Lipidomic Profiling of PFOA-Exposed Mouse Liver by Multi-Modal Mass Spectrometry Analysis.

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.

Evaluation of 6 MALDI-Matrices for 10 μm Lipid Imaging and On-Tissue MSn with AP-MALDI-Orbitrap.

Mass spectrometry imaging is a technique uniquely suited to localize and identify lipids in a tissue sample. Using an atmospheric pressure (AP-) matrix-assisted laser desorption ionization (MALDI) source coupled to an Orbitrap Elite, numerous lipid locations and structures can be determined in high mass resolution spectra and at cellular spatial resolution, but careful sample preparation is necessary. We tested 11 protocols on serial brain sections for the commonly used MALDI matrices CHCA, norharmane, DHB, DHAP, THAP, and DAN in combination with tissue washing and matrix additives to determine the lipid coverage, signal intensity, and spatial resolution achievable with AP-MALDI.

TOF-SIMS imaging reveals tumor heterogeneity and inflammatory response markers in the microenvironment of basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common skin malignancy. In fact, it is as common as the sum of all other skin malignancies combined and the incidence is rising. In this focused and histology-guided study, tissue from a patient diagnosed with aggressive BCC was analyzed by imaging mass spectrometry in order to probe the chemistry of the complex tumor environment.

Exploiting the Semidestructive Nature of Gas Cluster Ion Beam Time-of-Flight Secondary Ion Mass Spectrometry Imaging for Simultaneous Localization and Confident Lipid Annotations.

Lipids have been recognized as key players in cell signaling and disease. Information on their location and distribution within a biological system, under varying conditions, is necessary to understand the contributions of different lipid species to an altered phenotype. Imaging mass spectrometry techniques, such as time-of-flight secondary ion mass spectrometry (ToF-SIMS) and matrix-assisted laser desorption/ionization (MALDI), are capable of revealing global lipid distributions in tissues in an untargeted fashion.

Insights into the histology of planarian flatworm Phagocata gracilis based on location specific, intact lipid information provided by GCIB-ToF-SIMS imaging.

Planarian flatworms are known as the masters of regeneration, re-growing an entire organism from as little as 1/279th part of their body. While the proteomics of these processes has been studied extensively, the planarian lipodome remains relatively unknown. In this study we investigate the lipid profile of planarian tissue sections with imaging Time-of-Flight - Secondary-Ion-Mass-Spectrometry (ToF-SIMS).

Lipid Heterogeneity Resulting from Fatty Acid Processing in the Human Breast Cancer Microenvironment Identified by GCIB-ToF-SIMS Imaging.

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.

Cholesterol Alters the Dynamics of Release in Protein Independent Cell Models for Exocytosis.

Neurons communicate via an essential process called exocytosis. Cholesterol, an abundant lipid in both secretory vesicles and cell plasma membrane can affect this process. In this study, amperometric recordings of vesicular dopamine release from two different artificial cell models created from a giant unilamellar liposome and a bleb cell plasma membrane, show that with higher membrane cholesterol the kinetics for vesicular release are decelerated in a concentration dependent manner.

Investigating the Role of the Stringent Response in Lipid Modifications during the Stationary Phase in E. coli by Direct Analysis with Time-of-Flight-Secondary Ion Mass Spectrometry.

Escherichia coli is able to rapidly adjust the biophysical properties of its membrane phospholipids to adapt to environmental challenges including starvation stress. These membrane lipid modifications were investigated in glucose starved E. coli cultures and compared to a ΔrelAΔspoT (ppGpp(0)) mutant strain of E.

Optimizing sample preparation for anatomical determination in the hippocampus of rodent brain by ToF-SIMS analysis.

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.

Significant enhancement of negative secondary ion yields by cluster ion bombardment combined with cesium flooding.

In secondary ion mass spectrometry (SIMS), the beneficial effect of cesium implantation or flooding on the enhancement of negative secondary ion yields has been investigated in detail for various semiconductor and metal samples. All results have been obtained for monatomic ion bombardment. Recent progress in SIMS is based to a large extent on the development and use of cluster primary ions.

Measuring Compositions in Organic Depth Profiling: Results from a VAMAS Interlaboratory Study.

We report the results of a VAMAS (Versailles Project on Advanced Materials and Standards) interlaboratory study on the measurement of composition in organic depth profiling. Layered samples with known binary compositions of Irganox 1010 and either Irganox 1098 or Fmoc-pentafluoro-l-phenylalanine in each layer were manufactured in a single batch and distributed to more than 20 participating laboratories. The samples were analyzed using argon cluster ion sputtering and either X-ray photoelectron spectroscopy (XPS) or time-of-flight secondary ion mass spectrometry (ToF-SIMS) to generate depth profiles.

Analysis of liposome model systems by time-of-flight secondary ion mass spectrometry.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is an important technique for studying chemical composition of micrometer scale objects due to its high spatial resolution imaging capabilities and chemical specificity. In this work we focus on the application of ToF-SIMS to gain insight into the chemistry of micrometer size liposomes as a potential model for neurotransmitter vesicles. Two models of giant liposomes were analyzed: histamine and aqueous two phase system (ATPS)-containing liposomes.

Improved molecular imaging in rodent brain with time-of-flight-secondary ion mass spectrometry using gas cluster ion beams and reactive vapor exposure.

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.

Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan.

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.