Comparison of untargeted gas chromatography-mass spectrometry analysis algorithms with implications to the interpretation and putative identification of volatile aroma compositions.

The aroma profiling process requires the identification of the volatile compounds in a sample or its headspace. Typically, the identification of compounds relies on automated feature finding and matching algorithms to (putatively) identify and report compounds based on retention index and mass spectra matching against a compound library. We investigated the use of five different workflows and proposed three metrics (target accuracy A, identification percentage I, uniqueness U) to quantify their impact on generated aroma profiles of a mixture of fragrance standards and a commercial grade essential oil.

Optimization of extraction conditions for LC-ToF-MS analysis of mevalonate pathway metabolites in engineered E. coli strain via statistical experimental designs.

Isoprenoids give rise to many functional products used today such as flavours, fragrances and even pharmaceutical compounds. Mevalonate pathway metabolites are the key intermediates that affect the production yield of isoprenoids. With increasing demand and benefit of isoprenoids, the present study adopts Analytical Quality-by-Design (AQbD) approach to establish an efficacious extraction protocol prior to the determination of mevalonate pathway metabolites in an engineered Escherichia coli model.

Metabolomics and modelling approaches for systems metabolic engineering.

Metabolic engineering involves the manipulation of microbes to produce desirable compounds through genetic engineering or synthetic biology approaches. Metabolomics involves the quantitation of intracellular and extracellular metabolites, where mass spectrometry and nuclear magnetic resonance based analytical instrumentation are often used. Here, the experimental designs, sample preparations, metabolite quenching and extraction are essential to the quantitative metabolomics workflow.

Profiling of Aroma-Active Compounds in Ylang-Ylang Essential Oils by Aroma Extract Dilution Analysis (AEDA) and Chemometric Methods.

The aroma-active compounds in the extra, first, and third grades of ylang-ylang essential oils (YYEO) from Comoros and Madagascar were identified by gas chromatography-mass spectrometry with olfactometry (GC-MS/O) using an aroma extract dilution analysis (AEDA) technique. In the previous study, the authors investigated differences in volatile compound profiles between YYEO of different grades and regions using GC coupled with a flame ionization detector (FID) and GC-MS. This study follows up with identification of the aroma-active compounds present in YYEO of various grades from both origins and to profile the aroma of those oils.

The S1P receptor regulates blood-brain barrier integrity and leukocyte extravasation with implications for neurodegenerative disease.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid which modulates vascular integrity through its receptors, S1P-S1P. Notably, S1P has been shown to mediate the disruption of cerebrovascular integrity in vitro and in vivo. However, the mechanism underlying this process has not been fully elucidated.

Dietary Fat and Protein Intake in Relation to Plasma Sphingolipids as Determined by a Large-Scale Lipidomic Analysis.

Sphingolipid concentrations have been associated with risk of type 2 diabetes and cardiovascular diseases. Because sphingolipids can be synthesized de novo from saturated fatty acids (SFA), dietary fatty acids may affect plasma sphingolipid concentrations. We aimed to evaluate dietary fat and protein intakes in relation to circulating sphingolipid levels.

Preclinical and Clinical Evidence for the Involvement of Sphingosine 1-Phosphate Signaling in the Pathophysiology of Vascular Cognitive Impairment.

Sphingosine 1-phosphates (S1Ps) are bioactive lipids that mediate a diverse range of effects through the activation of cognate receptors, S1P-S1P. Scrutiny of S1P-regulated pathways over the past three decades has identified important and occasionally counteracting functions in the brain and cerebrovascular system. For example, while S1P and S1P mediate proinflammatory effects on glial cells and directly promote endothelial cell barrier integrity, S1P is anti-inflammatory but disrupts barrier integrity.

Immunomodulatory sphingosine-1-phosphates as plasma biomarkers of Alzheimer's disease and vascular cognitive impairment.

Background: There has been ongoing research impetus to uncover novel blood-based diagnostic and prognostic biomarkers for Alzheimer's disease (AD), vascular dementia (VaD), and related cerebrovascular disease (CEVD)-associated conditions within the spectrum of vascular cognitive impairment (VCI). Sphingosine-1-phosphates (S1Ps) are signaling lipids which act on the S1PR family of cognate G-protein-coupled receptors and have been shown to modulate neuroinflammation, a process known to be involved in both neurodegenerative and cerebrovascular diseases. However, the status of peripheral S1P in AD and VCI is at present unclear.

