Synthetic NPA diagnostic for energetic particles in JET plasmas

NASA Astrophysics Data System (ADS)

Varje, J.; Sirén, P.; Weisen, H.; Kurki-Suonio, T.; Äkäslompolo, S.; contributors, JET

2017-11-01

Neutral particle analysis (NPA) is one of the few methods for diagnosing fast ions inside a plasma by measuring neutral atom fluxes emitted due to charge exchange reactions. The JET tokamak features an NPA diagnostic which measures neutral atom fluxes and energy spectra simultaneously for hydrogen, deuterium and tritium species. A synthetic NPA diagnostic has been developed and used to interpret these measurements to diagnose energetic particles in JET plasmas with neutral beam injection (NBI) heating. The synthetic NPA diagnostic performs a Monte Carlo calculation of the neutral atom fluxes in a realistic geometry. The 4D fast ion distributions, representing NBI ions, were simulated using the Monte Carlo orbit-following code ASCOT. Neutral atom density profiles were calculated using the FRANTIC neutral code in the JINTRAC modelling suite. Additionally, for rapid analysis, a scan of neutral profiles was precalculated with FRANTIC for a range of typical plasma parameters. These were taken from the JETPEAK database, which includes a comprehensive set of data from the flat-top phases of nearly all discharges in recent JET campaigns. The synthetic diagnostic was applied to various JET plasmas in the recent hydrogen campaign where different hydrogen/deuterium mixtures and NBI configurations were used. The simulated neutral fluxes from the fast ion distributions were found to agree with the measured fluxes, reproducing the slowing-down profiles for different beam isotopes and energies and quantitatively estimating the fraction of hydrogen and deuterium fast ions.

The microtubule cytoskeleton does not integrate auxin transport and gravitropism in maize roots

NASA Technical Reports Server (NTRS)

Hasenstein, K. H.; Blancaflor, E. B.; Lee, J. S.

1999-01-01

The Cholodny-Went hypothesis of gravitropism suggests that the graviresponse is controlled by the distribution of auxin. However, the mechanism of auxin transport during the graviresponse of roots is still unresolved. To determine whether the microtubule (MT) cytoskeleton is participating in auxin transport, the cytoskeleton was examined and the movement of 3H-IAA measured in intact and excised taxol, oryzalin, and naphthylphthalamic acid (NPA)-treated roots of Zea mays cv. Merit. Taxol and oryzalin did not inhibit the graviresponse of roots but the auxin transport inhibitor NPA greatly inhibited both auxin transport and graviresponse. NPA had no effect on MT organization in vertical roots, but caused MT reorientation in horizontally placed roots. Regardless of treatment, the organization of MTs in intact roots differed from that in root segments. The MT inhibitors, taxol and oryzalin had opposite effects on the MTs, namely, depolymerization (oryzalin) and stabilization and thickening (taxol), but both treatments caused swelling of the roots. The data indicate that the MT cytoskeleton does not directly interfere with auxin transport or auxin-mediated growth responses in maize roots.

Radiosynthesis and ex vivo evaluation of (R)-(-)-2-chloro-N-[1-11C-propyl]n-propylnorapomorphine.

PubMed

Palner, Mikael; McCormick, Patrick; Gillings, Nic; Begtrup, Mikael; Wilson, Alan A; Knudsen, Gitte M

2010-01-01

Several dopamine D(2) agonist radioligands have been used with positron emission tomography (PET), including [(11)C-]-(-)-MNPA, [(11)C-]-(-)-NPA and [(11)C]-(+)-PHNO. These radioligands are considered particularly powerful for detection of endogenous dopamine release, but they either provide PET brain images with limited contrast or have affinity for both D(2) and D(3) receptors. We here present the carbon-11 radiolabeling and ex vivo evaluation of 2-Cl-(-)-NPA, a novel PET-tracer candidate with high in vitro D(2)/D(3) selectivity. 2-Cl-[(11)C]-(-)-NPA and [(11)C]-(-)-NPA were synthesized by a two step N-acylation-reduction process using [(11)C]-propionyl chloride. Awake rats were injected with either tracer, via the tail vein. The rats were decapitated at various times, the brains were removed and quickly dissected, and plasma metabolites were measured. Radioligand specificity, and P-glycoprotein involvement in brain uptake, was also assessed. 2-Cl-[(11)C]-(-)-NPA and [(11)C]-(-)-NPA were produced in high specific activity and purity. 2-Cl-[(11)C]-(-)-NPA accumulated slower in the striatum than [(11)C]-(-)-NPA, reaching maximum concentrations after 30 min. The maximal striatal uptake of 2-Cl-[(11)C]-(-)-NPA (standard uptake value 0.72+/-0.24) was approximately half that of [(11)C]-(-)-NPA (standard uptake value 1.37+/-0.18). Nonspecific uptake was similar for the two compounds. 2-Cl-[(11)C]-(-)-NPA was metabolized quickly, leaving only 17% of the parent compound in the plasma after 30 min. The specific binding of 2-Cl-[(11)C]-(-)-NPA was completely blocked and inhibition of P-glycoprotein did not alter the brain uptake. Ex vivo experiments showed, despite a favorable D(2)/D(3) selectivity, that 2-Cl-[(11)C]-(-)-NPA is inferior to [(11)C]-(-)-NPA as a PET tracer in rat, because of slower brain uptake and lower specific to nonspecific binding ratio. Copyright 2010 Elsevier Inc. All rights reserved.

Bacillus amyloliquefaciens SAY09 Increases Cadmium Resistance in Plants by Activation of Auxin-Mediated Signaling Pathways

PubMed Central

Zhou, Cheng; Zhu, Lin; Ma, Zhongyou; Wang, Jianfei

2017-01-01

Without physical contact with plants, certain plant growth-promoting rhizobacteria (PGPR) can release volatile organic compounds (VOCs) to regulate nutrient acquisition and induce systemic immunity in plants. However, whether the PGPR-emitted VOCs can induce cadmium (Cd) tolerance of plants and the underlying mechanisms remain elusive. In this study, we probed the effects of Bacillus amyloliquefaciens (strain SAY09)-emitted VOCs on the growth of Arabidopsis plants under Cd stress. SAY09 exposure alleviates Cd toxicity in plants with increased auxin biosynthesis. RNA-Seq analyses revealed that SAY09 exposure provoked iron (Fe) uptake- and cell wall-associated pathways in the Cd-treated plants. However, SAY09 exposure failed to increase Cd resistance of plants after treatment with 1-naphthylphthalamic acid (NPA) or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO). Under Cd stress, SAY09 exposure markedly promoted Fe absorption in plants with the increased hemicellulose 1 (HC1) content and Cd deposition in root cell wall, whereas these effects were almost abrogated by treatment with NPA or c-PTIO. Moreover, exogenous NPA remarkably repressed the accumulation of nitric oxide (NO) in the SAY09-exposed roots under Cd stress. Taken together, the findings indicated that NO acted as downstream signals of SAY09-induced auxin to regulate Fe acquisition and augment Cd fixation in roots, thereby ameliorating Cd toxicity. PMID:28657581

Effects of L-carnitine pretreatment in methamphetamine and 3-nitropropionic acid-induced neurotoxicity.

PubMed

Binienda, Zbigniew K; Przybyla, Beata D; Robinson, Bonnie L; Salem, Nadia; Virmani, Ashraf; Amato, Antonino; Ali, Syed F

2006-08-01

Adult, male Sprague-Dawley rats were injected with 3-ni-tropropionic acid (3-NPA) at 30 mg/kg or methamphetamine (METH) at 20 mg/kg alone or following pretreatment with L-cartnitine (LC) at 100 mg/kg. Rectal temperature was measured before and 4 h following treatment. Animals were sacrificed at 4 h posttreatment. Monoamine neurotransmitters, dopamine (DA) and serotonin (5-HT), and their metabolites were analyzed in the striatum using high-performance liquid chromatography method coupled with electrochemical detection (HPLC/ED). Transcripts of several genes related to DA metabolism were quantified using real time reverse transciption polymerase chain reaction (RT-PCR). Core temperature decreased significantly after 3-NPA acid and increased in METH-treated rats (P < 0.05). Temperature change at 4 h exhibited a significant LC effect for 3-NPA, preventing hypothermia (P < 0.05) and no effect for METH. Concentration of DA and 5-HT, and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), increased significantly in 3-NPA and decreased in METH-treated rats. An increase in DOPAC/DA turnover and serotonin observed after 3-NPA was abolished in LC-/3-NPA-treated rats. In both 3-NPA- and METH-treated rats, LC prevented an increase in DA receptor D(1) gene expression. It appears that carnitine effect preventing hypothermia after 3-NPA treatments may be related not only to its mitochondriotropic actions but also to inhibitory effect on the DA and 5-HT systems activated after the exposure to 3-NPA. The same effect observed at the transcriptional level, at least for the DA receptor D(1), may account for protection against METH toxicity.

NPH3- and PGP-like genes are exclusively expressed in the apical tip region essential for blue-light perception and lateral auxin transport in maize coleoptiles.

PubMed

Matsuda, Satomi; Kajizuka, Tomomi; Kadota, Akeo; Nishimura, Takeshi; Koshiba, Tomokazu

2011-06-01

Phototropic curvature results from differential growth on two sides of the elongating shoot, which is explained by asymmetrical indole-3-acetic acid (IAA) distribution. Using 2 cm maize coleoptile segments, 1st positive phototropic curvature was confirmed here after 8 s irradiation with unilateral blue light (0.33 μmol m(-2) s(-1)). IAA was redistributed asymmetrically by approximately 20 min after photo-stimulation. This asymmetric distribution was initiated in the top 0-3 mm region and was then transmitted to lower regions. Application of the IAA transport inhibitor, 1-N-naphthylphthalamic acid (NPA), to the top 2 mm region completely inhibited phototropic curvature, even when auxin was simultaneously applied below the NPA-treated zone. Thus, lateral IAA movement occurred only within the top 0-3 mm region after photo-stimulation. Localized irradiation experiments indicated that the photo-stimulus was perceived in the apical 2 mm region. The results suggest that this region harbours key components responsible for photo-sensing and lateral IAA transport. In the present study, it was found that the NPH3- and PGP-like genes were exclusively expressed in the 0-2 mm region of the tip, whereas PHOT1 and ZmPIN1a, b, and c were expressed relatively evenly along the coleoptile, and ZmAUX1, ZMK1, and ZmSAURE2 were strongly expressed in the elongation zone. These results suggest that the NPH3-like and PGP-like gene products have a key role in photo-signal transduction and regulation of the direction of auxin transport after blue light perception by phot1 at the very tip region of maize coleoptiles.

Participation of IAA in transduction of gravistimulus in apical cells of moss protonema

NASA Astrophysics Data System (ADS)

Oksyniuk, U. A.; Khorkavtsiv, O. Y.; Lesniak, Y. I.

Growth movements of vascular plant axis organs -- photo-, gravi- and other tropisms -- are tightly connected with IAA transport (Hertel, 1983; Medvedev, 1996; Kiss, 2000). Moss protonema synthesizes IAA (indole-3-acetic acid) and transports it basipetally favouring growth and differentiation of caulonema (Bopp, 1979; Rose, Bopp, 1983; Rose et al., 1983). We aimed at studying the role of IAA in moss protonema gravitropism using exogenous IAA, 1-NAA (1-naphthaleneacetic acid), 2,4D (2,4-dichlorophenoxyacetic acid) and inhibitors of polar IAA transport -- phytotropins NPA (N-1-naphthylphthalamic acid) and TIBA (2,3,5-triiodobenzoic acid). Six-day gravitropic protonema of Ceratodon purpureus and Pohlia nutans were taken for experiments. Auxin and phytotropins solutions were laid on protonema mats the latters being kept in solutions for 30 min. Then the surplus of solutions were poured off and Petri dishes were placed vertically for 6 h. 20 μ M of IAA and of other synthetic auxins did not significantly influence the angle of protonema gravity bending, 40 μ M of the agents, howewer, reduced the per cent of apical cells bendings and their angles. The most expressed influence on the angles of bending had the inhibitors of polar IAA transport -- NPA. 0,1 -- 3,0 μ M of this phytotropin did not change the form of apical cell, did not disturb the general distribution of amyloplasts and did not significantly lower the per cent and the value of gravity bending angle, though 10 μ M of the phytotropin - inhibited gravity bending. The mixture of 1-NAA and NPA having been added into the medium the influence of NPA was lowered and gravitropic growth renewed in course of time. 10 μ M of other phytopropin TIBA also inhibited gravitropism of Ceratodon purpureus and Pohlia nutans protonema. The analysis of basipetal transport of IAA in moss rhizoids and protonema may indicate the availability of special IAA transport in these structures (Bopp, Cerier, 1988). On the basis of the

The actin cytoskeleton may control the polar distribution of an auxin transport protein

NASA Technical Reports Server (NTRS)

Muday, G. K.; Hu, S.; Brady, S. R.; Davies, E. (Principal Investigator)

2000-01-01

The gravitropic bending of plants has long been linked to the changes in the transport of the plant hormone auxin. To understand the mechanism by which gravity alters auxin movement, it is critical to know how polar auxin transport is initially established. In shoots, polar auxin transport is basipetal (i.e., from the shoot apex toward the base). It is driven by the basal localization of the auxin efflux carrier complex. One mechanism for localizing this efflux carrier complex to the basal membrane may be through attachment to the actin cytoskeleton. The efflux carrier protein complex is believed to consist of several polypeptides, including a regulatory subunit that binds auxin transport inhibitors, such as naphthylphthalamic acid (NPA). Several lines of experimentation have been used to determine if the NPA binding protein interacts with actin filaments. The NPA binding protein has been shown to partition with the actin cytoskeleton during detergent extraction. Agents that specifically alter the polymerization state of the actin cytoskeleton change the amount of NPA binding protein and actin recovered in these cytoskeletal pellets. Actin-affinity columns were prepared with polymers of actin purified from zucchini hypocotyl tissue. NPA binding activity was eluted in a single peak from the actin filament column. Cytochalasin D, which fragments the actin cytoskeleton, was shown to reduce polar auxin transport in zucchini hypocotyls. The interaction of the NPA binding protein with the actin cytoskeleton may localize it in one plane of the plasma membrane, and thereby control the polarity of auxin transport.

The actin cytoskeleton may control the polar distribution of an auxin transport protein.

PubMed

Muday, G K; Hu, S; Brady, S R

2000-06-01

The gravitropic bending of plants has long been linked to the changes in the transport of the plant hormone auxin. To understand the mechanism by which gravity alters auxin movement, it is critical to know how polar auxin transport is initially established. In shoots, polar auxin transport is basipetal (i.e., from the shoot apex toward the base). It is driven by the basal localization of the auxin efflux carrier complex. One mechanism for localizing this efflux carrier complex to the basal membrane may be through attachment to the actin cytoskeleton. The efflux carrier protein complex is believed to consist of several polypeptides, including a regulatory subunit that binds auxin transport inhibitors, such as naphthylphthalamic acid (NPA). Several lines of experimentation have been used to determine if the NPA binding protein interacts with actin filaments. The NPA binding protein has been shown to partition with the actin cytoskeleton during detergent extraction. Agents that specifically alter the polymerization state of the actin cytoskeleton change the amount of NPA binding protein and actin recovered in these cytoskeletal pellets. Actin-affinity columns were prepared with polymers of actin purified from zucchini hypocotyl tissue. NPA binding activity was eluted in a single peak from the actin filament column. Cytochalasin D, which fragments the actin cytoskeleton, was shown to reduce polar auxin transport in zucchini hypocotyls. The interaction of the NPA binding protein with the actin cytoskeleton may localize it in one plane of the plasma membrane, and thereby control the polarity of auxin transport.

Ntann12 annexin expression is induced by auxin in tobacco roots

PubMed Central

Baucher, Marie; Oukouomi Lowe, Yves; Vandeputte, Olivier M.; Mukoko Bopopi, Johnny; Moussawi, Jihad; Vermeersch, Marjorie; Mol, Adeline; El Jaziri, Mondher; Homblé, Fabrice; Pérez-Morga, David

2011-01-01

Ntann12, encoding a polypeptide homologous to annexins, was found previously to be induced upon infection of tobacco with the bacterium Rhodococcus fascians. In this study, Ntann12 is shown to bind negatively charged phospholipids in a Ca2+-dependent manner. In plants growing in light conditions, Ntann12 is principally expressed in roots and the corresponding protein was mainly immunolocalized in the nucleus. Ntann12 expression was inhibited following plant transfer to darkness and in plants lacking the aerial part. However, an auxin (indole-3-acetic acid) treatment restored the expression of Ntann12 in the root system in dark conditions. Conversely, polar auxin transport inhibitors such as 1-naphthylphthalamic acid (NPA) or 2,3,5-triiodobenzoic acid (TIBA) inhibited Ntann12 expression in light condition. These results indicate that the expression of Ntann12 in the root is linked to the perception of a signal in the aerial part of the plant that is transmitted to the root via polar auxin transport. PMID:21543519

A mutation in the Arabidopsis HYL1 gene encoding a dsRNA binding protein affects responses to abscisic acid, auxin, and cytokinin

NASA Technical Reports Server (NTRS)

Lu, C.; Fedoroff, N.

2000-01-01

Both physiological and genetic evidence indicate interconnections among plant responses to different hormones. We describe a pleiotropic recessive Arabidopsis transposon insertion mutation, designated hyponastic leaves (hyl1), that alters the plant's responses to several hormones. The mutant is characterized by shorter stature, delayed flowering, leaf hyponasty, reduced fertility, decreased rate of root growth, and an altered root gravitropic response. It also exhibits less sensitivity to auxin and cytokinin and hypersensitivity to abscisic acid (ABA). The auxin transport inhibitor 2,3,5-triiodobenzoic acid normalizes the mutant phenotype somewhat, whereas another auxin transport inhibitor, N-(1-naph-thyl)phthalamic acid, exacerbates the phenotype. The gene, designated HYL1, encodes a 419-amino acid protein that contains two double-stranded RNA (dsRNA) binding motifs, a nuclear localization motif, and a C-terminal repeat structure suggestive of a protein-protein interaction domain. We present evidence that the HYL1 gene is ABA-regulated and encodes a nuclear dsRNA binding protein. We hypothesize that the HYL1 protein is a regulatory protein functioning at the transcriptional or post-transcriptional level.

Long-Term Inhibition by Auxin of Leaf Blade Expansion in Bean and Arabidopsis1

PubMed Central

Keller, Christopher P.; Stahlberg, Rainer; Barkawi, Lana S.; Cohen, Jerry D.

2004-01-01

The role of auxin in controlling leaf expansion remains unclear. Experimental increases to normal auxin levels in expanding leaves have shown conflicting results, with both increases and decreases in leaf growth having been measured. Therefore, the effects of both auxin application and adjustment of endogenous leaf auxin levels on midrib elongation and final leaf size (fresh weight and area) were examined in attached primary monofoliate leaves of the common bean (Phaseolus vulgaris) and in early Arabidopsis rosette leaves. Aqueous auxin application inhibited long-term leaf blade elongation. Bean leaves, initially 40 to 50 mm in length, treated once with α-naphthalene acetic acid (1.0 mm), were, after 6 d, approximately 80% the length and weight of controls. When applied at 1.0 and 0.1 mm, α-naphthalene acetic acid significantly inhibited long-term leaf growth. The weak auxin, β-naphthalene acetic acid, was effective at 1.0 mm; and a weak acid control, benzoic acid, was ineffective. Indole-3-acetic acid (1 μm, 10 μm, 0.1 mm, and 1 mm) required daily application to be effective at any concentration. Application of the auxin transport inhibitor, 1-N-naphthylphthalamic acid (1% [w/w] in lanolin), to petioles also inhibited long-term leaf growth. This treatment also was found to lead to a sustained elevation of leaf free indole-3-acetic acid content relative to untreated control leaves. Auxin-induced inhibition of leaf growth appeared not to be mediated by auxin-induced ethylene synthesis because growth inhibition was not rescued by inhibition of ethylene synthesis. Also, petiole treatment of Arabidopsis with 1-N-naphthylphthalamic acid similarly inhibited leaf growth of both wild-type plants and ethylene-insensitive ein4 mutants. PMID:14988474

Stage-specific regulation of four HD-ZIP III transcription factors during polar pattern formation in Larix leptolepis somatic embryos.

PubMed

Li, Shui-gen; Li, Wan-feng; Han, Su-ying; Yang, Wen-hua; Qi, Li-wang

2013-06-15

Polar auxin transport provides a developmental signal for cell fate specification during somatic embryogenesis. Some members of the HD-ZIP III transcription factors participate in regulation of auxin transport, but little is known about this regulation in somatic embryogenesis. Here, four HD-ZIP III homologues from Larix leptolepis were identified and designated LaHDZ31, 32, 33 and 34. The occurrence of a miR165/166 target sequence in all four cDNA sequences indicated that they might be targets of miR165/166. Identification of the cleavage products of LaHDZ31 and LaHDZ32 in vivo confirmed that they were regulated by miRNA. Their mRNA accumulation patterns during somatic embryogenesis and the effects of 1-N-naphthylphthalamic acid (NPA) on their transcript levels and somatic embryo maturation were investigated. The results showed that the four genes had higher transcript levels at mature stages than at the proliferation stage, and that NPA treatment down-regulated the mRNA abundance of LaHDZ31, 32 and 33 at cotyledonary embryo stages, but had no effect on the mRNA abundance of LaHDZ34. We concluded that these four members of Larix HD-ZIP III family might participate in polar auxin transport and the development of somatic embryos, providing new insights into the regulatory mechanisms of somatic embryogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity.

PubMed

Nadal, Xavier; Del Río, Carmen; Casano, Salvatore; Palomares, Belén; Ferreiro-Vera, Carlos; Navarrete, Carmen; Sánchez-Carnerero, Carolina; Cantarero, Irene; Bellido, Maria Luz; Meyer, Stefan; Morello, Gaetano; Appendino, Giovanni; Muñoz, Eduardo

2017-12-01

Phytocannabinoids are produced in Cannabis sativa L. in acidic form and are decarboxylated upon heating, processing and storage. While the biological effects of decarboxylated cannabinoids such as Δ 9 -tetrahydrocannabinol have been extensively investigated, the bioactivity of Δ 9 -tetahydrocannabinol acid (Δ 9 -THCA) is largely unknown, despite its occurrence in different Cannabis preparations. Here we have assessed possible neuroprotective actions of Δ 9 -THCA through modulation of PPARγ pathways. The effects of six phytocannabinoids on PPARγ binding and transcriptional activity were investigated. The effect of Δ 9 -THCA on mitochondrial biogenesis and PPARγ coactivator 1-α expression was investigated in Neuro-2a (N2a) cells. The neuroprotective effect was analysed in STHdh Q111/Q111 cells expressing a mutated form of the huntingtin protein and in N2a cells infected with an adenovirus carrying human huntingtin containing 94 polyQ repeats (mHtt-q94). The in vivo neuroprotective activity of Δ 9 -THCA was investigated in mice intoxicated with the mitochondrial toxin 3-nitropropionic acid (3-NPA). Cannabinoid acids bind and activate PPARγ with higher potency than their decarboxylated products. Δ 9 -THCA increased mitochondrial mass in neuroblastoma N2a cells and prevented cytotoxicity induced by serum deprivation in STHdh Q111/Q111 cells and by mutHtt-q94 in N2a cells. Δ 9 -THCA, through a PPARγ-dependent pathway, was neuroprotective in mice treated with 3-NPA, improving motor deficits and preventing striatal degeneration. In addition, Δ 9 -THCA attenuated microgliosis, astrogliosis and up-regulation of proinflammatory markers induced by 3-NPA. Δ 9 -THCA shows potent neuroprotective activity, which is worth considering for the treatment of Huntington's disease and possibly other neurodegenerative and neuroinflammatory diseases. © 2017 The British Pharmacological Society.

Role of Auxin-Induced Reactive Oxygen Species in Root Gravitropism1

PubMed Central

Joo, Jung Hee; Bae, Yun Soo; Lee, June Seung

2001-01-01

We report our studies on root gravitropism indicating that reactive oxygen species (ROS) may function as a downstream component in auxin-mediated signal transduction. A transient increase in the intracellular concentration of ROS in the convex endodermis resulted from either gravistimulation or unilateral application of auxin to vertical roots. Root bending was also brought about by unilateral application of ROS to vertical roots pretreated with the auxin transport inhibitor N-1-naphthylphthalamic acid. Furthermore, the scavenging of ROS by antioxidants (N-acetylcysteine, ascorbic acid, and Trolox) inhibited root gravitropism. These results indicate that the generation of ROS plays a role in root gravitropism. PMID:11457956

High-performance liquid chromatographic separation and electrochemical or spectrophotometric determination of R(-)N-n-propylnorapomorphine and R(-)10,11-methylenedioxy-N-n-propylnoraporphine in primate plasma.

PubMed

Lampen, P; Neumeyer, J L; Baldessarini, R J

1988-04-29

The dopamine receptor agonist R(-)N-n-propylnorapomorphine (NPA) and its proposed pro-drug R(-)10,11-methylenedioxy-N-n-propylnoraporphine (MDO-NPA) were isolated simultaneously from monkey plasma using a solid-phase extraction procedure. R(-)Apomorphine (APO) and R(-)10,11-methylenedioxyaporphine (MDO-APO) were added as internal standards, and separation and quantification were by high-performance liquid chromatography with electrochemical or ultraviolet detection of the free catechol and MDO compounds, respectively. The detection limits for NPA and MDO-NPA in plasma were 0.5 and 10 ng/ml and the coefficient of variation (S.D./mean) within assays and between days of assays for both drugs was 5.6% or less. Quantification of plasma levels of NPA and MDO-NPA was possible at ranges of 2-1000 and 40-5000 ng/ml, respectively, including concentrations found after intravenous administration of these agents.

Antitumour activity of 3-nitropropionic acid from Phomopsis sp. and optimization of fermentation conditions.

PubMed

Lu, F T; Ma, D C; Yan, W; Guo, J; Bai, L H

2015-08-01

In this study, 3-nitropropionic acid (3-NPA) was separated and purified from endophytic fungi belonging to Phomopsis sp. and its cytotoxicity was determined by MTT assay. Treatment with 3-NPA for 24 h resulted in a dose-dependent apoptosis in MCF-7 cells. Through quantitative detection of the genes that are closely related to the Bcl-2 signalling pathway, there was an increased expression of p53 and Bax and a decreased expression of Bcl-2, which indicated apoptosis in these cells. Meanwhile, the overexpression of PARA (poly ADP-ribose polymerase) and apoptosis inducing factor (AIF) also suggested that 3-NPA induced cellular apoptosis through a caspase-3-independent pathway in caspase-3-deficient MCF-7 cells. The fermentation condition was also improved to produce more 3-NPA: glucose as a carbon source and yeast extract as a nitrogen source, fermentation for 8 days at 32°C and a solution environment of pH 5·0. Under these conditions, the yield of 3-NPA was increased to 529 mg l(-1) compared with 410 mg l(-1) under traditional fermentation conditions. 3-Nitropropionic acid is a mitochondrial inhibitor and has some useful bioactivities such as antibacterial activity. In this paper we found that 3-NPA also has obvious cytotoxicity, so we studied its antitumour activity and tried to determine the antitumour molecular mechanism, opening a new perspective for potential antitumour prodrug development. As 3-NPA is often obtained from natural products with a low yield, in order to overcome the disadvantage of an endophytic fungi source of 3-NPA, we optimized the fermentation conditions for 3-NPA in Phomopsis sp. to obtain the maximum production of 3-NPA. © 2015 The Society for Applied Microbiology.

Opening of mitochondrial ATP-sensitive potassium channels is a trigger of 3-nitropropionic acid-induced tolerance to transient focal cerebral ischemia in rats.

