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Sample records for elevated triglycerides tg

  1. Induction of hypertriglyceridemia in rabbits by thermal injury: I. Time course of elevated plasma triglyceride levels.

    PubMed

    Vega, G L; Baxter, C R

    1988-01-01

    Thermal injury was produced in rabbits to determine (1) whether hypertriglyceridemia was inducible by thermal injury and, if so, (2) what was its time course and (3) how were the levels of apolipoproteins B, E, and A-I affected. In this study, seven New Zealand-specific pathogen-free male rabbits were inflicted with a burn to 27% of the total body surface area; another seven rabbits underwent a sham procedure. Plasma triglyceride levels rose markedly in the thermally injured group, and the hypertriglyceridemia persisted for ten days. Total plasma apolipoprotein B levels increased markedly by three days postburn and remained elevated for a period longer than the hypertriglyceridemia. In contrast, apolipoprotein E levels slowly increased, reaching a peak by day 10, and declined thereafter. Plasma levels of apolipoprotein A-I increased rapidly and remained elevated for two months. Thus, hypertriglyceridemia and concomitant changes in levels of apolipoproteins B, E, and A-I could be induced in rabbits by thermal injury. Plasma triglyceride levels were elevated for some time and then returned to normal, whereas apolipoprotein levels remained elevated for a longer time. These abnormalities may impair normal lipid transport in the postburn phase. PMID:3138242

  2. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    SciTech Connect

    Cheng, Jie; Krausz, Kristopher W.; Li, Feng; Ma, Xiaochao; Gonzalez, Frank J.

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria ?-oxidation. -- Highlights: ? Isoniazid metabolites were elevated only in wild-type mice. ? Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ? Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ? Bile acid transporters were significantly decreased in isoniazid-treated mice.

  3. Effects of switching from omega-3-acid ethyl esters to icosapent ethyl in a statin-treated patient with elevated triglycerides.

    PubMed

    Kedia, Anurag W; Lynch, Erin

    2015-11-01

    In patients with dyslipidemia, elevated triglyceride (TG) levels, or TG-rich lipoproteins, and cardiovascular risk may remain despite statin therapy. Prescription omega-3 fatty acid formulations containing the ethyl esters of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (omega-3-acid ethyl esters; Lovaza®) or high-purity EPA ethyl ester (icosapent ethyl; Vascepa®) are TG-lowering treatments that may be administered in addition to statins. Here we describe the effects of switching from omega-3-acid ethyl esters to icosapent ethyl in a 44-year-old obese man with dyslipidemia, hypertension, and hypothyroidism. The patient was receiving stable treatment with medications, including atorvastatin 40 mg/day and extended-release niacin 1000 mg/day. Owing to persistently elevated TG levels and other cardiovascular risk factors, the patient was initiated on omega-3-acid ethyl esters 4 g/day. After approximately 2 years on omega-3-acid ethyl esters, his total cholesterol (TC) level was 184 mg/dL, low-density lipoprotein cholesterol (LDL-C) level was 81 mg/dL, TG level was elevated at 307 mg/dL despite statin therapy, and non-high-density lipoprotein cholesterol (non-HDL-C) level was 144 mg/dL. After the switch to icosapent ethyl, TC level decreased by 34% to 121 mg/dL, LDL-C level decreased by 28% to 58 mg/dL, TG level decreased by 41% to 180 mg/dL, and non-HDL-C level decreased by 44% to 81 mg/dL. Switching from omega-3-acid ethyl esters containing both EPA and DHA to icosapent ethyl containing high-purity EPA resulted in beneficial and substantial changes in the lipid profile with a notable reduction of TG levels along with additional reductions in LDL-C levels in a statin-treated obese patient with persistently high TG levels. Treatment with icosapent ethyl was well tolerated. PMID:26453247

  4. Insulin resistance and elevated triglyceride in muscle: more important for survival than "thrifty" genes?

    PubMed

    Stannard, S R; Johnson, N A

    2004-02-01

    Elevated intramyocellular triglyceride (IMTG) is strongly associated with insulin resistance, though a cause and effect relationship has not been fully described. Insulin sensitivity and IMTG content are both dynamic and can alter rapidly in response to dietary variation, physical activity and thermoregulatory response. Physically active humans (athletes) display elevated IMTG content, but in contrast to obese persons, are insulin sensitive. This paradox has created confusion surrounding the role of IMTG in the development of insulin resistance. In this review we consider the modern athlete as the physiological archetype of the Late Palaeolithic hunter-gatherer to whom the selection pressures of food availability, predation and fluctuating environmental conditions applied and to whom the genotype of modern man is virtually identical. As food procurement by the hunter-gatherer required physical activity, "thrifty" genes that encouraged immediate energy storage upon refeeding after food deprivation (Neel, 1962) must have been of secondary importance in survival to genes that preserved physical capacity during food deprivation. Similarly genes that enabled survival during cold exposure whilst starved would be of primary importance. In this context, we discuss the advantage afforded by an elevated IMTG content, and how under these conditions, a concomitant muscle resistance to insulin-mediated glucose uptake would also be advantageous. In sedentary modern man, adiposity is high and skeletal muscle appears to respond as if a state of starvation exists. In this situation, elevated plasma lipids serve to accrue lipid and induce insulin resistance in skeletal muscle. Reversal of this physiological state is primarily dependent on adequate contractile activity, however, in modern Western society, physical inactivity combined with abundant food and warmth has rendered IMTG a redundant muscle substrate. PMID:14608009

  5. Fenofibrate Effect on Triglyceride and Postprandial Response of Apolipoprotein A5 Variants: The GOLDN Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated plasma triglyceride (TG) levels (hypertriglyceridemia), one of the characteristic features of the Metabolic Syndrome (MS), have been recognized as an independent risk factor of coronary heart disease (CHD). Lowering TG concentration by dietary or drug intervention reduces CHD risk. Fenofibr...

  6. In vivo determination of triglyceride (TG) secretion in rats fed different dietary saturated fats using (2- sup 3 H)-glycerol

    SciTech Connect

    Lai, H.C.; Yang, H.; Lasekan, J.; Clayton, M.; Ney, D.M. )

    1990-02-26

    Male, Sprague-Dawley rats (154{plus minus}1 g) were fed diets containing 2% corn oil (CO) + 14% butterfat (BF), beef tallow (BT), olive oil (OO) or coconut oil (CN) vs a 16% CO control diet for 5 weeks. Changes in plasma TG specific activity (dpm/mg TG) were determined in individual unanesthetized rats after injection of 100 {mu}Ci (2-{sup 3}H)-glycerol via a carotid cannula. Fractional rate constants were obtained using a 2-compartment model and nonlinear regression analysis. Results demonstrated no difference in the fractional rate constants among dietary groups; but, differences in the rates of hepatic TG secretion were noted. Rats fed BT showed a higher rate of hepatic TG secretion than rats fed CO. Rats fed BF, OO or CN showed somewhat higher rates of hepatic TG secretion than CO. VLDL TG, phospholipid, and apolipoprotein B and E levels were higher with saturated fats vs CO. The data suggest that the higher plasma TG levels noted in response to feeding saturated fats vs corn oil can be explained, in part, by an increased flux of hepatic TG secretion.

  7. Triglycerides and gallstone formation.

    PubMed

    Smelt, A H M

    2010-11-11

    Changes in bile acid (BA) metabolism and gallbladder function are critical factors in the pathogenesis of gallstones. Patients with hypertriglyceridemia (HTG) - often overweight and insulin resistant - are at risk for gallstone disease. The question arises whether HTG itself contributes to gallstone formation or whether gallstone disease only associates with this disorder. Triglycerides are formed in response to fluxes of non-esterified fatty acids and glucose. Hypertriglyceridemia results from either overproduction of triglycerides by the liver, impaired lipolysis or a combination of both. Hyperinsulinemia, as observed in the insulin resistant state, stimulates very low-density lipoprotein (VLDL)-triglyceride synthesis. Peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), farnesoid X receptor (FXR) and hepatocyte nuclear factor 4? (HNF4?) are the nuclear receptors involved in the regulation of lipogenesis. Microsomal triglyceride transfer protein (MTP) is involved in the production of VLDL and its activation is also under control of transcription factors as FXR and Forkhead box-O1 (FoxO1). Triglyceride and BA metabolism are linked. There is an inverse relationship between bile acid fluxes and pool size and VLDL production and SHP (small heterodimer partner) and FXR are the link between BAs and TG metabolism. BAs are also ligands for FXR and G-protein-coupled receptors, such as TGR5. FXR activation by BAs suppresses the expression of MTP, transcription factor sterol regulatory element binding protein (SREBP)-1c and other lipogenic genes. LXRs stimulate lipogenesis whereas FXRs inhibit the metabolic process. Synthesis of BAs from cholesterol occurs either via the classical pathway (7?-hydroxylation of cholesterol; CYP7A1) or via the alternate pathway (CYP39A1 or CYP7B1). BAs induce FXR, which inhibits CYP7A1 transcription by activation of SHP and inhibition of HNF4? transactivation. Bile composition (supersaturation with cholesterol), gallbladder dysmotility, inflammation, hypersecretion of mucin gel in the gallbladder and slow large intestinal motility and increased intestinal cholesterol absorption may contribute to the pathogenesis of cholesterol gallstones. In HTG patients supersaturated bile may be related to the presence of obesity rather than to HTG itself. Contraction and relaxation of the gallbladder are regulated by neuronal, hormonal and paracrine factors. Postprandial gallbladder emptying is regulated by cholecystokinin (CCK). Poor postprandial gallbladder contraction may be due to the magnitude of the CCK response and to the amount of CCK receptors in the gallbladder smooth muscle cells. In the fasting state gallbladder motility is associated with the intestinal migrating motor complex (MMC) activity and with elevated plasma motilin levels. Fibroblast growth factor (FGF19), produced on arrival of bile acids in the ileum, is also important for gallbladder motility. Gallbladder motility is impaired in HTG patients compared to BMI matched controls. There is evidence that the gallbladder in HTG is less sensitive to CCK and that this sensitivity improves after reversal of high serum TG levels by use of TG lowering agents. In hypertriglyceridemia TG lowering therapy (fibrates or fish-oil) is essential to prevent cardiovascular disease and pancreatitis. Fibrates, however, also increase the risk for cholelithiasis by increasing biliary cholesterol saturation and by reduction of bile acid synthesis. On the other hand fish-oil decreases biliary cholesterol saturation. Fish-oil may increase bile acid synthesis by activation of 7alpha-hydroxylase and may inhibit VLDL production and secretion through activation of nuclear factors and increased apoB degradation. In HTG patients, gallbladder motility improves during bezafibrate as well as during fish-oil therapy. The question remains whether improvement of gallbladder motility and increased lithogenicity of bile by bezafibrate therapy counteract each other or still result in gallstone formation in HTG patients. PMID:20699090

  8. Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[S

    PubMed Central

    van Diepen, Janna A.; Stienstra, Rinke; Vroegrijk, Irene O. C. M.; van den Berg, Sjoerd A. A.; Salvatori, Daniela; Hooiveld, Guido J.; Kersten, Sander; Tack, Cees J.; Netea, Mihai G.; Smit, Johannes W.A.; Joosten, Leo A. B.; Havekes, Louis M.; van Dijk, Ko Willems; Rensen, Patrick C. N.

    2013-01-01

    Caspase-1 is known to activate the proinflammatory cytokines IL-1? and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by an increased energy production. Increased feces secretion by caspase-1-deficient mice suggests that lipid malabsorption possibly further reduces adipose tissue mass. In this study we investigated whether caspase-1 plays a role in triglyceride-(TG)-rich lipoprotein metabolism using caspase-1-deficient and wild-type mice. Caspase-1 deficiency reduced the postprandial TG response to an oral lipid load, whereas TG-derived fatty acid (FA) uptake by peripheral tissues was not affected, demonstrated by unaltered kinetics of [3H]TG-labeled very low-density lipoprotein (VLDL)-like emulsion particles. An oral gavage of [3H]TG-containing olive oil revealed that caspase-1 deficiency reduced TG absorption and subsequent uptake of TG-derived FA in liver, muscle, and adipose tissue. Similarly, despite an elevated hepatic TG content, caspase-1 deficiency reduced hepatic VLDL-TG production. Intestinal and hepatic gene expression analysis revealed that caspase-1 deficiency did not affect FA oxidation or FA uptake but rather reduced intracellular FA transport, thereby limiting lipid availability for the assembly and secretion of TG-rich lipoproteins. The current study reveals a novel function for caspase-1, or caspase-1-cleaved substrates, in controlling intestinal TG absorption and hepatic TG secretion. PMID:23160218

  9. Triglyceride level

    MedlinePLUS

    ... may also cause swelling of your pancreas (called pancreatitis). The triglyceride level is usually included in a ... lower triglyceride levels may be used to prevent pancreatitis for levels above 500 mg/dL Low triglyceride ...

  10. ELEVATED REMNANT-LIKE PARTICLE (RLP) CHOLESTEROL AND TRIGLYCERIDE LEVELS INDIABETIC MEN AND WOMENT IN THE FRAMINGHAM OFFSPRING STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Remnants of triglyceride-rich lipoproteins are thought to be atherogenic. A new antibody-based assay allows isolation of remnant-like particles (RLP) from plasma or serum, and subsequent measurement of RLP cholesterol and triglyceride (RLPC and RLPTG). We hypothesized that diabetics (DM) would have ...

  11. The Protective Effect of Transcription Factor 7-Like 2 Risk Allele rs7903146 against Elevated Fasting Plasma Triglyceride in Type 2 Diabetes: A Meta-Analysis

    PubMed Central

    Wang, Shuxia; Song, Kangxing; Srivastava, Roshni; Fathzadeh, Mohsen; Li, Na; Mani, Arya

    2015-01-01

    Background. The results from published studies regarding association of transcription factor 7-like 2 (TCF7L2) variant rs7903146 with dyslipidemia have been conflicting and inconclusive. Methods. We carried out a meta-analysis that aimed to investigate the association of the rs7903146 variant with plasma lipid levels using electronic database and published studies. Data was extracted by a standard algorithm. Dominant, recessive, homozygote, and heterozygote comparison models were utilized. Results. 24 studies incorporating 52,785 subjects were included in this meta-analysis. Overall, the minor allele (T) was associated with lower risk for hypertriglyceridemia in subjects with type 2 diabetes (dominant model: SMD = ?0.04, 95% CI (?0.08, 0.00), P = 0.048, Pheterogeneity = 0.47; recessive model: SMD = ?0.10, 95% CI (?0.18, ?0.02), P = 0.01, Pheterogeneity = 0.56). No association was found between minor (T) allele and plasma TC, LDL-c, or HDL-c levels in subjects with type 2 diabetes or metabolic syndrome (MetS) and no association was found between minor (T) allele and plasma TG levels in nondiabetic subjects. Conclusions. Our meta-analysis indicated the association between TCF7L2 rs7903146 polymorphism and low plasma triglyceride (TG) level in subjects with type 2 diabetes. No association was found between rs7903146 variant and plasma lipids in nondiabetic subjects. PMID:26576435

  12. The Effect of Elevated Triglycerides on the Onset and Progression of Coronary Artery Disease: A Retrospective Chart Review

    PubMed Central

    Daniel, Deepu; Hardigan, Patrick; Jawaid, Asif; Bhandari, Rohit; Daniel, Mithun

    2015-01-01

    Background. The American College of Cardiology and American Heart Association did not indicate a correlation between treating hypertriglyceridemia and reducing cardiovascular events. Objective. This study investigated whether patients with hypertriglyceridemia were more prone to worse outcomes during cardiac catheterization. Methods. Data collected over a one-year period analyzed lipid panels obtained at the time of cardiac catheterization. Triglyceride levels were categorized into three groups: <150?mg/dL, 150?mg/dL–300?mg/dL, and >300?mg/dL. Controlled variables included age, gender, the presence of hypertension, diabetes, hyperlipidemia, and history of coronary artery disease. Results. Subjects with a triglyceride level <150?mg/dL have a 54% likelihood of being treated medically compared to 38% and 41% in the 150?mg/dL–300?mg/dL and >300?mg/dL groups, respectively (p < 0.01). Subjects with a triglyceride level >300?mg/dL have a 20% percent chance of being treated with a coronary artery bypass graft compared to 12% and 15% in the <150?mg/dL and 150?mg/dL–300?mg/dL groups, respectively (p < 0.01). Subjects with a triglyceride level between 150 and 300?mg/dL have a 44% percent of being treated with a percutaneous coronary intervention compared to 34% and 43% in the <150?mg/dL and >300?mg/dL groups, respectively (p < 0.01). Conclusion. Hypertriglyceridemia was associated with worse outcomes in percutaneous coronary intervention or surgery. PMID:26617998

  13. Triglyceride kinetics in fasted and fed E. coli septic rats

    SciTech Connect

    Lanza-Jacoby, S.; Tabares, A. )

    1990-02-26

    The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studies by examining the liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess the liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant intravenous infusion of (2-{sup 3}H) glycerol-labeled VLDL in fasted control, fasted E. coli-treated, fed control, and fed E.coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 {times} 10{sup 7} live E.coli colonies per 100 g body weight. Twenty-four hours following E.coli injection serum TG of fasted E.coli-treated rats was elevated by 170% which was attributed to a 67% decrease in the clearance rate of VLDL-TG in fasted E.coli-treated rats compared with their fasted controls. The secretion of VLDL-TG declined by 31% in the livers of the fasted E.coli-treated rats which was accompanied by a 2-fold increase in the composition of liver TG. In a second series of experiments control and E.coli-treated rats were fed intragastrically (IG) a balanced solution containing glucose plus fat as the sources of nonprotein calories. Serum TG were 26% lower in the fed E.coli-treated rats because the clearance rate increased by 86%. The secretion of TG in the fed septic rats increased by 40% but this difference was not significant. In the septic rat the ability to clear triglycerides from the plasma depends upon the nutritional state.

  14. Inhibition of Intestinal Bile Acid Transporter Slc10a2 Improves Triglyceride Metabolism and Normalizes Elevated Plasma Glucose Levels in Mice

    PubMed Central

    Snaith, Michael; Lindmark, Helena; Lundberg, Johanna; Östlund-Lindqvist, Ann-Margret; Angelin, Bo; Rudling, Mats

    2012-01-01

    Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2) and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c). Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF) 15 mRNA and normalized bile acid synthesis in Slc10a2?/? mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2 - Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes. PMID:22662222

  15. Triglyceride-Increasing Alleles Associated with Protection against Type-2 Diabetes

    PubMed Central

    Klimentidis, Yann C.; Chougule, Akshay; Arora, Amit; Frazier-Wood, Alexis C.; Hsu, Chiu-Hsieh

    2015-01-01

    Elevated plasma triglyceride (TG) levels are an established risk factor for type-2 diabetes (T2D). However, recent studies have hinted at the possibility that genetic risk for TG may paradoxically protect against T2D. In this study, we examined the association of genetic risk for TG with incident T2D, and the interaction of baseline TG with TG genetic risk on incident T2D in 13,247 European-Americans (EA) and 3,238 African-Americans (AA) from three prospective cohort studies. A TG genetic risk score (GRS) was calculated based on 31 validated single nucleotide polymorphisms (SNPs). We considered several baseline covariates, including body- mass index (BMI) and lipid traits. Among EA and AA, we find, as expected, that baseline levels of TG are strongly positively associated with incident T2D (p<2 x 10-10). However, the TG GRS is negatively associated with T2D (p=0.013), upon adjusting for only race, in the full dataset. Upon additionally adjusting for age, sex, BMI, high-density lipoprotein cholesterol and TG, the TG GRS is significantly and negatively associated with T2D incidence (p=7.0 x 10-8), with similar trends among both EA and AA. No single SNP appears to be driving this association. We also find a significant statistical interaction of the TG GRS with TG (pinteraction=3.3 x 10-4), whereby the association of TG with incident T2D is strongest among those with low genetic risk for TG. Further research is needed to understand the likely pleiotropic mechanisms underlying these findings, and to clarify the causal relationship between T2D and TG. PMID:26020539

  16. Triglycerides Test

    MedlinePLUS

    ... Cholesterol ; LDL Cholesterol ; Direct LDL Cholesterol ; VLDL Cholesterol ; Lipid Profile ; Cardiac Risk Assessment All content on Lab ... tests for triglycerides are usually part of a lipid profile used to identify the risk of developing ...

  17. Triglycerides and Cardiovascular Disease: FAQ

    MedlinePLUS

    ... of calories) should be considered for persons with metabolic syndrome who have elevated triglycerides or low HDL cholesterol (the good cholesterol). 3 6. What is metabolic syndrome? The metabolic syndrome is defined by a cluster ...

  18. Genetic determinants of plasma triglycerides

    PubMed Central

    Johansen, Christopher T.; Kathiresan, Sekar; Hegele, Robert A.

    2011-01-01

    Plasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might help specify new directions for therapeutic interventions. Recent genome-wide association studies (GWAS) have identified both known and novel loci associated with plasma TG concentration. However, genetic variation at these loci explains only ?10% of overall TG variation within the population. As the GWAS approach may be reaching its limit for discovering genetic determinants of TG, alternative genetic strategies, such as rare variant sequencing studies and evaluation of animal models, may provide complementary information to flesh out knowledge of clinically and biologically important pathways in TG metabolism. Herein, we review genes recently implicated in TG metabolism and describe how some of these genes likely modulate plasma TG concentration. We also discuss lessons regarding plasma TG metabolism learned from various genomic and genetic experimental approaches. Treatment of patients with moderate to severe hypertriglyceridemia with existing therapies is often challenging; thus, gene products and pathways found in recent genetic research studies provide hope for development of more effective clinical strategies. PMID:21041806

  19. Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver

    PubMed Central

    Yokota, Shin-Ichi; Nakamura, Kaai; Ando, Midori; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shibata, Shigenobu

    2014-01-01

    Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30 h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1) and liver-fatty acid binding-protein (L-FABP). Physostigmine promoted the 30 h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism. PMID:25383314

  20. Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice

    PubMed Central

    Shin, Mi-Kyung; Yao, Qiaoling; Bevans-Fonti, Shannon; Poole, James; Drager, Luciano F.; Polotsky, Vsevolod Y.

    2012-01-01

    Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and is associated with elevated triglycerides (TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO2 = 0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dose-dependently increased plasma TG, with levels peaking at FiO2 = 0.07. Hepatic TG levels also increased with hypoxia, peaking at FiO2 = 0.10. Plasma catecholamines also increased inversely with FiO2. Plasma ketones, glycerol, and FFA levels were more variable, with different degrees of hypoxia inducing WAT lipolysis and ketosis. FiO2 = 0.10 exposure stimulated WAT lipolysis but decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and reversibly delayed TG clearance while decreasing [3H]triolein-labeled Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In addition, hypoxia decreased the transcription of LPL, peroxisome proliferator-activated receptor-?, and fatty acid transporter CD36. We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion. PMID:22621867

  1. Impact of admission triglyceride for early outcome in diabetic patients with stable coronary artery disease

    PubMed Central

    2014-01-01

    Background The role of triglyceride (TG) in predicting the outcomes in diabetic patients with coronary artery disease (CAD) has not been well investigated. Methods A total of 329 cases with stable angina pectoris (SAP) were prospectively enrolled and followed up for an average of 12 months. They were classified into the two groups according to the cut-off values of predicting early outcome of fasting TG level (low group <1.2 mmol/L, n?=?103; High group ?1.2 mmol/L, n?=?226). The relationship between the TG levels and early outcomes were evaluated. Results High TG group showed severer lipid profile and elevated inflammatory markers. During an average of 12-month follow-up, 47 out of 329 patients suffered from pre-specified outcomes. Area under the receivers operating characteristic curve suggested that TG, similar to serum Hemoglobin A1C (HbA1C), was a significant predictor of early outcome for diabetic patients with SAP (P?=?0.002). In Cox regression models, after adjusted age, gender, body mass index, other lipid parameters, fasting blood glucose, high sensitivity C-reactive protein, neutrophil count and HbA1C, TG remained as an independent predictor of adverse prognosis. Conclusions High level of fasting TG (?1.2 mmol/L) was an independent predictor for early outcome of diabetic patients with SAP as like as HBA1c and number of affected coronary arteries in the era of revascularization and statin therapeutics. PMID:24766776

  2. Overactive endocannabinoid signaling impairs apolipoprotein E-mediated clearance of triglyceride-rich lipoproteins

    PubMed Central

    Ruby, Maxwell A.; Nomura, Daniel K.; Hudak, Carolyn S. S.; Mangravite, Lara M.; Chiu, Sally; Casida, John E.; Krauss, Ronald M.

    2008-01-01

    The endocannabinoid (EC) system regulates food intake and energy metabolism. Cannabinoid receptor type 1 (CB1) antagonists show promise in the treatment of obesity and its metabolic consequences. Although the reduction in adiposity resulting from therapy with CB1 antagonists may not account fully for the concomitant improvements in dyslipidemia, direct effects of overactive EC signaling on plasma lipoprotein metabolism have not been documented. The present study used a chemical approach to evaluate the direct effects of increased EC signaling in mice by inducing acute elevations of endogenously produced cannabinoids through pharmacological inhibition of their enzymatic hydrolysis by isopropyl dodecylfluorophosphonate (IDFP). Acute IDFP treatment increased plasma levels of triglyceride (TG) (2.0- to 3.1-fold) and cholesterol (1.3- to 1.4-fold) in conjunction with an accumulation in plasma of apolipoprotein (apo)E-depleted TG-rich lipoproteins. These changes did not occur in either CB1-null or apoE-null mice, were prevented by pretreatment with CB1 antagonists, and were not associated with reduced hepatic apoE gene expression. Although IDFP treatment increased hepatic mRNA levels of lipogenic genes (Srebp1 and Fas), there was no effect on TG secretion into plasma. Instead, IDFP treatment impaired clearance of an intravenously administered TG emulsion, despite increased postheparin lipoprotein lipase activity. Therefore, overactive EC signaling elicits an increase in plasma triglyceride levels associated with reduced plasma TG clearance and an accumulation in plasma of apoE-depleted TG-rich lipoproteins. These findings suggest a role of CB1 activation in the pathogenesis of obesity-related hypertriglyceridemia and underscore the potential efficacy of CB1 antagonists in treating metabolic disease. PMID:18794527

  3. [Triglyceride deposit cardiomyovasculopathy].

    PubMed

    Hirano, Ken-Ichi

    2013-09-01

    Cholesterol is a vital causal factor and focus of research into heart diseases, however the involvement of triglycerides remains unclear. We recently reported a patient suffering from severe congestive heart failure and needing cardiac transplantation. Massive accumulation of triglycerides was noted in coronary atherosclerotic lesions as well as in the myocardium. We named this phenotype"triglyceride deposit cardiomyovasculopathy (TGCV)". The patient was identified as homozygous for a genetic mutation in the adipose triglyceride lipase (ATGL), an essential molecule for hydrolysis of intracellular triglycerides. In this paper, we describe clinical characteristics of ATGL deficiency and discuss what we can learn from this disorder. PMID:24205734

  4. Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV-infected patients taking potent antiretroviral therapy: a randomized prospective study.

    PubMed

    De Truchis, Pierre; Kirstetter, Myriam; Perier, Antoine; Meunier, Claire; Zucman, David; Force, Gilles; Doll, Jacques; Katlama, Christine; Rozenbaum, Willy; Masson, Hélène; Gardette, Jean; Melchior, Jean-Claude

    2007-03-01

    To assess the evolution of triglyceride (TG) levels in HIV-infected patients receiving stable potent antiretroviral therapy treated with N-3 polyunsaturated fatty acids (PUFAs), a prospective double-blind randomized design for a reliable assessment of TG evolution was performed. One hundred twenty-two patients with TG levels >2 g/L and < or =10 g/L after a 4-week diet (baseline TG: 4.5 +/- 1.9 g/L) were randomized for 8 weeks to N-3 PUFAs (2 capsules containing 1 g of fish oil 3 times daily, n = 60), or placebo (1 g of paraffin oil capsules, n = 62). An 8-week open-label phase of N-3 PUFAs followed. Evaluation criteria were TG percent change at week 8, percentage of responders (normalization or > or =20% TG decrease), and safety issues. Ten patients with baseline TG levels >10 g/L were not randomized and received N-3 PUFAs as open treatment. The difference (PUFA - placebo) in TG percent change at week 8 was -24.6% (range: -40.9% to -8.4%; P = 0.0033), the median was -25.5% in the PUFA group versus 1% in the placebo group, and mean TG levels at week 8 were 3.4 +/- 1.8 g/L and 4.8 +/- 3.1 g/L, respectively. TG levels were normalized in 22.4% (PUFA) versus 6.5% (placebo) of patients (P = 0.013) with a > or =20% reduction in 58.6% (PUFA) versus 33.9% (placebo) of patients (P = 0.007). Under the open-label phase of N-3 PUFAs, the decrease in TG levels was sustained at week 16 for patients in the PUFA group (mean TG: 3.4 +/- 1.7 g/L), whereas a 21.2% decrease in TG levels occurred for patients in the placebo group (mean TG: 3.3 +/- 1.4 g/L). No significant differences were observed between groups in the occurrence of adverse events. The median TG change at week 8 was -43.6% (range: Q1-Q3; 95% CI: -66.5% to -4.6%) for patients with baseline TG levels >10 g/L. The difference in mean total cholesterol between groups (PUFA - placebo) at week 8 was -8.5% (P = 0.0117). This study demonstrated the efficacy of PUFAs to lower elevated TG levels in treated HIV-infected hypertriglyceridemic patients. N-3 PUFAs have a good safety profile. PMID:17179770

  5. Postprandial metabolism of meal triglyceride in humans*,**

    PubMed Central

    Lambert, Jennifer E.; Parks, Elizabeth J.

    2012-01-01

    The intake of dietary fat above energy needs has contributed to the growing rates of obesity worldwide. The concept of disease development occurring in the fed state now has much support and dysregulation of substrate flux may occur due to poor handling of dietary fat in the immediate postprandial period. The present paper will review recent observations implicating cephalic phase events in the control of enterocyte lipid transport, the impact of varying the composition of meals on subsequent fat metabolism, and the means by which dietary lipid carried in chylomicrons can lead to elevated postprandial non-esterified fatty acid concentrations. This discussion is followed by an evaluation of the data on quantitative meal fat oxidation at the whole body level and an examination of dietary fat clearance to peripheral tissues — with particular attention paid to skeletal muscle and liver given the role of ectopic lipid deposition in insulin resistance. Estimates derived from data of dietary-TG clearance show good agreement with clearance to the liver equaling 8–12% of meal fat in lean subjects and this number appears higher (10–16%) in subjects with diabetes and fatty liver disease. Finally, we discuss new methods with which to study dietary fatty acid partitioning in vivo. Future research is needed to include a more comprehensive understanding of 1) the potential for differential oxidation of saturated versus unsaturated fatty acids which might lead to meaningful energy deficit and whether this parameter varies based on insulin sensitivity, 2) whether compartmentalization exists for diet-derived fatty acids within tissues vs. intracellular pools, and 3) the role of reduced peripheral fatty acid clearance in the development of fatty liver disease. Further advancements in the quantitation of dietary fat absorption and disposal will be central to the development of therapies designed to treat diet-induced obesity. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID:22281699

  6. Identification of a small molecule that stabilizes lipoprotein lipase in vitro and lowers triglycerides in vivo.

    PubMed

    Larsson, Mikael; Caraballo, Rémi; Ericsson, Madelene; Lookene, Aivar; Enquist, Per-Anders; Elofsson, Mikael; Nilsson, Stefan K; Olivecrona, Gunilla

    2014-07-25

    Patients at increased cardiovascular risk commonly display high levels of plasma triglycerides (TGs), elevated LDL cholesterol, small dense LDL particles and low levels of HDL-cholesterol. Many remain at high risk even after successful statin therapy, presumably because TG levels remain high. Lipoprotein lipase (LPL) maintains TG homeostasis in blood by hydrolysis of TG-rich lipoproteins. Efficient clearance of TGs is accompanied by increased levels of HDL-cholesterol and decreased levels of small dense LDL. Given the central role of LPL in lipid metabolism we sought to find small molecules that could increase LPL activity and serve as starting points for drug development efforts against cardiovascular disease. Using a small molecule screening approach we have identified small molecules that can protect LPL from inactivation by the controller protein angiopoietin-like protein 4 during incubations in vitro. One of the selected compounds, 50F10, was directly shown to preserve the active homodimer structure of LPL, as demonstrated by heparin-Sepharose chromatography. On injection to hypertriglyceridemic apolipoprotein A-V deficient mice the compound ameliorated the postprandial response after an olive oil gavage. This is a potential lead compound for the development of drugs that could reduce the residual risk associated with elevated plasma TGs in dyslipidemia. PMID:24984153

  7. Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study.

    PubMed

    Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

    2015-01-01

    Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P?TG/HDL was shown to be significantly associated with serum Cr levels (??=?0.551; 95%CI, 0.394-0.708), and eGFR (??=?-0.481; 95%CI, -0.731--0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio?=?1.20; 95%CI, 1.11-1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P?elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism. PMID:26179571

  8. Postprandial Triglyceride Is Associated with Fasting Triglyceride and HOMA-IR in Korean Subjects with Type 2 Diabetes

    PubMed Central

    Lee, Seo Hee; Won, Hee Kwan; Moon, Jae Hoon; Kim, Kwang Joon; Kang, Eun Seok; Cha, Bong Soo

    2011-01-01

    Background Recent studies indicate postprandial triglyceride (TG) had a better association with cardiovascular events and metabolic syndrome than fasting TG. The authors of the present study investigated the metabolic and clinical relevance of postprandial TG. Methods In a cross-sectional retrospective study, the authors of the present study compared fasting and postprandial TG and analyzed the relationship between postprandial TG and various demographic and metabolic parameters in 639 Korean subjects with type 2 diabetes (T2D, group I, n=539) and impaired fasting glucose (IFG, group II, n=100) after ingestion of a standardized liquid meal (total 500 kcal, 17.5 g fat, 68.5 g carbohydrate, and 17.5 g protein). Results Fasting and postprandial TG were significantly correlated (r=0.973, r=0.937, P<0.001) in group I and II, respectively. Of the variables, total cholesterol, waist circumference and body mass index were significantly correlated with fasting and postprandial TG in both groups. Only postprandial TG showed a significant correlation with glucose metabolic parameters (e.g., postprandial glucose, homeostatic model assessment of insulin resistance [HOMA-IR], and fasting C-peptide) in subjects with T2D. Multiple regression analysis showed fasting TG and HOMA-IR could be predictable variables for postprandial TG in subjects with T2D. Conclusion Postprandial TG was very strongly correlated with fasting TG. The authors of the present study suggest insulin resistance may be more associated with postprandial TG than fasting TG in Korean T2D patients on a low-fat diet. PMID:21977461

  9. Central effects of humanin on hepatic triglyceride secretion.

    PubMed

    Gong, Zhenwei; Su, Kai; Cui, Lingguang; Tas, Emir; Zhang, Ting; Dong, H Henry; Yakar, Shoshana; Muzumdar, Radhika H

    2015-08-01

    Humanin (HN) is an endogenous mitochondria-associated peptide that has been shown to protect against various Alzheimer's disease-associated insults, myocardial ischemia-reperfusion injury, and reactive oxygen species-induced cell death. We have shown previously that HN improves whole body glucose homeostasis by improving insulin sensitivity and increasing glucose-stimulated insulin secretion (GSIS) from the ?-cells. Here, we report that intraperitoneal treatment with one of HN analogs, HNG, decreases body weight gain, visceral fat, and hepatic triglyceride (TG) accumulation in high-fat diet-fed mice. The decrease in hepatic TG accumulation is due to increased activity of hepatic microsomal triglyceride transfer protein (MTTP) and increased hepatic TG secretion. Both intravenous (iv) and intracerebroventricular (icv) infusion of HNG acutely increase TG secretion from the liver. Vagotomy blocks the effect on both iv and icv HNG on TG secretion, suggesting that the effects of HNG on hepatic TG flux are centrally mediated. Our data suggest that HN is a new player in central regulation of peripheral lipid metabolism. PMID:26058861

  10. Inborn errors of cytoplasmic triglyceride metabolism.

    PubMed

    Wu, Jiang Wei; Yang, Hao; Wang, Shu Pei; Soni, Krishnakant G; Brunel-Guitton, Catherine; Mitchell, Grant A

    2015-01-01

    Triglyceride (TG) synthesis, storage, and degradation together constitute cytoplasmic TG metabolism (CTGM). CTGM is mostly studied in adipocytes, where starting from glycerol-3-phosphate and fatty acyl (FA)-coenzyme A (CoA), TGs are synthesized then stored in cytoplasmic lipid droplets. TG hydrolysis proceeds sequentially, producing FAs and glycerol. Several reactions of CTGM can be catalyzed by more than one enzyme, creating great potential for complex tissue-specific physiology. In adipose tissue, CTGM provides FA as a systemic energy source during fasting and is related to obesity. Inborn errors and mouse models have demonstrated the importance of CTGM for non-adipose tissues, including skeletal muscle, myocardium and liver, because steatosis and dysfunction can occur. We discuss known inborn errors of CTGM, including deficiencies of: AGPAT2 (a form of generalized lipodystrophy), LPIN1 (childhood rhabdomyolysis), LPIN2 (an inflammatory condition, Majeed syndrome, described elsewhere in this issue), DGAT1 (protein loosing enteropathy), perilipin 1 (partial lipodystrophy), CGI-58 (gene ABHD5, neutral lipid storage disease (NLSD) with ichthyosis and "Jordan's anomaly" of vacuolated polymorphonuclear leukocytes), adipose triglyceride lipase (ATGL, gene PNPLA2, NLSD with myopathy, cardiomyopathy and Jordan's anomaly), hormone-sensitive lipase (HSL, gene LIPE, hypertriglyceridemia, and insulin resistance). Two inborn errors of glycerol metabolism are known: glycerol kinase (GK, causing pseudohypertriglyceridemia) and glycerol-3-phosphate dehydrogenase (GPD1, childhood hepatic steatosis). Mouse models often resemble human phenotypes but may diverge markedly. Inborn errors have been described for less than one-third of CTGM enzymes, and new phenotypes may yet be identified. PMID:25300978

  11. Triglyceride-Lowering Response To Plant Sterol and Stanol Consumption

    PubMed Central

    Rideout, Todd C; Marinangeli, Christopher PF; Harding, Scott V

    2015-01-01

    Phytosterols (PS) have long been recognized for their cholesterol-lowering action, however, recent work has highlighted triglyceride (TG)-lowering responses to PS that may have been overlooked in previous human interventions and mechanistic animal model studies. This review assesses the current state of knowledge regarding the effect of dietary PS supplementation on blood TG concentrations by examining the average therapeutic response, potential mechanisms, and metabolic and genetic factors that may contribute to inter-individual variability. Data from human intervention trials demonstrates that, compared to baseline concentrations, PS supplementation results in a variable TG-lowering response ranging from 0.8 to 28%. It is evident that hypertriglyceridemic individuals (>1.7 mmol/L) have a greater TG-lowering response to PS (11–28%) than subjects with normal plasma TG concentrations (0.8–7%). Although a genetic basis for the variable TG-lowering effects of PS is probable, there are only limited studies to draw on. The available data suggest that polymorphisms in the apolipoprotein E (apoE) gene may affect responsiveness, with PS-induced reductions in TG more readily evident in apoE2 than apoE3 or E4 subjects. Although only a minimal number of animal model studies have been conducted to specifically examine the mechanisms whereby PS may reduce blood TG concentrations, it appears that there may be multiple mechanisms involved including interruption of intestinal fatty acid absorption and modulation of hepatic lipogenesis and VLDL packaging and secretion. In summary, the available data suggest that PS may be an effective therapy to lower blood TG, particularly in hypertriglyceridemic individuals. However, before PS can be widely recommended as a TG-lowering therapy, studies that are specifically powered and designed to fully access therapeutic responses and the mechanisms involved are required. PMID:25941890

  12. Central nervous system neuropeptide Y regulates mediators of hepatic phospholipid remodeling and very low-density lipoprotein triglyceride secretion via sympathetic innervation

    PubMed Central

    Rojas, Jennifer M.; Bruinstroop, Eveline; Printz, Richard L.; Alijagic-Boers, Aldijana; Foppen, Ewout; Turney, Maxine K.; George, Leena; Beck-Sickinger, Annette G.; Kalsbeek, Andries; Niswender, Kevin D.

    2015-01-01

    Objective Elevated very low-density lipoprotein (VLDL)-triglyceride (TG) secretion from the liver contributes to an atherogenic dyslipidemia that is associated with obesity, diabetes and the metabolic syndrome. Numerous models of obesity and diabetes are characterized by increased central nervous system (CNS) neuropeptide Y (NPY); in fact, a single intracerebroventricular (icv) administration of NPY in lean fasted rats elevates hepatic VLDL-TG secretion and does so, in large part, via signaling through the CNS NPY Y1 receptor. Thus, our overarching hypothesis is that elevated CNS NPY action contributes to dyslipidemia by activating central circuits that modulate liver lipid metabolism. Methods Chow-fed Zucker fatty (ZF) rats were pair-fed by matching their caloric intake to that of lean controls and effects on body weight, plasma TG, and liver content of TG and phospholipid (PL) were compared to ad-libitum (ad-lib) fed ZF rats. Additionally, lean 4-h fasted rats with intact or disrupted hepatic sympathetic innervation were treated with icv NPY or NPY Y1 receptor agonist to identify novel hepatic mechanisms by which NPY promotes VLDL particle maturation and secretion. Results Manipulation of plasma TG levels in obese ZF rats, through pair-feeding had no effect on liver TG content; however, hepatic PL content was substantially reduced and was tightly correlated with plasma TG levels. Treatment with icv NPY or a selective NPY Y1 receptor agonist in lean fasted rats robustly activated key hepatic regulatory proteins, stearoyl-CoA desaturase-1 (SCD-1), ADP-ribosylation factor-1 (ARF-1), and lipin-1, known to be involved in remodeling liver PL into TG for VLDL maturation and secretion. Lastly, we show that the effects of CNS NPY on key liporegulatory proteins are attenuated by hepatic sympathetic denervation. Conclusions These data support a model in which CNS NPY modulates mediators of hepatic PL remodeling and VLDL maturation to stimulate VLDL-TG secretion that is dependent on the Y1 receptor and sympathetic signaling to the liver. PMID:25737956

  13. Gut triglyceride production

    PubMed Central

    Pan, Xiaoyue; Hussain, M. Mahmood

    2012-01-01

    Our knowledge of how the body absorbs triacylglycerols (TAG) from the diet and how this process is regulated has increased at a rapid rate in recent years. Dietary TAG are hydrolyzed in the intestinal lumen to free fatty acids (FFA) and monoacylglycerols (MAG), which are taken up by enterocytes from their apical side, transported to the endoplasmic reticulum (ER) and resynthesized into TAG. TAG are assembled into chylomicrons (CM) in the ER, transported to the Golgi via pre-chylomicron transport vesicles and secreted towards the basolateral side. In this review, we mainly focus on the roles of key proteins involved in uptake and intracellular transport of fatty acids, their conversion to TAG and packaging into CM. We will also discuss intracellular transport and secretion of CM. Moreover, we will bring to light few factors that regulate gut triglyceride production. Furthermore, we briefly summarize pathways involved in cholesterol absorption. PMID:21989069

  14. Short-term administration of conjugated linoleic acid reduces liver triglyceride concentration and phosphatidate phosphohydrolase activity in OLETF rats.

    PubMed

    Rahman, Shaikh Mizanoor; Huda, M Nazmul; Uddin, M Nasir; Akhteruzzaman, Sharif

    2002-09-30

    The present study explored the short-term effects of dietary conjugated-linoleic acid (CLA) on liver lipid metabolism in starved/refed Otsuka Long Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (12 weeks old) were starved for 24 hours, then refed for 48 hours with either a CLA diet [7.5% CLA and 7.5% Safflower oil (SAF)] or a SAF control diet (15% SAF). The results demonstrated a 30% reduction of hepatic triglyceride (TG) concentration in the CLA group when compared to the control group. Liver cholesterol concentration was also 26% lower in the CLA fed rats. The activity of mitochondrial carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, was moderately elevated by 1.2-fold in the livers of the CLA group when compared to the control. In contrast, phosphatidate phosphohydrolase, the rate-limiting enzyme for TG synthesis, was found to be 20% lower in the livers of the CLA-fed rats. Therefore, dietary CLA evidently lowers liver lipid concentrations through a reduced TG synthesis and enhanced fatty acid oxidation in starved/refed OLETF rats. PMID:12359092

  15. Association of apolipoprotein A5 concentration with serum insulin and triglyceride levels and coronary artery disease in Korean men

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: Whereas the relation between apolipoprotein A5 (APOA5) gene polymorphisms and triglycerides (TG) levels is well established, the associations between apoA5 concentrations, TG and coronary artery disease (CAD) remain controversial. Therefore, we investigated these relations in the setting ...

  16. PCSK9 and triglyceride-rich lipoprotein metabolism

    PubMed Central

    Druce, Irena; Abujrad, Hussein; Ooi, Teik Chye

    2015-01-01

    Abstract Pro-protein convertase subtilisin-kexin 9 (PCSK9) is known to affect low-density lipoprotein (LDL) metabolism, but there are indications from several lines of research that it may also influence the metabolism of other lipoproteins, especially triglyceride-rich lipoproteins (TRL). This review summarizes the current data on this possible role of PCSK9. A link between PCSK9 and TRL has been suggested through the demonstration of (1) a correlation between plasma PCSK9 and triglyceride (TG) levels in health and disease, (2) a correlation between plasma PCSK9 and markers of carbohydrate metabolism, which is closely related to TG metabolism, (3) an effect of TG-lowering fibrate therapy on plasma PCSK9 levels, (4) an effect of PCSK9 on postprandial lipemia, (5) an effect of PCSK9 on adipose tissue biology, (6) an effect of PCSK9 on apolipoprotein B production from the liver and intestines, (7) an effect of PCSK9 on receptors other than low density lipoprotein receptor (LDLR) that are involved in TRL metabolism, and (8) an effect of anti-PCSK9 therapy on serum TG levels. The underlying mechanisms are unclear but starting to emerge. PMID:26320603

  17. Characterization of triglyceride lipase genes of fission yeast Schizosaccharomyces pombe.

    PubMed

    Yazawa, Hisashi; Kumagai, Hiromichi; Uemura, Hiroshi

    2012-11-01

    Triglycerides (TG) are major storage lipids for eukaryotic cells. In this study, we characterized three genes of fission yeast Schizosaccharomyces pombe, SPCC1450.16c, SPAC1786.01c, and SPAC1A6.05c, that show high homology to Saccharomyces cerevisiae TG lipase genes, TGL3, TGL4, and TGL5. Deletion of each gene increased TG content by approximately 1.7-fold compared to the parental wild-type strain, and their triple deletion mutant further increased TG content to 2.7-fold of the wild-type strain, suggesting that all three genes encode TG lipase and are functioning in S. pombe. The triple deletion mutant showed no growth defect in rich and synthetic medium, but its growth was sensitive to cerulenin, an inhibitor of fatty acid synthesis. This growth defect by cerulenin was restored by adding oleic acid in media, suggesting that these genes were involved in the mobilization of TG in S. pombe. When ricinoleic acid was produced in the triple mutant by introducing CpFAH12 fatty acid hydroxylase gene from Claviceps purpurea, percent composition of ricinoleic acid increased by 1.1-fold compared to the wild-type strain, in addition to a 1.6-fold increase in total fatty acid content per dry cell weight (DCW). In total, the ricinoleic acid production per DCW increased by 1.8-fold in the triple deletion mutant. PMID:22592553

  18. Causes of the triglyceride-lowering effect of exercise training in rats

    NASA Technical Reports Server (NTRS)

    Mondon, C. E.; Dolkas, C. B.; Tobey, T.; Reaven, G. M.

    1984-01-01

    Studies conducted with human subjects and laboratory animals have consistently shown a reduction in serum triglyceride (TG) in exercise-trained subjects. The obtained data have suggested that this decrease was due to a reduction in hepatic TG secretion. The present investigation, which was conducted with rats trained to attain a high level of spontaneous running activity, provides support for the earlier results. In addition, insights are obtained regarding the mechanism by which exercise lowers TG levels. Since the liver accounts for the vast majority of endogenous very low density lipoprotein (VLDL)-TG secretion, the fall in TG secretion rate seen in exercise-trained (ET) rats must be due to a reduction in hepatic TG secretion.

  19. TG-21 versus TG-25: a comparison for electrons.

    PubMed

    Followill, D S; Davis, D S; Hanson, W F

    1997-07-01

    Since 1984, the Radiological Physics Center (RPC) has used the American Association of Physicists in Medicine Task Group 21 (TG-21) protocol (absorbed dose determination) as the basis of its On-site Dosimetry Review visits to institutions participating in the National Cancer Institute's cooperative clinical trials. Subsequent to the TG-21 protocol, the Task Group 25 (TG-25) report on electron-beam dosimetry was published. The TG-25 report was not intended to supercede the TG-21 protocol, but to supplement it for depths other than dmax. However, both reports included measurement techniques and data regarding the calibration of electron beams. TG-25 was not intended for absolute calibrations made clear by the fact that it does not present all of the data required for plastic phantom calibrations, i.e., unrestricted stopping power ratios. As a result, some confusion has arisen at various institutions as to which protocol should be used for machine calibration. In this study, possible discrepancies that arise when using TG-21, a version of TG-21 modified by the RPC, and TG-25 are compared. The differences in the results are calculated as a function of energy (6 and 20 MeV), chamber type (cylindrical or parallel plate), and the type of phantom material (water, polystyrene, or acrylic). The largest discrepancies noted were between TG-25 and the two TG-21 methods for low-energy electrons in either water or polystyrene. The mean difference for all conditions was 0.8% with a maximum value of 3.3% in polystyrene. The definition of the effective point of measurement; determination of the mean nominal incident energy (E0), mean energy at depth (EZ) and most probable energy at the surface (Ep,0) for each protocol, and subsequent stopping power ratio, chamber replacement factor, and electron fluence correction factor are the major contributors to the calculated differences. PMID:9243474

  20. Postabsorptive VLDL-TG fatty acid storage in adipose tissue in lean and obese women.

    PubMed

    Nellemann, Birgitte; Gormsen, Lars C; Christiansen, Jens S; Jensen, Michael D; Nielsen, Søren

    2010-07-01

    Adipose tissue lipoprotein lipase (LPL) is a necessary enzyme for storage of very-low-density lipoprotein-triglyceride (VLDL-TG), but whether it is a rate-determining step is unknown. To test this hypothesis we included 10 upper-body obese (UBO), 11 lower-body obese (LBO), and 8 lean women. We infused ex vivo-labeled VLDL-(14)C-TG and then performed adipose tissue biopsies to understand the relationship between VLDL-TG storage and LPL activity in femoral and upper-body subcutaneous fat. Both fractional tracer storage and rate of storage of the VLDL-TG tracer were evaluated. VLDL-TG storage was also examined as a function of regional adipose tissue blood flow (ATBF), insulin, VLDL-TG turnover, regional fat mass, fat-free mass (FFM), and fat cell size. LPL activity per adipocyte was significantly greater in obese than lean women but not significantly different per gram lipid. Both VLDL-TG fractional tracer storage per kg lipid and VLDL-TG storage rate per kg lipid were similar in abdominal and femoral fat in all three groups and were not significantly different between groups. Multiple regression analysis identified FFM and femoral fat mass as significant independent predictors of VLDL-TG fractional tracer storage and insulin as a significant predictor of VLDL-TG fatty acid storage rate. LPL activity, ATBF, and VLDL-TG turnover did not predict VLDL-TG storage. We conclude that lower FFM and greater plasma insulin are associated with greater VLDL-TG deposition in abdominal subcutaneous and femoral fat. Greater femoral fat mass signals greater femoral VLDL-TG storage. We suggest that the differences in VLDL-TG storage in abdominal and femoral fat that occur with progressive obesity are regulated through mechanisms other than LPL activity. PMID:19875996

  1. The genetic architecture of fasting plasma triglyceride response to fenofibrate treatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic response to the triglyceride (TG)-lowering drug, fenofibrate, is shaped by interactions between genetic and environmental factors, yet knowledge regarding the genetic determinants of this response is primarily limited to single gene effects. Since very low density lipoprotein (VLDL) is the...

  2. Dialkylphosphatidylcholine and egg yolk lecithin for emulsification of various triglycerides.

    PubMed

    Nii, Tomoko; Ishii, Fumiyoshi

    2005-04-10

    Synthesized saturated phosphatidylcholine (PC) and egg yolk lecithin (EYL) were investigated to explore their influence on particle sizes in emulsions when dispersing various triglycerides (TG). One of four different kinds of synthesized saturated PC (DLPC, DMPC, DPPC and DSPC) or three different kinds of EYL (purified EYL (PEL) and hydrogenated purified EYL with two different iodine values (IV), R-20 and R-5), 2.5% (w/w) glycerol solution and one of four kinds of TG (tricaprylin, tricaprin, trilaurin and trimyristin) were sonicated five times for 1 min with intervals of 0.5 min. When using four kinds of synthesized saturated PCs as emulsifiers, the carbon numbers of each PC had a strong correlation with the mean diameters of the emulsion when analyzed with each of the four kinds of TG used in the study (regression function ranged from 0.811 to 0.915). The carbon numbers of the TG had less correlation with the mean diameters than the PC in simple regression analysis (regression function ranged from 0.236 to 0.875). Multiple regression analysis using the carbon numbers both of the PC and TG as independent variables was remarkably significant in the regression function (2.0 x 10(-14)) and all regression coefficients (2.7 x 10(-13), 5.8 x 10(-7) and 1.9 x 10(-9) for PC, TG and intercept, respectively). Among the regression coefficients, the contribution of the carbon number of the PC was the most significant. These results indicated that a multiple regression function should be useful to estimate the mean diameters of emulsion droplets in any combinations of PC and TG used in this study. In the experiments using three kinds of EYL, the mean diameters also tended to increase according to the order of PEL, R-20 and R-5, which corresponds to the order of degrees of saturation (IV = 75, 20 and 2, respectively). The experimental values for EYL were compared with the estimated values calculated by the multiple regression function derived from synthesized PC data using the arithmetic carbon number, based on the components of each EYL. The estimated mean diameters were at comparable levels to the corresponding experimental mean diameters in the most saturated hydrogenated lecithin (R-5), while those were larger than the experimental mean diameters in two less saturated kinds of lecithin (R-20 and purified EYL). These findings gave useful information on the mean diameters of emulsion droplets when designing an emulsion formulation using a particular combination of a phospholipid and triglyceride. PMID:15748826

  3. Metabolic fate of an oral long-chain triglyceride load in humans.

    PubMed

    Binnert, C; Pachiaudi, C; Beylot, M; Croset, M; Cohen, R; Riou, J P; Laville, M

    1996-03-01

    To determine the steps involved in the metabolism of ingested triglycerides (TG), 10 healthy women were studied during 6 h after ingestion of 30 g olive oil labeled with [1,1,1-13C3] triolein. The appearance of 13C was followed in chylomicron-TG (CM-TG), nonesterified fatty acid (NEFA), very low-density lipoprotein (VLDL)-TG, and in expired gas. Indirect calorimetry was used to determine total lipid oxidation. After 90 min, labeling was higher in CM-TG than in NEFA or VLDL. At 180 min, a plateau of enrichment was obtained for CM-TG and NEFA, demonstrating the entry of exogenous lipids in the NEFA pool. After 300 min, a plateau was observed for VLDL-TG with levels of enrichment (0.38 +/- 0.04%) similar to those observed for NEFA (0.36 +/- 0.03%), suggesting a precursor-product relationship. Only 19 +/- 2% of the load was oxidized. From 300 to 360 min, 70% of total lipid oxidation was from exogenous TG. We conclude that, after ingestion of a lipid load, a cycle of fatty acids-TG occurs from CM to NEFA and from NEFA to VLDL. Furthermore, this lipid load has a sparing effect on endogenous lipid stores. PMID:8638691

  4. Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI genetics of lipid lowering drugs and diet network (GOLDN)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variant...

  5. Lowering triglycerides to modify cardiovascular risk: will icosapent deliver?

    PubMed Central

    Scherer, Daniel J; Nicholls, Stephen J

    2015-01-01

    Despite the clinical benefits of lowering levels of low-density lipoprotein cholesterol, many patients continue to experience cardiovascular events. This residual risk suggests that additional risk factors require aggressive modification to result in more effective prevention of cardiovascular disease. Hypertriglyceridemia has presented a considerable challenge with regard to understanding its role in the promotion of cardiovascular risk. Increasing evidence has established a clear causal role for elevated triglyceride levels in vascular risk. As a result, there is increasing interest in the development of specific therapeutic strategies that directly target hypertriglyceridemia. This has seen a resurgence in the use of omega-3 fatty acids for the therapeutic lowering of triglyceride levels. The role of these agents and other emerging strategies to reduce triglyceride levels in order to decrease vascular risk are reviewed. PMID:25848301

  6. Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions

    PubMed Central

    Nagano, Tomohisa; Seki, Nobuyoshi; Tomita, Yoichi; Sugita, Tomonori; Aida, Yuta; Itagaki, Munenori; Sutoh, Satoshi; Abe, Hiroshi; Tsubota, Akihito; Aizawa, Yoshio

    2015-01-01

    Reduced low-density lipoprotein (LDL) cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV) infection. However, abnormality in serum triglyceride (TG) has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b) infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL), LDL, and high-density lipoprotein (HDL). Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles. PMID:26334270

  7. Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-? in patients with triglyceride deposit cardiomyovasculopathy.

    PubMed

    Hirano, Ken-ichi; Tanaka, Tatsuya; Ikeda, Yoshihiko; Yamaguchi, Satoshi; Zaima, Nobuhiro; Kobayashi, Kazuhiro; Suzuki, Akira; Sakata, Yasuhiko; Sakata, Yasushi; Kobayashi, Kunihisa; Toda, Tatsushi; Fukushima, Norihide; Ishibashi-Ueda, Hatsue; Tavian, Daniela; Nagasaka, Hironori; Hui, Shu-Ping; Chiba, Hitoshi; Sawa, Yoshiki; Hori, Masatsugu

    2014-01-10

    Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, "Triglyceride deposit cardiomyovasculopathy (TGCV)". Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5' splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules' lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients' passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG is defective, the marked up-regulation of PPAR? and related genes may lead to increased uptake of LCFAs, the substrates for TG synthesis. This potentially vicious cycle of LCFAs could explain the massive accumulation of TG and severe clinical course for this rare disease. PMID:24332944

  8. Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men

    PubMed Central

    Yokoyama, Akira; Yokoyama, Tetsuji; Matsui, Toshifumi; Mizukami, Takeshi; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya

    2015-01-01

    Background Elevated serum triglyceride (TG) and high-density-lipoprotein cholesterol (HDL-C) levels are common in drinkers. The fast-metabolizing alcohol dehydrogenase-1B encoded by the ADH1B*2 allele (vs. ADH1B*1/*1 genotype) and inactive aldehyde dehydrogenase-2 encoded by the ALDH2*2 allele (vs. ALDH2*1/*1 genotype) modify ethanol metabolism and are prevalent (?90% and ?40%, respectively) in East Asians. We attempted to evaluate the associations between the ADH1B and ALDH2 genotypes and lipid levels in alcoholics. Methods The population consisted of 1806 Japanese alcoholic men (?40 years) who had undergone ADH1B and ALDH2 genotyping and whose serum TG, total cholesterol, and HDL-C levels in the fasting state had been measured within 3 days after admission. Results High serum levels of TG (?150 mg/dl), HDL-C (>80 mg/dl), and low-density-lipoprotein cholesterol (LDL-C calculated by the Friedewald formula ?140 mg/dl) were observed in 24.3%, 16.8%, and 15.6%, respectively, of the subjects. Diabetes, cirrhosis, smoking, and body mass index (BMI) affected the serum lipid levels. Multivariate analysis revealed that the presence of the ADH1B*2 allele and the active ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval) for a high TG level (2.22 [1.67–2.94] and 1.39 [0.99–1.96], respectively), and decreased the OR for a high HDL-C level (0.37 [0.28–0.49] and 0.51 [0.37–0.69], respectively). The presence of the ADH1B*2 allele decreased the OR for a high LDL-C level (0.60 [0.45–0.80]). The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs for high TG levels and lowest OR for a high HDL-C level. The genotype effects were more prominent in relation to the higher levels of TG (?220 mg/dl) and HDL-C (?100 mg/dl). Conclusions The fast-metabolizing ADH1B and active ALDH2, and especially a combination of the two were strongly associated with higher serum TG levels and lower serum HDL-C levels of alcoholics. The fast-metabolizing ADH1B was associated with lower serum LDL-C levels. PMID:26284938

  9. Metabolism of triglyceride-rich lipoproteins during alimentary lipemia.

    PubMed Central

    Karpe, F; Steiner, G; Olivecrona, T; Carlson, L A; Hamsten, A

    1993-01-01

    The metabolism of chylomicron remnants and VLDL was studied in healthy controls and normo- (NTG) and hypertriglyceridemic (HTG) patients with coronary artery disease after intake of an oral fat load. Specific determination of apo B-48 and B-100 enabled separation of the respective contribution of the two lipoprotein species. The postprandial plasma levels of small (Sf 20-60) and large (Sf 60-400) chylomicron remnants increased in controls and NTG patients. In contrast, only large chylomicron remnants increased in the HTG patients. An increase of large VLDL was seen in response to the oral fat load in all groups, whereas small VLDL were either unchanged in the controls and the NTG patients, or decreased in the HTG patient group. The whole plasma concentration of C apolipoproteins was essentially uninfluenced by the oral fat load, whereas the content in large triglyceride-rich lipoproteins paralleled the apo B elevations in controls and NTG patients. An even more prominent increase of apo B in large triglyceride-rich lipoproteins in the HTG group was not accompanied by an increase of C apolipoproteins. These findings indicate that chylomicrons compete with VLDL for removal of triglycerides by lipoprotein lipase and that the postprandial metabolism of triglyceride-rich lipoproteins is severely defective in hypertriglyceridemia. PMID:8450056

  10. Rare LPL gene variants attenuate triglyceride reduction and HDL cholesterol increase in response to fenofibric acid therapy in

    E-print Network

    Keinan, Alon

    Rare LPL gene variants attenuate triglyceride reduction and HDL cholesterol increase in response- protein cholesterol (HDL-C), and increased risk for coronary disease. Fibrate therapy is commonly used to lower TG and increase HDL-C. Common genetic variants are known to affect the response to fibrate therapy

  11. Packaged bulk micromachined triglyceride biosensor

    NASA Astrophysics Data System (ADS)

    Mohanasundaram, S. V.; Mercy, S.; Harikrishna, P. V.; Rani, Kailash; Bhattacharya, Enakshi; Chadha, Anju

    2010-02-01

    Estimation of triglyceride concentration is important for the health and food industries. Use of solid state biosensors like Electrolyte Insulator Semiconductor Capacitors (EISCAP) ensures ease in operation with good accuracy and sensitivity when compared to conventional sensors. In this paper we report on packaging of miniaturized EISCAP sensors on silicon. The packaging involves glass to silicon bonding using adhesive. Since this kind of packaging is done at room temperature, it cannot damage the thin dielectric layers on the silicon wafer unlike the high temperature anodic bonding technique and can be used for sensors with immobilized enzyme without denaturing the enzyme. The packaging also involves a teflon capping arrangement which helps in easy handling of the bio-analyte solutions. The capping solves two problems. Firstly, it helps in the immobilization process where it ensures the enzyme immobilization happens only on one pit and secondly it helps with easy transport of the bio-analyte into the sensor pit for measurements.

  12. Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-? in patients with triglyceride deposit cardiomyovasculopathy

    SciTech Connect

    Hirano, Ken-ichi; Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 ; Tanaka, Tatsuya; Ikeda, Yoshihiko; Yamaguchi, Satoshi; Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 ; Zaima, Nobuhiro; Kobayashi, Kazuhiro; Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 ; Sakata, Yasuhiko; Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1, Seiryo-cho, Aoba-ku, Sendai 980-8574 ; and others

    2014-01-10

    Highlights: •Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare severe heart disease. •PPAR? is up-regulated in myocardium in patients with TGCV. •Possible vicious cycle for fatty acid may be involved in pathophysiology of TGCV. -- Abstract: Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, “Triglyceride deposit cardiomyovasculopathy (TGCV)”. Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5? splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules’ lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients’ passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG is defective, the marked up-regulation of PPAR? and related genes may lead to increased uptake of LCFAs, the substrates for TG synthesis. This potentially vicious cycle of LCFAs could explain the massive accumulation of TG and severe clinical course for this rare disease.

  13. Very-low-density lipoprotein triglyceride kinetics in acute and chronic carbohydrate-fed rats

    SciTech Connect

    Hirano, T.; Mamo, J.; Poapst, M.; Steiner, G.

    1988-09-01

    Very-low-density lipoprotein (VLDL)-triglyceride (TG) kinetics were examined in rats maintained on either chow and water (control) or chow and a 10% carbohydrate drinking solution (fructose or glucose). The hexose solutions were available for an acute (16 h) or chronic (14 day) period. The acute fructose (AF), acute glucose (AG), and chronic fructose (CF) groups were hypertriglyceridemic (HTG) compared with control. Plasma TG concentration in chronic glucose (CG)-fed rats was similar to control. VLDL-TG was endogenously radiolabeled in donor rats with (2-3H)-glycerol. The fractional catabolic rate (FCR) was then determined by monitoring the clearance of plasma (3H)VLDL-TG in recipient animals. Donors and recipients were treated in an identical manner. AF and CF groups had an FCR significantly lower than rats given glucose for comparable periods. Both fructose groups and the AG group also had a lower FCR than control. In contrast, FCR in the CG group was significantly higher than controls. TG production rate (TGPR) in both AF and CF fed rats did not significantly differ from controls, suggesting that the HTG observed in these animals was solely from a catabolic defect. AG- and CG-treated glucose animals both had TGPR significantly higher than controls. Therefore, overproduction of VLDL-TG contributed to the HTG associated with this carbohydrate.

  14. Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells

    PubMed Central

    Taschler, Ulrike; Schreiber, Renate; Chitraju, Chandramohan; Grabner, Gernot F.; Romauch, Matthias; Wolinski, Heimo; Haemmerle, Guenter; Breinbauer, Rolf; Zechner, Rudolf; Lass, Achim; Zimmermann, Robert

    2015-01-01

    Hepatic stellate cells (HSCs) store triglycerides (TGs) and retinyl ester (RE) in cytosolic lipid droplets. RE stores are degraded following retinoid starvation or in response to pathogenic stimuli resulting in HSC activation. At present, the major enzymes catalyzing lipid degradation in HSCs are unknown. In this study, we investigated whether adipose triglyceride lipase (ATGL) is involved in RE catabolism of HSCs. Additionally, we compared the effects of ATGL deficiency and hormone-sensitive lipase (HSL) deficiency, a known RE hydrolase (REH), on RE stores in liver and adipose tissue. We show that ATGL degrades RE even in the presence of TGs, implicating that these substrates compete for ATGL binding. REH activity was stimulated and inhibited by comparative gene identification-58 and G0/G1 switch gene-2, respectively, the physiological regulators of ATGL activity. In cultured primary murine HSCs, pharmacological inhibition of ATGL, but not HSL, increased RE accumulation. In mice globally lacking ATGL or HSL, RE contents in white adipose tissue were decreased or increased, respectively, while plasma retinol and liver RE levels remained unchanged. In conclusion, our study shows that ATGL acts as REH in HSCs promoting the degradation of RE stores in addition to its established function as TG lipase. HSL is the predominant REH in adipocytes but does not affect lipid mobilization in HSCs. PMID:25732851

  15. The late addition of core lipids to nascent apolipoprotein B100, resulting in the assembly and secretion of triglyceride-rich lipoproteins, is independent of both microsomal triglyceride transfer protein activity and new triglyceride synthesis.

    PubMed

    Pan, Meihui; Liang Js, Jun-shan; Fisher, Edward A; Ginsberg, Henry N

    2002-02-01

    Although microsomal triglyceride transfer protein (MTP) and newly synthesized triglyceride (TG) are critical for co-translational targeting of apolipoprotein B (apoB100) to lipoprotein assembly in hepatoma cell lines, their roles in the later stages of lipoprotein assembly remain unclear. Using N-acetyl-Leu-Leu-norleucinal to prevent proteasomal degradation, HepG2 cells were radiolabeled and chased for 0-90 min (chase I). The medium was changed and cells chased for another 150 min (chase II) in the absence (control) or presence of Pfizer MTP inhibitor CP-10447 (CP). As chase I was extended, inhibition of apoB100 secretion by CP during chase II decreased from 75.9% to only 15% of control (no CP during chase II). Additional studies were conducted in which chase I was either 0 or 90 min, and chase II was in the presence of [(3)H]glycerol and either BSA (control), CP (inhibits both MTP activity and TG synthesis),BMS-1976360-1) (BMS) (inhibits only MTP activity), or triacsin C (TC) (inhibits only TG synthesis). When chase I was 0 min, CP, BMS, and TC reduced apoB100 secretion during chase II by 75.3, 73.9, and 53.9%. However, when chase I was 90 min, those agents reduced apoB100 secretion during chase II by only 16.0, 19.2, and 13.9%. Of note, all three inhibited secretion of newly synthesized TG during chase II by 80, 80, and 40%, whether chase I was 0 or 90 min. In both HepG2 cells and McA-RH7777 cells, if chase I was at least 60 min, inhibition of TG synthesis and/or MTP activity did not affect the density of secreted apoB100-lipoproteins under basal conditions. Oleic acid increased secretion of TG-enriched apoB100-lipoproteins similarly in the absence or presence of either of CP, BMS, or TC. We conclude that neither MTP nor newly synthesized TG is necessary for the later stages of apoB100-lipoprotein assembly and secretion in either HepG2 or McA-RH7777 cells. PMID:11704664

  16. Mitochondrial triglyceride transfer protein inhibition: new achievements in the treatment of dyslipidemias.

    PubMed

    Kostapanos, Michael S; Rizos, Evangelos C; Papanas, Nikolaos; Maltezos, Efstratios; Elisaf, Moses S

    2013-01-01

    Current lipid-lowering drugs are often unable to achieve low density lipoprotein cholesterol (LDL-C) goals. Moreover, despite LDL-C lowering mostly by statins, a considerable residual vascular risk remains. This is partly associated with atherogenic dyslipidemia where apolipoprotein (apo) B-containing lipoproteins predominate. Mitochondrial Triglyceride (TG) transfer protein (MTP) is a key enzyme for apoB-containing lipoprotein assembly and secretion. This is mostly attributed to its capacity to transfer lipid components (TGs, cholesterol esters and phospholipids) to the endoplasmic reticulum lumen, where these lipoproteins are assembled. Several agents were developed to inhibit MTP wherever it is expressed, namely the liver and/or the intestine. Liver-specific MTP inhibitors reduce secretion of very low density lipoproteins (VLDL) mostly containing apoB100, while the intestine-specific ones reduce secretion of chylomicrons containing apoB48. These drugs can significantly reduce total cholesterol, LDL-C, TGs, VLDL cholesterol, as well as apoB levels in vivo. They may also exert anti-atherosclerotic and insulin-sensitizing effects. Limited clinical data suggest that these compounds can also improve the serum lipid profile in patients with homozygous familial hypercholesterolemia (HoFH). The accumulation of unsecreted fat in the liver and intestinal lumen is associated with elevation of aminotransferases and steatorrhea. Liver steatosis can be avoided by the use of intestine-specific MTP inhibitors, while steatorrhea by low-fat diet. Future indications for these developing drugs may include dyslipidemia associated with insulin resistant states, familial combined hyperlipidemia and HoFH. Future clinical trials are warranted to assess the efficacy and safety of MTP inhibitors in various clinical states. PMID:23317403

  17. ?-Lipoic acid as a triglyceride-lowering nutraceutical.

    PubMed

    Pashaj, Anjeza; Xia, Mengna; Moreau, Régis

    2015-12-01

    Considering the current obesity epidemic in the United States (>100 million adults are overweight or obese), the prevalence of hypertriglyceridemia is likely to grow beyond present statistics of ?30% of the population. Conventional therapies for managing hypertriglyceridemia include lifestyle modifications such as diet and exercise, pharmacological approaches, and nutritional supplements. It is critically important to identify new strategies that would be safe and effective in lowering hypertriglyceridemia. ?-Lipoic acid (LA) is a naturally occurring enzyme cofactor found in the human body in small quantities. A growing body of evidence indicates a role of LA in ameliorating metabolic dysfunction and lipid anomalies primarily in animals. Limited human studies suggest LA is most efficacious in situations where blood triglycerides are markedly elevated. LA is commercially available as dietary supplements and is clinically shown to be safe and effective against diabetic polyneuropathies. LA is described as a potent biological antioxidant, a detoxification agent, and a diabetes medicine. Given its strong safety record, LA may be a useful nutraceutical, either alone or in combination with other lipid-lowering strategies, when treating severe hypertriglyceridemia and diabetic dyslipidemia. This review examines the current evidence regarding the use of LA as a means of normalizing blood triglycerides. Also presented are the leading mechanisms of action of LA on triglyceride metabolism. PMID:26235242

  18. Genetic analysis of proteoglycan-mediated clearance of triglycerides

    E-print Network

    Stanford, Kristin Irene

    2009-01-01

    major enzyme responsible for the hydrolysis of triglycerideshydrolysis of triglycerides in the plasma. Results Reduced plasma Lpl and enzymeenzyme in the metabolism of triglyceride-rich lipoproteins (TRLs) (30). It catalyzes the hydrolysis of triglycerides

  19. Effects of glucagon and insulin on plasma glucose, triglyceride, and triglyceride-rich lipoprotein concentrations in laying hens fed diets containing different types of fats.

