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971.
972.
We combined atomistic molecular-dynamics simulations with quantum-mechanical calculations to investigate the sequence dependence of the stretching behavior of duplex DNA. Our combined quantum-mechanical/molecular-mechanical approach demonstrates that molecular-mechanical force fields are able to describe both the backbone and base-base interactions within the highly distorted nucleic acid structures produced by stretching the DNA from the 5′ ends, which include conformations containing disassociated basepairs, just as well as these force fields describe relaxed DNA conformations. The molecular-dynamics simulations indicate that the force-induced melting pathway is sequence-dependent and is influenced by the availability of noncanonical hydrogen-bond interactions that can assist the disassociation of the DNA basepairs. The biological implications of these results are discussed. 相似文献
973.
We investigate the effects of two structurally similar small cyclic molecules: salicylic acid and perillic acid on a zwitterionic model lipid bilayer, and show that both molecules might have biological activity related to membrane thinning. Salicylic acid is a nonsteroidal antiinflammatory drug, some of the pharmacological properties of which arise from its interaction with the lipid bilayer component of the plasma membrane. Prior simulations show that salicylate orders zwitterionic lipid membranes. However, this is in conflict with Raman scattering and vesicle fluctuation analysis data, which suggest the opposite. We show using extensive molecular dynamics simulations, cumulatively >2.5 μs, that salicylic acid indeed disorders membranes with concomitant membrane thinning and that the conflict arose because prior simulations suffered from artifacts related to the sodium-ion induced condensation of zwitterionic lipids modeled by the Berger force field. Perillic acid is a terpenoid plant extract that has antiinfective and anticancer properties, and is extensively used in eastern medicine. We found that perillic acid causes large-scale membrane thinning and could therefore exert its antimicrobial properties via a membrane-lytic mechanism reminiscent of antimicrobial peptides. Being more amphipathic, perillic acid is more potent in disrupting lipid headgroup packing, and significantly modifies headgroup dipole orientation. Like salicylate, the membrane thinning effect of perillic acid is masked by the presence of sodium ions. As an alternative to sodium cations, we advocate the straightforward solution of using larger countercations like potassium or tetra-methyl-ammonium that will maintain electroneutrality but not interact strongly with, and thus not condense, the lipid bilayer. 相似文献
974.
ARTEMIS stabilizes the genome and modulates proliferative responses in multipotent mesenchymal cells
Background
Unrepaired DNA double-stranded breaks (DSBs) cause chromosomal rearrangements, loss of genetic information, neoplastic transformation or cell death. The nonhomologous end joining (NHEJ) pathway, catalyzing sequence-independent direct rejoining of DSBs, is a crucial mechanism for repairing both stochastically occurring and developmentally programmed DSBs. In lymphocytes, NHEJ is critical for both development and genome stability. NHEJ defects lead to severe combined immunodeficiency (SCID) and lymphoid cancer predisposition in both mice and humans. While NHEJ has been thoroughly investigated in lymphocytes, the importance of NHEJ in other cell types, especially with regard to tumor suppression, is less well documented. We previously reported evidence that the NHEJ pathway functions to suppress a range of nonlymphoid tumor types, including various classes of sarcomas, by unknown mechanisms. 相似文献975.
Willem Kuyken Sarah Byford Richard Byng Tim Dalgleish Glyn Lewis Rod Taylor Edward R Watkins Rachel Hayes Paul Lanham David Kessler Nicola Morant Alison Evans 《Trials》2010,11(1):1-10
Background
The total effect of a medication is the sum of its drug effect, placebo effect (meaning response), and their possible interaction. Current interpretation of clinical trials' results assumes no interaction. Demonstrating such an interaction has been difficult due to lack of an appropriate study design.Methods
180 adults were randomized to caffeine (300 mg) or placebo groups. Each group received the assigned intervention described by the investigators as caffeine or placebo, in a randomized crossover design. 4-hour-area-under-the-curve of energy, sleepiness, nausea (on 100 mm visual analog scales), and systolic blood pressure levels as well as caffeine pharmacokinetics (in 22 volunteers nested in the caffeine group) were determined. Caffeine drug, placebo, placebo-plus-interaction, and total effects were estimated by comparing outcomes after, receiving caffeine described as placebo to receiving placebo described as placebo, receiving placebo described as caffeine or placebo, receiving caffeine described as caffeine or placebo, and receiving caffeine described as caffeine to receiving placebo described as placebo, respectively.Results
The placebo effect on area-under-the-curve of energy (mean difference) and sleepiness (geometric mean ratio) was larger than placebo-plus-interaction effect (16.6 [95% CI, 4.1 to 29.0] vs. 8.4 [-4.2 to 21.0] mm*hr and 0.58 [0.39 to 0.86] vs. 0.69 [0.49 to 0.97], respectively), similar in size to drug effect (20.8 [3.8 to 37.8] mm*hr and 0.49 [0.30 to 0.91], respectively), and its combination with the later was larger than total caffeine effect (29.5 [11.9 to 47.1] mm*hr and 0.37 [0.22 to 0.64]). Placebo-plus-interaction effect increased caffeine terminal half-life by 0.40 [0.12 to 0.68] hr (P = 0.007).Conclusions
Drug and placebo effects of a medication may be less than additive, which influences the interpretation of clinical trials. The placebo effect may increase active drug terminal half-life, a novel mechanism of placebo action.Trial Registration
ClinicalTrials.gov identification number - NCT00426010. 相似文献976.
