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991.
Han SK Federico S Grillo A Giaquinta G Herzog W 《Biomechanics and modeling in mechanobiology》2007,6(3):139-150
The integrity of articular cartilage depends on the proper functioning and mechanical stimulation of chondrocytes, the cells
that synthesize extracellular matrix and maintain tissue health. The biosynthetic activity of chondrocytes is influenced by
genetic factors, environmental influences, extracellular matrix composition, and mechanical factors. The mechanical environment
of chondrocytes is believed to be an important determinant for joint health, and chondrocyte deformation in response to mechanical
loading is speculated to be an important regulator of metabolic activity. In previous studies of chondrocyte deformation,
articular cartilage was described as a biphasic material consisting of a homogeneous, isotropic, linearly elastic solid phase,
and an inviscid fluid phase. However, articular cartilage is known to be anisotropic and inhomogeneous across its depth. Therefore,
isotropic and homogeneous models cannot make appropriate predictions for tissue and cell stresses and strains. Here, we modelled
articular cartilage as a transversely isotropic, inhomogeneous (TI) material in which the anisotropy and inhomogeneity arose
naturally from the microstructure of the depth-dependent collagen fibril orientation and volumetric fraction, as well as the
chondrocyte shape and volumetric fraction. The purpose of this study was to analyse the deformation behaviour of chondrocytes
using the TI model of articular cartilage. In order to evaluate our model against experimental results, we simulated indentation
and unconfined compression tests for nominal compressions of 15%. Chondrocyte deformations were analysed as a function of
location within the tissue. The TI model predicted a non-uniform behaviour across tissue depth: in indentation testing, cell
height decreased by 43% in the superficial zone and between 11 and 29% in the deep zone. In unconfined compression testing,
cell height decreased by 32% in the superficial zone, 25% in the middle, and 18% in the deep zones. This predicted non-uniformity
is in agreement with experimental studies. The novelty of this study is the use of a cartilage material model accounting for
the intrinsic inhomogeneity and anisotropy of cartilage caused by its microstructure. 相似文献
992.
Replicate harvest simulations were conducted in a large natural population of Panax quinquefolius L.␣(Araliaceae) to determine the selective effects of harvest. We investigated how minimum size requirements and the influence
of size on apparency to human harvesters could result in preferential removal of large plants. To determine which plants were
encountered in the large population, harvesters were tracked using GPS as they searched for every legally harvestable, adult
plant they could find. Plants were assigned stage-specific fitness measures based on their contributions to population growth
rate (λ) under three demographically based harvest regimes: no harvest, harvest and harvest removing seeds. Plant size was
codified into a size-index equal to the product of total leaf area and stem height. Heterogeneity of slopes was tested to
determine if the selection gradients (β) describing the relationship between fitness and size varied among the three harvest
regimes. Harvest differentially reduced the fitness of larger plants in one of four individual harvest simulations. The combined
harvest simulation significantly altered the selection regime for size in the population of juvenile and adult (harvestable)
plants. Seed removal by harvesters intensified fitness declines for larger plants. Because larger plants contribute most to
population growth, the selective effects of harvest could result in a shift in the evolutionary dynamics of this species with
significant conservation implications. 相似文献
993.
994.
Upon starvation, Dictyostelium discoideum cells halt cell proliferation, aggregate into multicellular organisms, form migrating slugs, and undergo morphogenesis into fruiting bodies while differentiating into dormant spores and dead stalk cells. At almost any developmental stage cells can be forced to dedifferentiate when they are dispersed and diluted into nutrient broth. However, migrating slugs can traverse lawns of bacteria for days without dedifferentiating, ignoring abundant nutrients and continuing development. We now show that developing Dictyostelium cells revert to the growth phase only when bacteria are supplied during the first 4 to 6 h of development but that after this time, cells continue to develop regardless of the presence of food. We postulate that the cells' inability to revert to the growth phase after 6 h represents a commitment to development. We show that the onset of commitment correlates with the cells' loss of phagocytic function. By examining mutant strains, we also show that commitment requires extracellular cyclic AMP (cAMP) signaling. Moreover, cAMP pulses are sufficient to induce both commitment and the loss of phagocytosis in starving cells, whereas starvation alone is insufficient. Finally, we show that the inhibition of development by food prior to commitment is independent of contact between the cells and the bacteria and that small soluble molecules, probably amino acids, inhibit development during the first few hours and subsequently the cells become unable to react to the molecules and commit to development. We propose that commitment serves as a checkpoint that ensures the completion of cooperative aggregation of developing Dictyostelium cells once it has begun, dampening the response to nutritional cues that might inappropriately block development. 相似文献
995.
The pathogenesis of infantile hemangioma is unknown. In recent years, much of the focus has been placed at identifying the cell type(s) responsible for tumor initiation. New discoveries in infantile hemangioma suggest an involvement of progenitor cells in the pathogenesis of this vascular tumor. Both embryonic and extra-embryonic tissues have been postulated as potential sources for these progenitor cells. This review focuses on the placental theory, which proposes that a fetal placental progenitor is the cell type of origin for infantile hemangioma. Special emphasis will be placed on placental vasculogenesis and the presence and transit of placental progenitor cells during gestation. 相似文献
996.
Intermolecular failure of L-type Ca2+ channel and ryanodine receptor signaling in hypertrophy 下载免费PDF全文
Xu M Zhou P Xu SM Liu Y Feng X Bai SH Bai Y Hao XM Han Q Zhang Y Wang SQ 《PLoS biology》2007,5(2):e21
Pressure overload–induced hypertrophy is a key step leading to heart failure. The Ca2+-induced Ca2+ release (CICR) process that governs cardiac contractility is defective in hypertrophy/heart failure, but the molecular mechanisms remain elusive. To examine the intermolecular aspects of CICR during hypertrophy, we utilized loose-patch confocal imaging to visualize the signaling between a single L-type Ca2+ channel (LCC) and ryanodine receptors (RyRs) in aortic stenosis rat models of compensated (CHT) and decompensated (DHT) hypertrophy. We found that the LCC-RyR intermolecular coupling showed a 49% prolongation in coupling latency, a 47% decrease in chance of hit, and a 72% increase in chance of miss in DHT, demonstrating a state of “intermolecular failure.” Unexpectedly, these modifications also occurred robustly in CHT due at least partially to decreased expression of junctophilin, indicating that intermolecular failure occurs prior to cellular manifestations. As a result, cell-wide Ca2+ release, visualized as “Ca2+ spikes,” became desynchronized, which contrasted sharply with unaltered spike integrals and whole-cell Ca2+ transients in CHT. These data suggested that, within a certain limit, termed the “stability margin,” mild intermolecular failure does not damage the cellular integrity of excitation-contraction coupling. Only when the modification steps beyond the stability margin does global failure occur. The discovery of “hidden” intermolecular failure in CHT has important clinical implications. 相似文献
997.
998.
Drug and gene delivery using gold nanoparticles 总被引:2,自引:0,他引:2
Monolayer-functionalized gold nanoparticles provide attractive vehicles for pharmaceutical delivery applications as a result
of their size and the unique properties and release mechanisms imparted by their monolayer. This review provides examples
of recent advances in the field of drug and gene delivery using gold nanoparticles. 相似文献
999.