Distribution of secretory phospholipase A2 XIIA in the brain and its role in lipid metabolism and cognition.

Phospholipases A(2) (PLA(2)) catalyze the hydrolysis of membrane phospholipids to produce free fatty acids and lysophospholipids, which have important functions in cell signaling. The present study elucidated differential expression of PLA(2) isoforms in the rat cortex by quantitative reverse transcription PCR and demonstrated that sPLA(2)-XIIA had greater messenger RNA expression than iPLA(2)-VI or cPLA(2)-IVA in different brain regions, or compared to other sPLA(2) isoforms in the prefrontal cortex (PFC) and hippocampus. Western blots identified a 24-kDa band in different regions of the adult brain, and high levels of sPLA(2)-XIIA protein expression were detected in the PFC, striatum, and thalamus.

A computational framework for integration of lipidomics data into metabolic pathways.

Lipids are important compounds for human physiology and as renewable resources for fuels and chemicals. In lipid research, there is a big gap between the currently available pathway-level representations of lipids and lipid structure databases in which the number of compounds is expanding rapidly with high-throughput mass spectrometry methods. In this work, we introduce a computational approach to bridge this gap by making associations between metabolic pathways and the lipid structures discovered increasingly thorough lipidomics studies.

Targeting lipid esterases in mycobacteria grown under different physiological conditions using activity-based profiling with tetrahydrolipstatin (THL).

Tetrahydrolipstatin (THL) is bactericidal but its precise target spectrum is poorly characterized. Here, we used a THL analog and activity-based protein profiling to identify target proteins after enrichment from whole cell lysates of Mycobacterium bovis Bacillus Calmette-Guérin cultured under replicating and non-replicating conditions. THL targets α/β-hydrolases, including many lipid esterases (LipD, G, H, I, M, N, O, V, W, and TesA).

LipidGO: database for lipid-related GO terms and applications.

Motivation: Lipid, an essential class of biomolecules, is receiving increasing attention in the research community, especially with the development of analytical technique like mass spectrometry. Gene Ontology (GO) is the de facto standard function annotation scheme for gene products. Identification of both explicit and implicit lipid-related GO terms will help lipid research in many ways, e.

Critical role of SCD1 in autophagy regulation via lipogenesis and lipid rafts-coupled AKT-FOXO1 signaling pathway.

SCD1 (stearoyl-coenzyme A desaturase 1) is an endoplasmic reticulum-bound enzyme that catalyzes the formation of the first double bond at the cis-Δ9 position of saturated fatty acids (SFA) to form monounsaturated fatty acids (MUFA). Increasing evidence indicates that autophagy plays an important role in regulating lipid metabolism, while little is known about whether key enzymes of lipogenesis like SCD1 can regulate autophagy. In this study, we examined the role of SCD1 in autophagy using the tsc2(-/-) mouse embryonic fibroblasts (MEFs) possessing constitutively active MTORC1 as a cellular model.

Lipidomic analysis of human tear fluid reveals structure-specific lipid alterations in dry eye syndrome.

As current diagnostic markers for dry eye syndrome (DES) are lacking in both sensitivity and specificity, a pressing concern exists to develop activity markers that closely align with the principal axes of disease progression. In this study, a comprehensive lipidomic platform designated for analysis of the human tear lipidome was employed to characterize changes in tear lipid compositions from a cohort of 93 subjects of different clinical subgroups classified based on the presence of dry eye symptoms and signs. Positive correlations were observed between the tear levels of cholesteryl sulfates and glycosphingolipids with physiological secretion of tears, which indicated the possible lacrimal (instead of meibomian) origin of these lipids.

Extensive characterization of human tear fluid collected using different techniques unravels the presence of novel lipid amphiphiles.

