron-rich genes, including a number that encode cell adhesion and signalling protein domains that are otherwise restricted to metazoans. Here we show that the physical linkages among protein domains often differ between M. brevicollis and metazoans, suggesting that abundant domain shuffling followed the separation of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows us to reconstruct with increasing resolution the genomic changes that accompanied the origin of metazoans. 相似文献
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66.
Typical 2-Cys peroxiredoxins (Prxs) have an important role in regulating hydrogen peroxide-mediated cell signalling. In this process, Prxs can become inactivated through the hyperoxidation of an active site Cys residue to Cys sulphinic acid. The unique repair of this moiety by sulphiredoxin (Srx) restores peroxidase activity and terminates the signal. The hyperoxidized form of Prx exists as a stable decameric structure with each active site buried. Therefore, it is unclear how Srx can access the sulphinic acid moiety. Here we present the 2.6 A crystal structure of the human Srx-PrxI complex. This complex reveals the complete unfolding of the carboxy terminus of Prx, and its unexpected packing onto the backside of Srx away from the Srx active site. Binding studies and activity analyses of site-directed mutants at this interface show that the interaction is required for repair to occur. Moreover, rearrangements in the Prx active site lead to a juxtaposition of the Prx Gly-Gly-Leu-Gly and Srx ATP-binding motifs, providing a structural basis for the first step of the catalytic mechanism. The results also suggest that the observed interactions may represent a common mode for other proteins to bind to Prxs. 相似文献
67.
Haplotype tagging for the identification of common disease genes 总被引:61,自引:0,他引:61
Johnson GC Esposito L Barratt BJ Smith AN Heward J Di Genova G Ueda H Cordell HJ Eaves IA Dudbridge F Twells RC Payne F Hughes W Nutland S Stevens H Carr P Tuomilehto-Wolf E Tuomilehto J Gough SC Clayton DG Todd JA 《Nature genetics》2001,29(2):233-237
Genome-wide linkage disequilibrium (LD) mapping of common disease genes could be more powerful than linkage analysis if the appropriate density of polymorphic markers were known and if the genotyping effort and cost of producing such an LD map could be reduced. Although different metrics that measure the extent of LD have been evaluated, even the most recent studies have not placed significant emphasis on the most informative and cost-effective method of LD mapping-that based on haplotypes. We have scanned 135 kb of DNA from nine genes, genotyped 122 single-nucleotide polymorphisms (SNPs; approximately 184,000 genotypes) and determined the common haplotypes in a minimum of 384 European individuals for each gene. Here we show how knowledge of the common haplotypes and the SNPs that tag them can be used to (i) explain the often complex patterns of LD between adjacent markers, (ii) reduce genotyping significantly (in this case from 122 to 34 SNPs), (iii) scan the common variation of a gene sensitively and comprehensively and (iv) provide key fine-mapping data within regions of strong LD. Our results also indicate that, at least for the genes studied here, the current version of dbSNP would have been of limited utility for LD mapping because many common haplotypes could not be defined. A directed re-sequencing effort of the approximately 10% of the genome in or near genes in the major ethnic groups would aid the systematic evaluation of the common variant model of common disease. 相似文献
68.
A. R. Todd 《Cellular and molecular life sciences : CMLS》1962,18(10):433-438
Summary Many dark-coloured species ofAphididae contain a colouring matter (protoaphin) of unusual structure in the haemolymph. After death of the insect this undergoes a remarkable series of changes by enzymic action yielding successively the pigments xanthoaphin, chrysoaphin and erythroaphin. Recent investigations leading to the complete structural elucidation of all these pigments is described.
ViertePaul-Karrer-Vorlesung von Lord A. R. Todd F. R. S., gehalten an der Universität Zürich am 4, Juli 1962. 相似文献
ViertePaul-Karrer-Vorlesung von Lord A. R. Todd F. R. S., gehalten an der Universität Zürich am 4, Juli 1962. 相似文献
69.
A. Aboul-Enein F. Paccione I. A. D. Todd T. Shikata W. J. Dempster S. L. Kountz 《Cellular and molecular life sciences : CMLS》1965,21(9):546-548
Zusammenfassung Es gelingt die normale Nierenfunktion des 20 h bei 4°C tiefgekühlten Organs durch Perfusion mit Novocain und Reomacrodex von 40°C wieder herzustellen. 相似文献
70.
The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus) 总被引:1,自引:0,他引:1
Ming R Hou S Feng Y Yu Q Dionne-Laporte A Saw JH Senin P Wang W Ly BV Lewis KL Salzberg SL Feng L Jones MR Skelton RL Murray JE Chen C Qian W Shen J Du P Eustice M Tong E Tang H Lyons E Paull RE Michael TP Wall K Rice DW Albert H Wang ML Zhu YJ Schatz M Nagarajan N Acob RA Guan P Blas A Wai CM Ackerman CM Ren Y Liu C Wang J Wang J Na JK Shakirov EV Haas B Thimmapuram J Nelson D Wang X Bowers JE Gschwend AR Delcher AL Singh R Suzuki JY Tripathi S Neupane K Wei H Irikura B Paidi M Jiang N Zhang W 《Nature》2008,452(7190):991-996
Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of 'SunUp' papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho-physiological, medicinal and nutritional properties. 相似文献