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111.
112.
Yali Xue Yuan Chen Qasim Ayub Ni Huang Edward?V. Ball Matthew Mort Andrew?D. Phillips Katy Shaw Peter?D. Stenson David?N. Cooper Chris Tyler-Smith the Genomes Project Consortium 《American journal of human genetics》2012,91(6):1022-1032
We have assessed the numbers of potentially deleterious variants in the genomes of apparently healthy humans by using (1) low-coverage whole-genome sequence data from 179 individuals in the 1000 Genomes Pilot Project and (2) current predictions and databases of deleterious variants. Each individual carried 281–515 missense substitutions, 40–85 of which were homozygous, predicted to be highly damaging. They also carried 40–110 variants classified by the Human Gene Mutation Database (HGMD) as disease-causing mutations (DMs), 3–24 variants in the homozygous state, and many polymorphisms putatively associated with disease. Whereas many of these DMs are likely to represent disease-allele-annotation errors, between 0 and 8 DMs (0–1 homozygous) per individual are predicted to be highly damaging, and some of them provide information of medical relevance. These analyses emphasize the need for improved annotation of disease alleles both in mutation databases and in the primary literature; some HGMD mutation data have been recategorized on the basis of the present findings, an iterative process that is both necessary and ongoing. Our estimates of deleterious-allele numbers are likely to be subject to both overcounting and undercounting. However, our current best mean estimates of ∼400 damaging variants and ∼2 bona fide disease mutations per individual are likely to increase rather than decrease as sequencing studies ascertain rare variants more effectively and as additional disease alleles are discovered. 相似文献
113.
Wasserman K.; Beaver W. L.; Davis J. A.; Pu J. Z.; Heber D.; Whipp B. J. 《Journal of applied physiology》1985,59(3):935-940
The pattern of lactate increase and its relation to pyruvate and lactate-to-pyruvate (L/P) ratio were studied during exercise and early recovery in 10 normal subjects for incremental exercise on a cycle ergometer. Gas exchange was measured breath by breath. Lactate and pyruvate were measured by enzymatic techniques. Lactate and log lactate changed only slightly at low levels of O2 uptake (VO2) but both began to abruptly increase at approximately 40-55% of the maximal VO2. However, the point of abrupt increase in pyruvate occurred at higher work rates and the rate of increase was not as great as that for lactate. Thus L/P ratio increased at the same VO2 as the log lactate increase. Following the exercise, pyruvate continued to increase steeply for at least the first 5 recovery min, whereas at 2 min lactate increased only slightly or decreased. Thus arterial L/P ratio reversed its direction of change and decreased toward the resting value by 2 min of recovery. Lactate, as well as L/P ratios, decreased in all subjects by 5 min. This study demonstrates that lactate and pyruvate concentrations increase slightly at low levels of exercise without a change in L/P ratio until a threshold work rate at which lactate abruptly increases without pyruvate. The resulting increase in L/P ratio is progressive as work rate is incremented and abruptly reverses when exercise stops. 相似文献
114.
David Chiszar Barbara O'Connell Robin Greenlee Bela Demeter Trooper Walsh Joan Chiszar Katy Moran Hobart M. Smith 《Zoo biology》1985,4(3):291-294
Rattlesnakes typically strike and release adult rodent prey. Striking is followed by a sustained, high rate of tongue flicking that guides the snake to the envenomated, dead prey. Wild-caught rattlesnakes exhibited this chemosensory searching for about 2.5 h, and the present study demonstrated that long-term captive rattlesnakes (Crotalus atrox, C durissus, C horridus, C vegrandis, C unicolor) at three zoos did the same. Because these zoo-raised snakes had always been offered dead rodents and because the snakes had become accustomed to ingesting them without striking, the present snakes had rarely exercised their innate predatory repertoires. The duration of chemosensory searching in these snakes indicates that this important aspect of the predatory repertoire had not been degraded as a consequence of long-term captive husbandry. 相似文献
115.
