| 401. |
- Noguchi, Satoshi, et al.
(författare)
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An Integrative Analysis of the Tumorigenic Role of TAZ in Human Non-Small Cell Lung Cancer
- 2014
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 20:17, s. 4660-4672
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: TAZ, also known as WWTR1, has recently been suggested as an oncogene in non-small cell lung cancer (n =SCLC). We investigated the clinical relevance of TAZ expression and its functional role in NSCLC tumorigenesis. Experimental Design: We characterized TAZ at the DNA (n = 192), mRNA (n = 196), and protein levels (n = 345) in an NSCLC patient cohort. Gene expression analysis was complemented by a meta-analysis of public datasets (n = 1,382). The effects of TAZ on cell proliferation and cell cycle were analyzed in cell cultures and on tumor growth in mice. TAZ-dependent microarray-based expression profiles in NSCLC cells were combined with molecular profiles in human NSCLC tissues for in silico analysis. Results: Higher TAZmRNA and protein levels were associated with shorter patient survival. Transduction of TAZ enhanced cell proliferation and tumorigenesis in bronchial epithelial cells, whereas TAZ silencing suppressed cell proliferation and induced cell cycle arrest in NSCLC cells. Microarray and cell culture experiments showed that ErbB ligands (amphiregulin, epiregulin, and neuregulin 1) are downstream targets of TAZ. Our in silico analysis revealed a TAZ signature that substantiated the clinical impact of TAZ and confirmed its relationship to the epidermal growth factor receptor signaling pathway. Conclusion: TAZ expression defines a clinically distinct subgroup of patients with NSCLC. ErbB ligands are suggested to mediate the effects of TAZ on lung cancer progression. Our findings emphasize the tumorigenic role of TAZ and may serve as the basis for new treatment strategies.
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| 402. |
- Pruden, A., et al.
(författare)
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Management Options for Reducing the Release of Antibiotics and Antibiotic Resistance Genes to the Environment
- 2013
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:8, s. 878-885
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. OBJECTIVE: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. METHODS: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. DISCUSSION: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stake-holders and promote action. CONCLUSIONS: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action.
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| 403. |
- Reddington, James P, et al.
(författare)
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Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes
- 2013
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 14:3, s. R25-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: DNA methylation and the Polycomb repression system are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear.RESULTS: By genome-wide mapping of the Polycomb Repressive Complex 2-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and Polycomb Repressive Complex 2 from Polycomb target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression.CONCLUSIONS: An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining Polycomb Repressive Complex 2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease.
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| 404. |
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| 405. |
- Suzuki, H., et al.
(författare)
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Rules for aggregated satisfaction with work commutes
- 2014
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Ingår i: Transportation. - : Springer Science and Business Media LLC. - 0049-4488 .- 1572-9435. ; 41:3, s. 495-506
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Tidskriftsartikel (refereegranskat)abstract
- In general trips frequently entail several stages varying in mode, duration, and other factors. In some way travelers aggregate their satisfaction with the stages to satisfaction with the whole trip. In this paper we address the question of how this aggregation is made. We use data from a Swedish survey measuring satisfaction with commutes to and from work and with the stages of the commutes. We test several aggregation rules for their goodness of fit to the observations. Our results show that a normatively correct averaging rule that takes into account the relative durations of the stages out-perform heuristic aggregation rules such as the peak-end, summation, and equal-weight averaging rules. We note that this does not exclude that the heuristic aggregation rules apply to other trips than repetitive commute trips.
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| 406. |
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| 407. |
- Zhang, L., et al.
(författare)
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Electronic band structure of graphene from resonant soft x-ray spectroscopy : The role of core-hole effects
- 2012
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 86:24, s. 245430-
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure and band dispersion of graphene on SiO2 have been studied by x-ray-absorption spectroscopy (XAS), x-ray-emission spectroscopy (XES), and resonant inelastic x-ray scattering (RIXS). Using first-principles calculations, it is found that the core-hole effect is dramatic in XAS while it has negligible consequences in XES. Strong dispersive features, due to the conservation of crystal momentum, are observed in RIXS spectra. Simulated RIXS spectra based on the Kramers-Heisenberg theory agree well with the experimental results, provided a shift between RIXS and XAS due to the absence or presence of the core hole is taken into account.
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