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排序方式: 共有188条查询结果,搜索用时 15 毫秒
1.
DNA replication in Physarum polycephalum: electron microscopic and autoradiographic analysis of replicating DNA from defined stages of the S-period. 总被引:12,自引:2,他引:10 下载免费PDF全文
Electron microscopic and autoradiographic analysis of replicating DNA from Physarum showed that replication occurs at a rate of 0.4 micron/min/per replicon and that replicons of size 10--15 mu occur in temporal clusters with an average of about 4 replicons per cluster. These results are compared with previous hydrodynamic measurements and with those obtained in other organisms. 相似文献
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Ole?A. Andreassen Srdjan Djurovic Wesley?K. Thompson Andrew?J. Schork Kenneth?S. Kendler Michael?C. O’Donovan Dan Rujescu Thomas Werge Martijn van?de?Bunt Andrew?P. Morris Mark?I. McCarthy International Consortium for Blood Pressure GWAS Diabetes Genetics Replication Meta-analysis Consortium Psychiatric Genomics Consortium Schizophrenia Working Group J.?Cooper Roddey Linda?K. McEvoy Rahul?S. Desikan Anders?M. Dale 《American journal of human genetics》2013,92(2):197-209
Several lines of evidence suggest that genome-wide association studies (GWASs) have the potential to explain more of the “missing heritability” of common complex phenotypes. However, reliable methods for identifying a larger proportion of SNPs are currently lacking. Here, we present a genetic-pleiotropy-informed method for improving gene discovery with the use of GWAS summary-statistics data. We applied this methodology to identify additional loci associated with schizophrenia (SCZ), a highly heritable disorder with significant missing heritability. Epidemiological and clinical studies suggest comorbidity between SCZ and cardiovascular-disease (CVD) risk factors, including systolic blood pressure, triglycerides, low- and high-density lipoprotein, body mass index, waist-to-hip ratio, and type 2 diabetes. Using stratified quantile-quantile plots, we show enrichment of SNPs associated with SCZ as a function of the association with several CVD risk factors and a corresponding reduction in false discovery rate (FDR). We validate this “pleiotropic enrichment” by demonstrating increased replication rate across independent SCZ substudies. Applying the stratified FDR method, we identified 25 loci associated with SCZ at a conditional FDR level of 0.01. Of these, ten loci are associated with both SCZ and CVD risk factors, mainly triglycerides and low- and high-density lipoproteins but also waist-to-hip ratio, systolic blood pressure, and body mass index. Together, these findings suggest the feasibility of using genetic-pleiotropy-informed methods for improving gene discovery in SCZ and identifying potential mechanistic relationships with various CVD risk factors. 相似文献
4.
The African Black Oystercatcher Haematopus moquini is a charismatic, southern African near-endemic, wader species, that is often seen as a flagship species for coastal bird conservation, as it was recently down-listed regionally to Least Concern on the IUCN Red List of Threatened Species. To celebrate this rare conservation success story, BirdLife South Africa named it the 2018 Bird of the Year and ran a year-long programme in collaboration with the Nature’s Valley Trust highlighting aspects of the species’ biology, current threats, and conservation success. We used data collected by the Southern African Bird Atlas Project (SABAP1 and SABAP2) to examine changes in the species’ range and relative abundance, both in the records between the two projects, as well as trends within the SABAP2 sampling period (2008–2017). This case study enabled us to assess whether such metrics can accurately reflect abundance and distributional changes in a species. We found increases in the reported range and the reporting rates between the two Atlas projects, and that the SABAP2 reporting rate was stable. Regionally, across four coastal categories, the reporting rate was lowest in KwaZulu-Natal, though this region also showed an increase in the probability of reporting during the SABAP2 period. While corroborating the recent change in the species’ conservation status, we also provide good evidence that the long-term SABAP data can be used successfully to assess population trends and range changes over time. 相似文献
5.
Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis 总被引:22,自引:0,他引:22
Klivenyi P Ferrante RJ Matthews RT Bogdanov MB Klein AM Andreassen OA Mueller G Wermer M Kaddurah-Daouk R Beal MF 《Nature medicine》1999,5(3):347-350
Mitochondria are particularly vulnerable to oxidative stress, and mitochondrial swelling and vacuolization are among the earliest pathologic features found in two strains of transgenic amyotrophic lateral sclerosis (ALS) mice with SOD1 mutations. Mice with the G93A human SOD1 mutation have altered electron transport enzymes, and expression of the mutant enzyme in vitro results in a loss of mitochondrial membrane potential and elevated cytosolic calcium concentration. Mitochondrial dysfunction may lead to ATP depletion, which may contribute to cell death. If this is true, then buffering intracellular energy levels could exert neuroprotective effects. Creatine kinase and its substrates creatine and phosphocreatine constitute an intricate cellular energy buffering and transport system connecting sites of energy production (mitochondria) with sites of energy consumption, and creatine administration stabilizes the mitochondrial creatine kinase and inhibits opening of the mitochondrial transition pore. We found that oral administration of creatine produced a dose-dependent improvement in motor performance and extended survival in G93A transgenic mice, and it protected mice from loss of both motor neurons and substantia nigra neurons at 120 days of age. Creatine administration protected G93A transgenic mice from increases in biochemical indices of oxidative damage. Therefore, creatine administration may be a new therapeutic strategy for ALS. 相似文献
6.