    PubMed

    Pál, L; Grossmann, R; Dublecz, K; Husvéth, F; Wagner, L; Bartos, A; Kovács, G

    2002-11-01

    The influence of dietary fat supplementations differing in the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) on the effects of glucagon and insulin on plasma glucose, triglyceride (TG), and TG-rich lipoprotein concentrations was investigated in laying hens. Birds were fed either a low-fat control diet (LF) or diets supplemented with 4% pumpkin seed oil (PO; rich in n-6 PUFA) or 4% cod liver oil (CO; rich in n-3 PUFA). After 4 wk feeding of the experimental diets, hens were implanted with wing vein catheters and injected with porcine glucagon (20 microg/kg BW) and porcine insulin (0.5 IU/kg BW), 2 to 5 h after oviposition. Plasma glucose, TG, and TG-rich lipoprotein concentrations were determined from 10 min pre-injection to 60 min post-injection. PO diet resulted in a prolonged plasma glucose response to glucagon administration and altered hypoglycemic response to insulin. However, CO diet did not influence plasma glucose response to either glucagon or insulin administration compared to LF diet. The effects of glucagon and insulin on plasma TG and TG-rich lipoproteins were similar for all diets regardless of the amount or type of fat. The results suggest that feeding dietary fats with high n-6 to n-3 PUFA ratio alters the glucagon and insulin sensitivity of plasma glucose in laying hens. Fats rich in n-3 PUFA seem to have no influence on the plasma glucose response to glucagon and insulin. PMID:12455597

  20. Micro RNA-124a Regulates Lipolysis via Adipose Triglyceride Lipase and Comparative Gene Identification 58

    PubMed Central

    Das, Suman K.; Stadelmeyer, Elke; Schauer, Silvia; Schwarz, Anna; Strohmaier, Heimo; Claudel, Thiery; Zechner, Rudolf; Hoefler, Gerald; Vesely, Paul W.

    2015-01-01

    Lipolysis is the biochemical pathway responsible for the catabolism of cellular triacylglycerol (TG). Lipolytic TG breakdown is a central metabolic process leading to the generation of free fatty acids (FA) and glycerol, thereby regulating lipid, as well as energy homeostasis. The precise tuning of lipolysis is imperative to prevent lipotoxicity, obesity, diabetes and other related metabolic disorders. Here, we present our finding that miR-124a attenuates RNA and protein expression of the major TG hydrolase, adipose triglyceride lipase (ATGL/PNPLA2) and its co-activator comparative gene identification 58 (CGI-58/ABHD5). Ectopic expression of miR-124a in adipocytes leads to reduced lipolysis and increased cellular TG accumulation. This phenotype, however, can be rescued by overexpression of truncated Atgl lacking its 3'UTR, which harbors the identified miR-124a target site. In addition, we observe a strong negative correlation between miR-124a and Atgl expression in various murine tissues. Moreover, miR-124a regulates the expression of Atgl and Cgi-58 in murine white adipose tissue during fasting as well as the expression of Atgl in murine liver, during fasting and re-feeding. Together, these results point to an instrumental role of miR-124a in the regulation of TG catabolism. Therefore, we suggest that miR-124a may be involved in the regulation of several cellular and organismal metabolic parameters, including lipid storage and plasma FA concentration. PMID:25894224

  1. Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

    NASA Astrophysics Data System (ADS)

    Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

    2006-03-01

    Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

  2. Triglyceride enrichment of HDL enhances in vivo metabolic clearance of HDL apo A-I in healthy men

    PubMed Central

    Lamarche, Benoît; Uffelman, Kristine D.; Carpentier, André; Cohn, Jeffrey S.; Steiner, George; Barrett, P. Hugh; Lewis, Gary F.

    1999-01-01

    Triglyceride (TG) enrichment of HDL resulting from cholesteryl ester transfer protein–mediated exchange with TG-rich lipoproteins may enhance the lipolytic transformation and subsequent metabolic clearance of HDL particles in hypertriglyceridemic states. The present study investigates the effect of TG enrichment of HDL on the clearance of HDL-associated apo A-I in humans. HDL was isolated from plasma of six normolipidemic men (mean age: 29.7 ± 2.7 years) in the fasting state and after a five-hour intravenous infusion with a synthetic TG emulsion, Intralipid. Intralipid infusion resulted in a 2.1-fold increase in the TG content of HDL. Each tracer was then whole-labeled with 125I or 131I and injected intravenously into the subject. Apo A-I in TG-enriched HDL was cleared 26% more rapidly than apo A-I in fasting HDL. A strong correlation between the Intralipid-induced increase in the TG content of HDL and the increase in HDL apo A-I fractional catabolic rate reinforced the importance of TG enrichment of HDL in enhancing its metabolic clearance. HDL was separated further into lipoproteins containing apo A-II (LpAI:AII) and those without apo A-II (LpAI). Results revealed that the enhanced clearance of apo A-I from TG-enriched HDL could be largely attributed to differences in the clearance of LpAI but not LpAI:AII. This is, to our knowledge, the first direct demonstration in humans that TG enrichment of HDL enhances the clearance of HDL apo A-I from the circulation. This phenomenon could provide an important mechanism explaining how HDL apo A-I and HDL cholesterol are lowered in hypertriglyceridemic states. PMID:10207171

  3. Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance.

    PubMed

    Cai, Yin; Ying, Fan; Song, Erfei; Wang, Yu; Xu, Aimin; Vanhoutte, Paul M; Tang, Eva Hoi-Ching

    2015-12-01

    Upon high-fat feeding, prostaglandin E receptor subtype 4 (EP4)-knockout mice gain less body weight than their EP4(+/+) littermates. We investigated the cause of the lean phenotype. The mice showed a 68.8% reduction in weight gain with diminished fat mass that was not attributable to reduced food intake, fat malabsorption, or increased energy expenditure. Plasma triglycerides in the mice were elevated by 244.9%. The increase in plasma triglycerides was independent of changes in hepatic very low density lipoprotein (VLDL)-triglyceride production or intestinal chylomicron-triglyceride synthesis. However, VLDL-triglyceride clearance was drastically impaired in the EP4-knockout mice. The absence of EP4 in mice compromised the activation of lipoprotein lipase (LPL), the key enzyme responsible for trafficking of plasma triglycerides into peripheral tissues. Deficiency in EP4 reduced hepatic mRNA expression of the transcriptional factor cAMP response element binding protein H (by 36.8%) and LPL activators, including apolipoprotein (Apo)a5 (by 40.2%) and Apoc2 (by 61.3%). In summary, the lean phenotype of EP4-deficient mice resulted from reduction in adipose tissue and accretion of other peripheral organs caused by impaired triglyceride clearance. The findings identify a new metabolic dimension in the physiologic role played by endogenous EP4.-Cai, Y., Ying, F., Song, E., Wang, Y., Xu, A., Vanhoutte, P. M., Tang, E. H.-C. Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance. PMID:26271253

  4. Low fasting serum triglyceride level as a precocious marker of autoimmune disorders.

    PubMed

    Iannello, Silvia; Cavaleri, Antonina; Milazzo, Paolina; Cantarella, Santi; Belfiore, Francesco

    2003-08-01

    The authors recently reported the occurrence of low fasting serum triglyceride (TG) and high free fatty acid (FFA) levels in idiopathic pulmonary fibrosis. TG estimation in diverse groups of patients with autoimmune disease or hyperactive immune response confirmed the occurrence of a similar decrease of TG. In some patients, serum FFA level was also evaluated. TG value in lean and obese patients was compared with that in lean (n = 108) and obese (n = 208) control subjects without autoimmune disease. In patients affected by autoimmune chronic thyroiditis with enhanced concentration of antithyroglobulin antibodies and without thyroidal failure (n = 24), lean and obese patients had reduced TG (-69/%, P < .01 and -52%, P < .0001, respectively). Both lean and obese patients affected by chronic active B or C hepatitis (n = 26), with autoantibodies and without signs of hepatic insufficiency or cirrhosis, presented reduced TG (-57%, P < .01 and -61%, P < .001, respectively). A marked TG decrease (-73%, P < .001) was observed in the lean patients affected by lupus-like syndrome (n = 7). The lean and obese patients with systemic lupus erythematosus or rheumatoid arthritis (n = 11) showed TG decrease (-66%, P < .01 and -55%, P < .05, respectively). In patients affected by anamnestic allergy or atopic dermatitis/asthma (n = 66), both lean and obese, TGs were reduced (-67%, P < .0001 and -62%, P < .001, respectively). In isolated cases of diverse autoimmune diseases (scleroderma, APECED [autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy], urticaria or urticarial vasculitis, Reiter or Sjogren syndromes, ulcerative colitis or Crohn's disease, multiple sclerosis or Guillain-Barré syndrome) (n = 14), decreased TG was also observed both in the lean and obese subjects (-59%, P < .01 and -57%, P < .01, respectively). Concerning FFA (n = 69), value in lean patients (n = 22) vs that in lean controls (n = 18) was increased (520 +/- 31 vs 299 +/- 30 mcEq/L, +74%, P < .001), whereas value in obese patients (n = 18) vs that in obese control subjects (n = 11) was decreased (542 +/- 34 vs 774 +/- 62, -30%, P < .01). This opposite behavior of FFA in lean and obese patients needs to be confirmed. Data in this study seem to indicate that low TG value may be a precocious marker of autoimmunity or immune system hyperreactivity. PMID:14600656

  5. Identification of TgAtg8-TgAtg3 interaction in Toxoplasma gondii.

    PubMed

    Chen, Di; Lin, Jiaxin; Liu, Yangyang; Li, Xiangzhi; Chen, Gaozhi; Hua, Qianqian; Nie, Qinqin; Hu, Xin; Tan, Feng

    2016-01-01

    Autophagy is a catabolic process in eukaryotic cells involved in the targeted degradation of cellular organelles and the cytoplasm. Recent works in Toxoplasma gondii suggest that the autophagy processes may serve as an important pathway in modulating parasite survival or death. As an important modulator of Atg8 lipidation and autophagy, Atg8-Atg3 interaction has been attracting increasing attention. However, there is no direct evidence that TgAtg8-TgAtg3 interaction occurs in the parasite. In this study, we firstly found TgAtg8 partially colocalized with TgAtg3 in GFP-TgAtg8 transgenic strains using IFA. Then, lysates from GFP-TgAtg8 tachyzoites were directly subject to large-scale tandem affinity purification with anti-GFP antibody. Western blot and tandem mass spectrometry (MS/MS) analysis determined the interaction between TgAtg8 and TgAtg3. Additionally, we performed real-time interaction analysis with a surface plasmon resonance biosensor using BIAcore system. As expected, the result demonstrated a concentration-dependent increases in resonance signals and indicated the TgAtg8 could bind directly TgAtg3 in vitro. Noteworthily, A KD of 34.9nM obtained from TgAtg8-TgAtg3 interaction indicate a high-affinity between Atg8-Atg3 in Toxoplasma. Furthermore, homology modeling and sequence alignment showed that TgAtg8 has greatest sequence and structural conservation. Within TgAtg3, this protein possesses the core E2 enzymatic activity structure and a truncated handle region which may contain AIM sequence. Taken together, our findings would help elucidate the formation mechanism of autophagosome in Toxoplasma and provide a possibility for looking into parasitic drug targets. PMID:26407821

  6. Serum Triglyceride Levels Independently Contribute to the Estimation of Visceral Fat Amount Among Nondiabetic Obese Adults

    PubMed Central

    Huang, Chiao-Yu; Huang, Hsien-Liang; Yang, Kuen-Cheh; Lee, Long-Teng; Yang, Wei-Shiung; Huang, Kuo-Chin; Tseng, Fen-Yu

    2015-01-01

    Abstract Determining the visceral fat amount is important in the risk stratification for the prevention of type 2 diabetes and obesity-related disorders. The area-based measurement of visceral fat area (VFA) via magnetic resonance imaging (MRI) is an accurate but expensive and time-consuming method for estimating visceral fat amount. The aim of our study was to identify a practical predictive parameter for visceral obesity in clinical settings. In this cross-sectional study, we recruited 51 nondiabetic obese (body mass index [BMI] ? 27?kg/m2) adults in Taiwan (21 men and 30 women, mean age 35.6?±?9.2 years, mean BMI 33.3?±?3.9?kg/m2). VFA was quantified by a single-slice MRI image. Anthropometric indices and biochemical parameters including fasting plasma glucose, serum level of alanine aminotransferase, and lipid profiles were measured. The associations between different variables and VFA were analyzed by linear regression analysis. Increases in BMI, waist circumference, serum levels of alanine aminotransferase and triglycerides (TGs), and decreased serum levels of high-density lipoprotein cholesterol were correlated with larger VFA. After adjustment for age, sex, and anthropometric indices, only serum TG level remained as an independent correlate of VFA. Besides demographic and anthropometric indices, adding TG level may explain a greater variance of VFA. In stepwise multivariate regression analysis, male sex, age, waist circumference, and serum TG level remained significant predictors of VFA. In a subgroup analysis among subjects with BMI ?30?kg/m2, similar results were demonstrated and serum TG level remained as significant independent correlates of VFA in all of the predictive models. Among nondiabetic obese adults, serum TG level was positively associated with VFA. The combination of sex, age, anthropometric indices, and serum TG level may be used to estimate VFA in clinical settings. PMID:26061332

  7. Association between Myocardial Triglyceride Content and Cardiac Function in Healthy Subjects and Endurance Athletes

    PubMed Central

    Sai, Eiryu; Shimada, Kazunori; Yokoyama, Takayuki; Sato, Shuji; Miyazaki, Tetsuro; Hiki, Makoto; Tamura, Yoshifumi; Aoki, Shigeki; Watada, Hirotaka; Kawamori, Ryuzo; Daida, Hiroyuki

    2013-01-01

    Ectopic fat accumulation plays important roles in various metabolic disorders and cardiovascular diseases. Recent studies reported that myocardial triglyceride (TG) content measured by proton magnetic resonance spectroscopy (1H-MRS) is associated with aging, diabetes mellitus, and cardiac dysfunction. However, myocardial TG content in athletes has not yet been investigated. We performed 1H-MRS and cardiac magnetic resonance imaging in 10 male endurance athletes and 15 healthy male controls. Serum markers and other clinical parameters including arterial stiffness were measured. Cardiopulmonary exercise testing was also performed. There were no significant differences in clinical characteristics including age, anthropometric parameters, blood test results, or arterial stiffness between the two groups. Peak oxygen uptakes, end–diastolic volume (EDV), end–systolic volume (ESV), left ventricular (LV) mass, peak ejection rates and peak filling rates were significantly higher in the athlete group than in the control group (all P<0.02). Myocardial TG content was significantly lower in the athlete group than in the control group (0.60±0.20 vs. 0.89±0.41%, P<0.05). Myocardial TG content was negatively correlated with EDV (r?=??0.47), ESV (r?=??0.64), LV mass (r?=??0.44), and epicardial fat volume (r?=?0.47) (all P<0.05). In conclusion, lower levels of myocardial TG content were observed in endurance athletes and were associated with morphological changes related to physiological LV alteration in athletes, suggesting that metabolic imaging for measurement of myocardial TG content by 1H-MRS may be a useful technique for noninvasively assessing the “athlete’s heart”. PMID:23613879

  8. Triglyceride-Based Screening Tests Fail to Recognize Cardiometabolic Disease in African Immigrant and African-American Men

    PubMed Central

    Yu, Sophia S.K.; Ramsey, Natalie L.M.; Castillo, Darleen C.; Ricks, Madia

    2013-01-01

    Abstract Background The prevalence of cardiometabolic disease in Africa now rivals that of Western nations. Therefore, screening programs that lead to effective prevention of cardiometabolic disease in Africans is imperative. Most screening tests for cardiometabolic disease use triglyceride (TG) levels as a criterion. However, the failure rate of TG-based screening tests in African Americans is high. In Africans, the efficacy of TG-based screening tests is unknown. Our goal was to determine the association between hypertriglyceridemia (TG ?150?mg/dL) and cardiometabolic disease in African and African-American men. Research Design and Methods This was a cross-sectional study of 155 men (80 African immigrants, 75 African Americans) [age, 35±9 years, mean±standard deviation (SD), body mass index (BMI) 28.5±5.2?kg/m2] who self-identified as healthy. Lipid profiles were performed. Glucose tolerance and insulin resistance was determined by oral glucose tolerance tests (OGTT) and the insulin sensitivity index (SI), respectively. Cardiometabolic disease was defined by four possible subtypes—prediabetes, diabetes, insulin resistance, or metabolic triad [hyperinsulinemia, hyperapolipoprotein B, small low-density lipoprotein (LDL) particles]. Results TG levels were higher in men with cardiometabolic disease than without (88±43 versus 61±26?mg/dL, P<0.01). However, <10% of men with cardiometabolic disease had TG ?150?mg/dL. Even within each cardiometabolic disease subtype, the prevalence of TG ?150?mg/dL was <10%. Furthermore, TG levels in the 5% of men identified by OGTT as diabetic were ?100?mg/dL (mean 71±24, range 45–100?mg/dL). Conclusions Hypertriglyceridemia is a poor marker of cardiometabolic disease in men of African descent. Therefore TG-based screening tests fail to identify both African immigrants and African-American men with cardiometabolic disease. As a consequence, the opportunity for early intervention and prevention is lost. PMID:23215943

  9. Modified triglyceride oil through reactions with phenyltriazolinedione

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The synthesis of a modified triglyceride oil was achieved through the reactions with 4-phenyl-1,2-4-triazoline-3,5-dione (PTAD). 1H NMR was used for structure determination and to monitor the reactions. Several reaction products were produced, and their relative yields depended on the stoichiometry ...

  10. Effect of prolonged exercise and pre-exercise dietary manipulation on hepatic triglycerides in trained men.

    PubMed

    Johnson, N A; van Overbeek, D; Chapman, P G; Thompson, M W; Sachinwalla, T; George, J

    2012-05-01

    The purpose of this study was to examine the effect of exercise and pre-exercise dietary manipulation on hepatic triglyceride concentration (HTGC). HTGC was measured by proton magnetic resonance spectroscopy ((1)H-MRS) before and after 90 min of moderate intensity cycling in six endurance trained males following 67 h of mixed diet (M) and an isocaloric minimal carbohydrate (2%) high fat (83%) diet (HF). Diets were administered by balanced crossover design. Whole-body fat oxidation, plasma-free fatty acid (FFA), glycerol and triglyceride concentrations were significantly elevated during exercise in HF versus M (P < 0.05 for all). There was no significant treatment × time interaction for HTGC (P = 0.368). However, there was a significant net increase in HTGC (time effect) during the combined 6 h exercise and post-exercise period (P = 0.037). In conclusion, we observed no measurable net change in the hepatic triglyceride pool across a period involving a prolonged exercise bout. Furthermore, manipulation of pre-exercise dietary intake did not influence the interaction between the hepatic triglyceride concentration and exercise in lean trained men. This supports the contention that hepatic triglycerides do not meaningfully contribute to the high rate of fat oxidation observed during acute exercise, or the enhancement of this with regular exercise training and/or pre-exercise dietary manipulation. PMID:21915700

  11. Pathway-Based Genome-Wide Association Studies for Plasma Triglycerides in Obese Females and Normal-Weight Controls

    PubMed Central

    Grant, Struan F. A.; Hakonarson, Hakon; Price, R. Arlen; Li, Wei-Dong

    2015-01-01

    Pathway-based analysis as an alternative approach can provide complementary information to single-marker genome-wide association studies (GWASs), which always ignore the epistasis and does not have sufficient power to find rare variants. In this study, using genotypes from a genome-wide association study (GWAS), pathway-based association studies were carried out by a modified Gene Set Enrichment Algorithm (GSEA) method (GenGen) for triglyceride in 1028 unrelated European-American extremely obese females (BMI?35kg/m2) and normal-weight controls (BMI<25kg/m2), and another pathway association analysis (ICSNPathway) was also used to verify the GenGen result in the same data. The GO0009110 pathway (vitamin anabolism) was among the strongest associations with triglyceride (empirical P<0.001); the result remained significant after FDR correction (P = 0.022). MMAB, an obesity-related locus, included in this pathway. The ABCG1 and BCL6 gene was found in several triglyceride-related pathways (empirical P<0.05), which were also replicated by ICSNPathway (empirical P<0.05, FDR<0.05). We also performed single-marked GWAS using PLINK for TG levels (log-transformed). Significant associations were found between ASTN2 gene SNPs and plasma triglyceride levels (rs7035794, P = 2.24×10?10). Our study suggested that vitamin anabolism pathway, BCL6 gene pathways and ASTN2 gene may contribute to the genetic variation of plasma triglyceride concentrations. PMID:26308950

  12. Elevating your elevator talk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An important and often overlooked item that every early career researcher needs to do is compose an elevator talk. The elevator talk, named because the talk should not last longer than an average elevator ride (30 to 60 seconds), is an effective method to present your research and yourself in a clea...

  13. Link between obesity and cancer: role of triglyceride/free fatty acid cycling.

    PubMed

    Gong, Y; Dou, L-J; Liang, J

    2014-10-01

    Obesity has long been suspected to be a risk factor for cancer. The relationship between body fat deposition and the pathogenesis of cancer has been the subject of many studies, however, no clear consensus has emerged linking these two biological processes. Recent epidemiological studies showed a strong association between cancer-related deaths and increased body-mass index. In fact, obesity has been identified as a cause for oesophageal, colon, uterine, kidney and post-menopausal breast cancers and also as a significant risk factor for the cancers of prostate, pancreas and non-Hodgkin lymphoma. Approximately 16-20% of cancer deaths in women and 14% of cancer deaths in men were found to be due to obesity. It is also recognized that there is a positive relationship between type-2 diabetes associated hyperinsulinemia and cancer incidence. Though the recent annual report in US finds that the incidence and mortality rates for many cancers have dropped in 2003 since 1975, this decline is mostly due to a substantial decrease in tobacco use among men. However, during the same period the rise in the prevalence of obesity might have contributed to the increased risk and incidence of prostate, liver, kidney, oesophageal and breast cancers. Whether the elevated cancer risk in obesity arises from similar modulation of parallel signaling/metabolic pathways during adipogenesis and oncogenesis has not been hitherto addressed. In this Review we would like to bring out the similarities between adipogenesis and oncogenesis and how this relationship at molecular level may be relevant for the development of effective therapeutics for obesity, diabetes and cancer. While adipogenesis is the process of formation of mature adipocytes or fat cells under normal physiological conditions, oncogenesis is a pathological process, which results in the uncontrolled growth of cells leading to cancer. Though, both these processes at surface seem to be totally different, we believe that there are important common denominators for these processes that need to be recognized. We will discuss the role of two such underlying factors - (1) malonyl-CoA, an important regulator of fatty acid metabolism and (2) triglyceride/free fatty acid (TG/FFA) cycling which is central to the generation of multiple signals for controlling various metabolic, physiological and signaling pathways in the cell. PMID:25339474

  14. Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice.

    PubMed

    Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S

    2013-07-01

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model. PMID:23857172

  15. Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL) Receptor Knockout Mice

    PubMed Central

    Forrest, Lolita M.; Lough, Christopher M.; Chung, Soonkyu; Boudyguina, Elena Y.; Gebre, Abraham K.; Smith, Thomas L.; Colvin, Perry L.; Parks, John S.

    2013-01-01

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model. PMID:23857172

  16. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to...lipid metabolism, or various endocrine disorders. (b)...

  17. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to...lipid metabolism, or various endocrine disorders. (b)...

  18. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to...lipid metabolism, or various endocrine disorders. (b)...

  19. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to...lipid metabolism, or various endocrine disorders. (b)...

  20. Analysis of the Triglycerides of Some Vegetable Oils.

    ERIC Educational Resources Information Center

    Farines, Marie; And Others

    1988-01-01

    Explains that triglycerides consist of a mixture of different compounds, depending on the total number of fatty acid constituents. Details the method and instrumentation necessary for students to analyze a vegetable oil for its triglyceride content. Describes sample results. (CW)

  1. Mapping the double bonds in triglycerides.

    PubMed

    Bydder, Mark; Girard, Olivier; Hamilton, Gavin

    2011-10-01

    This study presents and validates a theoretical model for estimating the number of double bonds in triglyceride molecules using magnetic resonance imaging. The model enables reliable estimation of the number of double bonds from a small number of time points, as are typically acquired with chemical shift imaging. Prior knowledge from the US Department of Agriculture (USDA) is used to constrain the properties of triglyceride. Validation in oil phantoms shows agreement between the measured number of double bonds and USDA reference values (correlation 0.95, significance P=.0003, slope 0.95±0.31, intercept 0.08±1.24). Feasibility in a human subject was demonstrated using a long breath-hold (43 s) scan. PMID:21868182

  2. FSP27 Promotes Lipid Droplet Clustering and Then Fusion to Regulate Triglyceride Accumulation

    PubMed Central

    Khan, Waheed; Tamori, Yoshikazu; Puri, Vishwajeet

    2011-01-01

    Fat Specific Protein 27 (FSP27), a lipid droplet (LD) associated protein in adipocytes, regulates triglyceride (TG) storage. In the present study we demonstrate that FSP27 plays a key role in LD morphology to accumulate TGs. We show here that FSP27 promotes clustering of the LDs which is followed by their fusion into fewer and enlarged droplets. To map the domains of FSP27 responsible for these events, we generated GFP-fusion constructs of deletion mutants of FSP27. Microscopic analysis revealed that amino acids 173–220 of FSP27 are necessary and sufficient for both the targeting of FSP27 to LDs and the initial clustering of the droplets. Amino acids 120–140 are essential but not sufficient for LD enlargement, whereas amino acids 120–210 are necessary and sufficient for both clustering and fusion of LDs to form enlarged droplets. In addition, we found that FSP27-mediated enlargement of LDs, but not their clustering, is associated with triglyceride accumulation. These results suggest a model in which FSP27 facilitates LD clustering and then promotes their fusion to form enlarged droplets in two discrete, sequential steps, and a subsequent triglyceride accumulation. PMID:22194867

  3. Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway.

    PubMed

    Sun, Li; Zhang, Song; Yu, Chengyuan; Pan, Zhenwei; Liu, Yang; Zhao, Jing; Wang, Xiaoyu; Yun, Fengxiang; Zhao, Hongwei; Yan, Sen; Yuan, Yue; Wang, Dingyu; Ding, Xue; Liu, Guangzhong; Li, Wenpeng; Zhao, Xuezhu; Liu, Zhaorui; Li, Yue

    2015-12-01

    Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (NaHS, H2S donor) markedly reduced serum TG levels of male C57BL/6 mice fed a high-fat diet (HFD), which was abolished by coadministration of chloroquine (CQ), an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased the LC3BII-to-LC3BI ratio and decreased the p62 protein level. Meanwhile, NaSH increased the phosphorylation of AMPK and thus reduced the phosphorylation of mTOR in a Western blot study. In cultured LO2 cells, high-fat treatment reduced the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed by the coadministration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked the autophagic enhancing effects of NaSH. The same qualitative effect was observed in AMPK?2(-/-) mice. These results for the first time demonstrated that H2S could reduce serum TG level and ameliorate NAFLD by activating liver autophagy via the AMPK-mTOR pathway. PMID:26442880

  4. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Triglyceride test system. 862.1705 Section 862....1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to... diseases involving lipid metabolism, or various endocrine disorders. (b) Classification. Class I...

  5. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Triglyceride test system. 862.1705 Section 862....1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to... diseases involving lipid metabolism, or various endocrine disorders. (b) Classification. Class I...

  6. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Triglyceride test system. 862.1705 Section 862....1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to... diseases involving lipid metabolism, or various endocrine disorders. (b) Classification. Class I...

  7. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Triglyceride test system. 862.1705 Section 862....1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to... diseases involving lipid metabolism, or various endocrine disorders. (b) Classification. Class I...

  8. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Triglyceride test system. 862.1705 Section 862....1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to... diseases involving lipid metabolism, or various endocrine disorders. (b) Classification. Class I...

  9. PROPERTY ANALYSIS OF TRIGLYCERIDE-BASED THERMOSETS. (R829576)

    EPA Science Inventory

    Triglycerides with acrylate functionality were prepared from various oils and
    model triglycerides. The triglyceride-acrylates were homopolymerized and copolymerized
    with styrene. The cross-link densities of the resulting polymer networks were
    predicted utilizing the F...

  10. Contributions of de novo synthesis of fatty acids to total VLDL-triglyceride secretion during prolonged hyperglycemia/hyperinsulinemia in normal man.

    PubMed Central

    Aarsland, A; Chinkes, D; Wolfe, R R

    1996-01-01

    Triglycerides (TG) are synthesized in the liver principally from two sources of fatty acids (FA): FA synthesized de novo in the liver and preformed FA. We have measured the rate of secretion of de novo synthesized FA and total secretion of FA bound to VLDL-TG in healthy men (n = 5) in the basal state, and after 1 (day 1) and 4 d (day 4) of a hypercaloric carbohydrate diet (approximately 2.5 times energy expenditure) that generated a moderate endogenous hyperinsulinemia (plasma insulin approximately 60 microU/ml). Prolonged carbohydrate hyperalimentation/hyperinsulinemia increased plasma VLDL-TG approximately 10-fold in part due to a 3.4-fold increase in total VLDL-TG secretion rate (basal state = 72+/-23, day 4 = 242+/-78 micromol TG/kg/d). Although the secretion of de novo synthesized FA increased throughout the study (basal state = 1.1+/-0.4, day 1 = 15.9+/-7.9, day 4 = 50.0+/-18.8 micromol TG/ kg/d), the 2.7-fold increase in secretion rate of preformed FA (basal state = 70+/-23, day 4 = 191+/-57 micromol TG/kg/d) quantitatively contributed the most to total VLDL-TG secretion rate. Decreased catabolism of VLDL-TG also contributed to the hypertriglyceridemia as reflected by an approximately fourfold decrease in both fractional turnover rate (basal state = 9.2+/-3.8, day 1 = 2.1+/-0.2, day 4 = 2.1+/-0.3 pools/d) and rate of clearance (basal state = 0.35+/-0.08, day 1 = 0.11+/-0.01, day 4 = 0.09+/-0.01 liter/kg/d) of VLDL-TG. Thus, the primary difference between 1 and 4 d of hyperinsulinemia in conjunction with carbohydrate hyperalimentation is the increase in hepatic secretion of preformed FA into VLDL-TG. PMID:8903319

  11. Quantitative analysis of metabolism of hepatic triglyceride in ethanol-treated rats.

    PubMed Central

    Abrams, M A; Cooper, C

    1976-01-01

    An acute intraperitoneal injection of ethanol (0.7 or 2.1g/kg body wt.) causes the reversible, dose-dependent accumulation of hepatic triglyceride in rats. By using a pulse of [14C]palmitate injected into a tail vein, it was found that ethanol (2.1g/kg)had no effect on the flux of unesterified fatty acid of serum (4.3mumol/min per 100g body wt.). However, either dose increased the fraction of the total flux going to liver from 0.16 to0.27 as rapidly as could be measured (30s), and it remained elevated until all ethanol had been cleared from the blood. The fraction of the total radioactivity in lipids of liver that was in triglyceride increased linearly for 1 h from 30 to 50% and there was a simultaneous decrease in phospholipid from 60 to 40%. The rate of synthesis of hepatic triglyceride derived directly from unesterified fatty acid of serum was calculated by using the flux rate of unesterified fatty acid in serum, the fractional hepatic uptake of this flux, and the percentage of liver fatty acid esterified to triglyceride. This contribution is related to the total synthetic rate of hepatic triglyceride (rate of accumulation+rate of release) to determine quantitatively how much of the developing fatty liver is attributable to increased uptake of unesterfied fatty acid of serum. At the higher dose of ethanol, about half of the accumulating triglyceride is derived from this source, whereas with the lower dose of ethanol it can account for all of the build-up. PMID:942401

  12. The Association of Human Apolipoprotein C-III Sialylation Proteoforms with Plasma Triglycerides

    PubMed Central

    Yassine, Hussein N.; Trenchevska, Olgica; Ramrakhiani, Ambika; Parekh, Aarushi; Koska, Juraj; Walker, Ryan W.; Billheimer, Dean; Reaven, Peter D.; Yen, Frances T.; Nelson, Randall W.; Goran, Michael I.; Nedelkov, Dobrin

    2015-01-01

    Introduction Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III0a without glycosylation and apoC-III0b with glycosylation), monosialylated (apoC-III1) or disialylated (apoC-III2) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations. Methods In 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay. Results Compared with the healthy weight subgroup (n = 16), the ratios of apoC-III0a, apoC-III0b, and apoC-III1 to apoC-III2 were significantly greater in overweight (n = 33) and obese participants (n = 155). These ratios were positively correlated with BMI z-scores and negatively correlated with measures of insulin sensitivity (Si). The relationship of apoC-III1 / apoC-III2 with Si persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III0a / apoC-III2 (r = 0.47, p<0.001), apoC-III0b / apoC-III2 (r = 0.41, p<0.001), apoC-III1 / apoC-III2 (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III0a (r = 0.57, p<0.001), apoC-III0b (r = 0.56. p<0.001) and apoC-III1 (r = 0.67, p<0.001), but not apoC-III2 (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III2 compared with the other proteoforms. Conclusion We conclude that apoC-III0a, apoC-III0b, and apoC-III1, but not apoC- III2 appear to be under metabolic control and associate with fasting plasma TG. Measurement of apoC-III proteoforms can offer insights into the biology of TG metabolism in obesity. PMID:26633899

  13. Short-term overexpression of CD36 in the liver augments hepatic lipid storage and VLDL-triglyceride secretion: Implications for diet-induced obesity and type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Type 2 diabetes (T2D) is associated with a high risk of cardiovascular disease. The management of dyslipidemia in T2D is one element in the multifactorial approach to prevent coronary heart disease. Since the levels of plasma fatty acids (FA), triglycerides (TG). and lipoproteins are primarily contr...

  14. Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans.

    TOXLINE Toxicology Bibliographic Information

    Graham MJ; Lee RG; Bell TA 3rd; Fu W; Mullick AE; Alexander VJ; Singleton W; Viney N; Geary R; Su J; Baker BF; Burkey J; Crooke ST; Crooke RM

    2013-05-24

    RATIONALE: Elevated plasma triglyceride levels have been recognized as a risk factor for the development of coronary heart disease. Apolipoprotein C-III (apoC-III) represents both an independent risk factor and a key regulatory factor of plasma triglyceride concentrations. Furthermore, elevated apoC-III levels have been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no selective apoC-III therapeutic agent has been evaluated in the clinic.OBJECTIVE: To test the hypothesis that selective inhibition of apoC-III with antisense drugs in preclinical models and in healthy volunteers would reduce plasma apoC-III and triglyceride levels.METHODS AND RESULTS: Rodent- and human-specific second-generation antisense oligonucleotides were identified and evaluated in preclinical models, including rats, mice, human apoC-III transgenic mice, and nonhuman primates. We demonstrated the selective reduction of both apoC-III and triglyceride in all preclinical pharmacological evaluations. We also showed that inhibition of apoC-III was well tolerated and not associated with increased liver triglyceride deposition or hepatotoxicity. A double-blind, placebo-controlled, phase I clinical study was performed in healthy subjects. Administration of the human apoC-III antisense drug resulted in dose-dependent reductions in plasma apoC-III, concomitant lowering of triglyceride levels, and produced no clinically meaningful signals in the safety evaluations.CONCLUSIONS: Antisense inhibition of apoC-III in preclinical models and in a phase I clinical trial with healthy subjects produced potent, selective reductions in plasma apoC-III and triglyceride, 2 known risk factors for cardiovascular disease. This compelling pharmacological profile supports further clinical investigations in hypertriglyceridemic subjects.

  15. Genomic Determinants of Triglyceride and Cholesterol Distribution into Lipoprotein Fractions in the Rat

    PubMed Central

    Hodúlová, Miloslava; Šedová, Lucie; K?enová, Drahomíra; Liška, František; Krupková, Michaela; Kazdová, Ludmila; Tremblay, Johanne; Hamet, Pavel; K?en, Vladimír; Šeda, Ond?ej

    2014-01-01

    The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains) segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n?=?8–13/strain) and two progenitor strains SHR-Lx (n?=?13) and BXH2/Cub (n?=?18) were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG) and cholesterol (C) concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl). We have identified 14 loci (encompassing 1 to 65 genes) on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b). Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant inbred panel of rat model strains. PMID:25296178

  16. The triglyceride lipases of the pancreas.

    PubMed

    Lowe, Mark E

    2002-12-01

    Pancreatic triglyceride lipase (PTL) and its protein cofactor, colipase, are required for efficient dietary triglyceride digestion. In addition to PTL, pancreatic acinar cells synthesize two pancreatic lipase related proteins (PLRP1 and PLRP2), which have a high degree of sequence and structural homology with PTL. PLRP1 has no known activity. PTL and PLRP2 differ in substrate specificity, behavior in bile salts and dependence on colipase. Each protein has a globular amino-terminal (N-terminal) domain, which contains the catalytic site for PTL and PLRP2, and a beta-sandwich carboxyl-terminal (C-terminal) domain, which includes the predominant colipase-binding site for PTL. Inactive and active conformations of PTL have been described. They differ in the position of a surface loop, the lid domain, and of the beta5-loop. In the inactive conformation, the lid covers the active site and, upon activation by bile salt micelles and colipase or by lipid-water interfaces, the lid moves dramatically to open and configure the active site. After the lid movement, PTL and colipase create a large hydrophobic plateau that can interact with the lipid-water interface. A hydrophobic surface loop in the C-terminal domain, the beta5' loop, may also contribute to the interfacial-binding domain of the PTL-colipase complex. PMID:12454260

  17. Noninvasive Measurement of Plasma Triglycerides and Free Fatty Acids from Exhaled Breath

    PubMed Central

    Minh, Timothy Do Chau; Oliver, Stacy R; Flores, Rebecca L; Ngo, Jerry; Meinardi, Simone; Carlson, Matthew K; Midyett, Jason; Rowland, F Sherwood; Blake, Donald R; Galassetti, Pietro Renato

    2012-01-01

    Background Although altered metabolism has long been known to affect human breath, generating clinically usable metabolic tests from exhaled compounds has proven challenging. If developed, a breath-based lipid test would greatly simplify management of diabetes and serious pathological conditions (e.g., obesity, familial hyperlipidemia, and coronary artery disease), in which systemic lipid levels are a critical risk factor for onset and development of future cardiovascular events. Methods We, therefore, induced controlled fluctuations of plasma lipids (insulin-induced lipid suppression or intravenous infusion of Intralipid) during 4-h in vivo experiments on 23 healthy volunteers (12 males/11 females, 28.0 ± 0.3 years) to find correlations between exhaled volatile organic compounds and plasma lipids. In each subject, plasma triglycerides (TG) and free fatty acids (FFA) concentrations were both directly measured and calculated via individualized prediction equations based on the multiple linear regression analysis of a cluster of 4 gases. In the lipid infusion protocol, we also generated common prediction equations using a maximum of 10 gases. Results This analysis yielded strong correlations between measured and predicted values during both lipid suppression (r = 0.97 for TG; r = 0.90 for FFA) and lipid infusion (r = 0.97 for TG; r = 0.94 for FFA) studies. In our most accurate common prediction model, measured and predicted TG and FFA values also displayed very strong statistical agreement (r = 0.86 and r = 0.81, respectively). Conclusions Our results demonstrate the feasibility of measuring plasma lipids through breath analysis. Optimization of this technology may ultimately lead to the development of portable breath analyzers for plasma lipids, replacing blood-based bioassays. PMID:22401327

  18. The Impact of CDH13 Polymorphism and Statin Administration on TG/HDL Ratio in Cardiovascular Patients

    PubMed Central

    Choi, Jung Ran; Kim Yoon, Sungjoo; Park, Jong Keun; Sorn, Sungbin Richard; Park, Mi-Young

    2015-01-01

    Purpose Adiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs). Materials and Methods We investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment. Results Genetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cholesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-? (TNF-?), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels. Conclusion Plasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD. PMID:26446643

  19. F3MB(PANDER) Decreases Mice Hepatic Triglyceride and Is Associated with Decreased DGAT1 Expression

    PubMed Central

    Mo, Xiaoqing; Yang, Chijiao; Wang, Xuelan; Burkhardt, Brant R.; Li, Yangbin; Xia, Haipeng; Cao, Xiaopei

    2015-01-01

    Objective Pancreatic-derived factor (PANDER, also named as FAM3B) is secreted by pancreatic ? and ? cells. Increasing evidence suggests that it may serve a hormonal function related to glycemic and lipid metabolism. In this study, we investigated the effects of PANDER overexpression on hepatic and adipose triglyceride metabolism in high-fat diet-fed male C57BL/6 mice. Methods PANDER overexpression was achieved by tail-vein injection of recombinant Ad-PANDER and Ad-GFP injected mice served as a control. The TG metabolism in both groups were compared. Results Adenoviral-mediated overexpression of PANDER did not affect body weight, food consumption, or liver enzymes. The triglyceride (TG) content of both liver and adipose tissue was significantly decreased in Ad-PANDER mice (liver: 6.16±1.89 mg/g vs. control 14.95±2.27 mg/g, P<0.05; adipose: 39.31±1.99 mg/100mg vs. 47.22±2.21 mg/100mg, P<0.05). The free fatty acid (FFA) content of adipose tissue in Ad-PANDER mice was also decreased (1.38±0.18 mg/g vs. 2.77±0.31 mg/g, P<0.01). The investigation of key enzymes of triglyceride hydrolysis and FFA oxidation in liver and adipose tissue showed that p-HSL/HSL was significantly increased and that DGAT1 gene and protein expression were significantly reduced in the liver of PANDER-overexpressing mice. PKA phosphorylation was also significantly increased in the livers of Ad-PANDER mice. No differences in ATGL, CPT1, ACOX1, or DGAT2 expression were observed. Conclusion Overexpression of PANDER is associated with observable decreases in TG, increases in PKA phosphorylation, and decreased DGAT1 expression, suggesting a possible interrelationship. The mechanisms by which this occurs remain to be elucidated. PMID:25679806

  20. Bioconversion of Xylan to Triglycerides by Oil-Rich Yeasts

    PubMed Central

    Fall, Ray; Phelps, Patricia; Spindler, Diane

    1984-01-01

    A series of lipid-accumulating yeasts was examined for their potential to saccharify xylan and accumulate triglyceride. Of the genera tested, including Candida, Cryptococcus, Lipomyces, Rhodosporidium, Rhodotorula, and Trichosporon, only Cryptococcus and Trichosporon isolates saccharified xylan. All of the strains could assimilate xylose and accumuate triglyceride under nitrogen-limiting conditions. Strains of Cryptococcus albidus were found to be especially useful for a one-step saccharification of xylan coupled to triglyceride synthesis. Cryptococcus terricolus, a strain constitutive for lipid accumulation, lacked extracellular xylanase, but did assimilate xylose and xylobiose and was able to continuously convert xylan to triglyceride if the culture medium was supplemented with xylanase. PMID:16346541

  1. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification....

  2. Relationship between insulin sensitivity and the triglyceride-HDL-C ratio in overweight and obese postmenopausal women: a MONET study.

    PubMed

    Karelis, Antony D; Pasternyk, Stephanie M; Messier, Lyne; St-Pierre, David H; Lavoie, Jean-Marc; Garrel, Dominique; Rabasa-Lhoret, Rémi

    2007-12-01

    The objective of this cross-sectional study was to examine the relationship between the triglyceride-HDL-cholesterol ratio (TG:HDL-C) and insulin sensitivity in overweight and obese sedentary postmenopausal women. The study population consisted of 131 non-diabetic overweight and obese sedentary postmenopausal women (age; 57.7+/-5.0 y; body mass index (BMI), 32.2+/-4.3 kg/m2). Subjects were characterized by dividing the entire cohort into tertiles based on the TG:HDL-C (T1<0.86 vs. T2=0.86 to 1.35 vs. T3>1.35, respectively). We measured (i) insulin sensitivity (using the hyperinsulinenic-euglycemic clamp and homeostasis model assessment (HOMA)), (ii) body composition (using dual-energy X-ray absorptiometry), (iii) visceral fat (using computed tomography), (iv) plasma lipids, C-reactive protein, 2 h glucose concentration during an oral glucose tolerance test (2 h glucose), as well as fasting glucose and insulin, (v) peak oxygen consumption, and (vi) lower-body muscle strength (using weight training equipment). Significant correlations were observed between the TG:HDL-C and the hyperinsulinemic-euglycemic clamp (r=-0.45; p<0.0001), as well as with HOMA (r=0.42; p<0.0001). Moreover, the TG:HDL-C significantly correlated with lean body mass, visceral fat, 2 h glucose, C-reactive protein, and muscle strength. Stepwise regression analysis showed that the TG:HDL-C explained 16.4% of the variation in glucose disposal in our cohort, which accounted for the greatest source of unique variance. Other independent predictors of glucose disposal were 2 h glucose (10.1%), C-reactive protein (CRP; 7.6%), and peak oxygen consumption (5.8%), collectively (including the TG:HDL-C) explaining 39.9% of the unique variance. In addition, the TG:HDL-C was the second predictor for HOMA, accounting for 11.7% of the variation. High levels of insulin sensitivity were associated with low levels of the TG:HDL-C. In addition, the TG:HDL-C was a predictor for glucose disposal rates and HOMA values in our cohort of overweight and obese postmenopausal women. PMID:18059582

  3. N-3 Fatty Acid Rich Triglyceride Emulsions Are Neuroprotective after Cerebral Hypoxic-Ischemic Injury in Neonatal Mice

    PubMed Central

    Vannucci, Susan J.; Mastropietro, Christopher; Bazan, Nicolas G.; Ten, Vadim S.; Deckelbaum, Richard J.

    2013-01-01

    We questioned if acute administration of n-3 fatty acids (FA) carried in n-3 rich triglyceride (TG) emulsions provides neuroprotection in neonatal mice subjected to hypoxic-ischemic (H/I) brain injury. We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/I. H/I insult was induced in C57BL/6J 10-day-old mice by right carotid artery ligation followed by exposure to 8% O2 for 15 minutes at 37°C. Intraperitoneal injection with n-3-rich TG emulsions, n-6 rich TG emulsions or saline for control was administered at different time points before and/or after H/I. In separate experiments, dose responses were determined with TG containing only docosahexaenoic acid (Tri-DHA) or eicosapentaenoic acid (Tri-EPA) with a range of 0.1–0.375 g n-3 TG/kg, administered immediately after H/I insult. Infarct volume and cerebral blood flow (CBF) were measured. Treatment with n-3 TG emulsions both before- and after- H/I significantly reduced total infarct volume by a mean of 43% when administered 90 min prior to H/I and by 47% when administered immediately after H/I. In post-H/I experiments Tri-DHA, but not Tri-EPA exhibited neuroprotective effects with both low and high doses (p<0.05). Moreover, delayed post-H/I treatment with Tri-DHA significantly decreased total infarct volume by a mean of 51% when administered at 0 hr, by 46% at 1 hr, and by 51% at 2 hr after H/I insult. No protective effect occurred with Tri-DHA injection at 4 hr after H/I. There were no n-3 TG related differences in CBF. A significant reduction in brain tissue death was maintained after Tri-DHA injection at 8 wk after the initial brain injury. Thus, n-3 TG, specifically containing DHA, is protective against H/I induced brain infarction when administered up to 2 hr after H/I injury. Acute administration of TG-rich DHA may prove effective for treatment of stroke in humans. PMID:23437099

  4. Triglyceride sensing in the reward circuitry: A new insight in feeding behaviour regulation.

    PubMed

    Cansell, Celine; Luquet, Serge

    2016-01-01

    In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance and consequently obesity. Obesity often involves a behavioural component in which, similar to drugs abuse, compulsive consumption of palatable food rich in lipids and sugar drives energy intake far beyond metabolic demands. The hypothalamus is one of the primary integration sites of circulating energy-related signals like leptin or ghrelin and is therefore considered as one of the main central regulators of energy balance. However, food intake is also modulated by sensory inputs, such as tastes and odours, as well as by affective or emotional states. The mesolimbic pathway is well established as a key actor of the rewarding aspect of feeding. Particularly, the hedonic and motivational aspects of food are closely tied to the release of the neurotransmitter dopamine (DA) in striatal structure such as the Nucleus Accumbens (Nacc). In both rodent and humans several studies shows an attenuated activity of dopaminergic signal associated with obesity and there is evidence that consumption of palatable food per se leads to DA signalling alterations. Furthermore impaired cognition in obese mice is improved by selectively lowering triglycerides (TG) and intracerebroventricular administration of TG induces by itself acquisition impairment in several cognitive paradigms in normal body weight mice. Together, these observations raise the possibility that nutritional lipids, particularly TG, directly affect cognitive and reward processes by modulating the mesolimbic pathway and might contribute to the downward spiral of compulsive consumption of palatable food and obesity. This review is an attempt to capture recent evolution in the field that might point toward a direct action of nutritional lipid in the reward circuitry. PMID:26159487

  5. Association between colon diverticula and hemoglobin, triglyceride and uric acid levels

    PubMed Central

    TOMIZAWA, MINORU; SHINOZAKI, FUMINOBU; HASEGAWA, RUMIKO; SHIRAI, YOSHINORI; MOTOYOSHI, YASUFUMI; SUGIYAMA, TAKAO; YAMAMOTO, SHIGENORI; ISHIGE, NAOKI

    2015-01-01

    Colon diverticula cause bleeding and acute diverticulitis. The present study analyzed laboratory test variables, aiming to predict the presence of diverticula. Patient records from between April 2011 and March 2014 were analyzed retrospectively (1,520 patients) and a one-way analysis of variance was performed to analyze the association between the presence of diverticula and each variable. A ?2 test was then used to assess the correlation between the prevalence of diverticula and the percentage of patients with uric acid (UA) levels ?5.1 mg/dl. A receiver operating characteristic (ROC) analysis was performed to determine the threshold values required to predict the presence of diverticula. Hemoglobin (Hb) levels were lower in patients with diverticula than in those without diverticula (P=0.0027), and compared with patients without diverticula, UA and triglyceride (TG) levels were higher in patients with diverticula (P=0.0066 and P=0.0136, respectively). The patients were divided into two groups, as follows: Patients with UA levels ?5.1 mg/dl (the median value) and those with UA levels <5.1 mg/dl. The prevalence of diverticula was significantly higher in patients with UA levels ?5.1 mg/dl than in those with UA levels <5.1 mg/dl (P=0.0004). ROC analysis demonstrated that the threshold values of Hb, TG and UA were 12,400, 146 and 5.1 mg/dl, respectively. The sensitivity of the Hb and UA levels at the threshold values was 76.5 and 71.0%, respectively. The prevalence of diverticula was associated with low Hb levels, and high TG and UA levels. PMID:26668609

  6. Targeted delivery of a model immunomodulator to the lymphatic system: comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies.

    PubMed

    Han, Sifei; Quach, Tim; Hu, Luojuan; Wahab, Anisa; Charman, William N; Stella, Valentino J; Trevaskis, Natalie L; Simpson, Jamie S; Porter, Christopher J H

    2014-03-10

    A lipophilic prodrug approach has been used to promote the delivery of a model immunomodulator, mycophenolic acid (MPA), to the lymphatic system after oral administration. Lymphatic transport was employed to facilitate enhanced drug uptake into lymphocytes, as recent studies demonstrate that targeted drug delivery to lymph resident lymphocytes may enhance immunomodulatory effects. Two classes of lymph-directing prodrugs were synthesised. Alkyl chain derivatives (octyl mycophenolate, MPA-C8E; octadecyl mycophenolate, MPA-C18E; and octadecyl mycophenolamide, MPA-C18AM), to promote passive partitioning into lipids in lymphatic transport pathways, and a triglyceride mimetic prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) to facilitate metabolic integration into triglyceride deacylation-reacylation pathways. Lymphatic transport, lymphocyte uptake and plasma pharmacokinetics were assessed in mesenteric lymph and carotid artery cannulated rats following intraduodenal infusion of lipid-based formulations containing MPA or MPA prodrugs. Patterns of prodrug hydrolysis in rat digestive fluid, and cellular re-esterification in vivo, were evaluated to examine the mechanisms responsible for lymphatic transport. Poor enzyme stability and low absorption appeared to limit lymphatic transport of the alkyl derivatives, although two of the three alkyl chain prodrugs - MPA-C18AM (6-fold) and MPA-C18E (13-fold) still increased lymphatic drug transport when compared to MPA. In contrast, 2-MPA-TG markedly increased lymphatic drug transport (80-fold) and drug concentrations in lymphocytes (103-fold), and this was achieved via biochemical incorporation into triglyceride deacylation-reacylation pathways. The prodrug was hydrolysed rapidly to 2-mycophenoloyl glycerol (2-MPA-MG) in the presence of rat digestive fluid, and 2-MPA-MG was subsequently re-esterified in the enterocyte with oleic acid (most likely originating from the co-administered formulation) prior to accessing the lymphatics and lymphocytes. Importantly, after administration of 2-MPA-TG, the concentrations of free MPA in the mesenteric lymph nodes were significantly enhanced (up to 28 fold) when compared to animals administered equimolar quantities of MPA, suggesting the efficient conversion of the esterified prodrug back to the pharmacologically active parent drug. The data suggest that triglyceride mimetic prodrugs have potential as a means of enhancing immunotherapy via drug targeting to lymphocytes and lymph nodes. PMID:24398334

  7. Identification of Type 2 Diabetes Risk Factors Using Phenotypes Consisting of Anthropometry and Triglycerides based on Machine Learning.

    PubMed

    Lee, Bum Ju; Kim, Jong Yeol

    2016-01-01

    The hypertriglyceridemic waist (HW) phenotype is strongly associated with type 2 diabetes; however, to date, no study has assessed the predictive power of phenotypes based on individual anthropometric measurements and triglyceride (TG) levels. The aims of the present study were to assess the association between the HW phenotype and type 2 diabetes in Korean adults and to evaluate the predictive power of various phenotypes consisting of combinations of individual anthropometric measurements and TG levels. Between November 2006 and August 2013, 11 937 subjects participated in this retrospective cross-sectional study. We measured fasting plasma glucose and TG levels and performed anthropometric measurements. We employed binary logistic regression (LR) to examine statistically significant differences between normal subjects and those with type 2 diabetes using HW and individual anthropometric measurements. For more reliable prediction results, two machine learning algorithms, naive Bayes (NB) and LR, were used to evaluate the predictive power of various phenotypes. All prediction experiments were performed using a tenfold cross validation method. Among all of the variables, the presence of HW was most strongly associated with type 2 diabetes ( , adjusted odds ratio (OR) = 2.07 [95% CI, 1.72-2.49] in men; , adjusted OR = 2.09 [1.79-2.45] in women). When comparing waist circumference (WC) and TG levels as components of the HW phenotype, the association between WC and type 2 diabetes was greater than the association between TG and type 2 diabetes. The phenotypes tended to have higher predictive power in women than in men. Among the phenotypes, the best predictors of type 2 diabetes were waist-to-hip ratio + TG in men (AUC by NB = 0.653, AUC by LR = 0.661) and rib-to-hip ratio + TG in women (AUC by NB = 0.73, AUC by LR = 0.735). Although the presence of HW demonstrated the strongest association with type 2 diabetes, the predictive power of the combined measurements of the actual WC and TG values may not be the best manner of predicting type 2 diabetes. Our findings may provide clinical information concerning the development of clinical decision support systems for the initial screening of type 2 diabetes. PMID:25675467

  8. Resveratrol regulates lipolysis via adipose triglyceride lipase.

    PubMed

    Lasa, Arrate; Schweiger, Martina; Kotzbeck, Petra; Churruca, Itziar; Simón, Edurne; Zechner, Rudolf; Portillo, María del Puy

    2012-04-01

    Resveratrol has been reported to increase adrenaline-induced lipolysis in 3T3-L1 adipocytes. The general aim of the present work was to gain more insight concerning the effects of trans-resveratrol on lipid mobilization. The specific purpose was to assess the involvement of the two main lipases: adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in the activation of lipolysis induced by this molecule. For lipolysis experiments, 3T3-L1 and human SGBS adipocytes as well as adipose tissue from wild-type, ATGL knockout and HSL knockout mice were used. Moreover, gene and protein expressions of these lipases were analyzed. Resveratrol-induced free fatty acids release but not glycerol release in 3T3-L1 under basal and isoproterenol-stimulating conditions and under isoproterenol-stimulating conditions in SGBS adipocytes. When HSL was blocked by compound 76-0079, free fatty acid release was still induced by resveratrol. By contrast, in the presence of the compound C, an inhibitor of adenosine monophosphate-activated protein kinase, resveratrol effect was totally blunted. Resveratrol increased ATGL gene and protein expressions, an effect that was not observed for HSL. Resveratrol increased fatty acids release in epididymal adipose tissue from wild-type and HSL knockout mice but not in that adipose tissue from ATGL knockout mice. Taking as a whole, the present results provide novel evidence that resveratrol regulates lipolytic activity in human and murine adipocytes, as well as in white adipose tissue from mice, acting mainly on ATGL at transcriptional and posttranscriptional levels. Enzyme activation seems to be induced via adenosine monophosphate-activated protein kinase. PMID:21543206

  9. Dynamical behavior in f (T, TG) cosmology

    NASA Astrophysics Data System (ADS)

    Kofinas, Georgios; Leon, Genly; Saridakis, Emmanuel N.

    2014-09-01

    The f(T,{{T}_{G}}) class of gravitational modification, based on the quadratic torsion scalar T as well as on the new quartic torsion scalar TG, which is the teleparallel equivalent of the Gauss-Bonnet term, is a novel theory, different from both f (T) and f(R,G) ones. We perform a detailed dynamical analysis of a spatially flat universe governed by the simplest non-trivial model of f(T,{{T}_{G}}) gravity which does not introduce a new mass scale. We find that the universe can result in dark-energy dominated, quintessence-like, cosmological-constant-like, or phantom-like solutions, according to the parameter choices. Additionally, it may result in a dark energy-dark matter scaling solution; thus it can alleviate the coincidence problem. Finally, the analysis ‘at infinity’ reveals that the universe may exhibit future, past, or intermediate singularities, depending on the parameters.

  10. Top Ten Things to Know: Triglycerides and Cardiovascular Disease

    MedlinePLUS

    ... or use of unsaturated fats, especially those containing marine omega-3 fatty acids, lower triglyceride levels. 7. ... and Metabolism; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Nursing; and Council on the ...

  11. The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

    SciTech Connect

    Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H.; Giometti, C.S.; Mishler, K.; Slavin, B.G.

    1997-07-01

    Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

  12. ?-Tocotrienol attenuates triglyceride through effect on lipogenic gene expressions in mouse hepatocellular carcinoma Hepa 1-6.

    PubMed

    Burdeos, Gregor Carpentero; Nakagawa, Kiyotaka; Watanabe, Akio; Kimura, Fumiko; Miyazawa, Teruo

    2013-01-01

    Vitamin E is the generic name for tocopherol (Toc) and tocotrienol (T3), which have saturated and unsaturated side chains, respectively. Such differences allow T3 to be different from Toc in terms of their functions. T3 has been known to attenuate cholesterol (Cho) level by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR). Recent reports also showed the efficacy of T3 in improving triglyceride (TG) profiles in both in vivo and in vitro studies. However the mechanism involved in this biological activity is still unclear and needs to be further investigated. In the present study, we elucidated the effect of ?-T3 on lipid levels and lipogenic gene expressions in mouse hepatocellular carcinoma Hepa 1-6. ?-T3 showed attenuation of TG through effect on fatty acid synthase, sterol regulatory element-binding transcription factor 1, stearoyl CoA desaturase 1, and carnitine palmitoyl transferase 1A gene expression in Hepa 1-6. In contrast, the Cho level remained unchanged. These results expanded our previous finding of lipid-lowering effects of T3, especially for TG. Therefore, T3 is a potential lipid-lowering compound candidate with realistic prospects for its use as a therapy for lipid-related diseases in humans. PMID:23727646

  13. The hepatitis C virus core protein inhibits adipose triglyceride lipase (ATGL)-mediated lipid mobilization and enhances the ATGL interaction with comparative gene identification 58 (CGI-58) and lipid droplets.

    PubMed

    Camus, Gregory; Schweiger, Martina; Herker, Eva; Harris, Charles; Kondratowicz, Andrew S; Tsou, Chia-Lin; Farese, Robert V; Herath, Kithsiri; Previs, Stephen F; Roddy, Thomas P; Pinto, Shirly; Zechner, Rudolf; Ott, Melanie

    2014-12-26

    Liver steatosis is a common health problem associated with hepatitis C virus (HCV) and an important risk factor for the development of liver fibrosis and cancer. Steatosis is caused by triglycerides (TG) accumulating in lipid droplets (LDs), cellular organelles composed of neutral lipids surrounded by a monolayer of phospholipids. The HCV nucleocapsid core localizes to the surface of LDs and induces steatosis in cultured cells and mouse livers by decreasing intracellular TG degradation (lipolysis). Here we report that core at the surface of LDs interferes with the activity of adipose triglyceride lipase (ATGL), the key lipolytic enzyme in the first step of TG breakdown. Expressing core in livers or mouse embryonic fibroblasts of ATGL(-/-) mice no longer decreases TG degradation as observed in LDs from wild-type mice, supporting the model that core reduces lipolysis by engaging ATGL. Core must localize at LDs to inhibit lipolysis, as ex vivo TG hydrolysis is impaired in purified LDs coated with core but not when free core is added to LDs. Coimmunoprecipitation experiments revealed that core does not directly interact with the ATGL complex but, unexpectedly, increased the interaction between ATGL and its activator CGI-58 as well as the recruitment of both proteins to LDs. These data link the anti-lipolytic activity of the HCV core protein with altered ATGL binding to CGI-58 and the enhanced association of both proteins with LDs. PMID:25381252

  14. Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: Influence of insulin resistance on plasma triglyceride responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Context: Compared with glucose-sweetened beverages, consumption of fructose-sweetened beverages with meals elevates postprandial plasma triglycerides and lowers 24-h insulin and leptin profiles in normal weight women. The effects of fructose, compared with glucose, ingestion on metabolic profiles in...

  15. Uncoupling of endothelial nitric oxide synthase in cerebral vasculature of Tg2576 mice.

    PubMed

    Santhanam, Anantha Vijay R; d'Uscio, Livius V; He, Tongrong; Das, Pritam; Younkin, Steven G; Katusic, Zvonimir S

    2015-09-01

    In this study, we tested the hypothesis that reduced bioavailability of tetrahydrobiopterin (BH4) is a major mechanism responsible for pathogenesis of endothelial dysfunction in cerebral microvessels of transgenic mice expressing the Swedish double mutation of human amyloid precursor protein (APP) (Tg2576 mice). Endothelial nitric oxide synthase (eNOS) protein expression was significantly increased in cerebral vasculature of Tg2576 mice. In contrast, bioavailability of BH4 was significantly reduced (p < 0.05). Moreover, superoxide anion production was increased in cerebral microvessels of Tg2576 mice (p < 0.05). Incubation with NOS inhibitor, N?-nitro-L-arginine methyl ester, decreased superoxide anion indicating that uncoupled eNOS is most likely the source of superoxide anion. Increasing BH4 bioavailability either exogenously by BH4 supplementation or endogenously by treatment with the selective peroxisome proliferator-activated receptor--delta activator GW501516 (2 mg/kg/day, 14 days) attenuated eNOS uncoupling and decreased superoxide anion production in cerebral microvessels of Tg2576 mice (p < 0.05). Treatment with GW501516 restored the biological activity of endothelial nitric oxide in cerebral microvessels of Tg2576 mice, as indicated by the increased nitrite/nitrate content and 3,5-cyclic guanosine monophosphate levels (p < 0.05). Our studies indicate that sub-optimal BH4 bioavailability in cerebral vasculature is an important contributor to oxidant stress and endothelial dysfunction in Tg2576 mouse model of Alzheimer's disease. Existing evidence suggests that A? peptides-induced up-regulation of expression and activity of NADPH oxidase causes increased production of superoxide anion (.O2(-)). .O2(-) can also be converted to hydrogen peroxide (H2O2) by enzymatic activity of superoxide dismutase (SOD) or spontaneous dismutation. Elevation of .O2(-) and H2O2 might cause oxidation of tetrahydrobiopterin (BH4) to dihydrobiopterin (BH2) and subsequent uncoupling of endothelial nitric oxide synthase (eNOS) (a) thus reducing levels of nitric oxide (NO) and 3',5'-cyclic guanosine monophosphate (cGMP). Supplementation of BH4 or activation of PPAR? prevents detrimental effects of eNOS uncoupling by restoring bioavailability of BH4 and scavenging of .O2(-), respectively (b). Activation of PPAR? also increases expression of catalase thereby inactivating H2O2. Generation of H2O2 by uncoupled eNOS in cerebral microvessels of Tg2576 mice is hypothetical. PMID:26111938

  16. Effects of Polymorphisms in APOA4-APOA5-ZNF259-BUD13 Gene Cluster on Plasma Levels of Triglycerides and Risk of Coronary Heart Disease in a Chinese Han Population

    PubMed Central

    Su, Li; Zhang, Mingjun; Wang, Long; Jing, Jinjin; Zhou, Li

    2015-01-01

    Background/Aim Recent genome-wide association studies have identified several loci influencing lipid levels. The present study focused on the triglycerides (TG)-associated locus, the APOA4-APOA5-ZNF259-BUD13 gene cluster on chromosome 11, to explore the role of genetic variants in this gene cluster in the development of increasing TG levels and coronary heart disease (CHD). Methodology/Principal Findings Six single nucleotide polymorphisms (SNPs), rs4417316, rs651821, rs6589566, rs7396835, rs964184 and rs17119975, in the APOA4-APOA5-ZNF259-BUD13 gene cluster were selected and genotyped in 5374 healthy Chinese subjects. There were strong significant associations between the six SNPs and TG levels (P<1.0×10?8). Moreover, a weighted genotype score was found to be associated with TG levels (P = 3.28×10?13). The frequencies of three common haplotypes were observed to be significantly different between the high TG group and the low TG group (P<0.05). However, no significant effects were found for the SNPs regarding susceptibility to CHD in the Chinese case-control populations. Conclusions/Significance This study highlights the genotypes, genotype scores and haplotypes of the APOA4-APOA5-ZNF259-BUD13 gene cluster that were associated with TG levels in a Chinese population; however, the genetic variants in this gene cluster did not increase the risk of CHD in the Chinese population. PMID:26397108

  17. The TG/HDL Cholesterol Ratio Predicts All Cause Mortality in Women With Suspected Myocardial Ischemia A Report from the Women’s Ischemia Syndrome Evaluation (WISE)

    PubMed Central

    Bittner, Vera; Johnson, B. Delia; Zineh, Issam; Rogers, William J.; Vido, Diane; Marroquin, Oscar C.; Bairey-Merz, C. Noel; Sopko, George

    2009-01-01

    High triglycerides (TG) and low high density lipoprotein cholesterol (HDL-C) are important cardiovascular risk factors in women. The prognostic utility of the TG/HDL-C ratio, a marker for insulin resistance and small dense low density lipoprotein particles, is unknown among high risk women. Methods We studied 544 women without prior myocardial infarction or coronary revascularization, referred for clinically indicated coronary angiography and enrolled in the Women’s Ischemia Syndrome Evaluation (WISE). Fasting lipid profiles and detailed demographic and clinical data were obtained at baseline. Multi-variate Cox-proportional hazards models for all cause mortality and cardiovascular events (death, myocardial infarction, heart failure, stroke) over a median follow-up of 6 years were constructed using log TG/HDL-C ratio as a predictor variable and accounting for traditional cardiovascular risk factors. Results Mean age was 57±11 years, 84% were white, 55% hypertensive, 20% diabetic, 50% current or prior smokers. TG/HDL-C ranged from 0.3 to 18.4 (median 2.2, first quartile 0.35 to <1.4, fourth quartile 3.66–18.4). Deaths (n=33) and CV events (n=83) increased across TG/HDL-C quartiles (both p<0.05 for trend). TG/HDL-C was a strong independent predictor of mortality in models adjusted for age, race, smoking, hypertension, diabetes, and angiographic coronary disease severity (HR 1.95, 95% CI 1.05, 3.64, p=0.04). For cardiovascular events, the multivariate HR was 1.54 (95% CI 1.05, 2.22, p=0.03) when adjusted for demographic and clinical variables, but became non-significant when angiographic results were included. Conclusion Among women with suspected ischemia, the TG/HDL-C ratio is a powerful independent predictor of all cause mortality and cardiovascular events. PMID:19249427

  18. Ultra high efficiency/low pressure supercritical fluid chromatography with superficially porous particles for triglyceride separation.

    PubMed

    Lesellier, E; Latos, A; de Oliveira, A Lopes

    2014-01-31

    This paper reports the development of the separation of vegetable oil triglycerides (TG) in supercritical chromatography (SFC), using superficially porous particles (SPPs). The SPP, having a small diameter (2-3?m), provide a higher theoretical plate number (N), which allows to improve separation of critical pairs of compounds. However, compared to fully porous particles of larger diameter (5?m), the pressure drop is also increased. Fortunately, supercritical fluids have a low viscosity, which allows coupling several columns to achieve high N values, while maintaining flow rate above 1ml/min, ensuring a ultra high efficiency (UHE) at low pressure (LP) (below 40MPa), with regards to the one reached with liquid and sub-two micron particles (around 100MPa). The use of two detector systems (UV and ELSD) connected in series to the UHE-LP-SFC system provides complementary responses, due to their specific detection principles. Working in a first part with three coupled Kinetex C18 columns (45cm total length), the effect of modifier nature and percentage were studied with two reference oils, argan and rapeseed, chosen for their different and well-known TG composition. The analytical method was developed from previous studies performed with fully porous particles (FPP). Optimized conditions with three Kinetex were as follows: 17°C, 12% of ACN/MeOH (90/10; v/v). With these conditions, and by using an increased length of Kinetex C18 column (60cm), another additional column was selected from ten different commercial SPP C18 bonded phases, by applying a Derringer function on varied parameters: theoretical plate number (TPN), separation index (SI) for critical pairs of peaks (the peaks of compounds difficult to separate due to subtle structural differences), the analysis duration, and the total peak number. This function normalizes the values of any parameters, between 0 and 1, from the worst value to the better, allowing to take account of various parameters in the final choice. Finally, by using four Kinetex C18 plus one Accucore C18 (75cm total column length), a high-performance separation of triglycerides was achieved, with reasonable analysis duration and isocratic conditions. These conditions can be applied to varied vegetable oils. Identification of the numerous separated peaks of rapeseed oil was achieved by using published data and chromatographic retention behaviour. PMID:24411089

  19. Serum lipidomics profiling using LC-MS and high-energy collisional dissociation fragmentation: focus on triglyceride detection and characterization.

    PubMed

    Bird, Susan S; Marur, Vasant R; Sniatynski, Matthew J; Greenberg, Heather K; Kristal, Bruce S

    2011-09-01

    There is a growing need both clinically and experimentally to improve the characterization of blood lipids. A liquid chromatography-mass spectrometry (LC-MS) method, developed for the qualitative and semiquantitative detection of lipids in biological samples and previously validated in mitochondrial samples, was now evaluated for the profiling of serum lipids. Data were acquired using high-resolution, full scan MS and high-energy, collisional dissociation (HCD), all ion fragmentation. The method was designed for efficient separation and detection in both positive and negative ionization mode and evaluated using standards spanning seven lipid classes. Platform performance, related to the identification and characterization of serum triglycerides (TGs), was assessed using extracted ion chromatograms with mass tolerance windows of 5 ppm or less from full scan exact mass measurements determined using SIEVE nondifferential LC-MS analysis software. The platform showed retention time coefficients of variation (CV) of <0.3%, mass accuracy values of <2 ppm error, and peak area CV of <13%, with the majority of that error coming from sample preparation and extraction rather than the LC-MS analysis, and linearity was shown to be over 4 orders of magnitude (r(2) = 0.999) for the standard TG (15:0)(3) spiked into serum. Instrument mass accuracy and precision were critical to the identification of unknown TG species, in part because these parameters enabled us to reduce false positives. In addition to detection and relative quantitation of TGs in serum, TG structures were characterized through the use of alternating HCD scans at different energies to produce diagnostic fragmentations on all ions in the analysis. The lipidomics method was applied to serum samples from 192 rats maintained on diets differing in macronutrient composition. The analysis identified 86 TG species with 81 unique masses that varied over 3.5 orders of magnitude and showed diet-dependency, consistent with TGs linking diet and disease risk. PMID:21774539

  20. Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels.

    PubMed

    Peng, Xian-E; Wu, Yun-Li; Zhu, Yi-Bing; Huang, Rong-Dong; Lu, Qing-Qing; Lin, Xu

    2015-01-01

    Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD) and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (? = -0.320, P = 0.003), while serum TG levels were positively associated with serum FABP1 levels (? = 0.487, P = 0.014). Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans. PMID:26439934

  1. Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels

    PubMed Central

    Zhu, Yi-bing; Huang, Rong-dong; Lu, Qing-Qing; Lin, Xu

    2015-01-01

    Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD) and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (? = —0.320, P = 0.003), while serum TG levels were positively associated with serum FABP1 levels (? = 0.487, P = 0.014). Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans. PMID:26439934

  2. Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension

    PubMed Central

    Moura, Rafaela do Socorro Souza e Silva; Vasconcelos, Daniel França; Freitas, Eduardo; de Moura, Flavio José Dutra; Rosa, Tânia Torres; Veiga, Joel Paulo Russomano

    2014-01-01

    Background In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease. Objective To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL. Methods This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome. Results In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r2: 0.277, p < 0.05). Conclusion CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension. PMID:24162470

  3. Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia

    SciTech Connect

    Narcisi, T.M.E.; Shoulders, C.C.; Chester, S.A.

    1995-12-01

    Elevated plasma levels of apolipoprotein B (apoB)-containing lipoproteins constitute a major risk factor for the development of coronary heart disease. In the rare recessively inherited disorder abetalipoproteinemia (ABL) the production of apoB-containing lipoproteins is abolished, despite no abnormality of the apoB gene. In the current study we have characterized the gene encoding a microsomal triglyceride-transfer protein (MTP), localized to chromosome 4q22-24, and have identified a mutation of the MTP gene in both alleles of all individuals in a cohort of eight patients with classical ABL. Each mutant allele is predicted to encode a truncated form of MTP with a variable number of aberrant amino acids at its C-terminal end. Expression of genetically engineered forms of MTP in Cos-1 cells indicates that the C-terminal portion of MTP is necessary for triglyceride-transfer activity. Deletion of 20 amino acids from the carboxyl terminus of the 894-amino-acid protein and a missense mutation of cysteine 878 to serine both abolished activity. These results establish that defects of the MTP gene are the predominant, if not sole, cause of hereditary ABL and that an intact carboxyl terminus is necessary for activity. 49 refs., 4 figs., 5 tabs.

