共查询到20条相似文献,搜索用时 15 毫秒
1.
Maria J. Gomez-Lamarca Julia Falo-Sanjuan Robert Stojnic Sohaib Abdul Rehman Leila Muresan Matthew L. Jones Zoe Pillidge Gustavo Cerda-Moya Zhenyu Yuan Sarah Baloul Phillippe Valenti Kerstin Bystricky Francois Payre Kevin OHolleran Rhett Kovall Sarah J. Bray 《Developmental cell》2018,44(5):611-623.e7
2.
3.
4.
5.
Martin Bock Amit Kumar Tyagi Jan-Ulrich Kreft Wolfgang Alt 《Bulletin of mathematical biology》2010,72(7):1696-1731
Voronoi tessellations have been used to model the geometric arrangement of cells in morphogenetic or cancerous tissues, however,
so far only with flat hyper-surfaces as cell-cell contact borders. In order to reproduce the experimentally observed piecewise
spherical boundary shapes, we develop a consistent theoretical framework of multiplicatively weighted distance functions,
defining generalized finite Voronoi neighborhoods around cell bodies of varying radius, which serve as heterogeneous generators
of the resulting model tissue. The interactions between cells are represented by adhesive and repelling force densities on
the cell contact borders. In addition, protrusive locomotion forces are implemented along the cell boundaries at the tissue
margin, and stochastic perturbations allow for non-deterministic motility effects. Simulations of the emerging system of stochastic
differential equations for position and velocity of cell centers show the feasibility of this Voronoi method generating realistic
cell shapes. In the limiting case of a single cell pair in brief contact, the dynamical nonlinear Ornstein–Uhlenbeck process
is analytically investigated. In general, topologically distinct tissue conformations are observed, exhibiting stability on
different time scales, and tissue coherence is quantified by suitable characteristics. Finally, an argument is derived pointing
to a tradeoff in natural tissues between cell size heterogeneity and the extension of cellular lamellae. 相似文献
6.
7.
Suvi Kalliokoski Ana-Marija Sulic Ilma R. Korponay-Szabó Zsuzsa Szondy Rafael Frias Mileidys Alea Perez Stefania Martucciello Anne Roivainen Lauri J. Pelliniemi Carla Esposito Martin Griffin Daniele Sblattero Markku M?ki Katri Kaukinen Katri Lindfors Sergio Caja 《PloS one》2013,8(6)
A characteristic feature of celiac disease is the presence of circulating autoantibodies targeted against transglutaminase 2 (TG2), reputed to have a function in angiogenesis. In this study we investigated whether TG2-specific autoantibodies derived from celiac patients inhibit angiogenesis in both ex vivo and in vivo models and sought to clarify the mechanism behind this phenomenon. We used the ex vivo murine aorta-ring and the in vivo mouse matrigel-plug assays to address aforementioned issues. We found angiogenesis to be impaired as a result of celiac disease antibody supplementation in both systems. Our results also showed the dynamics of endothelial cells was affected in the presence of celiac antibodies. In the in vivo angiogenesis assays, the vessels formed were able to transport blood despite impairment of functionality after treatment with celiac autoantibodies, as revealed by positron emission tomography. We conclude that celiac autoantibodies inhibit angiogenesis ex vivo and in vivo and impair vascular functionality. Our data suggest that the anti-angiogenic mechanism of the celiac disease-specific autoantibodies involves extracellular TG2 and inhibited endothelial cell mobility. 相似文献
8.
Transport of proteins between cytoplasm and nucleus is mediated by transport factors of the importin α- and β-families and occurs along a gradient of the small GTPase Ran. To date, in vivo analysis as well as prediction of protein nuclear export remain tedious and difficult. We generated a novel bipartite assay called NEX-TRAP (Nuclear EXport Trapped by RAPamycin) for in vivo analysis of protein nuclear export. The assay is based on the rapamycin-induced dimerization of the modules FRB (FK506-rapamycin (FR)-binding domain) and FKBP (FK506-binding protein-12): a potential nuclear export cargo is fused to FRB, to EYFP for direct visualization as well as to an SV40-derived nuclear localization signal (NLS) for constitutive nuclear import. An integral membrane protein that resides at the trans Golgi network (TGN) is fused to a cytoplasmically exposed FKBP and serves as reporter. EYFP-NLS-FRB fusion proteins with export activity accumulate in the nucleus at steady state but continuously shuttle between nucleus and cytoplasm. Rapamycin-induced dimerization of FRB and FKBP at the TGN traps the shuttling protein outside of the nucleus, making nuclear export permanent. Using several example cargoes, we show that the NEX-TRAP is superior to existing assays owing to its ease of use, its sensitivity and accuracy. Analysis of large numbers of export cargoes is facilitated by recombinational cloning. The NEX-TRAP holds the promise of applicability in automated fluorescence imaging for systematic analysis of nuclear export, thereby improving in silico prediction of nuclear export sequences. 相似文献
9.
