bluuebunny/crossref_metadata_2025 huggingface dataset:
Inorganic‐organic Microporous Solid of Wells‐Dawson Type Polyoxometalate: Synthesis, Characterization, and Electrochemical Properties
Authors: Tian Aixiang , Han Zhangang , Peng Jun , Zhai Jiangli , Zhao Yulong
Published: February 2007

An inorganic‐organic hybrid solid (H6/5bppy)5[P2W18O62]·4.5H2O (1) (bppy = 4‐(5‐(4‐bromophenyl)pyridin‐2‐yl)pyridine) was hydrothermally synthesized by using pre‐constructed Wells‐Dawson type salt α‐K6P2W18O62·15H2O as inorganic moiety. The crystal structure keeps integrated and steady under the interactions together of aryl packing, hydrogen bonding and halogen bonding. X‐ray single crystal structure analysis reveals that compound 1 contains cavities with the sizes of about 6 × 8Å, in which H2O molecules are captured. The hybrid was used as a solid bulk modifier to fabricate a three‐dimensional bulk‐modified carbon paste electrode (1‐CPE) by direct mixing. The electrochemical and electrocatalytic behavior of the 1‐CPE has been studied in detail. The results exhibit that the redox ability of the Wells‐Dawson polyanions can be maintained in the hybrid solid, which has a good electrocatalytic activity toward the reduction of bromate and hydrogen peroxide. A hydrodynamic voltammetric experiment was performed to characterize the electrode as an amperometric sensor for the determination of hydrogen peroxide. The 1‐CPE showed long‐term stability and excellent reproducibility of surface renewal.
Chromatographic resolution of chiral diacylglycerol derivatives: Potential in the stereospecific analysis of triacyl‐sn‐glycerols
Authors: Laakso Paivi , Christie William W.
Published: February 2007

Diacylglycerols have been separated as their (S)‐(+)‐or (R)‐(−)‐1‐(1‐naphthyl)ethyl urethanes by high performance liquid chromatography (HPLC) on a column of silica gel with 0.5% 2‐propanol in hexane as the mobile phase. The elution order of components derivatized with the (S)‐form of the reagent was 1,3‐, followed by 1,2‐, and finally 2,3‐diacyl‐sn‐glycerols. The elution order of 1,2‐ and 2,3‐diastereomers was reversed when the (R)‐form of 1‐(1‐naphthyl)ethyl isocyanate was used for derivatization. Single‐acid 1,2‐ and 2,3‐diastereomers were separated to the baseline with a resolution factor from 5.2–5.7, and the resolution factor between 1,3‐ and 1,2‐ or 2,3‐diacyl‐sn‐glycerol derivatives was more than 23. Molecular species of single‐acid diacylglycerol derivatives were separated in the sequence 18∶1<18∶0<18∶2<16.0.

In order to assess this methodology as part of a procedure for the stereospecific analysis of triacyl‐sn‐glycerols, we prepared diacyl‐rac‐glycerols from maize oil, evening primrose oil and egg yolk triacylglycerols by partial hydrolysis with ethyl magnesium bromide. The 1,3‐, 1,2‐ and 2,3‐diacyl‐sn‐glycerols as (S)‐(+)‐1‐(1‐naphthyl)ethyl urethanes were isolated and their fatty acid compositions were determined. Although this only permitted an indirect determination of the compositions of positionssn‐1,‐2 and‐3, it was sufficient to indicate the potential of the methodology because results comparable to those published earlier were achieved.
Δ6 desaturase in brain and liver during development and aging
Authors: Bourre J. M. , Piciotti M. , Dumont O.
Published: February 2007

Δ6 Desaturase was measured in the mouse brain and liver using linoleic acid as substrate. During pre‐ and postnatal development, Δ6 desaturase in brain decreased dramatically (12‐fold) up to postnatal day 21 and remained nearly constant thereafter. In liver, the activity increased approximately 9‐fold between day 3 before birth and day 7 after birth. Then it decreased slightly up to weaning and was approximately constant up to 4 mo. From then on, Δ6 desaturase decreased with age (40% between 4 and 17 mo).
The effect of glutathione on the vitamin E requirement for inhibition of liver microsomal lipid peroxidation
Authors: Leedle R. A. , Aust S. D.
Published: February 2007

Vitamin E dependent inhibition of rat liver microsomal lipid peroxidation in an NADPH and ADP‐Fe+3 containing system occurred at lower vitamin E concentrations in the presence of glutathione (GSH). Using microsomes from rats fed a vitamin E deficient diet, vitamin E was shown to be rquired for inhibition. Inhibition also required the presence of a storage labile microsomal component, since no inhibition was observed when using microsomes that had been stored for one moth. This observation provides evidence that direct reduction of reversibly oxidized vitamin E by GSH does not appear to contribute significantly to inhibition of peroxidation. During GSH and vitamin E dependent inhibition of lipid peroxidation, vitamin E (reduced form) concentrations remained constant, indicating that GSH maintained vitamin E concentrations. Without GSH, vitamin E concentrations dropped rapidly. By adding vitamin E to microsomes, it was found that inhibition of lipid peroxidation in the presence of GSH occurred at about five‐fold less vitamin E than in the absence of GSH. Inhibition at these lower levels of vitamin E was 85–90% complete. Results indicate that GSH can be used to maintain vitamin E (reduced form) concentrations, thereby lowering the concentration of vitamin E necessary to inhibit microsomal lipid peroxidation.
Preparation and physical properties of some C18 unsaturated fatty esters containingL‐amino acid residues and methyl esters ofN‐stearoylamino acids
Authors: Lie Ken Jie Marcel S. F. , Lao H. B. , Leung David W. Y.
Published: February 2007