MRMkit: Automated Data Processing for Large-Scale Targeted Metabolomics Analysis.

MRMkit is an open-source software package designed for automated processing of large-scale targeted mass spectrometry-based metabolomics data. With improvements in the automation of sample preparation for LC-MS analysis, a challenging next step is to fully automate the workflow to process raw data and ensure the quality of measurements in large-scale analysis settings. MRMkit capitalizes on the richness of large-sample data in capturing peak shapes and interference patterns of transitions across many samples and delivers fully automated, reproducible peak integration results in a scalable and time-efficient manner.

Plasma sphingolipids and risk of cardiovascular diseases: a large-scale lipidomic analysis.

Introduction: Sphingolipids are a diverse class of lipids with various roles in cell functions and subclasses such as ceramides have been associated with cardiovascular diseases (CVD) in previous studies.

Objectives: We aimed to measure molecularly-distinct sphingolipids via a large-scale lipidomic analysis and expand the literature to an Asian population.

Methods: We performed a lipidomics evaluation of 79 molecularly distinct sphingolipids in the plasma of 2627 ethnically-Chinese Singaporeans.

Sphingosine 1-Phosphate Receptor 2 Induces Otoprotective Responses to Cisplatin Treatment.

Ototoxicity is a major adverse effect of platinum-based chemotherapeutics and currently, there remains a lack of United States Food and Drug Administration-approved therapies to prevent or treat this problem. In our study, we examined the role of the sphingosine 1-phosphate receptor 2 (S1P) in attenuating cisplatin-induced ototoxicity in several different animal models and cell lines. We found that ototoxicity in S1P knockout mice is dependent on reactive oxygen species (ROS) production and that S1P receptor activation with a specific agonist, CYM-5478, significantly attenuates cisplatin-induced defects, including hair cell degeneration in zebrafish and prolonged auditory brainstem response latency in rats.

Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy.

Platinum-based therapeutics are used to manage many forms of cancer, but frequently result in peripheral neuropathy. Currently, the only option available to attenuate chemotherapy-induced neuropathy is to limit or discontinue this treatment. Sphingosine 1-phosphate (S1P) is a lipid-based signaling molecule involved in neuroinflammatory processes by interacting with its five cognate receptors: S1P In this study, using a combination of drug pharmacodynamic analysis in human study participants, disease modeling in rodents, and cell-based assays, we examined whether S1P signaling may represent a potential target in the treatment of chemotherapy-induced neuropathy.

Associations with metabolites in Chinese suggest new metabolic roles in Alzheimer's and Parkinson's diseases.

Metabolites are small intermediate products of cellular metabolism perturbed in a variety of complex disorders. Identifying genetic markers associated with metabolite concentrations could delineate disease-related metabolic pathways in humans. We tested genetic variants for associations with 136 metabolites in 1954 Chinese from Singapore.

Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases.

Autotaxin (ATX) is a soluble extracellular enzyme that is abundant in mammalian plasma and cerebrospinal fluid (CSF). It has two known enzymatic activities, acting as both a phosphodiesterase and a phospholipase. The majority of its biological effects have been associated with its ability to liberate lysophosphatidic acid (LPA) from its substrate, lysophosphatidylcholine (LPC).

Large-scale lipidomics identifies associations between plasma sphingolipids and T2DM incidence.

Background: Sphingolipids (SPs) are ubiquitous, structurally diverse molecules that include ceramides, sphingomyelins, and sphingosines. They are involved in various pathologies including obesity and type 2 diabetes mellitus (T2DM). Therefore, it is likely that perturbations in plasma concentrations of SPs are associated with disease.

Lysophosphatidic acid and its receptor LPA mediate carrageenan induced inflammatory pain in mice.

Lysophosphatidic acid receptor 1 (LPA) is one of six G protein-coupled receptors (GPCRs) activated by the bioactive lipid, lysophosphatidic acid (LPA). Previous studies have shown that LPA signaling plays a major role in the pathophysiology of neuropathic pain. It has also been shown that the inhibition of phospholipase A, an enzyme upstream of LPA synthesis, reduces mechanical allodynia in experimental inflammatory orofacial pain.