The tear film covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health. The composition of the tear film amphiphilic lipid sublayer, in particular, has largely remained a matter of contention due to the limiting concentrations of these lipid amphiphiles in tears that render their detection and accurate quantitation tedious. Using systematic and sensitive lipidomic approaches, we validated different tear collection techniques and report the most comprehensive human tear lipidome to date; comprising more than 600 lipid species from 17 major lipid classes.

Impact of epidural analgesia on mortality and morbidity after surgery: systematic review and meta-analysis of randomized controlled trials.

Objective: To quantify benefit and harm of epidural analgesia, compared with systemic opioid analgesia, in adults having surgery under general anesthesia.

Background: It remains controversial whether adding epidural analgesia to general anesthesia decreases postoperative morbidity and mortality.

Methods: We searched CENTRAL, EMBASE, PubMed, CINAHL, and BIOSIS till July 2012.

Neonatal overnutrition in mice exacerbates high-fat diet-induced metabolic perturbations.

Neonatal overnutrition results in accelerated development of high-fat diet (HFD)-induced metabolic defects in adulthood. To understand whether the increased susceptibility was associated with aggravated inflammation and dysregulated lipid metabolism, we studied metabolic changes and insulin signaling in a chronic postnatal overnutrition (CPO) mouse model. Male Swiss Webster pups were raised with either three pups per litter to induce CPO or ten pups per litter as control (CTR) and weaned to either low-fat diet (LFD) or HFD.

Rapid and sensitive profiling of tear wax ester species using high performance liquid chromatography coupled with tandem mass spectrometry.

A rapid and sensitive method was developed for quantitative profiling of wax esters (WEs) in human tear lipidome. Individual WE species was separated by liquid chromatography and detected by electrospray ionisation mass spectrometry using specific multiple reaction monitoring (MRM) scanning. Palmitoyl palmitate and in-house synthesized wax esters (13)C18:1(oleic acid-1,2,3,7,8,9,10-(13)C7)C26:0 were used as internal standards for quantitation of WEs containing saturated and unsaturated fatty acids (FA), respectively.

Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans.

The circadian system regulates daily rhythms in lipid metabolism and adipose tissue function. Although disruption of circadian clock function is associated with negative cardiometabolic end points, very little is known about interindividual variation in circadian-regulated metabolic pathways. Here, we used targeted lipidomics-based approaches to profile the time course of 263 lipids in blood plasma in 20 healthy individuals.

Sialic acid linkage in glycosphingolipids is a molecular correlate for trafficking and delivery of extracellular cargo.

Gangliosides, glycosphingolipids containing sialic acid moieties, are well known mediators of transmembrane signaling and endocytosis at the plasma membrane. However, little is known about their precise regulatory role at the cell periphery for intracellular sorting of extracellular cargo. Here we inspected published scientific literature for two types of cargoes, namely bacterial toxins and viruses, regarding their usage of gangliosides.

Novel phage display-derived mycolic acid-specific antibodies with potential for tuberculosis diagnosis.

Tuberculosis is a major cause of mortality and morbidity due to infectious disease. However, current clinical diagnostic methodologies such as PCR, sputum culture, or smear microscopy are not ideal. Antibody-based assays are a suitable alternative but require specific antibodies against a suitable biomarker.

Combination of a reduced dose of an intrathecal local anesthetic with a small dose of an opioid: a meta-analysis of randomized trials.

We tested whether the combination of a reduced dose of a local anesthetic (LA) with an opioid compared with a standard dose of the same LA alone guaranteed adequate intraoperative anesthesia and postoperative analgesia and decreased LA-related adverse effects. We systematically searched (to November 2012) for randomized comparisons of combinations of a reduced dose of an LA with a concomitant opioid (experimental) with a standard dose of the LA alone (control) in adults undergoing surgery with single-injection intrathecal anesthesia without general anesthesia. We included 28 trials (1393 patients).

A mechanistic paradigm for broad-spectrum antivirals that target virus-cell fusion.