A series of five C18 unsaturated fatty esters (1–5) containing anL‐amino acid residue (glycine, alanine, valine, leucine, phenylalanine) was prepared from methyl 12‐amino‐9‐cis‐octadecenoate and five methylN‐stearoyl‐amino acid ester derivatives (6–10) from stearoyl chloride and the sameL‐amino acids. The infrared analysis of compounds 1–5 showed characteristic absorption bands at 3300 and 1665 cm−1 for the amino and amido functions, while the amido function in compounds 6–10 gave absorption bands at 3300 and 1680 cm−1. The position of the amido group (peptide linkage) in compounds 1–5 was readily determined by mass spectral analysis.1H nuclear magnetic resonance (NMR) analysis showed a doublet at 7.15 ppm for the amide proton (NHCO) in compounds 1–5, while in compounds 6–10 the amide proton signal appeared at 6.0 ppm. In13C NMR, the amido carbonyl resonance appeared at 171–175 ppm. In compounds 1–5 the effect of the amide function on the ethylene carbon (C‐9) gave a signal at 124.1–125.3 ppm, while the remaining ethylenic carbon appeared at 131.9–132.5 ppm. The methine carbon (C‐12) of the alkenyl chain was shifted to 48.4–49.8 ppm, and the assignment of the various carbon nuclei in the amino acid residue was readily achieved. In the methylN‐stearoylamino acid ester derivatives (6–10), the methine carbon adjacent to the amido system and alpha to the carbomethoxy group appeared between 41.2–57.0 ppm depending on the type of alkyl group present in the amino acid moiety. The phenyl system in compounds 5 and 10 was confirmed by the13C signals in the 127–136 ppm range and by the proton signals in the 7.0–7.27 ppm region.
Effect of dietary α‐linolenate/linoleate balance on crescent type‐anti‐glomerular basement membrane nephritis in rats
Authors: Watanabe Shiro , Suzuki Erika , Kojima Ryoji , Suzuki Yoshio , Okuyama Harumi
Published: February 2007

Rats were fed diets with three different ratios of α‐linolenate (18∶3 n−3) and linoleate (18∶2 n−6), and then crescentic‐type anti‐glomerular basement membrane (GBM) nephritis was induced. The urinary protein levels and the plasma urea nitrogen levels were significantly higher, and histological abnormalities of glomeruli were seen more frequently in the high‐α‐linolenate group than in the high‐linoleate group. The differences in dietary α‐linolenate/linoleate balances were reflected in the proportions of arachidonate and eicosapentaenoate in glomerular phospholipids. Our results indicate that dietary enrichment with α‐linolenate causes unfavorable effects in this anti‐GBM nephritis model.
Separation of the enantiomers of 1‐alkyl‐2‐acyl‐rac‐glycerol and of 1‐alkyl‐3‐acyl‐rac‐glycerol by high performance liquid chromatography on a chiral column
Authors: Takagi Toru , Okamoto Jiro , Ando Yasuhiro , Itabashi Yutaka
Published: February 2007

High performance liquid chromatographic separations of two enantiomeric pairs of 1‐alkyl‐2‐acyl‐rac‐glycerol (1‐alkyl‐2‐acyl‐ and 3‐alkyl‐2‐acyl‐sn‐glycerols) and 1‐alkyl‐3‐acyl‐rac‐glycerol (1‐alkyl‐3‐acyl‐ and 3‐alkyl‐1‐acyl‐sn‐glycerols) as 3,5‐dinitrophenylurethanes (3,5‐DNPUs) were carried out on a chiral stationary phase, N‐(R)‐1‐(α‐naphthyl)ethylaminocarbonyl‐(S)‐valine chemically bonded to γ‐aminopropyl silanized silica (Sumipax OA‐4100). Good separation of the enantiomers of 1‐hexadecyl‐2‐hexadecanoyl‐rac‐glycerol was easily achieved within 10 min using hexane/ethylene dichloride/ethanol (80∶20∶1, v/v/v) as a mobile phase. Separation of the enantiomers of 1‐hexadecyl‐3‐hexadecanoyl‐rac‐glycerol was more difficult and required about 80 min to achieve satisfactory peak resolution (0.8) using hexane/ethylene dichloride/ethanol (250∶20∶1, v/v/v) as a mobile phase.
Molecular species composition of phosphatidylcholine fromCrypthecodinium cohnii in relation to growth temperature
Authors: Bell Michael V. , Henderson R. James
Published: February 2007

The molecular species composition was determined for phosphatidylcholine (PC) isolated from the marine dinoflagellateCrypthecodinium cohnii grown at three different temperatures. At all three temperatures the didocosahexaenoyl species comprised about 25% of the PC with 14∶0/22∶6 and 16∶0/22∶6 also being of major importance; these three species comprised 75–82% of the total. Another 20 species were identified, including several short chain disaturated species. Only small differences in the composition of PC were found in response to growth at 16, 23 and 27°C. On dropping the growth temperature from 27°C to 16°C the largest changes were a decrease of 8.9% in saturated/saturated species and an increase of 5.3% in saturated/PUFA species; the 22∶6/22∶6 content only increased slightly (by 1.9% to 25.4%). This unusual molecular species composition is discussed.
Evidence for the unique function of docosahexaenoic acid during the evolution of the modern hominid brain
Authors: Crawford M. A. , Bloom M. , Broadhurst C. L. , Schmidt W. F. , Cunnane S. C. , Galli C. , Gehbremeskel K. , Linseisen F. , Lloyd‐Smith J. , Parkington J.
Published: February 2007

