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Zeinab Mokhtari Franziska Mech Carolin Zitzmann Mike Hasenberg Matthias Gunzer Marc Thilo Figge 《PloS one》2013,8(12)
Cell migration is the driving force behind the dynamics of many diverse biological processes. Even though microscopy experiments are routinely performed today by which populations of cells are visualized in space and time, valuable information contained in image data is often disregarded because statistical analyses are performed at the level of cell populations rather than at the single-cell level. Image-based systems biology is a modern approach that aims at quantitatively analyzing and modeling biological processes by developing novel strategies and tools for the interpretation of image data. In this study, we take first steps towards a fully automated characterization and parameter-free classification of cell track data that can be generally applied to tracked objects as obtained from image data. The requirements to achieve this aim include: (i) combination of different measures for single cell tracks, such as the confinement ratio and the asphericity of the track volume, and (ii) computation of these measures in a staggered fashion to retrieve local information from all possible combinations of track segments. We demonstrate for a population of synthetic cell tracks as well as for in vitro neutrophil tracks obtained from microscopy experiment that the information contained in the track data is fully exploited in this way and does not require any prior knowledge, which keeps the analysis unbiased and general. The identification of cells that show the same type of migration behavior within the population of all cells is achieved via agglomerative hierarchical clustering of cell tracks in the parameter space of the staggered measures. The recognition of characteristic patterns is highly desired to advance our knowledge about the dynamics of biological processes. 相似文献
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Nocturnal lorises and pottos (Lorisinae) are among the least gregarious of primates. Mothers start to leave their infants alone during the night as early as the day of birth. However, captive studies also indicate that weaning young lorisines closely follow their mothers nearly all the time and obtain their first solid food via scrounging. Accordingly, it has been suggested that young lorisines depend on their mothers to obtain dietary information and to achieve dietary independence by watching their mothers feeding or interacting directly with their mothers over food. We tested for a social dependence on dietary learning by infants in a social network of wild slow lorises (Nycticebus coucang). The social network included one male infant, his mother, and two subadult females. The infant only took to mouth food items that were also part of the females' diet and showed concordance in the frequency of use of food patches with the females. These results contradict dietary learning by trial and error. They indicate that dietary learning by infants depends on information obtained from older conspecifics. However, the infant was never involved in direct interactions with conspecifics over food and fed mostly alone. He was not within a distance where he could see the females feeding more often than expected from the configuration and utilization of home ranges. The infant never looked at conspecifics feeding in his vicinity, which suggests that visual observation or direct interaction over food may not be the mechanisms by which information about food resources is passed from older individuals to young, but that other ways of obtaining such information are used. 相似文献
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Scanlan CN Ritchie GE Baruah K Crispin M Harvey DJ Singer BB Lucka L Wormald MR Wentworth P Zitzmann N Rudd PM Burton DR Dwek RA 《Journal of molecular biology》2007,372(1):16-22
The HIV envelope has evolved a dense array of immunologically "self" carbohydrates that efficiently protect the virus from antibody recognition. Nonetheless, one broadly neutralising antibody, IgG1 2G12, has been shown to recognise a cluster of oligomannose glycans on the HIV-1 surface antigen gp120. Thus the self carbohydrates of HIV are now regarded as potential targets for viral neutralisation and vaccine design. Here, we show that chemical inhibition of mammalian glycoprotein synthesis, with the plant alkaloid kifunensine, creates multiple HIV (2G12) epitopes on the surface of previously non-antigenic self proteins and cells, including HIV gp120. This formally demonstrates the structural basis for self/non-self discrimination between viral and host glycans, by a neutralising antibody. Moreover, this study provides an alternative protein engineering approach to the design of a carbohydrate vaccine for HIV-1 by chemical synthesis. 相似文献