  4. Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia.

    PubMed

    Narcisi, T M; Shoulders, C C; Chester, S A; Read, J; Brett, D J; Harrison, G B; Grantham, T T; Fox, M F; Povey, S; de Bruin, T W

    1995-12-01

    Elevated plasma levels of apolipoprotein B (apoB)-containing lipoproteins constitute a major risk factor for the development of coronary heart disease. In the rare recessively inherited disorder abetalipoproteinemia (ABL) the production of apoB-containing lipoproteins is abolished, despite no abnormality of the apoB gene. In the current study we have characterized the gene encoding a microsomal triglyceride-transfer protein (MTP), localized to chromosome 4q22-24, and have identified a mutation of the MTP gene in both alleles of all individuals in a cohort of eight patients with classical ABL. Each mutant allele is predicted to encode a truncated form of MTP with a variable number of aberrant amino acids at its C-terminal end. Expression of genetically engineered forms of MTP in Cos-1 cells indicates that the C-terminal portion of MTP is necessary for triglyceride-transfer activity. Deletion of 20 amino acids from the carboxyl terminus of the 894-amino-acid protein and a missense mutation of cysteine 878 to serine both abolished activity. These results establish that defects of the MTP gene are the predominant, if not sole, cause of hereditary ABL and that an intact carboxyl terminus is necessary for activity. PMID:8533758

  5. A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans

    PubMed Central

    Timpson, Nicholas J.; Walter, Klaudia; Min, Josine L.; Tachmazidou, Ioanna; Malerba, Giovanni; Shin, So-Youn; Chen, Lu; Futema, Marta; Southam, Lorraine; Iotchkova, Valentina; Cocca, Massimiliano; Huang, Jie; Memari, Yasin; McCarthy, Shane; Danecek, Petr; Muddyman, Dawn; Mangino, Massimo; Menni, Cristina; Perry, John R. B.; Ring, Susan M.; Gaye, Amadou; Dedoussis, George; Farmaki, Aliki-Eleni; Burton, Paul; Talmud, Philippa J.; Gambaro, Giovanni; Spector, Tim D.; Smith, George Davey; Durbin, Richard; Richards, J Brent; Humphries, Steve E.; Zeggini, Eleftheria; Soranzo, Nicole; Al Turki, Saeed; Anderson, Carl; Anney, Richard; Antony, Dinu; Soler Artigas, Maria; Ayub, Muhammad; Balasubramaniam, Senduran; Barrett, Jeffrey C.; Barroso, Inês; Beales, Phil; Bentham, Jamie; Bhattacharya, Shoumo; Birney, Ewan; Blackwood, Douglas; Bobrow, Martin; Bochukova, Elena; Bolton, Patrick; Bounds, Rebecca; Boustred, Chris; Breen, Gerome; Calissano, Mattia; Carss, Keren; Chatterjee, Krishna; Chen, Lu; Ciampi, Antonio; Cirak, Sebhattin; Clapham, Peter; Clement, Gail; Coates, Guy; Collier, David; Cosgrove, Catherine; Cox, Tony; Craddock, Nick; Crooks, Lucy; Curran, Sarah; Curtis, David; Daly, Allan; Danecek, Petr; Davey Smith, George; Day-Williams, Aaron; Day, Ian N. M.; Down, Thomas; Du, Yuanping; Dunham, Ian; Durbin, Richard; Edkins, Sarah; Ellis, Peter; Evans, David; Faroogi, Sadaf; Fatemifar, Ghazaleh; Fitzpatrick, David R.; Flicek, Paul; Flyod, James; Foley, A Reghan; Franklin, Christopher S; Futema, Marta; Gallagher, Louise; Gaunt, Tom; Geihs, Matthias; Geschwind, Daniel; Greenwood, Celia; Griffin, Heather; Grozeva, Detelina; Guo, Xueqin; Guo, Xiaosen; Gurling, Hugh; Hart, Deborah; Hendricks, Audrey; Holmans, Peter; Howie, Bryan; Huang, Jie; Huang, Liren; Hubbard, Tim; Humphries, Steve E.; Hurles, Matthew E.; Hysi, Pirro; Jackson, David K.; Jamshidi, Yalda; Jing, Tian; Joyce, Chris; Kaye, Jane; Keane, Thomas; Keogh, Julia; Kemp, John; Kennedy, Karen; Kolb-Kokocinski, Anja; Lachance, Genevieve; Langford, Cordelia; Lawson, Daniel; Lee, Irene; Lek, Monkol; Liang, Jieqin; Lin, Hong; Li, Rui; Li, Yingrui; Liu, Ryan; Lönnqvist, Jouko; Lopes, Margarida; Lotchkova, Valentina; MacArthur, Daniel; Marchini, Jonathan; Maslen, John; Massimo, Mangino; Mathieson, Iain; Marenne, Gaëlle; McCarthy, Shane; McGuffin, Peter; McIntosh, Andrew; McKechanie, Andrew G.; McQuillin, Andrew; Memari, Yasin; Metrustry, Sarah; Min, Josine; Mitchison, Hannah; Moayyeri, Alireza; Morris, James; Muddyman, Dawn; Muntoni, Francesco; Northstone, Kate; O'Donnovan, Michael; Onoufriadis, Alexandros; O'Rahilly, Stephen; Oualkacha, Karim; Owen, Michael J.; Palotie, Aarno; Panoutsopoulou, Kalliope; Parker, Victoria; Parr, Jeremy R.; Paternoster, Lavinia; Paunio, Tiina; Payne, Felicity; Perry, John; Pietilainen, Olli; Plagnol, Vincent; Quaye, Lydia; Quail, Michael A.; Raymond, Lucy; Rehnström, Karola; Richards, Brent; Ring, Susan; Ritchie, Graham R. S.; Roberts, Nicola; Savage, David B.; Scambler, Peter; Schiffels, Stephen; Schmidts, Miriam; Schoenmakers, Nadia; Semple, Robert K.; Serra, Eva; Sharp, Sally I.; Shihab, Hasheem; Shin, So-Youn; Skuse, David; Small, Kerrin; Soranzo, Nicole; Southam, Lorraine; Spasic-Boskovic, Olivera; Spector, Tim; St Clair, David; Stalker, Jim; Stevens, Elizabeth; St Pourcian, Beate; Sun, Jianping; Surdulescu, Gabriela; Suvisaari, Jaana; Tachmazidou, Ionna; Timpson, Nicholas; Tobin, Martin D.; Valdes, Ana; Van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Visscher, Peter M.; Wain, Louise V.; Walter, Klaudia; Walters, James T. R.; Wang, Guangbiao; Wang, Jun; Wang, Yu; Ward, Kirsten; Wheeler, Elanor; Whyte, Tamieka; Williams, Hywel; Williamson, Kathleen A.; Wilson, Crispian; Wilson, Scott G.; Wong, Kim; Xu, ChangJiang; Yang, Jian; Zeggini, Eleftheria; Zhang, Fend; Zhang, Pingbo; Zheng, Hou-Feng

    2014-01-01

    The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (?1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 × 10?8)) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (?1.0 s.d. (s.e.=0.173), P-value=7.32 × 10?9). This is consistent with an effect between 0.5 and 1.5?mmol?l?1 dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale. PMID:25225788

  6. A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans.

    PubMed

    Timpson, Nicholas J; Walter, Klaudia; Min, Josine L; Tachmazidou, Ioanna; Malerba, Giovanni; Shin, So-Youn; Chen, Lu; Futema, Marta; Southam, Lorraine; Iotchkova, Valentina; Cocca, Massimiliano; Huang, Jie; Memari, Yasin; McCarthy, Shane; Danecek, Petr; Muddyman, Dawn; Mangino, Massimo; Menni, Cristina; Perry, John R B; Ring, Susan M; Gaye, Amadou; Dedoussis, George; Farmaki, Aliki-Eleni; Burton, Paul; Talmud, Philippa J; Gambaro, Giovanni; Spector, Tim D; Smith, George Davey; Durbin, Richard; Richards, J Brent; Humphries, Steve E; Zeggini, Eleftheria; Soranzo, Nicole

    2014-01-01

    The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (-1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 × 10(-8))) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (-1.0 s.d. (s.e.=0.173), P-value=7.32 × 10(-9)). This is consistent with an effect between 0.5 and 1.5 mmol l(-1) dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale. PMID:25225788

  7. Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice.

    PubMed

    Tripathy, Sasmita; Lytle, Kelli A; Stevens, Robert D; Bain, James R; Newgard, Christopher B; Greenberg, Andrew S; Huang, Li-Shin; Jump, Donald B

    2014-05-01

    Nonalcoholic fatty liver disease is a major public health concern in the obese and type 2 diabetic populations. The high-fat lard diet induces obesity and fatty liver in C57BL/6J mice and suppresses expression of the PPAR-target gene, FA elongase 5 (Elovl5). Elovl5 plays a key role in MUFA and PUFA synthesis. Increasing hepatic Elovl5 activity in obese mice lowered hepatic TGs and endoplasmic reticulum stress markers (X-box binding protein 1 and cAMP-dependent transcription factor 6?) and increased TG catabolism and fatty acyl carnitines. Increased hepatic Elovl5 activity did not increase hepatic capacity for ?-oxidation. Elovl5 effects on hepatic TG catabolism were linked to increased protein levels of adipocyte TG lipase (ATGL) and comparative gene identification 58 (CGI58). Elevated hepatic Elovl5 activity also induced the expression of some (pyruvate dehydrogenase kinase 4 and fibroblast growth factor 21), but not other cytochrome P450 4A10 (CYP4A10), PPAR-target genes. FA products of Elovl5 activity increased ATGL, but not CGI58, mRNA through PPAR?-dependent mechanisms in human HepG2 cells. Treatment of mouse AML12 hepatocytes with the PPAR? agonist (GW0742) decreased (14)C-18:2,n-6 in TGs but did not affect ?-oxidation. These studies establish that Elovl5 activity regulates hepatic levels of FAs controlling PPAR? activity, ATGL expression, and TG catabolism, but not FA oxidation. PMID:24814977

  8. Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice[S

    PubMed Central

    Tripathy, Sasmita; Lytle, Kelli A.; Stevens, Robert D.; Bain, James R.; Newgard, Christopher B.; Greenberg, Andrew S.; Huang, Li-Shin; Jump, Donald B.

    2014-01-01

    Nonalcoholic fatty liver disease is a major public health concern in the obese and type 2 diabetic populations. The high-fat lard diet induces obesity and fatty liver in C57BL/6J mice and suppresses expression of the PPAR-target gene, FA elongase 5 (Elovl5). Elovl5 plays a key role in MUFA and PUFA synthesis. Increasing hepatic Elovl5 activity in obese mice lowered hepatic TGs and endoplasmic reticulum stress markers (X-box binding protein 1 and cAMP-dependent transcription factor 6?) and increased TG catabolism and fatty acyl carnitines. Increased hepatic Elovl5 activity did not increase hepatic capacity for ?-oxidation. Elovl5 effects on hepatic TG catabolism were linked to increased protein levels of adipocyte TG lipase (ATGL) and comparative gene identification 58 (CGI58). Elevated hepatic Elovl5 activity also induced the expression of some (pyruvate dehydrogenase kinase 4 and fibroblast growth factor 21), but not other cytochrome P450 4A10 (CYP4A10), PPAR-target genes. FA products of Elovl5 activity increased ATGL, but not CGI58, mRNA through PPAR?-dependent mechanisms in human HepG2 cells. Treatment of mouse AML12 hepatocytes with the PPAR? agonist (GW0742) decreased 14C-18:2,n-6 in TGs but did not affect ?-oxidation. These studies establish that Elovl5 activity regulates hepatic levels of FAs controlling PPAR? activity, ATGL expression, and TG catabolism, but not FA oxidation. PMID:24814977

  9. Identification of a novel phosphorylation site in adipose triglyceride lipase as a regulator of lipid droplet localization.

    PubMed

    Xie, Xitao; Langlais, Paul; Zhang, Xiaodong; Heckmann, Bradlee L; Saarinen, Alicia M; Mandarino, Lawrence J; Liu, Jun

    2014-06-15

    Adipose triglyceride lipase (ATGL), the rate-limiting enzyme for triacylglycerol (TG) hydrolysis, has long been known to be a phosphoprotein. However, the potential phosphorylation events that are involved in the regulation of ATGL function remain incompletely defined. Here, using a combinatorial proteomics approach, we obtained evidence that at least eight different sites of ATGL can be phosphorylated in adipocytes. Among them, Thr³?² resides within the hydrophobic region known to mediate lipid droplet (LD) targeting. Although it had no impact on the TG hydrolase activity, substitution of phosphorylation-mimic Asp for Thr³?² eliminated LD localization and LD-degrading capacity of ATGL expressed in HeLa cells. In contrast, mutation of Thr³?² to Ala gave a protein that bound LDs and functioned the same as the wild-type protein. In nonstimulated adipocytes, the Asp mutation led to decreased LD association and basal lipolytic activity of ATGL, whereas the Ala mutation produced opposite effects. Moreover, the LD translocation of ATGL upon ?-adrenergic stimulation was also compromised by the Asp mutation. In accord with these findings, the Ala mutation promoted and the Asp mutation attenuated the capacity of ATGL to mediate lipolysis in adipocytes under both basal and stimulated conditions. Collectively, these studies identified Thr³?² as a novel phosphorylation site that may play a critical role in determining subcellular distribution as well as lipolytic action of ATGL. PMID:24801391

  10. Comparison of TG-43 and TG-186 in breast irradiation using a low energy electronic brachytherapy source

    SciTech Connect

    White, Shane A.; Landry, Guillaume; Reniers, Brigitte; Fonseca, Gabriel Paiva; Beaulieu, Luc; Verhaegen, Frank

    2014-06-15

    Purpose: The recently updated guidelines for dosimetry in brachytherapy in TG-186 have recommended the use of model-based dosimetry calculations as a replacement for TG-43. TG-186 highlights shortcomings in the water-based approach in TG-43, particularly for low energy brachytherapy sources. The Xoft Axxent is a low energy (<50 kV) brachytherapy system used in accelerated partial breast irradiation (APBI). Breast tissue is a heterogeneous tissue in terms of density and composition. Dosimetric calculations of seven APBI patients treated with Axxent were made using a model-based Monte Carlo platform for a number of tissue models and dose reporting methods and compared to TG-43 based plans. Methods: A model of the Axxent source, the S700, was created and validated against experimental data. CT scans of the patients were used to create realistic multi-tissue/heterogeneous models with breast tissue segmented using a published technique. Alternative water models were used to isolate the influence of tissue heterogeneity and backscatter on the dose distribution. Dose calculations were performed using Geant4 according to the original treatment parameters. The effect of the Axxent balloon applicator used in APBI which could not be modeled in the CT-based model, was modeled using a novel technique that utilizes CAD-based geometries. These techniques were validated experimentally. Results were calculated using two dose reporting methods, dose to water (D{sub w,m}) and dose to medium (D{sub m,m}), for the heterogeneous simulations. All results were compared against TG-43-based dose distributions and evaluated using dose ratio maps and DVH metrics. Changes in skin and PTV dose were highlighted. Results: All simulated heterogeneous models showed a reduced dose to the DVH metrics that is dependent on the method of dose reporting and patient geometry. Based on a prescription dose of 34 Gy, the average D{sub 90} to PTV was reduced by between ?4% and ?40%, depending on the scoring method, compared to the TG-43 result. Peak skin dose is also reduced by 10%–15% due to the absence of backscatter not accounted for in TG-43. The balloon applicator also contributed to the reduced dose. Other ROIs showed a difference depending on the method of dose reporting. Conclusions: TG-186-based calculations produce results that are different from TG-43 for the Axxent source. The differences depend strongly on the method of dose reporting. This study highlights the importance of backscatter to peak skin dose. Tissue heterogeneities, applicator, and patient geometries demonstrate the need for a more robust dose calculation method for low energy brachytherapy sources.

  11. Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1low Monocytes

    PubMed Central

    Saja, Maha F.; Baudino, Lucie; Jackson, William D.; Cook, H. Terence; Malik, Talat H.; Fossati-Jimack, Liliane; Ruseva, Marieta; Pickering, Matthew C.; Woollard, Kevin J.; Botto, Marina

    2015-01-01

    Summary Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. However, their response to hyperlipidemia remains poorly understood. Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1low monocytes drop, while the number of bone marrow progenitors remains similar. We observed an increased crawling and retention of the Gr1low monocytes at the endothelial interface and a marked accumulation of CD68+ macrophages in several organs. Hypertriglyceridemia was accompanied by an increased expression of tissue, and plasma CCL4 and blood Gr1low monocyte depletion involved a pertussis-toxin-sensitive receptor axis. Collectively, these findings demonstrate that a triglyceride-rich environment can alter blood monocyte distribution, promoting the extravasation of Gr1low cells. The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells. PMID:26344769

  12. Elevation of fasting insulin and its association with cardiovascular disease risk in women with systemic lupus erythematosus.

    PubMed

    Tso, Tim K; Huang, Wen-Nan

    2009-05-01

    Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis. We previously showed that SLE patients have a higher risk of insulin resistance (IR) and abnormal insulin secretion. The present study was to further investigate the relationship between fasting insulin levels and both classic and novel cardiovascular risk factors in patients with SLE. Body mass index (BMI), fasting glucose and insulin, lipid profile, oxidation markers, fibrinolytic factors, vascular function factors, and disease-specific variables were determined in a total of 87 female SLE patients. The homeostasis model assessment (HOMA) was used to evaluate the IR and secretion. SLE patients had significantly higher fasting insulin, HOMA IR, HOMA beta-cell, titers of autoantibodies against oxidized low density lipoprotein, systolic blood pressure, homocysteine, and brachial-ankle pulse wave velocity (baPWV) than age-matched healthy controls. There were no statistical differences in disease duration, anti-dsDNA, C3, C4, disease activity, and medication dosage between SLE patients stratified by fasting insulin levels. However, mean values for BMI, insulin, HOMA IR, HOMA beta-cell, triglyceride (TG), homocysteine, and baPWV were significantly higher in the SLE patients with hyperinsulinemia when compared with those SLE controls. In addition, fasting insulin levels were positively correlated with TG, homocysteine, blood pressure, plasminogen activator inhibitor 1, and baPWV in SLE patients. The elevation of fasting insulin levels in SLE patients is not only associated with IR, but is related to classic and novel cardiovascular risk factors. This study concludes that there is an insulin-related cardiovascular disease risk in SLE. PMID:19037607

  13. Patient Guide to the Assessment and Treatment of Hypertriglyceridemia (High Triglycerides)

    MedlinePLUS

    ... Triglycerides are fats in the blood (also called lipids). Your body needs some blood fats for energy. ... Also, many people with high triglycerides have other lipid problems or other risk factors for heart disease. ...

  14. NATO TG-25 joint field experiment in distributed sensor networks

    NASA Astrophysics Data System (ADS)

    Mays, Brian; Vu, Hao; Srour, Nino

    2003-09-01

    NATO's Task Group (TG-25) on acoustic and seismic sensing is responsible for assessing the potential technologies that can be cooperatively developed and shared within NATO's countries to provide effective, robust and low-cost battlefield sensor systems. The primary applications will be detection and/or classification of ground troops, ground vehicles, airborne vehicles, artillery and sniper. TG-25 has 3 main objectives: (1) to establish acoustic and seismic standards and data exchange procedures, (2) to compare, analyze, exchange, and develop analytical techniques, computational models and signal processing algorithms, and (3) to plan and conduct joint field experiments. In this paper, we discuss participation in the joint NATO field experiment conducted in France in October 2002. The experiment's goal is to demonstrate interoperability of unattended ground sensors from various participating nations. Results of the experiments will be briefed and discussed. Keywords: TG-25, unattended ground sensor, vehicle tracking

  15. Common variants associated with plasma triglycerides and risk for coronary artery disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common va...

  16. Isolation of the molecular species of monogalactosyldiacylglycerols from brown edible seaweed Sargassum horneri and their inhibitory effects on triglyceride accumulation in 3T3-L1 adipocytes.

    PubMed

    Ma, Ai-Cui; Chen, Zhen; Wang, Tao; Song, Ni; Yan, Qian; Fang, Yu-Chun; Guan, Hua-Shi; Liu, Hong-Bing

    2014-11-19

    The chemical composition of monogalactosyldiacylglycerols (MGDGs) from brown alga Sargassum horneri and their inhibitory effects on lipid accumulation were investigated in this study. A total of 10 molecular species of MGDGs were identified using nuclear magnetic resonance, alkaline hydrolysis, gas chromatography-flame ionization detector, and high-performance liquid chromatography-tandem mass spectrometry methods. Individual molecular species of MGDGs, including (2S)-1-O-myristoyl-2-O-palmitoleoyl-3-O-?-D-galactopyranosyl-sn-glycerol (1), (2S)-1-O-myristoyl-2-O-linoleyl-3-O-?-D-galactopyranosyl-sn-glycerol (3), (2S)-1-O-palmitoyl-2-O-linolenoyl-3-O-?-D-galactopyranosyl-sn-glycerol (5), (2S)-1-O-myristoyl-2-O-oleyl-3-O-?-D-galactopyranosyl-sn-glycerol (7), (2S)-1-O-palmitoyl-2-O-palmitoleoyl-3-O-?-D-galactopyranosyl-sn-glycerol (8), (2S)-1-O-palmitoyl-2-O-linoleyl-3-O-?-D-galactopyranosyl-sn-glycerol (9), and (2S)-1-O-palmitoyl-2-O-oleyl-3-O-?-D-galactopyranosyl-sn-glycerol (10), were then furnished using semi-preparative high-performance liquid chromatography, and their inhibitory effects on triglyceride (TG) accumulation and free fatty acid (FFA) levels in 3T3-L1 adipocytes were evaluated. Compounds 3 and 9 showed inhibitory effects on TG and FFA accumulation, with TG levels of 1.568 ± 0.2808 and 1.701 ± 0.1460 ?mol/L and FFA levels of 0.149 ± 0.0258 and 0.198 ± 0.0229 mequiv/L, respectively, which were more effective than other compounds. The primary structure-activity relationship suggested that linoleyl [18:2(?-6)] in the sn-2 position played an important role on triglyceride accumulation inhibition. PMID:25363514

  17. Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

    PubMed Central

    Marchese, Monica; Cowan, David; Head, Elizabeth; Ma, Donglai; Karimi, Khalil; Ashthorpe, Vanessa; Kapadia, Minesh; Zhao, Hui; Davis, Paulina; Sakic, Boris

    2015-01-01

    Background Immune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration. Objective The present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology. Methods A broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age. Results Aged AD mice displayed severe manifestations of systemic autoimmune/inflammatory disease, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired “cognitive” flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-? or tau pathology. Conclusion The results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD. PMID:24150111

  18. ApoC-III and visceral adipose tissue contribute to paradoxically normal triglyceride levels in insulin-resistant African-American women

    PubMed Central

    2013-01-01

    Background African-Americans are more insulin-resistant than whites but have lower triglyceride (TG) concentrations. The metabolic basis for this is unknown. Our goal was to determine in a cross-sectional study the effect of insulin resistance, visceral adipose tissue (VAT) and the apolipoproteins, B, C-III and E, on race differences in TG content of very low density lipoproteins (VLDL). Methods The participants were 31 women (16 African-American, 15 white) of similar age (37?±?9 vs. 38?±?11y (mean?±?SD), P =?0.72) and BMI (32.4?±?7.2 vs. 29.3?±?6.0 kg/m2, P =?0.21). A standard diet (33% fat, 52% carbohydrate, 15% protein) was given for 7 days followed by a test meal (40% fat, 40% carbohydrate, 20% protein) on Day 8. Insulin sensitivity index (SI) was calculated from the minimal model. VAT was measured at L2-3. The influence of race, SI, VAT and apolipoproteins on the TG content of VLDL was determined by random effects models (REM). Results African-Americans were more insulin-resistant (SI: 3.6?±?1.3 vs. 5.6?±?2.6 mU/L-1.min-1, P TG, apoB and apoC-III content of light and dense VLDL were lower in African-Americans (all P TG concentration of VLDL. In models with race, SI, VAT and all apolipoproteins entered, race was not significant but apoC-III and VAT remained significant determinants of TG concentration in light and dense VLDL. Conclusions Low concentrations of apoC-III and VAT in African-Americans contribute to race differences in TG concentrations. Trial registration ClinicalTrials.gov Identifier: NCT00484861 PMID:24365086

  19. Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion.

    PubMed

    Wang, Yan; Gusarova, Viktoria; Banfi, Serena; Gromada, Jesper; Cohen, Jonathan C; Hobbs, Helen H

    2015-07-01

    Humans and mice lacking angiopoietin-like protein 3 (ANGPTL3) have pan-hypolipidemia. ANGPTL3 inhibits two intravascular lipases, LPL and endothelial lipase, and the low plasma TG and HDL-cholesterol levels in ANGPTL3 deficiency reflect increased activity of these enzymes. The mechanism responsible for the low LDL-cholesterol levels associated with ANGPTL3 deficiency is not known. Here we used an anti-ANGPTL3 monoclonal antibody (REGN1500) to inactivate ANGPTL3 in mice with genetic deficiencies in key proteins involved in clearance of ApoB-containing lipoproteins. REGN1500 treatment consistently reduced plasma cholesterol levels in mice in which Apoe, Ldlr, Lrp1, and Sdc1 were inactivated singly or in combination, but did not alter clearance of rabbit (125)I-?VLDL or mouse (125)I-LDL. Despite a 61% reduction in VLDL-TG production, VLDL-ApoB-100 production was unchanged in REGN1500-treated animals. Hepatic TG content, fatty acid synthesis, and fatty acid oxidation were similar in REGN1500 and control antibody-treated animals. Taken together, our findings indicate that inactivation of ANGPTL3 does not affect the number of ApoB-containing lipoproteins secreted by the liver but alters the particles that are made such that they are cleared more rapidly from the circulation via a noncanonical pathway(s). The increased clearance of lipolytic remnants results in decreased production of LDL in ANGPTL3-deficient animals. PMID:25954050

  20. Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

    PubMed Central

    2010-01-01

    Background Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. Methods A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG ? 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. Results We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-?4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG. Conclusion Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the ?4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia. PMID:20429872

  1. Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans

    PubMed Central

    Chandak, Giriraj R; Ward, Kirsten J; Yajnik, Chittaranjan S; Pandit, Anand N; Bavdekar, Ashish; Joglekar, Charu V; Fall, Caroline HD; Mohankrishna, P; Wilkin, Terence J; Metcalf, Bradley S; Weedon, Michael N; Frayling, Timothy M; Hattersley, Andrew T

    2006-01-01

    Background The APOA5 gene variants, -1131T>C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian and East Asian descent. There are few studies of these variants in South Asians. We investigated whether the two APOA5 variants also show similar association with various lipid parameters in Indian population as in the UK white subjects. Methods We genotyped 557 Indian adults from Pune, India, and 237 UK white adults for -1131T>C and S19W variants in the APOA5 gene, compared their allelic and genotype frequency and determined their association with fasting serum triglycerides, total cholesterol, HDL and LDL cholesterol levels using univariate general linear analysis. APOC3 SstI polymorphism was also analyzed in 175 Pune Indian subjects for analysis of linkage disequilibrium with the APOA5 variants. Results The APOA5 -1131C allele was more prevalent in Indians from Pune (Pune Indians) compared to UK white subjects (allele frequency 20% vs. 4%, p = 0.00001), whereas the 19W allele was less prevalent (3% vs. 6% p = 0.0015). Patterns of linkage disequilibrium between the two variants were similar between the two populations and confirmed that they occur on two different haplotypes. In Pune Indians, the presence of -1131C allele and the 19W allele was associated with a 19% and 15% increase respectively in triglyceride concentrations although only -1131C was significant (p = 0.0003). This effect size was similar to that seen in the UK white subjects. Analysis of the APOC3 SstI polymorphism in 175 Pune Indian subjects showed that this variant is not in appreciable linkage disequilibrium with the APOA5 -1131T>C variant (r2 = 0.07). Conclusion This is the first study to look at the role of APOA5 in Asian Indian subjects that reside in India. The -1131C allele is more prevalent and the 19W allele is less prevalent in Pune Indians compared to UK Caucasians. We confirm that the APOA5 variants are associated with triglyceride levels independent of ethnicity and that this association is similar in magnitude in Asian Indians and Caucasians. The -1131C allele is present in 36% of the Pune Indian population making it a powerful marker for looking at the role of elevated triglycerides in important conditions such as pancreatitis, diabetes and coronary heart disease. PMID:17032446

  2. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    PubMed Central

    Chapman, M. John; Ginsberg, Henry N.; Amarenco, Pierre; Andreotti, Felicita; Borén, Jan; Catapano, Alberico L.; Descamps, Olivier S.; Fisher, Edward; Kovanen, Petri T.; Kuivenhoven, Jan Albert; Lesnik, Philippe; Masana, Luis; Nordestgaard, Børge G.; Ray, Kausik K.; Reiner, Zeljko; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Tybjærg-Hansen, Anne; Watts, Gerald F.

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (?1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal. PMID:21531743

  3. A new multienzyme-type biosensor for triglyceride determination.

    PubMed

    Yücel, Alp; Özcan, Hakk? Mevlüt; Sa??ro?lu, Ayten

    2016-01-01

    An amperometric multienzyme biosensor for determination of triglycerides (TGs) was constructed by mounting three gelatin membrane-bound enzymes on a glassy carbon electrode (working electrode), then connecting it to electrometer along with an Ag/AgCl reference electrode and a Pt auxiliary electrode. Characterization and optimization of the multienzyme biosensor, which is prepared with glycerol kinase (GK) (E.C.2.7.1.30), glycerol-3-phosphate oxidase (GPO) (EC 1.1.3.21), and lipase (EC 3.1.1.3), were studied. In the optimization studies for the bioactive layer components of the prepared biosensor, the optimum amounts of gelatin, bovine serum albumin (BSA), and glutaraldehyde was calculated as 1 mg/cm(2), 1 mg/cm(2), and 2.5%, respectively. Optimum pH and temperature of the reaction of biosensor were determined as 7.0 and 40°C, respectively. Linear range of triolein for the biosensor was found from the calibration curve between several substrate concentration and ? Current. After optimization and characterization of the biosensor, its operationability in triglycerides was also tested. PMID:25397961

  4. Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice

    PubMed Central

    DeTolla, L.; Sanchez, R.; Khan, E.; Tyler, B.; Guarnieri, M.

    2014-01-01

    Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3?mg/kg dose of drug. One male mouse treated with three 3?mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine. PMID:26464927

  5. A novel partial agonist of peroxisome proliferator-activated receptor-gamma (PPARgamma) recruits PPARgamma-coactivator-1alpha, prevents triglyceride accumulation, and potentiates insulin signaling in vitro.

    PubMed

    Burgermeister, Elke; Schnoebelen, Astride; Flament, Angele; Benz, Jörg; Stihle, Martine; Gsell, Bernard; Rufer, Arne; Ruf, Armin; Kuhn, Bernd; Märki, Hans Peter; Mizrahi, Jacques; Sebokova, Elena; Niesor, Eric; Meyer, Markus

    2006-04-01

    Partial agonists of peroxisome proliferator-activated receptor-gamma (PPARgamma), also termed selective PPARgamma modulators, are expected to uncouple insulin sensitization from triglyceride (TG) storage in patients with type 2 diabetes mellitus. These agents shall thus avoid adverse effects, such as body weight gain, exerted by full agonists such as thiazolidinediones. In this context, we describe the identification and characterization of the isoquinoline derivative PA-082, a prototype of a novel class of non-thiazolidinedione partial PPARgamma ligands. In a cocrystal with PPARgamma it was bound within the ligand-binding pocket without direct contact to helix 12. The compound displayed partial agonism in biochemical and cell-based transactivation assays and caused preferential recruitment of PPARgamma-coactivator-1alpha (PGC1alpha) to the receptor, a feature shared with other selective PPARgamma modulators. It antagonized rosiglitazone-driven transactivation and TG accumulation during de novo adipogenic differentiation of murine C3H10T1/2 mesenchymal stem cells. The latter effect was mimicked by overexpression of wild-type PGC1alpha but not its LXXLL-deficient mutant. Despite failing to promote TG loading, PA-082 induced mRNAs of genes encoding components of insulin signaling and adipogenic differentiation pathways. It potentiated glucose uptake and inhibited the negative cross-talk of TNFalpha on protein kinase B (AKT) phosphorylation in mature adipocytes and HepG2 human hepatoma cells. PGC1alpha is a key regulator of energy expenditure and down-regulated in diabetics. We thus propose that selective recruitment of PGC1alpha to favorable PPARgamma-target genes provides a possible molecular mechanism whereby partial PPARgamma agonists dissociate TG accumulation from insulin signaling. PMID:16373399

  6. Modified QCD ghost f(T,TG) gravity

    NASA Astrophysics Data System (ADS)

    Jawad, Abdul; Rani, Shamaila; Chattopadhyay, Surajit

    2015-12-01

    In this paper, we explore the reconstruction scenario of modified QCD ghost dark energy model and newly proposed f(T,TG) gravity in flat FRW universe. We consider the well-known assumption of scale factor, i.e., power law form. We construct the f(T,TG) model and discuss its cosmological consequences through various cosmological parameters such as equation of state parameter, squared speed of sound and ?_{DE}-? '_{DE}. The equation of state parameter provides the quintom-like behavior of the universe. The squared speed of sound exhibits the stability of model in the later time. Also, ?_{DE}- ? '_{DE} corresponds to freezing as well as thawing regions. It is also interesting to remark here that the results of equation of state parameter and w_{DE}-w'_{DE} coincide with the observational data.

  7. Red Blood Cell Docosapentaenoic Acid (DPA n-3) is Inversely Associated with Triglycerides and C-reactive Protein (CRP) in Healthy Adults and Dose-Dependently Increases Following n-3 Fatty Acid Supplementation

    PubMed Central

    Skulas-Ray, Ann C.; Flock, Michael R.; Richter, Chesney K.; Harris, William S.; West, Sheila G.; Kris-Etherton, Penny M.

    2015-01-01

    The role of the long-chain omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in lipid metabolism and inflammation has been extensively studied; however, little is known about the relationship between docosapentaenoic acid (DPA, 22:5 n-3) and inflammation and triglycerides (TG). We evaluated whether n-3 DPA content of red blood cells (RBC) was associated with markers of inflammation (interleukin-6 (IL-6), tumor necrosis factor ? (TNF-?), and C-reactive protein (CRP) and fasting TG prior to n-3 supplementation in two studies (Study 1: n = 115, aged 20–44 years, body mass index (BMI) 20–30 kg/m2, TG = 34–176 mg/dL; Study 2: n = 28, aged 22–65 years, BMI 24–37 kg/m2, TG = 141–339 mg/dL). We also characterized the dose-response effects of n-3 fatty acid supplementation on RBC n-3 DPA after five months of supplementation with fish oil (Study 1: 0, 300, 600, 900, and 1800 mg/day EPA + DHA) and eight weeks of prescription n-3 ethyl esters (Study 2: 0, 850, and 3400 mg/day EPA + DHA). In Study 1, RBC n-3 DPA was inversely correlated with CRP (R2 = 36%, p < 0.001) and with fasting TG (r = ?0.30, p = 0.001). The latter finding was replicated in Study 2 (r = ?0.33, p = 0.04). In both studies, n-3 supplementation significantly increased RBC n-3 DPA dose-dependently. Relative increases were greater for Study 1, with increases of 29%–61% vs. 14%–26% for Study 2. The associations between RBC n-3 DPA, CRP, and fasting TG may have important implications for the prevention of atherosclerosis and chronic inflammatory diseases and warrant further study. PMID:26247967

  8. Adventures in transformations: TG, TA, oh my! (Poster abstract)

    NASA Astrophysics Data System (ADS)

    Ciocca, M.

    2015-12-01

    (Abstract only) AAVSO made available, through the great volunteer work of Gordon Myers and George Silvis, two very useful tools, Transform Generator and Transform Applier (TG and TA) for transforming instrumental magnitudes to the standard system. I will juxtapose the steps necessary to obtain transformation parameters "the old fashion way" and how can the same result be achieved with these two tools. I will present transformation parameters for the Eastern Kentucky University (EKU) telescope and obtained with the standard field M67. These parameters were applied to photometric results for AE Uma, a short-period, high-amplitude delta Scuti star (Period ~ 0.086 d).

  9. Effects of dietary zinc and copper supplementation on serum triglyceride, total-cholesterol and HDL-cholesterol concentrations on young Sprague Dawley male rats

    SciTech Connect

    Frimpong, N.A.; Magee, A.C.

    1986-03-01

    To determine the effects of the level of zinc (Zn) and copper (Cu) supplementation and of Zn/Cu ratio on serum triglycerides (TG), total-cholesterol (TC), and HDL-cholesterol (HDL-C) concentrations, groups of weanling male Sprague Dawley rats were fed diets containing 4 levels of Cu (0, 0.56, 1.68, and 5.04 ppm) and 4 levels of Zn (0, 5, 10 and 20 ppm) for 6 weeks (Low supplementation, Expt I), or a high Zn and Cu supplements each at 4 levels (0, 5.6, 16.8, and 50.4 ppm Cu, plus 0, 50, 100, and 200 ppm Zn) for 6 weeks (Expt II). The effects of Zn/Cu ratios on the parameters were evaluated by combining data from Expt I and Expt II treatments with the same Zn/Cu ratios but different levels of Zn and Cu. Results of the combined data indicated that an increase in dietary Zn was associated with significant (p less than or equal to 0.01) increase in serum triglyceride concentrations, while an increase in dietary Cu was associated with significant (p less than or equal to 0.01) decrease in serum TC and HDL-C concentrations. Dietary Zn/Cu ratios had no significant effect on serum lipids. There is the indication that the absolute levels of the minerals in the diet may be more important in lipid metabolism. These results are in agreement with previous reports.

  10. Interactions of triglycerides with phospholipids: Incorporation into the bilayer structure and formation of emulsions

    SciTech Connect

    Hamilton, J.A. )

    1989-03-21

    Interactions of carbonyl {sup 13}C-enriched triacylglycerols (TG) with phospholipid bilayers were studied by {sup 13}C NMR spectroscopy. In spectra of DPPC vesicles with TG at 40-50{degree}C, both triolein (TO) and tripalmitin (TP) had narrow carbonyl resonances, indicative of rapid motions, and chemical shifts indicative of H bonding of the TG carbonyls with solvent (H{sub 2}O) at the aqueous interfaces of the vesicle bilayer. Below the phase transition temperature of the DPPC/TG vesicles, most phospholipid peaks broadened markedly. In DPPC vesicles with TP, the TP carbonyl peaks broadened beyond detection below the transition, whereas in vesicles with TO, the TO carbonyl peaks showed little change in line width or chemical shift and no change in the integrated intensity. These properties (extent of solubility in the PC surface, conformation, solvent accessibility, and molecular mobility) may be important for enzymatic hydrolysis and protein-mediated transfer of TG. In gel-phase DPPC, the molecular mobility of the TG depends on the nature of the TG acyl chains. In the DPPC/TG mixtures studied, attempts to incorporate TG in excess of the bilayer solubility resulted in production of emulsion particles. The significance of these results for TG metabolism is discussed.

  11. Common variants associated with plasma triglycerides and risk for coronary artery disease

    PubMed Central

    Do, Ron; Willer, Cristen J.; Schmidt, Ellen M.; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ay?e; Den Hertog, Heleen M.; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tõnu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Åsa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K.E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Müller-Nurasyid, Martina; Nolte, Ilja M.; O'Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S.F.; Döring, Angela; Elliott, Paul; Epstein, Stephen E.; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J.P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J.F.; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D.; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V.M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stan?áková, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; März, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Njølstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E.H.; Sheu, Wayne H-H; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H.R.; Altshuler, David

    2013-01-01

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiologic studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P<5×10?8 for each) to examine the role of triglycerides on risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglycerides, and show that the direction and magnitude of both are factors in determining CAD risk. Second, we consider loci with only a strong magnitude of association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol, a polymorphism's strength of effect on triglycerides is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. PMID:24097064

  12. Open TG-GATEs: a large-scale toxicogenomics database.

    PubMed

    Igarashi, Yoshinobu; Nakatsu, Noriyuki; Yamashita, Tomoya; Ono, Atsushi; Ohno, Yasuo; Urushidani, Tetsuro; Yamada, Hiroshi

    2015-01-01

    Toxicogenomics focuses on assessing the safety of compounds using gene expression profiles. Gene expression signatures from large toxicogenomics databases are expected to perform better than small databases in identifying biomarkers for the prediction and evaluation of drug safety based on a compound's toxicological mechanisms in animal target organs. Over the past 10 years, the Japanese Toxicogenomics Project consortium (TGP) has been developing a large-scale toxicogenomics database consisting of data from 170 compounds (mostly drugs) with the aim of improving and enhancing drug safety assessment. Most of the data generated by the project (e.g. gene expression, pathology, lot number) are freely available to the public via Open TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System). Here, we provide a comprehensive overview of the database, including both gene expression data and metadata, with a description of experimental conditions and procedures used to generate the database. Open TG-GATEs is available from http://toxico.nibio.go.jp/english/index.html. PMID:25313160

  13. Calculations of phase equilibria for mixtures of triglycerides, fatty acids, and their esters in lower alcohols

    NASA Astrophysics Data System (ADS)

    Stepanov, D. A.; Ermakova, A.; Anikeev, V. I.

    2011-01-01

    The objects of study were mixtures containing triglycerides and lower alcohols and also the products of the transesterification of triglycerides, glycerol and fatty acid esters. The Redlich-Kwong-Soave equation of state was used as a thermodynamic model for the phase state of the selected mixtures over wide temperature, pressure, and composition ranges. Group methods were applied to determine the critical parameters of pure substances and their acentric factors. The parameters obtained were used to calculate the phase diagrams and critical parameters of mixtures containing triglycerides and lower alcohols and the products of the transesterification of triglycerides, glycerol and fatty acid esters, at various alcohol/oil ratios. The conditions of triglyceride transesterification in various lower alcohols providing the supercritical state of reaction mixtures were selected.

  14. Medium chain triglycerides (MCT) in aging and arteriosclerosis.

    PubMed

    Kaunitz, H

    1986-01-01

    Some of the nutritional work with triglycerides consisting mainly of C8 and C10 fatty acids (MCT) lends itself to speculations about their influence on arteriosclerosis. Arteriosclerosis is thought to be part of the normal aging process which is due to age associated molecular biological changes. The lipid theory of arteriosclerosis is rejected. Pertinent studies with MCT include these observations. Feeding of MCT to rats resulted in animals of low body weight, small fat deposits and excellent survival rate. This deserves emphasis because of the beneficial influence of low body weight on aging and arteriosclerosis. MCT feeding was associated with low linoleate and low tocopherol requirements in rats. This may lead to reduced formation of those linoleate derived prostaglandins which favor thrombosis formation. Lower linoleate requirements may also lead to the presence of fewer uncontrolled free radicals in the cells. MCT feeding is associated with low levels of serum and liver cholesterol involving speculations that tissue conditions are such that an adaptive increase of cholesterol is unnecessary. The Demographic Yearbook of the United Nations (1978) reported that Sri Lanka has the lowest death rate from ischemic heart disease. Sri Lanka is the only of the countries giving reliable data where coconut oil (containing over 50% medium chain fatty acids) is the main dietary fat. PMID:3519928

  15. The mechanism of protein release from triglyceride microspheres.

    PubMed

    Zaky, A; Elbakry, A; Ehmer, A; Breunig, M; Goepferich, A

    2010-10-15

    The purpose of this study was to reveal factors that have an impact on the protein release kinetics from triglyceride microspheres prepared by spray congealing. We investigated the effect of protein particle size, morphology and distribution on protein release from microspheres by confocal laser scanning microscopy (CLSM)(.) The microspheres were loaded with three types of model particles made of FITC-labeled bovine serum albumin: freeze dried protein, spherical particles obtained by precipitation in the presence of PEG and micronized material. Investigation by light microscopy and laser light diffraction revealed that the freeze dried material consisted mainly of app. 29 ?m elongated shaped particles. The precipitated BSA consisted mainly of 9.0 ?m diameter spherically shaped particles while the micronized protein prepared by jet milling consisted of 4.9 ?m sized rounded particles of high uniformity. Microspheres were embedded into a cold-curing resin and cut with a microtome. Subsequent investigation by CLSM revealed major differences of distribution of the polydisperse protein particles inside the microsphere sections depending on the type of BSA that was used. Particles of micronized and precipitated protein were distributed almost throughout the microsphere cross section. The protein distribution had a marked impact on the release kinetics in phosphate buffer. Large protein particles led to a considerably faster release than small ones. By staining the release medium we demonstrated that in all three cases there was a strong correlation between protein release and buffer intrusion. PMID:20659511

  16. Validity of a portable glucose, total cholesterol, and triglycerides multi-analyzer in adults.

    PubMed

    Coqueiro, Raildo da Silva; Santos, Mateus Carmo; Neto, João de Souza Leal; Queiroz, Bruno Morbeck de; Brügger, Nelson Augusto Jardim; Barbosa, Aline Rodrigues

    2014-07-01

    This study investigated the accuracy and precision of the Accutrend Plus system to determine blood glucose, total cholesterol, and plasma triglycerides in adults and evaluated its efficiency in measuring these blood variables. The sample consisted of 53 subjects (? 18 years). For blood variable laboratory determination, venous blood samples were collected and processed in a Labmax 240 analyzer. To measure blood variables with the Accutrend Plus system, samples of capillary blood were collected. In the analysis, the following tests were included: Wilcoxon and Student's t-tests for paired samples, Lin's concordance coefficient, Bland-Altman method, receiver operating characteristic curve, McNemar test, and k statistics. The results show that the Accutrend Plus system provided significantly higher values (p ? .05) of glucose and triglycerides but not of total cholesterol (p > .05) as compared to the values determined in the laboratory. However, the system showed good reproducibility (Lin's coefficient: glucose = .958, triglycerides = .992, total cholesterol = .940) and high concordance with the laboratory method (Lin's coefficient: glucose = .952, triglycerides = .990, total cholesterol = .944) and high sensitivity (glucose = 80.0%, triglycerides = 90.5%, total cholesterol = 84.4%) and specificity (glucose = 100.0%, triglycerides = 96.9%, total cholesterol = 95.2%) in the discrimination of high values of the three blood variables analyzed. It could be concluded that despite the tendency to overestimate glucose and triglyceride levels, a portable multi-analyzer is a valid alternative for the monitoring of metabolic disorders and cardiovascular risk factors. PMID:23871994

  17. Glucagon-Like Peptide 2 (GLP-2) Stimulates Postprandial Chylomicron Production and Postabsorptive Release of Intestinal Triglyceride Storage Pools via Induction of Nitric Oxide Signaling in Male Hamsters and Mice.

    PubMed

    Hsieh, Joanne; Trajcevski, Karin E; Farr, Sarah L; Baker, Christopher L; Lake, Elizabeth J; Taher, Jennifer; Iqbal, Jahangir; Hussain, Mahmood M; Adeli, Khosrow

    2015-10-01

    The intestinal overproduction of apolipoprotein B48 (apoB48)-containing chylomicron particles is a common feature of diabetic dyslipidemia and contributes to cardiovascular risk in insulin resistant states. We previously reported that glucagon-like peptide-2 (GLP-2) is a key endocrine stimulator of enterocyte fat absorption and chylomicron output in the postprandial state. GLP-2's stimulatory effect on chylomicron production in the postabsorptive state has been confirmed in human studies. The mechanism by which GLP-2 regulates chylomicron production is unclear, because its receptor is not expressed on enterocytes. We provide evidence for a key role of nitric oxide (NO) in mediating the stimulatory effects of GLP-2 during the postprandial and postabsorptive periods. Intestinal chylomicron production was assessed in GLP-2-treated hamsters administered the pan-specific NO synthase (NOS) inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), and in GLP-2-treated endothelial NOS knockout mice. L-NAME blocked GLP-2-stimulated apoB48 secretion and reduced triglycerides (TGs) in the TG-rich lipoprotein (TRL) fraction of the plasma in the postprandial state. Endothelial NOS-deficient mice were resistant to GLP-2 stimulation and secreted fewer large apoB48-particles. When TG storage pools were allowed to accumulate, L-NAME mitigated the GLP-2-mediated increase in TRL-TG, suggesting that NO is required for early mobilization and secretion of stored TG and preformed chylomicrons. Importantly, the NO donor S-nitroso-L-glutathione was able to elicit an increase in TRL-TG in vivo and stimulate chylomicron release in vitro in primary enterocytes. We describe a novel role for GLP-2-mediated NO-signaling as a critical regulator of intestinal lipid handling and a potential contributor to postprandial dyslipidemia. PMID:26132919

  18. Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations

    SciTech Connect

    Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

    2003-08-15

    Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting ApoAV is a potent triglyceride modulator despite its low concentration. Together, these data indicate that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.

  19. Liver triglyceride accumulation after chronic ethanol administration: a possible protective role of metadoxina and ubiquinone.

    PubMed

    Marchi, S; Polloni, A; Costa, F; Bellini, M; Bonifazi, V; Tumino, E; Grassi, B; Romano, M R; De Bartolo, G; Bertelli, A

    1990-01-01

    Hepatoprotective actions of metadoxina and ubiquinone have been studied in alcoholic rats by evaluating hepatic triglyceride accumulation and serum biochemical parameters of liver function. The two drug-treated groups displayed significantly lower triglyceride concentrations as compared to the ethanol-treated group. No significant differences were found among the two drug-treated and the control groups. Electron-microscopic abnormalities were found only in ethanol-treated rats. Serum biochemical parameters of liver function did not show any significant difference among all four groups. These results suggest a possible protective role of metadoxina and ubiquinone in ethanol-induced liver triglyceride accumulation. PMID:2283204

  20. Enhanced caffeine-induced Ca2+ release in the 3xTg-AD mouse

    E-print Network

    Chen, Zhongping

    Enhanced caffeine-induced Ca2+ release in the 3xTg-AD mouse model of Alzheimer's disease Ian FTg-AD). Application of caffeine to mutant presenilin-1 knock-in neurons (PS1KI) and 3xTg-AD neurons evoked a peak rise are greater in both PS1KI and 3xTg- AD neurons as calculated by the integral of the caffeine- induced Ca2

  1. Esterification kinetics of triglycerides in n-hexane catalyzed by an immobilized lipase 

    E-print Network

    Gomez Ruiz, Alejandro

    1998-01-01

    The kinetics of enzyme-catalyzed esterification of triglycerides over immobilized lipase in n-hexane was investigated. The reaction kinetics were described in terms of a mechanism developed following the Langmuir-Hinshelwood-Hougen-Watson (LHHW...

  2. Antioxidant capacity and stability of liposomes containing a triglyceride derivative of lipoic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The multi-functional nutritional agent lipoic acid offers numerous beneficial effects to oxidatively stressed tissues. Lipoic acid was enzymatically incorporated into a triglyceride in conjunction with oleic acid, creating lipoyl dioleoylglycerol, and then chemically reduced to form dihydrolipoyl d...

  3. Lapacho tea (Tabebuia impetiginosa) extract inhibits pancreatic lipase and delays postprandial triglyceride increase in rats.

    PubMed

    Kiage-Mokua, Beatrice Nyanchama; Roos, Nils; Schrezenmeir, Jürgen

    2012-12-01

    Earlier work in our laboratory indicated that ethanolic extracts of Tabebuia impetiginosa, Arctium lappa L., Calendula officinalis, Helianthus annuus, Linum usitatissimum and L. propolis, inhibit pancreatic lipase in vitro. In a follow-up study we assessed their effects on plasma triglycerides in rats fed on a fatty meal. Extracts, orlistat or only ethanol were given orally to the rats together with the test meal and the rate of increase of postprandial triglycerides was assessed over 4?h. Clearing of the triglycerides from the blood compartment was abolished by inhibiting lipoprotein lipase with Triton WR-1339. Our results showed that out of all the extracts, the bark of Tabebuia impetiginosa led to a significant delay in the postprandial increase of plasma triglycerides. However, lapachol, which is contained in the bark of Tabebuia impetiginosa and soluble in ethanol, had no lipase inhibitory effect in vitro and hence this substance did not seem to mediate the pertinent effect. PMID:22431070

  4. Inhibition of apolipoprotein B and triglyceride secretion in human hepatoma cells (HepG2).

    PubMed

    Haghpassand, M; Wilder, D; Moberly, J B

    1996-07-01

    Apolipoprotein B (apoB), the major protein component of triglyceride-rich lipoproteins, is assembled into a lipoprotein particle via a complex, multistep process. Recent studies indicate that triglyceride-rich lipoprotein assembly requires the activity of the heterodimeric protein, microsomal triglyceride transfer protein (MTP). We identified a novel inhibitor of apolipoprotein B secretion using the human hepatoma cell line, HepG2. CP-10447, a derivative of the hypnotic drug methaqualone (Quaalude), inhibited apoB secretion from HepG2 cells with an IC50 of approximately 5 microM. CP-10447 also inhibited apoB secretion from Caco-2 cells, a model of intestinal lipoprotein production. In experiments using [3H]glycerol as a precursor for triglyceride synthesis, CP-10447 (20 microM) inhibited radiolabeled triglyceride secretion by approximately 83% (P < 0.0001) in HepG2 cells and 76% (P < 0.05) in Caco-2 cells with no effect on radiolabel incorporation into cellular triglyceride, indicating that CP-10447 inhibited triglyceride secretion without affecting triglyceride synthesis. RNA solution hybridization assay indicated that CP-10447 did not affect apoB or apoA-I mRNA levels. Pulse-chase experiments in HepG2 cells confirmed that CP-10447 inhibited the secretion of apoB (not its synthesis) without affecting secretion of total proteins or albumin and suggested that CP-10447 stimulates the early intracellular degradation of apoB in the endoplasmic reticulum (ER). Further studies demonstrated that CP-10447 is a potent inhibitor of human liver microsomal triglyceride transfer activity (IC50 approximately 1.7 microM) in an in vitro assay containing artificial liposomes and partially purified human MTP. These data suggest that CP-10447 may inhibit apoB and triglyceride secretion by inhibiting MTP activity and stimulating the early ER degradation of apoB. CP-10447 should provide a useful tool for further study of the mechanisms of apoB secretion and triglyceride-rich lipoprotein assembly. PMID:8827519

  5. Bleed of and biologic response to triglyceride filler used in radiolucent breast implants.

    PubMed

    Young, V L; Lund, H; Ueda, K; Pidgeon, L; Schorr, M W; Kreeger, J

    1996-05-01

    Radiolucent breast implants filled with triglyceride oil have recently entered limited clinical trials. To investigate the questions of oil bleed and the fate of triglycerides that might escape from ruptured breast implants, experiments reported here used peanut oil labeled with radioisotopes so that it could be traced in the urine, feces, and organs of two groups of rabbits. In one experiment, 18 rabbits were implanted with peanut oil-filled implants labeled with tritium to determine whether triglycerides diffuse across silicone elastomer shells. In another experiment, 19 rabbits were injected with 14C-labeled peanut oil to study what might happen to the oil if an implant ruptures. At the end of the follow-up period, we measured radioisotope levels in tissue samples taken from the periprosthetic capsule or injection site of each rabbit, as well as from major organs and the subcutaneous fat on the dorsum opposite the experimental site. One experiment revealed that triglycerides do bleed across the implant shells. Tritium levels were highest in the implant capsule, the omentum, the aorta, and the subcutaneous fat on the nonexperimental side. In the experiment simulating implant rupture, 14C levels were above the background radiation count at the injection site and in the same tissue sites as in the bleed experiment. Both in vivo radiolabeling studies indicate that triglycerides freed from implants by means of bleed or rupture would be absorbed, metabolized, and either excreted or redistributed to the body's normal fat storage sites if they are not needed for energy. In a third in vitro experiment, triglyceride oil specimens were inoculated with various microorganisms associated with wound infections: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, and diphtheroids. The data demonstrate that neutral triglycerides used as a breast implant filler do not support growth of common infection-producing bacteria and suggest that triglycerides may have bactericidal properties. PMID:8628800

  6. Long-term therapeutic silencing of miR-33 increases circulating triglyceride levels and hepatic lipid accumulation in mice

    PubMed Central

    Goedeke, Leigh; Salerno, Alessandro; Ramírez, Cristina M; Guo, Liang; Allen, Ryan M; Yin, Xiaoke; Langley, Sarah R; Esau, Christine; Wanschel, Amarylis; Fisher, Edward A; Suárez, Yajaira; Baldán, Angel; Mayr, Manuel; Fernández-Hernando, Carlos

    2014-01-01

    Plasma high-density lipoprotein (HDL) levels show a strong inverse correlation with atherosclerotic vascular disease. Previous studies have demonstrated that antagonism of miR-33 in vivo increases circulating HDL and reverse cholesterol transport (RCT), thereby reducing the progression and enhancing the regression of atherosclerosis. While the efficacy of short-term anti-miR-33 treatment has been previously studied, the long-term effect of miR-33 antagonism in vivo remains to be elucidated. Here, we show that long-term therapeutic silencing of miR-33 increases circulating triglyceride (TG) levels and lipid accumulation in the liver. These adverse effects were only found when mice were fed a high-fat diet (HFD). Mechanistically, we demonstrate that chronic inhibition of miR-33 increases the expression of genes involved in fatty acid synthesis such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in the livers of mice treated with miR-33 antisense oligonucleotides. We also report that anti-miR-33 therapy enhances the expression of nuclear transcription Y subunit gamma (NFYC), a transcriptional regulator required for DNA binding and full transcriptional activation of SREBP-responsive genes, including ACC and FAS. Taken together, these results suggest that persistent inhibition of miR-33 when mice are fed a high-fat diet (HFD) might cause deleterious effects such as moderate hepatic steatosis and hypertriglyceridemia. These unexpected findings highlight the importance of assessing the effect of chronic inhibition of miR-33 in non-human primates before we can translate this therapy to humans. PMID:25038053

  7. Allopregnanolone restores hippocampal-dependent learning and memory and neural progenitor survival in aging 3xTgAD and nonTg mice

    PubMed Central

    Singh, Chanpreet; Liu, Lifei; Wang, Jun Ming; Irwin, Ronald W.; Yao, Jia; Chen, Shuhua; Henry, Sherry; Thompson, Richard F.; Brinton, Roberta Diaz

    2011-01-01

    We previously demonstrated that allopregnanolone (AP?) increased proliferation of neural progenitor cells and reversed neurogenic and cognitive deficits prior to AD pathology (Wang et al., 2005; 2010). Herein, we determined efficacy of AP? to restore neural progenitor cell survival and associative learning and memory subsequent to AD pathology in male 3xTgAD mice and their non-transgenic (nonTg) counterparts. AP? significantly increased survival of BrdU+ cells and hippocampal-dependent associative learning and memory in 3xTgAD mice in the presence of intraneuronal A? whereas AP? was ineffective subsequent to development of extraneuronal A? plaques. Restoration of hippocampal-dependent associative learning was maximal by the first day and sustained throughout behavioral training. Learning and memory function in AP?-treated 3xTgAD mice was 100% greater than vehicle-treated and comparable to maximal normal nonTg performance. In aged 15-month-old nonTg mice, AP? significantly increased survival of BrdU+ cells and hippocampal-dependent associative learning and memory. Results provide preclinical evidence that AP? promoted survival of newly generated cells and restored cognitive performance in the pre-plaque phase of AD pathology and in late-stage normal aging. PMID:21803451

  8. Association of the Endotoxin Antagonist E5564 with High-Density Lipoproteins In Vitro: Dependence on Low-Density and Triglyceride-Rich Lipoprotein Concentrations

    PubMed Central

    Wasan, Kishor M.; Sivak, Olena; Cote, Richard A.; MacInnes, Aaron I.; Boulanger, Kathy D.; Lynn, Melvyn; Christ, William J.; Hawkins, Lynn D.; Rossignol, Daniel P.

    2003-01-01

    The objective of this study was to determine the distribution profile of the novel endotoxin antagonist E5564 in plasma obtained from fasted human subjects with various lipid concentrations. Radiolabeled E5564 at 1 ?M was incubated in fasted plasma from seven human subjects with various total cholesterol (TC) and triglyceride (TG) concentrations for 0.5 to 6 h at 37°C. Following these incubations, plasma samples were separated into their lipoprotein and lipoprotein-deficient fractions by ultracentrifugation and were assayed for E5564 radioactivity. TC, TG, and protein concentrations in each fraction were determined by enzymatic assays. Lipoprotein surface charge within control and phosphatidylinositol-treated plasma and E5564’s influence on cholesteryl ester transfer protein (CETP) transfer activity were also determined. We observed that the majority of E5564 was recovered in the high-density lipoprotein (HDL) fraction. We further observed that incubation in plasma with increased levels of TG-rich lipoprotein (TRL) lipid (TC and TG) concentrations resulted in a significant increase in the percentage of E5564 recovered in the TRL fraction. In further experiments, E5564 was preincubated in human TRL. Then, these mixtures were incubated in hypolipidemic human plasma for 0.5 and 6 h at 37°C. Preincubation of E5564 in purified TRL prior to incubation in human plasma resulted in a significant decrease in the percentage of drug recovered in the HDL fraction and an increase in the percentage of drug recovered in the TRL and low-density lipoprotein fractions. These findings suggest that the majority of the drug binds to HDLs. Preincubation of E5564 in TRL prior to incubation in normolipidemic plasma significantly decreased the percentage of drug recovered in the HDL fraction. Modifications to the lipoprotein negative charge did not alter the E5564 concentration in the HDL fraction. In addition, E5564 does not influence CETP-mediated transfer activity. Information from these studies could be used to help identify the possible components of lipoproteins which influence the interaction of E5564 with specific lipoprotein particles. PMID:12936976

  9. Defective macroautophagic turnover of brain lipids in the TgCRND8 Alzheimer mouse model: prevention by correcting lysosomal proteolytic deficits

    PubMed Central

    Stavrides, Philip; Saito, Mitsuo; Kumar, Asok; Rodriguez-Navarro, Jose A.; Pawlik, Monika; Huo, Chunfeng; Walkley, Steven U.; Saito, Mariko; Cuervo, Ana M.

    2014-01-01

    Autophagy, the major lysosomal pathway for the turnover of intracellular organelles is markedly impaired in neurons in Alzheimer’s disease and Alzheimer mouse models. We have previously reported that severe lysosomal and amyloid neuropathology and associated cognitive deficits in the TgCRND8 Alzheimer mouse model can be ameliorated by restoring lysosomal proteolytic capacity and autophagy flux via genetic deletion of the lysosomal protease inhibitor, cystatin B. Here we present evidence that macroautophagy is a significant pathway for lipid turnover, which is defective in TgCRND8 brain where lipids accumulate as membranous structures and lipid droplets within giant neuronal autolysosomes. Levels of multiple lipid species including several sphingolipids (ceramide, ganglioside GM3, GM2, GM1, GD3 and GD1a), cardiolipin, cholesterol and cholesteryl esters are elevated in autophagic vacuole fractions and lysosomes isolated from TgCRND8 brain. Lipids are localized in autophagosomes and autolysosomes by double immunofluorescence analyses in wild-type mice and colocalization is increased in TgCRND8 mice where abnormally abundant GM2 ganglioside-positive granules are detected in neuronal lysosomes. Cystatin B deletion in TgCRND8 significantly reduces the number of GM2-positive granules and lowers the levels of GM2 and GM3 in lysosomes, decreases lipofuscin-related autofluorescence, and eliminates giant lipid-containing autolysosomes while increasing numbers of normal-sized autolysosomes/lysosomes with reduced content of undigested components. These findings have identified macroautophagy as a previously unappreciated route for delivering membrane lipids to lysosomes for turnover, a function that has so far been considered to be mediated exclusively through the endocytic pathway, and revealed that autophagic-lysosomal dysfunction in TgCRND8 brain impedes lysosomal turnover of lipids as well as proteins. The amelioration of lipid accumulation in TgCRND8 by removing cystatin B inhibition on lysosomal proteases suggests that enhancing lysosomal proteolysis improves the overall environment of the lysosome and its clearance functions, which may be possibly relevant to a broader range of lysosomal disorders beyond Alzheimer’s disease. PMID:25270989

  10. The 55?kDa tissue transglutaminase cross-linking active isoform TG induces cell death.

    PubMed

    Fraij, Bassam M

    2015-09-01

    Transamidations are calcium-dependent reactions catalyzed by transglutaminase enzymes. Tissue transglutaminase (TG2 or TGC) is a multifunctional protein with a controversial role in apoptosis. The cross-linking function of transglutaminase enzymes has been shown to play a role in cell death. Human breast cancer cell lines (MCF7 and T47D), which express low endogenous levels of transglutaminase, were transiently transfected with the cross-linking 55?kDa active TG isoform or its precursor the 80?kDa full-length TGC. The increased frequency of apoptosis correlated with the increase in transglutaminase expression and the highest rates of apoptosis were found in cells transfected with the potent TG isoform as compared to the full length TGC. The calcium ionophores A231827 and maitotoxin, which are known to induce transamidation, were found to promote apoptosis, whereas cystamine, an active transglutaminase inhibitor, blocked apoptosis due to the over-expression of the active TG isoform. This is the first time that TG has been used in cellular transfections and the results presented show that TG is a potent inducer of cell death. This finding may help to clarify the conflicting functions of TG in the induction of cell death. The TG-dependent irreversible cross-linking of intracellular proteins, a function previously assigned to TGC, represents an important biochemical event in the induction of the structural changes present in cells during apoptosis. PMID:24464646

  11. USGS Elevation Monument

    USGS Multimedia Gallery

    USGS elevation monument for a level line run from Mojave, California to Keeler, California. The line ran through such places as 18-Mile Station, Dixie, Indan Wells, Little Lake, and Olancha. Elevations were based on Benecia datum....

  12. The Space Elevator

    NASA Astrophysics Data System (ADS)

    Laubscher, Bryan E.

    2005-09-01

    The Space Elevator is conceived to be a carbon nanotube ribbon stretching from an Earth station in the ocean on the equator to far beyond geosynchronous altitude. This elevator co-rotates with the Earth. Climbers ascend the ribbon using power beamed from Earth to launch spacecraft in orbit or to other worlds. The requirements of the ribbon material, challenges to the building of the space elevator, deployment and the promise of the space elevator are briefly discussed in this paper.

  13. National Elevation Dataset

    USGS Publications Warehouse

    U.S. Geological Survey

    1999-01-01

    The National Elevation Dataset (NED) is a new raster product assembled by the U.S. Geological Survey (USGS). The NED is designed to provide national elevation data in a seamless form with a consistent datum, elevation unit, and projection. Data corrections were made in the NED assembly process to minimize artifacts, permit edge matching, and fill sliver areas of missing data.

  14. Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5.

    PubMed

    Fruchart-Najib, Jamila; Baugé, Eric; Niculescu, Loredan-Stefan; Pham, Tatiana; Thomas, Benoit; Rommens, Corinne; Majd, Zouher; Brewer, Bryan; Pennacchio, Len A; Fruchart, Jean-Charles

    2004-06-25

    Overexpression of human APOA5 in mice results in dramatically decreased plasma triglyceride levels. In this study we explored the mechanism underlying this hypotriglyceridemic effect. Initially we found that triglyceride turnover was faster in hAPOA5 transgenic mice compared to controls, and this strongly correlated with increased LPL activity in postheparin plasma. Furthermore, we show that in vitro recombinant apoAV interacts physically with lipoprotein lipase and significantly increased its activity. We show that both apoB and apoCIII are decreased in hAPOA5 transgenic mice indicating a decrease in VLDL number. To further investigate the mechanism of hAPOA5 in a hyperlipidemic background, we inter-crossed hAPOA5 and hAPOC3 transgenic mice. We found a marked decrease in VLDL triglyceride and cholesterol, as well as apolipoprotein B and CIII levels. These data indicated that apoAV induces a decrease in VLDL size by activating lipolysis and an increase of VLDL clearance. In a postprandial state, the normal triglyceride response found in wild-type mice was significantly reduced in hAPOA5 transgenics. In addition, we demonstrated that in response to this fat load in hAPOA5xhAPOC3 mice, apoAV, but not apoCIII, was redistributed from primarily HDL to VLDL. This shift of apoAV in VLDL appears to limit the increase of triglyceride by activating the lipoprotein lipase. PMID:15178420

  15. Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models.

    PubMed

    Laplante, Marc-André; Charbonneau, Alexandre; Avramoglu, Rita Kohen; Pelletier, Patricia; Fang, Xiangping; Bachelard, Hélène; Ylä-Herttuala, Seppo; Laakso, Markku; Després, Jean-Pierre; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, André

    2013-09-01

    Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II × LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis. PMID:23820620

  16. Genomic interval engineering of mice identified a novel modulator of triglyceride production

    SciTech Connect

    Zhu, Y.; Jong, M.C.; Frazer, K.A.; Gong, E.; Krauss, R.M.; Cheng, J.F.; Boffelli, D.; Rubin, E.M.

    1999-10-01

    To accelerate the biological annotation of novel genes discovered in sequenced of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450 kb region on mouse chromosome 11 which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepatic very-low density lipoprotein (VLDL) triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450 kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine and hepatic triglyceride production is of particular importance due to the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion.

  17. Metabolism of triglyceride-rich nascent rat hepatic high density lipoproteins

    SciTech Connect

    Winkler, K.E.; Marsh, J.B. )

    1989-07-01

    Nascent high density lipoprotein (HDL) and nascent very low density lipoprotein (VLDL) were isolated from rat livers that had been perfused with (3H)glycerol to label the triglyceride. When injected into intact rats, the labeled HDL-triglyceride disappeared as rapidly as the VLDL-triglyceride, with only 10% of the injected label remaining in the plasma after 30 min. The protein moiety of nascent HDL was labeled with (35S)methionine in a similar fashion and the labeled nascent HDL was separated into nonretained (NR) and retained (R) fractions by heparin-Sepharose affinity chromatography. When injected into rats, 55% of the injected label in nascent fraction NR and 72% of that in nascent fraction R was recovered from plasma at 30 min, compared to only 10% of the triglyceride label from unfractionated nascent HDL, indicating dissociation of triglyceride and apolipoprotein clearance. The plasma decay curves for both triglyceride and protein were biexponential. By 5 min, 15% of the 35S label remaining in plasma represented apoE and apoC that had been transferred from nascent HDL fractions NR and R to the d less than 1.063 g/ml fraction of plasma. Plasma HDL was labeled in vivo with (35S)methionine, separated into fractions NR and R, and the clearance of the two plasma HDL fractions was compared with that of the corresponding nascent HDL fractions. Except for a faster rate of removal of the nascent HDL fractions during the first 5 min, the serum decay curves were very similar.

  18. A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase

    PubMed Central

    Fu, Zhiyao; Abou-Samra, Abdul B.; Zhang, Ren

    2015-01-01

    Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses. PMID:26687026

  19. A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase.

    PubMed

    Fu, Zhiyao; Abou-Samra, Abdul B; Zhang, Ren

    2015-01-01

    Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses. PMID:26687026

  20. [Investigating patients with differentiated thyroid carcinoma and elevated serum thyroglobulin but negative whole-body scan].

    PubMed

    Rosário, Pedro Weslley S; Maia, Flávia Coimbra P; Barroso, Alvaro Luís; Purisch, Saulo

    2005-04-01

    Findings of elevated thyroglobulin (Tg) and a negative whole-body scan (WBS) are not uncommon during the follow-up of differentiated thyroid carcinoma. In 12% of our patients submitted to thyroidectomy and radioiodine with Tg >10 ng/ml during hypothyroidism had a negative diagnostic WBS. This finding generally corresponds to a false-negative WBS. Inadequate preparation in terms of iodine exposure and insufficient elevation of TSH should be excluded. Micrometastases which do not accumulate sufficient iodine to be detected by low radioiodine activity and the loss of the capacity to express the sodium/iodine symporter explain many cases. In patients with elevated Tg, metastases can be identified after the administration of a therapeutic radioiodine dose, with this procedure being indicated in cases with Tg >10 ng/ml during hypothyroidism or >5 ng/ml after recombinant TSH, after exclusion of lung and cervical macrometastases. In the present study, 5 of 7 patients with these criteria showed ectopic uptake on post-therapy WBS. If the post-therapy scan is negative or reveals discrete uptake in the thyroid bed, other methods (e.g. FDG PET) can be performed, and the physician should not insist on radioiodine therapy. If WBS detect lymph node metastases, surgery is indicated, while in cases of diffuse lung metastases radioiodine is indicated until the occurrence of a negative WBS or normalization of stimulated Tg levels. Patients with a positive post-therapy scan may show a significant reduction in Tg, with even complete remission in some cases after radioiodine, but the impact of this treatment on mortality remains controversial. PMID:16184253

  1. Reaction Rate Acceleration and Tg Depression of Polycyanurate Under Nanopore Confinement

    NASA Astrophysics Data System (ADS)

    Lopez, Evelyn; Simon, Sindee L.

    2015-03-01

    Material properties such as Tg and the reaction kinetics are known to deviate from the bulk when subjected to nano-sized confinement. Previous work from our laboratory on the trimerization of cyanate esters found that the reaction kinetics were faster for a monofunctional reactant compared to a difunctional monomer, whereas the Tg depression was greater for the crosslinked product of the latter compared to the low molecular weight trimer of the former. The origin of the changes in nanoconfined reaction rates differs from those that govern changes in the Tg. The research objective is to further explore the effect that confinement has on reaction kinetics and Tg using a mixture consisting of mono- and di- cyanate ester monomers. The product is an uncrosslinked polycyanurate with Mn = 5240 g/mol and PDI = 1.78. The confinement mediums are controlled pore glasses with diameters ranging from 8.1 to 111.1 nm. The nanopore-confined material was synthesized in-situ and the reaction kinetics are followed by DSC; after the reaction, the Tg values of the nanoconfined polymer where also measured by DSC. An acceleration factor of 13 and a Tg depression of 38 °C are observed for the material confined in the smallest 8.1 nm-diameter pores. The Tg depression is between those of the trimer and network previously studied, while the acceleration of the reaction rate is lower. Our results are consistent with the reaction acceleration arising from packing effects at the pore wall and the Tg depression arising from intrinsic size effects.