The African savanna ecosystem of the large mammals and primates was associated with a dramatic decline in relative brain capacity associated with little docosahexaenoic acid (DHA), which is required for brain structures and growth. The biochemistry implies that the expansion of the human brain required a plentiful source of preformed DHA. The richest source of DHA is the marine food chain, while the savanna environment offers very little of it. ConsequentlyHomo sapiens could not have evolved on the savannas. Recent fossil evidence indicates that the lacustrine and marine food chain was being extensively exploited at the time cerebral expansion took place and suggests the alternative that the transition from the archaic to modern humans took place at the land/water interface. Contemporary data on tropical lakeshore dwellers reaffirm the above view with nutritional support for the vascular system, the development of which would have been a prerequisite for cerebral expansion. Both arachidonic acid and DHA would have been freely available from such habitats providing the double stimulus of preformed acyl components for the developing blood vessels and brain. The n‐3 docosapentaenoic acid precursor (n‐3 DPA) was the major n‐3‐metabolite in the savanna mammals. Despite this abundance, neither it nor the corresponding n‐6 DPA was used for the photoreceptor nor the synapse. A substantial difference between DHA and other fatty acids is required to explain this high specificity. Studies on fluidity and other mechanical features of cell membranes did not reveal a difference of such magnitude between even α‐linolenic acid and DHA sufficient to explain the exclusive use of DHA. We suggest that the evolution of the large human brain depended on a rich source of DHA from the land/water interface. We review a number of proposals for the possible influence of DHA on physical properties of the brain that are essential for its function.
New developments in phospholipase A2
Authors: Chaminade Brigitte , Le Balle François , Fourcade Olivier , Nauze Michel , Delagebeaudeuf Claire , Gassama‐Diagne Ama , Simon Marie‐Françoise , Fauvel Josette , Chap Hugues
Published: February 2007

Some of the most recent data concerning various phospholipases A2, with special emphasis on secretory, cytosolic, and calcium‐independent phospholipases A2 are summarized. Besides their contribution to the production of proinflammatory lipid mediators, the involvement of these enzymes in key cell responses such as apoptosis or tumor cell metastatic potential is also discussed, taking advantage of transgenic models based on gene invalidation by homologous recombination. The possible role of secretory and cytosolic platelet‐activating factor acetyl hydrolases is also briefly mentioned. Finally, the ectopic expression in epididymis of an intestinal phospholipase B opens some novel issues as to the possible function of phospholipases in reproduction.
Changes in membrane microdomains and caveolae constituents in multidrug‐resistant cancer cells
Authors: Lavie Yaakov , Fiucci Giusy , Czarny Malgorzata , Liscovitch Mordechai
Published: February 2007

Cancer chemotherapy often fails because of the development of tumors which are resistant to most commonly used cytotoxic drugs. This phenomenon, multidrug resistance (MDR), is usually mediated by overexpression of P‐glycoprotein (P‐gp), an ATPase that pumps out the drugs used in chemotherapy, thereby preventing their accumulation in cancer cells and greatly reducing their cytotoxic efficacy. A large body of work indicates that MDR is associated also with marked changes in membrane lipid composition. Most notably, elevated levels of cholesterol, glycosphingolipids (e.g., glucosylceramide), and sphingomyelin have been reported. These lipids are enriched in caveolae and in membrane microdomains termed detergent‐insoluble glycosphingolipid‐enriched complexes (DIGs). Recently we demonstrated that in multidrug‐resistant tumor cells there is a dramatic increase in the number of caveolae and in the level of caveolin‐1, an essential structural constituent of caveolae. Another constituent of membrane microdomains, phospholipase D, is also elevated in MDR cells. These findings may be related to the fact that a significant fraction of cellular P‐gp is associated with caveolin‐rich membrane domains. The possible role of DIGs and caveolae in the acquisition and/or maintenance of the multidrug resistant phenotype is discussed.
Tumor necrosis factor‐α and ceramides in insulin resistance
Authors: Brindley David N. , Wang Chuen‐Neu , Mei Jie , Xu James , Hanna Atef N.
Published: February 2007

The present studies tested the hypothesis that some effects of tumor necrosis factor‐α (TNF‐α) are mediated by activation of sphingomyelinases and the production of ceramides. Differentiated 3T3‐L1 adipocytes were incubated with short‐chain ceramide analogs, (C2‐ and C6‐ceramides:N‐acetyl‐ andN‐hexanoyl‐sphingosines, respectively), and this treatment increased 2‐deoxyglucose uptake in the absence of insulin progressively from 2–24 h. This effect was inhibited by blocking the activations of mitogen‐activated protein kinase, phosphatidylinositol 3‐kinase (PI 3‐kinase), and ribosomal S6 kinase which mediated an increase in GLUT1 concentrations. Long‐term increases in PI 3‐kinase activity associated with insulin receptor substrate‐1 (IRS‐1) increased the proportion of GLUT1 and GLUT4 in plasma membranes. These events explain the increases in noninsulin‐dependent glucose uptake and incorporation of this glucose into the fatty acid and glycerol moieties of triacylglycerol. The mechanisms by which TNF‐α and ceramides increase PI 3‐kinase activity were investigated further by using rat2 fibroblasts. Incubation for 20 min with TNF‐α, bacterial sphingomyelinase, or C2‐ceramides increased PI 3‐kinase activity by about fivefold, and this effect depended upon a stimulation of tyrosine kinase activity and an increase in Ras‐GTP. This demonstrates the existence of a novel signaling pathway for TNF‐α that could contribute to the effects of this cytokine in stimulating basal glucose uptake. By contrast, treating the 3T3‐L1 adipocytes for 2–24 h with C2‐ceramide diminished insulin‐stimulated glucose uptake by decreasing the insulin‐induced translocation of GLUT1 and GLUT4 to plasma membranes. This inhibition was observed when there was no increase in basal glucose uptake, and it occurred downstream of PI 3‐kinase. Our work provides further mechanisms whereby TNF‐α and ceramides produce insulin resistance and decrease the effectiveness of insulin in stimulating glucose disposal from the blood. Conversely, TNF‐α and ceramides increase the ability of adipocytes to take up glucose and store triacylglycerol in the absence of insulin.
Diabetes puts myocardial n‐3 fatty acid status at risk in the absence of supplementation in the rat
Authors: McLennan P. L. , Raederstorff D.
Published: February 2007

