Sample records for abundant endogenous lipid

  1. The role of endogenous lipids in the emulsifying properties of cocoa

    NASA Astrophysics Data System (ADS)

    Gould, Joanne; Furse, Samuel; Wolf, Bettina

    2016-03-01

    This paper describes a study in which the emulsifying properties of cocoa material with and without its lipid fraction were explored. This study was motivated by the commercial interest in naturally-occurring particulate emulsifiers as opposed to the chemically modified emulsifying particles presently available for commercial use. The hypothesis was that endogenous lipids from cocoa were responsible for driving the formation of stable oil-in-water (o/w) emulsions. The data presented includes relative quantification of phospholipids from different commercially available cocoa material using 31P NMR spectroscopy and analyses of the emulsifying power of delipidified cocoa material. The commercially available cocoa material comprised several phospholipids, with phosphatidylcholine being the most abundant in all samples. Dispersions of delipidified cocoa material were found to drive the formation of o/w emulsions despite the absence of lipids. We therefore concluded that the emulsifying behaviour of cocoa material is not entirely reliant upon the endogenous lipids. This suggests that cocoa material may have a new and potentially widespread use in industrial food preparation and may inform manufacturing strategies for novel food grade emulsifiers.

  2. Response of pigeon guillemots to variable abundance of high-lipid and low-lipid prey

    USGS Publications Warehouse

    Litzow, Michael A.; Piatt, John F.; Prichard, A.K.; Roby, D.D.

    2002-01-01

    Populations of the pigeon guillemot (Cepphus columba) and other piscivores have been in decline for several decades in the Gulf of Alaska and Bering Sea, and a decline in abundance of lipid-rich schooling fishes is hypothesized as the major cause. We tested this hypothesis by studying the breeding biology of pigeon guillemots during 1995-1999 while simultaneously measuring prey abundance with beach seines and bottom trawls. Our study area (Kachemak Bay, Alaska) comprises two oceanographically distinct areas. Populations of a lipid-rich schooling fish, Pacific sand lance (Ammodytes hexapterus), were higher in the warmer Inner Bay than in the colder Outer Bay, and sand lance abundance was higher during warm years. Populations of low-lipid content demersal fishes were similar between areas. Chick survival to age 15 days was 47% higher in the Inner Bay (high-lipid diet) than in the Outer Bay (low-lipid diet), and estimated reproductive success (chicks fledged nest-1) was 62% higher in the Inner Bay than in the Outer Bay. Chick provisioning rate (kJ chick-1 h-1) increased with the proportion of sand lance in the diet (r2=0.21), as did growth rate (g day-1) of younger (beta) chicks in two-chick broods (r2=0.14). Pigeon guillemots in the Inner Bay switched to demersal prey during years of below-average sand lance abundance, and these birds reacted to 38-fold interannual changes in sand lance abundance with reductions in beta chick growth rates, with no decline in beta chick survival. In contrast, the proportion of nests experiencing brood reduction in the Outer Bay (demersal diet) increased >300% during years of below-average demersal abundance, although demersal fish abundance varied only 4-fold among years. Our results support the hypothesis that recovery of pigeon guillemot populations from the effects of the Exxon Valdez oil spill is limited by availability of lipid-rich prey.

  3. Effect of endogenous proteins and lipids on starch digestibility in rice flour.

    PubMed

    Ye, Jiangping; Hu, Xiuting; Luo, Shunjing; McClements, David Julian; Liang, Lu; Liu, Chengmei

    2018-04-01

    The composition and structure of the food matrix can have a major impact on the digestion. The aim of this work was to investigate the effects of endogenous proteins and lipids on starch digestibility in rice flour, with an emphasis on establishing the underlying physicochemical mechanisms involved. Native long-grain indica rice flour and rice flour with the lipids and/or proteins removed were subjected to a simulated digestion in vitro. A significant increase in starch digestibility was observed after removal of proteins, lipids, or both. The starch digestibility of the rice flour without lipids was slightly lower than that without proteins, even though the proteins content was about 10-fold higher than the lipids content. Microstructural analysis suggested that the proteins and lipids were normally attached to the surfaces of the starch granules in the native rice flour, thus inhibiting their contact with digestive enzymes. Moreover, the proteins and lipids restricted the swelling of the starch granules, which may have decreased their digestion by reducing their surface areas. In addition, amylose-lipid complex was detected in the rice flour, which is also known to slow down starch digestion. These results have important implications for the design of foods with improved nutritional profiles. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Native and enzymatically modified wheat (Triticum aestivum L.) endogenous lipids in bread making: a focus on gas cell stabilization mechanisms.

    PubMed

    Gerits, Lien R; Pareyt, Bram; Masure, Hanne G; Delcour, Jan A

    2015-04-01

    Lipopan F and Lecitase Ultra lipases were used in straight dough bread making to study how wheat lipids affect bread loaf volume (LV) and crumb structure setting. Lipase effects on LV were dose and dough piece weight dependent. The bread quality improving mechanisms exerted by endogenous lipids were studied in terms of gluten network strengthening, which indirectly stabilizes gas cells, and in terms of direct interfacial gas cell stabilization. Unlike diacetyl tartaric esters of mono- and diacylglycerols (DATEM, used as control), lipase use did not impact dough extensibility. The effect on dough extensibility was therefore related to its lipid composition at the start of mixing. Both lipases and DATEM strongly increase the levels of polar lipids in dough liquor and their availability for and potential accumulation at gas cell interfaces. Lipases form lysolipids that emulsify other lipids. We speculate that DATEM competes with (endogenous) polar lipids for interacting with gluten proteins. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Role of Endogenous and Exogenous Tocopherols in the Lipid Stability of Marine Oil Systems: A Review

    PubMed Central

    Suárez-Jiménez, Guadalupe Miroslava; López-Saiz, Carmen María; Ramírez-Guerra, Hugo Enrique; Ezquerra-Brauer, Josafat Marina; Ruiz-Cruz, Saul; Torres-Arreola, Wilfrido

    2016-01-01

    In marine organisms primarily intended for human consumption, the quality of the muscle and the extracted oils may be affected by lipid oxidation during storage, even at low temperatures. This has led to a search for alternatives to maintain quality. In this sense, antioxidant compounds have been used to prevent such lipid deterioration. Among the most used compounds are tocopherols, which, due to their natural origin, have become an excellent alternative to prevent or retard lipid oxidation and maintain the quality of marine products. Tocopherols as antioxidants have been studied both exogenously and endogenously. Exogenous tocopherols are often used by incorporating them into plastic packaging films or adding them directly to fish oil. It has been observed that exogenous tocopherols incorporated in low concentrations maintain the quality of both muscle and the extracted oils during food storage. However, it has been reported that tocopherols applied at higher concentrations act as a prooxidant molecule, probably because their reactions with singlet oxygen may generate free radicals and cause the oxidation of polyunsaturated fatty acids in fish oils. However, when tocopherols are included in a fish diet (endogenous tocopherols), the antioxidant effect on the muscle lipids is more effective due to their incorporation into the membrane lipids, which can help extend the shelf life of seafood by reducing the lipid deterioration that occurs due to antioxidant synergy with other phenolic compounds used supplements in fish muscle. This review focuses on the most important studies in this field and highlights the potential of using tocopherols as antioxidants in marine oils. PMID:27886145

  6. Role of Endogenous and Exogenous Tocopherols in the Lipid Stability of Marine Oil Systems: A Review.

    PubMed

    Suárez-Jiménez, Guadalupe Miroslava; López-Saiz, Carmen María; Ramírez-Guerra, Hugo Enrique; Ezquerra-Brauer, Josafat Marina; Ruiz-Cruz, Saul; Torres-Arreola, Wilfrido

    2016-11-24

    In marine organisms primarily intended for human consumption, the quality of the muscle and the extracted oils may be affected by lipid oxidation during storage, even at low temperatures. This has led to a search for alternatives to maintain quality. In this sense, antioxidant compounds have been used to prevent such lipid deterioration. Among the most used compounds are tocopherols, which, due to their natural origin, have become an excellent alternative to prevent or retard lipid oxidation and maintain the quality of marine products. Tocopherols as antioxidants have been studied both exogenously and endogenously. Exogenous tocopherols are often used by incorporating them into plastic packaging films or adding them directly to fish oil. It has been observed that exogenous tocopherols incorporated in low concentrations maintain the quality of both muscle and the extracted oils during food storage. However, it has been reported that tocopherols applied at higher concentrations act as a prooxidant molecule, probably because their reactions with singlet oxygen may generate free radicals and cause the oxidation of polyunsaturated fatty acids in fish oils. However, when tocopherols are included in a fish diet (endogenous tocopherols), the antioxidant effect on the muscle lipids is more effective due to their incorporation into the membrane lipids, which can help extend the shelf life of seafood by reducing the lipid deterioration that occurs due to antioxidant synergy with other phenolic compounds used supplements in fish muscle. This review focuses on the most important studies in this field and highlights the potential of using tocopherols as antioxidants in marine oils.

  7. Endogenous Intoxication and Saliva Lipid Peroxidation in Patients with Lung Cancer.

    PubMed

    Bel'skaya, Lyudmila V; Kosenok, Victor K; Massard, Gilbert

    2016-11-16

    This research was aimed at a search for regularities in changes to parameters of endogenous intoxication and saliva lipid peroxidation in patients with lung cancer, non-malignant lung diseases, and apparently healthy people. All patients went through saliva sampling at an amount of 1 mL. A concentration of malondialdehyde (MDA) was measured according to a reaction with thiobarbituric acid, and a level of middle molecules (MM) was measured with UV spectroscopy at 254 and 280 nm, while the content of lipid peroxidation products was measured according to a degree of heptane extract light absorption at wavelengths of 220, 232, 278, and 400 nm. It has been revealed that in the context of lung cancer, the level of diene conjugates decreases, increasing the level of triene conjugates, Schiff's bases, and MM. As a tumor grows, there is a decrease in the level of lipid peroxidation primary products and an increase in endotoxemia phenomena. The process is more apparent when going from local to locally advanced disease states. The nature of the MDA change is nonlinearly associated with tumor progression. The findings might be used to optimize traditional aids of diagnostics, in disease state forecasting, in treatment monitoring, etc.

  8. Mild Lipid Stress Induces Profound Loss of MC4R Protein Abundance and Function

    PubMed Central

    Cragle, Faith K.

    2014-01-01

    Food intake is controlled at the central level by the melanocortin pathway in which the agonist α-MSH binds to melanocortin 4 receptor (MC4R), a Gs-coupled G protein-coupled receptor expressed by neurons in the paraventricular nuclei of the hypothalamus, which signals to reduce appetite. Consumption of a high-fat diet induces hypothalamic accumulation of palmitate, endoplasmic reticulum (ER) stress, apoptosis, and unresponsiveness to prolonged treatment with MC4R agonists. Here we have modeled effects of lipid stress on MC4R by using mHypoE-42 immortalized hypothalamic neurons expressing endogenous MC4R and Neuro2A cells expressing a tagged MC4R reporter, HA-MC4R-GFP. In the hypothalamic neurons, exposure to elevated palmitate in the physiological range induced splicing of X-box binding protein 1, but it did not activate C/EBP-homologous protein or induce increased levels of cleaved caspase-3, indicating mild ER stress. Such mild ER stress coexisted with a minimal loss of MC4R mRNA and yet a profound loss of cAMP signaling in response to incubation with the agonist. These findings were mirrored in the Neuro2A cells expressing HA-MC4R-GFP, in which protein abundance of the tagged receptor was decreased, whereas the activity per receptor number was maintained. The loss of cAMP signaling in response to α-MSH by elevated palmitate was corrected by treatment with a chemical chaperone, 4-phenylbutyrate in both mHypoE-42 hypothalamic neurons and in Neuro2A cells in which protein abundance of HA-MC4R-GFP was increased. The data indicate that posttranscriptional decrease of MC4R protein contribute to lower the response to α-MSH in hypothalamic neurons exposed to even a mild level of lipid stress and that a chemical chaperone corrects such a defect. PMID:24506538

  9. Endogenous anti-inflammatory neuropeptides and pro-resolving lipid mediators: a new therapeutic approach for immune disorders

    PubMed Central

    Anderson, Per; Delgado, Mario

    2008-01-01

    Identification of the factors that regulate the immune tolerance and control the appearance of exacerbated inflammatory conditions is crucial for the development of new therapies of inflammatory and autoimmune diseases. Although much is known about the molecular basis of initiating signals and pro-inflammatory chemical mediators in inflammation, it has only recently become apparent that endogenous stop signals are critical at early checkpoints within the temporal events of inflammation. Some neuropeptides and lipid mediators that are produced during the ongoing inflammatory response have emerged as endogenous anti-inflammatory agents that participate in the regulation of the processes that ensure self-tolerance and/or inflammation resolution. Here we examine the latest research findings, which indicate that neuropeptides participate in maintaining immune tolerance in two distinct ways: by regulating the balance between pro-inflammatory and anti-inflammatory factors, and by inducing the emergence of regulatory T cells with suppressive activity against autoreactive T-cell effectors. On the other hand, we also focus on lipid mediators biosynthesized from ω-3 and ω-6 polyunsaturated fatty-acids in inflammatory exudates that promote the resolution phase of acute inflammation by regulating leucocyte influx to and efflux from local inflamed sites. Both anti-inflammatory neuropeptides and pro-resolving lipid mediators have shown therapeutic potential for a variety of inflammatory and autoimmune disorders and could be used as biotemplates for the development of novel pharmacologic agents. PMID:18554314

  10. Regulation of GPR119 receptor activity with endocannabinoid-like lipids.

    PubMed

    Syed, Samreen K; Bui, Hai Hoang; Beavers, Lisa S; Farb, Thomas B; Ficorilli, James; Chesterfield, Amy K; Kuo, Ming-Shang; Bokvist, Krister; Barrett, David G; Efanov, Alexander M

    2012-12-15

    The GPR119 receptor plays an important role in the secretion of incretin hormones in response to nutrient consumption. We have studied the ability of an array of naturally occurring endocannabinoid-like lipids to activate GPR119 and have identified several lipid receptor agonists. The most potent receptor agonists identified were three N-acylethanolamines: oleoylethanolamine (OEA), palmitoleoylethanolamine, and linoleylethanolamine (LEA), all of which displayed similar potency in activating GPR119. Another lipid, 2-oleoylglycerol (2-OG), also activated GPR119 receptor but with significantly lower potency. Endogenous levels of endocannabinoid-like lipids were measured in intestine in fasted and refed mice. Of the lipid GPR119 agonists studied, the intestinal levels of only OEA, LEA, and 2-OG increased significantly upon refeeding. Intestinal levels of OEA and LEA in the fasted mice were low. In the fed state, OEA levels only moderately increased, whereas LEA levels rose drastically. 2-OG was the most abundant of the three GPR119 agonists in intestine, and its levels were radically elevated in fed mice. Our data suggest that, in lean mice, 2-OG and LEA may serve as physiologically relevant endogenous GPR119 agonists that mediate receptor activation upon nutrient uptake.

  11. Endogenous lipid (cholesterol) pneumonia in three captive Siberian tigers (Panthera tigris altaica).

    PubMed

    Bollo, Enrico; Scaglione, Frine Eleonora; Chiappino, Laura; Sereno, Alessandra; Triberti, Orfeo; Schröder, Cathrin

    2012-05-01

    During the years 2009-2011, 7 Siberian tigers (Panthera tigris altaica), aged between 2 and 14 years, from the Safaripark of Pombia were referred for necropsy to the Department of Animal Pathology of the University of Turin (Italy). Three tigers, aged 10 (2 animals) and 14 years, had multifocal, irregularly distributed, white, soft, subpleural, 3-mm nodules scattered throughout the lungs. Histologically, there was a marked infiltration of macrophages, with foamy cytoplasm, and multinucleate giant cells interspersed with numerous clusters of cholesterol clefts. A mild lymphocytic infiltration was localized around the lesion. The findings were consistent with endogenous lipid pneumonia, which was considered an incidental finding of no clinical significance.

  12. New assays for detection and localization of endogenous lipid peroxidation products in living boar sperm after BTS dilution or after freeze-thawing.

    PubMed

    Brouwers, Jos F; Silva, Patricia F N; Gadella, Barend M

    2005-01-15

    Reactive oxygen species have been implicated in sperm aberrations causing multiple pathologies including sub- and infertility. Freeze/thawing of sperm samples is routinely performed in the cattle breeding industries for semen storage prior to artificial insemination but unusual in porcine breeding industries as semen dilution and storage at 17 degrees C is sufficient for artificial insemination within 2-3 days. However, longer semen storage requires cryopreservation of boar semen. Freeze/thawing procedures induce sperm damage and induce reactive oxygen species in mammalian sperm and boar sperm seems to be more vulnerable for this than bull sperm. We developed a new method to detect reactive oxygen species induced damage at the level of the sperm plasma membrane in bull sperm. Lipid peroxidation in freshly stored and frozen/thawed sperm cells was assessed by mass spectrometric analysis of the main endogenous lipid classes, phosphatidylcholine and cholesterol and by fluorescence techniques using the lipid peroxidation reporter probe C11-BODIPY(581/591). Peroxidation as reported by the fluorescent probe, clearly corresponded with the presence of hydroxy- and hydroperoxyphosphatidylcholine in the sperm membranes, which are early stage products of lipid peroxidation. This allowed us, for the first time, to correlate endogenous lipid peroxidation with localization of this process in the living sperm cells. Cytoplasmatic droplets in incompletely matured sperm cells were intensely peroxidized. Furthermore, lipid peroxidation was particularly strong in the mid-piece and tail of frozen/thawed spermatozoa and significantly less intense in the sperm head. Induction of peroxidation in fresh sperm cells with the lipid soluble reactive oxygen species tert-butylhydroperoxide gave an even more pronounced effect, demonstrating antioxidant activity in the head of fresh sperm cells. Furthermore, we were able to show using the flow cytometer that spontaneous peroxidation was not a

  13. Laser Desorption/Ionization Mass Spectrometric Imaging of Endogenous Lipids from Rat Brain Tissue Implanted with Silver Nanoparticles

    NASA Astrophysics Data System (ADS)

    Muller, Ludovic; Baldwin, Kathrine; Barbacci, Damon C.; Jackson, Shelley N.; Roux, Aurélie; Balaban, Carey D.; Brinson, Bruce E.; McCully, Michael I.; Lewis, Ernest K.; Schultz, J. Albert; Woods, Amina S.

    2017-08-01

    Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate (AgNP) matrix generates reproducible imaging of lipids in rodent models of disease and injury. Gas-phase production and acceleration of size-selected 8 nm AgNP is followed by controlled ion beam rastering and soft landing implantation of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality images for most lipid classes in rat brain tissue (in positive mode: galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides, sulfatides, phosphatidylinositol, and sphingomyelins). Image reproducibility in serial sections of brain tissue is achieved within <10% tolerance by selecting argentated instead of alkali cationized ions. The imaging of brain tissues spotted with pure standards was used to demonstrate that Ag cationized ceramide and diacylglycerol ions are from intact, endogenous species. In contrast, almost all Ag cationized fatty acid ions are a result of fragmentations of numerous lipid types having the fatty acid as a subunit. Almost no argentated intact fatty acid ions come from the pure fatty acid standard on tissue.

  14. The Role of Tetraether Lipid Composition in the Adaptation of Thermophilic Archaea to Acidity

    PubMed Central

    Boyd, Eric S.; Hamilton, Trinity L.; Wang, Jinxiang; He, Liu; Zhang, Chuanlun L.

    2013-01-01

    Diether and tetraether lipids are fundamental components of the archaeal cell membrane. Archaea adjust the degree of tetraether lipid cyclization in order to maintain functional membranes and cellular homeostasis when confronted with pH and/or thermal stress. Thus, the ability to adjust tetraether lipid composition likely represents a critical phenotypic trait that enabled archaeal diversification into environments characterized by extremes in pH and/or temperature. Here we assess the relationship between geochemical variation, core- and polar-isoprenoid glycerol dibiphytanyl glycerol tetraether (C-iGDGT and P-iGDGT, respectively) lipid composition, and archaeal 16S rRNA gene diversity and abundance in 27 geothermal springs in Yellowstone National Park, Wyoming. The composition and abundance of C-iGDGT and P-iGDGT lipids recovered from geothermal ecosystems were distinct from surrounding soils, indicating that they are synthesized endogenously. With the exception of GDGT-0 (no cyclopentyl rings), the abundances of individual C-iGDGT and P-iGDGT lipids were significantly correlated. The abundance of a number of individual tetraether lipids varied positively with the relative abundance of individual 16S rRNA gene sequences, most notably crenarchaeol in both the core and polar GDGT fraction and sequences closely affiliated with Candidatus Nitrosocaldus yellowstonii. This finding supports the proposal that crenarchaeol is a biomarker for nitrifying archaea. Variation in the degree of cyclization of C- and P-iGDGT lipids recovered from geothermal mats and sediments could best be explained by variation in spring pH, with lipids from acidic environments tending to have, on average, more internal cyclic rings than those from higher pH ecosystems. Likewise, variation in the phylogenetic composition of archaeal 16S rRNA genes could best be explained by spring pH. In turn, the phylogenetic similarity of archaeal 16S rRNA genes was significantly correlated with the similarity

  15. Adipose triglyceride lipase protein abundance and translocation to the lipid droplet increase during leptin-induced lipolysis in bovine adipocytes.

    PubMed

    Koltes, D A; Spurlock, M E; Spurlock, D M

    2017-10-01

    Proper regulation of lipid metabolism is critical for preventing the development of metabolic diseases. It is clear that leptin plays a critical role in the regulation of energy homeostasis by regulating energy intake. However, leptin can also regulate energy homeostasis by inducing lipolysis in adipocytes, but it is unclear how the major lipases are involved in leptin-stimulated lipolysis. Therefore, the objectives of this study were to determine if (1) leptin acts directly to induce lipolysis in bovine adipocytes, (2) the potential lipases involved in leptin-induced lipolysis in bovine adipocytes, and (3) increases translocation of adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL) during leptin-stimulated lipolysis in bovine stromal vascular cell-derived adipocytes. As hypothesized, leptin induced a lipolytic response (P = 0.02) in isolated adipocytes which was accompanied by an increase in phosphorylation of signal transducer and activator of transcription (STAT)3 (P = 0.03), a well-documented secondary messenger of leptin, and ATGL protein abundance (P < 0.01). Protein abundance of STAT3, perilipin, HSL, and phosphorylation of HSL by PKA and AMPK were not altered during leptin-stimulated lipolysis (P > 0.05). Immunostaining techniques were employed to determine the location of HSL and ATGL. Both lipases translocated to the lipid droplet after 2 h of exposure to isoproterenol (P < 0.02). However, only ATGL was translocated to the lipid droplet during leptin-stimulated lipolysis (P = 0.04), indicating ATGL may be the active lipase in leptin-stimulated lipolysis. In summary, leptin stimulates lipolysis in bovine adipocytes. The lack of phosphorylated HSL and translocation of HSL to the lipid droplet during leptin-stimulated lipolysis suggest minimal activity by PKA. Interestingly, leptin-stimulated lipolysis is accompanied by an increase in ATGL protein abundance and translocation to the lipid droplet, indicating its involvement in leptin

  16. Endogenous Lunar Volatiles: Insights into the Abundances of Volatiles in the Moon from Lunar Apatite

    NASA Technical Reports Server (NTRS)

    McCubbin, Francis

    2016-01-01

    At the time of publication of New Views of the Moon, it was thought that the Moon was bone dry with less than about 1 ppb H2O. However in 2007, initial reports at the 38th Lunar and Planetary Science Conference speculated that H-species were present in both apatites and pyroclastic volcanic lunar glasses. These early reports were later confirmed through peer-review, which motivated many subsequent studies on magmatic volatiles in and on the Moon within the last decade. Some of these studies have cast into question the post-Apollo view of lunar formation, the distribution and sources of volatiles in the Earth-Moon system, and the thermal and magmatic evolution of the Moon. The mineral apatite has been one of the pillars of this new field of study, and it will be the primary focus of this abstract. Although apatite has been used both to understand the abundances of volatiles in lunar systems as well as the isotopic compositions of those volatiles, the focus here will be on the abundances of F, Cl, and H2O. This work demonstrates the utility of apatite in advancing our understanding of lunar volatiles, hence apatite should be among the topics covered in the endogenous lunar volatile chapter in NVM II. Truncated ternary plot of apatite X-site occupancy (mol%) from highlands apatite and mare basalt apatite plotted on the relative volatile abundance diagram from. The solid black lines delineate fields of relative abundances of F, Cl, and H2O (on a weight basis) in the melt from which the apatite crystallized. The diagram was constructed using available apatite/melt partitioning data for fluorine, chlorine, and hydroxyl.

  17. Endogenous Lunar Volatiles

    NASA Technical Reports Server (NTRS)

    McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Boyce, J. W.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Magna, T.; Ni, P.; Tartese, R.; hide

    2017-01-01

    The chapter will begin with an introduction that defines magmatic volatiles (e.g., H, F, Cl, S) versus geochemical volatiles (e.g., K, Rb, Zn). We will discuss our approach of understanding both types of volatiles in lunar samples and lay the ground work for how we will determine the overall volatile budget of the Moon. We will then discuss the importance of endogenous volatiles in shaping the "Newer Views of the Moon", specifically how endogenous volatiles feed forward into processes such as the origin of the Moon, magmatic differentiation, volcanism, and secondary processes during surface and crustal interactions. After the introduction, we will include a re-view/synthesis on the current state of 1) apatite compositions (volatile abundances and isotopic compositions); 2) nominally anhydrous mineral phases (moderately to highly volatile); 3) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar pyroclastic glass beads; 4) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar basalts; 5) volatile (moderately to highly volatile) abundances in and isotopic compositions of melt inclusions; and finally 6) experimental constraints on mineral-melt partitioning of moderately to highly volatile elements under lunar conditions. We anticipate that each section will summarize results since 2007 and focus on new results published since the 2015 Am Min review paper on lunar volatiles [9]. The next section will discuss how to use sample abundances of volatiles to understand the source region and potential caveats in estimating source abundances of volatiles. The following section will include our best estimates of volatile abundances and isotopic compositions (where permitted by available data) for each volatile element of interest in a number of important lunar reservoirs, including the crust, mantle, KREEP, and bulk Moon. The final section of the chapter will focus upon future work, outstanding questions

  18. Abundant Trimethylornithine Lipids and Specific Gene Sequences Are Indicative of Planctomycete Importance at the Oxic/Anoxic Interface in Sphagnum-Dominated Northern Wetlands.

    PubMed

    Moore, Eli K; Villanueva, Laura; Hopmans, Ellen C; Rijpstra, W Irene C; Mets, Anchelique; Dedysh, Svetlana N; Sinninghe Damsté, Jaap S

    2015-09-01

    Northern wetlands make up a substantial terrestrial carbon sink and are often dominated by decay-resistant Sphagnum mosses. Recent studies have shown that planctomycetes appear to be involved in degradation of Sphagnum-derived debris. Novel trimethylornithine (TMO) lipids have recently been characterized as abundant lipids in various Sphagnum wetland planctomycete isolates, but their occurrence in the environment has not yet been confirmed. We applied a combined intact polar lipid (IPL) and molecular analysis of peat cores collected from two northern wetlands (Saxnäs Mosse [Sweden] and Obukhovskoye [Russia]) in order to investigate the preferred niche and abundance of TMO-producing planctomycetes. TMOs were present throughout the profiles of Sphagnum bogs, but their concentration peaked at the oxic/anoxic interface, which coincided with a maximum abundance of planctomycete-specific 16S rRNA gene sequences. The sequences detected at the oxic/anoxic interface were affiliated with the Isosphaera group, while sequences present in the anoxic peat layers were related to an uncultured planctomycete group. Pyrosequencing-based analysis identified Planctomycetes as the major bacterial group at the oxic/anoxic interface at the Obukhovskoye peat (54% of total 16S rRNA gene sequence reads), followed by Acidobacteria (19% reads), while in the Saxnäs Mosse peat, Acidobacteria were dominant (46%), and Planctomycetes contributed to 6% of the total reads. The detection of abundant TMO lipids in planctomycetes isolated from peat bogs and the lack of TMO production by cultures of acidobacteria suggest that planctomycetes are the producers of TMOs in peat bogs. The higher accumulation of TMOs at the oxic/anoxic interface and the change in the planctomycete community with depth suggest that these IPLs could be synthesized as a response to changing redox conditions at the oxic/anoxic interface. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. Abundant Trimethylornithine Lipids and Specific Gene Sequences Are Indicative of Planctomycete Importance at the Oxic/Anoxic Interface in Sphagnum-Dominated Northern Wetlands

    PubMed Central

    Villanueva, Laura; Hopmans, Ellen C.; Rijpstra, W. Irene C.; Mets, Anchelique; Dedysh, Svetlana N.

    2015-01-01

    Northern wetlands make up a substantial terrestrial carbon sink and are often dominated by decay-resistant Sphagnum mosses. Recent studies have shown that planctomycetes appear to be involved in degradation of Sphagnum-derived debris. Novel trimethylornithine (TMO) lipids have recently been characterized as abundant lipids in various Sphagnum wetland planctomycete isolates, but their occurrence in the environment has not yet been confirmed. We applied a combined intact polar lipid (IPL) and molecular analysis of peat cores collected from two northern wetlands (Saxnäs Mosse [Sweden] and Obukhovskoye [Russia]) in order to investigate the preferred niche and abundance of TMO-producing planctomycetes. TMOs were present throughout the profiles of Sphagnum bogs, but their concentration peaked at the oxic/anoxic interface, which coincided with a maximum abundance of planctomycete-specific 16S rRNA gene sequences. The sequences detected at the oxic/anoxic interface were affiliated with the Isosphaera group, while sequences present in the anoxic peat layers were related to an uncultured planctomycete group. Pyrosequencing-based analysis identified Planctomycetes as the major bacterial group at the oxic/anoxic interface at the Obukhovskoye peat (54% of total 16S rRNA gene sequence reads), followed by Acidobacteria (19% reads), while in the Saxnäs Mosse peat, Acidobacteria were dominant (46%), and Planctomycetes contributed to 6% of the total reads. The detection of abundant TMO lipids in planctomycetes isolated from peat bogs and the lack of TMO production by cultures of acidobacteria suggest that planctomycetes are the producers of TMOs in peat bogs. The higher accumulation of TMOs at the oxic/anoxic interface and the change in the planctomycete community with depth suggest that these IPLs could be synthesized as a response to changing redox conditions at the oxic/anoxic interface. PMID:26150465

  20. FadD Is Required for Utilization of Endogenous Fatty Acids Released from Membrane Lipids ▿ †

    PubMed Central

    Pech-Canul, Ángel; Nogales, Joaquina; Miranda-Molina, Alfonso; Álvarez, Laura; Geiger, Otto; Soto, María José; López-Lara, Isabel M.

    2011-01-01

    FadD is an acyl coenzyme A (CoA) synthetase responsible for the activation of exogenous long-chain fatty acids (LCFA) into acyl-CoAs. Mutation of fadD in the symbiotic nitrogen-fixing bacterium Sinorhizobium meliloti promotes swarming motility and leads to defects in nodulation of alfalfa plants. In this study, we found that S. meliloti fadD mutants accumulated a mixture of free fatty acids during the stationary phase of growth. The composition of the free fatty acid pool and the results obtained after specific labeling of esterified fatty acids with a Δ5-desaturase (Δ5-Des) were in agreement with membrane phospholipids being the origin of the released fatty acids. Escherichia coli fadD mutants also accumulated free fatty acids released from membrane lipids in the stationary phase. This phenomenon did not occur in a mutant of E. coli with a deficient FadL fatty acid transporter, suggesting that the accumulation of fatty acids in fadD mutants occurs inside the cell. Our results indicate that, besides the activation of exogenous LCFA, in bacteria FadD plays a major role in the activation of endogenous fatty acids released from membrane lipids. Furthermore, expression analysis performed with S. meliloti revealed that a functional FadD is required for the upregulation of genes involved in fatty acid degradation and suggested that in the wild-type strain, the fatty acids released from membrane lipids are degraded by β-oxidation in the stationary phase of growth. PMID:21926226

  1. Screening molecular associations with lipid membranes using natural abundance 13C cross-polarization magic-angle spinning NMR and principal component analysis.

    PubMed

    Middleton, David A; Hughes, Eleri; Madine, Jillian

    2004-08-11

    We describe an NMR approach for detecting the interactions between phospholipid membranes and proteins, peptides, or small molecules. First, 1H-13C dipolar coupling profiles are obtained from hydrated lipid samples at natural isotope abundance using cross-polarization magic-angle spinning NMR methods. Principal component analysis of dipolar coupling profiles for synthetic lipid membranes in the presence of a range of biologically active additives reveals clusters that relate to different modes of interaction of the additives with the lipid bilayer. Finally, by representing profiles from multiple samples in the form of contour plots, it is possible to reveal statistically significant changes in dipolar couplings, which reflect perturbations in the lipid molecules at the membrane surface or within the hydrophobic interior.

  2. The expanding field of cannabimimetic and related lipid mediators

    PubMed Central

    Bradshaw, Heather B; Walker, J Michael

    2005-01-01

    The discovery of the endogenous cannabimimetic lipid mediators, anandamide and 2-arachidonoyl glycerol, opened the door to the discovery of other endogenous lipid mediators similar in structure and function. The majority of these compounds do not bind appreciably to known cannabinoid receptors; yet some of them produce cannabimimetic effects while others exert actions through novel mechanisms that remain to be elucidated. This review explores the growing diversity of recently discovered putative lipid mediators and their relationship to the endogenous cannabinoid system. The possibility that there remain many unidentified signalling lipids coupled with the evidence that many of these yield bioactive metabolites due to actions of known enzymes (e.g. cyclooxygenases, lipoxygenases, cytochrome P450s) suggests the existence of a large and complex family of lipid mediators about which only little is known at this time. The elucidation of the biochemistry and pharmacology of these compounds may provide therapeutic targets for a variety of conditions including sleep dysfunction, eating disorders, cardiovascular disease, as well as inflammation and pain. PMID:15655504

  3. Lipid Neuroprotectants and Traumatic Glaucomatous Neurodegeneration

    DTIC Science & Technology

    2016-05-01

    alter elastic TM, modulus and binding and functional assays with potential protein targets. Endogenous lipids, Aqueous humor, Trabecular meshwork...Intraocular pressure, sphingolipids, primary cell culture, elastic modulus, protein targets. Major goal 1. Test the hypothesis that selected lipids...glaucomatous TM with and without these lipids and atomic force microscope (AFM). Further elastic modulus using high flow and low flow areas of glaucomatous

  4. Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

    PubMed

    Panda, R; Ariyarathna, H; Amnuaycheewa, P; Tetteh, A; Pramod, S N; Taylor, S L; Ballmer-Weber, B K; Goodman, R E

    2013-02-01

    Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop. © 2012 John Wiley & Sons A/S.

  5. A Review About Lycopene-Induced Nuclear Hormone Receptor Signalling in Inflammation and Lipid Metabolism via still Unknown Endogenous Apo-10´-Lycopenoids.

    PubMed

    Caris-Veyrat, Catherine; Garcia, Ada L; Reynaud, Eric; Lucas, Renata; Aydemir, Gamze; Rühl, Ralph

    2017-10-20

    Lycopene is the red pigment in tomatoes and tomato products and is an important dietary carotenoid found in the human organism. Lycopene-isomers, oxidative lycopene metabolites and apo-lycopenoids are found in the food matrix. Lycopene intake derived from tomato consumption is associated with alteration of lipid metabolism and a lower incidence of cardiovascular diseases (CVD). Lycopene is mainly described as a potent antioxidant but novel studies are shifting towards its metabolites and their capacity to mediate nuclear receptor signalling. Di-/tetra-hydro-derivatives of apo-10´-lycopenoic acid and apo-15´-lycopenoic acids are potential novel endogenous mammalian lycopene metabolites which may act as ligands for nuclear hormone mediated activation and signalling. In this review, we postulate that complex lycopene metabolism results in various lycopene metabolites which have the ability to mediate transactivation of various nuclear hormone receptors like RARs, RXRs and PPARs. A new mechanistic explanation of how tomato consumption could positively modulate inflammation and lipid metabolism is discussed.

  6. Effects of positive acceleration on the metabolism of endogenous carbon monoxide and serum lipid in atherosclerotic rabbits

    PubMed Central

    Luo, Huilan; Chen, Yongsheng; Wang, Junhua

    2010-01-01

    Background: Atherosclerosis (AS) is caused mainly due to the increase in the serum lipid, thrombosis, and injuries of the endothelial cells. During aviation, the incremental load of positive acceleration that leads to dramatic stress reactions and hemodynamic changes may predispose pilots to functional disorders and even pathological changes of organs. However, much less is known on the correlation between aviation and AS pathogenesis. Methods and Results: A total of 32 rabbits were randomly divided into 4 groups with 8 rabbits in each group. The control group was given a high cholesterol diet but no acceleration exposure, whereas the other 3 experimental groups were treated with a high cholesterol diet and acceleration exposure for 4, 8, and 12 weeks, respectively. In each group, samples of celiac vein blood and the aorta were collected after the last exposure for the measurement of endogenous CO and HO-1 activities, as well as the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). As compared with the control group, the endocardial CO content and the HO-1 activity in aortic endothelial cells were significantly elevated at the 4th, 8th, and 12th weekend, respectively (P < 0.05 or <0.01). And these measures tended upward as the exposure time was prolonged. Levels of TC and LDL-C in the experimental groups were significantly higher than those in the control group, presenting an upward tendency. Levels of TG were found significantly increased in the 8-week-exposure group, but significantly declined in the 12-week-exposure group (still higher than those in the control group). Levels of the HDL-C were increased in the 4-week-exposure group, declined in the 8-week-exposure group, and once more increased in the 12-week-exposure group, without significant differences with the control group. Conclusions: Positive acceleration exposure may lead to a significant increase of

  7. How and When Do Insects Rely on Endogenous Protein and Lipid Resources during Lethal Bouts of Starvation? A New Application for 13C-Breath testing

    PubMed Central

    McCue, Marshall D.; Guzman, R. Marena; Passement, Celeste A.; Davidowitz, Goggy

    2015-01-01

    Most of our understanding about the physiology of fasting and starvation comes from studies of vertebrates; however, for ethical reasons, studies that monitor vertebrates through the lethal endpoint are scant. Insects are convenient models to characterize the comparative strategies used to cope with starvation because they have diverse life histories and have evolved under the omnipresent challenge of food limitation. Moreover, we can study the physiology of starvation through its natural endpoint. In this study we raised populations of five species of insects (adult grasshoppers, crickets, cockroaches, and larval beetles and moths) on diets labeled with either 13C-palmitic acid or 13C-leucine to isotopically enrich the lipids or the proteins in their bodies, respectively. The insects were allowed to become postabsorptive and then starved. We periodically measured the δ13C of the exhaled breath to characterize how each species adjusted their reliance on endogenous lipids and proteins as energy sources. We found that starving insects employ a wide range of strategies for regulating lipid and protein oxidation. All of the insects except for the beetle larvae were capable of sharply reducing reliance on protein oxidation; however, this protein sparing strategy was usually unsustainable during the entire starvation period. All insects increased their reliance on lipid oxidation, but while some species (grasshoppers, cockroaches, and beetle larvae) were still relying extensively on lipids at the time of death, other species (crickets and moth larvae) allowed rates of lipid oxidation to return to prestarvation levels. Although lipids and proteins are critical metabolic fuels for both vertebrates and insects, insects apparently exhibit a much wider range of strategies for rationing these limited resources during starvation. PMID:26465334

  8. How and When Do Insects Rely on Endogenous Protein and Lipid Resources during Lethal Bouts of Starvation? A New Application for 13C-Breath testing.

    PubMed

    McCue, Marshall D; Guzman, R Marena; Passement, Celeste A; Davidowitz, Goggy

    2015-01-01

    Most of our understanding about the physiology of fasting and starvation comes from studies of vertebrates; however, for ethical reasons, studies that monitor vertebrates through the lethal endpoint are scant. Insects are convenient models to characterize the comparative strategies used to cope with starvation because they have diverse life histories and have evolved under the omnipresent challenge of food limitation. Moreover, we can study the physiology of starvation through its natural endpoint. In this study we raised populations of five species of insects (adult grasshoppers, crickets, cockroaches, and larval beetles and moths) on diets labeled with either 13C-palmitic acid or 13C-leucine to isotopically enrich the lipids or the proteins in their bodies, respectively. The insects were allowed to become postabsorptive and then starved. We periodically measured the δ13C of the exhaled breath to characterize how each species adjusted their reliance on endogenous lipids and proteins as energy sources. We found that starving insects employ a wide range of strategies for regulating lipid and protein oxidation. All of the insects except for the beetle larvae were capable of sharply reducing reliance on protein oxidation; however, this protein sparing strategy was usually unsustainable during the entire starvation period. All insects increased their reliance on lipid oxidation, but while some species (grasshoppers, cockroaches, and beetle larvae) were still relying extensively on lipids at the time of death, other species (crickets and moth larvae) allowed rates of lipid oxidation to return to prestarvation levels. Although lipids and proteins are critical metabolic fuels for both vertebrates and insects, insects apparently exhibit a much wider range of strategies for rationing these limited resources during starvation.

  9. Dermal extracellular lipid in birds.

    PubMed

    Stromberg, M W; Hinsman, E J; Hullinger, R L

    1990-01-01

    A light and electron microscopic study of the skin of domestic chickens, seagulls, and antarctic penguins revealed abundant extracellular dermal lipid and intracellular epidermal lipid. Dermal lipid appeared ultrastructurally as extracellular droplets varying from less than 1 micron to more than 25 microns in diameter. The droplets were often irregularly contoured, sometimes round, and of relatively low electron density. Processes of fibrocytes were often seen in contact with extracellular lipid droplets. Sometimes a portion of such a droplet was missing, and this missing part appeared to have been "digested away" by the cell process. In places where cells or cell processes are in contact with fact droplets, there are sometimes extracellular membranous whorls or fragments which have been associated with the presence of fatty acids. Occasionally (in the comb) free fat particles were seen in intimate contact with extravasated erythrocytes. Fat droplets were seen in the lumen of small dermal blood and lymph vessels. We suggest that the dermal extracellular lipid originates in the adipocyte layer and following hydrolysis the free fatty acids diffuse into the epidermis. Here they become the raw material for forming the abundant neutral lipid contained in many of the epidermal cells of both birds and dolphins. The heretofore unreported presence and apparently normal utilization of abundant extracellular lipid in birds, as well as the presence of relatively large droplets of neutral lipid in dermal vessels, pose questions which require a thorough reappraisal of present concepts of the ways in which fat is distributed and utilized in the body.

  10. Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus

    PubMed Central

    Serhan, C N; Chiang, N

    2008-01-01

    Complete resolution of an acute inflammatory response and its return to homeostasis are essential for healthy tissues. Here, we overview ongoing efforts to characterize cellular and molecular mechanisms that govern the resolution of self-limited inflammation. Systematic temporal analyses of evolving inflammatory exudates using mediator lipidomics-informatics, proteomics, and cellular trafficking with murine resolving exudates demonstrate novel endogenous pathways of local-acting mediators that share both anti-inflammatory and pro-resolving properties. In murine systems, resolving-exudate leukocytes switch their phenotype to actively generate new families of mediators from major omega-3 fatty acids EPA and DHA termed resolvins and protectins. Recent advances on their biosynthesis and actions are reviewed with a focus on the E-series resolvins (RvE1, RvE2), D series resolvins (RvD1, RvD2) and the protectins including neuroprotectin D1/protectin D1 (NPD1/PD1) as well as their aspirin-triggered epimeric forms. Members of each new family demonstrate potent stereo-specific actions, joining the lipoxins as endogenous local signals that govern resolution and endogenous anti-inflammation mechanisms. In addition to their origins and roles in resolution biology in the immune system, recent findings indicate that these new mediator families also display potent protective actions in lung, kidney, and eye as well as enhance microbial clearance. Thus, these endogenous agonists of resolution pathways constitute a novel genus of chemical mediators that possess pro-resolving, anti-inflammatory, and antifibrotic as well as host-directed antimicrobial actions. These may be useful in the design of new therapeutics and treatments for diseases with the underlying trait of uncontrolled inflammation and redox organ stress. PMID:17965751

  11. Activation of iNKT cells by a distinct constituent of the endogenous glucosylceramide fraction

    PubMed Central

    Brennan, Patrick J.; Tatituri, Raju V. V.; Heiss, Christian; Watts, Gerald F. M.; Hsu, Fong-Fu; Veerapen, Natacha; Cox, Liam R.; Azadi, Parastoo; Besra, Gurdyal S.; Brenner, Michael B.

    2014-01-01

    Invariant natural killer T (iNKT) cells are a specialized T-cell subset that recognizes lipids as antigens, contributing to immune responses in diverse disease processes. Experimental data suggests that iNKT cells can recognize both microbial and endogenous lipid antigens. Several candidate endogenous lipid antigens have been proposed, although the contextual role of specific antigens during immune responses remains largely unknown. We have previously reported that mammalian glucosylceramides (GlcCers) activate iNKT cells. GlcCers are found in most mammalian tissues, and exist in variable molecular forms that differ mainly in N-acyl fatty acid chain use. In this report, we purified, characterized, and tested the GlcCer fractions from multiple animal species. Although activity was broadly identified in these GlcCer fractions from mammalian sources, we also found activity properties that could not be reconciled by differences in fatty acid chain use. Enzymatic digestion of β-GlcCer and a chromatographic separation method demonstrated that the activity in the GlcCer fraction was limited to a rare component of this fraction, and was not contained within the bulk of β-GlcCer molecular species. Our data suggest that a minor lipid species that copurifies with β-GlcCer in mammals functions as a lipid self antigen for iNKT cells. PMID:25197085

  12. Ultrafine particles affect the balance of endogenous pro- and anti-inflammatory lipid mediators in the lung: in-vitro and in-vivo studies

    PubMed Central

    2012-01-01

    increased also one day after UfCP exposure. Immunohistochemistry localized highest concentrations of PGE2 especially in AM one day after UfCP exposure. Conclusion Our results suggest that UfCP exposure affects the balance between pro- and anti-inflammatory lipid mediators. In allergic mice, where the endogenous balance of pro- and anti-inflammatory mediators is already altered, UfCP exposure aggravates the inflammation and the increase in anti-inflammatory, pro-resolving lipid mediators is insufficient to counterbalance the extensive inflammatory response. This may be a contributing mechanism that explains the increased susceptibility of asthmatic patients towards particle exposure. PMID:22809365

  13. The lipid language of plant-fungal interactions.

    PubMed

    Christensen, Shawn A; Kolomiets, Michael V

    2011-01-01

    Lipid mediated cross-kingdom communication between hosts and pathogens is a rapidly emerging field in molecular plant-fungal interactions. Amidst our growing understanding of fungal and plant chemical cross-talk lies the distinct, yet little studied, role for a group of oxygenated lipids derived from polyunsaturated fatty acids, termed oxylipins. Endogenous fungal oxylipins are known for their roles in carrying out pathogenic strategies to successfully colonize their host, reproduce, and synthesize toxins. While plant oxylipins also have functions in reproduction and development, they are largely recognized as agents that facilitate resistance to pathogen attack. Here we review the composition and endogenous functions of oxylipins produced by both plants and fungi and introduce evidence which suggests that fungal pathogens exploit host oxylipins to facilitate their own virulence and pathogenic development. Specifically, we describe how fungi induce plant lipid metabolism to utilize plant oxylipins in order to promote G-protein-mediated regulation of sporulation and mycotoxin production in the fungus. The use of host-ligand mimicry (i.e. coronatine) to manipulate plant defense responses that benefit the fungus are also implicated. Published by Elsevier Inc.

  14. Transcriptional Regulation of T-Cell Lipid Metabolism: Implications for Plasma Membrane Lipid Rafts and T-Cell Function.

    PubMed

    Robinson, George A; Waddington, Kirsty E; Pineda-Torra, Ines; Jury, Elizabeth C

    2017-01-01

    It is well established that cholesterol and glycosphingolipids are enriched in the plasma membrane (PM) and form signaling platforms called lipid rafts, essential for T-cell activation and function. Moreover, changes in PM lipid composition affect the biophysical properties of lipid rafts and have a role in defining functional T-cell phenotypes. Here, we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/β, peroxisome proliferator-activated receptor γ, estrogen receptors α/β (ERα/β), and sterol regulatory element-binding proteins in T-cells. These receptors lie at the interface between lipid metabolism and immune cell function and are endogenously activated by lipids and/or hormones. Importantly, they regulate cellular cholesterol, fatty acid, glycosphingolipid, and phospholipid levels but are also known to modulate a broad spectrum of immune responses. The current evidence supporting a role for lipid metabolism pathways in controlling immune cell activation by influencing PM lipid raft composition in health and disease, and the potential for targeting lipid biosynthesis pathways to control unwanted T-cell activation in autoimmunity is reviewed.

  15. Transcriptional Regulation of T-Cell Lipid Metabolism: Implications for Plasma Membrane Lipid Rafts and T-Cell Function

    PubMed Central

    Robinson, George A.; Waddington, Kirsty E.; Pineda-Torra, Ines; Jury, Elizabeth C.

    2017-01-01

    It is well established that cholesterol and glycosphingolipids are enriched in the plasma membrane (PM) and form signaling platforms called lipid rafts, essential for T-cell activation and function. Moreover, changes in PM lipid composition affect the biophysical properties of lipid rafts and have a role in defining functional T-cell phenotypes. Here, we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/β, peroxisome proliferator-activated receptor γ, estrogen receptors α/β (ERα/β), and sterol regulatory element-binding proteins in T-cells. These receptors lie at the interface between lipid metabolism and immune cell function and are endogenously activated by lipids and/or hormones. Importantly, they regulate cellular cholesterol, fatty acid, glycosphingolipid, and phospholipid levels but are also known to modulate a broad spectrum of immune responses. The current evidence supporting a role for lipid metabolism pathways in controlling immune cell activation by influencing PM lipid raft composition in health and disease, and the potential for targeting lipid biosynthesis pathways to control unwanted T-cell activation in autoimmunity is reviewed. PMID:29225604

  16. Microbial Diversity and Lipid Abundance in Microbial Mats from a Sulfidic, Saline, Warm Spring in Utah, USA

    NASA Astrophysics Data System (ADS)

    Gong, J.; Edwardson, C.; Mackey, T. J.; Dzaugis, M.; Ibarra, Y.; Course 2012, G.; Frantz, C. M.; Osburn, M. R.; Hirst, M.; Williamson, C.; Hanselmann, K.; Caporaso, J.; Sessions, A. L.; Spear, J. R.

    2012-12-01

    The microbial diversity of Stinking Springs, a sulfidic, saline, warm spring northeast of the Great Salt Lake was investigated. The measured pH, temperature, salinity, and sulfide concentration along the flow path ranged from 6.64-7.77, 40-28° C, 2.9-2.2%, and 250 μM to negligible, respectively. Five sites were selected along the flow path and within each site microbial mats were dissected into depth profiles based on the color and texture of the mat layers. Genomic DNA was extracted from each layer, and the 16S rRNA gene was amplified and sequenced on the Roche 454 Titanium platform. Fatty acids were also extracted from the mat layers and analyzed by liquid chromatography and mass spectrometry. The mats at Stinking Springs were classified into roughly two morphologies with respect to their spatial distribution: loose, sometimes floating mats proximal to the spring source; and thicker, well-laminated mats distal to the spring source. Loosely-laminated mats were found in turbulent stream flow environments, whereas well-laminated mats were common in less turbulent sheet flows. Phototrophs, sulfur oxidizers, sulfate reducers, methanogens, other bacteria and archaea were identified by 16S rRNA gene sequences. Diatoms, identified by microscopy and lipid analysis were found to increase in abundance with distance from the source. Methanogens were generally more abundant in deeper mat laminae. Photoheterotrophs were found in all mat layers. Microbial diversity increased significantly with depth at most sites. In addition, two distinct microbial streamers were identified and characterized at the two fast flowing sites. These two streamer varieties were dominated by either cyanobacteria or flavobacteria. Overall, our genomic and lipid analysis suggest that the physical and chemical environment is more predictive of the community composition than mat morphology. Site Map

  17. Endogenous Retroviruses in the Genomics Era.

    PubMed

    Johnson, Welkin E

    2015-11-01

    Endogenous retroviruses comprise millions of discrete genetic loci distributed within the genomes of extant vertebrates. These sequences, which are clearly related to exogenous retroviruses, represent retroviral infections of the deep past, and their abundance suggests that retroviruses were a near-constant presence throughout the evolutionary history of modern vertebrates. Endogenous retroviruses contribute in myriad ways to the evolution of host genomes, as mutagens and as sources of genetic novelty (both coding and regulatory) to be acted upon by the twin engines of random genetic drift and natural selection. Importantly, the richness and complexity of endogenous retrovirus data can be used to understand how viruses spread and adapt on evolutionary timescales by combining population genetics and evolutionary theory with a detailed understanding of retrovirus biology (gleaned from the study of extant retroviruses). In addition to revealing the impact of viruses on organismal evolution, such studies can help us better understand, by looking back in time, how life-history traits, as well as ecological and geological events, influence the movement of viruses within and between populations.

  18. Lipid profiling in sewage sludge.

    PubMed

    Zhu, Fenfen; Wu, Xuemin; Zhao, Luyao; Liu, Xiaohui; Qi, Juanjuan; Wang, Xueying; Wang, Jiawei

    2017-06-01

    High value-added reutilization of sewage sludge from wastewater treatment plants (WWTPs) is essential in sustainable development in WWTPs. However, despite the advantage of high value reutilization, this process must be based on a detailed study of organics in sludge. We used the methods employed in life sciences to determine the profile of lipids (cellular lipids, free fatty acids (FFAs), and wax/gum) in five sludge samples obtained from three typical WWTPs in Beijing; these samples include one sludge sample from a primary sedimentation tank, two activated sludge samples from two Anaerobic-Anoxic-Oxic (A2/O) tanks, and two activated sludge samples from two membrane bioreactor tanks. The percentage of total raw lipids varied from 2.90% to 12.3%. Sludge from the primary sedimentation tank showed the highest concentrations of lipid, FFA, and wax/gum and the second highest concentration of cellular lipids. All activated sludge contained an abundance of cellular lipids (>54%). Cells in sludge can from plants, animals, microbes and so on in wastewater. Approximately 14 species of cellular lipids were identified, including considerable high value-potential ceramide (9567-38774 mg/kg), coenzyme (937-3897 mg/kg), and some phosphatidylcholine (75-548 mg/kg). The presence of those lipid constituents would thus require a wider range of recovery methods for sludge. Both cellular lipids and FFAs contain an abundance of C16-C18 lipids at high saturation level, and they serve as good resources for biodiesel production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

    DOE PAGES

    Vrablik, Tracy L.; Petyuk, Vladislav A.; Larson, Emily M.; ...

    2015-06-27

    Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified Caenorhabditis elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols is rich in fatty acid species obtained from the dietary Escherichia coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type andmore » high-fat daf-2 mutant strains shows a very similar proteome in both strains, except that the most abundant protein in the C. elegans lipid droplet proteome, MDT-28, is relatively less abundant in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans. Finally, we confirmed the localization of one of the newly identified lipid droplet proteins, ACS-4. We found that ACS-4 localizes to the surface of lipid droplets in the C. elegans intestine and skin. This study bolsters C. elegans as a model to study the dynamics and functions of lipid droplets in a multicellular organism.« less

  20. Apolipoprotein gene involved in lipid metabolism

    DOEpatents

    Rubin, Edward [Berkeley, CA; Pennacchio, Len A [Sebastopol, CA

    2007-07-03

    Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

  1. Energy and lipid metabolism during direct and diapause development in a pierid butterfly.

    PubMed

    Lehmann, Philipp; Pruisscher, Peter; Posledovich, Diana; Carlsson, Mikael; Käkelä, Reijo; Tang, Patrik; Nylin, Sören; Wheat, Christopher W; Wiklund, Christer; Gotthard, Karl

    2016-10-01

    Diapause is a fundamental component of the life cycle in the majority of insects living in environments characterized by strong seasonality. The present study addresses poorly understood associations and trade-offs between endogenous diapause duration, thermal sensitivity of development, energetic cost of development and cold tolerance. Diapause intensity, metabolic rate trajectories and lipid profiles of directly developing and diapausing animals were studied using pupae and adults of Pieris napi butterflies from a population in which endogenous diapause has been well studied. Endogenous diapause was terminated after 3 months and termination required chilling. Metabolic and post-diapause development rates increased with diapause duration, while the metabolic cost of post-diapause development decreased, indicating that once diapause is terminated, development proceeds at a low rate even at low temperature. Diapausing pupae had larger lipid stores than the directly developing pupae, and lipids constituted the primary energy source during diapause. However, during diapause, lipid stores did not decrease. Thus, despite lipid catabolism meeting the low energy costs of the diapausing pupae, primary lipid store utilization did not occur until the onset of growth and metamorphosis in spring. In line with this finding, diapausing pupae contained low amounts of mitochondria-derived cardiolipins, which suggests a low capacity for fatty acid β-oxidation. While ontogenic development had a large effect on lipid and fatty acid profiles, only small changes in these were seen during diapause. The data therefore indicate that the diapause lipidomic phenotype is developed early, when pupae are still at high temperature, and retained until post-diapause development. © 2016. Published by The Company of Biologists Ltd.

  2. Immunomodulatory lipids in plants: plant fatty acid amides and the human endocannabinoid system.

    PubMed

    Gertsch, Jürg

    2008-05-01

    Since the discovery that endogenous lipid mediators show similar cannabimimetic effects as phytocannabinoids from CANNABIS SATIVA, our knowledge about the endocannabinoid system has rapidly expanded. Today, endocannabinoid action is known to be involved in various diseases, including inflammation and pain. As a consequence, the G-protein coupled cannabinoid receptors, endocannabinoid transport, as well as endocannabinoid metabolizing enzymes represent targets to block or enhance cannabinoid receptor-mediated signalling for therapeutic intervention. Based on the finding that certain endocannabinoid-like fatty acid N-alkylamides from purple coneflower ( ECHINACEA spp.) potently activate CB2 cannabinoid receptors we have focused our interest on plant fatty acid amides (FAAs) and their overall cannabinomodulatory effects. Certain FAAs are also able to partially inhibit the action of fatty acid amide hydrolase (FAAH), which controls the breakdown of endocannabinoids. Intriguingly, plants lack CB receptors and do not synthesize endocannabinoids, but express FAAH homologues capable of metabolizing plant endogenous N-acylethanolamines (NAEs). While the site of action of these NAEs in plants is unknown, endogenous NAEs and arachidonic acid glycerols in animals interact with distinct physiological lipid receptors, including cannabinoid receptors. There is increasing evidence that also plant FAAs other than NAEs can pharmacologically modulate the action of these endogenous lipid signals. The interference of plant FAAs with the animal endocannabinoid system could thus be a fortunate evolutionary cross point with yet unexplored therapeutic potential.

  3. Emerging Roles for the Lysosome in Lipid Metabolism.

    PubMed

    Thelen, Ashley M; Zoncu, Roberto

    2017-11-01

    Precise regulation of lipid biosynthesis, transport, and storage is key to the homeostasis of cells and organisms. Cells rely on a sophisticated but poorly understood network of vesicular and nonvesicular transport mechanisms to ensure efficient delivery of lipids to target organelles. The lysosome stands at the crossroads of this network due to its ability to process and sort exogenous and endogenous lipids. The lipid-sorting function of the lysosome is intimately connected to its recently discovered role as a metabolic command-and-control center, which relays multiple nutrient cues to the master growth regulator, mechanistic target of rapamycin complex (mTORC)1 kinase. In turn, mTORC1 potently drives anabolic processes, including de novo lipid synthesis, while inhibiting lipid catabolism. Here, we describe the dual role of the lysosome in lipid transport and biogenesis, and we discuss how integration of these two processes may play important roles both in normal physiology and in disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Intravenous Lipid Emulsions in Parenteral Nutrition123

    PubMed Central

    Fell, Gillian L; Nandivada, Prathima; Gura, Kathleen M; Puder, Mark

    2015-01-01

    Fat is an important macronutrient in the human diet. For patients with intestinal failure who are unable to absorb nutrients via the enteral route, intravenous lipid emulsions play a critical role in providing an energy-dense source of calories and supplying the essential fatty acids that cannot be endogenously synthesized. Over the last 50 y, lipid emulsions have been an important component of parenteral nutrition (PN), and over the last 10–15 y many new lipid emulsions have been manufactured with the goal of improving safety and efficacy profiles and achieving physiologically optimal formulations. The purpose of this review is to provide a background on the components of lipid emulsions, their role in PN, and to discuss the lipid emulsions available for intravenous use. Finally, the role of parenteral fat emulsions in the pathogenesis and management of PN-associated liver disease in PN-dependent pediatric patients is reviewed. PMID:26374182

  5. Lens lipids.

    PubMed

    Zelenka, P S

    1984-11-01

    Lens cells can synthesize, degrade, and remodel lipids. Endogenous lipid synthesis, in conjunction with uptake of exogenous cholesterol and certain fatty acids, leads to the formation of a plasma membrane that is especially rich in sphingomyelin, cholesterol, and long-chain saturated fatty acids. As a result of this unusual lipid composition, lens membranes have very low fluidity, which is restricted even further by lipid-protein interactions. The composition and metabolism of membrane lipids may affect the formation of various types of cataracts. Diets rich in vegetable oils offer some protection against the formation of osmotic cataracts and the hereditary cataract of the RCS rat, although the mechanism of this effect is not clear. Vitamin E also protects against the formation of several types of cataract in vivo and in vitro, suggesting that lipid peroxidation may play a role in cataractogenesis. Certain drugs which inhibit lipid synthesis or degradation are cataractogenic, and a deficiency in cataractogenic, and a deficiency in phosphatidylserine is associated with a loss of Na+/K+ ATPase activity in several types of cataract. Human senile cataracts show a marked loss of protein-lipid interactions, although the overall lipid composition is normal. This loss of protein-lipid interactions may be related to oxidative damage to membrane-associated proteins. Interestingly, the decrease in the fluidity of lens membranes with age would counteract the formation of aqueous pores in the membrane, which can result from the oxidative cross-linking of membrane-associated proteins. Certain pathways of lipid metabolism seem to have regulatory functions. Among these are phosphatidylinositol turnover, phosphatidylethanolamine methylation, and arachidonic acid metabolism. All of these pathways function in the lens. Phosphatidylinositol turnover is correlated with the rate of lens epithelial cell division, while phosphatidylethanolamine methylation seems to be related to the

  6. UVA-induced reset of hydroxyl radical ultradian rhythm improves temporal lipid production in Chlorella vulgaris.

    PubMed

    Balan, Ranjini; Suraishkumar, G K

    2014-01-01

    We report for the first time that the endogenous, pseudo-steady-state, specific intracellular levels of the hydroxyl radical (si-OH) oscillate in an ultradian fashion (model system: the microalga, Chlorella vulgaris), and also characterize the various rhythm parameters. The ultradian rhythm in the endogenous levels of the si-OH occurred with an approximately 6 h period in the daily cycle of light and darkness. Further, we expected that the rhythm reset to a shorter period could rapidly switch the cellular redox states that could favor lipid accumulation. We reset the endogenous rhythm through entrainment with UVA radiation, and generated two new ultradian rhythms with periods of approximately 2.97 h and 3.8 h in the light phase and dark phase, respectively. The reset increased the window of maximum lipid accumulation from 6 h to 12 h concomitant with the onset of the ultradian rhythms. Further, the saturated fatty acid content increased approximately to 80% of total lipid content, corresponding to the peak maxima of the hydroxyl radical levels in the reset rhythm. © 2014 American Institute of Chemical Engineers.

  7. Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor

    PubMed Central

    Perretti, Mauro; Chiang, Nan; La, Mylinh; Fierro, Iolanda M.; Marullo, Stefano; Getting, Stephen J; Solito, Egle; Serhan, Charles N.

    2009-01-01

    Aspirin (ASA) and dexamethasone (DEX) are widely used anti-inflammatory agents yet their mechanism(s) for blocking polymorphonuclear neutrophil (PMN) accumulation at sites of inflammation remains unclear. Here, we report that inhibition of PMN infiltration by ASA and DEX is a property shared by aspirin-triggered lipoxins (ATL) and the glucocorticoid-induced annexin 1 (ANXA1)-derived peptides that are both generated in vivo and act at the lipoxin A4 receptor (ALXR/FPRL1) to halt PMN diapedesis. These structurally diverse ligands specifically interact directly with recombinant human ALXR demonstrated by specific radioligand binding and function as well as immunoprecipitation of PMN receptors. In addition, the combination of both ATL and ANXA1-derived peptides limited PMN infiltration and reduced production of inflammatory mediators (that is, prostaglandins and chemokines) in vivo. Together, these results indicate functional redundancies in endogenous lipid and peptide anti-inflammatory circuits that are spatially and temporally separate, where both ATL and specific ANXA1-derived peptides act in concert at ALXR to downregulate PMN recruitment to inflammatory loci. PMID:12368905

  8. UPTAKE, DISTRIBUTION, AND BIOCONVERSION OF FLUORESCENT LIPID ANALOGS IN THE OYSTER PROTOZOAN PARASITE, PERKINSUS MARINUS

    EPA Science Inventory

    It has been established that host lipids play a unique role for long term survival and life cycle completion in endogenous parasites. Parasites exploit fatty acids and lipids from the host, not only for membrane synthesis, but also for modification of their surface integrity to a...

  9. Unique effect of 4-hydroxyestradiol and its methylation metabolites on lipid and cholesterol profiles in ovariectomized female rats.

    PubMed

    Wang, Pan; Zhu, Bao-Ting

    2017-04-05

    Animal studies have shown that endogenous estrogens such as 17β-estradiol (E 2 ) can modulate lipid profiles in vivo, and this effect is generally thought to be mediated by the estrogen receptors (ERs). The present study sought to test a hypothesis that some of the endogenous estrogen metabolites that have very weak estrogenic activity may exert some of their modulating effects on lipid metabolism in an ER-independent manner. Using ovariectomized female rats as an in vivo model, we found that 4-hydroxyestradiol (4-OH-E 2 ) has a markedly stronger effect in reducing the adipocyte size and serum cholesterol level in rats compared to E 2 , despite the weaker estrogenic activity of 4-OH-E 2 . Moreover, when E 2 or 4-OH-E 2 is used in combination with ICI-182,780 (an ER antagonist), some of their lipid-modulating effects are not blocked by this antiestrogen. Interestingly, two of the O-methylation metabolites of 4-OH-E 2 , namely, 4-methoxyestradiol and 4-methoxyestrone, which have much weaker estrogenic activity, were also found to have similar lipid-modulating effects compared to 4-OH-E 2 . Mechanistically, up-regulation of the expression of leptin, cytochrome P450 7A1 and LXRα genes is observed in the liver of animals treated with E 2 or 4-OH-E 2 , and the up-regulation is essentially not inhibited by co-treatment with ICI-182,780. These results demonstrate that some of the endogenous E 2 metabolites are functionally important modulators of lipid metabolic profiles in vivo. In addition, our findings indicate that an ER-independent pathway likely mediates some of the lipid-modulating effects of endogenous estrogens and their metabolic derivatives. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Quantifying lipid changes in various membrane compartments using lipid binding protein domains.

    PubMed

    Várnai, Péter; Gulyás, Gergő; Tóth, Dániel J; Sohn, Mira; Sengupta, Nivedita; Balla, Tamas

    2017-06-01

    One of the largest challenges in cell biology is to map the lipid composition of the membranes of various organelles and define the exact location of processes that control the synthesis and distribution of lipids between cellular compartments. The critical role of phosphoinositides, low-abundant lipids with rapid metabolism and exceptional regulatory importance in the control of almost all aspects of cellular functions created the need for tools to visualize their localizations and dynamics at the single cell level. However, there is also an increasing need for methods to determine the cellular distribution of other lipids regulatory or structural, such as diacylglycerol, phosphatidic acid, or other phospholipids and cholesterol. This review will summarize recent advances in this research field focusing on the means by which changes can be described in more quantitative terms. Published by Elsevier Ltd.

  11. Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in Asian Indians.

    PubMed

    Kim, Catherine; Kong, Shengchun; Krauss, Ronald M; Stanczyk, Frank Z; Reddy, Srinivasa T; Needham, Belinda L; Kanaya, Alka M

    2015-12-01

    Estradiol, testosterone (T), and sex hormone binding globulin (SHBG) levels are associated with lipid subfractions in men and women. Our objective was to determine if associations are independent from adipose tissue area among Asian Indians. We used data from 42 women and 57 Asian Indian men who did not use exogenous steroids or lipid-lowering medications. Lipoprotein subfractions including low-density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL), and intermediate density lipoprotein (IDL) were assessed by ion mobility spectrometry. Intra-abdominal adiposity was assessed by computed tomography. Multivariable regression models estimated the association between sex hormones with lipoprotein subfractions before and after adjustment for adiposity. Among women, lower logSHBG levels were associated with smaller logLDL particle size and higher logtriglycerides, logVLDL, and logIDL, although these associations were attenuated with adjustment for visceral adiposity in particular. Among women, lower logSHBG levels was significantly associated with lower logmedium LDL and logsmall LDL concentrations even after consideration of visceral and hepatic adiposity and insulin resistance as represented by the homeostasis model assessment of insulin resistance (HOMA-IR). Among men, lower logSHBG was also associated with smaller logLDL peak diameter size and higher logtriglycerides and logVLDL, even after adjustment for HOMA-IR and adiposity. Relationships between sex steroids and lipid subfractions were not significant among women. Among men, higher total testosterone was associated with higher logHDL and logLDL particle size, and lower logtriglycerides and logVLDL, but these associations were partially attenuated with adjustment for adiposity and HOMA-IR. Among Asian Indians, SHBG is associated with more favorable lipid subfraction concentrations, independent of hepatic and visceral fat.

  12. Abundant Type III Lipid Transfer Proteins in Arabidopsis Tapetum Are Secreted to the Locule and Become a Constituent of the Pollen Exine1[W][OPEN

    PubMed Central

    Huang, Ming-Der; Chen, Tung-Ling L.; Huang, Anthony H.C.

    2013-01-01

    Lipid transfer proteins (LTPs) are small secretory proteins in plants with defined lipid-binding structures for possible lipid exocytosis. Special groups of LTPs unique to the anther tapetum are abundant, but their functions are unclear. We studied a special group of LTPs, type III LTPs, in Arabidopsis (Arabidopsis thaliana). Their transcripts were restricted to the anther tapetum, with levels peaking at the developmental stage of maximal pollen-wall exine synthesis. We constructed an LTP-Green Fluorescent Protein (LTP-GFP) plasmid, transformed it into wild-type plants, and monitored LTP-GFP in developing anthers with confocal laser scanning microscopy. LTP-GFP appeared in the tapetum and was secreted via the endoplasmic reticulum-trans-Golgi network machinery into the locule. It then moved to the microspore surface and remained as a component of exine. Immuno-transmission electron microscopy of native LTP in anthers confirmed the LTP-GFP observations. The in vivo association of LTP-GFP and exine in anthers was not observed with non-type III or structurally modified type III LTPs or in transformed exine-defective mutant plants. RNA interference knockdown of individual type III LTPs produced no observable mutant phenotypes. RNA interference knockdown of two type III LTPs produced microscopy-observable morphologic changes in the intine underneath the exine (presumably as a consequence of changes in the exine not observed by transmission electron microscopy) and pollen susceptible to dehydration damage. Overall, we reveal a novel transfer pathway of LTPs in which LTPs bound or nonbound to exine precursors are secreted from the tapetum to become microspore exine constituents; this pathway explains the need for plentiful LTPs to incorporate into the abundant exine. PMID:24096413

  13. Differential abundance analysis of mesocarp protein from high- and low-yielding oil palms associates non-oil biosynthetic enzymes to lipid biosynthesis.

    PubMed

    Ooi, Tony Eng Keong; Yeap, Wan Chin; Daim, Leona Daniela Jeffery; Ng, Boon Zean; Lee, Fong Chin; Othman, Ainul Masni; Appleton, David Ross; Chew, Fook Tim; Kulaveerasingam, Harikrishna

    2015-01-01

    The oil palm Elaeis guineensis Jacq. which produces the highest yield per unit land area of the oil crops is the most important commercial oil crop in South East Asia. The fleshy mesocarp of oil palm fruit, where oil is mostly derived from, contains up to 90 % dry weight of oil (one of the most concentrated in plant tissues). Hence, there is attention given to gain insights into the processes of oil deposition in this oil rich tissue. For that purpose, two-dimensional differential gel electrophoresis (DIGE) coupled with western assays, were used here to analyze differential protein levels in genetically-related high-and low-yielding oil palm mesocarps. From the DIGE comparative analysis in combination with western analysis, 41 unique differentially accumulated proteins were discovered. Functional categorization of these proteins placed them in the metabolisms of lipid, carbohydrate, amino acids, energy, structural proteins, as well as in other functions. In particular, higher abundance of fructose-1,6-biphosphate aldolase combined with reduced level of triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase may be indicative of important flux balance changes in glycolysis, while amino acid metabolism also appeared to be closely linked with oil yield. Forty-one proteins in several important biological pathways were identified as exhibiting differential in abundance at critical oil production stages. These confirm that oil yield is a complex trait involving the regulation of genes in multiple biological pathways. The results also provide insights into key control points of lipid biosynthesis in oil palm and can assist in the development of genetic markers for use in oil palm breeding programmes.

  14. The bovine seminal plasma protein PDC-109 extracts phosphorylcholine-containing lipids from the outer membrane leaflet.

    PubMed

    Tannert, Astrid; Kurz, Anke; Erlemann, Karl-Rudolf; Müller, Karin; Herrmann, Andreas; Schiller, Jürgen; Töpfer-Petersen, Edda; Manjunath, Puttaswamy; Müller, Peter

    2007-04-01

    The bovine seminal plasma protein PDC-109 modulates the maturation of bull sperm cells by removing lipids, mainly phosphatidylcholine and cholesterol, from their cellular membrane. Here, we have characterized the process of extraction of endogenous phospholipids and of their respective analogues. By measuring the PDC-109-mediated release of fluorescent phospholipid analogues from lipid vesicles and from biological membranes (human erythrocytes, bovine epididymal sperm cells), we showed that PDC-109 extracts phospholipids with a phosphorylcholine headgroup mainly from the outer leaflet of these membranes. The ability of PDC-109 to extract endogenous phospholipids from epididymal sperm cells was followed by mass spectrometry, which allowed us to characterize the fatty acid pattern of the released lipids. From these cells, PDC-109 extracted phosphatidylcholine and sphingomyelin that contained an enrichment of mono- and di-unsaturated fatty acids as well as short-chain and lyso-phosphatidylcholine species. Based on the results, a model explaining the phospholipid specificity of PDC-109-mediated lipid release is presented.

  15. Saposins modulate human invariant Natural Killer T cells self-reactivity and facilitate lipid exchange with CD1d molecules during antigen presentation

    PubMed Central

    Salio, Mariolina; Ghadbane, Hemza; Dushek, Omer; Shepherd, Dawn; Cypen, Jeremy; Gileadi, Uzi; Aichinger, Michael C.; Napolitani, Giorgio; Qi, Xiaoyang; van der Merwe, P. Anton; Wojno, Justyna; Veerapen, Natacha; Cox, Liam R.; Besra, Gurdyal S.; Yuan, Weiming; Cresswell, Peter; Cerundolo, Vincenzo

    2013-01-01

    Lipid transfer proteins, such as molecules of the saposin family, facilitate extraction of lipids from biological membranes for their loading onto CD1d molecules. Although it has been shown that prosaposin-deficient mice fail to positively select invariant natural killer T (iNKT) cells, it remains unclear whether saposins can facilitate loading of endogenous iNKT cell agonists in the periphery during inflammatory responses. In addition, it is unclear whether saposins, in addition to loading, also promote dissociation of lipids bound to CD1d molecules. To address these questions, we used a combination of cellular assays and demonstrated that saposins influence CD1d-restricted presentation to human iNKT cells not only of exogenous lipids but also of endogenous ligands, such as the self-glycosphingolipid β-glucopyranosylceramide, up-regulated by antigen-presenting cells following bacterial infection. Furthermore, we demonstrated that in human myeloid cells CD1d-loading of endogenous lipids after bacterial infection, but not at steady state, requires trafficking of CD1d molecules through an endo-lysosomal compartment. Finally, using BIAcore assays we demonstrated that lipid-loaded saposin B increases the off-rate of lipids bound to CD1d molecules, providing important insights into the mechanisms by which it acts as a “lipid editor,” capable of fine-tuning loading and unloading of CD1d molecules. These results have important implications in understanding how to optimize lipid-loading onto antigen-presenting cells, to better harness iNKT cells central role at the interface between innate and adaptive immunity. PMID:24248359

  16. Linking isoprenoidal GDGT membrane lipid distributions with gene abundances of ammonia-oxidizing Thaumarchaeota and uncultured crenarchaeotal groups in the water column of a tropical lake (Lake Challa, East Africa).

    PubMed

    Buckles, Laura K; Villanueva, Laura; Weijers, Johan W H; Verschuren, Dirk; Damsté, Jaap S Sinninghe

    2013-09-01

    Stratified lakes are important reservoirs of microbial diversity and provide habitats for niche differentiation of Archaea. In this study, we used a lipid biomarker/DNA-based approach to reveal the diversity and abundance of Archaea in the water column of Lake Challa (East Africa). Concentrations of intact polar lipid (IPL) crenarchaeol, a specific biomarker of Thaumarchaeota, were enhanced (1 ng l(-1) ) at the oxycline/nitrocline. The predominance of the more labile IPL hexose-phosphohexose crenarchaeol indicated the presence of an actively living community of Thaumarchaeota. Archaeal 16S rRNA clone libraries revealed the presence of thaumarchaeotal groups 1.1a and 1.1b at and above the oxycline. In the anoxic deep water, amoA gene abundance was an order of magnitude lower than at the oxycline and high abundance (∼90 ng l(-1) ) of an IPL with the acyclic glycerol dialkyl glycerol tetraether (GDGT-0) was evident. The predominance of archaeal 16S rRNA sequences affiliated to the uncultured crenarchaeota groups 1.2 and miscellaneous crenarchaeotic group (MCG) points to an origin of GDGT-0 from uncultured crenarchaeota. This study demonstrates the importance of thermal stratification and nutrient availability in the distribution of archaeal groups in lakes, which is relevant to constrain and validate temperature proxies based on archaeal GDGTs (i.e. TEX86 ). © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

  17. Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans.

    PubMed

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Dávila-Román, Victor G; Ostlund, Richard E

    2017-12-01

    Epidemiological studies strongly suggest that lipid factors independent of low-density lipoprotein cholesterol contribute significantly to cardiovascular disease risk. Because circulating lipoproteins comprise only a small fraction of total body cholesterol, the mobilization and excretion of cholesterol from plasma and tissue pools may be an important determinant of cardiovascular disease risk. Our hypothesis is that fecal excretion of endogenous cholesterol is protective against atherosclerosis. Cholesterol metabolism and carotid intima-media thickness were quantitated in 86 nondiabetic adults. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 solubilized in a lipid emulsion and dietary cholesterol by cholesterol-d 5 and the nonabsorbable stool marker sitostanol-d 4 . Plasma and stool samples were collected while subjects consumed a cholesterol- and phytosterol-controlled metabolic kitchen diet and were analyzed by mass spectrometry. Carotid intima-media thickness was negatively correlated with fecal excretion of endogenous cholesterol ( r =-0.426; P <0.0001), total cholesterol ( r =-0.472; P ≤0.0001), and daily percent excretion of cholesterol from the rapidly mixing cholesterol pool ( r =-0.343; P =0.0012) and was positively correlated with percent cholesterol absorption ( r =+0.279; P =0.0092). In a linear regression model controlling for age, sex, systolic blood pressure, hemoglobin A1c, low-density lipoprotein, high-density lipoprotein cholesterol, and statin drug use, fecal excretion of endogenous cholesterol remained significant ( P =0.0008). Excretion of endogenous cholesterol is strongly, independently, and negatively associated with carotid intima-media thickness. The reverse cholesterol transport pathway comprising the intestine and the rapidly mixing plasma, and tissue cholesterol pool could be an unrecognized determinant of cardiovascular disease risk not reflected in circulating lipoproteins. Further work is needed to relate

  18. Emerging targets in lipid-based therapy☆

    PubMed Central

    Tucker, Stephanie C.; Honn, Kenneth V.

    2013-01-01

    The use of prostaglandins and NSAIDS in the clinic has proven that lipid mediators and their associated pathways make attractive therapeutic targets. When contemplating therapies involving lipid pathways, several basic agents come to mind. There are the enzymes and accessory proteins that lead to the metabolism of lipid substrates, provided through diet or through actions of lipases, the subsequent lipid products, and finally the lipid sensors or receptors. There is abundant evidence that molecules along this lipid continuum can serve as prognostic and diagnostic indicators and are in fact viable therapeutic targets. Furthermore, lipids themselves can be used as therapeutics. Despite this, the vernacular dialog pertaining to “biomarkers” does not routinely include mention of lipids, though this is rapidly changing. Collectively these agents are becoming more appreciated for their respective roles in diverse disease processes from cancer to preterm labor and are receiving their due appreciation after decades of ground work in the lipid field. By relating examples of disease processes that result from dysfunction along the lipid continuum, as well as examples of lipid therapies and emerging technologies, this review is meant to inspire further reading and discovery. PMID:23261527

  19. Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions.

    PubMed

    Fischer, Carol L; Walters, Katherine S; Drake, David R; Dawson, Deborah V; Blanchette, Derek R; Brogden, Kim A; Wertz, Philip W

    2013-09-01

    Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria; however, little is known about their spectrum of antimicrobial activity or mechanisms of action against oral bacteria. In this study, we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Minimal inhibitory concentrations, minimal bactericidal concentrations, and kill kinetics revealed variable, but potent, activity of oral mucosal and salivary lipids against P. gingivalis, indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria, although specific components of bacterial membranes are also likely important. Electron micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma membrane. This information, coupled with the association of treatment lipids with P. gingivalis lipids revealed via thin layer chromatography, suggests that the plasma membrane is a likely target of lipid antibacterial activity. Utilizing a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique P. gingivalis stress response, including proteins important in fatty acid biosynthesis, metabolism and energy production, protein processing, cell adhesion and virulence. Prophylactic or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

  20. Mitochondrial lipids in Bufo arenarum full-grown oocytes.

    PubMed

    Gili, Valeria; Alonso, Telma S

    2004-05-01

    Both the content and composition of polar and neutral lipids from the mitochondrial fraction of ovarian full-grown Bufo arenarum oocytes were analysed in the present study. Triacylglycerols (TAG) represent 33% of the total lipids, followed by phosphatidylcholine (PC), free fatty acids (FFA) and phosphatidylethanolamine (PE). Diphosphatidylglycerol (DPG) or cardiolipin, a specific component of the inner mitochondrial membrane, represents about 4% of the total lipid content. Palmitic (16:0) and arachidonic (20:4n6) acids are the most abundant fatty acids in PC and PE, respectively. DPG is enriched in fatty acids with carbon chain lengths of 18, the principal component being linoleic acid. In phosphatidylinositol (PI), 20:4n6 and stearic acid (18:0) represent about 72 mol% of the total acyl group level. The main fatty acids in TAG are linoleic (18:2), oleic (18:1), and palmitic acids. The fatty acid composition of FFA and diacylglycerols (DAG) is similar, 16:0 being the most abundant acyl group. PE is the most unsaturated lipid and sphingomyelin (SM) has the lowest unsaturation index.

