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11.
Quantitative understanding of nanoparticles delivery in a complex vascular networks is very challenging because it involves interplay of transport, hydrodynamic force, and multivalent interactions across different scales. Heterogeneous pulmonary network includes up to 16 generations of vessels in its arterial tree. Modeling the complete pulmonary vascular system in 3D is computationally unrealistic. To save computational cost, a model reconstructed from MRI scanned images is cut into an arbitrary pathway consisting of the upper 4-generations. The remaining generations are represented by an artificially rebuilt pathway. Physiological data such as branch information and connectivity matrix are used for geometry reconstruction. A lumped model is used to model the flow resistance of the branches that are cut off from the truncated pathway. Moreover, since the nanoparticle binding process is stochastic in nature, a binding probability function is used to simplify the carrier attachment and detachment processes. The stitched realistic and artificial geometries coupled with the lumped model at the unresolved outlets are used to resolve the flow field within the truncated arterial tree. Then, the biodistribution of 200 nm, 700 nm and 2 µm particles at different vessel generations is studied. At the end, 0.2–0.5% nanocarrier deposition is predicted during one time passage of drug carriers through pulmonary vascular tree. Our truncated approach enabled us to efficiently model hemodynamics and accordingly particle distribution in a complex 3D vasculature providing a simple, yet efficient predictive tool to study drug delivery at organ level. 相似文献
12.
N. Cappetti A. Naddeo G. F. Solitro 《Computer methods in biomechanics and biomedical engineering》2016,19(12):1278-1285
The aim of this work is to show a quick and simple procedure able to identify the geometrical parameters of the intervertebral disc that strongly affect the behavior of the FEM model. First, we allocated a selection criterion for the minimum number of geometrical parameters that describe, with a good degree of approximation, a healthy human vertebra. Next, we carried out a sensitivity analysis using the ‘Taguchi orthogonal array’ to arrive at a quick identification of the parameters that strongly affect the behavior of the Fem model. 相似文献
13.
Stefano Carenini Dirk Montag Harold Cremer Melitta Schachner Rudolf Martini 《Cell and tissue research》1996,287(1):3-9
We have previously shown that mice deficient in the gene for the myelin-associated glycoprotein (MAG) develop normal myelin
in the peripheral nerves, but show axon and myelin degeneration at eight months of age, suggesting that MAG is involved in
the maintenance of axon-Schwann cell integrity. The search for molecules that might replace MAG during myelination revealed
an overexpression of the neural cell adhesion molecule (N-CAM) at those aspects where MAG is detectable in wild type mice.
To test whether N-CAM might compensate for MAG during myelination in MAG-deficient mice, double mutants deficient in both
MAG and N-CAM (MAG−/N-CAM−mice) were generated by cross-breeding the single mutants. Whereas alterations of myelin development were not detectable in
either of the single or double mutants, degeneration of myelin and axons occurred approximately 4 weeks earlier in MAG−/N-CAM−than in MAG−mutants. Furthermore, at 8 weeks of age, single fiber preparation and electron microscopy revealed that the number of profiles
indicative of degeneration was substantially increased in MAG−/N-CAM−mutants when compared to MAG−mice. These data suggest that in MAG-deficient mice N-CAM does not compensate for MAG in myelin formation but partially substitutes
for it in the maintenance of axon-myelin integrity.
Received: 20 May 1996 / Accepted: 19 July 1996 相似文献
14.
Adherens junctions serve to couple individual cells into various arrangements required for tissue structure and function. The central structural components of adherens junctions are transmembrane adhesion receptors, and their associated actin-binding/regulatory proteins. The molecular machineries that organize these adhesion receptor complexes into higher order junction structures, and the functional consequences of this junctional organization will be discussed. 相似文献
15.
Abderrahman El Maarouf Damali Moyo-Lee Yaw Theresa Lindhout Damien D. Pearse Warren Wakarchuk Urs Rutishauser 《The Journal of biological chemistry》2012,287(39):32770-32779
In vertebrates, polysialic acid (PSA) is typically added to the neural cell adhesion molecule (NCAM) in the Golgi by PST or STX polysialyltransferase. PSA promotes plasticity, and its enhanced expression by viral delivery of the PST or STX gene has been shown to promote cellular processes that are useful for repair of the injured adult nervous system. Here we demonstrate a new strategy for PSA induction on cells involving addition of a purified polysialyltransferase from Neisseria meningitidis (PSTNm) to the extracellular environment. In the presence of its donor substrate (CMP-Neu5Ac), PSTNm synthesized PSA directly on surfaces of various cell types in culture, including Chinese hamster ovary cells, chicken DF1 fibroblasts, primary rat Schwann cells, and mouse embryonic stem cells. Similarly, injection of PSTNm and donor in vivo was able to produce PSA in different adult brain regions, including the cerebral cortex, striatum, and spinal cord. PSA synthesis by PSTNm requires the presence of the donor CMP-Neu5Ac, and the product could be degraded by the PSA-specific endoneuraminidase-N. Although PSTNm was able to add PSA to NCAM, most of its product was attached to other cell surface proteins. Nevertheless, the PSTNm-induced PSA displayed the ability to attenuate cell adhesion, promote neurite outgrowth, and enhance cell migration as has been reported for endogenous PSA-NCAM. Polysialylation by PSTNm occurred in vivo in less than 2.5 h, persisted in tissues, and then decreased within a few weeks. Together these characteristics suggest that a PSTNm-based approach may provide a valuable alternative to PST gene therapy. 相似文献
16.