Conclusions

The changes in fatty acid incorporation into myocardial membranes that occurred with acute diabetes in this study were indicative of depressed PUFA desaturation. However this was largely confined to the long‐chain n‐3 PUFA, DHA. Anti‐arrhythmic efficets of n‐3 PUFA diets were associated with elevated DHA levels. It is conclused that perturbed PUFA metabolism in diabetes puts myocardial n‐3 PUFA status at high risk which may have important implications for heart function and that this may be prevented by low‐level supplementation with purified DHA.
Postprandial hypertriglyceridemia induced by saturated vs. monounsaturated fatty acids is related to reduced hepatic lipoprotein receptors binding in NZW rabbits
Authors: Harbis A. , Juhel C. , Senft M. , Lairon D.
Published: February 2007

Conclusions

As compared to a low‐fat control diet, chronic ingestion of a SFA diet increased postprandial lipemia, did not noticeably modify lipoprotein lipase and hepatic lipase activities, and decreased binding activities to LDL‐R as well as LSR. On the contrary, a MUFA‐rich diet did not alter postprandial lipemia, had no effect on lipase activities, but increased binding activities to LDL‐R and to LSR measured on hepatocyte plasmic membrane. In both cases, postprandial triglyceridemia and accumulation of triglycerides from dietary origin were inversely correlated to LDL‐R and LSR binding activities.

The reduced LDL‐R as well as LSR binding activities could explain the postprandial hypertriglyceridemia observed in rabbits chronically ingesting SFA. MUFA could prevent postprandial accumulation of TRL by accelerating their hepatic uptake mediated by LDL‐R and LSR.
Effects of age and dietary n‐3 fatty acids on the metabolism of [13C]‐α‐linolenic acid
Authors: Vermunt S. H. F. , Mensink R. P. , Simonis A. M. G. , Hornstra G.
Published: February 2007

Conclusion

We conclude that13C α‐linolenic acid is converted into its LCP. The conversion of α‐linolenic acid into its LCP appears to be inhibited on diets rich in EPA/DHA, while it appears not to be influenced by age. In addition, oxidation of α‐linolenic acid is not dependent on age or dietary α‐linolenic acid, but may be slightly increased on diets rich in EPA/DHA.
A chronic ethanol‐feeding study in rhesus monkeys
Authors: Pawlosky Robert J. , Salem Norman
Published: February 2007

This study describes the effect of chronic ethanol‐feeding in rhesus monkeys. Animals which were maintained on a diet containing 18:2n‐6 and 18:3n‐3 as 1.4 and 0.08% of the calories, respectively, and consumed alcohol (mean 2.6 g kg−1 d−1) had decreased amounts of 20:4n‐6 and 22:6n‐3 in their livers and plasma lipids compared with controls. Alcohol consumption did not appear to effect the absorption of2H5‐18:2n‐6 and 18:3n‐3 esters into the blood following an oral dose. There was an increase in2H5 enrichment in plasma 20:4n‐6 and 22:6n‐3, indicating that alcohol may have increased production of these fatty acids. There was a greater concentration of 4‐hydroxynonenal in the plasma of alcohol‐exposed monkeys compared to controls.
The inhibition of endothelial activation by unsaturated fatty acids
Authors: De Caterina Raffaele , Spiecker Martin , Solaini Giancarlo , Basta Giuseppina , Bosetti Francesca , Libby Peter , Liao James
Published: February 2007

Dietary long‐chain fatty acids (FA) may influence pathological processes involving endothelial activation and leukocyte‐endothelial interactions, such as inflammation and atherosclerosis. We previously showed that the n‐3 FA docosahexaenoate (22:6n‐3, DHA) inhibits cytokine‐stimulated expression of endothelial‐leukocyte adhesion molecules and soluble cytokines in the range of nutritionally achievable plasma concentrations. More recently we assessed structural determinants of VCAM‐1 inhibition by FA. Cultured endothelial cells were incubated first with various saturated, monounsaturated, n‐6 or n‐3 polyunsaturated FA alone and then together with interleukin‐1 or tumor necrosis factor. Saturated FA did not inhibit cytokine‐induced endothelial activation, while a progressive increase in inhibitory activity was observed, for the same chain length, with the increase in double bonds accompanying the transition from monounsaturates to n‐6 and, further, to n‐3 FA. Comparison of various FA indicated no role of the double‐bond position or configuration; the greater number of double bonds could explain the greater inhibitory activity of n‐3 vs. n‐6 FA. In order to ascertain mechanisms for these effects, we demonstrated inhibition of nuclear factor‐κB (NF‐κB) activation by DHA in parallel with a reduction in hydrogen peroxide (a critical mediator of NF‐κB activation) released by endothelial cells either extracellularly or intracellularly. This suggests that a property related to fatty acid peroxidability (the presence of multiple double bonds) is related to inhibitory properties of hydrogen peroxide release and, consequently, of endothelial activation.
Dietary polyunsaturated fatty acids and hepatic gene expression
Authors: Jump Donald B. , Thelen Annette , Mater Michelle
Published: February 2007

