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21.
MacArthur DG Balasubramanian S Frankish A Huang N Morris J Walter K Jostins L Habegger L Pickrell JK Montgomery SB Albers CA Zhang ZD Conrad DF Lunter G Zheng H Ayub Q DePristo MA Banks E Hu M Handsaker RE Rosenfeld JA Fromer M Jin M Mu XJ Khurana E Ye K Kay M Saunders GI Suner MM Hunt T Barnes IH Amid C Carvalho-Silva DR Bignell AH Snow C Yngvadottir B Bumpstead S Cooper DN Xue Y Romero IG; Genomes Project Consortium Wang J Li Y Gibbs RA McCarroll SA Dermitzakis ET Pritchard JK Barrett JC 《Science (New York, N.Y.)》2012,335(6070):823-828
Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in nonessential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies. 相似文献
22.
Pascal C Poncet-Legrand C Imberty A Gautier C Sarni-Manchado P Cheynier V Vernhet A 《Journal of agricultural and food chemistry》2007,55(12):4895-4901
Interactions between salivary proline-rich proteins and tannins are involved in astringency, which is one of the most important organoleptic sensations perceived when drinking wine or tea. This work aimed to study interactions between a recombinant human salivary proline-rich protein, IB-5, and a flavan-3-ol monomer, epigallocatechin gallate (EGCG). IB-5 presented the characteristics of natively unfolded proteins. Interactions were studied by dynamic light scattering, isothermal titration microcalorimetry, and circular dichroism. The interaction mechanism was dependent on protein concentration. At low concentrations, a three-stage mechanism was evidenced. Saturation of the interaction sites (first stage) was followed by protein aggregation into metastable colloids at higher EGCG/protein ratios (second stage). Further increasing this ratio led to haze formation (third stage). At low ratios, a disorder-to-order transition of IB-5 structure upon binding was evidenced. At high protein concentrations, direct bridging between proteins and EGCG was observed, resulting in significantly lower aggregation and turbidity thresholds. 相似文献
23.
Catherine M. Ronning Stanley P. Kowalski Lind L. Sanford John R. Stommel 《Genetic Resources and Crop Evolution》2000,47(4):359-369
The Colorado Potato Beetle is a serious pest of the cultivated potato. Natural resistance has been found in a few wild species, including Solanum chacoense Bitter, in which the resistance is attributed to the presence of leptine glycoalkaloids. Production and accumulation of these compounds within S. chacoense varies widely and appears to be inherited in a quantitative fashion, but high leptine-producing clones occur rarely. In the present study, 15 different accessions from various locations and altitudes of origin within central to northern Argentina and Paraguay were analyzed for foliar glycoalkaloid (leptine, leptinine, solanine, chaconine) content. The objective was to infer the frequency of leptine production in ecogeographically distinct S. chacoense accessions, and to ascertain any possible association between leptine levels/concentrations and ecogeographical location. Leptines were detected in 8 of the 15 accessions, and the amounts within each accession varied widely. Most of the leptine-containing accessions originated from western Argentina except two in province Córdoba in central Argentina. There was no relationship between elevational level and leptine, but there was a negative trend with total glycoalkaloids (TGA) and elevation, due to solanine and chaconine levels which decreased with increasing elevation. In addition, nine unidentified, putative glycoalkaloids were detected, in very high proportions in some individuals and accessions. This study raises interesting questions about glycoalkaloid distribution, helps provide direction for new avenues of leptine and glycoalkaloid research, and proposes a systematic, ecogeographically based method for bioprospecting genes controlling rare plant secondary compounds. 相似文献
24.