  1. Mice exposed in situ to urban air pollution exhibit pulmonary alterations in gene expression in the lipid droplet synthesis pathways.

    PubMed

    Rowan-Carroll, Andrea; Halappanavar, Sabina; Williams, Andrew; Somers, Christophers M; Yauk, Carole L

    2013-05-01

    It is clear that particulate air pollution poses a serious risk to human health; however, the underlying mechanisms are not completely understood. We investigated pulmonary transcriptional responses in mice following in-situ exposure to ambient air in a heavily industrialized urban environment. Mature C57BL/CBA male mice were caged in sheds near two working steel mills and a major highway in Hamilton, Ontario, Canada in the spring/summer of 2004. Control mice were housed in the same environment, but received only high-efficiency particle filtered air (HEPA). Whole lung tissues were collected from mice exposed for 3, 10, or for 10 weeks followed by 6 weeks recovery in the laboratory (16 weeks). DNA microarrays were used to profile changes in pulmonary gene expression. Transcriptional profiling revealed changes in the expression of genes implicated in the lipid droplet synthesis (Plin I, Dgat2, Lpl, S3-12, and Agpat2), and antioxidant defense (Ucp1) pathways in mice breathing unfiltered air. We postulate that exposure to urban air, containing an abundance of particulate matter adsorbed with polycyclic aromatic hydrocarbons, triggers lipid droplet (holding depots for lipids and malformed/excess proteins tagged for degradation) synthesis in the lungs, which may act to sequester particulates. Increased lipid droplet synthesis could lead to endogenous/stressor-induced production of reactive oxygen species and activation of antioxidant mechanisms. Further investigation into the stimulation of lipid droplet synthesis in the lung in response to air pollution and the resulting health implications is warranted. Copyright © 2013 Wiley Periodicals, Inc.

  2. Lipid mediators and their metabolism in the nucleous: implications for Alzheimer's disease.

    PubMed

    Farooqui, Akhlaq A

    2012-01-01

    Lipid mediators are important endogenous regulators derived from enzymatic degradation of glycerophospholipids, sphingolipids, and cholesterol by phospholipases, sphingomyelinases, and cytochrome P450 hydroxylases, respectively. In neural cells, lipid mediators are associated with proliferation, differentiation, oxidative stress, inflammation, and apoptosis. A major group of lipid mediators, which originates from the enzymatic oxidation of arachidonic acid, is called eicosanoids (i.e., prostaglandins, leukotrienes, thromboxanes, and lipoxins). The corresponding lipid mediators of docosahexaenoic acid metabolism are named as docosanoids. They include resolvins, protectins (neuroprotectins), and maresins. Docosanoids produce antioxidant, anti-inflammatory, and antiapoptotic effects in brain tissue. Other glycerophospholipid-derived lipid mediators are platelet activating factor, lysophosphatidic acid, and endocannabinoids. Degradation of sphingolipids also results in the generation of sphingolipid-derived lipid mediators, such as ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. These mediators are involved in differentiation, growth, cell migration, and apoptosis. Similarly, cholesterol-derived lipid mediators, hydroxycholesterol, produce apoptosis. Abnormal metabolism of lipid mediators may be closely associated with pathogenesis of Alzheimer's disease.

  3. Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lasrich, Dorothee; Bartelt, Alexander; Grewal, Thomas, E-mail: thomas.grewal@sydney.edu.au

    Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tertmore » adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not

  4. Nuclear Receptors, Mitochondria, and Lipid Metabolism

    PubMed Central

    Alaynick, William A.

    2009-01-01

    Lipid metabolism is a continuum from emulsification and uptake of lipids in the intestine to cellular uptake and transport to compartments such as mitochondria. Whether fats are shuttled into lipid droplets in adipose tissue or oxidized in mitochondria and peroxisomes depends on metabolic substrate availability, energy balance and endocrine signaling of the organism. Several members of the nuclear hormone receptor superfamily are lipid-sensing factors that affect all aspects of lipid metabolism. The physiologic actions of glandular hormones (e.g. thyroid, mineralocorticoid and glucocorticoid), vitamins (e.g. vitamins A and D) and reproductive hormones (e.g. progesterone, estrogen and testosterone) and their cognate receptors are well established. The peroxisome proliferator activated receptors (PPARs) and Liver X receptors (LXRs), acting in concert with PPARγ Coactivator 1α (PGC-1α), have been shown to regulate insulin sensitivity and lipid handling. These receptors are the focus of intense pharmacologic studies to expand the armamentarium of small molecule ligands to treat diabetes and the metabolic syndrome (hypertension, insulin resistance, hyperglycemia, dyslipidemia, and obesity). Recently, additional partners of PGC-1α have moved to the forefront of metabolic research, the Estrogen-related Receptors (ERRs). Although no endogenous ligands for these receptors have been identified, phenotypic analyses of knockout mouse models demonstrate an important role for these molecules in substrate sensing and handling as well as mitochondrial function. PMID:18375192

  5. Archaeal and bacterial H-GDGTs are abundant in peat and their relative abundance is positively correlated with temperature

    NASA Astrophysics Data System (ADS)

    Naafs, B. D. A.; McCormick, D.; Inglis, G. N.; Pancost, R. D.; T-GRES Peat Database Collaborators

    2018-04-01

    Glycerol monoalkyl glycerol tetraether lipids (GMGTs; also called 'H-GDGTs') differ from the more commonly studied glycerol dialkyl glycerol tetraether (GDGTs) in that they have an additional covalent bond that links the two alkyl chains. Six different archaeal isoprenoidal H-GDGTs (H-isoGDGTs) and one branched H-GDGT (H-brGDGT), presumably produced by bacteria, have previously been found. However, the function of H-GDGTs in both domains of life is unknown. It is thought that the formation of this additional covalent bond results in enhanced membrane stability, accounting for the high abundance of H-GDGTs in extreme environments such as geothermal settings, but so far there has been little evidence to support this hypothesis. Here we report the distribution of H-GDGTs in a global peat database (n = 471) with a broad range in mean annual air temperature (MAAT) and pH. This is the first finding of H-GDGTs in soils (specifically, peat), highlighting that H-GDGTs are widespread in mesophilic settings. In addition, we report the presence of two new H-brGDGTs with one (H-1034) and two (H-1048) additional methyl groups, respectively. Our results suggest that the relative abundance of both bacterial and archaeal H-GDGTs compared to regular GDGTs is related to temperature with the highest relative abundance of H-GDGTs in tropical peats. Although other factors besides temperature likely also play a role, these results do support the hypothesis that H-GDGTs are an adaptation to temperature to maintain membrane stability. The observation that both bacterial and archaeal membrane lipids respond to temperature indicates the same adaption across the lipid divide between these two domains of life, suggesting parallel or convergent evolution (potentially facilitated by lateral gene transfer).

  6. Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vrablik, Tracy L.; Petyuk, Vladislav A.; Larson, Emily M.

    2015-06-27

    Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified C. elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols was rich in fatty acid species obtained from the dietary E. coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type andmore » high-fat daf-2 mutant strains shows a relative decrease of MDT-28 abundance in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans.« less

  7. Lipid Droplet-Associated Proteins (LDAPs) Are Required for the Dynamic Regulation of Neutral Lipid Compartmentation in Plant Cells1

    PubMed Central

    Park, Sunjung; Wu, Peng

    2016-01-01

    Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols in seeds, their biogenesis and function in nonseed tissues are poorly understood. Recently, we identified a class of plant-specific, lipid droplet-associated proteins (LDAPs) that are abundant components of LDs in nonseed cell types. Here, we characterized the three LDAPs in Arabidopsis (Arabidopsis thaliana) to gain insight to their targeting, assembly, and influence on LD function and dynamics. While all three LDAPs targeted specifically to the LD surface, truncation analysis of LDAP3 revealed that essentially the entire protein was required for LD localization. The association of LDAP3 with LDs was detergent sensitive, but the protein bound with similar affinity to synthetic liposomes of various phospholipid compositions, suggesting that other factors contributed to targeting specificity. Investigation of LD dynamics in leaves revealed that LD abundance was modulated during the diurnal cycle, and characterization of LDAP misexpression mutants indicated that all three LDAPs were important for this process. LD abundance was increased significantly during abiotic stress, and characterization of mutant lines revealed that LDAP1 and LDAP3 were required for the proper induction of LDs during heat and cold temperature stress, respectively. Furthermore, LDAP1 was required for proper neutral lipid compartmentalization and triacylglycerol degradation during postgerminative growth. Taken together, these studies reveal that LDAPs are required for the maintenance and regulation of LDs in plant cells and perform nonredundant functions in various physiological contexts, including stress response and postgerminative growth. PMID:26896396

  8. Production of n-alkyl lipids in living plants and implications for the geologic past

    NASA Astrophysics Data System (ADS)

    Diefendorf, Aaron F.; Freeman, Katherine H.; Wing, Scott L.; Graham, Heather V.

    2011-12-01

    Leaf waxes (i.e., n-alkyl lipids or n-alkanes) are land-plant biomarkers widely used to reconstruct changes in climate and the carbon isotopic composition of the atmosphere. There is little information available, however, on how the production of leaf waxes by different kinds of plants might influence the abundance and isotopic composition of n-alkanes in sedimentary archives. This lack of information increases uncertainty in interpreting n-alkyl lipid abundance and δ 13C signals in ancient settings. We provide here n-alkyl abundance distributions and carbon isotope fractionation data for deciduous and evergreen angiosperm and gymnosperm leaves from 46 tree species, representing 24 families. n-Alkane abundances are significantly higher in angiosperms than gymnosperms; many of the gymnosperm species investigated did not produce any n-alkanes. On average, deciduous angiosperms produce 200 times more n-alkanes than deciduous gymnosperms. Although differences between angiosperms and gymnosperms dominate the variance in n-alkane abundance, leaf life-span is also important, with higher n-alkane abundances in longer-lived leaves. n-Alkanol abundances covary with n-alkanes, but n-alkanoic acids have similar abundances across all plant groups. Isotopic fractionation between leaf tissue and individual alkanes ( ɛlipid) varies by as much as 10‰ among different chain lengths. Overall, ɛlipid values are slightly lower (-4.5‰) for angiosperm than for gymnosperm (-2.5‰) n-alkanes. Angiosperms commonly express slightly higher Δleaf (photosynthetic discrimination) relative to gymnosperms under similar growth conditions. As a result, angiosperm n-alkanes are expected to be generally 3-5‰ more depleted in 13C relative to gymnosperm alkanes for the same locality. Differences in n-alkane production indicate the biomarker record will largely (but not exclusively) reflect angiosperms if both groups were present, and also that evergreen plants will likely be overrepresented

  9. Are endogenous feline leukemia viruses really endogenous?

    PubMed

    Stewart, H; Jarrett, O; Hosie, M J; Willett, B J

    2011-10-15

    Full length endogenous feline leukemia virus (FeLV) proviruses exist within the genomes of many breeds of domestic cat raising the possibility that they may also exist in a transmissible exogenous form. Such viruses would share receptor usage with the recombinant FeLV-B subgroup, a viral subgroup that arises in vivo by recombination between exogenous subgroup A virus (FeLV-A) and endogenous FeLV. Accordingly, all isolates of FeLV-B made to date have contained a "helper" FeLV-A, consistent with their recombinatorial origin. In order to assess whether endogenous viruses are transmitted between cats, we examined primary isolates of FeLV for which the viral subgroup had been determined for the presence of a subgroup B virus that lacked an FeLV-A. Here we describe the identification of two primary field isolates of FeLV (2518 and 4314) that appeared to contain subgroup B virus only by classical interference assays, raising the possibility of between-host transmission of endogenous FeLV. Sequencing of the env gene and U3 region of the 3' long terminal repeat (LTR) confirmed that both viral genomes contained endogenous viral env genes. However the viral 3' LTRs appeared exogenous in origin with a putative 3' recombination breakpoint residing at the 3' end of the env gene. Further, the FeLV-2518 virions also co-packaged a truncated FeLV-A genome containing a defective env gene, termed FeLV-2518(A) whilst no helper subgroup A viral genome was detected in virions of FeLV-4314. The acquisition of an exogenous LTR by the endogenous FeLV in 4314 may have allowed a recombinant FeLV variant to outgrow an exogenous FeLV-A virus that was presumably present during first infection. Given time, a similar evolution may also occur within the 2518 isolate. The data suggest that endogenous FeLVs may be mobilised by acquisition of exogenous LTRs yielding novel viruses that type biologically as FeLV-B. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Endogenous antipyretics.

    PubMed

    Roth, Joachim

    2006-09-01

    The febrile increase of body temperature is regarded as a component of the complex host response to infection or inflammation that accompanies the activation of the immune system. Late phases of fever appear mediated by pro-inflammatory cytokines called endogenous pyrogens. The rise of body temperature is beneficial because it accelerates several components of the activated immune system. To prevent an excessive and dangerous rise of body temperature the febrile response is controlled, limited in strength and duration, and sometimes even prevented by the actions of endogenous antipyretic substances liberated systemically or within the brain during fever. In most cases the antipyretic effects are achieved by an inhibitory influence on the formation or action of endogenous pyrogens, or by effects on neuronal thermoregulatory circuits that are activated during fever. Endogenous antipyretic substances include steroid hormones, neuropeptides, cytokines and other molecules. It is the purpose of this review to consider the current state in the research on endogenous antipyretic systems.

  11. Ordered Nanostructured Amphiphile Self-Assembly Materials from Endogenous Nonionic Unsaturated Monoethanolamide Lipids in Water

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sagnella, Sharon M.; Conn, Charlotte E.; Krodkiewska, Irena

    2010-08-23

    The self-assembly, solid state and lyotropic liquid crystalline phase behavior of a series of endogenous n-acylethanolamides (NAEs) with differing degrees of unsaturation, viz., oleoyl monoethanolamide, linoleoyl monoethanolamide, and linolenoyl monoethanolamide, have been examined. The studied molecules are known to possess inherent biological function. Both the monoethanolamide headgroup and the unsaturated hydrophobe are found to be important in dictating the self-assembly behavior of these molecules. In addition, all three molecules form lyotropic liquid crystalline phases in water, including the inverse bicontinuous cubic diamond (Q{sub II}{sup D}) and gyroid (Q{sub II}{sup G}) phases. The ability of the NAE's to form inverse cubicmore » phases and to be dispersed into ordered nanostructured colloidal particles, cubosomes, in excess water, combined with their endogenous nature and natural medicinal properties, makes this new class of soft mesoporous amphiphile self-assembly materials suitable candidates for investigation in a variety of advanced multifunctional applications, including encapsulation and controlled release of therapeutic agents and incorporation of medical imaging agents.« less

  12. Molecular mechanism of metal-independent decomposition of lipid hydroperoxide 13-HPODE by halogenated quinoid carcinogens.

    PubMed

    Qin, Hao; Huang, Chun-Hua; Mao, Li; Xia, Hai-Ying; Kalyanaraman, Balaraman; Shao, Jie; Shan, Guo-Qiang; Zhu, Ben-Zhan

    2013-10-01

    Halogenated quinones are a class of carcinogenic intermediates and newly identified chlorination disinfection by-products in drinking water. 13-Hydroperoxy-9,11-octadecadienoic acid (13-HPODE) is the most extensively studied endogenous lipid hydroperoxide. Although it is well known that the decomposition of 13-HPODE can be catalyzed by transition metal ions, it is not clear whether halogenated quinones could enhance its decomposition independent of metal ions and, if so, what the unique characteristics and similarities are. Here we show that 2,5-dichloro-1,4-benzoquinone (DCBQ) could markedly enhance the decomposition of 13-HPODE and formation of reactive lipid alkyl radicals such as pentyl and 7-carboxyheptyl radicals, and the genotoxic 4-hydroxy-2-nonenal (HNE), through the complementary application of ESR spin trapping, HPLC-MS, and GC-MS methods. Interestingly, two chloroquinone-lipid alkoxyl conjugates were also detected and identified from the reaction between DCBQ and 13-HPODE. Analogous results were observed with other halogenated quinones. This represents the first report that halogenated quinoid carcinogens can enhance the decomposition of the endogenous lipid hydroperoxide 13-HPODE and formation of reactive lipid alkyl radicals and genotoxic HNE via a novel metal-independent nucleophilic substitution coupled with homolytic decomposition mechanism, which may partly explain their potential genotoxicity and carcinogenicity. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation

    PubMed Central

    Haldar, Saptarsi M.; Jeyaraj, Darwin; Anand, Priti; Zhu, Han; Lu, Yuan; Prosdocimo, Domenick A.; Eapen, Betty; Kawanami, Daiji; Okutsu, Mitsuharu; Brotto, Leticia; Fujioka, Hisashi; Kerner, Janos; Rosca, Mariana G.; McGuinness, Owen P.; Snow, Rod J.; Russell, Aaron P.; Gerber, Anthony N.; Bai, Xiaodong; Yan, Zhen; Nosek, Thomas M.; Brotto, Marco; Hoppel, Charles L.; Jain, Mukesh K.

    2012-01-01

    The ability of skeletal muscle to enhance lipid utilization during exercise is a form of metabolic plasticity essential for survival. Conversely, metabolic inflexibility in muscle can cause organ dysfunction and disease. Although the transcription factor Kruppel-like factor 15 (KLF15) is an important regulator of glucose and amino acid metabolism, its endogenous role in lipid homeostasis and muscle physiology is unknown. Here we demonstrate that KLF15 is essential for skeletal muscle lipid utilization and physiologic performance. KLF15 directly regulates a broad transcriptional program spanning all major segments of the lipid-flux pathway in muscle. Consequently, Klf15-deficient mice have abnormal lipid and energy flux, excessive reliance on carbohydrate fuels, exaggerated muscle fatigue, and impaired endurance exercise capacity. Elucidation of this heretofore unrecognized role for KLF15 now implicates this factor as a central component of the transcriptional circuitry that coordinates physiologic flux of all three basic cellular nutrients: glucose, amino acids, and lipids. PMID:22493257

  14. Lipid Accumulation during the Establishment of Kleptoplasty in Elysia chlorotica

    PubMed Central

    Pelletreau, Karen N.; Weber, Andreas P. M.; Weber, Katrin L.; Rumpho, Mary E.

    2014-01-01

    The establishment of kleptoplasty (retention of “stolen plastids”) in the digestive tissue of the sacoglossan Elysia chlorotica Gould was investigated using transmission electron microscopy. Cellular processes occurring during the initial exposure to plastids were observed in laboratory raised animals ranging from 1–14 days post metamorphosis (dpm). These observations revealed an abundance of lipid droplets (LDs) correlating to plastid abundance. Starvation of animals resulted in LD and plastid decay in animals <5 dpm that had not yet achieved permanent kleptoplasty. Animals allowed to feed on algal prey (Vaucheria litorea C. Agardh) for 7 d or greater retained stable plastids resistant to cellular breakdown. Lipid analysis of algal and animal samples supports that these accumulating LDs may be of plastid origin, as the often algal-derived 20∶5 eicosapentaenoic acid was found in high abundance in the animal tissue. Subsequent culturing of animals in dark conditions revealed a reduced ability to establish permanent kleptoplasty in the absence of photosynthetic processes, coupled with increased mortality. Together, these data support an important role of photosynthetic lipid production in establishing and stabilizing this unique animal kleptoplasty. PMID:24828251

  15. Lipid transfer proteins in the assembly of apoB-containing lipoproteins.

    PubMed

    Sirwi, Alaa; Hussain, M Mahmood

    2018-04-12

    A better understanding of intracellular lipoprotein assembly may help identify proteins with important roles in lipid disorders. ApoB-containing lipoproteins are macromolecular lipid and protein micelles that act as specialized transport vehicles for hydrophobic lipids. They are assembled predominantly in enterocytes and hepatocytes to transport dietary and endogenous fat, respectively, to different tissues. Assembly occurs in the endoplasmic reticulum and is dependent on lipid re-synthesis in the endoplasmic reticulum and on a chaperone, namely microsomal triglyceride transfer protein. Precursors for lipid synthesis are obtained from extracellular sources and from cytoplasmic lipid droplets. Microsomal triglyceride transfer protein is the major and essential lipid transfer protein that transfers phospholipids and triacylglycerols to nascent apoB for the assembly of lipoproteins. Assembly is aided by cell death-inducing DFF45-like effector B and by phospholipid transfer protein, which may facilitate additional deposition of triacylglycerols and phospholipids, respectively, to apoB. Here, we summarize the current understanding of the different steps in the assembly of apoB-containing lipoproteins and discuss the role of lipid transfer proteins in these steps to help identify new clinical targets for lipid-associated disorders, such as heart disease. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  16. HPLC-Based Mass Spectrometry Characterizes the Phospholipid Alterations in Ether-Linked Lipid Deficiency Models Following Oxidative Stress

    PubMed Central

    Drechsler, Robin; Chen, Shaw-Wen; Dancy, Blair C. R.; Mehrabkhani, Lena

    2016-01-01

    Despite the fact that the discovery of ether-linked phospholipids occurred nearly a century ago, many unanswered questions remain concerning these unique lipids. Here, we characterize the ether-linked lipids of the nematode with HPLC-MS/MS and find that more than half of the phosphoethanolamine-containing lipids are ether-linked, a distribution similar to that found in mammalian membranes. To explore the biological role of ether lipids in vivo, we target fatty acyl-CoA reductase (fard-1), an essential enzyme in ether lipid synthesis, with two distinct RNAi strategies. First, when fard-1 RNAi is initiated at the start of development, the treated animals have severely reduced ether lipid abundance, resulting in a shift in the phosphatidylethanolamine lipid population to include more saturated fatty acid chains. Thus, the absence of ether lipids during development drives a significant remodeling of the membrane landscape. A later initiation of fard-1 RNAi in adulthood results in a dramatic reduction of new ether lipid synthesis as quantified with 15N-tracers; however, there is only a slight decrease in total ether lipid abundance with this adult-only fard-1 RNAi. The two RNAi strategies permit the examination of synthesis and ether lipid abundance to reveal a relationship between the amount of ether lipids and stress survival. We tested whether these species function as sacrificial antioxidants by directly examining the phospholipid population with HPLC-MS/MS after oxidative stress treatment. While there are significant changes in other phospholipids, including polyunsaturated fatty acid-containing species, we did not find any change in ether-linked lipids, suggesting that the role of ether lipids in stress resistance is not through their general consumption as free radical sinks. Our work shows that the nematode will be a useful model for future interrogation of ether lipid biosynthesis and the characterization of phospholipid changes in various stress conditions

  17. Lipid markers of diet history and their retention during experimental starvation in the Bering Sea euphausiid Thysanoessa raschii

    NASA Astrophysics Data System (ADS)

    Pleuthner, Rachel L.; Shaw, C. Tracy; Schatz, Megan J.; Lessard, Evelyn J.; Harvey, H. Rodger

    2016-12-01

    Two extended pulsed feeding experiments, following the spring bloom period, investigated lipid retention in the prominent Bering Sea euphausiid (krill) Thysanoessa raschii. These experiments occurred during late spring and early summer of 2010. Concurrent taxonomic analysis of the natural algal community allowed prey type to be linked to lipid composition of the natural communities. In late spring, experimental periods of feeding followed by starvation showed an overall decrease in total lipid for T. raschii. In early summer, no consistent trend was observed for total lipid with the visible presence of storage lipid in some animals. Polar lipids, as phospholipids, were the dominant krill lipid class in both experiments constituting ≥88% of total lipid, and triacylglycerols reached a maximum of 5% of total lipid. The sterols cholesterol and brassicasterol+desmosterol comprised 98-99% of total sterol abundances in T. raschii throughout both experiments, even after feeding periods when alternative sterols (i.e. the algal sterol 24-methylenecholesterol) accounted for up to 39% of sterols in potential food particles. Cholesterol abundance and concentration increased during both incubations, likely due to the metabolism of dietary sterols. Major fatty acids observed in krill included C14:0n, C16:0n, C16:1(n-7), C18:1(n-7), C18:1(n-9), C20:5(n-3), and C22:6(n-3) with the diatom-attributed C16:1(n-7) decreasing in abundance and concentration during starvation. Low concentrations of the dinoflagellate-derived sterol and a novel C28:8 PUFA, typically found in dinoflagellates and prymnesiophytes, indicated predation on protozooplankton in early summer when diatom abundances were low. The stability of lipid distributions over periods of starvation and intermittent feeding suggest that fatty acid and sterol biomarkers present in this polar euphausiid principally reflect long-term diet history rather than short-term feeding episodes.

  18. Natural mutagenesis of human genomes by endogenous retrotransposons.

    PubMed

    Iskow, Rebecca C; McCabe, Michael T; Mills, Ryan E; Torene, Spencer; Pittard, W Stephen; Neuwald, Andrew F; Van Meir, Erwin G; Vertino, Paula M; Devine, Scott E

    2010-06-25

    Two abundant classes of mobile elements, namely Alu and L1 elements, continue to generate new retrotransposon insertions in human genomes. Estimates suggest that these elements have generated millions of new germline insertions in individual human genomes worldwide. Unfortunately, current technologies are not capable of detecting most of these young insertions, and the true extent of germline mutagenesis by endogenous human retrotransposons has been difficult to examine. Here, we describe technologies for detecting these young retrotransposon insertions and demonstrate that such insertions indeed are abundant in human populations. We also found that new somatic L1 insertions occur at high frequencies in human lung cancer genomes. Genome-wide analysis suggests that altered DNA methylation may be responsible for the high levels of L1 mobilization observed in these tumors. Our data indicate that transposon-mediated mutagenesis is extensive in human genomes and is likely to have a major impact on human biology and diseases.

  19. Light on fluorescent lipids in rafts: a lesson from model membranes.

    PubMed

    Kahya, Nicoletta

    2010-09-15

    Tracking fluorescent lipids in cellular membranes has been applied for decades to shed light on membrane trafficking, sorting, endocytosis and exocytosis, viral entry, and to understand the functional relevance of membrane heterogeneity, phase separation and lipid rafts. However, fluorescent probes may display different organizing behaviour from their corresponding endogenous lipids. A full characterization of these probes is therefore required for proper interpretation of fluorescence microscopy data in complex membrane systems. Model membrane studies provide essential clues that guide us to design and interpret our experiments, help us to avoid pitfalls and resolve artefacts in complex cellular environments. In the present issue of the Biochemical Journal, Juhasz, Davis and Sharom demonstrate the importance of testing lipid probes systematically in heterogeneous model membranes of specific composition and well-defined thermodynamic properties. The phase-partitioning behaviour of fluorescent probes, alone and/or in combination, cannot simply be assumed, but has to be fully characterized.

  20. The Lipid Raft Proteome of African Trypanosomes Contains Many Flagellar Proteins.

    PubMed

    Sharma, Aabha I; Olson, Cheryl L; Engman, David M

    2017-08-24

    Lipid rafts are liquid-ordered membrane microdomains that form by preferential association of 3-β-hydroxysterols, sphingolipids and raft-associated proteins often having acyl modifications. We isolated lipid rafts of the protozoan parasite Trypanosoma brucei and determined the protein composition of lipid rafts in the cell. This analysis revealed a striking enrichment of flagellar proteins and several putative signaling proteins in the lipid raft proteome. Calpains and intraflagellar transport proteins, in particular, were found to be abundant in the lipid raft proteome. These findings provide additional evidence supporting the notion that the eukaryotic cilium/flagellum is a lipid raft-enriched specialized structure with high concentrations of sterols, sphingolipids and palmitoylated proteins involved in environmental sensing and cell signaling.

  1. Exceptionally potent inhibitors of fatty acid amide hydrolase: The enzyme responsible for degradation of endogenous oleamide and anandamide

    PubMed Central

    Boger, Dale L.; Sato, Haruhiko; Lerner, Aaron E.; Hedrick, Michael P.; Fecik, Robert A.; Miyauchi, Hiroshi; Wilkie, Gordon D.; Austin, Bryce J.; Patricelli, Matthew P.; Cravatt, Benjamin F.

    2000-01-01

    The development of exceptionally potent inhibitors of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of oleamide (an endogenous sleep-inducing lipid), and anandamide (an endogenous ligand for cannabinoid receptors) is detailed. The inhibitors may serve as useful tools to clarify the role of endogenous oleamide and anandamide and may prove to be useful therapeutic agents for the treatment of sleep disorders or pain. The combination of several features—an optimal C12–C8 chain length, π-unsaturation introduction at the corresponding arachidonoyl Δ8,9/Δ11,12 and oleoyl Δ9,10 location, and an α-keto N4 oxazolopyridine with incorporation of a second weakly basic nitrogen provided FAAH inhibitors with Kis that drop below 200 pM and are 102–103 times more potent than the corresponding trifluoromethyl ketones. PMID:10805767

  2. Further comparisons of endogenous pyrogens and leukocytic endogenous mediators.

    PubMed

    Kampschmidt, R F; Upchurch, H F; Worthington, M L

    1983-07-01

    It was recently shown (Murphy et al., Infect. Immun. 34:177-183), that rabbit macrophages produce two biochemically and immunologically distinct endogenous pyrogens. One of these has or copurifies with substances having a molecular weight of 13,000 and a pI of 7.3. This protein was produced by blood monocytes or inflammatory cells elicited in 16-h rabbit peritoneal exudates. These acute peritoneal exudates were produced by the intraperitoneal injection of large volumes of saline containing shellfish glycogen. When the leukocytes in these exudates were washed and incubated at 37 degrees C in saline, they released an endogenous pyrogen. The injection of this pyrogen into rabbits, rats, or mice caused the biological manifestations which have been attributed to leukocytic endogenous mediator. These effects were increases in blood neutrophils, the lowering of plasma iron and zinc levels, and the increased synthesis of the acute-phase proteins. The other rabbit endogenous pyrogen seems to be a family of proteins with isoelectric points between 4.5 and 5.0. These proteins are produced by macrophages in the lung, liver, or in chronic peritoneal exudates. In these experiments, the lower-isoelectric-point endogenous pyrogens were produced by macrophages from the peritoneal cavity of rabbits that had been injected 4 days earlier with 50 ml of light mineral oil. These rabbit pyrogens were found to have leukocytic endogenous mediator activity in mice but to be completely inactive in rats. When injected into rabbits, these proteins produced fever, lowered plasma iron, increased blood neutrophils, but failed to elevate plasma fibrinogen.

  3. Further comparisons of endogenous pyrogens and leukocytic endogenous mediators.

    PubMed Central

    Kampschmidt, R F; Upchurch, H F; Worthington, M L

    1983-01-01

    It was recently shown (Murphy et al., Infect. Immun. 34:177-183), that rabbit macrophages produce two biochemically and immunologically distinct endogenous pyrogens. One of these has or copurifies with substances having a molecular weight of 13,000 and a pI of 7.3. This protein was produced by blood monocytes or inflammatory cells elicited in 16-h rabbit peritoneal exudates. These acute peritoneal exudates were produced by the intraperitoneal injection of large volumes of saline containing shellfish glycogen. When the leukocytes in these exudates were washed and incubated at 37 degrees C in saline, they released an endogenous pyrogen. The injection of this pyrogen into rabbits, rats, or mice caused the biological manifestations which have been attributed to leukocytic endogenous mediator. These effects were increases in blood neutrophils, the lowering of plasma iron and zinc levels, and the increased synthesis of the acute-phase proteins. The other rabbit endogenous pyrogen seems to be a family of proteins with isoelectric points between 4.5 and 5.0. These proteins are produced by macrophages in the lung, liver, or in chronic peritoneal exudates. In these experiments, the lower-isoelectric-point endogenous pyrogens were produced by macrophages from the peritoneal cavity of rabbits that had been injected 4 days earlier with 50 ml of light mineral oil. These rabbit pyrogens were found to have leukocytic endogenous mediator activity in mice but to be completely inactive in rats. When injected into rabbits, these proteins produced fever, lowered plasma iron, increased blood neutrophils, but failed to elevate plasma fibrinogen. PMID:6862633

  4. Omega-3 fatty acids, lipids, and apoE lipidation in Alzheimer's disease: a rationale for multi-nutrient dementia prevention.

    PubMed

    Grimm, Marcus O W; Michaelson, Daniel M; Hartmann, Tobias

    2017-11-01

    In the last decade, it has become obvious that Alzheimer's disease (AD) is closely linked to changes in lipids or lipid metabolism. One of the main pathological hallmarks of AD is amyloid-β (Aβ) deposition. Aβ is derived from sequential proteolytic processing of the amyloid precursor protein (APP). Interestingly, both, the APP and all APP secretases are transmembrane proteins that cleave APP close to and in the lipid bilayer. Moreover, apoE4 has been identified as the most prevalent genetic risk factor for AD. ApoE is the main lipoprotein in the brain, which has an abundant role in the transport of lipids and brain lipid metabolism. Several lipidomic approaches revealed changes in the lipid levels of cerebrospinal fluid or in post mortem AD brains. Here, we review the impact of apoE and lipids in AD, focusing on the major brain lipid classes, sphingomyelin, plasmalogens, gangliosides, sulfatides, DHA, and EPA, as well as on lipid signaling molecules, like ceramide and sphingosine-1-phosphate. As nutritional approaches showed limited beneficial effects in clinical studies, the opportunities of combining different supplements in multi-nutritional approaches are discussed and summarized. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  5. Development of an enrichment method for endogenous phosphopeptide characterization in human serum.

    PubMed

    La Barbera, Giorgia; Capriotti, Anna Laura; Cavaliere, Chiara; Ferraris, Francesca; Laus, Michele; Piovesana, Susy; Sparnacci, Katia; Laganà, Aldo

    2018-01-01

    The work describes the development of an enrichment method for the analysis of endogenous phosphopeptides in serum. Endogenous peptides can play significant biological roles, and some of them could be exploited as future biomarkers. In this context, blood is one of the most useful biofluids for screening, but a systematic investigation of the endogenous peptides, especially phosphorylated ones, is still lacking, mainly due to the lack of suitable analytical methods. Thus, in this paper, different phosphopeptide enrichment strategies were pursued, based either on metal oxide affinity chromatography (MOAC, in the form of commercial TiO 2 spin columns or magnetic graphitized carbon black-TiO 2 composite), or on immobilized metal ion affinity chromatography (IMAC, in the form of Ti 4+ -IMAC magnetic material or commercial Fe 3+ -IMAC spin columns). While MOAC strategies proved completely unsuccessful, probably due to interfering phospholipids displacing phosphopeptides, the IMAC materials performed very well. Different sample preparation strategies were tested, comprising direct dilution with the loading buffer, organic solvent precipitation, and lipid removal from the matrix, as well as the addition of phosphatase inhibitors during sample handling for maximized endogenous phosphopeptide enrichment. All data were acquired by a shotgun peptidomics approach, in which peptide samples were separated by reversed-phase nanoHPLC hyphenated with high-resolution tandem mass spectrometry. The devised method allowed the identification of 176 endogenous phosphopeptides in fresh serum added with inhibitors by the direct dilution protocol and the Ti 4+ -IMAC magnetic material enrichment, but good results could also be obtained from the commercial Fe 3+ -IMAC spin column adapted to the batch enrichment protocol.

  6. A systematic survey of lipids across mouse tissues

    PubMed Central

    Jain, Mohit; Ngoy, Soeun; Sheth, Sunil A.; Swanson, Raymond A.; Rhee, Eugene P.; Liao, Ronglih; Clish, Clary B.; Mootha, Vamsi K.

    2014-01-01

    Lipids are a diverse collection of macromolecules essential for normal physiology, but the tissue distribution and function for many individual lipid species remain unclear. Here, we report a mass spectrometry survey of lipid abundance across 18 mouse tissues, detecting ∼1,000 mass spectrometry features, of which we identify 179 lipids from the glycerolipids, glycerophospholipids, lysophospholipids, acylcarnitines, sphingolipids, and cholesteryl ester classes. Our data reveal tissue-specific organization of lipids and can be used to generate testable hypotheses. For example, our data indicate that circulating triglycerides positively and negatively associated with future diabetes in humans are enriched in mouse adipose tissue and liver, respectively, raising hypotheses regarding the tissue origins of these diabetes-associated lipids. We also integrate our tissue lipid data with gene expression profiles to predict a number of substrates of lipid-metabolizing enzymes, highlighting choline phosphotransferases and sterol O-acyltransferases. Finally, we identify several tissue-specific lipids not present in plasma under normal conditions that may be of interest as biomarkers of tissue injury, and we show that two of these lipids are released into blood following ischemic brain injury in mice. This resource complements existing compendia of tissue gene expression and may be useful for integrative physiology and lipid biology. PMID:24518676

  7. Direct observation of the influence of cardiolipin and antibiotics on lipid II binding to MurJ

    NASA Astrophysics Data System (ADS)

    Bolla, Jani Reddy; Sauer, Joshua B.; Wu, Di; Mehmood, Shahid; Allison, Timothy M.; Robinson, Carol V.

    2018-03-01

    Translocation of lipid II across the cytoplasmic membrane is essential in peptidoglycan biogenesis. Although most steps are understood, identifying the lipid II flippase has yielded conflicting results, and the lipid II binding properties of two candidate flippases—MurJ and FtsW—remain largely unknown. Here we apply native mass spectrometry to both proteins and characterize lipid II binding. We observed lower levels of lipid II binding to FtsW compared to MurJ, consistent with MurJ having a higher affinity. Site-directed mutagenesis of MurJ suggests that mutations at A29 and D269 attenuate lipid II binding to MurJ, whereas chemical modification of A29 eliminates binding. The antibiotic ramoplanin dissociates lipid II from MurJ, whereas vancomycin binds to form a stable complex with MurJ:lipid II. Furthermore, we reveal cardiolipins associate with MurJ but not FtsW, and exogenous cardiolipins reduce lipid II binding to MurJ. These observations provide insights into determinants of lipid II binding to MurJ and suggest roles for endogenous lipids in regulating substrate binding.

  8. Lipid flopping in the liver.

    PubMed

    Linton, Kenneth J

    2015-10-01

    Bile is synthesized in the liver and is essential for the emulsification of dietary lipids and lipid-soluble vitamins. It is a complex mixture of amphiphilic bile acids (BAs; which act as detergent molecules), the membrane phospholipid phosphatidylcholine (PC), cholesterol and a variety of endogenous metabolites and waste products. Over the last 20 years, the combined effort of clinicians, geneticists, physiologists and biochemists has shown that each of these bile components is transported across the canalicular membrane of the hepatocyte by its own specific ATP-binding cassette (ABC) transporter. The bile salt export pump (BSEP) ABCB11 transports the BAs and drives bile flow from the liver, but it is now clear that two lipid transporters, ABCB4 (which flops PC into the bile) and the P-type ATPase ATP8B1/CDC50 (which flips a different phospholipid in the opposite direction) play equally critical roles that protect the biliary tree from the detergent activity of the bile acids. Understanding the interdependency of these lipid floppases and flippases has allowed the development of an assay to measure ABCB4 function. ABCB4 harbours numerous mis-sense mutations which probably reflects the spectrum of liver disease rooted in ABCB4 aetiology. Characterization of the effect of these mutations at the protein level opens the possibility for the development of personalized prognosis and treatment. © 2015 Authors; published by Portland Press Limited.

  9. Deciphering the mechanisms for targeting and interaction of Arabidopsis Lipid Droplet Associated Protein (LDAP) to the lipid droplet surface

    USDA-ARS?s Scientific Manuscript database

    We recently identified a new class of lipid-droplet associated proteins (LDAPs) in plants that share extensive sequence similarity with abundant structural proteins that coat rubber particles in rubber-producing plants. A majority of higher plants, however, including those that do not produce rubber...

  10. Lipid oxidation by hypochlorous acid: chlorinated lipids in atherosclerosis and myocardial ischemia

    PubMed Central

    Ford, David A

    2011-01-01

    Leukocytes, containing myeloperoxidase (MPO), produce the reactive chlorinating species, HOCl, and they have important roles in the pathophysiology of cardiovascular disease. Leukocyte-derived HOCl can target primary amines, alkenes and vinyl ethers of lipids, resulting in chlorinated products. Plasmalogens are vinyl ether-containing phospholipids that are abundant in tissues of the cardiovascular system. The HOCl oxidation products derived from plasmalogens are α-chlorofatty aldehyde and unsaturated molecular species of lysophosphatidylcholine. α-chlorofatty aldehyde is the precursor of both α-chlorofatty alcohol and α-chlorofatty acid. Both α-chlorofatty aldehyde and α-chlorofatty acid accumulate in activated neutrophils and have disparate chemotactic properties. In addition, α-chlorofatty aldehyde increases in activated monocytes, human atherosclerotic lesions and rat infarcted myocardium. This article addresses the pathways for the synthesis of these lipids and their biological targets. PMID:21339854

  11. The Lipid Raft Proteome of African Trypanosomes Contains Many Flagellar Proteins

    PubMed Central

    Sharma, Aabha I.; Olson, Cheryl L.; Engman, David M.

    2017-01-01

    Lipid rafts are liquid-ordered membrane microdomains that form by preferential association of 3-β-hydroxysterols, sphingolipids and raft-associated proteins often having acyl modifications. We isolated lipid rafts of the protozoan parasite Trypanosoma brucei and determined the protein composition of lipid rafts in the cell. This analysis revealed a striking enrichment of flagellar proteins and several putative signaling proteins in the lipid raft proteome. Calpains and intraflagellar transport proteins, in particular, were found to be abundant in the lipid raft proteome. These findings provide additional evidence supporting the notion that the eukaryotic cilium/flagellum is a lipid raft-enriched specialized structure with high concentrations of sterols, sphingolipids and palmitoylated proteins involved in environmental sensing and cell signaling. PMID:28837104

  12. Endogenous and dietary lipids influencing feed intake and energy metabolism of periparturient dairy cows.

    PubMed

    Kuhla, B; Metges, C C; Hammon, H M

    2016-07-01

    The high metabolic priority of the mammary gland for milk production, accompanied by limited feed intake around parturition results in a high propensity to mobilize body fat reserves. Under these conditions, fuel selection of many peripheral organs is switched, for example, from carbohydrate to fat utilization to spare glucose for milk production and to ensure partitioning of tissue- and dietary-derived nutrients toward the mammary gland. For example, muscle tissue uses nonesterified fatty acids (NEFA) but releases lactate and amino acids in a coordinated order, thereby providing precursors for milk synthesis or hepatic gluconeogenesis. Tissue metabolism and in concert, nutrient partitioning are controlled by the endocrine system involving a reduction in insulin secretion and systemic insulin sensitivity and orchestrated changes in plasma hormones such as insulin, adiponectin, insulin growth factor-I, growth hormone, glucagon, leptin, glucocorticoids, and catecholamines. However, the endocrine system is highly sensitive and responsive to an overload of fatty acids no matter if excessive NEFA supply originates from exogenous or endogenous sources. Feeding a diet containing rumen-protected fat from late lactation to calving and beyond exerts similar negative effects on energy intake, glucose and insulin concentrations as does a high extent of body fat mobilization around parturition in regard to the risk for ketosis and fatty liver development. High plasma NEFA concentrations are thought not to act directly at the brain level, but they increase the energy charge of the liver which is, signaled to the brain to diminish feed intake. Cows differing in fat mobilization during the transition phase differ in their hepatic energy charge, whole body fat oxidation, glucose metabolism, plasma ghrelin, and leptin concentrations and in feed intake several week before parturition. Hence, a high lipid load, no matter if stored, mobilized or fed, affects the endocrine system

  13. Inflammation-related alterations of lipids after spinal cord injury revealed by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Tamosaityte, Sandra; Galli, Roberta; Uckermann, Ortrud; Sitoci-Ficici, Kerim H.; Koch, Maria; Later, Robert; Schackert, Gabriele; Koch, Edmund; Steiner, Gerald; Kirsch, Matthias

    2016-06-01

    Spinal cord injury (SCI) triggers several lipid alterations in nervous tissue. It is characterized by extensive demyelination and the inflammatory response leads to accumulation of activated microglia/macrophages, which often transform into foam cells by accumulation of lipid droplets after engulfment of the damaged myelin sheaths. Using an experimental rat model, Raman microspectroscopy was applied to retrieve the modifications of the lipid distribution following SCI. Coherent anti-Stokes Raman scattering (CARS) and endogenous two-photon fluorescence (TPEF) microscopies were used for the detection of lipid-laden inflammatory cells. The Raman mapping of CH2 deformation mode intensity at 1440 cm-1 retrieved the lipid-depleted injury core. Preserved white matter and inflammatory regions with myelin fragmentation and foam cells were localized by specifically addressing the distribution of esterified lipids, i.e., by mapping the intensity of the carbonyl Raman band at 1743 cm-1, and were in agreement with CARS/TPEF microscopy. Principal component analysis revealed that the inflammatory regions are notably rich in saturated fatty acids. Therefore, Raman spectroscopy enabled to specifically detect inflammation after SCI and myelin degradation products.

  14. A Conserved Circular Network of Coregulated Lipids Modulates Innate Immune Responses

    PubMed Central

    Köberlin, Marielle S.; Snijder, Berend; Heinz, Leonhard X.; Baumann, Christoph L.; Fauster, Astrid; Vladimer, Gregory I.; Gavin, Anne-Claude; Superti-Furga, Giulio

    2015-01-01

    Summary Lipid composition affects the biophysical properties of membranes that provide a platform for receptor-mediated cellular signaling. To study the regulatory role of membrane lipid composition, we combined genetic perturbations of sphingolipid metabolism with the quantification of diverse steps in Toll-like receptor (TLR) signaling and mass spectrometry-based lipidomics. Membrane lipid composition was broadly affected by these perturbations, revealing a circular network of coregulated sphingolipids and glycerophospholipids. This evolutionarily conserved network architecture simultaneously reflected membrane lipid metabolism, subcellular localization, and adaptation mechanisms. Integration of the diverse TLR-induced inflammatory phenotypes with changes in lipid abundance assigned distinct functional roles to individual lipid species organized across the network. This functional annotation accurately predicted the inflammatory response of cells derived from patients suffering from lipid storage disorders, based solely on their altered membrane lipid composition. The analytical strategy described here empowers the understanding of higher-level organization of membrane lipid function in diverse biological systems. PMID:26095250

  15. Endogenous Lunar Volatiles

    NASA Astrophysics Data System (ADS)

    McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Anand, M.; Boyce, J. W.; Burney, D.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Klima, R. L.; Magna, T.; Ni, P.; Steenstra, E.; Tartèse, R.; Vander Kaaden, K. E.

    2018-04-01

    This abstract discusses numerous outstanding questions on the topic of endogenous lunar volatiles that will need to be addressed in the coming years. Although substantial insights into endogenous lunar volatiles have been gained, more work remains.

  16. Preservation of Microbial Lipids in Geothermal Sinters

    NASA Astrophysics Data System (ADS)

    Kaur, Gurpreet; Mountain, Bruce W.; Hopmans, Ellen C.; Pancost, Richard D.

    2011-04-01

    Lipid biomarkers are widely used to study the earliest life on Earth and have been invoked as potential astrobiological markers, but few studies have assessed their survival and persistence in geothermal settings. Here, we investigate lipid preservation in active and inactive geothermal silica sinters, with ages of up to 900 years, from Champagne Pool, Waiotapu, New Zealand. Analyses revealed a wide range of bacterial biomarkers, including free and bound fatty acids, 1,2-di-O-alkylglycerols (diethers), and various hopanoids. Dominant archaeal lipids include archaeol and glycerol dialkyl glycerol tetraethers (GDGTs). The predominance of generally similar biomarker groups in all sinters suggests a stable microbial community throughout Champagne Pool's history and indicates that incorporated lipids can be well preserved. Moreover, subtle differences in lipid distributions suggest that past changes in environmental conditions can be elucidated. In this case, higher archaeol abundances relative to the bacterial diethers, a greater proportion of cyclic GDGTs, the high average chain length of the bacterial diethers, and greater concentrations of hopanoic acids in the older sinters all suggest hotter conditions at Champagne Pool in the past.

  17. Endogenous System Microbes as Treatment Process ...

    EPA Pesticide Factsheets

    Monitoring the efficacy of treatment strategies to remove pathogens in decentralized systems remains a challenge. Evaluating log reduction targets by measuring pathogen levels is hampered by their sporadic and low occurrence rates. Fecal indicator bacteria are used in centralized systems to indicate the presence of fecal pathogens, but are ineffective decentralized treatment process indicators as they generally occur at levels too low to assess log reduction targets. System challenge testing by spiking with high loads of fecal indicator organisms, like MS2 coliphage, has limitations, especially for large systems. Microbes that are endogenous to the decentralized system, occur in high abundances and mimic removal rates of bacterial, viral and/or parasitic protozoan pathogens during treatment could serve as alternative treatment process indicators to verify log reduction targets. To identify abundant microbes in wastewater, the bacterial and viral communities were examined using deep sequencing. Building infrastructure-associated bacteria, like Zoogloea, were observed as dominant members of the bacterial community in graywater. In blackwater, bacteriophage of the order Caudovirales constituted the majority of contiguous sequences from the viral community. This study identifies candidate treatment process indicators in decentralized systems that could be used to verify log removal during treatment. The association of the presence of treatment process indic

  18. The TULIP superfamily of eukaryotic lipid-binding proteins as a mediator of lipid sensing and transport.

    PubMed

    Alva, Vikram; Lupas, Andrei N

    2016-08-01

    lipids endogenous to the cell, and the BPI-like proteins (including the Takeout-like proteins of arthropods), which act on exogenous lipids. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Biased signaling of lipids and allosteric actions of synthetic molecules for GPR119.

    PubMed

    Hassing, Helle A; Fares, Suzan; Larsen, Olav; Pad, Hamideh; Hauge, Maria; Jones, Robert M; Schwartz, Thue W; Hansen, Harald S; Rosenkilde, Mette M

    2016-11-01

    GPR119 is a Gαs-coupled lipid-sensor in the gut, where it mediates release of incretin hormones from the enteroendocrine cells and in pancreatic α-cells, where it releases insulin. Naturally occurring lipids such as monoacylglycerols (MAGs) and N-acylethanolamines (NAEs), like oleoylethanolamide (OEA), activate GPR119, and multiple synthetic ligands have been described. Here, we extend the GPR119 signaling profile to Gαq and Gαi in addition to β-arrestin recruitment and the downstream transcription factors CRE (cAMP response element), SRE (serum response element) and NFAT (nuclear factor of activated T cells). The endogenous OEA and the synthetic AR231453 were full agonists in all pathways except for NFAT, where no ligand-modulation was observed. The potency of AR231453 varied <16-fold (EC 50 from 6 to 95nM) across the different signaling pathways, whereas that of OEA varied >175-fold (from 85nM to 15μM) indicating a biased signaling for OEA. The degree of constitutive activity was 1-10%, 10-30% and 30-70% of OEA-induced E max in Gαi, Gαq and Gαs-driven pathways, respectively. This coincided with the lowest and highest OEA potency observed in Gαi and Gαs-driven pathways, respectively. Incubation for 2h with the 2-MAG-lipase inhibitor JZL84 doubled the constitutive activity, indicating that endogenous lipids contribute to the apparent constitutive activity. Finally, besides being an agonist, AR231453 acted as a positive allosteric modulator of OEA and increased its potency by 54-fold at 100nM AR231453. Our studies uncovering broad and biased signaling, masked constitutive activity by endogenous MAGs, and ago-allosteric properties of synthetic ligands may explain why many GPR119 drug-discovery programs have failed so far. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins

    PubMed Central

    Spite, Matthew; Serhan, Charles N.

    2010-01-01

    The resolution of acute inflammation is a process that allows for inflamed tissues to return to homeostasis. Resolution was held to be a passive process, a concept now overturned with new evidence demonstrating that resolution is actively orchestrated by distinct cellular events and endogenous chemical mediators. Among these, lipid mediators, such as the lipoxins, resolvins, protectins and newly identified maresins, have emerged as a novel genus of potent and stereoselective players that counter-regulate excessive acute inflammation and stimulate molecular and cellular events that define resolution. Given that uncontrolled, chronic inflammation is associated with many cardiovascular pathologies, an appreciation of the endogenous pathways and mediators that control timely resolution can open new terrain for therapeutic approaches targeted at stimulating resolution of local inflammation, as well as correcting the impact of chronic inflammation in cardiovascular disorders. Here, we overview and update the biosynthesis and actions of pro-resolving lipid mediators, highlighting their diverse protective roles relevant to vascular systems and their relation to aspirin and statin therapies. PMID:21071715

  1. Circular RNAs are abundant, conserved, and associated with ALU repeats

    PubMed Central

    Jeck, William R.; Sorrentino, Jessica A.; Wang, Kai; Slevin, Michael K.; Burd, Christin E.; Liu, Jinze; Marzluff, William F.; Sharpless, Norman E.

    2013-01-01

    Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R. We identified >25,000 distinct RNA species in human fibroblasts that contained non-colinear exons (a “backsplice”) and were reproducibly enriched by exonuclease degradation of linear RNA. These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo. In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by >10-fold. By conservative estimate, we identified ecircRNAs from 14.4% of actively transcribed genes in human fibroblasts. Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs. Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice. Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes. Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs. Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats. These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression. PMID:23249747

  2. Microbial and endogenous metabolic conversions of rye phytochemicals.

    PubMed

    Koistinen, Ville M; Hanhineva, Kati

    2017-07-01

    Rye is one of the main cereals produced and consumed in the hemiboreal climate region. Due to its use primarily as wholegrain products, rye provides a rich source of dietary fibre as well as several classes of phytochemicals, bioactive compounds with potentially positive health implications. Here, we review the current knowledge of the metabolic pathways of phytochemical classes abundant in rye, starting from the microbial transformations occurring during the sourdough process and colonic fermentation and continuing with the endogenous metabolism. Additionally, we discuss the detection of specific metabolites by MS in different phases of their journey from the cereal to the target organs and excretion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Physiological aspects of human milk lipids.

    PubMed

    Koletzko, B; Rodriguez-Palmero, M; Demmelmair, H; Fidler, N; Jensen, R; Sauerwald, T

    2001-11-01

    Human milk from healthy and well-nourished mothers is the preferred form of feeding for all healthy newborn infants. The nutrient supply with human milk supports normal growth and development of the infant. Here the general characteristics of human milk lipids and recent knowledge on lactational physiology, composition and functional aspects of human milk lipids are discussed. Lipids in human milk represent the main source of energy for the breastfed baby and supply essential nutrients such as fat-soluble vitamins and polyunsaturated fatty acids (PUFA). The essential fatty acids linoleic and alpha-linolenic acids (LA and ALA) are precursors of long-chain polyunsaturated fatty acids (LC-PUFA), including arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acids (AA and DHA). LC-PUFA serve as indispensable structural components of cellular membranes and are deposited to a considerable extent in the growing brain and the retina during perinatal development. The supply of preformed LC-PUFA with human milk lipids has been related to functional outcomes of the recipient infants such as visual acuity and development of cognitive functions during the first year of life. Recent stable isotope studies indicate that the major portion of milk PUFA is not derived directly from the maternal diet, but stems from endogenous body stores. Thus, not only the woman's current but also her long-term dietary intake is of marked relevance for milk fat composition.

  4. LTRs of Endogenous Retroviruses as a Source of Tbx6 Binding Sites.

    PubMed

    Yasuhiko, Yukuto; Hirabayashi, Yoko; Ono, Ryuichi

    2017-01-01

    Retrotransposons are abundant in mammalian genomes and can modulate the gene expression of surrounding genes by disrupting endogenous binding sites for transcription factors (TFs) or providing novel TFs binding sites within retrotransposon sequences. Here, we show that a (C/T)CACACCT sequence motif in ORR1A, ORR1B, ORR1C, and ORR1D, Long Terminal Repeats (LTRs) of MaLR endogenous retrovirus (ERV), is the direct target of Tbx6, an evolutionary conserved family of T-box TFs. Moreover, by comparing gene expression between control mice (Tbx6 +/-) and Tbx6-deficient mice (Tbx6 -/-), we demonstrate that at least four genes, Twist2, Pitx2, Oscp1 , and Nfxl1 , are down-regulated with Tbx6 deficiency. These results suggest that ORR1A, ORR1B, ORR1C and ORR1D may contribute to the evolution of mammalian embryogenesis.

  5. LTRs of endogenous retroviruses as a source of Tbx6 binding sites

    NASA Astrophysics Data System (ADS)

    Yasuhiko, Yukuto; Hirabayashi, Yoko; Ono, Ryuichi

    2017-06-01

    Retrotransposons are abundant in mammalian genomes and can modulate the gene expression of surrounding genes by disrupting endogenous binding sites for transcription factors (TFs) or providing novel TFs binding sites within retrotransposon sequences. Here, we show that a (C/T)CACACCT sequence motif in ORR1A, ORR1B, ORR1C and ORR1D, Long Terminal Repeats (LTRs) of MaLR endogenous retrovirus (ERV), is the direct target of Tbx6, an evolutionary conserved family of T-box transcription factors. Moreover, by comparing gene expression between control mice (Tbx6 +/-) and Tbx6-deficient mice (Tbx6 -/-), we demonstrate that at least four genes, Twist2, Pitx2, Oscp1, and Nfxl1, are down-regulated with Tbx6 deficiency. These results suggest that ORR1A, ORR1B, ORR1C and ORR1D may contribute to the evolution of mammalian embryogenesis.

  6. Expression of lipoprotein receptor and apolipoprotein E genes by perinatal rat lipid-laden pulmonary fibroblasts.

    PubMed

    McGowan, S E; Doro, M M; Jackson, S

    Lipid-laden interstitial fibroblasts (LIFs) are abundant during alveolar septal formation in rats and accumulate droplets of neutral lipids. The mechanisms controlling lipid acquisition by LIFs are incompletely understood and accumulation varies during postnatal development, because lipid droplets are usually a transient phenotype. We hypothesized that plasma lipoproteins may be an important source of lipids and that the cells may alter their acquisition of lipoproteins by changing the expression of lipoprotein receptors and apolipoprotein E. We quantified the accumulation low-density lipoproteins (LDLs) and very-low-density lipoproteins (VLDLs) by LIFs and the expression of LDL and VLDL receptors mRNA and protein at various perinatal ages and found no significant age-related differences. Apolipoprotein E mRNA was maximal at postnatal day 15, whereas immunoreactive apolipoprotein E protein was maximal at gestational day 21, suggesting complex regulation. Our findings indicate that the age-related difference in the lipid droplet contents of LIFs is not primarily related to differences in LDL or VLDL receptor expression. They suggest that changes in the quantities of plasma lipoproteins, which are presented to LIFs in the lung at various perinatal ages, are more likely to be responsible for age-related alterations in lipid droplet size and abundance.

  7. Production of endogenous pyrogen.

    PubMed

    Dinarello, C A

    1979-01-01

    The production and release of endogenous pyrogen by the host is the first step in the pathogenesis of fever. Endogenous pyrogen is a low-molecular-weight protein released from phagocytic leukocytes in response to several substances of diverse nature. Some of these agents stimulate production of endogenous pyrogen because they are toxic; others act as antigens and interact with either antibody or sensitized lymphocytes in order to induce its production. Some tumors of macrophage origin produce the molecule spontaneously. Whatever the mechanism involved, endogenous pyrogen is synthesized following transcription of new DNA and translation of mRNA into new protein. Once synthesis is completed, the molecule is released without significant intracellular storage. Recent evidence suggests that following release, molecular aggregates form which are biologically active. In its monomer form, endogenous pyrogen is a potent fever-producing substance and mediates fever by its action on the thermoregulatory center.

  8. Influence of blood lipids on global coagulation test results.

    PubMed

    Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon; Kim, Hyun Kyung

    2015-01-01

    High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels.

  9. Fasting and refeeding induces changes in the mouse hepatic lipid droplet proteome.

    PubMed

    Kramer, David A; Quiroga, Ariel D; Lian, Jihong; Fahlman, Richard P; Lehner, Richard

    2018-06-15

    During fasting, the liver increases lipid storage as a mean to reserve and provide energy for vital cellular functions. After re-feeding, hepatocytes rapidly decrease the amount of triacylglycerol that is stored in lipid droplets (LDs), visible as the size of hepatic LDs significantly decreases after re-feeding. Little is known about the changes in the liver LD proteome that occur during the fasting/re-feeding transition. This study aimed to investigate the hepatic LD proteome in fasted and re-fed conditions in the mouse. Using label-free LC-MS/MS analysis the relative abundance of 817 proteins was determined in highly purified LDs. Comparative analysis for differential protein abundance with respect to feeding states revealed 130 with higher abundance in LDs from fasted mice and 31 in LDs from re-fed mice. Among proteins observed to have higher abundance on LDs in the fasted state we found perilipin-5, and several mitochondrial and peroxisomal marker proteins, supporting the role of LDs in the provision of substrates for fatty acid oxidation. Proteins of higher abundance upon re-feeding included several peroxisomal and mitochondrial marker proteins and expand our understanding of the dynamic nature of the hepatic LD proteome according to the energetic requirements of the cell. Proteomic investigations have been revealing the complexities and dynamics of cellular LDs from a variety of cell types. As these sub-cellular structures are truly dynamic in nature, our investigations reveal that simply the feeding state of an animal leads to significant changes to the protein composition of LDs and suggest a variety of dynamic interactions with other cellular organelles, such as the mitochondria and peroxisomes. As such, the experimental design for investigations of this cellular structure must consider this dynamic baseline. Lastly our analysis on global protein abundance has revealed the unforeseen high abundance of murine major urinary proteins associated with hepatic

  10. Possible human endogenous cryogens.

    PubMed

    Shido, Osamu; Sugimoto, Naotoshi

    2011-06-01

    Anapyrexia, which is a regulated fall in core temperature, is beneficial for animals and humans when the oxygen supply is limited, e.g., hypoxic, ischemic, or histotoxic hypoxia, since at low body temperature the tissues require less oxygen due to Q(10). Besides hypoxia, anapyrexia can be induced various exogenous and endogenous substances, named cryogens. However, there are only a few reports investigating endogenous cryogens in mammals. We have experienced one patient who suffered from severe hypothermia. The patient seemed to be excessively producing endogenous peptidergic cryogenic substances the molecular weight of which may be greater than 30 kDa. In animal studies, the patient's cryogen appeared to affect metabolic functions, including thermogenic threshold temperatures, and then to produce hypothermia. Since endogenous cryogenic substances may be regarded as useful tool in human activities, e.g., during brain hypothermia therapy or staying in a space station or spaceship, further studies may be needed to identify human endogenous cryogens.

  11. Anionic lipids and the maintenance of membrane electrostatics in eukaryotes

    PubMed Central

    Platre, Matthieu Pierre

    2017-01-01

    ABSTRACT A wide range of signaling processes occurs at the cell surface through the reversible association of proteins from the cytosol to the plasma membrane. Some low abundant lipids are enriched at the membrane of specific compartments and thereby contribute to the identity of cell organelles by acting as biochemical landmarks. Lipids also influence membrane biophysical properties, which emerge as an important feature in specifying cellular territories. Such parameters are crucial for signal transduction and include lipid packing, membrane curvature and electrostatics. In particular, membrane electrostatics specifies the identity of the plasma membrane inner leaflet. Membrane surface charges are carried by anionic phospholipids, however the exact nature of the lipid(s) that powers the plasma membrane electrostatic field varies among eukaryotes and has been hotly debated during the last decade. Herein, we discuss the role of anionic lipids in setting up plasma membrane electrostatics and we compare similarities and differences that were found in different eukaryotic cells. PMID:28102755

  12. Anionic lipids and the maintenance of membrane electrostatics in eukaryotes.

    PubMed

    Platre, Matthieu Pierre; Jaillais, Yvon

    2017-02-01

    A wide range of signaling processes occurs at the cell surface through the reversible association of proteins from the cytosol to the plasma membrane. Some low abundant lipids are enriched at the membrane of specific compartments and thereby contribute to the identity of cell organelles by acting as biochemical landmarks. Lipids also influence membrane biophysical properties, which emerge as an important feature in specifying cellular territories. Such parameters are crucial for signal transduction and include lipid packing, membrane curvature and electrostatics. In particular, membrane electrostatics specifies the identity of the plasma membrane inner leaflet. Membrane surface charges are carried by anionic phospholipids, however the exact nature of the lipid(s) that powers the plasma membrane electrostatic field varies among eukaryotes and has been hotly debated during the last decade. Herein, we discuss the role of anionic lipids in setting up plasma membrane electrostatics and we compare similarities and differences that were found in different eukaryotic cells.

  13. Effects of growth phase on the membrane lipid composition of the thaumarchaeon Nitrosopumilus maritimus and their implications for archaeal lipid distributions in the marine environment

    NASA Astrophysics Data System (ADS)

    Elling, Felix J.; Könneke, Martin; Lipp, Julius S.; Becker, Kevin W.; Gagen, Emma J.; Hinrichs, Kai-Uwe

    2014-09-01

    The characteristic glycerol dibiphytanyl glycerol tetraether membrane lipids (GDGTs) of marine ammonia-oxidizing archaea (AOA) are widely used as biomarkers for studying their occurrence and distribution in marine environments and for reconstructing past sea surface temperatures using the TEX86 index. Despite an increasing use of GDGT biomarkers in microbial ecology and paleoceanography, the physiological and environmental factors influencing lipid composition in AOA, in particular the cyclization of GDGTs, remain unconstrained. We investigated the effect of metabolic state on the composition of intact polar and core lipids and the resulting TEX86 paleothermometer in pure cultures of the marine AOA Nitrosopumilus maritimus as a function of growth phase. The cellular lipid content ranged from 0.9 to 1.9 fg cell-1 and increased during growth but was lower in the stationary phases, indicating changes in average cell size in response to metabolic status. The relative abundances of monoglycosidic GDGTs increased from 27% in early growth phase to 60% in late stationary phase, while monohydroxylated GDGTs increased only slightly. The proportions of characteristic hexose-phosphohexose GDGTs were up to 7-fold higher during growth than in stationary phase, suggesting that they are valuable biomarkers for the metabolically active fraction of AOA assemblages in the environment. Methoxy archaeol was identified as novel, genuine archaeal lipid of yet unknown function; it is one of the most abundant single compounds in the lipidome of N. maritimus. TEX86 values of individual intact GDGTs and total GDGTs differed substantially, were generally lower during early and late growth phases than in stationary phase, and did not reflect growth temperature. Consequently, our results strongly suggest that biosynthesis is at least partially responsible for the systematic offsets in TEX86 values between different intact polar GDGT classes observed previously in environmental samples

  14. Lysine and novel hydroxylysine lipids in soil bacteria: amino acid membrane lipid response to temperature and pH in Pseudopedobacter saltans

    PubMed Central

    Moore, Eli K.; Hopmans, Ellen C.; Rijpstra, W. Irene C.; Sánchez-Andrea, Irene; Villanueva, Laura; Wienk, Hans; Schoutsen, Frans; Stams, Alfons J. M.; Sinninghe Damsté, Jaap S.

    2015-01-01

    Microbial decomposition of organic matter is an essential process in the global carbon cycle. The soil bacteria Pseudopedobacter saltans and Flavobacterium johnsoniae are both able to degrade complex organic molecules, but it is not fully known how their membrane structures are adapted to their environmental niche. The membrane lipids of these species were extracted and analyzed using high performance liquid chromatography-electrospray ionization/ion trap/mass spectrometry (HPLC-ESI/IT/MS) and high resolution accurate mass/mass spectrometry (HRAM/MS). Abundant unknown intact polar lipids (IPLs) from P. saltans were isolated and further characterized using amino acid analysis and two dimensional nuclear magnetic resonance (NMR) spectroscopy. Ornithine IPLs (OLs) with variable (hydroxy) fatty acid composition were observed in both bacterial species. Lysine-containing IPLs (LLs) were also detected in both species and were characterized here for the first time using HPLC-MS. Novel LLs containing hydroxy fatty acids and novel hydroxylysine lipids with variable (hydroxy) fatty acid composition were identified in P. saltans. The confirmation of OL and LL formation in F. johnsoniae and P. saltans and the presence of OlsF putative homologs in P. saltans suggest the OlsF gene coding protein is possibly involved in OL and LL biosynthesis in both species, however, potential pathways of OL and LL hydroxylation in P. saltans are still undetermined. Triplicate cultures of P. saltans were grown at three temperature/pH combinations: 30°C/pH 7, 15°C/pH 7, and 15°C/pH 9. The fractional abundance of total amino acid containing IPLs containing hydroxylated fatty acids was significantly higher at higher temperature, and the fractional abundance of lysine-containing IPLs was significantly higher at lower temperature and higher pH. These results suggest that these amino acid-containing IPLs, including the novel hydroxylysine lipids, could be involved in temperature and pH stress

  15. Lipid biomarkers of thermal stress in scleractinian corals

    NASA Astrophysics Data System (ADS)

    Kneeland, J. M.; Hughen, K.; Cervino, J.; Eglinton, T. I.; Bartels, E.

    2007-12-01

    Lipid content and fatty acid profiles of corals and their symbiotic dinoflagellates are known to vary in response to heat stress and bleaching. To develop lipid biomarkers of heat stress and bleaching response in scleractinian corals, clones of Symbiodinium algae of clade subtypes C1 and D1 were cultured under a range of temperatures. The predominant lipids produced are palmitic (C16) and stearic (C18) saturated fatty acids and their unsaturated analogs. Other important compounds included a C22 penta-unsaturated fatty acid, which is thought to be a specific dinoflagellate marker, and a variety of sterols. Analysis of lipids extracted from coral skeleton indicated that palmitic and stearic acids were the most abundant compounds. The amount of unsaturated C16 and C18 fatty acids in coral skeleton relative to the saturated versions of those acids was much lower in coral skeleton than in the zooxanthellae tissue. This could indicate the incorporation of lipids from outside the coral host-symbiont system into the coral aragonite, or it could reflect diagenesis. A comparison between the lipids found in cloned zooxanthellae, coral tissue, and aragonitic skeleton will be presented to assess the usefulness of lipid biomarkers as indicators of temperature stress on corals.

  16. Polychlorinated biphenyl exposure, diabetes and endogenous hormones: a cross-sectional study in men previously employed at a capacitor manufacturing plant

    PubMed Central

    2012-01-01

    Background Studies have shown associations of diabetes and endogenous hormones with exposure to a wide variety of organochlorines. We have previously reported positive associations of polychlorinated biphenyls (PCBs) and inverse associations of selected steroid hormones with diabetes in postmenopausal women previously employed in a capacitor manufacturing plant. Methods This paper examines associations of PCBs with diabetes and endogenous hormones in 63 men previously employed at the same plant who in 1996 underwent surveys of their exposure and medical history and collection of bloods and urine for measurements of PCBs, lipids, liver function, hematologic markers and endogenous hormones. Results PCB exposure was positively associated with diabetes and age and inversely associated with thyroid stimulating hormone and triiodothyronine-uptake. History of diabetes was significantly related to total PCBs and all PCB functional groupings, but not to quarters worked and job score, after control for potential confounders. None of the exposures were related to insulin resistance (HOMA-IR) in non-diabetic men. Conclusions Associations of PCBs with specific endogenous hormones differ in some respects from previous findings in postmenopausal women employed at the capacitor plant. Results from this study, however, do confirm previous reports relating PCB exposure to diabetes and suggest that these associations are not mediated by measured endogenous hormones. PMID:22931295

  17. Polychlorinated biphenyl exposure, diabetes and endogenous hormones: a cross-sectional study in men previously employed at a capacitor manufacturing plant.

    PubMed

    Persky, Victoria; Piorkowski, Julie; Turyk, Mary; Freels, Sally; Chatterton, Robert; Dimos, John; Bradlow, H Leon; Chary, Lin Kaatz; Burse, Virlyn; Unterman, Terry; Sepkovic, Daniel W; McCann, Kenneth

    2012-08-29

    Studies have shown associations of diabetes and endogenous hormones with exposure to a wide variety of organochlorines. We have previously reported positive associations of polychlorinated biphenyls (PCBs) and inverse associations of selected steroid hormones with diabetes in postmenopausal women previously employed in a capacitor manufacturing plant. This paper examines associations of PCBs with diabetes and endogenous hormones in 63 men previously employed at the same plant who in 1996 underwent surveys of their exposure and medical history and collection of bloods and urine for measurements of PCBs, lipids, liver function, hematologic markers and endogenous hormones. PCB exposure was positively associated with diabetes and age and inversely associated with thyroid stimulating hormone and triiodothyronine-uptake. History of diabetes was significantly related to total PCBs and all PCB functional groupings, but not to quarters worked and job score, after control for potential confounders. None of the exposures were related to insulin resistance (HOMA-IR) in non-diabetic men. Associations of PCBs with specific endogenous hormones differ in some respects from previous findings in postmenopausal women employed at the capacitor plant. Results from this study, however, do confirm previous reports relating PCB exposure to diabetes and suggest that these associations are not mediated by measured endogenous hormones.

  18. LTRs of Endogenous Retroviruses as a Source of Tbx6 Binding Sites

    PubMed Central

    Yasuhiko, Yukuto; Hirabayashi, Yoko; Ono, Ryuichi

    2017-01-01

    Retrotransposons are abundant in mammalian genomes and can modulate the gene expression of surrounding genes by disrupting endogenous binding sites for transcription factors (TFs) or providing novel TFs binding sites within retrotransposon sequences. Here, we show that a (C/T)CACACCT sequence motif in ORR1A, ORR1B, ORR1C, and ORR1D, Long Terminal Repeats (LTRs) of MaLR endogenous retrovirus (ERV), is the direct target of Tbx6, an evolutionary conserved family of T-box TFs. Moreover, by comparing gene expression between control mice (Tbx6 +/−) and Tbx6-deficient mice (Tbx6 −/−), we demonstrate that at least four genes, Twist2, Pitx2, Oscp1, and Nfxl1, are down-regulated with Tbx6 deficiency. These results suggest that ORR1A, ORR1B, ORR1C and ORR1D may contribute to the evolution of mammalian embryogenesis. PMID:28664156

  19. CD1a presentation of endogenous antigens by group 2 innate lymphoid cells.

    PubMed

    Hardman, Clare S; Chen, Yi-Ling; Salimi, Maryam; Jarrett, Rachael; Johnson, David; Järvinen, Valtteri J; Owens, Raymond J; Repapi, Emmanouela; Cousins, David J; Barlow, Jillian L; McKenzie, Andrew N J; Ogg, Graham

    2017-12-22

    Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells. CD1a expression is up-regulated by TSLP (thymic stromal lymphopoietin) at levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a previously unrecognized role for ILC2 in lipid surveillance and identify shared pathways of CD1a- and PLA2G4A-dependent ILC2 inflammation amenable to therapeutic intervention. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  20. Bacterial and Archaeal Lipids Recovered from Subsurface Evaporites of Dalangtan Playa on the Tibetan Plateau and Their Astrobiological Implications

    NASA Astrophysics Data System (ADS)

    Cheng, Ziye; Xiao, Long; Wang, Hongmei; Yang, Huan; Li, Jingjing; Huang, Ting; Xu, Yi; Ma, Nina

    2017-11-01

    Qaidam Basin (Tibetan Plateau) is considered an applicable analogue to Mars with regard to sustained extreme aridity and abundant evaporites. To investigate the possibility of the preservation of microbial lipids under these Mars analog conditions, we conducted a mineralogical and organic geochemistry study on samples collected from two Quaternary sections in Dalangtan Playa, northwestern Qaidam Basin, which will enhance our understanding of the potential preservation of molecular biomarkers on Mars. Two sedimentary units were identified along two profiles: one salt unit characterized by a predominance of gypsum and halite, and one detrital unit with a decrease of gypsum and halite and enrichment in siliciclastic minerals. Bacterial fatty acids and archaeal acyclic diether and tetraether membrane lipids were detected, and they varied throughout the sections in concentration and abundance. Bacterial and archaeal biomolecules indicate a dominance of Gram-positive bacteria and halophilic archaea in this hypersaline ecosystem that is similar to those in other hypersaline environments. Furthermore, the abundance of bacterial lipids decreases with the increase of salinity, whereas archaeal lipids showed a reverse trend. The detection of microbial lipids in hypersaline environments would indicate, for example on Mars, a high potential for the detection of microbial biomarkers in evaporites over geological timescales.

  1. Influence of Blood Lipids on Global Coagulation Test Results

    PubMed Central

    Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon

    2015-01-01

    Background High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). Methods PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). Results The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. Conclusion High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels. PMID:25553275

  2. Effects of Consuming Xylitol on Gut Microbiota and Lipid Metabolism in Mice.

    PubMed

    Uebanso, Takashi; Kano, Saki; Yoshimoto, Ayumi; Naito, Chisato; Shimohata, Takaaki; Mawatari, Kazuaki; Takahashi, Akira

    2017-07-14

    The sugar alcohol xylitol inhibits the growth of some bacterial species including Streptococcus mutans . It is used as a food additive to prevent caries. We previously showed that 1.5-4.0 g/kg body weight/day xylitol as part of a high-fat diet (HFD) improved lipid metabolism in rats. However, the effects of lower daily doses of dietary xylitol on gut microbiota and lipid metabolism are unclear. We examined the effect of 40 and 200 mg/kg body weight/day xylitol intake on gut microbiota and lipid metabolism in mice. Bacterial compositions were characterized by denaturing gradient gel electrophoresis and targeted real-time PCR. Luminal metabolites were determined by capillary electrophoresis electrospray ionization time-of-flight mass spectrometry. Plasma lipid parameters and glucose tolerance were examined. Dietary supplementation with low- or medium-dose xylitol (40 or 194 mg/kg body weight/day, respectively) significantly altered the fecal microbiota composition in mice. Relative to mice not fed xylitol, the addition of medium-dose xylitol to a regular and HFD in experimental mice reduced the abundance of fecal Bacteroidetes phylum and the genus Barnesiella , whereas the abundance of Firmicutes phylum and the genus Prevotella was increased in mice fed an HFD with medium-dose dietary xylitol. Body composition, hepatic and serum lipid parameters, oral glucose tolerance, and luminal metabolites were unaffected by xylitol consumption. In mice, 40 and 194 mg/kg body weight/day xylitol in the diet induced gradual changes in gut microbiota but not in lipid metabolism.

  3. Effects of Consuming Xylitol on Gut Microbiota and Lipid Metabolism in Mice

    PubMed Central

    Uebanso, Takashi; Kano, Saki; Yoshimoto, Ayumi; Naito, Chisato; Shimohata, Takaaki; Takahashi, Akira

    2017-01-01

    The sugar alcohol xylitol inhibits the growth of some bacterial species including Streptococcus mutans. It is used as a food additive to prevent caries. We previously showed that 1.5–4.0 g/kg body weight/day xylitol as part of a high-fat diet (HFD) improved lipid metabolism in rats. However, the effects of lower daily doses of dietary xylitol on gut microbiota and lipid metabolism are unclear. We examined the effect of 40 and 200 mg/kg body weight/day xylitol intake on gut microbiota and lipid metabolism in mice. Bacterial compositions were characterized by denaturing gradient gel electrophoresis and targeted real-time PCR. Luminal metabolites were determined by capillary electrophoresis electrospray ionization time-of-flight mass spectrometry. Plasma lipid parameters and glucose tolerance were examined. Dietary supplementation with low- or medium-dose xylitol (40 or 194 mg/kg body weight/day, respectively) significantly altered the fecal microbiota composition in mice. Relative to mice not fed xylitol, the addition of medium-dose xylitol to a regular and HFD in experimental mice reduced the abundance of fecal Bacteroidetes phylum and the genus Barnesiella, whereas the abundance of Firmicutes phylum and the genus Prevotella was increased in mice fed an HFD with medium-dose dietary xylitol. Body composition, hepatic and serum lipid parameters, oral glucose tolerance, and luminal metabolites were unaffected by xylitol consumption. In mice, 40 and 194 mg/kg body weight/day xylitol in the diet induced gradual changes in gut microbiota but not in lipid metabolism. PMID:28708089

  4. High-throughput and rapid quantification of lipids by nanoflow UPLC-ESI-MS/MS: application to the hepatic lipids of rabbits with nonalcoholic fatty liver disease.

    PubMed

    Byeon, Seul Kee; Lee, Jong Cheol; Chung, Bong Chul; Seo, Hong Seog; Moon, Myeong Hee

    2016-07-01

    A rapid and high-throughput quantification method (approximately 300 lipids within 20 min) was established using nanoflow ultrahigh-pressure liquid chromatography-tandem mass spectrometry (nUPLC-ESI-MS/MS) with selective reaction monitoring (SRM) and applied to the quantitative profiling of the hepatic lipids of rabbits with different metabolic conditions that stimulate the development of nonalcoholic fatty liver disease (NAFLD). Among the metabolic conditions of rabbits in this study [inflammation (I), high-cholesterol diet (HC), and high-cholesterol diet combined with inflammation (HCI)], significant perturbation in hepatic lipidome (>3-fold and p < 0.01) was observed in the HC and HCI groups, while no single lipid showed a significant change in group I. In addition, this study revealed a dramatic increase (>2-fold) in relatively high-abundant monohexosylceramides (MHCs), sphingomyelins (SMs), and triacylglycerols (TGs) in both the HC and HCI groups, especially in MHCs as all 11 MHCs increased by larger than 3- to 12-fold. As the levels of the relatively high-abundant lipids in the above classes increased, the total lipidome level of each class increased significantly by approximately 2-fold to 5-fold. Other classes of lipids also generally increased, which was likely induced by the increase in mitogenic and nonapoptotic MHCs and SMs, as they promote cell proliferation. On the other hand, a slight decrease in the level of apoptotic ceramides (Cers) was observed, which agreed with the general increase in total lipid level. As distinct changes in hepatic lipidome were observed from HC groups, this suggests that HC or HCI is highly associated with NAFLD but not inflammation alone itself. Graphical Abstract Schematic of lipidomic analysis from hepatic tissue using nanoflow LC-ESI-MS/MS and nUPLC-ESI-MS/MS.

  5. Linking Archaeal Molecular Diversity and Lipid Biomarker Composition in a Hypersaline Microbial Mat Community

    NASA Technical Reports Server (NTRS)

    Jahnke, Linda; Orphan, Victoria; Turk, Kendra; Embaye, Tsegereda; Kubo, Mike; Summons, Roger

    2005-01-01

    Lipid biomarkers for discrete microbial groups are a valuable tool for establishing links to ancient microbial ecosystems. Lipid biomarkers can establish organism source and function in contemporary microbial ecosystems (membrane lipids) and by analogy, potential relevance to the fossilized carbon skeletons (geolipids) extracted from ancient sedimentary rock. The Mars Exploration Rovers have provided clear evidence for an early wet Mars and the presence of hypersaline evaporitic basins. Ongoing work on an early Earth analog, the hypersaline benthic mats in Guerrero Negro, Baja California Sur, may provide clues to what may have evolved and flourished on an early wet Mars, if only for a short period. Cyanobacterial mats are a pertinent early Earth analog for consideration of evolutionary and microbial processes within the aerobic photosynthetic and adjacent anoxic layers. Fluctuations in physio-chemical parameters associated with spatial and temporal scales are expressed through vast microbial metabolic diversity. Our recent work hopes to establish the dynamic of archaeal diversity, particularly as it relates to methane production in this high sulfate environment, through the use of lipid biomarker and phylogenetic analyses. Archaeal 16s rRNA and mcrA gene assemblages, demonstrated distinct spatial separation over the 130 mm core of at least three distinct genera within the order Methanosarcinales, as well as an abundance of uncultured members of the Thermoplasmales and Crenarchaeota. Ether-bound lipid analysis identified abundant 0-alkyl and 0-isopranyl chains throughout the core, and the presence of sn-2 hydroxyarchaeol, a biomarker for methylotrophic methanogens. A unique ether isoprenoid chain, a C30:1 , possibly related to the geolipid squalane, a paleobiomarker associated with hypersaline environments, was most abundant within the oxic-anoxic transition zone.