Dietary polyunsaturated fatty acids (PUFA) have profound effects on hepatic gene transcription leading to significant changes in lipid metabolism. PUFA rapidly suppress transcription of genes encoding specific lipogenic and glycolytic enzymes and induce genes encoding specific peroxisomal and cytochrome P450 (CYP) enzymes. Using the peroxisome proliferator‐activated receptor α (PPARα)‐null mouse, we showed that dietary PUFA induction of acyl PPARα is not required for the PUFA‐mediated suppression of fatty acid synthase (FAS), S14, or L‐pyruvate kinase (L‐PK). Studies in primary rat hepatocytes and cultured 3T3‐L1 adipocytes showed that metabolites of 20:4n‐6, like prostaglandin E2 (PGE2), suppress mRNA encoding FAS, S14, and L‐PK through a Gi/Go‐coupled signal transduction cascade. In contrast to adipocytes, 20:4n‐6‐mediated suppression of lipogenic gene expression in hepatic parenchymal cells does not require cyclooxygenase. Transfection analysis of S14CAT fusion genes in primary hepatocytes shows that peroxisome proliferator‐activated PPARα acts on the thyroid hormone response elements (−2.8/−2.5 kb). In contrast, both PGE2 and 20:4n‐6 regulate factors that act on the proximal promoter (−150/−80 bp) region, respectively. In conclusion, PUFA affects hepatic gene transcription through at least three distinct mechanisms: (i) a PPAR‐dependent pathway, (ii) a prostanoid pathway, and (iii) a PPAR and prostanoid‐independent pathway. PUFA regulation of hepatic lipid metabolism involves an integration of these multiple pathways.
The double bond in unsaturated fatty acids is the necessary and sufficient requirement for the inhibition of expression of endothelial leukocyte adhesion molecules through interference with nuclear factor‐κB activation
Authors: Massaro M. , Carluccio M. A. , Bonfrate C. , Siculella L. , Lazzerini G. , Bernini W. , Basta G. , De Caterina R.
Published: February 2007

Conclusions

These results indicate that the single double bond present in oleic acid is a necessary and sufficient requirement for FA inhibition of endothelial activation. Since this occurred independent of the stimuli used and was present also with PMA, bypassing membrane receptors, these results point to an interference with a common signal transduction pathway for cytokine signaling. These results are accounted for by an inhibition of NF‐χB activation, here demonstrated at the same concentrations required for the inhibition of surface protein. Relevance of these observations to explaining the alleged beneficial antiatherogenic effects of the Mediterranean diet, in which oleic acid in olive oil is a major nutritional component, could lie in the relatively selective displacement of saturated FA by oleate addition to endothelial cells which was also shown to occur in our system. Thus, an increase in the unsaturation index in cell membranes by oleic acid‐rich diets is theoretically additive to the effects of polyunsaturated FA. By these mechanisms, monocyte recruitment in response to atherogenic stimuli might be decreased (3).
Effects of third trimester consumption of eggs high in docosahexaenoic acid on docosahexaenoic acid status and pregnancy
Authors: Borod Emily , Atkinson Robin , Barclay William R. , Carlson Susan E.
Published: February 2007

High‐DHA eggs appear to be a practical way to increase maternal DHA status. The data suggest that high‐DHA eggs could decrease the incidence of preterm and low‐birth‐weight births, and this could be tested in a study with more statistical power. The neurodevelopment of infants from women fed low‐ and high‐DHA eggs could also provide helpful information.
Long‐chain n‐3 polyunsaturated fatty acids and triacylglycerol metabolism in the postprandial state
Authors: Roche Helen M. , Gibney Michael J.
Published: February 2007

Elevated plasma triacylglycerol (TG; triglyceride) concentrations, especially in the postprandial state, have been associated with an increased risk of coronary heart disease (CHD). Postprandial lipemia represents a complex series of reactions which occur following the ingestion of a meal containing fat and is associated with a number of adverse metabolic events including the production of atherogenic chylomicron remnants, the formation of the highly atherogenic small dense low density lipoprotein particles, a reduction in the concentration of the cardioprotective high density lipoprotein fraction and the activation of coagulation factor VII. Fish oils are a rich source of the long‐chain n‐3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid and docosahexaenoic acid. Long chain n‐3 PUFA are effective hypotriglyceridemic agents, lowering both fasting and postprandial TG concentrations. There is a large body of evidence which shows that n‐3 PUFA reduces plasma TG concentrations through reduced endogenous very low density lipoprotein production. This in turn may account for the reduced postprandial lipemic response following n‐3 PUFA supplementation. However, this does not preclude a contribution of enhanced chylomicron clearance, which may be mediated through altered chylomicron size, structure or chemical composition, or altered lipoprotein lipase metabolism in terms of enzyme concentration, activity, or affinity for chylomicrons. However the precise biochemical nature of this effect remains to be established. The reduction of postprandial plasma TG concentrations by n‐3 PUFA may partly explain why n‐3 PUFA intake is inversely related to CHD mortality.
n‐3 fatty acids and coronary heart disease—the urgent need of clinical trials
Authors: Schmidt Erik Berg , Dyerberg Jørn
Published: February 2007

Conclusions

Data from epidemiological studies, animal experiments, and clinical trials of biochemical effects in humans lend support for a beneficial role of n‐3 PUFA in CHD. So far only a few trials of n‐3 PUFA with clinical endpoints have been published. Further clinical studies in patients with acute myocardial ischemia, post‐MI patients, patients undergoing coronary bypass surgery or stenting during PTCA, and patients with arrhythmias should be undertaken. Only results from controlled clinical trials with hard end points can establish whether n‐3 PUFA reduce the risk of CHD and will have an impact on patient treatment.
Metabolism of anandamide and 2‐arachidonoylglycerol: An historical overview and some recent developments
Authors: Di Marzo Vincenzo , De Petrocellis Luciano , Bisogno Tiziana , Melck Dominique
Published: February 2007

