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91.
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Wanwisa Dejnirattisai Daming Zhou Helen M. Ginn Helen M.E. Duyvesteyn Piyada Supasa James Brett Case Yuguang Zhao Thomas S. Walter Alexander J. Mentzer Chang Liu Beibei Wang Guido C. Paesen Jose Slon-Campos César López-Camacho Natasha M. Kafai Adam L. Bailey Rita E. Chen Baoling Ying Gavin R. Screaton 《Cell》2021,184(8):2183-2200.e22
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93.
George M. Giambaşu Tyler Luchko Daniel Herschlag Darrin M. York David A. Case 《Biophysical journal》2014
The ionic atmosphere around nucleic acids remains only partially understood at atomic-level detail. Ion counting (IC) experiments provide a quantitative measure of the ionic atmosphere around nucleic acids and, as such, are a natural route for testing quantitative theoretical approaches. In this article, we replicate IC experiments involving duplex DNA in NaCl(aq) using molecular dynamics (MD) simulation, the three-dimensional reference interaction site model (3D-RISM), and nonlinear Poisson-Boltzmann (NLPB) calculations and test against recent buffer-equilibration atomic emission spectroscopy measurements. Further, we outline the statistical mechanical basis for interpreting IC experiments and clarify the use of specific concentration scales. Near physiological concentrations, MD simulation and 3D-RISM estimates are close to experimental results, but at higher concentrations (>0.7 M), both methods underestimate the number of condensed cations and overestimate the number of excluded anions. The effect of DNA charge on ion and water atmosphere extends 20–25 Å from its surface, yielding layered density profiles. Overall, ion distributions from 3D-RISMs are relatively close to those from corresponding MD simulations, but with less Na+ binding in grooves and tighter binding to phosphates. NLPB calculations, on the other hand, systematically underestimate the number of condensed cations at almost all concentrations and yield nearly structureless ion distributions that are qualitatively distinct from those generated by both MD simulation and 3D-RISM. These results suggest that MD simulation and 3D-RISM may be further developed to provide quantitative insight into the characterization of the ion atmosphere around nucleic acids and their effect on structure and stability. 相似文献
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Species distributional limits may coincide with hard dispersal barriers or physiological thresholds along environmental gradients, but they may also be influenced by species interactions. We explore a number of models of interspecific interactions that lead to (sometimes abrupt) distribution limits in the presence and absence of environmental gradients. We find that gradients in competitive ability can lead to spatial segregation of competitors into distinct ranges, but that spatial movement tends to broaden the region of sympatry between the two species, and that Allee effects tend to sharpen these boundaries. We generalize these simple models to include metapopulation dynamics and other types of interactions including predator–prey and host–parasite interactions. We derive conditions for range limits in each case. We also consider models that include coevolution and gene flow and find that character displacement along environmental gradients can lead to stable parapatric distributions. We conclude that it is essential to consider coevolved species interactions as a potential mechanism limiting species distributions, particularly when barriers to dispersal are weak and environmental gradients are gradual. 相似文献
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The purpose of this technical report is to determine the reproducibility of flow cytometry data for ploidy and cell cycle kinetics using paraffin-embedded blocks of breast cancer tissue. One block from each of 39 tumors was studied in this report with each block having multiple sections analyzed independently. All of these sections gave ploidy analyses, while only 34 gave cell kinetic values. The standard deviation for the DNA index value in the multiple analysis study was less than 0.1 in all but three cases. The cell kinetic values gave larger variability, and the actual values were dependent on the method of analysis. Comparison of the variability for each method of analysis could not predict which procedure was superior. These results would indicate that ploidy is a reproducible value, while cell kinetic parameters should only be used as an indicator of proliferative activity that has been normalized to the mean or median of a large set of observations processed and analyzed by the same procedure. 相似文献
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Halesha D. Basavarajappa Bit Lee Xiang Fei Daesung Lim Breedge Callaghan Julie A. Mund Jamie Case Gangaraju Rajashekhar Seung-Yong Seo Timothy W. Corson 《PloS one》2014,9(4)
Preventing pathological ocular angiogenesis is key to treating retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. At present there is no small molecule drug on the market to target this process and hence there is a pressing need for developing novel small molecules that can replace or complement the present surgical and biologic therapies for these neovascular eye diseases. Previously, an antiangiogenic homoisoflavanone was isolated from the bulb of a medicinal orchid, Cremastra appendiculata. In this study, we present the synthesis of a novel homoisoflavanone isomer of this compound. Our compound, SH-11052, has antiproliferative activity against human umbilical vein endothelial cells, and also against more ocular disease-relevant human retinal microvascular endothelial cells (HRECs). Tube formation and cell cycle progression of HRECs were inhibited by SH-11052, but the compound did not induce apoptosis at effective concentrations. SH-11052 also decreased TNF-α induced p38 MAPK phosphorylation in these cells. Intriguingly, SH-11052 blocked TNF-α induced IκB-α degradation, and therefore decreased NF-κB nuclear translocation. It decreased the expression of NF-κB target genes and the pro-angiogenic or pro-inflammatory markers VCAM-1, CCL2, IL8, and PTGS2. In addition SH-11052 inhibited VEGF induced activation of Akt but not VEGF receptor autophosphorylation. Based on these results we propose that SH-11052 inhibits inflammation induced angiogenesis by blocking both TNF-α and VEGF mediated pathways, two major pathways involved in pathological angiogenesis. Synthesis of this novel homoisoflavanone opens the door to structure-activity relationship studies of this class of compound and further evaluation of its mechanism and potential to complement existing antiangiogenic drugs. 相似文献