Search results for "IPA"
showing 10 items of 5795 documents
Localization of the cannabinoid type-1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus
2018
Astroglial type‐1 cannabinoid (CB1) receptors are involved in synaptic transmission, plasticity and behavior by interfering with the so‐called tripartite synapse formed by pre‐ and post‐synaptic neuronal elements and surrounding astrocyte processes. However, little is known concerning the subcellular distribution of astroglial CB1 receptors. In particular, brain CB1 receptors are mostly localized at cells' plasmalemma, but recent evidence indicates their functional presence in mitochondrial membranes. Whether CB1 receptors are present in astroglial mitochondria has remained unknown. To investigate this issue, we included conditional knock‐out mice lacking astroglial CB1 receptor expression …
Development of Novel Peptide-Based Michael Acceptors Targeting Rhodesain and Falcipain-2 for the Treatment of Neglected Tropical Diseases (NTDs)
2017
This paper describes the development of a class of peptide-based inhibitors as novel antitrypanosomal and antimalarial agents. The inhibitors are based on a characteristic peptide sequence for the inhibition of the cysteine proteases rhodesain of Trypanosoma brucei rhodesiense and falcipain-2 of Plasmodium falciparum. We exploited the reactivity of novel unsaturated electrophilic functions such as vinyl-sulfones, -ketones, -esters, and -nitriles. The Michael acceptors inhibited both rhodesain and falcipain-2, at nanomolar and micromolar levels, respectively. In particular, the vinyl ketone 3b has emerged as a potent rhodesain inhibitor (k2nd = 67 × 106 M-1 min-1), endowed with a picomolar b…
The transcriptome of mouse central nervous system myelin
2016
AbstractRapid nerve conduction in the CNS is facilitated by insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics remains elusive. Here we performed a comprehensive transcriptome analysis (RNA-seq) of myelin biochemically purified from mouse brains at various ages and find a surprisingly large pool of transcripts enriched in myelin. Further computational analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesti…
Scientific Reports
2019
Anthropogenic climate change ranks among the major global-scale threats to modern biodiversity. Extinction risks are known to increase via the interactions between rapid climatic alterations and environmentally-sensitive species traits that fail to adapt to those changes. Accumulating evidence reveals the influence of ecophysiological, ecological and phenological factors as drivers underlying demographic collapses that lead to population extinctions. However, the extent to which life-history traits influence population responses to climate change remains largely unexplored. The emerging 'cul-de-sac hypothesis' predicts that reptilian viviparity ('live-bearing' reproduction), a 'key innovati…
Principal components analysis: theory and application to gene expression data analysis
2018
Advances in computational power have enabled research to generate significant amounts of data related to complex biological problems. Consequently, applying appropriate data analysis techniques has become paramount to tackle this complexity. However, theoretical understanding of statistical methods is necessary to ensure that the correct method is used and that sound inferences are made based on the analysis. In this article, we elaborate on the theory behind principal components analysis (PCA), which has become a favoured multivariate statistical tool in the field of omics-data analysis. We discuss the necessary prerequisites and steps to produce statistically valid results and provide gui…
High-Performance Liquid Chromatography/Electrospray Ionization Tandem Mass Spectrometry (HPLC-ESI-MSn) Analysis and Bioactivity Useful for Prevention…
2019
This study aimed at evaluating and comparing the chemical profile obtained by HPLC-ESI-MSn analysis, the inhibitory activity of enzymes linked to obesity (α-amylase, α-glucosidase, and lipase) and the antioxidant properties (DPPH, ABTS, FRAP, and β-carotene bleaching tests) of ethanol extracts of bulbs (BE) and aerial parts (APE) from Allium commutatum Guss. (known in Italy as “aglio delle isole”). The chemical profile revealed alliin as the main abundant compound with values of 31.5 and 38.8 mg/g extract for BE and APE, respectively. APE is rich also in quercetin (38.5 mg/g extract) and luteolin (31.8 mg/g extract). Bulbs extract exhibited the highest activity as inhibitor of enzymes linke…
Chemical Proteomic Analysis of Serine Hydrolase Activity in Niemann-Pick Type C Mouse Brain
2018
The endocannabinoid system (ECS) is considered to be an endogenous protective system in various neurodegenerative diseases. Niemann-Pick type C (NPC) is a neurodegenerative disease in which the role of the ECS has not been studied yet. Most of the endocannabinoid enzymes are serine hydrolases, which can be studied using activity-based protein profiling (ABPP). Here, we report the serine hydrolase activity in brain proteomes of a NPC mouse model as measured by ABPP. Two ABPP methods are used: a gel-based method and a chemical proteomics method. The activities of the following endocannabinoid enzymes were quantified: diacylglycerol lipase (DAGL) α, α/β-hydrolase domain-containing protein 4, α…
Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases
2021
Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce HDL increases. Primary forms of HALP are caused by mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (HL), apolipoprotein C-III (apo C-III), scavenger receptor class B type I (SR-BI) and endothelial lipase (EL). However, in the last decades, genome-wide association studies (GWAS) have also suggested a polygenic inheritance o…
Chemometric Study on Alkaline Pre-treatments of Wood Chips Prior to Pulping
2016
Alkaline pre-treatments were performed for the production of organics-containing effluents from silver/white birch (Betula pendula/pubescens) and Scots pine (Pinus sylvestris) chips prior to chemical pulping. Pre-treatment conditions were varied with respect to time (from 30 min to 120 min), temperature (130 °C and 150 °C), and alkali charge (1, 2, 3, 4, 6, and 8% of NaOH on oven-dried wood). The analytical data (total content, weight average molar mass, and molar mass distribution) on dissolved lignin were subjected to principal component analysis to examine the relationship between molar mass and molar mass distributions in lignin removed from different wood species under varying alkaline…
Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway
2019
A number of antimalarial drugs interfere with the electron transport chain and heme-related reactions; however, the biosynthesis of heme derivatives in Plasmodium parasites has not been fully elucidated. Here, we characterized the steps that lead to the farnesylation of heme. After the identification of a gene encoding heme O synthase, we identified heme O synthesis in blood stage parasites through the incorporation of radioactive precursors. The presence of heme O synthesis in intraerythrocytic stages of Plasmodium falciparum was confirmed by mass spectrometry. Inabenfide and uniconazole–P appeared to interfere in heme synthesis, accordingly, parasite growth was also affected by the additi…