PubMed

Horiguchi, Takashi; Kis, Bela; Rajapakse, Nishadi; Shimizu, Katsuyoshi; Busija, David W

2003-04-01

The role of mitochondrial ATP-sensitive potassium channels (mitoK(ATP)) in ischemic tolerance has been well documented in heart, but little work has been done in brain. To investigate the involvement of mitoK(ATP) activation in chemical preconditioning in brain, we examined the effect of 5-hydroxydecanoate (5-HD), a selective mitoK(ATP) blocker, on neurotoxin 3-nitropropionic acid (3-NPA)-induced ischemic tolerance to transient focal cerebral ischemia in rats. Male Wistar rats were administrated 3-NPA (20 mg/kg IP; n=16) or vehicle (saline; n=16) 3 days before temporary occlusion (120 minutes) of the middle cerebral artery; 5-HD (40 mg/kg IP; n=16) was injected 20 minutes before 3-NPA administration. Infarct volumes were measured 4 days after reperfusion. To directly investigate whether chemical preconditioning activates mitoK(ATP), we tested the effect of prior incubation with 1 mmol/L 5-HD on 300 micromol/L 3-NPA-induced alterations of mitochondrial membrane potential (Delta(Psi)m) in cultured neurons and astrocytes using the fluorescent dye tetramethylrhodamine ethyl ester. Treatment with 3-NPA exhibited a 16% reduction (P<0.05) and 23% reduction in infarct volume (P<0.01) for total brain and cortex, respectively. Pretreatment with 5-HD completely abolished the neuroprotective effect of chemical preconditioning. In cultured cells, 3-NPA resulted in mitochondrial depolarization. This change of Delta(Psi)m was completely blocked by 5-HD pretreatment. These results strongly suggest that opening of mitoK(ATP) plays a key role as the trigger in the development of 3-NPA-induced ischemic tolerance in brain.

The role of multiple dopamine receptors in apomorphine and N-n-propylnorapomorphine-induced climbing and hypothermia.

PubMed

Moore, N A; Axton, M S

1990-03-20

Apomorphine and N-n-propylnorapomorphine (NPA) were compared for their ability to induce stereotyped cage climbing and hypothermia in mice. Climbing behavior was produced by similar doses of apomorphine and NPA (0.625-2.5 mg/kg s.c.), whereas NPA was 43 times more potent than apomorphine in inducing a hypothermic response. SKF38393 caused a shift to the left in the dose-response curve for NPA-induced climbing, the ED50 changing from 0.98 to 0.014 mg/kg. SKF38393 had no effect on apomorphine-induced climbing behaviour. The climbing response produced by apomorphine was antagonised by both D-1 and D-2 antagonists. Climbing behaviour induced by NPA (2.5 mg/kg) could be antagonised by SCH23390 but not by clebopride, however climbing behaviour induced by a low dose of NPA (0.06 mg/kg) plus SKF38393 could be blocked by both D-1 and D-2 receptor antagonists. The hypothermic responses produced by either apomorphine or NPA could only be reversed by the selective D-2 antagonist, clebopride. These results demonstrate that dopamine agonist-induced stereotyped cage climbing requires both D-1 and D-2 receptor stimulation, whereas the hypothermic response is D-2-mediated. The results also show that it is possible to assess the relative activity of a dopamine agonist at D-1 or D-2 receptors in vivo by comparing the ability of the compound to induce hypothermia and climbing behaviour.

Nitric oxide mediates strigolactone signaling in auxin and ethylene-sensitive lateral root formation in sunflower seedlings

PubMed Central

Bharti, Niharika; Bhatla, Satish C

2015-01-01

Strigolactones (SLs) play significant role in shaping root architecture whereby auxin-SL crosstalk has been observed in SL-mediated responses of primary root elongation, lateral root formation and adventitious root (AR) initiation. Whereas GR24 (a synthetic strigolactone) inhibits LR and AR formation, the effect of SL biosynthesis inhibitor (fluridone) is just the opposite (root proliferation). Naphthylphthalamic acid (NPA) leads to LR proliferation but completely inhibits AR development. The diffusive distribution of PIN1 in the provascular cells in the differentiating zone of the roots in response to GR24, fluridone or NPA treatments further indicates the involvement of localized auxin accumulation in LR development responses. Inhibition of LR formation by GR24 treatment coincides with inhibition of ACC synthase activity. Profuse LR development by fluridone and NPA treatments correlates with enhanced [Ca2+]cyt in the apical region and differentiating zones of LR, indicating a critical role of [Ca2+] in LR development in response to the coordinated action of auxins, ethylene and SLs. Significant enhancement of carotenoid cleavage dioxygenase (CCD) activity (enzyme responsible for SL biosynthesis) in tissue homogenates in presence of cPTIO (NO scavenger) indicates the role of endogenous NO as a negative modulator of CCD activity. Differences in the spatial distribution of NO in the primary and lateral roots further highlight the involvement of NO in SL-modulated root morphogenesis in sunflower seedlings. Present work provides new report on the negative modulation of SL biosynthesis through modulation of CCD activity by endogenous nitric oxide during SL-modulated LR development. PMID:26076049

Nitric oxide mediates strigolactone signaling in auxin and ethylene-sensitive lateral root formation in sunflower seedlings.

PubMed

Bharti, Niharika; Bhatla, Satish C

2015-01-01

Strigolactones (SLs) play significant role in shaping root architecture whereby auxin-SL crosstalk has been observed in SL-mediated responses of primary root elongation, lateral root formation and adventitious root (AR) initiation. Whereas GR24 (a synthetic strigolactone) inhibits LR and AR formation, the effect of SL biosynthesis inhibitor (fluridone) is just the opposite (root proliferation). Naphthylphthalamic acid (NPA) leads to LR proliferation but completely inhibits AR development. The diffusive distribution of PIN1 in the provascular cells in the differentiating zone of the roots in response to GR24, fluridone or NPA treatments further indicates the involvement of localized auxin accumulation in LR development responses. Inhibition of LR formation by GR24 treatment coincides with inhibition of ACC synthase activity. Profuse LR development by fluridone and NPA treatments correlates with enhanced [Ca(2+)]cyt in the apical region and differentiating zones of LR, indicating a critical role of [Ca(2+)] in LR development in response to the coordinated action of auxins, ethylene and SLs. Significant enhancement of carotenoid cleavage dioxygenase (CCD) activity (enzyme responsible for SL biosynthesis) in tissue homogenates in presence of cPTIO (NO scavenger) indicates the role of endogenous NO as a negative modulator of CCD activity. Differences in the spatial distribution of NO in the primary and lateral roots further highlight the involvement of NO in SL-modulated root morphogenesis in sunflower seedlings. Present work provides new report on the negative modulation of SL biosynthesis through modulation of CCD activity by endogenous nitric oxide during SL-modulated LR development.

Genistein improves 3-NPA-induced memory impairment in ovariectomized rats: impact of its antioxidant, anti-inflammatory and acetylcholinesterase modulatory properties.

PubMed

Menze, Esther T; Esmat, Ahmed; Tadros, Mariane G; Abdel-Naim, Ashraf B; Khalifa, Amani E

2015-01-01

Huntington's disease (HD) is a progressive neurodegenerative disorder. The pre-motor symptomatic stages of the disease are commonly characterized by cognitive problems including memory loss. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that produces selective lesions in the brain similar to that of HD and was proven to cause memory impairment in rodents. Phytoestrogens have well-established neuroprotective and memory enhancing effects with fewer side effects in comparison to estrogens. This study investigated the potential neuroprotective and memory enhancing effect of genistein (5, 10 and 20 mg/kg), a phytoestrogen, in ovariectomized rats challenged with 3-NPA (20 mg/kg). These potential effects were compared to those of 17β-estradiol (2.5 mg/kg). Systemic administration of 3-NPA for 4 consecutive days impaired locomotor activity, decreased retention latencies in the passive avoidance task, decreased striatal, cortical and hippocampal ATP levels, increased oxidative stress, acetylcholinesterase (AChE) activity, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. Pretreatment with genistein and 17β-estradiol attenuated locomotor hypoactivity, increased retention latencies in the passive avoidance task, increased ATP levels, improved the oxidative stress profile, attenuated the increase in AChE activity and decreased the expression of COX-2 and iNOS. Overall, the higher genistein dose (20 mg/kg) was the most effective. In conclusion, this study suggests neuroprotective and memory enhancing effects for genistein in a rat model of HD. These effects might be attributed to its antioxidant, anti-inflammatory and cholinesterase inhibitory activities.

Characterization of nitrate-reducing and amino acid-using bacteria prominent in nitrotoxin-enriched equine cecal populations

USDA-ARS?s Scientific Manuscript database

In the present study, populations of equine cecal microbes enriched for enhanced rates of 3-nitro-1-propionic acid (NPA) or nitrate metabolism were diluted and cultured for NPA-metabolizing bacteria on a basal enrichment medium (BEM) or tryptose soy agar (TSA) medium supplemented with either 5 mM NP...

40 CFR 721.3821 - L-Glutamic acid, N-(1-oxododecyl)-.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Substances § 721.3821 L-Glutamic acid, N-(1-oxododecyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic acid, N-(1-oxododecyl)- (PMN P...

Single-cell-based system to monitor carrier driven cellular auxin homeostasis

PubMed Central

2013-01-01

Background Abundance and distribution of the plant hormone auxin play important roles in plant development. Besides other metabolic processes, various auxin carriers control the cellular level of active auxin and, hence, are major regulators of cellular auxin homeostasis. Despite the developmental importance of auxin transporters, a simple medium-to-high throughput approach to assess carrier activities is still missing. Here we show that carrier driven depletion of cellular auxin correlates with reduced nuclear auxin signaling in tobacco Bright Yellow-2 (BY-2) cell cultures. Results We developed an easy to use transient single-cell-based system to detect carrier activity. We use the relative changes in signaling output of the auxin responsive promoter element DR5 to indirectly visualize auxin carrier activity. The feasibility of the transient approach was demonstrated by pharmacological and genetic interference with auxin signaling and transport. As a proof of concept, we provide visual evidence that the prominent auxin transport proteins PIN-FORMED (PIN)2 and PIN5 regulate cellular auxin homeostasis at the plasma membrane and endoplasmic reticulum (ER), respectively. Our data suggest that PIN2 and PIN5 have different sensitivities to the auxin transport inhibitor 1-naphthylphthalamic acid (NPA). Also the putative PIN-LIKES (PILS) auxin carrier activity at the ER is insensitive to NPA in our system, indicating that NPA blocks intercellular, but not intracellular auxin transport. Conclusions This single-cell-based system is a useful tool by which the activity of putative auxin carriers, such as PINs, PILS and WALLS ARE THIN1 (WAT1), can be indirectly visualized in a medium-to-high throughput manner. Moreover, our single cell system might be useful to investigate also other hormonal signaling pathways, such as cytokinin. PMID:23379388

Sporophytic ovule tissues modulate the initiation and progression of apomixis in Hieracium.

PubMed

Tucker, Matthew R; Okada, Takashi; Johnson, Susan D; Takaiwa, Fumio; Koltunow, Anna M G

2012-05-01

Apomixis in Hieracium subgenus Pilosella initiates in ovules when sporophytic cells termed aposporous initial (AI) cells enlarge near sexual cells undergoing meiosis. AI cells displace the sexual structures and divide by mitosis to form unreduced embryo sac(s) without meiosis (apomeiosis) that initiate fertilization-independent embryo and endosperm development. In some Hieracium subgenus Pilosella species, these events are controlled by the dominant LOSS OF APOMEIOSIS (LOA) and LOSS OF PARTHENOGENESIS (LOP) loci. In H. praealtum and H. piloselloides, which both contain the same core LOA locus, the timing and frequency of AI cell formation is altered in derived mutants exhibiting abnormal funiculus growth and in transgenic plants expressing rolB which alters cellular sensitivity to auxin. The impact on apomictic and sexual reproduction was examined here when a chimeric RNAse gene was targeted to the funiculus and basal portions of the ovule, and also when polar auxin transport was inhibited during ovule development following N-1-naphthylphthalamic acid (NPA) application. Both treatments led to ovule deformity in the funiculus and distal parts of the ovule and LOA-dependent alterations in the timing, position, and frequency of AI cell formation. In the case of NPA treatment, this correlated with increased expression of DR5:GFP in the ovule, which marks the accumulation of the plant hormone auxin. Our results show that sporophytic information potentiated by funiculus growth and polar auxin transport influences ovule development, the initiation of apomixis, and the progression of embryo sac development in Hieracium. Signals associated with ovule pattern formation and auxin distribution or perception may influence the capacity of sporophytic ovule cells to respond to LOA.

Sporophytic ovule tissues modulate the initiation and progression of apomixis in Hieracium

PubMed Central

Tucker, Matthew R.; Okada, Takashi; Johnson, Susan D.; Takaiwa, Fumio; Koltunow, Anna M. G.

2012-01-01

Apomixis in Hieracium subgenus Pilosella initiates in ovules when sporophytic cells termed aposporous initial (AI) cells enlarge near sexual cells undergoing meiosis. AI cells displace the sexual structures and divide by mitosis to form unreduced embryo sac(s) without meiosis (apomeiosis) that initiate fertilization-independent embryo and endosperm development. In some Hieracium subgenus Pilosella species, these events are controlled by the dominant LOSS OF APOMEIOSIS (LOA) and LOSS OF PARTHENOGENESIS (LOP) loci. In H. praealtum and H. piloselloides, which both contain the same core LOA locus, the timing and frequency of AI cell formation is altered in derived mutants exhibiting abnormal funiculus growth and in transgenic plants expressing rolB which alters cellular sensitivity to auxin. The impact on apomictic and sexual reproduction was examined here when a chimeric RNAse gene was targeted to the funiculus and basal portions of the ovule, and also when polar auxin transport was inhibited during ovule development following N-1-naphthylphthalamic acid (NPA) application. Both treatments led to ovule deformity in the funiculus and distal parts of the ovule and LOA-dependent alterations in the timing, position, and frequency of AI cell formation. In the case of NPA treatment, this correlated with increased expression of DR5:GFP in the ovule, which marks the accumulation of the plant hormone auxin. Our results show that sporophytic information potentiated by funiculus growth and polar auxin transport influences ovule development, the initiation of apomixis, and the progression of embryo sac development in Hieracium. Signals associated with ovule pattern formation and auxin distribution or perception may influence the capacity of sporophytic ovule cells to respond to LOA. PMID:22378948

Overexpression of 3β-hydroxysteroid dehydrogenases/C-4 decarboxylases causes growth defects possibly due to abnormal auxin transport in Arabidopsis.

PubMed

Kim, Bokyung; Kim, Gyusik; Fujioka, Shozo; Takatsuto, Suguru; Choe, Sunghwa

2012-07-01

Sterols play crucial roles as membrane components and precursors of steroid hormones (e.g., brassinosteroids, BR). Within membranes, sterols regulate membrane permeability and fluidity by interacting with other lipids and proteins. Sterols are frequently enriched in detergent-insoluble membranes (DIMs), which organize molecules involved in specialized signaling processes, including auxin transporters. To be fully functional, the two methyl groups at the C-4 position of cycloartenol, a precursor of plant sterols, must be removed by bifunctional 3β-hydroxysteroid dehydrogenases/C-4 decarboxylases (3βHSD/D). To understand the role of 3βHSD/D in Arabidopsis development, we analyzed the phenotypes of knock-out mutants and overexpression lines of two 3βHSD/D genes (At1g47290 and At2g26260). Neither single nor double knock-out mutants displayed a noticeable phenotype; however, overexpression consistently resulted in plants with wrinkled leaves and short inflorescence internodes. Interestingly, the internode growth defects were opportunistic; even within a plant, some stems were more severely affected than others. Endogenous levels of BRs were not altered in the overexpression lines, suggesting that the growth defect is not primarily due to a flaw in BR biosynthesis. To determine if overexpression of the sterol biosynthetic genes affects the functions of membrane-localized auxin transporters, we subjected plants to the auxin efflux carrier inhibitor, 1-N-naphthylphthalamic acid (NPA). Where-as the gravity vectors of wild-type roots became randomly scattered in response to NPA treatment, those of the overexpression lines continued to grow in the direction of gravity. Overexpression of the two Arabidopsis 3βHSD/D genes thus appears to affect auxin transporter activity, possibly by altering sterol composition in the membranes.

The existence and gas phase acidity of the HAlnF3n+1 superacids (n = 1-4)

NASA Astrophysics Data System (ADS)

Czapla, Marcin; Skurski, Piotr

2015-06-01

Novel strong superacids are proposed and investigated on the basis of ab initio calculations. The gas phase acidity of the HAlF4, HAl2F7, and HAl3F10 systems evaluated by the estimation of the Gibbs free energies of their deprotonation reactions were found significant and comparable to the corresponding value characterizing the HTaF6, whereas the strength of the HAl4F13 acid was predicted to exceed that of the HSbF6 acid (the strongest liquid superacid recognized). The deprotonation energies of the HAlnF3n+1 acids (n = 1-4) turned out to be closely related to the electronic stabilities of their corresponding (AlnF3n+1)- anions.

Effect of sole or combined administration of nitrate and 3-nitro-1-propionic acid on fermentation and Salmonella survivability in alfalfa-fed rumen cultures in vitro.

PubMed

Correa, Alejandro Castañeda; Trachsel, Julian; Allen, Heather K; Corral-Luna, Agustin; Gutierrez-Bañuelos, Hector; Ochoa-Garcia, Pedro Antonia; Ruiz-Barrera, Oscar; Hume, Michael E; Callaway, Todd R; Harvey, Roger B; Beier, Ross C; Anderson, Robin C; Nisbet, David J

2017-04-01

Ruminal methanogenesis is a digestive inefficiency resulting in the loss of dietary energy consumed by the host and contributing to environmental methane emission. Nitrate is being investigated as a feed supplement to reduce rumen methane emissions but safety and efficacy concerns persist. To assess potential synergies of co-administering sub-toxic amounts of nitrate and 3-nitro-1-propionate (NPA) on fermentation and Salmonella survivability with an alfalfa-based diet, ruminal microbes were cultured with additions of 8 or 16mM nitrate, 4 or 12mM NPA or their combinations. All treatments decreased methanogenesis compared to untreated controls but volatile fatty acid production and fermentation of hexose were also decreased. Nitrate was converted to nitrite, which accumulated to levels inhibitory to digestion. Salmonella populations were enriched in nitrate only-treated cultures but not in cultures co- or solely treated with NPA. These results reveal a need for dose optimization to safely reduce methane production with forage-based diets. Published by Elsevier Ltd.

α-Amidoalkylating agents from N-acyl-α-amino acids: 1-(N-acylamino)alkyltriphenylphosphonium salts.

PubMed

Mazurkiewicz, Roman; Adamek, Jakub; Październiok-Holewa, Agnieszka; Zielińska, Katarzyna; Simka, Wojciech; Gajos, Anna; Szymura, Karol

2012-02-17

N-Acyl-α-amino acids were efficiently transformed in a two-step procedure into 1-N-(acylamino)alkyltriphenylphosphonium salts, new powerful α-amidoalkylating agents. The effect of the α-amino acid structure, the base used [MeONa or a silica gel-supported piperidine (SiO(2)-Pip)], and the main electrolysis parameters (current density, charge consumption) on the yield and selectivity of the electrochemical decarboxylative α-methoxylation of N-acyl-α-amino acids (Hofer-Moest reaction) was investigated. For most proteinogenic and all studied unproteinogenic α-amino acids, very good results were obtained using a substoichiometric amount of SiO(2)-Pip as the base. Only in the cases of N-acylated cysteine, methionine, and tryptophan, attempts to carry out the Hofer-Moest reaction in the applied conditions failed, probably because of the susceptibility of these α-amino acids to an electrochemical oxidation on the side chain. The methoxy group of N-(1-methoxyalkyl)amides was effectively displaced with the triphenylphosphonium group by dissolving an equimolar amount of N-(1-methoxyalkyl)amide and triphenylphosphonium tetrafluoroborate in CH(2)Cl(2) at room temperature for 30 min, followed by the precipitation of 1-N-(acylamino)alkyltriphenylphosphonium salt with Et(2)O.

An ethylene and ROS-dependent pathway is involved in low ammonium-induced root hair elongation in Arabidopsis seedlings.

PubMed

Zhu, Changhua; Yang, Na; Guo, Zhengfei; Qian, Meng; Gan, Lijun

2016-08-01

Root hairs are plastic in response to nutrient supply, but relatively little is known about their development under low ammonium (NH4(+)) conditions. This study showed that reducing NH4(+) for 3 days in wild-type Arabidopsis seedlings resulted in drastic elongation of root hairs. To investigate the possible mediation of ethylene and auxin in this process, seedlings were treated with 2,3,5-triiodobenzoic acid (TIBA, auxin transport inhibitor), 1-naphthylphthalamic acid (NPA, auxin transport inhibitor), p-chlorophenoxy isobutyric acid (PCIB, auxin action inhibitor), aminoethoxyvinylglycine (AVG, chemical inhibitor of ethylene biosynthesis), or silver ions (Ag(+), ethylene perception antagonist) under low NH4(+) conditions. Our results showed that TIBA, NPA and PCIB did not inhibit root hair elongation under low NH4(+) conditions, while AVG and Ag(+) completely inhibited low NH4(+)-induced root hair elongation. This suggested that low NH4(+)-induced root hair elongation was dependent on the ethylene pathway, but not the auxin pathway. Further genetic studies revealed that root hair elongation in auxin-insensitive mutants was sensitive to low NH4(+) treatment, but elongation was less sensitive in ethylene-insensitive mutants than wild-type plants. In addition, low NH4(+)-induced root hair elongation was accompanied by reactive oxygen species (ROS) accumulation. Diphenylene iodonium (DPI, NADPH oxidase inhibitor) and dimethylthiourea (DMTU, ROS scavenger) inhibited low NH4(+)-induced root hair elongation, suggesting that ROS were involved in this process. Moreover, ethylene acted together with ROS to modulate root hair elongation under low NH4(+) conditions. These results demonstrate that a signaling pathway involving ethylene and ROS participates in regulation of root hair elongation when Arabidopsis seedlings are subjected to low NH4(+) conditions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Acute administration of 3-nitropropionic acid, a reactive oxygen species generator, boosts ethanol-induced locomotor stimulation. New support for the role of brain catalase in the behavioural effects of ethanol.

PubMed

Manrique, Héctor M; Miquel, Marta; Aragon, Carlos M G

2006-12-01

The antioxidant enzyme catalase by reacting with H(2)O(2), forms the compound known as compound I (catalase-H(2)O(2)). This compound is able to oxidise ethanol to acetaldehyde in the CNS. It has been demonstrated that 3-nitropropionic acid (3-NPA) induces the activity of the brain catalase-H(2)O(2) system. In this study, we tested the effect of 3-NPA on both the brain catalase-H(2)O(2) system and on the acute locomotor effect of ethanol. To find the optimal interval for the 3-NPA-ethanol interaction mice were treated with 3-NPA 0, 45, 90 and 135min before an ethanol injection (2.4mg/kg). In a second study, 3-NPA (0, 15, 30 or 45mg/kg) was administered SC to animals 90min before saline or several doses of ethanol (1.6 or 2.4g/kg), and the open-field behaviour was registered. The specificity of the effect of 3-NPA (45mg/kg) was evaluated on caffeine (10mg/kg IP) and cocaine (4mg/kg)-induced locomotion. The prevention of 3-NPA effects on both ethanol-induced locomotion and brain catalase activity by L-carnitine, a potent antioxidant, was also studied. Nitropropionic acid boosted ethanol-induced locomotion and brain catalase activity after 90min. The effect of 3-NPA was prevented by l-carnitine administration. These results indicate that 3-NPA enhanced ethanol-induced locomotion by increasing the activity of the brain catalase system.

Transport of Indole-3-Butyric Acid and Indole-3-Acetic Acid in Arabidopsis Hypocotyls Using Stable Isotope Labeling1[C][W][OA

PubMed Central

Liu, Xing; Barkawi, Lana; Gardner, Gary; Cohen, Jerry D.

2012-01-01

The polar transport of the natural auxins indole-3-butyric acid (IBA) and indole-3-acetic acid (IAA) has been described in Arabidopsis (Arabidopsis thaliana) hypocotyls using radioactive tracers. Because radioactive assays alone cannot distinguish IBA from its metabolites, the detected transport from applied [3H]IBA may have resulted from the transport of IBA metabolites, including IAA. To test this hypothesis, we used a mass spectrometry-based method to quantify the transport of IBA in Arabidopsis hypocotyls by following the movement of [13C1]IBA and the [13C1]IAA derived from [13C1]IBA. We also assayed [13C6]IAA transport in a parallel control experiment. We found that the amount of transported [13C1]IBA was dramatically lower than [13C6]IAA, and the IBA transport was not reduced by the auxin transport inhibitor N-1-naphthylphthalamic acid. Significant amounts of the applied [13C1]IBA were converted to [13C1]IAA during transport, but [13C1]IBA transport was independent of IBA-to-IAA conversion. We also found that most of the [13C1]IBA was converted to ester-linked [13C1]IBA at the apical end of hypocotyls, and ester-linked [13C1]IBA was also found in the basal end at a level higher than free [13C1]IBA. In contrast, most of the [13C6]IAA was converted to amide-linked [13C6]IAA at the apical end of hypocotyls, but very little conjugated [13C6]IAA was found in the basal end. Our results demonstrate that the polar transport of IBA is much lower than IAA in Arabidopsis hypocotyls, and the transport mechanism is distinct from IAA transport. These experiments also establish a method for quantifying the movement of small molecules in plants using stable isotope labeling. PMID:22323783

Hydrogen bonded 1D-3D supramolecular structures from Benzylamine and organic acidic components

NASA Astrophysics Data System (ADS)

Gao, Xingjun; Li, XiaoLiang; Jin, Shouwen; Hu, Kaikai; Guo, Jianzhong; Guo, Ming; Xu, Weiqiang; Wang, Daqi

2018-03-01

Cocrystallization of the commonly available organic amine, benzylamine, with a series of organic acids afforded a total of seven organic salts with the compositions: (benzylamine)2: (p-nitrophenol)2: (H2O) (1) [(HL)2+⋯(npl-)2⋯(H2O), npl- = p-nitrophenolate], (benzylamine): (4-tert-butylbenzoic acid) (2) [(HL+)⋯(tba-), tba- = 4-tert-butylbenzoate], (benzylamine): (3,4-dichlorobenzoic acid) (3) [(HL+)⋯dcba-), dcba- = 3,4-dichlorobenzoate], (benzylamine): (2,5-dihydroxybenzoic acid) (4) [(HL+)⋯(dhba-), dhba- = 2,5-dihydroxybenzoate], (benzylamine): (2-bromo-but-2-enedioic acid) (5) [(HL+)⋯(Hbba-), Hbba- = 2-bromo-hydrogenbut-2-enedioate], (benzylamine): (2,6-pyridinedicarboxylic acid) (6) [(HL+)⋯(Hpdc-), Hpdc- = 2,6-pyridine hydrogendicarboxylate], and (benzylamine)2: (3-nitrophthalic acid): 2(H2O) (7) [(HL+)2⋯(npa2-)⋯(H2O)2, npa2- = 3-nitrophthalate]. The seven salts have been characterised by X-ray diffraction analysis, IR, and elemental analysis, and the melting points of all the salts were also reported. And their structural and supramolecular aspects are fully analyzed. The results reveal that among the seven investigated crystals the NH2 in the benzylamine are protonated when the organic acids are deprotonated, and the crystal packing is interpreted in terms of the strong charge-assisted Nsbnd H⋯O hydrogen bond between the NH3+ and deprotonated acidic groups. Except the Nsbnd H⋯O hydrogen bond, the Osbnd H⋯O hydrogen bonds (charge assisted or neutral) were also found at the salts 1, 4, 5, 6, and 7. Further analysis of the crystal packing of the salts indicated that a different family of additional CHsbnd O/CH2sbnd O, CH-π/CH2-π, Cπ-Cπ, Osbnd O, O-Cπ, O-π, and Cl-π associations also contribute to the stabilization and expansion of the total high-dimensional framework structures. For the coexistence of the various weak nonbonding interactions, these structures adopted a variety of

Inactivation of H1N1 viruses exposed to acidic ozone water

NASA Astrophysics Data System (ADS)

Uhm, Han S.; Lee, Kwang H.; Seong, Baik L.