  2. Saccharomyces telomeres acquire single-strand TG1-3 tails late in S phase.

    PubMed

    Wellinger, R J; Wolf, A J; Zakian, V A

    1993-01-15

    Saccharomyces telomeres consist of approximately 300 bp of C1-3A/TG1-3 DNA. Nondenaturing Southern hybridization, capable of detecting approximately 60 to approximately 300 bases of TG1-3 DNA, revealed that yeast telomeres acquired and lost TG1-3 tails, the predicted intermediate in telomere replication, in a cell cycle-dependent manner. TG1-3 tails were also detected on the ends of a linear plasmid isolated from late S phase cells. In addition, a nonlinear form of this plasmid was detected: this structure migrated in two-dimensional agarose gels like a nicked circle of the same size as the linear plasmid, but had considerably more single-stranded character than a conventional nicked circle. The evidence indicates that these circles were formed by telomere-telomere interactions involving the TG1-3 tails. These data provide evidence for a cell cycle-dependent change in telomere structure and demonstrate that TG1-3 tails, generated during replication of a linear plasmid in vivo, are capable of mediating telomere-telomere interactions. PMID:8422682

  3. Aged Tg2576 mice are impaired on social memory and open field habituation tests.

    PubMed

    Deacon, R M J; Koros, E; Bornemann, K D; Rawlins, J N P

    2009-02-11

    In a previous publication [Deacon RMJ, Cholerton LL, Talbot K, Nair-Roberts RG, Sanderson DJ, Romberg C, et al. Age-dependent and -independent behavioral deficits in Tg2576 mice. Behav Brain Res 2008;189:126-38] we found that very few cognitive tests were suitable for demonstrating deficits in Tg2576 mice, an amyloid over-expression model of Alzheimer's disease, even at 23 months of age. However, in a retrospective analysis of a separate project on these mice, tests of social memory and open field habituation revealed large cognitive impairments. Controls showed good open field habituation, but Tg2576 mice were hyperactive and failed to habituate. In the test of social memory for a juvenile mouse, controls showed considerably less social investigation on the second meeting, indicating memory of the juvenile, whereas Tg2576 mice did not show this decrement.As a control for olfactory sensitivity, on which social memory relies, the ability to find a food pellet hidden under wood chip bedding was assessed. Tg2576 mice found the pellet as quickly as controls. As this test requires digging ability, this was independently assessed in tests of burrowing and directly observed digging. In line with previous results and the hippocampal dysfunction characteristic of aged Tg2576 mice, they both burrowed and dug less than controls. PMID:18977397

  4. A Toxoplasma gondii phosphoinositide phospholipase C (TgPI-PLC) with high affinity for phosphatidylinositol

    PubMed Central

    Fang, Jianmin; Marchesini, Norma; Moreno, Silvia N. J.

    2005-01-01

    The Toxoplasma gondii phosphoinositide-specific phospholipase C gene (TgPI-PLC) was cloned, sequenced and expressed in Escherichia coli and its enzymatic characteristics were investigated. TgPI-PLC is present in the genome as a single-copy gene consisting of 22 exons interrupted by 21 introns, and encodes a polypeptide of 1097 amino acids with a predicted molecular mass of 121 kDa. In addition to the conserved catalytic X and Y domains, TgPI-PLC contains an apparent N-terminal PH domain, an EF hand motif and a C-terminal C2 domain. When compared with mammalian ?-type PI-PLC, TgPI-PLC has an additional extended N-terminus and two insertions in the region between the X and Y domains, with a 31–35% identity over the whole sequence. Recombinant TgPI-PLC, as well as the native enzyme obtained from crude membrane extracts of the parasite, was more active with phosphatidylinositol than with phosphatidylinositol 4,5-bisphosphate as substrate. Indirect immunofluorescence analysis using an affinity-purified antibody against TgPI-PLC revealed that this enzyme localizes in the plasma membrane of the parasites. PMID:16288600

  5. Detection of triglycerides using immobilized enzymes in food and biological samples

    NASA Astrophysics Data System (ADS)

    Raichur, Ashish; Lesi, Abiodun; Pedersen, Henrik

    1996-04-01

    A scheme for the determination of total triglyceride (fat) content in biomedical and food samples is being developed. The primary emphasis is to minimize the reagents used, simplify sample preparation and develop a robust system that would facilitate on-line monitoring. The new detection scheme developed thus far involves extracting triglycerides into an organic solvent (cyclohexane) and performing partial least squares (PLS) analysis on the NIR (1100 - 2500 nm) absorbance spectra of the solution. A training set using 132 spectra of known triglyceride mixtures was complied. Eight PLS calibrations were generated and were used to predict the total fat extracted from commercial samples such as mayonnaise, butter, corn oil and coconut oil. The results typically gave a correlation coefficient (r) of 0.99 or better. Predictions were typically within 90% and better at higher concentrations. Experiments were also performed using an immobilized lipase reactor to hydrolyze the fat extracted into the organic solvent. Performing PLS analysis on the difference spectra of the substrate and product could enhance specificity. This is being verified experimentally. Further work with biomedical samples is to be performed. This scheme may be developed into a feasible detection method for triglycerides in the biomedical and food industries.

  6. Intercorrelations among plasma high density lipoprotein, obesity and triglycerides in a normal population

    SciTech Connect

    Albrink, M.J.; Krauss, R.M.; Lindgren, F.T.; von der Groeben, J.; Pan, S.; Wood, P.D.

    1980-01-01

    The interrelationships among fatness measures, plasma triglycerides and high density lipoproteins (HDL) were examined in 131 normal adult subjects: 38 men aged 27 to 46, 50 men aged 47 to 66, 29 women aged 27 to 46 and 24 women aged 47 to 66. None of the women were taking estrogens or oral contraceptive medication. The HDL concentration was subdivided into HDL/sub 2b/, HDL/sub 2a/ and HDL by a computerized fitting of the total schileren pattern to reference schlieren patterns. Anthropometric measures employed included skinfolds at 3 sites, 2 weight/height indices and 2 girth measurements. A high correlation was found among the various fatness measures. These measures were negatively correlated with total HDL, reflecting the negative correlation between fatness measures and HDL/sub 2/ (as the sum of HDL/sub 2a/ and /sub 2b/). Fatness measures showed no relationship to HDL/sub 3/. There was also an inverse correlation between triglyceride concentration and HDL/sub 2/. No particular fatness measure was better than any other for demonstrating the inverse correlation with HDL but multiple correlations using all of the measures of obesity improved the correlations. Partial correlations controlling for fatness did not reduce any of the significnt correlations between triglycerides and HDL/sub 2/ to insignificance. The weak correlation between fatness and triglycerides was reduced to insigifnicance when controlled for HDL/sub 2/.

  7. Endothelial inflammation correlates with subject triglycerides and waist size1 following a high fat meal2

    E-print Network

    Passerini, Tony

    fat meal2 3 Ying I. Wang; John Schulze; Nadine Raymond; Tyler Tomita; Kayan Tam; Scott I. Simon4 with PP-TGRLs, isolated from23 human serum at the peak following a moderately high-fat meal. Very low).46 The triglyceride spike following a high-fat meal is associated with transient endothelial47 dysfunction, notably

  8. Osage Orange (Maclura pomifera L.) Seed Oil Poly(?-hydroxydibutylamine) Triglycerides: Synthesis and Characterization.

    PubMed

    Harry-O'kuru, Rogers E; Tisserat, Brent; Gordon, Sherald H; Gravett, Alan

    2015-07-29

    Milled Osage orange seeds (Maclura pomifera (Raf.) Schneid) were Soxhlet extracted with hexane, and portions of the extract were treated with activated carbon before solvent removal. The crude oil was winterized and degummed by centrifugation at low temperature. Decantation of the centrifugate gave an admixture of the triglycerides and free fatty acids. The free fatty acid content of the oil was removed when portions of the admixture were diluted with hexane and shaken with cold aqueous ammonium hydroxide (0.1 M) solution. The desiccant-dried organic phase was concentrated under reduced pressure to give the cleaned Osage orange triglyceride after solvent removal by rotary evaporation at 67 °C. Epoxidation of the resulting cleaned triglyceride was effected by reaction with in situ generated peroxy performic acid in H2O2. The oxirane rings of the derivatized oil were then opened using N,N-dibutylamine catalyzed by anhydrous ZnCl2 to afford the poly(?-hydroxydibutylamine) triglyceride. The purpose of this work was to derivatize and thereby stabilize this highly unsaturated tree oil for its eventual use in lubrication applications. PMID:26189408

  9. Processing of coriander fruits for the production of essential oil, triglyceride, and high protein seed meal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Coriander (Coriandrum sativum L.) is a summer annual traditionally grown for use as a fresh green herb or as a spice. The essential oil extracted from coriander fruit is also widely used as flavoring in a variety of food products. The fatty oil (triglyceride) fraction in the seed is rich in petrosel...

  10. Effects of CETP inhibition on triglyceride-rich lipoprotein composition and apoB-48 metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cholesteryl ester transfer protein (CETP) facilitates the transfer of HDL cholesteryl ester (CE) to triglyceride-rich lipoproteins (TRL). This study aimed to determine the effects of CETP inhibition with torcetrapib on TRL composition and apoB-48 metabolism. Study subjects with low HDL cholesterol...

  11. Comprehensive Experiment--Clinical Biochemistry: Determination of Blood Glucose and Triglycerides in Normal and Diabetic Rats

    ERIC Educational Resources Information Center

    Jiao, Li; Xiujuan, Shi; Juan, Wang; Song, Jia; Lei, Xu; Guotong, Xu; Lixia, Lu

    2015-01-01

    For second year medical students, we redesigned an original laboratory experiment and developed a combined research-teaching clinical biochemistry experiment. Using an established diabetic rat model to detect blood glucose and triglycerides, the students participate in the entire experimental process, which is not normally experienced during a…

  12. Perturbations of triglycerides but not of cholesterol metabolism are prevented by anti-tumour necrosis factor treatment in rats bearing an ascites hepatoma (Yoshida AH-130).

    PubMed Central

    Dessì, S.; Batetta, B.; Spano, O.; Bagby, G. J.; Tessitore, L.; Costelli, P.; Baccino, F. M.; Pani, P.; Argilès, J. M.

    1995-01-01

    Rats transplanted with the ascites hepatoma Yoshida AH-130 developed a severely progressive cachexia, characterised by marked alterations in protein and lipid metabolism. In particular, high levels of serum triglycerides and free fatty acids were associated with altered levels and distribution of plasma cholesterol, with increased total and very low-density lipoprotein-low-density lipoprotein (VLDL-LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol. The tumour cells showed high rates of cholesterol synthesis and elevated content of free and esterified cholesterol, whereas total cholesterol synthesis was reduced in the host liver. To determine whether these perturbations could be related to the elevation of tumour necrosis factor alpha (TNF-alpha) previously shown in the AH-130 bearers (Tessitore L, Costelli P, Baccino FM 1993, Br J Cancer, 67, 15-23), either anti-TNF polyclonal antibodies or non-immune IgGs were injected daily after tumour transplantation. The anti-TNF treatment neither affected tumour growth nor prevented the serum cholesterol changes, while attenuating the hypertriglyceridaemia and the elevated serum free fatty acid levels. These data indicate that TNF does not appear to be directly involved in the altered cholesterol metabolism in AH-130 hosts, thus supporting the view that cholesterol metabolism and lipid metabolism are regulated differently during tumour growth. PMID:7577459

  13. SU-E-J-110: TG 51 Dosimetry : With Or Without Lead

    SciTech Connect

    Shah, M

    2014-06-01

    TG-51 Dosimetry: With or Without Lead. Purpose: In this project, an analytical method has been introduced for adjustment of the TG-51 recommended KQ in order to produce accurate dosimetric data for high energy photons without the lead foil. Methods: These investigations were performed using a 30 cm × 30 cm × 30 cm CIVCO water tank, A12 EXRADIN Water proof Farmer Chamber, a Standard Imaging MAX 4000 electrometer, and 1 mm thick lead foil from Standard Imaging. Complete TG-51 was performed every month with and without lead. The results were analyzed and an analytical model has been developed for comparing the values of KQ. TG-51 Table I was used to obtain KQ values. Results: The dosimetric evaluations were obtained for Varian Linear accelerators Model 21ix and 21ex. These results indicates that the measured data with lead foil in place as recommended by TG-51 is in excellent agreement (within 0.1%) with the calculated data obtained by the new model, from our dosimetry data without-lead. If equation 15 of the TG-51 report is used without any adjustments, it will lead to differences of about 1.6 % (on the average) in relative data which will Resultin differences of about 0.3 % (on the average) in the KQ Values. The KQ value for 18 MV obtained consistently with the equation of TG-51 “with lead” and “without lead” were 0.971 and 0.974, respectively. The 0.3 % higher results for KQ without lead eventually will lead to 0.3% larger output. However, by considering this model the KQ value was found to be 0.971 for dosimetry without lead. Conclusion: The analytical model that was introduced in this project was able to reproduce the dosimetric data of the high energy linear accelerators to within 0.1% without the use of the lead foil.

  14. Neuronal network activity in the hippocampus of tau transgenic (Tg4510) mice.

    PubMed

    Scott, Liam; Kiss, Tamás; Kawabe, Thomas T; Hajós, Mihály

    2016-01-01

    Development of neurofibrillary tangles in Alzheimer's disease correlates with neuronal loss and dementia. Transgenic Tg4510 mice model the tauopathy of the disease, with these mice exhibiting progressive, region-specific neuronal loss, and behavioral deficits. In the present study, neuronal network activity in the hippocampus of 7-month-old Tg4510 mice was investigated and compared with age-matched wild-type (WT) mice. Multisite field potentials were recorded using 16-site silicon probes, inserted across the hippocampus in urethane anesthetized mice. The hippocampal network theta oscillation was evaluated in these mice by stimulating the brainstem nucleus pontis oralis. Subsequently, population spikes in the dentate gyrus were identified in response to perforant path stimulation, and long-term potentiation was elicited by theta burst stimulation. Tg4510 mice showed dramatically reduced dentate gyrus population spike amplitude; however, the magnitude of theta burst stimulation-induced long-term potentiation was identical in WT and transgenic mice. WT and Tg4510 mice showed identical increase in frequency to nucleus pontis oralis stimulation, whereas absolute theta power was severely reduced in the Tg4510 animals. Because total signal power over the entire frequency band range was reduced, there was no difference in relative theta power between WT and Tg4510 mice. These presently described electrophysiological findings can be directly attributed to the drastic reduction of pyramidal/granule neurons in Tg4510 mice, which could be the main contributing factor to their impaired behavior and cognitive function. However, the remaining synapses and neuronal circuitry seem to function properly in these assays. PMID:26610388

  15. Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data

    PubMed Central

    2013-01-01

    Background The thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used. Results The kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporin’s decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one. The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energy’s values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC). Conclusion The simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the Ea values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps. PMID:23594763

  16. Genetic Predisposition to Increased Blood Cholesterol and Triglyceride Lipid Levels and Risk of Alzheimer Disease: A Mendelian Randomization Analysis

    PubMed Central

    Proitsi, Petroula; Lupton, Michelle K.; Velayudhan, Latha; Newhouse, Stephen; Fogh, Isabella; Tsolaki, Magda; Daniilidou, Makrina; Pritchard, Megan; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Williams, Julie; Stewart, Robert; Sham, Pak; Lovestone, Simon; Powell, John F.

    2014-01-01

    Background Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. Methods and Findings We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n?=?10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5×10?8 and trait specific scores using SNPs associated exclusively with each trait at p<5×10?8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR]?=?1.005, 95% CI 0.82–1.24, p?=?0.962 per 1 unit increase in HDL-c; OR?=?0.901, 95% CI 0.65–1.25, p?=?0.530 per 1 unit increase in LDL-c; OR?=?1.104, 95% CI 0.89–1.37, p?=?0.362 per 1 unit increase in triglycerides; and OR?=?0.954, 95% CI 0.76–1.21, p?=?0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance. Conclusions Genetic predisposition to increased blood cholesterol and triglyceride lipid levels is not associated with elevated LOAD risk. The observed epidemiological associations between abnormal lipid levels and LOAD risk could therefore be attributed to the result of biological pleiotropy or could be secondary to LOAD. Limitations of this study include the small proportion of lipid variance explained by the GRS, biases in case-control ascertainment, and the limitations implicit to Mendelian randomization studies. Future studies should focus on larger LOAD datasets with longitudinal sampled peripheral lipid measures and other markers of lipid metabolism, which have been shown to be altered in LOAD. Please see later in the article for the Editors' Summary PMID:25226301

  17. Hypertriglyceridemia and Cardiovascular Risk Reduction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated triglyceride (TG) levels are prevalent among the US population, often occurring in persons who are overweight or obese, or who have type 2 diabetes or the metabolic syndrome. Meta-analysis indicates that elevated TG levels may be a significant independent risk factor for coronary heart dise...

  18. The GCKR rs780094 polymorphism is associated with susceptibility of type 2 diabetes, reduced fasting plasma glucose levels, increased triglycerides levels and lower HOMA-IR in Japanese population.

    PubMed

    Onuma, Hiroshi; Tabara, Yasuharu; Kawamoto, Ryuichi; Shimizu, Ikki; Kawamura, Ryoichi; Takata, Yasunori; Nishida, Wataru; Ohashi, Jun; Miki, Tetsuro; Kohara, Katsuhiko; Makino, Hideichi; Osawa, Haruhiko

    2010-09-01

    It was recently reported that GCKR rs780094 was associated with fasting plasma glucose (FPG) and triglyceride (TG) levels in various ethnic populations (A allele for low FPG and high TG). An association between GCKR rs780094 and type 2 diabetes mellitus (T2DM) (A allele for low risk) has also been reported. We examined the association between GCKR rs780094 and T2DM in Japanese subjects by analyzing 488 cases and 398 controls. A meta-analysis was performed involving two previous association studies. We also analyzed the association between the single-nucleotide polymorphism and clinical parameters in the general Japanese population (n=1854). In the case-control study, the A allele of GCKR rs780094 was associated with a reduced risk of T2DM (odds ratio=0.711 (95% confidence interval=0.589-0.859), P=4.2 × 10(-4)). A meta-analysis confirmed the association of GCKR rs780094 with T2DM susceptibility. In the general Japanese population, subjects with the A/A genotype had lower levels of FPG, fasting plasma insulin and homeostasis model assessment of insulin resistance than those with the G/G genotype. Conversely, subjects with the A/A genotype had higher levels of TG than those with the G/G genotype. We replicated GCKR rs780094 as a marker of T2DM susceptibility in Japanese subjects. This suggests that GCKR rs780094 is a common variant for T2DM susceptibility in various ethnic groups. PMID:20574426

  19. Object recognition memory and BDNF expression are reduced in young TgCRND8 mice.

    PubMed

    Francis, Beverly M; Kim, John; Barakat, Meredith E; Fraenkl, Stephan; Yücel, Yeni H; Peng, Shiyong; Michalski, Bernadeta; Fahnestock, Margaret; McLaurin, Joanne; Mount, Howard T J

    2012-03-01

    The TgCRND8 mouse model of Alzheimer's disease exhibits progressive cortical and hippocampal ?-amyloid accumulation, resulting in plaque pathology and spatial memory impairment by 3 months of age. We tested whether TgCRND8 cognitive function is disrupted prior to the appearance of macroscopic plaques in an object recognition task. We found profound deficits in 8-week-old mice. Animals this age were not impaired on the Morris water maze task. TgCRND8 and littermate controls did not differ in their duration of object exploration or optokinetic responses. Thus, visual and motor dysfunction did not confound the phenotype. Object memory deficits point to the frontal cortex and hippocampus as early targets of functional disruption. Indeed, we observed altered levels of brain-derived neurotrophic factor (BDNF) messenger ribonucleic acid (mRNA) in these brain regions of preplaque TgCRND8 mice. Our findings suggest that object recognition provides an early index of cognitive impairment associated with amyloid exposure and reduced brain-derived neurotrophic factor expression in the TgCRND8 mouse. PMID:20447730

  20. Object recognition memory and BDNF expression are reduced in young TgCRND8 mice

    PubMed Central

    Francis, Beverly M.; Kim, John; Barakat, Meredith E.; Fraenkl, Stephan; Yücel, Yeni H.; Peng, Shiyong; Michalski, Bernadeta; Fahnestock, Margaret; McLaurin, JoAnne; Mount, Howard T.J.

    2012-01-01

    The TgCRND8 mouse model of Alzheimer’s disease exhibits progressive cortical and hippocampal ?-amyloid accumulation, resulting in plaque pathology and spatial memory impairment by 3 months of age. We tested whether TgCRND8 cognitive function is disrupted prior to the appearance of macroscopic plaques in an object recognition task. We found profound deficits in 8-week-old mice. Animals this age were not impaired on the Morris water maze task. TgCRND8 and littermate controls did not differ in their duration of object exploration or optokinetic responses. Thus, visual and motor dysfunction did not confound the phenotype. Object memory deficits point to the frontal cortex and hippocampus as early targets of functional disruption. Indeed, we observed altered levels of brain-derived neurotrophic factor (BDNF) messenger ribonucleic acid (mRNA) in these brain regions of preplaque TgCRND8 mice. Our findings suggest that object recognition provides an early index of cognitive impairment associated with amyloid exposure and reduced brain-derived neurotrophic factor expression in the TgCRND8 mouse. PMID:20447730

  1. Loaded sectioned space elevator

    NASA Astrophysics Data System (ADS)

    Sadov, Yu. A.; Nuralieva, A. B.

    2015-05-01

    New super strong materials discovered at the end of the 20th century have caused a surge of activity in work devoted to the space elevator (SE). A rather complete concept of the SE has been formulated. This concept, having many advantages, possesses, nevertheless, limited capabilities and insufficient reliability. In this paper we present a modified space elevator concept [1] that has higher reliability and extended capabilities. Such a construction is more complicated and its design is more expensive, so it can be realized only as a part of a large-scale space program. Inclusion of a space elevator in such a program will facilitate development of new technologies.

  2. 3. WEST ELEVATION; ELEVATIONS OF ROOM 'C' (DRAWING ROOM); EXTERIOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. WEST ELEVATION; ELEVATIONS OF ROOM 'C' (DRAWING ROOM); EXTERIOR ELEVATION DOORS A & B; REFLECTED PLAN PANELLED SOFFIT, DOORS A & B - Wakefield, State Route 204, Wakefield Corner, Westmoreland County, VA

  3. Light: Isometric Casing with Lens, South Elevation, North Elevation, Top ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Light: Isometric Casing with Lens, South Elevation, North Elevation, Top Plan, Base Plan; Fresnel Lens: Isometric, Elevation, Plan - Fort Washington, Fort Washington Light, Northeast side of Potomac River at Fort Washington Park, Fort Washington, Prince George's County, MD

  4. location map, floor plan, north elevation, north elevation with porch ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    location map, floor plan, north elevation, north elevation with porch removed, south elevation, building section - Chopawamsic Recreational Demonstration Area - Cabin Camp 1, Help's Quarters, Prince William Forest Park, Triangle, Prince William County, VA

  5. A combined QXRD/TG method to quantify the phase composition of hydrated Portland cements

    SciTech Connect

    Soin, Alexander V.; Catalan, Lionel J.J.; Kinrade, Stephen D.

    2013-06-15

    A new method is reported for quantifying the mineral phases in hydrated cement pastes that is based on a combination of quantitative X-ray diffractometry (QXRD) and thermogravimetry (TG). It differs from previous methods in that it gives a precise measure of the amorphous phase content without relying on an assumed stoichiometric relationship between the principal hydration products, calcium hydroxide (CH) and calcium silicate hydrate (C–S–H). The method was successfully applied to gray and white ordinary Portland cements (GOPC and WOPC, respectively) that were cured for up to 56 days. Phase distributions determined by QXRD/TG closely matched those from gray-level analysis of backscattered scanning electron microscope (BSEM) images, whereas elemental compositions obtained for the amorphous phase by QXRD/TG agreed well with those measured by quantitative energy dispersive X-ray spectroscopy (EDS)

  6. Comparison of the effects of enteral feeding with continuous and intermittent parenteral nutrition on hepatic triglyceride secretion in human beings

    SciTech Connect

    Isabel-Martinez, L.; Skinner, C.; Parkin, A.; Hall, R.I.

    1989-03-01

    Plasma triglyceride turnover was measured during steady-state conditions in 22 postoperative patients. Nine had received nutritional support with an enteral regimen, seven had received an equivalent regimen as continuous parenteral nutrition, and six received the same parenteral regimen as a cyclical infusion. After 5 days of nutritional support, each patient received an intravenous bolus of tritiated glycerol. Plasma radiolabeled triglyceride content was measured during the subsequent 24 hours. The data were analyzed by means of a simple deterministic model of plasma triglyceride kinetics and compared with the results obtained by stochastic analysis. The rates of hepatic triglyceride secretion obtained by deterministic analysis were higher than those obtained by the stochastic approach. However, the mode of delivery of the nutritional regimen did not affect the rate of hepatic triglyceride secretion regardless of the method of analysis. The results suggest that neither complete nutritional bypass of the gastrointestinal tract nor interruption of parenteral nutrition in an attempt to mimic normal eating has any effect on hepatic triglyceride secretion. Any beneficial effect that enteral feeding or cyclical parenteral nutrition may have on liver dysfunction associated with standard parenteral nutrition appears to be unrelated to changes in hepatic triglyceride secretion.

  7. Chronic Family Stress Moderates the Association between a TOMM40 Variant and Triglyceride Levels in Two Independent Caucasian Samples

    PubMed Central

    Jiang, Rong; Brummett, Beverly H.; Hauser, Elizabeth R.; Babyak, Michael A.; Siegler, Ilene C.; Singh, Abanish; Astrup, Arne; Pedersen, Oluf; Hansen, Torben; Holst, Claus; Sørensen, Thorkild I.A.; Williams, Redford B.

    2013-01-01

    TOMM40 SNP rs157580 has been associated with triglyceride levels in Genome-wide association studies (GWAS). Chronic caregiving stress moderates the association between triglyceride levels and a nearby SNP rs439401 that is associated with triglyceride levels in GWAS. Here, we report data from two independent Caucasian samples (242 U.S. women and men; 466 Danish men) testing the hypothesis that chronic family stress also moderates the association between rs157580 and triglyceride levels. The interaction of rs157580 and family stress in predicting triglyceride levels was statistically significant in the U.S. sample (p = 0.004) and marginally significant (p = 0.075) in the Danish sample. The G allele of rs157580 was associated with increased triglyceride levels among family stressed cases in both samples compared with A/A cases, but not among controls. Chronic family stress moderates the association of rs157580 variants with triglyceride levels and should be taken into account for disease risk assessment and potential intervention. PMID:23435269

  8. Physico-chemical characteristics of burfi prepared by using medium chain triglyceride rich margarines.

    PubMed

    Tiwari, Shipra; Chetana, Ramakrishna; Puttaraju, Shashikala; Khatoon, Sakina

    2014-01-01

    Medium chain triglyceride rich margarines were prepared using palm, coconut oil blends in the ratio of 80:20 (Margarine 1) and 60:40 (Margarine 2). The margarines were used to prepare burfi and compared with products prepared using commercial margarine, ghee and butter. The physicochemical characteristics such as texture, color, free fatty acid, peroxide value, saponification value, unsaponifiable matter and fatty acid composition of oils, fats and margarines were carried out. Results showed that 11.0 and 21.9% of medium chain triglycerides were present in margarine 1 and 2 respectively. The texture, colour, moisture content, peroxide value and sensory evaluation were carried out for the burfi samples. Laboratory prepared margarines improved the textural quality of burfi compared to commercial margarine, ghee and butter. The sensory analyses of the burfi samples revealed that burfi prepared from margarine 1 was more acceptable compared to commercial margarine. PMID:24426059

  9. Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism.

    PubMed

    Wang, Chao-Yung; Shie, Shian-Sen; Wen, Ming-Shien; Hung, Kuo-Chun; Hsieh, I-Chang; Yeh, Ta-Sen; Wu, Delon

    2015-01-01

    A common variant of the FTO (fat mass- and obesity-associated) gene is a risk factor for obesity. We found that mice with an adipocyte-specific deletion of FTO gained more weight than control mice on a high-fat diet. Analysis of mice lacking FTO in adipocytes fed a normal diet or adipocytes from these mice revealed alterations in triglyceride metabolism that would be expected to favor increased fatty acid storage by adipose tissue. Mice lacking FTO in adipocytes showed increased serum triglyceride breakdown and clearance, which was associated with lower serum triglyceride concentrations. In addition, lipolysis in response to ?-adrenergic stimulation was decreased in adipocytes and ex vivo adipose explants from the mutant mice. FTO is a nucleic acid demethylase that removes N(6)-methyladenosine (m(6)A) from mRNAs. We found that FTO bound to Angptl4, which encodes an adipokine that stimulates intracellular lipolysis in adipocytes. Unexpectedly, the adipose tissue of fasted or fed mice lacking FTO in adipocytes had greater Angptl4 mRNA abundance. However, after high-fat feeding, the mutant mice had less Angptl4 protein and more m(6)A-modified Angptl4 than control mice, suggesting that lack of FTO prevented the translation of Angptl4. Injection of Angptl4-encoding adenovirus into mice lacking FTO in adipocytes restored serum triglyceride concentrations and lipolysis to values similar to those in control mice and abolished excessive weight gain from a high-fat diet. These results reveal that FTO regulates fatty acid mobilization in adipocytes and thus body weight in part through posttranscriptional regulation of Angptl4. PMID:26671148

  10. (e.g. SiO2) Strong and high Tg, Tm

    E-print Network

    Katsumoto, Shingo

    effect Low-energy excitation #12;#12;Propane Propene 1-Butene 1-Pentene 3-Methylpentane Tg / K 45.5 56-Gibbs Theory) Propene 1-Butene 1-Pentene 3MP Propane #12;CS2 60 K 70 K #12;Q Q #12;Sm (Q) = Sm u (Q) + Sm (Q.5 0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16 #12;(1) CCl4, CS2, propene, propane (2) CS2 Tg (3) CRR (4

  11. Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice.

    PubMed

    Perez, Sylvia E; He, Bin; Muhammad, Nadeem; Oh, Kwang-Jin; Fahnestock, Margaret; Ikonomovic, Milos D; Mufson, Elliott J

    2011-02-01

    The cholinotrophic system, which is dependent upon nerve growth factor and its receptors for survival, is selectively vulnerable in Alzheimer's disease (AD). But, virtually nothing is known about how this deficit develops in relation to the hallmark lesions of this disease, amyloid plaques and tau containing neurofibrillary tangles. The vast majority of transgenic models of AD used to evaluate the effect of beta amyloid (A?) deposition upon the cholinotrophic system over-express the amyloid precursor protein (APP). However, nothing is known about how this system is affected in triple transgenic (3xTg)-AD mice, an AD animal model displaying A? plaque- and tangle-like pathology in the cortex and hippocampus, which receive extensive cholinergic innervation. We performed a detailed morphological and biochemical characterization of the cholinotrophic system in young (2-4 months), middle-aged (13-15 months) and old (18-20 months) 3xTg-AD mice. Cholinergic neuritic swellings increased in number and size with age, and were more conspicuous in the hippocampal-subicular complex in aged female than in 3xTg-AD male mice. Stereological analysis revealed a reduction in choline acetyltransferase (ChAT) positive cells in the medial septum/vertical limb of the diagonal band of Broca in aged 3xTg-AD mice. ChAT enzyme activity levels decreased significantly in the hippocampus of middle-aged 3xTg-AD mice compared to age-matched non-transgenic (or wild type) mice. ProNGF protein levels increased in the cortex of aged 3xTg-AD mice, whereas TrkA protein levels were reduced in a gender-dependent manner in aged mutant mice. In contrast, p75(NTR) protein cortical levels were stable but increased in the hippocampus of aged 3xTg-AD mice. These data demonstrate that cholinotrophic alterations in 3xTg-AD mice are age- and gender-dependent and more pronounced in the hippocampus, a structure more severely affected by A? plaque pathology. PMID:20937383

  12. Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice

    PubMed Central

    Perez, Sylvia E.; He, Bin; Muhammad, Nadeem; Oh, Kwang-Jin; Fahnestock, Margaret; Ikonomovic, Milos; Mufson, Elliott J.

    2010-01-01

    The cholinotrophic system, which is dependent upon nerve growth factor and its receptors for survival, is selectively vulnerable in Alzheimer's disease (AD). But, virtually nothing is known about how this deficit develops in relation to the hallmark lesions of this disease, amyloid plaques and tau containing neurofibrillary tangles. The vast majority of transgenic models of AD used to evaluate the effect of beta amyloid (A?) deposition upon the cholinotrophic system over-express the amyloid precursor protein (APP). However, nothing is known about how this system is affected in triple transgenic (3xTg)-AD mice, an AD animal model displaying A? plaque- and tangle-like pathology in the cortex and hippocampus, which receive extensive cholinergic innervation. We performed a detailed morphological and biochemical characterization of the cholinotrophic system in young (2-4 months), middle-aged (13-15 months), and old (18-20 months) 3xTg-AD mice. Cholinergic neuritic swellings increased in number and size with age, and were more conspicuous in the hippocampal-subicular complex in aged female than in 3xTg-AD male mice. Stereological analysis revealed a reduction in choline acetyltransferase (ChAT) positive cells in the medial septum/vertical limb of the diagonal band of Broca in aged 3xTg-AD mice. ChAT enzyme activity levels decreased significantly in the hippocampus of middle-aged 3xTg-AD mice compared to age-matched ntg mice. ProNGF protein levels increased in the cortex of aged 3xTg-AD mice, whereas TrkA protein levels were reduced in a gender-dependent manner in aged mutant mice. In contrast, p75NTR protein cortical levels were stable but increased in the hippocampus of aged 3xTg-AD mice. These data demonstrate that cholinotrophic alterations in 3xTg-AD mice are age and gender dependent and more pronounced in the hippocampus, a structure more severely affected with A? plaque pathology. PMID:20937383

  13. Metabolic MR imaging of regional triglyceride and creatine content in the human heart.

    PubMed

    Weiss, Kilian; Martini, Nicola; Boesiger, Peter; Kozerke, Sebastian

    2012-12-01

    An optimized echo-planar spectroscopic imaging sequence is proposed to facilitate spatial mapping of triglyceride and total creatine content in the human heart. The sequence integrates local-look field of view reduction, cardiac and respiratory gating, and dedicated reconstruction steps to account for gradient channel delays, field inhomogeneity, and phase incoherence due to residual motion. The technique is demonstrated in 12 volunteers in comparison to single voxel point-resolved spectroscopy in the septal wall at 1.5 T. Triglyceride-to-water and total creatine-to-water ratios derived from echo-planar spectroscopic imaging (0.48 ± 0.18% and 0.06 ± 0.03%) and point-resolved spectroscopy (0.52 ± 0.17% and 0.07 ± 0.02%) were found to agree well. In the septal region, intraclass correlation coefficients ranging from 0.67 to 0.72 were estimated. A relatively weak agreement (intraclass correlation coefficients: 0.34 and 0.52) was found for sectors in the lateral wall due to field gradients induced by the posterior vein and limited sensitivity of the receive coil array in this area. On the basis of the findings, it is concluded that fast spectroscopic imaging of both cardiac triglyceride and total creatine content is feasible. Shimming and sensitivity challenges in the lateral region remain, however, to be addressed. PMID:22294511

  14. Reactivity of triglycerides and fatty acids of rapeseed oil in supercritical alcohols.

    PubMed

    Warabi, Yuichiro; Kusdiana, Dadan; Saka, Shiro

    2004-02-01

    A catalyst-free biodiesel production method with supercritical methanol has been developed that allows a simple process and high yield because of simultaneous transesterification of triglycerides and methyl esterification of fatty acids. From these lines of evidence, we expected that similar results would be attained with the use of various alcohols by the supercritical treatment. However, it still remains unclear which type of reaction, transesterification or alkyl esterification, is faster. This parameter would be important in designing the optimum reaction conditions of the supercritical alcohol method. Therefore, we studied the effect of transesterification of triglycerides and esterification of fatty acids in rapeseed oil. Reaction temperature was set at 300 degrees C, and methanol, ethanol, 1-propanol, 1-butanol or 1-octanol was used as the reactant. The results showed that transesterification of triglycerides (rapeseed oil) was slower in reaction rates than alkyl esterification of fatty acids for any of the alcohols employed. Furthermore, saturated fatty acids such as palmitic and stearic acids had slightly lower reactivity than that of the unsaturated fatty acids; oleic, linoleic and linolenic. PMID:14607488

  15. Impaired intermediate-density lipoprotein triglyceride hydrolysis in familial lecithin:cholesterol acyltransferase (LCAT) deficiency.

    PubMed

    Murano, S; Shirai, K; Saito, Y; Yoshida, S; Ohta, Y; Tsuchida, H; Yamamoto, S; Asano, G; Chen, C H; Albers, J J

    1987-12-01

    A new lecithin:cholesterol acyltransferase (LCAT)-deficient family was found in Japan. In the proband, both LCAT activity and LCAT mass were deficient. The patient's parents, child, and sister, diagnosed as heterozygotes, had half-normal LCAT activity and LCAT mass. In the patient, an increase of intermediate-density lipoprotein (IDL, 1.006 less than d less than 1.019) fraction was observed. In postheparin plasma, both lipoprotein lipase and hepatic triglyceride lipase activities were low. Hydrolysis of [14C] triolein by human hepatic triglyceride lipase in patient IDL was decreased compared to that in IDL from normal postprandial serum. Preincubation of these IDL with normal plasma in the absence of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) increased the rate of hydrolysis, in the presence of DTNB, this increment was not observed. These results suggest that one cause of IDL increase in the LCAT-deficient patient might be the difficulty of hydrolysis of these lipoprotein particles by hepatic triglyceride lipase. PMID:3432999

  16. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment.

    PubMed

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; Fujimoto, Toyoshi

    2015-06-15

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf-GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD2 by RNA interference induced an increase in the amount of ATGL existing in LDs and decreased the total cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs, but palmitoylation was required only for distribution to LDs. An ELMOD2 mutant deficient in palmitoylation failed to reconstitute the ATGL transport after the ELMOD2 knockdown, indicating that distribution in LDs is indispensable to the functionality of ELMOD2. These results indicate that ELMOD2 regulates ATGL transport and cellular lipid metabolism by modulating the Arf1-COPI activity in LDs. PMID:25904333

  17. Effect of cholesterol and triglycerides levels on the rheological behavior of human blood

    NASA Astrophysics Data System (ADS)

    Moreno, Leonardo; Calderas, Fausto; Sanchez-Olivares, Guadalupe; Medina-Torres, Luis; Sanchez-Solis, Antonio; Manero, Octavio

    2015-02-01

    Important public health problems worldwide such as obesity, diabetes, hyperlipidemia and coronary diseases are quite common. These problems arise from numerous factors, such as hyper-caloric diets, sedentary habits and other epigenetic factors. With respect to Mexico, the population reference values of total cholesterol in plasma are around 200 mg/dL. However, a large proportion has higher levels than this reference value. In this work, we analyze the rheological properties of human blood obtained from 20 donors, as a function of cholesterol and triglyceride levels, upon a protocol previously approved by the health authorities. Samples with high and low cholesterol and triglyceride levels were selected and analyzed by simple-continuous and linear-oscillatory shear flow. Rheometric properties were measured and related to the structure and composition of human blood. In addition, rheometric data were modeled by using several constitutive equations: Bautista-Manero-Puig (BMP) and the multimodal Maxwell equations to predict the flow behavior of human blood. Finally, a comparison was made among various models, namely, the BMP, Carreau and Quemada equations for simple shear rate flow. An important relationship was found between cholesterol, triglycerides and the structure of human blood. Results show that blood with high cholesterol levels (400 mg/dL) has flow properties fully different (higher viscosity and a more pseudo-plastic behavior) than blood with lower levels of cholesterol (tendency to Newtonian behavior or viscosity plateau at low shear rates).

  18. Enhanced acetyl-CoA production is associated with increased triglyceride accumulation in the green alga Chlorella desiccata

    PubMed Central

    Avidan, Omri; Brandis, Alexander; Rogachev, Ilana; Pick, Uri

    2015-01-01

    Triglycerides (TAGs) from microalgae can be utilized as food supplements and for biodiesel production, but little is known about the regulation of their biosynthesis. This work aimed to test the relationship between acetyl-CoA (Ac-CoA) levels and TAG biosynthesis in green algae under nitrogen deprivation. A novel, highly sensitive liquid chromatography mass spectrometry (LC-MS/MS) technique enabled us to determine the levels of Ac-CoA, malonyl-CoA, and unacetylated (free) CoA in green microalgae. A comparative study of three algal species that differ in TAG accumulation levels shows that during N starvation, Ac-CoA levels rapidly rise, preceding TAG accumulation in all tested species. The levels of Ac-CoA in the high TAG accumulator Chlorella desiccata exceed the levels in the moderate TAG accumulators Dunaliella tertiolecta and Chlamydomonas reinhardtii. Similarly, malonyl-CoA and free CoA levels also increase, but to lower extents. Calculated cellular concentrations of Ac-CoA are far lower than reported K mAc-CoA values of plastidic Ac-CoA carboxylase (ptACCase) in plants. Transcript level analysis of plastidic pyruvate dehydrogenase (ptPDH), the major chloroplastic Ac-CoA producer, revealed rapid induction in parallel with Ac-CoA accumulation in C. desiccata, but not in D. tertiolecta or C. reinhardtii. It is proposed that the capacity to accumulate high TAG levels in green algae critically depends on their ability to divert carbon flow towards Ac-CoA. This requires elevation of the chloroplastic CoA pool level and enhancement of Ac-CoA biosynthesis. These conclusions may have important implications for future genetic manipulation to enhance TAG biosynthesis in green algae. PMID:25922486

  19. Identification and co-localization of perforin-like (TgPLP1) protein in Toxoplasma gondii bradyzoites.

    PubMed

    Shan, Dan; Qian, Weifeng; Liu, Jing; Liu, Renqiang; Liu, Qun

    2015-06-01

    For the first time, we show here that perforin-like (TgPLP1) is expressed in bradyzoites of Toxoplasma gondii. An immunofluorescence assay (IFA) and immunohistochemistry (IHC) revealed that TgPLP1 is expressed in T.?gondii-encysted and in vitro-induced bradyzoites, TgPLP1 is distributed in micronemes in a manner similar to its distribution in tachyzoites. To shed light on the function of TgPLP1 in bradyzoites, quantitative PCR revealed that the expression level of TgPLP1 gene decreased over time during differentiation into bradyzoites in vitro. This finding suggests that TgPLP1 may play a role in the rupture of tissue cysts or the maintenance of cyst structure, although the exact function of this gene in the bradyzoites is still unknown. PMID:25746893

  20. Space Elevator: Stability

    NASA Astrophysics Data System (ADS)

    Perek, Lubos

    2008-04-01

    Many papers have been published on engineering and economic aspects of the Space Elevator. The Elevator, however, is a very special and unusual astronomical body. Its behavior in space is affected not only by the attraction of the Earth and by the "centrifugal force" but also by the attraction of the Sun and the Moon, by the detailed shape of the Earth, by the presence of space debris, etc. Not all of the minor effects have been adequately studied. The size of the Space Elevator and its lack of resistance against buckling or bending require a detailed study of its stability, both in its initial phase as a geostationary (GEO) satellite as well as in its operational phase as a "sling". Lunisolar perturbations and other minor forces may affect the stability in the initial phase and will cause oscillations in the operational phase. Station-keeping thrusters will have to be mounted at selected points along the cable in order to maintain stability. In addition, the thrusters will perform local maneuvers for avoiding collisions with passing space debris. The control system of thrusters has to be adaptive, reacting fast to actual situation and rectifying the attitude of the Elevator whenever necessary. A further advantage of the thrusters is a possibility to locate the Elevator at any longitude, possibly looking for a region with minimum traffic at GEO distance. Extensive numerical simulations will have to be performed in order to determine elements of the thrusters and their control system.

  1. 60. FORWARD AIRPLANE ELEVATOR PIT WITH ELEVATOR IN RAISED POSITION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    60. FORWARD AIRPLANE ELEVATOR PIT WITH ELEVATOR IN RAISED POSITION AFT LOOKING FORWARD ON CENTERLINE SHOWING ELEVATOR GUIDES, WIREWAYS, SHEAVES, HYDRAULIC OIL TANKS AND ELEVATOR LANDING PADS. - U.S.S. HORNET, Puget Sound Naval Shipyard, Sinclair Inlet, Bremerton, Kitsap County, WA

  2. The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse model.

    PubMed

    Puri, Vanita; Wang, Xiaohai; Vardigan, Joshua D; Kuduk, Scott D; Uslaner, Jason M

    2015-07-01

    We have recently shown that the M1 muscarinic receptor positive allosteric modulator, PQCA, improves cognitive performance in rodents and non-human primates administered the muscarinic receptor antagonist scopolamine. The purpose of the present experiments was to characterize the effects of PQCA in a model more relevant to the disease pathology of Alzheimer's disease. Tg2576 transgenic mice that have elevated A? were tested in the novel object recognition task to characterize recognition memory as a function of age and treatment with the PQCA. The effects of PQCA were compared to the acetylcholinesterase inhibitor donepezil, the standard of care for Alzheimer's disease. In addition, the effect of co-administering PQCA and donepezil was evaluated. Aged Tg2576 mice demonstrated a deficit in recognition memory that was significantly attenuated by PQCA. The positive control donepezil also reversed the deficit. Furthermore, doses of PQCA and donepezil that were inactive on their own were found to improve recognition memory when given together. These studies suggest that M1 muscarinic receptor positive allosteric modulation can ameliorate memory deficits in disease relevant models of Alzheimer's disease. These data, combined with our previous findings demonstrating PQCA improves scopolamine-induced cognitive deficits in both rodents and non-human primates, suggest that M1 positive allosteric modulators have therapeutic potential for the treatment of Alzheimer's disease. PMID:25800972

  3. Cognitive and Disease-Modifying Effects of 11?-Hydroxysteroid Dehydrogenase Type 1 Inhibition in Male Tg2576 Mice, a Model of Alzheimer's Disease

    PubMed Central

    Sooy, Karen; Noble, June; McBride, Andrew; Binnie, Margaret; Yau, Joyce L. W.; Seckl, Jonathan R.; Walker, Brian R.

    2015-01-01

    Chronic exposure to elevated levels of glucocorticoids has been linked to age-related cognitive decline and may play a role in Alzheimer's disease. In the brain, 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) amplifies intracellular glucocorticoid levels. We show that short-term treatment of aged, cognitively impaired C57BL/6 mice with the potent and selective 11?-HSD1 inhibitor UE2316 improves memory, including after intracerebroventricular drug administration to the central nervous system alone. In the Tg2576 mouse model of Alzheimer's disease, UE2316 treatment of mice aged 14 months for 4 weeks also decreased the number of ?-amyloid (A?) plaques in the cerebral cortex, associated with a selective increase in local insulin-degrading enzyme (involved in A? breakdown and known to be glucocorticoid regulated). Chronic treatment of young Tg2576 mice with UE2316 for up to 13 months prevented cognitive decline but did not prevent A? plaque formation. We conclude that reducing glucocorticoid regeneration in the brain improves cognition independently of reduced A? plaque pathology and that 11?-HSD1 inhibitors have potential as cognitive enhancers in age-associated memory impairment and Alzheimer's dementia. PMID:26305888

  4. Cognitive and Disease-Modifying Effects of 11?-Hydroxysteroid Dehydrogenase Type 1 Inhibition in Male Tg2576 Mice, a Model of Alzheimer's Disease.

    PubMed

    Sooy, Karen; Noble, June; McBride, Andrew; Binnie, Margaret; Yau, Joyce L W; Seckl, Jonathan R; Walker, Brian R; Webster, Scott P

    2015-12-01

    Chronic exposure to elevated levels of glucocorticoids has been linked to age-related cognitive decline and may play a role in Alzheimer's disease. In the brain, 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) amplifies intracellular glucocorticoid levels. We show that short-term treatment of aged, cognitively impaired C57BL/6 mice with the potent and selective 11?-HSD1 inhibitor UE2316 improves memory, including after intracerebroventricular drug administration to the central nervous system alone. In the Tg2576 mouse model of Alzheimer's disease, UE2316 treatment of mice aged 14 months for 4 weeks also decreased the number of ?-amyloid (A?) plaques in the cerebral cortex, associated with a selective increase in local insulin-degrading enzyme (involved in A? breakdown and known to be glucocorticoid regulated). Chronic treatment of young Tg2576 mice with UE2316 for up to 13 months prevented cognitive decline but did not prevent A? plaque formation. We conclude that reducing glucocorticoid regeneration in the brain improves cognition independently of reduced A? plaque pathology and that 11?-HSD1 inhibitors have potential as cognitive enhancers in age-associated memory impairment and Alzheimer's dementia. PMID:26305888

  5. QUANTITATIVE DETERMINATION OF THE NUTRITIONAL STATUS OF DETRITAL MICROBIOTA AND THE GRAZING FAUNA BY TRIGLYCERIDE GLYCEROL ANALYSIS

    EPA Science Inventory

    Endogenous lipid storage components are accumulated or utilized by both microorganisms and marine invertebrates, depending upon their nutritional status. Triglycerides are commonly the lipid endogenous storage materials utilized by fungi, marine vertebrates and many invertebrates...

  6. Lymphocytic infiltration in the cutaneous lymphoma microenvironment after injection of TG1042

    PubMed Central

    2013-01-01

    Background Primary cutaneous lymphomas (CLs), characterized by an accumulation of clonal T or B lymphocytes preferentially localized in the skin, have been successfully treated with interferons (IFNs) which counterbalance the Th2-immunosuppressive state associated with this pathology. In a phase I/II clinical trial, we correlated the local immune infiltrate and the anti-tumor effects of repeated intralesional administrations of an adenovirus vector expressing human interferon-gamma (IFN-g) termed TG1042, in patients with advanced primary cutaneous T-cell lymphomas (CTCL) or multilesional cutaneous B-cell lymphomas (CBCL). Methods For each patient, variation in time of specific lymphocyte populations, defined by immunohistochemical stainings, was assessed in biopsies of injected lesions. For each patient, the change in local immune response was associated with the patient’s objective response at the end of the study. Results Immunohistochemical analyses of biopsies indicate that infiltration of CD8+ T lymphocytes and of TIA-1+ cytotoxic T-cells in lesions injected with TG1042 correlates with clinical benefit. Conclusions These data suggest for the first time that a CD8+ cytotoxic infiltrate, induced by local expression of IFN-g correlates with a clinical response. Trial registration The phase I step (TG1042.01) does not have a registration number. The phase II step (TG1042.06) registration number was NCT00394693. PMID:24063735

  7. Evaluation of the accuracy of fetal dose estimates using TG-36 data

    SciTech Connect

    Kry, Stephen F.; Starkschall, George; Antolak, John A.; Salehpour, Mohammad

    2007-04-15

    The American Association of Physicists in Medicine Radiation Therapy Committee Task Group 36 report (TG-36) provides guidelines for managing radiation therapy of pregnant patients. Included in the report are data that can be used to estimate the dose to the fetus. The purpose of this study is to evaluate the accuracy of these fetal dose estimates as compared to clinically measured values. TG-36 calculations were performed and compared with measurements of the fetal dose made in vivo or in appropriately-designed phantoms. Calculation and measurement data was collected for eight pregnant patients who underwent radiation therapy at the MD Anderson Cancer Center as well as for several fetal dose studies in the literature. The maximum measured unshielded fetal dose was 47 cGy, which was 1.5% of the prescription dose. For all cases, TG-36 calculations and measured fetal doses differed by up to a factor of 3--the ratio of the calculated to measured dose ranged from 0.34 to 2.93. On average, TG-36 calculations underestimated the measured dose by 31%. No significant trends in the relationship between the calculated and measured fetal doses were found based on the distance from, or the size of, the treatment field.

  8. Generalized second law of thermodynamics in f(T,TG) gravity

    NASA Astrophysics Data System (ADS)

    Zubair, M.; Jawad, Abdul

    2015-11-01

    We discuss the equilibrium picture of thermodynamic at the apparent horizon of FRW universe in f(T,TG) gravity, where T represents the torsion invariant and TG is the teleparallel equivalent of the Gauss-Bonnet term. It is found that one can translate the Friedmann equations to the standard form of first law of thermodynamics. We discuss GSLT in the locality of assumption that temperature of matter inside the horizon is similar to that of apparent horizon. Furthermore, we consider particular models in this theory and generate constraints on the coupling parameters for the validity of GSLT. For this purpose we set the present day values of cosmic parameters and find the possible constraints on f(T,TG) models. We also choose the power law cosmology and found that GSLT can be met in accelerated cosmic expansion. We have also presented the cosmological reconstruction of some viable f(T,TG) models and discussed the cosmic evolution and validity of GSLT.

  9. Is a distinctive single Tg a reliable indicator for the homogeneity of amorphous solid dispersion?

    PubMed

    Qian, Feng; Huang, Jun; Zhu, Qing; Haddadin, Raja; Gawel, John; Garmise, Robert; Hussain, Munir

    2010-08-16

    For an amorphous drug-polymer solid dispersion, a distinctive single T(g) intermediate of the two T(g) values of the two components has been widely considered as an indication of the mixing uniformity, which is critical for the stability of the amorphous drug against crystallization. In this study, two batches of amorphous solid dispersions consisting of BMS-A, a poorly water-soluble drug, and PVP-VA, were made by a twin-screw hot-melt extruder using different processing conditions. Both batches displayed an identical distinctive single T(g) that is consistent with the prediction of Fox equation assuming homogeneous mixing of the two components. Neither DSC nor PXRD detected any drug crystallinity in either batch. However, the two batches exhibited different physical stability against crystallization over time. The application of a Raman mapping method showed that the drug distributed over a much wider concentration range in the less stable solid dispersion. It is therefore experimentally demonstrated that, in the characterization of amorphous solid dispersions, a distinctive single T(g) may not always be a reliable indicator of homogeneity and optimal stability, and more examinations and new techniques may be required other than conventional studies. PMID:20562003

  10. Ruthenium polypyridyl TG6 dye for the sensitization of nanoparticle and nanocrystallite spherical aggregate photoelectrodes.

    PubMed

    Hosni, M; Kusumawati, Y; Farhat, S; Jouini, N; Ivansyah, A L; Martoprawiro, M A; Pauporté, Th

    2015-01-28

    A ruthenium polypyridyl dye containing a hexasulfanyl-styryl modified bipyridyl group as ancillary ligand, coded TG6, is investigated as a sensitizer for ZnO-based dye-sensitized solar cells (DSSCs). The advantages of this dye are a broad wavelength absorption spectrum, a large loading in ZnO photoelectrodes, a significantly larger extinction coefficient compared to more classical Ru-polypyridyl dyes, and the formation of less agglomerate in the pores of the ZnO layers. TG6 has been used to sensitize ZnO nanorod particle layers of high structural quality and ZnO layers made of submicrometer spheres composed of aggregated nanocrystallites and that develop an internal surface area. The latter are highly light-scattering in the visible wavelength region but more difficult to sensitize correctly. The TG6 dye has been compared with the metal-free D149 dye and has been shown more efficient for photoconversion. The best performances have been obtained by combining TG6 with the nanorod layer, the optimal power conversion efficiency being measured at 5.30% in that case. The cells have been investigated by impedance spectroscopy over a large applied voltage range. We especially show that the submicrometer sphere layers exhibit lower conductivity and lower charge collection efficiency as compared to the nanorod particle ones. PMID:25546020

  11. Apolipoprotein A-V Deficiency Results in MarkedHypertriglyceridemia Attributable to Decreased Lipolysis ofTriglyceride-Rich Lipoproteins and Removal of Their Remnants

    SciTech Connect

    Grosskopf, Itamar; Baroukh, Nadine; Lee, Sung-Joon; Kamari,Yehuda; Harats, Dror; Rubin, Edward M.; Pennacchio, Len A.; Cooper, AllenD.

    2005-09-01

    Objective--ApoAV, a newly discovered apoprotein, affectsplasma triglyceride level. To determine how this occurs, we studiedtriglyceride-rich lipoprotein (TRL) metabolism in mice deficient inapoAV. Methods and Results No significant difference in triglycerideproduction rate was found between apoa5_/_ mice and controls. Thepresence or absence of apoAV affected TRL catabolism. After the injectionof 14C-palmitate and 3H-cholesterol labeled chylomicrons and 125I-labeledchylomicron remnants, the disappearance of 14C, 3H, and 125I wassignificantly slower in apoa5_/_ mice relative to controls. This wasbecause of diminished lipolysis of TRL and the reduced rate of uptake oftheir remnants in apoa5_/_ mice. Observed elevated cholesterol level wascaused by increased high-density lipoprotein (HDL) cholesterol inapoa5_/_ mice. VLDL from apoa5_/_ mice were poor substrate forlipoprotein lipase, and did not bind to the low-density lipoprotein (LDL)receptor as well as normal very-low-density lipoprotein (VLDL). LDLreceptor levels were slightly elevated in apoa5_/_ mice consistent withlower remnant uptake rates. These alterations may be the result of thelower apoE-to-apoC ratio found in VLDL isolated from apoa5_/_mice.Conclusions These results support the hypothesis that the absence ofapoAV slows lipolysis of TRL and the removal of their remnants byregulating their apoproteins content after secretion.

  12. Age-Dependent Neuroplasticity Mechanisms in Alzheimer Tg2576 Mice Following Modulation of Brain Amyloid-? Levels

    PubMed Central

    Lilja, Anna M.; Röjdner, Jennie; Mustafiz, Tamanna; Thomé, Carina M.; Storelli, Elisa; Gonzalez, Daniel; Unger-Lithner, Christina; Greig, Nigel H.; Nordberg, Agneta; Marutle, Amelia

    2013-01-01

    The objective of this study was to investigate the effects of modulating brain amyloid-? (A?) levels at different stages of amyloid pathology on synaptic function, inflammatory cell changes and hippocampal neurogenesis, i.e. processes perturbed in Alzheimer’s disease (AD). Young (4- to 6-month-old) and older (15- to 18-month-old) APPSWE transgenic (Tg2576) mice were treated with the AD candidate drug (+)-phenserine for 16 consecutive days. We found significant reductions in insoluble A?1-42 levels in the cortices of both young and older transgenic mice, while significant reductions in soluble A?1-42 levels and insoluble A?1-40 levels were only found in animals aged 15–18 months. Autoradiography binding with the amyloid ligand Pittsburgh Compound B (3H-PIB) revealed a trend for reduced fibrillar A? deposition in the brains of older phenserine-treated Tg2576 mice. Phenserine treatment increased cortical synaptophysin levels in younger mice, while decreased interleukin-1? and increased monocyte chemoattractant protein-1 and tumor necrosis factor-alpha levels were detected in the cortices of older mice. The reduction in A?1-42 levels was associated with an increased number of bromodeoxyuridine-positive proliferating cells in the hippocampi of both young and older Tg2576 mice. To determine whether the increased cell proliferation was accompanied by increased neuronal production, the endogenous early neuronal marker doublecortin (DCX) was examined in the dentate gyrus (DG) using immunohistochemical detection. Although no changes in the total number of DCX+-expressing neurons were detected in the DG in Tg2576 mice at either age following (+)-phenserine treatment, dendritic arborization was increased in differentiating neurons in young Tg2576 mice. Collectively, these findings indicate that reducing A?1-42 levels in Tg2576 mice at an early pathological stage affects synaptic function by modulating the maturation and plasticity of newborn neurons in the brain. In contrast, lowering A? levels in Tg2576 mice when A? plaque pathology is prominent mainly alters the levels of proinflammatory cytokines and chemokines. PMID:23554921

  13. Dihydroisoxazole inhibitors of Anopheles gambiae seminal transglutaminase AgTG3

    PubMed Central

    2014-01-01

    Background Current vector-based malaria control strategies are threatened by the rise of biochemical and behavioural resistance in mosquitoes. Researching mosquito traits of immunity and fertility is required to find potential targets for new vector control strategies. The seminal transglutaminase AgTG3 coagulates male Anopheles gambiae seminal fluids, forming a ‘mating plug’ that is required for male reproductive success. Inhibitors of AgTG3 can be useful both as chemical probes of A. gambiae reproductive biology and may further the development of new chemosterilants for mosquito population control. Methods A targeted library of 3-bromo-4,5-dihydroxoisoxazole inhibitors were synthesized and screened for inhibition of AgTG3 in a fluorescent, plate-based assay. Positive hits were tested for in vitro activity using cross-linking and mass spectrometry, and in vivo efficacy in laboratory mating assays. Results A targeted chemical library was screened for inhibition of AgTG3 in a fluorescent plate-based assay using its native substrate, plugin. Several inhibitors were identified with IC50?TG3 were verified. Administration of an AgTG3 inhibitor to A. gambiae males by intrathoracic injection led to a 15% reduction in mating plug transfer in laboratory mating assays. Conclusions A targeted screen has identified chemical inhibitors of A. gambiae transglutaminase 3 (AgTG3). The most potent inhibitors are known inhibitors of human transglutaminase 2, suggesting a common binding pose may exist within the active site of both enzymes. Future efforts to develop additional inhibitors will provide chemical tools to address important biological questions regarding the role of the A. gambiae mating plug. A second use for transglutaminase inhibitors exists for the study of haemolymph coagulation and immune responses to wound healing in insects. PMID:24888439

  14. National Elevation Dataset

    USGS Publications Warehouse

    U.S. Geological Survey

    2002-01-01

    The National Elevation Dataset (NED) is a new raster product assembled by the U.S. Geological Survey. NED is designed to provide National elevation data in a seamless form with a consistent datum, elevation unit, and projection. Data corrections were made in the NED assembly process to minimize artifacts, perform edge matching, and fill sliver areas of missing data. NED has a resolution of one arc-second (approximately 30 meters) for the conterminous United States, Hawaii, Puerto Rico and the island territories and a resolution of two arc-seconds for Alaska. NED data sources have a variety of elevation units, horizontal datums, and map projections. In the NED assembly process the elevation values are converted to decimal meters as a consistent unit of measure, NAD83 is consistently used as horizontal datum, and all the data are recast in a geographic projection. Older DEM's produced by methods that are now obsolete have been filtered during the NED assembly process to minimize artifacts that are commonly found in data produced by these methods. Artifact removal greatly improves the quality of the slope, shaded-relief, and synthetic drainage information that can be derived from the elevation data. Figure 2 illustrates the results of this artifact removal filtering. NED processing also includes steps to adjust values where adjacent DEM's do not match well, and to fill sliver areas of missing data between DEM's. These processing steps ensure that NED has no void areas and artificial discontinuities have been minimized. The artifact removal filtering process does not eliminate all of the artifacts. In areas where the only available DEM is produced by older methods, then "striping" may still occur.

  15. [Complementary oligonucleotide invasion into (CA/TG)31-repetitive region of linear and circular DNA duplexes].

    PubMed

    Gasanova, V K; Riadninskaia, N V; Gaillard, C; Strauss, F; Belitski?, G A; Iakubovskaia, M G

    2010-01-01

    (CA/TG)n-repeats belong to microsatellite DNA and are the most widespread among dinucleotide repeats in mammalian genomes, occupying 0.25% of the genome. These repeats are known to be recombination "hot spots", however the molecular mechanisms of this effect are not known. We proposed that the high frequency of recombination in the repetitive regions may be due to duplex conformational characteristics resulting from a special geometry of base-stacking contacts, which permits the initiation of an invasion process of single-stranded DNA into the duplex homologous region. Here we show for the first time a DNA-DNA interaction of oligonucleotides d(CA)10 and d(TG)10 with linear and circular duplexes containing (CA/TG)31-repeats, upon incubation at 37 degrees C in the absence of proteins. Using radioactively labeled oligonucleotides, we showed that duplex-oligonucleotide interaction intensities depend on their molar ratio at a duplex concentration 30 nM. Decreasing the duplex concentration to 3 nM did not influence the intensity of oligonucleotide invasion. It was shown that more than 1%, but much less than 10% of the duplexes participate in the interaction with oligonucleotides, assuming that one molecule of the duplex interacts with one molecule of the oligonucleotide. Analysis of the kinetics of the process reveals invasion of d(CA)10 at the first minute of its incubation with the duplex, while d(TG)10 interacts with the duplex at an even higher rate. We discuss the role of DNA conformation plasticity of (CA/TG)n-repeats in the phenomenon observed, as well as its biological significance, in particular the role of CA-microsatellites in the initiation of homologous recombination. PMID:20608177

  16. Phosphorylation of a Myosin Motor by TgCDPK3 Facilitates Rapid Initiation of Motility during Toxoplasma gondii egress

    PubMed Central

    Gaji, Rajshekhar Y.; Johnson, Derrick E.; Treeck, Moritz; Wang, Mu; Hudmon, Andy; Arrizabalaga, Gustavo

    2015-01-01

    Members of the family of calcium dependent protein kinases (CDPK’s) are abundant in certain pathogenic parasites and absent in mammalian cells making them strong drug target candidates. In the obligate intracellular parasite Toxoplasma gondii TgCDPK3 is important for calcium dependent egress from the host cell. Nonetheless, the specific substrate through which TgCDPK3 exerts its function during egress remains unknown. To close this knowledge gap we applied the proximity-based protein interaction trap BioID and identified 13 proteins that are either near neighbors or direct interactors of TgCDPK3. Among these was Myosin A (TgMyoA), the unconventional motor protein greatly responsible for driving the gliding motility of this parasite, and whose phosphorylation at serine 21 by an unknown kinase was previously shown to be important for motility and egress. Through a non-biased peptide array approach we determined that TgCDPK3 can specifically phosphorylate serines 21 and 743 of TgMyoA in vitro. Complementation of the TgmyoA null mutant, which exhibits a delay in egress, with TgMyoA in which either S21 or S743 is mutated to alanine failed to rescue the egress defect. Similarly, phosphomimetic mutations in the motor protein overcome the need for TgCDPK3. Moreover, extracellular Tgcdpk3 mutant parasites have motility defects that are complemented by expression of S21+S743 phosphomimetic of TgMyoA. Thus, our studies establish that phosphorylation of TgMyoA by TgCDPK3 is responsible for initiation of motility and parasite egress from the host-cell and provides mechanistic insight into how this unique kinase regulates the lytic cycle of Toxoplasma gondii. PMID:26544049

  17. Phosphorylation of a Myosin Motor by TgCDPK3 Facilitates Rapid Initiation of Motility during Toxoplasma gondii egress.

    PubMed

    Gaji, Rajshekhar Y; Johnson, Derrick E; Treeck, Moritz; Wang, Mu; Hudmon, Andy; Arrizabalaga, Gustavo

    2015-11-01

    Members of the family of calcium dependent protein kinases (CDPK's) are abundant in certain pathogenic parasites and absent in mammalian cells making them strong drug target candidates. In the obligate intracellular parasite Toxoplasma gondii TgCDPK3 is important for calcium dependent egress from the host cell. Nonetheless, the specific substrate through which TgCDPK3 exerts its function during egress remains unknown. To close this knowledge gap we applied the proximity-based protein interaction trap BioID and identified 13 proteins that are either near neighbors or direct interactors of TgCDPK3. Among these was Myosin A (TgMyoA), the unconventional motor protein greatly responsible for driving the gliding motility of this parasite, and whose phosphorylation at serine 21 by an unknown kinase was previously shown to be important for motility and egress. Through a non-biased peptide array approach we determined that TgCDPK3 can specifically phosphorylate serines 21 and 743 of TgMyoA in vitro. Complementation of the TgmyoA null mutant, which exhibits a delay in egress, with TgMyoA in which either S21 or S743 is mutated to alanine failed to rescue the egress defect. Similarly, phosphomimetic mutations in the motor protein overcome the need for TgCDPK3. Moreover, extracellular Tgcdpk3 mutant parasites have motility defects that are complemented by expression of S21+S743 phosphomimetic of TgMyoA. Thus, our studies establish that phosphorylation of TgMyoA by TgCDPK3 is responsible for initiation of motility and parasite egress from the host-cell and provides mechanistic insight into how this unique kinase regulates the lytic cycle of Toxoplasma gondii. PMID:26544049

  18. Spontaneous loss of tolerance of autoreative B cell in Act1-deficient AM14 Tg rheumatoid factor (RF) mice

    PubMed Central

    Giltiay, Natalia V.; Lu, Yi; Cullen, Jaime L.; Jørgensen, Trine N.; Shlomchik, Mark J.; Li, Xiaoxia

    2013-01-01

    Self-reactive B cells in BALB/c AM14 transgenic (AM14 Tg) rheumatoid factor (RF) mice are not subject to central or peripheral toleralization. Instead, they remain at a stage of “clonal ignorance”, i.e. they do not proliferate and differentiate into Ab-producing cells. However, the immunoregulatory mechanisms that prevent autoantibody production in these mice remain unclear. In this study, we show that crossing AM14 Tg mice to a mouse strain deficient in Act1, a molecule involved in the regulation of BAFF-R and CD40-signaling in B cells, results in spontaneous activation of AM14 Tg B cells and production of AM14-specific antibodies. Three to five-month old AM14 Tg Act1?/? mice showed significant expansion of AM14 Tg B cells, including a 2–3 fold increase in the spleen and cLNs compared to AM14 Tg Act1+/+ mice. Furthermore, in the presence of endogenous self-Ag (IgHa congenic background), AM14 Tg Act1?/? B cells were spontaneously activated and differentiated into antibody forming cells (AFC). In contrast with previous studies using AM14 Tg MLR.Faslpr mice, we found that a significant number of AM14 Tg cells AM14 Tg Act1?/? mice displayed phenotypic characteristics of GC B cells. Anti-CD40L treatment significantly limited the expansion and activation of AM14 Tg Act1?/? B cells, suggesting that CD40L-mediated signals are required for the retention of these cells. Our results support the important role of Act1 in the regulation of self-reactive B cells and reveal how Act1 functions to prevent the production of autoantibodies. PMID:23904159

  19. Effect on days of lactation and methionine hydroxy analog on incorporation of plasma fatty acids into plasma triglycerides

    SciTech Connect

    Pullen, D.L.; Emergy, R.S. ); Palmquist, D.L. )

    1989-01-01

    Methionine hydroxy analog has been proposed to stimulate hepatic lipoprotein synthesis and incorporation of plasma fatty acids into plasma triglyceride. Seven cows were fed diets containing 0 to 30 g analog/d starting 14 d prepartum. At approximately 30 and 60 d postpartum, cows were continuously infused intravenously with 1-({sup 14}C)palmitic acid for 160 min to achieve steady-state labeling of plasma fatty acid and triglyceride. Turnover of fatty acid and transfer quotients for triglyceride and CO{sub 2} were 3.3 an 2.7 mmol min{sup {minus}1}; 13.0 and 10.0%; and 8.0 and 5.0%, for control and analog, respectively. Proportion of fatty acid turnover incorporated into triglyceride and CO{sub 2} were 14.0 and 15.0%; and 21.0 and 18.0, respectively, for control and analog. Analog increased {sup 14}C recovered in milk fat (52 vs. 36%). Plasma concentration of fatty acids, percent oxidized to CO{sub 2}, and percent of CO{sub 2} from fatty acids decreased with increasing lactation days. Milk fat percent and yield fatty acid turnover, and oxidation were positively correlated with concentration of plasma fatty acids, whereas fatty acid incorporated into plasma triglyceride was negatively correlated with fatty acid concentration. The data suggest that hepatic triglyceride secretion is not increased in early lactation; further, no effects of analog on lipid metabolism were detected.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26109679

  1. Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells.