977.
Spatial segregation of the sexes (SSS) occurs in many dioecious angiosperms, but little data are available on the fitness
advantages, if any, for males and females. We examined whether reciprocally transplanted male and female seedlings of Distichlis spicata, a dioecious grass species that exhibits extreme SSS, differed in their responses to microhabitats and competition treatments.
Plants grown without conspecific competitors grew equally well in both male- or female-majority habitats, suggesting that
male and female plants do not have differential resource needs at the juvenile life-history stage. However, plants subject
to intra-sexual competition were significantly larger than plants subject to inter-sexual competition, suggesting that niche
partitioning may occur in D. spicata. 相似文献
978.
Brooke E. Crowley Melinda L. Carter Sarah M. Karpanty Adrienne L. Zihlman Paul L. Koch Nathaniel J. Dominy 《Oecologia》2010,164(3):611-626
Isotopic studies of wild primates have used a wide range of tissues to infer diet and model the foraging ecologies of extinct
species. The use of mismatched tissues for such comparisons can be problematic because differences in amino acid compositions
can lead to small isotopic differences between tissues. Additionally, physiological and dietary differences among primate
species could lead to variable offsets between apatite carbonate and collagen. To improve our understanding of the isotopic
chemistry of primates, we explored the apparent enrichment (ε*) between bone collagen and muscle, collagen and fur or hair
keratin, muscle and keratin, and collagen and bone carbonate across the primate order. We found that the mean ε* values of
proteinaceous tissues were small (≤1‰), and uncorrelated with body size or phylogenetic relatedness. Additionally, ε* values
did not vary by habitat, sex, age, or manner of death. The mean ε* value between bone carbonate and collagen (5.6 ± 1.2‰)
was consistent with values reported for omnivorous mammals consuming monoisotopic diets. These primate-specific apparent enrichment
values will be a valuable tool for cross-species comparisons. Additionally, they will facilitate dietary comparisons between
living and fossil primates. 相似文献
979.
Manfred Türke Eric Heinze Kerstin Andreas Sarah M. Svendsen Martin M. Gossner Wolfgang W. Weisser 《Oecologia》2010,163(3):681-693
In beech-dominated forests in Central Europe, many spring geophytes show adaptations to seed dispersal by ants (myrmecochory). Ants, however, can be rare in such moist forests. Motivated by observations of slug feeding on seeds we investigated the seed consumption of two plant species, Anemone nemorosa and Asarum europaeum, by slugs, in a series of experiments. In a seed predation experiment in a beech forest, we found that seed removal was strongly reduced when gastropods were excluded from the seed depots. The contribution of insects, including ants, and rodents to seed removal was relatively less but differed between May and July. In the laboratory, slug species, in particular Arion sp., consumed seeds of both plant species. Slugs either consumed the elaiosomes of seeds or swallowed seeds intact. Swallowed seeds were defecated undamaged and germinated as well as control seeds when buried overwinter, indicating the potential for seed dispersal by slugs. We also recovered seeds of myrmecochores in the faeces of several slugs caught in forests. In a slug release experiment in the forest, slugs moved up to 14.6 m (mean 4.4 m) in 15 h, which is the median gut passage time of seeds based on measurements made in the laboratory. We also found that when slug-defecated seeds were offered to rodents, these were less attractive than control seeds, suggesting that passage through the slug gut reduces seed predation risk. Our results demonstrate that slugs are significant consumers of elaiosomes or entire seeds of ant-dispersed plants and that they can function as seed dispersers of these plants. 相似文献
980.
Federico Martin Sarah Dailey A. Mark Settles 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,121(4):697-704
The genome sequence of the B73 maize inbred enables map-based cloning of genetic variants underlying phenotypes. In parallel
to sequencing efforts, multiple public mutagenesis resources are being developed predominantly in the W22 and B73 inbreds.
Efficient platforms to map mutants in these genetic backgrounds would aid molecular genetic analysis of the public resources.
We screened 505 simple sequence repeat markers for polymorphisms between the B73, Mo17, and W22 inbreds. Using common thermocycling
conditions, 47.1% of the markers showed co-dominant polymorphisms in at least one pair of inbreds. Based on these results,
we identified 85 distributed markers for mapping in all three inbred pairs. For each inbred pair, the distributed set has
64–71 polymorphic markers with a mean distance of 27–29 cM between markers. The distributed markers give nearly complete coverage
of the genetic map for each inbred pair. We demonstrate the utility of the marker set for efficient placement of mutants on
the maize genetic map with an example mapping experiment of a seed mutant from the UniformMu mutagenesis resource. We conclude
that these distributed molecular markers enable rapid mapping of phenotypic variants from public mutagenesis populations. 相似文献