Distinct Cholesterol Localization in Glioblastoma Multiforme Revealed by Mass Spectrometry Imaging

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in adults and is highly resistant to chemo- and radiotherapies. GBM has been associated with alterations in lipid contents, but lipid metabolism reprogramming in tumor cells is not fully elucidated. One of the key hurdles is to localize the lipid species that are correlated with tumor growth and invasion. A better understanding of the localization of abnormal lipid metabolism and its vulnerabilities may open up to novel therapeutic approaches. Here, we use time-of-flight secondary ion mass spectrometry (ToF-SIMS) to spatially probe the lipid composition in a GBM biopsy from two regions with different histopathologies: one region with most cells of uniform size and shape, the homogeneous part, and the other with cells showing a great variation in size and shape, the heterogeneous part. Our results reveal elevated levels of cholesterol, diacylglycerols, and some phosphatidylethanolamine in the homogeneous part, while the heterogeneous part was dominated by a variety of fatty acids, phosphatidylcholine, and phosphatidylinositol species. We also observed a high expression of cholesterol in the homogeneous tumor region to be associated with large cells but not with macrophages. Our findings suggest that ToF-SIMS can distinguish in lipid distribution between parts within a human GBM tumor, which can be linked to different molecular mechanisms

Flexible polyandry in female flies is an adaptive response to infertile males

Infertility is common in nature despite its obvious cost to individual fitness. Rising global temperatures are predicted to decrease fertility, and male sterility is frequently used in attempts to regulate pest or disease vector populations. When males are infertile, females may mate with multiple males to ensure fertilization, and changes in female mating behavior in turn could intensify selection on male fertility. Fertility assurance is a potentially wide-spread explanation for polyandry, but whether and how it actually contributes to the evolution of polyandry is not clear. Moreover, whether a drop in male fertility would lead to a genetic increase in polyandry depends on whether females respond genetically or through behavioral plasticity to male infertility. Here, we experimentally manipulate male fertility through heat-exposure in Drosophila pseudoobscura, and test female discrimination against infertile males before and after mating. Using isogenic lines, we compare the roles of behaviorally plastic versus genetically fixed polyandry. We find that heat-exposed males are less active and attractive, and that females are more likely to remate after mating with these males. Remating rate increases with reduced reproductive output, indicating that females use current sperm storage threshold to make dynamic remating decisions. After remating with fertile males, females restore normal fecundity levels. Our results suggest that male infertility could explain the evolution of adaptively flexible polyandry, but is less likely to cause an increase in genetic polyandry

Polyandry and fecundity data

Data on: 1) female mating behaviour, remating, and fecundity in response to male heat-exposure; 2) male survival of heat-exposure; 3) fertility and mating capacity of heat-exposed male