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191.
An individual-based model (IbM) for bacterial adaptation and evolution, COSMIC-Rules, has been employed to simulate interactions of virtual temperate bacteriophages (phages) and their bacterial hosts. Outcomes of infection mimic those of a phage such as lambda, which can enter either the lytic or lysogenic cycle, depending on the nutritional status of the host. Infection of different hosts possessing differing restriction and modification systems is also simulated. Phages restricted upon infection of one restricting host can be adapted (by host-controlled modification of the phage genome) and subsequently propagate with full efficiency on this host. However, such ability is lost if the progeny phages are passaged through a new host with a different restriction and modification system before attempted re-infection of the original restrictive host. The simulations show that adaptation and re-adaptation to a particular host-controlled restriction and modification system result in lower efficiency and delayed lysis of bacterial cells compared with infection of non-restricting host bacteria. 相似文献
192.
To gain entry to plants, many pathogenic fungi develop specialized infection structures called appressoria. Here, we demonstrate that appressorium morphogenesis in the rice blast fungus Magnaporthe oryzae is tightly regulated by the cell cycle. Shortly after a fungus spore lands on the rice (Oryza sativa) leaf surface, a single round of mitosis always occurs in the germ tube. We found that initiation of infection structure development is regulated by a DNA replication-dependent checkpoint. Genetic intervention in DNA synthesis, by conditional mutation of the Never-in-Mitosis 1 gene, prevented germ tubes from developing nascent infection structures. Cellular differentiation of appressoria, however, required entry into mitosis because nimA temperature-sensitive mutants, blocked at mitotic entry, were unable to develop functional appressoria. Arresting the cell cycle after mitotic entry, by conditional inactivation of the Blocked-in-Mitosis 1 gene or expression of stabilized cyclinB-encoding alleles, did not impair appressorium differentiation, but instead prevented these cells from invading plant tissue. When considered together, these data suggest that appressorium-mediated plant infection is coordinated by three distinct cell cycle checkpoints that are necessary for establishment of plant disease. 相似文献
193.
High-intensity exercise results in reduced substrate levels and accumulation of metabolites in the skeletal muscle. The accumulation
of these metabolites (e.g. ADP, Pi and H+) can have deleterious effects on skeletal muscle function and force generation, thus contributing to fatigue. Clearly this
is a challenge to sport and exercise performance and, as such, any intervention capable of reducing the negative impact of
these metabolites would be of use. Carnosine (β-alanyl-l-histidine) is a cytoplasmic dipeptide found in high concentrations in the skeletal muscle of both vertebrates and non-vertebrates
and is formed by bonding histidine and β-alanine in a reaction catalysed by carnosine synthase. Due to the pKa of its imidazole
ring (6.83) and its location within skeletal muscle, carnosine has a key role to play in intracellular pH buffering over the
physiological pH range, although other physiological roles for carnosine have also been suggested. The concentration of histidine
in muscle and plasma is high relative to its K
m with muscle carnosine synthase, whereas β-alanine exists in low concentration in muscle and has a higher K
m with muscle carnosine synthase, which indicates that it is the availability of β-alanine that is limiting to the synthesis
of carnosine in skeletal muscle. Thus, the elevation of muscle carnosine concentrations through the dietary intake of carnosine,
or chemically related dipeptides that release β-alanine on absorption, or supplementation with β-alanine directly could provide
a method of increasing intracellular buffering capacity during exercise, which could provide a means of increasing high-intensity
exercise capacity and performance. This paper reviews the available evidence relating to the effects of β-alanine supplementation
on muscle carnosine synthesis and the subsequent effects on exercise performance. In addition, the effects of training, with
or without β-alanine supplementation, on muscle carnosine concentrations are also reviewed. 相似文献
194.
Marnie M. Saunders Linda A. Simmerman Gretchen L. Reed Neil A. Sharkey Amanda F. Taylor 《Biomechanics and modeling in mechanobiology》2010,9(5):539-550
The goal of this work was to develop and validate a whole bone organ culture model to be utilized in biomimetic mechanotransduction
research. Femurs harvested from 2-day-old neonatal rat pups were maintained in culture for 1 week post-harvest and assessed
for growth and viability. For stimulation studies, femurs were physiologically stimulated for 350 cycles 24 h post-harvest
then maintained in culture for 1 week at which time structural tests were conducted. Comparing 1 and 8 days in culture, bones
grew significantly in size over the 7-day culture period. In addition, histology supported adequate diffusion and organ viability
at 2 weeks in culture. For stimulation studies, 350 cycles of physiologic loading 24 h post-harvest resulted in increased
bone strength over the 7-day culture period. In this work, structural proof of concept was established for the use of whole
bone organ cultures as mechanotransduction models. Specifically, this work established that these cultures grow and remain
viable in culture, are adequately nourished via diffusion and are capable of responding to a brief bout of mechanical stimulation
with an increase in strength. 相似文献
195.
196.
