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21.
Alicia P. Higueruelo Adrian Schreyer G. Richard J Bickerton Tom L. Blundell Will R. Pitt 《PloS one》2012,7(12)
Efforts to increase affinity in the design of new therapeutic molecules have tended to lead to greater lipophilicity, a factor that is generally agreed to be contributing to the low success rate of new drug candidates. Our aim is to provide a structural perspective to the study of lipophilic efficiency and to compare molecular interactions created over evolutionary time with those designed by humans. We show that natural complexes typically engage in more polar contacts than synthetic molecules bound to proteins. The synthetic molecules also have a higher proportion of unmatched heteroatoms at the interface than the natural sets. These observations suggest that there are lessons to be learnt from Nature, which could help us to improve the characteristics of man-made molecules. In particular, it is possible to increase the density of polar contacts without increasing lipophilicity and this is best achieved early in discovery while molecules remain relatively small. 相似文献
22.
23.
Transnational Migration in Rural Oaxaca, Mexico: Dependency, Development, and the Household 总被引:1,自引:0,他引:1
Contradictory models of dependency and development have dominated the discussion of migration between Mexico and the United States. Transnational models of migration resolve these contradictions by defining a series of interdependencies (economy and society, for example). Using data collected in a rural Zapotec community in Oaxaca, Mexico, this article focuses on three areas: the stage-specific development of transnational movement; the domestic cycle, household decision making, and migration/remittance outcomes; and the changing nature of community participation. Rooting the discussion in household decision making captures the important role local social variability and economic dynamism play in understanding transnational processes and advancing migration studies. [ households, migration, transnationalism, dependency and development, Oaxaca, Mexico ] 相似文献
24.
Food sharing: a model of manipulation by harassment 总被引:3,自引:1,他引:2
Most analyses of food-sharing behavior invoke complex explanationssuch as indirect and delayed benefits for sharing via kin selectionand reciprocal altruism. However, food sharing can be a moregeneral phenomenon accounted for by more parsimonious, mutualisticexplanations. We propose a game theoretical model of a generalsharing situation in which food owners share because it is
in their own self-interestthey avoid high costs associatedwith beggar harassment. When beggars harass, owners may benefitfrom sharing part of the food if their consumption rate islow relative to the rate of cost accrual. Our model predictsthat harassment can be a profitable strategy for beggars if
they reap some direct benefits from harassing other than sharedfood (such as picking up scraps). Therefore, beggars may manipulatethe owner's fitness payoffs in such a way as to make sharingmutualistic. 相似文献
25.
Douglas G. Gilmour Walter M. Collins Tom L. Fredericksen Willard E. Urban Jr. Paul F. Ward Nancy L. DiFronzo 《Immunogenetics》1986,23(1):1-6
Chickens of Regional Poultry Research Laboratory (RPRL) inbred line 63 regress sarcomas induced by Bryan high-titer Rous sarcoma virus to a greater extent than chickens of line RPRL 100, although these lines are identical for the major histocompatibility B complex. They differ, however, at three independent autosomal loci: Ly-4 and Th-1 determine the surface alloantigens of partly overlapping subsets of T lymphocytes, and Bu-1 determines a surface alloantigen of B lymphocytes. The association of genotypes at these loci with quantitative variation in their ability to regress Rous sarcomas was tested in segregating F4 generation progeny derived from crosses of lines 100 and 63. The Ly-4 and Bu-1 genotypes showed association with Rous sarcoma regression, but the Th-1 genotype did not. Chickens of the Ly-4
a/Ly-4
a, Bu-1
b/Bu-1
b and Ly-4
b/Ly-4
b, Bu-1
a/Bu-1
a genotypes had a significantly higher regressor ability than the other two double homozygous genotypes. These results indicate that higher regression is associated with (1) interaction between the Ly-4 and Bu-1 loci, and (2) complementation between either the line 6 Ly-4
a allele and the line 100 Bu-1
b allele, or the line 100 Ly-4
b allele and the line 6 Bu-1
a allele. 相似文献
26.
Edmund H. Frank Boyce W. Burge Boleslaw H. Liwnicz Linda J. Lotspeich Jocelyn C. White Steven L. Wechsler Frank H. Mayfield Jeffrey T. Keller 《Experimental cell research》1983,146(2):371-376
Cells from cranial and spinal arachnoid membranes of humans were grown in culture. Their growth characteristics, morphology and details of their cytoskeletal composition are described. Arachnoid membranes, obtained at autopsy, were finely minced and incubated in tissue culture medium. Monolayers of cells of homogeneous morphology grew from these tissue fragments. The cells were flat and polygonal. They divided slowly to form non-overlapping monolayers of low cell density. Electron microscopic examination of cultured arachnoid cells revealed numerous desmosome-like tight junctions and abundant intermediate filaments (tonofilaments). Both morphological features are characteristic of arachnoid cells in situ, but not of cells in the fibroblast-rich dura mater. Immunofluorescence microscopy with monoclonal antibodies demonstrated cytokeratin in the cytoplasm of primary cultures of arachnoid cells. Thus we demonstrated that these cultured cells retained certain of the specific differentiated properties of arachnoid cells in situ and that they are not fibroblasts (which lack tight junctions and cytokeratins). To our knowledge, there have been no previous reports of in vitro growth of arachnoid cells. This in vitro model should be useful in studying the response of arachnoid cells to a variety of substances thought to be involved in the chronic inflammatory condition of the meninges known as arachnoiditis. 相似文献
27.
28.
Jeffrey P Mower Pascal Touzet Julie S Gummow Lynda F Delph Jeffrey D Palmer 《BMC evolutionary biology》2007,7(1):135
Background
It has long been known that rates of synonymous substitutions are unusually low in mitochondrial genes of flowering and other land plants. Although two dramatic exceptions to this pattern have recently been reported, it is unclear how often major increases in substitution rates occur during plant mitochondrial evolution and what the overall magnitude of substitution rate variation is across plants. 相似文献29.
30.