2009-10-01

The inactivation of H1N1 viruses upon exposure to acidic ozone water was investigated using chicken allantoic fluids of different dilutions, pH values, and initial ozone concentrations. The inactivation effect of the acidic ozone water was found to be stronger than the inactivation effect of the ozone water combined with the degree of acidity, indicating a synergic effect of acidity on ozone decay in water. It is also shown that acidic ozone water with a pH value of 4 or less is very effective means of virus inactivation if provided in conjunction with an ozone concentration of 20 mg/l or higher.

Crystal structures of eight 3D molecular adducts derived from bis-imidazole, bis(benzimidazole), and organic acids

NASA Astrophysics Data System (ADS)

Ding, Aihua; Jin, Shouwen; Jin, Shide; Hu, KaiKai; Lin, Zhihao; Liu, Hui; Wang, Daqi

2018-01-01

Cocrystallization of the bis(imidazole)/bis(benzimidazole) with a series of organic acids gave a total of eight molecular adducts with the compositions: (3,6-bis(imidazole-1-yl)pyridazine): (trichloroacetic acid)2(1) [(H2L1)2+ · (tca-)2, L1 = 3,6-bis(imidazole-1-yl)pyridazine, tca- = trichloroacetate], (bis(N-imidazolyl)methane): (suberic acid) (2) [(L2) · (H2suba), L2 = bis(N-imidazolyl)methane, H2suba = suberic acid], bis(N-imidazolyl)methane: (3-nitrophthalic acid): 3H2O (3) [(H2L2)2+ · (3-Hnpa-)2 · 3H2O, 3-Hnpa- = 3-nitro hydrogenphthalate], (bis(N-imidazolyl)butane)0.5: (4-nitrophthalic acid): H2O (4) [(H2L3)0.5+ · (4-Hnpa-)- · H2O, L3 = bis(N-imidazolyl)butane, 4-Hnpa- = 4-nitro hydrogenphthalate], (1-(3-(1H-benzimidazol-1-yl)propyl)-1H-benzimidazole): (3,5-dinitrosalicylic acid) (5) [(HL4) · (3,5-dns-), L4 = 1-(3-(1H-benzimidazol-1-yl)propyl)-1H-benzimidazole, 3,5-dns- = 3,5-dinitrosalicylate], (1-(3-(1H-benzimidazol-1-yl)propyl)-1H-benzimidazole): (3-nitrophthalic acid) (6) [(H2L4) · (3-npa2-), L4 = 1-(3-(1H-benzimidazol-1-yl)propyl)-1H-benzimidazole, 3-npa2-=3-nitrogenphthalate], (bis(N-imidazolyl)butane): (pamoic acid) (7) [(H2L3) · (pam), pam = pamoate], and (3,6-bis(imidazole-1-yl)pyridazine): (1,5-naphthalenedisulfonic acid) [(H2L1)2+ · (npda)2- = 1,5-naphthalenedisulfonate] (8). The eight adducts have been characterized by X-ray diffraction technique, infrared spectrum, and elemental analysis, and the melting points of all adducts were also reported. And their structural and supramolecular aspects are fully analyzed. The result reveals that among the eight investigated crystals both the end ring N in the bis(imidazole) moieties are protonated when the organic acids are deprotonated except 2, and 5, and the crystal packing is interpreted in terms of the strong ionic Nsbnd H⋯O H-bond between the imidazolium and the deprotonated acidic groups. Except the Nsbnd H⋯O H-bond, the Osbnd H⋯O H-bonds were also found at the salts 3, 4

In vitro cytotoxicity and differential cellular sensitivity of derivatives of diamino acids. II. N1-methyl, N1-allyl, N1-(2-chloroethyl) and N1-propargyl nitrosoureas.

PubMed

Dulude, H; Salvador, R; Gallant, G

1995-01-01

The in vitro cytotoxicity and differential cellular sensitivity of a series of new N1-methyl, N1-allyl, N1-2-chloroethyl and N1-propargyl nitrosourea derivatives of diamino acids were determined in the National Cancer Institute's primary antitumor drug screen. The compounds tested showed an in vitro anticancer activity similar to commercialized nitrosoureas such as CCNU, BCNU, MeCCNU, chlorozotocin, streptozotocin and PCNU. The alkylating moiety of the nitrosoureas seems to play a role in the general selectivity of our compounds. The N1-methyl and N1-2-chloroethyl nitrosourea derivatives are more selective for central nervous system cell lines, the N1-allyl nitrosourea derivatives are more selective for lung cancer cell lines and the N1-propargyl nitrosoureas are more selective for leukemia cell lines.

Anti-pandemic influenza A (H1N1) virus potential of catechin and gallic acid.

PubMed

You, Huey-Ling; Huang, Chao-Chun; Chen, Chung-Jen; Chang, Cheng-Chin; Liao, Pei-Lin; Huang, Sheng-Teng

2018-05-01

The pandemic influenza A (H1N1) virus has spread worldwide and infected a large proportion of the human population. Discovery of new and effective drugs for the treatment of influenza is a crucial issue for the global medical community. According to our previous study, TSL-1, a fraction of the aqueous extract from the tender leaf of Toonasinensis, has demonstrated antiviral activities against pandemic influenza A (H1N1) through the down-regulation of adhesion molecules and chemokine to prevent viral attachment. The aim of the present study was to identify the active compounds in TSL-1 which exert anti-influenza A (H1N1) virus effects. XTT assay was used to detect the cell viability. Meanwhile, the inhibitory effect on the pandemic influenza A (H1N1) virus was analyzed by observing plaque formation, qRT-PCR, neuraminidase activity, and immunofluorescence staining of influenza A-specific glycoprotein. Both catechin and gallic acid were found to be potent inhibitors in terms of influenza virus mRNA replication and MDCK plaque formation. Additionally, both compounds inhibited neuraminidase activities and viral glycoprotein. The 50% effective inhibition concentration (EC 50 ) of catechin and gallic acid for the influenza A (H1N1) virus were 18.4 μg/mL and 2.6 μg/mL, respectively; whereas the 50% cytotoxic concentrations (CC 50 ) of catechin and gallic acid were >100 μg/mL and 22.1 μg/mL, respectively. Thus, the selectivity indexes (SI) of catechin and gallic acid were >5.6 and 22.1, respectively. The present study demonstrates that catechin might be a safe reagent for long-term use to prevent influenza A (H1N1) virus infection; whereas gallic acid might be a sensitive reagent to inhibit influenza virus infection. We conclude that these two phyto-chemicals in TSL-1 are responsible for exerting anti-pandemic influenza A (H1N1) virus effects. Copyright © 2017. Published by Elsevier Taiwan LLC.

40 CFR 721.3820 - L-Glutamic acid, N-(1-oxododecyl)-, disodium salt.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic...

(-)-N-[(11)C]propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D(2) receptors.

PubMed

Hwang, D R; Kegeles, L S; Laruelle, M

2000-08-01

Imaging neuroreceptors with radiolabeled agonists might provide valuable information on the in vivo agonist affinity states of receptors of interest. We report here the radiosynthesis, biodistribution in rodents, and imaging studies in baboons of [(11)C]-labeled (-)-N-propyl-norapomorphine [(-)-NPA]. (-)-[(11)C]NPA was prepared by reacting norapomorphine with [(11)C]propionyl chloride and a lithium aluminum hydride reduction. [(11)C]Propionyl chloride was prepared by reacting [(11)C]CO(2) with ethylmagnesium bromide, followed by reacting with phthaloyl chloride. The radiochemical yield of (-)-[(11)C]NPA was 2.5% at end of synthesis (EOS), and the synthesis time was 60 min. The specific activity was 1700+/-1900 mCi/micromol ( N=7; ranged 110-5200 mCi/micromol at EOS). Rodent biodistribution studies showed high uptake of [(11)C](-)-NPA in D(2) receptor-rich areas, and the striatum/cerebellum ratios were 1.7, 3.4, and 4.4 at 5 min, 30 min, and 60 min postinjection, respectively. Pretreating the animals with haloperidol (1 mg/kg) decreased the striatum/cerebellum ratio at 30 min postinjection to 1.3. (-)-[(11)C]NPA was also evaluated via baboon positron emission tomography (PET) studies. Under control conditions ( N=4), rapid uptake of the tracer was observed and the striatum/cerebellum ratio reached 2.86+/-0.15 at 45 min postinjection. Following haloperidol pretreatment (0.2 mg/kg IV), the striatum/cerebellum ratio was 1.29 at 45 min postinjection. The result demonstrated the existence of specific binding of this new tracer to the D(2) receptor. To our knowledge, the current finding of a striatum/cerebellum ratio of 2.8 in baboon was the highest reported with a radiolabeled D(2) agonist. (-)-[(11)C]NPA is a promising new D(2) agonist PET tracer for probing D(2) receptors in vivo using PET.

40 CFR 721.4575 - L-aspartic acid, N,N′- [(1E) - 1,2 - ethenediylbis[(3-sulfo-4, 1-phenylene)imino [6-(phenylamino...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-aspartic acid, N,Nâ²- [(1E) - 1,2... Substances § 721.4575 L-aspartic acid, N,N′- [(1E) - 1,2 - ethenediylbis[(3-sulfo-4, 1-phenylene)imino [6... uses subject to reporting. (1) The chemical substance identified as l-aspartic acid, N,N′- [(1E) - 1,2...

Amino acid N-malonyltransferases from mung beans. Action on 1-aminocyclopropane-1-carboxylic acid and D-phenylalanine.

PubMed

Guo, L; Phillips, A T; Arteca, R N

1993-12-05

1-Aminocyclopropane-1-carboxylate (ACC) N-malonyltransferase from etiolated mung bean hypocotyls was examined for its relationship to D-phenylalanine N-malonyltransferase and other enzymes which transfer malonyl groups from malonyl-CoA to D-amino acids. Throughout a 3600-fold purification the ratio of D-phenylalanine N-malonyltransferase activity to ACC N-malonyltransferase activity was unchanged. Antibodies raised against purified ACC N-malonyltransferase 55-kDa protein were also able to precipitate all D-phenylalanine-directed activity from partially purified mung bean extracts. The irreversible inhibitors phenylglyoxal and tetranitromethane reduced malonyltransferase activity towards D-phenylalanine to the same extent as that for ACC. In addition, several other D-amino acids, particularly D-tryptophan and D-tyrosine, were able to inhibit action towards both ACC and D-phenylalanine. These lines of evidence suggest that a single enzyme is capable of promoting malonylation of both ACC and D-phenylalanine. Km values for D-phenylalanine and malonyl-CoA were found to be 48 and 43 microM, respectively; these values are 10-fold lower than the corresponding values when ACC was substrate. Coenzyme A was a noncompetitive (mixed type) product inhibitor towards malonyl-CoA at both unsaturated and saturated ACC concentrations. The enzyme was also inhibited uncompetitively at high concentrations of malonyl-CoA. We propose that the enzyme follows an Ordered Bi-Bi reaction pathway, with the amino acid substrate being bound initially.

Crystal structures of three co-crystals of 1,2-bis-(pyridin-4-yl)ethane with 4-alk-oxy-benzoic acids: 4-eth-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1), 4-n-propoxybenzoic acid-1,2-bis(pyridin-4-yl)ethane (2/1) and 4-n-but-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1).

PubMed

Tabuchi, Yohei; Gotoh, Kazuma; Ishida, Hiroyuki

2015-11-01

The crystal structures of three hydrogen-bonded co-crystals of 4-alk-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1), namely, 2C9H10O3·C12H12N2, (I), 2C10H12O3·C12H12N2, (II), and 2C11H14O3·C12H12N2, (III), have been determined at 93, 290 and 93 K, respectively. In (I), the asymmetric unit consists of one 4-eth-oxy-benzoic acid mol-ecule and one half-mol-ecule of 1,2-bis-(pyridin-4-yl)ethane, which lies on an inversion centre. In (II) and (III), the asymmetric units each comprise two crystallographically independent 4-alk-oxy-benzoic acid mol-ecules and one 1,2-bis-(pyridin-4-yl)ethane mol-ecule. In each crystal, the two components are linked by O-H⋯N hydrogen bonds, forming a linear hydrogen-bonded 2:1unit of the acid and the base. Similar to the structure of 2:1 unit of (I), the units of (II) and (III) adopt nearly pseudo-inversion symmetry. The 2:1 units of (I), (II) and (III) are linked via C-H⋯O hydrogen bonds, forming tape structures.

Development of a novel naphthoic acid ionic liquid and its application in "no-organic solvent microextraction" for determination of triclosan and methyltriclosan in human fluids and the method optimization by central composite design.

PubMed

Wang, Hui; Gao, Jiajia; Yu, Nana; Qu, Jingang; Fang, Fang; Wang, Huili; Wang, Mei; Wang, Xuedong

2016-07-01

In traditional ionic liquids (ILs)-based microextraction, the hydrophobic and hydrophilic ILs are often used as extractant and disperser, respectively. However, the functional effects of ILs are not utilized in microextraction procedures. Herein, we introduced 1-naphthoic acid into imidazolium ring to synthesize a novel ionic liquid 1-butyl-3-methylimidazolium naphthoic acid salt ([C4MIM][NPA]), and its structure was characterized by IR, (1)H NMR and MS. On the basis of its acidic property and lower solubility than common [CnMIM][BF4], it was used as a mixing dispersive solvent with [C4MIM][BF4] in "functionalized ionic liquid-based no organic solvent microextraction (FIL-NOSM)". Utilization of [C4MIM][NPA] in FIL-NOSM procedures has two obvious advantages: (1) it promoted the non-polar environment, increased volume of the sedimented phase, and thus could enhance the extraction recoveries of triclosan (TCS) and methyltriclosan (MTCS) by more than 10%; and (2) because of the acidic property, it can act as a pH modifier, avoiding extra pH adjustment step. By combining single factor optimization and central composite design, the main factors in the FIL-NOSM method were optimized. Under the optimal conditions, the relative recoveries of TCS and MTCS reached up to 98.60-106.09%, and the LODs of them were as low as 0.12-0.15µgL(-1) in plasma and urine samples. In total, this [C4MIM][NPA]-based FIL-NOSM method provided high extraction efficiency, and required less pretreatment time and unutilized any organic solvent. To the best of our knowledge, this is the first application of [C4mim][NPA]-based microextraction method for the simultaneous quantification of trace TCS and MTCS in human fluids. Copyright © 2016 Elsevier B.V. All rights reserved.

Palmitoleic acid (16:1n7) increases oxygen consumption, fatty acid oxidation and ATP content in white adipocytes.

PubMed

Cruz, Maysa M; Lopes, Andressa B; Crisma, Amanda R; de Sá, Roberta C C; Kuwabara, Wilson M T; Curi, Rui; de Andrade, Paula B M; Alonso-Vale, Maria I C

2018-03-20

We have recently demonstrated that palmitoleic acid (16:1n7) increases lipolysis, glucose uptake and glucose utilization for energy production in white adipose cells. In the present study, we tested the hypothesis that palmitoleic acid modulates bioenergetic activity in white adipocytes. For this, 3 T3-L1 pre-adipocytes were differentiated into mature adipocytes in the presence (or absence) of palmitic (16:0) or palmitoleic (16:1n7) acid at 100 or 200 μM. The following parameters were evaluated: lipolysis, lipogenesis, fatty acid (FA) oxidation, ATP content, oxygen consumption, mitochondrial mass, citrate synthase activity and protein content of mitochondrial oxidative phosphorylation (OXPHOS) complexes. Treatment with 16:1n7 during 9 days raised basal and isoproterenol-stimulated lipolysis, FA incorporation into triacylglycerol (TAG), FA oxidation, oxygen consumption, protein expression of subunits representing OXPHOS complex II, III, and V and intracellular ATP content. These effects were not observed in adipocytes treated with 16:0. Palmitoleic acid, by concerted action on lipolysis, FA esterification, mitochondrial FA oxidation, oxygen consumption and ATP content, does enhance white adipocyte energy expenditure and may act as local hormone.

Gravi-photomorphogenesis of the moss Pottia intermedia protonemata

NASA Astrophysics Data System (ADS)

Demkiv, O. T.; Kyjak, N. Y.; Khorkavtsiv, Y. D.; Kit, N. A.

sufficiently high and the addition of exogenous kinetin may be superfluous for bud formation being, however, not superfluous in diploid. It was established earlier that IAA participates gametophore bud formation stimulating caulonema differentiation and inducing the competence to cytokinins action. 3,0 μ M and 30,0 μ M phytotropin of N-1-naphthylphthalamic acid (NPA), the blockator of IAA efflux, were used in our investigations. 1,0 μ M of synthesized auxin I-NAA did not essentially influence gametophore bud formation in both haploid and diploid P. intermedia protonema. However, during combine action of NPA and NAA the inhibitory effect of 3,0 μ M of NPA was eliminated the ability of gravitropic protonema to form gametophore buds being renewed.

3-Nitropropionic acid production by the endophytic Diaporthe citri: Molecular taxonomy, chemical characterization, and quantification under pH variation.

PubMed

Polonio, Julio Cesar; Ribeiro, Marcos Alessandro Dos Santos; Rhoden, Sandro Augusto; Sarragiotto, Maria Helena; Azevedo, João Lúcio; Pamphile, João Alencar

2016-12-01

3-nitropropionic acid (3-NPA) is a nitrogenated compound produced by plants and fungi and has been associated with poisoning episodes in humans, animals, and to induction of Huntington disease symptoms in rats. The production of 3-NPA by endophytes has been reported, but the function and biosynthesis are not well-defined. The specie of endophytic strain G-01 was confirmed as Diaporthe citri using a multilocus sequence analysis, and was verified different concentrations of 3-NPA produced at different initial pHs by these strain. The chemical analysis indicated that 3-NPA was the majority compound present in the crude extracts. The better extraction condition was at an initial pH of 7.0 for 22 d, yielding about 80 % of 3-NPA per mg of extract. It was observed that the concentration of 3-NPA increased after the initial consumption of reduction sugars, indicating that the compound is produced after the high energetic production phase of the fungus. These and other studies demonstrate the production of this compound by plants and endophytic fungi, indicating that 3-NPA may be involved in defence and nutrition systems of endophytes and host plants, and they also might participate in the biogeochemical nitrogen cycle. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Gravity-stimulated changes in auxin and invertase gene expression in maize pulvinal cells

NASA Technical Reports Server (NTRS)

Long, Joanne C.; Zhao, Wei; Rashotte, Aaron M.; Muday, Gloria K.; Huber, Steven C.; Brown, C. S. (Principal Investigator)

2002-01-01

Maize (Zea mays) stem gravitropism involves differential elongation of cells within a highly specialized region, the stem internodal pulvinus. In the present study, we investigated factors that control gravitropic responses in this system. In the graviresponding pulvinus, hexose sugars (D-Glc and D-Fru) accumulated asymmetrically across the pulvinus. This correlated well with an asymmetric increase in acid invertase activity across the pulvinus. Northern analyses revealed asymmetric induction of one maize acid invertase gene, Ivr2, consistent with transcriptional regulation by gravistimulation. Several lines of evidence indicated that auxin redistribution, as a result of polar auxin transport, is necessary for gravity-stimulated Ivr2 transcript accumulation and differential cell elongation across the maize pulvinus. First, the auxin transport inhibitor, N-1-naphthylphthalamic acid, inhibited gravistimulated curvature and Ivr2 transcript accumulation. Second, a transient gradient of free indole-3-acetic acid (IAA) across the pulvinus was apparent shortly after initiation of gravistimulation. This temporarily free IAA gradient appears to be important for differential cell elongation and Ivr2 transcript accumulation. This is based on the observation that N-1-naphthylphthalamic acid will not inhibit gravitropic responses when applied to pulvinus tissue after the free IAA gradient peak has occurred. Third, IAA alone can stimulate Ivr2 transcript accumulation in non-gravistimulated pulvini. The gravity- and IAA-stimulated increase in Ivr2 transcripts was sensitive to the protein synthesis inhibitor, cycloheximide. Based on these results, a two-phase model describing possible relationships between gravitropic curvature, IAA redistribution, and Ivr2 expression is presented.

Equilibrium geometries, electronic and magnetic properties of small AunNi- (n = 1-9) clusters

NASA Astrophysics Data System (ADS)

Tang, Cui-Ming; Chen, Xiao-Xu; Yang, Xiang-Dong

2014-05-01

Geometrical, electronic and magnetic properties of small AunNi- (n = 1-9) clusters have been investigated based on density functional theory (DFT) at PW91P86 level. An extensive structural search shows that the relative stable structures of AunNi- (n = 1-9) clusters adopt 2D structure for n = 1-5, 7 and 3D structure for n = 6, 8-9. And the substitution of a Ni atom for an Au atom in the Au-n+1 cluster obviously changes the structure of the host cluster. Moreover, an odd-even alternation phenomenon has been found for HOMO-LUMO energy gaps, indicating that the relative stable structures of the AunNi- clusters with odd-numbered gold atoms have a higher relative stability. Finally, the natural population analysis (NPA) and the vertical detachment energies (VDE) are studied, respectively. The theoretical values of VDE are reported for the first time to our best knowledge.

Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses

PubMed Central

Koel, Björn F.; Mögling, Ramona; Chutinimitkul, Salin; Fraaij, Pieter L.; Burke, David F.; van der Vliet, Stefan; de Wit, Emmie; Bestebroer, Theo M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Smith, Derek J.; Fouchier, Ron A. M.

2015-01-01

ABSTRACT The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency in vitro compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity. IMPORTANCE Influenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus

Neuroprotective efficacy of a combination of fish oil and ferulic acid against 3-nitropropionic acid-induced oxidative stress and neurotoxicity in rats: behavioural and biochemical evidence.

PubMed

K M, Denny Joseph; Muralidhara

2014-04-01

The beneficial effects of fish oil (FO) supplements on the central nervous system have been adequately demonstrated. However, FO supplementation at higher doses for longer duration is likely to cause oxidative stress in vivo. To overcome this, attempts have been made to enrich FO with known antioxidants/phytochemicals. In the present study, we examined the hypothesis that a combination of FO with ferulic acid (FA), a naturally occurring phenolic compound, is likely to provide higher degree of neuroprotection. This was examined by employing 3-nitropropionic acid (NPA), a well-known neurotoxin used to mimic behavioural and neurochemical features of Huntington's disease. Growing male rats administered with NPA (25 mg/kg of body weight (bw) for 4 days) were provided with either FO (2 mL/kg bw), FA (50 mg/kg bw) or FO+FA for 2 weeks. Interestingly, FO+FA not only offered significant protection against NPA-induced behavioural impairments, but also markedly attenuated oxidative stress in brain regions (striatum/cerebellum) as evidenced by the reduction in reactive species, malondialdehyde, hydroperoxides and nitric oxide (NO) levels. Further, FO+FA combination restored the activities of various antioxidant enzymes and the levels of cytosolic calcium. In striatum, activity levels of acetylcholinesterase enzyme and dopamine levels were markedly restored among FO+FA rats. Interestingly, NPA-induced mitochondrial dysfunctions were also attenuated among FO+FA rats. Collectively, our findings suggest the advantage of co-treatment of FO with known antioxidants to achieve a higher therapeutic benefit in the treatment of oxidative stress-mediated neurodegenerative conditions.

Apigenin and quercetin promote. Delta. pH-dependent accumulation of IAA in membrane vesicles

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

Woolard, D.D.; Clark, K.A.

1990-05-01

Flavonoids may act as regulators of polar auxin transport. In the presence of a pH gradient (pH 8{sub in}/6{sub out}) the flavonoids quercetin and apigenin, as well as the synthetic herbicide napthylphthalamic acid (NPA), promote the accumulation of IAA in membrane vesicles from dark-grown zucchini hypocotyls. Simultaneous accumulation of {sup 3}H-IAA (10 nM) and {sup 14}C-butyric acid (5 {mu}M; included as a pH probe) was determined by a filtration assay after incubating the vesicles with 3 nM to 100 {mu}M quercetin, apigenin, NPA or unlabeled IAA. Maximal stimulation (% of Control) was observed with 3 {mu}M NPA (130%), 1 {mu}Mmore » quercetin (120%), or 3 {mu}M apigenin (115%); {Delta}pH was not affected by these concentrations. As reported by others, IAA uptake was saturable: 1 {mu}M unlabeled IAA eliminated {Delta}pH-dependent uptake of {sup 3}H-IAA without altering {Delta}pH. However, at 30 to 100 {mu}M, every compound tested collapsed the imposed pH gradient and therefore abolished specific {sup 3}H-IAA uptake.« less

[Effects of nitrogen preserving agent on composting process and nitrogen loss of Eichhornia crassipes].

PubMed

Li, Sen; Luo, Xue Mei; Tu, Wei Guo; Fan, Hua; Gou, Xiao Lin; DU, Yu Long; Li, Ling; Wang, Qiong Yao

2017-04-18

To study the effects of nitrogen preserving agent (NPA) on composting process and nitrogen loss of Eichhornia crassipes, an aerobic composting was conducted for 35 days using four treatments. The NPA was prepared by mixing ferrous sulfate, humic acid sodium, and superphosphate (M:M:M=75:20:5). Four treatments were included with different mass ratios of NPA, including 0% (CK), 1% (PN1), 2% (PN2), and 3% (PN3). The physical and chemical properties, N fraction concentrations, ammonia volatilization, and N loss rates were measured and explored during composting process. The results showed that the pile temperature of NPA treatments were higher than that of CK in thermophillic period, however their water contents were significantly (P＜0.05) lower than that in CK in cooling period. At the end of composting, the concentrations of total nitrogen and organic nitrogen increased significantly in NPA treatments (P＜0.05), and their highest concentrations in the PN3 treatment were 16.3% and 13.2% higher than those in CK, respectively. The ammonia volatilization losses of PN1, PN2 and PN3 treatments were 25.9%, 31.5% and 42.4% lower than that of CK, respectively, however, their nitrogen fixation rates reached 31.3%, 40.7% and 72.2% respectively. Therefore, adding NPA could accelerate start-up speed, shorten composting time, and also could effectively reduce ammonia volatilizations and nitrogen loss in the composting process of E. crassipes. Therefore, PN3 showed the best effects of nitrogen preserving.

Development and optimization of a naphthoic acid-based ionic liquid as a "non-organic solvent microextraction" for the determination of tetracycline antibiotics in milk and chicken eggs.

PubMed

Gao, Jiajia; Wang, Hui; Qu, Jingang; Wang, Huili; Wang, Xuedong

2017-01-15

In traditional ionic liquids (ILs)-based microextraction, ILs are often used as extraction and dispersive solvents; however, their functional effects are not fully utilized. Herein, we developed a novel ionic liquid 1-butyl-3-methylimidazolium naphthoic acid salt ([C4MIM][NPA]) with strong acidity. It was used as a mixed dispersive solvent with conventional [C2MIM][BF4] in "functionalized ionic liquid-based non-organic solvent microextraction (FIL-NOSM)" for determination of tetracycline antibiotics (TCs) in milk and eggs. Utilization of [C4MIM][NPA] in FIL-NOSM method increased extraction recoveries (ERs) of TCs by more than 20% and eliminated the pH adjustment step because of its strong acidity. Under optimized conditions based on central composite design, the ERs of four TCs were 94.1-102.1%, and the limitsofdetection were 0.08-1.12μgkg(-1) in milk and egg samples. This proposed method provides high extraction efficiency, less pretreatment time and requires non-organic solvents for determination of trace TC concentrations in complex animal-based food matrices. Copyright © 2016 Elsevier Ltd. All rights reserved.

