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51.
Nikolai W.F. Bode Daniel W. Franks A. Jamie Wood 《Journal of theoretical biology》2010,267(3):292-3049
Individual-based models of self-propelled particles (SPPs) are a popular and promising approach to explain features of the collective motion of animal aggregations. Many models that capture some features of group motion have been suggested but a common framework has yet to emerge. Key to all of these models is the inclusion of “noise” or stochastic errors in the individual behaviour of the SPPs. Here, we present a fully stochastic SPP model in one dimension that demonstrates a new way of introducing noise into SPP models whilst preserving emergent behaviours of previous models such as coherent groups and spontaneous direction switching. This purely individual-to-individual, local model is related to previous models in the literature and can easily be extended to higher dimensions. Its coarse-grained behaviour qualitatively reproduces recently reported locust movement data. We suggest that our approach offers an alternative to current reasoning about model construction and has the potential to offer mechanistic explanations for emergent properties of animal groups in nature. 相似文献
52.
Heparan sulfate plays a central role in a dynamic in vitro model of protein-losing enteropathy 总被引:5,自引:0,他引:5
Protein-losing enteropathy (PLE), the loss of plasma proteins through the intestine, is a symptom in ostensibly unrelated diseases. Emerging commonalities indicate that genetic insufficiencies predispose for PLE and environmental insults, e.g. viral infections and inflammation, trigger PLE onset. The specific loss of heparan sulfate (HS) from the basolateral surface of intestinal epithelial cells only during episodes of PLE suggests a possible mechanistic link. In the first tissue culture model of PLE using a monolayer of intestinal epithelial HT29 cells, we proved that HS loss directly causes protein leakage and amplifies the effects of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha). Here, we extend our in vitro model to assess the individual and combined effects of HS loss, interferon gamma (IFNgamma), TNFalpha, and increased pressure, and find that HS plays a central role in the patho-mechanisms underlying PLE. Increased pressure, mimicking venous hypertension seen in post-Fontan PLE patients, substantially increased protein leakage, but HS loss, IFNgamma, or TNFalpha alone had only minor effects. However, IFNgamma up-regulated TNFR1 expression and amplified TNFalpha-induced protein leakage. IFNgamma and TNFalpha compromised the integrity of the HT29 monolayer and made it more susceptible to increased pressure. HS loss itself compromises the integrity of the monolayer, amplifying the effects of pressure, but also amplifies the effects of both cytokines. In the absence of HS a combination of increased pressure, IFNgamma, and TNFalpha caused maximum protein leakage. Soluble heparin fully compensated for HS loss, providing a reasonable explanation for patient favorable response to heparin therapy. 相似文献
53.
Protein-losing enteropathy (PLE), the loss of plasma proteins through the intestine, is a life-threatening symptom associated with seemingly unrelated conditions including Crohn's disease, congenital disorder of glycosylation, or Fontan surgery to correct univentricular hearts. Emerging commonalities between these and other disorders led us to hypothesize that PLE develops when genetic insufficiencies collide with simultaneous or sequential environmental insults. Most intriguing is the loss of heparan sulfate (HS) proteoglycans (HSPG) specifically from the basolateral surface of intestinal epithelial cells only during PLE episodes suggesting a direct link to protein leakage. Reasons for HSPG loss are unknown, but genetic insufficiencies affecting HSPG biosynthesis, trafficking, or degradation may be involved. Here, we describe cell-based assays we devised to identify key players contributing to protein leakage. Results from these assays confirm that HS loss directly causes protein leakage, but more importantly, it amplifies the effects of other factors, e.g., cytokines and increased pressure. Thus, HS loss appears to play a central role for PLE. To transfer our in vitro results back to the in vivo situation, we established methods to assess enteric protein leakage in mice and present several genetically deficient strains mimicking intestinal HS loss observed in PLE patients. Preliminary results indicate that mice with haploinsufficient genes involved in HS biosynthesis or HSPG trafficking develop intestinal protein leakage upon additional environmental stress. Our goal is to model PLE in vitro and in vivo to unravel the pathomechanisms underlying PLE, identify patients at risk, and provide them with a safe and effective therapy. 相似文献
54.
Schubert W Bonnekoh B Pommer AJ Philipsen L Böckelmann R Malykh Y Gollnick H Friedenberger M Bode M Dress AW 《Nature biotechnology》2006,24(10):1270-1278
Temporal and spatial regulation of proteins contributes to function. We describe a multidimensional microscopic robot technology for high-throughput protein colocalization studies that runs cycles of fluorescence tagging, imaging and bleaching in situ. This technology combines three advances: a fluorescence technique capable of mapping hundreds of different proteins in one tissue section or cell sample; a method selecting the most prominent combinatorial molecular patterns by representing the data as binary vectors; and a system for imaging the distribution of these protein clusters in a so-called toponome map. By analyzing many cell and tissue types, we show that this approach reveals rules of hierarchical protein network organization, in which the frequency distribution of different protein clusters obeys Zipf's law, and state-specific lead proteins appear to control protein network topology and function. The technology may facilitate the development of diagnostics and targeted therapies. 相似文献
55.