Anandamide (N‐arachidonoylethanolamine) and 2‐arachidonoylglycerol are the two endogenous agonists of cannabinoid receptors discovered to date. Like other eicosanoids, and unlike classical neuromodulators, these two compounds are synthesized by neurons on demand, i.e., their biosynthesis, rather than release, is stimulated by Ca2+ influx and cell membrane depolarization. Both endocannabinoids can be produced from membrane phosphoglycerides through the action of phospholipases, althoughde novo pathways have also been suggested. Once released by cells, the action of both anandamide and 2‐arachidonoylglycerol is terminated—after their diffusion through the cell membrane—by the hydrolysis of the amide or ester bonds to yield arachidonic acid, which is then immediately reincorporated into phospholipids. One enzyme, fatty acid amide hydrolase, catalyzes the hydrolysis of both endocannabinoids in nervous and nonnervous cells. This enzyme also recognizesN‐palmitoylethanolamine, an antiinflammatory congener of anandamide, with a catalytic efficiency that depends on the cell type under study. However, the existence of different isozymes with different affinity for anandamide andN‐palmitoylethanolamine has not been investigated. Moreover, little work has been performed on the regulation of anandamide formation and breakdown, and several open questions remain as to the possible biosynthetic and degradative mechanisms of cannabimimetic 2‐arachidonoylglycerol in nucleated blood cells such as macrophages. Finally, the co‐existence of both endocannabinoids in invertebrates has not been fully established. Here we briefly review the state of the art, and present new data from our laboratory, on these four largely unexplored aspects of endocannabinoid metabolism.
Formation ofN‐acyl‐phosphatidylethanolamine andN‐acylethanolamine (including anandamide) during glutamate‐induced neurotoxicity
Authors: Hansen Harald S. , Moesgaard Birthe , Hansen Henrik H. , Schousboe Arne , Petersen Gitte
Published: February 2007

N‐Acyl‐phosphatidylethanolamine (NAPE) is present in very small amounts in mammalian tissues (less than 0.1% of total phospholipids). However, NAPE as well as its degradation product,N‐acylethanolamine (NAE), can be formed in certain neuronal tissues in response to increased [Ca2+]i. A high [Ca2+]i will activate the NAPE‐formingN‐acyl‐transferase using thesn‐1 acyl group of a donor phospholipid as substrate in the transfer reaction. This membrane‐bound enzyme seems to have no substrate specificity with respect to transfer of acyl groups; thus the fatty acids in theN‐acyl group of NAPE are mainly 16:0 and 18:1, corresponding to the fatty acids in thesn‐1 acyl group of the donor phospholipids. The NAPE‐hydrolyzing phospholipase D also seems not to be acyl‐group specific. In mouse neocortical neurons in primary culture, formation of NAPE and NAE is stimulated by glutamatevia activation of theN‐methyl‐d‐aspartate‐receptor. Both NAPE and, to a lesser extent, NAE accumulate in a linear fashion for many hours while at the same time the neurons are dying. Likewise, in neurons prelabeled with14C‐arachidonic acid,14C‐arachidonic acid‐labeled NAPE, and anandamide (=N‐arachi‐donoylethanolamine) are accumulating. The formation of NAPE and NAE may represent a cytoprotective response in relation to various forms of neurotoxicity.
The pool of fatty acids covalently bound to platelet proteins by thioester linkages can be altered by exogenously supplied fatty acids
Authors: Muszbek Laszlo , Haramura Gizella , Cluette‐Brown Joanne E. , Van Cott Elizabeth M. , Laposata Michael
Published: February 2007

The goals of this investigation were, first, to develop a chemical strategy to identify and quantitate the mass of fatty acid which is covalently bound to proteins by thioester linkage in unactivated platelets, and, second, to determine whether exogeneously added fatty acids can alter the fatty acid composition of thioester bound fatty acids. Studies with radio‐labeled fatty acids cannot identify and quantitate the actual fatty acids bound to proteins because they permit analysis of only the radiolabeled fatty acids added and their metabolites. Therefore, in the absence of metabolic labeling by radiolabeled fatty acids, we isolated the thioester‐linked fatty acids from platelet proteins using hydroxylamine at neutral pH to form fatty acid hydroxamates. The hydroxamates were subsequently converted to fatty acid methyl esters by acid methanolysis for quantitation by gas chromatography‐mass spectrometry. Using platelet specimens from 14 subjects, 74% of the fatty acid recovered from the unactivated platelet proteins as thioester linked was palmitate. Importantly, however, 22% was stearic acid, and oleate was 4% of the total thioester bound fatty acid. There was minimal variability (2.6‐fold at maximum) between the subjects in the amount of the thioester‐linked palmitate and thioester‐linked stearate. However, there was substantial variability (>100‐fold at maximum) between subjects in the amount of thioester‐linked oleate. We also demonstrated that incubation of platelets with exogenous fatty acids can alter the profile of fatty acids bound to platelet proteins by thioester linkages. Incubation of platelets with 100 µM palmitate for 3 h increased the amount of thioester‐linked palmitate by up to 26%, and incubation of platelets with 100 µM stearate increased the amount of thioester‐linked stearate up to 30%. In support of the observation that radiolabeled fatty acids other than palmitate were shown to be capable of binding to platelet proteins by thioester linkage, our results indicate that the fatty acids actually bound to unactivated platelet proteins include a significant amount of stearate, and variable amounts of oleate, as well as palmitate. In addition, the data show that palmitate and stearate can be increased, as a percentage of total protein‐bound fatty acid, by incubation with exogenous palmitate and stearate, respectively.
Recovery of fish oil‐derived fatty acids in lymph of thoracic duct‐cannulated wistar rats
Authors: Reicks Marla , Hoadley James , Satchithanandam Subramaniam , Morehouse Kim M.
Published: February 2007

The absorption of equivalent doses of eicosapentaenoic and docosahexaenoic acids was compared in rats when administered as the ethyl ester concentrate, ethyl ester concentrate plus olive oil, free fatty acid or triacylglycerol (menhaden oil). Lymph was collected from a thoracic duct cannula for 24 hr after dosing via an indwelling duodenal catheter. After 24 hr, the absorption of eicosapentaenoic acid was greater for the free fatty acid and menhaden oil than for the ethyl ester form, but docosahexaenoic acid absorption was comparable for all forms. Other rats had greater plasma levels of eicosapentaenoic and docosahexaenoic acids 5 hr after oral gavage dosing with menhaden oil than did rats dosed with the ethyl ester form.
Incorporation of linoleic acid and its conversion to λ‐linolenic acid in fungi
Authors: Kamisaka Yasushi , Yokochi Toshihiro , Nakahara Toro , Suzuki Osamu
Published: February 2007

