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71.
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
72.
Keller LP Bajt S Baratta GA Borg J Bradley JP Brownlee DE Busemann H Brucato JR Burchell M Colangeli L d'Hendecourt L Djouadi Z Ferrini G Flynn G Franchi IA Fries M Grady MM Graham GA Grossemy F Kearsley A Matrajt G Nakamura-Messenger K Mennella V Nittler L Palumbo ME Stadermann FJ Tsou P Rotundi A Sandford SA Snead C Steele A Wooden D Zolensky M 《Science (New York, N.Y.)》2006,314(5806):1728-1731
Infrared spectra of material captured from comet 81P/Wild 2 by the Stardust spacecraft reveal indigenous aliphatic hydrocarbons similar to those in interplanetary dust particles thought to be derived from comets, but with longer chain lengths than those observed in the diffuse interstellar medium. Similarly, the Stardust samples contain abundant amorphous silicates in addition to crystalline silicates such as olivine and pyroxene. The presence of crystalline silicates in Wild 2 is consistent with mixing of solar system and interstellar matter. No hydrous silicates or carbonate minerals were detected, which suggests a lack of aqueous processing of Wild 2 dust. 相似文献
73.
Hillenmeyer ME Fung E Wildenhain J Pierce SE Hoon S Lee W Proctor M St Onge RP Tyers M Koller D Altman RB Davis RW Nislow C Giaever G 《Science (New York, N.Y.)》2008,320(5874):362-365
Genetics aims to understand the relation between genotype and phenotype. However, because complete deletion of most yeast genes ( approximately 80%) has no obvious phenotypic consequence in rich medium, it is difficult to study their functions. To uncover phenotypes for this nonessential fraction of the genome, we performed 1144 chemical genomic assays on the yeast whole-genome heterozygous and homozygous deletion collections and quantified the growth fitness of each deletion strain in the presence of chemical or environmental stress conditions. We found that 97% of gene deletions exhibited a measurable growth phenotype, suggesting that nearly all genes are essential for optimal growth in at least one condition. 相似文献
74.
75.
Mike Greenblatt Christopher L. Brown Michael Lee Silvia Dauder Howard A. Bern 《Fish physiology and biochemistry》1989,6(5):261-278
Developmental profiles of thyroxin (T4), triiodothyronine (T3) and radioactive iodide uptake were established for eggs and T4 and T3 profiles were established for larvae (whole-body, yolk-only and body-only) of coho and chinook salmon. T4 and T3 were consistently present in all samples. In eggs, hormone levels remained fairly constant in all cohorst for at least the first three weeks of incubation, but then fluctuated in both directions in some sample groups. Large increases in T4 (from 9 ng/g to 245 ng/g) were seen in 1985 chinook eggs 28 days after fertilization. Radioactive iodide uptake (which was used as a possible indicator of thyroxinogenesis) increased at least 10-fold in both 1986 coho and chinook eggs from 23–30 days after fertilization. T4 (62 ng/g) and T3 (393 ng/g) were found in the bodies of 28-day-old 1986 chinook embryos. In whole larvae, hormone levels varied depending upon the cohort studied. In general, initial body-only concentrations of both T4 and T3 decreased as body weight increased, but before yolksac resorption was completed, both thyroid hormone content and concentration increased (except for chinook T3). T4 and T3 content in larval yolk stayed constant as yolksac size decreased, resulting in increased thyroid hormone concentration in the yolksac. All of these data suggest that the initial source of thyroid hormones in coho and chinook salmon eggs is maternal, but that by approximately 3–4 weeks after fertilization, the developing embryos begin to produce their own thyroid hormones. After hatching, increases in tissue T4 and T3 concentration coupled with constant T4 and T3 content in diminishing yolksacs suggest that larvae also produce their own thyroid hormones; yolksac content then may reflect both the original maternal hormones and the larva-producted hormones. 相似文献
76.
77.