Li Z Chen X Li L Liu S Yang L Ma X Tang M Bode AM Dong Z Sun L Cao Y 《The international journal of biochemistry & cell biology》2012,44(2):275-279
miRNAs (microRNAs) are a class of non-coding small RNAs. The Epstein-Barr-virus (EBV) encoded miR-BHRF1-1 is barely expressed in most nasopharyngeal carcinoma (NPC) cells with EBV latent infection. Here, we used a strategy of overexpression and inhibition of miR-BHRF1-1 and showed that miR-BHRF1-1 is involved in TPA-induced accumulation of EBV lytic proteins and viral copies in late lytic cycle. The data further suggested that the miR-BHRF1-1-potentiated induction of EBV lytic replication was accompanied by inhibiting p53 expression. Our results demonstrated that the EBV original pathogen miR-BHRF1-1 is involved in the control of EBV late lytic replication by directly targeting the host p53 gene. 相似文献
56.
Ahrendt M Hammerschmidt SI Pabst O Pabst R Bode U 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(3):1898-1907
Lymph nodes (LN) consist not only of highly motile immune cells coming from the draining area or from the systemic circulation, but also of resident stromal cells building the backbone of the LN. These two cell types form a unique microenvironment which is important for initiating an optimal immune response. The present study asked how the unique microenvironment of the mesenteric lymph node (mLN) is influenced by highly motile cells and/or by the stromal cells. A transplantation model in rats and mice was established. After resecting the mLN, fragments of peripheral lymph node (pLN) or mLN were inserted into the mesentery. The pLN and mLN have LN-specific properties, resulting in differences of, for example, the CD103(+) dendritic cell subset, the adhesion molecule mucosal addressin cell adhesion molecule 1, the chemokine receptor CCR9, the cytokine IL-4, and the enzyme retinal dehydrogenase 2. This new model clearly showed that during regeneration stromal cells survived and immune cells were replaced. Surviving high endothelial venules retained their site-specific expression (mucosal addressin cell adhesion molecule 1). In addition, the low expression of retinal dehydrogenase 2 and CCR9 persisted in the transplanted pLN, suggesting that stromal cells influence the lymph node-specific properties. To examine the functional relevance of this different expression pattern in transplanted animals, an immune response against orally applied cholera toxin was initiated. The data showed that the IgA response against cholera toxin is significantly diminished in animals transplanted with pLN. This model documents that stromal cells of the LN are active players in shaping a unique microenvironment and influencing immune responses in the drained area. 相似文献
57.
58.
Guangming Liu Yiguo Zhang Ann M Bode Wei-Ya Ma Zigang Dong 《The Journal of biological chemistry》2002,277(11):8810-8816
In resting cells, eIF4E-binding protein 1 (4E-BP1) binds to the eukaryotic initiation factor-4E (eIF-4E), preventing formation of a functional eIF-4F complex essential for cap-dependent initiation of translation. Phosphorylation of 4E-BP1 dissociates it from eIF-4E, relieving the translation block. Studies suggested that insulin- or growth factor-induced 4E-BP1 phosphorylation is mediated by phosphatidylinositol 3-kinase (PI3-kinase) and its downstream protein kinase, Akt. In the present study we demonstrated that UVB induced 4E-BP1 phosphorylation at multiple sites, Thr-36, Thr-45, Ser-64, and Thr-69, leading to dissociation of 4E-BP1 from eIF-4E. UVB-induced phosphorylation of 4E-BP1 was blocked by p38 kinase inhibitors, PD169316 and SB202190, and MSK1 inhibitor, H89, but not by mitogen-activated protein kinase kinase inhibitors, PD98059 or U0126. The PI3-kinase inhibitor, wortmannin, did not block UVB-induced 4E-BP1 phosphorylation, but blocked both UVB- and insulin-induced activation of PI3-kinase and phosphorylation of Akt. 4E-BP1 phosphorylation was blocked in JB6 Cl 41 cells expressing a dominant negative p38 kinase or dominant negative MSK1, but not in cells expressing dominant negative ERK2, JNK1, or PI3-kinase p85 subunit. Our results suggest that UVB induces phosphorylation of 4E-BP1, leading to the functional dissociation of 4E-BP1 from eIF-4E. The p38/MSK1 pathway, but not PI3-kinase or Akt, is required for mediating the UVB-induced 4E-BP1 phosphorylation. 相似文献
59.
F. Bode K. Baumann R. Kinne C. Hornung R. Maier G. Zimmerschied 《生物化学与生物物理学报:生物膜》1976,433(2):294-310
Pinocytic vesicles, brush border microvilli, lysosomes and basolateral plasma membranes were isolated from rat kidney cortex and their biochemical composition and membrane turnover compared. Pinocytic vesicles are devoid of marker enzymes of brush border microvilli, such as alkaline phosphatase and 5′-nucleotidase, and of lysosomes, such as acid phosphatase and β-glucuronidase. The protein pattern as revealed by polyacrylamide gel electrophoresis differs for all four membranes. Analysis of the phospholipid composition shows that pinocytic vesicles are rich in the negatively charged phospholipid phosphatidylserine and have a low content of sphingomyelin and phosphatidylethanolamine.[14C]guanido-arginine, [3H]fucose and were preferentially incorporated into the pinocytic vesicles. Using a double label technique with leucine also, evidence of a more rapid turnover of the pinocytic vesicle membrane proteins was obtained.The results suggest that pinocytic vesicles are not derived from the brush border microvillous membrane but are independent entities that are newly synthesized during the pinocytic process. 相似文献
60.