| 1. |
- Gräns, Johanna, 1979, et al.
(author)
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Regulation of pregnane-X-receptor, CYP3A and P-glycoprotein genes in the PCB-resistant killifish (Fundulus heteroclitus) population from New Bedford Harbor
- 2015
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In: Aquatic Toxicology. - : Elsevier BV. - 0166-445X. ; 159, s. 198-207
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Journal article (peer-reviewed)abstract
- Killifish survive and reproduce in the New Bedford Harbor (NBH) in Massachusetts (MA), USA, a site severely contaminated with polychlorinated biphenyls (PCBs) for decades. Levels of 22 different PCB congeners were analyzed in liver from killifish collected in 2008. Concentrations of dioxin-like PCBs in liver of NBH killifish were ~400 times higher, and the levels of non-dioxin-like PCBs ~3000 times higher than in killifish from a reference site, Scorton Creek (SC), MA. The NBH killifish are known to be resistant to the toxicity of dioxin-like compounds and to have a reduced aryl hydrocarbon receptor (AhR) signaling response. Little is known about the responses of these fish to non-dioxin-like PCBs, which are at extraordinarily high levels in NBH fish. In mammals, some non-dioxin-like PCB congeners act through nuclear receptor 1I2, the pregnane-X-receptor (PXR). To explore this pathway in killifish, a PXR cDNA was sequenced and its molecular phylogenetic relationship to other vertebrate PXRs was determined. Killifish were also collected in 2009 from NBH and SC, and after four months in the laboratory they were injected with a single dose of either the dioxin-like PCB 126 (an AhR agonist) or the non-dioxin-like PCB 153 (a mammalian PXR agonist). Gills and liver were sampled three days after injection and transcript levels of PXR, cytochrome P450 3A (CYP3A), P-glycoprotein (Pgp), AhR2 and cytochrome P450 1A (CYP1A) were measured by quantitative PCR. As expected, there was little effect of PCB exposure on AhR2 or CYP1A in liver and gills of NBH fish. In NBH fish, but not in SC fish, there was increased expression of hepatic PXR, CYP3A and Pgp genes upon exposure to either of the two PCB congeners. However, basal PXR and Pgp mRNA levels in liver of NBH fish were significantly lower than in SC fish. A different pattern was seen in gills, where there were no differences in basal expression of these genes between the two populations. In SC fish, but not in NBH fish, there was increased expression of branchial PXR and CYP3A upon exposure to PCB126 and of CYP3A upon exposure to PCB153. The results suggest a difference between the two populations in non-AhR transcription factor signaling in liver and gills, and that this could involve killifish PXR. It also implies possible cross-regulatory interactions between that factor (presumably PXR) and AhR2 in liver of these fish.
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| 2. |
- Tapfer, A., et al.
(author)
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Three-dimensional imaging of whole mouse models: comparing nondestructive X-ray phase-contrast micro-CT with cryotome-based planar epi-illumination imaging
- 2014
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In: Journal of Microscopy. - : Wiley. - 0022-2720. ; 253:1, s. 24-30
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Journal article (peer-reviewed)abstract
- In this study, we compare two evolving techniques for obtaining high-resolution 3D anatomical data of a mouse specimen. On the one hand, we investigate cryotome-based planar epi-illumination imaging (cryo-imaging). On the other hand, we examine X-ray phase-contrast micro-computed tomography (micro-CT) using synchrotron radiation. Cryo-imaging is a technique in which an electron multiplying charge coupled camera takes images of a cryo-frozen specimen during the sectioning process. Subsequent image alignment and virtual stacking result in volumetric data. X-ray phase-contrast imaging is based on the minute refraction of X-rays inside the specimen and features higher soft-tissue contrast than conventional, attenuation-based micro-CT. To explore the potential of both techniques for studying whole mouse disease models, one mouse specimen was imaged using both techniques. Obtained data are compared visually and quantitatively, specifically with regard to the visibility of fine anatomical details. Internal structure of the mouse specimen is visible in great detail with both techniques and the study shows in particular that soft-tissue contrast is strongly enhanced in the X-ray phase images compared to the attenuation-based images. This identifies phase-contrast micro-CT as a powerful tool for the study of small animal disease models.
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| 3. |
- Zanette, I., et al.
(author)
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Speckle-Based X-Ray Phase-Contrast and Dark-Field Imaging with a Laboratory Source
- 2014
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In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 112:25, s. 253903-
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Journal article (peer-reviewed)abstract
- We report on the observation and application of near-field speckles with a laboratory x-ray source. The detection of speckles is possible thanks to the enhanced brilliance properties of the used liquid-metal-jet source, and opens the way to a range of new applications in laboratory-based coherent x-ray imaging. Here, we use the speckle pattern for multimodal imaging of demonstrator objects. Moreover, we introduce algorithms for phase and dark-field imaging using speckle tracking, and we show that they yield superior results with respect to existing methods.
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| 4. |
- Zanette, I., et al.
(author)
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X-ray microtomography using correlation of near-field speckles for material characterization
- 2015
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:41, s. 12569-12573
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Journal article (peer-reviewed)abstract
- Nondestructive microscale investigation of objects is an invaluable tool in life and materials sciences. Currently, such investigation is mainly performed with X-ray laboratory systems, which are based on absorption-contrast imaging and cannot access the information carried by the phase of the X-ray waves. The phase signal is, nevertheless, of great value in X-ray imaging as it is complementary to the absorption information and in general more sensitive to visualize features with small density differences. Synchrotron facilities, which deliver a beam of high brilliance and high coherence, provide the ideal condition to develop such advanced phase-sensitive methods, but their access is limited. Here we show how a small modification of a laboratory setup yields simultaneously quantitative and 3D absorption and phase images of the object. This single-shot method is based on correlation of X-ray near-field speckles and represents a significant broadening of the capabilities of laboratory- based X-ray tomography.
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