Expression of a gymnosperm PIN homologous gene correlates with auxin immunolocalization pattern at cotyledon formation and in demarcation of the procambium during Picea abies somatic embryo development and in seedling tissues.

PubMed

Palovaara, Joakim; Hallberg, Henrik; Stasolla, Claudio; Luit, Bert; Hakman, Inger

2010-04-01

In seed plants, the body organization is established during embryogenesis and is uniform across gymnosperms and angiosperms, despite differences during early embryogeny. Evidence from angiosperms implicates the plant hormone auxin and its polar transport, mainly established by the PIN family of auxin efflux transporters, in the patterning of embryos. Here, PaPIN1 from Norway spruce (Picea abies [L.] Karst.), a gene widely expressed in conifer tissues and organs, was characterized and its expression and localization patterns were determined with reverse transcription polymerase chain reaction and in situ hybridization during somatic embryo development and in seedlings. PaPIN1 shares the predicted structure of other PIN proteins, but its central hydrophilic loop is longer than most PINs. In phylogenetic analyses, PaPIN1 clusters with Arabidopsis thaliana (L.) Heynh. PIN3, PIN4 and PIN7, but its expression pattern also suggests similarity to PIN1. The PaPIN1 expression signal was high in the protoderm of pre-cotyledonary embryos, but not if embryos were pre-treated with the auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). This, together with a high auxin immunolocalization signal in this cell layer, suggests a role of PaPIN1 during cotyledon formation. At later stages, high PaPIN1 expression was observed in differentiating procambium, running from the tip of incipient cotyledons down through the embryo axis and to the root apical meristem (RAM), although the mode of RAM specification in conifer embryos differs from that of most angiosperms. Also, the PaPIN1 in situ signal was high in seedling root tips including root cap columella cells. The results thus suggest that PaPIN1 provides an ancient function associated with auxin transport and embryo pattern formation prior to the separation of angiosperms and gymnosperms, in spite of some morphological differences.

Docosahexaenoic acid synthesis from n-3 fatty acid precursors in rat hippocampal neurons.

PubMed

Kaduce, Terry L; Chen, Yucui; Hell, Johannes W; Spector, Arthur A

2008-05-01

Docosahexaenoic acid (DHA), the most abundant n-3 polyunsaturated fatty acid in the brain, has important functions in the hippocampus. To better understand essential fatty acid homeostasis in this region of the brain, we investigated the contributions of n-3 fatty acid precursors in supplying hippocampal neurons with DHA. Primary cultures of rat hippocampal neurons incorporated radiolabeled 18-, 20-, 22-, and 24-carbon n-3 fatty acid and converted some of the uptake to DHA, but the amounts produced from either [1-14C]alpha-linolenic or [1-14C]eicosapentaenoic acid were considerably less than the amounts incorporated when the cultures were incubated with [1-14C]22:6n-3. Most of the [1-14C]22:6n-3 uptake was incorporated into phospholipids, primarily ethanolamine phosphoglycerides. Additional studies demonstrated that the neurons converted [1-14C]linoleic acid to arachidonic acid, the main n-6 fatty acid in the brain. These findings differ from previous results indicating that cerebral and cerebellar neurons cannot convert polyunsaturated fatty acid precursors to DHA or arachidonic acid. Fatty acid compositional analysis demonstrated that the hippocampal neurons contained only 1.1-2.5 mol% DHA under the usual low-DHA culture conditions. The relatively low-DHA content suggests that some responses obtained with these cultures may not be representative of neuronal function in the brain.

Dietary (n-6 : n-3) Fatty Acids Alter Plasma and Tissue Fatty Acid Composition in Pregnant Sprague Dawley Rats

PubMed Central

Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

2012-01-01

The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat. PMID:22489205

Expression pattern of four storage xyloglucan mobilization-related genes during seedling development of the rain forest tree Hymenaea courbaril L.

PubMed

Brandão, A D; Del Bem, L E V; Vincentz, M; Buckeridge, M S

2009-01-01

During seedling establishment, cotyledons of the rain forest tree Hymenaea courbaril mobilize storage cell wall xyloglucan to sustain growth. The polysaccharide is degraded and its products are transported to growing sink tissues. Auxin from the shoot controls the level of xyloglucan hydrolytic enzymes. It is not yet known how important the expression of these genes is for the control of storage xyloglucan degradation. In this work, partial cDNAs of the genes xyloglucan transglycosylase hydrolase (HcXTH1) and beta-galactosidase (HcBGAL1), both related to xyloglucan degradation, and two other genes related to sucrose metabolism [alkaline invertase (HcAlkIN1) and sucrose synthase (HcSUS1)], were isolated. The partial sequences were characterized by comparison with sequences available in the literature, and phylogenetic trees were assembled. Gene expression was evaluated at intervals of 6 h during 24 h in cotyledons, hypocotyl, roots, and leaves, using 45-d-old plantlets. HcXTH1 and HcBGAL1 were correlated to xyloglucan degradation and responded to auxin and light, being down-regulated when transport of auxin was prevented by N-1-naphthylphthalamic acid (NPA) and stimulated by constant light. Genes related to sucrose metabolism, HcAlkIN1 and HcSUS1, responded to inhibition of auxin transport in consonance with storage mobilization in the cotyledons. A model is proposed suggesting that auxin and light are involved in the control of the expression of genes related to storage xyloglucan mobilization in seedlings of H. courbaril. It is concluded that gene expression plays a role in the control of the intercommunication system of the source-sink relationship during seeding growth, favouring its establishment in the shaded environment of the rain forest understorey.

Expression pattern of four storage xyloglucan mobilization-related genes during seedling development of the rain forest tree Hymenaea courbaril L.

PubMed Central

Brandão, A. D.; Del Bem, L. E. V.; Vincentz, M.; Buckeridge, M. S.

2009-01-01

During seedling establishment, cotyledons of the rain forest tree Hymenaea courbaril mobilize storage cell wall xyloglucan to sustain growth. The polysaccharide is degraded and its products are transported to growing sink tissues. Auxin from the shoot controls the level of xyloglucan hydrolytic enzymes. It is not yet known how important the expression of these genes is for the control of storage xyloglucan degradation. In this work, partial cDNAs of the genes xyloglucan transglycosylase hydrolase (HcXTH1) and β-galactosidase (HcBGAL1), both related to xyloglucan degradation, and two other genes related to sucrose metabolism [alkaline invertase (HcAlkIN1) and sucrose synthase (HcSUS1)], were isolated. The partial sequences were characterized by comparison with sequences available in the literature, and phylogenetic trees were assembled. Gene expression was evaluated at intervals of 6 h during 24 h in cotyledons, hypocotyl, roots, and leaves, using 45-d-old plantlets. HcXTH1 and HcBGAL1 were correlated to xyloglucan degradation and responded to auxin and light, being down-regulated when transport of auxin was prevented by N-1-naphthylphthalamic acid (NPA) and stimulated by constant light. Genes related to sucrose metabolism, HcAlkIN1 and HcSUS1, responded to inhibition of auxin transport in consonance with storage mobilization in the cotyledons. A model is proposed suggesting that auxin and light are involved in the control of the expression of genes related to storage xyloglucan mobilization in seedlings of H. courbaril. It is concluded that gene expression plays a role in the control of the intercommunication system of the source–sink relationship during seeding growth, favouring its establishment in the shaded environment of the rain forest understorey. PMID:19221141

The mitochondrial toxin, 3-nitropropionic acid, induces extracellular Zn2+ accumulation in rat hippocampus slices.

PubMed

Wei, Guo; Hough, Christopher J; Sarvey, John M

2004-11-11

3-nitropropionic acid (3-NPA), a suicide inhibitor of succinate dehydrogenase (SDH; complex II), has been used to provide useful experimental models of Huntington's disease (HD) and "chemical hypoxia" in rodents. The trace ion Zn2+ has been shown to cause neurodegeneration. Employing real-time Newport Green fluorescence imaging of extracellular Zn2+, we found that 3-NPA (10-100 microM) caused a concentration-dependent increase in the concentration of extracellular Zn2+ ([Zn2+]o) in acute rat hippocampus slices. This increase in [Zn2+]o was abolished by 10 mM CaEDTA. The increase of [Zn2+]o was also accompanied by a rapid increase of cytoplasmic-free Zn2+ concentration ([Zn2+]i). The induction of Zn2+ release by 3-MPA in hippocampus slices points to a potential mechanism by which 3-NPA might induce neurodegeneration.

Risk Factors for Sporadic Non-Pregnancy Associated Listeriosis in Germany-Immunocompromised Patients and Frequently Consumed Ready-To-Eat Products.

PubMed

Preußel, Karina; Milde-Busch, Astrid; Schmich, Patrick; Wetzstein, Matthias; Stark, Klaus; Werber, Dirk

2015-01-01

Non-pregnancy associated (N-PA) listeriosis, caused by Listeria monocytogenes, is a rare but severe disease, and is predominantly food-borne. Most cases appear sporadic and their infection vehicle remains unknown. Incidence has increased since 2008 in Germany. We aimed to identify underlying conditions and foods associated with sporadic N-PA listeriosis in Germany. We performed a nationwide case-control study from March 2012-December 2013. Cases were sporadic N-PA listeriosis patients notified to public health. Control subjects were age (40-65 years, 66-75 years, ≥ 76 years) frequency-matched persons from a nationwide random telephone sample. A structured questionnaire collected information on underlying diseases, therapies and >60 food items. We conducted multivariable logistic regression analysis, adjusting for host factors identified by causal diagram theory, and calculated population attributable fractions. We enrolled 109 cases and 1982 controls. Cases' median age was 69 years, 55% were male, 44% received immunosuppressive therapy within 3 months prior to illness onset; a further 28% had at least one immunocompromising disease. In multivariable analysis, immunosuppressive therapy (OR 8.8, 95%CI 4.9-15.6), immunocompromising disease (OR 2.7; 95%CI 1.4-5.2), gastric acid suppression (OR 3.0; 95%CI 1.4-6.3), the consumption of cold cooked sausages (OR 2.6; 95%CI 1.6-4.4), the preferred consumption of packaged cheese (OR 2.1; 95%CI 1.3-3.5) and pre-sliced cheese (OR 2.2; 95%CI 1.3-3.7) were significantly associated with N-PA listeriosis. These foods accounted for 59% of all cases. Typical high risk foods, e.g. cold seafood, certain types of cheeses, tended to be negatively associated with disease. In conclusion, immunosuppressive therapy and frequently consumed ready-to-eat foods are the main risk factors for sporadic N-PA listeriosis in Germany. To reduce their risk, immunocompromised persons should consume the identified foods well before the 'use-by' date

Chiral discrimination of α-hydroxy acids and N-Ts-α-amino acids induced by tetraaza macrocyclic chiral solvating agents by using 1H NMR spectroscopy.

PubMed

Lv, Caixia; Feng, Lei; Zhao, Hongmei; Wang, Guo; Stavropoulos, Pericles; Ai, Lin

2017-02-21

In the field of chiral recognition, reported chiral discrimination by 1 H NMR spectroscopy has mainly focused on various chiral analytes with a single chiral center, regarded as standard chiral substrates to evaluate the chiral discriminating abilities of a chiral auxiliary. Among them, chiral α-hydroxy acids, α-amino acids and their derivatives are chiral organic molecules involved in a wide variety of biological processes, and also play an important role in the area of preparation of pharmaceuticals, as they are part of the synthetic process in the production of chiral drug intermediates and protein-based drugs. In this paper, several α-hydroxy acids and N-Ts-α-amino acids were used to evaluate the chiral discriminating abilities of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1d by 1 H NMR spectroscopy. The results indicate that α-hydroxy acids and N-Ts-α-amino acids were successfully discriminated in the presence of TAMCSAs 1a-1d by 1 H NMR spectroscopy in most cases. The enantiomers of the α-hydroxy acids and N-Ts-α-amino acids were assigned based on the change of integration of the 1 H NMR signals of the corresponding protons. The enantiomeric excesses (ee) of N-Ts-α-amino acids 11 with different optical compositions were calculated based on the integration of the 1 H NMR signals of the CH 3 protons (Ts group) of the enantiomers of (R)- and (S)-11 in the presence of TAMCSA 1b. At the same time, the possible chiral discriminating behaviors have been discussed by means of the Job plots of (±)-2 with TAMCSAs 1b and proposed theoretical models of the enantiomers of 2 and 6 with TAMCSA 1a, respectively.

Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay

NASA Astrophysics Data System (ADS)

Hariono, Maywan; Abdullah, Nurshariza; Damodaran, K. V.; Kamarulzaman, Ezatul E.; Mohamed, Nornisah; Hassan, Sharifah Syed; Shamsuddin, Shaharum; Wahab, Habibah A.

2016-12-01

We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ~0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.

Heterologous expression of C. elegans fat-1 decreases the n-6/n-3 fatty acid ratio and inhibits adipogenesis in 3T3-L1 cells

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

An, Lei, E-mail: anleim@yahoo.com.cn; Pang, Yun-Wei, E-mail: yunweipang@126.com; Gao, Hong-Mei, E-mail: Gaohongmei_123@yahoo.cn

Highlights: Black-Right-Pointing-Pointer Expression of C. elegans fat-1 reduces the n-6/n-3 PUFA ratio in 3T3-L1 cells. Black-Right-Pointing-Pointer fat-1 inhibits the proliferation and differentiation of 3T3-L1 preadipocytes. Black-Right-Pointing-Pointer fat-1 reduces lipid deposition in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer The lower n-6/n-3 ratio induces apoptosis in 3T3-L1 adipocytes. -- Abstract: In general, a diet enriched in polyunsaturated fatty acids (PUFAs) inhibits the development of obesity and decreases adipose tissue. The specific impacts of n-3 and n-6 PUFAs on adipogenesis, however, have not been definitively determined. Traditional in vivo and in vitro supplementation studies have yielded inconsistent or even contradictory results, which likely reflect insufficiently controlledmore » experimental systems. Caenorhabditiselegans fat-1 gene encodes an n-3 fatty acid desaturase, and its heterologous expression represents an effective method both for altering the n-6/n-3 PUFA ratio and for evaluating the biological effects of n-3 and n-6 PUFAs. We sought to determine whether a reduced n-6/n-3 ratio could influence adipogenesis in 3T3-L1 cells. Lentivirus-mediated introduction of the fat-1 gene into 3T3-L1 preadipocytes significantly reduced the n-6/n-3 ratio and inhibited preadipocyte proliferation and differentiation. In mature adipocytes, fat-1 expression reduced lipid deposition, as measured by Oil Red O staining, and induced apoptosis. Our results indicate that a reduced n-6/n-3 ratio inhibits adipogenesis through several mechanisms and that n-3 PUFAs more effectively inhibit adipogenesis (but not lipogenesis) than do n-6 PUFAs.« less

Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains.

PubMed Central

Tell, G; Perrone, L; Fabbro, D; Pellizzari, L; Pucillo, C; De Felice, M; Acquaviva, R; Formisano, S; Damante, G

1998-01-01

The thyroid transcription factor 1 (TTF-1) is a tissue-specific transcription factor involved in the development of thyroid and lung. TTF-1 contains two transcriptional activation domains (N and C domain). The primary amino acid sequence of the N domain does not show any typical characteristic of known transcriptional activation domains. In aqueous solution the N domain exists in a random-coil conformation. The increase of the milieu hydrophobicity, by the addition of trifluoroethanol, induces a considerable gain of alpha-helical structure. Acidic transcriptional activation domains are largely unstructured in solution, but, under hydrophobic conditions, folding into alpha-helices or beta-strands can be induced. Therefore our data indicate that the inducibility of alpha-helix by hydrophobic conditions is a property not restricted to acidic domains. Co-transfections experiments indicate that the acidic domain of herpes simplex virus protein VP16 (VP16) and the TTF-1 N domain are interchangeable and that a chimaeric protein, which combines VP16 linked to the DNA-binding domain of TTF-1, undergoes the same regulatory constraints that operate for the wild-type TTF-1. In addition, we demonstrate that the TTF-1 N domain possesses two typical properties of acidic activation domains: TBP (TATA-binding protein) binding and ability to activate transcription in yeast. Accordingly, the TTF-1 N domain is able to squelch the activity of the p65 acidic domain. Altogether, these structural and functional data suggest that a non-acidic transcriptional activation domain (TTF-1 N domain) activates transcription by using molecular mechanisms similar to those used by acidic domains. TTF-1 N domain and acidic domains define a family of proteins whose common property is to activate transcription through the use of mechanisms largely conserved during evolutionary development. PMID:9425125

N-3 fatty acids reduced trans fatty acids retention and increased docosahexaenoic acid levels in the brain.

PubMed

Lavandera, Jimena Verónica; Saín, Juliana; Fariña, Ana Clara; Bernal, Claudio Adrián; González, Marcela Aída

2017-09-01

The levels of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are critical for the normal structure and function of the brain. Trans fatty acids (TFA) and the source of the dietary fatty acids (FA) interfere with long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis. The aim of this study was to investigate the effect of TFA supplementation in diets containing different proportions of n-9, n-6, and n-3 FA on the brain FA profile, including the retention of TFA, LC-PUFA levels, and n-6/n-3 PUFA ratios. These parameters were also investigated in the liver, considering that LC-PUFA are mainly bioconverted from their dietary precursors in this tissue and transported by serum to the brain. Also, stearoyl-CoA desaturase-1 (SCD1) and sterol regulatory element-binding protein-1c (SREBP-1c) gene expressions were evaluated. Male CF1 mice were fed (16 weeks) diets containing different oils (olive, corn, and rapeseed) with distinct proportions of n-9, n-6, and n-3 FA (55.2/17.2/0.7, 32.0/51.3/0.9, and 61.1/18.4/8.6), respectively, substituted or not with 0.75% of TFA. FA composition of the brain, liver, and serum was assessed by gas chromatography. TFA were incorporated into, and therefore retained in the brain, liver, and serum. However, the magnitude of retention was dependent on the tissue and type of isomer. In the brain, total TFA retention was lower than 1% in all diets. Dietary n-3 PUFA decreased TFA retention and increased DHA accretion in the brain. The results underscore the importance of the type of dietary FA on the retention of TFA in the brain and also on the changes of the FA profile.

The Prion Protein N1 and N2 Cleavage Fragments Bind to Phosphatidylserine and Phosphatidic Acid; Relevance to Stress-Protection Responses.

PubMed

Haigh, Cathryn L; Tumpach, Carolin; Drew, Simon C; Collins, Steven J

2015-01-01

Internal cleavage of the cellular prion protein generates two well characterised N-terminal fragments, N1 and N2. These fragments have been shown to bind to anionic phospholipids at low pH. We sought to investigate binding with other lipid moieties and queried how such interactions could be relevant to the cellular functions of these fragments. Both N1 and N2 bound phosphatidylserine (PS), as previously reported, and a further interaction with phosphatidic acid (PA) was also identified. The specificity of this interaction required the N-terminus, especially the proline motif within the basic amino acids at the N-terminus, together with the copper-binding region (unrelated to copper saturation). Previously, the fragments have been shown to be protective against cellular stresses. In the current study, serum deprivation was used to induce changes in the cellular lipid environment, including externalisation of plasma membrane PS and increased cellular levels of PA. When copper-saturated, N2 could reverse these changes, but N1 could not, suggesting that direct binding of N2 to cellular lipids may be part of the mechanism by which this peptide signals its protective response.

The Prion Protein N1 and N2 Cleavage Fragments Bind to Phosphatidylserine and Phosphatidic Acid; Relevance to Stress-Protection Responses

PubMed Central

Haigh, Cathryn L.; Tumpach, Carolin; Drew, Simon C.; Collins, Steven J.

2015-01-01

Internal cleavage of the cellular prion protein generates two well characterised N-terminal fragments, N1 and N2. These fragments have been shown to bind to anionic phospholipids at low pH. We sought to investigate binding with other lipid moieties and queried how such interactions could be relevant to the cellular functions of these fragments. Both N1 and N2 bound phosphatidylserine (PS), as previously reported, and a further interaction with phosphatidic acid (PA) was also identified. The specificity of this interaction required the N-terminus, especially the proline motif within the basic amino acids at the N-terminus, together with the copper-binding region (unrelated to copper saturation). Previously, the fragments have been shown to be protective against cellular stresses. In the current study, serum deprivation was used to induce changes in the cellular lipid environment, including externalisation of plasma membrane PS and increased cellular levels of PA. When copper-saturated, N2 could reverse these changes, but N1 could not, suggesting that direct binding of N2 to cellular lipids may be part of the mechanism by which this peptide signals its protective response. PMID:26252007

The suppression of the N-nitrosating reaction by chlorogenic acid.

PubMed Central

Kono, Y; Shibata, H; Kodama, Y; Sawa, Y

1995-01-01

N-Nitrosation of a model aromatic amine (2,3-diamino-naphthalene) by the N-nitrosating agent produced by nitrite in acidic solution was inhibited by a polyphenol, chlorogenic acid, which is an ester of caffeic acid quinic acid. Caffeic acid also inhibited the N-nitrosation, but quinic acid did not. 1,2-Benzenediols and 3,4-dihydroxybenzoic acid had inhibitory activities. Chlorogenic acid, caffeic acid, 1,2-benzenediols and 3,4-dihydroxybenzoic acid were able to scavenge the stable free radical, 1,1-diphenyl-2-picrylhydrazyl. Chlorogenic acid was found to be nitrated by acidic nitrite. The kinetic studies and the nitration observed only by bubbling of nitric oxide plus nitrogen dioxide gases indicated that the nitrating agent was nitrogen sesquioxide. The observations showed that the mechanism by which chlorogenic acid inhibited N-nitrosation of 2,3-diamino-naphthalene is due to its ability to scavenge the nitrosating agent, nitrogen sesquioxide. Chlorogenic acid may be effective not only in protecting against oxidative damage but also in inhibiting potentially mutagenic and carcinogenic reactions in vivo. PMID:8554543

Risk Factors for Sporadic Non-Pregnancy Associated Listeriosis in Germany—Immunocompromised Patients and Frequently Consumed Ready-To-Eat Products

PubMed Central

Preußel, Karina; Milde-Busch, Astrid; Schmich, Patrick; Wetzstein, Matthias; Stark, Klaus; Werber, Dirk

2015-01-01

Non-pregnancy associated (N-PA) listeriosis, caused by Listeria monocytogenes, is a rare but severe disease, and is predominantly food-borne. Most cases appear sporadic and their infection vehicle remains unknown. Incidence has increased since 2008 in Germany. We aimed to identify underlying conditions and foods associated with sporadic N-PA listeriosis in Germany. We performed a nationwide case-control study from March 2012-December 2013. Cases were sporadic N-PA listeriosis patients notified to public health. Control subjects were age (40–65 years, 66–75 years, ≥76 years) frequency-matched persons from a nationwide random telephone sample. A structured questionnaire collected information on underlying diseases, therapies and >60 food items. We conducted multivariable logistic regression analysis, adjusting for host factors identified by causal diagram theory, and calculated population attributable fractions. We enrolled 109 cases and 1982 controls. Cases’ median age was 69 years, 55% were male, 44% received immunosuppressive therapy within 3 months prior to illness onset; a further 28% had at least one immunocompromising disease. In multivariable analysis, immunosuppressive therapy (OR 8.8, 95%CI 4.9–15.6), immunocompromising disease (OR 2.7; 95%CI 1.4–5.2), gastric acid suppression (OR 3.0; 95%CI 1.4–6.3), the consumption of cold cooked sausages (OR 2.6; 95%CI 1.6–4.4), the preferred consumption of packaged cheese (OR 2.1; 95%CI 1.3–3.5) and pre-sliced cheese (OR 2.2; 95%CI 1.3–3.7) were significantly associated with N-PA listeriosis. These foods accounted for 59% of all cases. Typical high risk foods, e.g. cold seafood, certain types of cheeses, tended to be negatively associated with disease. In conclusion, immunosuppressive therapy and frequently consumed ready-to-eat foods are the main risk factors for sporadic N-PA listeriosis in Germany. To reduce their risk, immunocompromised persons should consume the identified foods well before the

Serum n-6 and n-9 Fatty Acids Correlate With Serum IGF-1 and Growth Up to 4 Months of Age in Healthy Infants.

PubMed

Kjellberg, Emma; Roswall, Josefine; Bergman, Stefan; Strandvik, Birgitta; Dahlgren, Jovanna

2018-01-01

The aim of this study was to study the relationship between insulin-like growth factor-1 (IGF-1), serum phospholipid fatty acids, and growth in healthy full-term newborns during infancy. Prospective observational study of a population-based Swedish cohort comprising 126 healthy, term infants investigating cord blood and serum at 2 days and 4 months of age for IGF-1 and phospholipid fatty acid profile and breast milk for fatty acids at 2 days and 4 months, compared with anthropometric measurements (standard deviation scores). At all time-points arachidonic acid (AA) was negatively associated with IGF-1. IGF-1 had positive associations with linoleic acid (LA) at 2 days and 4 months and mead acid (MA) showed positive associations in cord blood. Multiple regression analyses adjusted for maternal factors (body mass index, weight gain, smoking, education), sex, birth weight and feeding modality confirmed a negative association for the ratio AA/LA to IGF-1. MA in cord blood correlated to birth size. Changes in the ratios of n-6/n-3 and AA/docosahexaenoic acid from day 2 to 4 months together with infants' weight and feeding modality determined 55% of the variability of delta-IGF-1. Breast-fed infants at 4 months had lower IGF-1 correlating with lower LA and higher AA concentrations, which in girls correlated with lower weight gain from birth to 4 months of age. Our data showed interaction of n-6 fatty acids with IGF-1 during the first 4 months of life, and an association between MA and birth size when adjusted for confounding factors. Further follow-up may indicate whether these correlations are associated with later body composition.

Mass spectrometry of analytical derivatives. 1. Cyanide cations in the spectra of N-alkyl-N-perfluoroacyl-α-amino acids and their methyl esters

PubMed Central

Todua, Nino G.; Tretyakov, Kirill V.; Mikaia, Anzor I.

2016-01-01

The central mission for the development of the National Institute of Standards and Technology/National Institutes of Health/Environmental Protection Agency Mass Spectral Library is the acquisition of reference gas chromatography–mass spectrometry data for important compounds and their chemical modification products. The addition of reliable reference data of various derivatives of amino acids to The Library, and the study of their behavior under electron ionization conditions may be useful for their identification, structure elucidation, and a better understanding of the data obtained when the same derivatives are subjected to other ionization methods. N-Alkyl-N-perfluoroacyl derivatives of amino acids readily produce previously unreported alkylnitrilium cations of composition [HC≡N-alkyl]+. Homologous [HC≡N-aryl]+ cations are typical for corresponding N-aryl analogs. The formation of other ions characteristic for these derivatives involves oxygen rearrangement giving rise to ions [CnF2n+1–C≡N+–CnH2n+1] and [CnF2n+1–C≡N+-aryl]. The introduction of an N-benzyl substituent in a molecule favors a process producing benzylidene iminium cations. l-Threonine and l-cysteine derivatives exhibit more fragmentation pathways not typical for other α-amino acids; additionally, the Nω-amino group in l-lysine directs the dissociation process and provides structural information on the substitution at the amino functions in the molecule. PMID:26307698

Molecular structures of N-ethylpiperidine betaine hydrate and its 1:1 complex with squaric acid

NASA Astrophysics Data System (ADS)

Dega-Szafran, Z.; Dutkiewicz, G.; Kosturkiewicz, Z.; Szafran, M.

2013-12-01

N-ethylpiperidine betaine, (N-carboxymethyl-N-ethylpiperidinium inner salt, EtPB) crystallizes as a hydrate. EtPB and water molecules are bonded by intermolecular OH⋯O hydrogen bonds of 2.817(1) and 2.863(1) Å, into a centrosymmetric dimer, in which only one carboxylate oxygen atom is involved in H-bonds formation. In the complex of EtPB with squaric acid (3,4-dihydroxy-3-cyclobutene-1,2-dione, H2SQ) both carboxylate oxygen atoms are engaged in the hydrogen bonds which links molecules through two short, non-symmetric OH⋯O hydrogen bonds of 2.489(1) and 2.500(1) Å. The preferences of the conformation of the EtPB unit in the hydrogen bond formation have been studied by X-ray diffraction, FTIR and NMR spectroscopy and the results are supported by DFT calculations. EtPB, in hydrate and in the complex, has a chair conformation with the CH3CH2 group in the axial position and the CH2COO substituent in the equatorial position.

