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221.
Austin Chen Christopher Bayly Olivier Bezençon Sylvia Richard-Bildstein Daniel Dubé Laurence Dubé Sébastien Gagné Michel Gallant Mireille Gaudreault Erich Grimm Robert Houle Patrick Lacombe Sébastien Laliberté Jean-François Lévesque Suzanna Liu Dwight MacDonald Bruce Mackay David Martin Dan McKay David Powell Sylvie Toulmond 《Bioorganic & medicinal chemistry letters》2010,20(7):2204-2209
The discovery and SAR of a new series of substituted amino propanamide renin inhibitors are herein described. This work has led to the preparation of compounds with in vitro and in vivo profiles suitable for further development. Specifically, challenges pertaining to oral bioavailability, covalent binding and time-dependent CYP 3A4 inhibition were overcome thereby culminating in the identification of compound 50 as an optimized renin inhibitor with good efficacy in the hypertensive double-transgenic rat model. 相似文献
222.
223.
Evolutionary conservation of the immediate-early gene ZENK 总被引:3,自引:0,他引:3
224.
Chromosome numbers forAster brachyactis, A. frondosus, andA. laurentianus were determined to be 2n=14. The latter two are the first documented records for these taxa. The basic chromosome number for sectionConyzopsis is confirmed asx=7. 相似文献
225.
Ake Vastermark Simon Wollwage Michael E. Houle Rita Rio Milton H. Saier Jr. 《Proteins》2014,82(10):2797-2811
The amino acid‐polyamine‐organoCation (APC) superfamily is the second largest superfamily of secondary carriers currently known. In this study, we establish homology between previously recognized APC superfamily members and proteins of seven new families. These families include the PAAP (Putative Amino Acid Permease), LIVCS (Branched Chain Amino Acid:Cation Symporter), NRAMP (Natural Resistance‐Associated Macrophage Protein), CstA (Carbon starvation A protein), KUP (K+ Uptake Permease), BenE (Benzoate:H+ Virginia Symporter), and AE (Anion Exchanger). The topology of the well‐characterized human Anion Exchanger 1 (AE1) conforms to a UraA‐like topology of 14 TMSs (12 α‐helical TMSs and 2 mixed coil/helical TMSs). All functionally characterized members of the APC superfamily use cation symport for substrate accumulation except for some members of the AE family which frequently use anion:anion exchange. We show how the different topologies fit into the framework of the common LeuT‐like fold, defined earlier (Proteins. 2014 Feb;82(2):336‐46), and determine that some of the new members contain previously undocumented topological variations. All new entries contain the two 5 or 7 TMS APC superfamily repeat units, sometimes with extra TMSs at the ends, the variations being greatest within the CstA family. New, functionally characterized members transport amino acids, peptides, and inorganic anions or cations. Except for anions, these are typical substrates of established APC superfamily members. Active site TMSs are rich in glycyl residues in variable but conserved constellations. This work expands the APC superfamily and our understanding of its topological variations. Proteins 2014; 82:2797–2811. © 2014 Wiley Periodicals, Inc. 相似文献
226.
The form of an organism is the combination of its size and its shape. For a sample of forms, biologists wish to characterize
both mean form and the variation in form. For geometric data, where form is characterized as the spatial locations of homologous
points, the first step in analysis superimposes the forms, which requires an assumption about what measure of size is appropriate.
Geometric morphometrics adopts centroid size as the natural measure of size, and assumes that variation around the mean form
is isometric with size. These assumptions limit the interpretation of the resulting estimates of mean and variance in form.
We illustrate these problems using allometric variation in shape. We show that superimposition based on subsets of relatively
isometric points can yield superior inferences about the overall pattern of variation. We propose and demonstrate two superimposition
techniques based on this idea. In subset superimposition, landmarks are progressively discarded from the data used for superimposition
if they result in significant decreases in the variation among the remaining landmarks. In outline superimposition, regularly
distributed pseudolandmarks on the continuous outline of a form are used as the basis for superimposition of the landmarks
contained within it. Simulations show that these techniques can result in dramatic improvements in the accuracy of estimated
variance-covariance matrices among landmarks when our assumptions are roughly satisfied. The pattern of variation inferred
by means of our superimposition techniques can be quite different from that recovered from full generalized Procrustes superimposition.
The pattern of shape variation in the wings of drosophilid flies appears to meet these assumptions. Adoption of superimposition
procedures that incorporate biological assumptions about the nature of size and of the variation in shape can dramatically
improve the ability to infer the pattern of variation in geometric morphometric data. 相似文献
227.
Gilles Houle 《American journal of botany》1990,77(11):1433-1439
The species-area relationship and its underlying explanatory mechanisms were investigated in a primary successional sere on a southeastern (United States) granite outcrop. There, plant communities occupy soil-filled depressions separated from one another by areas of bare rock. They have been termed “island communities.” Soil depth and area increase as succession proceeds from Sedum smallii, to lichen-annual, to annual-perennial, and to herb-shrub-tree stages. Although plant species richness is significantly and positively correlated with island area in the system studied (all successional stages considered), the relationship between species richness and island maximum soil depth is stronger. However, island maximum soil depth and area are significantly and positively correlated. The exponential function describes the speciesarea relationship better than the transformed power function. Within successional stage, species richness shows no significant relationship with area or depth, except for late-successional island communities. Processes related to community successional development may explain the species-area relationship that exists when islands of all stages are considered. However, mechanisms related to equilibrium between extinction and immigration may be responsible for the speciesarea relationship for late-successional island communities. 相似文献
228.
229.
David Houle Janna Fierst 《Evolution; international journal of organic evolution》2013,67(4):1116-1130
We estimated mutational variance–covariance matrices, M , for wing shape and size in two genotypes of Drosophila melanogaster after 192 generations of mutation accumulation. We characterized 21 potentially independent aspects of wing shape and size using geometric morphometrics, and analyzed the data using a likelihood‐based factor‐analytic approach. We implement a previously unused analysis that describes those directions with the greatest difference in evolvability between pairs of matrices. There are significant mutational effects on 19 of 21 possible aspects of wing form, consistent with the high dimensionality of standing genetic variation for wing shape previously identified in D. melanogaster. Mutations have partially recessive effects, consistent with average dominance around 0.25. Sex‐specific matrices are relatively similar, although male‐specific matrices are slightly larger, as expected due to dosage compensation on the X chromosome. Genotype‐specific matrices are quite different. Matrices may differ both because of sampling error based on small samples of mutations with large phenotypic effects, and because of the mutational properties of the genotypes. Genotypic differences are likely to be involved, as the two genotypes have different molecular mutation rates and properties. 相似文献
230.
Brown Sabrina R. Fritz Sherilyn C. 《Extremophiles : life under extreme conditions》2019,23(4):367-376
Extremophiles - Continental hydrothermal systems are a dynamic component of global thermal and geochemical cycles, exerting a pronounced impact on water chemistry and heat storage. As such, these... 相似文献