Mark A. Hughes Paul M. Brennan Andrew S. Bunting Mike J. Shipston Alan F. Murray 《Journal of visualized experiments : JoVE》2014,(85)
Cell patterning platforms support broad research goals, such as construction of predefined in vitro neuronal networks and the exploration of certain central aspects of cellular physiology. To easily combine cell patterning with Multi-Electrode Arrays (MEAs) and silicon-based ‘lab on a chip’ technologies, a microfabrication-compatible protocol is required. We describe a method that utilizes deposition of the polymer parylene-C on SiO2 wafers. Photolithography enables accurate and reliable patterning of parylene-C at micron-level resolution. Subsequent activation by immersion in fetal bovine serum (or another specific activation solution) results in a substrate in which cultured cells adhere to, or are repulsed by, parylene or SiO2 regions respectively. This technique has allowed patterning of a broad range of cell types (including primary murine hippocampal cells, HEK 293 cell line, human neuron-like teratocarcinoma cell line, primary murine cerebellar granule cells, and primary human glioma-derived stem-like cells). Interestingly, however, the platform is not universal; reflecting the importance of cell-specific adhesion molecules. This cell patterning process is cost effective, reliable, and importantly can be incorporated into standard microfabrication (chip manufacturing) protocols, paving the way for integration of microelectronic technology. 相似文献
17.
《Chronobiology international》2013,30(2):121-126
Thyroxine (T4) and triiodothyronine (T3) plasma concentrations have been determined during 24-hr sampling periods in six mongrels (age 12-36 months), six beagles (age 35-37 months), three labradors (age 3.5 months) and three beagles (age 5 months). The mean T4 levels of the labradors were significantly lower than the values found for mongrels or older beagles (P < 0.05), whereas T3 was higher in the 5 month old beagles compared to the mongrels (P < 0.001), young beagles (P < 0.05) or labradors (P < 0.01).Circadian and ultradian rhythmicities have been evaluated by cosinor and Fourier analysis. Mongrels and older beagles did have a 12-hr rhythmicity in plasma T4 (P < 0.05), whereas 5 month old beagles had a circadian one (P < 0.01). A 12-hr rhythmicity was also found for T3 in the older Beagles (P < 0.05). However, Fourier analysis indicated that the daily variation in T4 and T3 plasma levels was inadequately mathematically described by single sinusoidal rhythm and that more harmonic components are to be taken into account.The obtained data during a 24-hr period indicate that T4 and T3 concentrations in plasma may vary according to breed, age and sampling hour. 相似文献
18.
K. M. Louman-Gardiner D. Coombe 《Computer methods in biomechanics and biomedical engineering》2013,16(12):1071-1077
Lower back pain due to intervertebral disc (IVD) degeneration is a prevalent problem which drastically affects the quality of life of millions of sufferers. Healthy IVDs begin with high populations of notochordal cells in the nucleus pulposus, while by the second stage of degeneration, these cells will be replaced by chondrocyte-like cells. Because the IVD is avascular, these cells rely on passive diffusion of nutrients to survive. It is thought that this transition in cell phenotype causes the shift of the IVD's physical properties, which impede the flow of nutrients. Our computational model of the IVD illustrates its ability to simulate the evolving chemical and mechanical environments occurring during the early ageing process. We demonstrate that, due to the insufficient nutrient supply and accompanying changes in physical properties of the IVD, there was a resultant exponential decay in the number of notochordal cells over time. 相似文献
19.
Zeng-zhi Yuan Xiao-jie Yan An-ding Zhang Bo Chen Yue-quan Shen Mei-lin Jin 《The Journal of biological chemistry》2013,288(2):956-963
Streptococcus suis, one of the most important and prevalent pathogens in
swine, presents a major challenge to global public health. HP0197 is an S.
suis surface antigen that was previously identified by immunoproteomics and can
bind to the host cell surface. Here, we investigated the interaction between HP0197 and
the host cell surface glycosaminoglycans (GAGs) using indirect immunofluorescence and cell
adhesion inhibition assays. In addition, we determined that a novel 18-kDa domain in the
N-terminal region of HP0197 functions as the GAG-binding domain. We then solved the
three-dimensional structures of the N-terminal 18-kDa and C-terminal G5 domains using
x-ray crystallography. Based on this structural information, the GAG-binding sites in
HP0197 were predicted and subsequently verified using site-directed mutagenesis and
indirect immunofluorescence. The results indicate that the positively charged residues on
the exposed surface of the 18-kDa domain, which are primarily lysines, likely play a
critical role in the HP0197-heparin interaction that mediates bacterium-host cell
adhesion. Understanding this molecular mechanism may provide a basis for the development
of effective drugs and therapeutic strategies for treating streptococcal infections. 相似文献
20.
《Cell communication & adhesion》2013,20(6):213-225
AbstractAdhesion G-protein-coupled receptors (GPCRs) are the most recently identified and least understood subfamily of GPCRs. Adhesion GPCRs are characterized by unusually long ectodomains with adhesion-related repeats that facilitate cell– cell and cell–cell matrix contact, as well as a proteolytic cleavage site-containing domain that is a structural hallmark of the family. Their unusual chimeric structure of adhesion-related ectodomain with a seven-pass transmembrane domain and cytoplasmic signaling makes these proteins highly versatile in mediating cellular signaling in response to extracellular adhesion or cell motility events. The ligand binding and cytoplasmic signaling modes for members of this family are beginning to be elucidated, and recent studies have demonstrated critical roles for Adhesion GPCRs in planar polarity and other important cell–cell and cell–matrix interactions during development and morphogenesis, as well as heritable diseases and cancer. 相似文献