  6. Formation of 7-(2-oxoethyl) guanine from lipid peroxidation and vinyl chloride exposure in male sprague dawley rats.

    EPA Science Inventory

    With a development of a new sensitive LC-MS/MS method to analyze 7-(2-oxoethylguanine) (7OEG), we confirmed and differentiated 7-0EG DNA adduct formation endogenously from lipid peroxidation and exogenously from Vinyl Chloride (VC) exposure. VC is an industrial chemical that is ...

  7. Immunostimulatory Properties of Lipid Modified CpG Oligonucleotides.

    PubMed

    Yu, Chunsong; An, Myunggi; Li, Meng; Liu, Haipeng

    2017-08-07

    Innate immune responses recognizing pathogen associated molecular patterns play important roles in adaptive immunity. As such, ligands which mimic the conserved products of microbial and activate innate immunity are widely used as adjuvants for vaccines. Synthetic single strand oligodeoxynucleotides (ODNs) containing unmethylated cytosine-guanine (CpG) motifs which bind Toll-like receptor 9 (TLR9) are powerful molecular adjuvants, potentiating both humoral and cellular responses. However, CpG ODN's in vitro potency has not been translated to in vivo settings primarily due to issues associated with delivery and toxicity. A major challenge in clinical application of CpG ODN is the efficient delivery to lymph nodes, the anatomic sites where all the immune responses are initiated. Targeting CpG to the key antigen presenting cells (APC) is essential for its application as a vaccine adjuvant, as it not only enhances CpG's efficacy, but also greatly reduces the systemic toxicity. We recently discovered an "albumin-hitchhiking" approach by which CpG ODNs were conjugated to a lipophilic lipid tail and follow subcutaneous injection, accumulated in lymph nodes by binding and transporting with endogenous albumin. This molecular approach targets CpG to antigen presenting cells in the draining lymph nodes via an endogenous albumin-mediated mechanism and simultaneously improves both the efficacy and safety of CpG as a vaccine adjuvant. Since CpG ODNs can be divided into structurally distinct classes, and each class of CpG ODN activates different types of immune cells and triggers different types of immunostimulatory activities, it is important to thoroughly evaluate the efficacy of this "albumin-hitchhiking" strategy in each class of CpG. Here we compare the immunostimulatory activities of three classes of lipid conjugated CpG ODNs in vitro and in vivo. Three representative sequences of lipid modified CpG ODNs were synthesized and their stimulatory effects as a vaccine adjuvant

  8. Mechanistic Peptidomics: Factors That Dictate Specificity in the Formation of Endogenous Peptides in Human Milk*

    PubMed Central

    Guerrero, Andres; Dallas, David C.; Contreras, Stephanie; Chee, Sabrina; Parker, Evan A.; Sun, Xin; Dimapasoc, Lauren; Barile, Daniela; German, J. Bruce; Lebrilla, Carlito B.

    2014-01-01

    An extensive mass spectrometry analysis of the human milk peptidome has revealed almost 700 endogenous peptides from 30 different proteins. Two in-house computational tools were created and used to visualize and interpret the data through both alignment of the peptide quasi-molecular ion intensities and estimation of the differential enzyme participation. These results reveal that the endogenous proteolytic activity in the mammary gland is remarkably specific and well conserved. Certain proteins—not necessarily the most abundant ones—are digested by the proteases present in milk, yielding endogenous peptides from selected regions. Our results strongly suggest that factors such as the presence of specific proteases, the position and concentration of cleavage sites, and, more important, the intrinsic disorder of segments of the protein drive this proteolytic specificity in the mammary gland. As a consequence of this selective hydrolysis, proteins that typically need to be cleaved at specific positions in order to exert their activity are properly digested, and bioactive peptides encoded in certain protein sequences are released. Proteins that must remain intact in order to maintain their activity in the mammary gland or in the neonatal gastrointestinal tract are unaffected by the hydrolytic environment present in milk. These results provide insight into the intrinsic structural mechanisms that facilitate the selectivity of the endogenous milk protease activity and might be useful to those studying the peptidomes of other biofluids. PMID:25172956

  9. A statistical and experimental approach for assessing the preservation of plant lipids in soil

    NASA Astrophysics Data System (ADS)

    Mueller, K. E.; Eissenstat, D. M.; Oleksyn, J.; Freeman, K. H.

    2011-12-01

    Plant-derived lipids contribute to stable soil organic matter, but further interpretations of their abundance in soils are limited because the factors that control lipid preservation are poorly understood. Using data from a long-term field experiment and simple statistical models, we provide novel constraints on several predictors of the concentration of hydrolyzable lipids in forest mineral soils. Focal lipids included common monomers of cutin, suberin, and plant waxes present in tree leaves and roots. Soil lipid concentrations were most strongly influenced by the concentrations of lipids in leaves and roots of the overlying trees, but were also affected by the type of lipid (e.g. alcohols vs. acids), lipid chain length, and whether lipids originated in leaves or roots. Collectively, these factors explained ~80% of the variation in soil lipid concentrations beneath 11 different tree species. In order to use soil lipid analyses to test and improve conceptual models of soil organic matter stabilization, additional studies that provide experimental and quantitative (i.e. statistical) constraints on plant lipid preservation are needed.

  10. A scalable strategy for high-throughput GFP tagging of endogenous human proteins.

    PubMed

    Leonetti, Manuel D; Sekine, Sayaka; Kamiyama, Daichi; Weissman, Jonathan S; Huang, Bo

    2016-06-21

    A central challenge of the postgenomic era is to comprehensively characterize the cellular role of the ∼20,000 proteins encoded in the human genome. To systematically study protein function in a native cellular background, libraries of human cell lines expressing proteins tagged with a functional sequence at their endogenous loci would be very valuable. Here, using electroporation of Cas9 nuclease/single-guide RNA ribonucleoproteins and taking advantage of a split-GFP system, we describe a scalable method for the robust, scarless, and specific tagging of endogenous human genes with GFP. Our approach requires no molecular cloning and allows a large number of cell lines to be processed in parallel. We demonstrate the scalability of our method by targeting 48 human genes and show that the resulting GFP fluorescence correlates with protein expression levels. We next present how our protocols can be easily adapted for the tagging of a given target with GFP repeats, critically enabling the study of low-abundance proteins. Finally, we show that our GFP tagging approach allows the biochemical isolation of native protein complexes for proteomic studies. Taken together, our results pave the way for the large-scale generation of endogenously tagged human cell lines for the proteome-wide analysis of protein localization and interaction networks in a native cellular context.

  11. How relevant are assembled equilibrium samples in understanding structure formation during lipid digestion?

    PubMed

    Phan, Stephanie; Salentinig, Stefan; Hawley, Adrian; Boyd, Ben J

    2015-10-01

    Lipid-based formulations are gaining interest for use as drug delivery systems for poorly water-soluble drug compounds. During digestion, the lipolysis products self-assemble with endogenous surfactants in the gastrointestinal tract to form colloidal structures, enabling enhanced drug solubilisation. Although earlier studies in the literature focus on assembled equilibrium systems, little is known about structure formation under dynamic lipolysis conditions. The purpose of this study was to investigate the likely colloidal structure formation in the small intestine after the ingestion of lipids, under equilibrium and dynamic conditions. The structural aspects were studied using small angle X-ray scattering and dynamic light scattering, and were found to depend on lipid composition, lipid chain length, prandial state and emulsification. Incorporation of phospholipids and lipolysis products into bile salt micelles resulted in swelling of the structure. At insufficient bile salt concentrations, a co-existing lamellar phase was observed, due to a reduction in the solubilisation capacity for lipolysis products. Emulsification accelerated the rate of lipolysis and structure formation. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. [The influence of the actoprotectors on lipid peroxidation and erythrocyte membranes in rats poisoned with malathion ].

    PubMed

    Myshkin, V A; Guliaeva, I A; Ibatullina, R B; Savlukov, A I; Enikeev, D A; Sergeeva, S A

    2004-01-01

    Actoprotecting properties ofbemitil, tietasol in combination with atropin were studied in red cell membranes and lipid peroxidation of rats poisoned with MI in a dose 320 mg/kg (0.9 LD50). Atropin treatment showed a low effect. The addition of bemitil and tietasol normalized electric charge and osmotic resistance in red cell membranes, activity of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase and content of lipid peroxidation products--ketodienes and TBA-reacting products. Efficacy of the combined treatment is due primarily to noncholinergic mechanism of action of bemitil and tietasol--stimulation of endogenic antioxidant systems of erythron and antiradical activity (bemitil).

  13. Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review

    PubMed Central

    Meng, Shengxi; Cao, Jianmei; Feng, Qin; Peng, Jinghua; Hu, Yiyang

    2013-01-01

    Intracellular glucose and lipid metabolic homeostasis is vital for maintaining basic life activities of a cell or an organism. Glucose and lipid metabolic disorders are closely related with the occurrence and progression of diabetes, obesity, hepatic steatosis, cardiovascular disease, and cancer. Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in the human diet, is a group of phenolic secondary metabolites produced by certain plant species and is an important component of coffee. Accumulating evidence has demonstrated that CGA exerts many biological properties, including antibacterial, antioxidant, and anticarcinogenic activities. Recently, the roles and applications of CGA, particularly in relation to glucose and lipid metabolism, have been highlighted. This review addresses current studies investigating the roles of CGA in glucose and lipid metabolism. PMID:24062792

  14. Extended synaptotagmins are Ca2+-dependent lipid transfer proteins at membrane contact sites.

    PubMed

    Yu, Haijia; Liu, Yinghui; Gulbranson, Daniel R; Paine, Alex; Rathore, Shailendra S; Shen, Jingshi

    2016-04-19

    Organelles are in constant communication with each other through exchange of proteins (mediated by trafficking vesicles) and lipids [mediated by both trafficking vesicles and lipid transfer proteins (LTPs)]. It has long been known that vesicle trafficking can be tightly regulated by the second messenger Ca(2+), allowing membrane protein transport to be adjusted according to physiological demands. However, it remains unclear whether LTP-mediated lipid transport can also be regulated by Ca(2+) In this work, we show that extended synaptotagmins (E-Syts), poorly understood membrane proteins at endoplasmic reticulum-plasma membrane contact sites, are Ca(2+)-dependent LTPs. Using both recombinant and endogenous mammalian proteins, we discovered that E-Syts transfer glycerophospholipids between membrane bilayers in the presence of Ca(2+) E-Syts use their lipid-accommodating synaptotagmin-like mitochondrial lipid binding protein (SMP) domains to transfer lipids. However, the SMP domains themselves cannot transport lipids unless the two membranes are tightly tethered by Ca(2+)-bound C2 domains. Strikingly, the Ca(2+)-regulated lipid transfer activity of E-Syts was fully recapitulated when the SMP domain was fused to the cytosolic domain of synaptotagmin-1, the Ca(2+)sensor in synaptic vesicle fusion, indicating that a common mechanism of membrane tethering governs the Ca(2+)regulation of lipid transfer and vesicle fusion. Finally, we showed that microsomal vesicles isolated from mammalian cells contained robust Ca(2+)-dependent lipid transfer activities, which were mediated by E-Syts. These findings established E-Syts as a novel class of LTPs and showed that LTP-mediated lipid trafficking, like vesicular transport, can be subject to tight Ca(2+)regulation.

  15. Influence of liver cancer on lipid and lipoprotein metabolism

    PubMed Central

    Jiang, Jingting; Nilsson-Ehle, Peter; Xu, Ning

    2006-01-01

    Liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma (HCC) is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. This has been attributed to the high incidence of hepatitis B infection. Hepatitis B proteins, such as the hepatitis B X protein (HBx) that is large hepatitis B surface protein could regulate transcription of many candidate genes for liver carcinogenesis. It has known that patients who suffered from acute hepatitis B could have lipid disorders such as decreased plasma level of high-density lipoproteins (HDL). Furthermore, aberrations of lipid metabolism are often seen in the chronic hepatitis B infection. Plasma lipid profiles could be changed under HCC. In majority of the reports in HCC, plasma levels of triglycerides (TG), cholesterol, free fatty acids (FFA), HDL, low-density lipoproteins (LDL), lipoprotein (a) (Lp(a)), apolipoprotein AI (apoAI) and apoB were slight to significantly decreased, however, in some cases plasma levels of TG and Lp(a) might be increased. It has been suggested that analysis of plasma levels of lipids, lipoproteins and apolipoproteins in the patients suffered from HCC reflects on the hepatic cellular impairment status. Studies revealed that alterations seen in the plasma levels of lipids, lipoproteins and apolipoproteins reflecting patients' pathologic conditions. Decreased serum levels of cholesterol and apoAI may indicate a poor prognosis. Human leukaemic cells and certain tumor tissues have a higher receptor-mediated uptake of HDL and LDL than the corresponding normal cells or tissues. LDL and HDL have therefore been proposed as a carrier for the water-insoluble anti-cancer agents. PMID:16515689

  16. Distributions and Transformations of Natural Abundance 14C and 13C in Dissolved and Particulate Lipids in a Major Temperate Estuary

    NASA Astrophysics Data System (ADS)

    Bauer, J. E.; Canuel, E. A.; McIntosh, H.; Barrett, A.; Ferer, E.; Hossler, K.

    2013-12-01

    Limited previous studies have shown major differences in the natural 14C and 13C isotopic signatures and radiocarbon ages of different biochemical classes (e.g., proteins, carbohydrates, lipid, etc.) in river, estuarine and marine dissolved and particulate organic matter (DOM and POM, respectively). Of particular note are the much greater radiocarbon ages of lipophilic materials than other compound classes. Possible explanations for these findings include greater-than-expected inputs of fossil and highly aged lipid-containing organic matter to rivers and estuaries, extended sorptive-protection of lipophilic materials from degradation and/or lower overall reactivities of lipids vs. other major biochemical classes. We measured the Delta 14C and del 13C signatures and 14C ages of lipid classes in DOM and POM in a major temperate estuary, Delaware Bay (USA) over two years. Changes in DOM were also followed during large volume dark and light incubations to assess the microbial and photochemical reactivity and processing of DOM and lipids. Neutral lipids in DOM were among the most highly aged (> 30,000 yrs BP) of any materials measured in natural waters to date, and were significantly older than co-occurring polar lipids (~4,000-5,000 yrs BP). In general, DOM lipid ages were significantly greater than POM lipid ages across the river-estuary transect, arguing against sorptive protection as the major factor explaining greater ages of lipid than those of other compound classes. Both dark and light incubations of DOM resulted in losses of very highly aged material (30-50,000 y BP), with the remnant exported lipids being correspondingly younger. The microbial and photochemical alterations were most pronounced for lipids from freshwater reaches of the system (i.e., the Delaware River). These findings suggest that a) dissolved vs. particulate lipids have fundamentally different sources and/or physico-chemical partitioning, b) different lipid classes (e.g., neutral vs. polar

  17. Obesity in mares promotes uterine inflammation and alters embryo lipid fingerprints and homeostasis.

    PubMed

    Sessions-Bresnahan, Dawn R; Heuberger, Adam L; Carnevale, Elaine M

    2018-05-07

    Maternal body composition can be an important determinant for development of obesity and metabolic syndrome in adult offspring. Obesity-related outcomes in offspring may include epigenetic alterations; however, mechanisms of fetal programming remain to be fully elucidated. This study was conducted to determine the impact of maternal obesity in the absence of a high fat diet on equine endometrium and preimplantation embryos. Embryos were collected from normal and obese mares at 8 and 16 d and a uterine biopsy at 16 d (0 d = ovulation). With the exception of 8 d embryos, each sample was divided into two pieces. One piece was analyzed for gene expression markers related to carbohydrate metabolism, lipid homeostasis, inflammation, endoplasmic reticulum stress, oxidative stress, mitochondrial stress, and components of the insulin-like growth factor (IGF) system. The second piece was analyzed for lipid content using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Obese mares had elevated concentrations of insulin, leptin and total cholesterol, and they tended to have increased triglycerides and decreased insulin sensitivity. Embryos from obese mares had altered transcript abundance in genes for inflammation and lipid homeostasis, as well as, endoplasmic reticulum, oxidative and mitochondrial stress and altered lipid fingerprints. Endometrium from obese mares had increased expression of inflammatory cytokines, lipid homeostasis regulation, mitochondrial stress, and the IGF2 system. This study demonstrates increased adiposity in mares alters the uterine environment, transcript abundance of genes for cellular functions, and lipid profiles of embryos. These alterations could affect prenatal programming, with potential long-term effects in offspring.

  18. Organization of Lipids in the Tear Film: A Molecular-Level View

    PubMed Central

    Wizert, Alicja; Iskander, D. Robert; Cwiklik, Lukasz

    2014-01-01

    Biophysical properties of the tear film lipid layer are studied at the molecular level employing coarse grain molecular dynamics (MD) simulations with a realistic model of the human tear film. In this model, polar lipids are chosen to reflect the current knowledge on the lipidome of the tear film whereas typical Meibomian-origin lipids are included in the thick non-polar lipids subphase. Simulation conditions mimic those experienced by the real human tear film during blinks. Namely, thermodynamic equilibrium simulations at different lateral compressions are performed to model varying surface pressure, and the dynamics of the system during a blink is studied by non-equilibrium MD simulations. Polar lipids separate their non-polar counterparts from water by forming a monomolecular layer whereas the non-polar molecules establish a thick outermost lipid layer. Under lateral compression, the polar layer undulates and a sorting of polar lipids occurs. Moreover, formation of three-dimensional aggregates of polar lipids in both non-polar and water subphases is observed. We suggest that these three-dimensional structures are abundant under dynamic conditions caused by the action of eye lids and that they act as reservoirs of polar lipids, thus increasing stability of the tear film. PMID:24651175

  19. On the origins of the universal dynamics of endogenous granules in mammalian cells.

    PubMed

    Vanapalli, Siva A; Li, Yixuan; Mugele, Frieder; Duits, Michel H G

    2009-12-01

    Endogenous granules (EGs) that consist of lipid droplets and mitochondria have been commonly used to assess intracellular mechanical properties via multiple particle tracking microrheology (MPTM). Despite their widespread use, the nature of interaction of EGs with the cytoskeletal network and the type of forces driving their dynamics--both of which are crucial for the interpretation of the results from MPTM technique--are yet to be resolved. In this report, we study the dynamics of endogenous granules in mammalian cells using particle tracking methods. We find that the ensemble dynamics of EGs is diffusive in three types of mammalian cells (endothelial cells, smooth muscle cells and fibroblasts), thereby suggesting an apparent universality in their dynamical behavior. Moreover, in a given cell, the amplitude of the mean-squared displacement for EGs is an order of magnitude larger than that of injected particles. This observation along with results from ATP depletion and temperature intervention studies suggests that cytoskeletal active forces drive the dynamics of EGs. To elucidate the dynamical origin of the diffusive-like nonthermal motion, we consider three active force generation mechanisms--molecular motor transport, actomyosin contractility and microtubule polymerization forces. We test these mechanisms using pharmacological interventions. Experimental evidence and model calculations suggest that EGs are intimately linked to microtubules and that microtubule polymerization forces drive their dynamics. Thus, endogenous granules could serve as non-invasive probes for microtubule network dynamics in mammalian cells.

  20. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans

    PubMed Central

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

    2017-01-01

    Objective Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers LDL cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly-mixing endogenous cholesterol pool into the stool. Approach and Results In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with LDL cholesterol 100–200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/day or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d7 in a lipid emulsion and dietary cholesterol with cholesterol-d5 and sitostanol-d4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30 ± 4.3% (SE, P < 0.0001) and LDL cholesterol 19.8 ± 1.9% (P = 0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6 ± 12.2% (P < 0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7 ± 14.3% (P < 0.0001) while plasma cholesterol turnover rose 26.2 ± 3.6% (P = 0.0096). Fecal bile acids were unchanged. Conclusions Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly-mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. PMID:28279967

  1. Rapid quantification of neutral lipids and triglycerides during zebrafish embryogenesis.

    PubMed

    Yoganantharjah, Prusothman; Byreddy, Avinesh R; Fraher, Daniel; Puri, Munish; Gibert, Yann

    2017-01-01

    The zebrafish is a useful vertebrate model to study lipid metabolism. Oil Red-O (ORO) staining of zebrafish embryos, though sufficient for visualizing the localization of triglycerides, was previously inadequate to quantify neutral lipid abundance. For metabolic studies, it is crucial to be able to quantify lipids during embryogenesis. Currently no cost effective, rapid and reliable method exists to quantify the deposition of neutral lipids and triglycerides. Thin layer chromatography (TLC), gas chromatography and mass spectrometry can be used to accurately measure lipid levels, but are time consuming and costly in their use. Hence, we developed a rapid and reliable method to quantify neutral lipids and triglycerides. Zebrafish embryos were exposed to Rimonabant (Rimo) or WIN 55,212-2 mesylate (WIN), compounds previously shown to modify lipid content during zebrafish embryogenesis. Following this, ORO stain was extracted out of both the zebrafish body and yolk sac and optical density was measured to give an indication of neutral lipid and triglyceride accumulation. Embryos treated with 0.3 microM WIN resulted in increased lipid accumulation, whereas 3 microM Rimo caused a decrease in lipid accumulation during embryogenesis. TLC was performed on zebrafish bodies to validate the developed method. In addition, BODIPY free fatty acids were injected into zebrafish embryos to confirm quantification of changes in lipid content in the embryo. Previously, ORO was limited to qualitative assessment; now ORO can be used as a quantitative tool to directly determine changes in the levels of neutral lipids and triglycerides.

  2. In Vivo Anomalous Diffusion and Weak Ergodicity Breaking of Lipid Granules

    NASA Astrophysics Data System (ADS)

    Jeon, Jae-Hyung; Tejedor, Vincent; Burov, Stas; Barkai, Eli; Selhuber-Unkel, Christine; Berg-Sørensen, Kirstine; Oddershede, Lene; Metzler, Ralf

    2011-01-01

    Combining extensive single particle tracking microscopy data of endogenous lipid granules in living fission yeast cells with analytical results we show evidence for anomalous diffusion and weak ergodicity breaking. Namely we demonstrate that at short times the granules perform subdiffusion according to the laws of continuous time random walk theory. The associated violation of ergodicity leads to a characteristic turnover between two scaling regimes of the time averaged mean squared displacement. At longer times the granule motion is consistent with fractional Brownian motion.

  3. Anti-tumor activities of lipids and lipid analogues and their development as potential anticancer drugs.

    PubMed

    Murray, Michael; Hraiki, Adam; Bebawy, Mary; Pazderka, Curtis; Rawling, Tristan

    2015-06-01

    Lipids have the potential for development as anticancer agents. Endogenous membrane lipids, such as ceramides and certain saturated fatty acids, have been found to modulate the viability of tumor cells. In addition, many tumors over-express cyclooxygenase, lipoxygenase or cytochrome P450 enzymes that mediate the biotransformation of ω-6 polyunsaturated fatty acids (PUFAs) to potent eicosanoid regulators of tumor cell proliferation and cell death. In contrast, several analogous products from the biotransformation of ω-3 PUFAs impair particular tumorigenic pathways. For example, the ω-3 17,18-epoxide of eicosapentaenoic acid activates anti-proliferative and proapoptotic signaling cascades in tumor cells and the lipoxygenase-derived resolvins are effective inhibitors of inflammatory pathways that may drive tumor expansion. However, the development of potential anti-cancer drugs based on these molecules is complex, with in vivo stability a major issue. Nevertheless, recent successes with the antitumor alkyl phospholipids, which are synthetic analogues of naturally-occurring membrane phospholipid esters, have provided the impetus for development of further molecules. The alkyl phospholipids have been tested against a range of cancers and show considerable activity against skin cancers and certain leukemias. Very recently, it has been shown that combination strategies, in which alkyl phospholipids are used in conjunction with established anticancer agents, are promising new therapeutic approaches. In future, the evaluation of new lipid-based molecules in single-agent and combination treatments may also be assessed. This could provide a range of important treatment options in the management of advanced and metastatic cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. The influence of hair lipids in ethnic hair properties.

    PubMed

    Martí, M; Barba, C; Manich, A M; Rubio, L; Alonso, C; Coderch, L

    2016-02-01

    Biochemical studies have mainly focused on the composition of hair. African hair exhibited lower moisturization and less radial swelling when flushing with water compared with Asian or Caucasian hair, and they assumed a possible lipid differentiation among human populations. This study consists in the lipid characterization of different ethnic hairs (Caucasian, Asian and African hairs) and the influence of these lipids in different hair properties such as humidity and mechanical properties. Evaluation of water sorption and desorption of the different ethnic hairs and with and without lipids is also studied mainly to determine permeation changes of the keratin fibres. Extractions of exogenous and endogenous lipids with different organic solvents were performed; lipid analysis and its quantification using thin-layer chromatography coupled to an automated flame ionization detector (TLC/FID) were performed. Absorption and desorption curves were obtained in a thermogravimetric balance equipped with a controlled humidity chamber, the Q5000SA Sorption Analyzer (TA Instruments, New Castle, IL, U.S.A.). Also, mechanical properties (breaking stress and breaking elongation) were analysed using a computer programmable dynamometer (Instron 5500R). Lipid extraction showed the highest amount of total lipids for the African hair which may come from external sebaceous lipids compared with Asian or Caucasian hair. Caucasian fibres were found to be the most hydrated fibre, and a decrease in moisture was found in the extracted fibres, again, which is more important for the Caucasian hair. A superior lineal mass was found for the Asian fibres which supported their higher strength. The results obtained from the analysis of the mechanical properties of delipidized fibres indicate a surprising increase in the strength of African and Caucasian fibres. Perhaps this increase in strength could be related to the humidity decrease in lipid-extracted hair fibres. Results of water uptake and

  5. [Participation of final products of lipid peroxidation in the anticancer mechanism of ionizing radiation and radiomimetic cytostatics].

    PubMed

    Przybyszewski, W M

    2001-01-01

    This review reports the evidence for the participation of final products of lipid peroxidation in the anticancer mechanism of ionising radiation and radiomimetic cytostatics. Processes of lipid peroxidation occur endogenously in response to oxidative stress and great diversity of reactive metabolites is formed. However, direct observation of radical reaction in pathophysiology of cells, tissues and organs is limited technically. Most investigations focused on the indirect assessment of their final products, aldehydes. The peroxidative breakdown of polyunsaturated fatty acids is believed to be involved in the regulation of cell division, and antitumor effect through biochemical and genetic processes.

  6. Characterisation of the Native Lipid Moiety of Echinococcus granulosus Antigen B

    PubMed Central

    Obal, Gonzalo; Ramos, Ana Lía; Silva, Valeria; Lima, Analía; Batthyany, Carlos; Bessio, María Inés; Ferreira, Fernando; Salinas, Gustavo; Ferreira, Ana María

    2012-01-01

    Antigen B (EgAgB) is the most abundant and immunogenic antigen produced by the larval stage (metacestode) of Echinococcus granulosus. It is a lipoprotein, the structure and function of which have not been completely elucidated. EgAgB apolipoprotein components have been well characterised; they share homology with a group of hydrophobic ligand binding proteins (HLBPs) present exclusively in cestode organisms, and consist of different isoforms of 8-kDa proteins encoded by a polymorphic multigene family comprising five subfamilies (EgAgB1 to EgAgB5). In vitro studies have shown that EgAgB apolipoproteins are capable of binding fatty acids. However, the identity of the native lipid components of EgAgB remains unknown. The present work was aimed at characterising the lipid ligands bound to EgAgB in vivo. EgAgB was purified to homogeneity from hydatid cyst fluid and its lipid fraction was extracted using chloroform∶methanol mixtures. This fraction constituted approximately 40–50% of EgAgB total mass. High-performance thin layer chromatography revealed that the native lipid moiety of EgAgB consists of a variety of neutral (mainly triacylglycerides, sterols and sterol esters) and polar (mainly phosphatidylcholine) lipids. Gas-liquid chromatography analysis showed that 16∶0, 18∶0 and 18∶1(n-9) are the most abundant fatty acids in EgAgB. Furthermore, size exclusion chromatography coupled to light scattering demonstrated that EgAgB comprises a population of particles heterogeneous in size, with an average molecular mass of 229 kDa. Our results provide the first direct evidence of the nature of the hydrophobic ligands bound to EgAgB in vivo and indicate that the structure and composition of EgAgB lipoprotein particles are more complex than previously thought, resembling high density plasma lipoproteins. Results are discussed considering what is known on lipid metabolism in cestodes, and taken into account the Echinococcus spp. genomic information regarding both lipid

  7. Kinetic modeling of growth and lipid body induction in Chlorella pyrenoidosa under heterotrophic conditions.

    PubMed

    Sachdeva, Neha; Kumar, G Dinesh; Gupta, Ravi Prakash; Mathur, Anshu Shankar; Manikandan, B; Basu, Biswajit; Tuli, Deepak Kumar

    2016-10-01

    The aim of the present work was to develop a mathematical model to describe the biomass and (total) lipid productivity of Chlorella pyrenoidosa NCIM 2738 under heterotrophic conditions. Biomass growth rate was predicted by Droop's cell quota model, while changes observed in cell quota (utilization) under carbon excess conditions were used for the modeling and predicting the lipid accumulation rate. The model was simulated under non-limiting (excess) carbon and limiting nitrate concentration and validated with experimental data for the culture grown in batch (flask) mode under different nitrate concentrations. The present model incorporated two modes (growth and stressed) for the prediction of endogenous lipid synthesis/induction and aimed to predict the effect and response of the microalgae under nutrient starvation (stressed) conditions. MATLAB and Genetic Algorithm were employed for the prediction and validation of the model parameters. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. LipidPedia: a comprehensive lipid knowledgebase.

    PubMed

    Kuo, Tien-Chueh; Tseng, Yufeng Jane

    2018-04-10

    Lipids are divided into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and polyketides. Fatty acyls and glycerolipids are commonly used as energy storage, whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are common used as components of cell membranes. Lipids in fatty acyls, glycerophospholipids, sphingolipids and sterols classes play important roles in signaling. Although more than 36 million lipids can be identified or computationally generated, no single lipid database provides comprehensive information on lipids. Furthermore, the complex systematic or common names of lipids make the discovery of related information challenging. Here, we present LipidPedia, a comprehensive lipid knowledgebase. The content of this database is derived from integrating annotation data with full-text mining of 3,923 lipids and more than 400,000 annotations of associated diseases, pathways, functions, and locations that are essential for interpreting lipid functions and mechanisms from over 1,400,000 scientific publications. Each lipid in LipidPedia also has its own entry containing a text summary curated from the most frequently cited diseases, pathways, genes, locations, functions, lipids and experimental models in the biomedical literature. LipidPedia aims to provide an overall synopsis of lipids to summarize lipid annotations and provide a detailed listing of references for understanding complex lipid functions and mechanisms. LipidPedia is available at http://lipidpedia.cmdm.tw. yjtseng@csie.ntu.edu.tw. Supplementary data are available at Bioinformatics online.

  9. Lipid- and sugar-modified endomorphins: novel targets for the treatment of neuropathic pain

    PubMed Central

    Varamini, Pegah; Toth, Istvan

    2013-01-01

    Endomorphins are endogenous opioid peptides that cause potent antinociception in rodent models of acute and neuropathic pain with less undesirable side effects than opioid alkaloids. However, endomorphins are poorly suited to clinical applications because of low membrane permeability and a susceptibility to enzymatic degradation. Glycosylation and lipidation have proven to be two of the most robust approaches for the generation of new therapeutic endomorphin derivatives. Conjugation with lipoamino acids (LAA) confers an amphipathic character to the peptide, which improved interaction between the peptide and the lipid bilayer of the cell membranes, increasing permeability. Glycosylation can also improve peptide stability and blood brain barrier (BBB) transport. It is believed that an endocytotic mechanism (transcytosis) is responsible for the systemic delivery of water-soluble glycopeptides. This review discusses the application of glycosylation and lipidation strategies to improve the drug-like properties of endomorphins. Pharmacologically active endomorphin analogs with less adverse effects are also discussed. PMID:24379782

  10. Hippocampal lipid differences in Alzheimer's disease: a human brain study using matrix-assisted laser desorption/ionization-imaging mass spectrometry.

    PubMed

    Mendis, Lakshini H S; Grey, Angus C; Faull, Richard L M; Curtis, Maurice A

    2016-10-01

    Alzheimer's disease (AD), the leading cause of dementia, is pathologically characterized by β-amyloid plaques and tau tangles. However, there is also evidence of lipid dyshomeostasis-mediated AD pathology. Given the structural diversity of lipids, mass spectrometry is a useful tool for studying lipid changes in AD. Although there have been a few studies investigating lipid changes in the human hippocampus in particular, there are few reports on how lipids change in each hippocampal subfield (e.g., Cornu Ammonis [CA] 1-4, dentate gyrus [DG] etc.). Since each subfield has its own function, we postulated that there could be lipid changes that are unique to each. We used matrix-assisted laser desorption/ionization-imaging mass spectrometry to investigate specific lipid changes in each subfield in AD. Data from the hippocampus region of six age- and gender-matched normal and AD pairs were analyzed with SCiLS lab 2015b software (SCiLS GmbH, Germany; RRID:SCR_014426), using an analysis workflow developed in-house. Hematoxylin, eosin, and luxol fast blue staining were used to precisely delineate each anatomical hippocampal subfield. Putative lipid identities, which were consistent with published data, were assigned using MS/MS. Both positively and negatively charged lipid ion species were abundantly detected in normal and AD tissue. While the distribution pattern of lipids did not change in AD, the abundance of some lipids changed, consistent with trends that have been previously reported. However, our results indicated that the majority of these lipid changes specifically occur in the CA1 region. Additionally, there were many lipid changes that were specific to the DG. Matrix-assisted laser desorption/ionization-imaging mass spectrometry and our analysis workflow provide a novel method to investigate specific lipid changes in hippocampal subfields. Future work will focus on elucidating the role that specific lipid differences in each subfield play in AD pathogenesis.

  11. The main thylakoid membrane lipid monogalactosyldiacylglycerol (MGDG) promotes the de-epoxidation of violaxanthin associated with the light-harvesting complex of photosystem II (LHCII).

    PubMed

    Schaller, Susann; Latowski, Dariusz; Jemioła-Rzemińska, Małgorzata; Wilhelm, Christian; Strzałka, Kazimierz; Goss, Reimund

    2010-03-01

    In higher plants, the major part of the xanthophyll cycle pigment violaxanthin (Vx) is non-covalently bound to the main light-harvesting complex of PSII (LHCII). Under saturating light conditions Vx has to be released from its binding site into the surrounding lipid phase, where it is converted to zeaxanthin (Zx) by the enzyme Vx de-epoxidase (VDE). In the present study we investigated the influence of thylakoid lipids on the de-epoxidation of Vx, which was still associated with the LHCII. We isolated LHCII with different concentrations of native, endogenous lipids and Vx by sucrose gradient centrifugation or successive cation precipitation. Analysis of the different LHCII preparations showed that the concentration of LHCII-associated Vx was correlated with the concentration of the main thylakoid lipid monogalactosyldiacylglycerol (MGDG) associated with the complexes. Decreases in the MGDG content of the LHCII led to a diminished Vx concentration, indicating that a part of the total Vx pool was located in an MGDG phase surrounding the LHCII, whereas another part was bound to the LHCII apoproteins. We further studied the convertibility of LHCII-associated Vx in in-vitro enzyme assays by addition of isolated VDE. We observed an efficient and almost complete Vx conversion in the LHCII fractions containing high amounts of endogenous MGDG. LHCII preparations with low concentrations of MGDG exhibited a strongly reduced Vx de-epoxidation, which could be increased by addition of exogenous, pure MGDG. The de-epoxidation of LHCII-associated Vx was saturated at a much lower concentration of native, endogenous MGDG compared with the concentration of isolated, exogenous MGDG, which is needed for optimal VDE activity in in-vitro assays employing pure isolated Vx. Copyright 2009 Elsevier B.V. All rights reserved.

  12. Endogenous ω-3 Polyunsaturated Fatty Acid Production Confers Resistance to Obesity, Dyslipidemia, and Diabetes in Mice

    PubMed Central

    Li, Jie; Li, Fanghong R.; Wei, Dong; Jia, Wei; Kang, Jing X.; Stefanovic-Racic, Maja

    2014-01-01

    Despite the well-documented health benefits of ω-3 polyunsaturated fatty acids (PUFAs), their use in clinical management of hyperglycemia and obesity has shown little success. To better define the mechanisms of ω-3 PUFAs in regulating energy balance and insulin sensitivity, we deployed a transgenic mouse model capable of endogenously producing ω-3 PUFAs while reducing ω-6 PUFAs owing to the expression of a Caenorhabditis elegans fat-1 gene encoding an ω-3 fatty acid desaturase. When challenged with high-fat diets, fat-1 mice strongly resisted obesity, diabetes, hypercholesterolemia, and hepatic steatosis. Endogenous elevation of ω-3 PUFAs and reduction of ω-6 PUFAs did not alter the amount of food intake but led to increased energy expenditure in the fat-1 mice. The requirements for the levels of ω-3 PUFAs as well as the ω-6/ω-3 ratios in controlling blood glucose and obesity are much more stringent than those in lipid metabolism. These metabolic phenotypes were accompanied by attenuation of the inflammatory state because tissue levels of prostaglandin E2, leukotriene B4, monocyte chemoattractant protein-1, and TNF-α were significantly decreased. TNF-α–induced nuclear factor-κB signaling was almost completely abolished. Consistent with the reduction in chronic inflammation and a significant increase in peroxisome proliferator–activated receptor-γ activity in the fat-1 liver tissue, hepatic insulin signaling was sharply elevated. The activities of prolipogenic regulators, such as liver X receptor, stearoyl-CoA desaturase-1, and sterol regulatory element binding protein-1 were sharply decreased, whereas the activity of peroxisome proliferator–activated receptor-α, a nuclear receptor that facilitates lipid β-oxidation, was markedly increased. Thus, endogenous conversion of ω-6 to ω-3 PUFAs via fat-1 strongly protects against obesity, diabetes, inflammation, and dyslipidemia and may represent a novel therapeutic modality to treat these prevalent

  13. The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1)

    PubMed Central

    Morales-Lázaro, Sara L; Simon, Sidney A; Rosenbaum, Tamara

    2013-01-01

    Pain is a physiological response to a noxious stimulus that decreases the quality of life of those sufferring from it. Research aimed at finding new therapeutic targets for the treatment of several maladies, including pain, has led to the discovery of numerous molecular regulators of ion channels in primary afferent nociceptive neurons. Among these receptors is TRPV1 (transient receptor potential vanilloid 1), a member of the TRP family of ion channels. TRPV1 is a calcium-permeable channel, which is activated or modulated by diverse exogenous noxious stimuli such as high temperatures, changes in pH, and irritant and pungent compounds, and by selected molecules released during tissue damage and inflammatory processes. During the last decade the number of endogenous regulators of TRPV1's activity has increased to include lipids that can negatively regulate TRPV1, as is the case for cholesterol and PIP2 (phosphatidylinositol 4,5-biphosphate) while, in contrast, other lipids produced in response to tissue injury and ischaemic processes are known to positively regulate TRPV1. Among the latter, lysophosphatidic acid activates TRPV1 while amines such as N-acyl-ethanolamines and N-acyl-dopamines can sensitize or directly activate TRPV1. It has also been found that nucleotides such as ATP act as mediators of chemically induced nociception and pain and gases, such as hydrogen sulphide and nitric oxide, lead to TRPV1 activation. Finally, the products of lipoxygenases and omega-3 fatty acids among other molecules, such as divalent cations, have also been shown to endogenously regulate TRPV1 activity. Here we provide a comprehensive review of endogenous small molecules that regulate the function of TRPV1. Acting through mechanisms that lead to sensitization and desensitization of TRPV1, these molecules regulate pathways involved in pain and nociception. Understanding how these compounds modify TRPV1 activity will allow us to comprehend how some pathologies are associated with

  14. The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1).

    PubMed

    Morales-Lázaro, Sara L; Simon, Sidney A; Rosenbaum, Tamara

    2013-07-01

    Pain is a physiological response to a noxious stimulus that decreases the quality of life of those sufferring from it. Research aimed at finding new therapeutic targets for the treatment of several maladies, including pain, has led to the discovery of numerous molecular regulators of ion channels in primary afferent nociceptive neurons. Among these receptors is TRPV1 (transient receptor potential vanilloid 1), a member of the TRP family of ion channels. TRPV1 is a calcium-permeable channel, which is activated or modulated by diverse exogenous noxious stimuli such as high temperatures, changes in pH, and irritant and pungent compounds, and by selected molecules released during tissue damage and inflammatory processes. During the last decade the number of endogenous regulators of TRPV1's activity has increased to include lipids that can negatively regulate TRPV1, as is the case for cholesterol and PIP2 (phosphatidylinositol 4,5-biphosphate) while, in contrast, other lipids produced in response to tissue injury and ischaemic processes are known to positively regulate TRPV1. Among the latter, lysophosphatidic acid activates TRPV1 while amines such as N-acyl-ethanolamines and N-acyl-dopamines can sensitize or directly activate TRPV1. It has also been found that nucleotides such as ATP act as mediators of chemically induced nociception and pain and gases, such as hydrogen sulphide and nitric oxide, lead to TRPV1 activation. Finally, the products of lipoxygenases and omega-3 fatty acids among other molecules, such as divalent cations, have also been shown to endogenously regulate TRPV1 activity. Here we provide a comprehensive review of endogenous small molecules that regulate the function of TRPV1. Acting through mechanisms that lead to sensitization and desensitization of TRPV1, these molecules regulate pathways involved in pain and nociception. Understanding how these compounds modify TRPV1 activity will allow us to comprehend how some pathologies are associated with

  15. Endogenous Stem Cells Were Recruited by Defocused Low-Energy Shock Wave in Treating Diabetic Bladder Dysfunction.

    PubMed

    Jin, Yang; Xu, Lina; Zhao, Yong; Wang, Muwen; Jin, Xunbo; Zhang, Haiyang

    2017-04-01

    Defocused low-energy shock wave (DLSW) has been shown effects on activating mesenchymal stromal cells (MSCs) in vitro. In this study, recruitment of endogenous stem cells was firstly examined as an important pathway during the healing process of diabetic bladder dysfunction (DBD) treated by DLSW in vivo. Neonatal rats received intraperitoneal injection of 5-ethynyl-2-deoxyuridine (EdU) and then DBD rat model was created by injecting streptozotocin. Four weeks later, DLSW treatment was performed. Afterward, their tissues were examined by histology. Meanwhile, adipose tissue-derived stem cells (ADSCs) were treated by DLSW in vitro. Results showed DLSW ameliorated voiding function of diabetic rats by recruiting EdU + Stro-1 + CD34 - endogenous stem cells to release abundant nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). Some EdU + cells overlapped with staining of smooth muscle actin. After DLSW treatment, ADSCs showed higher migration ability, higher expression level of stromal cell-derived factor-1 and secreted more NGF and VEGF. In conclusion, DLSW could ameliorate DBD by recruiting endogenous stem cells. Beneficial effects were mediated by secreting NGF and VEGF, resulting into improved innervation and vascularization in bladder.

  16. A serine peptidase responsible for the inactivation of endogenous cholecystokinin in brain.

    PubMed

    Rose, C; Camus, A; Schwartz, J C

    1988-11-01

    A serine endopeptidase was characterized as a major inactivating enzyme for endogenous cholecystokinin (CCK) in brain. CCK-8 released by depolarization of slices of rat cerebral cortex, as measured by its immunoreactivity (CCK-ir), undergoes extensive degradation (approximately 85% of the amount released) before reaching the incubation medium. However, recovery of CCK-ir is enhanced up to 3-fold in the presence of serine-alkylating reagents (i.e., phenylmethylsulfonyl fluoride) as well as selected active site-directed inactivators (i.e., peptide chloromethyl ketones) or transition-state inhibitors (i.e., peptide boronic acids) of serine peptidases. Among these compounds, elastase inhibitors were the most potent protecting agents, whereas trypsin or chymotrypsin inhibitors were ineffective. HPLC analysis of endogenous CCK-ir recovered in media of depolarized slices indicated that endogenous CCK-5 [CCK-(29-33)-pentapeptide] was the most abundant fragment and that its formation was strongly decreased in the presence of an elastase inhibitor. HPLC analysis of fragments formed upon incubation of exogenous CCK-8 [CCK-(26-33)-octapeptide] with brain slices showed CCK-5, Gly-Trp-Met, and Trp-Met to be major metabolites of CCK-8 whose formation was prevented or at least diminished in the presence of the elastase inhibitor. It is concluded that there is an elastase-like serine endopeptidase in brain that cleaves the two peptide bonds of CCK-8 where the carboxyl group is donated by a methionine residue and constitutes a major inactivation ectoenzyme for the neuropeptide.

  17. A serine peptidase responsible for the inactivation of endogenous cholecystokinin in brain.

    PubMed Central

    Rose, C; Camus, A; Schwartz, J C

    1988-01-01

    A serine endopeptidase was characterized as a major inactivating enzyme for endogenous cholecystokinin (CCK) in brain. CCK-8 released by depolarization of slices of rat cerebral cortex, as measured by its immunoreactivity (CCK-ir), undergoes extensive degradation (approximately 85% of the amount released) before reaching the incubation medium. However, recovery of CCK-ir is enhanced up to 3-fold in the presence of serine-alkylating reagents (i.e., phenylmethylsulfonyl fluoride) as well as selected active site-directed inactivators (i.e., peptide chloromethyl ketones) or transition-state inhibitors (i.e., peptide boronic acids) of serine peptidases. Among these compounds, elastase inhibitors were the most potent protecting agents, whereas trypsin or chymotrypsin inhibitors were ineffective. HPLC analysis of endogenous CCK-ir recovered in media of depolarized slices indicated that endogenous CCK-5 [CCK-(29-33)-pentapeptide] was the most abundant fragment and that its formation was strongly decreased in the presence of an elastase inhibitor. HPLC analysis of fragments formed upon incubation of exogenous CCK-8 [CCK-(26-33)-octapeptide] with brain slices showed CCK-5, Gly-Trp-Met, and Trp-Met to be major metabolites of CCK-8 whose formation was prevented or at least diminished in the presence of the elastase inhibitor. It is concluded that there is an elastase-like serine endopeptidase in brain that cleaves the two peptide bonds of CCK-8 where the carboxyl group is donated by a methionine residue and constitutes a major inactivation ectoenzyme for the neuropeptide. PMID:3186727

  18. 4-Hydroxy-nonenal—A Bioactive Lipid Peroxidation Product †

    PubMed Central

    Schaur, Rudolf J.; Siems, Werner; Bresgen, Nikolaus; Eckl, Peter M.

    2015-01-01

    This review on recent research advances of the lipid peroxidation product 4-hydroxy-nonenal (HNE) has four major topics: I. the formation of HNE in various organs and tissues, II. the diverse biochemical reactions with Michael adduct formation as the most prominent one, III. the endogenous targets of HNE, primarily peptides and proteins (here the mechanisms of covalent adduct formation are described and the (patho-) physiological consequences discussed), and IV. the metabolism of HNE leading to a great number of degradation products, some of which are excreted in urine and may serve as non-invasive biomarkers of oxidative stress. PMID:26437435

  19. Unraveling the Complex Relationship Triad between Lipids, Obesity, and Inflammation

    PubMed Central

    Khan, Shahida A.; Khan, Sarah A.; Zahran, Solafa A.; Damanhouri, Ghazi

    2014-01-01

    Obesity today stands at the intersection between inflammation and metabolic disorders causing an aberration of immune activity, and resulting in increased risk for diabetes, atherosclerosis, fatty liver, and pulmonary inflammation to name a few. Increases in mortality and morbidity in obesity related inflammation have initiated studies to explore different lipid mediated molecular pathways of attempting resolution that uncover newer therapeutic opportunities of anti-inflammatory components. Majorly the thromboxanes, prostaglandins, leukotrienes, lipoxins, and so forth form the group of lipid mediators influencing inflammation. Of special mention are the omega-6 and omega-3 fatty acids that regulate inflammatory mediators of interest in hepatocytes and adipocytes via the cyclooxygenase and lipoxygenase pathways. They also exhibit profound effects on eicosanoid production. The inflammatory cyclooxygenase pathway arising from arachidonic acid is a critical step in the progression of inflammatory responses. New oxygenated products of omega-3 metabolism, namely, resolvins and protectins, behave as endogenous mediators exhibiting powerful anti-inflammatory and immune-regulatory actions via the peroxisome proliferator-activated receptors (PPARs) and G protein coupled receptors (GPCRs). In this review we attempt to discuss the complex pathways and links between obesity and inflammation particularly in relation to different lipid mediators. PMID:25258478

  20. Cytokines as endogenous pyrogens.

    PubMed

    Dinarello, C A

    1999-03-01

    Cytokines are pleiotropic molecules mediating several pathologic processes. Long before the discovery of cytokines as immune system growth factors or as bone marrow stimulants, investigators learned a great deal about cytokines when they studied them as the endogenous mediators of fever. The terms "granulocytic" or "endogenous pyrogen" were used to describe substances with the biologic property of fever induction. Today, we recognize that pyrogenicity is a fundamental biologic property of several cytokines and hence the clinically recognizeable property of fever links host perturbations during disease with fundamental perturbations in cell biology. In this review, the discoveries made on endogenous pyrogens are revisited, with insights into the importance of the earlier work to the present-day understanding of cytokines in health and in disease.

  1. The boosted biomass and lipid accumulation in Chlorella vulgaris by supplementation of synthetic phytohormone analogs.

    PubMed

    Liu, Tingting; Liu, Fei; Wang, Chao; Wang, Zhenyao; Li, Yuqin

    2017-05-01

    This study attempted at maximizing biomass and lipid accumulation in Chlorella vulgaris by supplementation of natural abscisic acid (ABA) or synthetic 2,4-dichlorophenoxyacetic acid (2,4-D) and 1-naphthaleneacetic acid (NAA) hormone analogs. Amongst three tested additives, NAA-treatment performed remarkable promoting effect on cell growth and lipid biosynthesis. The favorable lipid productivity (418.6mg/L/d) of NAA-treated cells showed 1.48 and 2.24 times more than that of 2,4-D and ABA. NAA-treatment also positively modified the proportions of saturated (C16:0 and C18:0) and monounsaturated fatty acids (C18:1) which were prone to high-quality biofuels-making. Further, NAA-treatment manipulated endogenous phytohormones metabolism leading to the elevated levels of indole-3-acetic acid, jasmonic acid, and salicylic acid and such hormone accumulation might be indispensable for signal transduction in regulating cell growth and lipid biosynthesis in microalgae. In addition, the economic-feasibility and eco-friendly estimation of NAA additive indicated the higher possibilities in developing affordable and scalable microalgal lipids for biofuels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The polar lipids of Clostridium psychrophilum, an anaerobic psychrophile

    PubMed Central

    Guan, Ziqiang; Tian, Bing; Perfumo, Amedea; Goldfine, Howard

    2013-01-01

    We have examined the polar lipids of Clostridium psychrophilum, a recently characterized psychrophilic Clostridium isolated from an Antarctic microbial mat. Lipids were extracted from cells grown near the optimal growth temperature (+5 °C) and at −5 °C, and analyzed by two-dimensional thin layer chromatography and liquid chromatography coupled with mass spectrometry. The major phospholipids of this species are: cardiolipin, phosphatidylethanolamine, and phosphatidylglycerol. Phosphatidylserine and lyso-phosphatidylethanolamine were found as minor components. The most abundant glycolipids are a monoglycosyldiradylglycerol (MGDRG) and a diglycosyldiradylglycerol (DGDRG). The latter was only seen in cells grown at −5 °C. An ethanolamine-phosphate derivative of N-acetylglucosaminyldiradylglycerol was seen in cells grown at −5 °C and an ethanolamine-phosphate derivative of MGDRG was found in cells grown at +5 °C. All lipids were present in both the all acyl and plasmalogen (alk-1′-enyl acyl) forms with the exception of PS and MGDRG, which were predominantly in the diacyl form. The significance of lipid changes at the two growth temperatures is discussed. PMID:23454375

  3. Effects of Acifluorfen on Endogenous Antioxidants and Protective Enzymes in Cucumber (Cucumis sativus L.) Cotyledons

    PubMed Central

    Kenyon, William H.; Duke, Stephen O.

    1985-01-01

    The herbicide acifluorfen (2-chloro-4-(trifluoromethyl)phenoxy-2-nitrobenzoate) causes strong photooxidative destruction of pigments and lipids in sensitive plant species. Antioxidants and oxygen radical scavengers slow the bleaching action of the herbicide. The effect of acifluorfen on glutathione and ascorbate levels in cucumber (Cucumis sativus L.) cotyledon discs was investigated to assess the relationship between herbicide activity and endogenous antioxidants. Acifluorfen decreased the levels of glutathione and ascorbate over 50% in discs exposed to less than 1.5 hours of white light (450 microeinsteins per square meter per second). Coincident increases in dehydroascorbate and glutathione disulfide were not observed. Acifluorfen also caused the rapid depletion of ascorbate in far-red light grown plants which were photosynthetically incompetent. Glutathione reductase, dehydroascorbate reductase, superoxide dismutase, ascorbate oxidase, ascorbate free radical reductase, peroxidase, and catalase activities rapidly decreased in acifluorfen-treated tissue exposed to white light. None of the enzymes were inhibited in vitro by the herbicide. Acifluorfen causes irreversible photooxidative destruction of plant tissue, in part, by depleting endogenous antioxidants and inhibiting the activities of protective enzymes. PMID:16664506

  4. Amelioration of cognitive, motor and endogenous defense functions with silymarin, piracetam and protocatechuic acid in the cerebral global ischemic rat model.

    PubMed

    Muley, Milind M; Thakare, Vishnu N; Patil, Rajesh R; Bafna, Pallavi A; Naik, Suresh R

    2013-07-19

    The neuroprotective activities of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) on cerebral global ischemic/reperfusion were evaluated in a rat model. A midline ventral incision was made in the throat region. The right and left common carotid arteries were located and a bilateral common carotid artery occlusion (BCCAO) was performed for 30min using atraumatic clamps followed by a 24h period of reperfusion. Neurological/behavioral functions (cognitive and motor), endogenous defense systems (lipid peroxidation, glutathione, catalase, and superoxide dismutase), reduced water content and infarct size and histopathological alterations were then studied. Silymarin and PCA treatments significantly improved cognitive, motor and endogenous defense functions, histopathological alterations, and, reduced both water content and infarct size compared to the vehicle-treated ischemic control group. Piracetam treatment improved neurological and histopathological alterations, reduced water content and infarct size, but failed to restore/prevent the impaired endogenous defense functions significantly. Silymarin showed better neuroprotection than piracetam and PCA in experimentally induced global ischemic/reperfusion and was able to facilitate mnemonic performance. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Current trends to comprehend lipid metabolism in diatoms.

    PubMed

    Zulu, Nodumo Nokulunga; Zienkiewicz, Krzysztof; Vollheyde, Katharina; Feussner, Ivo

    2018-04-01

    Diatoms are the most dominant phytoplankton species in oceans and they continue to receive a great deal of attention because of their significant contributions in ecosystems and the environment. Due to triacylglycerol (TAG) profiles that are abundant in medium-chain fatty acids, diatoms have emerged to be better feed stocks for biofuel production, in comparison to the commonly studied green microalgal species (chlorophytes). Importantly, diatoms are also known for their high levels of the essential ω3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and are considered to be a promising alternative source of these components. The two most commonly exploited diatoms include Thalassiosira pseudonana and Phaeodactylum tricornutum. Although obvious similarities between diatoms and chlorophytes exist, there are some substantial differences in their lipid metabolism. This review provides an overview on lipid metabolism in diatoms, with P. tricornutum as the most explored model. Special emphasis is placed on the synthesis and incorporation of very long chain ω3 fatty acids into lipids. Furthermore, current approaches including genetic engineering and biotechnological methods aimed at improving and maximizing lipid production in P. tricornutum are also discussed. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Sugar is an endogenous cue for juvenile-to-adult phase transition in plants

    PubMed Central

    Yu, Sha; Cao, Li; Zhou, Chuan-Miao; Zhang, Tian-Qi; Lian, Heng; Sun, Yue; Wu, Jianqiang; Huang, Jirong; Wang, Guodong; Wang, Jia-Wei

    2013-01-01

    The transition from the juvenile to adult phase in plants is controlled by diverse exogenous and endogenous cues such as age, day length, light, nutrients, and temperature. Previous studies have shown that the gradual decline in microRNA156 (miR156) with age promotes the expression of adult traits. However, how age temporally regulates the abundance of miR156 is poorly understood. We show here that the expression of miR156 responds to sugar. Sugar represses miR156 expression at both the transcriptional level and post-transcriptional level through the degradation of miR156 primary transcripts. Defoliation and photosynthetic mutant assays further demonstrate that sugar from the pre-existing leaves acts as a mobile signal to repress miR156, and subsequently triggers the juvenile-to-adult phase transition in young leaf primordia. We propose that the gradual increase in sugar after seed germination serves as an endogenous cue for developmental timing in plants. DOI: http://dx.doi.org/10.7554/eLife.00269.001 PMID:23543845

  7. Low-fat frankfurters formulated with a healthier lipid combination as functional ingredient: microstructure, lipid oxidation, nitrite content, microbiological changes and biogenic amine formation.

    PubMed

    Delgado-Pando, Gonzalo; Cofrades, Susana; Ruiz-Capillas, Claudia; Solas, Maria Teresa; Triki, Mehdi; Jiménez-Colmenero, Francisco

    2011-09-01

    Oil (healthier lipid combination of olive, linseed and fish oils)-in-water emulsions stabilized with different protein systems (prepared with sodium caseinate (SC), soy protein isolate (SPI), and microbial transglutaminase (MTG)) were used as pork backfat replacers in low-fat frankfurters. Microstructure, lipid oxidation, nitrite content, microbiological changes and biogenic amine formation of frankfurters were analyzed and found to be affected by the type of oil-in-water emulsion and by chilling storage (2° C, 41 days). Although the lipid oxidation levels attained were low, replacement of animal fat by healthier oil combinations in frankfurter formulation did promote a slight increase in lipid oxidation. Residual nitrite was affected (P < 0.05) by formulation and storage. Only 51-61% of the added nitrite was detectable in the product after processing and 17-46% at the end of storage. The microbial population was low in all formulations during chilling storage. Spermine was the most abundant amine (19-20 mg/kg), but similar in level to all samples. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Sedimentary archaeal amoA gene abundance reflects historic nutrient level and salinity fluctuations in Qinghai Lake, Tibetan Plateau

    PubMed Central

    Yang, Jian; Jiang, Hongchen; Dong, Hailiang; Hou, Weiguo; Li, Gaoyuan; Wu, Geng

    2015-01-01

    Integration of DNA derived from ancient phototrophs with their characteristic lipid biomarkers has been successfully employed to reconstruct paleoenvironmental conditions. However, it is poorly known that whether the DNA and lipids of microbial functional aerobes (such as ammonia-oxidizing archaea: AOA) can be used for reconstructing past environmental conditions. Here we identify and quantify the AOA amoA genes (encoding the alpha subunit of ammonia monooxygenases) preserved in a 5.8-m sediment core (spanning the last 18,500 years) from Qinghai Lake. Parallel analyses revealed that low amoA gene abundance corresponded to high total organic carbon (TOC) and salinity, while high amoA gene abundance corresponded to low TOC and salinity. In the Qinghai Lake region, TOC can serve as an indicator of paleo-productivity and paleo-precipitation, which is related to historic nutrient input and salinity. So our data suggest that temporal variation of AOA amoA gene abundance preserved in Qinghai Lake sediment may reflect the variations of nutrient level and salinity throughout the late Pleistocene and Holocene in the Qinghai Lake region. PMID:26666501

  9. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

    PubMed

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

    2017-05-01

    Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

  10. Rubisco mutants of Chlamydomonas reinhardtii display divergent photosynthetic parameters and lipid allocation.

    PubMed

    Esquível, M G; Matos, A R; Marques Silva, J

    2017-07-01

    Photosynthesis and lipid allocation were investigated in Rubisco small subunit mutants of the microalga Chlamydomonas reinhardtii. Comparative analyses were undertaken with cells grown photoheterotrophically under sulphur-replete or sulphur-depleted conditions. The Y67A Rubisco mutant, which has previously demonstrated a pronounced reduction in Rubisco levels and higher hydrogen production rates than the wild type, also shows the following divergences in photosynthetic phenotype and lipid allocation: (i) low Fv/Fm (maximum photochemical efficiency), (ii) low effective quantum yield of photosystem II (ΦPSII), (iii) low effectiveness at protection against high light intensities, (iv) a higher level of total lipids per pigment and (v) changes in the relative proportions of different fatty acids, with a marked decrease in unsaturated fatty acids (FAs). The most abundant thylakoid membrane lipid, monogalactosyldiacylglycerol, decreased in amount, while the neutral lipid/polar lipid ratio increased in the mutant. The low amount and activity of the mutated Rubisco Y67A enzyme seems to have an adverse effect on photosynthesis and causes changes in carbon allocation in terms of membrane fatty acid composition and storage lipid accumulation. Our results suggest that Rubisco mutants of Chlamydomonas might be useful in biodiesel production.

  11. Comparison of lipids in organs of the starfish Asterias amurensis associated with different treatments

    NASA Astrophysics Data System (ADS)

    Wang, Qi; Ikegame, Keita; Takahashi, Koretaro; Xue, Changhu; Zhang, Weinong; Wang, Hongxun; Hou, Wenfu; Wang, Yuming

    2013-09-01

    Lipids were extracted from organs of the starfish Asterias amurensis associated with different treatments (raw-control, boiling and heating), and then analyzed for lipid content, lipid oxidation index, lipid classes and fatty acid composition. Results showed that boiling softened the hard starfish shells, thus facilitating the collection of starfish organs. As compared with raw organs, the boiled organs had lower water content and higher lipid content, possibly due to the loss of water-holding capacity caused by protein denaturation. Both boiling and heating increased the peroxide value (PV), thiobarbituric acid (TBA) value and carbon value (CV) of lipids. Despite slight increases in the content of complex lipids, associated lipid composition had no substantial variations upon boiling and heating. For simple lipids, the content of 1, 2-diglyceride decreased in boiled and heated organs, with free fatty acids observed on thin layer chromatography (TLC). However, neither boiling nor heating significantly changed the fatty acid compositions of simple or complex lipids in starfish organs, suggesting that these two treatments had no significant effects on complex lipids in starfish organs. Together, our results indicated that boiling of starfish soon after capture facilitated the handling and extraction of useful complex lipids consisting of abundant glucosylceramide and eicosapentaenoic acid (EPA)-bounded phospholipids.

  12. Endogenous pyrogen-like substance produced by reptiles.

    PubMed

    Bernheim, H A; Kluger, M J

    1977-06-01

    1. Injection of lizards (Dipsosaurus dorsalis) with rabbit endogenous pyrogen led to a fever. Injections with denatured endogenous pyrogen did not affect body temperature. 2. Injection of lizards with lizard endogenous pyrogen led to a fever of short duration, while injection of denatured lizard endogenous pyrogen produced no change in body temperature. 3. These data support the hypothesis that the febrile mechanism observed in the higher vertebrates has its origins in some primitive vertebrate.

  13. Pathological hypertrophy and cardiac dysfunction are linked to aberrant endogenous unsaturated fatty acid metabolism

    PubMed Central

    Salomé Campos, Dijon Henrique; Grippa Sant’Ana, Paula; Okoshi, Katashi; Padovani, Carlos Roberto; Masahiro Murata, Gilson; Nguyen, Son; Kolwicz, Stephen C.; Cicogna, Antonio Carlos

    2018-01-01

    Pathological cardiac hypertrophy leads to derangements in lipid metabolism that may contribute to the development of cardiac dysfunction. Since previous studies, using high saturated fat diets, have yielded inconclusive results, we investigated whether provision of a high-unsaturated fatty acid (HUFA) diet was sufficient to restore impaired lipid metabolism and normalize diastolic dysfunction in the pathologically hypertrophied heart. Male, Wistar rats were subjected to supra-valvar aortic stenosis (SVAS) or sham surgery. After 6 weeks, diastolic dysfunction and pathological hypertrophy was confirmed and both sham and SVAS rats were treated with either normolipidic or HUFA diet. At 18 weeks post-surgery, the HUFA diet failed to normalize decreased E/A ratios or attenuate measures of cardiac hypertrophy in SVAS animals. Enzymatic activity assays and gene expression analysis showed that both normolipidic and HUFA-fed hypertrophied hearts had similar increases in glycolytic enzyme activity and down-regulation of fatty acid oxidation genes. Mass spectrometry analysis revealed depletion of unsaturated fatty acids, primarily linoleate and oleate, within the endogenous lipid pools of normolipidic SVAS hearts. The HUFA diet did not restore linoleate or oleate in the cardiac lipid pools, but did maintain body weight and adipose mass in SVAS animals. Overall, these results suggest that, in addition to decreased fatty acid oxidation, aberrant unsaturated fatty acid metabolism may be a maladaptive signature of the pathologically hypertrophied heart. The HUFA diet is insufficient to reverse metabolic remodeling, diastolic dysfunction, or pathologically hypertrophy, possibly do to preferentially partitioning of unsaturated fatty acids to adipose tissue. PMID:29494668

  14. Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1.

    PubMed

    Thiagarajan, Praveena S; Yakubenko, Valentin P; Elsori, Deena H; Yadav, Satya P; Willard, Belinda; Tan, Carmela D; Rodriguez, E René; Febbraio, Maria; Cathcart, Martha K

    2013-08-01

    Atherosclerosis is a chronic inflammatory disorder of cholesterol deposition in monocyte-derived macrophages (MDM) within the arterial wall leading to impingement on the lumen of the vessel. In atherosclerotic lesions, MDM are the primary source of NADPH oxidase-derived superoxide anion (O₂⁻) inducing low-density lipoprotein (LDL) oxidation leading to their unregulated uptake of oxidized LDL and foam cell formation. We recently discovered that zymosan potently activates monocyte NADPH oxidase via the non-toll pattern recognition receptor (PRR), Dectin-1. Other PRRs bind endogenous human ligands, yet no such ligands have been identified for Dectin-1. Our hypothesis was that inflammation generates endogenous ligands for Dectin-1 that activate O₂⁻ production and thereby contributes to atherogenesis. Human: anti-zymosan antibodies were used to identify similar, cross-reactive epitopes in human atherosclerotic tissue extracts. Immunoblot analysis revealed consistent antibody reactive protein bands on one- and two-dimensional gel electrophoreses. Vimentin was identified by mass spectrometry in the immunoreactive bands across different tissue samples. Direct binding of vimentin to Dectin-1 was observed using BIACORE. Further data revealed that vimentin induces O₂⁻ production by human monocytes. Analysis of human atherosclerotic lesions revealed that vimentin was detected extracellularly in the necrotic core and in areas of active inflammation. Vimentin also co-localized with Dectin-1 in macrophage-rich regions where O₂⁻ is produced. We conclude that vimentin is an endogenous, activating ligand for Dectin-1. Its presence in areas of artery wall inflammation and O₂⁻ production suggests that vimentin activates Dectin-1 and contributes to the oxidation of lipids and cholesterol accumulation in atherosclerosis.

  15. Endogenous pyrogen-like substance produced by reptiles.

    PubMed Central

    Bernheim, H A; Kluger, M J

    1977-01-01

    1. Injection of lizards (Dipsosaurus dorsalis) with rabbit endogenous pyrogen led to a fever. Injections with denatured endogenous pyrogen did not affect body temperature. 2. Injection of lizards with lizard endogenous pyrogen led to a fever of short duration, while injection of denatured lizard endogenous pyrogen produced no change in body temperature. 3. These data support the hypothesis that the febrile mechanism observed in the higher vertebrates has its origins in some primitive vertebrate. PMID:874874

  16. The green tea modulates large intestinal microbiome and exo/endogenous metabolome altered through chronic UVB-exposure.

    PubMed

    Jung, Eun Sung; Park, Hye Min; Hyun, Seung Min; Shon, Jong Cheol; Singh, Digar; Liu, Kwang-Hyeon; Whon, Tae Woong; Bae, Jin-Woo; Hwang, Jae Sung; Lee, Choong Hwan

    2017-01-01

    The attenuating effects of green tea supplements (GTS) against the ultraviolet (UV) radiation induced skin damages are distinguished. However, the concomitant effects of GTS on the large intestinal microbiomes and associated metabolomes are largely unclear. Herein, we performed an integrated microbiome-metabolome analysis to uncover the esoteric links between gut microbiome and exo/endogenous metabolome maneuvered in the large intestine of UVB-exposed mice subjected to dietary GTS. In UVB-exposed mice groups (UVB), class Bacilli and order Bifidobacteriales were observed as discriminant taxa with decreased lysophospholipid levels compared to the unexposed mice groups subjected to normal diet (NOR). Conversely, in GTS fed UVB-exposed mice (U+GTS), the gut-microbiome diversity was greatly enhanced with enrichment in the classes, Clostridia and Erysipelotrichia, as well as genera, Allobaculum and Lachnoclostridium. Additionally, the gut endogenous metabolomes changed with an increase in amino acids, fatty acids, lipids, and bile acids contents coupled with a decrease in nucleobases and carbohydrate levels. The altered metabolomes exhibited high correlations with GTS enriched intestinal microflora. Intriguingly, the various conjugates of green tea catechins viz., sulfated, glucuronided, and methylated ones including their exogenous derivatives were detected from large intestinal contents and liver samples. Hence, we conjecture that the metabolic conversions for the molecular components in GTS strongly influenced the gut micro-environment in UVB-exposed mice groups, ergo modulate their gut-microbiome as well as exo/endogenous metabolomes.

  17. Quantitative analysis of molecular partition towards lipid membranes using surface plasmon resonance

    NASA Astrophysics Data System (ADS)

    Figueira, Tiago N.; Freire, João M.; Cunha-Santos, Catarina; Heras, Montserrat; Gonçalves, João; Moscona, Anne; Porotto, Matteo; Salomé Veiga, Ana; Castanho, Miguel A. R. B.

    2017-03-01

    Understanding the interplay between molecules and lipid membranes is fundamental when studying cellular and biotechnological phenomena. Partition between aqueous media and lipid membranes is key to the mechanism of action of many biomolecules and drugs. Quantifying membrane partition, through adequate and robust parameters, is thus essential. Surface Plasmon Resonance (SPR) is a powerful technique for studying 1:1 stoichiometric interactions but has limited application to lipid membrane partition data. We have developed and applied a novel mathematical model for SPR data treatment that enables determination of kinetic and equilibrium partition constants. The method uses two complementary fitting models for association and dissociation sensorgram data. The SPR partition data obtained for the antibody fragment F63, the HIV fusion inhibitor enfuvirtide, and the endogenous drug kyotorphin towards POPC membranes were compared against data from independent techniques. The comprehensive kinetic and partition models were applied to the membrane interaction data of HRC4, a measles virus entry inhibitor peptide, revealing its increased affinity for, and retention in, cholesterol-rich membranes. Overall, our work extends the application of SPR beyond the realm of 1:1 stoichiometric ligand-receptor binding into a new and immense field of applications: the interaction of solutes such as biomolecules and drugs with lipids.

  18. Uridine prevents tamoxifen-induced liver lipid droplet accumulation

    PubMed Central

    2014-01-01

    Background Tamoxifen, an agonist of estrogen receptor, is widely prescribed for the prevention and long-term treatment of breast cancer. A side effect of tamoxifen is fatty liver, which increases the risk for non-alcoholic fatty liver disease. Prevention of tamoxifen-induced fatty liver has the potential to improve the safety of long-term tamoxifen usage. Methods Uridine, a pyrimidine nucleoside with reported protective effects against drug-induced fatty liver, was co-administered with tamoxifen in C57BL/6J mice. Liver lipid levels were evaluated with lipid visualization using coherent anti-Stokes Raman scatting (CARS) microscopy, biochemical assay measurement of triacylglyceride (TAG), and liquid chromatography coupled with mass spectrometry (LC-MS) measurement of membrane phospholipid. Blood TAG and cholesterol levels were measured. Mitochondrial respiration of primary hepatocytes in the presence of tamoxifen and/or uridine was evaluated by measuring oxygen consumption rate with an extracellular flux analyzer. Liver protein lysine acetylation profiles were evaluated with 1D and 2D Western blots. In addition, the relationship between endogenous uridine levels, fatty liver, and tamoxifen administration was evaluated in transgenic mice UPase1−/−and UPase1-TG. Results Uridine co-administration prevented tamoxifen-induced liver lipid droplet accumulation in mice. The most prominent effect of uridine co-administration with tamoxifen was the stimulation of liver membrane phospholipid biosynthesis. Uridine had no protective effect against tamoxifen-induced impairment to mitochondrial respiration of primary hepatocytes or liver TAG and cholesterol export. Uridine had no effect on tamoxifen-induced changes to liver protein acetylation profile. Transgenic mice UPase1−/−with increased pyrimidine salvage activity were protected against tamoxifen-induced liver lipid droplet accumulation. In contrast, UPase1-TG mice with increased pyrimidine catabolism activity had

  19. Uridine prevents tamoxifen-induced liver lipid droplet accumulation.

    PubMed

    Le, Thuc T; Urasaki, Yasuyo; Pizzorno, Giuseppe

    2014-05-23

    Tamoxifen, an agonist of estrogen receptor, is widely prescribed for the prevention and long-term treatment of breast cancer. A side effect of tamoxifen is fatty liver, which increases the risk for non-alcoholic fatty liver disease. Prevention of tamoxifen-induced fatty liver has the potential to improve the safety of long-term tamoxifen usage. Uridine, a pyrimidine nucleoside with reported protective effects against drug-induced fatty liver, was co-administered with tamoxifen in C57BL/6J mice. Liver lipid levels were evaluated with lipid visualization using coherent anti-Stokes Raman scatting (CARS) microscopy, biochemical assay measurement of triacylglyceride (TAG), and liquid chromatography coupled with mass spectrometry (LC-MS) measurement of membrane phospholipid. Blood TAG and cholesterol levels were measured. Mitochondrial respiration of primary hepatocytes in the presence of tamoxifen and/or uridine was evaluated by measuring oxygen consumption rate with an extracellular flux analyzer. Liver protein lysine acetylation profiles were evaluated with 1D and 2D Western blots. In addition, the relationship between endogenous uridine levels, fatty liver, and tamoxifen administration was evaluated in transgenic mice UPase1-/-and UPase1-TG. Uridine co-administration prevented tamoxifen-induced liver lipid droplet accumulation in mice. The most prominent effect of uridine co-administration with tamoxifen was the stimulation of liver membrane phospholipid biosynthesis. Uridine had no protective effect against tamoxifen-induced impairment to mitochondrial respiration of primary hepatocytes or liver TAG and cholesterol export. Uridine had no effect on tamoxifen-induced changes to liver protein acetylation profile. Transgenic mice UPase1-/-with increased pyrimidine salvage activity were protected against tamoxifen-induced liver lipid droplet accumulation. In contrast, UPase1-TG mice with increased pyrimidine catabolism activity had intrinsic liver lipid droplet

  20. A test of current models for the mechanism of milk-lipid droplet secretion

    PubMed Central

    Jeong, Jaekwang; Lisinski, Ivonne; Kadegowda, Anil K.G.; Shin, Hyunsu; Wooding, F.B. Peter; Daniels, Brian R.; Schaack, Jerome; Mather, Ian H.

    2013-01-01

    Milk lipid is secreted by a unique process, during which triacylglycerol droplets bud from mammary cells coated with an outer bilayer of apical membrane. In all current schemes, the integral protein butyrophilin 1A1 (BTN) is postulated to serve as a transmembrane scaffold, which interacts, either with itself, or with the peripheral proteins, xanthine oxidoreductase (XOR) and possibly perilipin-2 (PLIN2), to form an immobile bridging complex between the droplet and apical surface. In one such scheme, BTN on the surface of cytoplasmic lipid droplets interacts directly with BTN in the apical membrane without binding to either XOR or PLIN2. We tested these models using both biochemical and morphological approaches. BTN was concentrated in the apical membrane in all species examined and contained mature N-linked glycans. We found no evidence for the association of unprocessed BTN with intracellular lipid droplets. BTN-enhanced-green-fluorescent-protein was highly mobile in areas of mouse milk-lipid droplets that had not undergone post-secretion changes, and endogenous mouse BTN comprised only 0.5–0.7%, (w/w) of the total protein, i.e., over fifty-fold less than in the milk-lipid droplets of cow and other species. These data are incompatible with models of milk-lipid secretion in which BTN is the major component of an immobile global adhesive complex and suggest that interactions between BTN and other proteins at the time of secretion are more transient than previously predicted. The high mobility of BTN in lipid droplets, mark it as a potential mobile signaling molecule in milk. PMID:23738536

  1. Integrated femtosecond stimulated Raman scattering and two-photon fluorescence imaging of subcellular lipid and vesicular structures

    NASA Astrophysics Data System (ADS)

    Li, Xuesong; Lam, Wen Jiun; Cao, Zhe; Hao, Yan; Sun, Qiqi; He, Sicong; Mak, Ho Yi; Qu, Jianan Y.

    2015-11-01

    The primary goal of this study is to demonstrate that stimulated Raman scattering (SRS) as a new imaging modality can be integrated into a femtosecond (fs) nonlinear optical (NLO) microscope system. The fs sources of high pulse peak power are routinely used in multimodal nonlinear microscopy to enable efficient excitation of multiple NLO signals. However, with fs excitations, the SRS imaging of subcellular lipid and vesicular structures encounters significant interference from proteins due to poor spectral resolution and a lack of chemical specificity, respectively. We developed a unique NLO microscope of fs excitation that enables rapid acquisition of SRS and multiple two-photon excited fluorescence (TPEF) signals. In the in vivo imaging of transgenic C. elegans animals, we discovered that by cross-filtering false positive lipid signals based on the TPEF signals from tryptophan-bearing endogenous proteins and lysosome-related organelles, the imaging system produced highly accurate assignment of SRS signals to lipid. Furthermore, we demonstrated that the multimodal NLO microscope system could sequentially image lipid structure/content and organelles, such as mitochondria, lysosomes, and the endoplasmic reticulum, which are intricately linked to lipid metabolism.

  2. Factors influencing particulate lipid production in the East Atlantic Ocean

    NASA Astrophysics Data System (ADS)

    Gašparović, B.; Frka, S.; Koch, B. P.; Zhu, Z. Y.; Bracher, A.; Lechtenfeld, O. J.; Neogi, S. B.; Lara, R. J.; Kattner, G.

    2014-07-01

    Extensive analyses of particulate lipids and lipid classes were conducted to gain insight into lipid production and related factors along the biogeochemical provinces of the Eastern Atlantic Ocean. Data are supported by particulate organic carbon (POC), chlorophyll a (Chl a), phaeopigments, Chl a concentrations and carbon content of eukaryotic micro-, nano- and picophytoplankton, including cell abundances for the latter two and for cyanobacteria and prokaryotic heterotrophs. We focused on the productive ocean surface (2 m depth and deep Chl a maximum (DCM). Samples from the deep ocean provided information about the relative reactivity and preservation potential of particular lipid classes. Surface and DCM particulate lipid concentrations (3.5-29.4 μg L-1) were higher than in samples from deep waters (3.2-9.3 μg L-1) where an increased contribution to the POC pool was observed. The highest lipid concentrations were measured in high latitude temperate waters and in the North Atlantic Tropical Gyral Province (13-25°N). Factors responsible for the enhanced lipid synthesis in the eastern Atlantic appeared to be phytoplankton size (micro, nano, pico) and the low nutrient status with microphytoplankton having the most expressed influence in the surface and eukaryotic nano- and picophytoplankton in the DCM layer. Higher lipid to Chl a ratios suggest enhanced lipid biosynthesis in the nutrient poorer regions. The various lipid classes pointed to possible mechanisms of phytoplankton adaptation to the nutritional conditions. Thus, it is likely that adaptation comprises the replacement of membrane phospholipids by non-phosphorus containing glycolipids under low phosphorus conditions. The qualitative and quantitative lipid compositions revealed that phospholipids were the most degradable lipids, and their occurrence decreased with increasing depth. In contrast, wax esters, possibly originating from zooplankton, survived downward transport probably due to the fast sinking

  3. Adipose triglyceride lipase acts on neutrophil lipid droplets to regulate substrate availability for lipid mediator synthesis.

    PubMed

    Schlager, Stefanie; Goeritzer, Madeleine; Jandl, Katharina; Frei, Robert; Vujic, Nemanja; Kolb, Dagmar; Strohmaier, Heimo; Dorow, Juliane; Eichmann, Thomas O; Rosenberger, Angelika; Wölfler, Albert; Lass, Achim; Kershaw, Erin E; Ceglarek, Uta; Dichlberger, Andrea; Heinemann, Akos; Kratky, Dagmar

    2015-11-01

    In humans, mutations in ATGL lead to TG accumulation in LDs of most tissues and cells, including peripheral blood leukocytes. This pathologic condition is called Jordans' anomaly, in which functional consequences have not been investigated. In the present study, we tested the hypothesis that ATGL plays a role in leukocyte LD metabolism and immune cell function. Similar to humans with loss-of-function mutations in ATGL, we found that global and myeloid-specific Atgl(-/-) mice exhibit Jordans' anomaly with increased abundance of intracellular TG-rich LDs in neutrophil granulocytes. In a model of inflammatory peritonitis, lipid accumulation was also observed in monocytes and macrophages but not in eosinophils or lymphocytes. Neutrophils from Atgl(-/-) mice showed enhanced immune responses in vitro, which were more prominent in cells from global compared with myeloid-specific Atgl(-/-) mice. Mechanistically, ATGL(-/-) as well as pharmacological inhibition of ATGL led to an impaired release of lipid mediators from neutrophils. These findings demonstrate that the release of lipid mediators is dependent on the liberation of precursor molecules from the TG-rich pool of LDs by ATGL. Our data provide mechanistic insights into Jordans' anomaly in neutrophils and suggest that ATGL is a potent regulator of immune cell function and inflammatory diseases. © The Author(s).

  4. Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and are regulated in brain in an acute model of inflammation

    PubMed Central

    Raboune, Siham; Stuart, Jordyn M.; Leishman, Emma; Takacs, Sara M.; Rhodes, Brandon; Basnet, Arjun; Jameyfield, Evan; McHugh, Douglas; Widlanski, Theodore; Bradshaw, Heather B.

