Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein     

Willingham S  Outeiro TF  DeVit MJ  Lindquist SL  Muchowski PJ 《Science (New York, N.Y.)》2003,302(5651):1769-1772

Genome-wide screens were performed in yeast to identify genes that enhance the toxicity of a mutant huntingtin fragment or of alpha-synuclein. Of 4850 haploid mutants containing deletions of nonessential genes, 52 were identified that were sensitive to a mutant huntingtin fragment, 86 that were sensitive to alpha-synuclein, and only one mutant that was sensitive to both. Genes that enhanced toxicity of the mutant huntingtin fragment clustered in the functionally related cellular processes of response to stress, protein folding, and ubiquitin-dependent protein catabolism, whereas genes that modified alpha-synuclein toxicity clustered in the processes of lipid metabolism and vesicle-mediated transport. Genes with human orthologs were overrepresented in our screens, suggesting that we may have discovered conserved and nonoverlapping sets of cell-autonomous genes and pathways that are relevant to Huntington's disease and Parkinson's disease.  相似文献   

Increase in activity during calorie restriction requires Sirt1     

Chen D  Steele AD  Lindquist S  Guarente L 《Science (New York, N.Y.)》2005,310(5754):1641

Sir2 (silent information regulator 2) is a nicotinamide adenine dinucleotide-dependent deacetylase required for longevity due to calorie restriction in yeast and Drosophila. In mammals, calorie restriction induces a complex pattern of physiological and behavioral changes. Here we report that the mammalian Sir2 ortholog, Sirt1, is required for the induction of a phenotype by calorie restriction in mice.  相似文献   

The bee situation: africanized honey bees and bee mites     

Lindquist EE 《Science (New York, N.Y.)》1989,243(4898):1618

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Excitation Gap in the Normal State of Underdoped Bi2Sr2CaCu2O8+delta     

AG Loeser  Z Shen  DS Dessau  DS Marshall  CH Park  P Fournier  A Kapitulnik 《Science (New York, N.Y.)》1996,273(5273):325-329

Angle-resolved photoemission experiments reveal evidence of an energy gap in the normal state excitation spectrum of the cuprate superconductor Bi2Sr2CaCu2O8+delta. This gap exists only in underdoped samples and closes around the doping level at which the superconducting transition temperature Tc is a maximum. The momentum dependence and magnitude of the gap closely resemble those of the dx2-y2 gap observed in the superconducting state. This observation is consistent with results from several other experimental techniques, which also indicate the presence of a gap in the normal state. Some possible theoretical explanations for this effect are reviewed.  相似文献   

Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast     

Treusch S  Hamamichi S  Goodman JL  Matlack KE  Chung CY  Baru V  Shulman JM  Parrado A  Bevis BJ  Valastyan JS  Han H  Lindhagen-Persson M  Reiman EM  Evans DA  Bennett DA  Olofsson A  DeJager PL  Tanzi RE  Caldwell KA  Caldwell GA  Lindquist S 《Science (New York, N.Y.)》2011,334(6060):1241-1245

Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.  相似文献   

The ecoresponsive genome of Daphnia pulex     

Colbourne JK  Pfrender ME  Gilbert D  Thomas WK  Tucker A  Oakley TH  Tokishita S  Aerts A  Arnold GJ  Basu MK  Bauer DJ  Cáceres CE  Carmel L  Casola C  Choi JH  Detter JC  Dong Q  Dusheyko S  Eads BD  Fröhlich T  Geiler-Samerotte KA  Gerlach D  Hatcher P  Jogdeo S  Krijgsveld J  Kriventseva EV  Kültz D  Laforsch C  Lindquist E  Lopez J  Manak JR  Muller J  Pangilinan J  Patwardhan RP  Pitluck S  Pritham EJ  Rechtsteiner A  Rho M  Rogozin IB  Sakarya O  Salamov A  Schaack S  Shapiro H  Shiga Y  Skalitzky C  Smith Z  Souvorov A  Sung W 《Science (New York, N.Y.)》2011,331(6017):555-561

We describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges.  相似文献   

Effect of cultivation and within-field differences in soil conditions on feral Helianthus annuus growth in ridge-tillage maize     

Michael G. Burton  David A. Mortensen  John L. Lindquist 《Soil & Tillage Research》2006,88(1-2):8-15

