Mass Spectrometry Imaging Reveals Abnormalities in Cardiolipin Composition and Distribution in Astrocytoma Tumor Tissues.

Cardiolipin (CL) is a mitochondrial lipid with diverse roles in cellular respiration, signaling, and organelle membrane structure. CL content and composition are essential for proper mitochondrial function. Deranged mitochondrial energy production and signaling are key components of glial cell cancers and altered CL molecular species have been observed in mouse brain glial cell xenograft tumors. The objective of this study was to describe CL structural diversity trends in human astrocytoma tumors of varying grades and correlate these trends with histological regions within the heterogeneous astrocytoma microenvironment. To this aim, we applied desorption electrospray ionization coupled with high field asymmetric ion mobility mass spectrometry (DESI-FAIMS-MS) to map CL molecular species in human normal cortex (N = 29), lower-grade astrocytoma (N = 19), and glioblastoma (N = 28) tissues. With this platform, we detected 46 CL species and 12 monolysocardiolipin species from normal cortex samples. CL profiles detected from glioblastoma tissues lacked diversity and abundance of longer chain polyunsaturated fatty acid containing CL species when compared to CL detected from normal and lower-grade tumors. CL profiles correlated with trends in tumor viability and tumor infiltration. Structural characterization of the CL species by tandem MS experiments revealed differences in fatty acid and double bond isomer composition among astrocytoma tissues compared with normal cortex and glioblastoma tissues. The GlioVis platform was used to analyze astrocytoma gene expression data from the CGGA dataset. Decreased expression of several mitochondrial respiratory enzyme encoding-genes was observed for higher-grade versus lower-grade tumors, however no significant difference was observed for cardiolipin synthesis enzyme CRLS1.

Noninvasive Detection of Chemical Defenses in Poison Frogs Using the MasSpec Pen.

Poison frogs are well-known for their fascinating ability to store alkaloids in their skin as chemical defense against predators. Chemical methods used to study these alkaloids are limited by requirements for euthanasia or stress during sampling. Here, we demonstrate sensitive and biocompatible alkaloid detection and monitoring in vivo using the MasSpec Pen, a handheld, noninvasive chemical detection device coupled to a mass spectrometer. The MasSpec Pen allowed rapid (<15 s), gentle, and consecutive molecular analysis without harm or undue stress to the animals. Through a month-long alkaloid-feeding study with the dyeing poison frog, we observed temporal dynamics of chemical sequestration in vivo by comparing frogs fed the alkaloid decahydroquinoline (DHQ) to vehicle-fed frogs. We also demonstrate the feasibility of the MasSpec Pen for the untargeted detection of rich alkaloid profiles from skin extracts of the Diablito poison frog, collected from two distinct geographical populations in Ecuador. The results obtained in this study demonstrate the utility of the MasSpec Pen for direct, rapid, and biocompatible analysis of poison frog alkaloids.

Insight into the Effects of Plasmodium chabaudi on Platelets Using Carbon-Fiber Microelectrode Amperometry.

Platelets are anuclear circulating cell bodies within the bloodstream commonly known for their roles in clot formation during vascular injury to prevent blood loss. They also have significant impact in a range of diseases, including malaria. However, the role of platelets in malaria is controversial, with contradicting evidence suggesting either that they assist in destruction of malarial parasites or facilitate a severe form of malaria. Precedent work suggests that the timing of infection is critical in determining whether platelets switch roles from being protective to deleterious. As such, the work herein makes use of the unique mechanistic perspective offered by carbon-fiber microelectrode amperometry (CFMA) to understand how platelet secretion is impacted in malarial infection stages (ascending parasite count versus descending parasite count). Malarial platelet behavior was compared to platelets from noninfected control mice by probing their exocytotic function. Results suggest that mouse malaria caused by the parasite Plasmodium chabaudi, during both ascending and descending infection stages, reduces platelet exocytotic events and delays platelet granule fusion; in addition, platelets are more impacted by the disease early in the infection stages. In all, understanding platelet behavior in the malarial context may present new therapeutic routes to treat or cure malaria.