    2014-01-01

    A family of endogenous lipids, structurally analogous to the endogenous cannabinoid, N-arachidonoyl ethanolamine (Anandamide), and called N-acyl amides have emerged as a family of biologically active compounds at TRP receptors. N-acyl amides are constructed from an acyl group and an amine via an amide bond. This same structure can be modified by changing either the fatty acid or the amide to form potentially hundreds of lipids. More than 70 N-acyl amides have been identified in nature. We have ongoing studies aimed at isolating and characterizing additional members of the family of N-acyl amides in both central and peripheral tissues in mammalian systems. Here, using a unique in-house library of over 70 N-acyl amides we tested the following three hypotheses: (1) Additional N-acyl amides will have activity at TRPV1-4, (2) Acute peripheral injury will drive changes in CNS levels of N-acyl amides, and (3) N-acyl amides will regulate calcium in CNS-derived microglia. Through these studies, we have identified 20 novel N-acyl amides that collectively activate (stimulating or inhibiting) TRPV1-4. Using lipid extraction and HPLC coupled to tandem mass spectrometry we showed that levels of at least 10 of these N-acyl amides that activate TRPVs are regulated in brain after intraplantar carrageenan injection. We then screened the BV2 microglial cell line for activity with this N-acyl amide library and found overlap with TRPV receptor activity as well as additional activators of calcium mobilization from these lipids. Together these data provide new insight into the family of N-acyl amides and their roles as signaling molecules at ion channels, in microglia, and in the brain in the context of inflammation. PMID:25136293

  5. Hybrid and Nonhybrid Lipids Exert Common Effects on Membrane Raft Size and Morphology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Heberle, Frederick A; Doktorova, Milka; Goh, Shih Lin

    2013-01-01

    Nanometer-scale domains in cholesterolrich model membranes emulate lipid rafts in cell plasma membranes (PMs). The physicochemical mechanisms that maintain a finite, small domain size are, however, not well understood. A special role has been postulated for chainasymmetric or hybrid lipids having a saturated sn-1 chain and an unsaturated sn-2 chain. Hybrid lipids generate nanodomains in some model membranes and are also abundant in the PM. It was proposed that they align in a preferred orientation at the boundary of ordered and disordered phases, lowering the interfacial energy and thus reducing domain size. We used small-angle neutron scattering and fluorescence techniquesmore » to detect nanoscopic and modulated liquid phase domains in a mixture composed entirely of nonhybrid lipids and cholesterol. Our results are indistinguishable from those obtained previously for mixtures containing hybrid lipids, conclusively showing that hybrid lipids are not required for the formation of nanoscopic liquid domains and strongly implying a common mechanism for the overall control of raft size and morphology. We discuss implications of these findings for theoretical descriptions of nanodomains.« less

  6. Hypothesis: Leukocyte Endogenous Mediator/Endogenous Pyrogen/Lymphocyte-Activating Factor Modulates the Development of Nonspecific and Specific Immunity and Affects Nutritional Status

    DTIC Science & Technology

    1982-04-01

    Hypothesis: leukocyte endogenous mediator/ endogenous pyrogen /lymphocyte-activating factor modulates the development of nonspecific and specific... endogenous pyrogen /lympho- NI cyte-activating factor (LEM/EP/LAF) integrates the host’s nonspecific and specific immune responses to infection by...mediator/ endogenous pyrogen /lymphocyte-activating factor, nonspecific and specific immunity, infection, metabolism, nutrition. Introduction LAF which lead

  7. Endogenous digitalis-like factors.

    PubMed

    Schoner, W

    1992-01-01

    The postulate of a natriuretic factor inhibiting the sodium pump in the kidney led to the detection of increased concentrations of endogenous digitalis-like factors in blood after salt loading, in essential hypertension, in pregnancy-induced hypertension and in chronic hypervolaemia. The recent isolation of ouabain or a close isomer thereof from human plasma and the demonstration of a compound similar if not identical to digoxin in adrenals and human urine shows that mammals like non-vertebrates and toads may synthesize cardiac glycosides in their adrenals and possibly in hypothalamus. The hypothalamus also forms other compounds of unknown structure which bind to the cardiac glycoside receptor site. The differential functions of endogenously formed ouabain and of a digoxin-like substance are unclear. The detailed knowledge of the physiological role of both endogenously formed cardiac glycosides in the regulation of blood pressure has still to be worked out.

  8. Addition of electrophilic lipids to actin alters filament structure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gayarre, Javier; Sanchez, David; Sanchez-Gomez, Francisco J.

    2006-11-03

    Pathophysiological processes associated with oxidative stress lead to the generation of reactive lipid species. Among them, lipids bearing unsaturated aldehyde or ketone moieties can form covalent adducts with cysteine residues and modulate protein function. Through proteomic techniques we have identified actin as a target for the addition of biotinylated analogs of the cyclopentenone prostaglandins 15-deoxy-{delta}{sup 12,14}-PGJ{sub 2} (15d-PGJ{sub 2}) and PGA{sub 1} in NIH-3T3 fibroblasts. This modification could take place in vitro and mapped to the protein C-terminal end. Other electrophilic lipids, like the isoprostane 8-iso-PGA{sub 1} and 4-hydroxy-2-nonenal, also bound to actin. The C-terminal region of actin is importantmore » for monomer-monomer interactions and polymerization. Electron microscopy showed that actin treated with 15d-PGJ{sub 2} or 4-hydroxy-2-nonenal formed filaments which were less abundant and displayed shorter length and altered structure. Streptavidin-gold staining allowed mapping of biotinylated 15d-PGJ{sub 2} at sites of filament disruption. These results shed light on the structural implications of actin modification by lipid electrophiles.« less

  9. Circulatory Support with Venoarterial ECMO Unsuccessful in Aiding Endogenous Diltiazem Clearance after Overdose.

    PubMed

    Frazee, Erin N; Lee, Sarah J; Kalimullah, Ejaaz A; Personett, Heather A; Nelson, Darlene R

    2014-01-01

    Introduction. In cardiovascular collapse from diltiazem poisoning, extracorporeal membrane oxygenation (ECMO) may offer circulatory support sufficient to preserve endogenous hepatic drug clearance. Little is known about patient outcomes and diltiazem toxicokinetics in this setting. Case Report. A 36-year-old woman with a history of myocardial bridging syndrome presented with chest pain for which she self-medicated with 2.4 g of sustained release diltiazem over the course of 8 hours. Hemodynamics and mentation were satisfactory on presentation, but precipitously deteriorated after ICU transfer. She was given fluids, calcium, vasopressors, glucagon, high-dose insulin, and lipid emulsion. Due to circulatory collapse and multiorgan failure including ischemic hepatopathy, she underwent transvenous pacing and emergent initiation of venoarterial ECMO. The peak diltiazem level was 13150 ng/mL (normal 100-200 ng/mL) and it remained elevated at 6340 ng/mL at hour 90. Unfortunately, the patient developed multiple complications which resulted in her death on ICU day 9. Conclusion. This case describes the unsuccessful use of ECMO for diltiazem intoxication. Although past reports suggest that support with ECMO may facilitate endogenous diltiazem clearance, it may be dependent on preserved hepatic function at the time of cannulation, a factor not present in this case.

  10. Lipid rafts sense and direct electric field-induced migration.

    PubMed

    Lin, Bo-Jian; Tsao, Shun-Hao; Chen, Alex; Hu, Shu-Kai; Chao, Ling; Chao, Pen-Hsiu Grace

    2017-08-08

    Endogenous electric fields (EFs) are involved in developmental regulation and wound healing. Although the phenomenon is known for more than a century, it is not clear how cells perceive the external EF. Membrane proteins, responding to electrophoretic and electroosmotic forces, have long been proposed as the sensing molecules. However, specific charge modification of surface proteins did not change cell migration motility nor directionality in EFs. Moreover, symmetric alternating current (AC) EF directs cell migration in a frequency-dependent manner. Due to their charge and ability to coalesce, glycolipids are therefore the likely primary EF sensor driving polarization of membrane proteins and intracellular signaling. We demonstrate that detergent-resistant membrane nanodomains, also known as lipid rafts, are the primary response element in EF sensing. The clustering and activation of caveolin and signaling proteins further stabilize raft structure and feed-forward downstream signaling events, such as rho and PI3K activation. Theoretical modeling supports the experimental results and predicts AC frequency-dependent cell and raft migration. Our results establish a fundamental mechanism for cell electrosensing and provide a role in lipid raft mechanotransduction.

  11. Interaction of lysozyme with a tear film lipid layer model: A molecular dynamics simulation study.

    PubMed

    Wizert, Alicja; Iskander, D Robert; Cwiklik, Lukasz

    2017-12-01

    The tear film is a thin multilayered structure covering the cornea. Its outermost layer is a lipid film underneath of which resides on an aqueous layer. This tear film lipid layer (TFLL) is itself a complex structure, formed by both polar and nonpolar lipids. It was recently suggested that due to tear film dynamics, TFLL contains inhomogeneities in the form of polar lipid aggregates. The aqueous phase of tear film contains lachrymal-origin proteins, whereby lysozyme is the most abundant. These proteins can alter TFLL properties, mainly by reducing its surface tension. However, a detailed nature of protein-lipid interactions in tear film is not known. We investigate the interactions of lysozyme with TFLL in molecular details by employing coarse-grained molecular dynamics simulations. We demonstrate that lysozyme, due to lateral restructuring of TFLL, is able to penetrate the tear lipid film embedded in inverse micellar aggregates. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Optimized Rapeseed Oils Rich in Endogenous Micronutrients Protect High Fat Diet Fed Rats from Hepatic Lipid Accumulation and Oxidative Stress

    PubMed Central

    Xu, Jiqu; Liu, Xiaoli; Gao, Hui; Chen, Chang; Deng, Qianchun; Huang, Qingde; Ma, Zhonghua; Huang, Fenghong

    2015-01-01

    Micronutrients in rapeseed exert a potential benefit to hepatoprotection, but most of them are lost during the conventional refining processing. Thus some processing technologies have been optimized to improve micronutrient retention in oil. The aim of this study is to assess whether optimized rapeseed oils (OROs) have positive effects on hepatic lipid accumulation and oxidative stress induced by a high-fat diet. Methods: Rats received experiment diets containing 20% fat and refined rapeseed oil or OROs obtained with various processing technologies as lipid source. After 10 weeks of treatment, liver was assayed for lipid accumulation and oxidative stress. Results: All OROs reduced hepatic triglyceride contents. Microwave pretreatment-cold pressing oil (MPCPO) which had the highest micronutrients contents also reduced hepatic cholesterol level. MPCPO significantly decreased hepatic sterol regulatory element-binding transcription factor 1 (SREBP1) but increased peroxisome proliferator activated receptor α (PPARα) expressions, and as a result, MPCPO significantly suppressed acetyl CoA carboxylase and induced carnitine palmitoyl transferase-1 and acyl CoA oxidase expression. Hepatic catalase (CAT) and glutathione peroxidase (GPx) activities as well as reduced glutathione (GSH) contents remarkably increased and lipid peroxidation levels decreased in parallel with the increase of micronutrients. Conclusion: OROs had the ability to reduce excessive hepatic fat accumulation and oxidative stress, which indicated that OROs might contribute to ameliorating nonalcoholic fatty liver induced by high-fat diet. PMID:26473919

  13. Elevated levels of N-lauroylethanolamine, an endogenous constituent of desiccated seeds, disrupt normal root development in Arabidopsis thaliana seedlings

    NASA Technical Reports Server (NTRS)

    Blancaflor, Elison B.; Hou, Guichuan; Chapman, Kent D.

    2003-01-01

    N-Acylethanolamines (NAEs) are prevalent in desiccated seeds of various plant species, and their levels decline substantially during seed imbibition and germination. Here, seeds of Arabidopsis thaliana (L.) Heynh. were germinated in, and seedlings maintained on, micromolar concentrations of N-lauroylethanolamine (NAE 12:0). NAE 12:0 inhibited root elongation, increased radial swelling of root tips, and reduced root hair numbers in a highly selective and concentration-dependent manner. These effects were reversible when seedlings were transferred to NAE-free medium. Older seedlings (14 days old) acclimated to exogenous NAE by increased formation of lateral roots, and generally, these lateral roots did not exhibit the severe symptoms observed in primary roots. Cells of NAE-treated primary roots were swollen and irregular in shape, and in many cases showed evidence, at the light- and electron-microscope levels, of improper cell wall formation. Microtubule arrangement was disrupted in severely distorted cells close to the root tip, and endoplasmic reticulum (ER)-localized green fluorescent protein (mGFP5-ER) was more abundant, aggregated and distributed differently in NAE-treated root cells, suggesting disruption of proper cell division, endomembrane organization and vesicle trafficking. These results suggest that NAE 12:0 likely influences normal cell expansion in roots by interfering with intracellular membrane trafficking to and/or from the cell surface. The rapid metabolism of NAEs during seed imbibition/germination may be a mechanism to remove this endogenous class of lipid mediators to allow for synchronized membrane reorganization associated with cell expansion.

  14. Endogenous nandrolone metabolites in human urine: preliminary results to discriminate between endogenous and exogenous origin.

    PubMed

    Le Bizec, Bruno; Bryand, Fabrice; Gaudin, Isabelle; Monteau, Fabrice; Poulain, Frédéric; Andre, François

    2002-02-01

    When administered to human subjects, nandrolone is metabolized into two main products, 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE). Recent studies demonstrated the endogenous production of these compounds in man at concentrations very close to the threshold of the International Olympic Committee (IOC), i.e. 2 ng/ml. Because the possibility of reaching or exceeding this fateful limit is difficult to exclude, a complementary biochemical parameter is necessary for the differentiation of endogenous 19-NA and 19-NE production from residues resulting from nandrolone consumption. We measured the endogenous concentrations of 19-NA and 19-NE in 385 urine samples from professional football players, and we studied the phase II metabolite composition in individuals excreting the highest concentrations. The results showed that around 30% of endogenous 19-norandrosterone was sulfo-conjugated, whereas 100% of 19-norandrosterone was excreted conjugated to a glucuronic acid when nandrolone was administered. This significant qualitative difference appears to be a promising complementary criterion to more definitively conclude about an athlete's culpability, especially when nandrolone metabolites are found in the low ng/ml range.

  15. A Mouse Model to Evaluate the Impact of Species, Sex, and Lipid Load on Lymphatic Drug Transport

    PubMed Central

    Caliph, Suzanne M.; Nguyen, Gary; Tso, Patrick; Charman, William N.

    2014-01-01

    Purpose To establish a lymph-cannulated mouse model, and use the model to investigate the impact of lipid dose on exogenous and endogenous lipid recruitment, and drug transport, into the lymph of males versus females. Finally, lymphatic transport and drug absorption in the mouse were compared to other pre-clinical models (rats/dogs). Methods Animals were orally or intraduodenally administered 1.6 mg/kg halofantrine in low or high 14C-lipid doses. For bioavailability calculation, animals were intravenuosly administered halofantrine. Lymph or blood samples were taken and halofantrine, triglyceride, phospholipid and 14C-lipid concentrations measured. Results Lymphatic lipid transport increased linearly with lipid dose, was similar across species and in male/female animals. In contrast, lymphatic transport of halofantrine differed markedly across species (dogs>rats>mice) and plateaued at higher lipid doses. Lower bioavailability appeared responsible for some species differences in halofantrine lymphatic transport; however other systematic differences were involved. Conclusions A contemporary lymph-cannulated mouse model was established which will enable investigation of lymphatic transport in transgenic and disease models. The current study found halofantrine absorption and lymphatic transport are reduced in small animals. Future analyses will investigate mechanisms involved, and if similar trends occur for other drugs, to establish the most relevant model(s) to predict lymphatic transport in humans. PMID:23430484

  16. Systems analysis of phosphate-limitation-induced lipid accumulation by the oleaginous yeast Rhodosporidium toruloides.

    PubMed

    Wang, Yanan; Zhang, Sufang; Zhu, Zhiwei; Shen, Hongwei; Lin, Xinping; Jin, Xiang; Jiao, Xiang; Zhao, Zongbao Kent

    2018-01-01

    Lipid accumulation by oleaginous microorganisms is of great scientific interest and biotechnological potential. While nitrogen limitation has been routinely employed, low-cost raw materials usually contain rich nitrogenous components, thus preventing from efficient lipid production. Inorganic phosphate (Pi) limitation has been found sufficient to promote conversion of sugars into lipids, yet the molecular basis of cellular response to Pi limitation and concurrent lipid accumulation remains elusive. Here, we performed multi-omic analyses of the oleaginous yeast Rhodosporidium toruloides to shield lights on Pi-limitation-induced lipid accumulation. Samples were prepared under Pi-limited as well as Pi-repleted chemostat conditions, and subjected to analysis at the transcriptomic, proteomic, and metabolomic levels. In total, 7970 genes, 4212 proteins, and 123 metabolites were identified. Results showed that Pi limitation facilitates up-regulation of Pi-associated metabolism, RNA degradation, and triacylglycerol biosynthesis while down-regulation of ribosome biosynthesis and tricarboxylic acid cycle. Pi limitation leads to dephosphorylation of adenosine monophosphate and the allosteric activator of isocitrate dehydrogenase key to lipid biosynthesis. It was found that NADPH, the key cofactor for fatty acid biosynthesis, is limited due to reduced flux through the pentose phosphate pathway and transhydrogenation cycle and that this can be overcome by over-expression of an endogenous malic enzyme. These phenomena are found distinctive from those under nitrogen limitation. Our data suggest that Pi limitation activates Pi-related metabolism, RNA degradation, and TAG biosynthesis while inhibits ribosome biosynthesis and TCA cycle, leading to enhanced carbon fluxes into lipids. The information greatly enriches our understanding on microbial oleaginicity and Pi-related metabolism. Importantly, systems data may facilitate designing advanced cell factories for production of lipids

  17. In vivo study of lipid synthesis and lipolysis dynamics by stimulated Raman scattering microscopy

    NASA Astrophysics Data System (ADS)

    Li, Xuesong; Li, Yan; He, Sicong; Chen, Congping; Qin, Zhongya; Mak, Ho Yi; Qu, Jianan Y.

    2018-02-01

    To understand the mechanisms of important lipid-related biological processes and diseases, it is highly demanded to study the dynamics of lipids in living biological system with high spatiotemporal resolution. However, in vivo quantitative analysis of lipid synthesis and lipolysis has been technically difficult to achieve by conventional lipid extraction and fluorescent staining methods. Recently, SRS microscopy has emerged as a powerful tool to probe small molecules with alkyne (C≡C) or deuterium (C-D) labeling in cell-silent region. The Raman tags have been used for the quantitative study of lipids in cells. In this study, we investigated metabolic dynamics of lipid droplets (LDs) by tracing the alkyne-tagged fatty acid 17-ODYA and deuterium-labeled saturated and unsaturated fatty acids PA-D31 & OA-D34 in living C. elegans. Specifically, we developed a hyperspectral SRS microscope system for LDs characterization. The system can sequentially excite and probe the stimulated Raman scattering-induced CH2 stretching of endogenous lipids information (2863 cm-1), C≡C stretching from 17-ODYA (2125 cm-1) and C-D stretching from deuterium-labeled fatty acids (2117 cm-1). We first examined the concentration levels of fatty acids in E. coli OP50. Two major lipid metabolic processes, namely uptake and turnover, were further studied in adult C. elegans. We imaged alkyne-tagged and deuterated fatty acids using SRS and traced their uptake, transportation, incorporation and turnover over time. Additionally, several other treatments including starvation were also conducted to study their effects on metabolic dynamics of pulse labeled 17-ODYA, PA-D31 and OA-D34.

  18. Trapping toxins within lipid droplets is a resistance mechanism in fungi

    PubMed Central

    Chang, Wenqiang; Zhang, Ming; Zheng, Sha; Li, Ying; Li, Xiaobin; Li, Wei; Li, Gang; Lin, Zhaomin; Xie, Zhiyu; Zhao, Zuntian; Lou, Hongxiang

    2015-01-01

    Lipid droplets (LDs) act as intracellular storage organelles in most types of cells and are principally involved in energy homeostasis and lipid metabolism. However, the role of LDs in resistance to toxins in fungi remains largely unknown. Here, we show that the trapping of endogenous toxins by LDs is a self-resistance mechanism in the toxin producer, while absorbing external lipophilic toxins is a resistance mechanism in the toxin recipient that acts to quench the production of reactive oxygen species. We found that an endolichenic fungus that generates phototoxic perylenequinones (PQs) trapped the PQs inside LDs. Using a model that incorporates the fungicidal action of hypocrellin A (HA), a PQ derivative, we showed that yeast cells escaped killing by trapping toxins inside LDs. Furthermore, LD-deficient mutants were hypersusceptible to HA-mediated phototoxins and other fungicides. Our study identified a previously unrecognised function of LDs in fungi that has implications for our understanding of environmental adaptation strategies for fungi and antifungal drug discovery. PMID:26463663

  19. Food-induced changes of lipids in rat neuronal tissue visualized by ToF-SIMS imaging.

    PubMed

    Dowlatshahi Pour, Masoumeh; Jennische, Eva; Lange, Stefan; Ewing, Andrew G; Malmberg, Per

    2016-09-06

    Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to image the lipid localization in brain tissue sections from rats fed specially processed cereals (SPC). An IonTof 5 instrument equipped with a Bi cluster ion gun was used to analyze the tissue sections. Data from 15 brain samples from control and cereal-fed rats were recorded and exported to principal components analysis (PCA). The data clearly show changes of certain lipids in the brain following cereal feeding. PCA score plots show a good separation in lipid distribution between the control and the SPC-fed group. The loadings plot reveal that the groups separated mainly due to changes in cholesterol, vitamin E and c18:2, c16:0 fatty acid distribution as well as some short chain monocarboxylic fatty acid compositions. These insights relate to the working mechanism of SPC as a dietary supplement. SPC is thought to activate antisecretory factor (AF), an endogenous protein with regulatory function for inflammation and fluid secretion. These data provide insights into lipid content in brain following SPC feeding and suggest a relation to activating AF.

  20. Ciliary neurotrophic factor is an endogenous pyrogen.

    PubMed

    Shapiro, L; Zhang, X X; Rupp, R G; Wolff, S M; Dinarello, C A

    1993-09-15

    Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) following intravenous injection; CNTF fever was blocked by pretreatment with indomethacin. The fever induced by CNTF was not due to contaminating endotoxins. Increasing doses of CNTF resulted in prolongation of the fever, suggesting the subsequent induction of additional endogenous pyrogenic activity. After passive transfer of plasma obtained during CNTF-induced fever, endogenous pyrogen activity was not present in the circulation; CNTF also did not induce the endogenous pyrogens interleukin 1, tumor necrosis factor, or interleukin 6 in vitro. Nevertheless, a second endogenous pyrogen may originate within the central nervous system following the systemic injection of CNTF. Of the four endogenous pyrogens described to date (interleukin 1, tumor necrosis factor, interferon, and interleukin 6), CNTF, like interleukin 6, utilizes the cell-surface gp 130 signal-transduction apparatus.

  1. Mechanisms of Action of Compounds That Enhance Storage Lipid Accumulation in Daphnia magna

    PubMed Central

    2016-01-01

    Accumulation of storage lipids in the crustacean Daphnia magna can be altered by a number of exogenous and endogenous compounds, like 20-hydroxyecdysone (natural ligand of the ecdysone receptor, EcR), methyl farnesoate, pyrirproxyfen (agonists of the methyl farnesoate receptor, MfR), and tributyltin (agonist of the retinoid X acid receptor, RXR). This effect, analogous to the obesogenic disruption in mammals, alters Daphnia’s growth and reproductive investment. Here we propose that storage lipid accumulation in droplets is regulated in Daphnia by the interaction between the nuclear receptor heterodimer EcR:RXR and MfR. The model was tested by determining changes in storage lipid accumulation and on gene transcription in animals exposed to different effectors of RXR, EcR, and MfR signaling pathways, either individually or in combination. RXR, EcR, and MfR agonists increased storage lipid accumulation, whereas fenarimol and testosterone (reported inhibitors of ecdysteroid synthesis and an EcR antagonist, respectively) decreased it. Joint effects of mixtures with fenarimol, testosterone, and ecdysone were antagonistic, mixtures of juvenoids showed additive effects following a concentration addition model, and combinations of tributyltin with juvenoids resulted in greater than additive effects. Co-exposures of ecdysone with juvenoids resulted in deregulation of ecdysone- and farnesoid-regulated genes, accordingly with the observed changes in lipid accumulation These results indicate the requirement of ecdysone binding to the EcR:RXR:MfR complex to regulate lipid storage and that an excess of ecdysone disrupts the whole process, probably by triggering negative feedback mechanisms. PMID:27993043

  2. Synthesis, metabolism and systemic transport of a fluorinated mimic of the endogenous jasmonate precursor OPC-8:0.

    PubMed

    Jimenez-Aleman, Guillermo H; Scholz, Sandra S; Heyer, Monika; Reichelt, Michael; Mithöfer, Axel; Boland, Wilhelm

    2015-12-01

    Jasmonates (JAs) are fatty acid derivatives that mediate many developmental processes and stress responses in plants. Synthetic jasmonate derivatives (commonly isotopically labeled), which mimic the action of the endogenous compounds are often employed as internal standards or probes to study metabolic processes. However, stable-isotope labeling of jasmonates does not allow the study of spatial and temporal distribution of these compounds in real time by positron emission tomography (PET). In this study, we explore whether a fluorinated jasmonate could mimic the action of the endogenous compound and therefore, be later employed as a tracer to study metabolic processes by PET. We describe the synthesis and the metabolism of (Z)-7-fluoro-8-(3-oxo-2-(pent-2-en-1-yl)cyclopentyl)octanoic acid (7F-OPC-8:0), a fluorinated analog of the JA precursor OPC-8:0. Like endogenous jasmonates, 7F-OPC-8:0 induces the transcription of marker jasmonate responsive genes (JRG) and the accumulation of jasmonates after its application to Arabidopsis thaliana plants. By using UHPLC-MS/MS, we could show that 7F-OPC-8:0 is metabolized in vivo similarly to the endogenous OPC-8:0. Furthermore, the fluorinated analog was successfully employed as a probe to show its translocation to undamaged systemic leaves when it was applied to wounded leaves. This result suggests that OPC-8:0 - and maybe other oxylipins - may contribute to the mobile signal which triggers systemic defense responses in plants. We highlight the potential of fluorinated oxylipins to study the mode of action of lipid-derived molecules in planta, either by conventional analytical methods or fluorine-based detection techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Lipid14: The Amber Lipid Force Field

    PubMed Central

    2015-01-01

    The AMBER lipid force field has been updated to create Lipid14, allowing tensionless simulation of a number of lipid types with the AMBER MD package. The modular nature of this force field allows numerous combinations of head and tail groups to create different lipid types, enabling the easy insertion of new lipid species. The Lennard-Jones and torsion parameters of both the head and tail groups have been revised and updated partial charges calculated. The force field has been validated by simulating bilayers of six different lipid types for a total of 0.5 μs each without applying a surface tension; with favorable comparison to experiment for properties such as area per lipid, volume per lipid, bilayer thickness, NMR order parameters, scattering data, and lipid lateral diffusion. As the derivation of this force field is consistent with the AMBER development philosophy, Lipid14 is compatible with the AMBER protein, nucleic acid, carbohydrate, and small molecule force fields. PMID:24803855

  4. Unusual Butane- and Pentanetriol-Based Tetraether Lipids in Methanomassiliicoccus luminyensis, a Representative of the Seventh Order of Methanogens

    PubMed Central

    Elling, Felix J.; Yoshinaga, Marcos Y.; Söllinger, Andrea; Urich, Tim; Hinrichs, Kai-Uwe

    2016-01-01

    ABSTRACT A new clade of archaea has recently been proposed to constitute the seventh methanogenic order, the Methanomassiliicoccales, which is related to the Thermoplasmatales and the uncultivated archaeal clades deep-sea hydrothermal vent Euryarchaeota group 2 and marine group II Euryarchaeota but only distantly related to other methanogens. In this study, we investigated the membrane lipid composition of Methanomassiliicoccus luminyensis, the sole cultured representative of this seventh order. The lipid inventory of M. luminyensis comprises a unique assemblage of novel lipids as well as lipids otherwise typical for thermophilic, methanogenic, or halophilic archaea. For instance, glycerol sesterpanyl-phytanyl diether core lipids found mainly in halophilic archaea were detected, and so were compounds bearing either heptose or methoxylated glycosidic head groups, neither of which have been reported so far for other archaea. The absence of quinones or methanophenazines is consistent with a biochemistry of methanogenesis different from that of the methanophenazine-containing methylotrophic methanogens. The most distinctive characteristic of the membrane lipid composition of M. luminyensis, however, is the presence of tetraether lipids in which one glycerol backbone is replaced by either butane- or pentanetriol, i.e., lipids recently discovered in marine sediments. Butanetriol dibiphytanyl glycerol tetraether (BDGT) constitutes the most abundant core lipid type (>50% relative abundance) in M. luminyensis. We have thus identified a source for these unusual orphan lipids. The complementary analysis of diverse marine sediment samples showed that BDGTs are widespread in anoxic layers, suggesting an environmental significance of Methanomassiliicoccales and/or related BDGT producers beyond gastrointestinal tracts. IMPORTANCE Cellular membranes of members of all three domains of life, Archaea, Bacteria, and Eukarya, are largely formed by lipids in which glycerol serves as

  5. The SwissLipids knowledgebase for lipid biology

    PubMed Central

    Liechti, Robin; Hyka-Nouspikel, Nevila; Niknejad, Anne; Gleizes, Anne; Götz, Lou; Kuznetsov, Dmitry; David, Fabrice P.A.; van der Goot, F. Gisou; Riezman, Howard; Bougueleret, Lydie; Xenarios, Ioannis; Bridge, Alan

    2015-01-01

    Motivation: Lipids are a large and diverse group of biological molecules with roles in membrane formation, energy storage and signaling. Cellular lipidomes may contain tens of thousands of structures, a staggering degree of complexity whose significance is not yet fully understood. High-throughput mass spectrometry-based platforms provide a means to study this complexity, but the interpretation of lipidomic data and its integration with prior knowledge of lipid biology suffers from a lack of appropriate tools to manage the data and extract knowledge from it. Results: To facilitate the description and exploration of lipidomic data and its integration with prior biological knowledge, we have developed a knowledge resource for lipids and their biology—SwissLipids. SwissLipids provides curated knowledge of lipid structures and metabolism which is used to generate an in silico library of feasible lipid structures. These are arranged in a hierarchical classification that links mass spectrometry analytical outputs to all possible lipid structures, metabolic reactions and enzymes. SwissLipids provides a reference namespace for lipidomic data publication, data exploration and hypothesis generation. The current version of SwissLipids includes over 244 000 known and theoretically possible lipid structures, over 800 proteins, and curated links to published knowledge from over 620 peer-reviewed publications. We are continually updating the SwissLipids hierarchy with new lipid categories and new expert curated knowledge. Availability: SwissLipids is freely available at http://www.swisslipids.org/. Contact: alan.bridge@isb-sib.ch Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25943471

  6. Lipids and lipid binding proteins: a perfect match.

    PubMed

    Glatz, Jan F C

    2015-02-01

    Lipids serve a great variety of functions, ranging from structural components of biological membranes to signaling molecules affecting various cellular functions. Several of these functions are related to the unique physico-chemical properties shared by all lipid species, i.e., their hydrophobicity. The latter, however, is accompanied by a poor solubility in an aqueous environment and thus a severe limitation in the transport of lipids in aqueous compartments such as blood plasma and the cellular soluble cytoplasm. Specific proteins which can reversibly and non-covalently associate with lipids, designated as lipid binding proteins or lipid chaperones, greatly enhance the aqueous solubility of lipids and facilitate their transport between tissues and within tissue cells. Importantly, transport of lipids across biological membranes also is facilitated by specific (membrane-associated) lipid binding proteins. Together, these lipid binding proteins determine the bio-availability of their ligands, and thereby markedly influence the subsequent processing, utilization, or signaling effect of lipids. The bio-availability of specific lipid species thus is governed by the presence of specific lipid binding proteins, the affinity of these proteins for distinct lipid species, and the presence of competing ligands (including pharmaceutical compounds). Recent studies suggest that post-translational modifications of lipid binding proteins may have great impact on lipid-protein interactions. As a result, several levels of regulation exist that together determine the bio-availability of lipid species. This short review discusses the significance of lipid binding proteins and their potential application as targets for therapeutic intervention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Effect of chloroquine on intestinal lipid metabolism

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mansbach, C.M. 2d.; Arnold, A.; Garrett, M.

    1987-11-01

    Most studies that have quantitated recovery of infused lipid in the intestinal mucosa and mesenteric lymph have only been able to recapture 50-75%. One possibility is that the missing lipid enters a triacylglycerol (TG) storage pool in the enterocyte and is hydrolyzed by lysosomal lipase, and the free fatty acid released is transported by the portal vein. This postulate was tested by comparing glyceryl trioleate (TO)-infused rats pretreated with the lysosomotropic drug, chloroquine (6.3 mg.kg-1.h-1) with saline controls. Chloroquine increased mucosal TG from 94 +/- 6 to 128 +/- 8 mumol. Additionally, the specific activity of the mucosal TG relativemore » to the infused (/sup 3/H)TO was reduced in the treated rats. The mucosal TG increase was not due to impaired TG output, which remained the same as controls. We conclude that the TG in the acid lipase-sensitive pool derives most of its glyceride-glycerol from endogenous sources. Furthermore, the increment in mucosal TG caused by chloroquine is not enough to explain the majority of the acyl groups unaccounted for in the mucosa and lymph after a TG infusion. For these a direct passage of acyl groups through the enterocyte is postulated.« less

  8. Regulation of NF-κB-Induced Inflammatory Signaling by Lipid Peroxidation-Derived Aldehydes

    PubMed Central

    Yadav, Umesh C. S.; Ramana, Kota V.

    2013-01-01

    Oxidative stress plays a critical role in the pathophysiology of a wide range of diseases including cancer. This view has broadened significantly with the recent discoveries that reactive oxygen species initiated lipid peroxidation leads to the formation of potentially toxic lipid aldehyde species such as 4-hydroxy-trans-2-nonenal (HNE), acrolein, and malondialdehyde which activate various signaling intermediates that regulate cellular activity and dysfunction via a process called redox signaling. The lipid aldehyde species formed during synchronized enzymatic pathways result in the posttranslational modification of proteins and DNA leading to cytotoxicity and genotoxicty. Among the lipid aldehyde species, HNE has been widely accepted as a most toxic and abundant lipid aldehyde generated during lipid peroxidation. HNE and its glutathione conjugates have been shown to regulate redox-sensitive transcription factors such as NF-κB and AP-1 via signaling through various protein kinase cascades. Activation of redox-sensitive transcription factors and their nuclear localization leads to transcriptional induction of several genes responsible for cell survival, differentiation, and death. In this review, we describe the mechanisms by which the lipid aldehydes transduce activation of NF-κB signaling pathways that may help to develop therapeutic strategies for the prevention of a number of inflammatory diseases. PMID:23710287

  9. Response to glucose and lipid infusions in sepsis: a kinetic analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shaw, J.H.; Wolfe, R.R.

    The kinetics and oxidation of glucose and free fatty acid (FFA) metabolism were assessed in control and Escherichia coli septicemic dogs by using primed, constant infusions of U-/sup 14/C-glucose and 1,2, /sup 13/C-palmitic acid. In the controls, the infusion of glucose suppressed endogenous glucose production completely, whereas, in the septic dogs, only a 30% suppression of glucose production occurred. The ability of the septic dogs to oxidize endogenous or exogenous glucose was decreased significantly. The basal rate of appearance of FFA was significantly higher in the septic dogs, but their ability to oxidize FFA was comparable to that of themore » control dogs; therefore, the basal rate of FFA oxidation was higher in the septic dogs. These studies indicate that septic dogs have a decreased capacity to oxidize glucose, but that they retain their ability to oxidize long-chain fatty acids. Because the rate of lipolysis was increased in sepsis, lipid was the predominate energy substrate in this septic model.« less

  10. Ciliary neurotrophic factor is an endogenous pyrogen.

    PubMed Central

    Shapiro, L; Zhang, X X; Rupp, R G; Wolff, S M; Dinarello, C A

    1993-01-01

    Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) following intravenous injection; CNTF fever was blocked by pretreatment with indomethacin. The fever induced by CNTF was not due to contaminating endotoxins. Increasing doses of CNTF resulted in prolongation of the fever, suggesting the subsequent induction of additional endogenous pyrogenic activity. After passive transfer of plasma obtained during CNTF-induced fever, endogenous pyrogen activity was not present in the circulation; CNTF also did not induce the endogenous pyrogens interleukin 1, tumor necrosis factor, or interleukin 6 in vitro. Nevertheless, a second endogenous pyrogen may originate within the central nervous system following the systemic injection of CNTF. Of the four endogenous pyrogens described to date (interleukin 1, tumor necrosis factor, interferon, and interleukin 6), CNTF, like interleukin 6, utilizes the cell-surface gp 130 signal-transduction apparatus. PMID:8378338

  11. Thyroid hormone-induced oxidative damage on lipids, glutathione and DNA in the mouse heart.

    PubMed

    Gredilla, R; Barja, G; López-Torres, M

    2001-10-01

    Oxygen radicals of mitochondrial origin are involved in oxidative damage. In order to analyze the possible relationship between metabolic rate, oxidative stress and oxidative damage, OF1 female mice were rendered hyper- and hypothyroid by chronic administration of 0.0012% L-thyroxine (T4) and 0.05% 6-n-propyl-2-thiouracil (PTU), respectively, in their drinking water for 5 weeks. Hyperthyroidism significantly increased the sensitivity to lipid peroxidation in the heart, although the endogenous levels of lipid peroxidation were not altered. Thyroid hormone-induced oxidative stress also resulted in higher levels of GSSG and GSSG/GSH ratio. Oxidative damage to mitochondrial DNA was greater than that to genomic DNA. Hyperthyroidism decreased oxidative damage to genomic DNA. Hypothyroidism did not modify oxidative damage in the lipid fraction but significantly decreased GSSG and GSSG/GSH ratio and oxidative damage to mitochondrial DNA. These results indicate that thyroid hormones modulate oxidative damage to lipids and DNA, and cellular redox potential in the mouse heart. A higher oxidative stress in the hyperthyroid group is presumably neutralized in the case of nuclear DNA by an increase in repair activity, thus protecting this key molecule. Treatment with PTU, a thyroid hormone inhibitor, reduced oxidative damage in the different cell compartments.

  12. Using ambient ozone for assignment of double bond position in unsaturated lipids.

    PubMed

    Ellis, Shane R; Hughes, Jessica R; Mitchell, Todd W; in het Panhuis, Marc; Blanksby, Stephen J

    2012-03-07

    Unsaturated lipids deposited onto a range of materials are observed to react with the low concentrations of ozone present in normal laboratory air. Parent lipids and ozonolysis cleavage products are both detected directly from surfaces by desorption electrospray ionisation mass spectrometry (DESI-MS) with the resulting mass spectra providing clear evidence of the double bond position within these molecules. This serendipitous process has been coupled with thin-layer chromatography (TLC) to provide a simple but powerful approach for the detailed structural elucidation of lipids present in complex biological extracts. Lipid extracts from human lens were deposited onto normal phase TLC plates and then developed to separate components according to lipid class. Exposure of the developed plates to laboratory air for ca. 1 h prior to DESI-MS analysis gave rise to ozonolysis products allowing for the unambiguous identification of double bond positions in even low abundant, unsaturated lipids. In particular, the co-localization of intact unsaturated lactosylceramides (LacCer) with products from their oxidative cleavage provide the first evidence for the presence of three isomeric LacCer (d18:0/24:1) species in the ocular lens lipidome, i.e., variants with double bonds at the n-9, n-7 and n-5 positions.

  13. The constitutive lipid droplet protein PLIN2 regulates autophagy in liver.

    PubMed

    Tsai, Tsung-Huang; Chen, Elaine; Li, Lan; Saha, Pradip; Lee, Hsiao-Ju; Huang, Li-Shin; Shelness, Gregory S; Chan, Lawrence; Chang, Benny Hung-Junn

    2017-07-03

    Excess triglyceride (TG) accumulation in the liver underlies fatty liver disease, a highly prevalent ailment. TG occurs in the liver sequestered in lipid droplets, the major lipid storage organelle. Lipid droplets are home to the lipid droplet proteins, the most abundant of which are the perilipins (PLINs), encoded by 5 different genes, Plin1 to Plin5. Of the corresponding gene products, PLIN2 is the only constitutive and ubiquitously expressed lipid droplet protein that has been used as a protein marker for lipid droplets. We and others reported that plin2 -/- mice have an ∼60% reduction in TG content, and are protected against fatty liver disease. Here we show that PLIN2 overexpression protects lipid droplets against macroautophagy/autophagy, whereas PLIN2 deficiency enhances autophagy and depletes hepatic TG. The enhanced autophagy in plin2 -/- mice protects against severe ER stress-induced hepatosteatosis and hepatocyte apoptosis. In contrast, hepatic TG depletion resulting from other genetic and pharmacological manipulations has no effect on autophagy. Importantly, PLIN2 deficiency lowers cellular TG content in wild-type mouse embryonic fibroblasts (MEFs) via enhanced autophagy, but does not affect cellular TG content in atg7 -/- MEFs that are devoid of autophagic function. Conversely, adenovirus-shAtg7-mediated hepatic Atg7 knockdown per se does not alter the hepatic TG level, suggesting a more complex regulation in vivo. In sum, PLIN2 guards its own house, the lipid droplet. PLIN2 overexpression protects against autophagy, and its downregulation stimulates TG catabolism via autophagy.

  14. Characterization of Macrophage Endogenous S-Nitrosoproteome Using a Cysteine-Specific Phosphonate Adaptable Tag in Combination with TiO2 Chromatography.

    PubMed

    Ibáñez-Vea, María; Huang, Honggang; Martínez de Morentin, Xabier; Pérez, Estela; Gato, Maria; Zuazo, Miren; Arasanz, Hugo; Fernández-Irigoyen, Joaquin; Santamaría, Enrique; Fernandez-Hinojal, Gonzalo; Larsen, Martin R; Escors, David; Kochan, Grazyna

    2018-03-02

    Protein S-nitrosylation is a cysteine post-translational modification mediated by nitric oxide. An increasing number of studies highlight S-nitrosylation as an important regulator of signaling involved in numerous cellular processes. Despite the significant progress in the development of redox proteomic methods, identification and quantification of endogeneous S-nitrosylation using high-throughput mass-spectrometry-based methods is a technical challenge because this modification is highly labile. To overcome this drawback, most methods induce S-nitrosylation chemically in proteins using nitrosylating compounds before analysis, with the risk of introducing nonphysiological S-nitrosylation. Here we present a novel method to efficiently identify endogenous S-nitrosopeptides in the macrophage total proteome. Our approach is based on the labeling of S-nitrosopeptides reduced by ascorbate with a cysteine specific phosphonate adaptable tag (CysPAT), followed by titanium dioxide (TiO 2 ) chromatography enrichment prior to nLC-MS/MS analysis. To test our procedure, we performed a large-scale analysis of this low-abundant modification in a murine macrophage cell line. We identified 569 endogeneous S-nitrosylated proteins compared with 795 following exogenous chemically induced S-nitrosylation. Importantly, we discovered 579 novel S-nitrosylation sites. The large number of identified endogenous S-nitrosylated peptides allowed the definition of two S-nitrosylation consensus sites, highlighting protein translation and redox processes as key S-nitrosylation targets in macrophages.

  15. Dynamics of lipid and fatty acid composition of shallow-water corals under thermal stress: an experimental approach

    NASA Astrophysics Data System (ADS)

    Imbs, A. B.; Yakovleva, I. M.

    2012-03-01

    Coral bleaching induces changes in lipid and fatty acid composition that result in low lipid content, reducing the likelihood of coral survival. Species-specific differences in the metabolism of lipid reserves may contribute to the differential resistance of corals under acute heat exposures. Here, we examined the dynamics of lipids and fatty acid abundance in corals subjected to short-term heat stress. The stony corals Acropora intermedia, Montipora digitata, and the soft coral Sinularia capitalis all showed a 60-75% decline in both storage and structural lipids. However, S. capitalis and M. digitata exhibited no significant change in the percentages of structural lipids (i.e., polar lipids and sterols) until they had lost 90-95% of their endosymbionts, whereas A. intermedia showed a rapid decline in structural lipids after a 50% loss of symbionts. After a 90-95% loss of symbionts under heat stress, all three corals showed a relative depletion of polyunsaturated fatty acids that had symbiont biomarkers, suggesting that polyunsaturated fatty acids were translocated from the symbiont to the coral host tissue.

  16. Live Imaging of Endogenous PSD-95 Using ENABLED: A Conditional Strategy to Fluorescently Label Endogenous Proteins

    PubMed Central

    Fortin, Dale A.; Tillo, Shane E.; Yang, Guang; Rah, Jong-Cheol; Melander, Joshua B.; Bai, Suxia; Soler-Cedeño, Omar; Qin, Maozhen; Zemelman, Boris V.; Guo, Caiying

    2014-01-01

    Stoichiometric labeling of endogenous synaptic proteins for high-contrast live-cell imaging in brain tissue remains challenging. Here, we describe a conditional mouse genetic strategy termed endogenous labeling via exon duplication (ENABLED), which can be used to fluorescently label endogenous proteins with near ideal properties in all neurons, a sparse subset of neurons, or specific neuronal subtypes. We used this method to label the postsynaptic density protein PSD-95 with mVenus without overexpression side effects. We demonstrated that mVenus-tagged PSD-95 is functionally equivalent to wild-type PSD-95 and that PSD-95 is present in nearly all dendritic spines in CA1 neurons. Within spines, while PSD-95 exhibited low mobility under basal conditions, its levels could be regulated by chronic changes in neuronal activity. Notably, labeled PSD-95 also allowed us to visualize and unambiguously examine otherwise-unidentifiable excitatory shaft synapses in aspiny neurons, such as parvalbumin-positive interneurons and dopaminergic neurons. Our results demonstrate that the ENABLED strategy provides a valuable new approach to study the dynamics of endogenous synaptic proteins in vivo. PMID:25505322

  17. Niacin improves renal lipid metabolism and slows progression in chronic kidney disease.

    PubMed

    Cho, Kyu-hyang; Kim, Hyun-ju; Kamanna, Vaijinath S; Vaziri, Nosratola D

    2010-01-01

    Mounting evidence points to lipid accumulation in the diseased kidney and its contribution to progression of nephropathy. We recently found heavy lipid accumulation and marked dysregulation of lipid metabolism in the remnant kidneys of rats with chronic renal failure (CRF). Present study sought to determine efficacy of niacin supplementation on renal tissue lipid metabolism in CRF. Kidney function, lipid content, and expression of molecules involved in cholesterol and fatty acid metabolism were determined in untreated CRF (5/6 nephrectomized), niacin-treated CRF (50 mg/kg/day in drinking water for 12 weeks) and control rats. CRF resulted in hypertension, proteinuria, renal tissue lipid accumulation, up-regulation of scavenger receptor A1 (SR-A1), acyl-CoA cholesterol acyltransferase-1 (ACAT1), carbohydrate-responsive element binding protein (ChREBP), fatty acid synthase (FAS), acyl-CoA carboxylase (ACC), liver X receptor (LXR), ATP binding cassette (ABC) A-1, ABCG-1, and SR-B1 and down-regulation of sterol responsive element binding protein-1 (SREBP-1), SREBP-2, HMG-CoA reductase, PPAR-alpha, fatty acid binding protein (L-FABP), and CPT1A. Niacin therapy attenuated hypertension, proteinuria, and tubulo-interstitial injury, reduced renal tissue lipids, CD36, ChREBP, LXR, ABCA-1, ABCG-1, and SR-B1 abundance and raised PPAR-alpha and L-FABP. Niacin administration improves renal tissue lipid metabolism and renal function and structure in experimental CRF.

  18. Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism.

    PubMed

    Caesar, Robert; Nygren, Heli; Orešič, Matej; Bäckhed, Fredrik

    2016-03-01

    The gut microbiota influences many aspects of host metabolism. We have previously shown that the presence of a gut microbiota remodels lipid composition. Here we investigated how interaction between gut microbiota and dietary lipids regulates lipid composition in the liver and plasma, and gene expression in the liver. Germ-free and conventionally raised mice were fed a lard or fish oil diet for 11 weeks. We performed lipidomics analysis of the liver and serum and microarray analysis of the liver. As expected, most of the variation in the lipidomics dataset was induced by the diet, and abundance of most lipid classes differed between mice fed lard and fish oil. However, the gut microbiota also affected lipid composition. The gut microbiota increased hepatic levels of cholesterol and cholesteryl esters in mice fed lard, but not in mice fed fish oil. Serum levels of cholesterol and cholesteryl esters were not affected by the gut microbiota. Genes encoding enzymes involved in cholesterol biosynthesis were downregulated by the gut microbiota in mice fed lard and were expressed at a low level in mice fed fish oil independent of microbial status. In summary, we show that gut microbiota-induced regulation of hepatic cholesterol metabolism is dependent on dietary lipid composition. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  19. Lipid oxidation in baked products: impact of formula and process on the generation of volatile compounds.

    PubMed

    Maire, Murielle; Rega, Barbara; Cuvelier, Marie-Elisabeth; Soto, Paola; Giampaoli, Pierre

    2013-12-15

    This paper investigates the effect of ingredients on the reactions occurring during the making of sponge cake and leading to the generation of volatile compounds related to flavour quality. To obtain systems sensitive to lipid oxidation (LO), a formulation design was applied varying the composition of fatty matter and eggs. Oxidation of polyunsaturated fatty acids (PUFA) and formation of related volatile compounds were followed at the different steps of cake-making. Optimised dynamic Solid Phase Micro Extraction was applied to selectively extract either volatile or semi-volatile compounds directly from the baking vapours. We show for the first time that in the case of alveolar baked products, lipid oxidation occurs very early during the step of dough preparation and to a minor extent during the baking process. The generation of lipid oxidation compounds depends on PUFA content and on the presence of endogenous antioxidants in the raw matter. Egg yolk seemed to play a double role on reactivity: protecting unsaturated lipids from oxidation and being necessary to generate a broad class of compounds of the Maillard reaction during baking and linked to the typical flavour of sponge cake. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Endogenous Pyrogen Physiology.

    ERIC Educational Resources Information Center

    Beisel, William R.

    1980-01-01

    Discusses the physiology of endogenous pyrogen (EP), the fever-producing factor of cellular origin. Included are: its hormone-like role, its molecular nature, bioassay procedures, cellular production and mechanisms of EP action. (SA)

  1. Breathing 100% Oxygen After Global Brain Ischemia in Mongolian Gerbils Results in Increased Lipid Peroxidation and Increased Mortality

    DTIC Science & Technology

    1987-04-01

    fatty during ischemic injury,- possibly related to the pres- acids such as linolenic or eicosapentaenoic acids . ence of endogenous iron.’ In...is elevated. Instead, concern is carbon chain of polyunsaturated fatty acids . Among focused on whether hypoxia is occurring as a conse- these products... acids such as linoleic or arachidonic acids . ischemia. I Lipid peroxidation also occurs in the brain Ethane is produced in a similar manner from w-3

  2. Endogenous timing factors in bird migration

    NASA Technical Reports Server (NTRS)

    Gwinner, E. G.

    1972-01-01

    Several species of warbler birds were observed in an effort to determine what initiates and terminates migration. Environmental and endogenous timing mechanisms were analyzed. The results indicate that endogenous stimuli are dominant factors for bird migration especially for long distances. It was concluded that environmental factors act as an assist mechanism.

  3. Oxalomalate, a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase, enhances lipid peroxidation-mediated oxidative damage in U937 cells.

    PubMed

    Yang, Joon-Hyuck; Park, Jeen-Woo

    2003-08-01

    Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. Cytosolic NADP+-dependent isocitrate dehydrogenase (ICDH) in U937 cells produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of ICDH against lipid peroxidation-mediated oxidative damage in U937 cells was investigated in control cells pre-treated with oxalomalate, a competitive inhibitor of ICDH. Upon exposure to 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) to U937 cells, which induces lipid peroxidation in membranes, the viability was lower and the protein oxidation, lipid peroxidation, and oxidative DNA damage, reflected by an increase in 8-hydroxy-2'-deoxyguanosine, were higher in oxalomalate-treated cells as compared to control cells. We also observed the significant increase in the endogenous production of reactive oxygen species, as measured by the oxidation of 2',7'-dichlorodihydrofluorescin, as well as the significant decrease in the intracellular GSH level in oxalomalate-treated U937 cells upon exposure to AAPH. These results suggest that ICDH plays an important role as an antioxidant enzyme in cellular defense against lipid peroxidation-mediated oxidative damage through the removal of reactive oxygen species.

  4. Label-Free Proteomic Identification of Endogenous, Insulin-Stimulated Interaction Partners of Insulin Receptor Substrate-1

    NASA Astrophysics Data System (ADS)

    Geetha, Thangiah; Langlais, Paul; Luo, Moulun; Mapes, Rebekka; Lefort, Natalie; Chen, Shu-Chuan; Mandarino, Lawrence J.; Yi, Zhengping

    2011-03-01

    Protein-protein interactions are key to most cellular processes. Tandem mass spectrometry (MS/MS)-based proteomics combined with co-immunoprecipitation (CO-IP) has emerged as a powerful approach for studying protein complexes. However, a majority of systematic proteomics studies on protein-protein interactions involve the use of protein overexpression and/or epitope-tagged bait proteins, which might affect binding stoichiometry and lead to higher false positives. Here, we report an application of a straightforward, label-free CO-IP-MS/MS method, without the use of protein overexpression or protein tags, to the investigation of changes in the abundance of endogenous proteins associated with a bait protein, which is in this case insulin receptor substrate-1 (IRS-1), under basal and insulin stimulated conditions. IRS-1 plays a central role in the insulin signaling cascade. Defects in the protein-protein interactions involving IRS-1 may lead to the development of insulin resistance and type 2 diabetes. HPLC-ESI-MS/MS analyses identified eleven novel endogenous insulin-stimulated IRS-1 interaction partners in L6 myotubes reproducibly, including proteins play an important role in protein dephosphorylation [protein phosphatase 1 regulatory subunit 12A, (PPP1R12A)], muscle contraction and actin cytoskeleton rearrangement, endoplasmic reticulum stress, and protein folding, as well as protein synthesis. This novel application of label-free CO-IP-MS/MS quantification to assess endogenous interaction partners of a specific protein will prove useful for understanding how various cell stimuli regulate insulin signal transduction.

  5. Effects of induction/inhibition of endogenous heme oxygenase-1 on lipid metabolism, endothelial function, and atherosclerosis in rabbits on a high fat diet.

    PubMed

    Liu, Danan; He, Zuoyun; Wu, Lirong; Fang, Ying

    2012-01-01

    The heme oxygenase-1 (HO-1) / carbon monoxide (CO) system has been presumed as a therapeutic target for preventing atherosclerosis. However, the exact mechanism(s) underlying this system remains largely undefined. This study aims to examine the influence of induction/inhibition of HO-1 on atherosclerotic plaque using pharmacological approaches and to elucidate potential mechanisms. Rabbits were randomly assigned to receive a standard diet (control group), high fat diet (HFD), HFD plus HO inducer hemin (HFD + H group), and HFD plus an HO inhibitor, zinc protoporphyrin-9 (ZnPP9, HFD + Z group). Atherosclerotic plaque was evaluated using oil red O staining and histological analyses. Immunohistochemistry, western blotting, and RT-PCR were employed to study the expression of HO-1 and endothelin-1 (ET-1). Levels of CO, nitric oxide (NO), eNOS/iNOS activities, NF-κB activity, and TNF-α level were determined. No significant differences of serum lipid levels were observed among the HFD, HFD + Z, and HFD + H groups. In rabbits, HFD induced typical atherosclerotic plaque and increased intima/media thickness ratio, which was markedly reduced in the HFD + H group and further aggravated in the HFD + Z group. Furthermore, hemin increased HO-1 expression, CO levels, and eNOS activity, while decreasing iNOS levels, ET-1 expression, NF-κB activity, and TNF-α level. ZnPP9 caused opposite effects. Induction of the endogenous HO-1/CO system by hemin can prevent atherosclerosis though increasing CO levels, regulating eNOS activity, NF-κB activity, TNF-α levels, and ET-1 levels in rabbits. Our results add new evidence for the importance of HO-1 in the genesis and development of atherosclerosis and provide several possible mechanisms underlying the anti-atherosclerosis effects of HO-1.

  6. Enhanced dissolved lipid production as a response to the sea surface warming

    NASA Astrophysics Data System (ADS)

    Novak, Tihana; Godrijan, Jelena; Pfannkuchen, Daniela Marić; Djakovac, Tamara; Mlakar, Marina; Baricevic, Ana; Tanković, Mirta Smodlaka; Gašparović, Blaženka

    2018-04-01

    The temperature increase in oceans reflects on marine ecosystem functioning and surely has consequences on the marine carbon cycle and carbon sequestration. In this study, we examined dissolved lipid, lipid classes and dissolved organic carbon (DOC) production in the northern Adriatic Sea, isolated diatom Chaetoceros pseudocurvisetus batch cultures grown in a wide temperature range (10-30 °C) and in contrasting nutrient regimes, phosphorus (P)-depleted and P-replete conditions. Additionally, lipids and DOC were analyzed in the northern Adriatic (NA) in two stations characterized with different P availability, occupied from February to August 2010 that covered a temperature range from 9.3 to 31.1 °C. To gain insight into factors governing lipid and lipid classes' production in the NA, apart from temperature (T), Chlorophyll a, phytoplankton community abundance and structure, nutrient concentrations were measured together with hydrographic parameters. We found enhanced accumulation of dissolved lipids, particulary glycolipids, with increasing T, especially during the highest in situ temperature. The effect of T on enhanced dissolved lipid release is much more pronounced under P-deplete conditions indicating that oligotrophic regions might be more vulnerable to T rise. Temperature between 25 and 30 °C is a threshold T range for C. pseudocurvisetus, at which a significant part of lipid production is directed toward the dissolved phase. Unlike monocultures, there are multiple factors influencing produced lipid composition, distribution and cycling in the NA that may counteract the T influence. The possible role of enhanced dissolved lipid concentration for carbon sequestration at elevated T is discussed. On the one hand, lipids are buoyant and do not sink, which enhances their retention at the surface layer. In addition, they are surface active, and therefore prone to adsorb on sinking particles, contributing to the C sequestration.

  7. Endogenous Peer Effects: Fact or Fiction?

    ERIC Educational Resources Information Center

    Yeung, Ryan; Nguyen-Hoang, Phuong

    2016-01-01

    The authors examine endogenous peer effects, which occur when a student's behavior or outcome is a function of the behavior or outcome of his or her peer group. Endogenous peer effects have important implications for educational policies such as busing, school choice and tracking. In this study, the authors quantitatively review the literature on…

  8. Lipid rafts sense and direct electric field-induced migration

    PubMed Central

    Lin, Bo-jian; Tsao, Shun-hao; Chen, Alex; Hu, Shu-Kai; Chao, Ling

    2017-01-01

    Endogenous electric fields (EFs) are involved in developmental regulation and wound healing. Although the phenomenon is known for more than a century, it is not clear how cells perceive the external EF. Membrane proteins, responding to electrophoretic and electroosmotic forces, have long been proposed as the sensing molecules. However, specific charge modification of surface proteins did not change cell migration motility nor directionality in EFs. Moreover, symmetric alternating current (AC) EF directs cell migration in a frequency-dependent manner. Due to their charge and ability to coalesce, glycolipids are therefore the likely primary EF sensor driving polarization of membrane proteins and intracellular signaling. We demonstrate that detergent-resistant membrane nanodomains, also known as lipid rafts, are the primary response element in EF sensing. The clustering and activation of caveolin and signaling proteins further stabilize raft structure and feed-forward downstream signaling events, such as rho and PI3K activation. Theoretical modeling supports the experimental results and predicts AC frequency-dependent cell and raft migration. Our results establish a fundamental mechanism for cell electrosensing and provide a role in lipid raft mechanotransduction. PMID:28739955

  9. Identification of furan fatty acids in the lipids of common carp (Cyprinus carpio L.).

    PubMed

    Chvalová, Daniela; Špička, Jiří

    2016-06-01

    Fatty acid (FA) composition was analyzed in muscle and gonad tissues of marketed common carp (Cyprinus carpio). The extracted lipids were separated into four fractions: polar lipids (PL), diacylglycerols, free fatty acids and triacylglycerols (TAG) using thin layer chromatography. FA content within the lipid fractions was determined by gas chromatography with flame ionization detector (GC/FID). The muscle lipids consisted primarily of TAG (96.9% of total FA), while PL were the major component of both male (67.6%) and female gonad (58.6%) lipids. Polyunsaturated fatty acids predominated in PL of all tissues (52.2-55.8% of total FA); monounsaturated fatty acids were the most abundant FA group in TAG of muscle (51.8%) and female gonads (47.8%) whereas high proportion of furan fatty acids (F-acids) (38.2%) was detected in TAG of male gonads. Eight F-acids were identified by gas chromatography-mass spectrometry (GC/MS) in male gonad samples, including less common 12,15-epoxy-13,14-dimethylnonadeca-12,14-dienoic acid with even-numbered alkyl moiety. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Ultraperformance convergence chromatography-high resolution tandem mass spectrometry for lipid biomarker profiling and identification.

    PubMed

    Jones, Jace W; Carter, Claire L; Li, Fei; Yu, Jianshi; Pierzchalski, Keely; Jackson, Isabel L; Vujaskovic, Zeljko; Kane, Maureen A

    2017-03-01

    Lipids represent biologically ubiquitous and highly dynamic molecules in terms of abundance and structural diversity. Whereas the potential for lipids to inform on disease/injury is promising, their unique characteristics make detection and identification of lipids from biological samples analytically demanding. We report the use of ultraperformance convergence chromatography (UPC 2 ), a variant of supercritical fluid chromatography, coupled to high-resolution, data-independent tandem mass spectrometry for characterization of total lipid extracts from mouse lung tissue. The UPC 2 platform resulted in lipid class separation and when combined with orthogonal column chemistries yielded chromatographic separation of intra-class species based on acyl chain hydrophobicity. Moreover, the combined approach of using UPC 2 with orthogonal column chemistries, accurate mass measurements, time-aligned low- and high-collision energy total ion chromatograms, and positive and negative ion mode product ion spectra correlation allowed for confident lipid identification. Of great interest was the identification of differentially expressed ceramides that were elevated 24 h post whole thorax lung irradiation. The identification of lipids that were elevated 24 h post-irradiation signifies a unique opportunity to investigate early mechanisms of action prior to the onset of clinical symptoms in the whole thorax lung irradiation mouse model. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Live imaging of endogenous PSD-95 using ENABLED: a conditional strategy to fluorescently label endogenous proteins.

    PubMed

    Fortin, Dale A; Tillo, Shane E; Yang, Guang; Rah, Jong-Cheol; Melander, Joshua B; Bai, Suxia; Soler-Cedeño, Omar; Qin, Maozhen; Zemelman, Boris V; Guo, Caiying; Mao, Tianyi; Zhong, Haining

    2014-12-10

    Stoichiometric labeling of endogenous synaptic proteins for high-contrast live-cell imaging in brain tissue remains challenging. Here, we describe a conditional mouse genetic strategy termed endogenous labeling via exon duplication (ENABLED), which can be used to fluorescently label endogenous proteins with near ideal properties in all neurons, a sparse subset of neurons, or specific neuronal subtypes. We used this method to label the postsynaptic density protein PSD-95 with mVenus without overexpression side effects. We demonstrated that mVenus-tagged PSD-95 is functionally equivalent to wild-type PSD-95 and that PSD-95 is present in nearly all dendritic spines in CA1 neurons. Within spines, while PSD-95 exhibited low mobility under basal conditions, its levels could be regulated by chronic changes in neuronal activity. Notably, labeled PSD-95 also allowed us to visualize and unambiguously examine otherwise-unidentifiable excitatory shaft synapses in aspiny neurons, such as parvalbumin-positive interneurons and dopaminergic neurons. Our results demonstrate that the ENABLED strategy provides a valuable new approach to study the dynamics of endogenous synaptic proteins in vivo. Copyright © 2014 the authors 0270-6474/14/3416698-15$15.00/0.

  12. Susceptibility of human liver cells to porcine endogenous retrovirus.

    PubMed

    Lin, Xinzi; Qi, Lin; Li, Zhiguo; Chi, Hao; Lin, Wanjun; Wang, Yan; Jiang, Zesheng; Pan, Mingxin; Gao, Yi

    2013-12-01

    The risk of porcine endogenous retrovirus infection is a major barrier for pig-to-human xenotransplant. Porcine endogenous retrovirus, present in porcine cells, can infect many human and nonhuman primate cells in vitro, but there is no evidence available about in vitro infection of human liver cells. We investigated the susceptibility of different human liver cells to porcine endogenous retrovirus. The supernatant from a porcine kidney cell line was added to human liver cells, including a normal hepatocyte cell line (HL-7702 cells), primary hepatocytes (Phh cells), and a liver stellate cell line (Lx-2 cells), and to human embryonic kidney cells as a reference control. Expression of the porcine endogenous retrovirus antigen p15E in the human cells was evaluated with polymerase chain reaction, reverse transcription-polymerase chain reaction, and Western blot. The porcine endogenous retrovirus antigen p15E was not expressed in any human liver cells (HL-7702, Phh, or Lx-2 cells) that had been exposed to supernatants from porcine kidney cell lines. Porcine endogenous retrovirus-specific fragments were amplified in human kidney cells. Human liver cells tested were not susceptible to infection by porcine endogenous retrovirus. Therefore, not all human cells are susceptible to porcine endogenous retrovirus.

  13. Evaluation of endogenous control gene(s) for gene expression studies in human blood exposed to 60Co γ-rays ex vivo.

    PubMed

    Vaiphei, S Thangminlal; Keppen, Joshua; Nongrum, Saibadaiahun; Chaubey, R C; Kma, L; Sharan, R N

    2015-01-01

    In gene expression studies, it is critical to normalize data using a stably expressed endogenous control gene in order to obtain accurate and reliable results. However, we currently do not have a universally applied endogenous control gene for normalization of data for gene expression studies, particularly those involving (60)Co γ-ray-exposed human blood samples. In this study, a comparative assessment of the gene expression of six widely used housekeeping endogenous control genes, namely 18S, ACTB, B2M, GAPDH, MT-ATP6 and CDKN1A, was undertaken for a range of (60)Co γ-ray doses (0.5, 1.0, 2.0 and 4.0 Gy) at 8.4 Gy min(-1) at 0 and 24 h post-irradiation time intervals. Using the NormFinder algorithm, real-time PCR data obtained from six individuals (three males and three females) were analyzed with respect to the threshold cycle (Ct) value and abundance, ΔCt pair-wise comparison, intra- and inter-group variability assessments, etc. GAPDH, either alone or in combination with 18S, was found to be the most suitable endogenous control gene and should be used in gene expression studies, especially those involving qPCR of γ-ray-exposed human blood samples. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  14. Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers.

    PubMed

    Skotland, Tore; Ekroos, Kim; Kauhanen, Dimple; Simolin, Helena; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

    2017-01-01

    Exosomes have recently appeared as a novel source of noninvasive cancer biomarkers, since these nanovesicles contain molecules from cancer cells and can be detected in biofluids. We have here investigated the potential use of lipids in urinary exosomes as prostate cancer biomarkers. A high-throughput mass spectrometry quantitative lipidomic analysis was performed to reveal the lipid composition of urinary exosomes in prostate cancer patients and healthy controls. Control samples were first analysed to characterise the lipidome of urinary exosomes and test the reproducibility of the method. In total, 107 lipid species were quantified in urinary exosomes. Several differences, for example, in cholesterol and phosphatidylcholine, were found between urinary exosomes and exosomes derived from cell lines, thus showing the importance of in vivo studies for biomarker analysis. The 36 most abundant lipid species in urinary exosomes were then quantified in 15 prostate cancer patients and 13 healthy controls. Interestingly, the levels of nine lipids species were found to be significantly different when the two groups were compared. The highest significance was shown for phosphatidylserine (PS) 18:1/18:1 and lactosylceramide (d18:1/16:0), the latter also showed the highest patient-to-control ratio. Furthermore, combinations of these lipid species and PS 18:0-18:2 distinguished the two groups with 93% sensitivity and 100% specificity. Finally, in agreement with the reported dysregulation of sphingolipid metabolism in cancer cells, alteration in specific sphingolipid lipid classes were observed. This study shows for the first time the potential use of exosomal lipid species in urine as prostate cancer biomarkers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Molecular composition and surface properties of storage lipid particles in wax bean (Phaseolus vulgaris).

    PubMed

    Froese, Carol D; Nowack, Linda; Cholewa, Ewa; Thompson, John E

    2003-03-01

    Lipid particles have been isolated from seeds of wax bean (Phaseolus vulgaris), a species in which starch and protein rather than lipid are the major seed storage reserves. These lipid particles resemble oil bodies present in oil-rich seeds in that > 90% of their lipid is triacylglycerol. Moreover, this triacylglycerol is rapidly metabolized during seed germination indicating that it is a storage reserve. The phospholipid surfaces of oil bodies are known to be completely coated with oleosin which prevents their coalescence, particularly during desiccation of the developing seed. This would appear to be necessary since lipid is the major storage reserve in oil seeds, and there are very few alternate types of storage particles in the cytoplasm of oil seed endosperm to provide a buffer against coalescence of oil bodies by isolating them from one another. The present study indicates that the surfaces of lipid particles from wax bean are not completely coated with oleosin and feature regions of naked phospholipid. This finding has been interpreted as reflecting the fact that lipid particles in wax been seeds are less prone to coalescence than oil bodies of oil-rich seeds. This arises because the individual lipid particles are interspersed in situ among highly abundant protein bodies and starch grains and hence less likely to come in contact with one another, even during desiccation of the developing seed.

  16. Oxidation-Induced Increase In Photoreactivity of Bovine Retinal Lipid Extract.

    PubMed

    Koscielniak, A; Serafin, M; Duda, M; Oles, T; Zadlo, A; Broniec, A; Berdeaux, O; Gregoire, S; Bretillon, L; Sarna, T; Pawlak, A

    2017-12-01

    The mammalian retina contains a high level of polyunsaturated fatty acids, including docosahexaenoic acid (22:6) (DHA), which are highly susceptible to oxidation. It has been shown that one of the products of DHA oxidation-carboxyethylpyrrole (CEP), generated in situ, causes modifications of retinal proteins and induces inflammation response in the outer retina. These contributing factors may play a role in the development of age-related macular degeneration (AMD). It is also possible that some of the lipid oxidation products are photoreactive, and upon irradiation with blue light may generate reactive oxygen species. Therefore, in this work we analysed oxidation-induced changes in photoreactivity of lipids extracted from bovine neural retinas. Lipid composition of bovine neural retinas closely resembles that of human retinas making the bovine tissue a convenient model for studying the photoreactivity and potential phototoxicity of oxidized human retinal lipids. Lipid composition of bovine neural retinas Folch' extracts (BRex) was determined by gas chromatography (GC) and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS) analysis. Liposomes prepared from BRex, equilibrated with air, were oxidized in the dark at 37 °C for up to 400 h. The photoreactivity of BRex at different stages of oxidation was studied by EPR-oximetry and EPR-spin trapping. Photogeneration of singlet oxygen ( 1 O 2 , 1 Δ g ) by BRex was measured using time-resolved detection of the characteristic phosphorescence at 1270 nm. To establish contribution of lipid components to the analysed photoreactivity of Folch' extract of bovine retinas, a mixture of selected synthetic lipids in percent by weight (w/w %) ratio resembling that of the BRex has been also studied. Folch's extraction of bovine neural retinas was very susceptible to oxidation despite the presence of powerful endogenous antioxidants such as α-tocopherol and zeaxanthin. Non

  17. Are endogenous cardenolides controlled by atrial natriuretic peptide.

    PubMed

    Brar, Kanwarjeet S; Gao, Yonglin; El-Mallakh, Rif S

    2016-07-01

    Endogenous cardenolides are digoxin-like substances and ouabain-like substances that have been implicated in the pathogenesis of hypertension and mood disorders in clinical and pre-clinical studies. Regulatory signals for endogenous cardenolides are still unknown. These endogenous compounds are believed to be produced by the adrenal gland in the periphery and the hypothalamus in the central nervous system, and constitute part of an hormonal axis that may regulate the catalytic activity of the α subunit of Na(+)/K(+)-ATPase. A review of literature suggests that there is great overlap in physiological environments that are associated with either elevations or reductions in the levels of atrial natriuretic peptide (ANP) and endogenous cardenolides. This suggests that these two factors may share a common regulatory signal or perhaps that ANP may be involved in the regulation of endogenous cardenolides. Copyright © 2016. Published by Elsevier Ltd.

  18. Avanti lipid tools: connecting lipids, technology, and cell biology.

    PubMed

    Sims, Kacee H; Tytler, Ewan M; Tipton, John; Hill, Kasey L; Burgess, Stephen W; Shaw, Walter A

    2014-08-01

    Lipid research is challenging owing to the complexity and diversity of the lipidome. Here we review a set of experimental tools developed for the seasoned lipid researcher, as well as, those who are new to the field of lipid research. Novel tools for probing protein-lipid interactions, applications for lipid binding antibodies, enhanced systems for the cellular delivery of lipids, improved visualization of lipid membranes using gold-labeled lipids, and advances in mass spectrometric analysis techniques will be discussed. Because lipid mediators are known to participate in a host of signal transduction and trafficking pathways within the cell, a comprehensive lipid toolbox that aids the science of lipidomics research is essential to better understand the molecular mechanisms of interactions between cellular components. This article is part of a Special Issue entitled Tools to study lipid functions. Copyright © 2014. Published by Elsevier B.V.

  19. Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease.

    PubMed

    Aragno, Manuela; Mastrocola, Raffaella

    2017-04-14

    The rapid increase in metabolic diseases, which occurred in the last three decades in both industrialized and developing countries, has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as a consequence of a high dietary sugar intake. Animal models of high sugar consumption, in particular fructose, have reported AGE accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agents when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidence also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and the brain, affecting not only metabolic control, but global health. Indeed, the most recent reports on the effects of high sugar consumption and diet-derived AGEs on human health reviewed here suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.

  20. Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease

    PubMed Central

    Aragno, Manuela; Mastrocola, Raffaella

    2017-01-01

    The rapid increase in metabolic diseases, which occurred in the last three decades in both industrialized and developing countries, has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as a consequence of a high dietary sugar intake. Animal models of high sugar consumption, in particular fructose, have reported AGE accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agents when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidence also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and the brain, affecting not only metabolic control, but global health. Indeed, the most recent reports on the effects of high sugar consumption and diet-derived AGEs on human health reviewed here suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities. PMID:28420091

  1. Endogenous versus exogenous shocks in systems with memory

    NASA Astrophysics Data System (ADS)

    Sornette, D.; Helmstetter, A.

    2003-02-01

    Systems with long-range persistence and memory are shown to exhibit different precursory as well as recovery patterns in response to shocks of exogenous versus endogenous origins. By endogenous, we envision either fluctuations resulting from an underlying chaotic dynamics or from a stochastic forcing origin which may be external or be an effective coarse-grained description of the microscopic fluctuations. In this scenario, endogenous shocks result from a kind of constructive interference of accumulated fluctuations whose impacts survive longer than the large shocks themselves. As a consequence, the recovery after an endogenous shock is in general slower at early times and can be at long times either slower or faster than after an exogenous perturbation. This offers the tantalizing possibility of distinguishing between an endogenous versus exogenous cause of a given shock, even when there is no “smoking gun”. This could help in investigating the exogenous versus self-organized origins in problems such as the causes of major biological extinctions, of change of weather regimes and of the climate, in tracing the source of social upheaval and wars, and so on. Sornette et al., Volatility fingerprints of large stocks: endogenous versus exogenous, cond-mat/0204626 has already shown how this concept can be applied concretely to differentiate the effects on financial markets of the 11 September 2001 attack or of the coup against Gorbachev on 19 August 1991 (exogenous) from financial crashes such as October 1987 (endogenous).

  2. A simple and rapid method for the reversible removal of lipids from a membrane-bound enzyme.

    PubMed Central

    Goodman, S L; Isern de Caldentey, M; Wheeler, K P

    1978-01-01

    A simple, rapid and reproducible method for the reversible removal of lipids from a membrane-bound enzyme is described. Essentially, a membrane preparation containing (Na+ + K+)-dependent adenosine triphosphatase was extracted with the non-ionic detergent Lubrol WX in the presence of glycerol, and partial separation of protein from lipid was achieved with the use of only two centrifugations. About 74% of the endogenous phospholipid and 79% of the cholesterol were removed, concomitant with a virtually complete loss of ouabain-sensitive adenosine triphosphatase activity, but with retention of 60-100% of the K+-dependent phosphatase activity. The addition of pure phosphatidylserine re-activated the enzyme to more than 80% of the initial activity, and up to 30% of the protein was recovered. Excess of phosphatidylserine could be washed off the enzyme to give a stable 'reconstituted' preparation. The effects of variation in the experimental conditions were examined, and the results are discussed with respect to the possibility of adapting the method to the study of other lipid-dependent enzymes bound to membranes. PMID:147078

  3. Spontaneous charged lipid transfer between lipid vesicles.

    PubMed

    Richens, Joanna L; Tyler, Arwen I I; Barriga, Hanna M G; Bramble, Jonathan P; Law, Robert V; Brooks, Nicholas J; Seddon, John M; Ces, Oscar; O'Shea, Paul

    2017-10-03

    An assay to study the spontaneous charged lipid transfer between lipid vesicles is described. A donor/acceptor vesicle system is employed, where neutrally charged acceptor vesicles are fluorescently labelled with the electrostatic membrane probe Fluoresceinphosphatidylethanolamine (FPE). Upon addition of charged donor vesicles, transfer of negatively charged lipid occurs, resulting in a fluorescently detectable change in the membrane potential of the acceptor vesicles. Using this approach we have studied the transfer properties of a range of lipids, varying both the headgroup and the chain length. At the low vesicle concentrations chosen, the transfer follows a first-order process where lipid monomers are transferred presumably through the aqueous solution phase from donor to acceptor vesicle. The rate of transfer decreases with increasing chain length which is consistent with energy models previously reported for lipid monomer vesicle interactions. Our assay improves on existing methods allowing the study of a range of unmodified lipids, continuous monitoring of transfer and simplified experimental procedures.

  4. Effects of dietary lipid, vitamins and minerals on total amounts and redox status of glutathione and ubiquinone in tissues of Atlantic salmon (Salmo salar): a multivariate approach.

    PubMed

    Hamre, Kristin; Torstensen, Bente E; Maage, Amund; Waagbø, Rune; Berge, Rolf K; Albrektsen, Sissel

    2010-10-01

    The hypothesis of the present study was that Atlantic salmon (Salmo salar) would respond to large variations in supplementation of dietary pro- and antioxidants, and marine lipid, with adjustment of the endogenously synthesised antioxidants, glutathione (GSH) and ubiquinone (UQ). An experiment with 2(7-3) reduced factorial design (the number of cases reduced systematically from 2(7) (full design) to 2(4) (reduced design)) was conducted, where vitamins, minerals and lipid were supplemented in the diet at high and low levels. For the vitamins and minerals the high levels were chosen to be just below anticipated toxic levels and the low levels were just above the requirement (vitamin C, 30 and 1000 mg/kg; vitamin E, 70 and 430 mg/kg; Fe, 70 and 1200 mg/kg; Cu, 8 and 110 mg/kg; Mn, 12 and 200 mg/kg). For astaxanthin, the dietary levels were 10 and 50 mg/kg and for lipid, 150 and 330 g/kg. The experiment was started with post-smolts (148 (sd 17 g)) and lasted for 5 months. The only effect on GSH was a minor increase ( < 10 %) in total concentration in the liver in response to high dietary lipid. GSH redox state was not affected. UQ responded to dietary lipid, astaxanthin and vitamin E, both with regard to total concentration and redox state. Except for an effect of Fe on plasma GSH, the trace elements and vitamin C had no effect on tissue levels and oxidation state of GSH and UQ. This shows that the endogenous redox state is quite robust with regard to variation of dietary pro- and antioxidants in Atlantic salmon.

  5. Diacylglycerol kinase-δ regulates AMPK signaling, lipid metabolism, and skeletal muscle energetics.

    PubMed

    Jiang, Lake Q; de Castro Barbosa, Thais; Massart, Julie; Deshmukh, Atul S; Löfgren, Lars; Duque-Guimaraes, Daniella E; Ozilgen, Arda; Osler, Megan E; Chibalin, Alexander V; Zierath, Juleen R

    2016-01-01

    Decrease of AMPK-related signal transduction and insufficient lipid oxidation contributes to the pathogenesis of obesity and type 2 diabetes. Previously, we identified that diacylglycerol kinase-δ (DGKδ), an enzyme involved in triglyceride biosynthesis, is reduced in skeletal muscle from type 2 diabetic patients. Here, we tested the hypothesis that DGKδ plays a role in maintaining appropriate AMPK action in skeletal muscle and energetic aspects of contraction. Voluntary running activity was reduced in DGKδ(+/-) mice, but glycogen content and mitochondrial markers were unaltered, suggesting that DGKδ deficiency affects skeletal muscle energetics but not mitochondrial protein abundance. We next determined the role of DGKδ in AMPK-related signal transduction and lipid metabolism in isolated skeletal muscle. AMPK activation and signaling were reduced in DGKδ(+/-) mice, concomitant with impaired lipid oxidation and elevated incorporation of free fatty acids into triglycerides. Strikingly, DGKδ deficiency impaired work performance, as evident by altered force production and relaxation dynamics in response to repeated contractions. In conclusion, DGKδ deficiency impairs AMPK signaling and lipid metabolism, thereby highlighting the deleterious role of excessive lipid metabolites in the development of peripheral insulin resistance and type 2 diabetes pathogenesis. DGKδ deficiency also influences skeletal muscle energetics, which may lead to low physical activity levels in type 2 diabetes. Copyright © 2016 the American Physiological Society.

  6. Associations of polychlorinated biphenyl exposure and endogenous hormones with diabetes in post-menopausal women previously employed at a capacitor manufacturing plant.