Differences in weed population dynamics with respect to within-field heterogeneity are not well documented despite increasing interest in site-specific management of agro-ecosystems. The focus of this study was to determine if mechanical weed management (cultivation) and/or soil factors help to explain observed within-field distributions of feral common sunflower (Helianthus annuus L.). The ridges and furrows created by the ridge–tillage system adds additional microsites to existing spatial heterogeneity for soil characteristics such as soil organic carbon (SOC) concentration. Experimental areas were selected on the basis of naturally high or low SOC concentration. Cultivation resulted in 100% mortality of H. annuus seedlings growing in the middle of furrows. Cultivation of pre-emergence herbicide treated and no-herbicide ridges resulted in small but statistically significant ( = 0.05) reductions in seedling survival. No differences were detected in H. annuus canopy height, stem diameter, stem length, or vegetative biomass between high and low SOC environments. Neither total reproductive biomass (P = 0.49) nor the biomass of flowers near physiological maturity (an estimate of fecundity; P = 0.59) were affected by SOC environment. Late season H. annuus lodging was observed to reduce reproductive biomass. Juvenile plants that survived mechanical weed control efforts grew and produced reproductive biomass similarly across SOC environments. The lack of difference in vegetative and reproductive characteristics between high and low SOC environments suggests that SOC (or the edaphic conditions associated with greater or lesser SOC level) was not critical in contributing to the observed distribution of H. annuus from juvenile to flowering stages of growth within well-fertilized, irrigated agricultural habitats.  相似文献   

Persistent corneal erosion in an Australian dingo     

AG TURNER  JR PHELAN 《Australian veterinary journal》1996,74(6):435-436

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Advances in parasitology: Vol. 17. Editors W.H.R. Lumsden,R. Muller and J.R. Baker,Academic Press,U.K., 1979, xii + 415 pp., $53.00, ISBN 0.12.031717.6     

William D. Lindquist 《Veterinary parasitology》1981,8(1):103-104

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Effects of supplementation of whole corn germ on reproductive performance, calf performance, and leptin concentration in primiparous and mature beef cows     

Martin JL  Rasby RJ  Brink DR  Lindquist RU  Keisler DH  Kachman SD 《Journal of animal science》2005,83(11):2663-2670

A 2-yr study using primiparous and multiparous, spring-calving, crossbred beef cows was conducted to evaluate the effects of supplemental whole corn germ on reproductive performance, calf performance, and serum leptin concentrations. Each year, cows were blocked by age and BCS and assigned randomly to one of three treatments: PRE (n = 115) cows received 1.14 kg/d (DM basis) of whole corn germ for approximately 45 d before calving; POST (n = 109) cows were fed 1.14 kg/d of whole corn germ for approximately 45 d after calving; and control cows (n = 118) were fed similar energy and protein from dry-rolled corn (1.82 kg of DM/d) for 45 d before and after calving. Additionally, PRE cows were grouped with controls after calving, and POST cows were grouped with control cows before calving, so that corn germ-supplemented cows received the control supplement in the alternate feeding period. Cow BW (538 +/- 13 kg) and BCS (5.4 +/- 0.13) did not differ among treatments at any time during the experiment. Calf birth weight (39 +/- 2 kg), weaning weight (225 +/- 7 kg), and age-adjusted weaning weight (234 +/- 8 kg) did not differ because of dam supplementation regimen. Treatment did not affect the proportion of cows exhibiting ovarian luteal activity before the start of the breeding season (67%) or pregnancy rate (91%). The interval from exposure to bulls until subsequent calving did not differ (P = 0.16) among PRE (298 +/- 2.3 d), POST (303 +/- 2.6 d), and control (304 +/- 2.3 d) cows. Leptin concentrations did not differ among treatments and were 2.15 +/- 0.75, 1.88 +/- 0.76, and 1.91 +/- 0.75 ng/mL for control, POST, and PRE cows, respectively. Age and week relative to calving influenced leptin concentration. Primiparous cows had similar leptin concentrations to 3-yr-old and mature cows for wk -7 and -6 relative to calving, but lower (P < 0.10) concentrations than mature cows for wk -5, and lower (P < 0.05) concentrations than either 3-yr-old or mature cows for wk -4 to +7 relative to calving. Serum leptin was correlated with BCS (P < 0.0001; r = 0.35) at initiation of the feeding period and was correlated with BCS (P = 0.02; r = 0.12) and weight (P < 0.01; r = 0.14) at the completion of the supplement period, but it was not correlated with initial BW or interim BCS. Calving interval was not correlated (P > 0.12) with weekly measures of serum leptin concentration. Supplementing beef cows with whole corn germ had no effect on cow performance, calf performance, or serum leptin concentrations of cows.  相似文献