| 1. |
- Schosserer, Markus, et al.
(författare)
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Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Several pathways modulating longevity and stress resistance converge on translation by targeting ribosomal proteins or initiation factors, but whether this involves modifications of ribosomal RNA is unclear. Here, we show that reduced levels of the conserved RNA methyltransferase NSUN5 increase the lifespan and stress resistance in yeast, worms and flies. Rcm1, the yeast homologue of NSUN5, methylates C2278 within a conserved region of 25S rRNA. Loss of Rcm1 alters the structural conformation of the ribosome in close proximity to C2278, as well as translational fidelity, and favours recruitment of a distinct subset of oxidative stress-responsive mRNAs into polysomes. Thus, rather than merely being a static molecular machine executing translation, the ribosome exhibits functional diversity by modification of just a single rRNA nucleotide, resulting in an alteration of organismal physiological behaviour, and linking rRNA-mediated translational regulation to modulation of lifespan, and differential stress response.
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| 2. |
- Stoffels, Charlotte B. A., et al.
(författare)
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Lipidomic Profiling of PFOA-Exposed Mouse Liver by Multi-Modal Mass Spectrometry Analysis
- 2023
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 95:16, s. 6568-6576
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Tidskriftsartikel (refereegranskat)abstract
- Perfluorooctanoic acid (PFOA) is a synthetic perfluorinated chemical classified as a persistent organic pollutant. PFOA has been linked to many toxic effects, including liver injury. Many studies report that PFOA exposure alters serum and hepatic lipid metabolism. However, lipidomic pathways altered by PFOA exposure are largely unknown and only a few lipid classes, mostly triacylglycerol (TG), are usually considered in lipid analysis. Here, we performed a global lipidomic analysis on the liver of PFOA-exposed (high-dose and short-duration) and control mice by combining three mass spectrometry (MS) techniques: liquid chromatography with tandem mass spectrometry (LC-MS/MS), matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), and time-of-flight secondary ion mass spectrometry (TOF-SIMS). Among all hepatic lipids identified by LC-MS/MS analysis, more than 350 were statistically impacted (increased or decreased levels) after PFOA exposure, as confirmed by multi-variate data analysis. The levels of many lipid species from different lipid classes, most notably phosphatidylethanolamine (PE), phosphatidylcholine (PC), and TG, were significantly altered. Subsequent lipidomic analysis highlights the pathways significantly impacted by PFOA exposure, with the glycerophospholipid metabolism being the most impacted, and the changes in the lipidome network, which connects all the lipid species together. MALDI-MSI displays the heterogeneous distribution of the affected lipids and PFOA, revealing different areas of lipid expression linked to PFOA localization. TOF-SIMS localizes PFOA at the cellular level, supporting MALDI-MSI results. This multi-modal MS analysis unveils the lipidomic impact of PFOA in the mouse liver after high-dose and short-term exposure and opens new opportunities in toxicology.
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| 3. |
- Angerer, Tina B., 1987, et al.
(författare)
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3D Imaging of TiO2 nanoparticle accumulation in tetrahymena pyriformis
- 2014
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Ingår i: Surface and Interface Analysis. - : Wiley. - 0142-2421 .- 1096-9918. ; 46:S1, s. 198-203
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Tidskriftsartikel (refereegranskat)abstract
- The increasing use of nanoparticles in a wide range of applications means that there is a significant chance that these chemicals may enter the aquatic environment. We report on the use of time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis to determine the 3D distribution of TiO2 nanoparticles in the fresh water dwelling single cell organism Tetrahymena pyriformis. This organism is a popular model for toxicology studies where assays normally focus on the physical behaviour of the organism (motility, proliferation etc.) or where chemical analysis has been performed on large numbers of cells that have been combined for analysis. SIMS offers the opportunity for studying this single cell organism directly. Using ToF-SIMS analysis, the nanoparticles were shown to be accumulated in food vacuoles approximately 5μm in diameter that are distributed throughout the cell. Challenges associated with accurate 3D reconstruction of the data because of substantial differences in sputter rate between the natural cellular material and the TiO2-rich regions are demonstrated and discussed. © 2014 John Wiley & Sons, Ltd.