Sphingolipidomics analysis of large clinical cohorts. Part 2: Potential impact and applications.

It has been known for decades that the regulation of sphingolipids (SLs) is essential for the proper function of many cellular processes. However, a complete understanding of these processes has been complicated by the structural diversity of these lipids. A well-characterized metabolic pathway is responsible for homeostatic maintenance of hundreds of distinct SL species.

Sphingolipidomics analysis of large clinical cohorts. Part 1: Technical notes and practical considerations.

Lipids comprise an exceptionally diverse class of bioactive macromolecules. While quantitatively abundant lipid species serve fundamental roles in cell structure and energy metabolism, thousands of structurally-distinct, quantitatively minor species may serve as important regulators of cellular processes. Historically, a complete understanding of the biological roles of these lipids has been limited by a lack of sensitive, discriminating analytical techniques.

Microchemical Plant in a Liquid Droplet: Plasmonic Liquid Marble for Sequential Reactions and Attomole Detection of Toxin at Microliter Scale.

Miniaturizing the continuous multistep operations of a factory into a microchemical plant offers a safe and cost-effective approach to promote high-throughput screening in drug development and enforcement of industrial/environmental safety. While particle-assembled microdroplets in the form of liquid marble are ideal as microchemical plant, these platforms are mainly restricted to single-step reactions and limited to ex situ reaction monitoring. Herein, we utilize plasmonic liquid marble (PLM), formed by encapsulating liquid droplet with Ag nanocubes, to address these issues and demonstrate it as an ideal microchemical plant to conduct reaction-and-detection sequences on-demand in a nondisruptive manner.

To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling.

Sphingosine 1-phosphate (S1P) is an extracellular lipid signaling molecule that acts as a selective, high-affinity ligand for a family of five G protein-coupled receptors. This signaling system was first identified twenty years ago, and has since been shown to regulate a diverse range of physiological processes and disease states, such as cardiovascular development, immune function, hypoxic responses, and cancer. The therapeutic potential of targeting this system took center stage when it was demonstrated that the immune modulator, fingolimod (FTY720/Gilenya), exerts it lymphopenic effect by acting on S1P receptors, primarily on S1P receptor 1 (S1P).

Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs.

Sphingolipids (SPs) comprise a highly diverse class of lipids that serve biological roles both as structural components of cell membranes and as mediators of cell signaling. Pharmacologic and genetic manipulation of SPs and their signaling systems have underscored their importance in most biological processes, including central nervous system development and function. Likewise, perturbations of SP accumulation or signaling have been associated with a number of disease states, such as neural tube defects, neuroinflammation, stroke, and dementia.

Transcriptomic analysis of a moderately growing subisolate Botryococcus braunii 779 (Chlorophyta) in response to nitrogen deprivation.

Background: The colonial microalga Botryococcus braunii has been brought to people's attention for its conspicuous ability to accumulate a variety of lipids including hydrocarbons. B. braunii strains are classified into 3 races based on the types of hydrocarbons.

Catalytic liquid marbles: Ag nanowire-based miniature reactors for highly efficient degradation of methylene blue.

Ag nanowire-based catalytic liquid marbles are fabricated as miniature reactors, which demonstrate highly efficient, support-free and rate-controllable heterogeneous degradation of methylene blue, with catalytic efficiency close to 100%. Our miniature catalytic liquid marbles are essential for reactions involving highly toxic/hazardous or costly reactants, where small volume preliminary reactions are preferred.

Application of mid-infrared chemical imaging and multivariate chemometrics analyses to characterise a population of microalgae cells.

A suite of multivariate chemometrics methods was applied to a mid-infrared imaging dataset of a eustigmatophyte, marine Nannochloropsis sp. microalgae strain. This includes the improved leader-follower cluster analysis (iLFCA) to interrogate spectra in an unsupervised fashion, a resonant Mie optical scatter correction algorithm (RMieS-EMSC) that improves data linearity, the band-target entropy minimization (BTEM) self-modeling curve resolution for recovering component spectra, and a multi-linear regression (MLR) for estimating relative concentrations and plotting chemical maps of component spectra.