We have analyzed a total of 12 different global and local multiple
protein-sequence alignment methods. The purpose of this study is to
evaluate each method's ability to correctly identify the ordered series of
motifs found among all members of a given protein family. Four
phylogenetically distributed sets of sequences from the hemoglobin, kinase,
aspartic acid protease, and ribonuclease H protein families were used to
test the methods. The performance of all 12 methods was affected by (1) the
number of sequences in the test sets, (2) the degree of similarity among
the sequences, and (3) the number of indels required to produce a multiple
alignment. Global methods generally performed better than local methods in
the detection of motif patterns.
相似文献
7.
Anders V. Pedersen Thorvald F. Andreassen Claus J. Loland 《The Journal of biological chemistry》2014,289(50):35003-35014
Neurotransmitter transporters play an important role in termination of synaptic transmission by mediating reuptake of neurotransmitter, but the molecular processes behind translocation are still unclear. The crystal structures of the bacterial homologue, LeuT, provided valuable insight into the structural and dynamic requirements for substrate transport. These structures support the existence of gating domains controlling access to a central binding site. On the extracellular side, access is controlled by the “thin gate” formed by an interaction between Arg-30 and Asp-404. In the human dopamine transporter (DAT), the corresponding residues are Arg-85 and Asp-476. Here, we present results supporting the existence of a similar interaction in DAT. The DAT R85D mutant has a complete loss of function, but the additional insertion of an arginine in opposite position (R85D/D476R), causing a charge reversal, results in a rescue of binding sites for the cocaine analogue [3H]CFT. Also, the coordination of Zn2+ between introduced histidines (R85H/D476H) caused a ∼2.5-fold increase in [3H]CFT binding (Bmax). Importantly, Zn2+ also inhibited [3H]dopamine transport in R85H/D476H, suggesting that a dynamic interaction is required for the transport process. Furthermore, cysteine-reactive chemistry shows that mutation of the gating residues causes a higher proportion of transporters to reside in the outward facing conformation. Finally, we show that charge reversal of the corresponding residues (R104E/E493R) in the serotonin transporter also rescues [3H](S)-citalopram binding, suggesting a conserved feature. Taken together, these data suggest that the extracellular thin gate is present in monoamine transporters and that a dynamic interaction is required for substrate transport. 相似文献
8.
Rix BA 《Bioethics》1991,5(3):250-256
... The allocation of resources can indirectly control science by defining areas undesirable for research from the point of view of society. In the United States federal funds are not available for research on human embryos. The European experience represents a new approach to control of scientific research. The project is neither prohibited nor accepted in accordance with certain ethical rules, but is followed throughout the project. This new approach originates from the complexity of the human genome project and its unpredictable consequences for man. 相似文献
9.
Little is known about the effect of exercise training on the expression of adiponectin receptor genes in peripheral blood mononuclear cells (PBMCs). In this study, we investigated the effects of aerobic training on the expression of AdipoR1 and AidpoR2 mRNAs in PBMCs, whole body insulin sensitivity, and circulating adiponectins in men. Thirty young men were randomly assigned to either a control (n=15) or an exercise (n=15) group. Subjects assigned to the exercise group underwent a 12-week jogging and/or running programme on a motor-driven treadmill at an intensity of 60%-75% of the age-based maximum heart rate with duration of 40 minutes per session and a frequency of 5 days per week. Two-way mixed ANOVA with repeated measures was used to test any significant time-by-group interaction effects for the measured variables at p=0.05. We found significant time-by-group interaction effects for waist circumference (p=0.001), VO2max (p<0.001), fasting insulin (p=0.016), homeostasis model assessment for insulin resistance (HOMA-IR) (p=0.010), area under the curve (AUC) for insulin response during the 75-g oral glucose tolerance test (p=0.002), high-molecular weight (HMW) adiponectin (p=0.016), and the PBMC mRNA levels of AdipoR1 (p<0.001) and AdipoR2 (p=0.001). The exercise group had significantly increased mRNA levels of AdipoR1 and AdipoR2 in PBMCs, along with increased whole body insulin sensitivity and HMW adiponectin, decreased waist circumference, and increased VO2max compared with the control group. In summary, the current findings suggest that exercise training modulates the expression of AdipoR1 and AdipoR2 mRNAs in PBMCs, implying that manipulation of the expression of these genes could be a potential surrogate for lifestyle intervention-mediated improvements of whole body insulin sensitivity and glucose homeostasis. 相似文献
10.