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| 4. |
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| 5. |
- Angerer, Tina B., 1987, et al.
(författare)
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High energy gas cluster ions for organic and biological analysis by time-of-flight secondary ion mass spectrometry
- 2015
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Ingår i: International Journal of Mass Spectrometry. - : Elsevier BV. - 1387-3806 .- 1873-2798. ; 377, s. 591-598
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Tidskriftsartikel (refereegranskat)abstract
- There is considerable excitement surrounding the application of gas cluster ion beams (GCIBs) for SIMS analysis in order to study organic materials and biological samples such as cells and tissues. These ion beams, that often comprise several thousand argon atoms in the primary ion, have been used mainly for the etching of organic materials to remove damage from the surface allowing molecular depth profiling experiments to be performed. The energy of the ion beam is normally 2–20 keV. There have been relatively few studies reported on the use of GCIB as analysis beams, due to difficulties related to fast pulsing and focusing of the beam along with the sometimes low ionisation efficiency. In this study, we report on the use of a new higher energy (40 keV) GCIB operated in a continuous mode. When compared to lower energies depth profiles on thin films of Irganox 1010 show an increase in sputter yield signal while fragmentation, damage accumulation and ionisation efficiency remains unchanged. Experiments on brain tissues show increased signal levels especially for higher mass secondary ions (m/z 500+) in comparison to C60+ at 40 keV and Ar4000+ at 20 keV impact energy. The use of higher energies facilitates better focusing of the primary ion beam as demonstrated here on a human hair sample where we achieve a spatial resolution of
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| 6. |
- Angerer, Tina B., 1987, et al.
(författare)
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Improved Molecular Imaging in Rodent Brain with Time-of-Flight-Secondary Ion Mass Spectrometry Using Gas Cluster Ion Beams and Reactive Vapor Exposure
- 2015
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 87:8, s. 4305-4313
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Tidskriftsartikel (refereegranskat)abstract
- Imaging mass spectrometry has shown to be a valuable method in medical research and can be performed using different instrumentation and sample preparation methods, each one with specific advantages and drawbacks. Time-of-flight-secondary ion mass spectrometry (TOF-SIMS) has the advantage of high spatial resolution imaging but is often restricted to low mass molecular signals and can be very sensitive to sample preparation artifacts. In this report we demonstrate the advantages of using gas cluster ion beams (GCIBs) in combination with trifluoracetic acid (TFA) vapor exposure for the imaging of lipids in mouse brain sections. There is an optimum exposure to TFA that is beneficial for increasing high mass signal as well as producing signal from previously unobserved species in the mass spectrum. Cholesterol enrichment and crystallization on the sample surface is removed by TFA exposure uncovering a wider range of lipid species in the white matter regions of the tissue, greatly expanding the chemical coverage and the potential application of TOF-SIMS imaging in neurological studies. Ar-4000(+) (40 keV) in combination with TFA treatment facilitates high resolution, high mass imaging closing the gap between TOF-SIMS and matrix-assisted laser desorption ionization (MALDI).
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| 7. |
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| 8. |
- Angerer, Tina B., 1987, et al.
(författare)
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Lipid Heterogeneity Resulting from Fatty Acid Processing in the Human Breast Cancer Microenvironment Identified by GCIB-ToF-SIMS Imaging
- 2016
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 88:23, s. 11946-54
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is an umbrella term used to describe a collection of different diseases with broad inter- and intratumor heterogeneity. Understanding this variation is critical in order to develop, and precisely prescribe, new treatments. Changes in the lipid metabolism of cancerous cells can provide important indications as to the metabolic state of the cells but are difficult to investigate with conventional histological methods. Due to the introduction of new higher energy (40 kV) gas cluster ion beams (GCIBs), time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is now capable of providing information on the distribution of hundreds of molecular species simultaneously on a cellular to subcellular scale. GCIB-ToF-SIMS was used to elucidate changes in lipid composition in nine breast cancer biopsy samples. Improved molecular signal generation by the GCIB produced location-specific information that revealed elevated levels of essential lipids to be related to inflammatory cells in the stroma, while cancerous areas were dominated by nonessential fatty acids and a variety of phosphatidylinositol species with further in-tumor variety arising from decreased desaturase activity. These changes in lipid composition due to different enzyme activity are seemingly independent of oxygen availability and can be linked to favorable cell membrane properties for either proliferation/invasion or drug resistance/survival
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| 9. |
- Angerer, Tina B., 1987, et al.