Aligiannis N Mitaku S Tsitsa-Tsardis E Harvala C Tsaknis I Lalas S Haroutounian S 《Journal of agricultural and food chemistry》2003,51(25):7308-7312
The antioxidant properties of various fractions of a methanolic extract obtained from the aerial parts of Verbascum macrurum have been determined by monitoring their capacity to scavenge the stable free-radical DPPH. They were also evaluated as natural preservatives against oxidative rancidity using the accelerated Rancimat method. Their activities expressed as protection factor (PF(r)) indicated that the fractions rich with phenylpropanoid glycosides were more potent compared to alpha-tocopherol and of the same magnitude as BHT, which were used as reference standards. Ten natural compounds were identified as components of this methanolic extract and were isolated by medium-pressure liquid chromatography (MPLC). Assessment of their antioxidant activities established that acteoside, a polyhydroxylated phenylpropanoid glycoside derivative, is the most potent free radical scavenger and showed the highest protection factor (PF(r)) against sunflower-oil-induced oxidative rancidity. Its activity is comparable to the synthetic antioxidant BHT and clearly superior to natural alpha-tocopherol. This compound therefore represents a very interesting candidate for use in food preservation as natural protecting agent against oxidative rancidity. 相似文献
25.
A new monodesmosidic spirostanol saponin, along with three known saponins was isolated from Agave macroacantha Zucc leaves. The structure of the new saponin was established as hecogenin-3-O-α-l-rhamnopyranosyl (1→4) β-d-xylopyranosyl (1→3)[β-d-glucopyranosyl (1→2)] β-d-glucopyranosyl (1→4) β-d-galactopyranoside. The 1H and 13C resonances of the four compounds were assigned using a combination of 1D and 2D NMR techniques including 1H, 13C, COSY, TOCSY, ROESY, HSQC and HMBC NMR and confirmed by mass spectrometry. 相似文献
26.
Role of endothelium and nitric oxide in modulating in vitro responses of colonic arterial and venous rings to vasodilatory neuropeptides in horses 下载免费PDF全文
Rustin M. Moore Steven A. Sedrish Earnestine P. Holmes Catherine E. Koch Changaram S. Venugopal 《Canadian journal of veterinary research》2005,69(2):116-122
The objective of this study was to determine and compare the in vitro responses of equine large colon arterial and venous rings to vasodilatory neuropeptides; calcitonin gene-related peptide (CGRP); substance P (SP); vasoactive intestinal polypeptide (VIP); and acetylcholine (ACh), a standard nonpeptide endothelium-dependent vasodilator. Responses of vessel rings to graded concentrations (10(-11) M to 10(-5) M) of each drug were determined in endothelium-intact, denuded, and Nomega-nitro-L-arginine methyl ester (L-NAME, 10(-5) M)-treated rings that were pre-contracted with norepinephrine. Percentage maximal relaxation (PMR), defined as the % decrease from the contracted state, was determined. Because all rings did not relax at least 50%, EC50 values could not be consistently calculated. Arterial rings with intact endothelium were more sensitive to CGRP, compared with VIP and SP, and venous rings of all conditions were more sensitive to VIP than CGRP or SP. Overall, arteries had a greater PMR for ACh compared with SP and VIP. Intact and L-NAME treated arteries had a greater PMR than denuded arteries; there were no differences in PMR of intact and L-NAME treated arteries. Veins had a greater PMR for VIP than CGRP, SP, or ACh. Calcitonin gene-related peptide caused greater relaxation in intact arteries, whereas VIP causes greater relaxation in veins. Arterial relaxation was dependent upon the presence of intact endothelium. The response of veins to VIP among the conditions tested was not different, suggesting VIP has direct actions on venous smooth muscle. These neuropeptides modulate vasomotor tone via vasorelaxation in colonic arteries and veins. 相似文献
27.