Raising intracellular calcium levels can induce apoptosis or programmed cell death in many cells. While early rises in intracellular calcium are not universally associated with apoptotic cell death, calcium clearly plays a key role in many of the biochemical events which occur during apoptosis. In this paper we have determined intracellular calcium rises induced by 2, 10, and 100 nMthapsigargin in mouse thymocytes. These concentrations cause increases in cytosolic calcium of 100–250, 400–600, and >1000 nM,respectively. These rises are sustained for at least 85 min and the ratio between the maximum rise caused by 10 nMcompared to 2 nMthapsigargin is 2.1 ± 0.4 (n= 6). Both 2 and 10 nMthapsigargin cause apoptosis at 24 h as shown by DNA fragmentation and morphology when examined by electron microscopy. Cyclosporin A (CsA) inhibits apoptosis caused by 2 nMthapsigargin but not that caused by 10 nMthapsigargin. Electron microscopy of thymocytes treated with 2 nMthapsigargin at 24 h shows intact mitochondria although with altered morphology. There is no loss of ATP or decrease in the ATP/ADP ratio in these cells over 12 h. Mitochondria in cells treated with 10 nMthapsigargin, however, are swollen by 6 h and many are lost by 24 h. These cells show greatly diminished ATP content by 12 h and a decrease in ATP/ADP ratio. Examination of the effects of PMA, an activator of the plasma membrane calcium ATPase pump, on cells treated with 10 nMthapsigargin suggests that two pools of calcium may be responsible for the differential effects of the two calcium levels in the cells. Probing of the mitochondrial membrane potential (MMP) by rhodamine 123 staining of live cells shows that the collapse of the MMP caused by 10 nMthapsigargin is unaffected by CsA. The MMP is also reduced in cells treated with 2 nMthapsigargin but this is restored by CsA. Cells are also rescued from apoptosis caused by 2 nMthapsigargin by incubation with FK506. This immunosuppressive agent has no effect on the membrane permeability transition induced in isolated mitochondria. These results suggest that very low rises in intracellular calcium in thymocytes cause activation-induced cell death inhibited by CsA and FK506 and are without effect on ATP levels and therefore do not involve irreversible mitochondrial damage. Exceeding these calcium levels by only twofold results in apoptosis accompanied by reduced ATP levels and mitochondrial damage, although apoptotic cell death in this instance is unaffected by the classic inhibitor of mitochondrial permeability transition, CsA. 相似文献
116.
117.
Intrapopulation genomics in a model mutualist: Population structure and candidate symbiosis genes under selection in Medicago truncatula
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Michael A. Grillo Stephane De Mita Patricia V. Burke Kathryn L. S. Solórzano‐Lowell Katy D. Heath 《Evolution; international journal of organic evolution》2016,70(12):2704-2717
Bottom‐up evolutionary approaches, including geographically explicit population genomic analyses, have the power to reveal the mechanistic basis of adaptation. Here, we conduct a population genomic analysis in the model legume, Medicago truncatula, to characterize population genetic structure and identify symbiosis‐related genes showing evidence of spatially variable selection. Using RAD‐seq, we generated over 26,000 SNPs from 191 accessions from within three regions of the native range in Europe. Results from STRUCTURE analysis identify five distinct genetic clusters with divisions that separate east and west regions in the Mediterranean basin. Much of the genetic variation is maintained within sampling sites, and there is evidence for isolation by distance. Extensive linkage disequilibrium was identified, particularly within populations. We conducted genetic outlier analysis with FST‐based genome scans and a Bayesian modeling approach (PCAdapt). There were 70 core outlier loci shared between these distinct methods with one clear candidate symbiosis related gene, DMI1. This work sets that stage for functional experiments to determine the important phenotypes that selection has acted upon and complementary efforts in rhizobium populations. 相似文献
118.
Role of algae in the diet of Chironomus plumosus F. semireductus from the Bay of Quinte,Lake Ontario
The importance of algae and different algal species to the chironomid diet was investigated through examination of the guts of chironomids taken from 5 locations in Big Bay (Bay of Quinte, Lake Ontario) at 6 times during the ice-free period. A comparison of the density and condition of algal cells at the two ends of the gut provided information on the digestibility of each algal species and the algal biomass assimilated by the chironomids. Diatoms and two species of green algae were assimilated over much of the summer, but the blue green algae were digested only late in the season when their populations were aged and/or dying. In terms of energy contribution, diatoms, especially Stephanodiscus spp. and Melosira spp., were most important in May (99% of all algal biomass assimilated), August (98%), and Octobr (92%), while the blue green species, Microcystis aeruginosa, was predominant in September (76%). Only a few small greens were assimilated in June and July. The contribution of algae as a food source to chironomid energetics was small, and reached a maximum in August and September (15%–34%). It is postulated that bacteria are a more important food source. 相似文献
119.
We evaluated a biomanipulation program to test for short-term changes in water quality (chlorophyll a, Secchi depth, total phosphorus) and macrozooplankton biomass following partial removal of omnivorous gizzard shad Dorosoma cepedianum. The removal occurred at a eutrophic subtropical lake, and responses were compared to an unmanipulated control lake using
a before-after-control-impact paired series analysis. The removal reduced the biomass of large (>300 mm) gizzard shad by 75%
over 2 years via a subsidized commercial gill net fishery. However, the total population biomass of gizzard shad was reduced
by approximately 32% from an average pre-manipulation biomass of 224 kg ha−1 due to the size selectivity of the gear, which did not effectively capture small fish (<300 mm). No significant short-term
changes in chlorophyll a concentration, Secchi depth, total phosphorus concentration or macrozooplankton biomass were detected following biomanipulation.
The partial removal may have fallen short of the biomass reduction required to cause ecosystem responses. Our results suggest
that moderate omnivore removals (i.e., <40% biomass reduction) will have little short-term benefits to these lakes, and future
manipulations should use a less size-selective gear to achieve a larger total biomass reduction. 相似文献
120.