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91.
Mariano Barbieri Mita Chotalia James Fraser Liron-Mark Lavitas Josée Dostie Ana Pombo Mario Nicodemi 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(40):16173-16178
Chromatin has a complex spatial organization in the cell nucleus that serves vital functional purposes. A variety of chromatin folding conformations has been detected by single-cell imaging and chromosome conformation capture-based approaches. However, a unified quantitative framework describing spatial chromatin organization is still lacking. Here, we explore the “strings and binders switch” model to explain the origin and variety of chromatin behaviors that coexist and dynamically change within living cells. This simple polymer model recapitulates the scaling properties of chromatin folding reported experimentally in different cellular systems, the fractal state of chromatin, the processes of domain formation, and looping out. Additionally, the strings and binders switch model reproduces the recently proposed “fractal–globule” model, but only as one of many possible transient conformations. 相似文献
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Ruthann B. Pfau Devon Lamb Thrush Elizabeth Hamelberg Dennis Bartholomew Shaun Botes Matthew Pastore Christopher Tan Daniela del Gaudio Julie M. Gastier-Foster Caroline Astbury 《European journal of medical genetics》2013,56(11):609-613
A newborn with severe microcephaly and a history of parental consanguinity was referred for cytogenetic analysis and subsequently for genetic evaluation. While a 46,XY karyotype was eventually obtained, premature chromosome condensation was observed. A head MRI confirmed primary microcephaly. This combination of features focused clinical interest on the MCPH1 gene and directed genetic testing by sequence analysis and duplication/deletion studies disclosed a homozygous deletion of exons 1–11 of the MCPH1 gene. This case illustrates a strength of standard cytogenetic evaluation in directing molecular testing to a single target gene in this disorder, allowing much more rapid diagnosis at a substantial cost savings for this family. 相似文献
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Bakopoulou A Tsiftsoglou A Galaktidou G Markala D Triviai I Garefis P 《European journal of oral sciences》2007,115(5):397-407
Previous studies have shown that in vitro exposure to single compounds released from composite resins may induce cell death. In the present study the effects of eluates from commercially available composite resins used for direct or indirect restorations were evaluated on the cell cycle progression and type of cell death of cultured WEHI 13 var fibroblasts. Cells exposed to eluates of the materials were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cell death, for cell cycle profiles by flow cytometry, for caspase-3 biochemically and by immunocytochemistry, and for morphological changes by fluorescence microscopy with acridine orange. The direct composite resin eluates induced extensive apoptosis, followed by secondary necrosis. This was accompanied by cell enlargement, micromultinucleation, chromatin disintegration, cell cycle arrest at different phases, and caspase-3 activation. The composites for indirect restorations were much less cytotoxic at all biological end-points investigated. The findings suggest that composite resins used for direct and indirect dental restorations differ in their cytotoxic potential and their ability to affect basic cellular functions. This underlines the impact of improved polymerization with respect to their biologic behavior. 相似文献
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To extend the applications of engineered nanomaterials, such as graphene oxide (GO), it is necessary to minimize cytotoxicity. However, the mechanisms underlying this cytotoxicity are unclear. Dynamic chromosomal interactions have been used to illustrate the molecular bases of gene expression, which offers a more sensitive and cutting-edge technology to elucidate complex biological processes associated with epigenetic regulations. In this study, the role of GO-triggered chromatin interactions in the activation of cox2, a hallmark of inflammation, was investigated in normal human cells. Using chromosome conformation capture technology, we showed that GO triggers physical interactions between the downstream enhancer and the cox2 promoter in human embryonic kidney 293T (293T) via p65 and p300 complex-mediated dynamic chromatin looping, which was required for high cox2 expression. Moreover, tumor necrosis factor-α (TNF-α), located upstream of the p65 signaling pathway, contributed to the regulation of cox2 activation through dynamic chromatin architecture. Compared with pristine GO and aminated GO (GO-NH2), poly (acrylic acid)-functionalized GO (GO-PAA) induced a weaker inflammatory response and a weaker effect on chromatin architecture. Our results mechanistically link GO-mediated chromatin interactions with the regulation of cox2 and suggest that GO derivatives may minimize toxicity in practical applications. 相似文献
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Genome-wide studies highlight indirect links between human replication origins and gene regulation 总被引:1,自引:0,他引:1
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