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61.
Genetic analysis of autoimmune type 1 diabetes mellitus in mice. 总被引:57,自引:0,他引:57
J A Todd T J Aitman R J Cornall S Ghosh J R Hall C M Hearne A M Knight J M Love M A McAleer J B Prins 《Nature》1991,351(6327):542-547
Two genes, Idd-3 and Idd-4, that influence the onset of autoimmune type 1 diabetes in the nonobese diabetic mouse have been located on chromosomes 3 and 11, outside the chromosome 17 major histocompatibility complex. A genetic map of the mouse genome, analysed using the polymerase chain reaction, has been assembled specifically for the study. On the basis of comparative maps of the mouse and human genomes, the homologue of Idd-3 may reside on human chromosomes 1 or 4 and Idd-4 on chromosome 17. 相似文献
62.
HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus 总被引:27,自引:0,他引:27
Over half of the inherited predisposition to insulin-dependent diabetes mellitus maps to the region of chromosome 6 that contains the highly polymorphic HLA class II genes which determine immune responsiveness. Analysis of DNA sequences from diabetics indicates that alleles of HLA-DQ beta determine both disease susceptibility and resistance, and that the structure of the DQ molecule, in particular residue 57 of the beta-chain, specifies the autoimmune response against the insulin-producing islet cells. 相似文献
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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
66.
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
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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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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