    PubMed

    Persky, Victoria; Piorkowski, Julie; Turyk, Mary; Freels, Sally; Chatterton, Robert; Dimos, John; Bradlow, H Leon; Chary, Lin Kaatz; Burse, Virlyn; Unterman, Terry; Sepkovic, Daniel; McCann, Kenneth

    2011-08-01

    There is an increasing body of literature showing associations of organochlorine exposure with risk of diabetes and insulin resistance. Some studies suggest that associations differ by gender and that diabetes risk, in turn, may be affected by endogenous steroid hormones. This report examines the relationships of serum PCBs and endogenous hormones with history of diabetes in a cohort of persons previously employed at a capacitor manufacturing plant. A total of 118 women were post-menopausal with complete data, of whom 93 were not using steroid hormones in 1996, at the time of examination, which included a survey of exposure and medical history, height, weight and collection of blood and urine for measurements of lipids, liver function, hematologic markers and endogenous hormones. This analysis examines relationships of serum polychlorinated biphenyls (PCBs), work exposure and endogenous hormones with self-reported history of diabetes after control for potential confounders. All PCB exposure groups were significantly related to history of diabetes, but not to insulin resistance as measured by the homeostatic model assessment of insulin resistance (HOMA-IR) in non-diabetics. Diabetes was also independently and inversely associated with follicle stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS) and triiodothyronine (T3) uptake. HOMA-IR was positively associated with body mass index (BMI) and C-reactive protein (CRP) and inversely associated with sex hormone binding globulin (SHBG) and T3 uptake after control for PCB exposure. Possible biologic mechanisms are discussed. This study confirms previous reports relating PCB exposure to diabetes and suggests possible hormonal pathways deserving further exploration. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Development and characterization of lipid-polymeric nanoparticles for oral insulin delivery.

    PubMed

    Sgorla, Débora; Lechanteur, Anna; Almeida, Andreia; Sousa, Flávia; Melo, Eduardo; Bunhak, Élcio; Mainardes, Rubiana; Khalil, Najeh; Cavalcanti, Osvaldo; Sarmento, Bruno

    2018-03-01

    The oral route is widely accepted as the most physiological path for exogenous administration of insulin, as it closely mimic the endogenous insulin pathway. Thus, in this work it is proposed an innovative lipid-polymeric nanocarrier to delivery insulin orally. Areas covered: Nanoparticles were produced through a modified solvent emulsification-evaporation method, using ethyl palmitate and hydroxypropylmethylcellulose acetate succinate as matrix. Lipid-polymeric nanoparticles were around 300 nm in size, negatively charged (-20 mV) and associated insulin with efficiency higher than 80%. Differential scanning calorimetry suggested thermal stability of nanoparticles. In vitro release assays under simulated gastrointestinal conditions resulted in 9% and 14% of insulin released at pH 1.2 during 2 h and at pH 6.8 for 6 h, respectively, demonstrating the ability of those nanoparticles to protect insulin against premature degradation. Importantly, nanoparticles were observed to be safe at potential therapeutic concentrations as did not originate cytotoxicity to intestinal epithelial cells. Lastly, the permeability of nanoencapsulated insulin through Caco-2 monolayers and a triple Caco-2/HT29-MTX/Raji B cell model correlated well with slow release kinetics, and fosters the effectiveness of nanoparticles to promote intestinal absorption of peptidic drugs. Expert opinion: Lipid-polymeric nanoparticles were developed to encapsulate and carry insulin through intestine. Overall, nanoparticles provide insulin stability and intestinal permeability.

  8. Kynurenine 3-monooxygenase mediates inhibition of Th17 differentiation via catabolism of endogenous aryl hydrocarbon receptor ligands.

    PubMed

    Stephens, Geoffrey L; Wang, Qun; Swerdlow, Bonnie; Bhat, Geetha; Kolbeck, Roland; Fung, Michael

    2013-07-01

    The aryl hydrocarbon receptor (AhR) is a key transcriptional regulator of Th17-cell differentiation. Although endogenous ligands have yet to be identified, evidence suggests that tryptophan metabolites can act as agonists for the AhR. Tryptophan metabolites are abundant in circulation, so we hypothesized that cell intrinsic factors might exist to regulate the exposure of Th17 cells to AhR-dependent activities. Here, we find that Th17 cells preferentially express kynurenine 3-monooxygenase (KMO), which is an enzyme involved in catabolism of the tryptophan metabolite kynurenine. KMO inhibition, either with a specific inhibitor or via siRNA-mediated silencing, markedly increased IL-17 production in vitro, whereas IFN-γ production by Th1 cells was unaffected. Inhibition of KMO significantly exacerbated disease in a Th17-driven model of autoimmune gastritis, suggesting that expression of KMO by Th17 cells serves to limit their continuous exposure to physiological levels of endogenous AhR ligands in vivo. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Time to face the fats: what can mass spectrometry reveal about the structure of lipids and their interactions with proteins?

    PubMed

    Brown, Simon H J; Mitchell, Todd W; Oakley, Aaron J; Pham, Huong T; Blanksby, Stephen J

    2012-09-01

    Since the 1950s, X-ray crystallography has been the mainstay of structural biology, providing detailed atomic-level structures that continue to revolutionize our understanding of protein function. From recent advances in this discipline, a picture has emerged of intimate and specific interactions between lipids and proteins that has driven renewed interest in the structure of lipids themselves and raised intriguing questions as to the specificity and stoichiometry in lipid-protein complexes. Herein we demonstrate some of the limitations of crystallography in resolving critical structural features of ligated lipids and thus determining how these motifs impact protein binding. As a consequence, mass spectrometry must play an important and complementary role in unraveling the complexities of lipid-protein interactions. We evaluate recent advances and highlight ongoing challenges towards the twin goals of (1) complete structure elucidation of low, abundant, and structurally diverse lipids by mass spectrometry alone, and (2) assignment of stoichiometry and specificity of lipid interactions within protein complexes.

  10. Time to Face the Fats: What Can Mass Spectrometry Reveal about the Structure of Lipids and Their Interactions with Proteins?

    NASA Astrophysics Data System (ADS)

    Brown, Simon H. J.; Mitchell, Todd W.; Oakley, Aaron J.; Pham, Huong T.; Blanksby, Stephen J.

    2012-09-01

    Since the 1950s, X-ray crystallography has been the mainstay of structural biology, providing detailed atomic-level structures that continue to revolutionize our understanding of protein function. From recent advances in this discipline, a picture has emerged of intimate and specific interactions between lipids and proteins that has driven renewed interest in the structure of lipids themselves and raised intriguing questions as to the specificity and stoichiometry in lipid-protein complexes. Herein we demonstrate some of the limitations of crystallography in resolving critical structural features of ligated lipids and thus determining how these motifs impact protein binding. As a consequence, mass spectrometry must play an important and complementary role in unraveling the complexities of lipid-protein interactions. We evaluate recent advances and highlight ongoing challenges towards the twin goals of (1) complete structure elucidation of low, abundant, and structurally diverse lipids by mass spectrometry alone, and (2) assignment of stoichiometry and specificity of lipid interactions within protein complexes.

  11. Heat Stress Dictates Microbial Lipid Composition along a Thermal Gradient in Marine Sediments

    PubMed Central

    Sollich, Miriam; Yoshinaga, Marcos Y.; Häusler, Stefan; Price, Roy E.; Hinrichs, Kai-Uwe; Bühring, Solveig I.

    2017-01-01

    Temperature exerts a first-order control on microbial populations, which constantly adjust the fluidity and permeability of their cell membrane lipids to minimize loss of energy by ion diffusion across the membrane. Analytical advances in liquid chromatography coupled to mass spectrometry have allowed the detection of a stunning diversity of bacterial and archaeal lipids in extreme environments such as hot springs, hydrothermal vents and deep subsurface marine sediments. Here, we investigated a thermal gradient from 18 to 101°C across a marine sediment field and tested the hypothesis that cell membrane lipids provide a major biochemical basis for the bioenergetics of archaea and bacteria under heat stress. This paper features a detailed lipidomics approach with the focus on membrane lipid structure-function. Membrane lipids analyzed here include polar lipids of bacteria and polar and core lipids of archaea. Reflecting the low permeability of their ether-linked isoprenoids, we found that archaeal polar lipids generally dominate over bacterial lipids in deep layers of the sediments influenced by hydrothermal fluids. A close examination of archaeal and bacterial lipids revealed a membrane quandary: not only low permeability, but also increased fluidity of membranes are required as a unified property of microbial membranes for energy conservation under heat stress. For instance, bacterial fatty acids were composed of longer chain lengths in concert with higher degree of unsaturation while archaea modified their tetraethers by incorporation of additional methyl groups at elevated sediment temperatures. It is possible that these configurations toward a more fluidized membrane at elevated temperatures are counterbalanced by the high abundance of archaeal glycolipids and bacterial sphingolipids, which could reduce membrane permeability through strong intermolecular hydrogen bonding. Our results provide a new angle for interpreting membrane lipid structure

  12. The Endogenous-Exogenous Partition in Attribution Theory

    ERIC Educational Resources Information Center

    Kruglanski, Arie W.

    1975-01-01

    Within lay explanation of actions, several significant inferences are assumed to follow from the partition between endogenous and exogenous attributions. An endogenous action is judged to constitute an end in itself; an exogenous action is judged to serve as a means to some further end. (Editor/RK)

  13. Human age and skin physiology shape diversity and abundance of Archaea on skin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moissl-Eichinger, Christine; Probst, Alexander J.; Birarda, Giovanni

    The human skin microbiome acts as an important barrier protecting our body from pathogens and other environmental influences. Recent investigations have provided evidence that Archaea are a constant but highly variable component of the human skin microbiome, yet factors that determine their abundance changes are unknown. Here, we tested the hypothesis that the abundance of archaea on human skin is influenced by human age and skin physiology by quantitative PCR of 51 different skin samples taken from human subjects of various age. Our results reveal that archaea are more abundant in human subjects either older than 60 years or youngermore » than 12 years as compared to middle-aged human subjects. These results, together with results obtained from spectroscopy analysis, allowed us gain first insights into a potential link of lower sebum levels and lipid content and thus reduced skin moisture with an increase in archaeal signatures. In conclusion, amplicon sequencing of selected samples revealed the prevalence of specific eury- and mainly thaumarchaeal taxa, represented by a core archaeome of the human skin.« less

  14. Human age and skin physiology shape diversity and abundance of Archaea on skin

    DOE PAGES

    Moissl-Eichinger, Christine; Probst, Alexander J.; Birarda, Giovanni; ...

    2017-06-22

    The human skin microbiome acts as an important barrier protecting our body from pathogens and other environmental influences. Recent investigations have provided evidence that Archaea are a constant but highly variable component of the human skin microbiome, yet factors that determine their abundance changes are unknown. Here, we tested the hypothesis that the abundance of archaea on human skin is influenced by human age and skin physiology by quantitative PCR of 51 different skin samples taken from human subjects of various age. Our results reveal that archaea are more abundant in human subjects either older than 60 years or youngermore » than 12 years as compared to middle-aged human subjects. These results, together with results obtained from spectroscopy analysis, allowed us gain first insights into a potential link of lower sebum levels and lipid content and thus reduced skin moisture with an increase in archaeal signatures. In conclusion, amplicon sequencing of selected samples revealed the prevalence of specific eury- and mainly thaumarchaeal taxa, represented by a core archaeome of the human skin.« less

  15. High-speed vibrational imaging and spectral analysis of lipid bodies by compound Raman microscopy.

    PubMed

    Slipchenko, Mikhail N; Le, Thuc T; Chen, Hongtao; Cheng, Ji-Xin

    2009-05-28

    Cells store excess energy in the form of cytoplasmic lipid droplets. At present, it is unclear how different types of fatty acids contribute to the formation of lipid droplets. We describe a compound Raman microscope capable of both high-speed chemical imaging and quantitative spectral analysis on the same platform. We used a picosecond laser source to perform coherent Raman scattering imaging of a biological sample and confocal Raman spectral analysis at points of interest. The potential of the compound Raman microscope was evaluated on lipid bodies of cultured cells and live animals. Our data indicate that the in vivo fat contains much more unsaturated fatty acids (FAs) than the fat formed via de novo synthesis in 3T3-L1 cells. Furthermore, in vivo analysis of subcutaneous adipocytes and glands revealed a dramatic difference not only in the unsaturation level but also in the thermodynamic state of FAs inside their lipid bodies. Additionally, the compound Raman microscope allows tracking of the cellular uptake of a specific fatty acid and its abundance in nascent cytoplasmic lipid droplets. The high-speed vibrational imaging and spectral analysis capability renders compound Raman microscopy an indispensible analytical tool for the study of lipid-droplet biology.

  16. Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors.

    PubMed

    Melis, Miriam; Pillolla, Giuliano; Luchicchi, Antonio; Muntoni, Anna Lisa; Yasar, Sevil; Goldberg, Steven R; Pistis, Marco

    2008-12-17

    Nicotine stimulates the activity of mesolimbic dopamine neurons, which is believed to mediate the rewarding and addictive properties of tobacco use. Accumulating evidence suggests that the endocannabinoid system might play a major role in neuronal mechanisms underlying the rewarding properties of drugs of abuse, including nicotine. Here, we investigated the modulation of nicotine effects by the endocannabinoid system on dopamine neurons in the ventral tegmental area with electrophysiological techniques in vivo and in vitro. We discovered that pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme that catabolizes fatty acid ethanolamides, among which the endocannabinoid anandamide (AEA) is the best known, suppressed nicotine-induced excitation of dopamine cells. Importantly, this effect was mimicked by the administration of the FAAH substrates oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), but not methanandamide, the hydrolysis resistant analog of AEA. OEA and PEA are naturally occurring lipid signaling molecules structurally related to AEA, but devoid of affinity for cannabinoid receptors. They blocked the effects of nicotine by activation of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor transcription factor involved in several aspects of lipid metabolism and energy balance. Activation of PPAR-alpha triggered a nongenomic stimulation of tyrosine kinases, which might lead to phosphorylation and negative regulation of neuronal nicotinic acetylcholine receptors. These data indicate for the first time that the anorexic lipids OEA and PEA possess neuromodulatory properties as endogenous ligands of PPAR-alpha in the brain and provide a potential new target for the treatment of nicotine addiction.

  17. Purification and protein composition of endogenous rat viruses.

    PubMed

    Hlubinová, K; Prachar, J; Vrbenská, A; Matoska, J; Simkovic, D

    1984-01-01

    Endogenous retroviruses are not in the majority of cases the cause of any neoplasia, except for the laboratory conditions. As far as they might serve for the evolution of pathogenic retroviruses more attention should have been paid to them. In this paper we introduce some approaches to the purification of rat endogenous retroviruses to such a degree of purity that enabled satisfactory SDS-PAGE analysis of its structural proteins. Purities of samples obtained by usual purification methods, long-term isopycnic centrifugation at a high gravity force and velocity centrifugation are compared. Protein profile of rat endogenous virus in SDS-PAGE is compared with the ones of other retroviruses. For the first time the evidence was obtained for the striking similarity between electrophoretic protein profile of rat endogenous virus WERC and feline leukemia virus. The major structural proteins of rat endogenous retrovirus and feline leukemia virus cannot be distinguished even when resolution long gradient PAGE had been employed. The accordance of electrophoretic mobilities of major structural proteins in SDS-PAGE can indicate the relatedness of retroviruses.

  18. Lipid rafts are essential for peroxisome biogenesis in HepG2 cells.

    PubMed

    Woudenberg, Jannes; Rembacz, Krzysztof P; Hoekstra, Mark; Pellicoro, Antonella; van den Heuvel, Fiona A J; Heegsma, Janette; van Ijzendoorn, Sven C D; Holzinger, Andreas; Imanaka, Tsuneo; Moshage, Han; Faber, Klaas Nico

    2010-08-01

    Peroxisomes are particularly abundant in the liver and are involved in bile salt synthesis and fatty acid metabolism. Peroxisomal membrane proteins (PMPs) are required for peroxisome biogenesis [e.g., the interacting peroxisomal biogenesis factors Pex13p and Pex14p] and its metabolic function [e.g., the adenosine triphosphate-binding cassette transporters adrenoleukodystrophy protein (ALDP) and PMP70]. Impaired function of PMPs is the underlying cause of Zellweger syndrome and X-linked adrenoleukodystrophy. Here we studied for the first time the putative association of PMPs with cholesterol-enriched lipid rafts and their function in peroxisome biogenesis. Lipid rafts were isolated from Triton X-100-lysed or Lubrol WX-lysed HepG2 cells and analyzed for the presence of various PMPs by western blotting. Lovastatin and methyl-beta-cyclodextrin were used to deplete cholesterol and disrupt lipid rafts in HepG2 cells, and this was followed by immunofluorescence microscopy to determine the subcellular location of catalase and PMPs. Cycloheximide was used to inhibit protein synthesis. Green fluorescent protein-tagged fragments of PMP70 and ALDP were analyzed for their lipid raft association. PMP70 and Pex14p were associated with Triton X-100-resistant rafts, ALDP was associated with Lubrol WX-resistant rafts, and Pex13p was not lipid raft-associated in HepG2 cells. The minimal peroxisomal targeting signals in ALDP and PMP70 were not sufficient for lipid raft association. Cholesterol depletion led to dissociation of PMPs from lipid rafts and impaired sorting of newly synthesized catalase and ALDP but not Pex14p and PMP70. Repletion of cholesterol to these cells efficiently reestablished the peroxisomal sorting of catalase but not ALDP. Human PMPs are differentially associated with lipid rafts independently of the protein homology and/or their functional interaction. Cholesterol is required for peroxisomal lipid raft assembly and peroxisome biogenesis.

  19. Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Adebiyi, Adebowale, E-mail: aadebiyi@uthsc.edu; Soni, Hitesh; John, Theresa A.

    Angiotensin II (ANG-II) receptors (AGTRs) contribute to renal physiology and pathophysiology, but the underlying mechanisms that regulate AGTR function in glomerular mesangium are poorly understood. Here, we show that AGTR1 is the functional AGTR subtype expressed in neonatal pig glomerular mesangial cells (GMCs). Cyclodextrin (CDX)-mediated cholesterol depletion attenuated cell surface AGTR1 protein expression and ANG-II-induced intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub i}) elevation in the cells. The COOH-terminus of porcine AGTR1 contains a caveolin (CAV)-binding motif. However, neonatal GMCs express CAV-1, but not CAV-2 and CAV-3. Colocalization and in situ proximity ligation assay detected an association between endogenous AGTR1 and CAV-1more » in the cells. A synthetic peptide corresponding to the CAV-1 scaffolding domain (CSD) sequence also reduced ANG-II-induced [Ca{sup 2+}]{sub i} elevation in the cells. Real-time imaging of cell growth revealed that ANG-II stimulates neonatal GMC proliferation. ANG-II-induced GMC growth was attenuated by EMD 66684, an AGTR1 antagonist; BAPTA, a [Ca{sup 2+}]{sub i} chelator; KN-93, a Ca{sup 2+}/calmodulin-dependent protein kinase II inhibitor; CDX; and a CSD peptide, but not PD 123319, a selective AGTR2 antagonist. Collectively, our data demonstrate [Ca{sup 2+}]{sub i}-dependent proliferative effect of ANG-II and highlight a critical role for lipid raft microdomains in AGTR1-mediated signal transduction in neonatal GMCs. - Highlights: • AGTR1 is the functional AGTR subtype expressed in neonatal mesangial cells. • Endogenous AGTR1 associates with CAV-1 in neonatal mesangial cells. • Lipid raft disruption attenuates cell surface AGTR1 protein expression. • Lipid raft disruption reduces ANG-II-induced [Ca{sup 2+}]{sub i} elevation in neonatal mesangial cells. • Lipid raft disruption inhibits ANG-II-induced neonatal mesangial cell growth.« less

  20. Proteomic Analysis of Lipid Raft-Like Detergent-Resistant Membranes of Lens Fiber Cells.

    PubMed

    Wang, Zhen; Schey, Kevin L

    2015-12-01

    Plasma membranes of lens fiber cells have high levels of long-chain saturated fatty acids, cholesterol, and sphingolipids-key components of lipid rafts. Thus, lipid rafts are expected to constitute a significant portion of fiber cell membranes and play important roles in lens biology. The purpose of this study was to characterize the lens lipid raft proteome. Quantitative proteomics, both label-free and iTRAQ methods, were used to characterize lens fiber cell lipid raft proteins. Detergent-resistant, lipid raft membrane (DRM) fractions were isolated by sucrose gradient centrifugation. To confirm protein localization to lipid rafts, protein sensitivity to cholesterol removal by methyl-β-cyclodextrin was quantified by iTRAQ analysis. A total of 506 proteins were identified in raft-like detergent-resistant membranes. Proteins identified support important functions of raft domains in fiber cells, including trafficking, signal transduction, and cytoskeletal organization. In cholesterol-sensitivity studies, 200 proteins were quantified and 71 proteins were strongly affected by cholesterol removal. Lipid raft markers flotillin-1 and flotillin-2 and a significant fraction of AQP0, MP20, and AQP5 were found in the DRM fraction and were highly sensitive to cholesterol removal. Connexins 46 and 50 were more abundant in nonraft fractions, but a small fraction of each was found in the DRM fraction and was strongly affected by cholesterol removal. Quantification of modified AQP0 confirmed that fatty acylation targeted this protein to membrane raft domains. These data represent the first comprehensive profile of the lipid raft proteome of lens fiber cells and provide information on membrane protein organization in these cells.

  1. Multiplexed Quantitation of Endogenous Proteins in Dried Blood Spots by Multiple Reaction Monitoring - Mass Spectrometry

    PubMed Central

    Chambers, Andrew G.; Percy, Andrew J.; Yang, Juncong; Camenzind, Alexander G.; Borchers, Christoph H.

    2013-01-01

    Dried blood spot (DBS) sampling, coupled with multiple reaction monitoring mass spectrometry (MRM-MS), is a well-established approach for quantifying a wide range of small molecule biomarkers and drugs. This sampling procedure is simpler and less-invasive than those required for traditional plasma or serum samples enabling collection by minimally trained personnel. Many analytes are stable in the DBS format without refrigeration, which reduces the cost and logistical challenges of sample collection in remote locations. These advantages make DBS sample collection desirable for advancing personalized medicine through population-wide biomarker screening. Here we expand this technology by demonstrating the first multiplexed method for the quantitation of endogenous proteins in DBS samples. A panel of 60 abundant proteins in human blood was targeted by monitoring proteotypic tryptic peptides and their stable isotope-labeled analogs by MRM. Linear calibration curves were obtained for 40 of the 65 peptide targets demonstrating multiple proteins can be quantitatively extracted from DBS collection cards. The method was also highly reproducible with a coefficient of variation of <15% for all 40 peptides. Overall, this assay quantified 37 proteins spanning a range of more than four orders of magnitude in concentration within a single 25 min LC/MRM-MS analysis. The protein abundances of the 33 proteins quantified in matching DBS and whole blood samples showed an excellent correlation, with a slope of 0.96 and an R2 value of 0.97. Furthermore, the measured concentrations for 80% of the proteins were stable for at least 10 days when stored at −20 °C, 4 °C and 37 °C. This work represents an important first step in evaluating the integration of DBS sampling with highly-multiplexed MRM for quantitation of endogenous proteins. PMID:23221968

  2. Purification of α-Synuclein from Human Brain Reveals an Instability of Endogenous Multimers as the Protein Approaches Purity

    PubMed Central

    2015-01-01

    Despite two decades of research, the structure–function relationships of endogenous, physiological forms of α-synuclein (αSyn) are not well understood. Most in vitro studies of this Parkinson’s disease-related protein have focused on recombinant αSyn that is unfolded and monomeric, assuming that this represents its state in the normal human brain. Recently, we have provided evidence that αSyn exists in considerable part in neurons, erythrocytes, and other cells as a metastable multimer that principally sizes as a tetramer. In contrast to recombinant αSyn, physiological tetramers purified from human erythrocytes have substantial α-helical content and resist pathological aggregation into β-sheet rich fibers. Here, we report the first method to fully purify soluble αSyn from the most relevant source, human brain. We describe protocols that purify αSyn to homogeneity from nondiseased human cortex using ammonium sulfate precipitation, gel filtration, and ion exchange, hydrophobic interaction, and affinity chromatographies. Cross-linking of the starting material and the partially purified chromatographic fractions revealed abundant αSyn multimers, including apparent tetramers, but these were destabilized in large part to monomers during the final purification step. The method also fully purified the homologue β-synuclein, with a similar outcome. Circular dichroism spectroscopy showed that purified, brain-derived αSyn can display more helical content than the recombinant protein, but this result varied. Collectively, our data suggest that purifying αSyn to homogeneity destabilizes native, α-helix-rich multimers that exist in intact and partially purified brain samples. This finding suggests existence of a stabilizing cofactor (e.g., a small lipid) present inside neurons that is lost during final purification. PMID:25490121

  3. Modulation in Persistent Organic Pollutant Concentration and Profile by Prey Availability and Reproductive Status in Southern Resident Killer Whale Scat Samples.

    PubMed

    Lundin, Jessica I; Ylitalo, Gina M; Booth, Rebecca K; Anulacion, Bernadita; Hempelmann, Jennifer A; Parsons, Kim M; Giles, Deborah A; Seely, Elizabeth A; Hanson, M Bradley; Emmons, Candice K; Wasser, Samuel K

    2016-06-21

    Persistent organic pollutants (POPs), specifically PCBs, PBDEs, and DDTs, in the marine environment are well documented, however accumulation and mobilization patterns at the top of the food-web are poorly understood. This study broadens the understanding of POPs in the endangered Southern Resident killer whale population by addressing modulation by prey availability and reproductive status, along with endocrine disrupting effects. A total of 140 killer whale scat samples collected from 54 unique whales across a 4 year sampling period (2010-2013) were analyzed for concentrations of POPs. Toxicant measures were linked to pod, age, and birth order in genotyped individuals, prey abundance using open-source test fishery data, and pregnancy status based on hormone indices from the same sample. Toxicant concentrations were highest and had the greatest potential for toxicity when prey abundance was the lowest. In addition, these toxicants were likely from endogenous lipid stores. Bioaccumulation of POPs increased with age, with the exception of presumed nulliparous females. The exceptional pattern may be explained by females experiencing unobserved neonatal loss. Transfer of POPs through mobilization of endogenous lipid stores during lactation was highest for first-borns with diminished transfer to subsequent calves. Contrary to expectation, POP concentrations did not demonstrate an associated disruption of thyroid hormone, although this association may have been masked by impacts of prey abundance on thyroid hormone concentrations. The noninvasive method for measuring POP concentrations in killer whales through scat employed in this study may improve toxicant monitoring in the marine environment and promote conservation efforts.

  4. Effects of distillers' dried grains with solubles and soybean oil on dietary lipid, fiber, and amino acid digestibility in corn-based diets fed to growing pigs.

    PubMed

    Gutierrez, N A; Serão, N V L; Patience, J F

    2016-04-01

    The use of corn coproducts increases the concentration of fiber and, often, the use of supplemental lipids in swine diets, which may affect energy and nutrient digestibility. An experiment was conducted to determine the effects of reduced-oil distillers' dried grains with solubles (DDGS) and soybean oil (SBO) on dietary AA, acid hydrolyzed ether extract (AEE), and NDF digestibility in corn-based diets fed to growing pigs. Eighteen growing pigs (33.8 ± 2.2 kg BW) were surgically fitted with a T-cannula in the distal ileum and allocated to 1 of 6 dietary treatment groups in a 3-period incomplete Latin square design, with 9 observations per treatment. Six dietary treatments were obtained by adding 0, 20, and 40% DDGS to corn-casein diets formulated with 2 and 6% SBO. Ileal digesta and fecal samples were collected and the apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of AEE and NDF and the AID of AA were determined. Apparent values were corrected for endogenous losses of lipids, and true ileal (TID) and true total tract digestibility (TTTD) values of lipids were calculated. Results showed that the AID of Lys decreased ( < 0.001) with the inclusion of DDGS but was not affected ( = 0.63) by the inclusion of SBO. An interaction between DDGS and SBO on the AID ( = 0.002) and ATTD ( = 0.009) of NDF was observed, where the AID and ATTD of NDF decreased with DDGS at 6% SBO but no effect was observed at 2% SBO. The AID of NDF increased with SBO at 0% DDGS, but no effect was observed at 20 or 40% DDGS. An interaction between DDGS and SBO on the AID ( = 0.011) and ATTD ( = 0.008) of AEE was observed, where the AID and ATTD of AEE increased with SBO. The AID and ATTD of AEE increased with DDGS at 2% SBO, but no effect was observed at 6% SBO. Correction by ileal and fecal endogenous loss of AEE (9.5 and 13.6 g/kg of DMI, respectively) showed that increasing dietary AEE had no effect on the TID and TTD of AEE ( > 0.05). In conclusion, the AID of

  5. Explaining Cigarette Smoking: An Endogenous-Exogenous Analysis.

    ERIC Educational Resources Information Center

    McKillip, Jack

    Kruglanski's endogenous-exogenous partition, when applied to reasons given by smokers for smoking cigarettes, distinguishes two types of actions: (1) endogenous reasons implying that the behavior of consuming the cigarette is the goal of the action and the actor is positive toward the behavior, and (2) exogenous reasons implying that the behavior…

  6. Lipid biomarker and microbial community of 49.6°E hydrothermal field at Southwest Indian Ocean Ridge

    NASA Astrophysics Data System (ADS)

    Lei, J.; Chu, F.; Yu, X.; Li, X.; Tao, C.

    2012-12-01

    In 2007, Chinese Research Cruises Discovered the First Active Hydrothermal Vent Field at the Ultraslow Spreading Southwest Indian Ridge. This study intent to get composition, evolution and origin information of lipid compounds in SWIR, and recognize the style of lipid biomarkers which have obviously indicative significance for community structure.Soluble organic matter were extracted from geological samples (including chimney sulfide, oxide, around hydrothermal vents) in Southwest Indian Ridge (SWIR), and divided into hydrocarbon, fatty acid component by column chromatography. GC, GC-MS, HPLC-MS were applied for composition and abundance analysis. Lipid in hydrothermal sulfide contains obvious isoprenoidal hydrocarbon biomarkers (Sq, IS40) and GDGTs (m/z=653) that associated with methanogenic archaea which belongs to Euryarchaeota, and iso /anti-iso fatty acid (iC15:0, aiC15:0, iC17:0, aiC17:0)which may originated from sulfate reducing bacteria (SRB).Lipids extracted from hydrothermal oxide lack isoprenoidal hydrocarbon, and Ph/C18 (0.57) is much lower than sulfide (1.22). Fatty acid compound of oxide include abundant saturated fatty (C16:0, C18:0) acid and mono-unsaturated fatty acids (C16:1n7, C18:1n7), but much less iso/anti-iso was detected. Lipid composition of hydrothermal oxide showed that archaea activity was seldom in hydrothermal oxide, and sulfur-oxidizing bacteria was the main microbial community.Study of Jaeschke (2010) showed that high temperature hydrothermal venting encompassed different microbial community from low temperature hydrothermal venting. Our study showed that in different stage of hydrothermal, microbial community structure may be distinct.

  7. Lipid and fatty acid compositions of cod ( Gadus morhua), haddock ( Melanogrammus aeglefinus) and halibut ( Hippoglossus hippoglossus)

    NASA Astrophysics Data System (ADS)

    Zeng, Duan; Mai, Kangsen; Ai, Qinghui; Milley, Joyce E.; Lall, Santosh P.

    2010-12-01

    This study was conducted to compare lipid and fatty acid composition of cod, haddock and halibut. Three groups of cod (276 g ± 61 g), haddock (538 g ± 83 g) and halibut (3704 g ± 221 g) were maintained with commercial feeds mainly based on fish meal and marine fish oil for 12 weeks prior to sampling. The fatty acid compositions of muscle and liver were determined by GC/FID after derivatization of extracted lipids into fatty acid methyl esters (FAME). Lipids were also fractionated into neutral and polar lipids using Waters silica Sep-Pak?. The phospholipid fraction was further separated by high-performance thin-layer chromatography (HPTLC) and the FAME profile was obtained. Results of the present study showed that cod and haddock were lean fish and their total muscle lipid contents were 0.8% and 0.7%, respectively, with phospholipid constituting 83.6% and 87.5% of the total muscle lipid, respectively. Halibut was a medium-fat fish and its muscle lipid content was 8%, with 84% of the total muscle lipid being neutral lipid. Total liver lipid contents of cod, haddock and halibut were 36.9%, 67.2% and 30.7%, respectively, of which the neutral lipids accounted for the major fraction (88.1%-97.1%). Polyunsaturated fatty acids were the most abundant in cod and haddock muscle neutral lipid. Monounsaturated fatty acid level was the highest in halibut muscle neutral lipid. Fatty acid compositions of phospholipid were relatively constant. In summary, the liver of cod and haddock as lean fish was the main lipid reserve organ, and structural phospholipid is the major lipid form in flesh. However, as a medium-fat fish, halibut stored lipid in both their liver and muscle.

  8. Endogenous lipoid pneumonia associated with Legionella pneumophila serogroup 1.

    PubMed

    Hui, Chee-Kin

    2013-03-01

    Endogenous lipoid pneumonia is an uncommon condition. This is a report of a 29-year-old woman diagnosed with endogenous lipoid pneumonia associated with Legionella pneumophila serogroup 1 infection. The patient's endogenous lipoid pneumonia resolved completely after treatment for Legionella pneumophila infection. This suggests that early diagnosis and aggressive treatment of the underlying infection may prevent any long-term sequelae of lipoid pneumonia.

  9. Endogenous opiates and behavior: 2014.

    PubMed

    Bodnar, Richard J

    2016-01-01

    This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular

  10. The Increased Endogenous Sulfur Dioxide Acts as a Compensatory Mechanism for the Downregulated Endogenous Hydrogen Sulfide Pathway in the Endothelial Cell Inflammation

    PubMed Central

    Zhang, Da; Wang, Xiuli; Tian, Xiaoyu; Zhang, Lulu; Yang, Guosheng; Tao, Yinghong; Liang, Chen; Li, Kun; Yu, Xiaoqi; Tang, Xinjing; Tang, Chaoshu; Zhou, Jing; Kong, Wei; Du, Junbao; Huang, Yaqian; Jin, Hongfang

    2018-01-01

    Endogenous hydrogen sulfide (H2S) and sulfur dioxide (SO2) are regarded as important regulators to control endothelial cell function and protect endothelial cell against various injuries. In our present study, we aimed to investigate the effect of endogenous H2S on the SO2 generation in the endothelial cells and explore its significance in the endothelial inflammation in vitro and in vivo. The human umbilical vein endothelial cell (HUVEC) line (EA.hy926), primary HUVECs, primary rat pulmonary artery endothelial cells (RPAECs), and purified aspartate aminotransferase (AAT) protein from pig heart were used for in vitro experiments. A rat model of monocrotaline (MCT)-induced pulmonary vascular inflammation was used for in vivo experiments. We found that endogenous H2S deficiency caused by cystathionine-γ-lyase (CSE) knockdown increased endogenous SO2 level in endothelial cells and enhanced the enzymatic activity of AAT, a major SO2 synthesis enzyme, without affecting the expressions of AAT1 and AAT2. While H2S donor could reverse the CSE knockdown-induced increase in the endogenous SO2 level and AAT activity. Moreover, H2S donor directly inhibited the activity of purified AAT protein, which was reversed by a thiol reductant DTT. Mechanistically, H2S donor sulfhydrated the purified AAT1/2 protein and rescued the decrease in the sulfhydration of AAT1/2 protein in the CSE knockdown endothelial cells. Furthermore, an AAT inhibitor l-aspartate-β-hydroxamate (HDX), which blocked the upregulation of endogenous SO2/AAT generation induced by CSE knockdown, aggravated CSE knockdown-activated nuclear factor-κB pathway in the endothelial cells and its downstream inflammatory factors including ICAM-1, TNF-α, and IL-6. In in vivo experiment, H2S donor restored the deficiency of endogenous H2S production induced by MCT, and reversed the upregulation of endogenous SO2/AAT pathway via sulfhydrating AAT1 and AAT2. In accordance with the results of the in vitro experiment, HDX

  11. Increased levels of palmitoylethanolamide and other bioactive lipid mediators and enhanced local mast cell proliferation in canine atopic dermatitis

    PubMed Central

    2014-01-01

    Background Despite the precise pathogenesis of atopic dermatitis (AD) is unknown, an immune dysregulation that causes Th2-predominant inflammation and an intrinsic defect in skin barrier function are currently the two major hypotheses, according to the so-called outside-inside-outside model. Mast cells (MCs) are involved in AD both by releasing Th2 polarizing cytokines and generating pruritus symptoms through release of histamine and tryptase. A link between MCs and skin barrier defects was recently uncovered, with histamine being found to profoundly contribute to the skin barrier defects. Palmitoylethanolamide and related lipid mediators are endogenous bioactive compounds, considered to play a protective homeostatic role in many tissues: evidence collected so far shows that the anti-inflammatory effect of palmitoylethanolamide depends on the down-modulation of MC degranulation. Based on this background, the purpose of the present study was twofold: (a) to determine if the endogenous levels of palmitoylethanolamide and other bioactive lipid mediators are changed in the skin of AD dogs compared to healthy animals; (b) to examine if MC number is increased in the skin of AD dogs and, if so, whether it depends on MC in-situ proliferation. Results The amount of lipid extract expressed as percent of biopsy tissue weight was significantly reduced in AD skin while the levels of all analyzed bioactive lipid mediators were significantly elevated, with palmitoylethanolamide showing the highest increase. In dogs with AD, the number of MCs was significantly increased in both the subepidermal and the perifollicular compartments and their granule content was significantly decreased in the latter. Also, in situ proliferation of MCs was documented. Conclusions The levels of palmitoylethanolamide and other bioactive lipid mediators were shown to increase in AD skin compared to healthy samples, leading to the hypothesis that they may be part of the body’s innate mechanisms to

  12. ENDOGENOUS RETROVIRUSES MOBILIZED DURING FRIEND MURINE LEUKEMIA VIRUS INFECTION

    PubMed Central

    Hansen, Ethan; Hendrick, Duncan; Malik, Frank; Evans, Leonard H.

    2016-01-01

    We have demonstrated in a mouse model that infection with a retrovirus can lead not only to the generation of recombinants between exogenous and endogenous gammaretrovirus, but also to the mobilization of endogenous proviruses by pseudotyping entire polytropic proviral transcripts and facilitating their infectious spread to new cells. However, the frequency of this occurrence, the kinetics, and the identity of mobilized endogenous proviruses was unclear. Here we find that these mobilized transcripts are detected after only one day of infection. They predominate over recombinant polytropic viruses early in infection, persist throughout the course of disease and are comprised of multiple different polytropic proviruses. Other endogenous retroviral elements such as intracisternal A particles (IAPs) were not detected. The integration of the endogenous transcripts into new cells could result in loss of transcriptional control and elevated expression which may facilitate pathogenesis, perhaps by contributing to the generation of polytropic recombinant viruses. PMID:27657834

  13. [The endogenous opioid system and drug addiction].

    PubMed

    Maldonado, R

    2010-01-01

    Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits. Several neurotransmitters, including the endogenous opioid system are involved in these changes. The opioid system plays a pivotal role in different aspects of addiction. Thus, opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within the reward circuits. Opioid receptors and peptides are selectively involved in several components of the addictive processes induced by opioids, cannabinoids, psychostimulants, alcohol and nicotine. This review is focused on the contribution of each component of the endogenous opioid system in the addictive properties of the different drugs of abuse. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  14. Variation in lipid classes and fatty acid composition of salmon shark (Lamna ditropis) liver with season and gender.

    PubMed

    Jayasinghe, Chamila; Gotoh, Naohiro; Wada, Shun

    2003-02-01

    The influence of season and gender on lipid content, lipid classes, and fatty acid compositions was assessed in livers of salmon shark (Lamna ditropis), caught in the Pacific Ocean. No significant difference in the hepatosomatic index was noted with season, though the lipid content was significantly higher (P<0.05) in winter. Triacylglycerol (TAG) was identified as the predominant lipid class (78.5-82.0%), followed by sterol esters (5.7-9.1%) and hydrocarbons (3.4-5.4%). No significant differences were observed in TAG composition with respect to the season or gender. However, diacylglyceryl ether contents were significantly higher (P<0.05) in winter (3.8-5.3%) than those obtained in summer (1.3-1.1%). Polyunsaturated fatty acids constituted the major fatty acid class of salmon shark total liver lipid and docosahexaenoic acid (C22:6n-3) (22.7-28.4%) was the most abundant fatty acid which was significantly lower (P<0.05) in winter. These results suggested that lipid characteristics of salmon shark liver were influenced by season, but not by gender.

  15. Endogenous versus Exogenous Origins of Crises

    NASA Astrophysics Data System (ADS)

    Sornette, Didier

    Are large biological extinctions such as the Cretaceous/Tertiary KT boundary due to a meteorite, extreme volcanic activity or self-organized critical extinction cascades? Are commercial successes due to a progressive reputation cascade or the result of a well orchestrated advertisement? Determining the chain of causality for Xevents in complex systems requires disentangling interwoven exogenous and endogenous contributions with either no clear signature or too many signatures. Here, I review several efforts carried out with collaborators which suggest a general strategy for understanding the organizations of several complex systems under the dual effect of endogenous and exogenous fluctuations. The studied examples are: internet download shocks, book sale shocks, social shocks, financial volatility shocks, and financial crashes. Simple models are offered to quantitatively relate the endogenous organization to the exogenous response of the system. Suggestions for applications of these ideas to many other systems are offered.

  16. Optimized endogenous post-stratification in forest inventories

    Treesearch

    Paul L. Patterson

    2012-01-01

    An example of endogenous post-stratification is the use of remote sensing data with a sample of ground data to build a logistic regression model to predict the probability that a plot is forested and using the predicted probabilities to form categories for post-stratification. An optimized endogenous post-stratified estimator of the proportion of forest has been...

  17. Lipid biomarkers in Symbiodinium dinoflagellates: new indicators of thermal stress

    NASA Astrophysics Data System (ADS)

    Kneeland, J.; Hughen, K.; Cervino, J.; Hauff, B.; Eglinton, T.

    2013-12-01

    Lipid content and fatty acid profiles of corals and their dinoflagellate endosymbionts are known to vary in response to high-temperature stress. To better understand the heat-stress response in these symbionts, we investigated cultures of Symbiodinium goreauii type C1 and Symbiodinium sp. clade subtype D1 grown under a range of temperatures and durations. The predominant lipids produced by Symbiodinium are palmitic (C16) and stearic (C18) saturated fatty acids and their unsaturated analogs, the polyunsaturated fatty acid docosahexaenoic acid (C22:6, n-3; DHA), and a variety of sterols. Prolonged exposure to high temperature causes the relative amount of unsaturated acids within the C18 fatty acids in Symbiodinium tissue to decrease. Thermal stress also causes a decrease in abundance of fatty acids relative to sterols, as well as the more specific ratio of DHA to an algal 4-methyl sterol. These shifts in fatty acid unsaturation and fatty acid-to-sterol ratios are common to both types C1 and D1, but the apparent thermal threshold of lipid changes is lower for type C1. This work indicates that ratios among free fatty acids and sterols in Symbiodinium can be used as sensitive indicators of thermal stress. If the Symbiodinium lipid stress response is unchanged in hospite, the algal heat-stress biomarkers we have identified could be measured to detect thermal stress within the coral holobiont. These results provide new insights into the potential role of lipids in the overall Symbiodinium thermal stress response.

  18. Rapid Mobilization of Membrane Lipids in Wheat Leaf-Sheaths during Incompatible Interactions with Hessian Fly*

    PubMed Central

    Zhu, Lieceng; Liu, Xuming; Wang, Haiyan; Khajuria, Chitvan; Reese, John C.; Whitworth, R. Jeff; Welti, Ruth; Chen, Ming-Shun

    2013-01-01

    Hessian fly (HF) is a biotrophic insect that interacts with wheat on a gene-for-gene basis. We profiled changes in membrane lipids in two isogenic wheat lines: a susceptible line and its backcrossed offspring containing the resistance gene H13. Our results revealed a 32 to 45% reduction in total concentrations of 129 lipid species in resistant plants during incompatible interactions within 24 h after HF attack. A smaller and delayed response was observed in susceptible plants during compatible interactions. Microarray and real-time PCR analyses of 168 lipid-metabolism related transcripts revealed that the abundance of many of these transcripts increased rapidly in resistant plants after HF attack, but did not change in susceptible plants. In association with the rapid mobilization of membrane lipids, the concentrations of some fatty acids and 12-oxo-phytodienoic acid (OPDA) increased specifically in resistant plants. Exogenous application of OPDA increased mortality of HF larvae significantly. Collectively, our data, along with previously published results, indicate that the lipids were mobilized through lipolysis, producing free fatty acids, which were likely further converted into oxylipins and other defense molecules. Our results suggest that rapid mobilization of membrane lipids constitutes an important step for wheat to defend against HF attack. PMID:22668001

  19. Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems.

    PubMed

    Watson, Andrew D

    2006-10-01

    Lipids are water-insoluble molecules that have a wide variety of functions within cells, including: 1) maintenance of electrochemical gradients; 2) subcellular partitioning; 3) first- and second-messenger cell signaling; 4) energy storage; and 5) protein trafficking and membrane anchoring. The physiological importance of lipids is illustrated by the numerous diseases to which lipid abnormalities contribute, including atherosclerosis, diabetes, obesity, and Alzheimer's disease. Lipidomics, a branch of metabolomics, is a systems-based study of all lipids, the molecules with which they interact, and their function within the cell. Recent advances in soft-ionization mass spectrometry, combined with established separation techniques, have allowed the rapid and sensitive detection of a variety of lipid species with minimal sample preparation. A "lipid profile" from a crude lipid extract is a mass spectrum of the composition and abundance of the lipids it contains, which can be used to monitor changes over time and in response to particular stimuli. Lipidomics, integrated with genomics, proteomics, and metabolomics, will contribute toward understanding how lipids function in a biological system and will provide a powerful tool for elucidating the mechanism of lipid-based disease, for biomarker screening, and for monitoring pharmacologic therapy.

  20. Lipid emulsion enhances cardiac performance after ischemia-reperfusion in isolated hearts from summer-active arctic ground squirrels.

    PubMed

    Salzman, Michele M; Cheng, Qunli; Deklotz, Richard J; Dulai, Gurpreet K; Douglas, Hunter F; Dikalova, Anna E; Weihrauch, Dorothee; Barnes, Brian M; Riess, Matthias L

    2017-07-01

    Hibernating mammals, like the arctic ground squirrel (AGS), exhibit robust resistance to myocardial ischemia/reperfusion (IR) injury. Regulated preference for lipid over glucose to fuel metabolism may play an important role. We tested whether providing lipid in an emulsion protects hearts from summer-active AGS better than hearts from Brown Norway (BN) rats against normothermic IR injury. Langendorff-prepared AGS and BN rat hearts were perfused with Krebs solution containing 7.5 mM glucose with or without 1% Intralipid™. After stabilization and cardioplegia, hearts underwent 45-min global ischemia and 60-min reperfusion. Coronary flow, isovolumetric left ventricular pressure, and mitochondrial redox state were measured continuously; infarct size was measured at the end of the experiment. Glucose-only AGS hearts functioned significantly better on reperfusion than BN rat hearts. Intralipid™ administration resulted in additional functional improvement in AGS compared to glucose-only and BN rat hearts. Infarct size was not different among groups. Even under non-hibernating conditions, AGS hearts performed better after IR than the best-protected rat strain. This, however, appears to strongly depend on metabolic fuel: Intralipid™ led to a significant improvement in return of function in AGS, but not in BN rat hearts, suggesting that year-round endogenous mechanisms are involved in myocardial lipid utilization that contributes to improved cardiac performance, independent of the metabolic rate decrease during hibernation. Comparative lipid analysis revealed four candidates as possible cardioprotective lipid groups. The improved function in Intralipid™-perfused AGS hearts also challenges the current paradigm that increased glucose and decreased lipid metabolism are favorable during myocardial IR.

  1. Endogenous opioids regulate moment-to-moment neuronal communication and excitability.

    PubMed

    Winters, Bryony L; Gregoriou, Gabrielle C; Kissiwaa, Sarah A; Wells, Oliver A; Medagoda, Danashi I; Hermes, Sam M; Burford, Neil T; Alt, Andrew; Aicher, Sue A; Bagley, Elena E

    2017-03-22

    Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability. Ultrastructural localization of endogenous ligands support these functional findings. This study demonstrates a new role for endogenously released opioids as neuromodulators engaged by synaptic activity to regulate moment-to-moment neuronal communication and excitability. These distinct actions through MOR and DOR may underlie the opposing effect of these receptor systems on anxiety and fear.

  2. Endogenous siRNAs and noncoding RNA-derived small RNAs are expressed in adult mouse hippocampus and are up-regulated in olfactory discrimination training.

    PubMed

    Smalheiser, Neil R; Lugli, Giovanni; Thimmapuram, Jyothi; Cook, Edwin H; Larson, John

    2011-01-01

    We previously proposed that endogenous siRNAs may regulate synaptic plasticity and long-term gene expression in the mammalian brain. Here, a hippocampal-dependent task was employed in which adult mice were trained to execute a nose-poke in a port containing one of two simultaneously present odors in order to obtain a reward. Mice demonstrating olfactory discrimination training were compared to pseudo-training and nose-poke control groups; size-selected hippocampal RNA was subjected to Illumina deep sequencing. Sequences that aligned uniquely and exactly to the genome without uncertain nucleotide assignments, within exons or introns of MGI annotated genes, were examined further. The data confirm that small RNAs having features of endogenous siRNAs are expressed in brain; that many of them derive from genes that regulate synaptic plasticity (and have been implicated in neuropsychiatric diseases); and that hairpin-derived endo-siRNAs and the 20- to 23-nt size class of small RNAs show a significant increase during an early stage of training. The most abundant putative siRNAs arose from an intronic inverted repeat within the SynGAP1 locus; this inverted repeat was a substrate for dicer in vitro, and SynGAP1 siRNA was specifically associated with Argonaute proteins in vivo. Unexpectedly, a dramatic increase with training (more than 100-fold) was observed for a class of 25- to 30-nt small RNAs derived from specific sites within snoRNAs and abundant noncoding RNAs (Y1 RNA, RNA component of mitochondrial RNAse P, 28S rRNA, and 18S rRNA). Further studies are warranted to characterize the role(s) played by endogenous siRNAs and noncoding RNA-derived small RNAs in learning and memory.

  3. Proteomic Analysis of Lipid Raft-Like Detergent-Resistant Membranes of Lens Fiber Cells

    PubMed Central

    Wang, Zhen; Schey, Kevin L.

    2015-01-01

    Purpose Plasma membranes of lens fiber cells have high levels of long-chain saturated fatty acids, cholesterol, and sphingolipids—key components of lipid rafts. Thus, lipid rafts are expected to constitute a significant portion of fiber cell membranes and play important roles in lens biology. The purpose of this study was to characterize the lens lipid raft proteome. Methods Quantitative proteomics, both label-free and iTRAQ methods, were used to characterize lens fiber cell lipid raft proteins. Detergent-resistant, lipid raft membrane (DRM) fractions were isolated by sucrose gradient centrifugation. To confirm protein localization to lipid rafts, protein sensitivity to cholesterol removal by methyl-β-cyclodextrin was quantified by iTRAQ analysis. Results A total of 506 proteins were identified in raft-like detergent-resistant membranes. Proteins identified support important functions of raft domains in fiber cells, including trafficking, signal transduction, and cytoskeletal organization. In cholesterol-sensitivity studies, 200 proteins were quantified and 71 proteins were strongly affected by cholesterol removal. Lipid raft markers flotillin-1 and flotillin-2 and a significant fraction of AQP0, MP20, and AQP5 were found in the DRM fraction and were highly sensitive to cholesterol removal. Connexins 46 and 50 were more abundant in nonraft fractions, but a small fraction of each was found in the DRM fraction and was strongly affected by cholesterol removal. Quantification of modified AQP0 confirmed that fatty acylation targeted this protein to membrane raft domains. Conclusions These data represent the first comprehensive profile of the lipid raft proteome of lens fiber cells and provide information on membrane protein organization in these cells. PMID:26747763

  4. Hypersaline Microbial Mat Lipid Biomarkers

    NASA Technical Reports Server (NTRS)

    Jahnke, Linda L.; Embaye, Tsegereda; Turk, Kendra A.; Summons, Roger E.

    2002-01-01

    Lipid biomarkers and compound specific isotopic abundances are powerful tools for studies of contemporary microbial ecosystems. Knowledge of the relationship of biomarkers to microbial physiology and community structure creates important links for understanding the nature of early organisms and paleoenvironments. Our recent work has focused on the hypersaline microbial mats in evaporation ponds at Guerrero Negro, Baja California Sur, Mexico. Specific biomarkers for diatoms, cyanobacteria, archaea, green nonsulfur (GNS), sulfate reducing, sulfur oxidizing and methanotrophic bacteria have been identified. Analyses of the ester-bound fatty acids indicate a highly diverse microbial community, dominated by photosynthetic organisms at the surface. The delta C-13 of cyanobacterial biomarkers such as the monomethylalkanes and hopanoids are consistent with the delta C-13 measured for bulk mat (-10%o), while a GNS biomarker, wax esters (WXE), suggests a more depleted delta C-13 for GNS biomass (-16%o). This isotopic relationship is different than that observed in mats at Octopus Spring, Yellowstone National Park (YSNP) where GNS appear to grow photoheterotrophic ally. WXE abundance, while relatively low, is most pronounced in an anaerobic zone just below the cyanobacterial layer. The WXE isotope composition at GN suggests that these bacteria utilize photoautotrophy incorporating dissolved inorganic carbon (DIC) via the 3-hydroxypropionate pathway using H2S or H2.

  5. Protection by serine peptidase inhibitors of endogenous cholecystokinin released from brain slices.

    PubMed

    Rose, C; Camus, A; Schwartz, J C

    1989-01-01

    Endogenous cholecystokinin immunoreactivity released by depolarization of slices of rat cerebral cortex undergoes extensive degradation (85% of released immunoreactivity) before reaching the incubation medium. In order to identify the responsible peptidases, a large number of inhibitors of the four catalytic classes were tested for their protective effects. Inhibitors of metallopeptidases (bestatin, amastatin, puromycin, Thiorphan, captopril, o-phenantroline), thiol-peptidases, (leupeptin, antipain, p-hydroxymercuribenzoate) or carboxyl-peptidases (pepstatin) had generally low if any protective effect. By contrast, several serine peptidase inhibitors, i.e. diisopropyl-fluorophosphate, phenylmethylsulphonylfluoride or the chloromethylketone Ala-Ala-Pro-Val-CH2Cl, doubled the recovery of cholecystokinin immunoreactivity and the effect was amplified in the co-presence of bestatin, an aminopeptidase inhibitor and/or Thiorphan, an enkephalinase inhibitor. High-performance liquid chromatographic analysis of the cholecystokinin immunoreactivity recovered in medium in the absence of any inhibitor showed cholecystokinin-8 to be the major peak, representing 8% of the released immunoreactive material. Non-sulphated cholecystokinin-8 represented less than 1%, indicating that desulphation does not constitute a major inactivation pathway for the endogenous octapeptide. Cholecystokinin-5 was the major clearly identifiable immunoreactive fragment, representing 9% of released immunoreactivity in the absence of inhibitors. Its formation was decreased by about 50% in the presence of either diisopropyl-fluorophosphate or bestatin and Thiorphan and abolished when they were associated, suggesting that it resulted from the actions of a serine peptidase(s) and an aminopeptidase(s). Cholecystokinin-6 (or cholecystokinin-7) was less abundant, representing 4% of the released immunoreactivity, and its level was augmented in the presence of diisopropyl-fluorophosphate. Hence a serine

  6. Lipid profiles of follicular fluid from cows submitted to ovarian superstimulation.

    PubMed

    Santos, P H; Fontes, P K; Franchi, F F; Nogueira, M F G; Belaz, K R A; Tata, A; Eberlin, M N; Sudano, M J; Barros, C M; Castilho, A C S

    2017-05-01

    Ovarian superstimulation with exogenous gonadotropins has been extensively used to produce in vivo-derived embryos for embryo transfer in cattle. This process modifies the antral follicle microenvironment and affects oocyte and embryo quality as well the differentiation of granulosa cells. Lipids play significant roles in the cell, such as energy storage, cell structure, and fine-tuning of the physical properties and functions of biological membranes. The phospholipid (PL) contents as well as the effects of superstimulatory treatments on the PL profile of follicular fluid from cows, however, remain unknown. Therefore, to gain insight into the effects of superstimulation with follicle-stimulating hormone (FSH; P-36 protocol) or FSH combined with equine chorionic gonadotropin (eCG; P-36/eCG protocol) on the profile and abundance of PL from cows submitted or not submitted to superstimulatory protocols, were treated with these two superstimulatory protocols. As a control, non-superstimulated cows were only submitted to estrous synchronization. The follicular fluid was aspirated, the remaining cells removed and the follicular fluid stored at -80 °C until extraction. The lipid screening was performed by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and this technique allowed the identification of sphingomyelins (SM) and phosphatidylcholines (PC) and phosphoethanolamines (PE). The relative abundance of the ions observed in the three experimental groups was analyzed by multivariate and univariate statistical models. The phospholipid SM (16:0) and PC (36:4) and/or PC (34:1) were less (P < 0.05) abundant in the P-36 group compared to the control or P-36/eCG groups. However, the PC (34:2) was more (P < 0.05) abundant in both group of superstimulated cows compared to the control. In summary, ovarian superstimulation seems to modulate the PL content of bovine follicular fluid with a significant increase in PC (34:2), which jointly with others

  7. Effects of temperature on growth and lipid synthesis of diatom Chaetoceros Curvisetus and the Northern Adriatic (Mediteranean) plankton community

    NASA Astrophysics Data System (ADS)

    Novak, Tihana; Gašparović, Blaženka; Godrijan, Jelena; Maric, Daniela; Djakovac, Tamara; Mlakar, Marina

    2017-04-01

    Phytoplankton is the major primary producer in the world. Marine phytoplankton lives in a rather changing environment, with variations in temperature, light, salinity, nutrient availability, etc. In such changing environment phytoplankton should live, grow and reproduce, and, in order to achieve that, they fix carbon and nutrients to produce biomolecules (lipids, proteins and carbohydrates). Lipids are a good indicator of organic matter (OM) processes in the seas and oceans, also good bioindicators for OM origin, and phytoplankton adaptations to environmental stress. Marine lipids are produced by organisms, mostly in phototrophic part of the seas and oceans, and their crucial producer is phytoplankton. We were interested to see how the increasing temperature and different nutrient availability affect quantitative and qualitative lipid and lipid classes production by plankton community. To test how marine phytoplankton would respond to predicted increasing temperature we conducted monoculture batch experiments in laboratory on model diatom Chaetoceros curvisetus at five different temperatures from 10 to 30C. Also we conducted experiments in phosphorous replete and deplete conditions mimicking eutrophic and oligotrophic marine conditions. We have chosen Chaetoceros curvisetus as a model culture since it is a major component of Northern Adriatic (NA) phytoplankton, but also Chaetoceros genus of diatoms is most abundant in wide range of marine ecosystems. We also conducted annual sampling of the NA particulate matter that covers the same temperature range as for the batch experiments. NA samples were taken on two stations with different nutrient supply that were characterized as oligotrophic and mesotrophic stations. Samples were taken from 2013 to 2014 on a monthly basis. Lipid classes were characterized with thin-layer chromatography-flame ionization detection. Data are supported by particulate organic carbon (POC), chlorophyll a (Chl a) concentrations and

  8. Exercise induced asthma and endogenous opioids.

    PubMed Central

    Gaillard, R C; Bachman, M; Rochat, T; Egger, D; de Haller, R; Junod, A F

    1986-01-01

    Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma. PMID:2944240

  9. Lipid Cell Biology: A Focus on Lipids in Cell Division.

    PubMed

    Storck, Elisabeth M; Özbalci, Cagakan; Eggert, Ulrike S

    2018-06-20

    Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.

  10. Bee Abundance and Nutritional Status in Relation to Grassland Management Practices in an Agricultural Landscape.

    PubMed

    Smith, Griffin W; Debinski, Diane M; Scavo, Nicole A; Lange, Corey J; Delaney, John T; Moranz, Raymond A; Miller, James R; Engle, David M; Toth, Amy L

    2016-04-01

    Grasslands provide important resources for pollinators in agricultural landscapes. Managing grasslands with fire and grazing has the potential to benefit plant and pollinator communities, though there is uncertainty about the ideal approach. We examined the relationships among burning and grazing regimes, plant communities, and Bombus species and Apis mellifera L. abundance and nutritional indicators at the Grand River Grasslands in southern Iowa and northern Missouri. Treatment regimes included burn-only, grazed-and-burned, and patch-burn graze (pastures subdivided into three temporally distinct fire patches with free access by cattle). The premise of the experimental design was that patch-burn grazing would increase habitat heterogeneity, thereby providing more diverse and abundant floral resources for pollinators. We predicted that both bee abundance and individual bee nutritional indicators (bee size and lipid content) would be positively correlated with floral resource abundance. There were no significant differences among treatments with respect to bee abundance. However, some of the specific characteristics of the plant community showed significant relationships with bee response variables. Pastures with greater abundance of floral resources had greater bee abundance but lower bee nutritional indicators. Bee nutritional variables were positively correlated with vegetation height, but, in some cases, negatively correlated with stocking rate. These results suggest grassland site characteristics such as floral resource abundance and stocking rate are of potential importance to bee pollinators and suggest avenues for further research to untangle the complex interactions between grassland management, plant responses, and bee health. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Endogenous Cortical Oscillations Constrain Neuromodulation by Weak Electric Fields

    PubMed Central

    Schmidt, Stephen L.; Iyengar, Apoorva K.; Foulser, A. Alban; Boyle, Michael R.; Fröhlich, Flavio

    2014-01-01

    Background Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation modality that may modulate cognition by enhancing endogenous neocortical oscillations with the application of sine-wave electric fields. Yet, the role of endogenous network activity in enabling and shaping the effects of tACS has remained unclear. Objective We combined optogenetic stimulation and multichannel slice electrophysiology to elucidate how the effect of weak sine-wave electric field depends on the ongoing cortical oscillatory activity. We hypothesized that the structure of the response to stimulation depended on matching the stimulation frequency to the endogenous cortical oscillation. Methods We studied the effect of weak sine-wave electric fields on oscillatory activity in mouse neocortical slices. Optogenetic control of the network activity enabled the generation of in vivo like cortical oscillations for studying the temporal relationship between network activity and sine-wave electric field stimulation. Results Weak electric fields enhanced endogenous oscillations but failed to induce a frequency shift of the ongoing oscillation for stimulation frequencies that were not matched to the endogenous oscillation. This constraint on the effect of electric field stimulation imposed by endogenous network dynamics was limited to the case of weak electric fields targeting in vivo-like network dynamics. Together, these results suggest that the key mechanism of tACS may be enhancing but not overriding of intrinsic network dynamics. Conclusion Our results contribute to understanding the inconsistent tACS results from human studies and propose that stimulation precisely adjusted in frequency to the endogenous oscillations is key to rational design of non-invasive brain stimulation paradigms. PMID:25129402

  12. Extensive characterization of human tear fluid collected using different techniques unravels the presence of novel lipid amphiphiles1[S

    PubMed Central

    Lam, Sin Man; Tong, Louis; Duan, Xinrui; Petznick, Andrea; Wenk, Markus R.; Shui, Guanghou

    2014-01-01

    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. Our study confers novel insights to the compositional details of the existent tear film model, in particular the disputable amphiphilic lipid sublayer constituents, by demonstrating the presence of cholesteryl sulfate, O-acyl-ω-hydroxyfatty acids, and various sphingolipids and phospholipids in tears. The discovery and quantitation of the relative abundance of various tear lipid amphiphiles reported herein are expected to have a profound impact on the current understanding of the existent human tear film model. PMID:24287120

  13. Cationic lipid-conjugated hydrocortisone as selective antitumor agent.

    PubMed

    Rathore, Bhowmira; Chandra Sekhar Jaggarapu, Madhan Mohan; Ganguly, Anirban; Reddy Rachamalla, Hari Krishna; Banerjee, Rajkumar

    2016-01-27

    Hydrocortisone, the endogenously expressed steroidal, hormonal ligand for glucocorticoid receptor (GR), is body's natural anti-inflammatory and xenobiotic metabolizing agent. It has both palliative as well as adverse effects in different cancer patients. Herein, we show that conjugation product of C16-carbon chain-associated cationic lipid and hydrocortisone (namely, HYC16) induces selective toxicity in cancer (e.g. melanoma, breast cancer and lung adenocarcinoma) cells with least toxicity in normal cells, through induction of apoptosis and cell cycle arrest at G2/M phase. Further, significant tumor growth inhibition was observed in syngeneic melanoma tumor model with considerable induction of apoptosis in tumor-associated cells. In contrast to hydrocortisone, significantly higher anti-angiogenic behavior of HYC16 helped in effective tumor shrinkage. This is the first demonstration to convert natural hormone hydrocortisone into a selective bioactive entity possessing anti-tumor effect. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Analysis of Lipids and Lipid Rafts in Borrelia.

    PubMed

    Toledo, Alvaro; Huang, Zhen; Benach, Jorge L; London, Erwin

    2018-01-01

    Lipid rafts are membrane microdomains that are involved in cellular processes such as protein trafficking and signaling processes, and which play a fundamental role in membrane fluidity and budding. The lipid composition of the membrane and the biochemical characteristics of the lipids found within rafts define the ability of cells to form microdomains and compartmentalize the membrane. In this chapter, we describe the biophysical, biochemical, and molecular approaches used to define and characterize lipid rafts in the Lyme disease agent, Borrelia burgdorferi.

  15. A Lipid Pathway for Ligand Binding Is Necessary for a Cannabinoid G Protein-coupled Receptor*

    PubMed Central

    Hurst, Dow P.; Grossfield, Alan; Lynch, Diane L.; Feller, Scott; Romo, Tod D.; Gawrisch, Klaus; Pitman, Michael C.; Reggio, Patricia H.

    2010-01-01

    Recent isothiocyanate covalent labeling studies have suggested that a classical cannabinoid, (−)-7′-isothiocyanato-11-hydroxy-1′,1′dimethylheptyl-hexahydrocannabinol (AM841), enters the cannabinoid CB2 receptor via the lipid bilayer (Pei, Y., Mercier, R. W., Anday, J. K., Thakur, G. A., Zvonok, A. M., Hurst, D., Reggio, P. H., Janero, D. R., and Makriyannis, A. (2008) Chem. Biol. 15, 1207–1219). However, the sequence of steps involved in such a lipid pathway entry has not yet been elucidated. Here, we test the hypothesis that the endogenous cannabinoid sn-2-arachidonoylglycerol (2-AG) attains access to the CB2 receptor via the lipid bilayer. To this end, we have employed microsecond time scale all-atom molecular dynamics (MD) simulations of the interaction of 2-AG with CB2 via a palmitoyl-oleoyl-phosphatidylcholine lipid bilayer. Results suggest the following: 1) 2-AG first partitions out of bulk lipid at the transmembrane α-helix (TMH) 6/7 interface; 2) 2-AG then enters the CB2 receptor binding pocket by passing between TMH6 and TMH7; 3) the entrance of the 2-AG headgroup into the CB2 binding pocket is sufficient to trigger breaking of the intracellular TMH3/6 ionic lock and the movement of the TMH6 intracellular end away from TMH3; and 4) subsequent to protonation at D3.49/D6.30, further 2-AG entry into the ligand binding pocket results in both a W6.48 toggle switch change and a large influx of water. To our knowledge, this is the first demonstration via unbiased molecular dynamics that a ligand can access the binding pocket of a class A G protein-coupled receptor via the lipid bilayer and the first demonstration via molecular dynamics of G protein-coupled receptor activation triggered by a ligand binding event. PMID:20220143

  16. Characterization of nonpolar lipids and selected steroids by using laser-induced acoustic desorption/chemical ionization, atmospheric pressure chemical ionization, and electrospray ionization mass spectrometry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jin, Zhicheng; Daiya, Shivani; Kenttämaa, Hilkka I.

    2011-03-01

    Laser-induced acoustic desorption (LIAD) combined with ClMn(H2O)+ chemical ionization (CI) was tested for the analysis of nonpolar lipids and selected steroids in a Fourier-transform ion cyclotron resonance mass spectrometer (FT-ICR). The nonpolar lipids studied, cholesterol, 5α-cholestane, cholesta-3,5-diene, squalene, and β-carotene, were found to solely form the desired water replacement product (adduct-H2O) upon reaction with the ClMn(H2O)+ ions. The steroids, androsterone, dehydroepiandrosterone (DHEA), estrone, estradiol, and estriol, also form abundant adduct-H2O ions, but less abundant adduct-2H2O ions were also observed. Neither (+)APCI nor (+)ESI can ionize the saturated hydrocarbon lipid, cholestane. APCI successfully ionizes the unsaturated hydrocarbon lipids to form exclusivelymore » the intact protonated analytes. However, it causes extensive fragmentation for cholesterol and the steroids. The worst case is cholesterol that does not produce any stable protonated molecules. On the other hand, ESI cannot ionize any of the hydrocarbon analytes, saturated or unsaturated. However, ESI can be used to protonate the oxygen-containing analytes with substantially less fragmentation than for APCI in all cases except for cholesterol and estrone. In conclusion, LIAD/ClMn(H2O)+ chemical ionization is superior over APCI and ESI for the mass spectrometric characterization of underivatized nonpolar lipids and steroids.« less

  17. Lipids and Fatty Acids of Nudibranch Mollusks: Potential Sources of Bioactive Compounds

    PubMed Central

    Zhukova, Natalia V.

    2014-01-01

    The molecular diversity of chemical compounds found in marine animals offers a good chance for the discovery of novel bioactive compounds of unique structures and diverse biological activities. Nudibranch mollusks, which are not protected by a shell and produce chemicals for various ecological uses, including defense against predators, have attracted great interest for their lipid composition. Lipid analysis of eight nudibranch species revealed dominant phospholipids, sterols and monoalkyldiacylglycerols. Among polar lipids, 1-alkenyl-2-acyl glycerophospholipids (plasmalogens) and ceramide-aminoethyl phosphonates were found in the mollusks. The fatty acid compositions of the nudibranchs differed greatly from those of other marine gastropods and exhibited a wide diversity: very long chain fatty acids known as demospongic acids, a series of non-methylene-interrupted fatty acids, including unusual 21:2∆7,13, and an abundance of various odd and branched fatty acids typical of bacteria. Symbiotic bacteria revealed in some species of nudibranchs participate presumably in the production of some compounds serving as a chemical defense for the mollusks. The unique fatty acid composition of the nudibranchs is determined by food supply, inherent biosynthetic activities and intracellular symbiotic microorganisms. The potential of nudibranchs as a source of biologically active lipids and fatty acids is also discussed. PMID:25196731

  18. Lipid nanocarriers: influence of lipids on product development and pharmacokinetics.

    PubMed

    Pathak, Kamla; Keshri, Lav; Shah, Mayank

    2011-01-01

    Lipid nanocarriers are on the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery. Owing to their size-dependent properties, lipid nanoparticles offer the possibility for development of new therapeutics and an alternative system to other colloidal counterparts for drug administration. An important point to be considered in the selection of a lipid for the carrier system is its effect on the properties of the nanocarrier and also its intended use, as different types of lipids differ in their nature. Researchers around the globe have tapped the potential of solid lipid nanoparticles (SLNs) in developing formulation(s) that can be administered by various routes such as oral, ocular, parenteral, topical, and pulmonary. Since the start of this millennium, a new generation of lipid nanoparticles, namely nanostructured lipid carriers (NLCs), lipid drug conjugates (LDCs), and pharmacosomes, has evolved that have the potential to overcome the limitations of SLNs. The current review article presents broad considerations on the influence of various types of lipids on the diverse characteristics of nanocarriers, encompassing their physicochemical, formulation, pharmacokinetic, and cytotoxic aspects.

  19. LIPID11: A Modular Framework for Lipid Simulations using Amber

    PubMed Central

    Skjevik, Åge A.; Madej, Benjamin D.; Walker, Ross C.; eigen, Knut T

    2013-01-01

    Accurate simulation of complex lipid bilayers has long been a goal in condensed phase molecular dynamics (MD). Structure and function of membrane-bound proteins are highly dependent on the lipid bilayer environment and are challenging to study through experimental methods. Within Amber, there has been limited focus on lipid simulations, although some success has been seen with the use of the General Amber Force Field (GAFF). However, to date there are no dedicated Amber lipid force fields. In this paper we describe a new charge derivation strategy for lipids consistent with the Amber RESP approach, and a new atom and residue naming and type convention. In the first instance, we have combined this approach with GAFF parameters. The result is LIPID11, a flexible, modular framework for the simulation of lipids that is fully compatible with the existing Amber force fields. The charge derivation procedure, capping strategy and nomenclature for LIPID11, along with preliminary simulation results and a discussion of the planned long-term parameter development are presented here. Our findings suggest that Lipid11 is a modular framework feasible for phospholipids and a flexible starting point for the development of a comprehensive, Amber-compatible lipid force field. PMID:22916730

  20. Effect of saturated fatty acid-rich dietary vegetable oils on lipid profile, antioxidant enzymes and glucose tolerance in diabetic rats

    PubMed Central

    Kochikuzhyil, Benson Mathai; Devi, Kshama; Fattepur, Santosh Raghunandan

    2010-01-01

    Objective: To study the effect of saturated fatty acid (SFA)-rich dietary vegetable oils on the lipid profile, endogenous antioxidant enzymes and glucose tolerance in type 2 diabetic rats. Materials and Methods: Type 2 diabetes was induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rats. Twenty-eight-day-old normal (N) and diabetic (D) male Wistar rats were fed for 45 days with a fat-enriched special diet (10%) prepared with coconut oil (CO) – lauric acid-rich SFA, palm oil (PO) – palmitic acid-rich SFA and groundnut oil (GNO) – control (N and D). Lipid profile, endogenous antioxidant enzymes and oral glucose tolerance tests were monitored. Results: D rats fed with CO (D + CO) exhibited a significant decrease in the total cholesterol and non-high-density lipoprotein cholesterol. Besides, they also showed a trend toward improving antioxidant enzymes and glucose tolerance as compared to the D + GNO group, whereas D + PO treatment aggravated the dyslipidemic condition while causing a significant decrease in the superoxide dismutase levels when compared to N rats fed with GNO (N + GNO). D + PO treatment also impaired the glucose tolerance when compared to N + GNO and D + GNO. Conclusion: The type of FA in the dietary oil determines its deleterious or beneficial effects. Lauric acid present in CO may protect against diabetes-induced dyslipidemia. PMID:20871763

  1. Invasive fungal infections in endogenous Cushing's syndrome

    PubMed Central

    Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

    2010-01-01

    Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

  2. [Formation of endogenous pyrogen by mononuclear phagocytes].

    PubMed

    Agasarov, L G; Sorokin, A V; Ukhanova, I K

    1984-07-01

    Production of endogenous pyrogen by human and rabbit blood monocytes in response to stimulation with agents of different origin was studied by inhibitory analysis under comparable conditions. Actinomycin D and cytochalasin B were applied. New evidence was obtained about an important role in the mechanism of activation of mononuclear phagocytes of initial interaction between a stimulating agent and the leukocyte membrane and of the biphasic process of endogenous pyrogen production.

  3. Effects of dietary crude oil exposure on molecular and physiological parameters related to lipid homeostasis in polar cod (Boreogadus saida).

    PubMed

    Vieweg, Ireen; Bilbao, Eider; Meador, James P; Cancio, Ibon; Bender, Morgan Lizabeth; Cajaraville, Miren P; Nahrgang, Jasmine

    2018-04-01

    Polar cod is an abundant Arctic key species, inhabiting an ecosystem that is subjected to rapid climate change and increased petroleum related activities. Few studies have investigated biological effects of crude oil on lipid metabolism in this species, despite lipids being a crucial compound for Arctic species to adapt to the high seasonality in food abundance in their habitat. This study examines the effects of dietary crude oil exposure on transcription levels of genes related to lipid metabolism (peroxisome proliferator-activated receptors [ppar-α, ppar-γ], retinoic X receptor [rxr-β], palmitoyl-CoA oxidase [aox1], cytochrome P4507A1 [cyp7α1]), reproduction (vitellogenin [vtg-β], gonad aromatase [cyp19a1]) and biotransformation (cytochrome P4501A1 [cyp1a1], aryl hydrocarbon receptor [ahr2]). Exposure effects were also examined through plasma chemistry parameters. Additional fish were exposed to a PPAR-α agonist (WY-14,643) to investigate the role of PPAR-α in their lipid metabolism. The dose-dependent up-regulation of cyp1a1 reflected the activation of genes related to PAH biotransformation upon crude oil exposure. The crude oil exposure did not significantly alter the mRNA expression of genes involved in lipid homeostasis except for cyp7α1 transcription levels. Plasma levels of cholesterol and alanine transaminase showed significant alterations in fish exposed to crude oil at the end of the experiment. WY exposure induced a down-regulation of ppar-α, an effect contrary to studies performed on other fish species. In conclusion, this study showed clear effects of dietary crude oil exposure at environmentally relevant concentrations on xenobiotic biotransformation but revealed only weak alterations in the lipid metabolism of polar cod. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Heat stress dictates microbial lipid composition in hydrothermal marine sediments

    NASA Astrophysics Data System (ADS)

    Sollich, M.; Yoshinaga, M. Y.; Häusler, S.; Hinrichs, K. U.; Bühring, S. I.

    2016-02-01

    Abundant and diverse microbial communities inhabit hydrothermal marine sediments. Since ion permeability of membranes increases with temperature archaea and bacteria that use proton/sodium as coupling ions for bioenergetics must constantly adjust their cytoplasmic membrane permeability, which in turn is mostly controlled by the lipid composition. Here, we investigated a thermal gradient across a marine sediment field (ranging from 18 to over 100°C) and tested the concept that membrane lipids provide a major biochemical basis for cellular bioenergetics of archaea and bacteria under stressful conditions. Reflecting the lower ion permeability of the ether-linked isoprenoidal lipids, we found that archaea dominate over bacteria in sediments of >50 °C. Moreover, a detailed examination of the molecular lipid species revealed a quandary: low membrane permeability concomitantly with increased fluidity is required for energy conservation of both archaea and bacteria under heat stress. For instance, bacterial fatty acids were found to increase chain length in concert with a higher degree of unsaturation at elevated sediment temperatures while archaeal tetraethers were observed to show a higher degree of bulking (e.g. methylation and H-shaped) and fluidity (i.e. cyclization) under elevated temperatures. In addition, our data indicate that strong intermolecular hydrogen bonding at the headgroup level of archaeal glycolipids and bacterial sphingolipids may provide ideal membrane stability to attain the required balance between low permeability and a more fluidized configuration. For example, sphingolipids may stabilize bacterial phospholipids into lipid domains, enabling bacteria to thrive in heated sediments under unfavorable thermodynamic conditions. The scientific marriage of lipidomics and bioenergetics described here provides a new dimension for understanding microbial life in natural environments.

  5. New insights into the role of phosphate-free lipids in anaerobic environments

    NASA Astrophysics Data System (ADS)

    Schubotz, F.; De Santiago Torio, A.; Kuehl, J.; Grant, C.; Rahn-Lee, L.; Arkin, A. P.; Deutschbauer, A. M.; Summons, R. E.; Bosak, T.

    2016-02-01

    Recent investigations have revealed an abundance of phosphate-free glycolipids and aminolipids, classically assigned to oxygenic phototrophs, in anoxic environments where anaerobic microorganisms prevail. Phosphorus-free lipids in oxic environments are thought to indicate an adaptation to phosphorus limitation, but their significance in anoxic environments is unclear, because these environments are not typically thought of as phosphorus-limited. We hypothesize that glycolipids and aminolipids play an overlooked and potentially integral role in anaerobic bacteria from marine and terrestrial environments and test this hypothesis in environmentally relevant model anaerobic deltaproteobacteria. None of the investigated strains of the sulfate-reducing genus Desulfovibrio synthesize glycolipids under normal growth conditions or during nitrogen limitation. However, when growing in phosphate-limited conditions, all investigated organisms undergo a nearly complete replacement of phospholipids by glycolipids. Some phosphate-starved organisms, such as D. fructosivorans, are also able to synthesize betaine lipids. Analyses of mutants of Desulfovibrio alaskensis G20 identify genes responsible for the biosynthesis of aminolipids (Dde_3661) and glycolipids (Dde_3613). Fitness experiments using tagged transposon mutant libraries of G20 identify these two genes and 90 other genes important for fitness of this organism during phosphate limitation. These experiments identify for the first time betaine lipids and glycolipids in sulfate-reducing bacteria and demonstrate the importance of these non-phosphorus lipids as substitute lipids in obligate anaerobes. These findings suggest that phosphorus availability limits microbial growth and activity in a more widespread range of environments than previously thought.

  6. Endogenous Enzymes, Heat, and pH Affect Flavone Profiles in Parsley (Petroselinum crispum var. neapolitanum) and Celery (Apium graveolens) during Juice Processing

    PubMed Central

    Hostetler, Gregory L.; Riedl, Ken M.; Schwartz, Steven J.

    2013-01-01

    Flavones are abundant in parsley and celery and possess unique anti-inflammatory properties in vitro and in animal models. However, their bioavailability and bioactivity depend in part on the conjugation of sugars and other functional groups to the flavone core. The effects of juice extraction, acidification, thermal processing, and endogenous enzymes on flavone glycoside profile and concentration in both parsley and celery were investigated. Parsley yielded 72% juice with 64% of the total flavones extracted, whereas celery yielded 79% juice with 56% of flavones extracted. Fresh parsley juice averaged 281 mg flavones/100 g and fresh celery juice, 28.5 mg/100 g. Flavones in steamed parsley and celery were predominantly malonyl apiosylglucoside conjugates, whereas those in fresh samples were primarily apiosylglucoside conjugates; this was apparently the result of endogenous malonyl esterases. Acidification and thermal processing of celery converted flavone apiosylglucosides to flavone glucosides, which may affect the intestinal absorption and metabolism of these compounds. PMID:22224550

  7. Endogenous enzymes, heat, and pH affect flavone profiles in parsley (Petroselinum crispum var. neapolitanum) and celery (Apium graveolens) during juice processing.

    PubMed

    Hostetler, Gregory L; Riedl, Ken M; Schwartz, Steven J

    2012-01-11

    Flavones are abundant in parsley and celery and possess unique anti-inflammatory properties in vitro and in animal models. However, their bioavailability and bioactivity depend in part on the conjugation of sugars and other functional groups to the flavone core. The effects of juice extraction, acidification, thermal processing, and endogenous enzymes on flavone glycoside profile and concentration in both parsley and celery were investigated. Parsley yielded 72% juice with 64% of the total flavones extracted, whereas celery yielded 79% juice with 56% of flavones extracted. Fresh parsley juice averaged 281 mg flavones/100 g and fresh celery juice, 28.5 mg/100 g. Flavones in steamed parsley and celery were predominantly malonyl apiosylglucoside conjugates, whereas those in fresh samples were primarily apiosylglucoside conjugates; this was apparently the result of endogenous malonyl esterases. Acidification and thermal processing of celery converted flavone apiosylglucosides to flavone glucosides, which may affect the intestinal absorption and metabolism of these compounds.

  8. Role of lipids for the reproductive success of the Arctic copepod Calanus glacialis

    NASA Astrophysics Data System (ADS)

    Hatlebakk, M. K.; Graeve, M.; Niehoff, B.; Johnsen, G.; Søreide, J.

