The royal food of termites shows king and queen specificity.

Society in eusocial insects is based on the reproductive division of labor, with a small number of reproductive individuals supported by a large number of nonreproductive individuals. Because inclusive fitness of all colony members depends on the survival and fertility of reproductive members, sterile members provide royals with special treatment. Here, we show that termite kings and queens each receive special food of a different composition from workers. Sequential analysis of feeding processes demonstrated that workers exhibit discriminative trophallaxis, indicating their decision-making capacity in allocating food to the kings and queens. Liquid chromatography tandem-mass spectrometry analyses of the stomodeal food and midgut contents revealed king- and queen-specific compounds, including diacylglycerols and short-chain peptides. Desorption electrospray ionization mass spectrometry imaging analyses of 13C-labeled termites identified phosphatidylinositol and acetyl-l-carnitine in the royal food. Comparison of the digestive tract structure showed remarkable differences in the volume ratio of the midgut-to-hindgut among castes, indicating that digestive division of labor underlies reproductive division of labor. Our demonstration of king- and queen-specific foods in termites provides insight into the nutritional system that underpins the extraordinary reproduction and longevity of royals in eusocial insects.

UBL3 Interacts with Alpha-Synuclein in Cells and the Interaction Is Downregulated by the EGFR Pathway Inhibitor Osimertinib.

Ubiquitin-like 3 (UBL3) acts as a post-translational modification (PTM) factor and regulates protein sorting into small extracellular vesicles (sEVs). sEVs have been reported as vectors for the pathology propagation of neurodegenerative diseases, such as α-synucleinopathies. Alpha-synuclein (α-syn) has been widely studied for its involvement in α-synucleinopathies. However, it is still unknown whether UBL3 interacts with α-syn, and is influenced by drugs or compounds. In this study, we investigated the interaction between UBL3 and α-syn, and any ensuing possible functional and pathological implications. We found that UBL3 can interact with α-syn by the Gaussia princeps based split luciferase complementation assay in cells and immunoprecipitation, while cysteine residues at its C-terminal, which are considered important as PTM factors for UBL3, were not essential for the interaction. The interaction was upregulated by 1-methyl-4-phenylpyridinium exposure. In drug screen results, the interaction was significantly downregulated by the treatment of osimertinib. These results suggest that UBL3 interacts with α-syn in cells and is significantly downregulated by epidermal growth factor receptor (EGFR) pathway inhibitor osimertinib. Therefore, the UBL3 pathway may be a new therapeutic target for α-synucleinopathies in the future.

Plastic brain structure changes associated with the division of labor and aging in termites.

Division of labor is a prominent feature of social insect societies, where different castes engage in different specialized tasks. As brain differences are associated with behavioral differences, brain anatomy may be linked to caste polymorphism. Here, we show that termite brain morphology changes markedly with caste differentiation and age in the termite, Reticulitermes speratus. Brain morphology was shown to be associated with reproductive division of labor, with reproductive individuals (alates and neotenic reproductives) having larger brains than nonreproductives (workers and soldiers). Micro-computed tomography (CT) imaging and dissection observations showed that the king's brain morphology changed markedly with shrinkage of the optic lobes during their long life in the dark. Behavioral experiments showed that mature primary kings lose visual function as a result of optic lobe shrinkage. These results suggested that termites restructure their nervous systems to perform necessary tasks as they undergo caste differentiation, and that they also show flexible changes in brain morphology even after the final molt. This study showed that brain morphology in social insects is linked to caste and aging, and that the evolution of the division of labor is underpinned by the development of diverse neural systems for specialized tasks.

Lipidomics-based tissue heterogeneity in specimens of luminal breast cancer revealed by clustering analysis of mass spectrometry imaging: A preliminary study.