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Summary From 1986 onwards increasing numbers of Great Tits (Parus major) and Blue Tits (Parus caeruleus) were registered breeding on empty nests. In 1987 and 1988 up to 4% of all found sitting on nests did not lay any egg. The rate of breeding failures might be considerably higher because many individuals breeding on empty nests could have been overlooked by weekly checks of the nest boxes. 相似文献
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SOCS-1 and SOCS-3 inhibit IFN-alpha-induced expression of the antiviral proteins 2,5-OAS and MxA 总被引:4,自引:0,他引:4
Vlotides G Sörensen AS Kopp F Zitzmann K Cengic N Brand S Zachoval R Auernhammer CJ 《Biochemical and biophysical research communications》2004,320(3):1007-1014
Although the use of IFN-alpha in combination with ribavirin has improved the treatment efficacy of chronic hepatitis C virus (HCV) infection, 20-50% of patients still fail to eradicate the virus depending on the HCV genotype. Recently, overexpression of HCV core protein has been shown to inhibit IFN signaling and induce SOCS-3 expression. Aim of this study was to examine the putative role of SOCS proteins in IFN resistance. By Western blot analysis, a 4-fold induction of STAT-1/3 phosphorylation by IFN-alpha was observed in mock-transfected HepG2 clones. In contrast, IFN-induced STAT-1/3 phosphorylation was considerably downregulated by SOCS-1/3 overexpression. In mock-transfected cells, IFN-alpha induced 2',5'-OAS and myxovirus resistance A (MxA) promoter activity 40- to 80-fold and 10- to 35-fold, respectively, and this effect was abrogated in SOCS-1/3 overexpressing cells. As detected by Northern blot technique, IFN-alpha potently induced 2',5'-OAS and MxA mRNA expression in the control clones. Overexpression of SOCS-1 completely abolished both 2',5'-OAS and MxA mRNA expression, whereas SOCS-3 mainly inhibited 2',5'-OAS mRNA expression. Our results demonstrate that SOCS-1 and SOCS-3 proteins inhibit IFN-alpha-induced activation of the Jak-STAT pathway and expression of the antiviral proteins 2',5'-OAS and MxA. These data suggest a potential role of SOCS proteins in IFN resistance during antiviral treatment. 相似文献
6.
Pardo M Piñeiro A de la Fuente M García A Prabhakar S Zitzmann N Dwek RA Sánchez-Salorio M Domínguez F Capeans C 《Journal of cellular biochemistry》2004,93(4):708-720
Uveal malignant melanoma is the most frequent primary intraocular tumor in adult humans. The cellular events leading to neoplasic transformation of normal uveal melanocytes are not well known when compared to other cancers. In this study, we investigated the role of G1 and G1/S regulatory proteins of the cell cycle in human uveal melanoma (UM) primary cell cultures, since these proteins are common targets in tumor development. Further, freshly established and characterized tumor cells are a better model for in vitro studies when compared to cell lines established long ago. Human primary cell cultures from eight different UM were established, as well as one primary culture from rhesus uveal normal melanocytes (UNM). Primary human UM cultures were characterized by a low establishment and growing rate. From four successful cultures, three showed a high expression of cyclin D1, cyclin E, p16NK4A, and p27KIP1 with no variations in cyclin A, cyclin-dependent kinase 2 (CDK2), and CDK4. Interestingly, in one of the cultured tumors, tumor suppressor protein retinoblastoma (Rb) did not bind E2F despite the fact that Rb was found in its hypophosphorylated form. No mutations in either RB1 or the Rb-binding pocket of E2F-1 were detected. Furthermore, we identified seven proteins co-immunoprecipitating with Rb in this tumor, including Lamin A/C and six proteins not previously reported to bind Rb: Hsc70, high mobility group protein 1 (HMG-1), hnRPN, glyceraldehyde 3 phosphate dehydrogenase (G3PDH), EF-1, and EF-2. Our results indicate that the overexpression of cyclins D1/E and CDKIs p16 and p27, together with a deregulation of the Rb/E2F pathway, may be implicated in the development of human UM. 相似文献
7.
Uveal melanoma (UM) is the most frequent primary intraocular tumor in adult humans. Despite the significant advances in diagnosis and treatment of UM in the last decades, the prognosis of UM sufferers is still poor. Metastatic liver disease is the leading cause of death in UM and can develop after a long disease-free interval, suggesting the presence of occult micrometastasis. Proteomics technology has opened new opportunities for elucidating the molecular mechanism of complex diseases, such as cancer. This article will review the recent developments in biomarker discovery for UM research by proteomics. In the last few years, the first UM proteomics-based analyses have been launched, yielding promising results. An update on recent developments on this field is presented. 相似文献
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Young Chan Kim Cesar Lopez-Camacho Joanne E. Nettleship Nahid Rahman Michelle L. Hill Laura Silva-Reyes Georgina Ortiz-Martinez Gloria Figueroa-Aguilar María Antonieta Mar Héctor Vivanco-Cid Christine S. Rollier Nicole Zitzmann Martha Eva Viveros-Sandoval Raymond J. Owens Arturo Reyes-Sandoval 《Virology journal》2018,15(1):193