The incorporation of [1‐14C]linoleic acid (LA) into lipids ofMortierella ramanniana var.angulispora was studied to determine which lipid classes participated in the δ6‐desaturation of [1‐14C]LA. [1‐14C]LA was rapidly taken up into fungal cells and esterified into various lipids. Comparison of the profile of [1‐14C]LA incorporation between fungal cells at the exponential growth phase and the stationary growth phase showed that [1‐14C]LA incorporation into most lipids—except for triacylglycerol (TG) and phosphatidylcholine (PC)—were greatly reduced at the stationary growth phase. Desaturation of [1‐14C]LA into λ‐linolenic acid (GLA) readily occurred at the exponential growth phase, but was greatly decreased at the stationary growth phase. Moreover, pulse‐chase experiments revealed that the radiolabel incorporated into phosphatidylserine (PS) and PC rapidly turned over, while that in TG and diacylglycerol (DG) accumulated after the 4 hr chase. In addition to the change of the radiolabel in individual lipids, the content of radiolabeled GLA converted from [1‐14C]LA varied with individual lipids. In phospholipids such as PC, phosphatidylethanolamine (PE) and PS, radiolabeled GLA rapidly increased after 1 hr and then decreased after 4 hr. On the other hand, a gradual increase in radiolabeled GLA until 4 hr was observed in TG. These results suggest that LA, which has been esterified into phospholipids such as PC, PE and PS, is readily desaturated to GLA, which is then transferred to TG. These differences in the fate of GLA derived from LA between phospholipids and neutral lipids may be reflected in the GLA content in the individual lipids.
The distribution and phylogenetic significance of desmethylsterols inChenopodium andAtriplex: Coexistence of Δ7‐ and Δ5 ‐sterols
Authors: Xu Sihua , Patterson Glenn W. , Lusby William R. , Schmid Kathy M. , Salt Thomas A.
Published: February 2007

Twenty‐one species in the Chenopodiaceae were analyzed for sterol composition. In ten of eleven species ofChenopodium, the major desmethylsterols were Δ7‐sterols accompanied by lower proportions of Δ5‐sterols. InC. fremontii this pattern was reversed. The sterol profiles of five species ofAtriplex were characterized by the coexistence of Δ7‐ and Δ5‐sterols in ratios of 0.3∶1 to 0.4∶1. MaleAtriplex plants contained higher proportions of Δ5‐sterols than femaleAtriplex plants. OneCeratoides and twoSalicornia species contained Δ5‐sterols as their predominant sterols.
Identification of the new 23‐methyl‐5,9‐pentacosadienoic acid in the spongeCribrochalina vasculum
Authors: Carballeria Néstor M. , Reyes Elba D.
Published: February 2007

The phospholipid fatty acids from the spongeCribrochalina vasculum were studied, revealing the presence of the new 23‐methyl‐5,9‐pentacosadienoic acid (26∶2) which completes theiso‐anteiso 26∶2 (Δ5,9) series. Other phospholipid fatty acids isolated include 26‐methyl‐5,9‐heptacosadienoic (28∶2) and 25‐ methyl‐5,9‐heptacosadienoic (28∶2), as well as the branched acids 8‐methylhexadecanoic and 11‐methyloctadecanoic. The fatty acids described in this work were found in phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. The sterol composition ofC. vasculum consisted of petrosterol, and interesting cyclopropane containing sterol, and the more common sitosterol. The phospholipid fatty acid composition of the demospongeIrcinia strobilina is also reported upon.
Predicting the outcome of Legg-Calve-Perthes’ disease in children under 6 years old
Authors: Gent Edward , Antapur Prasad , Mehta Rajnikant L. , Sudheer Vastara M. , Clarke Nicholas M. P.
Published: February 2007

Purpose

In this study, we investigated the outcome of Legg-Calve-Perthes disease in children presenting under 6 years old. Firstly, we wished to know the outcome in terms of femoral head deformity in this age group. Secondly, we investigated the potential for improvement in femoral head deformity with growth and remodelling after the Perthes lesion had healed. Thirdly, we assessed the ability of Herring's lateral pillar classification to predict femoral head deformity in this age group.

Methods

The outcome in this group was assessed using Stulberg's classification of femoral head deformity and compared to that for older children with Perthes seen at our institution over the same period. To investigate the potential for improvement of Stulberg grade with growth we assessed the hips at the stage of final healing (Waldenstrom IV) and again at skeletal maturity. To assess whether Herring's classification of lateral column collapse is predictive of deformity at this age we recorded the Herring class A, B or C at the time of maximum fragmentation and compared this to Stulberg grade.

Results

Out of a total of 127 children (131 hips) seen at our institution, 67 children (69 hips) presented before the age of 6 years. The number of Stulberg III and IV hips was 14 (20%) and 10 (15%), respectively. Chi-squared test of age against outcome confirmed that the younger children overall had a better outcome ( P < 0.001). Stulberg grade did not improve predictably after the stage of final healing. Twenty-three hips graded as Stulberg III and IV at Waldenstrom IV were reassessed at skeletal maturity. Three changed from Stulberg III to IV and five changed from Stulberg IV to III, but none had improved to Stulberg I/II. Herring's classification was predictive of outcome, with 96% of Herring A hips having Stulberg I or II outcome, 61% of Herring B hips having Stulberg I or II outcome, while 60% of Herring C hips (18 hips) had significant femoral head deformity, and 10 hips Stulberg III and 6 hips Stulberg IV.

