The role of brain cholesterol metabolism in Alzheimer’s disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the role of brain cholesterol homeostasis in AD. We first tested whether metabolite markers of brain cholesterol biosynthesis and catabolism were altered in AD and associated with AD pathology using linear mixed-effects models in two brain autopsy samples from the Baltimore Longitudinal Study of Aging (BLSA) and the Religious Orders Study (ROS). We next tested whether genetic regulators of brain cholesterol biosynthesis and catabolism were altered in AD using the ANOVA test in publicly available brain tissue transcriptomic datasets. Finally, using regional brain transcriptomic data, we performed genome-scale metabolic network modeling to assess alterations in cholesterol biosynthesis and catabolism reactions in AD. We show that AD is associated with pervasive abnormalities in cholesterol biosynthesis and catabolism. Using transcriptomic data from Parkinson’s disease (PD) brain tissue samples, we found that gene expression alterations identified in AD were not observed in PD, suggesting that these changes may be specific to AD. Our results suggest that reduced de novo cholesterol biosynthesis may occur in response to impaired enzymatic cholesterol catabolism and efflux to maintain brain cholesterol levels in AD. This is accompanied by the accumulation of nonenzymatically generated cytotoxic oxysterols. Our results set the stage for experimental studies to address whether abnormalities in cholesterol metabolism are plausible therapeutic targets in AD.
Objectives In this study, we aimed to identify tissue-specific genes for various human tissues/organs more robustly and rigorously by extending the tau score algorithm. Introduction Tissue-specific genes are a class of genes whose functions and expressions are preferred in one or several tissues restrictedly. Identification of tissue-specific genes is essential for discovering multi-cellular biological processes such as tissue-specific molecular regulations, tissue development, physiology, and the pathogenesis of tissue-associated diseases. Materials and Methods Gene expression data derived from five large RNA sequencing (RNA-seq) projects, spanning 96 different human tissues, were retrieved from ArrayExpress and ExpressionAtlas. The first step is categorizing genes using significant filters and tau score as a specificity index. After calculating tau for each gene in all datasets separately, statistical distance from the maximum expression level was estimated using a new meaningful procedure. Specific expression of a gene in one or several tissues was calculated after the integration of tau and statistical distance estimation, which is called as extended tau approach. Obtained tissue-specific genes for 96 different human tissues were functionally annotated, and some comparisons were carried out to show the effectiveness of the extended tau method. Results and Discussion Categorization of genes based on expression level and identification of tissue-specific genes for a large number of tissues/organs were executed. Genes were successfully assigned to multiple tissues by generating the extended tau approach as opposed to the original tau score, which can assign tissue specificity to single tissue only.
Plant essential oils are preferred in cosmetics, medicine, food, and beverage industries for various purposes. α-Pinene is found mainly in eucalyptus oils, eugenol is the active ingredient in clove oil, and limonene is the major component in the oil of citrus fruit peels. In this study, we aimed to determine the antifungal activity of α-pinene, eugenol, and limonene against Saccharomyces cerevisiae yeast cells. Besides, we focused on revealing the target side of the compounds on the yeast cells. Firstly, the antifungal activity of compounds was tested via minimum inhibitory concentration (MIC) measurement. After that, we performed a sorbitol effect assay to understand whether it acts on the cell wall or not. With sorbitol, the MIC values were not changed. It means that they are not effective on the yeast cell wall. Then, we measured the extracellular conductivity increase upon treatment with the compounds to understand the effect on the cell membrane. Eugenol and limonene were not changed the extracellular conductivity, and there was no ion leakage from the cell membrane. On the other hand, α-pinene damaged the yeast cell membrane causing a sudden increase in conductivity due to ion leakage. An ergosterol effect assay with α-pinene was performed to detect cell membrane disruption via ergosterol or not. With ergosterol, the MIC value was not changed. α-Pinene must have another target than the ergosterol in the yeast cell membrane. Finally, revealing the mode of action of compounds against yeast cells will provide new insights into their usage in various fields.
This research aims to improve antimicrobial materials based on functional silica nanoparticles. Three different methods were used in the study to create silica nanoparticles with other properties. The nanoparticles' morphological structures are porous, hollow, and filled with spherical forms. The surface of these nanoparticles was grafted with poly(1-vinyl-1,2,4-triazole) (PVTri). The morphological properties of nanocomposites were used for analyze. In contrast, thermal gravimetric analysis was used to characterize the thermal properties of nanocomposites (TGA). The silica nanoparticles were evaluated for them in vitro antimicrobial activity against, Escherichia coli, Staphylococcus aureus, Saccharomyces cerevisiae using minimum inhibitory concentration (MIC) measurement. Silica nanoparticles have different antifungal and antibacterial properties related to their structure. The cytotoxic effects of the silica nanoparticles on HaCaT cells were performed with an MTS assay. In this study, we observed that high doses of HSS and e-SiO2 decreased cell growth, while HSS and e-SiO2 composite with PVTri increased cell proliferation.
Introduction: Tissue-specific genes are a class of genes whose functions and expressions are preferred in one or several tissues, restrictedly. Identification of tissue-specific genes is essential for discovery of multi-cellular biological processes such as tissue-specific molecular regulations, tissue development, physiology and also pathogenesis of tissue-associated diseases. In this study, we aimed to identify tissue-specific genes for various human tissues/organs in more robust and rigorous fashion. Method: Gene expression data, derived from five large RNA sequencing(RNA-seq) projects, spanning 96 different human tissues was retrieved fromArrayExpress and ExpressionAtlas. The first step is categorization of genes using significant filters and tau score as specificity index. After calculation of tau for each gene in all datasets separately, statistical distance from maximum expression level was estimated using a new meaningful procedure. Specific expression of agene in one or several tissues was calculated after integration of tau and statistical distance estimation that is called as extended tau approach. Obtainedtissue-specific genes for 96 different human tissues were functionally annotated and some comparison were carried out to show effectiveness of extended taumethod. Results: Categorization of genes based on expression level and identification of tissue-specific genes for a large number of tissues/organs were executed. Genes were successfully assigned to multiple tissues by generating extended tau approach as opposed to original tau score which can assign tissue specificity to single tissue only. Keywords: Tissue-specific genes, RNA-Seq, Tau score
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