Cancer tissues reflect a greater number of pathological characteristics of cancer compared to cancer cells, so the evaluation of cancer tissues can be effective in determining cancer treatment strategies. Mass spectrometry imaging (MSI) can evaluate cancer tissues and even identify molecules while preserving spatial information. Cluster analysis of cancer tissues' MSI data is currently used to evaluate the phenotype heterogeneity of the tissues. Interestingly, it has been reported that phenotype heterogeneity does not always coincide with genotype heterogeneity in HER2-positive breast cancer. We thus investigated the phenotype heterogeneity of luminal breast cancer, which is generally known to have few gene mutations. As a result, we identified phenotype heterogeneity based on lipidomics in luminal breast cancer tissues. Clusters were composed of phosphatidylcholine (PC), triglycerides (TG), phosphatidylethanolamine, sphingomyelin, and ceramide. It was found that mainly the proportion of PC and TG correlated with the proportion of cancer and stroma on HE images. Furthermore, the number of carbons in these lipid class varied from cluster to cluster. This was consistent with the fact that enzymes that synthesize long-chain fatty acids are increased through cancer metabolism. It was then thought that clusters containing PCs with high carbon counts might reflect high malignancy. These results indicate that lipidomics-based phenotype heterogeneity could potentially be used to classify cancer for which genetic analysis alone is insufficient for classification.

A New Potential Therapeutic Target for Cancer in Ubiquitin-Like Proteins-UBL3.

Ubiquitin-like proteins (Ubls) are involved in a variety of biological processes through the modification of proteins. Dysregulation of Ubl modifications is associated with various diseases, especially cancer. Ubiquitin-like protein 3 (UBL3), a type of Ubl, was revealed to be a key factor in the process of small extracellular vesicle (sEV) protein sorting and major histocompatibility complex class II ubiquitination. A variety of sEV proteins that affects cancer properties has been found to interact with UBL3. An increasing number of studies has implied that UBL3 expression affects cancer cell growth and cancer prognosis. In this review, we provide an overview of the relationship between various Ubls and cancers. We mainly introduce UBL3 and its functions and summarize the current findings of UBL3 and examine its potential as a therapeutic target in cancers.

A convenient online desalination tube coupled with mass spectrometry for the direct detection of iodinated contrast media in untreated human spent hemodialysates.

BACKGROUND: Mass spectrometry (MS) analysis using direct infusion of biological fluids is often problematic due to high salts/buffers. Iodinated contrast media (ICM) are frequently used for diagnostic imaging purposes, sometimes inducing acute kidney injury (AKI) in patients with reduced kidney function. Therefore, detection of ICM in spent hemodialysates is important for AKI patients who require urgent continuous hemodiafiltration (CHDF) because it allows noninvasive assessment of the patient's treatment. In this study, we used a novel desalination tube before MS to inject the sample directly and detect ICM. METHODS: Firstly, spent hemodialysates of one patient were injected directly into the electrospray ionization (ESI) source equipped with a quadrupole time-of-flight mass spectrometer (Q-TOF MS) coupled to an online desalination tube for the detection of ICM and other metabolites. Thereafter, spent hemodialysates of two patients were injected directly into the ESI source equipped with a triple quadrupole mass spectrometer (TQ-MS) connected to that online desalination tube to confirm the detection of ICM. RESULTS: We detected iohexol (an ICM) from untreated spent hemodialysates of the patient-administered iohexol for computed tomography using Q-TOF MS. Using MRM profile analysis, we have confirmed the detection of ICM in the untreated spent hemodialysates of the patients administered for coronary angiography before starting CHDF. Using the desalination tube, we observed approximately 178 times higher signal intensity and 8 times improved signal-to-noise ratio for ioversol (an ICM) compared to data obtained without the desalination tube. This system was capable of tracking the changes of ioversol in spent hemodialysates of AKI patients by measuring spent hemodialysates. CONCLUSION: The online desalination tube coupled with MS showed the capability of detecting iohexol and ioversol in spent hemodialysates without additional sample preparation or chromatographic separation. This approach also demonstrated the capacity to monitor the ioversol changes in patients' spent hemodialysates.