Pathways of sphingomyelin metabolism in cultured fibroblasts from normal and sphingomyelin lipidosis subjects.

PubMed

Spence, M W; Clarke, J T; Cook, H W

1983-07-25

The metabolism of endogenous sphingomyelin labeled with 32P or [methyl-3H]choline and of exogenous [choline-methyl-3H], [32P]-, or [N-acyl-1-14C]sphingomyelin was studied in normal and Niemann-Pick Type A (NP-A) cultured fibroblasts. Despite a greater than 96% decrease in lysosomal sphingomyelinase activity in the NP-A cells, they were able to degrade endogenously produced [32P]- or [methyl-3H]sphingomyelin at normal or near normal rates. Exogenous [methyl-3H]-, [methyl-3H, 32P]-, and [methyl-3H, N-acyl-1-14C] sphingomyelin was taken up intact by normal and NP-A cells, with NP-A cells accumulating 4-8 times more lipid. By 20 h, 50% of the control cell-associated 3H and 32P was recovered in lecithin, and the ratio of activities (3H/32P) indicated most of the phosphorylcholine derived from sphingomyelin had been transferred intact. By comparison in NP-A cells, after a 40-h incubation only 20% of the labeled phosphorylcholine derived from sphingomyelin was recovered in lecithin. With both cell lines, 20 to 50 times more sphingomyelin was hydrolyzed than was taken up by the cells; the reaction products in the medium were ceramide and a mixture of water-soluble compounds such as phosphorylcholine and choline. These results indicate that there are at least two metabolic pathways for sphingomyelin modification in cultured fibroblasts in addition to degradation by the lysosomal acid sphingomyelinase. One route is hydrolysis by a cellular sphingomyelinase. The second is the hydrolysis and/or transfer of phosphorylcholine from sphingomyelin and results in the synthesis of lecithin.

Ruminal Fermentation of Anti-Methanogenic Nitrate- and Nitro-Containing Forages In Vitro

PubMed Central

Anderson, Robin C.; Ripley, Laura H.; Bowman, Jan G. P.; Callaway, Todd R.; Genovese, Kenneth J.; Beier, Ross C.; Harvey, Roger B.; Nisbet, David J.

2016-01-01

Nitrate, 3-nitro-1-propionic acid (NPA) and 3-nitro-1-propanol (NPOH) can accumulate in forages and be poisonous to animals if consumed in high enough amounts. These chemicals are also recognized as potent anti-methanogenic compounds, but plants naturally containing these chemicals have been studied little in this regard. Presently, we found that nitrate-, NPA-, or NPOH-containing forages effectively decreased methane production, by 35–87%, during in vitro fermentation by mixed cultures of ruminal microbes compared to fermentation by cultures incubated similarly with alfalfa. Methane production was further decreased during the incubation of mixed cultures also inoculated with Denitrobacterium detoxificans, a ruminal bacterium known to metabolize nitrate, NPA, and NPOH. Inhibition of methanogens within the mixed cultures was greatest with the NPA- and NPOH-containing forages. Hydrogen accumulated in all the mixed cultures incubated with forages containing nitrate, NPA or NPOH and was dramatically higher, exceeding 40 μmol hydrogen/mL, in mixed cultures incubated with NPA-containing forage but not inoculated with D. detoxificans. This possibly reflects the inhibition of hydrogenase-catalyzed uptake of hydrogen produced via conversion of 50 μmol added formate per milliliter to hydrogen. Accumulations of volatile fatty acids revealed compensatory changes in fermentation in mixed cultures incubated with the nitrate-, NPA-, and NPOH-containing forages as evidenced by lower accumulations of acetate, and in some cases, higher accumulations of butyrate and lower accumulations of ammonia, iso-buytrate, and iso-valerate compared to cultures incubated with alfalfa. Results reveal that nitrate, NPA, and NPOH that accumulate naturally in forages can be made available within ruminal incubations to inhibit methanogenesis. Further research is warranted to determine if diets can be formulated with nitrate-, NPA-, and NPOH-containing forages to achieve efficacious mitigation

Effects of differentiation on the phospholipid and phospholipid fatty acid composition of N1E-115 neuroblastoma cells.

PubMed

Murphy, E J; Horrocks, L A

1993-04-07

The effects of differentiation on the phospholipid and phospholipid fatty acid composition of N1E-115 neuroblastoma cells were determined. The cellular lipids were extracted on days 0, 3 and 7, following the addition of 1.2% dimethylsulfoxide to induce cellular differentiation. Proportions of ethanolamine glycerophospholipids (EtnGpl), phosphatidylinositol (PtdIns) and sphingomyelin (CerPCho) were significantly elevated following differentiation. The mole percentage of choline glycerophospholipids (ChoGpl) decreased with differentiation. The plasmalogens, both choline and ethanolamine, increased by 1.3- and 2.3-fold, respectively, during differentiation. The fatty acid composition of the phospholipid classes was also altered. PtdIns and ChoGpl had decreased proportions of polyenoic fatty acids, while these proportions were increased in EtnGpl. Both ChoGpl and EtnGpl had increased n-3/n-6 series fatty acid ratios, but this ratio was decreased in PtdIns. The mole percentage of arachidonic acid was significantly decreased in both PtdIns and ChoGpl, but elevated in EtnGpl and may be a result of the increase in ethanolamine plasmalogen. Thus, differentiation did not increase the overall mole percentage of polyenoic FA in the cells nor increase the n-6 series fatty acid proportions. We speculate plasmalogens may have a role in the differentiation process or in maintaining the cell in the differentiated state.

The Aquaporin Splice Variant NbXIP1;1α Is Permeable to Boric Acid and Is Phosphorylated in the N-terminal Domain

PubMed Central

Ampah-Korsah, Henry; Anderberg, Hanna I.; Engfors, Angelica; Kirscht, Andreas; Norden, Kristina; Kjellstrom, Sven; Kjellbom, Per; Johanson, Urban

2016-01-01

Aquaporins (AQPs) are membrane channel proteins that transport water and uncharged solutes across different membranes in organisms in all kingdoms of life. In plants, the AQPs can be divided into seven different subfamilies and five of these are present in higher plants. The most recently characterized of these subfamilies is the XIP subfamily, which is found in most dicots but not in monocots. In this article, we present data on two different splice variants (α and β) of NbXIP1;1 from Nicotiana benthamiana. We describe the heterologous expression of NbXIP1;1α and β in the yeast Pichia pastoris, the subcellular localization of the protein in this system and the purification of the NbXIP1;1α protein. Furthermore, we investigated the functionality and the substrate specificity of the protein by stopped-flow spectrometry in P. pastoris spheroplasts and with the protein reconstituted in proteoliposomes. The phosphorylation status of the protein and localization of the phosphorylated amino acids were verified by mass spectrometry. Our results show that NbXIP1;1α is located in the plasma membrane when expressed in P. pastoris, that it is not permeable to water but to boric acid and that the protein is phosphorylated at several amino acids in the N-terminal cytoplasmic domain of the protein. A growth assay showed that the yeast cells expressing the N-terminally His-tagged NbXIP1;1α were more sensitive to boric acid as compared to the cells expressing the C-terminally His-tagged isoform. This might suggest that the N-terminal His-tag functionally mimics the phosphorylation of the N-terminal domain and that the N-terminal domain is involved in gating of the channel. PMID:27379142

Spectroscopic and structural characterization of the charge-transfer interaction of N,N'-bis-alkyl derivatives of 1,4,6,8-naphthalenediimide with chloranilic and picric acids.

PubMed

Refat, Moamen S; Ahmed, Hamdy A; Grabchev, Ivo; El-Zayat, Lamia A

2008-09-01

Charge-transfer (CT) complexes formed from the reactions of two N,N'-bis-alkyl derivatives of 1,4,6,8-naphthalenediimide such as N,N'-bis[2-hydroxyethyl)]-1,4,6,8-naphthalenediimide (BHENDI) and N,N'-bis-[2-N,N-dimethylaminoethyl)]-1,4,6,8-naphthalenediimide (BDMAENDI) with chloranilic acid (CLA) and piciric acid (PA) as pi-acceptors, have been studied spectrophotometrically in methanol and chloroform, respectively at 25 degrees C. The photometric titration curves for the reactions indicated that the data obtained refer to 1:1 charge-transfer complexes of [(BHENDI)(CLA)], [(BDMAENDI)(CLA)], [(BHENDI)(PA)] and [(BDMAENDI)(PA)] were formed. Benesi-Hildebrand and its modification methods were applied to the determination of association constant (K), molar extinction coefficient (epsilon). The solid CT complexes have been synthesized and characterization by different spectral methods.

Spectroscopic and structural characterization of the charge-transfer interaction of N,N'-bis-alkyl derivatives of 1,4,6,8-naphthalenediimide with chloranilic and picric acids

NASA Astrophysics Data System (ADS)

Refat, Moamen S.; Ahmed, Hamdy A.; Grabchev, Ivo; El-Zayat, Lamia A.

2008-09-01

Charge-transfer (CT) complexes formed from the reactions of two N,N'-bis-alkyl derivatives of 1,4,6,8-naphthalenediimide such as N, N'-bis[2-hydroxyethyl)]-1,4,6,8-naphthalenediimide (BHENDI) and N, N'-bis-[2- N, N-dimethylaminoethyl)]-1,4,6,8-naphthalenediimide (BDMAENDI) with chloranilic acid (CLA) and piciric acid (PA) as π-acceptors, have been studied spectrophotometrically in methanol and chloroform, respectively at 25 °C. The photometric titration curves for the reactions indicated that the data obtained refer to 1:1 charge-transfer complexes of [(BHENDI)(CLA)], [(BDMAENDI)(CLA)], [(BHENDI)(PA)] and [(BDMAENDI)(PA)] were formed. Benesi-Hildebrand and its modification methods were applied to the determination of association constant ( K), molar extinction coefficient ( ɛ). The solid CT complexes have been synthesized and characterization by different spectral methods.

N-3 polyunsaturated fatty acid regulation of hepatic gene transcription

PubMed Central

Jump, Donald B.

2009-01-01

Purpose of review The liver plays a central role in whole body lipid metabolism and adapts rapidly to changes in dietary fat composition. This adaption involves changes in the expression of genes involved in glycolysis, de-novo lipogenesis, fatty acid elongation, desaturation and oxidation. This review brings together metabolic and molecular studies that help explain n-3 (omega-3) polyunsaturated fatty acid regulation of hepatic gene transcription. Recent findings Dietary n-3 polyunsaturated fatty acid regulates hepatic gene expression by targeting three major transcriptional regulatory networks: peroxisome proliferator-activated receptor α, sterol regulatory element binding protein-1 and the carbohydrate regulatory element binding protein/Max-like factor X heterodimer. 22 : 6,n-3, the most prominent n-3 polyunsaturated fatty acid in tissues, is a weak activator of peroxisome proliferator-activated receptor α. Hepatic metabolism of 22 : 6,n-3, however, generates 20 : 5,n-3, a strong peroxisome proliferator-activated receptor α activator. In contrast to peroxisome proliferator-activated receptor α, 22 : 6,n-3 is the most potent fatty acid regulator of hepatic sterol regulatory element binding protein-1. 22 : 6,n-3 suppresses sterol regulatory element binding protein-1 gene expression while enhancing degradation of nuclear sterol regulatory element binding protein-1 through 26S proteasome and Erk1/2-dependent mechanisms. Both n-3 and n-6 polyunsaturated fatty acid suppress carbohydrate regulatory element binding protein and Max-like factor X nuclear abundance and interfere with glucose-regulated hepatic metabolism. Summary These studies have revealed unique mechanisms by which specific polyunsaturated fatty acids control peroxisome proliferator activated receptor α, sterol regulatory element binding protein-1 and carbohydrate regulatory element binding protein/Max-like factor X function. As such, specific metabolic and signal transduction pathways contribute

Clinical and Virological Factors Associated with Viremia in Pandemic Influenza A/H1N1/2009 Virus Infection

PubMed Central

Tse, Herman; To, Kelvin K. W.; Wen, Xi; Chen, Honglin; Chan, Kwok-Hung; Tsoi, Hoi-Wah; Li, Iris W. S.; Yuen, Kwok-Yung

2011-01-01

Background Positive detection of viral RNA in blood and other non-respiratory specimens occurs in severe human influenza A/H5N1 viral infection but is not known to occur commonly in seasonal human influenza infection. Recently, viral RNA was detected in the blood of patients suffering from severe pandemic influenza A/H1N1/2009 viral infection, although the significance of viremia had not been previously studied. Our study aims to explore the clinical and virological factors associated with pandemic influenza A/H1N1/2009 viremia and to determine its clinical significance. Methodology/Principal Findings Clinical data of patients admitted to hospitals in Hong Kong between May 2009 and April 2010 and tested positive for pandemic influenza A/H1N1/2009 was collected. Viral RNA was detected by reverse-transcription polymerase chain reactions (RT-PCR) targeting the matrix (M) and HA genes of pandemic influenza A/H1N1/2009 virus from the following specimens: nasopharyngeal aspirate (NPA), endotracheal aspirate (ETA), blood, stool and rectal swab. Stool and/ or rectal swab was obtained only if the patient complained of any gastrointestinal symptoms. A total of 139 patients were included in the study, with viral RNA being detected in the blood of 14 patients by RT-PCR. The occurrence of viremia was strongly associated with a severe clinical presentation and a higher mortality rate, although the latter association was not statistically significant. D222G/N quasispecies were observed in 90% of the blood samples. Conclusion Presence of pandemic influenza A/H1N1/2009 viremia is an indicator of disease severity and strongly associated with D222G/N mutation in the viral hemagglutinin protein. PMID:21980333

Can long chain n-3 fatty acids from feed be converted into very long chain n-3 fatty acids in fillets from farmed rainbow trout (Oncorhynchus mykiss)?

NASA Astrophysics Data System (ADS)

Lušnic Polak, M.; Demšar, L.; Luzar, U.; Polak, T.

2017-09-01

The link between the basic chemical and fatty acid composition of trout feed on one hand and trout (Oncorhynchus mykiss) meat (fillet) was investigated.. The content of 52 fatty acids from feed and trout meat lipids was determined by in-situ transesterification and capillary column gas-liquid chromatography. On average, 100 g of trout feed contained 7.4 g of moisture, 47.7 g of proteins, 6.09 g of ash, 21.4 g of fat, and as for fatty acid composition, 47.8 wt. % were monounsaturated, 34.0 wt. % were polyunsaturated and 18.1 wt. % were saturated fatty acids, with the PS ratio 1.88, n-6/n-3 ratio 1.74, 0.80 wt. % of trans and 3.28 wt. % of very long chain n-3 fatty acids. On average, 100 g of trout meat contained 76.1 g of moisture, 21.4 g of proteins, 1.34 g of ash, 2.52 g of fat, and in the fatty acid composition 42.1 wt. % were monounsaturated, 38.2 wt. % were polyunsaturated and 18.9 wt. % were saturated fatty acids, with the PS ratio 2.02, n-6/n-3 ratio 0.98, 0.95 wt. % of trans and 13.25 wt. % of very long chain n-3 fatty acids.

Purification and thermal analysis of perfluoro-n-alkanoic acids.

PubMed

Tsuji, Minami; Inoue, Tohru; Shibata, Osamu

2008-01-15

Purification of perfluoro-n-alkanoic acids (C(n)F(2n+1)COOH, n=7, 9, 11, 13, 15 and 17) was made by repeated recrystallizations from n-hexane/acetone mixed solvent, and their purity was found to be more than 99.5% by GC-MS, NMR, and elemental analysis. The thermal behaviors such as melting point and enthalpy change of fusion were investigated using differential scanning calorimetry (DSC). The melting point monotonously increased with increasing carbon number (n) of the acids, while the enthalpy change showed irregularity at n=14. The crystal structure of these acids was found to be dependent upon solvent used for recrystallization; that is, the acids recrystallized from the above solvent becomes more stable energetically, indicating their higher enthalpy change of fusion than that of the solidified acids from fused ones. The solid state was also found to vary depending upon the thermal history, indicating that a few crystal structures of the solid state are quite similar energetically. The melting points (T(m)) of perfluoro-n-alkanoic acids are higher than those of corresponding n-alkanoic acids, and the difference in T(m) increases with increasing carbon number in the acids.

Formation of pyroglutamic acid from N-terminal glutamic acid in immunoglobulin gamma antibodies.

PubMed

Chelius, Dirk; Jing, Kay; Lueras, Alexis; Rehder, Douglas S; Dillon, Thomas M; Vizel, Alona; Rajan, Rahul S; Li, Tiansheng; Treuheit, Michael J; Bondarenko, Pavel V

2006-04-01

The status of the N-terminus of proteins is important for amino acid sequencing by Edman degradation, protein identification by shotgun and top-down techniques, and to uncover biological functions, which may be associated with modifications. In this study, we investigated the pyroglutamic acid formation from N-terminal glutamic acid residues in recombinant monoclonal antibodies. Almost half the antibodies reported in the literature contain a glutamic acid residue at the N-terminus of the light or the heavy chain. Our reversed-phase high-performance liquid chromatography-mass spectrometry method could separate the pyroglutamic acid-containing light chains from the native light chains of reduced and alkylated recombinant monoclonal antibodies. Tryptic peptide mapping and tandem mass spectrometry of the reduced and alkylated proteins was used for the identification of the pyroglutamic acid. We identified the formation of pyroglutamic acid from N-terminal glutamic acid in the heavy chains and light chains of several antibodies, indicating that this nonenzymatic reaction does occur very commonly and can be detected after a few weeks of incubation at 37 and 45 degrees C. The rate of this reaction was measured in several aqueous buffers with different pH values, showing minimal formation of pyroglutamic acid at pH 6.2 and increased formation of pyroglutamic acid at pH 4 and pH 8. The half-life of the N-terminal glutamic acid was approximately 9 months in a pH 4.1 buffer at 45 degrees C. To our knowledge, we showed for the first time that glutamic acid residues located at the N-terminus of proteins undergo pyroglutamic acid formation in vitro.

Cardiometabolic risk factors are influenced by Stearoyl-CoA Desaturase (SCD) -1 gene polymorphisms and n-3 polyunsaturated fatty acid supplementation.

PubMed

Rudkowska, Iwona; Julien, Pierre; Couture, Patrick; Lemieux, Simone; Tchernof, André; Barbier, Olivier; Vohl, Marie-Claude

2014-05-01

To determine if single nucleotide polymorphisms (SNPs) in stearoyl-CoA desaturase (SCD)-1 gene that encodes a key enzyme for fatty acid metabolism are associated with the response of cardiometabolic risk factors to n-3 PUFA supplementation. Two hundred and ten subjects completed a 2-week run-in period followed by 6-week supplementation with 5 g of fish oil (1.9-2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid). Risk factors were measured pre and post n-3 supplementation. Fatty acid composition of plasma phospholipids was analyzed by GC and the desaturase indices SCD16 (16:1n-7/16:0) and SCD18 (18:1n-9/18:0) were calculated. Genotyping of eight SNPs of the SCD1 gene was performed. N-3 PUFA supplementation decreased plasma triglycerides, as well as SCD16 and SCD18 indices, but increased fasting plasma glucose concentrations. SNPs in SCD1-modified cardiometabolic risk factors pre and post n-3 PUFA supplementation: triglyceride (rs508384, p = 0.0086), IL6 (rs3071, p = 0.0485), C-reactive protein (rs3829160, p = 0.0489), and SCD18 indices (rs2234970, p = 0.0337). A significant interaction effect between the SNP and n-3 PUFA supplementation was also observed for fasting plasma glucose levels (rs508384, p = 0.0262). These results suggest that cardiometabolic risk factors are modulated by genetic variations in the SCD1 gene alone or in combination with n-3 PUFA supplementation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chronically administered 3-nitropropionic acid produces selective lesions in the striatum and reduces muscle tonus.

PubMed

Shimano, Y; Kumazaki, M; Sakurai, T; Hida, H; Fujimoto, I; Fukuda, A; Nishino, H

1995-12-01

Systemically administered 3-nitropropionic acid (3- NPA), irreversible inhibitor of succinate dehydrogenase, produced characteristic bilateral lesions in the striatum (STR) in the rat. Inside the lesion, neutrophils invaded and strong immunoreaction for IgG as well as complement factor C3b/C4b receptor (C3b/C4br) were observed. The core of the lesion lost the immunoreaction for glial fibrillary acidic protein (GFAP) while the marginal area had abundant GFAP-labeled astrocytes around the vessels. Intoxicated rats often became somnolent and were awkward in cooperative movement on a pole climbing test, but they had a quite good memory retention in a passive avoidance learning. Muscle tonus in some of the intoxicated rats became hypotonic with low voltage electromyogram (EMG) activity, especially in lower limbs. In summary, 3-NPA intoxicated rats had selective bilateral lesions in the STR and exhibited disturbances in a cooperative movement owing to the impairment in muscle tonus, thus it would be a useful animal model to deduce the central pathogenesis of Huntington's disease.

On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress.

PubMed

Lugo-Huitrón, R; Blanco-Ayala, T; Ugalde-Muñiz, P; Carrillo-Mora, P; Pedraza-Chaverrí, J; Silva-Adaya, D; Maldonado, P D; Torres, I; Pinzón, E; Ortiz-Islas, E; López, T; García, E; Pineda, B; Torres-Ramos, M; Santamaría, A; La Cruz, V Pérez-De

2011-01-01

Kynurenic acid (KYNA) is an endogenous metabolite of the kynurenine pathway for tryptophan degradation and an antagonist of both N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α7nACh) receptors. KYNA has also been shown to scavenge hydroxyl radicals (OH) under controlled conditions of free radical production. In this work we evaluated the ability of KYNA to scavenge superoxide anion (O(2)(-)) and peroxynitrite (ONOO(-)). The scavenging ability of KYNA (expressed as IC(50) values) was as follows: OH=O(2)(-)>ONOO(-). In parallel, the antiperoxidative and scavenging capacities of KYNA (0-150 μM) were tested in cerebellum and forebrain homogenates exposed to 5 μM FeSO(4) and 2.5 mM 3-nitropropionic acid (3-NPA). Both FeSO(4) and 3-NPA increased lipid peroxidation (LP) and ROS formation in a significant manner in these preparations, whereas KYNA significantly reduced these markers. Reactive oxygen species (ROS) formation were determined in the presence of FeSO(4) and/or KYNA (0-100 μM), both at intra and extracellular levels. An increase in ROS formation was induced by FeSO(4) in forebrain and cerebellum in a time-dependent manner, and KYNA reduced this effect in a concentration-dependent manner. To further know whether the effect of KYNA on oxidative stress is independent of NMDA and nicotinic receptors, we also tested KYNA (0-100 μM) in a biological preparation free of these receptors - defolliculated Xenopus laevis oocytes - incubated with FeSO(4) for 1 h. A 3-fold increase in LP and a 2-fold increase in ROS formation were seen after exposure to FeSO(4), whereas KYNA attenuated these effects in a concentration-dependent manner. In addition, the in vivo formation of OH evoked by an acute infusion of FeSO(4) (100 μM) in the rat striatum was estimated by microdialysis and challenged by a topic infusion of KYNA (1 μM). FeSO(4) increased the striatal OH production, while KYNA mitigated this effect. Altogether, these data strongly suggest that KYNA

Dietary n-6 and n-3 fatty acids in immunity and autoimmune disease.

PubMed

Harbige, L S

1998-11-01

Clearly there is much evidence to show that under well-controlled laboratory and dietary conditions fatty acid intake can have profound effects on animal models of autoimmune disease. Studies in human autoimmune disease have been less dramatic; however, human trials have been subject to uncontrolled dietary and genetic backgrounds, infection and other environmental influences, and basic trial designs have been inadequate. The impact of dietary fatty acids on animal autoimmune disease models appears to depend on the animal model and the type and amount of fatty acids fed. Diets low in fat, essential fatty acid-deficient, or high in n-3 fatty acids from fish oils increase the survival and reduce disease severity in spontaneous autoantibody-mediated disease, whilst linoleic acid-rich diets appear to increase disease severity. In experimentally-induced T-cell-mediated autoimmune disease, essential fatty acid-deficient diets or diets supplemented with n-3 fatty acids appear to augment disease, whereas n-6 fatty acids prevent or reduce the severity. In contrast, in both T-cell and antibody-mediated auto-immune disease the desaturated and elongated metabolites of linoleic acid are protective. Suppression of autoantibody and T lymphocyte proliferation, apoptosis of autoreactive lymphocytes, and reduced pro-inflammatory cytokine production by high-dose fish oils are all likely mechanisms by which n-3 fatty acids ameliorate autoimmune disease. However, these could be undesirable long-term effects of high-dose fish oil which may compromise host immunity. The protective mechanism(s) of n-6 fatty acids in T-cell- mediated autoimmune disease are less clear, but may include dihomo-gamma-linolenic acid- and arachidonic acid-sensitive immunoregulatory circuits such as Th1 responses, TGF beta 1-mediated effects and Th3-like responses. It is often claimed that n-6 fatty acids promote autoimmune and inflammatory disease based on results obtained with linoleic acid only. It should be

Comparison of PFDA (Perfluoro-n-Decanoic Acid) and TCDD on Heart Membranes.

DTIC Science & Technology

1986-06-18

AD-A171 960 COMPARISON OF PFDA ( PERFLUORO -N-DECANOIC ACID) AND TCDD 1/1 ON HEART NEMBRANES(U) WRIGHT STATE UNIY DAYTON OH SCHOOL OF MEDICINE A E...1986) Toxicol. Appl. Pharmacol. Perfluoro -n-decanoic acid ( PFDA ) is a synthetic chemical resembling a 10 carbon fatty acid. Several studies have...3 INTRODUCTION Perfluoro -n-decanoic acid ( PFDA ; nonadecafluorodecanoic acid, C10 F19 0 2H) is a straight-chain 10 carbon carboxylic acid with fluorine

Self-Healing Organic Fluorophore of Cyanine-Conjugated Amphiphilic Polypeptide for Near-Infrared Photostable Bioimaging.

PubMed

Li, Tuanwei; Liu, Le; Jing, Titao; Ruan, Zheng; Yuan, Pan; Yan, Lifeng

2018-05-02

Photobleaching and biotoxicity are the main bottlenecks for organic fluorescent dyes applied in real-time dynamic monitoring of living cells. Here, an unnatural amino acid, 4-nitro-3-phenyl-l-alanine (NPA), was used as a scaffold to covalently link a near-infrared fluorophore Cy5.5 and an amphiphilic polypeptide, poly[oligo(ethylene glycol) methyl ether methacrylate]- block-poly[2-amino-N 4 -(2-diisopropylamino-ethyl)-l-aspartic acid] (P(OEGMA) 21 -P(Asp) 16 -iPr), was then conjugated for increasing the photostability and improving the biocompatibility simultaneously. The protective agent of NPA can service as an effective triplet state quenching by intramolecular electron transfer between Cy5.5 and NPA. The less sensitivity of the electron-transfer process for molecular oxygen makes it an ideal photostabilized strategy for fluorophores applied in live-cell imaging. Bonding to copolymer is a common way for hydrophobic dyes to expand their application in biomedical imaging and increase their functionality, depending on the delivery system. The results indicate that Cy5.5-NPA-linked polypeptide copolymer exhibited an enhanced photostability and an excellent biocompatibility, which means this scaffolding strategy has a potential application in fluorescence-guided surgery, lived-cell imaging, and super-resolution microscopy.