    PubMed

    Dichlberger, Andrea; Schlager, Stefanie; Maaninka, Katariina; Schneider, Wolfgang J; Kovanen, Petri T

    2014-12-01

    Human mast cells (MCs) contain TG-rich cytoplasmic lipid droplets (LDs) with high arachidonic acid (AA) content. Here, we investigated the functional role of adipose TG lipase (ATGL) in TG hydrolysis and the ensuing release of AA as substrate for eicosanoid generation by activated human primary MCs in culture. Silencing of ATGL in MCs by siRNAs induced the accumulation of neutral lipids in LDs. IgE-dependent activation of MCs triggered the secretion of the two major eicosanoids, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The immediate release of PGD2 from the activated MCs was solely dependent on cyclooxygenase (COX) 1, while during the delayed phase of lipid mediator production, the inducible COX-2 also contributed to its release. Importantly, when ATGL-silenced MCs were activated, the secretion of both PGD2 and LTC4 was significantly reduced. Interestingly, the inhibitory effect on the release of LTC4 was even more pronounced in ATGL-silenced MCs than in cytosolic phospholipase A2-silenced MCs. These data show that ATGL hydrolyzes AA-containing TGs present in human MC LDs and define ATGL as a novel regulator of the substrate availability of AA for eicosanoid generation upon MC activation. PMID:25114172

  2. Polyamine Triglycerides: Synthesis and Study of Their Potential in Lubrication, Neutralization, and Sequestration.

    PubMed

    Harry-O'kuru, Rogers E; Biresaw, Girma; Murray, Rex E

    2015-07-22

    Renewable resources have evoked a new awakening in both scientific and industrial circles in the past decade. Vegetable oil is one category of renewables that is amenable as a source of new industrial products. Because the source feedstock, seeds, are environmentally friendly, the derivatized products from these at the end of their lifetime could also be benign when designed appropriately. Bioethanol and biodiesel are examples of biobased industrial products currently in the market place and have become resources for uplifting the rural economy. Biolubricants also are playing a more prominent role because they have become closely competitive with petroleum-based lubricants. These products are renewable because the crops from which the feedstuff for the biofuels and biolubricants are produced are grown annually in contrast to nonrenewable mineral sources. Added to their renewability is the inherent biodegradability of their end-use products after their useful lifetime. In a recent study of the lubricity characteristics of peracylated polyhydroxy milkweed oil, the derivatives were found to exhibit good oxidative stability as well as excellent antiwear properties. To further explore an expansion in the properties of such materials in lubrication and other applications, in this study the polyhydroxy (OH) moieties of derivatized milkweed triglycerides were replaced with -NHR groupings in the oil. In this process novel polyketo triglyceride intermediates leading to polyamine derivatives of the vegetable oil have been synthesized. The polyamine triglyceride markedly improved the stability of the parent oil to oxidative stress. It has also attenuated the extreme viscosity of the starting polyhydroxy oil to a more useful product that could be amenable for use as a lubricating agent, for example, hydraulic fluid. Both the polyketone and polyimine intermediates of the polyamine have chelating properties. The intermediates and the polyamine were characterized spectroscopically, tribologically, and rheologically for their intrinsic properties. PMID:26154265

  3. Impact of medium and long chain triglycerides consumption on appetite and food intake in overweight men

    PubMed Central

    St-Onge, Marie-Pierre; Mayrsohn, Brian; O’Keeffe, Majella; Kissileff, Harry R.; Choudhury, Arindam Roy; Laferrère, Blandine

    2014-01-01

    Background Medium chain triglycerides (MCT) enhance thermogenesis and may reduce food intake relative to long chain triglycerides (LCT). The goal of this study was to establish the effects of MCT on appetite and food intake and determine whether differences were due to differences in hormone concentrations. Methods Two randomized, crossover studies were conducted in which overweight men consumed 20 g of MCT or corn oil (LCT) at breakfast. Blood samples were obtained over 3 h. In Study 1 (n=10), an ad lib lunch was served after 3 h. In Study 2 (n=7), a pre-load containing 10 g of test oil was given at 3 h and lunch was served 1 h later. Linear mixed model analyses were performed to determine the effects of MCT and LCT oil on change in hormones and metabolites from fasting, adjusting for body weight. Correlations were computed between differences in hormones just before the test meals and differences in intakes after the two oils for Study 1 only. Results Food intake at the lunch test meal after the MCT pre-load (Study 2) was (mean ± SEM) 532 ± 389 kcal vs. 804 ± 486 kcal after LCT (P < 0.05). MCT consumption resulted in a lower rise in triglycerides (P = 0.014) and glucose (P = 0.066) and a higher rise in peptide YY (P = 0.017) and leptin (P = 0.036) compared to LCT (combined data). Correlations between differences in hormone levels (GLP-1, PYY) and differences in food intake were in the opposite direction to expectations. Conclusions MCT consumption reduced food intake acutely but this does not seem to be mediated by changes in GLP-1, PYY, and insulin. PMID:25074387

  4. WE-PIS-Exhibit Hall-01: Tools for TG-142 Linac Imaging QA II

    SciTech Connect

    Childress, N; Murray, B

    2014-06-15

    Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The therapy topic this year is solutions for TG-142 recommendations for linear accelerator imaging QA. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Using DoseLab to Perform TG-142 Imaging QA The goals of this session will be to present a clinical overview of acquiring images for TG-142 Imaging QA, as well as analyzing and evaluating results using DoseLab software. DoseLab supports planar imaging QA analysis using almost any QA phantom provided by numerous vendors. General advantages and disadvantages of selecting each of these phantoms will be briefly summarized. Best practices for selecting image acquisition parameters will be presented. A demonstration of using DoseLab software to perform a series of TG-142 tests will be performed. We will disuss why DoseLab uses its own set of imaging QA formulas, and why imaging QA measurement values of the same nominal properties will vary between TG- 142 software packages. Because TG-142 does not specify baseline and tolerance values for imaging QA, the presentation will recommend performing the manufacturer's acceptance test procedure to validate the equipment is functioning correctly. Afterwards, results can be obtained using the clinic's selected set of phantoms, image acquisition parameters, and TG-142 software to set proper baseline values. This presentation will highlight the reasons why comparing imaging QA results can be trickier than comparing linear accelerator treatment results and what physicists should keep in mind when comparing imaging QA results for different machines. Physicists are often unsure of the next step when there is an issue discovered during Imaging QA. Therefore, a few common examples of imaging issues and recommended solutions will be discussed. TG-142 Imaging QA Simplified: Lessons From Diagnostic Physics Collaboration There are many commercial options for the performance of imaging quality assurance tests for the linear accelerator imaging systems as required by the AAPM TG-142 report. Imaging quality assurance testing is largely performed by the diagnostic physicist so routine performance of these tests by the practicing oncology physicist can be complicated and confusing given all of the commercially available options. This presentation focuses on the performance of imaging quality assurance testing for linear accelerators using methods similar to that of diagnostic physicists. This presentation will address the ability to perform the required testing without complicated software and explores solutions for the performance of these tests in an efficient manner while still maintaining the ability to ascertain image quality changes that may ultimately affect clinical decisions.

  5. Age-dependent impairment of glucose tolerance in the 3xTg-AD mouse model of Alzheimer's disease.

    PubMed

    Vandal, Milene; White, Phillip J; Chevrier, Geneviève; Tremblay, Cyntia; St-Amour, Isabelle; Planel, Emmanuel; Marette, Andre; Calon, Frederic

    2015-10-01

    Alzheimer's disease (AD) has been associated with type II diabetes (T2D) and obesity in several epidemiologic studies. To determine whether AD neuropathology can cause peripheral metabolic impairments, we investigated metabolic parameters in the triple-transgenic (3xTg)-AD mouse model of AD, compared with those in nontransgenic (non-Tg) controls, at 6, 8, and 14 mo of age. We found a more pronounced cortical A? accumulation (2- and 3.5-fold increase in A?42 in the soluble and insoluble protein fractions, respectively) in female 3xTg-AD mice than in the males. Furthermore, female 3xTg-AD mice displayed a significant deterioration in glucose tolerance (AUC, +118% vs. non-Tg mice at 14 mo). Fasting plasma insulin levels rose 2.5-fold from 6 to 14 mo of age in female 3xTg-AD mice. Glucose intolerance and cortical amyloid pathology worsened with age, and both were more pronounced in the females. Pancreatic amyloidopathy was revealed and could underlie the observed deficit in glycemic response in 3xTg-AD mice. The present results suggest that AD-like neuropathology extends to the pancreas in the 3xTg-AD mouse, leading to glucose intolerance and contributing to a pathologic self-amplifying loop between AD and T2D. PMID:26108977

  6. MO-PIS-Exhibit Hall-01: Tools for TG-142 Linac Imaging QA I

    SciTech Connect

    Clements, M; Wiesmeyer, M

    2014-06-15

    Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The therapy topic this year is solutions for TG-142 recommendations for linear accelerator imaging QA. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Automated Imaging QA for TG-142 with RIT Presentation Time: 2:45 – 3:15 PM This presentation will discuss software tools for automated imaging QA and phantom analysis for TG-142. All modalities used in radiation oncology will be discussed, including CBCT, planar kV imaging, planar MV imaging, and imaging and treatment coordinate coincidence. Vendor supplied phantoms as well as a variety of third-party phantoms will be shown, along with appropriate analyses, proper phantom setup procedures and scanning settings, and a discussion of image quality metrics. Tools for process automation will be discussed which include: RIT Cognition (machine learning for phantom image identification), RIT Cerberus (automated file system monitoring and searching), and RunQueueC (batch processing of multiple images). In addition to phantom analysis, tools for statistical tracking, trending, and reporting will be discussed. This discussion will include an introduction to statistical process control, a valuable tool in analyzing data and determining appropriate tolerances. An Introduction to TG-142 Imaging QA Using Standard Imaging Products Presentation Time: 3:15 – 3:45 PM Medical Physicists want to understand the logic behind TG-142 Imaging QA. What is often missing is a firm understanding of the connections between the EPID and OBI phantom imaging, the software “algorithms” that calculate the QA metrics, the establishment of baselines, and the analysis and interpretation of the results. The goal of our brief presentation will be to establish and solidify these connections. Our talk will be motivated by the Standard Imaging, Inc. phantom and software solutions. We will present and explain each of the image quality metrics in TG-142 in terms of the theory, mathematics, and algorithms used to implement them in the Standard Imaging PIPSpro software. In the process, we will identify the regions of phantom images that are analyzed by each algorithm. We then will discuss the process of the creation of baselines and typical ranges of acceptable values for each imaging quality metric.

  7. Molecular-weight Dependent Tg Depression of Silica-supported Poly(alpha-methyl styrene) Films

    NASA Astrophysics Data System (ADS)

    Tsui, Ophelia; Geng, Kun

    2015-03-01

    The glass transition temperature (Tg) of poly(?-methyl styrene) (P ?MS) films supported by silica is studied as a function of film thicknesses from 17 to 168 nm at three molecular weights of 1.3, 20 and 420 kg/mol. For the 20 and 420 kg/mol films, the glass transition temperature decreases with decreasing film thickness, consistent with previous results. But for the 1.3 kg/mol films, it becomes independent of the film thickness. We tentatively suggest the Tg depression to be caused by free volume excess at the polymer-air interface and that its influence diminishes at low enough molecular weights because of a chain stiffness effect. We acknowledge support of NSF through the Projects DMR-1004648 and DMR-1310536.

  8. Molecular-weight Dependent Tg Depression of Silica-supported Poly(?-methyl styrene) Films

    NASA Astrophysics Data System (ADS)

    Geng, Kun; Chen, Fei; Tsui, Ophelia K. C.

    2015-03-01

    The glass transition temperature (Tg) of poly(?-methyl styrene) (P ?MS) films supported by silica is studied as a function of film thicknesses from 17 to 168 nm at three molecular weights of 1.3, 20 and 420 kg/mol. For the 20 and 420 kg/mol films, the glass transition temperature decreases with decreasing film thickness, consistent with previous results. But for the 1.3 kg/mol films, it becomes independent of the film thickness. We tentatively suggest the Tg depression to be caused by free volume excess at the polymer-air interface and that its influence diminishes at low enough molecular weights because of a chain stiffness effect. Support from National Science Foundation (Award No. DMR-1310536) is gratefully acknowledged.

  9. Elevated temperature envelope forming

    NASA Technical Reports Server (NTRS)

    Burg, Bruce M. (Inventor); Gane, David H. (Inventor); Starowski, Robert M. (Inventor)

    1992-01-01

    Elevated temperature envelope forming includes enclosing a part blank and form tool within an envelope sealed against the atmosphere, heat treating the combination while forming pressure holds the envelope and part against the form tool, and allowing part cool down to occur in an inert atmosphere with forming pressure removed. The forming pressure is provided by evacuating the envelope and may be aided by differential force applied between the envelope and the form tool.

  10. Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides

    PubMed Central

    McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin

    2014-01-01

    Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of ?-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6?Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain. PMID:24169853

  11. Investigation of some characteristics of polyhydroxy milkweed triglycerides and their acylated derivatives in relation to lubricity.

    PubMed

    Harry-O'kuru, Rogers E; Biresaw, Girma; Cermak, Steven C; Gordon, Sherald H; Vermillion, Karl

    2011-05-11

    Most industrial lubricants are derived from nonrenewable petroleum-based sources. As useful as these lubricants are, their unintended consequences are the pollution of the Earth's environment as a result of the slow degradation of the spent materials. Native seed oils, on the other hand, are renewable and are also biodegradable in the environment, but these oils often suffer a drawback in having lower thermal stability and a shorter shelf life because of the intrinsic -C?C- unsaturation in their structures. This drawback can be overcome, yet the inherent biodegradative property retained, by appropriate derivatization of the oil. Pursuant to this, this study investigated derivatized polyhydroxy milkweed oil to assess its suitability as lubricant. The milkweed plant is a member of the Asclepiadaceae, a family with many genera including the common milkweeds, Asclepias syriaca L., Asclepias speciosa L., Asclepias tuberosa L., etc. The seeds of these species contain mainly C-18 triglycerides that are highly unsaturated, 92%. The olefinic character of this oil has been chemically modified by generating polyhydroxy triglycerides (HMWO) that show high viscosity and excellent moisturizing characteristics. In this work, HMWO have been chemically modified by esterifying their hydroxyl groups with acyl groups of various chain lengths (C2-C5). The results of investigation into the effect of the acyl derivatives' chemical structure on kinematic and dynamic viscosity, oxidation stability, cold-flow (pour point, cloud point) properties, coefficient of friction, wear, and elastohydrodynamic film thickness are discussed. PMID:21428293

  12. The neural signature of satiation is associated with ghrelin response and triglyceride metabolism

    PubMed Central

    Sun, Xue; Veldhuizen, Maria G; Wray, Amanda E; de Araujo, Ivan E; Sherwin, Robert S; Sinha, Rajita; Small, Dana M

    2014-01-01

    Eating behavior is guided by a complex interaction between signals conveying information about energy stores, food availability, and palatability. How peripheral signals regulate brain circuits that guide feeding during sensation and consumption of a palatable food is poorly understood. We used fMRI to measure brain response to a palatable food (milkshake) when n=32 participants were fasted and fed with either a fixed-portion or ad libitum meal. We found that larger post-prandial reductions in ghrelin and increases in triglycerides were associated with greater attenuation of response to the milkshake in brain regions regulating reward and feeding including the midbrain, amygdala, pallidum, hippocampus, insula and medial orbitofrontal cortex. Satiation-induced brain responses to milkshake were not related to acute changes in circulating insulin, glucose, or free fatty acids. The impact of a meal on the response to milkshake in the midbrain and dorsolateral prefrontal cortex differed depending upon whether meal termination was fixed or volitional, irrespective of the amount of food consumed. We conclude that satiation-induced changes in brain response to a palatable food are strongly and specifically associated with changes in circulating ghrelin and triglycerides and by volitional meal termination. PMID:24732416

  13. Porcine pancreatic lipase related protein 2 has high triglyceride lipase activity in the absence of colipase.

    PubMed

    Xiao, Xunjun; Ross, Leah E; Sevilla, Wednesday A; Wang, Yan; Lowe, Mark E

    2013-09-01

    Efficient dietary fat digestion is essential for newborns who consume more dietary fat per body weight than at any other time of life. In many mammalian newborns, pancreatic lipase related protein 2 (PLRP2) is the predominant duodenal lipase. Pigs may be an exception since PLRP2 expression has been documented in the intestine but not in the pancreas. Because of the differences in tissue-specific expression, we hypothesized that the kinetic properties of porcine PLRP2 would differ from those of other mammals. To characterize its properties, recombinant porcine PLRP2 was expressed in HEK293T cells and purified to homogeneity. Porcine PLRP2 had activity against tributyrin, trioctanoin and triolein. The activity was not inhibited by bile salts and colipase, which is required for the activity of pancreatic triglyceride lipase (PTL), minimally stimulated PLRP2 activity. Similar to PLRP2 from other species, PLRP2 from pigs had activity against galactolipids and phospholipids. Importantly, porcine PLRP2 hydrolyzed a variety of dietary substrates including pasteurized human mother's milk and infant formula and its activity was comparable to that of PTL. In conclusion, porcine PLRP2 has broad substrate specificity and has high triglyceride lipase activity even in the absence of colipase. The data suggest that porcine PLRP2 would be a suitable lipase for inclusion in recombinant preparations for pancreatic enzyme replacement therapy. PMID:23770034

  14. Elevated temperature reference spectra

    SciTech Connect

    Brown, D.; Phillips, B.; Tussey, L.

    1997-12-31

    A compilation of infrared spectra at elevated temperatures is required for the accurate quantification of gas concentrations for Fourier transform infrared (FTIR) extractive sampling of stack gases and FTIR in-situ process monitoring. Analysis of high temperature gases utilizing ambient temperature reference spectra can result in significant quantification errors. The US Air Force`s Arnold Engineering Development Center (AEDC) is currently assisting the EPA in measuring reference spectra and making existing and new data available to the public through two ongoing efforts. One of these efforts is the measurement of elevated temperature infrared reference spectra of the low vapor pressure hazardous air pollutants (HAP) compounds, as well as spectral interfering compounds. The equipment and procedures used for the elevated temperature reference spectra measurements is described as well as some of the challenges encountered in these measurements. Examples of the reference spectra are also presented. To make the reference spectra developed by AEDC and other EPA programs easily accessible, AEDC has also been tasked to maintain a site on the World Wide Web containing reference spectra, reports, and software tools of interest to the optical sensing community. This web site has seen increased use during the three years that it has been in existence with users from academia, commercial, and government, both domestic and foreign. The site has undergone several improvements since inception and actively solicits inputs for further improvements from its users. A description of this web site and recent improvements and additions is given in this paper.

  15. 3. A general elevation view looking west highlights the Elevator ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. A general elevation view looking west highlights the Elevator and Silo Complex C, commonly known as the 'Landmark' (1940). - Quaker Oats Cereal Factory, Southeast corner of Broadway & Mill Streets, Akron, Summit County, OH

  16. 49. EAST ELEVATION OF ASSEMBLING BUILDING #2 AND SOUTH ELEVATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    49. EAST ELEVATION OF ASSEMBLING BUILDING #2 AND SOUTH ELEVATION OF BODY BUILDING, 1980 (MMI) - Dodge Brothers Motor Car Company Plant, Between Joseph Campau & Conant Avenues, Hamtramck, Wayne County, MI

  17. 33. Coal Fuel Elevator (diagonal in foreground), Fuel Elevator (left), ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    33. Coal Fuel Elevator (diagonal in foreground), Fuel Elevator (left), Fuel Storage Bins (center), and Power Plant (right) Photographs taken by Joseph E.B. Elliot - Huber Coal Breaker, 101 South Main Street, Ashley, Luzerne County, PA

  18. 43. ELEVATOR HEADHOUSE INTERIOR: Interior view towards southeast of elevator ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    43. ELEVATOR HEAD-HOUSE INTERIOR: Interior view towards southeast of elevator head-house at the Washington and Mason Street powerhouse. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

  19. Refrigeration Plant, North Elevation, Second Floor Plan, East Elevation, Ground ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Refrigeration Plant, North Elevation, Second Floor Plan, East Elevation, Ground Floor Plan, Section A-A - Kennecott Copper Corporation, On Copper River & Northwestern Railroad, Kennicott, Valdez-Cordova Census Area, AK

  20. New Mechanism Responsible for the Tg-broadening and Nonlinear Response of Nanoparticle-Reinforced Elastomers

    NASA Astrophysics Data System (ADS)

    Wang, Xiaorong

    2010-03-01

    Particle-filled elastomers are employed extensively in modern industry, because they are high-elasticity and relatively low- cost materials that can potentially have their physical characteristics matched to a given design specification. Despite their technological importance, particle-filled elastomers are extremely complicated with pronounced mechanical nonlinearity and temperature dependence and Tg-broadening. In this presentation, we report the fundamentals accounting for this nonlinear effect and Tg-broadening using hairy polymeric nanoparticles of well-defined core-shell structure that are dispersed in polymer matrices of identical chains. By adjusting the filler interaction potential, we are able to show that much of this rheological phenomenon comes from the phase behavior of particles in the polymer matrices and there is a strong connection between the rheological dynamics of particle-filled system and the thermodynamics of phase behavior of particles. The phenomenon of Tg-broadening in one-phase regime appears to differ significantly from that in two-phase regime despite the fact that the polymer around the particles is the same. The strain-induced nonlinearity in particle-filled system is found to display features of singularity near the phase transition point. Although there were attempts in the past to interpret this phenomenon as arising from formation of polymer glassy shells around particles, the present study clearly demonstrates that a glassy shell model is not capable to describe the behavior of particle-filled systems in a unified way. Our finding also suggests new mechanism responsible for the Tg- broadening and nonlinear response of nanoparticle-reinforced elastomers.

  1. Interaction and kinetic analysis for coal and biomass co-gasification by TG-FTIR.

    PubMed

    Xu, Chaofen; Hu, Song; Xiang, Jun; Zhang, Liqi; Sun, Lushi; Shuai, Chao; Chen, Qindong; He, Limo; Edreis, Elbager M A

    2014-02-01

    This study aims to investigate the interaction and kinetic behavior of CO2 gasification of coal, biomass and their blends by thermogravimetry analysis (TG). The gas products evolved from gasification were measured online with Fourier Transform Infrared Spectroscopy (FTIR) coupled with TG. Firstly, TG experiments indicated that interaction between the coals and biomasses mainly occurred during co-gasification process. The most significant synergistic interaction occurred for LN with SD at the blending mass ratio 4:1. Furthermore, thermal kinetic analysis indicated that the activation energy involved in co-gasification decreased as the SD content increased until the blending ratio of SD with coal reached 4:1. The rise of the frequency factor indicated that the increase of SD content favored their synergistic interaction. Finally, FTIR analysis of co-gasification of SD with LN indicated that except for CO, most gases including CH3COOH, C6H5OH, H2O, etc., were detected at around 50-700°C. PMID:24412857

  2. 3. Occident Terminal Elevator. Reinforced concrete. First total "electric" elevator ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Occident Terminal Elevator. Reinforced concrete. First total "electric" elevator at Duluth. (Powered by electrical substation instead of steam generator). - Occident Terminal Elevator & Storage Annex, South side of second slip, north from outer end of Rice's Point, east of Garfield Avenue, Duluth, St. Louis County, MN

  3. Elevations and Floor Plan of Shed No. 1, Elevations and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Elevations and Floor Plan of Shed No. 1, Elevations and Floor Plan of Work Shed, Elevations and Floor Plan of Garage - Roberts-Dolezal Farmstead, 75 miles northeast of the intersection of CR27 and FM 1722, Garrett, Ellis County, TX

  4. Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration.

    PubMed

    Laursen, Bettina; Mørk, Arne; Plath, Niels; Kristiansen, Uffe; Bastlund, Jesper Frank

    2014-01-16

    The Alzheimer's disease (AD) mouse model Tg2576 overexpresses an AD associated mutant variant of human APP and accumulates amyloid beta (A?) in an age-dependent manner. Using the selective cholinergic immunotoxin mu p75-saporin (SAP), we induced a partial basal forebrain cholinergic degeneration (BFCD) in 3 months old male Tg2576 mice to co-express cholinergic degeneration with A? overexpression as these characteristics constitutes key hallmarks of AD. At 9 months, SAP lesioned Tg2576 mice were cognitively impaired in two spatial paradigms addressing working memory and mid to long-term memory. Conversely, there was no deterioration of cognitive functioning in sham lesioned Tg2576 mice or wild type littermates (wt) receiving the immunotoxin. At 10 months of age, release of acetylcholine (ACh) was addressed by microdialysis in conscious mice. Scopolamine-induced increases in hippocampal ACh efflux was significantly reduced in SAP lesioned Tg2576 mice compared to sham lesioned Tg2576 mice. Intriguingly, there was no significant difference in ACh efflux between wt treatment groups. Following SAP treatment, choline acetyltransferase activity was reduced in the hippocampus and frontal cortex and the reduction was comparable between groups. Our results suggest that partial BFCD acts collectively with increased levels of A? to induce cognitive decline and to compromise cholinergic release. Tg2576 mice with BFCD may constitute a new and suitable AD mouse model to study the interrelations between cholinergic deficits and amsyloid deposition. PMID:24231553

  5. Limitations of the TG-43 formalism for skin high-dose-rate brachytherapy dose calculations

    SciTech Connect

    Granero, Domingo; Perez-Calatayud, Jose; Vijande, Javier; Ballester, Facundo; Rivard, Mark J.

    2014-02-15

    Purpose: In skin high-dose-rate (HDR) brachytherapy, sources are located outside, in contact with, or implanted at some depth below the skin surface. Most treatment planning systems use the TG-43 formalism, which is based on single-source dose superposition within an infinite water medium without accounting for the true geometry in which conditions for scattered radiation are altered by the presence of air. The purpose of this study is to evaluate the dosimetric limitations of the TG-43 formalism in HDR skin brachytherapy and the potential clinical impact. Methods: Dose rate distributions of typical configurations used in skin brachytherapy were obtained: a 5 cm × 5 cm superficial mould; a source inside a catheter located at the skin surface with and without backscatter bolus; and a typical interstitial implant consisting of an HDR source in a catheter located at a depth of 0.5 cm. Commercially available HDR{sup 60}Co and {sup 192}Ir sources and a hypothetical {sup 169}Yb source were considered. The Geant4 Monte Carlo radiation transport code was used to estimate dose rate distributions for the configurations considered. These results were then compared to those obtained with the TG-43 dose calculation formalism. In particular, the influence of adding bolus material over the implant was studied. Results: For a 5 cm × 5 cm{sup 192}Ir superficial mould and 0.5 cm prescription depth, dose differences in comparison to the TG-43 method were about ?3%. When the source was positioned at the skin surface, dose differences were smaller than ?1% for {sup 60}Co and {sup 192}Ir, yet ?3% for {sup 169}Yb. For the interstitial implant, dose differences at the skin surface were ?7% for {sup 60}Co, ?0.6% for {sup 192}Ir, and ?2.5% for {sup 169}Yb. Conclusions: This study indicates the following: (i) for the superficial mould, no bolus is needed; (ii) when the source is in contact with the skin surface, no bolus is needed for either {sup 60}Co and {sup 192}Ir. For lower energy radionuclides like {sup 169}Yb, bolus may be needed; and (iii) for the interstitial case, at least a 0.1 cm bolus is advised for {sup 60}Co to avoid underdosing superficial target layers. For {sup 192}Ir and {sup 169}Yb, no bolus is needed. For those cases where no bolus is needed, its use might be detrimental as the lack of radiation scatter may be beneficial to the patient, although the 2% tolerance for dose calculation accuracy recommended in the AAPM TG-56 report is not fulfilled.

  6. Genome-wide association study of the plasma triglyceride response to an n-3 polyunsaturated fatty acid supplementation[S

    PubMed Central

    Rudkowska, Iwona; Guénard, Frédéric; Julien, Pierre; Couture, Patrick; Lemieux, Simone; Barbier, Olivier; Calder, Philip C.; Minihane, Anne Marie; Vohl, Marie-Claude

    2014-01-01

    Studies have shown a large interindividual variability in plasma TG response to long-chain n-3 PUFA supplementation, which may likely be attributable to genetic variability within the populations studied. The objective is to compare the frequency of SNPs in a genome-wide association study between responders (reduction in plasma TG levels ?0.01 mM) and nonresponders (increase in plasma TG of ?0 mM) to supplementation. Genomic DNA from 141 subjects who completed a 2-week run-in period followed by 6-week supplementation with 5 g of fish oil daily (1.9–2.2 g EPA and 1.1 g DHA daily) were genotyped on Illumina HumanOmni-5-QuadBeadChip. Thirteen loci had frequency differences between responders and nonresponders (P < 1 × 10?5), including SNPs in or near IQCJ-SCHIP1, MYB, NELL1, NXPH1, PHF17, and SLIT2 genes. A genetic risk score (GRS) was constructed by summing the number of risk alleles. This GRS explained 21.53% of the variation in TG response to n-3 PUFA supplementation when adjusted for age, sex, and BMI (P = 0.0002). Using Fish Oil Intervention and Genotype as a replication cohort, the GRS was able to explain 2% of variation in TG response when adjusted. In conclusion, subjects who decrease their plasma TG levels following n-3 PUFA supplementation may have a different genetic profile than individuals who do not respond. PMID:24847101

  7. Rapid thermogravimetric measurements of boiling points and vapor pressure of saturated medium- and long-chain triglycerides.

    PubMed

    Goodrum, John W; Geller, Daniel P

    2002-08-01

    In developing compositional models for biomass-based diesel fuel extenders, volatility properties of medium- and long-chain saturated triglycerides are essential to predict the impact of low levels of these compounds in mixtures with short-chain triglycerides. A thermogravimetric analysis (TGA) method for rapid measurement of boiling points and vapor pressure was used to obtain data for four pure medium- and long-chain triglycerides. Normal boiling points at 1 atm and the temperature dependence of vapor pressure from 760 mm down to 25 mm Hg were obtained for trilaurin (C12:0), trimyristin (C14:0), tripalmitin (C16:0), and tristearin (C18:0). The data showed good agreement with the Clausius-Clapeyron model for temperature dependence of vapor pressure up to 1 atm pressure. The results of this study were consistent with those obtained using differential scanning calorimetry (DSC) and with data previously reported for reduced pressure. PMID:12137273

  8. Apolipoprotein AV Accelerates Plasma Hydrolysis OfTriglyceride-Rich Lipoproteins By Interaction With Proteoglycan BoundLipoprotein Lipase

    SciTech Connect

    Merkel, Martin; Loeffler, Britta; Kluger, Malte; Fabig, Nathalie; Geppert, Gesa; Pennacchio, Len A.; Laatsch, Alexander; Heeren, Joerg

    2005-02-22

    Apolipoprotein A5 (APOA5) is associated with differences intriglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasmatriglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In hAPOA5 transgenic mice(hAPOA5tr), catabolism of chylomicrons and VLDL was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL).Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by crossbreeding a human LPL transgene with the apoa5 knockout, and the hAPOA5tr to an LPL deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5 deficient mice,however, over expression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr HDL, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line.A direct interaction between LPL and apoAV was found by ligand blotting.It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycans bound LPL for lipolysis.

  9. Supplementary Figure S1. IHC of TG worms expressing (b)opsin in neurons and in muscles. a-g, Representative IHC images of live day 1 TG worms expressing (b)opsin in neurons Alexa-488-

    E-print Network

    Palczewski, Krzysztof

    Supplementary Figure S1. IHC of TG worms expressing (b)opsin in neurons and in muscles. a-g, Representative IHC images of live day 1 TG worms expressing (b)opsin in neurons Alexa-488- conjugated 1D4 mAb was injected into pseudocoelom of a worm head (a-d) or middle body section (e-g) together with Triton X-100

  10. Digital Elevation Models

    USGS Publications Warehouse

    U.S. Geological Survey

    1993-01-01

    The Earth Science Information Center (ESIC) distributes digital cartographic/geographic data files produced by the U.S. Geological Survey (USGS) as part of the National Mapping Program. Digital cartographic data files may be grouped into four basic types. The first of these, called a Digital Line Graph (DLG), is the line map information in digital form. These data files include information on base data categories, such as transportation, hypsography, hydrography, and boundaries. The second type, called a Digital Elevation Model (DEM), consists of a sampled array of elevations for a number of ground positions at regularly spaced intervals. The third type is Land Use and Land Cover digital data which provides information on nine major classes of land use such as urban, agricultural, or forest as well as associated map data such as political units and Federal land ownership. The fourth type, the Geographic Names Information System, provides primary information for all known places, features, and areas in the United States identified by a proper name.

  11. Continuous Flow Metathesis for Direct Valorization of Food Waste: An Example of Cocoa Butter Triglyceride

    PubMed Central

    2015-01-01

    The direct chemical conversion of cocoa butter triglycerides, a material available as a postmanufacture waste stream from the food industry, to 1-decene by way of ethenolysis is reported. The conversion of the raw waste material was made possible by use of 1 mol % of the [RuCl2(iBu-phoban)2(3-phenylindenyl)] catalyst. The process has been investigated in both batch and flow conditions, where the latter approach employs a Teflon AF-2400 tube-in-tube gas–liquid membrane contactor to deliver ethylene to the reaction system. These preliminary studies culminate in a continuous processing system, which maintained a constant output over a 150 min period tested. PMID:26322250

  12. Evaluation of inhibitory effect of phlorotannins from Ecklonia cava on triglyceride accumulation in adipocyte.

    PubMed

    Kim, Haejin; Kong, Chang-Suk; Lee, Jung Im; Kim, Hojun; Baek, Seungoh; Seo, Youngwan

    2013-09-11

    In the present study, a methanolic extract of Ecklonia cava and its solvent-partitioned fractions were evaluated for their antiadipogenic effect in 3T3-L1 adipocytes. One of them, the n-BuOH fraction, effectively reduced lipid accumulation and glucose consumption. In addition, the presence of the n-BuOH fraction in adipocytes suppressed the regulations of adipogenic transcription factors, PPAR? and SREBP1c, and adipogenic specific genes, FABP4, FABP1, FAS, LPL, HSL, and ACS1. Further purification of n-BuOH fractions led to the isolation of six phlorotannins (1-6). The six phlorotannins effectively suppressed triglyceride accumulation. Comparative analysis showed that lipid accumulation in adipocytes was dramatically attenuated in the presence of eckstolonol (4). PMID:23957842

  13. Elevation of serum high density lipoprotein cholesterol by rowachol, a proprietary mixture of six pure monoterpenes.

    PubMed

    Bell, G D; Bradshaw, J P; Burgess, A; Ellis, W; Hatton, J; Middleton, A; Middleton, B; Orchard, T; White, D A

    1980-05-01

    Rowachol, a proprietary choleretic containing 6 pure monoterpenes markedly elevates serum HDL cholesterol (SHDL-C) concentrations in man. The concentration of SHDL-C showed a progressive increase in 16 patients treated with 6-9 capsules of Rowachol daily for periods of 2-28 weeks. There was no accompanying significant change in the concentrations of serum total cholesterol or triglyceride. In view of the significant inverse relationship between SHDL-C concentration and the risk of developing ischaemic heart disease, it is suggested that Rowachol and possibly other terpenes merit further investigation as possible therapeutic agents in the prevention and treatment of atheroma. PMID:7387775

  14. Determination of Free Fatty Acids and Triglycerides by Gas Chromatography Using Selective Esterification Reactions

    SciTech Connect

    Kail, Brian W.; Link, Dirk D.; Morreale, Bryan D

    2012-11-01

    A method for selectively determining both free fatty acids (FFA) and triacylglycerides (TAGs) in biological oils was investigated and optimized using gas chromatography after esterification of the target species to their corresponding fatty acid methyl esters (FAMEs). The method used acid catalyzed esterification in methanolic solutions under conditions of varying severity to achieve complete conversion of more reactive FFAs while preserving the concentration of TAGs. Complete conversion of both free acids and glycerides to corresponding FAMEs was found to require more rigorous reaction conditions involving heating to 120°C for up to 2 h. Method validation was provided using gas chromatography–flame ionization detection, gas chromatography–mass spectrometry, and liquid chromatography–mass spectrometry. The method improves on existing methods because it allows the total esterified lipid to be broken down by FAMEs contributed by FFA compared to FAMEs from both FFA and TAGs. Single and mixed-component solutions of pure fatty acids and triglycerides, as well as a sesame oil sample to simulate a complex biological oil, were used to optimize the methodologies. Key parameters that were investigated included: HCl-to-oil ratio, temperature and reaction time. Pure free fatty acids were found to esterify under reasonably mild conditions (10 min at 50°C with a 2.1:1 HCl to fatty acid ratio) with 97.6 ± 2.3% recovery as FAMEs, while triglycerides were largely unaffected under these reaction conditions. The optimized protocol demonstrated that it is possible to use esterification reactions to selectively determine the free acid content, total lipid content, and hence, glyceride content in biological oils. This protocol also allows gas chromatography analysis of FAMEs as a more ideal analyte than glyceride species in their native state.

  15. Cardiac dysfunction in adipose triglyceride lipase deficiency: treatment with a PPAR? agonist

    PubMed Central

    Wölkart, G; Schrammel, A; Dörffel, K; Haemmerle, G; Zechner, R; Mayer, B

    2012-01-01

    BACKGROUND AND PURPOSE Adipose triglyceride lipase (ATGL) has been identified as a rate-limiting enzyme of mammalian triglyceride catabolism. Deletion of the ATGL gene in mice results in severe lipid accumulation in a variety of tissues including the heart. In the present study we investigated cardiac function in ATGL-deficient mice and the potential therapeutic effects of the PPAR? and ? agonists Wy14,643 and rosiglitazone, respectively. EXPERIMENTAL APPROACH Hearts isolated from wild-type (WT) mice and ATGL(-/-) mice treated with Wy14,643 (PPAR? agonist), rosiglitazone (PPAR? agonist) or vehicle were perfused at a constant flow using the Langendorff technique. Left ventricular (LV) pressure–volume relationships were established, and the response to adrenergic stimulation was determined with noradrenaline (NA). KEY RESULTS Hearts from ATGL(-/-) mice generated higher LV end-diastolic pressure and lower LV developed pressure as a function of intracardiac balloon volume compared to those from WT mice. Likewise, passive wall stress was increased and active wall stress decreased in ATGL(-/-) hearts. Contractile and microvascular responses to NA were substantially reduced in ATGL(-/-) hearts. Cardiac contractility was improved by treating ATGL(-/-) mice with the PPAR? agonist Wy14,643 but not with the PPAR? agonist rosiglitazone. CONCLUSIONS AND IMPLICATIONS Our results indicate that lipid accumulation in mouse hearts caused by ATGL gene deletion severely affects systolic and diastolic function, as well as the response to adrenergic stimulation. The beneficial effects of Wy14,643 suggest that the cardiac phenotype of these mice is partially due to impaired PPAR? signalling. PMID:21585347

  16. Supported phosphate and carbonate salts for heterogeneous catalysis of triglycerides to fatty acid methyl esters

    NASA Astrophysics Data System (ADS)

    Britton, Stephanie Lynne

    Fatty acid methyl esters made from vegetable oil, or biodiesel, have been identified as a substitute for diesel derived from crude oil. Biodiesel is currently made using a homogeneous base catalyst to perform the transesterification of triglycerides with methanol to generate fatty acid methyl esters (FAME). The use of a homogeneous catalyst necessitates additional purification of the product and byproducts before sale, and the catalyst is consumed and discarded. The development of a heterogeneous basic catalyst for the production of FAME is desirable. Tribasic phosphate salts and dibasic carbonate salts are active for the production of FAME but generally operate as homogeneous catalysts. Supporting these phosphate and carbonate salts on mesoporous MCM-41, microporous silica gel, and nonporous a-alumina proved successful to greater or lesser degrees depending on the identity of the support and pretreatment of the support. Although these salts were supported and were active for the production of FAME from canola oil, they proved to be operating as homogeneous catalysts due to leaching of the active species off the surface of the support. Further investigation of the active species present in the tribasic phosphate catalysts identified the active support as orthophosphate, and NMR studies revealed the phosphorus to be present as orthophosphate and diphosphate in varying proportions in each catalyst. Evaluation of the acid-washing support pretreatment process revealed that the exposure of the support to acid plays a large role in the development of activity on the surface of the catalyst, but manipulation of these parameters did not prevent leaching of the active site off the surface of the catalyst. Alternate methods of support pretreatment were no more effective in preventing leaching. Tribasic phosphate supported on silica gel is not effective as a heterogeneous catalyst for FAME production from triglycerides because of the lack of stability of the phosphate on the support. The support is not stable under the reaction conditions, and alternatives should be explored to develop a heterogeneous base catalyst for the production of FAME.

  17. Secular trends in cholesterol lipoproteins and triglycerides and prevalence of dyslipidemias in an urban Indian population

    PubMed Central

    Gupta, Rajeev; Guptha, Soneil; Agrawal, Aachu; Kaul, Vijay; Gaur, Kiran; Gupta, Vijay P

    2008-01-01

    Background Coronary heart disease is increasing in urban Indian subjects and lipid abnormalities are important risk factors. To determine secular trends in prevalence of various lipid abnormalities we performed studies in an urban Indian population. Methods Successive epidemiological Jaipur Heart Watch (JHW) studies were performed in Western India in urban locations. The studies evaluated adults ? 20 years for multiple coronary risk factors using standardized methodology (JHW-1, 1993–94, n = 2212; JHW-2, 1999–2001, n = 1123; JHW-3, 2002–03, n = 458, and JHW-4 2004–2005, n = 1127). For the present analyses data of subjects 20–59 years (n = 4136, men 2341, women 1795) have been included. In successive studies, fasting measurements for cholesterol lipoproteins (total cholesterol, LDL cholesterol, HDL cholesterol) and triglycerides were performed in 193, 454, 179 and 252 men (n = 1078) and 83, 472, 195, 248 women (n = 998) respectively (total 2076). Age-group specific levels of various cholesterol lipoproteins, triglycerides and their ratios were determined. Prevalence of various dyslipidemias (total cholesterol ? 200 mg/dl, LDL cholesterol ? 130 mg/dl, non-HDL cholesterol ? 160 mg/dl, triglycerides ? 150 mg/dl, low HDL cholesterol <40 mg/dl, high cholesterol remnants ? 25 mg/dl, and high total:HDL cholesterol ratio ? 5.0, and ? 4.0 were also determined. Significance of secular trends in prevalence of dyslipidemias was determined using linear-curve estimation regression. Association of changing trends in prevalence of dyslipidemias with trends in educational status, obesity and truncal obesity (high waist:hip ratio) were determined using two-line regression analysis. Results Mean levels of various lipoproteins increased sharply from JHW-1 to JHW-2 and then gradually in JHW-3 and JHW-4. Age-adjusted mean values (mg/dl) in JHW-1, JHW-2, JHW-3 and JHW-4 studies respectively showed a significant increase in total cholesterol (174.9 ± 45, 196.0 ± 42, 187.5 ± 38, 193.5 ± 39, 2-stage least-squares regression R = 0.11, p < 0.001), LDL cholesterol (106.2 ± 40, 127.6 ± 39, 122.6 ± 44, 119.2 ± 31, R = 0.11, p < 0.001), non-HDL cholesterol (131.3 ± 43, 156.4 ± 43, 150.1 ± 41, 150.9 ± 32, R = 0.12, p < 0.001), remnant cholesterol (25.1 ± 11, 28.9 ± 14, 26.0 ± 11, 31.7 ± 14, R = 0.06, p = 0.001), total:HDL cholesterol ratio (4.26 ± 1.3, 5.18 ± 1.7, 5.21 ± 1.7, 4.69 ± 1.2, R = 0.10, p < 0.001) and triglycerides (125.6 ± 53, 144.5 ± 71, 130.1 ± 57, 158.7 ± 72, R = 0.06, p = 0.001) and decrease in HDL cholesterol (43.6 ± 14, 39.7 ± 8, 37.3 ± 6, 42.5 ± 6, R = 0.04, p = 0.027). Trends in age-adjusted prevalence (%) of dyslipidemias in JHW-1, JHW-2, JHW-3 and JHW-4 studies respectively showed insignificant changes in high total cholesterol (26.3, 35.1, 25.6, 26.0, linear curve-estimation coefficient multiple R = 0.034), high LDL cholesterol ? 130 mg/dl (24.2, 36.2, 31.0, 22.2, R = 0.062), and high low HDL cholesterol < 40 mg/dl (46.2, 53.3, 55.4, 33.7, R = 0.136). Increase was observed in prevalence of high non-HDL cholesterol (23.0, 33.5, 27.4, 26.6, R = 0.026), high remnant cholesterol (40.1, 40.3, 30.1, 60.6, R = 0.143), high total:HDL cholesterol ratio ? 5.0 (22.2, 47.6, 53.2, 26.3, R = 0.031) and ? 4.0 (58.6, 72.5, 70.1, 62.0, R = 0.006), and high triglycerides (25.7, 28.2, 17.5, 34.2, R = 0.047). Greater correlation of increasing non-HDL cholesterol, remnant cholesterol, triglycerides and total:HDL cholesterol ratio was observed with increasing truncal obesity than generalized obesity (two-line regression analysis p < 0.05). Greater educational level, as marker of socioeconomic status, correlated significantly with increasing obesity (r2 men 0.98, women 0.99), and truncal obesity (r2 men 0.71, women 0.90). Conclusion In an urban Indian population, trends reveal increase

  18. Increased Hippocampal Excitability in the 3xTgAD Mouse Model for Alzheimer's Disease In Vivo

    PubMed Central

    Davis, Katherine E.; Fox, Sarah; Gigg, John

    2014-01-01

    Mouse Alzheimer's disease (AD) models develop age- and region-specific pathology throughout the hippocampal formation. One recently established pathological correlate is an increase in hippocampal excitability in vivo. Hippocampal pathology also produces episodic memory decline in human AD and we have shown a similar episodic deficit in 3xTg AD model mice aged 3–6 months. Here, we tested whether hippocampal synaptic dysfunction accompanies this cognitive deficit by probing dorsal CA1 and DG synaptic responses in anaesthetized, 4–6 month-old 3xTgAD mice. As our previous reports highlighted a decline in episodic performance in aged control mice, we included aged cohorts for comparison. CA1 and DG responses to low-frequency perforant path stimulation were comparable between 3xTgAD and controls at both age ranges. As expected, DG recordings in controls showed paired-pulse depression; however, paired-pulse facilitation was observed in DG and CA1 of young and old 3xTgAD mice. During stimulus trains both short-latency (presumably monosynaptic: ‘direct’) and long-latency (presumably polysynaptic: ‘re-entrant’) responses were observed. Facilitation of direct responses was modest in 3xTgAD animals. However, re-entrant responses in DG and CA1 of young 3xTgAD mice developed earlier in the stimulus train and with larger amplitude when compared to controls. Old mice showed less DG paired-pulse depression and no evidence for re-entrance. In summary, DG and CA1 responses to low-frequency stimulation in all groups were comparable, suggesting no loss of synaptic connectivity in 3xTgAD mice. However, higher-frequency activation revealed complex change in synaptic excitability in DG and CA1 of 3xTgAD mice. In particular, short-term plasticity in DG and CA1 was facilitated in 3xTgAD mice, most evidently in younger animals. In addition, re-entrance was facilitated in young 3xTgAD mice. Overall, these data suggest that the episodic-like memory deficit in 3xTgAD mice could be due to the development of an abnormal hyper-excitable state in the hippocampal formation. PMID:24621690

  19. Calibration of the Gamma Knife Perfexion using TG-21 and the solid water Leksell dosimetry phantom

    SciTech Connect

    McDonald, Daniel; Yount, Caroline; Koch, Nicholas; Ashenafi, Michael; Peng, Jean; Vanek, Kenneth

    2011-03-15

    Purpose: To calibrate a Gamma Knife (GK) Perfexion using TG-21 with updated chamber-dependent values for modern microionization chambers in the new solid water Leksell dosimetry phantom. This work illustrates a calibration method using commercially available equipment, instruments, and an established dosimetry protocol that may be adopted at any GK center, thus reducing the interinstitutional variation in GK calibration. The calibration was verified by three third-party dosimetry checks. In addition, measurements of the relative output factors are presented and compared to available data and the new manufacturer-provided relative output factors yet to be released. Methods: An absolute dose calibration based on the TG-21 formalism, utilizing recently reported phantom material and chamber-dependent factors, was performed using a microionization chamber in a spherical solid water phantom. The result was compared to other calibration protocols based on TG-51. Independent verification of the machine output was conducted through M.D. Anderson Dosimetry Services (MDADS), using thermoluminescent dosimeters (TLDs) in an anthropomorphic head phantom; the Radiological Physics Center (RPC), using TLDs in the standard Elekta ABS plastic calibration phantom (gray phantom), included with the GK; and through a collaborative international calibration survey by the University of Pittsburgh Medical Center (UPMC) using alanine dosimeters, also in the gray phantom. The alanine dosimeters were read by the National Institute of Standards and Technology. Finally, Gafchromic EBT film was used to measure relative output factors and these factors were compared to values reported in the literature as well as new values announced for release by Elekta. The films were exposed in the solid water phantom using an included film insert accessory. Results: Compared to the TG-21 protocol in the solid water phantom, the modified and unmodified TG-51 calibrations resulted in dose rates which were 1.8% and 1.3% lower, respectively. Ratios of the doses measured by third parties to the dose reported showed excellent agreement. MDADS returned ratios of 1.00 and 0.98 for the two TLDs irradiated. The RPC returned a mean ratio of 0.98 of the dose reported and the UPMC alanine study returned a mean ratio of 1.008. Relative output factors were found to be 0.817{+-}0.009 and 0.897{+-}0.008 for the 4 and 8 mm collimators, respectively, which are in excellent agreement with revised Monte Carlo-derived relative output factors Elekta is expected to recommend with the next version of the GK treatment planning software (GAMMAPLAN version 10). Conclusions: The TG-21 dosimetry protocol, performed in a solid water phantom in conjunction with modern dosimeters and phantom material and chamber-dependent factors, can yield an accurate dose measurement in the unique GK treatment geometry. The technique described here can be easily adopted by institutions worldwide since all equipment and instruments used are commercially available, thus reducing the existing interinstitutional variation in GK calibration techniques. Relative output factor measurements made in this same solid water phantom were used to verify the relative output factors provided by Elekta and agreed excellently with output factors expected to be released in conjunction with GAMMAPLAN version 10.

  20. Rapid nuclear transit and impaired degradation of amyloid ? and glypican-1-derived heparan sulfate in Tg2576 mouse fibroblasts.

    PubMed

    Cheng, Fang; Fransson, Lars-Åke; Mani, Katrin

    2015-05-01

    Anhydromannose (anMan)-containing heparan sulfate (HS) derived from S-nitrosylated glypican-1 is generated in endosomes by an endogenously or ascorbate induced S-nitrosothiol-catalyzed reaction. Expression and processing of amyloid precursor protein (APP) is required to initiate formation and endosome-to-nucleus translocation of anMan-containing HS in wild-type mouse embryonic fibroblasts (WT MEF). HS is then transported to autophagosomes and finally degraded in lysosomes. To investigate how APP-derived amyloid ? (A?) peptide affects intracellular trafficking of HS, we have studied nuclear transit as well as autophagosome/lysosome targeting and degradation in transgenic Alzheimer disease mouse (Tg2576) MEF which produce increased amounts of A?. Deconvolution immunofluorescence microscopy with an anMan-specific monoclonal antibody showed anMan staining in the nuclei of Tg2576 MEF after 5 min of ascorbate treatment and after 15 min in WT MEF. There was also greater nuclear accumulation of HS in Tg2576 MEF as determined by (35)S-sulfate-labeling experiments. Tg2576 MEF was less sensitive to inhibition of NO production and copper-chelation than WT MEF. By using APP- and A?-recognizing antibodies, we observed nuclear translocation of A? peptide in Tg2576 MEF but not in WT MEF. HS remained in the nucleus of WT MEF for at least 8 h and was then transported to autophagosomes. By 8 h, HS had disappeared from the nuclei of Tg2576 MEF but colocalized poorly with the autophagosome marker LC3. A? also disappeared rapidly from the nuclei of Tg2576 MEF. Initially, it appeared in acidic vesicles and later it accumulated extracellularly. Thus, in Tg2576 MEF there is nuclear accumulation as well as secretion of A? and impaired degradation of HS. PMID:25527428

  1. Vogan-Zuckerman , $GL(n, R)$ $G$ $GL(n, R)$ Cartan involution $g$ }$arrow {}^{t}g^{-1}$

    E-print Network

    Kobayashi, Toshiyuki

    ­ Vogan-Zuckerman , ( ) 1. $GL(n, R)$ $G$ $GL(n, R)$ Cartan involution $g$ }$arrow {}^{t}g^{-1}$ $G$ $G$ $Z(G)=\\{g\\in G:gx=xg(\\forall x\\in G)\\}$ , $G$ , $GL(n, R)\\supset G\\supset H$ $grightarrow {}^{t}g^{-1}$ $G/H$ $GL(n, R)$ , $G$ 9, $\\mathfrak{g}\\otimes C$ $\\emptyset c$ , $G$ ( ) , $\\mathfrak{g

  2. Elevated A beta and apolipoprotein E in A betaPP transgenic mice and its relationship to amyloid accumulation in Alzheimer's disease.

    PubMed Central

    Kuo, Y. M.; Crawford, F.; Mullan, M.; Kokjohn, T. A.; Emmerling, M. R.; Weller, R. O.; Roher, A. E.

    2000-01-01

    BACKGROUND: Amyloid-beta (A beta) accumulates in plaques and as cerebral amyloid angiopathy (CAA) in the brains of both Alzheimer's disease (AD) patients and transgenic A betaPPswe/tg2576 (tg2576) mice. Increasingly, evidence in humans and mice shows this process to be modulated by apolipoprotein E (apoE). MATERIALS AND METHODS: To explore this relationship, we measured apoE and A beta levels in brains of tg2576 mice and controls at intervals between 2 and 20 months. In addition, A beta concentrations in plasma and muscle of these animals were also quantified. RESULTS: Quite strikingly, we found that the amount of tg2576 mice brain apoE was elevated by an average of 45%, relative to the control mice from 2 months on. The level of brain apoE soared after 14 months to almost 60% greater than the level found in control mice. A beta concentrations in brains before 9 months were less than 2 ng/mg of protein, but by 14 months concentrations rose to 8.7 ng/mg, and by 20 months to 47 ng/mg. In plasma, we noted that the levels of A beta in tg2576 mice declined from above 30 ng/ml prior to 12 months to 14 ng/ml by 14 months. Histology showed that A beta plaques and CAA began to be discernible in the tg2576 mice at about 9 and 20 months of age, respectively. CONCLUSIONS: ApoE was immunocytochemically detected in neuritic plaques that were positive for thioflavine-S. We suggest that the elevation of brain apoE in tg2576 mice participates in an age-related dysregulation of A beta clearance and signals the start of A beta sequestration during the time of cognitive dysfunction. PMID:10952022

  3. NATO TG-53: acoustic detection of weapon firing joint field experiment

    NASA Astrophysics Data System (ADS)

    Robertson, Dale N.; Pham, Tien; Scanlon, Michael V.; Srour, Nassy; Reiff, Christian G.; Sim, Leng K.; Solomon, Latasha; Thompson, Dorothea F.

    2006-05-01

    In this paper, we discuss the NATO Task Group 53 (TG-53) acoustic detection of weapon firing field joint experiment at Yuma Proving Ground during 31 October to 4 November 2005. The participating NATO countries include France, the Netherlands, UK and US. The objectives of the joint experiments are: (i) to collect acoustic signatures of direct and indirect firings from weapons such as sniper, mortar, artillery and C4 explosives and (ii) to share signatures among NATO partners from a variety of acoustic sensing platforms on the ground and in the air distributed over a wide area.

  4. Elevated temperature crack growth

    NASA Technical Reports Server (NTRS)

    Kim, K. S.; Vanstone, R. H.

    1992-01-01

    The purpose of this program was to extend the work performed in the base program (CR 182247) into the regime of time-dependent crack growth under isothermal and thermal mechanical fatigue (TMF) loading, where creep deformation also influences the crack growth behavior. The investigation was performed in a two-year, six-task, combined experimental and analytical program. The path-independent integrals for application to time-dependent crack growth were critically reviewed. The crack growth was simulated using a finite element method. The path-independent integrals were computed from the results of finite-element analyses. The ability of these integrals to correlate experimental crack growth data were evaluated under various loading and temperature conditions. The results indicate that some of these integrals are viable parameters for crack growth prediction at elevated temperatures.

  5. Elevated temperature biaxial fatigue

    NASA Technical Reports Server (NTRS)

    Jordan, E. H.

    1984-01-01

    A three year experimental program for studying elevated temperature biaxial fatigue of a nickel based alloy Hastelloy-X has been completed. A new high temperature fatigue test facility with unique capabilities has been developed. Effort was directed toward understanding multiaxial fatigue and correlating the experimental data to the existing theories of fatigue failure. The difficult task of predicting fatigue lives for non-proportional loading was used as an ultimate test for various life prediction methods being considered. The primary means of reaching improved undertanding were through several critical non-proportional loading experiments. It was discovered that the cracking mode switched from primarily cracking on the maximum shear planes at room temperature to cracking on the maximum normal strain planes at 649 C.

  6. Environmental enrichment does not influence hypersynchronous network activity in the Tg2576 mouse model of Alzheimer’s disease

    PubMed Central

    Bezzina, Charlotte; Verret, Laure; Halley, Hélène; Dahan, Lionel; Rampon, Claire

    2015-01-01

    The cognitive reserve hypothesis claims that the brain can overcome pathology by reinforcing preexistent processes or by developing alternative cognitive strategies. Epidemiological studies have revealed that this reserve can be built throughout life experiences as education or leisure activities. We previously showed that an early transient environmental enrichment (EE) durably improves memory performances in the Tg2576 mouse model of Alzheimer’s disease (AD). Recently, we evidenced a hypersynchronous brain network activity in young adult Tg2576 mice. As aberrant oscillatory activity can contribute to memory deficits, we wondered whether the long-lasting memory improvements observed after EE were associated with a reduction of neuronal network hypersynchrony. Thus, we exposed non-transgenic (NTg) and Tg2576 mice to standard or enriched housing conditions for 10 weeks, starting at 3 months of age. Two weeks after EE period, Tg2576 mice presented similar seizure susceptibility to a GABA receptor antagonist. Immediately after and 2 weeks after this enrichment period, standard and enriched-housed Tg2576 mice did not differ with regards to the frequency of interictal spikes on their electroencephalographic (EEG) recordings. Thus, the long-lasting effect of this EE protocol on memory capacities in Tg2576 mice is not mediated by a reduction of their cerebral aberrant neuronal activity at early ages. PMID:26441640

  7. Hemoglobin of the bloody clam Tegillarca granosa (Tg-HbI) is involved in the immune response against bacterial infection.

    PubMed

    Bao, Yongbo; Wang, Qing; Lin, Zhihua

    2011-10-01

    Hemoglobins (Hb) are the major protein components of erythrocytes circulating in the red blood, but can serve additional functions besides the transport of oxygen. Here, the cDNA of the bloody clam (Tegillarca granosa) Hb dimer (designated Tg-HbI) was cloned and was found to be 748 bp in length, consisting of an open reading frame of 441 bp encoding a polypeptide of 147 amino acids. The deduced amino acid sequence of Tg-HbI shared 81.6% similarity with HbI from two species of the genus Scapharca and 46-51% similarity with the Hb proteins from other mollusks. The 3D structure of bloody clam Tg-HbI was predicted by the SWISS-MODEL Protein Modelling Server and compared with that of Scapharca kagoshimensis. The mRNA transcript of Tg-HbI was detected in all of the clam cells/tissues examined, including haemocytes, the adductor muscle, foot, hepatopancreas, gill and mantle. The mRNA expression of Tg-HbI was significantly up-regulated after Vibrio parahaemolyticus, lipopolysaccharide and peptidoglycan challenge, indicating that Tg-HbI was involved in the immune defence responses against bacterial infection and exposure to bacterial pathogenic factors. As the first functional research on the Hb protein in bloody clam, our findings provide new insight into the innate immune defence mechanisms of T. granosa and other mollusks. PMID:21782953

  8. Triglyceride High-Density Lipoprotein Ratios Predict Glycemia-Lowering in Response to Insulin Sensitizing Drugs in Type 2 Diabetes: A Post Hoc Analysis of the BARI 2D

    PubMed Central

    Zonszein, Joel; Lombardero, Manuel; Ismail-Beigi, Faramarz; Palumbo, Pasquale; Foucher, Suzy; Groenewoud, Yolanda; Cushing, Gary; Wajchenberg, Bernardo; Genuth, Saul; BARI 2D Study Group

    2015-01-01

    Glycemic management is central in prevention of small vessel and cardiovascular complications in type 2 diabetes. With the plethora of newer medications and recommendations for a patient centered approach, more information is necessary to match the proper drug to each patient. We showed that BARI 2D, a five-year trial designed to compare two different glycemic treatment strategies, was suitable for assessing different responses according to different phenotypic characteristics. Treatment with insulin sensitizing medications such as thiazolidinediones and metformin was more effective in improving glycemic control, particularly in the more insulin resistant patient, when compared to the insulin provision strategy using insulin and or sulfonylureas. Triglyceride and high density lipoprotein ratio (TG/HDL-cholesterol ratio) was found to be a readily available and practical biomarker that helps to identify the insulin resistant patient. These results support the concept that not all medications for glycemic control work the same in all patients. Thus, tailored therapy can be done using phenotypic characteristics rather than a “one-size-fits-all approach.” PMID:26106623

  9. Triglyceride High-Density Lipoprotein Ratios Predict Glycemia-Lowering in Response to Insulin Sensitizing Drugs in Type 2 Diabetes: A Post Hoc Analysis of the BARI 2D.

    PubMed

    Zonszein, Joel; Lombardero, Manuel; Ismail-Beigi, Faramarz; Palumbo, Pasquale; Foucher, Suzy; Groenewoud, Yolanda; Cushing, Gary; Wajchenberg, Bernardo; Genuth, Saul

    2015-01-01

    Glycemic management is central in prevention of small vessel and cardiovascular complications in type 2 diabetes. With the plethora of newer medications and recommendations for a patient centered approach, more information is necessary to match the proper drug to each patient. We showed that BARI 2D, a five-year trial designed to compare two different glycemic treatment strategies, was suitable for assessing different responses according to different phenotypic characteristics. Treatment with insulin sensitizing medications such as thiazolidinediones and metformin was more effective in improving glycemic control, particularly in the more insulin resistant patient, when compared to the insulin provision strategy using insulin and or sulfonylureas. Triglyceride and high density lipoprotein ratio (TG/HDL-cholesterol ratio) was found to be a readily available and practical biomarker that helps to identify the insulin resistant patient. These results support the concept that not all medications for glycemic control work the same in all patients. Thus, tailored therapy can be done using phenotypic characteristics rather than a "one-size-fits-all approach." PMID:26106623

  10. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol are risk factors for cardiovascular disease and blood triglycerides reflect key metabolic processes including sensitivity to insulin. Blood lipoprotein and lipid concentrations are heritable. To date, the identification o...

  11. Developmental, hormonal, and nutritional regulation of expression of porcine adipose tissue triglyceride lipase (pATGL) gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose triglyceride lipase (ATGL) is a newly identified lipase. We report for the first time the porcine ATGL sequence and characterize ATGL gene and protein expression in vitro and in vivo. Adult pig tissue expresses ATGL at high levels in the white adipose and muscle tissue relative to other te...

  12. TRIGLYCERIDE-RICH LIPOPROTEIN LIPOLYSIS RELEASES NEUTRAL AND OXIDIZED FREE FATTY ACIDS THAT INDUCE ENDOTHELIAL CELL INFLAMMATION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective–Increased products of triglyceride-rich lipoprotein (TGRL) lipolysis provide a pro-inflammatory stimulus that may alter endothelial barrier function. To probe the mechanism of this lipolysis-induced dysfunction, we evaluated the pro-inflammatory potential of lipid classes derived from huma...

  13. Co-firing of coal and manure biomass: a TG-MS approach.

    PubMed

    Otero, M; Sánchez, M E; Gómez, X

    2011-09-01

    Manure is a rich organic waste which, apart from its traditional use as a fertilizer, could be used as a bioenergy feedstock. In this sense, its utilization as a sole fuel or its co-combustion together with coal would be a choice for the management of this sort of biowaste. However, little is known about the behavior of this biowaste when submitted to high-temperature energy-conversion processes. Thus, the separate combustion of swine manure and coal and their co-combustion (10% dried weight of manure) were studied by simultaneous TG/MS dynamic runs. TG-MS analysis was successfully used as an easy rapid tool to assess the combustion of manure, alone or together with coal. Furthermore, non-isothermal kinetic analysis showed that the Arrhenius activation energy corresponding to the combustion of the blend (125.8-138.9 kJ/mol) was only slightly higher than that of manure (106.4-114.4 kJ/mol) or coal (107.0-119.6 kJ/mol). PMID:21737261

  14. Positron Emission Tomography Imaging of Fibrillar Parenchymal and Vascular Amyloid-? in TgCRND8 Mice

    PubMed Central

    2013-01-01

    Few quantitative diagnostic and monitoring, tools are available to clinicians treating patients with Alzheimer’s disease. Further, many of the promising quantitative imaging tools under development lack clear specificity toward different types of Amyloid-? (A?) pathology such as vascular or oligomeric species. Antibodies offer an opportunity to image specific types of A? pathology because of their excellent specificity. In this study, we developed a method to translate a panel of anti-A? antibodies, which show excellent histological performance, into live animal imaging contrast agents. In the TgCRND8 mouse model of Alzheimer’s disease, we tested two antibodies, M64 and M116, that target parenchyma aggregated A? plaques and one antibody, M31, that targets vascular A?. All three antibodies were administered intravenously after labeling with both poly(ethylene glycol) to enhance circulation and 64Cu to allow detection via positron emission tomography (PET) imaging. We were clearly able to differentiate TgCRND8 mice from wild type controls by PET imaging using either M116, the anti-A? antibody targeting parenchymal A? or M31, the antivascular A? antibody. To confirm the validity of the noninvasive imaging of specific A? pathology, brains were examined after imaging and showed clear evidence of binding to A? plaques. PMID:23509918

  15. TG-FTIR study on urea-formaldehyde resin residue during pyrolysis and combustion.

    PubMed

    Jiang, Xuguang; Li, Chunyu; Chi, Yong; Yan, Jianhua

    2010-01-15

    The pyrolysis and combustion characteristics of urea-formaldehyde resin (UFR) residue were investigated by using thermogravimetric analysis, coupled with Fourier transform infrared spectroscopy (TG-FTIR). It is indicated that the pyrolysis process can be subdivided into three stages: drying the sample, fast thermal decomposition and further cracking process. The total weight loss of 90 wt.% at 950 degrees C is found in pyrolysis, while 74 wt.% of the original mass lost in the second stage is between 195 degrees C and 430 degrees C. The emissions of carbon dioxide, isocyanic acid, ammonia, hydrocyanic acid and carbon monoxide are identified in UFR residue pyrolysis, moreover, isocyanic acid emitted at low temperature is found as the most important nitrogen-containing gaseous product in UFR residue pyrolysis, and there is a large amount of hydrocyanic acid emitted at high temperature. The similar TG and emission characteristics as the first two stages during pyrolysis are found in UFR residue combustion at low temperature. The combustion process almost finishes at 600 degrees C; moreover, carbon dioxide and water are identified as the main gaseous products at high temperature. It is indicated that the UFR residue should be pyrolyzed at low temperature to remove the initial nitrogen, and the gaseous products during pyrolysis should be burnt in high temperature furnace under oxygen-rich conditions for pollutant controlling. PMID:19735979

  16. WE-A-18A-01: TG246 On Patient Dose From Diagnostic Radiation

    SciTech Connect

    Supanich, M; Dong, F; Andersson, J; Pavlicek, W; Bolch, W; Fetterly, K

    2014-06-15

    Radiation dose from diagnostic and interventional radiations continues to be a focus of the regulatory, accreditation and standards organizations in the US and Europe. A Joint AAPM/EFOMP effort has been underway in the past year — having the goal to assist the clinical medical physicist with communicating optional and varied approaches in estimating (and validating) patient dose. In particular, the tools provided by DICOM Radiation Dose Structured Reports, either by themselves or as part of a networked data repository of dose related information are a rich source of actionable information. The tools of the medical physicist have evolved to include using DICOM data in meaningful ways to look at patient dose with respect to imaging practices. In addition to how accurate or reproducible a dose value is (totally necessary and our traditional workspace) it is now being asked how reproducible (patient to patient, device to device) are the delivered doses (new tasking)? Clinical medical physicists are best equipped to assist our radiology and technologist colleagues with this effort. The purpose of this session is to review the efforts of TG246 - bringing forward a summary content of the TG246 Report including specific dose descriptors for CT and Fluoroscopy — particularly in a focus of leveraging the RDSR as a means for monitoring good practices ALARA. Additionally, rapidly evolving technologies for more refined dose estimates are now in use. These will be presented as they look to having highly patient specific dose estimates in automated use.

  17. High T(g) bio-based aliphatic polyesters from bicyclic D-mannitol.

    PubMed

    Lavilla, Cristina; Alla, Abdelilah; Martínez de Ilarduya, Antxon; Muñoz-Guerra, Sebastián

    2013-03-11

    The carbohydrate-based diol 2,4:3,5-di-O-methylene-d-mannitol (Manx) has been used to obtain aliphatic polyesters. Manx is a symmetric bicyclic compound consisting of two fused 1,3-dioxane rings and bearing two primary hydroxyl groups. In terms of stiffness, it is comparable to the widely known isosorbide, but it affords the additional advantages of being much more reactive in polycondensation and capable of producing stereoregular polymers with fairly high molecular weights. A fully bio-based homopolyester (PManxS) has been synthesized by polycondensation in the melt from dimethyl succinate and Manx. The high thermal stability of PManxS, its relatively high glass transition temperature (Tg = 68 °C) and elastic modulus, and its enhanced sensitivity to the action of lipases point to PManxS as a polyester of exceptional interest for those applications where biodegradability and molecular stiffness are priority requirements. In addition, random copolyesters (PBxManxyS) covering a broad range of compositions have been obtained using mixtures of Manx and 1,4-butanediol in the reaction with dimethyl succinate. All PBxManxyS were semicrystalline and displayed Tg values from -29 to +51 °C steadily increasing with the content in Manx units. The stress-strain behavior of these copolyesters largely depended on their content in Manx and they were enzymatically degraded faster than PBS. PMID:23363397

  18. Triglyceride Response to an Intensive Lifestyle Intervention Is Enhanced in Carriers of the GCKR Pro446Leu Polymorphism

    PubMed Central

    Jablonski, Kathleen A.; McAteer, Jarred B.; Saxena, Richa; Kathiresan, Sekar; Kahn, Steven E.; Goldberg, Ronald B.; Altshuler, David; Florez, Jose C.

    2011-01-01

    Context: Glucokinase regulatory protein (GCKR) regulates the trafficking and enzymatic activity of hepatic glucokinase, the rate-limiting enzyme in glycogen synthesis and glycolysis. The intronic single-nucleotide polymorphism (SNP) rs780094 (intron 16) and the missense SNP rs1260326 (P446L) in the GCKR gene are strongly associated with increased circulating triglyceride and C-reactive protein levels and, paradoxically, reductions in diabetes incidence, fasting glucose levels, and insulin resistance. Objective, Setting, and Patients: We sought to replicate these associations and evaluate interactions with lifestyle and metformin interventions in the multiethnic Diabetes Prevention Program (DPP). Interventions and Main Outcome Measures: We genotyped the two GCKR SNP in 3346 DPP participants and evaluated association with progression to diabetes and both baseline levels and changes in triglycerides, homeostasis model assessment of insulin resistance (HOMA-IR), oral disposition index, and inflammatory markers along with their interactions with DPP interventions. Results: GCKR variation did not predict development of type 2 diabetes. At baseline, the 446L allele was associated with higher triglyceride and C-reactive protein levels (both P < 0.0001) and lower fasting glucose (P = 0.001) and HOMA-IR (P = 0.06). The lifestyle intervention was associated with a decrease in magnitude of the effect of the 446L allele on triglyceride levels (interaction P = 0.04). Metformin was more effective in reducing HOMA-IR in carriers of the P446 allele (interaction P = 0.05). Conclusions: Intensive lifestyle intervention appears to partially mitigate the effect of the 446L allele on higher triglycerides, whereas the P446 allele appears to enhance responsiveness to the HOMA-IR-lowering effect of metformin. PMID:21525158

  19. Effects of stress on serum triglycerides, nonsterified fatty acids, and total cholesterol levels in male rats after ethanol administration

    SciTech Connect

    Hershock, D.; Vogel, W.H. )

    1989-02-09

    Serum triglycerides, nonesterified fatty acids (NEFA), and total cholesterol were determined during one hour immobilization stress in adult male Sprague-Dawley rats after ethanol administration (2g/kg, i.p.). Stress and ethanol effects were evaluated in two experiments: (1) rats maintained on Purina Rodent Chow for six weeks and fasted for 24 hours; and (2) rats maintained on the same diet supplemented with 1% cholesterol and 10% peanut oil for six weeks and nonfasted prior to experimentation. Blood was obtained from indwelling jugular catheters. In each experiment, differences were seen in triglyceride and NEFA levels but not in total cholesterol. In the regular diet-fed rats (1), serum triglyceride levels were not affected by either stress or ethanol. However, NEFA levels did show differences in the response to ethanol and stress. A 63% decrease from baseline after 5{prime} of stress was partially abolished by ethanol; instead, a 24% increase was observed. Also, a stress-induced increase in NEFA which occurred after 15{prime} was not observed in the ethanol treated rats; rather, a decrease in NEFA was noted. Total cholesterol did not change in response to stress or ethanol. In the high cholesterol diet-fed rats (2), ethanol did not suppress a stress-induced increase in triglyceride levels. NEFA levels in ethanol-treated rats were higher during the first 15{prime} of stress as compared to stress alone. A decrease in NEFA was however seen in the ethanol-treated rats after 30{prime} of stress and these levels remained lower than the stress alone group. A diet-induced increase in total cholesterol levels was observed; however, no changes were seen due to either or ethanol. Thus, ethanol administration prior to acute immobilization stress did affect serum triglyceride and NEFA levels but did not change total cholesterol.

  20. Serum Thyroglobulin (Tg) Monitoring of Patients with Differentiated Thyroid Cancer Using Sensitive (Second-Generation) Immunometric Assays Can Be Disrupted by False-Negative and False-Positive Serum Thyroglobulin Autoantibody Misclassifications

    PubMed Central

    Petrovic, Ivana; Fatemi, Shireen; LoPresti, Jonathan

    2014-01-01

    Context: Reliable thyroglobulin (Tg) autoantibody (TgAb) detection before Tg testing for differentiated thyroid cancer (DTC) is critical when TgAb status (positive/negative) is used to authenticate sensitive second-generation immunometric assay (2GIMA) measurements as free from TgAb interference and when reflexing “TgAb-positive” sera to TgAb-resistant, but less sensitive, Tg methodologies (radioimmunoassay [RIA] or liquid chromatography-tandem mass spectrometry [LC-MS/MS]). Objective: The purpose of this study was to assess how different Kronus (K) vs Roche (R) TgAb method cutoffs for “positivity” influence false-negative vs false-positive serum TgAb misclassifications that may reduce the clinical utility of reflex Tg testing. Methods: Serum Tg2GIMA, TgRIA, and TgLC-MS/MS measurements for 52 TgAb-positive and 37 TgAb-negative patients with persistent/recurrent DTC were compared. A total of 1426 DTC sera with TgRIA of ?1.0 ?g/L had false-negative and false-positive TgAb frequencies determined using low Tg2GIMA/TgRIA ratios (<75%) to indicate TgAb interference. Results: TgAb-negative patients with disease displayed Tg2GIMA, TgRIA, and TgLC-MS/MS serum discordances (% coefficient of variation = 24 ± 20%, range, 0%–100%). Of the TgAb-positive patients with disease, 98% had undetectable/lower Tg2GIMA vs either TgRIA or TgLC-MS/MS (P < .01), whereas 8 of 52 (15%) had undetectable Tg2GIMA + TgLC-MS/MS associated with TgRIA of ?1.0 ?g/L. Receiver operating characteristic curve analysis reported more sensitivity for TgAb method K vs R (81.9% vs 69.1%, P < .001), but receiver operating characteristic curve cutoffs (>0.6 kIU/L [K] vs >40 kIU/L [R]) had unacceptably high false-negative frequencies (22%–32%), whereas false positives approximated 12%. Functional sensitivity cutoffs minimized false negatives (13.5% [K] vs 21.3% [R], P < .01) and severe interferences (Tg2GIMA, <0.10 ?g/L) (0.7% [K] vs 2.4% [R], P < .05) but false positives approximated 23%. Conclusions: Reliable detection of interfering TgAbs is method and cutoff dependent. No cutoff eliminated both false-negative and false-positive TgAb misclassifications. Functional sensitivity cutoffs were optimal for minimizing false negatives but have inherent imprecision (20% coefficient of variation) that, exacerbated by TgAb biologic variability during DTC monitoring, could cause TgAb status to fluctuate for patients with low TgAb concentrations, prompting unnecessary Tg method changes and disrupting Tg monitoring. Laboratories using reflexing should limit Tg method changes by considering a patient's Tg + TgAb testing history in addition to current TgAb status before Tg method selection. PMID:25226290

  1. 38. Second Floor Plan, North Elevation, South Elevation and Details. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. Second Floor Plan, North Elevation, South Elevation and Details. Addition to Bacteriology Laboratory at Letterman General Hospital, San Francisco, Cal. January 1916. BUILDING 1006. - Presidio of San Francisco, Letterman General Hospital, Building No. 27, Letterman Hospital Complex, Edie Road, San Francisco, San Francisco County, CA

  2. 35. Coal Fuel Elevator (diagonal in center), Fuel Elevator (left), ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    35. Coal Fuel Elevator (diagonal in center), Fuel Elevator (left), Fuel Storage Bins (center), and Power Plant (far center), and Retail Coal Storage Bins (right) Photograph taken by George Harven - Huber Coal Breaker, 101 South Main Street, Ashley, Luzerne County, PA

  3. 34. Coal Fuel Elevator (diagonal in foreground), Fuel Elevator (left), ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    34. Coal Fuel Elevator (diagonal in foreground), Fuel Elevator (left), Fuel Storage Bins (center), and Power Plant (far center), and Retail Coal Storage Bins (right) Photograph taken by George Harven - Huber Coal Breaker, 101 South Main Street, Ashley, Luzerne County, PA

  4. Elevated temperature biaxial fatigue

    NASA Technical Reports Server (NTRS)

    Jordan, E. H.