    2016-02-01

    Extensive energy storage is common among polar animals, and a range of reproductive strategies have evolved from pure capital breeders, relying on stored energy only, to 100% income breeders where freshly ingested food fuel reproduction. The Arctic calanoid copepod Calanus glacialis is primarily a grazer that accumulates large lipid stores during spring and summer. The breeding strategy to this relatively large and lipid-rich copepod is somewhere on the continuum from pure capital to 100% income breeder. To investigate the importance of stored lipids versus freshly ingested food for the reproductive success of this key copepod we conducted a combined laboratory and field study on a high-Arctic population of C. glacialis in Svalbard from January to May. Total lipids, lipid composition, gonad maturation, egg production and egg hatching success were carefully followed for starved and algal fed females in the laboratory and for females in situ. Lipid stores decreased significantly over time even when food was available, both in laboratory and in field, suggesting that the females largely depended on stored resources for reproduction no matter of the food availability. Lipid reduction was most rapid during gonad maturation prior to first egg production. Almost all fed females spawned compared to only half of the starved ones, and number of eggs and the egg hatching success were significantly improved for fed females. When food was scarce, females produced fewer but more lipid-rich eggs as opposed to more eggs with less lipids when food was abundant - a strategy not previously described for C. glacialis. The fatty acid composition appeared to be more important than the total lipid content for ensuring high egg hatching success, and the polyunsaturated fatty acids 20:5(n-3) and 22:6(n-3), as well as the saturated fatty acids 16:0 and 18:0 seemed to be particularly important. We conclude that C. glacialis is capable of capital breeding, but primarily rely on fresh food for

  9. [Research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration].

    PubMed

    Liang, Hang; Deng, Xiangyu; Shao, Zengwu

    2017-10-01

    To summarize the research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration and deduce the therapeutic potential of endogenous repair for intervertebral disc degeneration. The original articles about intervertebral disc endogenous stem cells for intervertebral disc regeneration were extensively reviewed; the reparative potential in vivo and the extraction and identification in vitro of intervertebral disc endogenous stem cells were analyzed; the prospect of endogenous stem cells for intervertebral disc regeneration was predicted. Stem cell niche present in the intervertebral discs, from which stem cells migrate to injured tissues and contribute to tissues regeneration under certain specific microenvironment. Moreover, the migration of stem cells is regulated by chemokines system. Tissue specific progenitor cells have been identified and successfully extracted and isolated. The findings provide the basis for biological therapy of intervertebral disc endogenous stem cells. Intervertebral disc endogenous stem cells play a crucial role in intervertebral disc regeneration. Therapeutic strategy of intervertebral disc endogenous stem cells is proven to be a promising biological approach for intervertebral disc regeneration.

  10. Abundance of introduced species at home predicts abundance away in herbaceous communities

    USGS Publications Warehouse

    Firn, Jennifer; Moore, Joslin L.; MacDougall, Andrew S.; Borer, Elizabeth T.; Seabloom, Eric W.; HilleRisLambers, Janneke; Harpole, W. Stanley; Cleland, Elsa E.; Brown, Cynthia S.; Knops, Johannes M.H.; Prober, Suzanne M.; Pyke, David A.; Farrell, Kelly A.; Bakker, John D.; O'Halloran, Lydia R.; Adler, Peter B.; Collins, Scott L.; D'Antonio, Carla M.; Crawley, Michael J.; Wolkovich, Elizabeth M.; La Pierre, Kimberly J.; Melbourne, Brett A.; Hautier, Yann; Morgan, John W.; Leakey, Andrew D.B.; Kay, Adam; McCulley, Rebecca; Davies, Kendi F.; Stevens, Carly J.; Chu, Cheng-Jin; Holl, Karen D.; Klein, Julia A.; Fay, Phillip A.; Hagenah, Nicole; Kirkman, Kevin P.; Buckley, Yvonne M.

    2011-01-01

    Many ecosystems worldwide are dominated by introduced plant species, leading to loss of biodiversity and ecosystem function. A common but rarely tested assumption is that these plants are more abundant in introduced vs. native communities, because ecological or evolutionary-based shifts in populations underlie invasion success. Here, data for 26 herbaceous species at 39 sites, within eight countries, revealed that species abundances were similar at native (home) and introduced (away) sites - grass species were generally abundant home and away, while forbs were low in abundance, but more abundant at home. Sites with six or more of these species had similar community abundance hierarchies, suggesting that suites of introduced species are assembling similarly on different continents. Overall, we found that substantial changes to populations are not necessarily a pre-condition for invasion success and that increases in species abundance are unusual. Instead, abundance at home predicts abundance away, a potentially useful additional criterion for biosecurity programmes.

  11. Basal deposits and drusen in eyes with age-related maculopathy: evidence for solid lipid particles.

    PubMed

    Curcio, Christine A; Presley, J Brett; Millican, C Leigh; Medeiros, Nancy E

    2005-06-01

    Neutral lipid, including esterified cholesterol, and apolipoproteins B and E are abundant in basal deposits and drusen of aged and age-related maculopathy (ARM) eyes. The principal component of basal linear deposit (BlinD), a specific ARM lesion, is membranous debris, which if actually derived from membranes cannot account for extracellular neutral lipid. We therefore used a lipid-preserving ultrastructural method to obtain improved images of membranous debris. Maculas from 44 human donors (71-96 yr) were preserved <7.5 hr after death. Blocks were post-fixed in 2% osmium or osmium-tannic acid-paraphenylenediamine (OTAP) to preserve neutral lipid for thin-section transmission electron microscopic (TEM) examination. Solid particles identified by OTAP were considered closest to the in vivo state of extracellular lipids. Micrographs were examined for intermediate forms, with greatest weight given to comparable images from different preparations of same or fellow eyes. Twenty eyes of older adults (12 with ARM including fellows treated with photodynamic and radiation therapies) had adequately preserved extracellular lipid. The exterior surface of membranous debris was thicker and more electron-dense than basal infoldings of retinal pigment epithelium (RPE) cells. By OTAP, individual membranous debris profiles were solid (diameters, 80-200 nm) and formed tracks across or aggregations within basal laminar deposits. Solid particles and/or pools of neutral lipid were visible in BlinD and drusen. When processed to preserve lipid, membranous debris resembles neither membranes of surrounding cells nor vesicles possessing aqueous interiors but rather solid particles. These results are consistent with recent evidence implicating lipoprotein particles of intra-ocular origin as a potential source of neutral lipids, including esterified cholesterol, in the specific lesions of ARM.

  12. Proteolysis Controls Endogenous Substance P Levels

    PubMed Central

    Mitchell, Andrew J.; Lone, Anna Mari; Tinoco, Arthur D.; Saghatelian, Alan

    2013-01-01

    Substance P (SP) is a prototypical neuropeptide with roles in pain and inflammation. Numerous mechanisms regulate endogenous SP levels, including the differential expression of SP mRNA and the controlled secretion of SP from neurons. Proteolysis has long been suspected to regulate extracellular SP concentrations but data in support of this hypothesis is scarce. Here, we provide evidence that proteolysis controls SP levels in the spinal cord. Using peptidomics to detect and quantify endogenous SP fragments, we identify the primary SP cleavage site as the C-terminal side of the ninth residue of SP. If blocking this pathway increases SP levels, then proteolysis controls SP concentration. We performed a targeted chemical screen using spinal cord lysates as a proxy for the endogenous metabolic environment and identified GM6001 (galardin, ilomastat) as a potent inhibitor of the SP 1–9-producing activity present in the tissue. Administration of GM6001 to mice results in a greater-than-three-fold increase in the spinal cord levels of SP, which validates the hypothesis that proteolysis controls physiological SP levels. PMID:23894327

  13. Proteolysis controls endogenous substance P levels.

    PubMed

    Mitchell, Andrew J; Lone, Anna Mari; Tinoco, Arthur D; Saghatelian, Alan

    2013-01-01

    Substance P (SP) is a prototypical neuropeptide with roles in pain and inflammation. Numerous mechanisms regulate endogenous SP levels, including the differential expression of SP mRNA and the controlled secretion of SP from neurons. Proteolysis has long been suspected to regulate extracellular SP concentrations but data in support of this hypothesis is scarce. Here, we provide evidence that proteolysis controls SP levels in the spinal cord. Using peptidomics to detect and quantify endogenous SP fragments, we identify the primary SP cleavage site as the C-terminal side of the ninth residue of SP. If blocking this pathway increases SP levels, then proteolysis controls SP concentration. We performed a targeted chemical screen using spinal cord lysates as a proxy for the endogenous metabolic environment and identified GM6001 (galardin, ilomastat) as a potent inhibitor of the SP(1-9)-producing activity present in the tissue. Administration of GM6001 to mice results in a greater-than-three-fold increase in the spinal cord levels of SP, which validates the hypothesis that proteolysis controls physiological SP levels.

  14. Maternal diets deficient in folic acid and related methyl donors modify mechanisms associated with lipid metabolism in the fetal liver of the rat.

    PubMed

    McNeil, Christopher J; Hay, Susan M; Rucklidge, Garry J; Reid, Martin D; Duncan, Gary J; Rees, William D

    2009-11-01

    Previously we have examined the effects of diets deficient in folic acid ( - F) or folate deficient with low methionine and choline ( - F LM LC) on the relative abundance of soluble proteins in the liver of the pregnant rat. In the present study we report the corresponding changes in the fetal liver at day 21 of gestation. The abundance of eighteen proteins increased when dams were fed the - F diet. When dams were fed the - F LM LC diet, thirty-three proteins increased and eight decreased. Many of the differentially abundant proteins in the fetal liver could be classified into the same functional groups as those previously identified in the maternal liver, namely protein synthesis, metabolism, lipid metabolism and proteins associated with the cytoskeleton and endoplasmic reticulum. The pattern was consistent with reduced cell proliferation in the - F LM LC group but not in the - F group. Metabolic enzymes associated with lipid metabolism changed in both the - F and - F LM LC groups. The mRNA for carnitine palmitoyl transferase were up-regulated and CD36 (fatty acid translocase) down-regulated in the - F group, suggesting increased mitochondrial oxidation of fatty acids as an indirect response to altered maternal lipid metabolism. In the - F LM LC group the mRNA for acetyl CoA carboxylase was down-regulated, suggesting reduced fatty acid synthesis. The mRNA for transcriptional regulators including PPARalpha and sterol response element-binding protein-1c were unchanged. These results suggest that an adequate supply of folic acid and the related methyl donors may benefit fetal development directly by improving lipid metabolism in fetal as well as maternal tissues.

  15. Distinct lipid rafts in subdomains from human placental apical syncytiotrophoblast membranes.

    PubMed

    Godoy, Valeria; Riquelme, Gloria

    2008-01-01

    We report on the characteristics of raft domains in the apical membrane from human placental syncytiotrophoblast (hSTB), an epithelium responsible for maternal-fetal exchange. Previously, we described two isolated fractions of the hSTB apical membrane: a classical microvillous membrane (MVM) and a light microvillous membrane (LMVM). Detergent-resistant microdomains (DRMs) from MVM and LMVM were prepared with Triton X-100 followed by flotation in a sucrose gradient and tested by Western and dot blot with raft markers (placental alkaline phosphatase, lipid ganglioside, annexin 2) and transferrin receptor as a nonraft marker. DRMs from both fractions showed a consistent peak for these markers, except that the DRMs from MVM had no annexin 2 mark. Cholesterol depletion modified the segregation in both groups of DRMs. Our results show two distinguishable lipid raft subsets from MVM and LMVM. Additionally, we found significant differences between MVM and LMVM in cholesterol content and in expression of cytoskeletal proteins. MVM is enriched in ezrin and beta-actin; in contrast, cholesterol and cytokeratin-7 are more abundant in LMVM. These differences may explain the distinct properties of the lipid raft subtypes.

  16. A New Method for Quantitative Immunoblotting of Endogenous α-Synuclein

    PubMed Central

    Newman, Andrew J.; Selkoe, Dennis; Dettmer, Ulf

    2013-01-01

    β-Sheet-rich aggregates of α-synuclein (αSyn) are the hallmark neuropathology of Parkinson’s disease and related synucleinopathies, whereas the principal native structure of αSyn in healthy cells - unfolded monomer or α-helically folded oligomer - is under debate. Our recent crosslinking analysis of αSyn in intact cells showed that a large portion of endogenous αSyn can be trapped as oligomers, most notably as apparent tetramers. One challenge in such studies is accurately quantifying αSyn Western blot signals among samples, as crosslinked αSyn trends toward increased immunoreactivity. Here, we analyzed this phenomenon in detail and found that treatment with the reducible amine-reactive crosslinker DSP strongly increased αSyn immunoreactivity even after cleavage with the reducing agent β-mercaptoethanol. The effect was observed with all αSyn antibodies tested and in all sample types from human brain homogenates to untransfected neuroblastoma cells, permitting easy detection of endogenous αSyn in the latter, which had long been considered impossible. Coomassie staining of blots before and after several hours of washing revealed complete retention of αSyn after DSP/β-mercaptoethanol treatment, in contrast to a marked loss of αSyn without this treatment. The treatment also enhanced immunodetection of the homologs β- and γ-synuclein and of histones, another group of small, lysine-rich proteins. We conclude that by neutralizing positive charges and increasing protein hydrophobicity, amine crosslinker treatment promotes adhesion of αSyn to blotting membranes. These data help explain the recent report of fixing αSyn blots with paraformaldehyde after transfer, which we find produces similar but weaker effects. DSP/β-mercaptoethanol treatment of Western blots should be particularly useful to quantify low-abundance αSyn forms such as extracellular and post-translationally modified αSyn and splice variants. PMID:24278419

  17. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    NASA Astrophysics Data System (ADS)

    Anantachaisilp, Suranan; Meejoo Smith, Siwaporn; Treetong, Alongkot; Pratontep, Sirapat; Puttipipatkhachorn, Satit; Rungsardthong Ruktanonchai, Uracha

    2010-03-01

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812® as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance (1H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

  18. Compartmentalization of endocannabinoids into lipid rafts in a microglial cell line devoid of caveorrlin-1

    PubMed Central

    Rimmerman, Neta; Bradshaw, Heather B; Kozela, Ewa; Levy, Rivka; Juknat, Ana; Vogel, Zvi

    2012-01-01

    BACKGROUND AND PURPOSE N-acyl ethanolamines (NAEs) and 2-arachidonoyl glycerol (2-AG) are endogenous cannabinoids and along with related lipids are synthesized on demand from membrane phospholipids. Here, we have studied the compartmentalization of NAEs and 2-AG into lipid raft fractions isolated from the caveolin-1-lacking microglial cell line BV-2, following vehicle or cannabidiol (CBD) treatment. Results were compared with those from the caveolin-1-positive F-11 cell line. EXPERIMENTAL APPROACH BV-2 cells were incubated with CBD or vehicle. Cells were fractionated using a detergent-free continuous OptiPrep density gradient. Lipids in fractions were quantified using HPLC/MS/MS. Proteins were measured using Western blot. KEY RESULTS BV-2 cells were devoid of caveolin-1. Lipid rafts were isolated from BV-2 cells as confirmed by co-localization with flotillin-1 and sphingomyelin. Small amounts of cannabinoid CB1 receptors were found in lipid raft fractions. After incubation with CBD, levels and distribution in lipid rafts of 2-AG, N-arachidonoyl ethanolamine (AEA), and N-oleoyl ethanolamine (OEA) were not changed. Conversely, the levels of the saturated N-stearoyl ethanolamine (SEA) and N-palmitoyl ethanolamine (PEA) were elevated in lipid raft fractions. In whole cells with growth medium, CBD treatment increased AEA and OEA time-dependently, while levels of 2-AG, PEA and SEA did not change. CONCLUSIONS AND IMPLICATIONS Whereas levels of 2-AG were not affected by CBD treatment, the distribution and levels of NAEs showed significant changes. Among the NAEs, the degree of acyl chain saturation predicted the compartmentalization after CBD treatment suggesting a shift in cell signalling activity. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10

  19. Pycnogenol® inhibits lipid accumulation in 3T3-L1 adipocytes with the modulation of reactive oxygen species (ROS) production associated with antioxidant enzyme responses.

    PubMed

    Lee, Ok-Hwan; Seo, Min-Jung; Choi, Hyeon-Son; Lee, Boo-Yong

    2012-03-01

    Pycnogenol® is a group of flavonoids with antioxidant effects. Adipogenesis is the process of adipocyte differentiation. It causes the increase of lipids as well as ROS (reactive oxygen species). Lipid accumulation and ROS production were determined in 3 T3-L1 adipocyte, and the effect of Pycnogenol® was evaluated. Lipid accumulation was elevated in adipocyte treated with hydrogen peroxide, one of the ROS. Pycnogenol® showed an inhibitory effect on the lipid accumulation and ROS production during the adipogenesis. We also investigated the molecular events associated with ROS production and lipid accumulation. Our results showed that Pycnogenol® inhibited the mRNA expression of pro-oxidant enzymes, such as NOX4 (NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) oxidase 4), and the NADPH-producing G6PDH (glucose-6-phosphate dehydrogenase) enzyme. In addition, Pycnogenol® suppressed the mRNA abundance of adipogenic transcription factors, PPAR-γ (peroxisome proliferator-activated receptor γ) and C/EBP-α (CCAAT/enhancer binding protein α), and their target gene, aP2 (adipocyte protein 2) responsible for fatty acid transportation. On the other hand, Pycnogenol® increased the abundance of antioxidant proteins such as Cu/Zn-SOD (copper-zinc superoxide dismutase), Mn-SOD (manganese superoxide dismutase), GPx (glutathione peroxidase) and GR (glutathione reductase). Our results suggest that Pycnogenol® inhibits lipid accumulation and ROS production by regulating adipogenic gene expression and pro-/antioxidant enzyme responses in adipocytes. Copyright © 2011 John Wiley & Sons, Ltd.

  20. Lipid content and fatty acid profile during lake whitefish embryonic development at different incubation temperatures.

    PubMed

    Mueller, Casey A; Doyle, Liam; Eme, John; Manzon, Richard G; Somers, Christopher M; Boreham, Douglas R; Wilson, Joanna Y

    2017-01-01

    Lipids serve as energy sources, structural components, and signaling molecules during fish embryonic development, and utilization of lipids may vary with temperature. Embryonic energy utilization under different temperatures is an important area of research in light of the changing global climate. Therefore, we examined percent lipid content and fatty acid profiles of lake whitefish (Coregonus clupeaformis) throughout embryonic development at three incubation temperatures. We sampled fertilized eggs and embryos at gastrulation, eyed and fin flutter stages following chronic incubation at temperatures of 1.8, 4.9 and 8.0°C. Hatchlings were also sampled following incubation at temperatures of 3.3, 4.9 and 8.0°C. Fertilized eggs had an initial high percentage of dry mass composed of lipid (percent lipid content; ~29%) consisting of ~20% saturated fatty acids (SFA), ~32% monounsaturated fatty acids (MUFA), ~44% polyunsaturated fatty acids (PUFA), and 4% unidentified. The most abundant fatty acids were 16:0, 16:1, 18:1(n-9c), 20:4(n-6), 20:5(n-3) and 22:6(n-3). This lipid profile matches that of other cold-water fish species. Percent lipid content increased during embryonic development, suggesting protein or other yolk components were preferentially used for energy. Total percentage of MUFA decreased during development, which indicated MUFA were the primary lipid catabolized for energy during embryonic development. Total percentage of PUFA increased during development, driven largely by an increase in 22:6(n-3). Temperature did not influence percent lipid content or percent MUFA at any development stage, and had inconsistent effects on percent SFA and percent PUFA during development. Thus, lake whitefish embryos appear to be highly adapted to low temperatures, and do not alter lipids in response to temperature within their natural incubation conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Lipid Biomarkers for a Hypersaline Microbial Mat Community

    NASA Technical Reports Server (NTRS)

    Jahnke, Linda; Orphan, Victoria; Embaye, Tsegereda; Turk, Kendra; Kubo, Mike; Summons, Roger

    2004-01-01

    The use of lipid biomarkers and their carbon isotopic compositions are valuable tools for establishing links to ancient microbial ecosystems. Various lipids associated with specific microbial groups can serve as biomarkers for establishing organism source and function in contemporary microbial ecosystems (membrane lipids), and by analogy, potential relevance to ancient organic-rich sedimentary rocks (geolipids). As witnessed by the stromatolite record, benthic microbial mats grew in shallow water lagoonal environments. Our recent work has focused on lipid biomarker analysis of a potential analogue for such ancient mats growing in a set of hypersaline evaporation ponds at Guerrero Negro, Baja California Sur, Mexico. The aerobic, surface layer of this mat (0 to 1 mm) contained a variety of ester-bound fatty acids (FA) representing a diverse bacterial population including cyanobacteria, sulphate reducers (SRB) and heterotrophs. Biomarkers for microeukaryotes detected in this layer included sterols, C-20 polyunsaturated FA and a highly branched isoprenoid, diagnostic for diatoms. Cyanobacteria were also indicated by the presence of a diagnostic set of mid-chain methylalkanes. C-28, to C-34 wax esters (WXE) present in relatively small amounts in the upper 3 mm of the mat are considered biomarkers for green non-sulphur bacteria. Ether-bound isoprenoids were also identified although in considerably lower abundance than ester-bound FA (approx. 1:l0). These complex ether lipids included archatol, hydroxyarchaeol and a C-40 tetraether, all in small amounts. After ether cleavage with boron tribromide, the major recovered isoprenyl was a C-30:1. This C(sub 30;1) yelded squalane after hydrogenation, a known geobiomarker for hypersaline environments in ancient oils and sediments. In this mat, it represents the dominant Archaeal population. The carbon isotopic composition of biomarker lipids were generally depleted relative to the bulk organic material (delta C-13 TOC -10%). Most

  2. Schistosoma mansoni venom allergen-like protein 4 (SmVAL4) is a novel lipid-binding SCP/TAPS protein that lacks the prototypical CAP motifs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kelleher, Alan; Darwiche, Rabih; Rezende, Wanderson C.

    2014-08-01

    The first structure of an S. mansoni venom allergen-like protein is presented. Schistosomiasis is a parasitic disease that affects over 200 million people. Vaccine candidates have been identified, including Schistosoma mansoni venom allergen-like proteins (SmVALs) from the SCP/TAPS (sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily. The first SmVAL structure, SmVAL4, was refined to a resolution limit of 2.16 Å. SmVAL4 has a unique structure that could not be predicted from homologous structures, with longer loops and an unusual C-terminal extension. SmVAL4 has the characteristic α/β-sandwich and central SCP/TAPS cavity. Furthermore, SmVAL4 has only one of the signature CAP cavity tetrad amino-acid residuesmore » and is missing the histidines that coordinate divalent cations such as Zn{sup 2+} in other SCP/TAPS proteins. SmVAL4 has a cavity between α-helices 1 and 4 that was observed to bind lipids in tablysin-15, suggesting the ability to bind lipids. Subsequently, SmVAL4 was shown to bind cholesterol in vitro. Additionally, SmVAL4 was shown to complement the in vivo sterol-export phenotype of yeast mutants lacking their endogenous CAP proteins. Expression of SmVAL4 in yeast cells lacking endogenous CAP function restores the block in sterol export. These studies suggest an evolutionarily conserved lipid-binding function shared by CAP proteins such as SmVAL4 and yeast CAP proteins such as Pry1.« less

  3. Alpha Power Modulates Perception Independently of Endogenous Factors.

    PubMed

    Brüers, Sasskia; VanRullen, Rufin

    2018-01-01

    Oscillations are ubiquitous in the brain. Alpha oscillations in particular have been proposed to play an important role in sensory perception. Past studies have shown that the power of ongoing EEG oscillations in the alpha band is negatively correlated with visual outcome. Moreover, it also co-varies with other endogenous factors such as attention, vigilance, or alertness. In turn, these endogenous factors influence visual perception. Therefore, it remains unclear how much of the relation between alpha and perception is indirectly mediated by such endogenous factors, and how much reflects a direct causal influence of alpha rhythms on sensory neural processing. We propose to disentangle the direct from the indirect causal routes by introducing modulations of alpha power, independently of any fluctuations in endogenous factors. To this end, we use white-noise sequences to constrain the brain activity of 20 participants. The cross-correlation between the white-noise sequences and the concurrently recorded EEG reveals the impulse response function (IRF), a model of the systematic relationship between stimulation and brain response. These IRFs are then used to reconstruct rather than record the brain activity linked with new random sequences (by convolution). Interestingly, this reconstructed EEG only contains information about oscillations directly linked to the white-noise stimulation; fluctuations in attention and other endogenous factors may still modulate brain alpha rhythms during the task, but our reconstructed EEG is immune to these factors. We found that the detection of near-perceptual threshold targets embedded within these new white-noise sequences depended on the power of the ~10 Hz reconstructed EEG over parieto-occipital channels. Around the time of presentation, higher power led to poorer performance. Thus, fluctuations in alpha power, induced here by random luminance sequences, can directly influence perception: the relation between alpha power and

  4. PPAR-α, a lipid-sensing transcription factor, regulates blood–brain barrier efflux transporter expression

    PubMed Central

    More, Vijay R; Campos, Christopher R; Evans, Rebecca A; Oliver, Keith D; Chan, Gary NY; Miller, David S

    2016-01-01

    Lipid sensor peroxisome proliferator-activated receptor alpha (PPAR-α) is the master regulator of lipid metabolism. Dietary release of endogenous free fatty acids, fibrates, and certain persistent environmental pollutants, e.g. perfluoroalkyl fire-fighting foam components, are peroxisome proliferator-activated receptor alpha ligands. Here, we define a role for peroxisome proliferator-activated receptor alpha in regulating the expression of three ATP-driven drug efflux transporters at the rat and mouse blood–brain barriers: P-glycoprotein (Abcb1), breast cancer resistance protein (Bcrp/Abcg2), and multidrug resistance-associated protein 2 (Mrp2/Abcc2). Exposing isolated rat brain capillaries to linoleic acid, clofibrate, or PKAs increased the transport activity and protein expression of the three ABC transporters. These effects were blocked by the PPAR-α antagonist, GW6471. Dosing rats with 20 mg/kg or 200 mg/kg of clofibrate decreased the brain accumulation of the P-glycoprotein substrate, verapamil, by 50% (in situ brain perfusion; effects blocked by GW6471) and increased P-glycoprotein expression and activity in capillaries ex vivo. Fasting C57Bl/6 wild-type mice for 24 h increased both serum lipids and brain capillary P-glycoprotein transport activity. Fasting did not alter P-glycoprotein activity in PPAR-α knockout mice. These results indicate that hyperlipidemia, lipid-lowering fibrates and exposure to certain fire-fighting foam components activate blood–brain barrier peroxisome proliferator-activated receptor alpha, increase drug efflux transporter expression and reduce drug delivery to the brain. PMID:27193034

  5. Novel endogenous angiogenesis inhibitors and their therapeutic potential

    PubMed Central

    Rao, Nithya; Lee, Yu Fei; Ge, Ruowen

    2015-01-01

    Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis. Endogenous angiogenesis inhibitors are proteins or protein fragments that are formed in the body and have the ability to limit angiogenesis. Many endogenous angiogenesis inhibitors have been discovered, and the list continues to grow. Endogenous protein/peptide inhibitors are relatively less toxic, better tolerated and have a lower risk of drug resistance, which makes them attractive as drug candidates. In this review, we highlight ten novel endogenous protein angiogenesis inhibitors discovered within the last five years, including ISM1, FKBPL, CHIP, ARHGAP18, MMRN2, SOCS3, TAp73, ZNF24, GPR56 and JWA. Although some of these proteins have been well characterized for other biological functions, we focus on their new and specific roles in angiogenesis inhibition and discuss their potential for therapeutic application. PMID:26364800

  6. Novel endogenous angiogenesis inhibitors and their therapeutic potential.

    PubMed

    Rao, Nithya; Lee, Yu Fei; Ge, Ruowen

    2015-10-01

    Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis. Endogenous angiogenesis inhibitors are proteins or protein fragments that are formed in the body and have the ability to limit angiogenesis. Many endogenous angiogenesis inhibitors have been discovered, and the list continues to grow. Endogenous protein/peptide inhibitors are relatively less toxic, better tolerated and have a lower risk of drug resistance, which makes them attractive as drug candidates. In this review, we highlight ten novel endogenous protein angiogenesis inhibitors discovered within the last five years, including ISM1, FKBPL, CHIP, ARHGAP18, MMRN2, SOCS3, TAp73, ZNF24, GPR56 and JWA. Although some of these proteins have been well characterized for other biological functions, we focus on their new and specific roles in angiogenesis inhibition and discuss their potential for therapeutic application.

  7. Particulate sulfur-containing lipids: Production and cycling from the epipelagic to the abyssopelagic zone

    NASA Astrophysics Data System (ADS)

    Gašparović, Blaženka; Penezić, Abra; Frka, Sanja; Kazazić, Saša; Lampitt, Richard S.; Holguin, F. Omar; Sudasinghe, Nilusha; Schaub, Tanner

    2018-04-01

    There are major gaps in our understanding of the distribution and role of lipids in the open ocean especially with regard to sulfur-containing lipids (S-lipids). Here, we employ a powerful analytical approach based on high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to elucidate depth-related S-lipid production and molecular transformations in suspended particulate matter from the Northeast Atlantic Ocean in this depth range. We show that within the open-ocean environment S-lipids contribute up to 4.2% of the particulate organic carbon, and that up to 95% of these compounds have elemental compositions that do not match those found in the Nature Lipidomics Gateway database (termed "novel"). Among the remaining 5% of lipids that match the database, we find that sulphoquinovosyldiacylglycerol (SQDG) are efficiently removed while sinking through the mesopelagic zone. The relative abundance of other assigned lipids (sulphoquinovosylmonoacylglycerol (SQMG), sulfite and sulfate lipids, Vitamin D2 and D3 derivatives, and sphingolipids) did not change substantially with depth. The novel S-lipids, represented by hundreds of distinct elemental compositions (160-300 molecules at any one depth), contribute increasingly to the lipid and particulate organic matter pools with increased depth. Depth-related transformations cause (i) incomplete degradation/transformation of unsaturated S-lipids which leads to the depth-related accumulation of the refractory saturated compounds with reduced molecular weight (average 455 Da) and (ii) formation of highly unsaturated S-lipids (average abyssopelagic molecular double bond equivalents, DBE=7.8) with lower molecular weight (average 567 Da) than surface S-lipids (average 592 Da). A depth-related increase in molecular oxygen content is observed for all novel S-lipids and indicates that oxidation has a significant role in their transformation while (bio)hydrogenation possibly impacts the formation of

  8. Wheat leaf lipids during heat stress: II. Lipids experiencing coordinated metabolism are detected by analysis of lipid co-occurrence

    PubMed Central

    Narayanan, Sruthi; Prasad, P.V. Vara; Welti, Ruth

    2016-01-01

    Identifying lipids that experience coordinated metabolism during heat stress would provide information regarding lipid dynamics under stress conditions and assist in developing heat-tolerant wheat varieties. We hypothesized that co-occurring lipids, which are up-or-down-regulated together through time during heat stress, represent groups that can be explained by coordinated metabolism. Wheat plants (Triticum aestivum L.) were subjected to 12 days of high day and/or night temperature stress, followed by a 4-day recovery period. Leaves were sampled at four time points, and 165 lipids were measured by electrospray ionization-tandem mass spectrometry. Correlation analysis of lipid levels in 160 leaf samples from each of two wheat genotypes revealed 13 groups of lipids. Lipids within each group co-occurred through the high day and night temperature stress treatments. The lipid groups can be broadly classified as groups containing: extraplastidic phospholipids, plastidic glycerolipids, oxidized glycerolipids, triacylglycerols, acylated sterol glycosides, and sterol glycosides. Current knowledge of lipid metabolism suggests that the lipids in each group co-occur because they are regulated by the same enzyme(s). The results suggest that increases in activities of desaturating, oxidizing, glycosylating, and acylating enzymes lead to simultaneous changes in levels of multiple lipid species during high day and night temperature stress in wheat. PMID:26436445

  9. Ovarian Lipid Metabolism Modulates Circulating Lipids in Premenopausal Women.

    PubMed

    Jensen, Jeffrey T; Addis, Ilana B; Hennebold, Jon D; Bogan, Randy L

    2017-09-01

    The premenopausal circulating lipid profile may be linked to the hormonal profile and ovarian lipid metabolism. Assess how estradiol, progesterone, and ovarian lipid metabolism contributes to the premenopausal lipid profile; and evaluate the acute effects of a common hormonal oral contraceptive (OC) on circulating lipids. Experimental crossover with repeated measures. Academic hospitals. Eight healthy, regularly menstruating women. Participants underwent periodic serum sampling during a normal menstrual cycle; a standard 21-day, monophasic combined hormonal OC cycle (30 µg of ethinyl estradiol and 150 µg of levonorgestrel per day); menopause simulated by leuprolide acetate (22.5-mg depot); and an artificial menstrual cycle achieved via transdermal estradiol (50 to 300 µg/d) and vaginal micronized progesterone (100 to 300 mg/d). Primary outcomes included evaluation of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, triglycerides, and the total cholesterol to HDL cholesterol ratio. To estimate the effect of estradiol, progesterone, and ovarian lipid metabolism, all specimens except those from the OC cycle were analyzed. Subgroup analysis was conducted on the follicular and luteal phases. In a separate analysis, the effect of the OC was evaluated relative to the normal menstrual cycle. Estradiol was significantly associated with increased levels of HDL cholesterol throughout the menstrual cycle and in the follicular phase. Ovarian effects were associated with reduced lipid levels, especially during the luteal phase. The OC was associated with an increased total cholesterol to HDL cholesterol ratio and triglycerides. Previously unappreciated factors including ovarian lipid metabolism may contribute to the premenopausal lipid profile. Copyright © 2017 by the Endocrine Society

  10. Synthesis of FAEEs from glycerol in engineered Saccharomyces cerevisiae using endogenously produced ethanol by heterologous expression of an unspecific bacterial acyltransferase.

    PubMed

    Yu, Kyung Ok; Jung, Ju; Kim, Seung Wook; Park, Chul Hwan; Han, Sung Ok

    2012-01-01

    The high price of petroleum-based diesel fuel has led to the development of alternative fuels, such as ethanol. Saccharomyces cerevisiae was metabolically engineered to utilize glycerol as a substrate for ethanol production. For the synthesis of fatty acid ethyl esters (FAEEs) by engineered S. cerevisiae that utilize glycerol as substrate, heterologous expression of an unspecific acyltransferase from Acinetobacter baylyi with glycerol utilizing genes was established. As a result, the engineered YPH499 (pGcyaDak, pGupWs-DgaTCas) strain produced 0.24 g/L FAEEs using endogenous ethanol produced from glycerol. And this study also demonstrated the possibility of increasing FAEE production by enhancing ethanol production by minimizing the synthesis of glycerol. The overall FAEE production in strain YPH499 fps1Δ gpd2Δ (pGcyaDak, pGupWs-DgaTCas) was 2.1-fold more than in YPH499 (pGcyaDak, pGupWs-DgaTCas), with approximately 0.52 g/L FAEEs produced, while nearly 17 g/L of glycerol was consumed. These results clearly indicated that FAEEs were synthesized in engineered S. cerevisiae by esterifying exogenous fatty acids with endogenously produced ethanol from glycerol. This microbial system acts as a platform in applying metabolic engineering that allows the production of FAEEs from cheap and abundant substrates specifically glycerol through the use of endogenous bioethanol. Copyright © 2011 Wiley Periodicals, Inc.

  11. Differences between endogenous and exogenous emotion inhibition in the human brain.

    PubMed

    Kühn, Simone; Haggard, Patrick; Brass, Marcel

    2014-05-01

    The regulation of emotions is an integral part of our mental health. It has only recently been investigated using brain imaging techniques. In most studies, participants are instructed by a cue to inhibit a specific emotional reaction. The aim of the present study was to investigate the alternative situation where a person decides to inhibit an emotion as an act of endogenous self-control. Healthy participants viewed highly arousing pictures with negative valence. In the endogenous condition, participants could freely choose on each trial to inhibit or feel the emotions elicited by the picture. In an exogenous condition, a visual cue instructed them to either feel or inhibit the emotion elicited by the picture. Participants' subjective ratings of intensity of experienced emotion showed an interaction effect between source of control (endogenous/exogenous) and feel/inhibit based on a stronger modulation between feel and inhibition for the endogenous compared to the exogenous condition. Endogenous inhibition of emotions was associated with dorso-medial prefrontal cortex activation, whereas exogenous inhibition was found associated with lateral prefrontal cortex activation. Thus, the brain regions for both endogenous and exogenous inhibition of emotion are highly similar to those for inhibition of motor actions in Brass and Haggard (J Neurosci 27:9141-9145, 2007), Kühn et al. (Hum Brain Mapp 30:2834-2843, 2009). Functional connectivity analyses showed that dorsofrontomedial cortex exerts greater control onto pre-supplementary motor area during endogenous inhibition compared to endogenous feel. This functional dissociation between an endogenous, fronto-medial and an exogenous, fronto-lateral inhibition centre has important implications for our understanding of emotion regulation in health and psychopathology.

  12. Estimating abundance

    USGS Publications Warehouse

    Sutherland, Chris; Royle, Andy

    2016-01-01

    This chapter provides a non-technical overview of ‘closed population capture–recapture’ models, a class of well-established models that are widely applied in ecology, such as removal sampling, covariate models, and distance sampling. These methods are regularly adopted for studies of reptiles, in order to estimate abundance from counts of marked individuals while accounting for imperfect detection. Thus, the chapter describes some classic closed population models for estimating abundance, with considerations for some recent extensions that provide a spatial context for the estimation of abundance, and therefore density. Finally, the chapter suggests some software for use in data analysis, such as the Windows-based program MARK, and provides an example of estimating abundance and density of reptiles using an artificial cover object survey of Slow Worms (Anguis fragilis).

  13. Fatty Acid Composition and Lipid Profile of Diospyros mespiliformis, Albizia lebbeck, and Caesalpinia pulcherrima Seed Oils from Nigeria.

    PubMed

    Adewuyi, Adewale; Oderinde, Rotimi Ayodele

    2014-01-01

    The screening of lesser-known underutilized seeds as source of food has been a way of finding solution to food insecurity in developing nations. In this regard, oil as a class of food was extracted from the seeds of Diospyros mespiliformis  (4.72 ± 0.2%), Albizia lebbeck  (6.40 ± 0.60%), and Caesalpinia pulcherrima  (7.2 ± 0.30%). The oils were finally analyzed for their fatty acid composition, lipid classes, fatty acid distribution in the lipid fractions, and molecular speciation of the triacylglycerols, glycolipids, and phospholipids. The fatty acid composition of the oils varied with C18:2 fatty acid being the most dominant in the oils. Neutral lipids were the most abundant lipid class found in the oils while molecular species of the triacylglycerol with equivalent carbon chain number C40 was majorly present in the oils of Diospyros mespiliformis and Caesalpinia pulcherrima. The present study presents lesser-known underutilized seeds as possible sources of food.

  14. Fatty Acid Composition and Lipid Profile of Diospyros mespiliformis, Albizia lebbeck, and Caesalpinia pulcherrima Seed Oils from Nigeria

    PubMed Central

    Oderinde, Rotimi Ayodele

    2014-01-01

    The screening of lesser-known underutilized seeds as source of food has been a way of finding solution to food insecurity in developing nations. In this regard, oil as a class of food was extracted from the seeds of Diospyros mespiliformis  (4.72 ± 0.2%), Albizia lebbeck  (6.40 ± 0.60%), and Caesalpinia pulcherrima  (7.2 ± 0.30%). The oils were finally analyzed for their fatty acid composition, lipid classes, fatty acid distribution in the lipid fractions, and molecular speciation of the triacylglycerols, glycolipids, and phospholipids. The fatty acid composition of the oils varied with C18:2 fatty acid being the most dominant in the oils. Neutral lipids were the most abundant lipid class found in the oils while molecular species of the triacylglycerol with equivalent carbon chain number C40 was majorly present in the oils of Diospyros mespiliformis and Caesalpinia pulcherrima. The present study presents lesser-known underutilized seeds as possible sources of food. PMID:26904625

  15. Preparation of different types of miso with mixture of starters and their effects on endogenous antioxidant of liver and kidney of mice.

    PubMed

    El-Shenawy, N S; Abu Zaid, A; Amin, G A

    2012-02-01

    The present study was undertaken to evaluate the effects of feeding the male mice with miso that was prepared with a mixture of microbial starters on the level of lipid peroxidation as a marker of oxidative stress, antioxidant power of hepatocytes, the enzymatic and non-enzymatic antioxidant. The starters that were used in the preparation of miso were Aspergillus oryzae and Pleurotus ostreaus or A. oryzae and Bacillus subtilis. The miso that was prepared with A. oryzae and Bacillus subtilis has more effect on suppressing the oxidative stress and enhancement of endogenous antioxidant of hepatocytes and renal tissue of mice. © 2011 Blackwell Verlag GmbH.

  16. Lipid Biomarkers for a Hypersaline Microbial Mat Community

    NASA Technical Reports Server (NTRS)

    Jahnke, Linda L.; Embaye, Tsege; Turk, Kendra A.

    2003-01-01

    The use of lipid biomarkers and their carbon isotopic compositions are valuable tools for establishing links to ancient microbial ecosystems. As witnessed by the stromatolite record, benthic microbial mats grew in shallow water lagoonal environments where microorganisms had virtually no competition apart from the harsh conditions of hypersalinity, desiccation and intense light. Today, the modern counterparts of these microbial ecosystems find appropriate niches in only a few places where extremes eliminate eukaryotic grazers. Answers to many outstanding questions about the evolution of microorganisms and their environments on early Earth are best answered through study of these extant analogs. Lipids associated with various groups of bacteria can be valuable biomarkers for identification of specific groups of microorganisms both in ancient organic-rich sedimentary rocks (geolipids) and contemporary microbial communities (membrane lipids). Use of compound specific isotope analysis adds additional refinement to the identification of biomarker source, so that it is possible to take advantage of the 3C-depletions associated with various functional groups of organisms (i.e. autotrophs, heterotrophs, methanotrophs, methanogens) responsible for the cycling of carbon within a microbial community. Our recent work has focused on a set of hypersaline evaporation ponds at Guerrero Negro, Baja California Sur, Mexico which support the abundant growth of Microcoleus-dominated microbial mats. Specific biomarkers for diatoms, cyanobacteria, archaea, green nonsulfur (GNS), sulfate reducing, and methanotrophic bacteria have been identified. Analyses of the ester-bound fatty acids indicate a highly diverse microbial community, dominated by photosynthetic organisms at the surface.

  17. Lipidomic Approaches towards Deciphering Glycolipids from Microalgae as a Reservoir of Bioactive Lipids

    PubMed Central

    da Costa, Elisabete; Silva, Joana; Mendonça, Sofia Hoffman; Abreu, Maria Helena; Domingues, Maria Rosário

    2016-01-01

    In recent years, noteworthy research has been performed around lipids from microalgae. Among lipids, glycolipids (GLs) are quite abundant in microalgae and are considered an important source of fatty acids (FAs). GLs are rich in 16- and 18-carbon saturated and unsaturated fatty acids and often contain polyunsaturated fatty acids (PUFAs) like n-3 α-linolenic (ALA 18:3), eicosapentaenoic (EPA, 20:5) and docosahexaenoic (DHA, 22:6). GLs comprise three major classes: monogalactosyldiacyl glycerolipids (MGDGs), digalactosyl diacylglycerolipids (DGDGs) and sulfoquinovosyl diacylglycerolipids (SQDGs), whose composition in FA directly depends on the growth conditions. Some of these lipids are high value-added compounds with antitumoral, antimicrobial and anti-inflammatory activities and also with important nutritional significance. To fully explore GLs’ bioactive properties it is necessary to fully characterize their structure and to understand the relation between the structure and their biological properties, which can be addressed using modern mass spectrometry (MS)-based lipidomic approaches. This review will focus on the up-to-date FA composition of GLs identified by MS-based lipidomics and their potential as phytochemicals. PMID:27213410

  18. Wheat leaf lipids during heat stress: II. Lipids experiencing coordinated metabolism are detected by analysis of lipid co-occurrence.

    PubMed

    Narayanan, Sruthi; Prasad, P V Vara; Welti, Ruth

    2016-03-01

    Identifying lipids that experience coordinated metabolism during heat stress would provide information regarding lipid dynamics under stress conditions and assist in developing heat-tolerant wheat varieties. We hypothesized that co-occurring lipids, which are up-regulated or down-regulated together through time during heat stress, represent groups that can be explained by coordinated metabolism. Wheat plants (Triticum aestivum L.) were subjected to 12 days of high day and/or night temperature stress, followed by a 4-day recovery period. Leaves were sampled at four time points, and 165 lipids were measured by electrospray ionization-tandem mass spectrometry. Correlation analysis of lipid levels in 160 leaf samples from each of two wheat genotypes revealed 13 groups of lipids. Lipids within each group co-occurred through the high day and night temperature stress treatments. The lipid groups can be broadly classified as groups containing extraplastidic phospholipids, plastidic glycerolipids, oxidized glycerolipids, triacylglycerols, acylated sterol glycosides and sterol glycosides. Current knowledge of lipid metabolism suggests that the lipids in each group co-occur because they are regulated by the same enzyme(s). The results suggest that increases in activities of desaturating, oxidizing, glycosylating and acylating enzymes lead to simultaneous changes in levels of multiple lipid species during high day and night temperature stress in wheat. © 2015 John Wiley & Sons Ltd.

  19. Exogenic and endogenic Europa minerals

    NASA Astrophysics Data System (ADS)

    Maynard-Casely, H. E.; Brand, H. E. A.; Wilson, S. A.

    2016-12-01

    The Galileo Near Infrared Mapping Spectrometer (NIMS) identified a significant `non-ice' component upon the surface of Jupiter's moon Europa. Current explanations invoke both endogenic and exogenic origins for this material. It has long been suggested that magnesium and sodium sulfate minerals could have leached from the rock below a putative ocean (endogenic) 1 and that sulfuric acid hydrate minerals could have been radiologically produced from ionised sulfur originally from Io's volcanoes (exogenic) 2. However, a more recent theory proposes that the `non-ice' component could be radiation damaged NaCl leached from Europa's speculative ocean 3. What if the minerals are actually from combination of both endogenic and exogenic sources? To investigate this possibility we have focused on discovering new minerals that might form in the combination of the latter two cases, that is a mixture of leached sulfates hydrates with radiologically produced sulfuric acid. To this end we have explored a number of solutions in the MgSO4-H2SO4-H2O and Na2SO4-H2SO4-H2O systems, between 80 and 280 K with synchrotron x-ray powder diffraction. We report a number of new materials formed in this these ternary systems. This suggests that it should be considered that the `non-ice' component of the Europa's surface could be a material derived from endogenic and exogenic components. 1 Kargel, J. S. Brine volcanism and the interior structures of asteroids and icy satellites. Icarus 94, 368-390 (1991). 2 Carlson, R. W., Anderson, M. S., Mehlman, R. & Johnson, R. E. Distribution of hydrate on Europa: Further evidence for sulfuric acid hydrate. Icarus 177, 461-471, doi:10.1016/j.icarus.2005.03.026 (2005). 3 Hand, K. P. & Carlson, R. W. Europa's surface color suggests an ocean rich with sodium chloride. Geophysical Research Letters, 2015GL063559, doi:10.1002/2015gl063559 (2015).

  20. Pro-Inflammatory Activated Kupffer Cells by Lipids Induce Hepatic NKT Cells Deficiency through Activation-Induced Cell Death

    PubMed Central

    Tang, Tongfang; Sui, Yongheng; Lian, Min; Li, Zhiping; Hua, Jing

    2013-01-01

    Background Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response. Aims The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. Methods Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. Results High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. Conclusion High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD. PMID:24312613

  1. Accumulation and processing of a recombinant protein designed as a cleavable fusion to the endogenous Rubisco LSU protein in Chlamydomonas chloroplast

    PubMed Central

    Muto, Machiko; Henry, Ryan E; Mayfield, Stephen P

    2009-01-01

    Background Expression of recombinant proteins in green algal chloroplast holds substantial promise as a platform for the production of human therapeutic proteins. A number of proteins have been expressed in the chloroplast of Chlamydomonas reinhardtii, including complex mammalian proteins, but many of these proteins accumulate to significantly lower levels than do endogenous chloroplast proteins. We examined if recombinant protein accumulation could be enhanced by genetically fusing the recombinant reporter protein, luciferase, to the carboxy-terminal end of an abundant endogenous protein, the large subunit of ribulose bisphosphate carboxylase (Rubisco LSU). Additionally, as recombinant proteins fused to endogenous proteins are of little clinical or commercial value, we explored the possibility of engineering our recombinant protein to be cleavable from the endogenous protein in vivo. This strategy would obviate the need for further in vitro processing steps in order to produce the desired recombinant protein. To achieve this, a native protein-processing site from preferredoxin (preFd) was placed between the Rubisco LSU and luciferase coding regions in the fusion protein construct. Results The luciferase from the fusion protein accumulated to significantly higher levels than luciferase expressed alone. By eliminating the endogenous Rubisco large subunit gene (rbcL), we achieved a further increase in luciferase accumulation with respect to luciferase expression in the WT background. Importantly, near-wild type levels of functional Rubisco holoenzyme were generated following the proteolytic removal of the fused luciferase, while luciferase activity for the fusion protein was almost ~33 times greater than luciferase expressed alone. These data demonstrate the utility of using fusion proteins to enhance recombinant protein accumulation in algal chloroplasts, and also show that engineered proteolytic processing sites can be used to liberate the exogenous protein from

  2. Charge-reversal Lipids, Peptide-based Lipids, and Nucleoside-based Lipids for Gene Delivery

    PubMed Central

    LaManna, Caroline M.; Lusic, Hrvoje; Camplo, Michel; McIntosh, Thomas J.; Barthélémy, Philippe; Grinstaff, Mark W.

    2013-01-01

    Conspectus Twenty years after gene therapy was introduced in the clinic, advances in the technique continue to garner headlines as successes pique the interest of clinicians, researchers, and the public. Gene therapy’s appeal stems from its potential to revolutionize modern medical therapeutics by offering solutions to a myriad of diseases by tailoring the treatment to a specific individual’s genetic code. Both viral and non-viral vectors have been used in the clinic, but the low transfection efficiencies when utilizing non-viral vectors have lead to an increased focus on engineering new gene delivery vectors. To address the challenges facing non-viral or synthetic vectors, specifically lipid-based carriers, we have focused on three main themes throughout our research: 1) that releasing the nucleic acid from the carrier will increase gene transfection; 2) that utilizing biologically inspired designs, such as DNA binding proteins, to create lipids with peptide-based headgroups will improve delivery; and 3) that mimicking the natural binding patterns observed within DNA, by using lipids having a nucleoside headgroup, will give unique supramolecular assembles with high transfection efficiency. The results presented in this Account demonstrate that cellular uptake and transfection efficacy can be improved by engineering the chemical components of the lipid vectors to enhance nucleic acid binding and release kinetics. Specifically, our research has shown that the incorporation of a charge-reversal moiety to initiate change of the lipid from positive to negative net charge during the transfection process improves transfection. In addition, by varying the composition of the spacer (rigid, flexible, short, long, and aromatic) between the cationic headgroup and the hydrophobic chains, lipids can be tailored to interact with different nucleic acids (DNA, RNA, siRNA) and accordingly affect delivery, uptake outcomes, and transfection efficiency. Introduction of a peptide

  3. Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

    PubMed Central

    Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

  4. Proteomic analysis of oil bodies in mature Jatropha curcas seeds with different lipid content.

    PubMed

    Liu, Hui; Wang, Cuiping; Chen, Fan; Shen, Shihua

    2015-01-15

    To reveal the difference among three mature Jatropha curcas seeds (JcVH, variant with high lipid content; JcW, wild type and JcVL, variant with low lipid content) with different lipid content, comparative proteomics was employed to profile the changes of oil body (OB) associated protein species by using gels-based proteomic technique. Eighty-three protein species were successfully identified through LTQ-ES-MS/MS from mature JcW seeds purified OBs. Two-dimensional electrophoresis analysis of J. curcas OB associated protein species revealed they had essential interactions with other organelles and demonstrated that oleosin and caleosin were the most abundant OB structural protein species. Twenty-eight OB associated protein species showed significant difference among JcVH, JcW and JcVL according to statistical analysis. Complementary transient expression analysis revealed that calcium ion binding protein (CalBP) and glycine-rich RNA binding protein (GRP) were well targeted in OBs apart from the oleosins. This study demonstrated that ratio of lipid content to caleosins abundance was involved in the regulation of OB size, and the mutant induced by ethylmethylsulfone treatment might be related to the caleosin like protein species. These findings are important for biotechnological improvement with the aim to alter the lipid content in J. curcas seeds. The economic value of Jatropha curcas largely depends on the lipid content in seeds which are mainly stored in the special organelle called oil bodies (OBs). In consideration of the biological importance and applications of J. curcas OB in seeds, it is necessary to further explore the components and functions of J. curcas OBs. Although a previous study concerning the J. curcas OB proteome revealed oleosins were the major OB protein component and additional protein species were similar to those in other oil seed plants, these identified OB associated protein species were corresponding to the protein bands instead of protein

  5. The influence of diet, consumption and lipid use on recruitment of white bass

    USGS Publications Warehouse

    Eckmayer, W.J.; Margraf, F.J.

    2004-01-01

    The abundance of white bass (Morone chrysops) in Lake Erie has declined in recent years, sparking interest in mechanisms influencing its recruitment. We evaluate two mechanisms affecting recruitment: diet and the potential for competition, and storage of lipid energy reserves and the relationship to overwinter survival. The fish in our study were characteristic of white bass in the northern portion of their range, feeding predominantly on zooplankton. Only the largest age-0 white bass ate fish as a significant portion of their diet. Over the summer sampling period, we found decreasing ration sizes, expressed as a percentage of maximum ration, as the summer progressed with a concomitant decrease in the relative amount of lipid storage. In laboratory experiments, age-0 white bass held at 5??C and given food ad libitum did feed, but at rates that were insufficient to maintain body weight. Loss in weight was accompanied with a loss in lipids at a rate of 2.8 mg of lipids per gram of body weight per day. Based on our data, we concluded that age-0 white bass in Lake Erie were food-limited. Food limitation resulted in reduced growth rates, presumably related to competition with other planktivorous fishes. Reduced growth results in increased mortality and, ultimately, low recruitment through increased risk of predation by larger piscivorous fishes, reduced ability for white bass to switch to more energetically profitable piscivory and the increased likelihood of higher overwinter mortality because of reduced lipid stores.

  6. A reversed-phase capillary ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method for comprehensive top-down/bottom-up lipid profiling

    PubMed Central

    Gao, Xiaoli; Zhang, Qibin; Meng, Da; Issac, Giorgis; Zhao, Rui; Fillmore, Thomas L.; Chu, Rosey K.; Zhou, Jianying; Tang, Keqi; Hu, Zeping; Moore, Ronald J.; Smith, Richard D.; Katze, Michael G.; Metz, Thomas O.

    2012-01-01

    Lipidomics is a critical part of metabolomics and aims to study all the lipids within a living system. We present here the development and evaluation of a sensitive capillary UPLC-MS method for comprehensive top-down/bottom-up lipid profiling. Three different stationary phases were evaluated in terms of peak capacity, linearity, reproducibility, and limit of quantification (LOQ) using a mixture of lipid standards representative of the lipidome. The relative standard deviations of the retention times and peak abundances of the lipid standards were 0.29% and 7.7%, respectively, when using the optimized method. The linearity was acceptable at >0.99 over 3 orders of magnitude, and the LOQs were sub-fmol. To demonstrate the performance of the method in the analysis of complex samples, we analyzed lipids extracted from a human cell line, rat plasma, and a model human skin tissue, identifying 446, 444, and 370 unique lipids, respectively. Overall, the method provided either higher coverage of the lipidome, greater measurement sensitivity, or both, when compared to other approaches of global, untargeted lipid profiling based on chromatography coupled with MS. PMID:22354571

  7. Effects of MeJA on Arabidopsis metabolome under endogenous JA deficiency

    NASA Astrophysics Data System (ADS)

    Cao, Jingjing; Li, Mengya; Chen, Jian; Liu, Pei; Li, Zhen

    2016-11-01

    Jasmonates (JAs) play important roles in plant growth, development and defense. Comprehensive metabolomics profiling of plants under JA treatment provides insights into the interaction and regulation network of plant hormones. Here we applied high resolution mass spectrometry based metabolomics approach on Arabidopsis wild type and JA synthesis deficiency mutant opr3. The effects of exogenous MeJA treatment on the metabolites of opr3 were investigated. More than 10000 ion signals were detected and more than 2000 signals showed significant variation in different genotypes and treatment groups. Multivariate statistic analyses (PCA and PLS-DA) were performed and a differential compound library containing 174 metabolites with high resolution precursor ion-product ions pairs was obtained. Classification and pathway analysis of 109 identified compounds in this library showed that glucosinolates and tryptophan metabolism, amino acids and small peptides metabolism, lipid metabolism, especially fatty acyls metabolism, were impacted by endogenous JA deficiency and exogenous MeJA treatment. These results were further verified by quantitative reverse transcription PCR (RT-qPCR) analysis of 21 related genes involved in the metabolism of glucosinolates, tryptophan and α-linolenic acid pathways. The results would greatly enhance our understanding of the biological functions of JA.

  8. Xeropreservation of Functionalized Lipid Biomarkers in Hyperarid Soils in the Atacama Desert

    NASA Technical Reports Server (NTRS)

    Wilhelm, Mary Beth; Davila, Alfonso F.; Eigenbrode, Jennifer L.; Parenteau, Mary N.; Jahnke, Linda L.; Liu, Xiao-Lei; Summons, Roger E.; Wray, James J.; Stamos, Brian N.; O'Reilly, Shane S.; hide

    2016-01-01

    Our understanding of long-term organic matter preservation comes mostly from studies in aquatic systems. In contrast, taphonomic processes in extremely dry environments are relatively understudied and are poorly understood. We investigated the accumulation and preservation of lipid biomarkers in hyperarid soils in the Yungay region of the Atacama Desert. Lipids from seven soil horizons in a 2.5 meter vertical profile were extracted and analyzed using GC-MS ( Gas Chromatography-Mass Spectrometry) and LC-MS (Liquid Chromatography-Mass Spectrometry). Diagnostic functionalized lipids and geolipids were detected and increased in abundance and diversity with depth. Deeper clay units contain fossil organic matter (radiocarbon dead) that has been protected from rainwater since the onset of hyperaridity. We show that these clay units contain lipids in an excellent state of structural preservation with functional groups and unsaturated bonds in carbon chains. This indicates that minimal degradation of lipids has occurred in these soils since the time of their deposition between more than 40,000 and up to 2 million years ago. The exceptional structural preservation of biomarkers is likely due to the long-term hyperaridity that has minimized microbial and enzymatic activity, a taphonomic process we term xeropreservation (i.e. preservation by drying). The degree of biomarker preservation allowed us to reconstruct major changes in ecology in the Yungay region that reflect a shift in hydrological regime from wet to dry since the early Quaternary. Our results suggest that hyperarid environments, which comprise 7.5 percent of the continental landmass, could represent a rich and relatively unexplored source of paleobiological information on Earth.

  9. Xeropreservation of Functionalized Lipid Biomarkers in Hyperarid Soils in the Atacama Desert

    NASA Technical Reports Server (NTRS)

    Wilhelm, Mary Beth; Davila, Alfonso F.; Eigenbrode, Jennifer L.; Parenteau, Mary N.; Jahnke, Linda L.; Liu, Xiao-Lei; Summons, Rogers E.; Wray, James J.; Stamos, Brian N.; O'Reilly, Shane S.; hide

    2016-01-01

    Our understanding of long-term organic matter preservation comes mostly from studies in aquatic systems. In contrast, taphonomic processes in extremely dry environments are relatively understudied and are poorly understood. We investigated the accumulation and preservation of lipid biomarkers in hyperarid soils in the Yungay region of the Atacama Desert. Lipids from seven soil horizons in a 2.5 m vertical profile were extracted and analyzed using GC-MS and LC-MS. Diagnostic functionalized lipids and geolipids were detected and increased in abundance and diversity with depth. Deeper clay units contain fossil organic matter (radiocarbon dead) that has been protected from rainwater since the onset of hyperaridity. We show that these clay units contain lipids in an excellent state of structural preservation with functional groups and unsaturated bonds in carbon chains. This indicates that minimal degradation of lipids has occurred in these soils since the time of their deposition between greater than 40,000 and 2 million years ago. The exceptional structural preservation of biomarkers is likely due to the long-term hyperaridity that has minimized microbial and enzymatic activity, a taphonomic process we term xeropreservation (i.e., preservation by drying). The degree of biomarker preservation allowed us to reconstruct major changes in ecology in the Yungay region that reflect a shift in hydrological regime from wet to dry since the early Quaternary. Our results suggest that hyperarid environments, which comprise 7.5 percent of the continental landmass, could represent a rich and relatively unexplored source of paleobiological informationon Earth.

  10. Xeropreservation of functionalized lipid biomarkers in hyperarid soils in the Atacama Desert

    PubMed Central

    Wilhelm, Mary Beth; Davila, Alfonso F.; Eigenbrode, Jennifer L.; Parenteau, Mary N.; Jahnke, Linda L.; Liu, Xiao-Lei; Summons, Roger E.; Wray, James J.; Stamos, Brian N.; O’Reilly, Shane S.; Williams, Amy

    2018-01-01

    Our understanding of long-term organic matter preservation comes mostly from studies in aquatic systems. In contrast, taphonomic processes in extremely dry environments are relatively understudied and are poorly understood. We investigated the accumulation and preservation of lipid biomarkers in hyperarid soils in the Yungay region of the Atacama Desert. Lipids from seven soil horizons in a 2.5 m vertical profile were extracted and analyzed using GC-MS and LC-MS. Diagnostic functionalized lipids and geolipids were detected and increased in abundance and diversity with depth. Deeper clay units contain fossil organic matter (radiocarbon dead) that has been protected from rainwater since the onset of hyperaridity. We show that these clay units contain lipids in an excellent state of structural preservation with functional groups and unsaturated bonds in carbon chains. This indicates that minimal degradation of lipids has occurred in these soils since the time of their deposition between >40,000 and 2 million years ago. The exceptional structural preservation of biomarkers is likely due to the long-term hyperaridity that has minimized microbial and enzymatic activity, a taphonomic process we term xeropreservation (i.e. preservation by drying). The degree of biomarker preservation allowed us to reconstruct major changes in ecology in the Yungay region that reflect a shift in hydrological regime from wet to dry since the early Quaternary. Our results suggest that hyperarid environments, which comprise 7.5% of the continental landmass, could represent a rich and relatively unexplored source of paleobiological information on Earth. PMID:29743757

  11. Protective role of endogenous plasmalogens against hepatic steatosis and steatohepatitis in mice.

    PubMed

    Jang, Jung Eun; Park, Han-Sol; Yoo, Hyun Ju; Baek, In-Jeoung; Yoon, Ji Eun; Ko, Myoung Seok; Kim, Ah-Ram; Kim, Hyoun Sik; Park, Hye-Sun; Lee, Seung Eun; Kim, Seung-Whan; Kim, Su Jung; Leem, Jaechan; Kang, Yu Mi; Jung, Min Kyo; Pack, Chan-Gi; Kim, Chong Jai; Sung, Chang Ohk; Lee, In-Kyu; Park, Joong-Yeol; Fernández-Checa, José C; Koh, Eun Hee; Lee, Ki-Up

    2017-08-01

    Free cholesterol (FC) accumulation in the liver is an important pathogenic mechanism of nonalcoholic steatohepatitis (NASH). Plasmalogens, key structural components of the cell membrane, act as endogenous antioxidants and are primarily synthesized in the liver. However, the role of hepatic plasmalogens in metabolic liver disease is unclear. In this study, we found that hepatic levels of docosahexaenoic acid (DHA)-containing plasmalogens, expression of glyceronephosphate O-acyltransferase (Gnpat; the rate-limiting enzyme in plasmalogen biosynthesis), and expression of Pparα were lower in mice with NASH caused by accumulation of FC in the liver. Cyclodextrin-induced depletion of FC transactivated Δ-6 desaturase by increasing sterol regulatory element-binding protein 2 expression in cultured hepatocytes. DHA, the major product of Δ-6 desaturase activation, activated GNPAT, thereby explaining the association between high hepatic FC and decreased Gnpat expression. Gnpat small interfering RNA treatment significantly decreased peroxisome proliferator-activated receptor α (Pparα) expression in cultured hepatocytes. In addition to GNPAT, DHA activated PPARα and increased expression of Pparα and its target genes, suggesting that DHA in the DHA-containing plasmalogens contributed to activation of PPARα. Accordingly, administration of the plasmalogen precursor, alkyl glycerol (AG), prevented hepatic steatosis and NASH through a PPARα-dependent increase in fatty acid oxidation. Gnpat +/- mice were more susceptible to hepatic lipid accumulation and less responsive to the preventive effect of fluvastatin on NASH development, suggesting that endogenous plasmalogens prevent hepatic steatosis and NASH. Increased hepatic FC in animals with NASH decreased plasmalogens, thereby sensitizing animals to hepatocyte injury and NASH. Our findings uncover a novel link between hepatic FC and plasmalogen homeostasis through GNPAT regulation. Further study of AG or other agents that

  12. GPS-Lipid: a robust tool for the prediction of multiple lipid modification sites.

    PubMed

    Xie, Yubin; Zheng, Yueyuan; Li, Hongyu; Luo, Xiaotong; He, Zhihao; Cao, Shuo; Shi, Yi; Zhao, Qi; Xue, Yu; Zuo, Zhixiang; Ren, Jian

    2016-06-16

    As one of the most common post-translational modifications in eukaryotic cells, lipid modification is an important mechanism for the regulation of variety aspects of protein function. Over the last decades, three classes of lipid modifications have been increasingly studied. The co-regulation of these different lipid modifications is beginning to be noticed. However, due to the lack of integrated bioinformatics resources, the studies of co-regulatory mechanisms are still very limited. In this work, we developed a tool called GPS-Lipid for the prediction of four classes of lipid modifications by integrating the Particle Swarm Optimization with an aging leader and challengers (ALC-PSO) algorithm. GPS-Lipid was proven to be evidently superior to other similar tools. To facilitate the research of lipid modification, we hosted a publicly available web server at http://lipid.biocuckoo.org with not only the implementation of GPS-Lipid, but also an integrative database and visualization tool. We performed a systematic analysis of the co-regulatory mechanism between different lipid modifications with GPS-Lipid. The results demonstrated that the proximal dual-lipid modifications among palmitoylation, myristoylation and prenylation are key mechanism for regulating various protein functions. In conclusion, GPS-lipid is expected to serve as useful resource for the research on lipid modifications, especially on their co-regulation.

  13. Correlation of circular RNA abundance with proliferation--exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues.

    PubMed

    Bachmayr-Heyda, Anna; Reiner, Agnes T; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Bachleitner-Hofmann, Thomas; Mesteri, Ildiko; Grunt, Thomas W; Zeillinger, Robert; Pils, Dietmar

    2015-01-27

    Circular RNAs are a recently (re-)discovered abundant RNA species with presumed function as miRNA sponges, thus part of the competing endogenous RNA network. We analysed the expression of circular and linear RNAs and proliferation in matched normal colon mucosa and tumour tissues. We predicted >1,800 circular RNAs and proved the existence of five randomly chosen examples using RT-qPCR. Interestingly, the ratio of circular to linear RNA isoforms was always lower in tumour compared to normal colon samples and even lower in colorectal cancer cell lines. Furthermore, this ratio correlated negatively with the proliferation index. The correlation of global circular RNA abundance (the circRNA index) and proliferation was validated in a non-cancerous proliferative disease, idiopathic pulmonary fibrosis, ovarian cancer cells compared to cultured normal ovarian epithelial cells, and 13 normal human tissues. We are the first to report a global reduction of circular RNA abundance in colorectal cancer cell lines and cancer compared to normal tissues and discovered a negative correlation of global circular RNA abundance and proliferation. This negative correlation seems to be a general principle in human tissues as validated with three different settings. Finally, we present a simple model how circular RNAs could accumulate in non-proliferating cells.

  14. School system evaluation by value added analysis under endogeneity.

    PubMed

    Manzi, Jorge; San Martín, Ernesto; Van Bellegem, Sébastien

    2014-01-01

    Value added is a common tool in educational research on effectiveness. It is often modeled as a (prediction of a) random effect in a specific hierarchical linear model. This paper shows that this modeling strategy is not valid when endogeneity is present. Endogeneity stems, for instance, from a correlation between the random effect in the hierarchical model and some of its covariates. This paper shows that this phenomenon is far from exceptional and can even be a generic problem when the covariates contain the prior score attainments, a typical situation in value added modeling. Starting from a general, model-free definition of value added, the paper derives an explicit expression of the value added in an endogeneous hierarchical linear Gaussian model. Inference on value added is proposed using an instrumental variable approach. The impact of endogeneity on the value added and the estimated value added is calculated accurately. This is also illustrated on a large data set of individual scores of about 200,000 students in Chile.

  15. Endogenous Pyrogen Physiology

    DTIC Science & Technology

    1980-01-01

    neutrophilic pyrogen, the fever-producing factors of cellular origin are now generally known as endogenous NEURONE $ M E pyrogen, or EP. FFECTS , ,, The entire...which release well known hormones. EP in turn produces its effect on a distant Assay of EP . target tissue, i.e., certein.. neurons within the central...expenditure, since it is not blocked by fluoride, cause CAMP formation within the neurons , or they could alter the In combination, these data suggest that

  16. Hepatic cytochrome P450 activity, abundance, and expression throughout human development

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sadler, Natalie C.; Nandhikonda, Premchendar; Webb-Robertson, Bobbie-Jo M.

    Cytochrome P450s are Phase I metabolic enzymes that play critical roles in the biotransformation of endogenous compounds and xenobiotics. The expression and activity of P450 enzymes can vary considerably throughout human development, especially when comparing fetal development to neonates, children, and adults. In an effort to develop a more comprehensive understanding of the ontogeny of P450 expression and activity we employed a multi-omic characterization of P450 transcript expression, protein abundance, and functional activity. To quantify the functional activity of individual P450s we employ activity-based protein profiling, which uses modified mechanism-based inhibitors of P450s as chemical probes, in tandem with proteomicmore » analyses to quantify activity. Our results reveal life-stage-dependent variability in P450 expression, abundance, and activity throughout human development and frequent discordant relationships between expression and activity. The results were used to distribute P450s into three general classes based upon developmental stage of expression and activity. We have significantly expanded the knowledge of P450 ontogeny, particularly at the level of individual P450 activity. We anticipate that our ontogeny results will be useful for enabling predictive therapeutic dosing, and for avoiding potentially adverse and harmful reactions during maturation from both therapeutic drugs and environmental xenobiotics.« less

  17. Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway

    PubMed Central

    Li, Shiwei; Li, Qi; Kong, Yuanyuan; Wu, Shuang; Cui, Qingpo; Zhang, Mingming; Zhang, Shaobing O.

    2017-01-01

    Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans. This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to Δ7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12–dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans. This finding suggests the existence of a conserved CYP4V2-POR–nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage. PMID:28760992

  18. Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway.

    PubMed

    Li, Shiwei; Li, Qi; Kong, Yuanyuan; Wu, Shuang; Cui, Qingpo; Zhang, Mingming; Zhang, Shaobing O

    2017-08-15

    Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to Δ7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12-dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans This finding suggests the existence of a conserved CYP4V2-POR-nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage.

  19. Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids.

    PubMed

    Cruz-Garcia, Lourdes; Schlegel, Amnon

    2014-09-01

    Liver X receptors (Lxrs) are master regulators of cholesterol catabolism, driving the elimination of cholesterol from the periphery to the lumen of the intestine. Development of pharmacological agents to activate Lxrs has been hindered by synthetic Lxr agonists' induction of hepatic lipogenesis and hypertriglyceridemia. Elucidating the function of Lxrs in regulating enterocyte lipid handling might identify novel aspects of lipid metabolism that are pharmacologically amenable. We took a genetic approach centered on the single Lxr gene nr1h3 in zebrafish to study the role of Lxr in enterocyte lipid metabolism. Loss of nr1h3 function causes anticipated gene regulatory changes and cholesterol intolerance, collectively reflecting high evolutionary conservation of zebrafish Lxra function. Intestinal nr1h3 activation delays transport of absorbed neutral lipids, with accumulation of neutral lipids in enterocyte cytoplasmic droplets. This delay in transport of ingested neutral lipids protects animals from hypercholesterolemia and hepatic steatosis induced by a high-fat diet. On a gene regulatory level, Lxra induces expression of acsl3a, which encodes acyl-CoA synthetase long-chain family member 3a, a lipid droplet-anchored protein that directs fatty acyl chains into lipids. Forced overexpression of acls3a in enterocytes delays, in part, the appearance of neutral lipids in the vasculature of zebrafish larvae. Activation of Lxr in the intestine cell-autonomously regulates the rate of delivery of absorbed lipids by inducting a temporary lipid intestinal droplet storage depot. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  20. Social Laughter Triggers Endogenous Opioid Release in Humans.

    PubMed

    Manninen, Sandra; Tuominen, Lauri; Dunbar, Robin I; Karjalainen, Tomi; Hirvonen, Jussi; Arponen, Eveliina; Hari, Riitta; Jääskeläinen, Iiro P; Sams, Mikko; Nummenmaa, Lauri

    2017-06-21

    The size of human social networks significantly exceeds the network that can be maintained by social grooming or touching in other primates. It has been proposed that endogenous opioid release after social laughter would provide a neurochemical pathway supporting long-term relationships in humans (Dunbar, 2012), yet this hypothesis currently lacks direct neurophysiological support. We used PET and the μ-opioid-receptor (MOR)-specific ligand [ 11 C]carfentanil to quantify laughter-induced endogenous opioid release in 12 healthy males. Before the social laughter scan, the subjects watched laughter-inducing comedy clips with their close friends for 30 min. Before the baseline scan, subjects spent 30 min alone in the testing room. Social laughter increased pleasurable sensations and triggered endogenous opioid release in thalamus, caudate nucleus, and anterior insula. In addition, baseline MOR availability in the cingulate and orbitofrontal cortices was associated with the rate of social laughter. In a behavioral control experiment, pain threshold-a proxy of endogenous opioidergic activation-was elevated significantly more in both male and female volunteers after watching laughter-inducing comedy versus non-laughter-inducing drama in groups. Modulation of the opioidergic activity by social laughter may be an important neurochemical pathway that supports the formation, reinforcement, and maintenance of human social bonds. SIGNIFICANCE STATEMENT Social contacts are vital to humans. The size of human social networks significantly exceeds the network that can be maintained by social grooming in other primates. Here, we used PET to show that endogenous opioid release after social laughter may provide a neurochemical mechanism supporting long-term relationships in humans. Participants were scanned twice: after a 30 min social laughter session and after spending 30 min alone in the testing room (baseline). Endogenous opioid release was stronger after laughter versus the

  1. Antibacterial characteristics of newly developed amphiphilic lipids and DNA-lipid complexes against bacteria.

    PubMed

    Inoue, Y; Fukushima, T; Hayakawa, T; Takeuchi, H; Kaminishi, H; Miyazaki, K; Okahata, Y

    2003-05-01

    The purpose of this study was to investigate the antibacterial activity of newly developed amphiphilic lipids and DNA/lipid complexes against two types of oral bacteria and two types of hospital infection bacteria. Nine amphiphilic lipids were quantitatively prepared from the reaction of n-alkyl alcohol, alpha-amino acids, and p-toluenesulfonic acid. Nine DNA-lipid complexes were prepared by the simple mixing of DNA and amphiphilic lipids. The DNA-lipid complexes were insoluble in water. The antibacterial activity of lipids and DNA-lipid complexes against Porphyromonas gingivalis, Streptococcus mutans, Staphylococcus aureus, and Pseudomonas aeruginosa were evaluated by the disk-diffusion method. Seven artificial lipids showed antibacterial behavior; in particular, the lipids prepared from n-decyl alcohol and glycine and from n-decyl alcohol and L-alanine showed antibacterial activity against the four bacterial strains used in this study. On the other hand, the lipids of glutamic acid derivatives did not show any antibacterial activity against the four bacteria strains except for the lipid with an n-octyl group. Five DNA-lipid complexes also had an antibacterial effect. The complex prepared from DNA and glycine decyl ester p-toluenesulfonic acid salt exhibited antibacterial activity against the four types of bacteria strains. In this study it was found that lipids and DNA-lipid complexes with a mono-decyl group or a mono-dodecyl group have more favorable antibacterial activity. Copyright 2003 Wiley Periodicals, Inc.

  2. Fluorinated colloidal gold immunolabels for imaging select proteins in parallel with lipids using high-resolution secondary ion mass spectrometry

    PubMed Central

    Wilson, Robert L.; Frisz, Jessica F.; Hanafin, William P.; Carpenter, Kevin J.; Hutcheon, Ian D.; Weber, Peter K.; Kraft, Mary L.

    2014-01-01

    The local abundance of specific lipid species near a membrane protein is hypothesized to influence the protein’s activity. The ability to simultaneously image the distributions of specific protein and lipid species in the cell membrane would facilitate testing these hypotheses. Recent advances in imaging the distribution of cell membrane lipids with mass spectrometry have created the desire for membrane protein probes that can be simultaneously imaged with isotope labeled lipids. Such probes would enable conclusive tests of whether specific proteins co-localize with particular lipid species. Here, we describe the development of fluorine-functionalized colloidal gold immunolabels that facilitate the detection and imaging of specific proteins in parallel with lipids in the plasma membrane using high-resolution SIMS performed with a NanoSIMS. First, we developed a method to functionalize colloidal gold nanoparticles with a partially fluorinated mixed monolayer that permitted NanoSIMS detection and rendered the functionalized nanoparticles dispersible in aqueous buffer. Then, to allow for selective protein labeling, we attached the fluorinated colloidal gold nanoparticles to the nonbinding portion of antibodies. By combining these functionalized immunolabels with metabolic incorporation of stable isotopes, we demonstrate that influenza hemagglutinin and cellular lipids can be imaged in parallel using NanoSIMS. These labels enable a general approach to simultaneously imaging specific proteins and lipids with high sensitivity and lateral resolution, which may be used to evaluate predictions of protein co-localization with specific lipid species. PMID:22284327

  3. The Neural Cell Adhesion Molecule-Derived (NCAM)-Peptide FG Loop (FGL) Mobilizes Endogenous Neural Stem Cells and Promotes Endogenous Regenerative Capacity after Stroke.

    PubMed

    Klein, Rebecca; Mahlberg, Nicolas; Ohren, Maurice; Ladwig, Anne; Neumaier, Bernd; Graf, Rudolf; Hoehn, Mathias; Albrechtsen, Morten; Rees, Stephen; Fink, Gereon Rudolf; Rueger, Maria Adele; Schroeter, Michael

    2016-12-01

    The neural cell adhesion molecule (NCAM)-derived peptide FG loop (FGL) modulates synaptogenesis, neurogenesis, and stem cell proliferation, enhances cognitive capacities, and conveys neuroprotection after stroke. Here we investigated the effect of subcutaneously injected FGL on cellular compartments affected by degeneration and regeneration after stroke due to middle cerebral artery occlusion (MCAO), namely endogenous neural stem cells (NSC), oligodendrocytes, and microglia. In addition to immunohistochemistry, we used non-invasive positron emission tomography (PET) imaging with the tracer [ 18 F]-fluoro-L-thymidine ([ 18 F]FLT) to visualize endogenous NSC in vivo. FGL significantly increased endogenous NSC mobilization in the neurogenic niches as evidenced by in vivo and ex vivo methods, and it induced remyelination. Moreover, FGL affected neuroinflammation. Extending previous in vitro results, our data show that the NCAM mimetic peptide FGL mobilizes endogenous NSC after focal ischemia and enhances regeneration by amplifying remyelination and modulating neuroinflammation via affecting microglia. Results suggest FGL as a promising candidate to promote recovery after stroke.

  4. tirant, a newly discovered active endogenous retrovirus in Drosophila simulans.

    PubMed

    Akkouche, Abdou; Rebollo, Rita; Burlet, Nelly; Esnault, Caroline; Martinez, Sonia; Viginier, Barbara; Terzian, Christophe; Vieira, Cristina; Fablet, Marie

    2012-04-01

    Endogenous retroviruses have the ability to become permanently integrated into the genomes of their host, and they are generally transmitted vertically from parent to progeny. With the exception of gypsy, few endogenous retroviruses have been identified in insects. In this study, we describe the tirant endogenous retrovirus in a subset of Drosophila simulans natural populations. By focusing on the envelope gene, we show that the entire retroviral cycle (transcription, translation, and retrotransposition) can be completed for tirant within one population of this species.

  5. Localization and Ordering of Lipids Around Aquaporin-0: Protein and Lipid Mobility Effects.

    PubMed

    Briones, Rodolfo; Aponte-Santamaría, Camilo; de Groot, Bert L

    2017-01-01

    Hydrophobic matching, lipid sorting, and protein oligomerization are key principles by which lipids and proteins organize in biological membranes. The Aquaporin-0 channel (AQP0), solved by electron crystallography (EC) at cryogenic temperatures, is one of the few protein-lipid complexes of which the structure is available in atomic detail. EC and room-temperature molecular dynamics (MD) of dimyristoylglycerophosphocholine (DMPC) annular lipids around AQP0 show similarities, however, crystal-packing and temperature might affect the protein surface or the lipids distribution. To understand the role of temperature, lipid phase, and protein mobility in the localization and ordering of AQP0-lipids, we used MD simulations of an AQP0-DMPC bilayer system. Simulations were performed at physiological and at DMPC gel-phase temperatures. To decouple the protein and lipid mobility effects, we induced gel-phase in the lipids or restrained the protein. We monitored the lipid ordering effects around the protein. Reducing the system temperature or inducing lipid gel-phase had a marginal effect on the annular lipid localization. However, restraining the protein mobility increased the annular lipid localization around the whole AQP0 surface, resembling EC. The distribution of the inter-phosphate and hydrophobic thicknesses showed that stretching of the DMPC annular layer around AQP0 surface is the mechanism that compensates the hydrophobic mismatch in this system. The distribution of the local area-per-lipid and the acyl-chain order parameters showed particular fluid- and gel-like areas that involved several lipid layers. These areas were in contact with the surfaces of higher and lower protein mobility, respectively. We conclude that the AQP0 surfaces induce specific fluid- and gel-phase prone areas. The presence of these areas might guide the AQP0 lipid sorting interactions with other membrane components, and is compatible with the squared array oligomerization of AQP0 tetramers

  6. Endogenous opiates and behavior: 2007.

    PubMed

    Bodnar, Richard J

    2008-12-01

    This paper is the thirtieth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2007 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia; stress and social status; tolerance and dependence; learning and memory; eating and drinking; alcohol and drugs of abuse; sexual activity and hormones, pregnancy, development and endocrinology; mental illness and mood; seizures and neurologic disorders; electrical-related activity and neurophysiology; general activity and locomotion; gastrointestinal, renal and hepatic functions; cardiovascular responses; respiration and thermoregulation; and immunological responses.