'Designer oils' low in n-6:n-3 fatty acid ratio beneficially modifies cardiovascular risks in mice.

PubMed

Riediger, Natalie D; Azordegan, Nazila; Harris-Janz, Sydney; Ma, David W L; Suh, Miyoung; Moghadasian, Mohammed H

2009-08-01

Cardiovascular benefits of dietary n-3 fatty acids have been shown. However, benefits of n-3 fatty acids as part of a high fat, low n-6:n-3 fatty acid ratio diet has not been fully characterized. Aim of this study is to investigate cardiovascular and metabolic benefits of 'designer oils' containing a low ratio of n-6:n-3 fatty acids in C57BL/6 mice. Three groups of C57BL/6 mice were fed an atherogenic diet supplemented with either a fish oil- or flaxseed oil-based 'designer oil' with an approximate n-6:n-3 fatty acid ratio of 2:1 (treated groups, n = 6 each) or with a safflower oil-based formulation with a high ratio (25:1) of n-6:n-3 fatty acids (control group, n = 6) for 6 weeks. Food intake, body weight, and blood lipid levels were monitored regularly. Fatty acid profile of the heart tissues was assessed. Histological assessment of liver samples was conducted. At the end of the study body weight and food intake was significantly higher in the flax group compared to control. The levels of 20:5n-3 and 22:6n-3 was significantly increased in the heart phospholipids in both flax and fish groups compared to control; tissue 20:4n-6 was significantly reduced in the fish group compared to control. Significant liver pathology was observed in the control group only. Lowering dietary ratio of n-6:n-3 fatty acids may significantly reduce cardiovascular and metabolic risks in mice regardless of the source of n-3 fatty acids.

Thermodynamic characteristics of the protolytic equilibria of tetramethylenediamine- N,N,N', N'-tetraacetic acid

NASA Astrophysics Data System (ADS)

Gridchin, S. N.; Nikol'skii, V. M.

2014-04-01

The stepwise dissociation constants of tetramethylenediamine- N,N,N', N'-tetraacetic acid (H4L) are determined by means of potentiometry at 298.15 K and ionic strength values of 0.1, 0.5, and 1.0 (KNO3). The heat effects of the dissociation of the betaine groups of the complexone are measured by direct calorimetry. The standard thermodynamic characteristics of the protolytic equilibria of H4L are calculated via combined use of the results from thermochemical and potentiometric studies performed under identical experimental conditions. Our results are compared with the corresponding data on relative compounds.

Activation of Big Grain1 significantly improves grain size by regulating auxin transport in rice.

PubMed

Liu, Linchuan; Tong, Hongning; Xiao, Yunhua; Che, Ronghui; Xu, Fan; Hu, Bin; Liang, Chengzhen; Chu, Jinfang; Li, Jiayang; Chu, Chengcai

2015-09-01

Grain size is one of the key factors determining grain yield. However, it remains largely unknown how grain size is regulated by developmental signals. Here, we report the identification and characterization of a dominant mutant big grain1 (Bg1-D) that shows an extra-large grain phenotype from our rice T-DNA insertion population. Overexpression of BG1 leads to significantly increased grain size, and the severe lines exhibit obviously perturbed gravitropism. In addition, the mutant has increased sensitivities to both auxin and N-1-naphthylphthalamic acid, an auxin transport inhibitor, whereas knockdown of BG1 results in decreased sensitivities and smaller grains. Moreover, BG1 is specifically induced by auxin treatment, preferentially expresses in the vascular tissue of culms and young panicles, and encodes a novel membrane-localized protein, strongly suggesting its role in regulating auxin transport. Consistent with this finding, the mutant has increased auxin basipetal transport and altered auxin distribution, whereas the knockdown plants have decreased auxin transport. Manipulation of BG1 in both rice and Arabidopsis can enhance plant biomass, seed weight, and yield. Taking these data together, we identify a novel positive regulator of auxin response and transport in a crop plant and demonstrate its role in regulating grain size, thus illuminating a new strategy to improve plant productivity.

The spectroscopic (FT-IR, UV-vis), Fukui function, NLO, NBO, NPA and tautomerism effect analysis of (E)-2-[(2-hydroxy-6-methoxybenzylidene)amino]benzonitrile.

PubMed

Demircioğlu, Zeynep; Kaştaş, Çiğdem Albayrak; Büyükgüngör, Orhan

2015-03-15

A new o-hydroxy Schiff base, (E)-2-[(2-hydroxy-6-methoxybenzylidene)amino]benzonitrile was isolated and investigated by experimental and theoretical methodologies. The solid state molecular structure was determined by X-ray diffraction method. The vibrational spectral analysis was carried out by using FT-IR spectroscopy in the range of 4000-400cm(-)(1). Theoretical calculations were performed by density functional theory (DFT) method using 6-31G(d,p) basis set. The results of the calculations were applied to simulated spectra of the title compound, which show excellent agreement with observed spectra. The UV-vis spectrum of the compound was recorded in the region 200-800 nm in several solvents and electronic properties such as excitation energies, and wavelengths were calculated by TD-DFT/B3LYP method. The most prominent transitions were corresponds to π→π∗. Hybrid density functional theory (DFT) was used to investigate the enol-imine and keto-amine tautomers of titled compound. The titled compound showed the preference of enol form, as supported by X-ray and spectroscopic analysis results. The geometric and molecular properties were compaired for both enol-imine and keto-amine forms. Additionally, geometry optimizations in solvent media were performed with the same level of theory by the integral equation formalism polarizable continuum (IEF-PCM). Stability of the molecule arises from hyperconjugative interactions, charge delocalization and intramolecular hydrogen bond has been analyzed using natural bond orbital (NBO) analysis. Mulliken population method and natural population analysis (NPA) have been studied. Also, condensed Fukui function and relative nucleophilicity indices calculated from charges obtained with orbital charge calculation methods (NPA). Molecular electrostatic potential (MEP) and non linear optical (NLO) properties are also examined. Copyright © 2014 Elsevier B.V. All rights reserved.

Rapid acquisition adaptive amino acid substitutions involved in the virulence enhancement of an H1N2 avian influenza virus in mice.

PubMed

Yu, Zhijun; Sun, Weiyang; Zhang, Xinghai; Cheng, Kaihui; Zhao, Chuqi; Xia, Xianzhu; Gao, Yuwei

2017-08-01

Although H1N2 avian influenza virus (AIV) only infect birds, documented cases of swine infection with H1N2 influenza viruses suggest this subtype AIV may pose a potential threat to mammals. Here, we generated mouse-adapted variants of a H1N2 AIV to identify adaptive changes that increased virulence in mammals. MLD 50 of the variants were reduced >1000-fold compared to the parental virus. Variants displayed enhanced replication in vitro and in vivo, and replicate in extrapulmonary organs. These data show that enhanced replication capacity and expanded tissue tropism may increase the virulence of H1N2 AIV in mice. Sequence analysis revealed multiple amino acid substitutions in the PB2 (L134H, I647L, and D701N), HA (G228S), and M1 (D231N) proteins. These results indicate that H1N2 AIV can rapidly acquire adaptive amino acid substitutions in mammalian hosts, and these amino acid substitutions collaboratively enhance the ability of H1N2 AIV to replicate and cause severe disease in mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and biological evaluation of N-difluoromethyl-1,2-dihydropyrid-2-one acetic acid regioisomers: dual inhibitors of cyclooxygenases and 5-lipoxygenase.

PubMed

Yu, Gang; Praveen Rao, P N; Chowdhury, Morshed A; Abdellatif, Khaled R A; Dong, Ying; Das, Dipankar; Velázquez, Carlos A; Suresh, Mavanur R; Knaus, Edward E

2010-04-01

A new group of acetic acid (7a-c, R(1) = H), and propionic acid (7d-f, R(1) = Me), regioisomers wherein a N-difluoromethyl-1,2-dihydropyrid-2-one moiety is attached via its C-3, C-4, and C-5 position was synthesized. This group of compounds exhibited a more potent inhibition, and hence selectivity, for the cyclooxygenase-2 (COX-2) relative to the COX-1 isozyme. Attachment of the N-difluoromethyl-1,2-dihydropyrid-2-one ring system to an acetic acid, or propionic acid, moiety confers potent 5-LOX inhibitory activity, that is, absent in traditional arylacetic acid NSAIDs. 2-(1-Difluoromethyl-2-oxo-1,2-dihydropyridin-5-yl)acetic acid (7c) exhibited the best combination of dual COX-2 and 5-LOX inhibitory activities. Molecular modeling (docking) studies showed that the highly electronegative CHF(2) substituent present in 7c, that showed a modest selectivity for the COX-2 isozyme, is oriented within the secondary pocket (Val523) present in COX-2 similar to the sulfonamide (SO(2)NH(2)) COX-2 pharmacophore present in celecoxib, and that the N-difluoromethyl-1,2-dihydropyrid-2-one pharmacophore is oriented close to the region containing the LOX enzyme catalytic iron (His361, His366, and His545). Accordingly, the N-difluoromethyl-1,2-dihyrdopyrid-2-one moiety possesses properties suitable for the design of dual COX-2/5-LOX inhibitory drugs. 2010 Elsevier Ltd. All rights reserved.

Diets rich in starch increase the posthepatic availability of amino acids in dairy cows fed diets at low and normal protein levels.

PubMed

Cantalapiedra-Hijar, G; Lemosquet, S; Rodriguez-Lopez, J M; Messad, F; Ortigues-Marty, I

2014-01-01

Five mid-lactation multicatheterized Jersey cows were used in a 4×4 Latin square design to investigate whether the increase in milk N yield associated with diets rich in starch versus fiber could originate from changes in the splanchnic AA metabolism and if these changes depended upon the dietary crude protein (CP) content. Four isoenergetic diets were formulated to provide 2 different carbohydrate compositions [diets rich in starch (350g of starch and 310g of neutral detergent fiber/kg of dry matter) versus rich in fiber (45g of starch and 460g of neutral detergent fiber/kg of dry matter)] crossed by 2 different CP contents (12.0 vs. 16.5% CP). At the end of each treatment period, 6 hourly blood samples were collected from the portal and hepatic veins as well as the mesenteric artery to determine net nutrient fluxes across the portal-drained viscera (PDV), liver, and total splanchnic tissues. Dry matter and calculated energy intake as well as total absorbed energy were similar across treatments. However, the net portal appearance (NPA) of acetate, total volatile fatty acids, and β-hydroxybutyrate were higher with diets rich in fiber versus starch, whereas that of oxygen, glucose, butyrate, and insulin were lower. Concomitant to these changes, the percentage of N intake recovered as total AA (TAA) in the portal vein was lower for diets rich in fiber versus starch (42.3 vs. 51.4%, respectively), without, however, any difference observed in the NPA of the main AA used as energy fuels by the PDV (Glu, Gln, and Asp). Despite a higher NPA of TAA with starch versus fiber diets, no differences in the net hepatic flux of TAA, essential and nonessential AA were observed, resulting in a higher (+22%) net splanchnic release of AA and, hence, a greater (+7%) milk N yield. The net hepatic flux and hepatic fractional removal of none of the individual AA was affected as the main carbohydrate changed from fiber to starch, except for Gly and Lys, which were higher for the latter

n3- polyunsaturated Fat Acid Content of Some Edible Fish from Bahrain Waters

NASA Astrophysics Data System (ADS)

Al-Arrayedu, F. H.; Al Maskati, H. A.; Abdullah, F. J.

1999-08-01

This study was performed to determine the content of n3- polyunsaturated fatty acids in 10 fish species that are commonly consumed in Bahrain in addition to the main commercial shrimp species. White sardinella, which is a plankton feeder, had the highest content of n3- polyunsaturated fatty acids. It had the highest value of eicosapentaenoic acid (146.5 ± 20 mg 100 g-1) and linolenic acid (98.9±f 100 g-1) and the second highest value of docosahexaenoic acid at (133.7 ± 22 mg 100 g-1). Spanish mackerel which feeds mainly on sardinella was second with eicosapentaenoc acid at 55 ± 5.4 mg 100 g-1, docosahexaenoic acid at 161 ± 19.8 mg 100 g-1, linolenic acid at 16.4 mg 100 g-1 and docosapentaenoic acid at 25 ± 1.9 mg 100 g-1. Rabbitfish, the most popular edible fish in Bahrain which feeds mainly on benthic algae had the third highest content of n3- polyunsaturated fatty acids with eicosapentaenoic acid at 37.5 ± 3.9 mg 100 g-1, docosahexaenoic acid at 76 ± 6.7 mg 100 g-1, and docosapentaenoic acid at 85.8 ± 10 mg 100 g-1. The other fish and crustacean species studied were Arabian carpet shark, doublebar bream, grouper, gray grunt, golden travally, keeled mullet, spangled emperor and shrimp. The study explores the transfer of n3- polyunsaturated fatty acids through the food webs of the examined fish. It is apparent, generally, that plankton feeders displayed the highest content of n3- polyunsaturated fatty acids followed by seaweed and algae grazers, with benthic carnivores feeding on invertebrates displaying the poorest content. The values reported here, however, are much lower than those reported for fish available in American markets and in Mediterranean fish. Warm water temperature and high salinity which lead to lowering of the density of phytoplankton and phytoplankton content of n3- polyunsaturated fatty acids are suggested as the reason for the observed low values of n3- polyunsaturated fatty acids in Bahrain fish.

Organic salts formed by 2,4,6-triaminopyrimidine and selected carboxylic acids via a variety of hydrogen bonds: Synthons cooperation, and crystal structures

NASA Astrophysics Data System (ADS)

Xing, Peiqi; Li, Qingyun; Li, Yingying; Wang, Kunpeng; Zhang, Qi; Wang, Lei

2017-05-01

By using solvent evaporation method, 2,4,6-triaminopyrimidine (TAPI) is employed to crystallize with a variety of acids, including 3,5-dihydroxybenzoic acid (HDHBA), 3-nitrophthalic acid (H2NPA), 5-amino-2,4,6-triiodoisophthalic acid (H2ATIPIA), 2,5-dibromoterephthalic acid (H2DBTPA), 1,5-naphthalenedisulfonic acid (H2NDSA), sebacic acid (H2SA), 1,2,4-benzenetricarboxylic acid (H3BTA), and biphenyl-2,2‧,5,5'-tetracarboxylic acid (H4BPTA). In all eight complexes, protons are completely exchanged from O atom of acid to nitrogen of TAPI in 1, 3, 4, and, 5, partly transferred in 2, 6, 7, and 8. The crystal structure of all eight complexes exhibit that classical robust hydrogen bonds X-H⋯X (X = O/N) direct the molecular crystals to bind together in a stacking modes. Classical hydrogen bond Nsbnd H⋯O is participated in forming all eight organic salts, while hydrogen bonding Osbnd H⋯O are found in constructing the diversity structures in salts 1, 2, 3, 4, 6, and 7. The analysis shows that some classical supramolecular synthons, such as I R22(8), V R24(12), and VI S(6), are observed again in the construction of hydrogen-bonding networks. In the formation of layered and reticular structure, strong hydrogen bonds between water molecules and ligands having well-refined hydrogen atoms have been considered. Water molecules play an important role in building supramolecular structures of 1, 2, 3, 4, 7, and 8. Moreover, salts 1-8 are further characterized and analyzed by element analysis, infrared radiation, thermogravimetric analysis, proton nuclear magnetic resonance spectra, and mass spectra.

Fatty acid methyl ester from Neurospora intermedia N-1 isolated from Indonesian red peanut cake (oncom merah).

PubMed

Priatni, S; Hartati, S; Dewi, P; Kardono, L B S; Singgih, M; Gusdinar, T

2010-08-01

The objective of this study was to identify the Fatty Acid Methyl Ester (FAME) from Neurospora intermedia N-1 that isolated from Indonesian red peanut cake (oncom). FAME profiles have been used as biochemical characters to study many different groups of organisms, such as bacteria and yeasts. FAME from N. intermedia N-1 was obtained by some stages of extraction the orange spores and fractination using a chromatotron. The pure compound (1) was characterized by 500 mHz NMR (1H and 13C), FTIR and LC-MS. Summarized data's of 1H and 13C NMR spectra of compound 1 contained 19 Carbon, 34 Hydrogen and 2 Oxygen (C19H34O2). The position of the double bonds at carbon number 8 and 12 were indicated in the HMBC spectrum (2D-NMR). LC-MS spectrum indicates molecular weight of the compound 1 as 294 which is visible by the presence of protonated molecular ion [M+H] at m/z 295. Methyl esters of long chain fatty acids was presented by a 3 band pattern of IR spectrum with bands near 1249, 1199 and 1172 cm(-1). We suggested that the structure of the pure compound 1 is methyl octadeca-8,12-dienoate. The presence methyl octadeca-8,12-dienoate in N. intermedia is the first report.

Fiberboards treated with N’-N-(1, 8-Naphthalyl) hydroxylamine (NHA-Na), borax, and boric acid

Treesearch

Turgay Akbulut; S. Nami Kartal; Frederick Green

2004-01-01

This paper reports on the physical and mechanical properties and decay and termite resistance of fiberboard panels made from pine and beech treated with N’-N-(1, 8-Naphthalyl) hydroxylamine sodium salt(NHA-Na), borax, and boric acid at varying loadings. The panels were manufactured using 10 percent urea-formaldehyde resin and 1 percent NH4Cl. Mechanical and physical...

Effects of dietary saturated and n-6 polyunsaturated fatty acids on the incorporation of long-chain n-3 polyunsaturated fatty acids into blood lipids.

PubMed

Dias, C B; Wood, L G; Garg, M L

2016-07-01

Omega-3 polyunsaturated fatty acids (n-3PUFA) are better absorbed when they are combined with high-fat meals. However, the role of different dietary fats in modulating the incorporation of n-3PUFA in blood lipids in humans has not been previously explored. Omega-6 polyunsaturated fatty acids (n-6PUFA) are known to compete with n-3PUFA in the metabolic pathways and for the incorporation into phospholipids, whereas saturated fats (SFA) may enhance n-3PUFA incorporation into tissues. In a randomized parallel-design trial, we aimed to investigate the long-term effects of n-3PUFA supplementation in subjects consuming a diet enriched with either SFA or n-6PUFA on fatty acid incorporation into plasma and erythrocytes and on blood lipid profiles (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides). Dietary supplementation with n-3PUFA co-administered with SFA for 6 weeks resulted in a significant rise in total cholesterol (0.46±0.60 mmol/L; P=0.020) and LDL-C (0.48±0.48 mmol/L; P=0.011) in comparison with combination with n-6PUFA. The diet enriched with SFA also induced a greater increase in eicosapentaenoic acid (2.07±0.79 vs 1.15±0.53; P=0.004), a smaller decrease in docosapentaenoic acid (-0.12±0.23 vs -0.30±0.20; P=0.034) and a similar increase in docosahexaenoic acid (3.85±1.14 vs 3.10±1.07; P=0.128) percentage in plasma compared with the diet enriched with n-6PUFA. A similar effect was seen in erythrocytes. N-3PUFA supplementation resulted in similar changes in HDL-C and triglyceride levels. The results suggest that dietary substitution of SFA with n-6PUFA, despite maintaining low levels of circulating cholesterol, hinders n-3PUFA incorporation into plasma and tissue lipids.

A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs

PubMed Central

Wang, Zeng; Yang, Huanliang; Chen, Yan; Tao, Shiyu; Liu, Liling; Kong, Huihui; Ma, Shujie; Meng, Fei; Suzuki, Yasuo; Qiao, Chuanling

2017-01-01

ABSTRACT Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains. IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by

The auxin transporter, OsAUX1, is involved in primary root and root hair elongation and in Cd stress responses in rice (Oryza sativa L.).

PubMed

Yu, ChenLiang; Sun, ChenDong; Shen, Chenjia; Wang, Suikang; Liu, Fang; Liu, Yan; Chen, YunLong; Li, Chuanyou; Qian, Qian; Aryal, Bibek; Geisler, Markus; Jiang, De An; Qi, YanHua

2015-09-01

Auxin and cadmium (Cd) stress play critical roles during root development. There are only a few reports on the mechanisms by which Cd stress influences auxin homeostasis and affects primary root (PR) and lateral root (LR) development, and almost nothing is known about how auxin and Cd interfere with root hair (RH) development. Here, we characterize rice osaux1 mutants that have a longer PR and shorter RHs in hydroponic culture, and that are more sensitive to Cd stress compared to wild-type (Dongjin). OsAUX1 expression in root hair cells is different from that of its paralogous gene, AtAUX1, which is expressed in non-hair cells. However, OsAUX1, like AtAUX1, localizes at the plasma membrane and appears to function as an auxin tranporter. Decreased auxin distribution and contents in the osaux1 mutant result in reduction of OsCyCB1;1 expression and shortened PRs, LRs and RHs under Cd stress, but may be rescued by treatment with the membrane-permeable auxin 1-naphthalene acetic acid. Treatment with the auxin transport inhibitors 1-naphthoxyacetic acid and N-1-naphthylphthalamic acid increased the Cd sensitivity of WT rice. Cd contents in the osaux1 mutant were not altered, but reactive oxygen species-mediated damage was enhanced, further increasing the sensitivity of the osaux1 mutant to Cd stress. Taken together, our results indicate that OsAUX1 plays an important role in root development and in responses to Cd stress. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A.

PubMed

Long, Yan; Xu, Miao; Li, Rong; Dai, Sheng; Beers, Jeanette; Chen, Guokai; Soheilian, Ferri; Baxa, Ulrich; Wang, Mengqiao; Marugan, Juan J; Muro, Silvia; Li, Zhiyuan; Brady, Roscoe; Zheng, Wei

2016-12-01

: Niemann-Pick disease type A (NPA) is a lysosomal storage disease caused by mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM). Deficiency in ASM function results in lysosomal accumulation of sphingomyelin and neurodegeneration. Currently, there is no effective treatment for NPA. To accelerate drug discovery for treatment of NPA, we generated induced pluripotent stem cells from two patient dermal fibroblast lines and differentiated them into neural stem cells. The NPA neural stem cells exhibit a disease phenotype of lysosomal sphingomyelin accumulation and enlarged lysosomes. By using this disease model, we also evaluated three compounds that reportedly reduced lysosomal lipid accumulation in Niemann-Pick disease type C as well as enzyme replacement therapy with ASM. We found that α-tocopherol, δ-tocopherol, hydroxypropyl-β-cyclodextrin, and ASM reduced sphingomyelin accumulation and enlarged lysosomes in NPA neural stem cells. Therefore, the NPA neural stem cells possess the characteristic NPA disease phenotype that can be ameliorated by tocopherols, cyclodextrin, and ASM. Our results demonstrate the efficacies of cyclodextrin and tocopherols in the NPA cell-based model. Our data also indicate that the NPA neural stem cells can be used as a new cell-based disease model for further study of disease pathophysiology and for high-throughput screening to identify new lead compounds for drug development. Currently, there is no effective treatment for Niemann-Pick disease type A (NPA). To accelerate drug discovery for treatment of NPA, NPA-induced pluripotent stem cells were generated from patient dermal fibroblasts and differentiated into neural stem cells. By using the differentiated NPA neuronal cells as a cell-based disease model system, α-tocopherol, δ-tocopherol, and hydroxypropyl-β-cyclodextrin significantly reduced sphingomyelin accumulation in these NPA neuronal cells. Therefore, this cell-based NPA model can be used for further study of

Thermodynamic characteristics of the acid-base equilibria of ethylenediamine- N, N'-diglutaric acid in aqueous solutions using calorimetric data

NASA Astrophysics Data System (ADS)

Gridchin, S. N.; Nikol'skii, V. M.

2017-10-01

The enthalpies of reaction of betaine group neutralization of ethylenediamine- N, N'-diglutaric acid (H4L) at 298.15 K and at different values of ionic strength of 0.1, 0.5, 1.0 (KNO3) is measured by direct calorimetry. The standard thermodynamic characteristics of the protolytic equilibria of H4L are calculated.

Empirical prediction of net portal appearance of volatile fatty acids, glucose, and their secondary metabolites (beta-hydroxybutyrate, lactate) from dietary characteristics in ruminants: A meta-analysis approach.

PubMed

Loncke, C; Ortigues-Marty, I; Vernet, J; Lapierre, H; Sauvant, D; Nozière, P

2009-01-01

The current trend in energy feeding systems for ruminants toward a nutrient-based system requires dietary energy supply to be determined in terms of amount and nature of absorbed energy-yielding nutrients. The objective of this study was to establish response equations on the net portal appearance (NPA) of VFA and glucose, and their secondary metabolites beta-hydroxybutyrate (BHBA) and lactate, to changes in intake level and chemical dietary characteristics based on the Institut National de la Recherche Agronomique Feed Evaluation System for Ruminants. Meta-analyses were applied on published data compiled from the FLORA database, which pools the results on net splanchnic nutrient fluxes in multi-catheterized ruminants from international publications. For each nutrient, several prediction variables were tested. We obtained robust models for intakes up to 30 g of DM x d(-1) x kg of BW(-1) and diets containing less than 70 g of concentrate per 100 g of DM. These models were designed to predict the NPA (mmol x h(-1) x kg of BW(-1)) of total VFA based on the amount of ruminally fermented OM (RfOM) intake [adjusted R(2) (R(2)(adj)) = 0.95; residual means square errors (RMSE) = 0.24], to predict VFA profile (mol/100 mol of total VFA) based on type of RfOM intake (acetate: R(2)(adj) = 0.85, RMSE = 2.2; propionate: R(2)(adj) = 0.76, RMSE = 2.2; butyrate: R(2)(adj) = 0.76, RMSE = 1.09), and to predict the NPA (mmol x h(-1) x kg of BW(-1)) of glucose based on the starch digested in the small intestine independent of ruminant species, and while presenting no interfering factors on the residuals and individual slopes. The model predicting the NPA (mmol x h(-1) x kg of BW(-1)) of BHBA based on the amount of RfOM intake (R(2)(adj) = 0.91; RMSE = 0.036) was species-dependent, and the model predicting NPA (mmol x h(-1) x kg of BW(-1)) of lactate based on starch digested in the rumen (R(2)(adj) = 0.77; RMSE = 0.042) presented a wide dispersion. However, the NPA (mmol x h(-1) x kg of

Mass spectrometric studies of 1-ethyl-3-methylimidazolium and 1-propyl-2,3-dimethylimidazolium bis(trifluoromethyl)-sulfonylimides.

PubMed

Chilingarov, Norbert S; Medvedev, Artem A; Deyko, Grigoriy S; Kustov, Leonid M; Chernikova, Elena A; Glukhov, Lev M; Markov, Vitaliy Yu; Ioffe, Il'ya N; Senyavin, Vladimir M; Polyakova, Marina V; Sidorov, Lev N

2015-07-15

Ionic liquids ([Cat(+)][An(-)]) were believed to decompose before reaching vaporization temperatures, but recently some of them have been shown to vaporize congruently. Low-temperature vaporization of ionic substances is an intriguing phenomenon, so the vapor-phase composition and reactions of ionic liquids deserve more extensive study. Evaporation of two ionic liquids, [C2MIM(+)][Tf2 N(-)] and [C3MMIM(+)][Tf2N(-)], was studied by means of Knudsen effusion mass spectrometry. These liquids were also characterized using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, UV/Vis, IR, NMR spectroscopy, and elemental analysis. The vaporization enthalpies of (118 ± 3) and (124 ± 2) kJ·mol(-1) were determined for [C2MIM(+)][Tf2N(-)] and [C3MMIM(+)][Tf2N(-)], respectively. The corresponding equations for their saturated vapor pressures are: ln(p{[C2MIM(+)][Tf2N(-)]}/Pa) = -(14213 ± 325)/(T/K) + (26.57 ± 1.04), ln(p{[C2MMIM(+)][Tf2N(-)]}/Pa) = -(14868 ± 221)/(T/K) + (27.19 ± 0.60). The MALDI studies (positive and negative ion modes) enabled detection of monomeric [Cat(+)] and [An(-)] ions, the cluster ions {[Cat(+)]2 [An(-)]}(+) and {[Cat(+)][An(-)]2}(-), and some complex anions {2[An(-)] + Na(+)}(-), {2[An(-)] + K(+)}(-), {2[An(-)] + Cu(+)}(-) and {3[An(-)] + Ca(2+)}(-). Knudsen effusion mass spectrometry proved to be a valuable method to study the thermodynamics of ionic liquids. The saturated vapor pressure and vaporization enthalpy of [C3MMIM(+)][Tf2N(-)] were accurately determined for the first time. MALDI is also capable of providing indirect information on hydrogen bonding. Copyright © 2015 John Wiley & Sons, Ltd.