    1985-01-01

    A 3 year experimental program for studying elevated temperature biaxial fatigue of a nickel based alloy Hastelloy-X has been completed. A new high temperature fatigue test facility with unique capabilities has been developed. Effort was directed toward understanding multiaxial fatigue and correlating the experimental data to the existing theories of fatigue failure. The difficult task of predicting fatigue lives for nonproportional loading was used as an ultimate test for various life prediction methods being considered. The primary means of reaching improved understanding were through several critical nonproportional loading experiments. The direction of cracking observed on failed specimens was also recorded and used to guide the development of the theory. Cyclic deformation responses were permanently recorded digitally during each test. It was discovered that the cracking mode switched from primarily cracking on the maximum shear planes at room temperature to cracking on the maximum normal strain planes at 649 C. In contrast to some other metals, loading path in nonproportional loading had little effect on fatigue lives. Strain rate had a small effect on fatigue lives at 649 C. Of the various correlating parameters the modified plastic work and octahedral shear stress were the most successful.

  5. Seed oil triglyceride profiling of thirty-two hybrid grape varieties.

    PubMed

    De Marchi, Fabiola; Seraglia, Roberta; Molin, Laura; Traldi, Pietro; De Rosso, Mirko; Panighel, Annarita; Dalla Vedova, Antonio; Gardiman, Massimo; Giust, Mirella; Flamini, Riccardo

    2012-09-01

    Triglyceride profile of seed oil samples from 32 hybrid grape varieties not studied before was investigated. A new method for the analysis of triacylglycerols (TAGs) has been developed based on the direct infusion in the electrospray ionization (ESI) source and employing tetrahydrofuran/methanol/water (85:10:5 v|v|v) as solvent; the formation of [M?+?Na](+) ions in high yield has been observed. TAGs were identified by ESI-tandem mass spectrometry analysis, and the matrix-assisted-laser-desorption-ionization and time-of-flight profile of samples was determined. Six were the principal TAGs identified in seed oil: trilinolein (LLL) was the most abundant (43%), followed by dilinoleoyl-oleoylglycerol (LOL, 23%), and dilinoleoyl-palmitoylglycerol (LPL, 15%). Compounds present in lower concentration were LSL and LOO (11%), LOP (6%), and LSP (2%). Compared with seed oils produced from V. Vinifera grapes, some significant differences in the relative abundances of TAGs were found, in particular hybrid grape seed oils showed higher LOL and lower LPL content, respectively. Among the samples studied, a particularly high content of LLL (rich in unsaturated fatty acids) was found in seed oils from two red varieties. PMID:22972779

  6. Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis.

    PubMed

    Wagschal, Alexandre; Najafi-Shoushtari, S Hani; Wang, Lifeng; Goedeke, Leigh; Sinha, Sumita; deLemos, Andrew S; Black, Josh C; Ramírez, Cristina M; Li, Yingxia; Tewhey, Ryan; Hatoum, Ida; Shah, Naisha; Lu, Yong; Kristo, Fjoralba; Psychogios, Nikolaos; Vrbanac, Vladimir; Lu, Yi-Chien; Hla, Timothy; de Cabo, Rafael; Tsang, John S; Schadt, Eric; Sabeti, Pardis C; Kathiresan, Sekar; Cohen, David E; Whetstine, Johnathan; Chung, Raymond T; Fernández-Hernando, Carlos; Kaplan, Lee M; Bernards, Andre; Gerszten, Robert E; Näär, Anders M

    2015-11-01

    Genome-wide association studies (GWASs) have linked genes to various pathological traits. However, the potential contribution of regulatory noncoding RNAs, such as microRNAs (miRNAs), to a genetic predisposition to pathological conditions has remained unclear. We leveraged GWAS meta-analysis data from >188,000 individuals to identify 69 miRNAs in physical proximity to single-nucleotide polymorphisms (SNPs) associated with abnormal levels of circulating lipids. Several of these miRNAs (miR-128-1, miR-148a, miR-130b, and miR-301b) control the expression of key proteins involved in cholesterol-lipoprotein trafficking, such as the low-density lipoprotein (LDL) receptor (LDLR) and the ATP-binding cassette A1 (ABCA1) cholesterol transporter. Consistent with human liver expression data and genetic links to abnormal blood lipid levels, overexpression and antisense targeting of miR-128-1 or miR-148a in high-fat diet-fed C57BL/6J and Apoe-null mice resulted in altered hepatic expression of proteins involved in lipid trafficking and metabolism, and in modulated levels of circulating lipoprotein-cholesterol and triglycerides. Taken together, these findings support the notion that altered expression of miRNAs may contribute to abnormal blood lipid levels, predisposing individuals to human cardiometabolic disorders. PMID:26501192

  7. Exercise-induced lactate accumulation regulates intramuscular triglyceride metabolism via transforming growth factor-?1 mediated pathways.

    PubMed

    Nikooie, Rohollah; Samaneh, Sajadian

    2016-01-01

    The mechanism regulating the utilization of intramuscular triacylglycerol (IMTG) during high-intensity interval training (HIIT) and post-exercise recovery period remains elusive. In this study, the acute and long-term effects of HIIT on transforming growth factor beta 1 (TGF-?1) abundance in rat skeletal muscle and role of lactate and TGF-?1 in IMTG lipolysis during post-exercise recovery period were examined. TGF-?1 and Adipose triacylglycerol lipase (ATGL) abundance as well as total lipase activity in the gastrocnemius muscle significantly increased to a maximum value 10 h after acute bout of HIIT. Inhibition of TGF-?1 signaling by intramuscular injection of SB431542 30 min prior to the acute exercise attenuated ATGL abundance and total lipase activity in the gastrocnemius muscle in response to acute exercise. Intramuscular acute injection of lactate increased TGF-?1 and ATGL abundance in the gastrocnemius muscle and there were a significant increase in Muscle TGF-?1 and ATGL abundance after 5 weeks of HIIT/lactate treatment. These results indicate that exercise-induced lactate accumulation regulates intramuscular triglyceride metabolism via transforming growth factor-?1 mediated pathways during post-exercise recovery from strenuous exercise. PMID:26522131

  8. Increased expression of enzymes of triglyceride synthesis is essential for the development of hepatic steatosis

    PubMed Central

    Jin, Jingling; Iakova, Polina; Breaux, Meghan; Sullivan, Emily; Jawanmardi, Nicole; Chen, Dahu; Jiang, Yanjun; Medrano, Estela M.; Timchenko, Nikolai A.

    2013-01-01

    Summary Molecular mechanisms underpinning nonalcoholic fatty liver disease (NAFLD) are not well understood. The earliest step of NAFLD is hepatic steatosis, which is one of the main characteristics of aging liver. Here we present a molecular scenario of age-related liver steatosis. We show that C/EBP?-S193D knock-in mice have age-associated epigenetic changes and develop hepatic steatosis at 2 months of age. The underlying mechanism of the hepatic steatosis in old wild-type (WT) mice and in young S193D mice includes increased amounts of tripartite p300-C/EBP?/? complexes that activate promoters of five genes that drive triglyceride synthesis. Knock-down of p300 in old WT mice inhibits hepatic steatosis. Indeed, transgenic mice expressing dominant-negative p300 have fewer C/EBP?/?-p300 complexes and do not develop age-dependent hepatic steatosis. Notably, p300-C/EBP?/? pathway is activated in livers of patients with NAFLD. Thus, our results show that p300 and C/EBP proteins are essential participants in hepatic steatosis. PMID:23499441

  9. Biobased Fat Mimicking Molecular Structuring Agents for Medium-Chain Triglycerides (MCTs) and Other Edible Oils.

    PubMed

    Silverman, Julian R; John, George

    2015-12-01

    To develop sustainable value-added materials from biomass, novel small-molecule sugar ester gelators were synthesized using biocatalysis. The facile one-step regiospecific coupling of the pro-antioxidant raspberry ketone glucoside and unsaturated or saturated long- and medium-chain fatty acids provides a simple approach to tailor the structure and self-assembly of the amphiphilic product. These low molecular weight molecules demonstrated the ability to self-assemble in a variety of solvents and exhibited supergelation, with a minimum gelation concentration of 0.25 wt %, in numerous organic solvents, as well as in a range of natural edible oils, specifically a relatively unstudied group of liquids: natural medium-chain triglyceride oils, notably coconut oil. Spectroscopic analysis details the gelator structure as well as the intermolecular noncovalent interactions, which allow for gelation. X-ray diffraction studies indicate fatty acid chain packing of gelators is similar to that of natural fats, signifying the crystalline nature may lead to desirable textural properties and mouthfeel. PMID:26624525

  10. Proline oxidase-adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation.

    PubMed

    Lettieri Barbato, D; Aquilano, K; Baldelli, S; Cannata, S M; Bernardini, S; Rotilio, G; Ciriolo, M R

    2014-01-01

    The nutrient-sensing lipolytic enzyme adipose triglyceride lipase (ATGL) has a key role in adipose tissue function, and alterations in its activity have been implicated in many age-related metabolic disorders. In adipose tissue reduced blood vessel density is related to hypoxia state, cell death and inflammation. Here we demonstrate that adipocytes of poorly vascularized enlarged visceral adipose tissue (i.e. adipose tissue of old mice) suffer from limited nutrient delivery. In particular, nutrient starvation elicits increased activity of mitochondrial proline oxidase/dehydrogenase (POX/PRODH) that is causal in triggering a ROS-dependent induction of ATGL. We demonstrate that ATGL promotes the expression of genes related to mitochondrial oxidative metabolism (peroxisome proliferator-activated receptor-?, peroxisome proliferator-activated receptor-? coactivator-1?), thus setting a metabolic switch towards fat utilization that supplies energy to starved adipocytes and prevents cell death, as well as adipose tissue inflammation. Taken together, these results identify ATGL as a stress resistance mediator in adipocytes, restraining visceral adipose tissue dysfunction typical of age-related metabolic disorders. PMID:24096872

  11. Modulation of triglyceride accumulation in adipocytes by psychopharmacological agents in vitro.

    PubMed

    Löffler, Dennis; Landgraf, Kathrin; Körner, Antje; Kratzsch, Jürgen; Kirkby, Kenneth Clifford; Himmerich, Hubertus

    2016-01-01

    Weight gain is a major problem during psychopharmacological treatment. Research has concentrated on the appetite inducing properties and mechanisms of these drugs in the central nervous system. The potential contribution of direct effects of drugs on metabolically relevant peripheral cells such as adipocytes is less well understood. We examined the influence of the antidepressant imipramine, the antipsychotic clozapine, and the mood stabilizer lithium on preadipocytes and adipocytes in vitro, using Simpson-Golabi-Behmel syndrome (SGBS) cells, an established human preadipocyte model. Parameters of cell differentiation and signaling, and cell metabolism were measured. We found significantly increased triglyceride accumulation in adipocytes after supplementation with imipramine and lithium at therapeutic concentrations, compared to non-supplemented control samples. However, gene expression levels of an early marker of adipogenesis, the peroxisome proliferator-activated receptor gamma (PPAR-?) and a late marker of adipogenesis, the fatty acid binding protein 4 (FABP4), as well as expression of adiponectin (ADIPOQ) did not change significantly in the presence of these psychopharmacological agents. The results suggest a direct influence of imipramine and lithium but not clozapine on fat storage of adipocytes. The underlying mechanisms of fatty acid storage and adipocyte differentiation however remain to be elucidated. PMID:26524413

  12. Effect of a counterion on the glass transition temperature (T(g)') during lyophilization of ganciclovir salt forms.

    PubMed

    Kumar, Lokesh; Baheti, Ankit; Bansal, Arvind K

    2011-02-01

    This manuscript deals with the effect of a counterion on the glass transition temperature for lyophilization of ganciclovir salts. Salt forms of ganciclovir, namely, sodium, potassium, rubidium, and cesium salts, were prepared by an in situ technique and analyzed by modulated differential scanning calorimetry (MDSC) for the determination of the critical process parameter for lyophilization. Nonionized ganciclovir and its salt forms showed a glass transition (T(g)') in the reversing MDSC signal, confirming their amorphous nature. T(g)' of the nonionized ganciclovir and ganciclovir sodium, potassium, rubidium, and cesium salts followed the order: sodium salt (-34.94°C) > nonionized ganciclovir (-40.15°C) > potassium salt (-46.23°C) > rubidium salt (-49.95°C) > cesium salt (-53.62°C). The analysis of the freezable water content for ganciclovir and its salts showed the trend: pure water > nonionized ganciclovir > potassium salt ? sodium salt > rubidium salt > cesium salt. This showed that a majority of water in the salts is present as an unfrozen fraction, thus leading to a lowering of T(g)' because of the plasticizing effect of unfrozen water. Density functional theory (DFT) further suggested a positive contribution of the strength of intra- and intermolecular force of interactions to the T(g)' value, with a higher intramolecular and intermolecular force of interaction leading to a higher T(g)'. PMID:21133416

  13. DHA Improves Cognition and Prevents Dysfunction of Entorhinal Cortex Neurons in 3xTg-AD Mice

    PubMed Central

    Arsenault, Dany; Julien, Carl; Tremblay, Cyntia; Calon, Frédéric

    2011-01-01

    Defects in neuronal activity of the entorhinal cortex (EC) are suspected to underlie the symptoms of Alzheimer's disease (AD). Whereas neuroprotective effects of docosahexaenoic acid (DHA) have been described, the effects of DHA on the physiology of EC neurons remain unexplored in animal models of AD. Here, we show that DHA consumption improved object recognition (?12%), preventing deficits observed in old 3xTg-AD mice (?12%). Moreover, 3xTg-AD mice displayed seizure-like akinetic episodes, not detected in NonTg littermates and partly prevented by DHA (?50%). Patch-clamp recording revealed that 3xTg-AD EC neurons displayed (i) loss of cell capacitance (CC), suggesting reduced membrane surface area; (ii) increase of firing rate versus injected current (F-I) curve associated with modified action potentials, and (iii) overactivation of glutamatergic synapses, without changes in synaptophysin levels. DHA consumption increased CC (?12%) and decreased F-I slopes (?21%), thereby preventing the opposite alterations observed in 3xTg-AD mice. Our results indicate that cognitive performance and basic physiology of EC neurons depend on DHA intake in a mouse model of AD. PMID:21383850

  14. Quality assurance for image-guided radiation therapy utilizing CT-based technologies: A report of the AAPM TG-179

    SciTech Connect

    Bissonnette, Jean-Pierre; Balter, Peter A.; Dong Lei; Langen, Katja M.; Lovelock, D. Michael; Miften, Moyed; Moseley, Douglas J.; Pouliot, Jean; Sonke, Jan-Jakob; Yoo, Sua

    2012-04-15

    Purpose: Commercial CT-based image-guided radiotherapy (IGRT) systems allow widespread management of geometric variations in patient setup and internal organ motion. This document provides consensus recommendations for quality assurance protocols that ensure patient safety and patient treatment fidelity for such systems. Methods: The AAPM TG-179 reviews clinical implementation and quality assurance aspects for commercially available CT-based IGRT, each with their unique capabilities and underlying physics. The systems described are kilovolt and megavolt cone-beam CT, fan-beam MVCT, and CT-on-rails. A summary of the literature describing current clinical usage is also provided. Results: This report proposes a generic quality assurance program for CT-based IGRT systems in an effort to provide a vendor-independent program for clinical users. Published data from long-term, repeated quality control tests form the basis of the proposed test frequencies and tolerances.Conclusion: A program for quality control of CT-based image-guidance systems has been produced, with focus on geometry, image quality, image dose, system operation, and safety. Agreement and clarification with respect to reports from the AAPM TG-101, TG-104, TG-142, and TG-148 has been addressed.

  15. Space Station tethered elevator system

    NASA Technical Reports Server (NTRS)

    Haddock, Michael H.; Anderson, Loren A.; Hosterman, K.; Decresie, E.; Miranda, P.; Hamilton, R.

    1989-01-01

    The optimized conceptual engineering design of a space station tethered elevator is presented. The tethered elevator is an unmanned, mobile structure which operates on a ten-kilometer tether spanning the distance between Space Station Freedom and a platform. Its capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The report discusses the potential uses, parameters, and evolution of the spacecraft design. Emphasis is placed on the elevator's structural configuration and three major subsystem designs. First, the design of elevator robotics used to aid in elevator operations and tethered experimentation is presented. Second, the design of drive mechanisms used to propel the vehicle is discussed. Third, the design of an onboard self-sufficient power generation and transmission system is addressed.

  16. Pyrolysis of chitin biomass: TG-MS analysis and solid char residue characterization.

    PubMed

    Qiao, Yan; Chen, Shuai; Liu, Ying; Sun, Haizhen; Jia, Shiyu; Shi, Junyan; Pedersen, Christian Marcus; Wang, Yingxiong; Hou, Xianglin

    2015-11-20

    The thermal degradation of chitin biomass with various molecular structures was investigated by thermogravimetric analysis (TG), and the gaseous products were analyzed by connected mass spectroscopy (MS). The chemical structure and morphology of char residues collected at 750°C using the model substrates GlcNH2 and GlcNAc, were characterized systematically. The experimental results disclosed that one main mass loss stage was observed for each substrate. Chitosan samples with high molecular weight shown the more thermal stability, and chitin showed the highest thermal stability. Additionally, it was found that catalysts play a significant role during the pyrolysis. The gaseous evolution components, including NH3, H2O, CO, and CO2 were observed by on line MS. The experimental results disclosed that the obtained carbonaceous materials had lost the original hydrocarbon structure totally, and transformed into an aromatic structure with high carbon and nitrogen content, which was identified by XPS and solid state NMR. PMID:26344268

  17. Dynamic traffic grooming with Spectrum Engineering (TG-SE) in flexible grid optical networks

    NASA Astrophysics Data System (ADS)

    Yu, Xiaosong; Zhao, Yongli; Zhang, Jiawei; Wang, Jianping; Zhang, Guoying; Chen, Xue; Zhang, Jie

    2015-12-01

    Flexible grid has emerged as an evolutionary technology to satisfy the ever increasing demand for higher spectrum efficiency and operational flexibility. To optimize the spectrum resource utilization, this paper introduces the concept of Spectrum Engineering in flex-grid optical networks. The sliceable optical transponder has been proposed to offload IP traffic to the optical layer and reduce the number of IP router ports and transponders. We discuss the impact of sliceable transponder in traffic grooming and propose several traffic-grooming schemes with Spectrum Engineering (TG-SE). Our results show that there is a tradeoff among different traffic grooming policies, which should be adopted based on the network operator's objectives. The proposed traffic grooming with Spectrum Engineering schemes can reduce OPEX as well as increase spectrum efficiency by efficiently utilizing the bandwidth variability and capability of sliceable optical transponders.

  18. Evaluating CMA equalization of SOQPSK-TG data for aeronautical telemetry

    NASA Astrophysics Data System (ADS)

    Cole-Rhodes, Arlene; KoneDossongui, Serge; Umuolo, Henry; Rice, Michael

    2015-05-01

    This paper presents the results of using a constant modulus algorithm (CMA) to recover shaped offset quadrature-phase shift keying (SOQPSK)-TG modulated data, which has been transmitted using the iNET data packet structure. This standard is defined and used for aeronautical telemetry. Based on the iNET-packet structure, the adaptive block processing CMA equalizer can be initialized using the minimum mean square error (MMSE) equalizer [3]. This CMA equalizer is being evaluated for use on iNET structured data, with initial tests being conducted on measured data which has been received in a controlled laboratory environment. Thus the CMA equalizer is applied at the receiver to data packets which have been experimentally generated in order to determine the feasibility of our equalization approach, and its performance is compared to that of the MMSE equalizer. Performance evaluation is based on computed bit error rate (BER) counts for these equalizers.

  19. The Polyphenol Oleuropein Aglycone Protects TgCRND8 Mice against Aß Plaque Pathology

    PubMed Central

    Grossi, Cristina; Rigacci, Stefania; Ambrosini, Stefano; Ed Dami, Teresa; Luccarini, Ilaria; Traini, Chiara; Failli, Paola; Berti, Andrea; Casamenti, Fiorella; Stefani, Massimo

    2013-01-01

    The claimed beneficial effects of the Mediterranean diet include prevention of several age-related dysfunctions including neurodegenerative diseases and Alzheimer-like pathology. These effects have been related to the protection against cognitive decline associated with aging and disease by a number of polyphenols found in red wine and extra virgin olive oil. The double transgenic TgCRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein), aged 1.5 and 4, and age-matched wild type control mice were used to examine in vivo the effects of 8 weeks dietary supplementation of oleuropein aglycone (50 mg/kg of diet), the main polyphenol found in extra virgin olive oil. We report here that dietary supplementation of oleuropein aglycone strongly improves the cognitive performance of young/middle-aged TgCRND8 mice, a model of amyloid-ß deposition, respect to age-matched littermates with un-supplemented diet. Immunofluorescence analysis of cerebral tissue in oleuropein aglycone-fed transgenic mice showed remarkably reduced ß-amyloid levels and plaque deposits, which appeared less compact and “fluffy”; moreover, microglia migration to the plaques for phagocytosis and a remarkable reduction of the astrocyte reaction were evident. Finally, oleuropein aglycone-fed mice brain displayed an astonishingly intense autophagic reaction, as shown by the increase of autophagic markers expression and of lysosomal activity. Data obtained with cultured cells confirmed the latter evidence, suggesting mTOR regulation by oleuropein aglycone. Our results support, and provide mechanistic insights into, the beneficial effects against Alzheimer-associated neurodegeneration of a polyphenol enriched in the extra virgin olive oil, a major component of the Mediterranean diet. PMID:23951225

  20. The RenTg Mice: A Powerful Tool to Study Renin-Dependent Chronic Kidney Disease

    PubMed Central

    Huby, Anne-Cecile; Kavvadas, Panagiotis; Alfieri, Carlo; Abed, Ahmed; Toubas, Julie; Rastaldi, Maria-Pia; Dussaule, Jean-Claude; Chatziantoniou, Christos; Chadjichristos, Christos E.

    2012-01-01

    Background Several studies have shown that activation of the renin-angiotensin system may lead to hypertension, a major risk factor for the development of chronic kidney disease (CKD). The existing hypertension-induced CDK mouse models are quite fast and consequently away from the human pathology. Thus, there is an urgent need for a mouse model that can be used to delineate the pathogenic process leading to progressive renal disease. The objective of this study was dual: to investigate whether mice overexpressing renin could mimic the kinetics and the physiopathological characteristics of hypertension-induced renal disease and to identify cellular and/or molecular events characterizing the different steps of the progression of CKD. Methodology/Principal Findings We used a novel transgenic strain, the RenTg mice harboring a genetically clamped renin transgene. At 3 months, heterozygous mice are hypertensive and slightly albuminuric. The expression of adhesion markers such as vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 are increased in the renal vasculature indicating initiation of endothelial dysfunction. At 5 months, perivascular and periglomerular infiltrations of macrophages are observed. These early renal vascular events are followed at 8 months by leukocyte invasion, decreased expression of nephrin, increased expression of KIM-1, a typical protein of tubular cell stress, and of several pro-fibrotic agents of the TGF? family. At 12 months, mice display characteristic structural alterations of hypertensive renal disease such as glomerular ischemia, glomerulo- and nephroangio-sclerosis, mesangial expansion and tubular dilation. Conclusions/Significance The RenTg strain develops CKD progressively. In this model, endothelial dysfunction is an early event preceding the structural and fibrotic alterations which ultimately lead to the development of CKD. This model can provide new insights into the mechanisms of chronic renal failure and help to identify new targets for arresting and/or reversing the development of the disease. PMID:23300650

  1. The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology.

    PubMed

    Grossi, Cristina; Rigacci, Stefania; Ambrosini, Stefano; Ed Dami, Teresa; Luccarini, Ilaria; Traini, Chiara; Failli, Paola; Berti, Andrea; Casamenti, Fiorella; Stefani, Massimo

    2013-01-01

    The claimed beneficial effects of the Mediterranean diet include prevention of several age-related dysfunctions including neurodegenerative diseases and Alzheimer-like pathology. These effects have been related to the protection against cognitive decline associated with aging and disease by a number of polyphenols found in red wine and extra virgin olive oil. The double transgenic TgCRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein), aged 1.5 and 4, and age-matched wild type control mice were used to examine in vivo the effects of 8 weeks dietary supplementation of oleuropein aglycone (50 mg/kg of diet), the main polyphenol found in extra virgin olive oil. We report here that dietary supplementation of oleuropein aglycone strongly improves the cognitive performance of young/middle-aged TgCRND8 mice, a model of amyloid-ß deposition, respect to age-matched littermates with un-supplemented diet. Immunofluorescence analysis of cerebral tissue in oleuropein aglycone-fed transgenic mice showed remarkably reduced ß-amyloid levels and plaque deposits, which appeared less compact and "fluffy"; moreover, microglia migration to the plaques for phagocytosis and a remarkable reduction of the astrocyte reaction were evident. Finally, oleuropein aglycone-fed mice brain displayed an astonishingly intense autophagic reaction, as shown by the increase of autophagic markers expression and of lysosomal activity. Data obtained with cultured cells confirmed the latter evidence, suggesting mTOR regulation by oleuropein aglycone. Our results support, and provide mechanistic insights into, the beneficial effects against Alzheimer-associated neurodegeneration of a polyphenol enriched in the extra virgin olive oil, a major component of the Mediterranean diet. PMID:23951225

  2. Mannan-Abeta28 conjugate prevents Abeta-plaque deposition, but increases microhemorrhages in the brains of vaccinated Tg2576 (APPsw) mice

    PubMed Central

    Petrushina, Irina; Ghochikyan, Anahit; Mkrtichyan, Mikayel; Mamikonyan, Grigor; Movsesyan, Nina; Ajdari, Rodmehr; Vasilevko, Vitaly; Karapetyan, Adrine; Lees, Andrew; Agadjanyan, Michael G; Cribbs, David H

    2008-01-01

    Background New pre-clinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse responses that occurred during the clinical trials with AN-1792 vaccine formulation. Recently, we have pursued an alternative immunization strategy that replaces QS21 the Th1 type adjuvant used in the AN-1792 clinical trial with a molecular adjuvant, mannan that can promote a Th2-polarized immune response through interactions with mannose-binding and CD35/CD21 receptors of the innate immune system. Previously we established that immunization of wild-type mice with mannan-A?28 conjugate promoted Th2-mediated humoral and cellular immune responses. In the current study, we tested the efficacy of this vaccine configuration in amyloid precursor protein (APP) transgenic mice (Tg2576). Methods Mannan was purified, activated and chemically conjugated to A?28 peptide. Humoral immune responses induced by the immunization of mice with mannan-A?28 conjugate were analyzed using a standard ELISA. A?42 and A?40 amyloid burden, cerebral amyloid angiopathy (CAA), astrocytosis, and microgliosis in the brain of immunized and control mice were detected using immunohistochemistry. Additionally, cored plaques and cerebral vascular microhemorrhages in the brains of vaccinated mice were detected by standard histochemistry. Results Immunizations with low doses of mannan-A?28 induced potent and long-lasting anti-A? humoral responses in Tg2576 mice. Even 11 months after the last injection, the immunized mice were still producing low levels of anti-A? antibodies, predominantly of the IgG1 isotype, indicative of a Th2 immune response. Vaccination with mannan-A?28 prevented A? plaque deposition, but unexpectedly increased the level of microhemorrhages in the brains of aged immunized mice compared to two groups of control animals of the same age either injected with molecular adjuvant fused with an irrelevant antigen, BSA (mannan-BSA) or non-immunized mice. Of note, mice immunized with mannan-A?28 showed a trend toward elevated levels of CAA in the neocortex and in the leptomeninges compared to that in mice of both control groups. Conclusion Mannan conjugated to A?28 provided sufficient adjuvant activity to induce potent anti-A? antibodies in APP transgenic mice, which have been shown to be hyporesponsive to immunization with A? self-antigen. However, in old Tg2576 mice there were increased levels of cerebral microhemorrhages in mannan-A?28 immunized mice. This effect was likely unrelated to the anti-mannan antibodies induced by the immunoconjugate, because control mice immunized with mannan-BSA also induced antibodies specific to mannan, but did not have increased levels of cerebral microhemorrhages compared with non-immunized mice. Whether these anti-mannan antibodies increased the permeability of the blood brain barrier thus allowing elevated levels of anti-A? antibodies entry into cerebral perivascular or brain parenchymal spaces and contributed to the increased incidence of microhemorrhages remains to be investigated in the future studies. PMID:18823564

  3. Influence of immobilization on the stability of pTG201 recombinant plasmid in some strains of Escherichia coli

    SciTech Connect

    Nasri, M.; Sayadi, S.; Barbotin, J.N.; Dhulster, P.; Thomas, D.

    1987-04-01

    The stability of pTG201 plasmid was examined by continuous culture in three genetically different Escherichia coli hosts. Two types of experiment were carried out, one with free cells and one with immobilized cells. When cells were cultivated in free continuous culture in the absence of antibiotic selection, the plasmid was maintained with various degree of stability in the three host organisms. By contrast, in continuous culture with immobilized cells, plasmid pTG201 was stably maintained in the three strains. The authors showed that the increase in pTG201 stability in immobilized cells is due neither to plasmid transfer between immobilized cells nor to an increase of the plasmid copy number of immobilized cells. They also showed that plasmid-free cells, when coimmobilized and grown in competition with plasmid-containing cells, cannot overrun the culture.

  4. Kinetics of thermolysis of lanthanum nitrate with hexamethylenetetramine: Crystal structure, TG-DSC, impact and friction sensitivity studies, Part-96

    NASA Astrophysics Data System (ADS)

    Nibha; Baranwal, B. P.; Singh, Gurdip; Singh, C. P.; Daniliuc, Constantin G.; Soni, P. K.; Nath, Yogeshwar

    2014-11-01

    The development of high energetic materials includes process ability and the ability to attain insensitive munitions (IM). This paper investigates the preparation of lanthanum metal nitrate complex of hexamethylenetetramine in water at room temperature. This complex of molecular formulae [La (NO3)2(H2O)6] (2HMTA) (NO3-) (H2O) was characterized by X-ray crystallography. Thermal decomposition was investigated using TG, TG-DSC and ignition delay measurements. Kinetic analysis of isothermal TG data has been investigated using model fitting methods as well as model free isoconversional methods. The sensitivity measurements towards mechanical destructive stimuli such as impact and friction were carried out and the complex was found to be insensitive. In order to identify the end product of thermolysis, X-ray diffraction patterns of end product was carried out which proves the formation of La2O3.

  5. Competition between substrate-mediated ?-? stacking and surface-mediated T(g) depression in ultrathin conjugated polymer films.

    PubMed

    Wang, Tao; Pearson, Andrew J; Dunbar, Alan D F; Staniec, Paul A; Watters, Darren C; Coles, David; Yi, Hunan; Iraqi, Ahmed; Lidzey, David G; Jones, Richard A L

    2012-12-01

    We report surface and interface effects in dynamics and chain conformation in the thin film of conjugated polymer PCDTBT. To probe dynamic anomalies, we measure the glass transition temperature (T(g)) of PCDTBT films as a function of thickness, and find that there is a significant depression in T(g) for films less than 100 nm thick; a result qualitatively similar to that observed in many other polymer film systems. However, for films less than 40 nm, the T(g) converges to a constant value of 20 K below its bulk value. Grazing incidence X-ray diffraction shows depth-dependent molecular organization that is associated with the unusual thickness-dependent dynamics. PMID:23239269

  6. APOA5 gene variation interacts with dietary fat intake to modulate obesity and circulating triglycerides in a Mediterranean population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    APOA5 is one of the strongest regulators of plasma TG concentrations; nevertheless, its mechanisms of action are poorly characterized. Genetic variability at the APOA5 locus has also been associated with increased cardiovascular disease risk; however, this predisposition could be attenuated in the c...

  7. Do Negative 124I Pretherapy Positron Emission Tomography Scans in Patients with Elevated Serum Thyroglobulin Levels Predict Negative 131I Posttherapy Scans?

    PubMed Central

    Khorjekar, Gauri R.; Garcia, Carlos; O'Neil, Jeffrey; Moreau, Shari; Atkins, Francis B.; Mete, Mihriye; Orquiza, Michael H.; Burman, Kenneth; Wartofsky, Leonard

    2014-01-01

    Background: The management of patients with differentiated thyroid cancer (DTC) who have elevated serum thyroglobulin (Tg) levels and negative 131I or 123I scans is problematic, and the decision regarding whether or not to administer 131I therapy (a “blind” therapy) is also problematic. While 124I positron emission tomography (PET) imaging has been shown to detect more foci of residual thyroid tissue and/or metastases secondary to DTC than planar 131I images, the utility of a negative 124I PET scan in deciding whether or not to consider performing blind 131I therapy is unknown. The objective of this study was to determine whether a negative 124I pretherapy PET scan in patients with elevated serum Tg levels and negative 131I or 123I scans predicts a negative 131I posttherapy scan. Methods: Several prospective studies have been performed to compare the radiopharmacokinetics of 124I PET versus 131I planar imaging in patients who 1) had histologically proven DTC, 2) were suspected to have metastatic DTC (e.g., elevated Tg, positive recent fine-needle aspiration cytology, suspicious enlarging mass), and 3) had 131I planar and 124I PET imaging performed. Using these criteria, we retrospectively identified patients who had an elevated Tg, a negative diagnostic 131I/123I scan, a negative diagnostic 124I PET scan, therapy with 131I, a post-therapy 131I scan, and a prior 131I therapy with a subsequent positive post-131I therapy scan. For each scan, two readers categorized every focus of 131I and 124I uptake as positive for thyroid tissue/metastases or physiological. Results: Twelve patients met the above criteria. Ten of these 12 patients (83%) had positive foci on 131I posttherapy scan. Conclusion: In our selected patient population, 131I posttherapy scans are frequently positive in patients with elevated serum Tg levels, a negative diagnostic 131I or 123I scan, and a negative 124I PET scan. Thus, for a patient with elevated serum Tg level, negative diagnostic 131I planar scan, and a prior post-131I therapy scan that was positive, a negative 124I PET scan will have a low predictive value for a negative post-131I therapy scan and should not be used to exclude the option of blind 131I therapy. PMID:24820222

  8. Cotinine halts the advance of Alzheimer's disease-like pathology and associated depressive-like behavior in Tg6799 mice

    PubMed Central

    Patel, Sagar; Grizzell, J. Alex; Holmes, Rosalee; Zeitlin, Ross; Solomon, Rosalynn; Sutton, Thomas L.; Rohani, Adeeb; Charry, Laura C.; Iarkov, Alexandre; Mori, Takashi; Echeverria Moran, Valentina

    2014-01-01

    Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-? (A?) plaque pathology in transgenic 6799 mice (Tg6799 mice) when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in Tg6799 mice when left untreated until after a more advanced stage of the disease's development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant A? plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment to Tg6799 mice, withheld until after a mid-level progression of AD-like pathology, reduced A? levels/plaques and depressive-like behavior. Moreover, this treatment paradigm dramatically improved working memory as compared to control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed. PMID:25100990

  9. Electrochemistry for biofuel generation: transformation of fatty acids and triglycerides to diesel-like olefin/ether mixtures and olefins.

    PubMed

    dos Santos, Tatiane R; Harnisch, Falk; Nilges, Peter; Schröder, Uwe

    2015-03-01

    Electroorganic synthesis can be exploited for the production of biofuels from fatty acids and triglycerides. With Coulomb efficiencies (CE) of up to 50?%, the electrochemical decarboxylation of fatty acids in methanolic and ethanolic solutions leads to the formation of diesel-like olefin/ether mixtures. Triglycerides can be directly converted in aqueous solutions by using sonoelectrochemistry, with olefins as the main products (with a CE of more than 20?%). The latter reaction, however, is terminated at around 50?% substrate conversion by the produced side-product glycerol. An energy analysis shows that the electrochemical olefin synthesis can be an energetically competitive, sustainable, and--in comparison with established processes--economically feasible alternative for the exploitation of fats and oils for biofuel production. PMID:25648972

  10. Elevation Derivatives for National Applications

    USGS Publications Warehouse

    U.S. Geological Survey

    2005-01-01

    The Elevation Derivatives for National Applications (EDNA) project is a multi-agency effort to develop standard topographically derived layers for use in hydrologic and environmental modeling. The EDNA takes advantage of the seamless and filtered characteristics for the National Elevation Dataset (NED) to create a hydrologically conditioned Digital Elevation Model (DEM) useful for modeling applications. The goals of the project are to create a hydrologically conditioned DEM and systematically extract a set of standard derivatives that can be used to facilitate data integration with other U.S. Geological Survey (USGS) framework data sets such as the National Hydrography Dataset (NHD) and the Watershed Boundaries Dataset (WBD).

  11. Actinide Thermodynamics at Elevated Temperatures

    SciTech Connect

    Friese, Judah I.; Rao, Linfeng; Xia, Yuanxian; Bachelor, Paula P.; Tian, Guoxin

    2007-11-16

    The postclosure chemical environment in the proposed Yucca Mountain repository is expected to experience elevated temperatures. Predicting migration of actinides is possible if sufficient, reliable thermodynamic data on hydrolysis and complexation are available for these temperatures. Data are scarce and scattered for 25 degrees C, and nonexistent for elevated temperatures. This collaborative project between LBNL and PNNL collects thermodynamic data at elevated temperatures on actinide complexes with inorganic ligands that may be present in Yucca Mountain. The ligands include hydroxide, fluoride, sulfate, phosphate and carbonate. Thermodynamic parameters of complexation, including stability constants, enthalpy, entropy and heat capacity of complexation, are measured with a variety of techniques including solvent extraction, potentiometry, spectrophotometry and calorimetry

  12. The Correlation between the Triglyceride to High Density Lipoprotein Cholesterol Ratio and Computed Tomography-Measured Visceral Fat and Cardiovascular Disease Risk Factors in Local Adult Male Subjects

    PubMed Central

    Park, Hye-Rin; Han, A Lum; Jeong, Yong Joon

    2015-01-01

    Background We studied the association between the triglyceride to high-density lipoprotein cholesterol ratio and computed tomography-measured visceral fat as well as cardiovascular risk factors among Korean male adults. Methods We measured triglycerides, high density lipoprotein cholesterol, body mass, waist circumference, fasting plasma glucose, hemoglobin A1c, systolic blood pressure, diastolic blood pressure, visceral fat, and subcutaneous fat among 372 Korean men. The visceral fat and subcutaneous fat areas were measured by computed tomography using a single computed tomography slice at the L4-5 lumbar level. We analyzed the association between the triglyceride to high density lipoprotein cholesterol ratio and visceral fat as well as cardiovascular risk factors. Results A positive correlation was found between the triglyceride to high density lipoprotein cholesterol ratio and variables such as body mass index, waist circumference, fasting plasma glucose, hemoglobin A1c, visceral fat, and the visceral-subcutaneous fat ratio. However, there was no significant correlation between the triglyceride to high density lipoprotein cholesterol ratio and subcutaneous fat or blood pressure. Multiple logistic regression analyses revealed significant associations between a triglyceride to high density lipoprotein cholesterol ratio ?3 and diabetes, a body mass index ?25 kg/m2, a waist circumference ?90 cm, and a visceral fat area ?100 cm2. The triglyceride to high density lipoprotein cholesterol ratio was not significantly associated with hypertension. Conclusion There were significant associations between the triglyceride to high density lipoprotein cholesterol ratio and body mass, waist circumference, diabetes, and visceral fat among a clinical sample of Korean men. In the clinical setting, the triglyceride to high density lipoprotein cholesterol ratio may be a simple and useful indicator for visceral obesity and cardiovascular disease. PMID:26634102

  13. Pigment epithelium-derived factor regulates microvascular permeability through adipose triglyceride lipase in sepsis.

    PubMed

    He, Ting; Hu, Jiongyu; Yan, Guangning; Li, Lingfei; Zhang, Dongxia; Zhang, Qiong; Chen, Bing; Huang, Yuesheng

    2015-07-01

    The integrity of the vascular barrier, which is essential to blood vessel homoeostasis, can be disrupted by a variety of soluble permeability factors during sepsis. Pigment epithelium-derived factor (PEDF), a potent endogenous anti-angiogenic molecule, is significantly increased in sepsis, but its role in endothelial dysfunction has not been defined. To assess the role of PEDF in the vasculature, we evaluated the effects of exogenous PEDF in vivo using a mouse model of cecal ligation and puncture (CLP)-induced sepsis and in vitro using human dermal microvascular endothelial cells (HDMECs). In addition, PEDF was inhibited using a PEDF-monoclonal antibody (PEDF-mAb) or recombinant lentivirus vectors targeting PEDF receptors, including adipose triglyceride lipase (ATGL) and laminin receptor (LR). Our results showed that exogenous PEDF induced vascular hyperpermeability, as measured by extravasation of Evan's Blue (EB), dextran and microspheres in the skin, blood, trachea and cremaster muscle, both in a normal state and under conditions of sepsis. In control and LR-shRNA-treated HDMECs, PEDF alone or in combination with inflammatory mediators resulted in activation of RhoA, which was accompanied by actin rearrangement and disassembly of intercellular junctions, impairing endothelial barrier function. But in ATGL-shRNA-treated HDMECs, PEDF failed to induce the aforementioned alterations, suggesting that PEDF-induced hyperpermeability was mediated through the ATGL receptor. These results reveal a novel role for PEDF as a potential vasoactive substance in septic vascular hyperpermeability. Furthermore, our results suggest that PEDF and ATGL may serve as therapeutic targets for managing vascular hyperpermeability in sepsis. PMID:25700221

  14. Enzymatically Modified Starch Ameliorates Postprandial Serum Triglycerides and Lipid Metabolome in Growing Pigs

    PubMed Central

    Metzler-Zebeli, Barbara U.; Eberspächer, Eva; Grüll, Dietmar; Kowalczyk, Lidia; Molnar, Timea; Zebeli, Qendrim

    2015-01-01

    Developing host digestion-resistant starches to promote human health is of great research interest. Chemically modified starches (CMS) are widely used in processed foods and although the modification of the starch molecule allows specific reduction in digestibility, the metabolic effects of CMS have been less well described. This short-term study evaluated the impact of enzymatically modified starch (EMS) on fasting and postprandial profiles of blood glucose, insulin and lipids, and serum metabolome in growing pigs. Eight jugular-vein catheterized pigs (initial body weight, 37.4 kg; 4 months of age) were fed 2 diets containing 72% purified starch (EMS or waxy corn starch (control)) in a cross-over design for 7 days. On day 8, an 8-hour meal tolerance test (MTT) was performed with serial blood samplings. Besides biochemical analysis, serum was analysed for 201 metabolites through targeted mass spectrometry-based metabolomic approaches. Pigs fed the EMS diet showed increased (P<0.05) immediate serum insulin and plasma glucose response compared to pigs fed the control diet; however, area-under-the-curves for insulin and glucose were not different among diets. Results from MTT indicated reduced postprandial serum triglycerides with EMS versus control diet (P<0.05). Likewise, serum metabolome profiling identified characteristic changes in glycerophospholipid, lysophospholipids, sphingomyelins and amino acid metabolome profiles with EMS diet compared to control diet. Results showed rapid adaptations of blood metabolites to dietary starch shifts within 7 days. In conclusion, EMS ingestion showed potential to attenuate postprandial raise in serum lipids and suggested constant alteration in the synthesis or breakdown of sphingolipids and phospholipids which might be a health benefit of EMS consumption. Because serum insulin was not lowered, more research is warranted to reveal possible underlying mechanisms behind the observed changes in the profile of serum lipid metabolome in response to EMS consumption. PMID:26076487

  15. Effects of CETP inhibition on triglyceride-rich lipoprotein composition and apoB-48 metabolism

    PubMed Central

    Diffenderfer, Margaret R.; Brousseau, Margaret E.; Millar, John S.; Barrett, P. Hugh R.; Nartsupha, Chorthip; Schaefer, Peter M.; Wolfe, Megan L.; Dolnikowski, Gregory G.; Rader, Daniel J.; Schaefer, Ernst J.

    2012-01-01

    Cholesteryl ester transfer protein (CETP) facilitates the transfer of HDL cholesteryl ester to triglyceride-rich lipoproteins (TRL). This study aimed to determine the effects of CETP inhibition with torcetrapib on TRL composition and apoB-48 metabolism. Study subjects with low HDL cholesterol (<40 mg/dl), either untreated (n = 9) or receiving atorvastatin 20 mg daily (n = 9), received placebo for 4 weeks, followed by torcetrapib 120 mg once daily for the next 4 weeks. A subset of the subjects not treated with atorvastatin participated in a third phase (n = 6), in which they received torcetrapib 120 mg twice daily for an additional 4 weeks. At the end of each phase, all subjects received a primed-constant infusion of [5,5,5-2H3]L-leucine, while in the constantly fed state, to determine the kinetics of TRL apoB-48 and TRL composition. Relative to placebo, torcetrapib markedly reduced TRL CE levels in all groups (??69%; P < 0.005). ApoB-48 pool size (PS) and production rate (PR) decreased in the nonatorvastatin once daily (PS: ?49%, P = 0.007; PR: ?49%, P = 0.005) and twice daily (PS: ?30%, P = 0.01; PR: ?27%, P = 0.13) cohorts. In the atorvastatin cohort, apoB-48 PS and PR, which were already lowered by atorvastatin, did not change with torcetrapib. Our findings indicate that CETP inhibition reduced plasma apoB-48 concentrations by reducing apoB-48 production but did not have this effect in subjects already treated with atorvastatin. PMID:22474066

  16. Development, characterisation and evaluation of supersaturated triglyceride free drug delivery (s-TFDDS) of lornoxicam.

    PubMed

    Bramhane, D M; Jadhav, N V; Vavia, P R

    2013-10-01

    The present work was aimed at formulating a supersaturated triglyceride free drug delivery system (s-TFDDS) of lornoxicam and evaluating its in vitro and in vivo potential. s-TFDDS contain the drug above its saturation solubility and consists of a hydrophilic surfactant, a hydrophobic surfactant, solubiliser and pH modifier. D-optimal mixture experimental design was applied to optimise s-TFDDS. Three formulation variables, X 1 (Tween 20®), the surfactant X 2 (Capryl PGMC®) and X 3 (Transcutol P), were included in the design. The systems were assessed for light transmittance and solubility of lornoxicam. The values of optimised formulation components (X 1, X 2 and X 3) were 60.0, 10.0 and 30.0 %, respectively. The combination of components was optimised for maximum solubilisation capacity of lornoxicam by combined effect of pH and temperature. The optimised liquid preconcentrate was evaluated for particle size (small-angle neutron scattering study), robustness to precipitation, effect of polymer on precipitation inhibition and by in vitro dissolution. The liquid preconcentrate was adsorbed on solid carrier (Neusilin US2, Sylysia 320) and characterised by in vitro dissolution, X-ray diffraction, differential scanning calorimetry and scanning electron microscopy study. An increase in dissolution (DE15min, 100 %) in simulated gastric fluid at pH 1.2 was achieved without precipitation of lornoxicam. Spectral characterisation reveals no sign of lornoxicam precipitation on solid carriers. Comparative pharmacodynamic evaluation was investigated in terms of anti-inflammatory efficacy using a rat paw oedema model in rats. The s-TFDDS formulation showed the maximum percent inhibition of oedema as compared with plain and micronised lornoxicam. PMID:25788347

  17. Elevated cholecystokininergic tone constitutes an important molecular/neuronal mechanism for the expression of anxiety in the mouse

    PubMed Central

    Chen, Qian; Nakajima, Akira; Meacham, Corbin; Tang, Ya-Ping

    2006-01-01

    Cholecystokinin (CCK), one of the most abundant neuropeptides in the brain, plays an important role in anxiogenesis through the activation of CCK receptor-2 (CCKR-2). Accumulating evidence, however, has suggested this role depends on endogenous CCKergic “tone,” which is largely determined by the expression level of the CCKR-2. Using the tTA/tetO-inducible transgenic (tg) approach, we show here that overexpression of the CCKR-2 in neurons of the forebrain significantly increases CCKR-2 binding capacity in tg mice compared with their littermate controls. Interestingly, these tg mice consistently exhibit increased fear responses, which are generally interpreted as anxiety-like behaviors in the rodent, in a battery of behavioral tests, which represented conflict situations or delivered stress to the subjects. The inhibition of transgene expression with doxycycline treatment completely diminished both increased receptor-binding activity and all behavioral phenotypes. Furthermore, treatment of tg mice with diazepam significantly attenuated these anxiety-like behaviors. Our results directly demonstrate that the elevated CCKergic tone via overexpression of the CCKR-2 in the brain may constitute an underlying molecular/neuronal mechanism for the expression of anxiety. In addition, our study has validated a robust genetic anxiety model in the mouse in terms of their face, constructive, and predictive validity. PMID:16537459

  18. Elevated levels of TWEAK in skeletal muscle promote visceral obesity, insulin resistance, and metabolic dysfunction.

    PubMed

    Sato, Shuichi; Ogura, Yuji; Tajrishi, Marjan M; Kumar, Ashok

    2015-03-01

    Skeletal muscle is responsible for the majority of glucose disposal in body. Impairment in skeletal muscle glucose handling capacity leads to the state of insulin resistance. The TNF-like weak inducer of apoptosis (TWEAK) cytokine has now emerged as a major regulator of skeletal muscle mass and function. However, the role of TWEAK in skeletal muscle metabolic function remains less understood. Here, we demonstrate that with progressive age, skeletal muscle-specific TWEAK-transgenic (TWEAK-Tg) mice gain increased body weight (?16%) and fat mass (?64%) and show glucose intolerance and insulin insensitivity. TWEAK-Tg mice also exhibit adipocyte hypertrophy in the epididymal fat. Oxygen uptake, voluntary physical activity, and exercise capacity were significantly reduced in TWEAK-Tg mice compared with controls. Overexpression of TWEAK inhibited (?31%) 5' AMP-activated protein kinase (AMPK) and reduced (?31%) the levels of glucose transporter type 4 (GLUT4) without affecting the Akt pathway. TWEAK also inhibited insulin-stimulated glucose uptake (?32%) and repressed the levels of GLUT4 (?50%) in cultured myotubes from C57BL6 mice. TWEAK represses the levels of Krüppel-like factor 15; myocyte enhancer factor 2, and peroxisome proliferator-activated receptor-? coactivator-1?, which are required for the activation of the GLUT4 locus. Collectively our study demonstrates that elevated levels of TWEAK in skeletal muscle cause metabolic abnormalities. Inhibition of TWEAK could be a potential approach to prevent weight gain and type 2 diabetes. PMID:25466899

  19. Temperature-dependent reaction pathways for the anomalous hydrocracking of triglycerides in the presence of sulfided Co-Mo-catalyst.

    PubMed

    Anand, Mohit; Sinha, Anil K

    2012-12-01

    Kinetic studies and product profiling was done to understand the anomalous cracking of jathropha oil triglycerides in the presence of sulfided Co-Mo/Al(2)O(3) catalyst. At temperatures between 320 and 340 °C, only deoxygenation and oligomerization reactions took place whereas at temperatures above 340 °C, internal conversions between the products and direct conversion to lighter and middle distillates were favored High pressures (80 bar) and H(2)/feed ratios (>1500) were necessary to minimize oligomerization of the products and to increase the lifespan of the catalyst. Lumped kinetic models were validated with experimental results. Activation energies for the formation of lighter (83 kJ/mol) and middle fractions (126 kJ/mol) were higher than those for the heavy (47 kJ/mol) and deoxygenated (47 kJ/mol) products. Jatropha oil triglycerides hydroconversion pathways were dependent on temperature and the triglycerides could be hydrocracked to lower range hydrocarbons (C5-C14) by increasing the reaction temperatures. PMID:23073102

  20. The effect of unsaturated fatty acid and triglyceride oil addition on the mechanical and antibacterial properties of acrylic bone cements.

    PubMed

    Persson, Cecilia; Robert, Elise; Carlsson, Elin; Robo, Céline; López, Alejandro; Godoy-Gallardo, Maria; Ginebra, Maria-Pau; Engqvist, Håkan

    2015-09-01

    Acrylic bone cements have an elastic modulus several times higher than the surrounding trabecular bone. This has been hypothesized to contribute to certain clinical complications. There are indications that the addition of specific fatty acids and triglyceride oils may reduce the elastic modulus of these types of cements. Some of these additives also appear to have inherent antibiotic properties, although this has never been evaluated in bone cements. In this study, several types of fatty acids and triglyceride oils were evaluated for use in acrylic bone cements. Their mechanical properties were evaluated under uniaxial compression testing and selected cements were then further characterized in terms of microstructure, handling and antibacterial properties using scanning electron microscopy, polymerization temperature measurements, agar diffusion tests and bactericidal activity assays of cement extracts. It was found that any of the evaluated fatty acids or triglyceride oils could be used to tailor the stiffness of acrylic bone cements, although at varying concentrations, which also depended on the type of commercial base cement used. In particular, the addition of very small amounts of linoleic acid (<2.0?wt%) resulted in Young's moduli and compressive strengths in the range of human trabecular bone, while maintaining a similar setting time. Further, the addition of 12.6?wt% ricinoleic acid to Osteopal V cement was found to have a significant antibacterial effect, inhibiting growth of Staphylococcus aureus in an agar diffusion test as well as demonstrating 100% bactericidal activity against the same strain. PMID:25876889

  1. ASPP2 attenuates triglycerides to protect against hepatocyte injury by reducing autophagy in a cell and mouse model of non-alcoholic fatty liver disease.

    PubMed

    Xie, Fang; Jia, Lin; Lin, Minghua; Shi, Ying; Yin, Jiming; Liu, Yin; Chen, Dexi; Meng, Qinghua

    2015-01-01

    ASPP2 is a pro-apoptotic member of the p53 binding protein family. ASPP2 has been shown to inhibit autophagy, which maintains energy balance in nutritional deprivation. We attempted to identify the role of ASPP2 in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In a NAFLD cell model, control treated and untreated HepG2 cells were pre-incubated with GFP-adenovirus (GFP-ad) for 12 hrs and then treated with oleic acid (OA) for 24 hrs. In the experimental groups, the HepG2 cells were pre-treated with ASPP2-adenovirus (ASPP2-ad) or ASPP2-siRNA for 12 hrs and then treated with OA for 24 hrs. BALB/c mice fed a methionine- and choline-deficient (MCD) diet were used to generate a mouse model of NAFLD. The mice with fatty livers in the control group were pre-treated with injections of GFP-ad for 10 days. In the experimental group, the mice that had been pre-treated with ASPP2-ad were fed an MCD diet for 10 days. ASPP2-ad or GFP-ad was administered once every 5 days. Liver tissue from fatty liver patients and healthy controls were used to analyse the role of ASPP2. Autophagy, apoptosis markers and lipid metabolism mediators, were assessed with confocal fluorescence microscopy, immunohistochemistry, western blot and biochemical assays. ASPP2 overexpression decreased the triglyceride content and inhibited autophagy and apoptosis in the HepG2 cells. ASPP2-ad administration suppressed the MCD diet-induced autophagy, steatosis and apoptosis and decreased the previously elevated alanine aminotransferase levels. In conclusion, ASPP2 may participate in the lipid metabolism of non-alcoholic steatohepatitis and attenuate liver failure. PMID:25256142

  2. Space Elevator: Path to Space

    NASA Astrophysics Data System (ADS)

    Kaushal, A. K.

    2012-05-01

    The Space Elevator is the most promising Space Transportation system on the drawing boards today, combining scalability, qualify of ride, and safety to deliver truly commercial-grade space access-practically comparable to a train ride to space.

  3. Space Elevators Preliminary Architectural View

    NASA Astrophysics Data System (ADS)

    Pullum, L.; Swan, P. A.

    Space Systems Architecture has been expanded into a process by the US Department of Defense for their large scale systems of systems development programs. This paper uses the steps in the process to establishes a framework for Space Elevator systems to be developed and provides a methodology to manage complexity. This new approach to developing a family of systems is based upon three architectural views: Operational View OV), Systems View (SV), and Technical Standards View (TV). The top level view of the process establishes the stages for the development of the first Space Elevator and is called Architectural View - 1, Overview and Summary. This paper will show the guidelines and steps of the process while focusing upon components of the Space Elevator Preliminary Architecture View. This Preliminary Architecture View is presented as a draft starting point for the Space Elevator Project.

  4. Space Elevator Base Leg Architecture

    NASA Astrophysics Data System (ADS)

    Swan, C.; Swan, P. A.

    While the Space Elevator stretches for 104,000 kilometers, the region of most concern, from the survival perspective, is 2,500 kms and below. The threats inside this dangerous arena include debris, spacecraft, meteorites, lightening, winds, rogue waves, aircraft, and intentional human acts. Two major questions will be addressed that will influence the overall systems architecture of a Space Elevator. While the deployment phase of the development of the Space Elevator will only have a single ribbon from the surface of the Earth to well beyond the Geosynchronous altitude, a mature Space Elevator must never allow a complete sever of the system. Design approaches, materials selections, international policy development and assembly must ensure that the integrity of the Space Elevator be maintained. The trade space analysis will address the probability of an individual ribbon being severed, the length of time to repair, and the potential for a catastrophic Space Elevator cut. The architecture proposed for the base leg portion will address two questions: Shall there be multiple base legs to 2,500 kms altitude? And Should the anchor be based on land or at sea?

  5. Elevated Serum Thyroglobulin and Low Iodine Intake Are Associated with Nontoxic Nodular Goiter among Adults Living near the Eastern Mediterranean Coast

    PubMed Central

    Ovadia, Yaniv S.; Gefel, Dov; Turkot, Svetlana; Aharoni, Dorit; Fytlovich, Shlomo; Troen, Aron M.

    2014-01-01

    Background. Information about iodine intake is crucial for preventing thyroid diseases. Inadequate iodine intake can lead to thyroid diseases, including nontoxic nodular goiter (NNG). Objective. To estimate iodine intake and explore its correlation with thyroid diseases among Israeli adults living near the Mediterranean coast, where iodine-depleted desalinated water has become a major source of drinking water. Methods. Cross-sectional study of patients attending Barzilai Medical Center Ashkelon. Participants, who were classified as either NNG (n = 17), hypothyroidism (n = 14), or control (n = 31), provided serum thyroglobulin (Tg) and completed a semiquantitative iodine food frequency questionnaire. Results. Elevated serum Tg values (Tg > 60?ng/mL) were significantly more prevalent in the NNG group than in the other groups (29% versus 7% and 0% for hypothyroidism and controls, resp., P < 0.05). Mean estimated iodine intake was significantly lower in the NNG group (65 ± 30??g/d) than in controls (115 ± 60??g/d) (P < 0.05) with intermediate intake in the hypothyroid group (73 ± 38??g/d). Conclusions. Elevated serum Tg values and low dietary iodine intake are associated with NNG among adult patients in Ashkelon District, Israel. Larger studies are needed in order to expand on these important initial findings. PMID:25610705

  6. Elevated Serum Thyroglobulin and Low Iodine Intake Are Associated with Nontoxic Nodular Goiter among Adults Living near the Eastern Mediterranean Coast.

    PubMed

    Ovadia, Yaniv S; Gefel, Dov; Turkot, Svetlana; Aharoni, Dorit; Fytlovich, Shlomo; Troen, Aron M

    2014-01-01

    Background. Information about iodine intake is crucial for preventing thyroid diseases. Inadequate iodine intake can lead to thyroid diseases, including nontoxic nodular goiter (NNG). Objective. To estimate iodine intake and explore its correlation with thyroid diseases among Israeli adults living near the Mediterranean coast, where iodine-depleted desalinated water has become a major source of drinking water. Methods. Cross-sectional study of patients attending Barzilai Medical Center Ashkelon. Participants, who were classified as either NNG (n = 17), hypothyroidism (n = 14), or control (n = 31), provided serum thyroglobulin (Tg) and completed a semiquantitative iodine food frequency questionnaire. Results. Elevated serum Tg values (Tg > 60?ng/mL) were significantly more prevalent in the NNG group than in the other groups (29% versus 7% and 0% for hypothyroidism and controls, resp., P < 0.05). Mean estimated iodine intake was significantly lower in the NNG group (65 ± 30??g/d) than in controls (115 ± 60??g/d) (P < 0.05) with intermediate intake in the hypothyroid group (73 ± 38??g/d). Conclusions. Elevated serum Tg values and low dietary iodine intake are associated with NNG among adult patients in Ashkelon District, Israel. Larger studies are needed in order to expand on these important initial findings. PMID:25610705

  7. Significant structural but not physiological changes in cortical neurons of 12-month-old Tg2576 mice

    PubMed Central

    Rocher, Anne B.; Kinson, Michael S.; Luebke, Jennifer I.

    2008-01-01

    Amyloid-beta (A?) plays a key role in the etiology of Alzheimer’s disease. Pyramidal cell dendrites exposed to A? exhibit dramatic structural alterations, including reduced dendritic spine densities. To determine whether such structural alterations lead to electrophysiological changes, whole-cell patch clamp recordings with biocytin filling were used to assess both the electrophysiological and morphological properties of layer 3 pyramidal cells in frontal cortical slices prepared from 12-month-old Tg2576 amyloid precursor protein (APP) mutant vs. wild-type (Wt) mice. Tg2576 cells exhibited significantly increased dendritic lengths and volumes and decreased spine densities, while the total number of spines was not different from Wt. Tg2576 and Wt cells did not differ with regard to passive membrane, action potential firing or glutamatergic spontaneous excitatory postsynaptic current properties. Thus, overexpression of mutated APP in young Tg2576 mice leads to significant changes in neuronal morphological properties which do not have readily apparent functional consequences. PMID:18721884

  8. Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer’s Disease

    PubMed Central

    Guo, Jun-Peng; Pan, Jin-Xiu; Xiong, Lei; Xia, Wen-Fang; Cui, Shun; Xiong, Wen-Cheng

    2015-01-01

    Patients of Alzheimer’s disease (AD) frequently have lower bone mineral density and higher rate of hip fracture. Tg2576, a well characterized AD animal model that ubiquitously express Swedish mutant amyloid precursor protein (APPswe), displays not only AD-relevant neuropathology, but also age-dependent bone deficits. However, the underlying mechanisms remain poorly understood. As APP is implicated as a regulator of iron export, and the metal chelation is considered as a potential therapeutic strategy for AD, we examined iron chelation’s effect on the osteoporotic deficit in Tg2576 mice. Remarkably, in vivo treatment with iron chelator, clinoquinol (CQ), increased both trabecular and cortical bone-mass, selectively in Tg2576, but not wild type (WT) mice. Further in vitro studies showed that low concentrations of CQ as well as deferoxamine (DFO), another iron chelator, selectively inhibited osteoclast (OC) differentiation, without an obvious effect on osteoblast (OB) differentiation. Intriguingly, both CQ and DFO’s inhibitory effect on OC was more potent in bone marrow macrophages (BMMs) from Tg2576 mice than that of wild type controls. The reduction of intracellular iron levels in BMMs by CQ was also more dramatic in APPswe-expressing BMMs. Taken together, these results demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits. PMID:26575486

  9. Ospemifene and 4-Hydroxyospemifene Effectively Prevent and Treat Breast Cancer in the MTag.Tg Transgenic Mouse Model

    PubMed Central

    Burich, Rebekah A.; McCall, Jamie L.; Mehta, Neelima R.; Greenberg, Brittany E.; Bell, Katie E.; Griffey, Stephen M.; DeGregorio, Michael W.; Wurz, Gregory T.

    2011-01-01

    Objective Ospemifene, a new drug indicated for the treatment of vulvovaginal atrophy, has completed Phase III clinical trials. A condition affecting millions of women worldwide, vulvovaginal atrophy has long been treated with estrogen therapy. Estrogen treatment carries with it risks of thromboembolism, endometrial proliferative effects, and breast cancer promotion. In this study, we test the effects of three dosing levels of ospemifene in both the prevention and treatment of breast cancer in the MTag.Tg mouse model. Methods The polyomavirus middle-T transgenic mouse model (MTag.Tg), which produces synchronized, multifocal mammary tumors in the immunologically intact C57BL/6 background, was used to examine the impact of ospemifene treatment. First, a cell line derived from an MTag.Tg mouse tumor (Mtag 34) was treated in vitro with ospemifene and its major metabolite, 4-OH ospemifene. MTag.Tg mice were treated daily by gavage with three different doses of ospemifene (5, 25, and 50 mg/kg) before or after the development of mammary tumors. Survival and tumor development results were used to determine the effect of ospemifene treatment on mammary tumors in both the preventive and treatment settings. Results Tumors and the MTag 34 cell line were positive for estrogen receptor expression. The MTag 34 line was not stimulated by ospemifene or its major, active metabolite 4-OH ospemifene in vitro. Ospemifene increased survival time and exerted an antitumor effect on the development and growth of estrogen receptor positive mammary tumors in the MTag.Tg mouse model at the 50 mg/kg dose. Levels of ospemifene and 4-OH ospemifene in both the tumors and plasma of mice confirmed dosing. Ospemifene did not exert an estrogenic effect in the breast tissue at doses equivalent to human dosing. Conclusions Ospemifene prevents and treats estrogen receptor positive MTag.Tg mammary tumors in this immune intact mouse model in a dose-dependent fashion. Ospemifene drug levels in the plasma of treated mice were comparable to those found in humans. Combined with our previous data, ospemifene does not appear to pose a breast cancer risk in animals, and slows cancer development and progression in the MTag.Tg model. PMID:21926925

  10. Evidence for Conformational Mechanism on the Binding of TgMIC4 with ?-Galactose-Containing Carbohydrate Ligand.

    PubMed

    Santos, Adriano; Carvalho, Fernanda C; Roque-Barreira, Maria-Cristina; Zorzetto-Fernandes, André Luiz; Gimenez-Romero, David; Monzó, Isidro; Bueno, Paulo R

    2015-11-10

    A deeper understanding of the role of sialic/desialylated groups during TgMIC4-glycoproteins interactions has importance to better clarify the odd process of host cell invasion by members of the apicomplexan phylum. Within this context, we evaluated the interaction established by recombinant TgMIC4 (the whole molecule) with sialylated (bovine fetuin) and desialylated (asialofetuin) glycoproteins by using functionalized quartz crystal microbalance with dissipation monitoring (QCM-D). A suitable receptive surface containing recombinant TgMIC4 for monitoring ?-galactose-containing carbohydrate ligand (limit of quantification ? 40 ?M) was designed and used as biomolecular recognition platform to study the binding and conformational mechanisms of TgMIC4 during the interaction with glycoprotein containing (fetuin), or not, terminal sialic group (asialofetuin). It was inferred that the binding/interaction monitoring depends on the presence/absence of sialic groups in target protein and is possible to be differentiated through a slower binding kinetic step using QCM-D approach (which we are inferring to be thus associated with ?-galactose ligand). This slower binding/interaction step is likely supposed (from mechanical energetic analysis obtained in QCM-D measurements) to be involved with Toxoplasma gondii (the causative agent of toxoplasmosis) parasitic invasion accompanied by ligand (galactose) induced binding conformational change (i.e., cell internalization process can be additionally dependent on structural conformational changes, controlled by the absence of sialic groups and to the specific binding with galactose), in addition to TgMIC4-glycoprotein solely recognition binding process. PMID:26488670

  11. Application of thermogravimetric Fourier transform infrared spectroscopy (TG-FTIR) to the analysis of oxygen functional groups in coal

    SciTech Connect

    L. Giroux; J.-P. Charland; J.A. MacPhee

    2006-10-15

    This paper attempts to relate oxygen-containing gases H{sub 2}O, CO{sub 2}, and CO evolved during pyrolysis of the Argonne premium coals to oxygen-containing functional groups as a function of rank. Our approach to functional group analysis of oxygen-containing species in coal has been to use a pyrolysis technique, thermogravimetric Fourier transform infrared spectroscopy (TG-FTIR), involving thermogravimetric analysis with the measurement of the gaseous decomposition products via IR detection. Under suitable heating conditions, TG-FTIR pyrolysis of a coal sample in a stream of inert gas has been shown to expel quantitatively all of the organic oxygen in the form of H{sub 2}O, CO{sub 2}, and CO, and consequently, this technique can be effectively applied for determining the total oxygen content. Focusing on the Argonne premium coals, which cover a wide range in rank between lignite (Ro = 0.25) and low-volatile bituminous (Ro = 1.68), TG-FTIR provided complex pyrolysis profiles of oxygen-containing gases, which yield information on the sources of the different peaks observed in coal as a function of rank from a chemical-structure standpoint. Deconvolution of the complex profiles was performed to assign peaks to the different sources of oxygen-containing gases. Model polymers containing various oxygen functional groups in aliphatic and/or aromatic molecular environments were also pyrolyzed by TG-FTIR in an attempt to assign peaks in the gas evolution profiles of the Argonne premium coals. Although complex evolution profiles were observed for the three oxygen-containing gas species H{sub 2}O, CO{sub 2}, and CO in the Argonne premium coals, the strength of the TG-FTIR technique in revealing both similarities and differences in profiles depending upon the coal rank was evident. 19 refs., 6 figs., 9 tabs.

  12. Study of glass transition temperature (Tg) of novel stress-sensitive composites using molecular dynamic simulation

    NASA Astrophysics Data System (ADS)

    Koo, B.; Liu, Y.; Zou, J.; Chattopadhyay, A.; Dai, L. L.

    2014-09-01

    This study investigates the glass transition temperature (Tg) of novel stress-sensitive composites capable of detecting a damage precursor using molecular dynamics (MD) simulations. The molecular structures of a cross-linked epoxy network (which consist of epoxy resin, hardener and stress-sensitive material) have been simulated and experimentally validated. The chemical constituents of the molecular structures are di-glycidyl ether of bisphenol F (DGEBF: epoxy resin), di-ethylene tri-amine (DETA: hardener) and tris-(cinnamoyloxymethyl)-ethane (TCE: stress-sensitive material). The cross-linking degree is varied by manipulating the number of covalent bonds through tuning a cutoff distance between activated DGEBF and DETA during the non-equilibrium MD simulation. A relationship between the cross-linking degree and Tgs has been studied numerically. In order to validate a proposed MD simulation framework, MD-predicted Tgs of materials used in this study have been compared to the experimental results obtained by the differential scanning calorimetry (DSC). Two molecular models have been constructed for comparative study: (i) neat epoxy (epoxy resin with hardener) and (ii) smart polymer (neat epoxy with stress-sensitive material). The predicted Tgs show close agreement with the DSC results.

  13. Kinetic investigations of thermal degradation of poly(vinyl butyral) using TG/FT-IR

    NASA Astrophysics Data System (ADS)

    Liau, Leo Chau-Kuang

    Mechanism of poly(vinyl butyral) (PVB) thermal degradation in different environments were investigated based on a proposed analytical algorithm. The evolved gaseous products of PVB thermal degradation and reaction pathways were identified and constructed by GC/MS measurements. Kinetic models of PVB thermal degradation with or without ceramics were determined on the basis of weight loss and evolved gas analysis (EGA) by thermogravimetry (TG) and Fourier transform infrared spectroscopy (FT-IR) measurements. A spectral resolution method was proposed to resolve the evolved gaseous IR spectra into each constituent species spectra on a dynamic basis. The dynamic resolved spectra of each evolved species were used to construct kinetic models of PVB degradation in different environments. The models associated with Arrhenius equation were elucidated as first order parallel reactions for each volatile product. The kinetic parameters of PVB thermal degradation in the proposed mechanisms were determined. The kinetic results using isothermal and nonisothermal approaches showed excellent agreement. Activation energies of PVB thermal degradation are ˜300 in nitrogen and ˜200 in air for pure PVB, and ˜100 KJ/mole for PVB with oxide (Alsb2Osb3) or nonoxide (AlN) ceramics in nitrogen. The Polymer residues were subjected to DRIFTS technique and Leco Analyzer.

  14. Ruthenium Red Colorimetric and Birefringent Staining of Amyloid-? Aggregates in Vitro and in Tg2576 Mice

    PubMed Central

    2012-01-01

    Alzheimer’s disease (AD) is a devastating neurodegenerative disease most notably characterized by the misfolding of amyloid-? (A?) into fibrils and its accumulation into plaques. In this Article, we utilize the affinity of A? fibrils to bind metal cations and subsequently imprint their chirality to bound molecules to develop novel imaging compounds for staining A? aggregates. Here, we investigate the cationic dye ruthenium red (ammoniated ruthenium oxychloride) that binds calcium-binding proteins, as a labeling agent for A? deposits. Ruthenium red stained amyloid plaques red under light microscopy, and exhibited birefringence under crossed polarizers when bound to A? plaques in brain tissue sections from the Tg2576 mouse model of AD. Staining of A? plaques was confirmed via staining of the same sections with the fluorescent amyloid binding dye Thioflavin S. In addition, it was confirmed that divalent cations such as calcium displace ruthenium red, consistent with a mechanism of binding by electrostatic interaction. We further characterized the interaction of ruthenium red with synthetic A? fibrils using independent biophysical techniques. Ruthenium red exhibited birefringence and induced circular dichroic bands at 540 nm upon binding to A? fibrils due to induced chirality. Thus, the chirality and cation binding properties of A? aggregates could be capitalized for the development of novel amyloid labeling methods, adding to the arsenal of AD imaging techniques and diagnostic tools. PMID:23509974

  15. THE EFFECT OF ELEVATED [CO2] AND ELEVATED TEMPERATURE ON TREE GROWTH AND PHYSIOLOGY

    E-print Network

    Teskey, Robert O.