  7. Obesogens beyond Vertebrates: Lipid Perturbation by Tributyltin in the Crustacean Daphnia magna

    PubMed Central

    Jordão, Rita; Casas, Josefina; Fabrias, Gemma; Campos, Bruno; Piña, Benjamín; Lemos, Marco F.L.; Soares, Amadeu M.V.M.; Tauler, Romà

    2015-01-01

    Background The analysis of obesogenic effects in invertebrates is limited by our poor knowledge of the regulatory pathways of lipid metabolism. Recent data from the crustacean Daphnia magna points to three signaling hormonal pathways related to the molting and reproductive cycles [retinoic X receptor (RXR), juvenile hormone (JH), and ecdysone] as putative targets for exogenous obesogens. Objective The present study addresses the disruptive effects of the model obesogen tributyltin (TBT) on the lipid homeostasis in Daphnia during the molting and reproductive cycle, its genetic control, and health consequences of its disruption. Methods D. magna individuals were exposed to low and high levels of TBT. Reproductive effects were assessed by Life History analysis methods. Quantitative and qualitative changes in lipid droplets during molting and the reproductive cycle were studied using Nile red staining. Lipid composition and dynamics were analyzed by ultra-performance liquid chromatography coupled to a time-of-flight mass spectrometer. Relative abundances of mRNA from different genes related to RXR, ecdysone, and JH signaling pathways were studied by qRT-PCR. Results and Conclusions TBT disrupted the dynamics of neutral lipids, impairing the transfer of triacylglycerols to eggs and hence promoting their accumulation in adult individuals. TBT’s disruptive effects translated into a lower fitness for offspring and adults. Co-regulation of gene transcripts suggests that TBT activates the ecdysone, JH, and RXR receptor signaling pathways, presumably through the already proposed interaction with RXR. These findings indicate the presence of obesogenic effects in a nonvertebrate species. Citation Jordão R, Casas J, Fabrias G, Campos B, Piña B, Lemos MF, Soares AM, Tauler R, Barata C. 2015. Obesogens beyond vertebrates: lipid perturbation by tributyltin in the crustacean Daphnia magna. Environ Health Perspect 123:813–819; http://dx.doi.org/10.1289/ehp.1409163 PMID

  8. Tissue lipid metabolism and hepatic metabolomic profiling in response to supplementation of fermented cottonseedmeal in the diets of broiler chickens*

    PubMed Central

    Nie, Cun-xi; Zhang, Wen-ju; Wang, Yong-qiang; Liu, Yan-feng; Ge, Wen-xia; Liu, Jian-cheng

    2015-01-01

    This study investigated the effects of fermented cottonseed meal (FCSM) on lipid metabolites, lipid metabolism-related gene expression in liver tissues and abdominal adipose tissues, and hepatic metabolomic profiling in broiler chickens. One hundred and eighty 21-d-old broiler chickens were randomly divided into three diet groups with six replicates of 10 birds in each group. The three diets consisted of a control diet supplemented with unfermented cottonseed meal, an experimental diet of cottonseed meal fermented by Candida tropicalis, and a second experimental diet of cottonseed meal fermented by C. tropicalis plus Saccharomyces cerevisae. The results showed that FCSM intake significantly decreased the levels of abdominal fat and hepatic triglycerides (P<0.05 for both). Dietary FCSM supplementation down-regulated the mRNA expression of fatty acid synthase and acetyl CoA carboxylase in liver tissues and the lipoprotein lipase expression in abdominal fat tissues (P<0.05 for both). FCSM intake resulted in significant metabolic changes of multiple pathways in the liver involving the tricarboxylic acid cycle, synthesis of fatty acids, and the metabolism of glycerolipid and amino acids. These findings indicated that FCSM regulated lipid metabolism by increasing or decreasing the expression of the lipid-related gene and by altering multiple endogenous metabolites. Lipid metabolism regulation is a complex process, this discovery provided new essential information about the effects of FCSM diets in broiler chickens and demonstrated the great potential of nutrimetabolomics in researching complex nutrients added to animal diets. PMID:26055906

  9. Amplification and chromosomal dispersion of human endogenous retroviral sequences

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Steele, P.E.; Martin, M.A.; Rabson, A.B.

    1986-09-01

    Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification andmore » dispersion events may be linked.« less

  10. Detection of endogenous boldenone in the entire male horses.

    PubMed

    Ho, Emmie N M; Yiu, Kenneth C H; Tang, Francis P W; Dehennin, Louis; Plou, Philippe; Bonnaire, Yves; Wan, Terence S M

    2004-09-05

    Boldenone (1,2-dehydrotestosterone) is a common veterinary anabolic agent. Its structure is very similar to testosterone. Testosterone is endogenous in the horse, whereas there has been no report concerning the detection of endogenous boldenone. This paper reports the direct observation of sulphate conjugate of boldenone in equine urine from entires. The detection procedures involved solid-phase extraction, immunoaffinity column (IAC) purification, and then LC-MS-MS analysis on a Q-ToF instrument. The identification of boldenone sulphate has provided direct evidence for the endogenous nature of boldenone in entire male horses. Quantification data for the normal level of boldenone in Hong Kong racehorses will also be discussed.

  11. Phytoplankton in the ocean use non-phosphorus lipids in response to phosphorus scarcity.

    PubMed

    Van Mooy, Benjamin A S; Fredricks, Helen F; Pedler, Byron E; Dyhrman, Sonya T; Karl, David M; Koblízek, Michal; Lomas, Michael W; Mincer, Tracy J; Moore, Lisa R; Moutin, Thierry; Rappé, Michael S; Webb, Eric A

    2009-03-05

    Phosphorus is an obligate requirement for the growth of all organisms; major biochemical reservoirs of phosphorus in marine plankton include nucleic acids and phospholipids. However, eukaryotic phytoplankton and cyanobacteria (that is, 'phytoplankton' collectively) have the ability to decrease their cellular phosphorus content when phosphorus in their environment is scarce. The biochemical mechanisms that allow phytoplankton to limit their phosphorus demand and still maintain growth are largely unknown. Here we show that phytoplankton, in regions of oligotrophic ocean where phosphate is scarce, reduce their cellular phosphorus requirements by substituting non-phosphorus membrane lipids for phospholipids. In the Sargasso Sea, where phosphate concentrations were less than 10 nmol l-1, we found that only 1.3 +/- 0.6% of phosphate uptake was used for phospholipid synthesis; in contrast, in the South Pacific subtropical gyre, where phosphate was greater than 100 nmol l-1, plankton used 17 6% (ref. 6). Examination of the planktonic membrane lipids at these two locations showed that classes of sulphur- and nitrogen-containing membrane lipids, which are devoid of phosphorus, were more abundant in the Sargasso Sea than in the South Pacific. Furthermore, these non-phosphorus, 'substitute lipids' were dominant in phosphorus-limited cultures of all of the phytoplankton species we examined. In contrast, the marine heterotrophic bacteria we examined contained no substitute lipids and only phospholipids. Thus heterotrophic bacteria, which compete with phytoplankton for nutrients in oligotrophic regions like the Sargasso Sea, appear to have a biochemical phosphorus requirement that phytoplankton avoid by using substitute lipids. Our results suggest that phospholipid substitutions are fundamental biochemical mechanisms that allow phytoplankton to maintain growth in the face of phosphorus limitation.

  12. On the Endogeneity of the Mean-Variance Efficient Frontier.

    ERIC Educational Resources Information Center

    Somerville, R. A.; O'Connell, Paul G. J.

    2002-01-01

    Explains that the endogeneity of the efficient frontier in the mean-variance model of portfolio selection is commonly obscured in portfolio selection literature and in widely used textbooks. Demonstrates endogeneity and discusses the impact of parameter changes on the mean-variance efficient frontier and on the beta coefficients of individual…

  13. Alleviation of Waterlogging Damage in Winter Rape by Uniconazole Application: Effects on Enzyme Activity, Lipid Peroxidation, and Membrane Integrity.

    PubMed

    Leul; Zhou

    1999-08-01

    Oilseed rape (Brassica napus L.) seedlings treated with uniconazole [(E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(1,2,4-triazol-l-yl)-l-penten-3-ol] were transplanted at the five-leaf stage into specially designed experimental containers and then exposed to waterlogging for 3 weeks. After waterlogging stress, uniconazole-treated seedlings had significantly higher activities of superoxide dismutase, catalase, and peroxidase enzymes and endogenous free proline content at both the seedling and flowering stages. Uniconazole plus waterlogging-treated plants had a significantly higher content of unsaturated fatty acids than the waterlogged plants. There was a parallel increase in the lipid peroxidation level and electrolyte leakage rate from the leaves of waterlogged plants. Leaves from uniconazole plus waterlogging-treated plants had a significantly lower lipid peroxidation level and electrolyte leakage rate compared with waterlogged plants at both the seedling and flowering stages. Pretreatment of seedlings with uniconazole could effectively delay stress-induced degradation of chlorophyll and reduction of root oxidizability. Uniconazole did not alter the soluble sugar content of leaves and stems, after waterlogging of seedlings. Uniconazole improved waterlogged plant performance and increased seed yield, possibly because of improved antioxidation defense mechanisms, and it retarded lipid peroxidation and membrane deterioration of plants.Key Words. Waterlogging-Uniconazole-Brassica napus L.-Enzymes-Lipid peroxidation-Membrane integrityhttp://link.springer-ny.com/link/service/journals/00344/bibs/18n1p9.html

  14. Evidence for a structural role for acid-fast lipids in oocyst walls of Cryptosporidium, Toxoplasma, and Eimeria.

    PubMed

    Bushkin, G Guy; Motari, Edwin; Carpentieri, Andrea; Dubey, Jitender P; Costello, Catherine E; Robbins, Phillips W; Samuelson, John

    2013-09-03

    Coccidia are protozoan parasites that cause significant human disease and are of major agricultural importance. Cryptosporidium spp. cause diarrhea in humans and animals, while Toxoplasma causes disseminated infections in fetuses and untreated AIDS patients. Eimeria is a major pathogen of commercial chickens. Oocysts, which are the infectious form of Cryptosporidium and Eimeria and one of two infectious forms of Toxoplasma (the other is tissue cysts in undercooked meat), have a multilayered wall. Recently we showed that the inner layer of the oocyst walls of Toxoplasma and Eimeria is a porous scaffold of fibers of β-1,3-glucan, which are also present in fungal walls but are absent from Cryptosporidium oocyst walls. Here we present evidence for a structural role for lipids in the oocyst walls of Cryptosporidium, Toxoplasma, and Eimeria. Briefly, oocyst walls of each organism label with acid-fast stains that bind to lipids in the walls of mycobacteria. Polyketide synthases similar to those that make mycobacterial wall lipids are abundant in oocysts of Toxoplasma and Eimeria and are predicted in Cryptosporidium. The outer layer of oocyst wall of Eimeria and the entire oocyst wall of Cryptosporidium are dissolved by organic solvents. Oocyst wall lipids are complex mixtures of triglycerides, some of which contain polyhydroxy fatty acyl chains like those present in plant cutin or elongated fatty acyl chains like mycolic acids. We propose a two-layered model of the oocyst wall (glucan and acid-fast lipids) that resembles the two-layered walls of mycobacteria (peptidoglycan and acid-fast lipids) and plants (cellulose and cutin). Oocysts, which are essential for the fecal-oral spread of coccidia, have a wall that is thought responsible for their survival in the environment and for their transit through the stomach and small intestine. While oocyst walls of Toxoplasma and Eimeria are strengthened by a porous scaffold of fibrils of β-1,3-glucan and by proteins cross

  15. Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells.

    PubMed

    Morel, Etienne; Ghezzal, Sara; Lucchi, Géraldine; Truntzer, Caroline; Pais de Barros, Jean-Paul; Simon-Plas, Françoise; Demignot, Sylvie; Mineo, Chieko; Shaul, Philip W; Leturque, Armelle; Rousset, Monique; Carrière, Véronique

    2018-02-01

    Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Characterization of 3D Voronoi Tessellation Nearest Neighbor Lipid Shells Provides Atomistic Lipid Disruption Profile of Protein Containing Lipid Membranes

    PubMed Central

    Cheng, Sara Y.; Duong, Hai V.; Compton, Campbell; Vaughn, Mark W.; Nguyen, Hoa; Cheng, Kwan H.

    2015-01-01

    Quantifying protein-induced lipid disruptions at the atomistic level is a challenging problem in membrane biophysics. Here we propose a novel 3D Voronoi tessellation nearest-atom-neighbor shell method to classify and characterize lipid domains into discrete concentric lipid shells surrounding membrane proteins in structurally heterogeneous lipid membranes. This method needs only the coordinates of the system and is independent of force fields and simulation conditions. As a proof-of-principle, we use this multiple lipid shell method to analyze the lipid disruption profiles of three simulated membrane systems: phosphatidylcholine, phosphatidylcholine/cholesterol, and beta-amyloid/phosphatidylcholine/cholesterol. We observed different atomic volume disruption mechanisms due to cholesterol and beta-amyloid Additionally, several lipid fractional groups and lipid-interfacial water did not converge to their control values with increasing distance or shell order from the protein. This volume divergent behavior was confirmed by bilayer thickness and chain orientational order calculations. Our method can also be used to analyze high-resolution structural experimental data. PMID:25637891

  17. Lipid-binding proteins modulate ligand-dependent trans-activation by peroxisome proliferator-activated receptors and localize to the nucleus as well as the cytoplasm.

    PubMed

    Helledie, T; Antonius, M; Sorensen, R V; Hertzel, A V; Bernlohr, D A; Kølvraa, S; Kristiansen, K; Mandrup, S

    2000-11-01

    Peroxisome proliferator-activated receptors (PPARs) are activated by a variety of fatty acids, eicosanoids, and hypolipidemic and insulin-sensitizing drugs. Many of these compounds bind avidly to members of a family of small lipid-binding proteins, the fatty acid-binding proteins (FABPs). Fatty acids are activated to CoA esters, which bind with high affinity to the acyl-CoA-binding protein (ACBP). Thus, the availability of known and potential PPAR ligands may be regulated by lipid-binding proteins. In this report we show by transient transfection of CV-1 cells that coexpression of ACBP and adipocyte lipid-binding protein (ALBP) exerts a ligand- and PPAR subtype-specific attenuation of PPAR-mediated trans-activation, suggesting that lipid-binding proteins, when expressed at high levels, may function as negative regulators of PPAR activation by certain ligands. Expression of ACBP, ALBP, and keratinocyte lipid-binding protein (KLBP) is induced during adipocyte differentiation, a process during which PPARgamma plays a prominent role. We present evidence that endogenous ACBP, ALBP, and KLBP not only localize to the cytoplasm but also exhibit a prominent nuclear localization in 3T3-L1 adipocytes. In addition, forced expression of ACBP, ALBP, and KLBP in CV-1 cells resulted in a substantial accumulation of all three proteins in the nucleus. These results suggest that lipid-binding proteins, contrary to the general assumption, may exert their action in the nucleus as well as in the cytoplasm.

  18. Lipid Metabolism and Lipid Droplets in Pancreatic Cancer and Stellate Cells

    PubMed Central

    Sunami, Yoshiaki; Rebelo, Artur; Kleeff, Jörg

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second deadliest cancer by 2030, and the overall 5-year survival rate is currently less than 7%. Cancer cells frequently exhibit reprogramming of their metabolic activity. It is increasingly recognized that aberrant de novo lipid synthesis and reprogrammed lipid metabolism are both associated with the development and progression of various cancers, including pancreatic cancer. In this review, the current knowledge about lipid metabolism and lipid droplets in pancreatic cancer is discussed. In the first part, molecular mechanisms of lipid metabolism and roles of enzymes involved in lipid metabolism which are relevant for pancreatic cancer research are presented. Further, preclinical studies and clinical trials with drugs/inhibitors targeting cancer metabolic systems in cancer are summarized. An increase of our knowledge in lipid metabolism in pancreatic cancer cells and in tumor stroma is important for developing novel strategies of future individualized therapies of pancreatic cancer. PMID:29295482

  19. Hepatic gene expression involved in glucose and lipid metabolism in transition cows: effects of fat mobilization during early lactation in relation to milk performance and metabolic changes.

    PubMed

    Weber, C; Hametner, C; Tuchscherer, A; Losand, B; Kanitz, E; Otten, W; Sauerwein, H; Bruckmaier, R M; Becker, F; Kanitz, W; Hammon, H M

    2013-09-01

    Insufficient feed intake during early lactation results in elevated body fat mobilization to meet energy demands for milk production. Hepatic energy metabolism is involved by increasing endogenous glucose production and hepatic glucose output for milk synthesis and by adaptation of postcalving fuel oxidation. Given that cows differ in their degree of fat mobilization around parturition, indicated by variable total liver fat concentration (LFC), the study investigated the influence of peripartum fat mobilization on hepatic gene expression involved in gluconeogenesis, fatty acid oxidation, ketogenesis, and cholesterol synthesis, as well as transcriptional factors referring to energy metabolism. German Holstein cows were grouped according to mean total LFC on d 1, 14, and 28 after parturition as low [<200mg of total fat/g of dry matter (DM); n=10], medium (200-300 mg of total fat/g of DM; n=10), and high (>300 mg of total fat/g of DM; n=7), indicating fat mobilization during early lactation. Cows were fed total mixed rations ad libitum and held under equal conditions. Liver biopsies were taken at d 56 and 15 before and d 1, 14, 28, and 49 after parturition to measure mRNA abundances of pyruvate carboxylase (PC); phosphoenolpyruvate carboxykinase; glucose-6-phosphatase; propionyl-coenzyme A (CoA) carboxylase α; carnitine palmitoyl-transferase 1A (CPT1A); acyl-CoA synthetase, long chain 1 (ASCL1); acyl-CoA dehydrogenase, very long chain; 3-hydroxy-3-methylglutaryl-CoA synthase 1 and 2; sterol regulatory element-binding factor 1; and peroxisome proliferator-activated factor α. Total LFC postpartum differed greatly among cows, and the mRNA abundance of most enzymes and transcription factors changed with time during the experimental period. Abundance of PC mRNA increased at parturition to a greater extent in high- and medium-LFC groups than in the low-LFC group. Significant LFC × time interactions for ACSL1 and CPT1A during the experimental period indicated variable

  20. Space-based measurements of elemental abundances and their relation to solar abundances

    NASA Technical Reports Server (NTRS)

    Coplan, M. A.; Ogilvie, K. W.; Bochsler, P.; Geiss, J.

    1990-01-01

    The Ion Composition Instrument (ICI) aboard the ISEE-3/ICE spacecraft was in the solar wind continuously from August 1978 to December 1982. The results made it possible to establish long-term average solar wind abundance values for helium, oxygen, neon, silicon, and iron. The Charge-Energy-Mass instrument aboard the CCE spacecraft of the AMPTE mission has measured the abundance of these elements in the magnetosheath and has also added carbon, nitrogen, magnesium, and sulfur to the list. There is strong evidence that these magnetosheath abundances are representative of the solar wind. Other sources of solar wind abundances are Solar Energetic Particle experiments and Apollo lunar foils. When comparing the abundances from all of these sources with photospheric abundances, it is clear that helium is depleted in the solar wind while silicon and iron are enhanced. Solar wind abundances for carbon, nitrogen, oxygen, and neon correlate well with the photospheric values. The incorporation of minor ions into the solar wind appears to depend upon both the ionization times for the elements and the Coulomb drag exerted by the outflowing proton flux.

  1. Increased plasma lipid levels exacerbate muscle pathology in the mdx mouse model of Duchenne muscular dystrophy.

    PubMed

    Milad, Nadia; White, Zoe; Tehrani, Arash Y; Sellers, Stephanie; Rossi, Fabio M V; Bernatchez, Pascal

    2017-09-12

    primary contributors to human DMD severity and that the notoriously mild phenotype of mdx mice might be attributable in part to their endogenously low plasma lipid profiles. Hence, DMD patients may benefit from lipid-lowering and vascular-targeted therapies.

  2. Using RNA as a tool to modify lipid nanoparticles

    NASA Astrophysics Data System (ADS)

    Wilner, Samantha E.

    Lipid nanoparticles (LNPs) provide an attractive option for therapeutic applications because they can self-assemble and carry a diverse set of cargoes ranging from hydrophobic drugs to small interfering RNA (siRNA). Liposomes and micelles represent two classes of LNPs that have been developed for medicinal purposes; however, active targeting of LNPs to specific tissues and LNP stability in vivo remain significant challenges. We have exploited the structural characteristics and targeting ability of nucleic acids to address these obstacles. Specifically, we have introduced short nucleic acid targeting species, called aptamers, to the surface of stable nucleic acid lipid particles (SNALPs), a subset of liposomes used in siRNA delivery. In this manner, we have actively targeted SNALPs to cancer cells that overexpress the transferrin receptor (TfR). HeLa cells expressing enhanced green fluorescent protein (EGFP) were treated with SNALPs bearing an antiTfR aptamer (C2) that was identified in our lab. C2-conjugated SNALPs showed increased levels of uptake by cells by flow cytometry. More importantly, the enhanced uptake by C2-conjugated SNALPs translated to an increased level of gene knockdown when SNALPs were loaded with anti-EGFP siRNA or anti-Lamin NC siRNA. Expression of EGFP and Lamin NC decreased, respectively. These preliminary studies illustrate that aptamer-conjugated SNALPs can be designed to knock down both endogenous and exogenous genes in cancer cells with high specificity. We have also used nucleic acids to stabilize lipid micelles by introducing short quadruplex forming oligonucleotide sequences at the lipid headgroup. Micelle formation was confirmed via dynamic light scattering, transmission electron microscopy, and small angle X-ray scattering. Micelle stability was assessed using NMR and by a FRET-based assay in the presence of serum proteins. Quadruplex-stabilized micelles demonstrated enhanced stability suggesting that alterations to oligonucleotide

  3. Anandamide and analogous endocannabinoids: a lipid self-assembly study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sagnella, Sharon M.; Conn, Charlotte E.; Krodkiewska, Irena

    Anandamide, the endogenous agonist of the cannabinoid receptors, has been widely studied for its interesting biological and medicinal properties and is recognized as a highly significant lipid signaling molecule within the nervous system. Few studies have, however, examined the effect of the physical conformation of anandamide on its function. The study presented herein has focused on characterizing the self-assembly behaviour of anandamide and four other endocannabinoid analogues of anandamide, viz., 2-arachidonyl glycerol, arachidonyl dopamine, 2-arachidonyl glycerol ether (noladin ether), and o-arachidonyl ethanolamide (virodhamine). Molecular modeling of the five endocannabinoid lipids indicates that the highly unsaturated arachidonyl chain has a preferencemore » for a U or J shaped conformation. Thermal phase studies of the neat amphiphiles showed that a glass transition was observed for all of the endocannabinoids at {approx} -110 C with the exception of anandamide, with a second glass transition occurring for 2-arachidonyl glycerol, 2-arachidonyl glycerol ether, and virodhamine (-86 C, -95 C, -46 C respectively). Both anandamide and arachidonyl dopamine displayed a crystal-isotropic melting point (-4.8 and -20.4 C respectively), while a liquid crystal-isotropic melting transition was seen for 2-arachidonyl glycerol (-40.7 C) and 2-arachidonyl glycerol ether (-71.2 C). No additional transitions were observed for virodhamine. Small angle X-ray scattering and cross polarized optical microscopy studies as a function of temperature indicated that in the presence of excess water, both 2-arachidonyl glycerol and anandamide form co-existing Q{sub II}{sup G} (gyroid) and Q{sub II}{sup D} (diamond) bicontinuous cubic phases from 0 C to 20 C, which are kinetically stable over a period of weeks but may not represent true thermodynamic equilibrium. Similarly, 2-arachidonyl glycerol ether acquired an inverse hexagonal (HII) phase in excess water from 0 C to 40 C, while

  4. Correlation of circular RNA abundance with proliferation – exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues

    PubMed Central

    Bachmayr-Heyda, Anna; Reiner, Agnes T.; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Bachleitner-Hofmann, Thomas; Mesteri, Ildiko; Grunt, Thomas W.; Zeillinger, Robert; Pils, Dietmar

    2015-01-01

    Circular RNAs are a recently (re-)discovered abundant RNA species with presumed function as miRNA sponges, thus part of the competing endogenous RNA network. We analysed the expression of circular and linear RNAs and proliferation in matched normal colon mucosa and tumour tissues. We predicted >1,800 circular RNAs and proved the existence of five randomly chosen examples using RT-qPCR. Interestingly, the ratio of circular to linear RNA isoforms was always lower in tumour compared to normal colon samples and even lower in colorectal cancer cell lines. Furthermore, this ratio correlated negatively with the proliferation index. The correlation of global circular RNA abundance (the circRNA index) and proliferation was validated in a non-cancerous proliferative disease, idiopathic pulmonary fibrosis, ovarian cancer cells compared to cultured normal ovarian epithelial cells, and 13 normal human tissues. We are the first to report a global reduction of circular RNA abundance in colorectal cancer cell lines and cancer compared to normal tissues and discovered a negative correlation of global circular RNA abundance and proliferation. This negative correlation seems to be a general principle in human tissues as validated with three different settings. Finally, we present a simple model how circular RNAs could accumulate in non-proliferating cells. PMID:25624062

  5. Do Endogenous and Exogenous Action Control Compete for Perception?

    ERIC Educational Resources Information Center

    Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

    2012-01-01

    Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the…

  6. Quantum therapy in correction of the lipidic metabolism at acute pancreatitis

    NASA Astrophysics Data System (ADS)

    Anaskin, S. G.; Vlasov, A. P.; Spirina, M. A.; Vlasova, T. I.; Muratova, T. A.; Korniletsky, I. D.; Geraskin, V. S.

    2017-01-01

    Attempt to establish efficiency of laser therapy in correction of a lipid metabolism at patients with acute pancreatitis was the purpose of work. There were clinical laboratory researches of 48 patients with acute heavy pancreatitis. To the first clinical group (comparison) standard therapy was carried out. To patients of the second clinical group (main) in addition to basic therapy within 10 days daily sessions of laser therapy by the device "Matrix" were held later. Radiation with the wavelength of 635 nanometers, 2 MW was used. Percutaneous laser radiation of blood was carried out to projections of a cubital vein within 30 minutes daily. Inclusion of laser therapy in complex treatment of patients with pancreatitis led to more significant positive dynamics. Reduction of weight of endotoxemia in the main group is set that was verified by decrease in level of both hydrophilic, and hydrophobic toxins. The analysis of the data obtained as a result of research in the main group revealed decrease in concentration of products of free radical oxidation of lipids in comparison with group of comparison for 12,1 - 17,3% of % (p. <. 0,05). Laser radiation of blood as a part of complex treatment led to reliable inhibition of activity of enzymes of phospholipase system in blood plasma, in particular activity of a phospholipase of A2 fell for 13,2 - 34,4% (p <0,05). Thus, inclusion of laser therapy in structure of complex treatment of sharp pancreatitis allowed to reduce significantly expressiveness of endogenous intoxication, intensity of processes of free radical oxidation of membrane lipids and activity of phospholipase systems.

  7. Lipid-converter, a framework for lipid manipulations in molecular dynamics simulations

    PubMed Central

    Larsson, Per; Kasson, Peter M.

    2014-01-01

    Construction of lipid membrane and membrane protein systems for molecular dynamics simulations can be a challenging process. In addition, there are few available tools to extend existing studies by repeating simulations using other force fields and lipid compositions. To facilitate this, we introduce lipidconverter, a modular Python framework for exchanging force fields and lipid composition in coordinate files obtained from simulations. Force fields and lipids are specified by simple text files, making it easy to introduce support for additional force fields and lipids. The converter produces simulation input files that can be used for structural relaxation of the new membranes. PMID:25081234

  8. Do endogenous and exogenous action control compete for perception?

    PubMed

    Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

    2012-04-01

    Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the endogenous representation has to be deactivated first to give way to the exogenous system. Here we show that interference of endogenous and exogenous action control is not limited to motor-related aspects but also affects the perception of action-related stimuli. Participants associated two actions with contingent sensory effects in learning blocks. In subsequent test blocks, preparing one of these actions specifically impaired responding to the associated effect in an exogenous speeded detection task, yielding a blindness-like effect for arbitrary, learned action effects. In accordance with the theory of event coding, this finding suggests that action planning influences perception even in the absence of any physical similarities between action and to-be-perceived stimuli.

  9. High muscle lipid content in obesity is not due to enhanced activation of key triglyceride esterification enzymes or the suppression of lipolytic proteins

    PubMed Central

    Li, Minghua; Paran, Christopher; Wolins, Nathan E.

    2011-01-01

    The mechanisms underlying alterations in muscle lipid metabolism in obesity are poorly understood. The primary aim of this study was to compare the abundance and/or activities of key proteins that regulate intramyocellular triglyceride (IMTG) concentration in the skeletal muscle obtained from obese (OB; n = 8, BMI 38 ± 1 kg/m2) and nonobese (NOB; n = 9, BMI 23 ± 1 kg/m2) women. IMTG concentration was nearly twofold greater in OB vs. NOB subjects (75 ± 15 vs. 40 ± 8 μmol/g dry wt, P < 0.05). In contrast, the activity and protein abundance of key enzymes that regulate the esterification of IMTG (i.e., glycerol-3-phosphate acyltransferase and diacylglycerol acyltransferase) were not elevated. We also found no differences between groups in muscle adipose triglyceride lipase and hormone-sensitive lipase (HSL) protein abundance and no differences in phosphorylation of specific sites known to affect HSL activity. However, we did find the elevated IMTG in obesity to be accompanied by a greater abundance of the fatty acid transporter FAT/CD36 in the membrane fraction of muscle from OB vs. NOB subjects (P < 0.05), suggestive of an elevated fatty acid transport capacity. Additionally, protein abundance of the lipid-trafficking protein perilipin 3 was lower (P < 0.05) in muscle from OB vs. NOB when expressed relative to IMTG content. Our findings indicate that the elevated IMTG content found in obese women was not due to an upregulation of key lipogenic proteins or to the suppression of lipolytic proteins. The impact of a low perilipin protein abundance relative to the amount of IMTG in obesity remains to be clarified. PMID:21285405

  10. Lipid antigens in immunity

    PubMed Central

    Dowds, C. Marie; Kornell, Sabin-Christin

    2014-01-01

    Lipids are not only a central part of human metabolism but also play diverse and critical roles in the immune system. As such, they can act as ligands of lipid-activated nuclear receptors, control inflammatory signaling through bioactive lipids such as prostaglandins, leukotrienes, lipoxins, resolvins, and protectins, and modulate immunity as intracellular phospholipid- or sphingolipid-derived signaling mediators. In addition, lipids can serve as antigens and regulate immunity through the activation of lipid-reactive T cells, which is the topic of this review. We will provide an overview of the mechanisms of lipid antigen presentation, the biology of lipid-reactive T cells, and their contribution to immunity. PMID:23999493

  11. Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins.

    PubMed

    Singh, Abhishek K; Aryal, Binod; Zhang, Xinbo; Fan, Yuhua; Price, Nathan L; Suárez, Yajaira; Fernández-Hernando, Carlos

    2017-11-29

    Alterations in lipoprotein metabolism enhance the risk of cardiometabolic disorders including type-2 diabetes and atherosclerosis, the leading cause of death in Western societies. While the transcriptional regulation of lipid metabolism has been well characterized, recent studies have uncovered the importance of microRNAs (miRNAs), long-non-coding RNAs (lncRNAs) and RNA binding proteins (RBP) in regulating the expression of lipid-related genes at the posttranscriptional level. Work from several groups has identified a number of miRNAs, including miR-33, miR-122 and miR-148a, that play a prominent role in controlling cholesterol homeostasis and lipoprotein metabolism. Importantly, dysregulation of miRNA expression has been associated with dyslipidemia, suggesting that manipulating the expression of these miRNAs could be a useful therapeutic approach to ameliorate cardiovascular disease (CVD). The role of lncRNAs in regulating lipid metabolism has recently emerged and several groups have demonstrated their regulation of lipoprotein metabolism. However, given the high abundance of lncRNAs and the poor-genetic conservation between species, much work will be needed to elucidate the specific role of lncRNAs in controlling lipoprotein metabolism. In this review article, we summarize recent findings in the field and highlight the specific contribution of lncRNAs and RBPs in regulating lipid metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Endogenous Opiates and Behavior: 2015.

    PubMed

    Bodnar, Richard J

    2017-02-01

    This paper is the thirty-eighth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2015 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia, stress and social status, tolerance and dependence, learning and memory, eating and drinking, drug abuse and alcohol, sexual activity and hormones, pregnancy, development and endocrinology, mental illness and mood, seizures and neurologic disorders, electrical-related activity and neurophysiology, general activity and locomotion, gastrointestinal, renal and hepatic functions, cardiovascular responses, respiration and thermoregulation, and immunological responses. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Endogenous opiates and behavior: 2013.

    PubMed

    Bodnar, Richard J

    2014-12-01

    This paper is the thirty-sixth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2013 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia; stress and social status; tolerance and dependence; learning and memory; eating and drinking; alcohol and drugs of abuse; sexual activity and hormones, pregnancy, development and endocrinology; mental illness and mood; seizures and neurologic disorders; electrical-related activity and neurophysiology; general activity and locomotion; gastrointestinal, renal and hepatic functions; cardiovascular responses; respiration and thermoregulation; and immunological responses. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Endogenous opiates and behavior: 2004.

    PubMed

    Bodnar, Richard J; Klein, Gad E

    2005-12-01

    This paper is the 27th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning over 30 years of research. It summarizes papers published during 2004 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia; stress and social status; tolerance and dependence; learning and memory; eating and drinking; alcohol and drugs of abuse; sexual activity and hormones, pregnancy, development and endocrinology; mental illness and mood; seizures and neurologic disorders; electrical-related activity and neurophysiology; general activity and locomotion; gastrointestinal, renal and hepatic functions; cardiovascular responses; respiration and thermoregulation; and immunological responses.

  15. High fat diet-induced modifications in membrane lipid and mitochondrial-membrane protein signatures precede the development of hepatic insulin resistance in mice

    PubMed Central

    Kahle, M.; Schäfer, A.; Seelig, A.; Schultheiß, J.; Wu, M.; Aichler, M.; Leonhardt, J.; Rathkolb, B.; Rozman, J.; Sarioglu, H.; Hauck, S.M.; Ueffing, M.; Wolf, E.; Kastenmueller, G.; Adamski, J.; Walch, A.; Hrabé de Angelis, M.; Neschen, S.

    2014-01-01

    Objective Excess lipid intake has been implicated in the pathophysiology of hepatosteatosis and hepatic insulin resistance. Lipids constitute approximately 50% of the cell membrane mass, define membrane properties, and create microenvironments for membrane-proteins. In this study we aimed to resolve temporal alterations in membrane metabolite and protein signatures during high-fat diet (HF)-mediated development of hepatic insulin resistance. Methods We induced hepatosteatosis by feeding C3HeB/FeJ male mice an HF enriched with long-chain polyunsaturated C18:2n6 fatty acids for 7, 14, or 21 days. Longitudinal changes in hepatic insulin sensitivity were assessed via the euglycemic-hyperinsulinemic clamp, in membrane lipids via t-metabolomics- and membrane proteins via quantitative proteomics-analyses, and in hepatocyte morphology via electron microscopy. Data were compared to those of age- and litter-matched controls maintained on a low-fat diet. Results Excess long-chain polyunsaturated C18:2n6 intake for 7 days did not compromise hepatic insulin sensitivity, however, induced hepatosteatosis and modified major membrane lipid constituent signatures in liver, e.g. increased total unsaturated, long-chain fatty acid-containing acyl-carnitine or membrane-associated diacylglycerol moieties and decreased total short-chain acyl-carnitines, glycerophosphocholines, lysophosphatidylcholines, or sphingolipids. Hepatic insulin sensitivity tended to decrease within 14 days HF-exposure. Overt hepatic insulin resistance developed until day 21 of HF-intervention and was accompanied by morphological mitochondrial abnormalities and indications for oxidative stress in liver. HF-feeding progressively decreased the abundance of protein-components of all mitochondrial respiratory chain complexes, inner and outer mitochondrial membrane substrate transporters independent from the hepatocellular mitochondrial volume in liver. Conclusions We assume HF-induced modifications in membrane lipid

  16. Biogenesis of the multifunctional lipid droplet: Lipids, proteins, and sites

    PubMed Central

    Gross, Steven P.

    2014-01-01

    Lipid droplets (LDs) are ubiquitous dynamic organelles that store and supply lipids in all eukaryotic and some prokaryotic cells for energy metabolism, membrane synthesis, and production of essential lipid-derived molecules. Interest in the organelle’s cell biology has exponentially increased over the last decade due to the link between LDs and prevalent human diseases and the discovery of new and unexpected functions of LDs. As a result, there has been significant recent progress toward understanding where and how LDs are formed, and the specific lipid pathways that coordinate LD biogenesis. PMID:24590170

  17. Body macronutrient composition is predicted by lipid and not protein content of the diet.

    PubMed

    Moatt, Joshua P; Hambly, Catherine; Heap, Elizabeth; Kramer, Anna; Moon, Fiona; Speakman, John R; Walling, Craig A

    2017-12-01

    Diet is an important determinant of fitness-related traits including growth, reproduction, and survival. Recent work has suggested that variation in protein:lipid ratio and particularly the amount of protein in the diet is a key nutritional parameter. However, the traits that mediate the link between dietary macronutrient ratio and fitness-related traits are less well understood. An obvious candidate is body composition, given its well-known link to health. Here, we investigate the relationship between dietary and body macronutrient composition using a first-generation laboratory population of a freshwater fish, the three-spine stickleback ( Gasterosteus aculeatus ). Carbohydrate is relatively unimportant in the diet of predatory fish, facilitating the exploration of how dietary protein-to-lipid ratio affects their relative deposition in the body. We find a significant effect of lipid intake, rather than protein, on body protein:lipid ratio. Importantly, this was not a result of absorbing macronutrients in relation to their relative abundance in the diet, as the carcass protein:lipid ratios differed from those of the diets, with ratios usually lower in the body than in the diet. This indicates that individuals can moderate their utilization, or uptake, of ingested macronutrients to reach a target balance within the body. We found no effect of diet on swimming endurance, activity, or testes size. However, there was an effect of weight on testes size, with larger males having larger testes. Our results provide evidence for the adjustment of body protein:lipid ratio away from that of the diet. As dietary lipid intake was the key determinant of body composition, we suggest this occurs via metabolism of excess protein, which conflicts with the predictions of the protein leverage hypothesis. These results could imply that the conversion and excretion of protein is one of the causes of the survival costs associated with high-protein diets.

  18. Nitrooleic Acid Attenuates Lipid Metabolic Disorders and Liver Steatosis in DOCA-Salt Hypertensive Mice

    PubMed Central

    Sun, Jing; Jia, Zhanjun; Yang, Tianxin; Xu, Liang; Zhao, Bing; Yu, Kezhou; Wang, Rong

    2015-01-01

    Nitrooleic acid (OA-NO2) is endogenous ligands for peroxisome proliferator-activated receptors. The present study was aimed at investigating the beneficial effects of OA-NO2 on the lipid metabolism and liver steatosis in deoxycorticosterone acetate- (DOCA-) salt induced hypertensive mice model. Male C57BL/6 mice were divided to receive DOCA-salt plus OA-NO2 or DOCA-salt plus vehicle and another group received neither DOCA-salt nor OA-NO2 (control group). After 3-week treatment with DOCA-salt plus 1% sodium chloride in drinking fluid, the hypertension was noted; however, OA-NO2 had no effect on the hypertension. In DOCA-salt treated mice, the plasma triglyceride and total cholesterol levels were significantly increased compared to control mice, and pretreatment with OA-NO2 significantly reduced these parameters. Further, the histopathology of liver exhibited more lipid distribution together with more serious micro- and macrovesicular steatosis after DOCA-salt treatment and that was consistent with liver tissue triglyceride and nonesterified fatty acids (NEFA) content. The mice pretreated with OA-NO2 showed reduced liver damage accompanied with low liver lipid content. Moreover, the liver TBARS, together with the expressions of gp91phox and p47phox, were parallelly decreased. These findings indicated that OA-NO2 had the protective effect on liver injury against DOCA-salt administration and the beneficial effect could be attributed to its antihyperlipidemic activities. PMID:25861250

  19. Nitrooleic Acid Attenuates Lipid Metabolic Disorders and Liver Steatosis in DOCA-Salt Hypertensive Mice.

    PubMed

    Wang, Haiping; Sun, Jing; Jia, Zhanjun; Yang, Tianxin; Xu, Liang; Zhao, Bing; Yu, Kezhou; Wang, Rong

    2015-01-01

    Nitrooleic acid (OA-NO2) is endogenous ligands for peroxisome proliferator-activated receptors. The present study was aimed at investigating the beneficial effects of OA-NO2 on the lipid metabolism and liver steatosis in deoxycorticosterone acetate- (DOCA-) salt induced hypertensive mice model. Male C57BL/6 mice were divided to receive DOCA-salt plus OA-NO2 or DOCA-salt plus vehicle and another group received neither DOCA-salt nor OA-NO2 (control group). After 3-week treatment with DOCA-salt plus 1% sodium chloride in drinking fluid, the hypertension was noted; however, OA-NO2 had no effect on the hypertension. In DOCA-salt treated mice, the plasma triglyceride and total cholesterol levels were significantly increased compared to control mice, and pretreatment with OA-NO2 significantly reduced these parameters. Further, the histopathology of liver exhibited more lipid distribution together with more serious micro- and macrovesicular steatosis after DOCA-salt treatment and that was consistent with liver tissue triglyceride and nonesterified fatty acids (NEFA) content. The mice pretreated with OA-NO2 showed reduced liver damage accompanied with low liver lipid content. Moreover, the liver TBARS, together with the expressions of gp91phox and p47phox, were parallelly decreased. These findings indicated that OA-NO2 had the protective effect on liver injury against DOCA-salt administration and the beneficial effect could be attributed to its antihyperlipidemic activities.

  20. The lipid response of aerobic marine methanotroph communities under changing environmental conditions.

    NASA Astrophysics Data System (ADS)

    Rush, D.; Villanueva, L.; van der Meer, M.; S Sinninghe Damsté, J.

    2017-12-01

    Methane (CH4) originating from marine environments accounts for a significant amount of atmospheric greenhouse gas. Aerobic methanotrophs, which convert CH4 to CO­2, are responsible for quenching a part of this methane before its release. Modern-day climate projections show a rapid shift towards a warmer, more acidic ocean. How do these important methanotrophic communities respond to such changes to their environment? Here, we present the results of microcosm experiments from three marine regions influenced by CH4. Particulate organic matter and sediment were collected from the Black Sea, the Baltic Sea, and the North Sea, at depths ideal for aerobic methanotroph communities at the time of sampling (e.g. oxic, in area of active CH4 release). These were incubated under different temperatures, pHs, and labelled 13CH4 concentrations. We monitored methane concentration in these microcosms as an indication of 13CH4 consumption by methanotrophs. Once the methane concentration was <0.1%, incubations were terminated. We will trace isotopically heavy 13C in the DNA and lipids of the organisms oxidising methane in order to elucidate which organisms are performing methane oxidation and whether they synthesize specific biomarker lipids. Particular attention will be paid to the abundances and diversity of bacteriohopanepolyol lipids, known methanotroph biomarkers. The ultimate goal of our investigation is to determine the effect changes in these environmental parameters have on aerobic methanotroph community structures and their lipid fingerprints. By establishing reliable biomarker lipids for aerobic methanotrophy at certain conditions, we will then be able to investigate the contribution of aerobic methanotrophy throughout Earth's history, especially at times when CH4 concentrations were higher than they are at present.

  1. Endogenous analgesic effect of pregabalin: A double-blind and randomized controlled trial.

    PubMed

    Sugimine, S; Saito, S; Araki, T; Yamamoto, K; Obata, H

    2017-07-01

    Conditioned pain modulation (CPM) is widely used to measure endogenous analgesia, and a recent study indicated that drugs that act on endogenous analgesia are more effective in individuals with lower CPM. Recent animal studies have indicated that pregabalin activates endogenous analgesia by stimulating the descending pain inhibitory system. The present study examined whether the analgesic effect of pregabalin is greater in individuals with lower original endogenous analgesia using CPM. Fifty-nine healthy subjects were randomly assigned to either a pregabalin group or a placebo group, and 50 of them completed the study. CPM was measured before and after pregabalin or placebo administration. The correlation of initial CPM to change in CPM was compared between the pregabalin and placebo groups. Initial CPM was significantly correlated with the change in CPM in the pregabalin group (r = -0.73, p < 0.0001) but not in the placebo group (p = 0.56) (difference in correlation coefficients between groups; p = 0.004). Furthermore, the initial CPM significantly affected the change in CPM in the pregabalin group but not in the placebo group (pregabalin group: adj R 2  = 0.51, p < 0.001, y = -0.54x + 2.98; placebo group: p = 0.56, significant difference in regression slopes; p = 0.015). These results indicate that pregabalin has a higher endogenous analgesic effect in individuals with lower original endogenous analgesia. The analgesic effect of pregabalin depends on the original endogenous analgesia status. Its effect on conditioned pain modulation (CPM) was stronger for subjects with lower original endogenous analgesia, suggesting that the mechanism of pregabalin involves the improvement of endogenous analgesia. © 2017 European Pain Federation - EFIC®.

  2. Saturation of SERCA's lipid annulus may protect against its thermal inactivation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fajardo, Val Andrew; Center for Bone and Muscle Health, Brock University, St. Catharines, ON; Department of Health Sciences, Brock University, St. Catharines, ON

    The sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase (SERCA) pumps are integral membrane proteins that catalyze the active transport of Ca{sup 2+} into the sarcoplasmic reticulum, thereby eliciting muscle relaxation. SERCA pumps are highly susceptible to oxidative damage, and cytoprotection of SERCA dampens thermal inactivation and is a viable therapeutic strategy in combating diseases where SERCA activity is impaired, such as muscular dystrophy. Here, we sought to determine whether increasing the percent of saturated fatty acids (SFA) within SERCA's lipid annulus through diet could protect SERCA pumps from thermal inactivation. Female Wistar rats were fed either a semi-purified control diet (AIN93G, 7% soybeanmore » oil by weight) or a modified AIN93G diet containing high SFA (20% lard by weight) for 17 weeks. Soleus muscles were extracted and SERCA lipid annulus and activity under thermal stress were analyzed. Our results show that SERCA's lipid annulus is abundant with short-chain (12–14 carbon) fatty acids, which corresponds well with SERCA's predicted bilayer thickness of 21 Å. Under control-fed conditions, SERCA's lipid annulus was already highly saturated (79%), and high-fat feeding did not increase this any further. High-fat feeding did not mitigate the reductions in SERCA activity seen with thermal stress; however, correlational analyses revealed significant and strong associations between % SFA and thermal stability of SERCA activity with greater %SFA being associated with lower thermal inactivation and greater % polyunsaturation and unsaturation index being associated with increased thermal inactivation. Altogether, these findings show that SERCA's lipid annulus may influence its susceptibility to oxidative damage, which could have implications in muscular dystrophy and age-related muscle wasting. - Highlights: • SERCA's lipid annulus in rat soleus was measured after immunoconcentration. • Short fatty acid chains surround SERCA and may ensure

  3. Endogenous network of firms and systemic risk

    NASA Astrophysics Data System (ADS)

    Ma, Qianting; He, Jianmin; Li, Shouwei

    2018-02-01

    We construct an endogenous network characterized by commercial credit relationships connecting the upstream and downstream firms. Simulation results indicate that the endogenous network model displays a scale-free property which exists in real-world firm systems. In terms of the network structure, with the expansion of the scale of network nodes, the systemic risk increases significantly, while the heterogeneities of network nodes have no effect on systemic risk. As for firm micro-behaviors, including the selection range of trading partners, actual output, labor requirement, price of intermediate products and employee salaries, increase of all these parameters will lead to higher systemic risk.

  4. [Mechanisms of leukocyte formation of endogenous pyrogen].

    PubMed

    Rybakina, E G; Sorokin, A V

    1982-06-01

    A study was made of the kinetics of endogenous pyrogen production by rabbit blood and exudate leukocytes and possible role played by the products of activated leukocytes in autoregulation of the process. It was established that accumulation of endogenous pyrogen in the cell precedes its release by stimulated cells. Then the processes of active pyrogen formation and release gel interdependent: pyrogen formed releases from the cell; the lowering of pyrogen concentration in the cell is accompanied by the decrease of its content in the medium. No stimulating effect of the products activated during leukocyte inflammation on pyrogen formation by blood leukocytes was discovered.

  5. Endogenous opioids encode relative taste preference.

    PubMed

    Taha, Sharif A; Norsted, Ebba; Lee, Lillian S; Lang, Penelope D; Lee, Brian S; Woolley, Joshua D; Fields, Howard L

    2006-08-01

    Endogenous opioid signaling contributes to the neural control of food intake. Opioid signaling is thought to regulate palatability, the reward value of a food item as determined by orosensory cues such as taste and texture. The reward value of a food reflects not only these sensory properties but also the relative value of competing food choices. In the present experiment, we used a consummatory contrast paradigm to manipulate the relative value of a sucrose solution for two groups of rats. Systemic injection of the nonspecific opioid antagonist naltrexone suppressed sucrose intake; for both groups, however, this suppression was selective, occurring only for the relatively more valuable sucrose solution. Our results indicate that endogenous opioid signaling contributes to the encoding of relative reward value.

  6. The Membrane and Lipids as Integral Participants in Signal Transduction: Lipid Signal Transduction for the Non-Lipid Biochemist

    ERIC Educational Resources Information Center

    Eyster, Kathleen M.

    2007-01-01

    Reviews of signal transduction have often focused on the cascades of protein kinases and protein phosphatases and their cytoplasmic substrates that become activated in response to extracellular signals. Lipids, lipid kinases, and lipid phosphatases have not received the same amount of attention as proteins in studies of signal transduction.…

  7. Lipids, lysosomes, and autophagy

    PubMed Central

    2016-01-01

    Lipids are essential components of a cell providing energy substrates for cellular processes, signaling intermediates, and building blocks for biological membranes. Lipids are constantly recycled and redistributed within a cell. Lysosomes play an important role in this recycling process that involves the recruitment of lipids to lysosomes via autophagy or endocytosis for their degradation by lysosomal hydrolases. The catabolites produced are redistributed to various cellular compartments to support basic cellular function. Several studies demonstrated a bidirectional relationship between lipids and lysosomes that regulate autophagy. While lysosomal degradation pathways regulate cellular lipid metabolism, lipids also regulate lysosome function and autophagy. In this review, we focus on this bidirectional relationship in the context of dietary lipids and provide an overview of recent evidence of how lipid-overload lipotoxicity, as observed in obesity and metabolic syndrome, impairs lysosomal function and autophagy that may eventually lead to cellular dysfunction or cell death. PMID:27330054

  8. Endogenous Serratia marcescens endophthalmitis.

    PubMed

    Shah, Sonya B; Bansal, Alok S; Rabinowitz, Michael P; Park, Carl; Bedrossian, Edward H; Eagle, Ralph C

    2014-01-01

    The purpose of this study was to describe a rare case of endogenous endophthalmitis associated with dental disease secondary to Serratia marcescens in an HIV-negative individual. Retrospective case report. A 50-year-old white man with a history of intravenous drug use presented with pain and decreased vision in his right eye. Slit-lamp examination showed a hazy cornea, hypopyon with fibrin in the anterior chamber, and elevated intraocular pressure. B-scan ultrasound showed vitritis and choroidal thickening. Computed tomography showed gingival inflammation and lucencies of several teeth. Blood and urine cultures were negative, and HIV testing was negative. Echocardiography was negative for vegetations. Intravitreal culture revealed S. marcescens. Despite intravitreal and systemic antibiotics, the patient's clinical situation rapidly deteriorated, and the eye was eviscerated. The patient underwent dental extraction and was subsequently discharged in stable condition. The first case of endogenous endophthalmitis secondary to S. marcescens in an otherwise healthy, HIV-negative, intravenous drug user in association with severe dental disease is reported. Serratia may be found in oral biofilm, and this mechanism should be considered in cases where other etiologies have been ruled out.

  9. Binary lipids-based nanostructured lipid carriers for improved oral bioavailability of silymarin.

    PubMed

    Shangguan, Mingzhu; Lu, Yi; Qi, Jianping; Han, Jin; Tian, Zhiqiang; Xie, Yunchang; Hu, Fuqiang; Yuan, Hailong; Wu, Wei

    2014-02-01

    The main purpose of this study was to prepare binary lipids-based nanostructured lipid carriers to improve the oral bioavailability of silymarin, a poorly water-soluble liver protectant. Silymarin-loaded nanostructured lipid carriers were prepared by the method of high-pressure homogenization with glycerol distearates (Precirol ATO-5) and oleic acid as the solid and liquid lipids, respectively, and lecithin (Lipoid E 100) and Tween-80 as the emulsifiers. The silymarin-nanostructured lipid carrier prepared under optimum conditions was spherical in shape with mean particle size of ∼78.87 nm, entrapment efficiency of 87.55%, loading capacity of 8.32%, and zeta potential of -65.3 mV, respectively. In vitro release of silymarin-nanostructured lipid carriers was very limited even after 12 h, while in vitro lipolysis showed fast digestion of nanostructured lipid carriers within 1 h. Relative oral bioavailability of silymarin-nanostructured lipid carriers in Beagle dogs was 2.54- and 3.10-fold that of marketed Legalon® and silymarin solid dispersion pellets, respectively. It was concluded that nanostructured lipid carriers were potential drug delivery systems to improve the bioavailability of silymarin. Other than improved dissolution, alternative mechanisms such as facilitated absorption as well as lymphatic transport may contribute to bioavailability enhancement.

  10. Residential water demand with endogenous pricing: The Canadian Case

    NASA Astrophysics Data System (ADS)

    Reynaud, Arnaud; Renzetti, Steven; Villeneuve, Michel

    2005-11-01

    In this paper, we show that the rate structure endogeneity may result in a misspecification of the residential water demand function. We propose to solve this endogeneity problem by estimating a probabilistic model describing how water rates are chosen by local communities. This model is estimated on a sample of Canadian local communities. We first show that the pricing structure choice reflects efficiency considerations, equity concerns, and, in some cases, a strategy of price discrimination across consumers by Canadian communities. Hence estimating the residential water demand without taking into account the pricing structures' endogeneity leads to a biased estimation of price and income elasticities. We also demonstrate that the pricing structure per se plays a significant role in influencing price responsiveness of Canadian residential consumers.

  11. Immobilized lipid-bilayer materials

    DOEpatents

    Sasaki, Darryl Y.; Loy, Douglas A.; Yamanaka, Stacey A.

    2000-01-01

    A method for preparing encapsulated lipid-bilayer materials in a silica matrix comprising preparing a silica sol, mixing a lipid-bilayer material in the silica sol and allowing the mixture to gel to form the encapsulated lipid-bilayer material. The mild processing conditions allow quantitative entrapment of pre-formed lipid-bilayer materials without modification to the material's spectral characteristics. The method allows for the immobilization of lipid membranes to surfaces. The encapsulated lipid-bilayer materials perform as sensitive optical sensors for the detection of analytes such as heavy metal ions and can be used as drug delivery systems and as separation devices.

  12. An endogenous small interfering RNA pathway in Drosophila

    PubMed Central

    Czech, Benjamin; Malone, Colin D.; Zhou, Rui; Stark, Alexander; Schlingeheyde, Catherine; Dus, Monica; Perrimon, Norbert; Kellis, Manolis; Wohlschlegel, James A.; Sachidanandam, Ravi; Hannon, Gregory J.; Brennecke, Julius

    2009-01-01

    Drosophila endogenous small RNAs are categorized according to their mechanisms of biogenesis and the Argonaute protein to which they bind. MicroRNAs are a class of ubiquitously expressed RNAs of ~22 nucleotides in length, which arise from structured precursors through the action of Drosha–Pasha and Dicer-1–Loquacious complexes1–7. These join Argonaute-1 to regulate gene expression8,9. A second endogenous small RNA class, the Piwi-interacting RNAs, bind Piwi proteins and suppress transposons10,11. Piwi-interacting RNAs are restricted to the gonad, and at least a subset of these arises by Piwi-catalysed cleavage of single-stranded RNAs12,13. Here we show that Drosophila generates a third small RNA class, endogenous small interfering RNAs, in both gonadal and somatic tissues. Production of these RNAs requires Dicer-2, but a subset depends preferentially on Loquacious1,4,5 rather than the canonical Dicer-2 partner, R2D2 (ref. 14). Endogenous small interfering RNAs arise both from convergent transcription units and from structured genomic loci in a tissue-specific fashion. They predominantly join Argonaute-2 and have the capacity, as a class, to target both protein-coding genes and mobile elements. These observations expand the repertoire of small RNAs in Drosophila, adding a class that blurs distinctions based on known biogenesis mechanisms and functional roles. PMID:18463631

  13. The search for an endogenous activator.

    PubMed Central

    Gekowski, K. M.; Atkins, E.

    1985-01-01

    Certain febrile diseases are unaccompanied by infection or apparent hypersensitivity. In myocardial infarction or pulmonary embolism, for example, fever has been attributed to inflammation and/or tissue necrosis. Exogenous (microbial) pyrogens stimulate both human and animal monocytes/macrophages to produce endogenous pyrogen (EP) in vitro. To determine if plasma and cellular endogeneous mediators (EMs) of inflammation induced EP production, human mononuclear cells (M/L) were incubated for 18 hours with varying amounts of EM and the supernates assayed for EP in rabbits. Neutrophils (PMNs), which do not generate EP and yet are a feature of acute inflammation, were tested. Neither viable, phorbol myristic acetate-stimulated PMNs nor sonicated PMNs, red blood cells, or M/L stimulated human monocytes to produce EP. Human C3b and C5a, which mediate phagocytosis and chemotaxis, respectively, were also inactive. Despite its chemoattractant properties, the synthetic peptide FMLP failed to induce EP release. Since Poly I:Poly C (PIC: a synthetic, double-stranded RNA) is a potent pyrogen in rabbits, we investigated PIC, as well as a native, single-stranded RNA (from E. coli) and DNA (from calf thymus). None was active in vitro, and only PIC caused fever when given to rabbits intravenously. In summary, we have been unable to find an endogenous activator of EP from human monocytes to explain fevers associated with inflammation alone. PMID:3875936

  14. Trifunctional lipid probes for comprehensive studies of single lipid species in living cells

    PubMed Central

    Nadler, André; Haberkant, Per; Kirkpatrick, Joanna; Schifferer, Martina; Stein, Frank; Hauke, Sebastian; Porter, Forbes D.; Schultz, Carsten

    2017-01-01

    Lipid-mediated signaling events regulate many cellular processes. Investigations of the complex underlying mechanisms are difficult because several different methods need to be used under varying conditions. Here we introduce multifunctional lipid derivatives to study lipid metabolism, lipid−protein interactions, and intracellular lipid localization with a single tool per target lipid. The probes are equipped with two photoreactive groups to allow photoliberation (uncaging) and photo–cross-linking in a sequential manner, as well as a click-handle for subsequent functionalization. We demonstrate the versatility of the design for the signaling lipids sphingosine and diacylglycerol; uncaging of the probe for these two species triggered calcium signaling and intracellular protein translocation events, respectively. We performed proteomic screens to map the lipid-interacting proteome for both lipids. Finally, we visualized a sphingosine transport deficiency in patient-derived Niemann−Pick disease type C fibroblasts by fluorescence as well as correlative light and electron microscopy, pointing toward the diagnostic potential of such tools. We envision that this type of probe will become important for analyzing and ultimately understanding lipid signaling events in a comprehensive manner. PMID:28154130

  15. Parenteral Nutrition and Lipids.

    PubMed

    Raman, Maitreyi; Almutairdi, Abdulelah; Mulesa, Leanne; Alberda, Cathy; Beattie, Colleen; Gramlich, Leah

    2017-04-14

    Lipids have multiple physiological roles that are biologically vital. Soybean oil lipid emulsions have been the mainstay of parenteral nutrition lipid formulations for decades in North America. Utilizing intravenous lipid emulsions in parenteral nutrition has minimized the dependence on dextrose as a major source of nonprotein calories and prevents the clinical consequences of essential fatty acid deficiency. Emerging literature has indicated that there are benefits to utilizing alternative lipids such as olive/soy-based formulations, and combination lipids such as soy/MCT/olive/fish oil, compared with soybean based lipids, as they have less inflammatory properties, are immune modulating, have higher antioxidant content, decrease risk of cholestasis, and improve clinical outcomes in certain subgroups of patients. The objective of this article is to review the history of IVLE, their composition, the different generations of widely available IVLE, the variables to consider when selecting lipids, and the complications of IVLE and how to minimize them.

  16. Parenteral Nutrition and Lipids

    PubMed Central

    Raman, Maitreyi; Almutairdi, Abdulelah; Mulesa, Leanne; Alberda, Cathy; Beattie, Colleen; Gramlich, Leah

    2017-01-01

    Lipids have multiple physiological roles that are biologically vital. Soybean oil lipid emulsions have been the mainstay of parenteral nutrition lipid formulations for decades in North America. Utilizing intravenous lipid emulsions in parenteral nutrition has minimized the dependence on dextrose as a major source of nonprotein calories and prevents the clinical consequences of essential fatty acid deficiency. Emerging literature has indicated that there are benefits to utilizing alternative lipids such as olive/soy-based formulations, and combination lipids such as soy/MCT/olive/fish oil, compared with soybean based lipids, as they have less inflammatory properties, are immune modulating, have higher antioxidant content, decrease risk of cholestasis, and improve clinical outcomes in certain subgroups of patients. The objective of this article is to review the history of IVLE, their composition, the different generations of widely available IVLE, the variables to consider when selecting lipids, and the complications of IVLE and how to minimize them. PMID:28420095

  17. Recombinant probes for visualizing endogenous synaptic proteins in living neurons

    PubMed Central

    Gross, Garrett G.; Junge, Jason A.; Mora, Rudy J.; Kwon, Hyung-Bae; Olson, C. Anders; Takahashi, Terry T.; Liman, Emily R.; Ellis-Davies, Graham C.R.; McGee, Aaron W.; Sabatini, Bernardo L.; Roberts, Richard W.; Arnold, Don B.

    2013-01-01

    Summary The ability to visualize endogenous proteins in living neurons provides a powerful means to interrogate neuronal structure and function. Here we generate recombinant antibody-like proteins, termed FingRs (Fibronectin intrabodies generated with mRNA display), that bind endogenous neuronal proteins PSD-95 and Gephyrin with high affinity and which, when fused to GFP, allow excitatory and inhibitory synapses to be visualized in living neurons. Design of the FingR incorporates a novel transcriptional regulation system that ties FingR expression to the level of the target and reduces background fluorescence. In dissociated neurons and brain slices FingRs generated against PSD-95 and Gephyrin did not affect the expression patterns of their endogenous target proteins or the number or strength of synapses. Together, our data indicate that PSD-95 and Gephyrin FingRs can report the localization and amount of endogenous synaptic proteins in living neurons and thus may be used to study changes in synaptic strength in vivo. PMID:23791193

  18. Biochemical Modulation of Lipid Pathway in Microalgae Dunaliella sp. for Biodiesel Production

    PubMed Central

    Talebi, Ahmad Farhad; Tohidfar, Masoud; Mousavi Derazmahalleh, Seyedeh Mahsa; Sulaiman, Alawi; Baharuddin, Azhari Samsu; Tabatabaei, Meisam

    2015-01-01

    Exploitation of renewable sources of energy such as algal biodiesel could turn energy supplies problem around. Studies on a locally isolated strain of Dunaliella sp. showed that the mean lipid content in cultures enriched by 200 mg L−1 myoinositol was raised by around 33% (1.5 times higher than the control). Similarly, higher lipid productivity values were achieved in cultures treated by 100 and 200 mg L−1 myoinositol. Fluorometry analyses (microplate fluorescence and flow cytometry) revealed increased oil accumulation in the Nile red-stained algal samples. Moreover, it was predicted that biodiesel produced from myoinositol-treated cells possessed improved oxidative stability, cetane number, and cloud point values. From the genomic point of view, real-time analyses revealed that myoinositol negatively influenced transcript abundance of AccD gene (one of the key genes involved in lipid production pathway) due to feedback inhibition and that its positive effect must have been exerted through other genes. The findings of the current research are not to interprete that myoinositol supplementation could answer all the challenges faced in microalgal biodiesel production but instead to show that “there is a there there” for biochemical modulation strategies, which we achieved, increased algal oil quantity and enhanced resultant biodiesel quality. PMID:26146623

  19. Biochemical Modulation of Lipid Pathway in Microalgae Dunaliella sp. for Biodiesel Production.

    PubMed

    Talebi, Ahmad Farhad; Tohidfar, Masoud; Mousavi Derazmahalleh, Seyedeh Mahsa; Sulaiman, Alawi; Baharuddin, Azhari Samsu; Tabatabaei, Meisam

    2015-01-01

    Exploitation of renewable sources of energy such as algal biodiesel could turn energy supplies problem around. Studies on a locally isolated strain of Dunaliella sp. showed that the mean lipid content in cultures enriched by 200 mg L(-1) myoinositol was raised by around 33% (1.5 times higher than the control). Similarly, higher lipid productivity values were achieved in cultures treated by 100 and 200 mg L(-1) myoinositol. Fluorometry analyses (microplate fluorescence and flow cytometry) revealed increased oil accumulation in the Nile red-stained algal samples. Moreover, it was predicted that biodiesel produced from myoinositol-treated cells possessed improved oxidative stability, cetane number, and cloud point values. From the genomic point of view, real-time analyses revealed that myoinositol negatively influenced transcript abundance of AccD gene (one of the key genes involved in lipid production pathway) due to feedback inhibition and that its positive effect must have been exerted through other genes. The findings of the current research are not to interprete that myoinositol supplementation could answer all the challenges faced in microalgal biodiesel production but instead to show that "there is a there there" for biochemical modulation strategies, which we achieved, increased algal oil quantity and enhanced resultant biodiesel quality.

  20. Evaluation of treadmill exercise effect on muscular lipid profiles of diabetic fatty rats by nanoflow liquid chromatography-tandem mass spectrometry

    NASA Astrophysics Data System (ADS)

    Lee, Jong Cheol; Kim, Il Yong; Son, Yeri; Byeon, Seul Kee; Yoon, Dong Hyun; Son, Jun Seok; Song, Han Sol; Song, Wook; Seong, Je Kyung; Moon, Myeong Hee

    2016-07-01

    We compare comprehensive quantitative profiling of lipids at the molecular level from skeletal muscle tissues (gastrocnemius and soleus) of Zucker diabetic fatty rats and Zucker lean control rats during treadmill exercise by nanoflow liquid chromatography-tandem mass spectrometry. Because type II diabetes is caused by decreased insulin sensitivity due to excess lipids accumulated in skeletal muscle tissue, lipidomic analysis of muscle tissues under treadmill exercise can help unveil the mechanism of lipid-associated insulin resistance. In total, 314 lipid species, including phospholipids, sphingolipids, ceramides, diacylglycerols (DAGs), and triacylglycerols (TAGs), were analyzed to examine diabetes-related lipid species and responses to treadmill exercise. Most lysophospholipid levels increased with diabetes. While DAG levels (10 from the gastrocnemius and 13 from the soleus) were >3-fold higher in diabetic rats, levels of most of these decreased after exercise in soleus but not in gastrocnemius. Levels of 5 highly abundant TAGs (52:1 and 54:3 in the gastrocnemius and 48:2, 50:2, and 52:4 in the soleus) displaying 2-fold increases in diabetic rats decreased after exercise in the soleus but not in the gastrocnemius in most cases. Thus, aerobic exercise has a stronger influence on lipid levels in the soleus than in the gastrocnemius in type 2 diabetic rats.

  1. Elemental ratios and lipid classes in a coral reef food web under river influence

    NASA Astrophysics Data System (ADS)

    Carreón-Palau, Laura; Parrish, Christopher C.; Pérez-España, Horacio; Aguiñiga-Garcia, Sergio

    2018-05-01

    Coral reefs in the Caribbean and Gulf of Mexico are increasingly suffering from anthropogenic nutrient inputs principally from fertilizers as identified by their δ15N signatures. To determine if primary producers are passively affected by anthropogenic nitrogen enrichment in a coral reef community, carbon: nitrogen ratios (C:N mol mol-1) were measured. The C:N ratio was used as a proxy for nitrogen enrichment in primary producers when the ratio decreases, and for lipid plus carbohydrate in terms of C, and protein in terms of N in primary producers and consumers. Lipid classes and the triacylglycerol to sterol (TAG:ST) ratio were used to evaluate energy storage as an indication of nutritional quality in the six most abundant primary producers, and of nutritional condition in ten ubiquitous consumers in a coral reef in the Gulf of Mexico under river influence. A low C:N ratio revealed nitrogen enrichment in primary producers. Among the lipids, high TAG proportions were detected in phytoplankton and zooxanthellae suggesting that they have a higher nutritional quality in terms of energy, followed by sea grass, mangrove, and macroalgae. During the rainy season TAG:ST increased in primary consumers such as echinoderms, and top predators such as the perciform fish Bodianus rufus, Ocyurus chrysurus and Caranx hippos, suggesting an increase in energy storage. In contrast, TAG:ST decreased in the principal habitat providing coral Montastrea cavernosa, along with a decrease in the phospholipid proportion suggesting a poor nutritional condition. There were three species with no change in their TAG:ST ratio: the sponge Aplysina sp., the masked goby Coryphopterus personatus and the surgeon fish Achanturus chirurgus. The lower value of TAG, TAG:ST ratio and phospholipid proportion in the coral M. cavernosa suggests that the reported abundance of zooplankton does not satisfy the energy demand of M. cavernosa during the rainy season.

  2. Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy.

    PubMed

    Jaffrès, Paul-Alain; Gajate, Consuelo; Bouchet, Ana Maria; Couthon-Gourvès, Hélène; Chantôme, Aurélie; Potier-Cartereau, Marie; Besson, Pierre; Bougnoux, Philippe; Mollinedo, Faustino; Vandier, Christophe

    2016-09-01

    Synthetic alkyl lipids, such as the ether lipids edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and ohmline (1-O-hexadecyl-2-O-methyl-rac-glycero-3-β-lactose), are forming a class of antitumor agents that target cell membranes to induce apoptosis and to decrease cell migration/invasion, leading to the inhibition of tumor and metastasis development. In this review, we present the structure-activity relationship of edelfosine and ohmline, and we point out differences and similarities between these two amphiphilic compounds. We also discuss the mechanisms of action of these synthetic alkyl ether lipids (involving, among other structures and molecules, membrane domains, Fas/CD95 death receptor signaling, and ion channels), and highlight a key role for lipid rafts in the underlying process. The reorganization of lipid raft membrane domains induced by these alkyl lipids affects the function of death receptors and ion channels, thus leading to apoptosis and/or inhibition of cancer cell migration. The possible therapeutic use of these alkyl lipids and the clinical perspectives for these lipids in prevention or/and treatment of tumor development and metastasis are also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. LMSD: LIPID MAPS structure database

    PubMed Central

    Sud, Manish; Fahy, Eoin; Cotter, Dawn; Brown, Alex; Dennis, Edward A.; Glass, Christopher K.; Merrill, Alfred H.; Murphy, Robert C.; Raetz, Christian R. H.; Russell, David W.; Subramaniam, Shankar

    2007-01-01

    The LIPID MAPS Structure Database (LMSD) is a relational database encompassing structures and annotations of biologically relevant lipids. Structures of lipids in the database come from four sources: (i) LIPID MAPS Consortium's core laboratories and partners; (ii) lipids identified by LIPID MAPS experiments; (iii) computationally generated structures for appropriate lipid classes; (iv) biologically relevant lipids manually curated from LIPID BANK, LIPIDAT and other public sources. All the lipid structures in LMSD are drawn in a consistent fashion. In addition to a classification-based retrieval of lipids, users can search LMSD using either text-based or structure-based search options. The text-based search implementation supports data retrieval by any combination of these data fields: LIPID MAPS ID, systematic or common name, mass, formula, category, main class, and subclass data fields. The structure-based search, in conjunction with optional data fields, provides the capability to perform a substructure search or exact match for the structure drawn by the user. Search results, in addition to structure and annotations, also include relevant links to external databases. The LMSD is publicly available at PMID:17098933

  4. Identification of endogenous flurophores in the layered retina

    NASA Astrophysics Data System (ADS)

    Xu, Gaixia; Chen, Danni; Sun, Yiwen; Qu, Junle; Lin, Ziyang; Ding, Zhihua; Niu, Hanben

    2007-05-01

    In this paper, we measured and analyzed the characteristic of endogenous fluorophores in porcine layered retina by using advanced fluorescence spectroscopy and microscopy imaging technology. It was found that there were obvious contrasts corresponding to the different layers of retina, which may be important for fundus disease diagnosis. The retinal pigment epithelium cells exhibited strong autofluorescence with as emission peak of 600+/-10nm when excited with 860-nm light. The emission peak of photoreceptors was at 652+/-5nm, and the emission peak of retinal vessels layer was weak and at 640~700nm, when excited with 488-nm light. Autofluorescence images of three layers of retina were obtained using the same setup. We concluded that the main endogenous fluorophore in PRE was lipofuscin and that in retinal vessels was porphyrin. What's more, the FMHW (full width at half. maximum) of retinal fluorescence spectrum was broad, which suggested that there wasn't only one endogenous fluorophores of tissues excited.

  5. Endogenous small RNAs and antibacterial immunity in plants.

    PubMed

    Jin, Hailing

    2008-08-06

    Small RNAs are non-coding regulatory RNA molecules that control gene expression by mediating mRNA degradation, translational inhibition, or chromatin modification. Virus-derived small RNAs induce silencing of viral RNAs and are essential for antiviral defense in both animal and plant systems. The role of host endogenous small RNAs on antibacterial immunity has only recently been recognized. Host disease resistance and defense responses are achieved by activation and repression of a large array of genes. Certain endogenous small RNAs in plants, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), are induced or repressed in response to pathogen attack and subsequently regulate the expression of genes involved in disease resistance and defense responses by mediating transcriptional or post-transcriptional gene silencing. Thus, these small RNAs play an important role in gene expression reprogramming in plant disease resistance and defense responses. This review focuses on the recent findings of plant endogenous small RNAs in antibacterial immunity.

  6. Effects of theobroxide, a natural product, on the level of endogenous jasmonoids.

    PubMed

    Yang, Qing; Gao, Xiquan; Fujino, Yumiko; Matsuura, Hideyuki; Yoshihara, Teruhiko

    2004-01-01

    The natural potato microtuber inducing substance, theobroxide, strongly induces the formation of tuber of potato (Solanum tuberosum L.) and flower bud of morning glory (Pharbitis nil) plants under non-inducing conditions (long days) (Yoshihara et al., 2000). In the present study, theobroxide was evaluated for its effect on the level of endogenous jasmonoids in different tissues of such two plants. An in vitro bioassay using cultures of single-node segments of potato stems was performed with the supplement of theobroxide in the medium. The endogenous jasmonic acid (JA) and its analogue tuberonic acid (TA, 12-hydroxyjasmonic acid) in segments and microtubers were quantitatively analyzed. The increase in the endogenous JA level caused by theobroxide was observed in both segments and microtubers. Endogenous TA was only detected in segments, and the content increased with the concentration of theobroxide. As for morning glory, the whole plant was sprayed with theobroxide for 1 approximately 5 weeks under different photoperiods and endogenous JA in the leaves was quantitatively analyzed. Theobroxide spraying increased the level of endogenous JA in the leaves of the plants grown under both long and short days.

  7. Obesity and lipid stress inhibit carnitine acetyltransferase activity.

    PubMed

    Seiler, Sarah E; Martin, Ola J; Noland, Robert C; Slentz, Dorothy H; DeBalsi, Karen L; Ilkayeva, Olga R; An, Jie; Newgard, Christopher B; Koves, Timothy R; Muoio, Deborah M

    2014-04-01

    Carnitine acetyltransferase (CrAT) is a mitochondrial matrix enzyme that catalyzes the interconversion of acetyl-CoA and acetylcarnitine. Emerging evidence suggests that this enzyme functions as a positive regulator of total body glucose tolerance and muscle activity of pyruvate dehydrogenase (PDH), a mitochondrial enzyme complex that promotes glucose oxidation and is feedback inhibited by acetyl-CoA. Here, we used tandem mass spectrometry-based metabolic profiling to identify a negative relationship between CrAT activity and muscle content of lipid intermediates. CrAT specific activity was diminished in muscles from obese and diabetic rodents despite increased protein abundance. This reduction in enzyme activity was accompanied by muscle accumulation of long-chain acylcarnitines (LCACs) and acyl-CoAs and a decline in the acetylcarnitine/acetyl-CoA ratio. In vitro assays demonstrated that palmitoyl-CoA acts as a direct mixed-model inhibitor of CrAT. Similarly, in primary human myocytes grown in culture, nutritional and genetic manipulations that promoted mitochondrial influx of fatty acids resulted in accumulation of LCACs but a pronounced decrease of CrAT-derived short-chain acylcarnitines. These results suggest that lipid-induced antagonism of CrAT might contribute to decreased PDH activity and glucose disposal in the context of obesity and diabetes.

  8. Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics.

    PubMed

    Maier, Martin A; Jayaraman, Muthusamy; Matsuda, Shigeo; Liu, Ju; Barros, Scott; Querbes, William; Tam, Ying K; Ansell, Steven M; Kumar, Varun; Qin, June; Zhang, Xuemei; Wang, Qianfan; Panesar, Sue; Hutabarat, Renta; Carioto, Mary; Hettinger, Julia; Kandasamy, Pachamuthu; Butler, David; Rajeev, Kallanthottathil G; Pang, Bo; Charisse, Klaus; Fitzgerald, Kevin; Mui, Barbara L; Du, Xinyao; Cullis, Pieter; Madden, Thomas D; Hope, Michael J; Manoharan, Muthiah; Akinc, Akin

    2013-08-01

    In recent years, RNA interference (RNAi) therapeutics, most notably with lipid nanoparticle-based delivery systems, have advanced into human clinical trials. The results from these early clinical trials suggest that lipid nanoparticles (LNPs), and the novel ionizable lipids that comprise them, will be important materials in this emerging field of medicine. A persistent theme in the use of materials for biomedical applications has been the incorporation of biodegradability as a means to improve biocompatibility and/or to facilitate elimination. Therefore, the aim of this work was to further advance the LNP platform through the development of novel, next-generation lipids that combine the excellent potency of the most advanced lipids currently available with biodegradable functionality. As a representative example of this novel class of biodegradable lipids, the lipid evaluated in this work displays rapid elimination from plasma and tissues, substantially improved tolerability in preclinical studies, while maintaining in vivo potency on par with that of the most advanced lipids currently available.

  9. Altered temporal lobe white matter lipid ion profiles in an experimental model of sporadic Alzheimer's disease.

    PubMed

    Tong, Ming; Leão, Raiane; Vimbela, Gina V; Yalcin, Emine B; Kay, Jared; Krotow, Alexander; de la Monte, Suzanne M

    2017-07-01

    White matter is an early and important yet under-evaluated target of Alzheimer's disease (AD). Metabolic impairments due to insulin and insulin-like growth factor resistance contribute to white matter degeneration because corresponding signal transduction pathways maintain oligodendrocyte function and survival. This study utilized a model of sporadic AD in which adult Long Evans rats administered intracerebral streptozotocin (i.c. STZ) developed AD-type neurodegeneration. Temporal lobe white matter lipid ion profiles were characterized by matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Although the lipid ion species expressed in the i.c. STZ and control groups were virtually identical, i.c. STZ mainly altered the abundances of various lipid ions. Correspondingly, the i.c. STZ group was distinguished from control by principal component analysis and data bar plots. i.c. STZ mainly reduced expression of lipid ions with low m/z's (less than 810) as well as the upper range m/z lipids (m/z 964-986), and increased expression of lipid ions with m/z's between 888 and 937. Phospholipids were mainly included among the clusters inhibited by i.c. STZ, while both sulfatides and phospholipids were increased by i.c. STZ. However, Chi-Square analysis demonstrated significant i.c. STZ-induced trend reductions in phospholipids and increases in sulfatides (P<0.00001). The i.c. STZ model of sporadic AD is associated with broad and sustained abnormalities in temporal lobe white matter lipids. The findings suggest that the i.c. STZ model could be used for pre-clinical studies to assess therapeutic measures for their ability to restore white matter integrity in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Animal spirits, competitive markets, and endogenous growth

    NASA Astrophysics Data System (ADS)

    Miyazaki, Kenji

    2013-10-01

    This paper uses a simple model with an endogenous discount rate and linear technology to investigate whether a competitive equilibrium has a higher balanced growth path (BGP) than the social planning solution and whether the BGP is determinate or indeterminate. The implications are as follows. To start with, people with an instinct to compare themselves with others possess an endogenous discount rate. In turn, this instinct affects the economic growth rate in a competitive market economy. The competitive market economy also sometimes achieves higher economic growth than a social planning economy. However, the outcomes of market economy occasionally fluctuate because of the presence of the self-fulfilling prophecy or animal spirits.

  11. Proteomic analysis of lipid body from the alkenone‐producing marine haptophyte alga Tisochrysis lutea

    PubMed Central

    Shi, Qing; Araie, Hiroya; Bakku, Ranjith Kumar; Fukao, Yoichiro; Rakwal, Randeep; Suzuki, Iwane

    2015-01-01

    Lipid body (LB) is recognized as the cellular carbon and energy storage organelle in many organisms. LBs have been observed in the marine haptophyte alga Tisochrysis lutea that produces special lipids such as long‐chain (C37‐C40) ketones (alkenones) with 2–4 trans‐type double bonds. In this study, we succeeded in developing a modified method to isolate LB from T. lutea. Purity of isolated LBs was confirmed by the absence of chlorophyll auto‐fluorescence and no contamination of the most abundant cellular protein ribulose‐1,5‐bisphosphate carboxylase/oxygenase. As alkenones predominated in the LB by GC‐MS analysis, the LB can be more appropriately named as “alkenone body (AB).” Extracted AB‐containing proteins were analyzed by the combination of 1DE (SDS‐PAGE) and MS/MS for confident protein identification and annotated using BLAST tools at National Center for Biotechnology Information. Totally 514 proteins were identified at the maximum. The homology search identified three major proteins, V‐ATPase, a hypothetical protein EMIHUDRAFT_465517 found in other alkenone‐producing haptophytes, and a lipid raft‐associated SPFH domain‐containing protein. Our data suggest that AB of T. lutera is surrounded by a lipid membrane originating from either the ER or the ER‐derived four layer‐envelopes chloroplast and function as the storage site of alkenones and alkenes. PMID:25914246

  12. Studying lipid-protein interactions with electron paramagnetic resonance spectroscopy of spin-labeled lipids.

    PubMed

    Páli, Tibor; Kóta, Zoltán

    2013-01-01

    Spin label electron paramagnetic resonance (EPR) of lipid-protein interactions reveals crucial features of the structure and assembly of integral membrane proteins. Spin label EPR spectroscopy is the technique of choice to characterize the protein-solvating lipid shell in its highly dynamic nature, because the EPR spectra of lipids that are spin labeled close to the terminal methyl end of their acyl chains display two spectral components, those corresponding to lipids directly contacting the protein and those corresponding to lipids in the bulk fluid bilayer regions of the membrane. In this chapter, typical spin label EPR procedures are presented that allow determination of the stoichiometry of interaction of spin-labeled lipids with the intra-membranous region of membrane proteins or polypeptides, as well as the association constant of the spin-labeled lipid with respect to the host lipid. The lipids giving rise to the so-called immobile spectral component in the EPR spectrum of such samples are identified as the motionally restricted first-shell lipids solvating membrane proteins in biomembranes. Stoichiometry and selectivity are directly related to the structure of the intra-membranous sections of membrane-associated proteins or polypeptides and can be used to study the state of assembly of such proteins in the membrane. Since these characteristics of lipid-protein interactions are discussed in detail in the literature [see Marsh (Eur Biophys J 39:513-525, 2010) for a most recent review], here we focus more on how to spin label model and biomembranes and how to measure and analyze the two-component EPR spectra of spin-labeled lipids in phospholipid bilayers that contain proteins or polypeptides. After a description of how to prepare spin-labeled model and native biological membranes, we present the reader with computational procedures for determining the molar fraction of motionally restricted lipids when both, one, or none of the pure isolated-mobile or

  13. Ionization behavior of amino lipids for siRNA delivery: determination of ionization constants, SAR, and the impact of lipid pKa on cationic lipid-biomembrane interactions.