Catherine Grondeau Alexandre Mabiala Rachid Ait-Oumeziane Régine Samson 《European journal of plant pathology / European Foundation for Plant Pathology》1996,102(4):353-363
Pseudomonas syringae pv.pisi, pea bacterial blight agent, is seed-transmitted. Some aspects of its life cycle and its biology were investigated. The colonization of pea plants obtained from naturally infected seeds was studied in natural conditions while high populations of bacteria developed on plants showing no symptoms. Two streptomycin-resistant mutants were used to study the epiphytic life of the pathogen. Populations were monitored in different host-parasite compatibilities. When race 2 or race 6 of the pathogen was surface-inoculated on susceptible cultivars, a decrease of population size was observed during the following one to three days but was followed by an increase to levels 1000 times greater than the initial number detected, without symptoms for most of the plants. When race 2 was surface-inoculated on resistant genotypes or race 6 on non-host plants, bacteria did not multiply but population levels slightly decreased.Pseudomonas syringae pv.pisi shows a resident phase and its development is race-specific. Weeds collected in naturally contaminated pea fields, diseased or not, often harboured the pathogen but with levels smaller than those observed on peas. Pea crop debris and volunteers kept high levels of bacteria for at least eight months after the harvest of a diseased crop. As long as two pea crops are not grown one after the other in the same field, it is unlikely that debris and volunteers will act as an important inoculum source. The development of this pathogen during the growing season is considered as an important parameter to take into account for controlling the disease through seed health testing. 相似文献
28.
Catherine Albertini Michel Gredt Pierre Leroux 《European journal of plant pathology / European Foundation for Plant Pathology》2003,109(2):117-128
Cereal eyespot fungi Tapesia acuformis and Tapesia yallundae are closely related species which show different behaviours upon treatment with sterol 14-demethylase inhibitors (DMIs). T. acuformis is naturally resistant to DMIs belonging to the triazole family and susceptible to the imidazole ones, whilst T. yallundae is sensitive to both inhibitors. Cloning of the target enzyme gene, CYP51, from the two species revealed an important polymorphism between them. Further sequencing of CYP51 from sixteen T. acuformis and eleven T. yallundae strains with different phenotypes with regards to resistance to DMIs confirmed that at least eleven variations are species related. Among them, a conserved phenylalanine residue at position 180, found both in T. yallundae and in all known CYP51 proteins from filamentous fungi and yeast, was replaced in T. acuformis by a leucine. Therefore, a leucine at 180 could be possibly involved in natural resistance of T. acuformis to triazoles. Other mutations were observed in some resistant strains, sometimes simultaneously, but in contrast to what was reported for other filamentous fungi, where a mutation at the 136 position of the CYP51 gene product seemed to correlate with resistance to DMIs, we did not find a clear relationship between a given mutation and a particular phenotype. This result suggests that resistance to DMIs could have a polygenic nature in Tapesia. We took advantage of species-related variations to develop a PCR-based assay allowing rapid and easy discrimination between field strains of the two species. 相似文献
29.
Alinovi CA Ward MP Couëtil LL Wu CC 《Journal of the American Veterinary Medical Association》2003,223(11):1640-1644
OBJECTIVES: To assess methods of detecting environmental contamination with Salmonella organisms and evaluate a cleaning and disinfection protocol for horse stalls in a veterinary teaching hospital. DESIGN: Original study. SAMPLE POPULATION: 37 horses with diarrhea likely to be caused by Salmonella infection and their stall environments. PROCEDURES: Fecal samples were collected from horses daily during hospitalization; samples were obtained from stall sites after cleaning and application of disinfectants. Fecal and environmental samples were cultured for Salmonella spp and tested via polymerase chain reaction (PCR) assay to detect Salmonella DNA. RESULTS: 1 horse died and 2 were discharged prior to sample collection. Fecal samples from 9 of 34 horses yielded growth of Salmonella organisms on bacteriologic culture, and 23 yielded positive results via PCR assay on > or = 1 occasion. Among environmental samples from 21 stalls, salmonellae were detected at > or = 1 stall site on 6 of 78 occasions, and > or = 1 stall site yielded positive results via PCR assay on 69 of 77 occasions. Salmonella DNA was detected more frequently in samples of stall drains, cracks, and corners. Salmonella spp were cultured from samples of 3 stalls after both initial and second cleaning and disinfection cycles, but no organisms were detected in samples obtained after use of a peroxygen disinfectant. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that stalls in which horses with salmonellosis were housed should only be used to accommodate newly hospitalized horses after samples (collected after 2 cycles of cleaning and disinfection) from drains, cracks, and corners yield negative results on bacteriologic culture. 相似文献
30.