Olga Ya Ivanova Yulia V. Dobryakova Sergey V. Salozhin Viktor A. Aniol Mikhail V. Onufriev Natalia V. Gulyaeva Vladimir A. Markevich 《Cellular and molecular neurobiology》2017,37(7):1227-1241
Wnt signaling is involved in hippocampal development and synaptogenesis. Numerous recent studies have been focused on the role of Wnt ligands in the regulation of synaptic plasticity. Inhibitors and activators of canonical Wnt signaling were demonstrated to decrease or increase, respectively, in vitro long-term potentiation (LTP) maintenance in hippocampal slices (Chen et al. in J Biol Chem 281:11910–11916, 2006; Vargas et al. in J Neurosci 34:2191–2202, 2014, Vargas et al. in Exp Neurol 264:14–25, 2015). Using lentiviral approach to down- and up-regulate the canonical Wnt signaling, we explored whether Wnt/β-catenin signaling is critical for the in vivo LTP. Chronic suppression of Wnt signaling induced an impairment of in vivo LTP expression 14 days after lentiviral suspension injection, while overexpression of Wnt3 was associated with a transient enhancement of in vivo LTP magnitude. Both effects were related to the early phase LTP and did not affect LTP maintenance. A loss-of-function study demonstrated decreased initial paired pulse facilitation ratio, β-catenin, and phGSK-3β levels. A gain-of-function study revealed not only an increase in PSD-95, β-catenin, and Cyclin D1 protein levels, but also a reduced phGSK-3β level and enhanced GSK-3β kinase activity. These results suggest a presynaptic dysfunction predominantly underlying LTP impairment while postsynaptic modifications are primarily involved in transient LTP amplification. This study is the first demonstration of the involvement of Wnt/β-catenin signaling in synaptic plasticity regulation in an in vivo LTP model. 相似文献
10.
11.
12.
Force–Velocity Curves of Motor Proteins Cooperating In Vivo 总被引:1,自引:0,他引:1
Shtridelman Y Cahyuti T Townsend B DeWitt D Macosko JC 《Cell biochemistry and biophysics》2008,52(1):19-29
Motor proteins convert chemical energy into work, thereby generating persistent motion of cellular and subcellular objects.
The velocities of motor proteins as a function of opposing loads have been previously determined in vitro for single motors.
These single molecule “force–velocity curves” have been useful for elucidating motor kinetics and for estimating motor performance
under physiological loads due to, for example, the cytoplasmic drag force on transported organelles. Here we report force–velocity
curves for single and multiple motors measured in vivo. Using motion enhanced differential interference contrast (MEDIC) movies
of living NT2 (neuron-committed teratocarcinoma) cells at 37°C, three parameters were measured—velocity (v), radius (a), and effective cytoplasmic viscosity (η′)—as they applied to moving vesicles. These parameters were combined in Stokes’
equation, F = 6πaη′v, to determine the force, F, required to transport a single intracellular particle at velocity, v. In addition, the number of active motors was inferred from the multimodal pattern seen in a normalized velocity histogram.
Using this inference, the resulting in vivo force–velocity curve for a single motor agrees with previously reported in vitro
single motor force–velocity curves. Interestingly, however, the curves for two and three motors lie significantly higher in
both measured velocity and computed force, which suggests that motors can work cooperatively to attain higher transport forces
and velocities.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
13.
14.
15.
16.
17.
Junjie Wang Lisa Tucker-Kellogg Inn Chuan Ng Ruirui Jia P. S. Thiagarajan Jacob K. White Hanry Yu 《PLoS computational biology》2014,10(6)
The TGF-β/Smad signaling system decreases its activity through strong negative regulation. Several molecular mechanisms of negative regulation have been published, but the relative impact of each mechanism on the overall system is unknown. In this work, we used computational and experimental methods to assess multiple negative regulatory effects on Smad signaling in HaCaT cells. Previously reported negative regulatory effects were classified by time-scale: degradation of phosphorylated R-Smad and I-Smad-induced receptor degradation were slow-mode effects, and dephosphorylation of R-Smad was a fast-mode effect. We modeled combinations of these effects, but found no combination capable of explaining the observed dynamics of TGF-β/Smad signaling. We then proposed a negative feedback loop with upregulation of the phosphatase PPM1A. The resulting model was able to explain the dynamics of Smad signaling, under both short and long exposures to TGF-β. Consistent with this model, immuno-blots showed PPM1A levels to be significantly increased within 30 min after TGF-β stimulation. Lastly, our model was able to resolve an apparent contradiction in the published literature, concerning the dynamics of phosphorylated R-Smad degradation. We conclude that the dynamics of Smad negative regulation cannot be explained by the negative regulatory effects that had previously been modeled, and we provide evidence for a new negative feedback loop through PPM1A upregulation. This work shows that tight coupling of computational and experiments approaches can yield improved understanding of complex pathways. 相似文献
18.
19.
Paulo A. Garcia John H. Rossmeisl Jr. Robert E. Neal II Thomas L. Ellis John D. Olson Natalia Henao-Guerrero John Robertson Rafael V. Davalos 《The Journal of membrane biology》2010,236(1):127-136
Nonthermal irreversible electroporation (NTIRE) is a new minimally invasive technique to treat cancer. It is unique because
of its nonthermal mechanism of tumor ablation. Intracranial NTIRE procedures involve placing electrodes into the targeted
area of the brain and delivering a series of short but intense electric pulses. The electric pulses induce irreversible structural
changes in cell membranes, leading to cell death. We correlated NTIRE lesion volumes in normal brain tissue with electric
field distributions from comprehensive numerical models. The electrical conductivity of brain tissue was extrapolated from
the measured in vivo data and the numerical models. Using this, we present results on the electric field threshold necessary
to induce NTIRE lesions (495–510 V/cm) in canine brain tissue using 90 50-μs pulses at 4 Hz. Furthermore, this preliminary
study provides some of the necessary numerical tools for using NTIRE as a brain cancer treatment. We also computed the electrical
conductivity of brain tissue from the in vivo data (0.12–0.30 S/m) and provide guidelines for treatment planning and execution.
Knowledge of the dynamic electrical conductivity of the tissue and electric field that correlates to lesion volume is crucial
to ensure predictable complete NTIRE treatment while minimizing damage to surrounding healthy tissue. 相似文献