Conclusions

Perthes in children presenting before 6 years of age can result in significant femoral head deformity which does not predictably improve with time. The risk of a poor outcome can be predicted by Herring's classification of lateral pillar collapse.
Aminoacyl‐coenzyme A synthesis catalyzed by adenylation domains
Authors: Linne Uwe , Schäfer Antje , Stubbs Milton T. , Marahiel Mohamed A.
Published: February 2007

Adenylate forming enzymes play an important role in nature as they are involved in a number of essential biochemical pathways. In this study, we investigated the ability of a set of structurally related recombinant bacterial adenylate forming enzymes derived from nonribosomal peptide synthetases for their ability to synthesize acyl‐CoAs in vitro. Adenylation‐domains normally transfer their reactive aminoacyl‐adenylates onto the covalently attached 4′‐phosphopantetheine moiety of small carrier proteins. In detail, DltA, DhbE, GrsA‐A, TycB3‐A, and TycC3‐A were investigated for their ability to synthesize acyl‐CoAs. As reference, acetyl‐CoA‐synthetase (Acs) of B. subtilis was utilized, which naturally synthesizes acetyl‐CoA from acetate, CoA‐SH and ATP. Interestingly, all enzymes were capable of producing acyl‐CoAs, albeit with differing efficiencies. Surprisingly, both CoA‐SH and ATP were observed to inhibit the adenylation reaction at higher concentrations. Product quantification for kinetic determination was carried out by ESI‐SIM‐MS. Our results allow speculation as to evolutionary relationships within the large class of adenylate forming enzymes.
Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP‐PNP
Authors: Dawson Roger J.P. , Locher Kaspar P.
Published: February 2007

Staphylococcus aureus Sav1866 is a bacterial homolog of the human ABC transporter Mdr1 that causes multidrug resistance in cancer cells. We report the crystal structure of Sav1866 in complex with adenosine‐5′‐(β,γ‐imido)triphosphate (AMP‐PNP) at 3.4 Å resolution and compare it with the previously determined structure of Sav1866 with bound ADP. Besides differences in the ATP‐binding sites, no significant conformational changes were observed. The results confirm that the ATP‐bound state of multidrug ABC transporters is coupled to an outward‐facing conformation of the transmembrane domains.
Hypoxia increases cytoplasmic expression of NDRG1, but is insufficient for its membrane localization in human hepatocellular carcinoma
Authors: Sibold Sonja , Roh Vincent , Keogh Adrian , Studer Peter , Tiffon Céline , Angst Eliane , Vorburger Stephan A. , Weimann Rosemarie , Candinas Daniel , Stroka Deborah
Published: February 2007

NDRG1 is a hypoxia‐inducible protein, whose modulated expression is associated with the progression of human cancers. Here, we reveal that NDRG1 is markedly upregulated in the cytoplasm and on the membrane in human hepatocellular carcinoma (HCC). We demonstrate further that hypoxic stress increases the cytoplasmic expression of NDRG1 in vitro, but does not result in its localization on the plasma membrane. However, grown within an HCC‐xenograft in vivo, cells express NDRG1 in the cytoplasm and on the plasma membrane. In conclusion, hypoxia is a potent inducer of NDRG1 in HCCs, albeit requiring additional stimuli within the tumour microenvironment for its recruitment to the membrane.
Intensified mid-Holocene Asian monsoon recorded in corals from Kikai Island, subtropical northwestern Pacific
Authors: Morimoto Maki , Kayanne Hajime , Abe Osamu , McCulloch Malcolm T.
Published: February 2007

Coupled records of Sr/Ca and oxygen isotope ratios (δ18O) of coral skeletons have been used to produce quantitative estimates of paleo-sea surface temperature (SST) and δ18O of surface seawater that can in some cases be converted to sea surface salinity (SSS). Two fossil corals from Kikai Island in the subtropical northwestern Pacific, a location affected by East Asian summer and winter monsoons, were analyzed to investigate differences between mid-Holocene and present-day SST and SSS. At 6180 cal yr BP, SSTs were roughly the same as today, both in summer and winter; δ18Oseawater and SSS values were higher both in summer (+ 0.5‰, +1.1 psu) and in winter (+ 0.2‰, + 0.6 psu) than modern values. At 7010 cal yr BP, SSTs were slightly cooler both in summer and winter (−0.8 and −0.6 °C), whereas δ18Oseawater and SSS had higher values in summer (+ 0.3‰, + 0.6 psu) and in winter (+ 0.8‰, + 1.9 psu) than present-day values. These results are consistent with other marine records for the mid-Holocene of the low and midlatitudes in the northwestern Pacific. Such regional conditions indicate that the East Asian summer and winter monsoons were more intense in the mid-Holocene, which was likely a function of the mid-Holocene insolation regime.
Is tenure justified? An experimental study of faculty beliefs about tenure, promotion, and academic freedom
Authors: Ceci Stephen J. , Williams Wendy M. , Mueller-Johnson Katrin
Published: February 2007

The behavioral sciences have come under attack for writings and speech that affront sensitivities. At such times, academic freedom and tenure are invoked to forestall efforts to censure and terminate jobs. We review the history and controversy surrounding academic freedom and tenure, and explore their meaning across different fields, at different institutions, and at different ranks. In a multifactoral experimental survey, 1,004 randomly selected faculty members from top-ranked institutions were asked how colleagues would typically respond when confronted with dilemmas concerning teaching, research, and wrong-doing. Full professors were perceived as being more likely to insist on having the academic freedom to teach unpopular courses, research controversial topics, and whistle-blow wrong-doing than were lower-ranked professors (even associate professors with tenure). Everyone thought that others were more likely to exercise academic freedom than they themselves were, and that promotion to full professor was a better predictor of who would exercise academic freedom than was the awarding of tenure. Few differences emerged related either to gender or type of institution, and behavioral scientists' beliefs were similar to scholars from other fields. In addition, no support was found for glib celebrations of tenure's sanctification of broadly defined academic freedoms. These findings challenge the assumption that tenure can be justified on the basis of fostering academic freedom, suggesting the need for a re-examination of the philosophical foundation and practical implications of tenure in today's academy.