NAD+ Levels Are Augmented in Aortic Tissue of ApoE-/- Mice by Dietary Omega-3 Fatty Acids.

BACKGROUND: Maintaining bioenergetic homeostasis provides a means to reduce the risk of cardiovascular events during chronological aging. Nicotinamide adenine dinucleotide (NAD+) acts as a signaling molecule, and its levels were used to govern several biological pathways, for example, promoting angiogenesis by SIRT1 (sirtuin 1)-mediated inhibition of Notch signaling to rejuvenate capillary density of old-aged mice. NAD+ modulation shows promise in the vascular remodeling of endothelial cells. However, NAD+ distribution in atherosclerotic regions remains uncharacterized. Omega-3 polyunsaturated fatty acids consumption, such as docosahexaenoic acid and eicosapentaenoic acid, might increase the abundance of cofactors in blood vessels due to omega-3 polyunsaturated fatty acids metabolism. METHODS: Apolipoprotein E-deficient (ApoE-/-) mice were fed a Western diet, and the omega-3 polyunsaturated fatty acids-treated groups were supplemented with docosahexaenoic acid (1%, w/w) or eicosapentaenoic acid (1%, w/w) for 3 weeks. Desorption electrospray ionization mass spectrometry imaging was exploited to detect exogenous and endogenous NAD+ imaging. RESULTS: NAD+, NADH, NADP+, NADPH, FAD+, FADH, and nicotinic acid adenine dinucleotide of the aortic arches were detected higher in the omega-3 polyunsaturated fatty acids-treated mice than the nontreated control. Comparing the distribution in the outer and inner layers of the arterial walls, only NADPH was detected slightly higher in the outer part in eicosapentaenoic acid-treated mice. CONCLUSIONS: Supplementation of adding docosahexaenoic acid or eicosapentaenoic acid to the Western diet led to a higher NAD+, FAD+, and their metabolites in the aortic arch. Considering the pleiotropic roles of NAD+ in biology, this result serves as a beneficial therapeutic strategy in the animal model counter to pathological conditions.

Mass Spectrometry Imaging for Glycome in the Brain.

Glycans are diverse structured biomolecules that play crucial roles in various biological processes. Glycosylation, an enzymatic system through which various glycans are bound to proteins and lipids, is the most common and functionally crucial post-translational modification process. It is known to be associated with brain development, signal transduction, molecular trafficking, neurodegenerative disorders, psychopathologies, and brain cancers. Glycans in glycoproteins and glycolipids expressed in brain cells are involved in neuronal development, biological processes, and central nervous system maintenance. The composition and expression of glycans are known to change during those physiological processes. Therefore, imaging of glycans and the glycoconjugates in the brain regions has become a "hot" topic nowadays. Imaging techniques using lectins, antibodies, and chemical reporters are traditionally used for glycan detection. However, those techniques offer limited glycome detection. Mass spectrometry imaging (MSI) is an evolving field that combines mass spectrometry with histology allowing spatial and label-free visualization of molecules in the brain. In the last decades, several studies have employed MSI for glycome imaging in brain tissues. The current state of MSI uses on-tissue enzymatic digestion or chemical reaction to facilitate successful glycome imaging. Here, we reviewed the available literature that applied MSI techniques for glycome visualization and characterization in the brain. We also described the general methodologies for glycome MSI and discussed its potential use in the three-dimensional MSI in the brain.

The human vermilion surface contains a rich amount of cholesterol sulfate than the skin.