Feng He Timothy E. Saunders Ying Wen David Cheung Pieter Rein ten Wolde Jun Ma 《Biophysical journal》2010,99(3):697-707
Morphogen gradients, which provide positional information to cells in a developing tissue, could in principle adopt any nonuniform profile. To our knowledge, how the profile of a morphogen gradient affects positional precision has not been well studied experimentally. Here, we compare the positional precision provided by the Drosophila morphogenetic protein Bicoid (Bcd) in wild-type (wt) embryos with embryos lacking an interacting cofactor. The Bcd gradient in the latter case exhibits decreased positional precision around mid-embryo compared with its wt counterpart. The domain boundary of Hunchback (Hb), a target activated by Bcd, becomes more variable in mutant embryos. By considering embryo-to-embryo, internal, and measurement fluctuations, we dissect mathematically the relevant sources of fluctuations that contribute to the error in positional information. Using this approach, we show that the defect in Hb boundary positioning in mutant embryos is directly reflective of an altered Bcd gradient profile with increasing flatness toward mid-embryo. Furthermore, we find that noise in the Bcd input signal is dominated by internal fluctuations but, due to time and spatial averaging, the spatial precision of the Hb boundary is primarily affected by embryo-to-embryo variations. Our results demonstrate that the positional information provided by the wt Bcd gradient profile is highly precise and necessary for patterning precision. 相似文献
197.
Three new nomenclatural combinations are validated in Dasymaschalon (Annonaceae), with the elevation of varietal names to the specific rank: D. longiusculum (Bân) Jing Wang & R. M. K. Saunders, D. megalanthum (Merr.) Jing Wang & R. M. K. Saunders, and D. minutiflorum (Nurmawati) Jing Wang & R. M. K. Saunders. New nomenclatural combinations are furthermore validated in Goniothalamus (Annonaceae), following the successful conservation of the generic name over Richella. Two species names in Richella are here transferred to Goniothalamus as G. monospermus (A. Gray) R. M. K. Saunders and G. obtusatus (Baill.) R. M. K. Saunders. 相似文献
198.
Zhang J Dalal N Matthews MA Waller LN Saunders C Fox KF Fox A 《Journal of microbiological methods》2007,70(3):442-451
The present work examines chemical and structural response in B. anthracis spores killed by a mixture of supercritical carbon dioxide (SCCO2) and hydrogen peroxide (H2O2). Deactivation of 6-log of B. anthracis spores by SCCO2 + H2O2 was demonstrated, but changes in structure were observed in only a small portion of spores. Results from phase contrast microscopy proved that this treatment is mild and does not trigger germination-like changes. TEM imaging revealed mild damage in a portion of spores while the majority remained intact. Dipicolinic acid (DPA) analysis showed that < 10% of the DPA was released from the spore core into the external milieu, further demonstrating only modest damage to the spores. Confocal fluorescent microscopy, assessing uptake of DNA-binding dyes, directly demonstrated compromise of the permeability barrier. However, the magnitude of uptake was small compared to spores that had been autoclaved. This work suggests that SCCO2 + H2O2 is quite mild compared to other sterilization methods, which has major implications in its application. These results provide some insight on the possible interactions between spores and the SCCO2 + H2O2 sterilization process. 相似文献
199.
Gu W Ding J Wang X de Kluyver RL Saunders NA Frazer IH Zhao KN 《Nucleic acids research》2007,35(14):4820-4832
Recently we reported that gene codon composition determines differentiation-dependent expression of the PV L1 genes in mouse primary keratinocytes (KCs) in vitro and in vivo (Zhao et al. 2005, Mol. Cell Biol. 25:8643–8655). Here, we investigated whether generalized substitution of isoencoding codons affects the duration of expression of PV L1 genes in mouse and human KCs in day 1 culture transiently transfected with native (Nat) and codon modified (Mod) L1 genes. Following transient transfection, KC continuously transcribed both Nat and Mod PV L1 genes for at least 12 days, with the levels of L1 mRNAs from the Mod L1 genes significantly higher than those from the Nat L1 genes. However, continuous L1 protein expression at day 9 post-transfection was observed for both mouse and human KCs transfected with the Nat L1 genes only. Further, aa-tRNAs prepared from D8 KC cultures enhanced translation of two PV Nat L1 DNAs in RRL lysate and PV Nat L1 mRNAs in D0 cell-free lysate, whereas aa-tRNAs from D0 KCs enhanced translation of PV Mod L1 mRNAs in D8 cell-free lysate. It appears that aa-tRNAs in less-differentiated and differentiated KCs differentially match the PV Nat and Mod L1 mRNAs to regulate their translations in vitro. 相似文献
200.
Rowbottom MW Vickers TD Tamiya J Zhang M Dyck B Grey J Schwarz D Heise CE Hedrick M Wen J Tang H Wang H Fisher A Aparicio A Saunders J Goodfellow VS 《Bioorganic & medicinal chemistry letters》2007,17(8):2171-2178
The design, synthesis, and SAR of a series of substituted spirohydantoins are described. Optimization of an in-house screening hit gave compounds that exhibited potent binding affinity and functional activity at MCH-R1. 相似文献