    THE EFFECT OF ELEVATED [CO2] AND ELEVATED TEMPERATURE ON TREE GROWTH AND PHYSIOLOGY by TIMOTHY #12;THE EFFECT OF ELEVATED [CO2] AND ELEVATED TEMPERATURE ON TREE GROWTH AND PHYSIOLOGY by TIMOTHY EFFECT OF ELEVATED [CO2] AND ELEVATED TEMPERATURE ON TREE GROWTH AND SPECIES DISTRIBUTION by TIMOTHY

  16. Toxoplasma gondii: humoral and cellular immune response of BALB/c mice immunized via intranasal route with rTgROP2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    TgROP2 is an intracellular protein associated with rhoptries of Toxoplama gondii and an antigen component of a candidate vaccine for toxoplasmosis. The purpose of the present study was to evaluate the efficacy of rTgROP2 to stimulate humoral and cellular immune responses in BALB/c mice via intranasa...

  17. Analysis of a Space Elevator

    NASA Astrophysics Data System (ADS)

    Langston, J. L.

    2003-12-01

    This paper investigates the engineering principles that govern the design of a Space Elevator. The presentation includes extensive mathematical analysis of several basic approaches, reviews historical approaches and looks at some novel implementations. The technical challenges that must be overcome and the potential application of new technology to meet these challenges are discussed. While the paper focuses on the engineering aspects of the space elevator concept, some space is devoted to the potential use and benefit of a successful implementation. The primary objective of this paper is to show that no fundamental physical principles preclude the concept, but that technology development is required before a practical implementation can be realized.

  18. Tether Elevator Crawler Systems (TECS)

    NASA Technical Reports Server (NTRS)

    Swenson, Frank R.

    1987-01-01

    One of the needs of the experimenters on the space station is access to steady and controlled-variation microgravity environments. A method of providing these environments is to place the experiment on a tether attached to the space station. This provides a high degree of isolation from structural oscillations and vibrations. Crawlers can move these experiments along the tethers to preferred locations, much like an elevator. This report describes the motion control laws developed for these crawlers and the testing of laboratory models of these tether elevator crawlers.

  19. Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice

    PubMed Central

    Li, Jianing; Wang, Yu; Tang, Lihua; de Villiers, Willem JS; Cohen, Donald; Woodward, Jerold; Finkelman, Fred D; Eckhardt, Erik RM

    2012-01-01

    BACKGROUND The prevalence of peanut allergies is rising. Peanuts and many other allergen sources contain significant amounts of triglycerides, which affect absorption of antigens but have unknown effects on sensitization and anaphylaxis. We recently reported that dietary medium-chain triglycerides (MCT), which bypass mesenteric lymph and directly enter portal blood, reduce intestinal antigen absorption into blood compared to long-chain triglycerides (LCT), which stimulate mesenteric lymph flow and are absorbed in chylomicrons via mesenteric lymph. OBJECTIVE Test how dietary MCT affect food allergy. METHODS C3H/HeJ mice were fed peanut butter protein in MCT, LCT (peanut oil), or LCT plus an inhibitor of chylomicron formation (Pluronic L81; “PL81”). Peanut-specific antibodies in plasma, responses of the mice to antigen challenges, and intestinal epithelial cytokine expression were subsequently measured. RESULTS MCT suppressed antigen absorption into blood, but stimulated absorption into Peyer's patches. A single gavage of peanut protein with MCT as well as prolonged feeding in MCT-based diets caused spontaneous allergic sensitization. MCT-sensitized mice experienced IgG-dependent anaphylaxis upon systemic challenge and IgE-dependent anaphylaxis upon oral challenge. MCT feeding stimulated jejunal-epithelial TSLP, IL-25 and IL-33 expression compared to LCT, and promoted Th2 cytokine responses in splenocytes. Moreover, oral challenges of sensitized mice with antigen in MCT significantly aggravated anaphylaxis compared to challenges with LCT. Importantly, effects of MCT could be mimicked by adding PL81 to LCT, and in vitro assays indicated that chylomicrons prevent basophil activation. CONCLUSION Dietary MCT promote allergic sensitization and anaphylaxis by affecting antigen absorption and availability and by stimulating Th2 responses. PMID:23182172

  20. Microsomal Triglyceride Transfer Protein (MTP) Associates with Cytosolic Lipid Droplets in 3T3-L1 Adipocytes

    PubMed Central

    Robinson, Delia B.; Harris, Carla M.; Johnson, Joyce E.; Mohler, Peter J.; Jerome, W. Gray; Swift, Larry L.

    2015-01-01

    Lipid droplets are intracellular energy storage organelles composed of a hydrophobic core of neutral lipid, surrounded by a monolayer of phospholipid and a diverse array of proteins. The function of the vast majority of these proteins with regard to the formation and/or turnover of lipid droplets is unknown. Our laboratory was the first to report that microsomal triglyceride transfer protein (MTP), a lipid transfer protein essential for the assembly of triglyceride-rich lipoproteins, was expressed in adipose tissue of humans and mice. In addition, our studies suggested that MTP was associated with lipid droplets in both brown and white fat. Our observations led us to hypothesize that MTP plays a key role in lipid droplet formation and/or turnover. The objective of these studies was to gain insight into the function of MTP in adipocytes. Using molecular, biochemical, and morphologic approaches we have shown: 1) MTP protein levels increase nearly five-fold as 3T3-L1 cells differentiate into adipocytes. 2) As 3T3-L1 cells undergo differentiation, MTP moves from the juxtanuclear region of the cell to the surface of lipid droplets. MTP and perilipin 2, a major lipid droplet surface protein, are found on the same droplets; however, MTP does not co-localize with perilipin 2. 3) Inhibition of MTP activity has no effect on the movement of triglyceride out of the cell either as a lipid complex or via lipolysis. 4) MTP is found associated with lipid droplets within hepatocytes from human fatty livers, suggesting that association of MTP with lipid droplets is not restricted to adipocytes. In summary, our data demonstrate that MTP is a lipid droplet-associated protein. Its location on the surface of the droplet in adipocytes and hepatocytes, coupled with its known function as a lipid transfer protein and its increased expression during adipocyte differentiation suggest a role in lipid droplet biology. PMID:26267806

  1. Adipose triglyceride lipase expression in human adipose tissue and muscle. Role in insulin resistance and response to training and pioglitazone

    PubMed Central

    Yao-Borengasser, Aiwei; Varma, Vijayalakshmi; Coker, Robert H.; Ranganathan, Gouri; Phanavanh, Bounleut; Rasouli, Neda; Kern, Philip A.

    2010-01-01

    Objective Adipose triglyceride lipase (ATGL) catalyzes the first step in adipocyte and muscle triglyceride hydrolysis, and Comparative Gene Identification-58 (CGI-58) is an essential cofactor. We studied the expression of ATGL and CGI-58 in human adipose and muscle, and examined correlations with markers of muscle fatty acid oxidation. Materials/Methods Non diabetic volunteers were studied. Subjects with impaired glucose tolerance were treated with pioglitazone or metformin for 10 weeks. Normal glucose tolerant subjects underwent a 12 week training program. We examined changes in ATGL and CGI-58 with obesity and insulin resistance, and effects of exercise and pioglitazone. Results ATGL mRNA expression showed no correlation with either body mass index (BMI) or insulin sensitivity (SI) in either adipose or muscle. However, adipose ATGL protein levels were inversely correlated with BMI (r=?0.64, p<0.02), and positively correlated with SI (r=0.67, p<0.02). In muscle, ATGL mRNA demonstrated a strong positive relationship with carnitine palmitoyltransferase I mRNA (r=0.82, p<0.0001), and the adiponectin receptors AdipoR1 mRNA (r=0.71, p<0.0001), and AdipoR2 mRNA (r=0.74, p<0.0001). Muscle CGI-58 mRNA was inversely correlated with intramyocellular triglyceride in both type 1 (r=?0.35, p<0.05) and type 2 (r=?0.40, p<0.05) fibers. Exercise training resulted in increased muscle ATGL and pioglitazone increased adipose ATGL by 31% (p<0.05). Pioglitazone also increased ATGL in adipocytes. Conclusions Adipose ATGL protein is decreased with insulin resistance and obesity, and muscle ATGL mRNA is associated with markers of fatty acid oxidation in muscle, as is CGI-58. The regulation of ATGL and CGI-58 have important implications for the control of lipotoxicity. PMID:21129760

  2. Plasma triglyceride and HDL-cholesterol concentrations in Vietnamese girls are affected by lipoprotein lipase, but not apolipoprotein CIII polymorphism.

    PubMed

    Thu, Nghiem Nguyet; Mai, Ta Thi Tuyet; Ohmori, Reiko; Kuroki, Masatoshi; Chuyen, Nguyen Van; Hung, Nguyen Thi Kim; Kawakami, Masanobu; Kondo, Kazuo

    2006-06-01

    Lipoprotein lipase (LPL) and apolipoprotein CIII (apoCIII) play an important role in HDL-cholesterol and triglyceride metabolism. This study examined the effects of LPL S447X and apoCIII SstI polymorphisms on the plasma lipid and lipoprotein concentrations in Vietnamese girls. Three hundred and fifty-one Vietnamese girls, from 7 to 9 y of age, were randomly selected from the urban and rural areas of Ho Chi Minh City, Vietnam. The presence of LPL S447X and apoCIII polymorphism was determined using the Invader assay, and the plasma lipid concentrations were measured by an enzymatic method. Dietary intakes and anthropometrics were assessed for each child. The frequencies of LPL 447X (11.9%) and apoCIII S2 (32.6%) polymorphisms in the Vietnamese were similar to those of other Asian populations. The frequency of LPL 447X was the same as that in Caucasians but the frequency of apoCIII S2 was approximately 3.8 times that in Caucasians. Overall, LPL 447X polymorphism was associated with a higher HDL-cholesterol concentration (7.4%, P = 0.007) and a lower triglyceride concentration (-13.6%, P = 0.04) than LPL 447S. The apoCIII S2 polymorphism was not associated with an increase in the plasma triglyceride concentration in Vietnamese girls with a low fat intake. However, due to the high frequency of the apoCIII SstI polymorphism and the increasingly westernized diet in Vietnam, attention should be paid to the interaction of genotype with the Vietnamese diet. PMID:16702309

  3. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    SciTech Connect

    Hashimoto, Takeshi; Yokokawa, Takumi; Endo, Yuriko; Iwanaka, Nobumasa; Higashida, Kazuhiko; Faculty of Sport Science, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192 ; Taguchi, Sadayoshi

    2013-10-11

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via decreased glucose uptake and lipogenic protein expression and increased basal lipolysis. Such an hypoxia-induced decrease in lipogenesis may be an attractive therapeutic target against lipid-associated metabolic diseases.

  4. Hydrothermal deoxygenation of triglycerides over Pd/C aided by in situ hydrogen production from glycerol reforming.

    PubMed

    Hollak, Stefan A W; Ariëns, Maxim A; de Jong, Krijn P; van Es, Daan S

    2014-04-01

    A one-pot catalytic hydrolysis-deoxygenation reaction for the conversion of unsaturated triglycerides and free fatty acids to linear paraffins and olefins is reported. The hydrothermal deoxygenation reactions are performed in hot compressed water at 250 °C over a Pd/C catalyst in the absence of external H2 . We show that aqueous-phase reforming (APR) of glycerol and subsequent water-gas-shift reaction result in the in situ formation of H2 . While this has a significant positive effect on the deoxygenation activity, the product selectivity towards high-value, long-chain olefins remains high. PMID:24596129

  5. Dietary long-chain, but not medium-chain, triglycerides impair exercise performance and uncouple cardiac mitochondria in rats

    E-print Network

    Murray, Andrew J.; Knight, Nicholas S.; Little, Sarah E.; Cochlin, Lowri E.; Clements, Mary; Clarke, Kieran

    2011-08-01

    -chain, but not medium-chain, triglycerides impair exercise performance and uncouple cardiac mitochondria in rats Andrew J Murray*, Nicholas S Knight, Sarah E Little, Lowri E Cochlin, Mary Clements and Kieran Clarke Abstract Short-term consumption of a high-fat diet... and during running days 1-5, whilst eating chow (grey), MCT-rich (white) or LCT-rich (black) diets. * p < 0.05 compared with baseline. Table 3 State III (ADP-stimulated) and state IV (ADP phosphorylated) respiration rates of interfibrillar and subsarcolemmal...

  6. Effect of heparin-induced lipolysis on the distribution of apolipoprotein e among lipoprotein subclasses. Studies with patients deficient in hepatic triglyceride lipase and lipoprotein lipase.

    PubMed Central

    Rubinstein, A; Gibson, J C; Paterniti, J R; Kakis, G; Little, A; Ginsberg, H N; Brown, W V

    1985-01-01

    In normal subjects, apolipoprotein E (apo E) is present on very low density lipoproteins (VLDL) (fraction I) and on particles of a size intermediate between VLDL and low density lipoproteins (LDL) (fraction II). The major portion of apo E is, however, on particles smaller than LDL but larger than the average high density lipoproteins (HDL) (fraction III). To investigate the possible role of the vascular lipases in determining this distribution of apo E among the plasma lipoproteins, we studied subjects with primary deficiency of either hepatic lipase or of lipoprotein lipase and compared them with normal subjects. Subjects with familial hepatic triglyceride lipase deficiency (n = 2) differ markedly from normal in that fraction II is the dominant apo E-containing group of lipoproteins. When lipolysis of VLDL was enhanced in these subjects upon release of lipoprotein lipase by intravenous heparin, a shift of the apo E from VLDL into fractions II and III was observed. In contrast, apolipoproteins CII and CIII (apo CII and CIII, respectively) did not accumulate in intermediate-sized particles but were shifted markedly from triglyceride rich lipoproteins to HDL after treatment with heparin. In subjects with primary lipoprotein lipase deficiency (n = 4), apo E was confined to fractions I and III. Release of hepatic triglyceride lipase by heparin injection in these subjects produced a shift of apo E from fraction I to III with no significant increase in fraction II. This movement of apo E from large VLDL and chylomicron-sized particles occurred with little hydrolysis of triglyceride and no significant shift of apo CII or CIII into HDL from triglyceride rich lipoproteins. When both lipoprotein lipase and hepatic triglyceride lipase were released by intravenous heparin injection into normal subjects (n = 3), fraction I declined and the apo E content of fraction III increased by an equivalent amount. Either moderate or no change was noted in the intermediate sized particles (fraction II). These data strongly support the hypothesis that fraction II is the product of the action of lipoprotein lipase upon triglyceride rich lipoproteins and is highly dependent on hepatic triglyceride lipase for its further catabolism. In addition, the hydrolysis by hepatic triglyceride lipase of triglyceride rich lipoproteins in general results in a preferential loss of apo E and its transfer to a specific group of large HDL. PMID:3973025

  7. SU-E-T-159: Evaluation of a Patient Specific QA Tool Based On TG119

    SciTech Connect

    Ashmeg, S; Zhang, Y; O'Daniel, J; Yin, F; Ren, L

    2014-06-01

    Purpose: To evaluate the accuracy of a 3D patient specific QA tool by analysis of the results produced from associated software in homogenous phantom and heterogonous patient CT. Methods: IMRT and VMAT plans of five test suites introduced by TG119 were created in ECLIPSE on a solid water phantom. The ten plans -of increasing complexity- were delivered to Delta4 to give a 3D measurement. The Delta4's “Anatomy” software uses the measured dose to back-calculate the energy fluence of the delivered beams, which is used for dose calculation in a patient CT using a pencilbeam algorithm. The effect of the modulated beams' complexity on the accuracy of the “Anatomy” calculation was evaluated. Both measured and Anatomy doses were compared to ECLIPSE calculation using 3% - 3mm gamma criteria.We also tested the effect of heterogeneity by analyzing the results of “Anatomy” calculation on a Brain VMAT and a 3D conformal lung cases. Results: In homogenous phantom, the gamma passing rates were found to be as low as 74.75% for a complex plan with high modulation. The mean passing rates were 91.47% ± 6.35% for “Anatomy” calculation and 99.46% ± 0.62% for Delta4 measurements.As for the heterogeneous cases, the rates were 96.54%±3.67% and 83.87%±9.42% for Brain VMAT and 3D lung respectively. This increased error in the lung case could be due to the use of the pencil beam algorithm as opposed to the AAA used by ECLIPSE.Also, gamma analysis showed high discrepancy along the beam edge in the “Anatomy” calculated results. This suggests a poor beam modeling in the penumbra region. Conclusion: The results show various sources of errors in “Anatomy” calculations. These include beam modeling in the penumbra region, complexity of a modulated beam (shown in homogenous phantom and brain cases) and dose calculation algorithms (3D conformal lung case)

  8. [Influence of urea formaldehyde resin on pyrolysis of biomass: a modeling study by TG-FTIR].

    PubMed

    Li, Si-jin; Mu, Jun; Zhang, Yu

    2014-06-01

    Pyrolysis is an efficient and recycling way to utilize waste wood-based panels, in which urea-formaldehyde resin (UF) is the main difference between wood-based board and other kinds of biomass. The present paper studied the three main components (cellulose, hemicelluloses, lignin) of poplar wood, in order to effectively and environmentally utilize or dispose of waste wood-based panels with pyrolysis technique, to study the influence of urea formaldehyde resin on pyrolytic characteristic of wood during the process of the pyrolysis of waste wood-based panels, and to in-depth explore the mechanism of the effect of UF on each component of wood. Innovatively, the weight-loss character and gas evolution rule of the model (made from cellulose, xylan and lignin, based on the chemical components stud of poplar wood), the main components as well as the ones mixed with UF were analyzed by TG-FTIR (thermogravimetric analyzer coupled to a Fourier transform infrared spectrometer). Results indicated that UF promoted the generation of water and carboxylic acid substances during the cellulose pyrolysis process. UF combined with lignin, formed some kind of unstable nitrogenous structure which produced a large amount of NH3, which took part in the low-temperature (200-300 degrees C) pyrolysis of lignin, and directly affected the production of pyrolysis products. It can be concluded that during the process of the pyrolysis of waste wood-based panels, lignin was the one that UF mainly impacted among the three main components of wood. PMID:25358153

  9. Ethanolic Extract of Butea monosperma Leaves Elevate Blood Insulin Level in Type 2 Diabetic Rats, Stimulate Insulin Secretion in Isolated Rat Islets, and Enhance Hepatic Glycogen Formation

    PubMed Central

    Samad, Mehdi Bin; Kabir, Ashraf Ul; Ahmed, Arif; Jahan, Mohammad Rajib; Hannan, J. M. A.

    2014-01-01

    We measured a vast range of parameters, in an attempt to further elucidate previously claimed antihyperglycemic activity of Butea monosperma. Our study clearly negates the possibility of antidiabetic activity by inhibited gastrointestinal enzyme action or by reduced glucose absorption. Reduction of fasting and postprandial glucose level was reconfirmed (P < 0.05). Improved serum lipid profile via reduced low density lipoprotein (LDL), cholesterol, triglycerides (TG), and increased high density lipoprotein (HDL) was also reestablished (P < 0.05). Significant insulin secretagogue activity of B. monosperma was found in serum insulin assay of B. monosperma treated type 2 diabetic rats (P < 0.01). This was further ascertained by our study on insulin secretion on isolated rat islets (P < 0.05). Improved sensitivity of glucose was shown by the significant increase in hepatic glycogen deposition (P < 0.05). Hence, we concluded that antihyperglycemic activity of B. monosperma was mediated by enhanced insulin secretion and enhanced glycogen formation in the liver. PMID:24860609

  10. Flyway-scale variation in plasma triglyceride levels as an index of refueling rate in spring-migrating western sandpipers (Calidris mauri)

    USGS Publications Warehouse

    Williams, T.D.; Warnock, N.; Takekawa, J.Y.; Bishop, M.A.

    2007-01-01

    We combined radiotelemetry, plasma metabolite analyses, and macro-invertebrate prey sampling to investigate variation in putative fattening rates (estimated as plasma triglyceride levels) at the flyway scale in Western Sandpipers (Calidris mauri) migrating between Punta Banda, Mexico (31??N), and Hartney Bay, Alaska (60??N), a distance of 4,240 km. Birds were caught at a wintering site (San Francisco Bay) and eight stopover sites along this Pacific Flyway. Body mass was higher in females than in males at six sites, but variation was not correlated with latitude for either sex, and the relationship of change in mass by date within sites was uninformative with regard to possible latitudinal variation in fattening rates. At San Francisco Bay, triglyceride levels were higher in the spring than in the winter. Mean plasma triglyceride varied among stopover sites, and there was a significant linear trend of increasing triglyceride levels with latitude as birds migrated north. At San Francisco Bay, length of stay was negatively related to triglyceride levels. However, plasma triglyceride levels at wintering or initial stopover sites (San Francisco and Punta Banda) did not predict individual variation in subsequent rates of travel during migration. We found no significant relationship between triglyceride levels and prey biomass at different stopover sites, which suggests that the latitudinal pattern is not explained by latitudinal changes in food availability. Rather, we suggest that differences in physiology of migratory birds at southern versus northern stopover sites or behavioral differences may allow birds to sustain higher fattening rates closer to the breeding grounds. ?? The American Ornithologists' Union, 2007.

  11. A novel PRD I and TG binding activity involved in virus-induced transcription of IFN-A genes.

    PubMed Central

    Génin, P; Bragança, J; Darracq, N; Doly, J; Civas, A

    1995-01-01

    Comparative analysis of the inducible elements of the mouse interferon A4 and A11 gene promoters (IE-A4 and IE-A11) by transient transfection experiments, DNase 1 footprinting and electrophoretic mobility shift assays resulted in identification of a virus-induced binding activity suggested to be involved in NDV-induced activation of transcription of these genes. The virus-induced factor, termed VIF, is activated early by contact of virions with cells. It specifically recognizes the PRD I-like domain shared by both inducible elements, as well as the TG-like domain of IE-A4. This factor, distinct from the IRF-1, IRF-2 and the alpha F1 binding proteins and presenting a different affinity pattern from that of the TG protein, is proposed as a candidate for IFN-type I gene regulation. Images PMID:8559665

  12. 3xTg-AD Mice Exhibit an Activated Central Stress Axis during Early-Stage Pathology

    PubMed Central

    Hebda-Bauer, Elaine K.; Simmons, Tracy A.; Sugg, Andrew; Ural, Eren; Stewart, James A.; Beals, James L.; Wei, Qiang; Watson, Stanley J.; Akil, Huda

    2012-01-01

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in response to the organism’s innate need for homeostasis. The glucocorticoids (GCs) that are released into the circulation upon acute activation of the HPA axis perform stress-adaptive functions and provide negative feedback to turn off the HPA axis, but can be detrimental when in excess. Long-term activation of the HPA axis (such as with chronic stress) enhances susceptibility to neuronal dysfunction and death, and increases vulnerability to Alzheimer’s disease (AD). However, little is known how components of the HPA axis, upstream of GCs, impact vulnerability to AD. This study examined basal gene expression of stress-related molecules in brains of 3xTg-AD mice during early-stage pathology. Basal glucocorticoid levels and mRNA expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and corticotropic releasing hormone (CRH) in several stress- and emotionality-related brain regions were measured in 3–4-month-old 3xTg-AD mice. Despite normal glucocorticoid levels, young 3xTg-AD mice exhibit an activated central HPA axis, with altered mRNA levels of MR and GR in the hippocampus, GR and CRH in the paraventricular nucleus of the hypothalamus, GR and CRH in the central nucleus of the amygdala, and CRH in the bed nucleus of the stria terminalis. This HPA axis activation is present during early-stage neuropathology when 3xTg-AD mice show mild behavioral changes, suggesting an ongoing neuroendocrine regulation that precedes the onset of severe AD-like pathology and behavioral deficits. PMID:22976078

  13. Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG): toward integrated treatment of symptoms related to traumatic loss

    PubMed Central

    Smid, Geert E.; Kleber, Rolf J.; de la Rie, Simone M.; Bos, Jannetta B. A.; Gersons, Berthold P. R.; Boelen, Paul A.

    2015-01-01

    Background Traumatic events such as disasters, accidents, war, or criminal violence are often accompanied by the loss of loved ones, and may then give rise to traumatic grief. Traumatic grief refers to a clinical diagnosis of persistent complex bereavement disorder (PCBD) with comorbid (symptoms of) posttraumatic stress disorder (PTSD) and/or major depressive disorder (MDD) following confrontation with a traumatic loss. Trauma survivors, who are frequently from different cultural backgrounds, have often experienced multiple losses and ambiguous loss (missing family members or friends). Current evidence-based treatments for PTSD do not focus on traumatic grief. Objective To develop a treatment for traumatic grief combining treatment interventions for PTSD and PCBD that may accommodate cultural aspects of grief. Method To provide a rationale for treatment, we propose a cognitive stress model of traumatic grief. Based on this model and on existing evidence-based treatments for PTSD and complicated grief, we developed Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG) for the treatment of patients with traumatic grief. The treatment is presented along with a case vignette. Results Processes contributing to traumatic grief include inadequately integrating the memory of the traumatic loss, negative appraisal of the traumatic loss, sensitivity to matching triggers and new stressors, and attempting to avoid distress. BEP-TG targets these processes. The BEP-TG protocol consists of five parts with proven effectiveness in the treatment of PCBD, PTSD, and MDD: information and motivation, grief-focused exposure, memorabilia and writing assignments, finding meaning and activation, and a farewell ritual. Conclusion Tailored to fit the needs of trauma survivors, BEP-TG can be used to address traumatic grief symptoms related to multiple losses and ambiguous loss, as well as cultural aspects of bereavement through its different components. PMID:26154434

  14. Mouse microsomal triglyceride transfer protein large subunit: cDNA cloning, tissue-specific expression, and chromosomal localization

    SciTech Connect

    Nakamuta, Makoto; Chang, Benny Hung-Junn; Hoogeveen, R.

    1996-04-15

    Microsomal triglyceride transfer protein (MTP) catalyzes the transfer of triglyceride, cholesteryl ester, and phospholipid between membranes. It is essential for the secretion of apolipoprotein B from the cell. Mutations in MTP are a major cause of abetalipoproteinemia. The mouse is a popular animal model for lipoprotein metabolism. We have cloned and sequenced mouse MTP cDNA. The DNA-deduced amino acid sequence indicates that mouse protein shows 93, 86, and 83% sequence indicates that mouse MTP contains 894 amino acids; the mouse protein shows 93, 86, and 83% sequence identity to the hamster, human, and bovine sequences, respectively. Northern blot analysis indicates that mouse MTP mRNA is expressed at high levels in the small intestine and at substantially lower levels in the liver and that it is not detectable in six other tissues examined. The mouse MTP gene has been localized to the distal region of chromosome 3 by Southern blots of interspecific backcross panels using progeny derived from matings of (C57BL/6J x SPRET/Ei)F1 x SPRET/Ei. Comparison of MTP sequences from human, bovine, hamster, and mouse indicates that the C-terminal region of MTP is better conserved than its N-terminal region. 21 refs., 2 figs.

  15. Water-Soluble Extract of Pacific Krill Prevents Triglyceride Accumulation in Adipocytes by Suppressing PPAR? and C/EBP? Expression

    PubMed Central

    Yamada, Hidetoshi; Ueda, Tomohiro; Yano, Akira

    2011-01-01

    Background Pacific Krill (Euphausia pacifica) are small, red crustaceans, similar to shrimp, that flourish in the North Pacific and are eaten in Japan. Methods and Findings We investigated the effect of a water-soluble extract of Pacific Krill on adipocytes and discovered that this extract suppressed triglyceride accumulation in adipocytes. Furthermore, the water-soluble extract of Pacific Krill suppressed the expression of two master regulators of adipocyte differentiation, peroxisome proliferator-activated receptor gamma (PPAR?) and CCAAT enhancer binding protein alpha (C/EBP?). C/EBP? promotes PPAR? and C/EBP? expression, but the water-soluble extract of Pacific Krill did not inhibit the expression of C/EBP? or C/EBP?-mediated transcriptional activation. The Pacific Krill extract was more effective than a PPAR? antagonist in suppressing PPAR? and C/EBP? expression. Conclusions These results indicated that the water-soluble extract of Pacific Krill was not simply a PPAR? antagonist, but that it prevented triglyceride accumulation in adipocytes by suppression of PPAR? and C/EBP? via a pathway that is independent of C/EBP?. PMID:21760932

  16. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

    PubMed Central

    Schweiger, Martina; Paar, Margret; Eder, Christina; Brandis, Janina; Moser, Elena; Gorkiewicz, Gregor; Grond, Susanne; Radner, Franz P. W.; Cerk, Ines; Cornaciu, Irina; Oberer, Monika; Kersten, Sander; Zechner, Rudolf; Zimmermann, Robert; Lass, Achim

    2012-01-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL), which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1 switch gene-2 (G0S2). CGI-58 activates and G0S2 inhibits ATGL activity. In contrast to mice, the functional role of G0S2 in human adipocyte lipolysis is poorly characterized. Here we show that overexpression or silencing of G0S2 in human SGBS adipocytes decreases and increases lipolysis, respectively. Human G0S2 is upregulated during adipocyte differentiation and inhibits ATGL activity in a dose-dependent manner. Interestingly, C-terminally truncated ATGL mutants, which fail to localize to lipid droplets, translocate to the lipid droplet upon coexpression with G0S2, suggesting that G0S2 anchors ATGL to lipid droplets independent of ATGL's C-terminal lipid binding domain. Taken together, our results indicate that G0S2 also regulates human lipolysis by affecting enzyme activity and intracellular localization of ATGL. Increased lipolysis is known to contribute to the pathogenesis of insulin resistance, and G0S2 expression has been shown to be reduced in poorly controlled type 2 diabetic patients. Our data indicate that downregulation of G0S2 in adipose tissue could represent one of the underlying causes leading to increased lipolysis in the insulin-resistant state. PMID:22891293

  17. Solid lipid nanoparticle formulations of docetaxel prepared with high melting point triglycerides: in vitro and in vivo evaluation.

    PubMed

    Naguib, Youssef Wahib; Rodriguez, B Leticia; Li, Xinran; Hursting, Stephen D; Williams, Robert O; Cui, Zhengrong

    2014-04-01

    Docetaxel (DCX) is a second generation taxane. It is approved by the U.S. Food and Drug Administration for the treatment of various types of cancer, including breast, non-small cell lung, and head and neck cancers. However, side effects, including those related to Tween 80, an excipient in current DCX formulations, can be severe. In the present study, we developed a novel solid lipid nanoparticle (SLN) composition of DCX. Trimyristin was selected from a list of high melting point triglycerides as the core lipid component of the SLNs, based on the rate at which the DCX was released from the SLNs and the stability of the SLNs. The trimyristin-based, PEGylated DCX-incorporated SLNs (DCX-SLNs) showed significantly higher cytotoxicity against various human and murine cancer cells in culture, as compared to DCX solubilized in a Tween 80/ethanol solution. Moreover, in a mouse model with pre-established tumors, the new DCX-SLNs were significantly more effective than DCX solubilized in a Tween 80/ethanol solution in inhibiting tumor growth without toxicity, likely because the DCX-SLNs increased the concentration of DCX in tumor tissues, but decreased the levels of DCX in major organs such as liver, spleen, heart, lung, and kidney. DCX-incorporated SLNs prepared with one or more high-melting point triglycerides may represent an improved DCX formulation. PMID:24621456

  18. Solid Lipid Nanoparticle Formulations of Docetaxel Prepared with High Melting Point Triglycerides: In Vitro and in Vivo Evaluation

    PubMed Central

    2015-01-01

    Docetaxel (DCX) is a second generation taxane. It is approved by the U.S. Food and Drug Administration for the treatment of various types of cancer, including breast, non-small cell lung, and head and neck cancers. However, side effects, including those related to Tween 80, an excipient in current DCX formulations, can be severe. In the present study, we developed a novel solid lipid nanoparticle (SLN) composition of DCX. Trimyristin was selected from a list of high melting point triglycerides as the core lipid component of the SLNs, based on the rate at which the DCX was released from the SLNs and the stability of the SLNs. The trimyristin-based, PEGylated DCX-incorporated SLNs (DCX-SLNs) showed significantly higher cytotoxicity against various human and murine cancer cells in culture, as compared to DCX solubilized in a Tween 80/ethanol solution. Moreover, in a mouse model with pre-established tumors, the new DCX-SLNs were significantly more effective than DCX solubilized in a Tween 80/ethanol solution in inhibiting tumor growth without toxicity, likely because the DCX-SLNs increased the concentration of DCX in tumor tissues, but decreased the levels of DCX in major organs such as liver, spleen, heart, lung, and kidney. DCX-incorporated SLNs prepared with one or more high-melting point triglycerides may represent an improved DCX formulation. PMID:24621456

  19. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase.

    PubMed

    Schweiger, Martina; Paar, Margret; Eder, Christina; Brandis, Janina; Moser, Elena; Gorkiewicz, Gregor; Grond, Susanne; Radner, Franz P W; Cerk, Ines; Cornaciu, Irina; Oberer, Monika; Kersten, Sander; Zechner, Rudolf; Zimmermann, Robert; Lass, Achim

    2012-11-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL), which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1 switch gene-2 (G0S2). CGI-58 activates and G0S2 inhibits ATGL activity. In contrast to mice, the functional role of G0S2 in human adipocyte lipolysis is poorly characterized. Here we show that overexpression or silencing of G0S2 in human SGBS adipocytes decreases and increases lipolysis, respectively. Human G0S2 is upregulated during adipocyte differentiation and inhibits ATGL activity in a dose-dependent manner. Interestingly, C-terminally truncated ATGL mutants, which fail to localize to lipid droplets, translocate to the lipid droplet upon coexpression with G0S2, suggesting that G0S2 anchors ATGL to lipid droplets independent of ATGL's C-terminal lipid binding domain. Taken together, our results indicate that G0S2 also regulates human lipolysis by affecting enzyme activity and intracellular localization of ATGL. Increased lipolysis is known to contribute to the pathogenesis of insulin resistance, and G0S2 expression has been shown to be reduced in poorly controlled type 2 diabetic patients. Our data indicate that downregulation of G0S2 in adipose tissue could represent one of the underlying causes leading to increased lipolysis in the insulin-resistant state. PMID:22891293

  20. Rescue of heart lipoprotein lipase-knockout mice confirms a role for triglyceride in optimal heart metabolism and function.

    PubMed

    Khan, Raffay S; Lin, Yan; Hu, Yunying; Son, Ni-Huiping; Bharadwaj, Kalyani G; Palacios, Carla; Chokshi, Aalap; Ji, Ruiping; Yu, Shuiqing; Homma, Sunichi; Schulze, P Christian; Tian, Rong; Goldberg, Ira J

    2013-12-01

    Hearts utilize fatty acids as a primary source of energy. The sources of those lipids include free fatty acids and lipoprotein triglycerides. Deletion of the primary triglyceride-hydrolyzing enzyme lipoprotein lipase (LPL) leads to cardiac dysfunction. Whether heart LPL-knockout (hLPL0) mice are compromised due a deficiency in energetic substrates is unknown. To test whether alternative sources of energy will prevent cardiac dysfunction in hLPL0 mice, two different models were used to supply nonlipid energy. 1) hLPL0 mice were crossed with mice transgenically expressing GLUT1 in cardiomyocytes to increase glucose uptake into the heart; this cross-corrected cardiac dysfunction, reduced cardiac hypertrophy, and increased myocardial ATP. 2) Mice were randomly assigned to a sedentary or training group (swimming) at 3 mo of age, which leads to increased skeletal muscle production of lactate. hLPL0 mice had greater expression of the lactate transporter monocarboxylate transporter-1 (MCT-1) and increased cardiac lactate uptake. Compared with hearts from sedentary hLPL0 mice, hearts from trained hLPL0 mice had adaptive hypertrophy and improved cardiac function. We conclude that defective energy intake and not the reduced uptake of fat-soluble vitamins or cholesterol is responsible for cardiac dysfunction in hLPL0 mice. In addition, our studies suggest that adaptations in cardiac metabolism contribute to the beneficial effects of exercise on the myocardium of patients with heart failure. PMID:24085031

  1. Adipose Triglyceride Lipase, Not Hormone-Sensitive Lipase, Is the Primary Lipolytic Enzyme in Fasting Elephant Seals (Mirounga angustirostris).

    PubMed

    Fowler, Melinda A; Costa, Daniel P; Crocker, Daniel E; Shen, Wen-Jun; Kraemer, Fredric B

    2015-01-01

    Little is known about the mechanisms that allow capital breeders to rapidly mobilize large amounts of body reserves. Northern elephant seals (Mirounga angustirostris) utilize fat reserves for maternal metabolism and to create high fat milk for the pup. Hormone-sensitive lipase (HSL) has been hypothesized to be an important lipolytic enzyme in fasting seals, but the activity of HSL and adipose triglyceride lipase (ATGL) has not been quantified in fasting adult seals, nor has their relationship to milk lipid content been assessed. Blubber and milk samples were obtained from 18 early lactation and 19 late lactation females, as well as blubber from five early and five late molting female seals. Blubber lipolytic activity was assessed with radiometric assays. HSL activity was negligible in seal blubber at all fasting stages. Total triglyceride lipase activity was stable among early and late lactation and early molt but increased in late molting seals. Relative abundance of ATGL protein increased across fasting, but neither activity nor relative protein levels were related to circulating nonesterified fatty acids or milk lipid content, suggesting the possibility of other regulatory pathways between lipolytic activity and milk lipid content. These results demonstrate that HSL is not the primary lipolytic enzyme in fasting adult female seals and that ATGL contributes more to lipolysis than HSL. PMID:25860827

  2. Oxidative Stress during the Progression of ?-Amyloid Pathology in the Neocortex of the Tg2576 Mouse Model of Alzheimer's Disease

    PubMed Central

    Porcellotti, Sara; Fanelli, Francesca; Fracassi, Anna; Sepe, Sara; Cecconi, Francesco; Bernardi, Cinzia; Cimini, AnnaMaria; Cerù, Maria Paola; Moreno, Sandra

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive neurodegeneration. Pathogenetic mechanisms, triggered by ?-amyloid (A?) accumulation, include oxidative stress, derived from energy homeostasis deregulation and involving mitochondria and peroxisomes. We here addressed the oxidative stress status and the elicited cellular response at the onset and during the progression of A? pathology, studying the neocortex of Tg2576 model of AD. Age-dependent changes of oxidative damage markers, antioxidant enzymes, and related transcription factors were analysed in relation to the distribution of A? peptide and oligomers, by a combined molecular/morphological approach. Nucleic acid oxidative damage, accompanied by defective antioxidant defences, and decreased PGC1? expression are already detected in 3-month-old Tg2576 neurons. Conversely, PPAR? is increased in these cells, with its cytoplasmic localization suggesting nongenomic, anti-inflammatory actions. At 6 months, when intracellular A? accumulates, PMP70 is downregulated, indicating impairment of fatty acids peroxisomal translocation and their consequent harmful accumulation. In 9-month-old Tg2576 neocortex, A? oligomers and acrolein deposition correlate with GFAP, GPX1, and PMP70 increases, supporting a compensatory response, involving astroglial peroxisomes. At severe pathological stages, when senile plaques disrupt cortical cytoarchitecture, antioxidant capacity is gradually lost. Overall, our data suggest early therapeutic intervention in AD, also targeting peroxisomes. PMID:25973140

  3. Oxidative Stress during the Progression of ?-Amyloid Pathology in the Neocortex of the Tg2576 Mouse Model of Alzheimer's Disease.

    PubMed

    Porcellotti, Sara; Fanelli, Francesca; Fracassi, Anna; Sepe, Sara; Cecconi, Francesco; Bernardi, Cinzia; Cimini, AnnaMaria; Cerù, Maria Paola; Moreno, Sandra

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive neurodegeneration. Pathogenetic mechanisms, triggered by ?-amyloid (A?) accumulation, include oxidative stress, derived from energy homeostasis deregulation and involving mitochondria and peroxisomes. We here addressed the oxidative stress status and the elicited cellular response at the onset and during the progression of A? pathology, studying the neocortex of Tg2576 model of AD. Age-dependent changes of oxidative damage markers, antioxidant enzymes, and related transcription factors were analysed in relation to the distribution of A? peptide and oligomers, by a combined molecular/morphological approach. Nucleic acid oxidative damage, accompanied by defective antioxidant defences, and decreased PGC1? expression are already detected in 3-month-old Tg2576 neurons. Conversely, PPAR? is increased in these cells, with its cytoplasmic localization suggesting nongenomic, anti-inflammatory actions. At 6 months, when intracellular A? accumulates, PMP70 is downregulated, indicating impairment of fatty acids peroxisomal translocation and their consequent harmful accumulation. In 9-month-old Tg2576 neocortex, A? oligomers and acrolein deposition correlate with GFAP, GPX1, and PMP70 increases, supporting a compensatory response, involving astroglial peroxisomes. At severe pathological stages, when senile plaques disrupt cortical cytoarchitecture, antioxidant capacity is gradually lost. Overall, our data suggest early therapeutic intervention in AD, also targeting peroxisomes. PMID:25973140

  4. Retinal Remodeling in the Tg P347L Rabbit, a Large-Eye Model of Retinal Degeneration

    PubMed Central

    Jones, Bryan William; Kondo, Mineo; Terasaki, Hiroko; Watt, Carl Brock; Rapp, Kevin; Anderson, James; Lin, Yanhua; Shaw, Marguerite Victoria; Yang, Jia-Hui; Marc, Robert Edward

    2013-01-01

    Retinitis pigmentosa (RP) is an inherited blinding disease characterized by progressive loss of retinal photo-receptors. There are numerous rodent models of retinal degeneration, but most are poor platforms for interventions that will translate into clinical practice. The rabbit possesses a number of desirable qualities for a model of retinal disease including a large eye and an existing and substantial knowledge base in retinal circuitry, anatomy, and ophthalmology. We have analyzed degeneration, remodeling, and reprogramming in a rabbit model of retinal degeneration, expressing a rhodopsin proline 347 to leucine transgene in a TgP347L rabbit as a powerful model to study the pathophysiology and treatment of retinal degeneration. We show that disease progression in the TgP347L rabbit closely tracks human cone-sparing RP, including the cone-associated preservation of bipolar cell signaling and triggering of reprogramming. The relatively fast disease progression makes the TgP347L rabbit an excellent model for gene therapy, cell biological intervention, progenitor cell transplantation, surgical interventions, and bionic prosthetic studies. PMID:21681749

  5. Retinal remodeling in the Tg P347L rabbit, a large-eye model of retinal degeneration.

    PubMed

    Jones, B W; Kondo, M; Terasaki, H; Watt, C B; Rapp, K; Anderson, J; Lin, Y; Shaw, M V; Yang, J-H; Marc, R E

    2011-10-01

    Retinitis pigmentosa (RP) is an inherited blinding disease characterized by progressive loss of retinal photoreceptors. There are numerous rodent models of retinal degeneration, but most are poor platforms for interventions that will translate into clinical practice. The rabbit possesses a number of desirable qualities for a model of retinal disease including a large eye and an existing and substantial knowledge base in retinal circuitry, anatomy, and ophthalmology. We have analyzed degeneration, remodeling, and reprogramming in a rabbit model of retinal degeneration, expressing a rhodopsin proline 347 to leucine transgene in a TgP347L rabbit as a powerful model to study the pathophysiology and treatment of retinal degeneration. We show that disease progression in the TgP347L rabbit closely tracks human cone-sparing RP, including the cone-associated preservation of bipolar cell signaling and triggering of reprogramming. The relatively fast disease progression makes the TgP347L rabbit an excellent model for gene therapy, cell biological intervention, progenitor cell transplantation, surgical interventions, and bionic prosthetic studies. PMID:21681749

  6. Role of protein glycosylation on the expression of muscarinic receptors of N4TG1 neuroblastoma cells

    SciTech Connect

    Ahmad, A.; Chiang, P.K.

    1986-05-01

    Muscarinic acetylcholine receptors (mAChR) are glycoproteins. Experiments were conducted to determine whether active glycosylation of proteins in N4TG1 neuroblastoma cells could affect the expression of muscarinic receptors on the cell surface. The binding of radioactive N-methylscopolamine, a membrane impermeable ligand, to intact cells was used as a measure of mAChR. In the presence of the inhibitors of glycosylation, such as tunicamycin, monensin and amphomycin, N-linked glycosylation of proteins in the N4TG1 cells was inhibited, as measured by the incorporation of radioactive glucosamine or mannose in proteins. At the concentrations of tunicamycin and monensin used, the glycosylation of proteins after 3 hours were drastically reduced, but the number of mAChR in the cells was not altered. The apparent lack of effect within a short incubation period could be attributed to the presence of preformed oligosaccharide dolichol readily available for N-glycosylation. However, after 24 hours, tunicamycin (0.05 ..mu..g/ml) caused a decrease in the number of mAChR by 17% without having any effect on protein synthesis. Therefore, de novo glycosylation of proteins may be required for the expression of mAChR receptors in the N4TG1 neuroblastoma cell surface.

  7. Formation and dissolution processes of the 6-thioguanine (6TG) self-assembled monolayer. A kinetic study.

    PubMed

    Madueño, Rafael; Pineda, Teresa; Sevilla, José Manuel; Blázquez, Manuel

    2005-02-01

    This is a report on the kinetics of the destruction and formation processes of the 6-thioguanine self-assembled monolayer (6TG SAM) on a mercury electrode from acid solutions by chronoamperometry. The destruction of the 6TG SAM that has been previously formed under open circuit potential conditions is carried out by stepping the potential from an initial value where the chemisorbed layer is stable up to potentials where the molecules are no longer chemisorbed. The destruction of the SAM has been described by a model that involves three types of contributions: (i) a Langmuir-type adsorption process, (ii) a 2D nucleation mechanism followed by a growth controlled by surface diffusion, and (iii) a 2D nucleation mechanism followed by a growth at a constant rate. The nonlinear fit of the experimental transients by using this procedure allows the quantitative determination of the individual contributions to the overall process. The kinetics of the formation process is studied under electrochemical conditions. The chronoamperometric experiment allows us to monitor the early stages of 6TG SAM formation. The implications of the physisorbed state at low potentials in the type of monolayer formation and destruction processes as well as the influence of temperature are also discussed. PMID:16851120

  8. PVA:LiClO4: a robust, high Tg polymer electrolyte for adjustable ion gating of 2D materials

    NASA Astrophysics Data System (ADS)

    Kinder, Erich; Fullerton, Susan; CenterLow Energy Systems Technology Team

    2015-03-01

    Polymer electrolytes are an effective way to gate organic semiconductors and nanomaterials, such as nanotubes and 2D materials, by establishing an electrostatic double layer with large capacitance. Widely used solid electrolytes, such as those based on polyethylene oxide, have a glass transition temperature below room temperature. This permits relatively fast ion mobility at T = 23 °C, but requires a constant applied field to maintain a doping profile. Moreover, PEO-based electrolytes cannot withstand a variety of solvents, limiting its use. Here, we demonstrate a polymer electrolyte using polyvinyl alcohol (PVA) with Tg >23 °C, through which a doping profile can be defined by a potential applied when the polymer is heated above Tg, then ``locked-in'' by cooling the electrolyte to room temperature (<Tg) to limit ion mobility. Current-voltage measurements of a graphene field effect transistor verify the ``lock-in'' process, showing constant drain current regardless of the applied electrolyte gate bias. Hall bar measurements are used to quantify the charge carrier density. Owing to PVA's chemical stability, photolithography can be performed directly on the polymer electrolyte, which allows for the deposition of a patterned, metal gate directly on the electrolyte, as well as the ability to pattern the electrolyte itself. This work was supported in part by the Center for Low Energy Systems Technology (LEAST), one of the six SRC STARnet Centers, sponsored by MARCO and DARPA.

  9. The acquisition and association of TG{sub 1-3} single-strand tails during replication of Saccharomyce telomeres

    SciTech Connect

    Wellinger, R.J.; Wolf, A.J.; Zakian, V.A.

    1993-12-31

    Telomeres in virtually all organisms bear multiple copies of simple repeated DNA. Typically, these simple repeats have a strand bias in base composition such that the strand running 5{prime} to 3{prime} from the center towards the end of the molecule has clusters of G residues, hereafter called the G-strand. For example, Saccharomyces cerevisiae chromosomes end in {approximately}300 bps of C{sub 2-3}A(CA){sub 1-6}/(TG){sub 1-6}TG{sub 2-3}, commonly abbreviated C{sub 1-3}A/TG{sub 1-3}. Oligonucleotides with the sequence of G-strand telomeric DNA from different organisms can form non-B form DNA in vitro involving G-G bps. Conventional DNA polymerases can synthesize DNA only in the 5{prime} to 3{prime} direction and require a 3{prime} direction and require a 3{prime} OH primer. For chromosomal DNA replication in yeast and other eukaryotes, the primer is an 8 to 12 base stretch of RNA. DNA termini replicated by a conventional DNA polymerase are expected to have 8-12 base gaps at the 5{prime} ends of newly replicated strands that arise by removal of the terminal RNA primers. Telomeres are thought to prevent the slow but continuous DNA loss that would result from replication by a conventional DNA polymerase by providing a substrate for an alternative replication mechanism.

  10. Addendum to the AAPM's TG-51 protocol for clinical reference dosimetry of high-energy photon beams

    SciTech Connect

    McEwen, Malcolm; DeWerd, Larry; Ibbott, Geoffrey; Followill, David; Rogers, David W. O.; Seltzer, Stephen; Seuntjens, Jan

    2014-04-15

    An addendum to the AAPM's TG-51 protocol for the determination of absorbed dose to water in megavoltage photon beams is presented. This addendum continues the procedure laid out in TG-51 but new k{sub Q} data for photon beams, based on Monte Carlo simulations, are presented and recommendations are given to improve the accuracy and consistency of the protocol's implementation. The components of the uncertainty budget in determining absorbed dose to water at the reference point are introduced and the magnitude of each component discussed. Finally, the consistency of experimental determination of N{sub D,w} coefficients is discussed. It is expected that the implementation of this addendum will be straightforward, assuming that the user is already familiar with TG-51. The changes introduced by this report are generally minor, although new recommendations could result in procedural changes for individual users. It is expected that the effort on the medical physicist's part to implement this addendum will not be significant and could be done as part of the annual linac calibration.

  11. Olive Leaf Extract Elevates Hepatic PPAR ? mRNA Expression and Improves Serum Lipid Profiles in Ovariectomized Rats.

    PubMed

    Yoon, Leena; Liu, Ya-Nan; Park, Hyunjin; Kim, Hyun-Sook

    2015-07-01

    We hypothesized that olive leaf extract might alleviate dyslipidemia resulting from estrogen deficiency. Serum lipid profile and mRNA expression of the related genes in the liver and adipose tissue were analyzed after providing olive leaf extract (200 or 400?mg/kg body weight; n=7 for each group) to ovariectomized rats for 10 weeks. After 10 weeks' administration, the rats in the olive leaf extract-administered groups showed significantly lower levels of serum triglyceride and very-low-density lipoprotein (VLDL)-cholesterol compared with the rats in the control group, whereas the administration of olive leaf extract did not significantly change the elevated low-density lipoprotein cholesterol levels. In addition, administration of high dose of olive leaf extract significantly decreased the liver triglyceride and increased serum estradiol levels. mRNA expressions of peroxisome proliferator-activated receptor alpha (PPAR ?) and acyl-CoA oxidase (ACO) were not affected by ovariectomy, however, administration of olive leaf extract significantly increased both PPAR ? and ACO mRNA expression. Expression of adiponectin mRNA in adipose tissue was significantly decreased in the ovariectomized control group. Rats administered low-dose olive leaf extract showed significantly elevated adiponectin mRNA expression compared with rats in the ovariectomized control group. Even though dose-dependent effects were not observed in most of the measurements, these results suggest that genes involved in lipid metabolism may be regulated by olive leaf extract administration in ovariectomized rats. PMID:25714618

  12. MO-E-9A-01: Risk Based Quality Management: TG100 In Action

    SciTech Connect

    Huq, M; Palta, J; Dunscombe, P; Thomadsen, B

    2014-06-15

    One of the goals of quality management in radiation therapy is to gain high confidence that patients will receive the prescribed treatment correctly. To accomplish these goals professional societies such as the American Association of Physicists in Medicine (AAPM) has published many quality assurance (QA), quality control (QC), and quality management (QM) guidance documents. In general, the recommendations provided in these documents have emphasized on performing device-specific QA at the expense of process flow and protection of the patient against catastrophic errors. Analyses of radiation therapy incidents find that they are most often caused by flaws in the overall therapy process, from initial consult through final treatment, than by isolated hardware or computer failures detectable by traditional physics QA. This challenge is shared by many intrinsically hazardous industries. Risk assessment tools and analysis techniques have been developed to define, identify, and eliminate known and/or potential failures, problems, or errors, from a system, process and/or service before they reach the customer. These include, but are not limited to, process mapping, failure modes and effects analysis (FMEA), fault tree analysis (FTA), and establishment of a quality management program that best avoids the faults and risks that have been identified in the overall process. These tools can be easily adapted to radiation therapy practices because of their simplicity and effectiveness to provide efficient ways to enhance the safety and quality of treatment processes. Task group 100 (TG100) of AAPM has developed a risk-based quality management program that uses these tools. This session will be devoted to a discussion of these tools and how these tools can be used in a given radiotherapy clinic to develop a risk based QM program. Learning Objectives: Learn how to design a process map for a radiotherapy process. Learn how to perform a FMEA analysis for a given process. Learn what Fault tree analysis is all about. Learn how to design a quality management program based upon the information obtained from process mapping, FMEA and FTA.

  13. Impaired Rapid Eye Movement Sleep in the Tg2576 APP Murine Model of Alzheimer’s Disease with Injury to Pedunculopontine Cholinergic Neurons

    PubMed Central

    Zhang, Bin; Veasey, Sigrid C.; Wood, Marcelo A.; Leng, Lewis Z.; Kaminski, Christine; Leight, Susan; Abel, Ted; Lee, Virginia M.-Y.; Trojanowski, John Q.

    2005-01-01

    Impaired rapid eye movement sleep (REMS) is commonly observed in Alzheimer’s disease, suggesting injury to mesopontine cholinergic neurons. We sought to determine whether abnormal ?-amyloid peptides impair REMS and injure mesopontine cholinergic neurons in transgenic (hAPP695.SWE) mice (Tg2576) that model brain amyloid pathologies. Tg2576 mice and wild-type littermates were studied at 2, 6, and 12 months by using sleep recordings, contextual fear conditioning, and immunohistochemistry. At 2 months of age, REMS was indistinguishable by genotype but was reduced in Tg2576 mice at 6 and 12 months. Choline acetyltransferase-positive neurons in the pedunculopontine tegmentum of Tg2576 mice at 2 months evidenced activated caspase-3 immunoreactivity, and at 6 and 12 months the numbers of pedunculopontine tegmentum choline acetyltransferase-positive neurons were reduced in the Tg2576 mice. Other cholinergic groups involved in REMS were unperturbed. At 12 months, Tg2576 mice demonstrated increased 3-nitrotyrosine immunoreactivity in cholinergic projection sites but not in cholinergic soma. We have identified a population of selectively compromised cholinergic neurons in young Tg2576 mice that manifest early onset REMS impairment. The differential vulnerability of these cholinergic neurons to A? injury provides an invaluable tool with which to understand mechanisms of sleep/wake perturbations in Alzheimer’s disease. PMID:16251420

  14. Fragile-to-fragile Liquid Transition at Tg and Stable-Glass Phase Nucleation Rate Maximum at the Kauzmann Temperature TK

    E-print Network

    Robert Felix Tournier

    2015-02-23

    An undercooled liquid is unstable. The driving force of the glass transition at Tg is a change of the undercooled-liquid Gibbs free energy. The classical Gibbs free energy change for a crystal formation is completed including an enthalpy saving. The crystal growth critical nucleus is used as a probe to observe the Laplace pressure change Dp accompanying the enthalpy change -Vm *Dp at Tg where Vm is the molar volume. A stable glass-liquid transition model predicts the specific heat jump of fragile liquids at temperatures smaller than Tg, the Kauzmann temperature TK where the liquid entropy excess with regard to crystal goes to zero, the equilibrium enthalpy between TK and Tg, the maximum nucleation rate at TK of superclusters containing magic atom numbers, and the equilibrium latent heats at Tg and TK. Strong-to-fragile and strong-to-strong liquid transitions at Tg are also described and all their thermodynamic parameters are determined from their specific heat jumps. The existence of fragile liquids quenched in the amorphous state, which do not undergo liquid-liquid transition during heating preceding their crystallization, is predicted. Long ageing times leading to the formation at TK of a stable glass composed of superclusters containing up to 147 atoms, touching and interpenetrating, are evaluated from nucleation rates. A fragile-to-fragile liquid transition occurs at Tg without stable-glass formation while a strong glass is stable after transition.

  15. Fragile-to-fragile liquid transition at Tg and stable-glass phase nucleation rate maximum at the Kauzmann temperature TK

    NASA Astrophysics Data System (ADS)

    Tournier, Robert F.

    2014-12-01

    An undercooled liquid is unstable. The driving force of the glass transition at Tg is a change of the undercooled-liquid Gibbs free energy. The classical Gibbs free energy change for a crystal formation is completed including an enthalpy saving. The crystal growth critical nucleus is used as a probe to observe the Laplace pressure change ?p accompanying the enthalpy change -Vm×?p at Tg where Vm is the molar volume. A stable glass-liquid transition model predicts the specific heat jump of fragile liquids at T?Tg, the Kauzmann temperature TK where the liquid entropy excess with regard to crystal goes to zero, the equilibrium enthalpy between TK and Tg, the maximum nucleation rate at TK of superclusters containing magic atom numbers, and the equilibrium latent heats at Tg and TK. Strong-to-fragile and strong-to-strong liquid transitions at Tg are also described and all their thermodynamic parameters are determined from their specific heat jumps. The existence of fragile liquids quenched in the amorphous state, which do not undergo liquid-liquid transition during heating preceding their crystallization, is predicted. Long ageing times leading to the formation at TK of a stable glass composed of superclusters containing up to 147 atom, touching and interpenetrating, are evaluated from nucleation rates. A fragile-to-fragile liquid transition occurs at Tg without stable-glass formation while a strong glass is stable after transition.

  16. Caprylic Triglyceride as a Novel Therapeutic Approach to Effectively Improve the Performance and Attenuate the Symptoms Due to the Motor Neuron Loss in ALS Disease

    PubMed Central

    Zhao, Wei; Varghese, Merina; Vempati, Prashant; Dzhun, Anastasiya; Cheng, Alice; Wang, Jun; Lange, Dale; Bilski, Amanda; Faravelli, Irene; Pasinetti, Giulio Maria

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients. PMID:23145119

  17. Sleep-Wake Cycle Dysfunction in the TgCRND8 Mouse Model of Alzheimer’s Disease: From Early to Advanced Pathological Stages

    PubMed Central

    Colby-Milley, Jessica; Cavanagh, Chelsea; Jego, Sonia; Breitner, John C. S.; Quirion, Rémi; Adamantidis, Antoine

    2015-01-01

    In addition to cognitive decline, individuals affected by Alzheimer’s disease (AD) can experience important neuropsychiatric symptoms including sleep disturbances. We characterized the sleep-wake cycle in the TgCRND8 mouse model of AD, which overexpresses a mutant human form of amyloid precursor protein resulting in high levels of ?-amyloid and plaque formation by 3 months of age. Polysomnographic recordings in freely-moving mice were conducted to study sleep-wake cycle architecture at 3, 7 and 11 months of age and corresponding levels of ?-amyloid in brain regions regulating sleep-wake states were measured. At all ages, TgCRND8 mice showed increased wakefulness and reduced non-rapid eye movement (NREM) sleep during the resting and active phases. Increased wakefulness in TgCRND8 mice was accompanied by a shift in the waking power spectrum towards fast frequency oscillations in the beta (14-20 Hz) and low gamma range (20-50 Hz). Given the phenotype of hyperarousal observed in TgCRND8 mice, the role of noradrenergic transmission in the promotion of arousal, and previous work reporting an early disruption of the noradrenergic system in TgCRND8, we tested the effects of the alpha-1-adrenoreceptor antagonist, prazosin, on sleep-wake patterns in TgCRND8 and non-transgenic (NTg) mice. We found that a lower dose (2 mg/kg) of prazosin increased NREM sleep in NTg but not in TgCRND8 mice, whereas a higher dose (5 mg/kg) increased NREM sleep in both genotypes, suggesting altered sensitivity to noradrenergic blockade in TgCRND8 mice. Collectively our results demonstrate that amyloidosis in TgCRND8 mice is associated with sleep-wake cycle dysfunction, characterized by hyperarousal, validating this model as a tool towards understanding the relationship between ?-amyloid overproduction and disrupted sleep-wake patterns in AD. PMID:26076358

  18. Ion implantation at elevated temperatures

    SciTech Connect

    Lam, N.Q.; Leaf, G.K.

    1985-11-01

    A kinetic model has been developed to investigate the synergistic effects of radiation-enhanced diffusion, radiation-induced segregation and preferential sputtering on the spatial redistribution of implanted solutes during implantation at elevated temperatures. Sample calculations were performed for Al and Si ions implanted into Ni. With the present model, the influence of various implantation parameters on the evolution of implant concentration profiles could be examined in detail.

  19. Communication: Experimentally determined profile of local glass transition temperature across a glassy-rubbery polymer interface with a Tg difference of 80 K

    NASA Astrophysics Data System (ADS)

    Baglay, Roman R.; Roth, Connie B.

    2015-09-01

    Studying the local glass transition temperature Tg across a boundary, we investigate the characteristic length scales of cooperative dynamics. High molecular weight polymers have a large separation in time scales between cooperative segmental motion (?-relaxation) and chain diffusion allowing us to measure the local Tg(z) profile across a glassy-rubbery interface of polystyrene/poly(n-butyl methacrylate) using fluorescence. We find this profile in cooperative dynamics does not correlate with the 7-nm wide symmetric composition profile of the interface, but instead is very broad, spanning 350-400 nm from one bulk Tg value to another, and highly asymmetric, extending further into the glassy side.

  20. Linkage between C-reactive protein and triglyceride-rich lipoprotein metabolism

    PubMed Central

    Thongtang, Nuntakorn; Diffenderfer, Margaret R.; Ooi, Esther M.M.; Asztalos, Bela F.; Dolnikowski, Gregory G.; Lamon-Fava, Stefania; Schaefer, Ernst J.

    2015-01-01

    Objective Inflammation plays an important role in atherosclerosis. Elevated C-reactive protein (CRP) levels are associated with a greater risk of cardiovascular disease. Our goal was to study CRP metabolism, and to determine its relationship with lipoprotein metabolism using stable isotope methodology. Material/Methods Eight subjects with combined hyperlipidemia underwent a 15-h primed-constant infusion with deuterated leucine. CRP was purified from the plasma density fraction greater than 1.21g/ml by affinity chromatography. Lipoprotein fractions were separated by sequential ultracentrifugation. Isotope enrichment was determined by gas chromatography/mass spectrometry. Results The subjects had mean LDL-C levels of 147.5mg/dl and mean CRP levels of 3.4mg/ l. The mean CRP production rate (PR) was 0.050±0.012mg/kg/day and the mean CRP fractional catabolic rate (FCR) was 0.343±0.056 pools/day (residence time 2.92days). CRP pool size (PS) was significantly related to production (r=0.93; p<0.001), but not FCR. CRP PS was also related to body mass index (r=0.79; p=0.02). There was a significant association between CRP FCR and TRL apoB-100 FCR (r=0.74, p=0.04), as well as between CRP PS and TRL apoB-48 FCR (r=-0.90, p=0.002), indicating linkage between CRP and TRL metabolism. Conclusion The main determinant of plasma CRP levels was CRP production rate. Moreover a significant linkage between CRP metabolism and both TRL apoB-100 and apoB-48 catabolism was noted. PMID:23018145

  1. Lipoprotein cholesterol and triglyceride concentrations associated with dog body condition score; effect of recommended fasting duration on sample concentrations in Japanese private clinics.

    PubMed

    Usui, Shiho; Yasuda, Hidemi; Koketsu, Yuzo

    2015-10-01

    The objectives of this study were to survey clinics' guidance about recommended fasting duration (FD) prior to lipoprotein analysis, and to characterize lipoprotein cholesterol and triglyceride concentrations in obese and overweight dogs categorized on the basis of the 5-point body condition score (BCS) scale. A dataset was created from lipoprotein analysis medical records of 1,538 dogs from 75 breeds in 354 clinics from 2012 to 2013. A phone survey was conducted to obtain the clinics' FD. Two-level linear mixed-effects models were applied to the data. Over 50% of the clinics said they recommended fasting for 12 hr or more. Dogs in clinics with FD 12 hr or more had lower chylomicron triglyceride concentrations than those in clinics with FD less than 8 hr (P=0.05). Mean (± SEM) BCS at sampling was 3.7 ± 0.02. Obese and overweight dogs had higher very low density lipoprotein (VLDL) and high density lipoprotein (HDL) cholesterol and triglyceride concentrations than ideal dogs (P<0.05), but no such difference was found for low density lipoprotein cholesterol and triglyceride concentrations (P?0.07). Across all BCS, as dog age rose from 0 to 8 years old, HDL cholesterol concentrations decreased by 13.5 mg/dl, whereas VLDL triglyceride concentrations increased by 81.7 mg/dl (P<0.05). In conclusion, FD of 8 hr or less may affect lipoprotein lipid concentrations. Obese and overweight dogs were characterized as having high VLDL and HDL cholesterol and triglyceride concentrations. PMID:25866404

  2. Lipoprotein cholesterol and triglyceride concentrations associated with dog body condition score; effect of recommended fasting duration on sample concentrations in Japanese private clinics

    PubMed Central

    USUI, Shiho; YASUDA, Hidemi; KOKETSU, Yuzo

    2015-01-01

    The objectives of this study were to survey clinics’ guidance about recommended fasting duration (FD) prior to lipoprotein analysis, and to characterize lipoprotein cholesterol and triglyceride concentrations in obese and overweight dogs categorized on the basis of the 5-point body condition score (BCS) scale. A dataset was created from lipoprotein analysis medical records of 1,538 dogs from 75 breeds in 354 clinics from 2012 to 2013. A phone survey was conducted to obtain the clinics’ FD. Two-level linear mixed-effects models were applied to the data. Over 50% of the clinics said they recommended fasting for 12 hr or more. Dogs in clinics with FD 12 hr or more had lower chylomicron triglyceride concentrations than those in clinics with FD less than 8 hr (P=0.05). Mean (± SEM) BCS at sampling was 3.7 ± 0.02. Obese and overweight dogs had higher very low density lipoprotein (VLDL) and high density lipoprotein (HDL) cholesterol and triglyceride concentrations than ideal dogs (P<0.05), but no such difference was found for low density lipoprotein cholesterol and triglyceride concentrations (P?0.07). Across all BCS, as dog age rose from 0 to 8 years old, HDL cholesterol concentrations decreased by 13.5 mg/dl, whereas VLDL triglyceride concentrations increased by 81.7 mg/dl (P<0.05). In conclusion, FD of 8 hr or less may affect lipoprotein lipid concentrations. Obese and overweight dogs were characterized as having high VLDL and HDL cholesterol and triglyceride concentrations. PMID:25866404

  3. 21 CFR 890.3930 - Wheelchair elevator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3930 Wheelchair elevator. (a) Identification. A wheelchair elevator is a motorized lift...

  4. 21 CFR 890.3930 - Wheelchair elevator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3930 Wheelchair elevator. (a) Identification. A wheelchair elevator is a motorized lift...

  5. 21 CFR 890.3930 - Wheelchair elevator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3930 Wheelchair elevator. (a) Identification. A wheelchair elevator is a motorized lift...

  6. A new bed elevation dataset for Greenland

    E-print Network

    Bamber, J. L.; Griggs, J. A.; Hurkmans, R. T. W. L.; Dowdeswell, J. A.; Gogineni, Sivaprasad; Howat, I.; Mouginot, J.; Jaden, John D.; Palmer, S.; Rignot, E.; Steinhage, D.

    2013-03-22

    combination of surface elevation and radar soundings. The across-track spacing between flight lines warranted interpolation at 1 km postings for significant sectors of the ice sheet. Grids of ice surface elevation, error estimates for the DEM, ice thickness...

  7. Global variation in elevational diversity patterns.

    PubMed

    Guo, Qinfeng; Kelt, Douglas A; Sun, Zhongyu; Liu, Hongxiao; Hu, Liangjun; Ren, Hai; Wen, Jun

    2013-01-01

    While horizontal gradients of biodiversity have been examined extensively in the past, vertical diversity gradients (elevation, water depth) are attracting increasing attention. We compiled data from 443 elevational gradients involving diverse organisms worldwide to investigate how elevational diversity patterns may vary between the Northern and Southern hemispheres and across latitudes. Our results show that most elevational diversity curves are positively skewed (maximum diversity below the middle of the gradient) and the elevation of the peak in diversity increases with the elevation of lower sampling limits and to a lesser extent with upper limit. Mountains with greater elevational extents, and taxonomic groups that are more inclusive, show proportionally more unimodal patterns whereas other ranges and taxa show highly variable gradients. The two hemispheres share some interesting similarities but also remarkable differences, likely reflecting differences in landmass and mountain configurations. Different taxonomic groups exhibit diversity peaks at different elevations, probably reflecting both physical and physiological constraints. PMID:24157658

  8. 75 FR 68710 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-09

    ...selected locations in each community are shown. National Environmental...Siskiyou County Public Health and Community Development Department, 806...s) elevation above ground Communities affected [caret] Elevation...Unincorporated Areas of downstream of Gay Street. Crawford...

  9. Intelligent elevator management system using image processing

    NASA Astrophysics Data System (ADS)

    Narayanan, H. Sai; Karunamurthy, Vignesh; Kumar, R. Barath

    2015-03-01

    In the modern era, the increase in the number of shopping malls and industrial building has led to an exponential increase in the usage of elevator systems. Thus there is an increased need for an effective control system to manage the elevator system. This paper is aimed at introducing an effective method to control the movement of the elevators by considering various cases where in the location of the person is found and the elevators are controlled based on various conditions like Load, proximity etc... This method continuously monitors the weight limit of each elevator while also making use of image processing to determine the number of persons waiting for an elevator in respective floors. Canny edge detection technique is used to find out the number of persons waiting for an elevator. Hence the algorithm takes a lot of cases into account and locates the correct elevator to service the respective persons waiting in different floors.

  10. 77 FR 66555 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-06

    ...FEMA-2012-0003] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  11. 78 FR 6745 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-31

    ...FEMA-2013-0002] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  12. 77 FR 30220 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ...FEMA-2012-0003] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  13. 75 FR 64165 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-19

    ...FEMA-2010-0003] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street, SW...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  14. 77 FR 21471 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-10

    ...FEMA-2012-0003] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  15. 77 FR 41323 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ...FEMA-2012-0003] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster [[Page...AMENDED] 0 1. The authority...

  16. 76 FR 76055 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-06

    ...FEMA-2011-0002] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  17. 77 FR 45262 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-31

    ...FEMA-2012-0003] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  18. 77 FR 76929 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-31

    ...FEMA-2012-0003] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  19. 77 FR 49360 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ...FEMA-2012-0003] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  20. 76 FR 35111 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ...FEMA-2011-0002] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street, SW...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  1. 78 FR 14697 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-07

    ...FEMA-2013-0002] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  2. 77 FR 46972 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-07

    ...FEMA-2012-0003] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  3. 76 FR 21664 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-18

    ...FEMA-2011-0002] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street, SW...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  4. 75 FR 59989 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-29

    ...FEMA-2010-0003] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street, SW...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  5. 77 FR 26959 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-08

    ...FEMA-2012-0003] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  6. 76 FR 43923 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-22

    ...FEMA-2011-0002] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  7. 77 FR 3625 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ...FEMA-2011-0002] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  8. 77 FR 6976 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ...FEMA-2011-0002] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  9. 76 FR 39011 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-05

    ...FEMA-2011-0002] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  10. 78 FR 5738 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    ...FEMA-2013-0002] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street SW., Washington...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  11. 76 FR 3531 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-20

    ...FEMA-2011-0002] Final Flood Elevation Determinations...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street, SW...section 110 of the Flood Disaster Protection...AMENDED] 0 1. The authority...

  12. Studies on acrylated epoxydised triglyceride resin-co-butyl methacrylate towards the development of biodegradable pressure sensitive adhesives.

    PubMed

    David, S Begila; Sathiyalekshmi, K; Gnana Raj, G Allen

    2009-12-01

    The potential chemical utility of Soya bean oil for the preparation of novel biodegradable polymeric pressure sensitive adhesive has been investigated. Epoxy resin was prepared through in situ epoxidation of Soya bean oil under controlled reaction conditions. Acrylated epoxidised triglyceride resin (AET resin) and copolymer of AET resin with butyl methacrylate were prepared and evaluated. Higher the concentration of butyl methacrylate higher is the degree of copolymerization of AET resin with butyl methacrylate. An optimum concentration of AET resin with butyl methacrylate (100 : 0.40) yields favourable shear holding time and peel strength to qualify as pressure sensitive adhesive. The candidate PSA formulation is biodegradable with antimicrobial activity against gram positive S. aureus ATCC 25923. PMID:18584126

  13. Coarse-grained modelling of triglyceride crystallisation: a molecular insight into tripalmitin tristearin binary mixtures by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Pizzirusso, Antonio; Brasiello, Antonio; De Nicola, Antonio; Marangoni, Alejandro G.; Milano, Giuseppe

    2015-12-01

    The first simulation study of the crystallisation of a binary mixture of triglycerides using molecular dynamics simulations is reported. Coarse-grained models of tristearin (SSS) and tripalmitin (PPP) molecules have been considered. The models have been preliminarily tested in the crystallisation of pure SSS and PPP systems. Two different quenching procedures have been tested and their performances have been analysed. The structures obtained from the crystallisation procedures show a high orientation order and a high content of molecules in the tuning fork conformation, comparable with the crystalline ? phase. The behaviour of melting temperatures for the ? phase of the mixture SSS/PPP obtained from the simulations is in qualitative agreement with the behaviour that was experimentally determined.