(författare)
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Optimizing sample preparation for anatomical determination in the hippocampus of rodent brain by ToF-SIMS analysis
- 2016
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Ingår i: Biointerphases. - : American Vacuum Society. - 1934-8630 .- 1559-4106. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Lipidomics has been an expanding field since researchers began to recognize the signaling functions of lipids and their involvement in disease. Time-of-flight secondary ion mass spectrometry is a valuable tool for studying the distribution of a wide range of lipids in multiple brain regions, but in order to make valuable scientific contributions, one has to be aware of the influence that sample treatment can have on the results. In this article, the authors discuss different sample treatment protocols for rodent brain sections focusing on signal from the hippocampus and surrounding areas. The authors compare frozen hydrated analysis to freeze drying, which is the standard in most research facilities, and reactive vapor exposure (trifluoroacetic acid and NH3). The results show that in order to preserve brain chemistry close to a native state, frozen hydrated analysis is the most suitable, but execution can be difficult. Freeze drying is prone to produce artifacts as cholesterol migrates to surface, masking other signals. This effect can be partially reversed by exposing freeze dried sections to reactive vapor. When analyzing brain sections in negative ion mode, exposing those sections to NH3 vapor can re-establish the diversity in lipid signal found in frozen hydrated analyzed sections. This is accomplished by removing cholesterol and uncovering sulfatide signals, allowing more anatomical regions to be visualized.
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| 10. |
- Burke, R. D., et al.
(författare)
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A genomic view of the sea urchin nervous system
- 2006
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Ingår i: Developmental Biology. - : Elsevier BV. - 0012-1606 .- 1095-564X. ; 300:1, s. 434-460
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Tidskriftsartikel (refereegranskat)abstract
- The sequencing of the Strongylocentrotus purpuratus genome provides a unique opportunity to investigate the function and evolution of neural genes. The neurobiology of sea urchins is of particular interest because they have a close phylogenetic relationship with chordates, yet a distinctive pentaradiate body plan and unusual neural organization. Orthologues of transcription factors that regulate neurogenesis in other animals have been identified and several are expressed in neurogenic domains before gastrulation indicating that they may operate near the top of a conserved neural gene regulatory network. A family of genes encoding voltage-gated ion channels is present but, surprisingly, genes encoding gap junction proteins (connexins and pannexins) appear to be absent. Genes required for synapse formation and function have been identified and genes for synthesis and transport of neurotransmitters are present. There is a large family of G-protein-coupled receptors, including 874 rhodopsin-type receptors, 28 metabotropic glutamate-like receptors and a remarkably expanded group of 161 secretin receptor-like proteins. Absence of cannabinoid, lysophospholipid and melanocortin receptors indicates that this group may be unique to chordates. There are at least 37 putative G-protein-coupled peptide receptors and precursors for several neuropeptides and peptide hormones have been identified, including SALMFamides, NGFFFamide, a vasotocin-like peptide, glycoprotein hormones and insulin/insulin-like growth factors. Identification of a neurotrophin-like gene and Trk receptor in sea urchin indicates that this neural signaling system is not unique to chordates. Several hundred chemoreceptor genes have been predicted using several approaches, a number similar to that for other animals. Intriguingly, genes encoding homologues of rhodopsin, Pax6 and several other key mammalian retinal transcription factors are expressed in tube feet, suggesting tube feet function as photosensory organs. Analysis of the sea urchin genome presents a unique perspective on the evolutionary history of deuterostome nervous systems and reveals new approaches to investigate the development and neurobiology of sea urchins. (c) 2006 Elsevier Inc. All rights reserved.
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