Editorial: Seismic microzonation and risk reduction

Editorial on the Research Topic Seismic microzonation and risk reductio

Exponentially Modified Protein Abundance Index (emPAI) for Estimation of Absolute Protein Amount in Proteomics by the Number of Sequenced Peptides per Protein

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Synaptic activity prompts γ-secretase–mediated cleavage of EphA4 and dendritic spine formation

Alzheimer's disease is an age-dependent neurodegenerative disorder that is characterized by a progressive decline in cognitive function. γ-secretase dysfunction is evident in many cases of early onset familial Alzheimer's disease. However, the mechanism by which γ-secretase dysfunction results in memory loss and neurodegeneration is not fully understood. Here, we demonstrate that γ-secretase is localized at synapses and regulates spine formation. We identify EphA4, one of the Ephrin receptor family members, as a substrate of γ-secretase, and find that EphA4 processing is enhanced by synaptic activity. Moreover, overexpression of EphA4 intracellular domain increases the number of dendritic spines by activating the Rac signaling pathway. These findings reveal a function for EphA4-mediated intracellular signaling in the morphogenesis of dendritic spines and suggest that the processing of EphA4 by γ-secretase affects the pathogenesis of Alzheimer's disease

Isobaric mass tagging and triple quadrupole mass spectrometry to determine lipid biomarker candidates for Alzheimer's disease.

The isobaric tagging method widely used in proteomic and lipidomic fields, with the multiple reaction monitoring (MRM) approach using a triple quadrupole mass spectrometer, was applied to identify biomarker candidates from plasma samples for Alzheimer's disease (AD). We focused on the following phospholipids that have amino groups as the functional group: phosphatidylethanolamine (PE), Lyso-PE, phosphatidylserine, and Lyso-phosphatidylserine. We also investigated fatty acids that have a carboxy group. A sixplex tandem mass tag (TMT) was used for the isobaric tagging method in this study. The TMT reaction had high reproducibility in human plasma. A total of 196 human plasma samples from three AD cohorts were used for the study, and compared to pooled plasma quality control (QC) samples. The described method required only 40 MRM measurements, including the pooled QC samples, for a full comparison of the data. We found that the content of free fatty acids increased in AD samples in all the three cohorts, alkenyl PEs (ePEs) decreased over a one-year interval in AD patients, and ePEs weakly correlated with amyloid peptide (a-beta) 1-42 in cerebrospinal fluid. In conclusion, total free fatty acids in plasma are a risk factor for AD, and ePEs monitor candidates for AD. Therefore, TMT-lipidomics is a powerful approach for the determination of plasma biomarkers because of the high sample throughput

TRACES: A Lightweight Browser for Liquid Chromatography–Multiple Reaction Monitoring–Mass Spectrometry Chromatograms

In targeted metabolomic analysis using liquid chromatography–multiple reaction monitoring–mass spectrometry (LC-MRM-MS), hundreds of MRMs are performed in a single run, yielding a large dataset containing thousands of chromatographic peaks. Automation tools for processing large MRM datasets have been reported, but a visual review of chromatograms is still critical, as real samples with biological matrices often cause complex chromatographic patterns owing to non-specific, insufficiently separated, isomeric, and isotopic components. Herein, we report the development of new software, TRACES, a lightweight chromatogram browser for MRM-based targeted LC-MS analysis. TRACES provides rapid access to all MRM chromatograms in a dataset, allowing users to start ad hoc data browsing without preparations such as loading compound libraries. As a special function of the software, we implemented a chromatogram-level deisotoping function that facilitates the identification of regions potentially affected by isotopic signals. Using MRM libraries containing precursor and product formulae, the algorithm reveals all possible isotopic interferences in the dataset and generates deisotoped chromatograms. To validate the deisotoping function in real applications, we analyzed mouse tissue phospholipids in which isotopic interference by molecules with different fatty-acyl unsaturation levels is known. TRACES successfully removed isotopic signals within the MRM chromatograms, helping users avoid inappropriate regions for integration