    PubMed

    Zhang, Jingtao; Fan, Haihong; Levorse, Dorothy A; Crocker, Louis S

    2011-03-01

    Ionizable amino lipids are being pursued as an important class of materials for delivering small interfering RNA (siRNA) therapeutics, and research is being conducted to elucidate the structure-activity relationships (SAR) of these lipids. The pK(a) of cationic lipid headgroups is one of the critical physiochemical properties of interest due to the strong impact of lipid ionization on the assembly and performance of these lipids. This research focused on developing approaches that permit the rapid determination of the relevant pK(a) of the ionizable amino lipids. Two distinct approaches were investigated: (1) potentiometric titration of amino lipids dissolved in neutral surfactant micelles; and (2) pH-dependent partitioning of a fluorescent dye to cationic liposomes formulated from amino lipids. Using the approaches developed here, the pK(a) values of cationic lipids with distinct headgroups were measured and found to be significantly lower than calculated values. It was also found that lipid-lipid interaction has a strong impact on the pK(a) values of lipids. Lysis of model biomembranes by cationic lipids was used to evaluate the impact of lipid pK(a) on the interaction between cationic lipids and cell membranes. It was found that cationic lipid-biomembrane interaction depends strongly on lipid pK(a) and solution pH, and this interaction is much stronger when amino lipids are highly charged. The presence of an optimal pK(a) range of ionizable amino lipids for siRNA delivery was suggested based on these results. The pK(a) methods reported here can be used to support the SAR screen of cationic lipids for siRNA delivery, and the information revealed through studying the impact of pK(a) on the interaction between cationic lipids and cell membranes will contribute significantly to the design of more efficient siRNA delivery vehicles.

  14. Drug solubility in lipid nanocarriers: Influence of lipid matrix and available interfacial area.

    PubMed

    Göke, Katrin; Bunjes, Heike

    2017-08-30

    Amongst other strategies for the formulation of poorly water-soluble drugs, solubilization of these drugs in lipid-based formulations is a promising option. Most screening methods for the identification of a suitable lipid-based formulation fail to elucidate the role interfacial effects play for drug solubility in disperse systems. In a novel screening approach called passive drug loading, different preformed lipid nanocarrier dispersions are incubated with drug powder. Afterwards, undissolved drug is filtered off and the amount of solubilized drug is determined. The aim of this study was to identify parameters for drug solubility in pure lipids as well as for drug loading to the lipid-water interface of lipid nanoparticles. Using passive loading, the solubility of eight poorly water-soluble drugs in seven lipid nanocarriers varying in particle size or lipid matrix was investigated. Drug solubility in the nanocarriers did not follow any apparent trend and different drugs dissolved best in different carriers. Drugs with a melting point below approximately 150°C displayed distinctly better solubility than higher melting drugs. Additionally, relating the specific lipid nanocarrier surface area to the drug solubility allowed drawing conclusions on the drug localization. Fenofibrate, dibucaine and, less distinctly also clotrimazole, which all melt below 150°C, were predominantly located in the lipid droplet core of the nanoparticles. In contrast, the five remaining drugs (betamethasone valerate, flufenamic acid, itraconazole, ketoconazole, mefenamic acid) were also located at the lipid-water interface to different, but substantial degrees. The ability to account for drug loading to the lipid-water interface is thus a major advantage of passive loading. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Interdigitation between Triglycerides and Lipids Modulates Surface Properties of Lipid Droplets.

    PubMed

    Bacle, Amélie; Gautier, Romain; Jackson, Catherine L; Fuchs, Patrick F J; Vanni, Stefano

    2017-04-11

    Intracellular lipid droplets (LDs) are the main cellular site of metabolic energy storage. Their structure is unique inside the cell, with a core of esterified fatty acids and sterols, mainly triglycerides and sterol esters, surrounded by a single monolayer of phospholipids. Numerous peripheral proteins, including several that were previously associated with intracellular compartments surrounded by a lipid bilayer, have been recently shown to target the surface of LDs, but how they are able to selectively target this organelle remains largely unknown. Here, we use atomistic and coarse-grained molecular dynamics simulations to investigate the molecular properties of the LD surface and to characterize how it differs from that of a lipid bilayer. Our data suggest that although several surface properties are remarkably similar between the two structures, key differences originate from the interdigitation between surface phospholipids and core neutral lipids that occurs in LDs. This property is extremely sensitive to membrane undulations, unlike in lipid bilayers, and it strongly affects both lipid-packing defects and the lateral pressure profile. We observed a marked change in overall surface properties for surface tensions >10 mN/m, indicative of a bimodal behavior. Our simulations provide a comprehensive molecular characterization of the unique surface properties of LDs and suggest how the molecular properties of the surface lipid monolayer can be modulated by the underlying neutral lipids. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  16. Lipids of mitochondria.

    PubMed

    Horvath, Susanne E; Daum, Günther

    2013-10-01

    A unique organelle for studying membrane biochemistry is the mitochondrion whose functionality depends on a coordinated supply of proteins and lipids. Mitochondria are capable of synthesizing several lipids autonomously such as phosphatidylglycerol, cardiolipin and in part phosphatidylethanolamine, phosphatidic acid and CDP-diacylglycerol. Other mitochondrial membrane lipids such as phosphatidylcholine, phosphatidylserine, phosphatidylinositol, sterols and sphingolipids have to be imported. The mitochondrial lipid composition, the biosynthesis and the import of mitochondrial lipids as well as the regulation of these processes will be main issues of this review article. Furthermore, interactions of lipids and mitochondrial proteins which are highly important for various mitochondrial processes will be discussed. Malfunction or loss of enzymes involved in mitochondrial phospholipid biosynthesis lead to dysfunction of cell respiration, affect the assembly and stability of the mitochondrial protein import machinery and cause abnormal mitochondrial morphology or even lethality. Molecular aspects of these processes as well as diseases related to defects in the formation of mitochondrial membranes will be described. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Can Occupancy–Abundance Models Be Used to Monitor Wolf Abundance?

    PubMed Central

    Latham, M. Cecilia; Latham, A. David M.; Webb, Nathan F.; Mccutchen, Nicole A.; Boutin, Stan

    2014-01-01

    Estimating the abundance of wild carnivores is of foremost importance for conservation and management. However, given their elusive habits, direct observations of these animals are difficult to obtain, so abundance is more commonly estimated from sign surveys or radio-marked individuals. These methods can be costly and difficult, particularly in large areas with heavy forest cover. As an alternative, recent research has suggested that wolf abundance can be estimated from occupancy–abundance curves derived from “virtual” surveys of simulated wolf track networks. Although potentially more cost-effective, the utility of this approach hinges on its robustness to violations of its assumptions. We assessed the sensitivity of the occupancy–abundance approach to four assumptions: variation in wolf movement rates, changes in pack cohesion, presence of lone wolves, and size of survey units. Our simulations showed that occupancy rates and wolf pack abundances were biased high if track surveys were conducted when wolves made long compared to short movements, wolf packs were moving as multiple hunting units as opposed to a cohesive pack, and lone wolves were moving throughout the surveyed landscape. We also found that larger survey units (400 and 576 km2) were more robust to changes in these factors than smaller survey units (36 and 144 km2). However, occupancy rates derived from large survey units rapidly reached an asymptote at 100% occupancy, suggesting that these large units are inappropriate for areas with moderate to high wolf densities (>15 wolves/1,000 km2). Virtually-derived occupancy–abundance relationships can be a useful method for monitoring wolves and other elusive wildlife if applied within certain constraints, in particular biological knowledge of the surveyed species needs to be incorporated into the design of the occupancy surveys. Further, we suggest that the applicability of this method could be extended by directly incorporating some of its

  18. Conserved Lipid and Small-Molecule Modulation of COQ8 Reveals Regulation of the Ancient Kinase-like UbiB Family.

    PubMed

    Reidenbach, Andrew G; Kemmerer, Zachary A; Aydin, Deniz; Jochem, Adam; McDevitt, Molly T; Hutchins, Paul D; Stark, Jaime L; Stefely, Jonathan A; Reddy, Thiru; Hebert, Alex S; Wilkerson, Emily M; Johnson, Isabel E; Bingman, Craig A; Markley, John L; Coon, Joshua J; Dal Peraro, Matteo; Pagliarini, David J

    2018-02-15

    Human COQ8A (ADCK3) and Saccharomyces cerevisiae Coq8p (collectively COQ8) are UbiB family proteins essential for mitochondrial coenzyme Q (CoQ) biosynthesis. However, the biochemical activity of COQ8 and its direct role in CoQ production remain unclear, in part due to lack of known endogenous regulators of COQ8 function and of effective small molecules for probing its activity in vivo. Here, we demonstrate that COQ8 possesses evolutionarily conserved ATPase activity that is activated by binding to membranes containing cardiolipin and by phenolic compounds that resemble CoQ pathway intermediates. We further create an analog-sensitive version of Coq8p and reveal that acute chemical inhibition of its endogenous activity in yeast is sufficient to cause respiratory deficiency concomitant with CoQ depletion. Collectively, this work defines lipid and small-molecule modulators of an ancient family of atypical kinase-like proteins and establishes a chemical genetic system for further exploring the mechanistic role of COQ8 in CoQ biosynthesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Detection of an endogenous urinary biomarker associated with CYP2D6 activity using global metabolomics.

    PubMed

    Tay-Sontheimer, Jessica; Shireman, Laura M; Beyer, Richard P; Senn, Taurence; Witten, Daniela; Pearce, Robin E; Gaedigk, Andrea; Gana Fomban, Cletus L; Lutz, Justin D; Isoherranen, Nina; Thummel, Kenneth E; Fiehn, Oliver; Leeder, J Steven; Lin, Yvonne S

    2014-12-01

    We sought to discover endogenous urinary biomarkers of human CYP2D6 activity. Healthy pediatric subjects (n = 189) were phenotyped using dextromethorphan and randomized for candidate biomarker selection and validation. Global urinary metabolomics was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. Candidate biomarkers were tested in adults receiving fluoxetine, a CYP2D6 inhibitor. A biomarker, M1 (m/z 444.3102) was correlated with CYP2D6 activity in both the pediatric training and validation sets. Poor metabolizers had undetectable levels of M1, whereas it was present in subjects with other phenotypes. In adult subjects, a 9.56-fold decrease in M1 abundance was observed during CYP2D6 inhibition. Identification and validation of M1 may provide a noninvasive means of CYP2D6 phenotyping.

  20. Lysosomal Lipid Storage Diseases

    PubMed Central

    Schulze, Heike; Sandhoff, Konrad

    2011-01-01

    Lysosomal lipid storage diseases, or lipidoses, are inherited metabolic disorders in which typically lipids accumulate in cells and tissues. Complex lipids, such as glycosphingolipids, are constitutively degraded within the endolysosomal system by soluble hydrolytic enzymes with the help of lipid binding proteins in a sequential manner. Because of a functionally impaired hydrolase or auxiliary protein, their lipid substrates cannot be degraded, accumulate in the lysosome, and slowly spread to other intracellular membranes. In Niemann-Pick type C disease, cholesterol transport is impaired and unesterified cholesterol accumulates in the late endosome. In most lysosomal lipid storage diseases, the accumulation of one or few lipids leads to the coprecipitation of other hydrophobic substances in the endolysosomal system, such as lipids and proteins, causing a “traffic jam.” This can impair lysosomal function, such as delivery of nutrients through the endolysosomal system, leading to a state of cellular starvation. Therapeutic approaches are currently restricted to mild forms of diseases with significant residual catabolic activities and without brain involvement. PMID:21502308

  1. Lipid interactions in breadmaking.

    PubMed

    Carr, N O; Daniels, N W; Frazier, P J

    1992-01-01

    Both the natural lipids of flour and added fats are known to play an important role during the production of bread. In this review, the chemical and physical interactions of fat have been assessed in an attempt to explain these technological functions. Particular emphasis has been placed on the "binding" or complexing of lipid by flour proteins during the development of dough. While publications in this field have frequently been contradictory, evidence now indicates that observed lipid binding may involve lipid mesophase transformation and the nonspecific occlusion of lipid phases within the gluten network. The significance of these suggested events has been compared with current theories of lipid function in the breadmaking process.

  2. Endogenous lentivirus in Malayan colugo (Galeopterus variegatus), a close relative of primates.

    PubMed

    Hron, Tomáš; Fábryová, Helena; Pačes, Jan; Elleder, Daniel

    2014-10-04

    A significant fraction of mammalian genomes is composed of endogenous retroviral (ERV) sequences that are formed by germline infiltration of various retroviruses. In contrast to other retroviral genera, lentiviruses only rarely form ERV copies. We performed a computational search aimed at identification of novel endogenous lentiviruses in vertebrate genomes. Using the in silico strategy, we have screened 104 publicly available vertebrate genomes for the presence of endogenous lentivirus sequences. In addition to the previously described cases, the search revealed the presence of endogenous lentivirus in the genome of Malayan colugo (Galeopterus variegatus). At least three complete copies of this virus, denoted ELVgv, were detected in the colugo genome, and approximately one hundred solo LTR sequences. The assembled consensus sequence of ELVgv had typical lentivirus genome organization including three predicted accessory genes. Phylogenetic analysis placed this virus as a distinct subgroup within the lentivirus genus. The time of insertion into the dermopteran lineage was estimated to be more than thirteen million years ago. We report the discovery of the first endogenous lentivirus in the mammalian order Dermoptera, which is a taxon close to the Primates. Lentiviruses have infiltrated the mammalian germline several times across millions of years. The colugo virus described here represents possibly the oldest documented endogenization event and its discovery can lead to new insights into lentivirus evolution. This is also the first report of an endogenous lentivirus in an Asian mammal, indicating a long-term presence of this retrovirus family in Asian continent.

  3. Single Lipid Molecule Dynamics on Supported Lipid Bilayers with Membrane Curvature.

    PubMed

    Cheney, Philip P; Weisgerber, Alan W; Feuerbach, Alec M; Knowles, Michelle K

    2017-03-15

    The plasma membrane is a highly compartmentalized, dynamic material and this organization is essential for a wide variety of cellular processes. Nanoscale domains allow proteins to organize for cell signaling, endo- and exocytosis, and other essential processes. Even in the absence of proteins, lipids have the ability to organize into domains as a result of a variety of chemical and physical interactions. One feature of membranes that affects lipid domain formation is membrane curvature. To directly test the role of curvature in lipid sorting, we measured the accumulation of two similar lipids, 1,2-Dihexadecanoyl- sn -glycero-3-phosphoethanolamine (DHPE) and hexadecanoic acid (HDA), using a supported lipid bilayer that was assembled over a nanopatterned surface to obtain regions of membrane curvature. Both lipids studied contain 16 carbon, saturated tails and a head group tag for fluorescence microscopy measurements. The accumulation of lipids at curvatures ranging from 28 nm to 55 nm radii was measured and fluorescein labeled DHPE accumulated more than fluorescein labeled HDA at regions of membrane curvature. We then tested whether single biotinylated DHPE molecules sense curvature using single particle tracking methods. Similar to groups of fluorescein labeled DHPE accumulating at curvature, the dynamics of single molecules of biotinylated DHPE was also affected by membrane curvature and highly confined motion was observed.

  4. Rutin exhibits hepatoprotective effects in a mouse model of non-alcoholic fatty liver disease by reducing hepatic lipid levels and mitigating lipid-induced oxidative injuries.

    PubMed

    Liu, Qingsheng; Pan, Ran; Ding, Lei; Zhang, Fuli; Hu, Linfeng; Ding, Bin; Zhu, Linwensi; Xia, Yongliang; Dou, Xiaobing

    2017-08-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of hepatic lipids and oxidative injury of hepatocytes. Rutin is a natural flavonoid with significant roles in combating cellular oxidative stress and regulating lipid metabolism. The current study aims to investigate the molecular mechanisms underlying rutin's hypolipidemic and hepatoprotective effects in nonalcoholic fatty liver disease. Rutin treatment was applied to male C57BL/6 mice maintained on a high-fat diet and HepG2 cells challenged with oleic acid. Hepatic lipid accumulation was evaluated by triglyceride assay and Oil Red O staining. Oxidative hepatic injury was assessed by malondialdehyde assay, superoxide dismutase assay and reactive oxygen species assay. The expression levels of various lipogenic and lipolytic genes were determined by quantitative real-time polymerase chain reactions. In addition, liver autophagy was investigated by enzyme-linked immunosorbent assay. In both fat-challenged murine liver tissues and HepG2 cells, rutin treatment was shown to significantly lower triglyceride content and the abundance of lipid droplets. Rutin was also found to reduce cellular malondialdehyde level and restore superoxide dismutase activity in hepatocytes. Among the various lipid-related genes, rutin treatment was able to restore the expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and its downstream targets, carnitine palmitoyltransferase 1 and 2 (CPT-1 and CPT-2), while suppressing those of sterol regulatory element-binding protein 1c (SREBP-1c), diglyceride acyltransfase 1 and 2 (DGAT-1 and 2), as well as acyl-CoA carboxylase (ACC). In addition, rutin was shown to repress the autophagic function of liver tissues by down-regulating key autophagy biomarkers, including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β). The experimental data demonstrated that rutin could reduce triglyceride content and mitigate oxidative injuries in fat

  5. WINTERING YELLOW-RUMPED WARBLERS (DENDROICA CORONATA) TRACK MANIPULATED ABUNDANCE OF MYRICA CERIFERA FRUITS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    K.L. Borgmann; S.F. Pearson; D.J. Levey

    2004-01-01

    Borgmann, K.L., S.F. Pearson, D.J. Levey, and C.H. Greenberg. 2004. Wintering yellow-rumped warblers (Dendroica coronata) track manipulated abundance of Myrica cerifera fruits. The Auk 121(1):74-87. Abstract: Food availability during winter may determine habitat use and limit populations of overwintering birds, yet its importance is difficult to judge because few studies have experimentally tested the response of nonbreeding birds to changes in resource abundance. We experimentally examined the link between fruit availability and habitat use by manipulating winter abundance of Myrica cerifera L. (Myricaceae) fruits in managed longleaf (Pinus palustris) and loblolly (P. taeda) pine stands in South Carolina. Myrica ceriferamore » is a common understory shrub in the southeastern United States and provides lipid-rich fruit in late winter (February and March), when insects and other fruits are scarce. On treatment plots, we covered fruiting M. cerifera shrubs with netting in early winter to prevent birds from eating their fruits. In late February, when M. cerifera fruit crops were largely depleted elsewhere on our study site, we uncovered the shrubs and documented the response of the bird community to those patches of high fruit availability. Relative to control plots, total bird abundance (excluding the most common species, Yellow-rumped Warbler [Dendroica coronata]) and species richness did not change after net removal. Yellow-rumped Warblers, however, became significantly more abundant on treatment plots after net removal, which suggests that they track M. cerifera fruit abundance. We suggest that M. cerifera plays a role in determining the local distribution of wintering Yellow-rumped Warblers at our study site. To put these results into a management context, we also examined the effect of prescribed fire frequencies on M. cerifera fruit production. Across pine stands with different fire regimes, M. cerifera fruit abundance increased with the number of years since

  6. Solubilization of lipids and lipid phases by the styrene-maleic acid copolymer.

    PubMed

    Dominguez Pardo, Juan J; Dörr, Jonas M; Iyer, Aditya; Cox, Ruud C; Scheidelaar, Stefan; Koorengevel, Martijn C; Subramaniam, Vinod; Killian, J Antoinette

    2017-01-01

    A promising tool in membrane research is the use of the styrene-maleic acid (SMA) copolymer to solubilize membranes in the form of nanodiscs. Since membranes are heterogeneous in composition, it is important to know whether SMA thereby has a preference for solubilization of either specific types of lipids or specific bilayer phases. Here, we investigated this by performing partial solubilization of model membranes and analyzing the lipid composition of the solubilized fraction. We found that SMA displays no significant lipid preference in homogeneous binary lipid mixtures in the fluid phase, even when using lipids that by themselves show very different solubilization kinetics. By contrast, in heterogeneous phase-separated bilayers, SMA was found to have a strong preference for solubilization of lipids in the fluid phase as compared to those in either a gel phase or a liquid-ordered phase. Together the results suggest that (1) SMA is a reliable tool to characterize native interactions between membrane constituents, (2) any solubilization preference of SMA is not due to properties of individual lipids but rather due to properties of the membrane or membrane domains in which these lipids reside and (3) exploiting SMA resistance rather than detergent resistance may be an attractive approach for the isolation of ordered domains from biological membranes.

  7. Incorporation of liquid lipid in lipid nanoparticles for ocular drug delivery enhancement

    NASA Astrophysics Data System (ADS)

    Shen, Jie; Sun, Minjie; Ping, Qineng; Ying, Zhi; Liu, Wen

    2010-01-01

    The present work investigates the effect of liquid lipid incorporation on the physicochemical properties and ocular drug delivery enhancement of nanostructured lipid carriers (NLCs) and attempts to elucidate in vitro and in vivo the potential of NLCs for ocular drug delivery. The CyA-loaded or fluorescein-marked nanocarriers composed of Precifac ATO 5 and Miglyol 840 (as liquid lipid) were prepared by melting-emulsion technology, and the physicochemical properties of nanocarriers were determined. The uptake of nanocarriers by human corneal epithelia cell lines (SDHCEC) and rabbit cornea was examined. Ex vivo fluorescence imaging was used to investigate the ocular distribution of nanocarriers. The in vitro cytotoxicity and in vivo acute tolerance were evaluated. The higher drug loading capacity and improved in vitro sustained drug release behavior of lipid nanoparticles was found with the incorporation of liquid lipid in lipid nanoparticles. The uptake of nanocarriers by the SDHCEC was increased with the increase in liquid lipid loading. The ex vivo fluorescence imaging of the ocular tissues indicated that the liquid lipid incorporation could improve the ocular retention and penetration of ocular therapeutics. No alternation was macroscopically observed in vivo after ocular surface exposure to nanocarriers. These results indicated that NLC was a biocompatible and potential nanocarrier for ocular drug delivery enhancement.

  8. Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease

    PubMed Central

    Uderhardt, Stefan; Ackermann, Jochen A.; Fillep, Tobias; Hammond, Victoria J.; Willeit, Johann; Stark, Konstantin; Rossaint, Jan; Schubert, Irene; Mielenz, Dirk; Dietel, Barbara; Raaz-Schrauder, Dorette; Ay, Cihan; Thaler, Johannes; Heim, Christian; Collins, Peter W.; Schabbauer, Gernot; Mackman, Nigel; Voehringer, David; Nadler, Jerry L.; Lee, James J.; Massberg, Steffen; Rauh, Manfred; O’Donnell, Valerie B.

    2017-01-01

    Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease. PMID:28566277

  9. Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Structure, Preparation and Application

    PubMed Central

    Naseri, Neda; Valizadeh, Hadi; Zakeri-Milani, Parvin

    2015-01-01

    Lipid nanoparticles (LNPs) have attracted special interest during last few decades. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are two major types of Lipid-based nanoparticles. SLNs were developed to overcome the limitations of other colloidal carriers, such as emulsions, liposomes and polymeric nanoparticles because they have advantages like good release profile and targeted drug delivery with excellent physical stability. In the next generation of the lipid nanoparticle, NLCs are modified SLNs which improve the stability and capacity loading. Three structural models of NLCs have been proposed. These LNPs have potential applications in drug delivery field, research, cosmetics, clinical medicine, etc. This article focuses on features, structure and innovation of LNPs and presents a wide discussion about preparation methods, advantages, disadvantages and applications of LNPs by focusing on SLNs and NLCs. PMID:26504751

  10. Recruiting endogenous stem cells: a novel therapeutic approach for erectile dysfunction

    PubMed Central

    Xin, Zhong-Cheng; Xu, Yong-De; Lin, Guiting; Lue, Tom F; Guo, Ying-Lu

    2016-01-01

    Transplanted stem cells (SCs), owing to their regenerative capacity, represent one of the most promising methods to restore erectile dysfunction (ED). However, insufficient source, invasive procedures, ethical and regulatory issues hamper their use in clinical applications. The endogenous SCs/progenitor cells resident in organ and tissues play critical roles for organogenesis during development and for tissue homeostasis in adulthood. Even without any therapeutic intervention, human body has a robust self-healing capability to repair the damaged tissues or organs. Therefore, SCs-for-ED therapy should not be limited to a supply-side approach. The resident endogenous SCs existing in patients could also be a potential target for ED therapy. The aim of this review was to summarize contemporary evidence regarding: (1) SC niche and SC biological features in vitro; (2) localization and mobilization of endogenous SCs; (3) existing evidence of penile endogenous SCs and their possible mode of mobilization. We performed a search on PubMed for articles related to these aspects in a wide range of basic studies. Together, numerous evidences hold the promise that endogenous SCs would be a novel therapeutic approach for the therapy of ED. PMID:25926601

  11. Biochemistry of ungerminated and germinated spores of the vesicular-arbuscular mycorrhizal fungus, Glomus caledonius: changes in neutral and polar lipids.

    PubMed

    Beilby, J P; Kidby, D K

    1980-08-01

    Neutral and polar spore lipids of the vesicular-arbuscular (VA) endophyte Glomus caledonius, were identified and quantitatively determined during spore germination, germ tube growth, and germ tube senescence. There are no previous reports detailing the spore lipid components of any member of the Endogenaceae, which is in the Zygomycotina. The fungus contained 45 to 72% total lipid depending upon its stage of growth. The concentration of neutral lipids decreased during germination while the polar lipids increased. Triacylglycerides were the most abundant neutral lipid, and lesser amounts of diacylglycerides, monoacylglycerides, free fatty acids, bound fatty acids, hydrocarbons, and sterols. The major fatty acids identified by gas--liquid chromatography and mass spectrometry were 16:1, 16:0, and 18:1. The minor fatty acids identified were n-3 and n-6 polyunsaturates. The n-3 polyunsaturated fatty acids have not been reported before in Zygomycetes. The fatty acid composition of the individual lipid classes was examined. The major phospholipids were phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine, with smaller amounts of diphosphatidylglycerol and phosphatidic acid. The free sterol fraction was in greater quantity than sterol esters during germination and germ tube elongation. The capacity to synthesize sterols was demonstrated. Approximate net rates of change in the different lipid components were calculated. During spore germination and early germ tube growth, there was a net synthesis of lipids, with a large production of free fatty acids, in the germinating spore. Later in the growth period there was a net degradation of lipid, characterized by a large conversion of free fatty acids to unidentified compounds. During this period net free sterol synthesis ceased and sterol ester synthesis continued using the existing free sterol.

  12. Expanding roles for lipid droplets

    PubMed Central

    Welte, Michael A.

    2015-01-01

    Summary Lipid droplets are the intracellular sites for neutral lipid storage. They are critical for lipid metabolism and energy homeostasis, and their dysfunction has been linked to many diseases. Accumulating evidence suggests that the roles lipid droplets play in biology are significantly broader than previously anticipated. Lipid droplets are the source of molecules important in the nucleus: they can sequester transcription factors and chromatin components and generate the lipid ligands for certain nuclear receptors. Lipid droplets have also emerged as important nodes for fatty acid trafficking, both inside the cell and between cells. In immunity, new roles for droplets, not directly linked to lipid metabolism, have been uncovered, as assembly platforms for specific viruses and as reservoirs for proteins that fight intracellular pathogens. Until recently, knowledge about droplets in the nervous system has been minimal, but now there are multiple links between lipid droplets and neurodegeneration: Many candidate genes for Hereditary Spastic Paraplegia also have central roles in lipid-droplet formation and maintenance, and mitochondrial dysfunction in neurons can lead to transient accumulating of lipid droplets in neighboring glial cells, an event that may, in turn, contribute to neuronal damage. As the cell biology and biochemistry of lipid droplets are increasingly well understood, the next few years should yield many new mechanistic insights into these novel functions of lipid droplets. PMID:26035793

  13. Protection from experimental asthma by an endogenous bronchodilator.

    PubMed

    Que, Loretta G; Liu, Limin; Yan, Yun; Whitehead, Gregory S; Gavett, Stephen H; Schwartz, David A; Stamler, Jonathan S

    2005-06-10

    Mechanisms that protect against asthma remain poorly understood. S-nitrosoglutathione (GSNO), an endogenous bronchodilator, is depleted from asthmatic airways, suggesting a protective role. We report that, following allergen challenge, wild-type mice exhibiting airway hyperresponsivity have increased airway levels of the enzyme GSNO reductase (GSNOR) and are depleted of lung S-nitrosothiols (SNOs). In contrast, mice with genetic deletion of GSNOR exhibit increases in lung SNOs and are protected from airway hyperresponsivity. Our results indicate that endogenous SNOs, governed by GSNOR, are critical regulators of airway responsivity and may provide new therapeutic approaches to asthma.

  14. Lipid droplets accumulation and other biochemical changes induced in the fungal pathogen Ustilago maydis under nitrogen-starvation.

    PubMed

    Aguilar, Lucero Romero; Pardo, Juan Pablo; Lomelí, Mónica Montero; Bocardo, Oscar Ivan Luqueño; Juárez Oropeza, Marco A; Guerra Sánchez, Guadalupe

    2017-10-01

    In many organisms, the growth under nitrogen-deprivation or a poor nitrogen source impacts on the carbon flow distribution and causes accumulation of neutral lipids, which are stored as lipid droplets (LDs). Efforts are in progress to find the mechanism of LDs synthesis and degradation, and new organisms capable of accumulating large amounts of lipids for biotechnological applications. In this context, when Ustilago maydis was cultured in the absence of a nitrogen source, there was a large accumulation of lipid bodies containing mainly triacylglycerols. The most abundant fatty acids in lipid bodies at the stationary phase were palmitic, linoleic, and oleic acids, and they were synthesized de novo by the fatty-acid synthase. In regard to the production of NADPH for the synthesis of fatty acids, the cytosolic NADP + -dependent isocitrate dehydrogenase and the glucose-6-phosphate and 6-phosphogluconate dehydrogenases couple showed the highest specific activities, with a lower activity of the malic enzyme. The ATP-citrate lyase activity was not detected in any of the culture conditions, which points to a different mechanism for the transfer of acetyl-CoA into the cytosol. Protein and RNA contents decreased when U. maydis was grown without a nitrogen source. Due to the significant accumulation of triacylglycerols and the particular composition of fatty acids, U. maydis can be considered an alternative model for biotechnological applications.

  15. Seasonal variability in the abundance and stable carbon-isotopic composition of lipid biomarkers in suspended particulate matter from a stratified equatorial lake (Lake Chala, Kenya/Tanzania): Implications for the sedimentary record

    NASA Astrophysics Data System (ADS)

    van Bree, L. G. J.; Peterse, F.; van der Meer, M. T. J.; Middelburg, J. J.; Negash, A. M. D.; De Crop, W.; Cocquyt, C.; Wieringa, J. J.; Verschuren, D.; Sinninghe Damsté, J. S.

    2018-07-01

    We studied the distribution and stable carbon-isotopic (δ13C) composition of various lipid biomarkers in suspended particulate matter (SPM) from the water column of Lake Chala, a permanently stratified crater lake in equatorial East Africa, to evaluate their capacity to reflect seasonality in water-column processes and associated changes in the lake's phytoplankton community. This lake has large seasonal variation in water-column dynamics (stratified during wet seasons and mixing during dry seasons) with associated phytoplankton succession. We analyzed lipid biomarkers in SPM collected monthly at 5 depths (0-80 m) from September 2013 to January 2015. Seasonal variation in total phytoplankton biovolume is strongly reflected in the concentration of phytadienes, a derivative of the general photosynthetic pigment chlorophyll. The wax and wane of several specific biomarker lipids between June and December 2014 reflect pronounced phytoplankton succession after deep mixing, starting with a long and sustained chlorophyte bloom (reflected by C23:1, C25:1 and C27:1n-alkenes, and C21 and C23n-alkanes), followed by a peak in diatoms between July and October (loliolide and isololiolide), and then eustigmatophytes (C30 and C32 1,15 diols) once stratification resumes in October. Peak abundance of the C19:1n-alkene during shallow mixing of the water column in January-February 2014 can be tentatively linked to the seasonal distribution of cyanobacteria. The concentration, seasonal variability, and low δ13C values of the C28 fatty acid in the SPM suggest that this biomarker is produced in the water column of Lake Chala instead of having the typically assumed vascular plant origin. The δ13C signature of particulate carbon and all aquatic biomarkers become increasingly more negative (by up to 16‰) during mixing-induced episodes of high productivity, whereas enrichment would be expected during such blooms. This reversed fractionation may be attributed to chemically enhanced

  16. Preservation of Lipid Biomarkers Under Prolonged and Extreme Hyperaridity in Atacama Desert Soils

    NASA Technical Reports Server (NTRS)

    Wilhelm, Mary Beth

    2015-01-01

    Molecular biomarkers are the most direct biosignatures of life on early Earth and a key target in the search for life on Mars. Lipid biomarkers are of particular interest given their ability to survive oxidative degradation and record microbial presence and activity of microorganisms that occurred billions of years ago (Eigenbrode, 2008). Environmental conditions that suspend biotic and abiotic degradative processes prior to lithification can lead to enhanced biomolecular preservation over geological time-scales. The hyperarid core of the Atacama Desert in northern Chile offers a unique environment to investigate lipid biomarker taphonomy under extreme and prolonged dryness. We investigated the accumulation and degree of preservation of lipid biomarkers in million-year-old hyperarid soils where primarily abiotic conditions influence their taphonomy. Soils were extracted and free and membrane bound lipids were analyzed across a vertical profile of 2.5 meters in the Yungay hyper-arid core of the Atacama Desert. Due to the extremely low inventory of biomass in Atacama soils, samples were collected by scientists wearing cleanroom suits to minimize anthropogenic contamination during sampling. Fatty acids were found to be well preserved in Yungay soils, and were most abundant in the clay-rich soils at approx.2 m depth (approx.750 ng of fatty acid methyl ester/g of soil). These buried clays layers were fluvially deposited approximately 2 million years ago, and have been excluded from exposure to rainwater and modern surficial processes since their emplacement (Ewing et al., 2008). Monocarboxylic fatty acid, monohydroxy fatty acid, glycerol tetraether, and n-alkane hydrocarbon content was found to change with depth. Lipid biomarker content in deeper soil layers is suggestive of soils having been formed at a time when environmental conditions were capable of supporting active microbial communities and plants. In short, total lipid extracts reveal a remarkable degree of

  17. Preservation of Lipid Biomarkers Under Prolonged and Extreme Hyperaridity in Atacama Desert Soils

    NASA Astrophysics Data System (ADS)

    Wilhelm, M. B.; Davila, A. F.; Eigenbrode, J. L.; Parenteau, M. N.; Jahnke, L. L.; Summons, R. E.; Liu, X.; Wray, J. J.; Stamos, B.; O'Reilly, S. S.; Williams, A. J.

    2015-12-01

    Molecular biomarkers are the most direct biosignatures of life on early Earth and a key target in the search for life on Mars. Lipid biomarkers are of particular interest given their ability to survive oxidative degradation and record microbial presence and activity of microorganisms that occurred billions of years ago (Eigenbrode, 2008). Environmental conditions that suspend biotic and abiotic degradative processes prior to lithification can lead to enhanced biomolecular preservation over geological time-scales. The hyperarid core of the Atacama Desert in northern Chile offers a unique environment to investigate lipid biomarker taphonomy under extreme and prolonged dryness. We investigated the accumulation and degree of preservation of lipid biomarkers in million-year-old hyperarid soils where primarily abiotic conditions influence their taphonomy. Soils were extracted and free and membrane bound lipids were analyzed across a vertical profile of 2.5 meters in the Yungay hyper-arid core of the Atacama Desert. Due to the extremely low inventory of biomass in Atacama soils, samples were collected by scientists wearing cleanroom suits to minimize anthropogenic contamination during sampling. Fatty acids were found to be well preserved in Yungay soils, and were most abundant in the clay-rich soils at ~2 m depth (~750 ng of fatty acid methyl ester/g of soil). These buried clays layers were fluvially deposited approximately 2 million years ago, and have been excluded from exposure to rainwater and modern surficial processes since their emplacement (Ewing et al., 2008). Monocarboxylic fatty acid, monohydroxy fatty acid, glycerol tetraether, and n-alkane hydrocarbon content was found to change with depth. Lipid biomarker content in deeper soil layers is suggestive of soils having been formed at a time when environmental conditions were capable of supporting active microbial communities and plants. In short, total lipid extracts reveal a remarkable degree of lipid biomarker

  18. Effective non-viral delivery of siRNA to acute myeloid leukemia cells with lipid-substituted polyethylenimines.

    PubMed

    Landry, Breanne; Aliabadi, Hamidreza Montazeri; Samuel, Anuja; Gül-Uludağ, Hilal; Jiang, Xiaoyan; Kutsch, Olaf; Uludağ, Hasan

    2012-01-01

    Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ≈ 0.5 and led to siRNA/polymer complexes of ≈ 100 nm size. While the native PEI2 did not display cytotoxicity on AML cell lines THP-1, KG-1 and HL-60, lipid-modification on PEI2 slightly increased the cytotoxicity, which was consistent with increased interaction of polymers with cell membranes. Cellular delivery of siRNA was dependent on the nature of lipid substituent and the extent of lipid substitution, and varied among the three AML cell lines used. Linoleic acid-substituted polymers performed best among the prepared polymers and gave a siRNA delivery equivalent to better performing commercial reagents. Using THP-1 cells and a reporter (GFP) and an endogenous (CXCR4) target, effective silencing of the chosen targets was achieved with 25 to 50 nM of siRNA concentrations, and without adversely affecting subsequent cell growth. We conclude that lipid-substituted PEI2 can serve as an effective delivery of siRNA to leukemic cells and could be employed in molecular therapy of leukemia.

  19. Effective Non-Viral Delivery of siRNA to Acute Myeloid Leukemia Cells with Lipid-Substituted Polyethylenimines

    PubMed Central

    Landry, Breanne; Aliabadi, Hamidreza Montazeri; Samuel, Anuja; Gül-Uludağ, Hilal; Jiang, Xiaoyan; Kutsch, Olaf; Uludağ, Hasan

    2012-01-01

    Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ∼0.5 and led to siRNA/polymer complexes of ∼100 nm size. While the native PEI2 did not display cytotoxicity on AML cell lines THP-1, KG-1 and HL-60, lipid-modification on PEI2 slightly increased the cytotoxicity, which was consistent with increased interaction of polymers with cell membranes. Cellular delivery of siRNA was dependent on the nature of lipid substituent and the extent of lipid substitution, and varied among the three AML cell lines used. Linoleic acid-substituted polymers performed best among the prepared polymers and gave a siRNA delivery equivalent to better performing commercial reagents. Using THP-1 cells and a reporter (GFP) and an endogenous (CXCR4) target, effective silencing of the chosen targets was achieved with 25 to 50 nM of siRNA concentrations, and without adversely affecting subsequent cell growth. We conclude that lipid-substituted PEI2 can serve as an effective delivery of siRNA to leukemic cells and could be employed in molecular therapy of leukemia. PMID:22952927

  20. Brassica rapa Has Three Genes That Encode Proteins Associated with Different Neutral Lipids in Plastids of Specific Tissues1

    PubMed Central

    Kim, Hyun Uk; Wu, Sherry S.H.; Ratnayake, Chandra; Huang, Anthony H.C.

    2001-01-01

    Plastid lipid-associated protein (PAP), a predominant structural protein associated with carotenoids and other non-green neutral lipids in plastids, was shown to be encoded by a single nuclear gene in several species. Here we report three PAP genes in the diploid Brassica rapa; the three PAPs are associated with different lipids in specific tissues. Pap1 and Pap2 are more similar to each other (84% amino acid sequence identity) than to Pap3 (46% and 44%, respectively) in the encoded mature proteins. Pap1 transcript was most abundant in the maturing anthers (tapetum) and in lesser amounts in leaves, fruit coats, seeds, and sepals; Pap2 transcript was abundant only in the petals; and Pap3 transcript had a wide distribution, but at minimal levels in numerous organs. Immunoblotting after sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that most organs had several nanograms of PAP1 or PAP2 per milligram of total protein, the highest amounts being in the anthers (10.9 μg mg−1 PAP1) and petals (6.6 μg mg−1 PAP2), and that they had much less PAP3 (<0.02 μg mg−1). In these organs PAP was localized in isolated plastid fractions. Plants were subjected to abiotic stresses; drought and ozone reduced the levels of the three Pap transcripts, whereas mechanical wounding and altering the light intensity enhanced their levels. We conclude that the PAP gene family consists of several members whose proteins are associated with different lipids and whose expressions are controlled by distinct mechanisms. Earlier reports of the expression of one Pap gene in various organs in a species need to be re-examined. PMID:11351096

  1. Nutrients and neurodevelopment: lipids.

    PubMed

    González, Horacio F; Visentin, Silvana

    2016-10-01

    Nutrients, lipids in particular, make up the central nervous system structure and play major functional roles: they stimulate development, migration, and nerve cell differentiation. They are part of gray matter, white matter, nerve nuclei, and synaptogenesis. Breast milk contains lipids which are crucial for infant brain development. The lipid profile of breast milk was used as a guideline for the development of breast milk substitutes. However, to date, no substitute has matched it. Complementary feeding should include docosahexaenoic acid, arachidonic acid, other polyunsaturated fatty acids, saturated fatty acids, and complex lipids found in milk fat. The lipid composition of breast milk depends on maternal intake and nutritional status during pregnancy and breast-feeding. It has a great impact on development. Our goal is to review scientific literature regarding the role of lipids on infant brain development and the importance of breast milk lipid composition, maternal diet, and complementary feeding. Sociedad Argentina de Pediatría.

  2. Lipid catabolism in microalgae.

    PubMed

    Kong, Fantao; Romero, Ismael Torres; Warakanont, Jaruswan; Li-Beisson, Yonghua

    2018-06-01

    Lipid degradation processes are important in microalgae because survival and growth of microalgal cells under fluctuating environmental conditions require permanent remodeling or turnover of membrane lipids as well as rapid mobilization of storage lipids. Lipid catabolism comprises two major spatially and temporarily separated steps, namely lipolysis, which releases fatty acids and head groups and is catalyzed by lipases at membranes or lipid droplets, and degradation of fatty acids to acetyl-CoA, which occurs in peroxisomes through the β-oxidation pathway in green microalgae, and can sometimes occur in mitochondria in some other algal species. Here we review the current knowledge on the enzymes and regulatory proteins involved in lipolysis and peroxisomal β-oxidation and highlight gaps in our understanding of lipid degradation pathways in microalgae. Metabolic use of acetyl-CoA products via glyoxylate cycle and gluconeogenesis is also reviewed. We then present the implication of various cellular processes such as vesicle trafficking, cell cycle and autophagy on lipid turnover. Finally, physiological roles and the manipulation of lipid catabolism for biotechnological applications in microalgae are discussed. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

  3. Gastrointestinal Endogenous Proteins as a Source of Bioactive Peptides - An In Silico Study

    PubMed Central

    Dave, Lakshmi A.; Montoya, Carlos A.; Rutherfurd, Shane M.; Moughan, Paul J.

    2014-01-01

    Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein. PMID:24901416

  4. Early LC3 lipidation induced by d-limonene does not rely on mTOR inhibition, ERK activation and ROS production and it is associated with reduced clonogenic capacity of SH-SY5Y neuroblastoma cells.

    PubMed

    Berliocchi, Laura; Chiappini, Carlotta; Adornetto, Annagrazia; Gentile, Debora; Cerri, Silvia; Russo, Rossella; Bagetta, Giacinto; Corasaniti, Maria Tiziana

    2018-02-01

    d-Limonene is a natural monoterpene abundant in Citrus essential oils. It is endowed with several biological activities, including inhibition of carcinogenesis and promotion of tumour regression. Recently, d-limonene has been shown to modulate autophagic markers in vitro at concentrations found in vivo, in clinical pharmacokinetic studies. Autophagy is an intracellular catabolic process serving as both an adaptive metabolic response and a quality control mechanism. Because autophagy defects have been linked to a wide range of human pathologies, including neurodegeneration and cancer, there is a need for new pharmacological tools to control deregulated autophagy. To better understand the effects of d-limonene on autophagy, to identify the molecular mechanisms through which this monoterpene rapidly triggers LC3 lipidation and to evaluate the role for autophagy in long-term effects of d-limonene. Human SH-SY5Y neuroblastoma, HepG2 hepatocellular carcinoma and MCF7 breast cancer cells were used. Endogenous LC3-II levels were evaluated by western blotting. Autophagic flux assay was performed using bafilomycin A1 and chloroquine. Intracellular distribution of LC3 protein was studied by confocal microscopy analysis of LC3B-GFP transduced cells. Expression of lysosomal-membrane protein LAMP-1 was assessed by immunofluorescence analysis. Phosphorylated levels of downstream substrates of mTOR kinase (p70S6 kinase, 4E-BP1, and ULK1) and ERK were analyzed by western blotting. Production of reactive oxygen species (ROS) was assessed by live confocal microscopy of cells loaded with CellROX ® Green Reagent. Clonogenic assay was used to evaluate the ability of treated cells to proliferate and form colonies. LC3 lipidation promoted by d-limonene correlates with autophagosome formation and stimulation of basal autophagy. LC3 lipidation does not rely on inhibition of mTOR kinase, which instead appears to be transiently activated. In addition, d-limonene rapidly activates ERK and

  5. SLDP: a novel protein related to caleosin is associated with the endosymbiotic Symbiodinium lipid droplets from Euphyllia glabrescens.

    PubMed

    Pasaribu, Buntora; Lin, I-Ping; Tzen, Jason T C; Jauh, Guang-Yuh; Fan, Tung-Yung; Ju, Yu-Min; Cheng, Jing-O; Chen, Chii-Shiarng; Jiang, Pei-Luen

    2014-10-01

    Intracellular lipid droplets (LDs) have been proposed to play a key role in the mutualistic endosymbiosis between reef-building corals and the dinoflagellate endosymbiont Symbiodinium spp. This study investigates and identifies LD proteins in Symbiodinium from Euphyllia glabrescens. Discontinuous Percoll gradient centrifugation was used to separate Symbiodinium cells from E. glabrescens tentacles. Furthermore, staining with a fluorescent probe, Nile red, indicated that lipids accumulated in that freshly isolated Symbiodinium cells and lipid analyses further showed polyunsaturated fatty acids (PUFA) was abundant. The stable LDs were purified from endosymbiotic Symbiodinium cells. The structural integrity of the Symbiodinium LDs was maintained via electronegative repulsion and steric hindrance possibly provided by their surface proteins. Protein extracts from the purified LDs revealed a major protein band with a molecular weight of 20 kDa, which was termed Symbiodinium lipid droplet protein (SLDP). Interestingly, immunological cross-recognition analysis revealed that SLDP was detected strongly by the anti-sesame and anti-cycad caleosin antibodies. It was suggested that the stable Symbiodinium LDs were sheltered by this unique structural protein and was suggested that SLDP might be homologous to caleosin to a certain extent.

  6. Embryo-specific expression of soybean oleosin altered oil body morphogenesis and increased lipid content in transgenic rice seeds.

    PubMed

    Liu, Wen Xian; Liu, Hua Liang; Qu, Le Qing

    2013-09-01

    Oleosin is the most abundant protein in the oil bodies of plant seeds, playing an important role in regulating oil body formation and lipid accumulation. To investigate whether lipid accumulation in transgenic rice seeds depends on the expression level of oleosin, we introduced two soybean oleosin genes encoding 24 kDa proteins into rice under the control of an embryo-specific rice promoter REG-2. Overexpression of soybean oleosin in transgenic rice leads to an increase of seed lipid content up to 36.93 and 46.06 % higher than that of the non-transgenic control, respectively, while the overall fatty acid profiles of triacylglycerols remained unchanged. The overexpression of soybean oleosin in transgenic rice seeds resulted in more numerous and smaller oil bodies compared with wild type, suggesting that an inverse relationship exists between oil body size and the total oleosin level. The increase in lipid content is accompanied by a reduction in the accumulation of total seed protein. Our results suggest that it is possible to increase rice seed oil content for food use and for use as a low-cost feedstock for biodiesel by overexpressing oleosin in rice seeds.

  7. Endogenous opiates and behavior: 2005.

    PubMed

    Bodnar, Richard J; Klein, Gad E

    2006-12-01

    This paper is the 28th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning over a quarter-century of research. It summarizes papers published during 2005 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity, neurophysiology and transmitter release (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); immunological responses (Section 17).

  8. Endogenous opiates and behavior: 2010.

    PubMed

    Bodnar, Richard J

    2011-12-01

    This paper is the thirty-third consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2010 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration (Section 16); and immunological responses (Section 17). Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Endogenous opiates and behavior: 2002.

    PubMed

    Bodnar, Richard J; Hadjimarkou, Maria M

    2003-08-01

    This paper is the twenty-fifth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning over a quarter-century of research. It summarizes papers published during 2002 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17).

  10. Endogenous opiates and behavior: 2006.

    PubMed

    Bodnar, Richard J

    2007-12-01

    This paper is the 29th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning 30 years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17).

  11. Endogenous opiates and behavior: 2009.

    PubMed

    Bodnar, Richard J

    2010-12-01

    This paper is the 32nd consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2009 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Endogenous opiates and behavior: 2011.

    PubMed

    Bodnar, Richard J

    2012-12-01

    This paper is the thirty-fourth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2011 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration (Section 16); and immunological responses (Section 17). Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Endogenous opiates and behavior: 2003.

    PubMed

    Bodnar, Richard J; Klein, Gad E

    2004-12-01

    This paper is the 26th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning over a quarter-century of research. It summarizes papers published during 2003 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17).

  14. Endogenous opiates and behavior: 2008.

    PubMed

    Bodnar, Richard J

    2009-12-01

    This paper is the 31st consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2008 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17).

  15. Endogenous Opiates and Behavior: 2006

    PubMed Central

    Bodnar, Richard J.

    2009-01-01

    This paper is the twenty-ninth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning thirty years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:17949854

  16. Endogenous opiates and behavior: 2012.

    PubMed

    Bodnar, Richard J

    2013-12-01

    This paper is the thirty-fifth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2012 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Neural correlates of endogenous attention, exogenous attention and inhibition of return in touch.

    PubMed

    Jones, Alexander; Forster, Bettina

    2014-07-01

    Selective attention helps process the myriad of information constantly touching our body. Both endogenous and exogenous mechanisms are relied upon to effectively process this information; however, it is unclear how they relate in the sense of touch. In three tasks we contrasted endogenous and exogenous event-related potential (ERP) and behavioural effects. Unilateral tactile cues were followed by a tactile target at the same or opposite hand. Clear behavioural effects showed facilitation of expected targets both when the cue predicted targets at the same (endogenous predictive task) and opposite hand (endogenous counter-predictive task), and these effects also correlated with ERP effects of endogenous attention. In an exogenous task, where the cue was non-informative, inhibition of return (IOR) was observed. The electrophysiological results demonstrated early effects of exogenous attention followed by later endogenous attention modulations. These effects were independent in both the endogenous predictive and exogenous tasks. However, voluntarily directing attention away from a cued body part influenced the early exogenous marker (N80). This suggests that the two mechanisms are interdependent, at least when the task requires more demanding shifts of attention. The early marker of exogenous tactile attention, the N80, was not directly related to IOR, which may suggest that exogenous attention and IOR are not necessarily two sides of the same coin. This study adds valuable new insight into how we process and select information presented to our body, showing both independent and interdependent effects of endogenous and exogenous attention in touch. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period.

    PubMed

    Pappa, Theodora; Alevizaki, Maria

    2012-08-01

    Cardio- and cerebro-vascular diseases are two leading causes of death and long-term disability in postmenopausal women. The acute fall of estrogen in menopause is associated with increased cardiovascular risk. The relative contribution of androgen to this risk is also being recognized. The use of more sensitive assays for estradiol measurement and the study of receptor and carrier protein gene polymorphisms have provided some new information on the clinical relevance of endogenous sex steroids. We provide an update on the role of endogenous sex steroids on cardio- and cerebro-vascular disease in the postmenopausal period. We performed a PubMed search using the terms 'endogenous estrogen', 'androgen', 'cardiovascular disease', 'cerebro-vascular disease', 'stroke', 'carotid artery disease', and 'subclinical atherosclerosis'. The majority of studies show a beneficial effect of endogenous estrogen on the vasculature; however, there are a few studies reporting the contrary. A significant body of literature has reported associations of endogenous estrogen and androgen with early markers of atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex steroids in heart disease and stroke are inconclusive. Most studies support a beneficial role of endogenous estrogens and, probably, an adverse effect of androgens in the vasculature in postmenopausal women. However, the described associations may not always be considered as causal. It is possible that circulating estrogen might represent a marker of general health status or alternatively reflect the sum of endogenous androgens aromatized in the periphery. Elucidating the role of sex steroids in cardio- and cerebro-vascular disease remains an interesting field of future research.

  19. Hybrid lipid-based nanostructures

    NASA Astrophysics Data System (ADS)

    Dayani, Yasaman

    Biological membranes serve several important roles, such as structural support of cells and organelles, regulation of ionic and molecular transport, barriers to non-mediated transport, contact between cells within tissues, and accommodation of membrane proteins. Membrane proteins and other vital biomolecules incorporated into the membrane need a lipid membrane to function. Due to importance of lipid bilayers and their vital function in governing many processes in the cell, the development of various models as artificial lipid membranes that can mimic cell membranes has become a subject of great interest. Using different models of artificial lipid membranes, such as liposomes, planar lipid bilayers and supported or tethered lipid bilayers, we are able to study many biophysical processes in biological membranes. The ability of different molecules to interact with and change the structure of lipid membranes can be also investigated in artificial lipid membranes. An important application of lipid bilayer-containing interfaces is characterization of novel membrane proteins for high throughput drug screening studies to investigate receptor-drug interactions and develop biosensor systems. Membrane proteins need a lipid bilayer environment to preserve their stability and functionality. Fabrication of materials that can interact with biomolecules like proteins necessitates the use of lipid bilayers as a mimic of cell membranes. The objective of this research is to develop novel hybrid lipid-based nanostructures mimicking biological membranes. Toward this aim, two hybrid biocompatible structures are introduced: lipid bilayer-coated multi-walled carbon nanotubes (MWCNTs) and hydrogel-anchored liposomes with double-stranded DNA anchors. These structures have potential applications in biosensing, drug targeting, drug delivery, and biophysical studies of cell membranes. In the first developed nanostructure, lipid molecules are covalently attached to the surfaces of MWCNTs, and

  20. A not-stop-flow online normal-/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry method for comprehensive lipid profiling of human plasma from atherosclerosis patients.

    PubMed

    Li, Min; Tong, Xunliang; Lv, Pu; Feng, Baosheng; Yang, Li; Wu, Zheng; Cui, Xinge; Bai, Yu; Huang, Yining; Liu, Huwei

    2014-11-03

    A not-stop-flow online two-dimensional (2D) liquid chromatography (LC) method was developed for comprehensive lipid profiling by coupling normal- and reversed-phase LC with quadrupole time-of-flight mass spectrometry (QToF-MS), which was then applied to separate and identify the lipid species in plasma, making its merits in quality and quantity of the detection of lipids. Total 540 endogenous lipid species from 17 classes were determined in human plasma, and the differences in lipid metabolism products in human plasma between atherosclerosis patients and control subjects were explored in detail. The limit of detections (LODs) of 19 validation standards could all reach ng/mL magnitude, and the RSDs of peak area and retention time ranged 0.4-8.0% and 0.010-0.47%, respectively. In addition, a pair of isomers, galactosylceramides (GalC) and glucosylceramides (GluC), was successfully separated, showing that only the levels of GalC in atherosclerosis patients were significantly increasing, rather than GluC, compared with the controls (controls vs. patients: the ratio was 1.5-2.8-fold increasing). It would be helpful to the further research of the atherosclerosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Isolation and analysis of membrane lipids and lipid rafts in common carp (Cyprinus carpio L.).

    PubMed

    Brogden, Graham; Propsting, Marcus; Adamek, Mikolaj; Naim, Hassan Y; Steinhagen, Dieter

    2014-03-01

    Cell membranes act as an interface between the interior of the cell and the exterior environment and facilitate a range of essential functions including cell signalling, cell structure, nutrient uptake and protection. It is composed of a lipid bilayer with integrated proteins, and the inner leaflet of the lipid bilayer comprises of liquid ordered (Lo) and liquid disordered (Ld) domains. Lo microdomains, also named as lipid rafts are enriched in cholesterol, sphingomyelin and certain types of proteins, which facilitate cell signalling and nutrient uptake. Lipid rafts have been extensively researched in mammals and the presence of functional lipid rafts was recently demonstrated in goldfish, but there is currently very little knowledge about their composition and function in fish. Therefore a protocol was established for the analysis of lipid rafts and membranous lipids in common carp (Cyprinus carpio L.) tissues. Twelve lipids were identified and analysed in the Ld domain of the membrane with the most predominant lipids found in all tissues being; triglycerides, cholesterol, phosphoethanolamine and phosphatidylcholine. Four lipids were identified in lipid rafts in all tissues analysed, triglycerides (33-62%) always found in the highest concentration followed by cholesterol (24-32%), phosphatidylcholine and sphingomyelin. Isolation of lipid rafts was confirmed by identifying the presence of the lipid raft associated protein flotillin, present at higher concentrations in the detergent resistant fraction. The data provided here build a lipid library of important carp tissues as a baseline for further studies into virus entry, protein trafficking or environmental stress analysis. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Effect of storage temperature on endogenous GHB levels in urine.

    PubMed

    LeBeau, M A; Miller, M L; Levine, B

    2001-06-15

    Because gamma-hydroxybutyrate (GHB) is an endogenous substance present in the body and is rapidly eliminated after ingestion, toxicologists investigating drug-facilitated sexual assault cases are often asked to differentiate between endogenous and exogenous levels of GHB in urine samples. This study was designed to determine the effects of storage temperature on endogenous GHB levels in urine. Specifically, it was designed to ascertain whether endogenous levels can be elevated to a range considered indicative of GHB ingestion. Urine specimens from two subjects that had not been administered exogenous GHB were collected during a 24h period and individually pooled. The pooled specimens were separated into standard sample cups and divided into three storage groups: room temperature ( approximately 25 degrees C), refrigerated (5 degrees C), and frozen (-10 degrees C). Additionally, some specimens were put through numerous freeze/thaw cycles to mimic situations that may occur if multiple laboratories analyze the same specimen. Periodic analysis of the samples revealed increases in the levels of endogenous GHB over a 6-month period. The greatest increase (up to 404%) was observed in the samples maintained at room temperature. The refrigerated specimens showed increases of 140-208%, while the frozen specimens showed smaller changes (88-116%). The specimens subjected to multiple freeze/thaw cycles mirrored specimens that had been thawed only once. None of the stored urine specimens demonstrated increases in GHB concentrations that would be consistent with exogenous GHB ingestion.

  3. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras

    PubMed Central

    Das, Anusuya; Segar, Claire E.; Chu, Yihsuan; Wang, Tiffany W.; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C.; Cui, Quanjun; Botchwey, Edward A.

    2015-01-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. PMID:26125501

  4. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

    PubMed

    Das, Anusuya; Segar, Claire E; Chu, Yihsuan; Wang, Tiffany W; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C; Cui, Quanjun; Botchwey, Edward A

    2015-09-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. NEON AND OXYGEN ABUNDANCES AND ABUNDANCE RATIO IN THE SOLAR CORONA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Landi, E.; Testa, P., E-mail: elandi@umich.edu

    2015-02-20

    In this work we determine the Ne/O abundance ratio from Solar and Heliospheric Observatory (SOHO)/Solar Ultraviolet Measurement of Emitted Radiation (SUMER) off-disk observations of quiescent streamers over the 1996-2008 period. We find that the Ne/O ratio is approximately constant over solar cycle 23 from 1996 to 2005, at a value of 0.099 ± 0.017; this value is lower than the transition region determinations from the quiet Sun used to infer the neon photospheric abundance from the oxygen photospheric abundance. Also, the Ne/O ratio we determined from SUMER is in excellent agreement with in situ determinations from ACE/SWICS. In 2005-2008, the Ne/O abundancemore » ratio increased with time and reached 0.25 ± 0.05, following the same trend found in the slowest wind analyzed by ACE/SWICS. Further, we measure the absolute abundance in the corona for both oxygen and neon from the data set of 1996 November 22, obtaining A {sub o} = 8.99 ± 0.04 and A {sub Ne} = 7.92 ± 0.03, and we find that both elements are affected by the first ionization potential (FIP) effect, with oxygen being enhanced by a factor of 1.4-2.1 over its photospheric abundance, and neon being changed by a factor of 0.75-1.20. We conclude that the Ne/O ratio is not constant in the solar atmosphere, both in time and at different heights, and that it cannot be reliably used to infer the neon abundance in the photosphere. Also, we argue that the FIP effect was less effective during the minimum of solar cycle 24, and that the Ne/O = 0.25 ± 0.05 value measured at that time is closer to the true photospheric value, leading to a neon photospheric abundance larger than assumed by ≈40%. We discuss the implications of these results for the solar abundance problem, for the FIP effect, and for the identification of the source regions of the solar wind.« less

  6. LipidFrag: Improving reliability of in silico fragmentation of lipids and application to the Caenorhabditis elegans lipidome

    PubMed Central

    Neumann, Steffen; Schmitt-Kopplin, Philippe

    2017-01-01

    Lipid identification is a major bottleneck in high-throughput lipidomics studies. However, tools for the analysis of lipid tandem MS spectra are rather limited. While the comparison against spectra in reference libraries is one of the preferred methods, these libraries are far from being complete. In order to improve identification rates, the in silico fragmentation tool MetFrag was combined with Lipid Maps and lipid-class specific classifiers which calculate probabilities for lipid class assignments. The resulting LipidFrag workflow was trained and evaluated on different commercially available lipid standard materials, measured with data dependent UPLC-Q-ToF-MS/MS acquisition. The automatic analysis was compared against manual MS/MS spectra interpretation. With the lipid class specific models, identification of the true positives was improved especially for cases where candidate lipids from different lipid classes had similar MetFrag scores by removing up to 56% of false positive results. This LipidFrag approach was then applied to MS/MS spectra of lipid extracts of the nematode Caenorhabditis elegans. Fragments explained by LipidFrag match known fragmentation pathways, e.g., neutral losses of lipid headgroups and fatty acid side chain fragments. Based on prediction models trained on standard lipid materials, high probabilities for correct annotations were achieved, which makes LipidFrag a good choice for automated lipid data analysis and reliability testing of lipid identifications. PMID:28278196

  7. Mercury distribution and lipid oxidation in fish muscle: Effects of washing and isoelectric protein precipitation

    USGS Publications Warehouse

    Gong, Y.; Krabbenhoft, D.P.; Ren, L.; Egelandsdal, B.; Richards, M.P.

    2011-01-01

    Nearly all the mercury (Hg) in whole muscle from whitefish (Coregonus clupeaformis) and walleye (Sander vitreus) was present as methyl mercury (MeHg). The Hg content in whole muscle from whitefish and walleye was 0.04-0.09 and 0.14-0.81 ppm, respectively. The myofibril fraction contained approximately three-fourths of the Hg in whitefish and walleye whole muscle. The sarcoplasmic protein fraction (e.g., press juice) was the next most abundant source of Hg. Isolated myosin, triacylglycerols, and cellular membranes contained the least Hg. Protein isolates prepared by pH shifting in the presence of citric acid did not decrease Hg levels. Addition of cysteine during washing decreased the Hg content in washed muscle probably through the interaction of the sulfhydryl group in cysteine with MeHg. Primary and secondary lipid oxidation products were lower during 2 ??C storage in isolates prepared by pH shifting compared to those of washed or unwashed mince from whole muscle. This was attributed to removing some of the cellular membranes by pH shifting. Washing the mince accelerated lipid peroxide formation but decreased secondary lipid oxidation products compared to that of the unwashed mince. This suggested that there was a lipid hydroperoxide generating system that was active upon dilution of aqueous antioxidants and pro-oxidants. ?? 2011 American Chemical Society.

  8. The Influence of Endogenous and Exogenous Spatial Attention on Decision Confidence.

    PubMed

    Kurtz, Phillipp; Shapcott, Katharine A; Kaiser, Jochen; Schmiedt, Joscha T; Schmid, Michael C

    2017-07-25

    Spatial attention allows us to make more accurate decisions about events in our environment. Decision confidence is thought to be intimately linked to the decision making process as confidence ratings are tightly coupled to decision accuracy. While both spatial attention and decision confidence have been subjected to extensive research, surprisingly little is known about the interaction between these two processes. Since attention increases performance it might be expected that confidence would also increase. However, two studies investigating the effects of endogenous attention on decision confidence found contradictory results. Here we investigated the effects of two distinct forms of spatial attention on decision confidence; endogenous attention and exogenous attention. We used an orientation-matching task, comparing the two attention conditions (endogenous and exogenous) to a control condition without directed attention. Participants performed better under both attention conditions than in the control condition. Higher confidence ratings than the control condition were found under endogenous attention but not under exogenous attention. This finding suggests that while attention can increase confidence ratings, it must be voluntarily deployed for this increase to take place. We discuss possible implications of this relative overconfidence found only during endogenous attention with respect to the theoretical background of decision confidence.

  9. Synthesis of Lipidated Proteins.

    PubMed

    Mejuch, Tom; Waldmann, Herbert

    2016-08-17

    Protein lipidation is one of the major post-translational modifications (PTM) of proteins. The attachment of the lipid moiety frequently determines the localization and the function of the lipoproteins. Lipidated proteins participate in many essential biological processes in eukaryotic cells, including vesicular trafficking, signal transduction, and regulation of the immune response. Malfunction of these cellular processes usually leads to various diseases such as cancer. Understanding the mechanism of cellular signaling and identifying the protein-protein and protein-lipid interactions in which the lipoproteins are involved is a crucial task. To achieve these goals, fully functional lipidated proteins are required. However, access to lipoproteins by means of standard expression is often rather limited. Therefore, semisynthetic methods, involving the synthesis of lipidated peptides and their subsequent chemoselective ligation to yield full-length lipoproteins, were developed. In this Review we summarize the commonly used methods for lipoprotein synthesis and the development of the corresponding chemoselective ligation techniques. Several key studies involving full-length semisynthetic lipidated Ras, Rheb, and LC3 proteins are presented.

  10. Optimization of lipids' ultrasonic extraction and production from Chlorella sp. using response-surface methodology.

    PubMed

    Hadrich, Bilel; Akremi, Ismahen; Dammak, Mouna; Barkallah, Mohamed; Fendri, Imen; Abdelkafi, Slim

    2018-04-17

    extraction relative to the second step of optimization (p < 0.05). The two most abundant fatty acid methyl esters (≈72%) derived from the Chlorella sp. microalga cultured in the determined optimal conditions are: palmitic acid (C16:0) and oleic acid (C18:1) with the corresponding yields of 51.69% and 20.55% of total fatty acids, respectively. Only the nitrate deficiency and the high intensity of light can influence the microalgal lipids production. The corresponding fatty acid methyl esters composition is very suitable for biodiesel production. Lipids extraction is efficient only over long periods of time when using a solvent with a 2/1 chloroform/methanol ratio.

  11. Microbial endogenous response to acute inhibitory impact of antibiotics.

    PubMed

    Pala-Ozkok, I; Kor-Bicakci, G; Çokgör, E U; Jonas, D; Orhon, D

    2017-06-13

    Enhanced endogenous respiration was observed as the significant/main response of the aerobic microbial culture under pulse exposure to antibiotics: sulfamethoxazole, tetracycline and erythromycin. Peptone mixture and acetate were selected as organic substrates to compare the effect of complex and simple substrates. Experiments were conducted with microbial cultures acclimated to different sludge ages of 10 and 2 days, to visualize the effect of culture history. Evaluation relied on modeling of oxygen uptake rate profiles, reflecting the effect of all biochemical reactions associated with substrate utilization. Model calibration exhibited significant increase in values of endogenous respiration rate coefficient with all antibiotic doses. Enhancement of endogenous respiration was different with antibiotic type and initial dose. Results showed that both peptone mixture and acetate cultures harbored resistance genes against the tested antibiotics, which suggests that biomass spends cellular maintenance energy for activating the required antibiotic resistance mechanisms to survive, supporting higher endogenous decay rates. [Formula: see text]: maximum growth rate for X H (day -1 ); K S : half saturation constant for growth of X H (mg COD/L); b H : endogenous decay rate for X H (day -1 ); k h : maximum hydrolysis rate for S H1 (day -1 ); K X : hydrolysis half saturation constant for S H1 (mg COD/L); k hx : maximum hydrolysis rate for X S1 (day -1 ); K XX : hydrolysis half saturation constant for X S1 (mg COD/L); k STO : maximum storage rate of PHA by X H (day -1 ); [Formula: see text]: maximum growth rate on PHA for X H (day -1 ); K STO : half saturation constant for storage of PHA by X H (mg COD/L); X H1 : initial active biomass (mg COD/L).

  12. Actinide abundances in ordinary chondrites

    NASA Technical Reports Server (NTRS)

    Hagee, B.; Bernatowicz, T. J.; Podosek, F. A.; Johnson, M. L.; Burnett, D. S.

    1990-01-01

    Measurements of actinide and light REE (LREE) abundances and of phosphate abundances in equilibrated ordinary chondrites were obtained and were used to define the Pu abundance in the solar system and to determine the degree of variation of actinide and LREE abundances. The results were also used to compare directly the Pu/U ratio with the earlier obtained ratio determined indirectly, as (Pu/Nd)x(Nd/U), assuming that Pu behaves chemically as a LREE. The data, combined with high-accuracy isotope-dilution data from the literature, show that the degree of gram-scale variability of the Th, U, and LREE abundances for equilibrated ordinary chondrites is a factor of 2-3 for absolute abundances and up to 50 percent for relative abundances. The observed variations are interpreted as reflecting the differences in the compositions and/or proportions of solar nebula components accreted to ordinary chondrite parent bodies.

  13. Untargeted Metabolite Profiling Reveals that Nitric Oxide Bioynthesis is an Endogenous Modulator of Carotenoid Biosynthesis in Deinococcus radiodurans and is Required for Extreme Ionizing Radiation Resistance

    PubMed Central

    Hansler, Alex; Chen, Qiuying; Ma, Yuliang; Gross, Steven S.

    2015-01-01

    Deinococcus radiodurans (Drad) is the most radioresistant organism known. Although mechanisms that underlie the extreme radioresistance of Drad are incompletely defined, resistance to UV irradiation-induced killing was found to be greatly attenuated in an NO synthase (NOS) knockout strain of Drad (Δnos). We now show that endogenous NO production is also critical for protection of Drad against γ-irradiation (3000 Gy), a result of accelerated growth recovery, not protection against killing. NO-donor treatment rescued radiosensitization in Δnos Drad but did not influence radiosensitivity in wild type Drad. To discover molecular mechanisms by which endogenous NO confers radioresistance, metabolite profiling studies were performed. Untargeted LC-MS-based metabolite profiling in Drad quantified relative abundances of 1,425 molecules and levels of 294 of these were altered by >5-fold (p< 0.01). Unexpectedly, these studies identified a dramatic perturbation in carotenoid biosynthetic intermediates in Δnos Drad, including a reciprocal switch in the pathway end-products from deoxydeinoxanthin to deinoxanthin. NO supplementation rescued these nos deletion-associated changes in carotenoid biosynthesis, and fully-restored radioresistance to wildtype levels. Because carotenoids were shown to be important contributors to radioprotection in Drad, our findings suggest that endogenously-produced NO serves to maintain a spectrum of carotenoids critical for Drad’s ability to withstand radiation insult. PMID:26550929

  14. The thrifty lipids: Endocannabinoids and the neural control of energy conservation

    PubMed Central

    DiPatrizio, Nicholas V.; Piomelli, Daniele

    2013-01-01

    The “thrifty gene hypothesis” posits that evolution preferentially selects physiological mechanisms that optimize energy storage to increase survival under alternating conditions of abundance and scarcity of food. Recent experiments suggest that endocannabinoids – a class of lipid-derived mediators that activate cannabinoid receptors in many cells of the body – are key agents of energy conservation. The new evidence indicates that these compounds increase energy intake and decrease energy expenditure by controlling the activity of peripheral and central neural pathways involved in the sensing and hedonic processing of sweet and fatty foods, as well as in the storage of their energy content for future use. PMID:22622030

  15. Multi-spectral endogenous fluorescence imaging for bacterial differentiation

    NASA Astrophysics Data System (ADS)

    Chernomyrdin, Nikita V.; Babayants, Margarita V.; Korotkov, Oleg V.; Kudrin, Konstantin G.; Rimskaya, Elena N.; Shikunova, Irina A.; Kurlov, Vladimir N.; Cherkasova, Olga P.; Komandin, Gennady A.; Reshetov, Igor V.; Zaytsev, Kirill I.

    2017-07-01

    In this paper, the multi-spectral endogenous fluorescence imaging was implemented for bacterial differentiation. The fluorescence imaging was performed using a digital camera equipped with a set of visual bandpass filters. Narrowband 365 nm ultraviolet radiation passed through a beam homogenizer was used to excite the sample fluorescence. In order to increase a signal-to-noise ratio and suppress a non-fluorescence background in images, the intensity of the UV excitation was modulated using a mechanical chopper. The principal components were introduced for differentiating the samples of bacteria based on the multi-spectral endogenous fluorescence images.

  16. Serum microRNA miR-206 is decreased in hyperthyroidism and mediates thyroid hormone regulation of lipid metabolism in HepG2 human hepatoblastoma cells.

    PubMed

    Zheng, Yingjuan; Zhao, Chao; Zhang, Naijian; Kang, Wenqin; Lu, Rongrong; Wu, Huadong; Geng, Yingxue; Zhao, Yaping; Xu, Xiaoyan

    2018-04-01

    The actions of thyroid hormone (TH) on lipid metabolism in the liver are associated with a number of genes involved in lipogenesis and lipid metabolism; however, the underlying mechanisms through which TH impacts on lipid metabolism remain to be elucidated. The present study aimed to investigate the effects of hyperthyroidism on the serum levels of the microRNA (miR) miR‑206 and the role of miR‑206 on TH‑regulated lipid metabolism in liver cells. Serum was obtained from 12 patients diagnosed with hyperthyroidism and 10 healthy control subjects. Human hepatoblastoma (HepG2) cells were used to study the effects of triiodothyronine (T3) and miR‑206 on lipid metabolism. Expression of miR‑206 in serum and cells was determined by reverse transcription‑quantitative polymerase chain reaction analysis. Lipid accumulation in HepG2 cells was assessed with Oil Red O staining. Suppression or overexpression of miR‑206 was performed via transfection with a miR‑206 mimic or miR‑206 inhibitor. Serum miR‑206 was significantly decreased in patients with hyperthyroidism compared with euthyroid controls. Treatment of HepG2 cells with T3 led to reduced total cholesterol (TC) and triglyceride (TG) content, accompanied by reduced miR‑206 expression. Inhibition of endogenous miR‑206 expression decreased intracellular TG and TC content in HepG2 cells. By contrast, overexpression of miR‑206 in HepG2 partially prevented the reduction in TG content induced by treatment with T3. In conclusion, serum miR‑206 expression is reduced in patients with hyperthyroidism. In addition, miR‑206 is involved in T3‑mediated regulation of lipid metabolism in HepG2 cells, indicating a role for miR‑206 in thyroid hormone‑induced disorders of lipid metabolism in the liver.

  17. Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight

    PubMed Central

    Lybbert, Jared; Gullingsrud, Justin; Chesnokov, Olga; Turyakira, Eleanor; Dhorda, Mehul; Guerin, Philippe J.; Piola, Patrice; Muehlenbachs, Atis; Oleinikov, Andrew V.

    2016-01-01

    Placental malaria caused by Plasmodium falciparum contributes to ~200,000 child deaths annually, mainly due to low birth weight (LBW). Parasitized erythrocyte sequestration and consequent inflammation in the placenta are common attributes of placental malaria. The precise molecular details of placental changes leading to LBW are still poorly understood. We hypothesized that placental malaria may disturb maternofetal exchange of vitamins, lipids, and hormones mediated by the multi-ligand (n ~ 50) scavenging/signaling receptor megalin, which is abundantly expressed in placenta but was not previously analyzed in pregnancy outcomes. We studied abundance of megalin and its intracellular adaptor protein Dab2 by immunofluorescence microscopy in placental biopsies from Ugandan women with (n = 8) and without (n = 20) active placental malaria. We found that: (a) abundances of both megalin (p = 0.01) and Dab2 (p = 0.006) were significantly reduced in brush border of syncytiotrophoblast of infected placentas; (b) amounts of megalin and Dab2 were strongly correlated (Spearman’s r = 0.53, p = 0.003); (c) abundances of megalin and Dab2 (p = 0.046) were reduced in infected placentas from women with LBW deliveries. This study provides first evidence that placental malaria infection is associated with reduced abundance of megalin transport/signaling system and indicate that these changes may contribute to the pathology of LBW. PMID:27072056

  18. Evidence for a Structural Role for Acid-Fast Lipids in Oocyst Walls of Cryptosporidium, Toxoplasma, and Eimeria

    PubMed Central

    Bushkin, G. Guy; Motari, Edwin; Carpentieri, Andrea; Dubey, Jitender P.; Costello, Catherine E.; Robbins, Phillips W.; Samuelson, John

    2013-01-01

    ABSTRACT Coccidia are protozoan parasites that cause significant human disease and are of major agricultural importance. Cryptosporidium spp. cause diarrhea in humans and animals, while Toxoplasma causes disseminated infections in fetuses and untreated AIDS patients. Eimeria is a major pathogen of commercial chickens. Oocysts, which are the infectious form of Cryptosporidium and Eimeria and one of two infectious forms of Toxoplasma (the other is tissue cysts in undercooked meat), have a multilayered wall. Recently we showed that the inner layer of the oocyst walls of Toxoplasma and Eimeria is a porous scaffold of fibers of β-1,3-glucan, which are also present in fungal walls but are absent from Cryptosporidium oocyst walls. Here we present evidence for a structural role for lipids in the oocyst walls of Cryptosporidium, Toxoplasma, and Eimeria. Briefly, oocyst walls of each organism label with acid-fast stains that bind to lipids in the walls of mycobacteria. Polyketide synthases similar to those that make mycobacterial wall lipids are abundant in oocysts of Toxoplasma and Eimeria and are predicted in Cryptosporidium. The outer layer of oocyst wall of Eimeria and the entire oocyst wall of Cryptosporidium are dissolved by organic solvents. Oocyst wall lipids are complex mixtures of triglycerides, some of which contain polyhydroxy fatty acyl chains like those present in plant cutin or elongated fatty acyl chains like mycolic acids. We propose a two-layered model of the oocyst wall (glucan and acid-fast lipids) that resembles the two-layered walls of mycobacteria (peptidoglycan and acid-fast lipids) and plants (cellulose and cutin). PMID:24003177

  19. A Lipid Extraction and Analysis Method for Characterizing Soil Microbes in Experiments with Many Samples

    PubMed Central

    Oates, Lawrence G.; Read, Harry W.; Gutknecht, Jessica L. M.; Duncan, David S.; Balser, Teri B.; Jackson, Randall D.

    2017-01-01

    Microbial communities are important drivers and regulators of ecosystem processes. To understand how management of ecosystems may affect microbial communities, a relatively precise but effort-intensive technique to assay microbial community composition is phospholipid fatty acid (PLFA) analysis. PLFA was developed to analyze phospholipid biomarkers, which can be used as indicators of microbial biomass and the composition of broad functional groups of fungi and bacteria. It has commonly been used to compare soils under alternative plant communities, ecology, and management regimes. The PLFA method has been shown to be sensitive to detecting shifts in microbial community composition. An alternative method, fatty acid methyl ester extraction and analysis (MIDI-FA) was developed for rapid extraction of total lipids, without separation of the phospholipid fraction, from pure cultures as a microbial identification technique. This method is rapid but is less suited for soil samples because it lacks an initial step separating soil particles and begins instead with a saponification reaction that likely produces artifacts from the background organic matter in the soil. This article describes a method that increases throughput while balancing effort and accuracy for extraction of lipids from the cell membranes of microorganisms for use in characterizing both total lipids and the relative abundance of indicator lipids to determine soil microbial community structure in studies with many samples. The method combines the accuracy achieved through PLFA profiling by extracting and concentrating soil lipids as a first step, and a reduction in effort by saponifying the organic material extracted and processing with the MIDI-FA method as a second step. PMID:28745639

  20. Effect of brown seaweed lipids on fatty acid composition and lipid hydroperoxide levels of mouse liver.

    PubMed

    Airanthi, M K Widjaja-Adhi; Sasaki, Naoya; Iwasaki, Sayaka; Baba, Nobuko; Abe, Masayuki; Hosokawa, Masashi; Miyashita, Kazuo

    2011-04-27

    Brown seaweed lipids from Undaria pinnatifida (Wakame), Sargassum horneri (Akamoku), and Cystoseira hakodatensis (Uganomoku) contained several bioactive compounds, namely, fucoxanthin, polyphenols, and omega-3 polyunsaturated fatty acids (PUFA). Fucoxanthin and polyphenol contents of Akamoku and Uganomoku lipids were higher than those of Wakame lipids, while Wakame lipids showed higher total omega-3 PUFA content than Akamoku and Uganomoku lipids. The levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in liver lipids of KK-A(y) mouse significantly increased by Akamoku and Uganomoku lipid feeding as compared with the control, but not by Wakame lipid feeding. Fucoxanthin has been reported to accelerate the bioconversion of omega-3 PUFA and omega-6 PUFA to DHA and AA, respectively. The higher hepatic DHA and AA level of mice fed Akamoku and Uganomoku lipids would be attributed to the higher content of fucoxanthin of Akamoku and Uganomoku lipids. The lipid hydroperoxide levels of the liver of mice fed brown seaweed lipids were significantly lower than those of control mice, even though total PUFA content was higher in the liver of mice fed brown seaweed lipids. This would be, at least in part, due to the antioxidant activity of fucoxanthin metabolites in the liver.