Fluorescence properties of Schiff base - N,N‧-bis(salicylidene) - 1,2-Phenylenediamine in presence of bile acid host

NASA Astrophysics Data System (ADS)

Roy, Nayan; Paul, Pradip C.; Singh, T. Sanjoy

2015-05-01

Fluorescence properties of Schiff base - N,N‧-bis(salicylidene) - 1,2-phenylenediamine (LH2) is used to study the micelles formed by aggregation of different important bile acids like cholic acid, deoxycholic acid, chenodeoxycholic acid and glycocholic acid by steady state and picosecond time-resolved fluorescence spectroscopy. The fluorescence band intensity was found out to increase with concomitant red shift with gradual addition of different bile acids. Binding constant of the probe with different bile acids as well as critical micelle concentration was obtained from the variation of fluorescence intensity on increasing concentration of bile acids in the medium. The increase in fluorescence quantum yields, fluorescence decay times and substantial decrease in nonradiative decay rate constants in bile acids micellar environment points to the restricted motion of the fluorophore inside the micellar subdomains.

Physiological role of D-amino acid-N-acetyltransferase of Saccharomyces cerevisiae: detoxification of D-amino acids.

PubMed

Yow, Geok-Yong; Uo, Takuma; Yoshimura, Tohru; Esaki, Nobuyoshi

2006-03-01

Saccharomyces cerevisiae is sensitive to D-amino acids: those corresponding to almost all proteinous L-amino acids inhibit the growth of yeast even at low concentrations (e.g. 0.1 mM). We have determined that D-amino acid-N-acetyltransferase (DNT) of the yeast is involved in the detoxification of D-amino acids on the basis of the following findings. When the DNT gene was disrupted, the resulting mutant was far less tolerant to D-amino acids than the wild type. However, when the gene was overexpressed with a vector plasmid p426Gal1 in the wild type or the mutant S. cerevisiae as a host, the recombinant yeast, which was found to show more than 100 times higher DNT activity than the wild type, was much more tolerant to D-amino acids than the wild type. We further confirmed that, upon cultivation with D-phenylalanine, N-acetyl-D-phenylalanine was accumulated in the culture but not in the wild type and hpa3Delta cells overproducing DNT cells. Thus, D-amino acids are toxic to S. cerevisiae but are detoxified with DNT by N-acetylation preceding removal from yeast cells.

n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia.

PubMed

Bosch, Jackie; Gerstein, Hertzel C; Dagenais, Gilles R; Díaz, Rafael; Dyal, Leanne; Jung, Hyejung; Maggiono, Aldo P; Probstfield, Jeffrey; Ramachandran, Ambady; Riddle, Matthew C; Rydén, Lars E; Yusuf, Salim

2012-07-26

The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown. In this double-blind study with a 2-by-2 factorial design, we randomly assigned 12,536 patients who were at high risk for cardiovascular events and had impaired fasting glucose, impaired glucose tolerance, or diabetes to receive a 1-g capsule containing at least 900 mg (90% or more) of ethyl esters of n-3 fatty acids or placebo daily and to receive either insulin glargine or standard care. The primary outcome was death from cardiovascular causes. The results of the comparison between n-3 fatty acids and placebo are reported here. During a median follow up of 6.2 years, the incidence of the primary outcome was not significantly decreased among patients receiving n-3 fatty acids, as compared with those receiving placebo (574 patients [9.1%] vs. 581 patients [9.3%]; hazard ratio, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72). The use of n-3 fatty acids also had no significant effect on the rates of major vascular events (1034 patients [16.5%] vs. 1017 patients [16.3%]; hazard ratio, 1.01; 95% CI, 0.93 to 1.10; P=0.81), death from any cause (951 [15.1%] vs. 964 [15.4%]; hazard ratio, 0.98; 95% CI, 0.89 to 1.07; P=0.63), or death from arrhythmia (288 [4.6%] vs. 259 [4.1%]; hazard ratio, 1.10; 95% CI, 0.93 to 1.30; P=0.26). Triglyceride levels were reduced by 14.5 mg per deciliter (0.16 mmol per liter) more among patients receiving n-3 fatty acids than among those receiving placebo (P<0.001), without a significant effect on other lipids. Adverse effects were similar in the two groups. Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).

Chemoselective synthesis of sialic acid 1,7-lactones.

PubMed

Allevi, Pietro; Rota, Paola; Scaringi, Raffaella; Colombo, Raffaele; Anastasia, Mario

2010-08-20

The chemoselective synthesis of the 1,7-lactones of N-acetylneuraminic acid, N-glycolylneuraminic acid, and 3-deoxy-d-glycero-d-galacto-nononic acid is accomplished in two steps: a simple treatment of the corresponding free sialic acid with benzyloxycarbonyl chloride and a successive hydrogenolysis of the formed 2-benzyloxycarbonyl 1,7-lactone. The instability of the 1,7-lactones to protic solvents has been also evidenced together with the rationalization of the mechanism of their formation under acylation conditions. The results permit to dispose of authentic 1,7-sialolactones to be used as reference standards and of a procedure useful for the preparation of their isotopologues to be used as inner standards in improved analytical procedures for the gas liquid chromatography-mass spectrometry (GLC-MS) analysis of 1,7-sialolactones in biological media.

A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs.

PubMed

Wang, Zeng; Yang, Huanliang; Chen, Yan; Tao, Shiyu; Liu, Liling; Kong, Huihui; Ma, Shujie; Meng, Fei; Suzuki, Yasuo; Qiao, Chuanling; Chen, Hualan

2017-11-01

Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains. IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by

Adaptations of hepatic amino acid uptake and net utilisation contributes to nitrogen economy or waste in lambs fed nitrogen- or energy-deficient diets.

PubMed

Kraft, G; Ortigues-Marty, I; Durand, D; Rémond, D; Jardé, T; Bequette, B; Savary-Auzeloux, I

2011-04-01

We investigated the effect of relative changes in dietary nitrogen (N) and energy supply and the subsequent variations in net portal appearance (NPA) of nitrogenous and energy nutrients on the net amino acid (AA) uptake by the liver and net N supply to the peripheral tissues. Six lambs were catheterised across the splanchnic tissues and received, in a replicated Latin square, one of three dietary treatments. The diets were formulated to either match the requirements of N and energy (C), or supply only 0.8 of the N requirement (LN) or 0.8 of the energy requirement (LE). Net fluxes of AA and urea-N were measured across the portal-drained viscera, and estimation of arterial hepatic flow allowed the estimation of hepatic fluxes. Catheters were implanted into the portal and hepatic veins as well as in the abdominal aorta for the measurement of AA fluxes. Animals fed the LN diet showed more efficient N retention (0.59 of digested N) than did the C and LE diet (0.50 and 0.33, respectively; P < 0.001). The NPA of total AA-N for the LN diet was only 0.60 of the value measured for the control (C) diet (P < 0.01). Despite this, the total estimated AA-N net splanchnic fluxes were not significantly different across the three diets (3.3, 1.9 and 2.6 g total AA-N/day for C, LN and LE, respectively, P = 0.52). Thus, different metabolic regulations must have taken place across the liver between the three experimental diets. A combination of decreased net uptake of total AA-N by the liver of animals in the LN diet (0.61 of the C diet; P = 0.002) and reduced urinary urea-N production (0.52 of the C diet; P = 0.001) spared AA from catabolism in the LN diet relative to the other two diets. For the LE diet, the urinary urea-N output was 1.3 times the value of the C diet (P = 0.01). This may relate to an increased catabolism of AA by the muscle and/or, to a lesser extent, to an increased utilisation of AA for gluconeogenesis in the liver. These effects may explain the reduced whole body

Identification of the n-1 fatty acid as an antibacterial constituent from the edible freshwater cyanobacterium Nostoc verrucosum.

PubMed

Oku, Naoya; Yonejima, Kohsuke; Sugawa, Takao; Igarashi, Yasuhiro

2014-01-01

The cyanobacterium Nostoc verrucosum occurs in cool, clear streams and its gelatinous colonies, called "ashitsuki," have been eaten in ancient Japan. Its ethanolic extract was found to inhibit the growth of Gram-positive bacteria and activity-guided fractionation yielded an unusual n-1 fatty acid, (9Z,12Z)-9,12,15-hexadecatrienoic acid (1), as one of the active principles. It inhibited the growth of Staphylococcus aureus at MIC 64 μg/mL.

Cadmium Alters the Concentration of Fatty Acids in THP-1 Macrophages.

PubMed

Olszowski, Tomasz; Gutowska, Izabela; Baranowska-Bosiacka, Irena; Łukomska, Agnieszka; Drozd, Arleta; Chlubek, Dariusz

2018-03-01

Fatty acid composition of human immune cells influences their function. The aim of this study was to evaluate the effects of known toxicant and immunomodulator, cadmium, at low concentrations on levels of selected fatty acids (FAs) in THP-1 macrophages. The differentiation of THP-1 monocytes into macrophages was achieved by administration of phorbol myristate acetate. Macrophages were incubated with various cadmium chloride (CdCl 2 ) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM, and 2 μM CdCl 2 . Fatty acids were extracted from samples according to the Folch method. The fatty acid levels were determined using gas chromatography. The following fatty acids were analyzed: long-chain saturated fatty acids (SFAs) palmitic acid and stearic acid, very long-chain saturated fatty acid (VLSFA) arachidic acid, monounsaturated fatty acids (MUFAs) palmitoleic acid, oleic acid and vaccenic acid, and n-6 polyunsaturated fatty acids (PUFAs) linoleic acid and arachidonic acid. Treatment of macrophages with very low concentrations of cadmium (5-200 nM) resulted in significant reduction in the levels of arachidic, palmitoleic, oleic, vaccenic, and linoleic acids and significant increase in arachidonic acid levels (following exposure to 5 nM Cd), without significant reduction of palmitic and stearic acid levels. Treatment of macrophages with the highest tested cadmium concentration (2 μM) produced significant reduction in the levels of all examined FAs: SFAs, VLSFA, MUFAs, and PUFAs. In conclusion, cadmium at tested concentrations caused significant alterations in THP-1 macrophage fatty acid levels, disrupting their composition, which might dysregulate fatty acid/lipid metabolism thus affecting macrophage behavior and inflammatory state.

Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid.

PubMed

Markworth, James F; Kaur, Gunveen; Miller, Eliza G; Larsen, Amy E; Sinclair, Andrew J; Maddipati, Krishna Rao; Cameron-Smith, David

2016-11-01

In contrast to the well-characterized effects of specialized proresolving lipid mediators (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little is known about the metabolic fate of the intermediary long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) docosapentaenoic acid (DPA). In this double blind crossover study, shifts in circulating levels of n-3 and n-6 PUFA-derived bioactive lipid mediators were quantified by an unbiased liquid chromatography-tandem mass spectrometry lipidomic approach. Plasma was obtained from human subjects before and after 7 d of supplementation with pure n-3 DPA, n-3 EPA or placebo (olive oil). DPA supplementation increased the SPM resolvin D5 n -3DPA (RvD5 n -3DPA ) and maresin (MaR)-1, the DHA vicinal diol 19,20-dihydroxy-DPA and n-6 PUFA derived 15-keto-PG E 2 (15-keto-PGE 2 ). EPA supplementation had no effect on any plasma DPA or DHA derived mediators, but markedly elevated monohydroxy-eicosapentaenoic acids (HEPEs), including the e-series resolvin (RvE) precursor 18-HEPE; effects not observed with DPA supplementation. These data show that dietary n-3 DPA and EPA have highly divergent effects on human lipid mediator profile, with no overlap in PUFA metabolites formed. The recently uncovered biologic activity of n-3 DPA docosanoids and their marked modulation by dietary DPA intake reveals a unique and specific role of n-3 DPA in human physiology.-Markworth, J. F., Kaur, G., Miller, E. G., Larsen, A. E., Sinclair, A. J., Maddipati, K. R., Cameron-Smith, D. Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid. © FASEB.

Health benefits of n-3 polyunsaturated fatty acids: eicosapentaenoic acid and docosahexaenoic acid.

PubMed

Siriwardhana, Nalin; Kalupahana, Nishan S; Moustaid-Moussa, Naima

2012-01-01

Marine-based fish and fish oil are the most popular and well-known sources of n-3 polyunsaturated fatty acids (PUFAs), namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These n-3 PUFAs are known to have variety of health benefits against cardiovascular diseases (CVDs) including well-established hypotriglyceridemic and anti-inflammatory effects. Also, various studies indicate promising antihypertensive, anticancer, antioxidant, antidepression, antiaging, and antiarthritis effects. Moreover, recent studies also indicate anti-inflammatory and insulin-sensitizing effects of these fatty acids in metabolic disorders. Classically, n-3 PUFAs mediate some of these effects by antagonizing n-6 PUFA (arachidonic acid)-induced proinflammatory prostaglandin E₂ (PGE₂) formation. Another well-known mechanism by which n-3 PUFAs impart their anti-inflammatory effects is via reduction of nuclear factor-κB activation. This transcription factor is a potent inducer of proinflammatory cytokine production, including interleukin 6 and tumor necrosis factor-α, both of which are decreased by EPA and DHA. Other evidence also demonstrates that n-3 PUFAs repress lipogenesis and increase resolvins and protectin generation, ultimately leading to reduced inflammation. Finally, beneficial effects of EPA and DHA in insulin resistance include their ability to increase secretion of adiponectin, an anti-inflammatory adipokine. In summary, n-3 PUFAs have multiple health benefits mediated at least in part by their anti-inflammatory actions; thus their consumption, especially from dietary sources, should be encouraged. Copyright © 2012 Elsevier Inc. All rights reserved.

Benzamide-picric acid (1/1).

PubMed

Sivaramkumar, M S; Velmurugan, R; Sekar, M; Ramesh, P; Ponnuswamy, M N

2010-06-26

In the title compound, C(7)H(7)NO·C(6)H(3)N(3)O(7), one of the nitro groups of the picric acid mol-ecule lies in the plane of the attached benzene ring [dihedral angle = 1.4 (1)°] while the other two are twisted away by 9.9 (1) and 30.3 (1)°. In the benzamide mol-ecule, the amide group is almost coplanar with the benzene ring [dihedral angle = 4.4 (1)°]. An intra-molecular O-H⋯O hydrogen bond generates an S6 ring motif. In the crystal, mol-ecules are linked into a ribbon-like structure along the b axis by O-H⋯O and N-H⋯O inter-molecular hydrogen bonds. In addition, C-H⋯O hydrogen bonds and short O⋯O contacts [2.828 (2) Å] are observed.

Mitochondrial inhibitor models of Huntington's disease and Parkinson's disease induce zinc accumulation and are attenuated by inhibition of zinc neurotoxicity in vitro or in vivo.

PubMed

Sheline, Christian T; Zhu, Julia; Zhang, Wendy; Shi, Chunxiao; Cai, Ai-Li

2013-01-01

Inhibition of mitochondrial function occurs in many neurodegenerative diseases, and inhibitors of mitochondrial complexes I and II are used to model them. The complex II inhibitor, 3-nitroproprionic acid (3-NPA), kills the striatal neurons susceptible in Huntington's disease. The complex I inhibitor N-methyl-4-phenylpyridium (MPP(+)) and 6-hydroxydopamine (6-OHDA) are used to model Parkinson's disease. Zinc (Zn(2+)) accumulates after 3-NPA, 6-OHDA and MPP(+) in situ or in vivo. We will investigate the role of Zn(2+) neurotoxicity in 3-NPA, 6-OHDA and MPP(+). Murine striatal/midbrain tyrosine hydroxylase positive, or near-pure cortical neuronal cultures, or animals were exposed to 3-NPA or MPP(+) and 6-OHDA with or without neuroprotective compounds. Intracellular zinc ([Zn(2+)](i)), nicotinamide adenine dinucleotide (NAD(+)), NADH, glycolytic intermediates and neurotoxicity were measured. We showed that compounds or genetics which restore NAD(+) and attenuate Zn(2+) neurotoxicity (pyruvate, nicotinamide, NAD(+), increased NAD(+) synthesis, sirtuin inhibition or Zn(2+) chelation) attenuated the neuronal death induced by these toxins. The increase in [Zn(2+)](i) preceded a reduction in the NAD(+)/NADH ratio that caused a reversible glycolytic inhibition. Pyruvate, nicotinamide and NAD(+) reversed the reductions in the NAD(+)/NADH ratio, glycolysis and neuronal death after challenge with 3-NPA, 6-OHDA or MPP(+), as was previously shown for exogenous Zn(2+). To test efficacy in vivo, we injected 3-NPA into the striatum of rats and systemically into mice, with or without pyruvate. We observed early striatal Zn(2+) fluorescence, and pyruvate significantly attenuated the 3-NPA-induced lesion and restored behavioral scores. Together, these studies suggest that Zn(2+) accumulation caused by MPP(+) and 3-NPA is a novel preventable mechanism of the resultant neurotoxicity. Copyright © 2012 S. Karger AG, Basel.

The effects of n-3 fatty acid deficiency and repletion upon the fatty acid composition and function of the brain and retina.

PubMed

Connor, W E; Neuringer, M

1988-01-01

It is now apparent that both n-6 and n-3 fatty acids are essential for normal development in mammals, and that each has specific functions in the body. N-6 fatty acids are necessary primarily for growth, reproduction, and the maintenance of skin integrity, whereas n-3 fatty acids are involved in the development and function of the retina and cerebral cortex and perhaps other organs such as the testes. Fetal life and infancy are particularly critical for the nervous tissue development. Therefore, with respect to human nutrition, adequate amounts of omega-3 fatty acids should be provided during pregnancy, lactation and infancy, but probably throughout life. We estimate that adequate levels are provided by diets containing 6-8% kcals from linoleic acid and 1% from n-3 fatty acids (alpha-linolenic acid, EPA and DHA), resulting in a ratio of n-6 to n-3 fatty acids of 4:1 to 10:1. The essentiality of n-3 fatty acids resides in their presence as DHA in vital membranes of the photoreceptors of the retina and the synaptosomes and other subcellular membranes of the brain. The replacement of DHA in deficient animals by the n-6 fatty acid, 22:5, results in abnormal functioning of the membranes for reasons as yet to be ascertained. Most significant is the lability of fatty acid composition in the retinal and brain of deficient animals. Dietary fish oil, which contains EPA and DHA, will readily lead to a change in the composition of the membrane of retina and brain, fatty acids, with DHA replacing the n-6 fatty acid, 22:5. The interrelationships between the chemistry of neural and retinal membranes as affected by diet and their biological functioning provides an exciting prospect for future investigations.

The Control of Storage Xyloglucan Mobilization in Cotyledons of Hymenaea courbaril1

PubMed Central

dos Santos, Henrique Pessoa; Purgatto, Eduardo; Mercier, Helenice; Buckeridge, Marcos Silveira

2004-01-01

Hymenaea courbaril is a leguminous tree species from the neotropical rain forests. Its cotyledons are largely enriched with a storage cell wall polysaccharide (xyloglucan). Studies of cell wall storage polymers have been focused mostly on the mechanisms of their disassembly, whereas the control of their mobilization and the relationship between their metabolism and seedling development is not well understood. Here, we show that xyloglucan mobilization is strictly controlled by the development of first leaves of the seedling, with the start of its degradation occurring after the beginning of eophyll (first leaves) expansion. During the period of storage mobilization, an increase in the levels of xyloglucan hydrolases, starch, and free sugars were observed in the cotyledons. Xyloglucan mobilization was inhibited by shoot excision, darkness, and by treatment with the auxin-transport inhibitor N-1-naphthylphthalamic acid. Analyses of endogenous indole-3-acetic acid in the cotyledons revealed that its increase in concentration is followed by the rise in xyloglucan hydrolase activities, indicating that auxin is directly related to xyloglucan mobilization. Cotyledons detached during xyloglucan mobilization and treated with 2,4-dichlorophenoxyacetic acid showed a similar mobilization rate as in attached cotyledons. This hormonal control is probably essential for the ecophysiological performance of this species in their natural environment since it is the main factor responsible for promoting synchronism between shoot growth and reserve degradation. This is likely to increase the efficiency of carbon reserves utilization by the growing seedling in the understorey light conditions of the rain forest. PMID:15133152

Identification of swine H1N2/pandemic H1N1 reassortant influenza virus in pigs, United States.

PubMed

Ali, Ahmed; Khatri, Mahesh; Wang, Leyi; Saif, Yehia M; Lee, Chang-Won

2012-07-06

In October and November 2010, novel H1N2 reassortant influenza viruses were identified from pigs showing mild respiratory signs that included cough and depression. Sequence and phylogenetic analysis showed that the novel H1N2 reassortants possesses HA and NA genes derived from recent H1N2 swine isolates similar to those isolated from Midwest. Compared to the majority of reported reassortants, both viruses preserved human-like host restrictive and putative antigenic sites in their HA and NA genes. The four internal genes, PB2, PB1, PA, and NS were similar to the contemporary swine triple reassortant viruses' internal genes (TRIG). Interestingly, NP and M genes of the novel reassortants were derived from the 2009 pandemic H1N1. The NP and M proteins of the two isolates demonstrated one (E16G) and four (G34A, D53E, I109T, and V313I) amino acid changes in the M2 and NP proteins, respectively. Similar amino acid changes were also noticed upon incorporation of the 2009 pandemic H1N1 NP in other reassortant viruses reported in the U.S. Thus the role of those amino acids in relation to host adaptation need to be further investigated. The reassortments of pandemic H1N1 with swine influenza viruses and the potential of interspecies transmission of these reassortants from swine to other species including human indicate the importance of systematic surveillance of swine population to determine the origin, the prevalence of similar reassortants in the U.S. and their impact on both swine production and public health. Copyright © 2012 Elsevier B.V. All rights reserved.

Supplementation with n-3, n-6, n-9 fatty acids in an insulin-resistance animal model: does it improve VLDL quality?

PubMed

Lucero, D; Olano, C; Bursztyn, M; Morales, C; Stranges, A; Friedman, S; Macri, E V; Schreier, L; Zago, V

2017-05-24

Insulin-resistance (IR), of increased cardiovascular risk, is characterized by the production of altered VLDL with greater atherogenicity. Dietary fatty acids influence the type of circulating VLDL. But, it is not clear how dietary fatty acids impact VLDL characteristics in IR. to evaluate the effects of n-3, n-6 and n-9 fatty acid supplementation on preventing atherogenic alterations in VLDL, in a diet-induced IR rat model. Male Wistar rats (180-200 g) were fed: standard diet (control, n = 8) and a sucrose rich diet (30% sucrose in water/12 weeks, SRD; n = 24). Simultaneously, SRD was subdivided into SRD-C (standard diet), and three other groups supplemented (15% w/w) with: fish oil (SRD-n3), sunflower oil (SRD-n6) and high oleic sunflower oil (SRD-n9). Lipid profile, free fatty acids, glucose, and insulin were measured. Isolated VLDL (d < 1.006 g ml -1 ) was characterized by chemical composition and size (size exclusion-HPLC). In comparison with SRD-C: SRD-n3 showed an improved lipoprotein profile (p < 0.01), with lower levels of insulin and HOMA-IR (p < 0.05). SRD-n6 showed increased levels of HDL-cholesterol and lower insulin levels. SRD-n9 did not exhibit differences in lipid and IR profile, and even favored weight gain and visceral fat. Only SRD-n3 prevented the alterations in VLDL-TG% (54.2 ± 4.4% vs. 68.6 ± 8.2, p < 0.05) and showed lower large VLDL-% (22.5[19.7-35.6] vs. 49.1[15.5-82.0], p < 0.05), while SRD-n6 and SRD-n9 did not show effects. In IR, while n-3 PUFA showed expected favorable effects, supplementation with n-6 PUFA and n-9 MUFA did not prevent atherogenic alterations of VLDL. Thus, the recommendations of supplementation with these fatty acids in general diet should be revised.

Postprandial PYY increase by resistant starch supplementation is independent of net portal appearance of short-chain fatty acids in pigs.

PubMed

Ingerslev, Anne Krog; Mutt, Shivaprakash Jagalur; Lærke, Helle Nygaard; Hedemann, Mette Skou; Theil, Peter Kappel; Nielsen, Kirstine Lykke; Jørgensen, Henry; Herzig, Karl-Heinz; Bach Knudsen, Knud Erik

2017-01-01

Increased dietary fiber (DF) fermentation and short-chain fatty acid (SCFA) production may stimulate peptide tyrosine-tyrosine (PYY) secretion. In this study, the effects of hindgut SCFA production on postprandial PYY plasma levels were assessed using different experimental diets in a porto-arterial catheterized pig model. The pigs were fed experimental diets varying in source and levels of DF for one week in 3×3 Latin square designs. The DF sources were whole-wheat grain, wheat aleurone, rye aleurone-rich flour, rye flakes, and resistant starch. Postprandial blood samples were collected from the catheters and analyzed for PYY levels and net portal appearance (NPA) of PYY was correlated to NPA of SCFA. No significant effects of diets on NPA of PYY were observed (P > 0.05), however, resistant starch supplementation increased postprandial NPA of PYY levels by 37 to 54% compared with rye-based and Western-style control diets (P = 0.19). This increase was caused by higher mesenteric artery and portal vein PYY plasma levels (P < 0.001) and was independent of SCFA absorption (P > 0.05). The PYY levels were higher in response to the second daily meal compared with the first daily meal (P < 0.001), but similar among diets (P > 0.10). In conclusion, the increased postprandial PYY responses in pigs fed with different levels and sources of DF are not caused by an increased SCFA absorption and suggest that other mechanisms such as neural reflexes and possibly an increased flow of digesta in the small intestine may be involved. The content of DF and SCFA production did not affect PYY levels.

Cysteine Substitution of Transmembrane Domain Amino Acids Alters the Ethanol Inhibition of GluN1/GluN2A N-Methyl-d-Aspartate Receptors

PubMed Central

Xu, Minfu; Smothers, C. Thetford

2015-01-01

N-Methyl-d-aspartate receptors (NMDARs) are inhibited by behaviorally relevant concentrations of ethanol, and residues within transmembrane (TM) domains of NMDARs, including TM3 GluN1 phenylalanine 639 (F639), regulate this sensitivity. In the present study, we used cysteine (C) mutagenesis to determine whether there are additional residues within nearby TM domains that regulate ethanol inhibition on NMDARs. GluN1(F639C)/GluN2A receptors were less inhibited by ethanol than wild-type receptors, and inhibition was restored to wild-type levels following treatment with ethanol-like methanethiosulfonate reagents. Molecular modeling identified six residues in the GluN1 TM1 domain (valine V566; serine S569) and the GluN2A TM4 domain (methionine, M817; V820, F821, and leucine, L824) that were in close vicinity to the TM3 F639 residue, and these were individually mutated to cysteine and tested for ethanol inhibition and receptor function. The F639C-induced decrease in ethanol inhibition was blunted by coexpression of GluN1 TM1 mutants V566C and S569C, and statistically significant interactions were observed for ethanol inhibition among V566C, F639C, and GluN2A TM4 mutants V820C and F821C and S569C, F639C, and GluN2A TM4 mutants F821C and L824C. Ethanol inhibition was also reduced when either GluN1 TM1 mutant V566C or S569C was combined with GluN2A V820C, suggesting a novel TM1:TM4 intrasubunit site of action for ethanol. Cysteines substituted at TM3 and TM4 sites previously suggested to interact with ethanol had less dramatic effects on ethanol inhibition. Overall, the results from these studies suggest that interactions among TM1, TM3, and TM4 amino acids in NMDARs are important determinants of ethanol action at these receptors. PMID:25635140

Fatty Acids Change the Conformation of Uncoupling Protein 1 (UCP1)*

PubMed Central

Divakaruni, Ajit S.; Humphrey, Dickon M.; Brand, Martin D.

