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131.
Tess V. Clendenen Justin Rendleman Wenzhen Ge Karen L. Koenig Isaac Wirgin Diane Currie Roy E. Shore Tomas Kirchhoff Anne Zeleniuch-Jacquotte 《PloS one》2015,10(8)
Background
Large epidemiologic studies have the potential to make valuable contributions to the assessment of gene-environment interactions because they prospectively collected detailed exposure data. Some of these studies, however, have only serum or plasma samples as a low quantity source of DNA.Methods
We examined whether DNA isolated from serum can be used to reliably and accurately genotype single nucleotide polymorphisms (SNPs) using Sequenom multiplex SNP genotyping technology. We genotyped 81 SNPs using samples from 158 participants in the NYU Women’s Health Study. Each participant had DNA from serum and at least one paired DNA sample isolated from a high quality source of DNA, i.e. clots and/or cell precipitates, for comparison.Results
We observed that 60 of the 81 SNPs (74%) had high call frequencies (≥95%) using DNA from serum, only slightly lower than the 85% of SNPs with high call frequencies in DNA from clots or cell precipitates. Of the 57 SNPs with high call frequencies for serum, clot, and cell precipitate DNA, 54 (95%) had highly concordant (>98%) genotype calls across all three sample types. High purity was not a critical factor to successful genotyping.Conclusions
Our results suggest that this multiplex SNP genotyping method can be used reliably on DNA from serum in large-scale epidemiologic studies. 相似文献132.
An individual-based, mass-spring modeling framework has been developed to investigate the effect of cell properties on the structure of biofilms and microbial aggregates through Lagrangian modeling. Key features that distinguish this model are variable cell morphology described by a collection of particles connected by springs and a mechanical representation of deformable intracellular, intercellular, and cell-substratum links. A first case study describes the colony formation of a rod-shaped species on a planar substratum. This case shows the importance of mechanical interactions in a community of growing and dividing rod-shaped cells (i.e., bacilli). Cell-substratum links promote formation of mounds as opposed to single-layer biofilms, whereas filial links affect the roundness of the biofilm. A second case study describes the formation of flocs and development of external filaments in a mixed-culture activated sludge community. It is shown by modeling that distinct cell-cell links, microbial morphology, and growth kinetics can lead to excessive filamentous proliferation and interfloc bridging, possible causes for detrimental sludge bulking. This methodology has been extended to more advanced microbial morphologies such as filament branching and proves to be a very powerful tool in determining how fundamental controlling mechanisms determine diverse microbial colony architectures. 相似文献
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Martin Welin J?rg Günter Grossmann Susanne Flodin Tomas Nyman P?l Stenmark Lionel Trésaugues Tetyana Kotenyova Ida Johansson P?r Nordlund Lari Lehti? 《Nucleic acids research》2010,38(20):7308-7319
Human purine de novo synthesis pathway contains several multi-functional enzymes, one of which, tri-functional GART, contains three enzymatic activities in a single polypeptide chain. We have solved structures of two domains bearing separate catalytic functions: glycinamide ribonucleotide synthetase and aminoimidazole ribonucleotide synthetase. Structures are compared with those of homologous enzymes from prokaryotes and analyzed in terms of the catalytic mechanism. We also report small angle X-ray scattering models for the full-length protein. These models are consistent with the enzyme forming a dimer through the middle domain. The protein has an approximate seesaw geometry where terminal enzyme units display high mobility owing to flexible linker segments. This resilient seesaw shape may facilitate internal substrate/product transfer or forwarding to other enzymes in the pathway. 相似文献
136.
Avery O. Tatters Harris I. Muhlstein Carmelo R. Tomas 《Journal of applied phycology》2010,22(4):435-442
Blooms of the toxic dinoflagellate, Karenia brevis, occur annually along the Gulf coast of Florida. Other species, like Karenia selliformis, are at times found in association. Hemolytic activity, the ability to lyse red blood cells, of two K. brevis clones (SP3 non-toxic (N-tox) and SP3 super toxic (S-tox)) from the Gulf of Mexico and a single clone of K. selliformis from New Zealand was investigated throughout a growth cycle. Activity is reported as effective concentration (EC50) values, the quantitative measure of hemolysis of human erythrocytes expressed as cell numbers. Both cells and media of K. selliformis cultures consistently produced potent levels of hemolysis (maximum EC50 = 4.88 × 103 cells) from inoculation until the population declined 35 days later. For SP3 N-tox and S-tox, no hemolytic activity was detectable
until day 26 of sampling. The media of both SP3 N-tox and SP3 S-tox cultures consistently contained non-detectable or low
levels of hemolysis compared to K. selliformis. Maximum EC50s for the SP3 clones were 1.80 × 106 and 1.97 × 106 cells, respectively. The experimental EC50 values observed represent ecologically relevant cell densities for K. selliformis, but not for the K. brevis clones. In addition, the hemolytic activity of gymnodimine A and various PbTx derivatives was examined in this study. Our
findings indicate that the hemolytic capability of these dinoflagellates, especially K. selliformis, represents an additional component of toxicity aside from their already recognized toxins and that this activity may play
a larger role than was previously considered. The purpose of this study was to extend the knowledge of the biology and toxicology
of species within the genus Karenia. 相似文献
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Hanessian S Larsson A Fex T Knecht W Blomberg N 《Bioorganic & medicinal chemistry letters》2010,20(23):6925-6928
The synthesis of a series of novel macrocyclic compounds designed to target blood coagulation Factor XIa is described. The compounds were evaluated for their inhibition of a small set of serine proteases. Several compounds displayed modest activity and good selectivity for Factor XIa. Within the series, a promising lead structure for developing novel macrocyclic inhibitors of thrombin was identified. 相似文献
140.
Yuanqing Tang Sergio Wittlin Susan A. Charman Jacques Chollet Francis C.K. Chiu Julia Morizzi Lisa M. Johnson Josefina Santo Tomas Christian Scheurer Chistopher Snyder Lin Zhou Yuxiang Dong William N. Charman Hugues Matile Heinrich Urwyler Arnulf Dorn Jonathan L. Vennerstrom 《Bioorganic & medicinal chemistry letters》2010,20(2):563-566
Thirty-three N-acyl 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. For these ozonides, weak base functional groups were not required for high antimalarial potency against Plasmodium falciparum in vitro, but were necessary for high antimalarial efficacy in Plasmodium berghei-infected mice. A wide range of Log P/DpH 7.4 values were tolerated, although more lipophilic ozonides tended to be less metabolically stable. 相似文献