BACKGROUND: The vermilion of the human lip presents characteristic features and undergoes aging faster than the skin. Therefore, knowledge of the vermilion surface-specific functional molecules is important to understand lip aging and formulate lip care products. Previously, we analyzed the free fatty acids distributions and showed that docosahexaenoic acid highly accumulated in the vermilion's epithelium than in the skin. OBJECTIVE: We aimed to explore the functional molecules other than the free fatty acids on the vermilion's surface. METHODS: Human lip tissues from children and tape-stripped samples from smooth and rough lips of adults were measured by desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). RESULTS: DESI-MSI of children's lip sections revealed a major distribution of five phospholipid species in the viable layer, but not in the superficial area, of both the vermilion and the skin than that in the underlying tissue. Interestingly, a remarkably higher distribution of cholesterol sulfate was observed in the vermilion's superficial area compared to that in the skin in all subjects under this study. Furthermore, DESI-MSI of tape-stripped lip samples showed an overall higher accumulation of cholesterol sulfate in the stratum corneum of the rough lips than that in the smooth lips. CONCLUSION: Our study concluded that cholesterol sulfate has a characteristic distribution to the vermilion's surface and showed an association with the roughness of the lip.

Mass spectrometry in the lipid study of cancer.

Introduction: Cancer is a heterogeneous disease that exploits various metabolic pathways to meet the demand for increased energy and structural components. Lipids are biomolecules that play essential roles as high energy sources, mediators, and structural components of biological membranes. Accumulating evidence has established that altered lipid metabolism is a hallmark of cancer.Areas covered: Mass spectrometry (MS) is a label-free analytical tool that can simultaneously identify and quantify hundreds of analytes. To date, comprehensive lipid studies exclusively rely on this technique. Here, we reviewed the use of MS in the study of lipids in various cancers and discuss its instrumental limitations and challenges.Expert opinion: MS and MS imaging have significantly contributed to revealing altered lipid metabolism in a variety of cancers. Currently, a single MS approach cannot profile the entire lipidome because of its lack of sensitivity and specificity for all lipid classes. For the metabolic pathway investigation, lipid study requires the integration of MS with other molecular approaches. Future developments regarding the high spatial resolution, mass resolution, and sensitivity of MS instruments are warranted.

Desorption ionization using through-hole alumina membrane offers higher reproducibility than 2,5-dihydroxybenzoic acid, a widely used matrix in Fourier transform ion cyclotron resonance mass spectrometry imaging analysis.

RATIONALE: DIUTHAME (desorption ionization using through-hole alumina membrane), a recently developed matrix-free ionization-assisting substrate, was examined for reproducibility in terms of mass accuracy and intensity using standard lipid and mouse brain sections. The impregnation property of DIUTHAME significantly improved the reproducibility of mass accuracy and intensity compared with 2,5-dihydroxybenzoic acid (DHB). METHODS: Frozen tissue sections were mounted on indium tin oxide-coated glass slides. DIUTHAME and DHB were applied to individual sections. Subsequently, a solution of a phosphatidylcholine standard, PC(18:2/18:2), was poured onto the DIUTHAME and matrix. Finally, the samples were subjected to laser desorption ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry. The reproducibility was tested by calculating the mean ± standard deviation values of mass errors and intensities of individual ion species. RESULTS: Analysis of the PC(18:2/18:2) standard showed significantly (p < 0.01) lower mass error for DIUTHAME-MS than for MALDI-MS. Endogenous PC(36:4) analysis in mouse brain section also showed significantly (p < 0.05) lower mass errors for DIUTHAME-MS. Furthermore, we investigated the mass error of some abundant lipid ions in brain sections and observed similar results. DIUTHAME-MS displayed lower signal intensity in standard PC analysis. Interestingly, it offered higher signal intensities for all the endogenous lipid ions. Lower fluctuations of both mass accuracies and signal intensities were observed in DIUTHAME-MS. CONCLUSIONS: Our results demonstrated that DIUTHAME-MS offers higher reproducibility for mass accuracies and intensities than MALDI-MS in both standard lipid and mouse brain tissue analyses. It can potentially be used instead of conventional MALDI-MS and mass spectrometry imaging analyses to achieve highly reproducible data for mass accuracy and intensity.