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1.
EMBO J ; 41(10): e109202, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35451102

RESUMO

Nonsense-mediated mRNA decay (NMD) is governed by the three conserved factors-UPF1, UPF2, and UPF3. While all three are required for NMD in yeast, UPF3B is dispensable for NMD in mammals, and its paralog UPF3A is suggested to only weakly activate or even repress NMD due to its weaker binding to the exon junction complex (EJC). Here, we characterize the UPF3A/B-dependence of NMD in human cell lines deleted of one or both UPF3 paralogs. We show that in human colorectal cancer HCT116 cells, NMD can operate in a UPF3B-dependent and -independent manner. While UPF3A is almost dispensable for NMD in wild-type cells, it strongly activates NMD in cells lacking UPF3B. Notably, NMD remains partially active in cells lacking both UPF3 paralogs. Complementation studies in these cells show that EJC-binding domain of UPF3 paralogs is dispensable for NMD. Instead, the conserved "mid" domain of UPF3 paralogs is consequential for their NMD activity. Altogether, our results demonstrate that the mammalian UPF3 proteins play a more active role in NMD than simply bridging the EJC and the UPF complex.


Assuntos
Degradação do RNAm Mediada por Códon sem Sentido , Proteínas de Ligação a RNA , Éxons , Células HCT116 , Humanos , RNA Helicases/genética , RNA Helicases/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transativadores/genética , Transativadores/metabolismo
2.
Langmuir ; 34(37): 10905-10912, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30122042

RESUMO

Surface pressure-area isotherms were recorded under different irradiation conditions for single-component Langmuir films of three photochromic amphiphilic dithienylethenes. Nonirradiated films of these photochromic amphiphiles were mechanically stable. In addition, a shift of the isotherms to larger mean molecular areas was observed for films prepared from UV-light-irradiated dithienylethenes. Unexpectedly, a significant expansion was observed for a film prepared from visible-light-irradiated dithienylethene incorporating large branched alkyl chains. Upon further study, atomic force microscopy and transmission electron microscopy images of Langmuir-Schaefer films revealed that this pronged dialkyl derivative undergoes a photoinduced change in morphology, as circular aggregates coalesce into larger continuous aggregated structures. Nevertheless, its photoisomerization was completely reversible as single-component multilayer thin films upon direct UV or visible light irradiation.

3.
Multiscale Model Simul ; 15(1): 537-574, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29046619

RESUMO

Numerous centrality measures have been developed to quantify the importances of nodes in time-independent networks, and many of them can be expressed as the leading eigenvector of some matrix. With the increasing availability of network data that changes in time, it is important to extend such eigenvector-based centrality measures to time-dependent networks. In this paper, we introduce a principled generalization of network centrality measures that is valid for any eigenvector-based centrality. We consider a temporal network with N nodes as a sequence of T layers that describe the network during different time windows, and we couple centrality matrices for the layers into a supra-centrality matrix of size NT × NT whose dominant eigenvector gives the centrality of each node i at each time t. We refer to this eigenvector and its components as a joint centrality, as it reflects the importances of both the node i and the time layer t. We also introduce the concepts of marginal and conditional centralities, which facilitate the study of centrality trajectories over time. We find that the strength of coupling between layers is important for determining multiscale properties of centrality, such as localization phenomena and the time scale of centrality changes. In the strong-coupling regime, we derive expressions for time-averaged centralities, which are given by the zeroth-order terms of a singular perturbation expansion. We also study first-order terms to obtain first-order-mover scores, which concisely describe the magnitude of nodes' centrality changes over time. As examples, we apply our method to three empirical temporal networks: the United States Ph.D. exchange in mathematics, costarring relationships among top-billed actors during the Golden Age of Hollywood, and citations of decisions from the United States Supreme Court.

4.
IEEE Trans Vis Comput Graph ; 20(7): 1048-61, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26357360

RESUMO

We introduce a web-based computing infrastructure to assist the visual integration, mining and interactive navigation of large-scale astronomy observations. Following an analysis of the application domain, we design a client-server architecture to fetch distributed image data and to partition local data into a spatial index structure that allows prefix-matching of spatial objects. In conjunction with hardware-accelerated pixel-based overlays and an online cross-registration pipeline, this approach allows the fetching, displaying, panning and zooming of gigabit panoramas of the sky in real time. To further facilitate the integration and mining of spatial and non-spatial data, we introduce interactive trend images-compact visual representations for identifying outlier objects and for studying trends within large collections of spatial objects of a given class. In a demonstration, images from three sky surveys (SDSS, FIRST and simulated LSST results) are cross-registered and integrated as overlays, allowing cross-spectrum analysis of astronomy observations. Trend images are interactively generated from catalog data and used to visually mine astronomy observations of similar type. The front-end of the infrastructure uses the web technologies WebGL and HTML5 to enable cross-platform, web-based functionality. Our approach attains interactive rendering framerates; its power and flexibility enables it to serve the needs of the astronomy community. Evaluation on three case studies, as well as feedback from domain experts emphasize the benefits of this visual approach to the observational astronomy field; and its potential benefits to large scale geospatial visualization in general.

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