LJ001 is a lipophilic thiazolidine derivative that inhibits the entry of numerous enveloped viruses at non-cytotoxic concentrations (IC50 ≤ 0.5 µM), and was posited to exploit the physiological difference between static viral membranes and biogenic cellular membranes. We now report on the molecular mechanism that results in LJ001's specific inhibition of virus-cell fusion.

Effects of a high-fat, high-cholesterol diet on brain lipid profiles in apolipoprotein E ε3 and ε4 knock-in mice.

Apolipoprotein E (ApoE) is important in facilitating the transport of lipids (cholesterol, phospholipids, and sulfatides) and plays a fundamental role in normal lipid metabolism. High cholesterol levels increases the risk of developing Alzheimer's disease. In this study, we investigated the effects of a high-fat high cholesterol (HFHC) diet on brain lipid profiles in 95 young and aged APOE ε3 and ε4 knock-in mice to determine whether diet leads to altered brain levels of a number of glycerophospholipids, sphingolipids, cholesterol precursors, cholesterol, cholesterol oxidation products, and cholesterol esters.

Lipidomic analysis of human placental syncytiotrophoblast microvesicles in adverse pregnancy outcomes.

Problem: Syncytiotrophoblast microvesicles (STBM) are shed from placenta into the maternal circulation. STBM circulate in increased amounts in adverse pregnancies, e.g.

Lipid anti-lipid antibody responses correlate with disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by broad clinical manifestations including cardiovascular and renal complications with periodic disease flares and significant morbidity and mortality. One of the main contributing factors to the pathology of SLE is the accumulation and impaired clearance of immune complexes of which the principle components are host auto-antigens and antibodies. The contribution of host lipids to the formation of these autoimmune complexes remains poorly defined.

Historical control data of spontaneous tumors in transgenic CByB6F1-Tg(HRAS)2Jic (Tg.rasH2) mice.

The Tg.rasH2 mouse is a hemizygous transgenic mouse, approved by regulatory agencies for carcinogenicity assessment. However, the absence of a historical database for the incidence of spontaneous neoplasms has subsequently led to reluctance by some pharmaceutical companies to adopt the use of this short-term carcinogenicity assay.

Deep whole-genome sequencing of 100 southeast Asian Malays.

Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups.

Specific inhibition of p25/Cdk5 activity by the Cdk5 inhibitory peptide reduces neurodegeneration in vivo.

The aberrant hyperactivation of Cyclin-dependent kinase 5 (Cdk5), by the production of its truncated activator p25, results in the formation of hyperphosphorylated tau, neuroinflammation, amyloid deposition, and neuronal death in vitro and in vivo. Mechanistically, this occurs as a result of a neurotoxic insult that invokes the intracellular elevation of calcium to activate calpain, which cleaves the Cdk5 activator p35 into p25. It has been shown previously that the p25 transgenic mouse as a model to investigate the mechanistic implications of p25 production in the brain, which recapitulates deregulated Cdk5-mediated neuropathological changes, such as hyperphosphorylated tau and neuronal death.

The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response.

Recent studies suggest that the sterol metabolic network participates in the interferon (IFN) antiviral response. However, the molecular mechanisms linking IFN with the sterol network and the identity of sterol mediators remain unknown. Here we report a cellular antiviral role for macrophage production of 25-hydroxycholesterol (cholest-5-en-3β,25-diol, 25HC) as a component of the sterol metabolic network linked to the IFN response via Stat1.

Biochemical membrane lipidomics during Drosophila development.

Lipids play critical roles in energy homeostasis, membrane structure, and signaling. Using liquid chromatography and mass spectrometry, we provide a comprehensive semiquantification of lipids during the life cycle of Drosophila melanogaster (230 glycerophospholipids, 210 sphingolipids, 6 sterols and sterol esters, and 60 glycerolipids) and obtain biological insights through this biochemical resource. First, we find a high and constant triacylglycerol-to-membrane lipid ratio during pupal stage, which is nonobvious in the absence of nutrient uptake and tissue remodeling.