Yuwaraj K. Narnaware Bridget I. Baker Mike G. Tomlinson 《Fish physiology and biochemistry》1994,13(1):31-40
The effect of acute and chronic stress on the phagocytic activity of putative macrophages from the rainbow trout. Oncorhynchus mykiss has been assessed, using an in vitro phagocytic index, in which the average number of engulfed yeast cells in a population of phagocytes is determined. An injection
stress given under light anaesthesia, or a longer noise stress combined with confinement, both significantly reduced, within
3 h, the level of phagocytic activity of macrophages from the spleen and pronephros. Daily injection stress over six days
had a lesser effect on the proportion of phagocytically active cells even though plasma cortisol levels were equally raised.
Daily dexamethasone injection depressed the proportion of phagocytically active cells more than saline injection. In these
in vivo experiments, it was not possible to determine whether stress and steroids depressed the phagocytic activity of individual
macrophages or caused the active macrophages to migrate out of the spleen and pronephros. Administration of cortisol (200
nM) to trout macrophages in vitro failed to depress phagocytic activity within a 3h period but both α- and β-adrenergic agonists (10 μM) were usually depressive.
It is proposed that the autonomic nervous system may be an early regulator of macrophage phagocytosis following stress and
that corticosteroids only exert their suppressive effect on macrophage activity in the longer term.
To whom reprint requests should be addressed. 相似文献
78.
Niels Madsen Roar Skeide Mike Breen Ludvig A. Krag Irene Huse Aud V. Soldal 《Fisheries Research》2008,91(2-3):168-174
The selectivity of a 99 mm trawl codend was assessed using a codend cover fitted with a MultiSampler, which was acoustically triggered to take separate samples at three different phases of the haul. The first sample was collected during towing, the second during haul-up and the third at the surface. A total of 18 hauls were conducted with a commercial fishing vessel west of Scotland. It was demonstrated that escapes take place not only during the tow but also in the short period when the trawl is hauled back from the seabed and when the codend is at the surface. For haddock (Melanogrammus aeglefinus), whiting (Merlangius merlangus) and Norway lobster (Nephrops norvegicus), respectively, the mean percentages escaping at the surface were 16, 12 and 38% of the total escape while 17, 8 and 28% escaped during the haul-up phase. Compared to towing, the escape rate (no./min) increased for haddock by a factor 2.7 during haul-up and by a factor 1.7 at the surface, whereas the escape rates of whiting were similar for the three phases. The escape rate of Norway lobster increased by a factor of approximately 7 for both the haul-up and surface phases, compared to the towing phase. The selectivity parameters L50 (50% retention length) and SR (selection range = L75–L25) were estimated and compared for the three different phases and for the whole haul for haddock, whiting and Norway lobster. For all three species there was no significant (P > 0.05) difference in L50 between the three phases of the haul. There was also no significant difference for whiting and Norway lobster when comparing the SR of the three phases, whereas the SR was significantly lower for haddock when comparing the surface phase with towing and haul-up. The estimate of L50 when towing was about 6 cm lower for haddock and whiting and 9 mm for Norway lobster compared to the selection curve estimated conventionally for the whole haul. Finally, the effect of sea state, duration and codend catch on the selectivity parameters were estimated for the individual phases and for the whole haul. A significant effect of at least one variable was found in all phases. 相似文献
79.
Herdt TH Neuder LM Green CD Fordyce MG Dill KJ Mahoney JH 《Journal of veterinary medical education》2008,35(1):48-50
Cooperative programs with agribusiness offer opportunities for colleges of veterinary medicine to expand their instructional programs in agricultural practice. Agribusinesses associated with livestock agriculture recognize the importance of veterinary medicine in maintaining a vibrant and successful industry. Stewardship of corporate support involves close communication with advocates within the companies, providing them with documentation of the potential effects of corporate investments. This article describes the creation of the Michigan State University (MSU) Training Center for Dairy Professionals, a key aspect of which was the identification of innovative and productive areas of mutual interest and benefit. In addition to supporting the dairy industry by training veterinary students, the program offers specific benefits to investors, including the use of MSU facilities and direct participation in veterinary instruction. 相似文献
80.