  14. Structure–activity studies in the development of a hydrazone based inhibitor of adipose-triglyceride lipase (ATGL)

    PubMed Central

    Mayer, Nicole; Schweiger, Martina; Melcher, Michaela-Christina; Fledelius, Christian; Zechner, Rudolf; Zimmermann, Robert; Breinbauer, Rolf

    2015-01-01

    Adipose triglyceride lipase (ATGL) catalyzes the degradation of cellular triacylglycerol stores and strongly determines the concentration of circulating fatty acids (FAs). High serum FA levels are causally linked to the development of insulin resistance and impaired glucose tolerance, which eventually progresses to overt type 2 diabetes. ATGL-specific inhibitors could be used to lower circulating FAs, which can counteract the development of insulin resistance. In this article, we report about structure–activity relationship (SAR) studies of small molecule inhibitors of ATGL based on a hydrazone chemotype. The SAR indicated that the binding pocket of ATGL requests rather linear compounds without bulky substituents. The best inhibitor showed an IC50 = 10 ?M in an assay with COS7-cell lysate overexpressing murine ATGL. PMID:25778769

  15. History of Elevators and Related Research

    NASA Astrophysics Data System (ADS)

    Abe, Shigeru; Watanabe, Eiki

    The history of traction drive elevators in Japan is described. The electrical technologies such as the microprocessor car control and the VVVF motor control made remarkable progress leading to higher reliability and energy savings. Then, the various machine-room-less elevators have been developed and the space saving technology, such as the shuttle and the double-deck elevators become important, too. The elevators used for evacuation in case of emergencies are also discussed.

  16. The oscillating wing with aerodynamically balanced elevator

    NASA Technical Reports Server (NTRS)

    Kussner, H G; Schwartz, I

    1941-01-01

    The two-dimensional problem of the oscillating wing with aerodynamically balanced elevator is treated in the manner that the wing is replaced by a plate with bends and stages and the airfoil section by a mean line consisting of one or more straights. The computed formulas and tables permit, on these premises, the prediction of the pressure distribution and of the aerodynamic reactions of oscillating elevators and tabs with any position of elevator hinge in respect to elevator leading edge.

  17. A novel criterion for identifying metabolically obese but normal weight individuals using the product of triglycerides and glucose

    PubMed Central

    Lee, S-H; Han, K; Yang, H K; Kim, H-S; Cho, J-H; Kwon, H-S; Park, Y-M; Cha, B-Y; Yoon, K-H

    2015-01-01

    Objectives: Metabolically obese but normal weight (MONW) individuals constitute a subgroup of normal weight individuals that display impaired insulin sensitivity with a higher risk of developing diabetes, cardiovascular disease and mortality. We aimed to propose a novel criterion for defining MONW by examining the usefulness and the cutoff value of the TyG index, a product of the levels of triglycerides and glucose, in identifying MONW individuals. In addition, the performance of this criterion in predicting the future incidence of diabetes was assessed. Subjects/methods: A total of 7541 non-diabetic, normal weight (body mass index ?18.5 and <25?kg?m?2) subjects were selected from the Korea National Health and Nutrition Examination Survey conducted in 2009–2010. Another 3185 participants with follow-up studies were selected from a prospective community-based cohort study. The TyG index was calculated as ln(fasting triglycerides (mg?dl?1) × fasting glucose (mg?dl?1)/2). Results: The levels of the TyG index paralleled the prevalence of metabolic syndrome and its components. The cutoff value of the TyG index that reflected MONW based on the receiver operating characteristics analysis was 8.82 for men and 8.73 for women, with the area under the curve values being 0.855 and 0.868, respectively. The sensitivity and the specificity were 84.2 and 77.6% in men and 69.1 and 89.4% in women, respectively. Individuals designated as MONW, who have a normal weight and TyG levels higher than cutoff, displayed a metabolically unhealthy phenotype and an approximately twofold higher risk of developing diabetes compared with metabolically healthy normal weight subjects. Conclusions: We propose a simple diagnostic criterion of MONW, which might be used to discriminate subjects with a higher risk of metabolic diseases. PMID:25915739

  18. Influence of total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease: the Copenhagen City Heart Study.

    PubMed Central

    Lindenstrøm, E.; Boysen, G.; Nyboe, J.

    1994-01-01

    OBJECTIVE--To estimate the influence of plasma total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease. DESIGN--The Copenhagen City Heart Study is a prospective observational survey with two cardiovascular examinations at five year intervals. Non-fasting plasma lipids were measured in participants once at each examination, along with other variables. The Cox regression model was used to establish the effect of the factors recorded on cerebrovascular events of mostly, but not exclusively, ischaemic origin. SUBJECTS--19,698 women and men at least 20 years old, randomly selected after age stratification from an area of central Copenhagen. MAIN OUTCOME MEASURES--Initial cases of stroke and transient ischaemic attack recorded from hospital records and death certificates from 1976 through 1988. RESULTS--660 non-haemorrhagic and 33 haemorrhagic events were recorded. Total cholesterol was positively associated with risk of non-haemorrhagic events, but only for levels > 8 mmol/l, corresponding to the upper 5% of the distribution in the study population. For lower plasma cholesterol values the relative risk remained nearly constant. Plasma triglyceride concentration was significantly, positively associated with risk of non-haemorrhagic events. The relative risk corresponding to an increase of 1 mmol/l was 1.12 (95% confidence interval 1.07 to 1.16). There was a negative, log linear association between high density lipoprotein cholesterol and risk of non-haemorrhagic events (0.53 (0.34 to 0.83)). There was no indication that the effects of plasma lipids were different in women and men. CONCLUSIONS--The pattern of the association between plasma cholesterol and risk of ischaemic cerebrovascular disease was not log linear, and the increased risk was confined to the upper 5% of the cholesterol distribution. Further studies should concentrate on the association between plasma cholesterol and verified haemorrhagic stroke. PMID:8044059

  19. High triglyceride is a risk factor for silent osteonecrosis of the femoral head in systemic lupus erythematosus.

    PubMed

    Kuroda, Takeshi; Tanabe, Naohito; Wakamatsu, Ayako; Takai, Chinatsu; Sato, Hiroe; Nakatsue, Takeshi; Wada, Yoko; Nakano, Masaaki; Narita, Ichiei

    2015-12-01

    The purpose of this study was to clarify the factors related to silent osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE). Seventy-eight patients with SLE were selected on the basis of having been newly diagnosed and requiring high-dose prednisolone, including pulse therapy with methylprednisolone, as the initial treatment. All the patients initially underwent MRI at 3 months after the start of corticosteroid treatment to detect any early changes in the femoral head. These examinations were then performed again 3 months later. Laboratory parameters were evaluated at the start of steroid treatment and at 1 month thereafter. By 3 months after the start of corticosteroid treatment, silent ONFH was diagnosed by MRI in 21 patients (26.9 %), being bilateral in 11 patients and unilateral in 10. The occurrence of silent ONFH was not related to SLE disease activity index, serological activity, or renal function; it was also unrelated to body mass index (BMI), body surface area (BSA), and the initial dose of prednisolone per unit body weight. However, the total cholesterol level at 4 weeks after the start of steroid treatment tended to be higher in patients with silent ONFH. Patients with a higher triglyceride level showed a significantly higher frequency of silent ONFH both before (p?=?0.002) and 4 weeks after (p?=?0.036) steroid initiation.A high triglyceride level is an important risk factor for silent ONFH in patients with SLE, and large-scale epidemiologic surveys of such early events are needed in this patient population. PMID:26384821

  20. 75 FR 52868 - Final Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-30

    ...SUMMARY: Base (1% annual-chance) Flood Elevations (BFEs...Management Agency, 500 C Street, SW...Street (Base Flood Elevations extend...Street (Base Flood Elevations extend...the nearest 0.1 meter. ADDRESSES...Approximately 500 feet +989...

  1. A high LDL-C to HDL-C ratio predicts poor prognosis for initially metastatic colorectal cancer patients with elevations in LDL-C

    PubMed Central

    Liao, Fangxin; He, Wenzhuo; Jiang, Chang; Yin, Chenxi; Guo, Guifang; Chen, Xuxian; Qiu, Huijuan; Rong, Yuming; Zhang, Bei; Xu, Dazhi; Xia, Liangping

    2015-01-01

    Although lipid disequilibrium has been documented for several types of cancer including colorectal cancer (CRC), it remains unknown whether lipid parameters are associated with the outcome of metastatic CRC (mCRC) patients. Here, we retrospectively examined the lipid profiles of 453 mCRC patients and investigated whether any of the lipid parameters correlated with the outcome of mCRC patients. Pretreatment serum lipids, including triglyceride, cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were collected in 453 initially mCRC patients. The LDL-C to HDL-C ratio (LHR) was calculated and divided into the first, second, and third tertiles. Univariate and multivariate analyses were performed to evaluate the impact of lipids on overall survival (OS) and progression-free survival (PFS). Nearly two-fifths of the patients (41.3%) exhibited elevations in LDL-C while most patients (88.3%) showed normal HDL-C levels. Decreased HDL-C (P=0.542) and increased LDL-C (P=0.023) were prognostic factors for poor OS, while triglyceride (P=0.542) and cholesterol (P=0.215) were not. Multivariate analysis revealed that LDL-C (P=0.031) was an independent prognostic factor. Triglyceride, cholesterol, HDL-C, and LDL-C did not correlate with PFS. Among patients with elevations in LDL-C levels, patients in the third tertile of the LHR had a markedly shorter median OS compared to those in the first or second tertile (P=0.012). Thus, increased LDL-C level is an independent prognostic factor for poor prognosis in mCRC patients, and a high LHR predicts poor prognosis for initially mCRC patients with elevations in LDL-C. PMID:26604782

  2. Tail-flick test response in 3×Tg-AD mice at early and advanced stages of disease.

    PubMed

    Baeta-Corral, Raquel; Defrin, Ruti; Pick, Chagi G; Giménez-Llort, Lydia

    2015-07-23

    Despite the impact of pain in cognitive dysfunctions and affective disorders has been largely studied, the research that examines pain dimensions in cognitive impairment or dementia is still scarce. In patients with Alzheimer's disease (AD) and related dementias, management of pain is challenging. While the sensory-discriminative dimension of pain is preserved, the cognitive-evaluative and the affective-motivational pain dimensions are affected. Due to the complexity of the disease and the poor self-reports, pain is underdiagnosed and undertreated. In confluence with an impaired thermoregulatory behavior, the patients' ability to confront environmental stressors such as cold temperature can put them at risk of fatal accidental hypothermia. Here, 3xTg-AD mice demonstrate that the sensorial-discriminative threshold to a noxious cold stimulus, as measured by the latency of tail-flicking, was preserved at early and advances stages of disease (7 and 11 month-old, respectively) as compared to age-matched (adulthood and middle aged, respectively) non-transgenic mice (NTg). In both genotypes, the sensory deterioration and poor thermoregulatory behavior associated to age was observed as an increase of tail-flick response and poor sensorimotor performance. At both stages studied, 3xTg-AD mice exhibited BPSD (Behavioral and Psychological Symptoms of Dementia)-like alterations in the corner, open-field, dark-light box and the T-maze tests. In the adult NTg mice, this nociceptive withdrawal response was correlated with copying with stress-related behaviors. This integrative behavioral profile was lost in both groups of 3xTg-AD mice and middle aged controls, suggesting derangements in their subjacent networks and the complex interplay between the pain dimensions in the elderly with dementia. PMID:26091881

  3. PAK Inactivation Impairs Social Recognition in 3xTg-AD Mice without Increasing Brain Deposition of Tau and A?

    PubMed Central

    Arsenault, Dany; Dal-Pan, Alexandre; Tremblay, Cyntia; Bennett, David A.; Guitton, Matthieu J.; De Koninck, Yves; Tonegawa, Susumu

    2013-01-01

    Defects in p21-activated kinase (PAK) are suspected to play a role in cognitive symptoms of Alzheimer's disease (AD). Dysfunction in PAK leads to cofilin activation, drebrin displacement from its actin-binding site, actin depolymerization/severing, and, ultimately, defects in spine dynamics and cognitive impairment in mice. To determine the role of PAK in AD, we first quantified PAK by immunoblotting in homogenates from the parietal neocortex of subjects with a clinical diagnosis of no cognitive impairment (n = 12), mild cognitive impairment (n = 12), or AD (n = 12). A loss of total PAK, detected in the cortex of AD patients (?39% versus controls), was correlated with cognitive impairment (r2 = 0.148, p = 0.027) and deposition of total and phosphorylated tau (r2 = 0.235 and r2 = 0.206, respectively), but not with A?42 (r2 = 0.056). Accordingly, we found a decrease of total PAK in the cortex of 12- and 20-month-old 3xTg-AD mice, an animal model of AD-like A? and tau neuropathologies. To determine whether PAK dysfunction aggravates AD phenotype, 3xTg-AD mice were crossed with dominant-negative PAK mice. PAK inactivation led to obliteration of social recognition in old 3xTg-AD mice, which was associated with a decrease in cortical drebrin (?25%), but without enhancement of A?/tau pathology or any clear electrophysiological signature. Overall, our data suggest that PAK decrease is a consequence of AD neuropathology and that therapeutic activation of PAK may exert symptomatic benefits on high brain function. PMID:23804095

  4. Prolonged oral cannabinoid administration prevents neuroinflammation, lowers ?-amyloid levels and improves cognitive performance in Tg APP 2576 mice

    PubMed Central

    2012-01-01

    Background Alzheimer's disease (AD) brain shows an ongoing inflammatory condition and non-steroidal anti-inflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective and anti-inflammatory agents with therapeutic potential. Methods We have studied the effects of prolonged oral administration of transgenic amyloid precursor protein (APP) mice with two pharmacologically different cannabinoids (WIN 55,212-2 and JWH-133, 0.2 mg/kg/day in the drinking water during 4 months) on inflammatory and cognitive parameters, and on 18F-fluoro-deoxyglucose (18FDG) uptake by positron emission tomography (PET). Results Novel object recognition was significantly reduced in 11 month old Tg APP mice and 4 month administration of JWH was able to normalize this cognitive deficit, although WIN was ineffective. Wild type mice cognitive performance was unaltered by cannabinoid administration. Tg APP mice showed decreased 18FDG uptake in hippocampus and cortical regions, which was counteracted by oral JWH treatment. Hippocampal GFAP immunoreactivity and cortical protein expression was unaffected by genotype or treatment. In contrast, the density of Iba1 positive microglia was increased in Tg APP mice, and normalized following JWH chronic treatment. Both cannabinoids were effective at reducing the enhancement of COX-2 protein levels and TNF-? mRNA expression found in the AD model. Increased cortical ?-amyloid (A?) levels were significantly reduced in the mouse model by both cannabinoids. Noteworthy both cannabinoids enhanced A? transport across choroid plexus cells in vitro. Conclusions In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased A? clearance. PMID:22248049

  5. SU-E-CAMPUS-J-01: TG142 Complied Comprehensive Commissioning and Quality Assurance Procedure for Respiratory Gating

    SciTech Connect

    Woods, K; Rong, Y; Weldon, M; Gupta, N

    2014-06-15

    Purpose: To develop and establish a comprehensive gating commissioning and quality assurance procedure in compliance with TG142. Methods: Quality assurance tests on three Varian LINACs included beam output and energy constancy, calibration of surrogate, as well as phase and amplitude gating temporal accuracy. A diode array (MapCHECK 2) and film (Gafchromic EBT2) were used to measure the temporal accuracy of phase and amplitude gating windows. A motion simulation device (MotionSim) was used to simulate respiratory motion for both detectors. An end-to-end test was also performed on all three machines. The overall accuracy and uncertainty was analyzed and compared. Results: The end-to-end test using an anthropomorphic lung phantom (CIRS) results in an OSL dose difference reading within 5% (within measurement uncertainty) for both phase and amplitude gated treatment. Film results showed < 1% agreement between profiles for gated delivery and predicted dose. The diode array demonstrated an 80% passing rate for gamma criteria of 2%/0.2 mm, which results in a 111 msec temporal accuracy. However, the diode array is limited by its spatial resolution of measurements, due to its 7.07 mm diode spacing. Film provided higher measuring resolution, thus demonstrated a temporal accuracy of <100 msec. Conclusion: Results showed consistent respiratory gating stability and accuracy. MapCHECK 2 may not be sufficient for the temporal accuracy test in the respiratory gating treatment in order to meet the corresponding tolerance in TG142. One would need to decrease respiratory motion speed from the surrogate or tighten the gating window in order to be within tolerance of 100 msec temporal accuracy per TG-142. The end-to-end test offers insight to the overall accuracy and uncertainties with a gated protocol. Compared to static delivery, respiratory motion increases the overall uncertainty of treatment delivery from 3% to 5% dose difference.

  6. Characterization of Two Different Clay Materials by Thermogravimetry (TG), Differential Scanning Calorimetry (DSC), Dilatometry (DIL) and Mass Spectrometry (MS) - 12215

    SciTech Connect

    Post, Ekkehard; Henderson, Jack B.

    2012-07-01

    An illitic clay containing higher amounts of organic materials was investigated by dilatometry, thermogravimetry and differential scanning calorimetric. The evolved gases were studied during simultaneous TG-DSC (STA) and dilatometer measurements with simultaneous mass spectrometry in inert gas and oxidizing atmosphere. The dilatometer results were compared with the STA-MS results which confirmed and explained the reactions found during heating of the clay, like dehydration, dehydroxylation, shrinkage, sintering, quartz phase transition, combustion or pyrolysis of organics and the solid state reactions forming meta-kaolinite and mullite. The high amount of organic material effects in inert gas atmosphere most probably a reduction of the oxides which leads to a higher mass loss than in oxidizing atmosphere. Due to this reduction an additional CO{sub 2} emission at around 1000 deg. C was detected which did not occur in oxidizing atmosphere. Furthermore TG-MS results of a clay containing alkali nitrates show that during heating, in addition to water and CO{sub 2}, NO and NO{sub 2} are also evolved, leading to additional mass loss steps. These types of clays showed water loss starting around 100 deg. C or even earlier. This relative small mass loss affects only less shrinkage during the expansion of the sample. The dehydroxylation and the high crystalline quartz content result in considerable shrinkage and expansion of the clay. During the usual solid state reaction where the clay structure collapses, the remaining material finally shrinks down to a so-called clinker. With the help of MS the TG steps can be better interpreted as the evolved gases are identified. With the help of the MS it is possible to distinguish between CO{sub 2} and water (carbonate decomposition, oxidation of organics or dehydration/dehydroxylation). The MS also clearly shows that mass number 44 is found during the TG step of the illitic clay at about 900 deg. C in inert gas, which was interpreted as oxidation of pyrolytic carbon by reducing oxides. Additionally, without MS results, the mass loss steps of the nitrate contaminated clay could hardly be interpreted. (authors)

  7. The novel GRN g.1159_1160delTG mutation is associated with behavioral variant frontotemporal dementia.

    PubMed

    Calvi, Alberto; Cioffi, Sara M G; Caffarra, Paolo; Fenoglio, Chiara; Serpente, Maria; Pietroboni, Anna M; Arighi, Andrea; Ghezzi, Laura; Gardini, Simona; Scarpini, Elio; Galimberti, Daniela

    2015-01-01

    Mutations in progranulin gene (GRN) are a common cause of autosomal dominant frontotemporal lobar degeneration and are associated with a wide phenotypic heterogeneity. Here, we describe two probands with behavioral variant frontotemporal dementia with a novel mutation in this gene (1159_1160delTG). Both had a positive family history for dementia and showed atypical features at imaging. Their progranulin plasma levels were undetectable, and the mutation was not present in cDNA, suggesting haploinsufficiency. Progranulin levels were low even in asymptomatic carriers of the variant. Results described enlarge current knowledge on genetic causes of the disease and clinical characteristics of carriers. PMID:25261445

  8. Effects of sub-Tg annealing on Cu64.5Zr35.5 glasses: A molecular dynamics study

    SciTech Connect

    Zhang, Feng; Mendelev, Mikhail I.; Zhang, Yue; Wang, Cai-Zhuang; Kramer, Matthew J.; Ho, Kai-Ming

    2014-02-11

    Creating metallic glasses by cooling liquid melts in molecular dynamics simulations faces a well-known challenge that the cooling rate is too fast compared with experiments. Taking the prototypical Cu 64.5Zr35.5 glasses as an example, we propose an efficient cooling strategy in which most of the computer time is spent on a prolonged isothermal process slightly below the glass-transition temperature, Tg . The glassy sample prepared in this way demonstrates significant energetic stability, slow dynamics, and well-developed short-range icosahedral order. By conventional uniform cooling, similar properties can only be obtained using a cooling rate more than 15 times slower.

  9. Distribution of glass transition temperatures Tg in polystyrene thin films as revealed by low-energy muon spin relaxation: A comparison with neutron reflectivity results.

    PubMed

    Kanaya, Toshiji; Ogawa, Hiroki; Kishimoto, Mizuki; Inoue, Rintaro; Suter, Andreas; Prokscha, Thomas

    2015-08-01

    In a previous paper [Phys. Rev. E 83, 021801 (2011)] we performed neutron reflectivity (NR) measurements on a five-layer polystyrene (PS) thin film consisting of alternatively stacked deuterated polystyrene (dPS) and hydrogenated polystyrene (hPS) layers (dPS/hPS/dPS/hPS/dPS, ?100 nm thick) on a Si substrate to reveal the distribution of Tg along the depth direction. Information on the Tg distribution is very useful to understand the interesting but unusual properties of polymer thin films. However, one problem that we have to clarify is if there are effects of deuterium labeling on Tg or not. To tackle the problem we performed low-energy muon spin relaxation (?SR) measurements on the above-mentioned deuterium-labeled five-layer PS thin film as well as dPS and hPS single-layer thin films ?100 nm thick as a function of muon implantation energy. It was found that the deuterium labeling had no significant effects on the Tg distribution, guaranteeing that we can safely discuss the unusual thin film properties based on the Tg distribution revealed by NR on the deuterium-labeled thin films. In addition, the ?SR result suggested that the higher Tg near the Si substrate is due to the strong orientation of phenyl rings. PMID:26382423

  10. Interleukin 12B rs3212227 T?>?G polymorphism was associated with an increased risk of gastric cardiac adenocarcinoma in a Chinese population.

    PubMed

    Yin, J; Wang, X; Wei, J; Wang, L; Shi, Y; Zheng, L; Tang, W; Ding, G; Liu, C; Liu, R; Chen, S; Xu, Z; Gu, H

    2015-04-01

    Gastric cardiac adenocarcinoma (GCA) is one of common malignant tumors in the world. Multiple genes that play critical roles in inflammatory pathways probably are associated with GCA risk. We conducted a hospital-based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): interleukin 9 (IL9) rs31563 C?>?T, IL9 rs31564 G?>?T, IL10 rs1800872 T?>?G, IL12A rs2243115 T?>?G, IL12B rs3212227 T?>?G, and IL13 rs1800925 C?>?T on the development of GCA. Two hundred and forty-three GCA cases and 476 controls were recruited. Their genotypes were determined using a custom-by-design 48-Plex SNPscan kit. IL12B rs3212227 T?>?G polymorphism was associated with the increased risk of GCA. However, there was no significant association between the other five SNPs and GCA risk. Stratified analyses indicated that the risk of GCA associated with the IL12B rs3212227 T?>?G polymorphism was evident among female patients and patients who never smoked or consumed alcoholic drinks. These findings indicated that functional polymorphism IL12B rs3212227 T?>?G might correlate with GCA risk. However, our results were obtained with a limited sample size; the power of our analysis was low. Larger studies are required to confirm the current findings. PMID:24529168

  11. Reduced tissue levels of noradrenaline are associated with behavioral phenotypes of the TgCRND8 mouse model of Alzheimer's disease.

    PubMed

    Francis, Beverly M; Yang, Jimao; Hajderi, Enid; Brown, Mary E; Michalski, Bernadeta; McLaurin, Joanne; Fahnestock, Margaret; Mount, Howard T J

    2012-07-01

    Noradrenergic cell loss is well documented in Alzheimer's disease (AD). We have measured the tissue levels of catecholamines in an amyloid precursor protein-transgenic 'TgCRND8' mouse model of AD and found reductions in noradrenaline (NA) within hippocampus, temporoparietal and frontal cortices, and cerebellum. An age-related increase in cortical NA levels was observed in non-Tg controls, but not in TgCRND8 mice. In contrast, NA levels declined with aging in the TgCRND8 hippocampus. Dopamine levels were unaffected. Reductions in the tissue content of NA were found to coincide with altered expression of brain-derived neurotrophic factor (BDNF) mRNA and to precede the onset of object memory impairment and behavioral despair. To test whether these phenotypes might be associated with diminished NA, we treated mice with dexefaroxan, an antagonist of presynaptic inhibitory ?(2)-adrenoceptors on noradrenergic and cholinergic terminals. Mice 12 weeks of age were infused systemically for 28 days with dexefaroxan or rivastigmine, a cholinesterase inhibitor. Both dexefaroxan and rivastigmine improved TgCRND8 behavioral phenotypes and increased BDNF mRNA expression without affecting amyloid-? peptide levels. Our results highlight the importance of noradrenergic depletion in AD-like phenotypes of TgCRND8 mice. PMID:22491352

  12. Reduced Tissue Levels of Noradrenaline Are Associated with Behavioral Phenotypes of the TgCRND8 Mouse Model of Alzheimer's Disease

    PubMed Central

    Francis, Beverly M; Yang, Jimao; Hajderi, Enid; Brown, Mary E; Michalski, Bernadeta; McLaurin, JoAnne; Fahnestock, Margaret; Mount, Howard T J

    2012-01-01

    Noradrenergic cell loss is well documented in Alzheimer's disease (AD). We have measured the tissue levels of catecholamines in an amyloid precursor protein-transgenic ‘TgCRND8' mouse model of AD and found reductions in noradrenaline (NA) within hippocampus, temporoparietal and frontal cortices, and cerebellum. An age-related increase in cortical NA levels was observed in non-Tg controls, but not in TgCRND8 mice. In contrast, NA levels declined with aging in the TgCRND8 hippocampus. Dopamine levels were unaffected. Reductions in the tissue content of NA were found to coincide with altered expression of brain-derived neurotrophic factor (BDNF) mRNA and to precede the onset of object memory impairment and behavioral despair. To test whether these phenotypes might be associated with diminished NA, we treated mice with dexefaroxan, an antagonist of presynaptic inhibitory ?2-adrenoceptors on noradrenergic and cholinergic terminals. Mice 12 weeks of age were infused systemically for 28 days with dexefaroxan or rivastigmine, a cholinesterase inhibitor. Both dexefaroxan and rivastigmine improved TgCRND8 behavioral phenotypes and increased BDNF mRNA expression without affecting amyloid-? peptide levels. Our results highlight the importance of noradrenergic depletion in AD-like phenotypes of TgCRND8 mice. PMID:22491352

  13. Distribution of glass transition temperatures Tg in polystyrene thin films as revealed by low-energy muon spin relaxation: A comparison with neutron reflectivity results

    NASA Astrophysics Data System (ADS)

    Kanaya, Toshiji; Ogawa, Hiroki; Kishimoto, Mizuki; Inoue, Rintaro; Suter, Andreas; Prokscha, Thomas

    2015-08-01

    In a previous paper [Phys. Rev. E 83, 021801 (2011), 10.1103/PhysRevE.83.021801] we performed neutron reflectivity (NR) measurements on a five-layer polystyrene (PS) thin film consisting of alternatively stacked deuterated polystyrene (dPS) and hydrogenated polystyrene (hPS) layers (dPS/hPS/dPS/hPS/dPS, ˜100 nm thick) on a Si substrate to reveal the distribution of Tg along the depth direction. Information on the Tg distribution is very useful to understand the interesting but unusual properties of polymer thin films. However, one problem that we have to clarify is if there are effects of deuterium labeling on Tg or not. To tackle the problem we performed low-energy muon spin relaxation (? SR ) measurements on the above-mentioned deuterium-labeled five-layer PS thin film as well as dPS and hPS single-layer thin films ˜100 nm thick as a function of muon implantation energy. It was found that the deuterium labeling had no significant effects on the Tg distribution, guaranteeing that we can safely discuss the unusual thin film properties based on the Tg distribution revealed by NR on the deuterium-labeled thin films. In addition, the ? SR result suggested that the higher Tg near the Si substrate is due to the strong orientation of phenyl rings.

  14. Approach to managing elevated creatinine.

    PubMed Central

    Tremblay, Richard

    2004-01-01

    OBJECTIVE: To describe a systematic approach to finding the underlying cause of an elevated creatinine level. QUALITY OF EVIDENCE: This diagnostic approach is based on a synthesis of information from reference works on nephrology, articles found through a MEDLINE search, and the author's personal experience. MAIN MESSAGE: Elevated creatinine levels suggest the differential diagnosis of renal failure (RF). History and a complete physical examination are important, keeping in mind that RF is often asymptomatic in the early stages. After repeating the creatinine test to verify results, baseline tests should be ordered to identify the cause of the RF. Comparing results of serial tests is essential for determining whether RF is acute or chronic, stable or progressive. An ultrasound scan is particularly useful for eliminating an obstructive cause; the size of the kidney can indicate whether disease is acute or chronic. Complementary blood tests and imaging studies might be useful. CONCLUSION: Diagnosing and managing RF can appear complex, but a systematic approach will help you find the cause and treat the condition. PMID:15171676

  15. Autonomic and prefrontal events during moral elevation.

    PubMed

    Piper, Walter T; Saslow, Laura R; Saturn, Sarina R

    2015-05-01

    Moral elevation, or elevation, is a specific emotional state triggered by witnessing displays of profound virtue and moral beauty. This study set out to characterize the physiology underlying elevation with measurements of heart rate (HR), respiratory sinus arrhythmia (RSA), and medial prefrontal cortex (mPFC) activity. During elevation, HR and RSA increased. These findings illustrate that elevation involves an uncommon combination of both sympathetic and parasympathetic activation, which is present in circumstances where arousal and social engagement are both required. In addition, we show evidence of content-dependent alterations of mPFC activity during elevation peaks. Altogether, this study shows that the induction of moral elevation recruits an uncommon autonomic and neural pattern that is consistent with previous understanding of socioemotional-induced allostasis. PMID:25813121

  16. 1-Meter Digital Elevation Model specification

    USGS Publications Warehouse

    Arundel, Samantha T.; Archuleta, Christy-Ann M.; Phillips, Lori A.; Roche, Brittany L.; Constance, Eric W.

    2015-01-01

    In January 2015, the U.S. Geological Survey National Geospatial Technical Operations Center began producing the 1-Meter Digital Elevation Model data product. This new product was developed to provide high resolution bare-earth digital elevation models from light detection and ranging (lidar) elevation data and other elevation data collected over the conterminous United States (lower 48 States), Hawaii, and potentially Alaska and the U.S. territories. The 1-Meter Digital Elevation Model consists of hydroflattened, topographic bare-earth raster digital elevation models, with a 1-meter x 1-meter cell size, and is available in 10,000-meter x 10,000-meter square blocks with a 6-meter overlap. This report details the specifications required for the production of the 1-Meter Digital Elevation Model.

  17. Hypoxia-inducible Lipid Droplet-associated (HILPDA) Is a Novel Peroxisome Proliferator-activated Receptor (PPAR) Target Involved in Hepatic Triglyceride Secretion*

    PubMed Central

    Mattijssen, Frits; Georgiadi, Anastasia; Andasarie, Tresty; Szalowska, Ewa; Zota, Annika; Krones-Herzig, Anja; Heier, Christoph; Ratman, Dariusz; De Bosscher, Karolien; Qi, Ling; Zechner, Rudolf; Herzig, Stephan; Kersten, Sander

    2014-01-01

    Peroxisome proliferator-activated receptors (PPARs) play major roles in the regulation of hepatic lipid metabolism through the control of numerous genes involved in processes such as lipid uptake and fatty acid oxidation. Here we identify hypoxia-inducible lipid droplet-associated (Hilpda/Hig2) as a novel PPAR target gene and demonstrate its involvement in hepatic lipid metabolism. Microarray analysis revealed that Hilpda is one of the most highly induced genes by the PPAR? agonist Wy14643 in mouse precision cut liver slices. Induction of Hilpda mRNA by Wy14643 was confirmed in mouse and human hepatocytes. Oral dosing with Wy14643 similarly induced Hilpda mRNA levels in livers of wild-type mice but not Ppara?/? mice. Transactivation studies and chromatin immunoprecipitation showed that Hilpda is a direct PPAR? target gene via a conserved PPAR response element located 1200 base pairs upstream of the transcription start site. Hepatic overexpression of HILPDA in mice via adeno-associated virus led to a 4-fold increase in liver triglyceride storage, without any changes in key genes involved in de novo lipogenesis, ?-oxidation, or lipolysis. Moreover, intracellular lipase activity was not affected by HILPDA overexpression. Strikingly, HILPDA overexpression significantly impaired hepatic triglyceride secretion. Taken together, our data uncover HILPDA as a novel PPAR target that raises hepatic triglyceride storage via regulation of triglyceride secretion. PMID:24876382

  18. A Common Missense Variant in the Glucokinase Regulatory Protein Gene (GCKR) Is Associated with Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE-Using the genome-wide-association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metaboli...

  19. Control of Adipose Triglyceride Lipase Action by Serine 517 of Perilipin A Globally Regulates Protein Kinase A-stimulated Lipolysis in Adipocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phosphorylation of the lipid droplet-associated protein perilipin A (Peri A) mediates the actions of cyclic AMP-dependent protein kinase A (PKA) to stimulate triglyceride hydrolysis (lipolysis) in adipocytes. Studies addressing how Peri A PKA sites regulate adipocyte lipolysis have relied on non-ad...

  20. Change of caged dynamics at T(g) in hydrated proteins: trend of mean squared displacements after correcting for the methyl-group rotation contribution.

    PubMed

    Ngai, K L; Capaccioli, S; Paciaroni, A

    2013-06-21

    The question whether the dynamics of hydrated proteins changes with temperature on crossing the glass transition temperature like that found in conventional glassformers is an interesting one. Recently, we have shown that a change of temperature dependence of the mean square displacement (MSD) at Tg is present in proteins solvated with bioprotectants, such as sugars or glycerol with or without the addition of water, coexisting with the dynamic transition at a higher temperature Td. The dynamical change at Tg is similar to that in conventional glassformers at sufficiently short times and low enough temperatures, where molecules are mutually caged by the intermolecular potential. This is a general and fundamental property of glassformers which is always observed at or near Tg independent of the energy resolution of the spectrometer, and is also the basis of the dynamical change of solvated proteins at Tg. When proteins are solvated with bioprotectants they show higher Tg and Td than the proteins hydrated by water alone, due to the stabilizing action of excipients, thus the observation of the change of T-dependence of the MSD at Tg is unobstructed by the methyl-group rotation contribution at lower temperatures [S. Capaccioli, K. L. Ngai, S. Ancherbak, and A. Paciaroni, J. Phys. Chem. B 116, 1745 (2012)]. On the other hand, in the case of proteins hydrated by water alone unambiguous evidence of the break at Tg is hard to find, because of their lower Tg and Td. Notwithstanding, in this paper, we provide evidence for the change at Tg of the T-dependence of proteins hydrated by pure water. This evidence turns out from (i) neutron scattering experimental investigations where the sample has been manipulated by either full or partial deuteration to suppress the methyl-group rotation contribution, and (ii) neutron scattering experimental investigations where the energy resolution is such that only motions with characteristic times shorter than 15 ps can be sensed, thus shifting the onset of both the methyl-group rotation and the dynamic transition contribution to higher temperatures. We propose that, in general, coexistence of the break of the elastic intensity or the MSD at Tg with the dynamic transition at Td in hydrated and solvated proteins. Recognition of this fact helps to remove inconsistency and conundrum encountered in interpreting data of hydrated proteins that thwart progress in understanding the origin of the dynamic transition. PMID:23802985

  1. Change of caged dynamics at Tg in hydrated proteins: Trend of mean squared displacements after correcting for the methyl-group rotation contribution

    NASA Astrophysics Data System (ADS)

    Ngai, K. L.; Capaccioli, S.; Paciaroni, A.

    2013-06-01

    The question whether the dynamics of hydrated proteins changes with temperature on crossing the glass transition temperature like that found in conventional glassformers is an interesting one. Recently, we have shown that a change of temperature dependence of the mean square displacement (MSD) at Tg is present in proteins solvated with bioprotectants, such as sugars or glycerol with or without the addition of water, coexisting with the dynamic transition at a higher temperature Td. The dynamical change at Tg is similar to that in conventional glassformers at sufficiently short times and low enough temperatures, where molecules are mutually caged by the intermolecular potential. This is a general and fundamental property of glassformers which is always observed at or near Tg independent of the energy resolution of the spectrometer, and is also the basis of the dynamical change of solvated proteins at Tg. When proteins are solvated with bioprotectants they show higher Tg and Td than the proteins hydrated by water alone, due to the stabilizing action of excipients, thus the observation of the change of T-dependence of the MSD at Tg is unobstructed by the methyl-group rotation contribution at lower temperatures [S. Capaccioli, K. L. Ngai, S. Ancherbak, and A. Paciaroni, J. Phys. Chem. B 116, 1745 (2012)], 10.1021/jp2057892. On the other hand, in the case of proteins hydrated by water alone unambiguous evidence of the break at Tg is hard to find, because of their lower Tg and Td. Notwithstanding, in this paper, we provide evidence for the change at Tg of the T-dependence of proteins hydrated by pure water. This evidence turns out from (i) neutron scattering experimental investigations where the sample has been manipulated by either full or partial deuteration to suppress the methyl-group rotation contribution, and (ii) neutron scattering experimental investigations where the energy resolution is such that only motions with characteristic times shorter than 15 ps can be sensed, thus shifting the onset of both the methyl-group rotation and the dynamic transition contribution to higher temperatures. We propose that, in general, coexistence of the break of the elastic intensity or the MSD at Tg with the dynamic transition at Td in hydrated and solvated proteins. Recognition of this fact helps to remove inconsistency and conundrum encountered in interpreting data of hydrated proteins that thwart progress in understanding the origin of the dynamic transition.

  2. Tg-SwDI Transgenic Mice Exhibit Novel Alterations in A?PP Processing, A? Degradation, and Resilient Amyloid Angiopathy

    PubMed Central

    Van Vickle, Gregory D.; Esh, Chera L.; Daugs, Ian D.; Kokjohn, Tyler A.; Kalback, Walter M.; Patton, R. Lyle; Luehrs, Dean C.; Walker, Douglas G.; Lue, Lih-Fen; Beach, Thomas G.; Davis, Judianne; Van Nostrand, William E.; Castaño, Eduardo M.; Roher, Alex E.

    2008-01-01

    Alzheimer’s disease (AD) is characterized by the accumulation of extracellular insoluble amyloid, primarily derived from polymerized amyloid-? (A?) peptides. We characterized the chemical composition of the A? peptides deposited in the brain parenchyma and cerebrovascular walls of triple transgenic Tg-SwDI mice that produce a rapid and profuse A? accumulation. The processing of the N- and C-terminal regions of mutant A?PP differs substantially from humans because the brain parenchyma accumulates numerous, diffuse, nonfibrillar plaques, whereas the thalamic microvessels harbor overwhelming amounts of compact, fibrillar, thioflavine-S- and apolipoprotein E-positive amyloid deposits. The abundant accretion of vascular amyloid, despite low A?PP transgene expression levels, suggests that inefficient A? proteolysis because of conformational changes and dimerization may be key pathogenic factors in this animal model. The disruption of amyloid plaque cores by immunotherapy is accompanied by increased perivascular deposition in both humans and transgenic mice. This analogous susceptibility and response to the disruption of amyloid deposits suggests that Tg-SwDI mice provide an excellent model in which to study the functional aftermath of immunotherapeutic interventions. These mice might also reveal new avenues to promote amyloidogenic A?PP processing and fundamental insights into the faulty degradation and clearance of A? in AD, pivotal issues in understanding AD pathophysiology and the assessment of new therapeutic agents. PMID:18599612

  3. Extra-virgin olive oil attenuates amyloid-? and tau pathologies in the brains of TgSwDI mice.

    PubMed

    Qosa, Hisham; Mohamed, Loqman A; Batarseh, Yazan S; Alqahtani, Saeed; Ibrahim, Baher; LeVine, Harry; Keller, Jeffrey N; Kaddoumi, Amal

    2015-12-01

    Extra-virgin olive oil (EVOO) is one of the main elements of Mediterranean diet. Several studies have suggested that EVOO has several health promoting effects that could protect from and decrease the risk of Alzheimer's disease (AD). In this study, we investigated the effect of consumption of EVOO-enriched diet on amyloid- and tau-related pathological alterations that are associated with the progression of AD and cerebral amyloid angiopathy (CAA) in TgSwDI mice. Feeding mice with EVOO-enriched diet for 6months, beginning at an age before amyloid-? (A?) accumulation starts, has significantly reduced total A? and tau brain levels with a significant improvement in mouse cognitive behavior. This reduction in brain A? was explained by the enhanced A? clearance pathways and reduced brain production of A? via modulation of amyloid-? precursor protein processing. On the other hand, although feeding mice with EVOO-enriched diet for 3months, beginning at an age after A? accumulation starts, showed improved clearance across the blood-brain barrier and significant reduction in A? levels, it did not affect tau levels or improve cognitive functions of TgSwDI mouse. Collectively, results of this study suggest that the long-term consumption of EVOO-containing diet starting at early age provides a protective effect against AD and its related disorder CAA. PMID:26344778

  4. Elevation Map of Kathmandu, Nepal

    NASA Technical Reports Server (NTRS)

    2002-01-01

    These Shuttle Radar Topgraphy Mission (SRTM) images show the basin of Kathmandu, the capital of Nepal: On the left a detail (27 km x 20.5 km) of the X-SAR digital elevation model (shown below), on the right the corresponding radar amplitude image. The amplitude is a measure of the backscattering of the transmitted microwaves. In the amplitude image the 'Bagmati-River' is visible south of the city center and the international Airport in the eastern part. The runway appears as a dark stripe. The airport is infamous for its difficult landing/takeoff conditions due to the close vicinity of the surrounding high mountains. For more information and a image of the region around Kathmandu, visit the German Remote Sensing Data Center SRTM Treasure Vault. Image courtesy German Remote Sensing Data Center

  5. [Unexplained, subclinical chronically elevated transaminases].

    PubMed

    Vital Durand, D; Lega, J-C; Fassier, T; Zenone, T; Durieu, I

    2013-08-01

    Unexplained, subclinical chronically elevated transaminases is mainly a marker of non-alcoholic fatty liver disease, metabolic syndrome, alcoholism and diabetes, which are very common situations but viral hepatitis and iatrogenic origin must also be considered. Before looking for hepatic or genetic rare diseases, it is worth considering hypertransaminasemia as a clue for muscular disease, particularly in paediatric settings, and creatine phosphokinase is a specific marker. Then, patient history, examination and appropriate biologic requests can permit the identification of less frequent disorders where isolated hypertransaminasemia is possibly the unique marker of the disease for a long while: hemochromatosis, celiac disease, autoimmune hepatitis, Wilson's disease, ?1-anti-trypsine deficiency, thyroid dysfunctions, Addison's disease. Liver biopsy should be performed only in patients with aspartate aminotransferases upper the normal range or alanine aminotransferases higher than twice the normal range after 6 months delay with dietetic corrections. PMID:23623710

  6. Rat, Mouse, and Primate Models of Chronic Glaucoma Show Sustained Elevation of Extracellular ATP and Altered Purinergic Signaling in the Posterior Eye

    PubMed Central

    Lu, Wennan; Hu, HuiLing; Sévigny, Jean; Gabelt, B'Ann T.; Kaufman, Paul L.; Johnson, Elaine C.; Morrison, John C.; Zode, Gulab S.; Sheffield, Val C.; Zhang, Xiulan; Laties, Alan M.; Mitchell, Claire H.

    2015-01-01

    Purpose. The cellular mechanisms linking elevated IOP with glaucomatous damage remain unresolved. Mechanical strains and short-term increases in IOP can trigger ATP release from retinal neurons and astrocytes, but the response to chronic IOP elevation is unknown. As excess extracellular ATP can increase inflammation and damage neurons, we asked if sustained IOP elevation was associated with a sustained increase in extracellular ATP in the posterior eye. Methods. No ideal animal model of chronic glaucoma exists, so three different models were used. Tg-MyocY437H mice were examined at 40 weeks, while IOP was elevated in rats following injection of hypertonic saline into episcleral veins and in cynomolgus monkeys by laser photocoagulation of the trabecular meshwork. The ATP levels were measured using the luciferin-luciferase assay while levels of NTPDase1 were assessed using qPCR, immunoblots, and immunohistochemistry. Results. The ATP levels were elevated in the vitreal humor of rats, mice, and primates after a sustained period of IOP elevation. The ecto-ATPase NTPDase1 was elevated in optic nerve head astrocytes exposed to extracellular ATP for an extended period. NTPDase1 was also elevated in the retinal tissue of rats, mice, and primates, and in the optic nerve of rats, with chronic elevation in IOP. Conclusions. A sustained elevation in extracellular ATP, and upregulation of NTPDase1, occurs in the posterior eye of rat, mouse, and primate models of chronic glaucoma. This suggests the elevation in extracellular ATP may be sustained in chronic glaucoma, and implies a role for altered purinergic signaling in the disease. PMID:26024091

  7. Dynamic multibody modeling for tethered space elevators

    NASA Astrophysics Data System (ADS)

    Williams, Paul

    2009-08-01

    This paper presents a fundamental modeling strategy for dealing with powered and propelled bodies moving along space tethers. The tether is divided into a large number of discrete masses, which are connected by viscoelastic springs. The tether is subject to the full range of forces expected in Earth orbit in a relatively simple manner. Two different models of the elevator dynamics are presented. In order to capture the effect of the elevator moving along the tether, the elevator dynamics are included as a separate body in both models. One model treats the elevator's motion dynamically, where propulsive and friction forces are applied to the elevator body. The second model treats the elevator's motion kinematically, where the distance along the tether is determined by adjusting the lengths of tether on either side of the elevator. The tether model is used to determine optimal configurations for the space elevator. A modal analysis of two different configurations is presented which show that the fundamental mode of oscillation is a pendular one around the anchor point with a period on the order of 160 h for the in-plane motion, and 24 h for the out-of-plane motion. Numerical simulation results of the effects of the elevator moving along the cable are presented for different travel velocities and different elevator masses.

  8. Role of lipase from community-associated methicillin-resistant Staphylococcus aureus strain USA300 in hydrolyzing triglycerides into growth-inhibitory free fatty acids.

    PubMed

    Cadieux, Brigitte; Vijayakumaran, Vithooshan; Bernards, Mark A; McGavin, Martin J; Heinrichs, David E

    2014-12-01

    Part of the human host innate immune response involves the secretion of bactericidal lipids on the skin and delivery of triglycerides into abscesses to control invading pathogens. Two Staphylococcus aureus lipases, named SAL1 and SAL2, were identified in the community-associated methicillin-resistant S. aureus strain USA300, which, presumably, are produced and function to degrade triglycerides to release free fatty acids. We show that the SAL2 lipase is one of the most abundant proteins secreted by USA300 and is proteolytically processed from the 72-kDa proSAL2 to the 44-kDa mature SAL2 by the metalloprotease aureolysin. We show that spent culture supernatants had lipase activity on both short- and long-chain fatty acid substrates and that deletion of gehB, encoding SAL2, resulted in the complete loss of these activities. With the use of gas chromatography-mass spectrometry, we show that SAL2 hydrolyzed trilinolein to linoleic acid, a fatty acid with known antistaphylococcal properties. When added to cultures of USA300, trilinolein and, to a lesser extent, triolein inhibited growth in a SAL2-dependent manner. This effect was shown to be due to the enzymatic activity of SAL2 on these triglycerides, since the catalytically inactive SAL2 Ser412Ala mutant was incapable of hydrolyzing the triglycerides or yielding delayed growth in their presence. Overall, these results reveal that SAL2 hydrolyzes triglycerides of both short- and long-chain fatty acids and that the released free fatty acids have the potential to cause significant delays in growth, depending on the chemical nature of the free fatty acid. PMID:25225262

  9. The space station tethered elevator system

    NASA Technical Reports Server (NTRS)

    Anderson, Loren A.

    1989-01-01

    The optimized conceptual engineering design of a space station tethered elevator is presented. The elevator is an unmanned mobile structure which operates on a ten kilometer tether spanning the distance between the Space Station and a tethered platform. Elevator capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The potential uses, parameters, and evolution of the spacecraft design are discussed. Engineering development of the tethered elevator is the result of work conducted in the following areas: structural configurations; robotics, drive mechanisms; and power generation and transmission systems. The structural configuration of the elevator is presented. The structure supports, houses, and protects all systems on board the elevator. The implementation of robotics on board the elevator is discussed. Elevator robotics allow for the deployment, retrieval, and manipulation of tethered objects. Robotic manipulators also aid in hooking the elevator on a tether. Critical to the operation of the tethered elevator is the design of its drive mechanisms, which are discussed. Two drivers, located internal to the elevator, propel the vehicle along a tether. These modular components consist of endless toothed belts, shunt-wound motors, regenerative power braking, and computer controlled linear actuators. The designs of self-sufficient power generation and transmission systems are reviewed. Thorough research indicates all components of the elevator will operate under power provided by fuel cells. The fuel cell systems will power the vehicle at seven kilowatts continuously and twelve kilowatts maximally. A set of secondary fuel cells provides redundancy in the unlikely event of a primary system failure. Power storage exists in the form of Nickel-Hydrogen batteries capable of powering the elevator under maximum loads.

  10. Prolonged Running, not Fluoxetine Treatment, Increases Neurogenesis, but does not Alter Neuropathology, in the 3xTg Mouse Model of Alzheimer’s Disease

    PubMed Central

    Marlatt, Michael W.; Potter, Michelle C.; Bayer, Thomas A.; van Praag, Henriette

    2015-01-01

    Reductions in adult neurogenesis have been documented in the original 3xTg mouse model of Alzheimer’s disease (AD), notably occurring at the same age when spatial memory deficits and amyloid plaque pathology appeared. As this suggested reduced neurogenesis was associated with behavioral deficits, we tested whether activity and pharmacological stimulation could prevent memory deficits and modify neurogenesis and/or neuropathology in the 3xTg model backcrossed to the C57Bl/6 strain. We chronically administered the antidepressant fluoxetine to one group of mice, allowed access to a running wheel in another, and combined both treatments in a third cohort. All treatments lasted for 11 months. The female 3xTg mice failed to exhibit any deficits in spatial learning and memory as measured in the Morris water maze, indicating that when backcrossed to the C57Bl/6 strain, the 3xTg mice lost the behavioral phenotype that was present in the original 3xTg mouse maintained on a hybrid background. Despite this, the backcrossed 3xTg mice expressed prominent intraneuronal amyloid beta (A?) levels in the cortex and amygdala, with lower levels in the CA1 area of the hippocampus. In the combined cohort, fluoxetine treatment interfered with exercise and reduced the total distance run. The extent of A? neuropathology, the tau accumulations, or BDNF levels, were not altered by prolonged exercise. Thus, neuropathology was present but not paralleled by spatial memory deficits in the backcrossed 3xTg mouse model of AD. Prolonged exercise for 11 months did improve the long-term survival of newborn neurons generated during middle-age, whereas fluoxetine had no effect. We further review and discuss the relevant literature in this respect. PMID:23670818

  11. SU-E-T-367: Optimization of DLG Using TG-119 Test Cases and a Weighted Mean Approach

    SciTech Connect

    Sintay, B; Vanderstraeten, C; Terrell, J; Maurer, J; Pursley, J; Wiant, D

    2014-06-01

    Purpose: Optimization of the dosimetric leaf gap (DLG) is an important step in commissioning the Eclipse treatment planning system for sliding window intensity-modulated radiation therapy (SW-IMRT) and RapidArc. Often the values needed for optimal dose delivery differ markedly from those measured at commissioning. We present a method to optimize this value using the AAPM TG-119 test cases. Methods: For SW-IMRT and RapidArc, TG-119 based test plans were created using a water-equivalent phantom. Dose distributions measured on film and ion chamber (IC) readings taken in low-gradient regions within the targets were analyzed separately. Since DLG is a single value per energy, SW-IMRT and RapidArc must be considered simultaneously. Plans were recalculated using a linear sweep from 0.02cm (the minimum DLG) to 0.3 cm. The calculated point doses were compared to the measured doses for each plan, and based on these comparisons an optimal DLG value was computed for each plan. TG-119 cases are designed to push the system in various ways, thus, a weighted mean of the DLG was computed where the relative importance of each type of plan was given a score from 0.0 to 1.0. Finally, SW-IMRT and RapidArc are assigned an overall weight based on clinical utilization. Our routine patient-QA (PQA) process was performed as independent validation. Results: For a Varian TrueBeam, the optimized DLG varied with ? = 0.044cm for SW-IMRT and ? = 0.035cm for RapidArc. The difference between the weighted mean SW-IMRT and RapidArc value was 0.038cm. We predicted utilization of 25% SW-IMRT and 75% RapidArc. The resulting DLG was ~1mm different than that found by commissioning and produced an average error of <1% for SW-IMRT and RapidArc PQA test cases separately. Conclusion: The weighted mean method presented is a useful tool for determining an optimal DLG value for commissioning Eclipse.

  12. High-flux magnetorheology at elevated temperatures

    E-print Network

    Ocalan, Murat

    Commercial applications of magnetorheological (MR) fluids often require operation at elevated temperatures as a result of surrounding environmental conditions or intense localized viscous heating. Previous experimental ...

  13. 76 FR 26981 - Proposed Flood Elevation Determinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-10

    ...elevations, and communities affected for Yolo County, California, and Incorporated...entitled ``Unincorporated Areas of Yolo County, California'' addressed the flooding...Yolo County, California, and...

  14. 21 CFR 890.3930 - Wheelchair elevator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3930 Wheelchair elevator. (a) Permanently mounted wheelchair...

  15. 21 CFR 890.3930 - Wheelchair elevator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3930 Wheelchair elevator. (a) Permanently mounted wheelchair...

  16. JAK2 inhibitor TG101348 overcomes erlotinib-resistance in non-small cell lung carcinoma cells with mutated EGF receptor

    PubMed Central

    Duan, Shan-zhou; Xia, Ying-chen; Zhu, Rong-ying; Chen, Yong-bing

    2015-01-01

    Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are responsive to EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, NSCLC patients with secondary somatic EGFR mutations are resistant to EGFR-TKI treatment. In this study, we investigated the effect of TG101348 (a JAK2 inhibitor) on the tumor growth of erlotinib-resistant NSCLC cells. Cell proliferation, apoptosis, gene expression and tumor growth were evaluated by diphenyltetrazolium bromide (MTT) assay, flow cytometry, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining, Western Blot and a xenograft mouse model, respectively. Results showed that erlotinib had a stronger impact on the induction of apoptosis in erlotinib-sensitive PC-9 cells but had a weaker effect on erlotinib-resistant H1975 and H1650 cells than TG101348. TG101348 significantly enhanced the cytotoxicity of erlotinib to erlotinib-resistant NSCLC cells, stimulated erlotinib-induced apoptosis and downregulated the expressions of EGFR, p-EGFR, p-STAT3, Bcl-xL and survivin in erlotinib-resistant NSCLC cells. Moreover, the combined treatment of TG101348 and erlotinib induced apoptosis, inhibited the activation of p-EGFR and p-STAT3, and inhibited tumor growth of erlotinib-resistant NSCLC cells in vivo. Our results indicate that TG101348 is a potential adjuvant for NSCLC patients during erlotinib treatment. PMID:25869210

  17. Homologous prime-boost strategy with TgPI-1 improves the immune response and protects highly susceptible mice against chronic Toxoplasma gondii infection.

    PubMed

    Sánchez, Vanesa R; Fenoy, Ignacio M; Picchio, Mariano S; Soto, Ariadna S; Arcon, Nadia; Goldman, Alejandra; Martin, Valentina

    2015-10-01

    Subunit-based vaccines are safer than live or attenuated pathogen vaccines, although they are generally weak immunogens. Thus, proper combination of immunization strategies and adjuvants are needed to increase their efficacy. We have previously protected C3H/HeN mice from Toxoplasma gondii infection by immunization with the serine protease inhibitor-1 (TgPI-1) in combination with alum. In this work, we explore an original vaccination protocol that combines administration of recombinant TgPI-1 by intradermal and intranasal routes in order to enhance protection in the highly susceptible C57BL/6 strain. Mice primed intradermally with rTgPI-1 plus alum and boosted intranasally with rTgPI-1 plus CpG-ODN elicited a strong specific Th1/Th2 humoral response, along with a mucosal immune response characterized by specific-IgA in intestinal lavages. A positive cellular response of mesentheric lymph node cells and Th1/Th2 cytokine secretion in the ileon were also detected. When immunized mice were challenged with the cystogenic Me49 T. gondii strain, they displayed up to 62% reduction in brain parasite burden. Moreover, adoptive transfer of mesenteric lymph node cells from vaccinated to naïve mice induced significant protection against infection. These results demonstrate that this strategy that combines the administration of TgPI-1 by two different routes, intradermal priming and intranasal boost, improves protective immunity against T. gondii chronic infection in highly susceptible mice. PMID:26200784

  18. Hypoxia induces triglycerides accumulation in prostate cancer cells and extracellular vesicles supporting growth and invasiveness following reoxygenation

    PubMed Central

    Kumar, Rahul; Dhar, Deepanshi; Agarwal, Chapla; Bergman, Bryan; Graner, Michael; Maroni, Paul; Singh, Rana P.; Agarwal, Rajesh; Deep, Gagan

    2015-01-01

    Hypoxia is an independent prognostic indicator of poor outcome in several malignancies. However, precise mechanism through which hypoxia promotes disease aggressiveness is still unclear. Here, we report that under hypoxia (1% O2), human prostate cancer (PCA) cells, and extracellular vesicles (EVs) released by these cells, are significantly enriched in triglycerides due to the activation of lipogenesis-related enzymes and signaling molecules. This is likely a survival response to hypoxic stress as accumulated lipids could support growth following reoxygenation. Consistent with this, significantly higher proliferation was observed in hypoxic PCA cells following reoxygenation associated with rapid use of accumulated lipids. Importantly, lipid utilization inhibition by CPT1 inhibitor etomoxir and shRNA-mediated CPT1-knockdown significantly compromised hypoxic PCA cell proliferation following reoxygenation. Furthermore, COX2 inhibitor celecoxib strongly reduced growth and invasiveness following hypoxic PCA cells reoxygenation, and inhibited invasiveness induced by hypoxic PCA EVs. This establishes a role for COX2 enzymatic products in the enhanced PCA growth and invasiveness. Importantly, concentration and loading of EVs secreted by PCA cells were significantly compromised under delipidized serum condition and by lipogenesis inhibitors (fatostatin and silibinin). Overall, present study highlights the biological significance of lipid accumulation in hypoxic PCA cells and its therapeutic relevance in PCA. PMID:26087400

  19. Raman Spectroscopic Analysis of Biochemical Changes in Individual Triglyceride-Rich Lipoproteins in the Pre- and Postprandial State

    SciTech Connect

    Chan, J; Motton, D; Rutledge, J; Keim, N; Huser, T

    2004-09-13

    Individual triglyceride-rich lipoprotein (TGRL) particles derived from human volunteers are non-destructively analyzed by laser tweezers Raman microspectroscopy and information on their composition and distribution is obtained. The Raman signature of single optically trapped very low-density lipoproteins (VLDL), a subclass of TGRL, which play an important role in cardiovascular disease, exhibits distinct peaks associated with molecular vibrations of fatty acids, proteins, lipids, and structural rearrangements of lipids. Our analysis of pre- and postprandial VLDL exhibits the signature of biochemical changes in individual lipoprotein particles following the consumption of meals. Interaction of VLDL with endothelium leads to the breakdown of complex triacylglycerols and the formation of a highly ordered core of free saturated fatty acids in the particle. A particle distribution analysis reveals trends in the degree to which this process has occurred in particles at different times during the postprandial period. Differences in particle distributions based on the different ratios of polyunsaturated to saturated fats in the consumed meals are also easily discerned. Individual lipoprotein particles hydrolyzed in-vitro through addition of lipoprotein lipase (LpL) exhibit strikingly similar changes in their Raman spectra. These results demonstrate the feasibility of monitoring the dynamics of lipid metabolism of individual TGRL particles as they interact with LpL in the endothelial cell wall using Raman spectroscopy.

  20. Increased Production of Fatty Acids and Triglycerides in Aspergillus oryzae by Enhancing Expressions of Fatty Acid Synthesis-Related Genes

    SciTech Connect

    Tamano, Koichi; Bruno, Kenneth S.; Karagiosis, Sue A.; Culley, David E.; Deng, Shuang; Collett, James R.; Umemura, Myco; Koike, Hideaki; Baker, Scott E.; Machida, Masa

    2013-01-01

    Microbial production of fats and oils is being developedas a means of converting biomass to biofuels. Here we investigate enhancing expression of enzymes involved in the production of fatty acids and triglycerides as a means to increase production of these compounds in Aspergillusoryzae. Examination of the A.oryzaegenome demonstrates that it contains twofatty acid synthases and several other genes that are predicted to be part of this biosynthetic pathway. We enhancedthe expressionof fatty acid synthesis-related genes by replacing their promoters with thepromoter fromthe constitutively highly expressedgene tef1. We demonstrate that by simply increasing the expression of the fatty acid synthasegenes we successfullyincreasedtheproduction of fatty acids and triglyceridesby more than two fold. Enhancement of expression of the fatty acid pathway genes ATP-citrate lyase and palmitoyl-ACP thioesteraseincreasedproductivity to a lesser extent.Increasing expression ofacetyl-CoA carboxylase caused no detectable change in fatty acid levels. Increases in message level for each gene were monitored usingquantitative real-time RT-PCR. Our data demonstrates that a simple increase in the abundance of fatty acid synthase genes can increase the detectable amount of fatty acids.

  1. Hypoxia induces triglycerides accumulation in prostate cancer cells and extracellular vesicles supporting growth and invasiveness following reoxygenation.

    PubMed

    Schlaepfer, Isabel R; Nambiar, Dhanya K; Ramteke, Anand; Kumar, Rahul; Dhar, Deepanshi; Agarwal, Chapla; Bergman, Bryan; Graner, Michael; Maroni, Paul; Singh, Rana P; Agarwal, Rajesh; Deep, Gagan

    2015-09-01

    Hypoxia is an independent prognostic indicator of poor outcome in several malignancies. However, precise mechanism through which hypoxia promotes disease aggressiveness is still unclear. Here, we report that under hypoxia (1% O2), human prostate cancer (PCA) cells, and extracellular vesicles (EVs) released by these cells, are significantly enriched in triglycerides due to the activation of lipogenesis-related enzymes and signaling molecules. This is likely a survival response to hypoxic stress as accumulated lipids could support growth following reoxygenation. Consistent with this, significantly higher proliferation was observed in hypoxic PCA cells following reoxygenation associated with rapid use of accumulated lipids. Importantly, lipid utilization inhibition by CPT1 inhibitor etomoxir and shRNA-mediated CPT1-knockdown significantly compromised hypoxic PCA cell proliferation following reoxygenation. Furthermore, COX2 inhibitor celecoxib strongly reduced growth and invasiveness following hypoxic PCA cells reoxygenation, and inhibited invasiveness induced by hypoxic PCA EVs. This establishes a role for COX2 enzymatic products in the enhanced PCA growth and invasiveness. Importantly, concentration and loading of EVs secreted by PCA cells were significantly compromised under delipidized serum condition and by lipogenesis inhibitors (fatostatin and silibinin). Overall, present study highlights the biological significance of lipid accumulation in hypoxic PCA cells and its therapeutic relevance in PCA. PMID:26087400

  2. Adipose Triglyceride Lipase (ATGL) and Hormone-Sensitive Lipase (HSL) Deficiencies Affect Expression of Lipolytic Activities in Mouse Adipose Tissues*

    PubMed Central

    Morak, Maria; Schmidinger, Hannes; Riesenhuber, Gernot; Rechberger, Gerald N.; Kollroser, Manfred; Haemmerle, Guenter; Zechner, Rudolf; Kronenberg, Florian; Hermetter, Albin

    2012-01-01

    Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular degradation of triacylglycerols. It was the aim of this study to elucidate how the deficiency in one of these proteins affects the residual lipolytic proteome in adipose tissue. For this purpose, we compared the lipase patters of brown and white adipose tissue from ATGL (?/?) and HSL (?/?) mice using differential activity-based gel electrophoresis. This method is based on activity-recognition probes possessing the same substrate analogous structure but carrying different fluorophores for specific detection of the enzyme patterns of two different tissues in one electrophoresis gel. We found that ATGL-deficiency in brown adipose tissue had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas HSL-deficiency hardly showed any effect in brown adipose tissue. Neither ATGL- nor HSL-deficiency greatly influenced the lipase patterns in white adipose tissue. Enzyme activities of mouse tissues on acylglycerol substrates were analyzed as well, showing that ATGL-and HSL-deficiencies can be compensated for at least in part by other enzymes. The proteins that responded to ATGL-deficiency in brown adipose tissue were overexpressed and their activities on acylglycerols were analyzed. Among these enzymes, Es1, Es10, and Es31-like represent lipase candidates as they catalyze the hydrolysis of long-chain acylglycerols. PMID:22984285

  3. Microemulsions of triglyceride-based oils: The effect of co-oil and salinity on phase diagrams.

    PubMed

    Komesvarakul, Napaporn; Sanders, Monica D; Szekeres, Erika; Acosta, Edgar J; Faller, James F; Mentlik, Tony; Fisher, Louis B; Nicoll, Gregg; Sabatini, David A; Scamehorn, John F

    2006-01-01

    Microemulsification of triglyceride-based oil is challenging due to the formation of undesirable phases such as macroemulsions, liquid crystals, or sponge phases. This research evaluates the formation of artificial sebum microemulsions using linker molecules, with the addition of co-oil to help enhance sebum solubilization. The microemulsion consists of a lipophilic linker (sorbitan monooleate), a hydrophilic linker (hexylglucocide), a main surfactant (sodium dioctyl sulfosuccinate), a co-oil, and artificial sebum. The effect of adding co-oil to the phase behavior and the microstructure of the resulting microemulsion is described. The effect of several types of co-oil is also studied; the co-oils evaluated here are squalene, squalane, isopropyl myristate, and ethyl laurate. The effect of salinity on the microemulsion phase behavior is also presented. Fish diagrams are obtained by plotting total surfactant/linker concentration as a function of sebum fraction in the oil mixture (co-oil + sebum). Different microemulsion types (Winsor Types I, II, III, and IV) are formed, depending on the total surfactant/linker concentration and the fraction of co-oil in the oil mixture. Winsor Type IV (single-phase) microemulsions are observed at high surfactant/linker concentrations. These single-phase, isotropic, and low-viscous fluids are particularly useful for cleansing and delivery of functional ingredients in skin care products. Salt addition shifts the fish diagram towards more hydrophobic oil systems and higher surfactant/linker concentrations. PMID:16957810

  4. Space elevator systems level analysis

    SciTech Connect

    Laubscher, B. E.

    2004-01-01

    The Space Elevator (SE) represents a major paradigm shift in space access. It involves new, untried technologies in most of its subsystems. Thus the successful construction of the SE requires a significant amount of development, This in turn implies a high level of risk for the SE. This paper will present a systems level analysis of the SE by subdividing its components into their subsystems to determine their level of technological maturity. such a high-risk endeavor is to follow a disciplined approach to the challenges. A systems level analysis informs this process and is the guide to where resources should be applied in the development processes. It is an efficient path that, if followed, minimizes the overall risk of the system's development. systems level analysis is that the overall system is divided naturally into its subsystems, and those subsystems are further subdivided as appropriate for the analysis. By dealing with the complex system in layers, the parameter space of decisions is kept manageable. Moreover, A rational way to manage One key aspect of a resources are not expended capriciously; rather, resources are put toward the biggest challenges and most promising solutions. This overall graded approach is a proven road to success. The analysis includes topics such as nanotube technology, deployment scenario, power beaming technology, ground-based hardware and operations, ribbon maintenance and repair and climber technology.

  5. TG-interacting factor 1 acts as a transcriptional repressor of sterol O-acyltransferase 2[S

    PubMed Central

    Pramfalk, Camilla; Melhuish, Tiffany A.; Wotton, David; Jiang, Zhao-Yan; Eriksson, Mats; Parini, Paolo

    2014-01-01

    Acat2 [gene name: sterol O-acyltransferase 2 (SOAT2)] esterifies cholesterol in enterocytes and hepatocytes. This study aims to identify repressor elements in the human SOAT2 promoter and evaluate their in vivo relevance. We identified TG-interacting factor 1 (Tgif1) to function as an important repressor of SOAT2. Tgif1 could also block the induction of the SOAT2 promoter activity by hepatocyte nuclear factor 1? and 4?. Women have ?30% higher hepatic TGIF1 mRNA compared with men. Depletion of Tgif1 in mice increased the hepatic Soat2 expression and resulted in higher hepatic lipid accumulation and plasma cholesterol levels. Tgif1 is a new player in human cholesterol metabolism. PMID:24478032

  6. Study of organic compounds evolved during the co-firing of coal and refuse derived fuel using TG/MS

    SciTech Connect

    Puroshothama, Shobha; Lu, R.; Yang, Xiaodong

    1996-10-01

    The evolution of organic compounds during the combustion of carbonaceous fuel coupled with solid waste disposal and limited landfill space has been a cause for concern. Co-firing high sulfur coal with refuse derived fuel seems an attractive alternative technique to tackle the dual problem of controlling SO{sub x} emissions as well as those of the chlorinated organic toxins. The TG serves to emulate the conditions of the fluidized bed combustor and the MS serves as the detector for evolved gases. This versatile combination is used to study the decomposition pathway as well as predict the conditions at which various compounds are formed and may serve as a means of reducing the formation of these chlorinated organic compounds.

  7. Acoustic Doppler current profiling from the JGOFS Arabian Sea cruises aboard the RV T.G. Thompson

    SciTech Connect

    Kim, H.S.; Flagg, C.N.; Shi, Y.

    1996-12-01

    Acoustic Doppler current profiler (ADCP) data is part of the core data for the US JGOFS Arabian Sea project, along with hydrographic and nutrient data. Seventeen cruises are scheduled to take place between September 1994 and January 1996 on the R/V T.G. Thompson. Seven of the cruises follow a standard cruise track, taking hydrographic, chemical and biological measurements. The rest of the cruises, which take place generally within the standard cruise region defined by a set track, are for the deployment and recovery of moored equipment and towing of a SeaSoar. Detailed description of ADCP hardware, the AutoADCP data acquisition system, and the collection of navigation and compass data on the Thompson is documented in Section 2. Followed by data collection for each cruise together with a cruise track, Section 3 presents the processing and analysis of velocity and acoustic backscatter intensity data. Section 5 shows results of profile quality diagnosis.

  8. The effect of IL6-174C/G polymorphisms on postprandial triglycerides metabolism in the GOLDN study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronically elevated IL-6 affects lipid and lipoprotein metabolism. Individuals genetically predisposed to higher IL-6 secretion may be at risk of dyslipidemia, especially during the postprandial phase. We investigated the effect of genetic variants at the IL6 locus on postprandial lipemia in US Whi...

  9. Characteristics of TBS-extractable hyperphosphorylated tau species: Aggregation intermediates in rTg4510 mouse brain

    PubMed Central

    Sahara, Naruhiko; DeTure, Michael; Ren, Yan; Ebrahim, Abdul-Shukkur; Kang, Dongcheul; Knight, Joshua; Volbracht, Christiane; Pedersen, Jan Torleif; Dickson, Dennis W.; Yen, Shu-Hui; Lewis, Jada

    2012-01-01

    Conditional overexpression of four-repeat human tau containing the P301L missense mutation in the rTg4510 mouse model of tauopathy leads to progressive accumulation of neurofibrillary tangles and hyperphosphorylated, sarkosyl-insoluble tau species, which are biochemically comparable to abnormal tau characteristic of hereditary tauopathies termed FTDP-17. To fully understand the impact of tau species at different stages of self-assembly on neurodegeneration, we fractionated rTg4510 brain representing several stages of tauopathy to obtain TBS-extractable (S1), high salt/sarkosyl-extractable (S3), and sarkosyl-insoluble (P3) fractions. Under reducing condition, the S1 fraction was demonstrated by Western blotting to contain both 50–60 kDa normally-sized and 64 kDa tau. Both are thermo-stable, but the 64 kDa tau showed a higher degree of phosphorylation. Under non-reducing condition, nearly all TBS-extractable 64 kDa tau were detected as ~130 kDa species consistent with the size of dimer. Quantitative analysis showed ~80 times more 64 kDa tau in S1 than P3 fraction. Immunoelectron microscopy revealed tau-positive granules/short filaments in S1 fraction. These structures displayed MC1 immunoreactivities indicative of conformational/pathological change of tau. MC1 immunoreactivity was detected by dot blotting in samples from 2.5 month-old mice, whereas Ab39 immunoreactivity indicative of late stages of tau assembly was detected only in P3 fraction. Quantitative analysis also demonstrated a significant inverse correlation between brain weight and 64 kDa tau, but the level of TBS-extractable 64 kDa tau reflects neurodegeneration better than that of sarkosyl-insoluble 64 kDa tau. Together, the findings suggest that TBS-extractable 64 kDa tau production is a potential target for therapeutic intervention of tauopathies. PMID:22941973

  10. Inclusion complexes of cypermethrin and permethrin with monochlorotriazinyl-beta-cyclodextrin: A combined spectroscopy, TG/DSC and DFT study