Matrix assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) is largely performed on fresh frozen tissue whereas clinical tissue samples stored long term are fixed in formalin, and the fixation process is thought to cause signal suppression for lipid molecules. Studies have shown that fresh frozen brain tissue sections washed with ammonium formate (AF) prior to matrix application in the MALDI-IMS procedure display an increase in signal intensity and sensitivity for lipid molecules while maintaining molecular spatial distribution throughout the tissue. Work in this thesis compares MALDI data of ganglioside molecules from fresh frozen and post-fixed rat brain samples, and post-fixed human brain samples washed with AF. Results demonstrate that MALDI-IMS spectra for gangliosides are significantly enhanced in fresh frozen rat brain, formalin-fixed rat brain and formalin fixed human brain samples washed with AF. This method will allow for the analysis of gangliosides from formalin-fixed clinical samples, which can open additional avenues for neurodegenerative disease research.
Periventricular white matter hyperintensities (pvWMHs) are a neurological feature detected with magnetic resonance imaging that are clinically associated with an increased risk of stroke and dementia. pvWMHs represent white matter lesions characterized by regions of myelin and axon rarefaction and as such likely involve changes in lipid composition; however, these alterations remain unknown. Lipids are critical in determining cell function and survival. Perturbations in lipid expression have previously been associated with neurological disorders. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an emerging technique for untargeted, high-throughput investigation of lipid expression and spatial distribution in situ; however, the use of MALDI IMS has been previously been limited by the need for nonembedded, non-fixed, fresh-frozen samples. In the current study, we demonstrate the novel use of MALDI IMS to distinguish regional lipid abnormalities that correlate with magnetic resonance imaging (MRI) defined pvWMHs within ammonium formate washed, formalin-fixed human archival samples. MALDI IMS scans were conducted in positive or negative ion detection mode on tissues sublimated with 2,5-dihydroxybenzoic acid or 1,5-diaminonaphthalene matrices, respectively. Using a broad, untargeted approach to lipid analysis, we consistently detected 116 lipid ion species in 21 tissue blocks from 11 different post-mortem formalin-fixed human brains. Comparing the monoisotopic mass peaks of these lipid ions elucidated significant differences in lipid expression between pvWMHs and NAWM for 31 lipid ion species. Expanding our understanding of alterations in lipid composition will provide greater knowledge of molecular mechanisms underpinning ischemic white matter lesions and provides the potential for novel therapeutic interventions targeting lipid composition abnormalities.
Self‐organization through communication is observed in many systems throughout nature, often resulting in a collective response to a change in the environment. Herein, we demonstrate a synthetic system that exhibits chemical communication between small active and larger inactive particles which drives the reversible assembly of the latter into colloidal crystals. Specifically, we report the autonomous hexagonal packing of inert silica particles due to the oscillatory behavior of neighboring silver phosphate micromotors under UV light in the presence of hydrogen peroxide. The colloidal crystals are formed under UV illumination and relax into a disordered state when the light is turned off. Furthermore, oscillatory waves generated by the active particles cause “autonomous annealing”, or elimination of defects between crystal boundaries of the silica colloidal crystals.
The front cover artwork is provided by the Sen group at Penn State (USA). The image shows how active Ag3PO4 particles herd inactive SiO2 particles into colloidal crystals that exhibit oscillatory motion. The crystals disperse then rejoin/reorganize, undergoing “autonomous annealing”. Read the full text of the Communication at 10.1002/syst.201900021.
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