2012-01-01

UCP1 catalyzes proton leak across the mitochondrial inner membrane to disengage substrate oxidation from ATP production. It is well established that UCP1 is activated by fatty acids and inhibited by purine nucleotides, but precisely how this regulation occurs remains unsettled. Although fatty acids can competitively overcome nucleotide inhibition in functional assays, fatty acids have little effect on purine nucleotide binding. Here, we present the first demonstration that fatty acids induce a conformational change in UCP1. Palmitate dramatically changed the binding kinetics of 2′/3′-O-(N-methylanthraniloyl)-GDP, a fluorescently labeled nucleotide analog, for UCP1. Furthermore, palmitate accelerated the rate of enzymatic proteolysis of UCP1. The altered kinetics of both processes indicate that fatty acids change the conformation of UCP1, reconciling the apparent discrepancy between existing functional and ligand binding data. Our results provide a framework for how fatty acids and nucleotides compete to regulate the activity of UCP1. PMID:22952235

Crystal structures of 4-meth-oxy-benzoic acid-1,3-bis-(pyridin-4-yl)propane (2/1) and biphenyl-4,4'-di-carb-oxy-lic acid-4-meth-oxy-pyridine (1/2).

PubMed

Gotoh, Kazuma; Ishida, Hiroyuki

2017-07-01

The crystal structures of two hydrogen-bonded compounds, namely 4-meth-oxy-benzoic acid-1,3-bis-(pyridin-4-yl)propane (2/1), C 13 H 14.59 N 2 ·C 8 H 7.67 O 3 ·C 8 H 7.74 O 3 , (I), and biphenyl-4,4'-di-carb-oxy-lic acid-4-meth-oxy-pyridine (1/2), C 14 H 9.43 O 4 ·C 6 H 7.32 NO·C 6 H 7.25 NO, (II), have been determined at 93 K. In (I), the asymmetric unit consists of two crystallographically independent 4-meth-oxy-benzoic acid mol-ecules and one 1,3-bis-(pyridin-4-yl)propane mol-ecule. The asymmetric unit of (II) comprises one biphenyl-4,4'-di-carb-oxy-lic acid mol-ecule and two independent 4-meth-oxy-pyridine mol-ecules. In each crystal, the acid and base mol-ecules are linked by short O-H⋯N/N-H⋯O hydrogen bonds, in which H atoms are disordered over the acid O-atom and base N-atom sites, forming a linear hydrogen-bonded 2:1 or 1:2 unit of the acid and the base. The 2:1 units of (I) are linked via C-H⋯π, π-π and C-H⋯O inter-actions into a tape structure along [101], while the 1:2 units of (II) form a double-chain structure along [-101] through π-π and C-H⋯O inter-actions.

Unexpected Hydrolytic Instability of N-Acylated Amino Acid Amides and Peptides

PubMed Central

2015-01-01

Remote amide bonds in simple N-acyl amino acid amide or peptide derivatives 1 can be surprisingly unstable hydrolytically, affording, in solution, variable amounts of 3 under mild acidic conditions, such as trifluoroacetic acid/water mixtures at room temperature. This observation has important implications for the synthesis of this class of compounds, which includes N-terminal-acylated peptides. We describe the factors contributing to this instability and how to predict and control it. The instability is a function of the remote acyl group, R2CO, four bonds away from the site of hydrolysis. Electron-rich acyl R2 groups accelerate this reaction. In the case of acyl groups derived from substituted aromatic carboxylic acids, the acceleration is predictable from the substituent’s Hammett σ value. N-Acyl dipeptides are also hydrolyzed under typical cleavage conditions. This suggests that unwanted peptide truncation may occur during synthesis or prolonged standing in solution when dipeptides or longer peptides are acylated on the N-terminus with electron-rich aromatic groups. When amide hydrolysis is an undesired secondary reaction, as can be the case in the trifluoroacetic acid-catalyzed cleavage of amino acid amide or peptide derivatives 1 from solid-phase resins, conditions are provided to minimize that hydrolysis. PMID:24617596

2,3-Diamino-pyridinium sorbate-sorbic acid (1/1).

PubMed

Hemamalini, Madhukar; Goh, Jia Hao; Fun, Hoong-Kun

2012-01-01

In the title mol-ecular salt-adduct, C(5)H(8)N(3) (+)·C(6)H(7)O(2) (-)·C(6)H(8)O(2), the 2,3-diamino-pyridinium cation is essentially planar, with a maximum deviation of 0.013 (2) Å, and is protanated at its pyridine N atom. The sorbate anion and sorbic acid mol-ecules exist in extended conformations. In the crystal, the protonated N atom and one of the two amino-group H atoms are hydrogen bonded to the sorbate anion through a pair of N-H⋯O hydrogen bonds, forming an R(1) (2)(6) ring motif. The carboxyl groups of the sorbic acid mol-ecules and the carboxyl-ate groups of the sorbate anions are connected via O-H⋯O hydrogen bonds. Furthermore, the ion pairs and neutral mol-ecules are connected via inter-molecular N-H⋯O hydrogen bonds, forming sheets lying parallel to (100).

Foamy Monocytes Are Enriched in cis-7-Hexadecenoic Fatty Acid (16:1n-9), a Possible Biomarker for Early Detection of Cardiovascular Disease.

PubMed

Guijas, Carlos; Meana, Clara; Astudillo, Alma M; Balboa, María A; Balsinde, Jesús

2016-06-23

Human monocytes respond to arachidonic acid, a secretory product of endothelial cells, by activating the de novo pathway of fatty acid biosynthesis, resulting in the acquisition of a foamy phenotype due to accumulation of cytoplasmic lipid droplets. Recruitment of foamy monocytes to endothelium is a key step in the formation of atherosclerotic plaques. Here we describe that lipid droplets of foamy monocytes are enriched in a rather uncommon fatty acid, cis-7-hexadecenoic acid (16:1n-9), a positional isomer of palmitoleic acid. 16:1n-9 was found to possess an anti-inflammatory activity both in vitro and in vivo that is comparable with that of omega-3 fatty acids and clearly distinguishable from the effects of palmitoleic acid. Selective accumulation in neutral lipids of phagocytic cells of an uncommon fatty acid reveals an early phenotypic change that may provide a biomarker of proatherogenicity, and a potential target for intervention in the early stages of cardiovascular disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Glutamic Acid as a Precursor to N-Terminal Pyroglutamic Acid in Mouse Plasmacytoma Protein

PubMed Central

Twardzik, Daniel R.; Peterkofsky, Alan

1972-01-01

Cell suspensions derived from a mouse plasmacytoma (RPC-20) that secretes an immunoglobulin light chain containing N-terminal pyroglutamic acid can synthesize protein in vitro. Chromatographic examination of an enzymatic digest of protein labeled with glutamic acid shows only labeled glutamic acid and pyroglutamic acid; hydrolysis of protein from cells labeled with glutamine, however, yields substantial amounts of glutamic acid in addition to glutamine and pyroglutamic acid. The absence of glutamine synthetase and presence of glutaminase in plasmacytoma homogenates is consistent with these findings. These data indicate that N-terminal pyroglutamic acid can be derived from glutamic acid without prior conversion of glutamic acid to glutamine. Since free or bound forms of glutamine cyclize nonezymatically to pyroglutamate with ease, while glutamic acid does not, the data suggest that N-terminal pyroglutamic acid formation from glutamic acid is enzymatic rather than spontaneous. Images PMID:4400295

UV and fluorescence spectral changes induced by neodymium binding of N,N'-ethylenebis[2-(o-hydroxyphenolic)glycine] and N,N'-di(2-hydroxybenzyl)ethylenediamine-N,N' diacetic acid.

PubMed

Wang, Zhijun; Yang, Binsheng

2006-11-01

In 0.01 M 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (Hepes), pH 7.4 and room temperature, the binding of neodymium to N,N'-ethylenebis[2-(o-hydroxyphenolic)glycine] (EHPG), or N,N'-di(2-hydroxybenzyl)ethylenediamine-N,N' diacetic acid (HBED) had been studied from 210 to 330 nm by means of difference UV spectra. Two peaks at 240 and 292 nm appear in difference UV spectra after neodymium binding to EHPG or HBED. The 1:1 stable complex can be confirmed from spectral titration curves. The molar extinction coefficient of Nd-EHPG and Nd-HBED complexes are Deltaepsilon(Nd-EHPG)=(12.93+/-0.21) x 10(3)cm(-1)M(-1), Deltaepsilon(Nd-HBED)=(14.45+/-0.51) x 10(5)cm(-1)M(-1) at 240 nm, respectively. Using EDTA as a competitor, the conditional equilibrium constants of the complexes are logK(Nd-EHPG)=11.89+/-0.09 and logK(Nd-HBED)=12.19+/-0.15, respectively. At the same conditions, fluorescence measurements show that neodymium binding to EHPG leads to a quenching of the fluorescence of EHPG at near 310 nm. However, there is no obvious fluorescence change of HBED at 318 nm with the binding of neodymium to HBED.

Maternal Diet Supplementation with n-6/n-3 Essential Fatty Acids in a 1.2 : 1.0 Ratio Attenuates Metabolic Dysfunction in MSG-Induced Obese Mice

PubMed Central

Martin, Josiane Morais; Miranda, Rosiane Aparecida; Palma-Rigo, Kesia; Alves, Vander Silva; Fabricio, Gabriel Sergio; Pavanello, Audrei; Franco, Claudinéia Conationi da Silva; Ribeiro, Tatiane Aparecida; Visentainer, Jesuí Vergílio; Banafé, Elton Guntendeorfer; Martin, Clayton Antunes; Mathias, Paulo Cezar de Freitas

2016-01-01

Essential polyunsaturated fatty acids (PUFAs) prevent cardiometabolic diseases. We aimed to study whether a diet supplemented with a mixture of n-6/n-3 PUFAs, during perinatal life, attenuates outcomes of long-term metabolic dysfunction in prediabetic and obese mice. Seventy-day-old virgin female mice were mated. From the conception day, dams were fed a diet supplemented with sunflower oil and flaxseed powder (containing an n-6/n-3 PUFAs ratio of 1.2 : 1.0) throughout pregnancy and lactation, while control dams received a commercial diet. Newborn mice were treated with monosodium L-glutamate (MSG, 4 mg g−1 body weight per day) for the first 5 days of age. A batch of weaned pups was sacrificed to quantify the brain and pancreas total lipids; another batch were fed a commercial diet until 90 days of age, where glucose homeostasis and glucose-induced insulin secretion (GIIS) as well as retroperitoneal fat and Lee index were assessed. MSG-treated mice developed obesity, glucose intolerance, insulin resistance, pancreatic islet dysfunction, and higher fat stores. Maternal flaxseed diet-supplementation decreased n-6/n-3 PUFAs ratio in the brain and pancreas and blocked glucose intolerance, insulin resistance, GIIS impairment, and obesity development. The n-6/n-3 essential PUFAs in a ratio of 1.2 : 1.0 supplemented in maternal diet during pregnancy and lactation prevent metabolic dysfunction in MSG-obesity model. PMID:28050167

Synthesis of structured triacylglycerols enriched in n-3 fatty acids by immobilized microbial lipase.

PubMed

Araújo, Maria Elisa Melo Branco de; Campos, Paula Renata Bueno; Alberto, Thiago Grando; Contesini, Fabiano Jares; Carvalho, Patrícia de Oliveira

The search for new biocatalysts has aroused great interest due to the variety of micro-organisms and their role as enzyme producers. Native lipases from Aspergillus niger and Rhizopus javanicus were used to enrich the n-3 long-chain polyunsaturated fatty acids content in the triacylglycerols of soybean oil by acidolysis with free fatty acids from sardine oil in solvent-free media. For the immobilization process, the best lipase/support ratios were 1:3 (w/w) for Aspergillus niger lipase and 1:5 (w/w) for Rhizopus javanicus lipase using Amberlite MB-1. Both lipases maintained constant activity for 6 months at 4°C. Reaction time, sardine-free fatty acids:soybean oil mole ratio and initial water content of the lipase were investigated to determine their effects on n-3 long-chain polyunsaturated fatty acids incorporation into soybean oil. Structured triacylglycerols with 11.7 and 7.2% of eicosapentaenoic acid+docosahexaenoic acid were obtained using Aspergillus niger lipase and Rhizopus javanicus lipase, decreasing the n-6/n-3 fatty acids ratio of soybean oil (11:1 to 3.5:1 and 4.7:1, respectively). The best reaction conditions were: initial water content of lipase of 0.86% (w/w), sardine-free faty acids:soybean oil mole ratio of 3:1 and reaction time of 36h, at 40°C. The significant factors for the acidolysis reaction were the sardine-free fatty acids:soybean oil mole ratio and reaction time. The characterization of structured triacylglycerols was obtained using easy ambient sonic-spray ionization mass spectrometry. The enzymatic reaction led to the formation of many structured triacylglycerols containing eicosapentaenoic acid, docosahexaenoic acid or both polyunsaturated fatty acids. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Primary fatty acid amide metabolism: conversion of fatty acids and an ethanolamine in N18TG2 and SCP cells1[S

PubMed Central

Farrell, Emma K.; Chen, Yuden; Barazanji, Muna; Jeffries, Kristen A.; Cameroamortegui, Felipe; Merkler, David J.

2012-01-01

Primary fatty acid amides (PFAM) are important signaling molecules in the mammalian nervous system, binding to many drug receptors and demonstrating control over sleep, locomotion, angiogenesis, and many other processes. Oleamide is the best-studied of the primary fatty acid amides, whereas the other known PFAMs are significantly less studied. Herein, quantitative assays were used to examine the endogenous amounts of a panel of PFAMs, as well as the amounts produced after incubation of mouse neuroblastoma N18TG2 and sheep choroid plexus (SCP) cells with the corresponding fatty acids or N-tridecanoylethanolamine. Although five endogenous primary amides were discovered in the N18TG2 and SCP cells, a different pattern of relative amounts were found between the two cell lines. Higher amounts of primary amides were found in SCP cells, and the conversion of N-tridecanoylethanolamine to tridecanamide was observed in the two cell lines. The data reported here show that the N18TG2 and SCP cells are excellent model systems for the study of PFAM metabolism. Furthermore, the data support a role for the N-acylethanolamines as precursors for the PFAMs and provide valuable new kinetic results useful in modeling the metabolic flux through the pathways for PFAM biosynthesis and degradation. PMID:22095832

Docosahexaenoic Acid (DHA) and Hepatic Gene Transcription1,3

PubMed Central

Jump, Donald B.; Botolin, Daniela; Wang, Yun; Xu, Jinghua; Demeure, Olivier; Christian, Barbara

2008-01-01

The type and quantity of dietary fat ingested contributes to the onset and progression of chronic diseases, like diabetes and atherosclerosis. The liver plays a central role in whole body lipid metabolism and responds rapidly to changes in dietary fat composition. Polyunsaturated fatty acids (PUFA) play a key role in membrane composition and function, metabolism and the control of gene expression. Certain PUFA, like the n-3 PUFA, enhance hepatic fatty acid oxidation and inhibit fatty acid synthesis and VLDL secretion, in part, by regulating gene expression. Our studies have established that key transcription factors, like PPARα, SREBP-1, ChREBP and MLX, are regulated by n-3 PUFA, which in turn control levels of proteins involved in lipid and carbohydrate metabolism. Of the n-3 PUFA, 22:6,n-3 has recently been established as a key controller of hepatic lipid synthesis. 22:6,n-3 controls the 26S proteasomal degradation of the nuclear form of SREBP-1. SREBP-1 is a major transcription factor that controls the expression of multiple genes involved fatty acid synthesis and desaturation. 22:6,n-3 suppresses nuclear SREBP-1 which, in turn suppresses lipogenesis. This mechanism is achieved, in part, through control of the phosphorylation status of protein kinases. This review will examine both the general features of PUFA-regulated hepatic gene transcription and highlight the unique mechanisms by which 22:6,n-3 impacts gene expression. The outcome of this analysis will reveal that changes in hepatic 22:6,n-3 content has a major impact on hepatic lipid and carbohydrate metabolism. Moreover, the mechanisms involve 22:6,n-3 control of several well-known signaling pathways, such as Akt, Erk1/2, Gsk3β and PKC (novel or atypical). 22:6,n-3 control of these same signaling pathways in non-hepatic tissues may help explain the diverse actions of n-3 PUFA on such complex physiological processes as visual acuity and learning. PMID:18343222

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 α (TNF-α), 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

Incorporation of Oxygen into Abscisic Acid and Phaseic Acid from Molecular Oxygen 1

PubMed Central

Creelman, Robert A.; Zeevaart, Jan A. D.

1984-01-01

Abscisic acid accumulates in detached, wilted leaves of Xanthium strumarium. When these leaves are subsequently rehydrated, phaseic acid, a catabolite of abscisic acid, accumulates. Analysis by gas chromatography-mass spectrometry of phaseic acid isolated from stressed and subsequently rehydrated leaves placed in an atmosphere containing 20% 18O2 and 80% N2 indicates that one atom of 18O is incorporated in the 6′-hydroxymethyl group of phaseic acid. This suggests that the enzyme that converts abscisic acid to phaseic acid is an oxygenase. Analysis by gas chromatography-mass spectrometry of abscisic acid isolated from stressed leaves kept in an atmosphere containing 18O2 indicates that one atom of 18O is present in the carboxyl group of abscisic acid. Thus, when abscisic acid accumulates in water-stressed leaves, only one of the four oxygens present in the abscisic acid molecule is derived from molecular oxygen. This suggests that either (a) the oxygen present in the 1′-, 4′-, and one of the two oxygens at the 1-position of abscisic acid arise from water, or (b) there exists a stored precursor with oxygen atoms already present in the 1′- and 4′-positions of abscisic acid which is converted to abscisic acid under conditions of water stress. PMID:16663564

R(-)-4-(3-Isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole, a fluorescent chiral tagging reagent: sensitive resolution of chiral amines and amino acids by reversed-phase liquid chromatography.

PubMed

Toyo'oka, T; Jin, D; Tomoi, N; Oe, T; Hiranuma, H

2001-02-01

The usefulness of R(-)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole [R(-)-DBD-PyNCS], a fluorescent chiral tagging reagent, for the determination of racemic amines and amino acids, was studied. The reagent reacted with beta-blockers selected as representative secondary amines to produce corresponding fluorescent diastereomers (excitation at 460 nm and emission at 550 nm). The yields of the derivatization reaction were dependent on the stereostructure arround the NH group in beta-blockers. The resulting diastereomers were completely separated with single chromatographic run using linear gradient elutions by reversed-phase chromatography. R(-)-DBD-PyNCS was also applied to the determination of DL-amino acid, considered to be one of the primary amines, in human urine and foodstuffs. DL-amino acids tested equally reacted with the reagent, and the thiocarbamoyl derivatives were separated with an ODS column. The epimerization during the derivatization reaction was negligible judging from the resolution of opposite diastereomers on the chromatogram. The occurence of D-amino acids (D-Ala, D-Ser, D-Asp and/or D-Glu) was identified in the samples tested. The structures and the purities were elucidated with on-line HPLC-MS. The chiral reagent possessing an isothiocyanate group (-NCS) in the structure seems to be applicable to continuous sequential analysis of peptides containing D-amino acids. The thiocarbamoyl derivatives obtained from the reaction with DL-amino acids were converted to thiohydantoins via thiazolinones in acidic medium. The thiohydantoins produced from acidic, basic, neutral, hydroxyl and aromatic amino acids were completely separated with isocratic elutions using acidic mobile phase containing 0.1% TFA. The separations were sufficient for the identification of DL-amino acid in peptide sequences. Although the epimerization during the conversion reaction to thiohydantoins was not avoidable, the descrimination of D- and

Metal chelates of phosphonate-containing ligands-III Analytical applications of N,N,N',N'-ethylenediaminetetra(methylenephosphonic) acid.

PubMed

Zaki, M T; Rizkalla, E N

1980-05-01

N,N*,N',N'-Ethylenediaminetetra(methylenephosphonic) acid is used as a titrant for the direct determination of Cu, Co and Ni, with murexide as indicator. Indirect titrimetric procedures are suggested for the determination of silver, mercury, zinc and cyanide and both direct and indirect methods are applied for the analysis of binary mixtures of silver (or mercury) and copper (cobalt or nickel). The stoichiometry of the reaction, interferences of some metal ions and the pH effects on the complexation reactions are discussed. The values of the equilibrium constants of the protonated CuH(n)L (n = 1, 2, 3 and 4) as well as the unprotonated CuL chelates have been measured.

Increased urinary excretion rates of serotonin and metabolites during bedrest

NASA Astrophysics Data System (ADS)

Platen, Petra; Lebenstedt, Marion; Schneider, Myriam; Boese, Andrea; Heer, Martina

2005-05-01

Astronauts are often on a voluntarily reduced energy intake during space missions, possibly caused by a metabolic or emotional stress response with involvement of the central serotonergic system (SES). We investigated 24 h urinary excretion (24 h-E) of serotonin (5-HT) and 5-hydroxyindol acidic acid as indicators of the SES in healthy males under two different normocaloric conditions: normal physical activity (NPA) and -6∘ head-down-tilt (HDT). HDT or NPA were randomly arranged with a recovery period of 6 months in between. 24 h-E of hormones varied widely among individuals. Values were higher in HDT compared to NPA. Assuming that the 24 h-E values are, beside being indicators for alterations in the number and metabolism of platelets, Also indicators of central SES, HDT condition seems to activate central SES in a higher degree compared to NPA. Therefore, changes in central SES might be involved in the mechanisms associated with space flight or microgravity, including possible maladaptations such as voluntary undernutrition.

Kinetics study on the degradation of a model naphthenic acid by ethylenediamine-N,N'-disuccinic acid-modified Fenton process.

PubMed

Zhang, Ying; Klamerth, Nikolaus; Messele, Selamawit Ashagre; Chelme-Ayala, Pamela; Gamal El-Din, Mohamed

2016-11-15

Naphthenic acids (NAs) are reported to be the main species responsible for the oil sands process-affected water (OSPW) toxicity. In this study, the degradation of cyclohexanoic acid (CHA) as a model compound for NAs by an ethylenediamine-N,N'-disuccinic acid (EDDS)-modified Fenton process was investigated at pH 8. Optimum dose for Fe-EDDS (EDDS:Fe=2:1) was 0.45mM, and 2.94mM for hydrogen peroxide (H2O2). The time profiles of the main species in the process were studied, including CHA, H2O2, Fe(II), total Fe, and Fe-EDDS (in the main form of Fe(III)EDDS). The second-order rate constant between EDDS and hydroxyl radical (OH) at pH 8 was obtained as 2.48±0.43×10(9)M(-1)s(-1). OH was proved to be the main species responsible for the CHA degradation, while superoxide radical (O2(-)) played a minor role. The consecutive addition of H2O2 and Fe-EDDS led to a higher removal of CHA compared to that achieved by adding the reagents at a time. The half-wave potential of Fe(III/II)EDDS was measured at pH 7-9. The EDDS-modified Fenton process is a promising alternative to degrade NAs. Copyright © 2016 Elsevier B.V. All rights reserved.

Supramolecular hydrogen-bonding patterns in 1:1 cocrystals of 5-fluorouracil with 4-methylbenzoic acid and 3-nitrobenzoic acid.

PubMed

Mohana, Marimuthu; Muthiah, Packianathan Thomas; McMillen, Colin D

2017-03-01

The design of a pharmaceutical cocrystal is based on the identification of specific hydrogen-bond donor and acceptor groups in active pharmaceutical ingredients (APIs) in order to choose a `complementary interacting' molecule that can act as an efficient coformer. 5-Fluorouracil (5FU) is a pyrimidine derivative with two N-H donors and C=O acceptors and shows a diversity of hydrogen-bonding motifs. Two 1:1 cocrystals of 5-fluorouracil (5FU), namely 5-fluorouracil-4-methylbenzoic acid (5FU-MBA), C 4 H 3 FN 2 O 2 ·C 8 H 8 O 2 , (I), and 5-fluorouracil-3-nitrobenzoic acid (5FU-NBA), C 4 H 3 FN 2 O 2 ·C 7 H 5 NO 4 , (II), have been prepared and characterized by single-crystal X-ray diffraction. In (I), the MBA molecules form carboxylic acid dimers [R 2 2 (8) homosynthon]. Similarly, the 5FU molecules form two types of base pair via a pair of N-H...O hydrogen bonds [R 2 2 (8) homosynthon]. In (II), 5FU interacts with the carboxylic acid group of NBA via N-H...O and O-H...O hydrogen bonds, generating an R 2 2 (8) ring motif (heterosynthon). Furthermore, the 5FU molecules form base pairs [R 2 2 (8) homosynthon] via N-H...O hydrogen bonds. Both of the crystal structures are stabilized by C-H...F interactions.

Forms of n-3 (ALA, C18:3n-3 or DHA, C22:6n-3) Fatty Acids Affect Carcass Yield, Blood Lipids, Muscle n-3 Fatty Acids and Liver Gene Expression in Lambs.

PubMed

Ponnampalam, Eric N; Lewandowski, Paul A; Fahri, Fahri T; Burnett, Viv F; Dunshea, Frank R; Plozza, Tim; Jacobs, Joe L

2015-11-01

The effects of supplementing diets with n-3 alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) on plasma metabolites, carcass yield, muscle n-3 fatty acids and liver messenger RNA (mRNA) in lambs were investigated. Lambs (n = 120) were stratified to 12 groups based on body weight (35 ± 3.1 kg), and within groups randomly allocated to four dietary treatments: basal diet (BAS), BAS with 10.7 % flaxseed supplement (Flax), BAS with 1.8 % algae supplement (DHA), BAS with Flax and DHA (FlaxDHA). Lambs were fed for 56 days. Blood samples were collected on day 0 and day 56, and plasma analysed for insulin and lipids. Lambs were slaughtered, and carcass traits measured. At 30 min and 24 h, liver and muscle samples, respectively, were collected for determination of mRNA (FADS1, FADS2, CPT1A, ACOX1) and fatty acid composition. Lambs fed Flax had higher plasma triacylglycerol, body weight, body fat and carcass yield compared with the BAS group (P < 0.001). DHA supplementation increased carcass yield and muscle DHA while lowering plasma insulin compared with the BAS diet (P < 0.01). Flax treatment increased (P < 0.001) muscle ALA concentration, while DHA treatment increased (P < 0.001) muscle DHA concentration. Liver mRNA FADS2 was higher and CPT1A lower in the DHA group (P < 0.05). The FlaxDHA diet had additive effects, including higher FADS1 and ACOX1 mRNA than for the Flax or DHA diet. In summary, supplementation with ALA or DHA modulated plasma metabolites, muscle DHA, body fat and liver gene expression differently.

Reaction of N-acetylneuraminic acid derivatives with perfluorinated anhydrides: a short access to N-perfluoracylated glycals with antiviral properties.

PubMed

Rota, Paola; Allevi, Pietro; Mattina, Roberto; Anastasia, Mario

2010-08-21

An efficient short protocol for the preparation of N-perfluoroacylated glycals of neuraminic acid, by simple short treatment of differently protected N-acetylneuraminic acid with perfluorinated anhydrides in acetonitrile at 135 degrees C, is reported, together with a rationalitazion of the reaction that allows the alternative formation of N-perfluoroacylated 1,7-lactones to be previewed under the same reaction conditions.

Identification of single amino acid substitutions (SAAS) in neuraminidase from influenza a virus (H1N1) via mass spectrometry analysis coupled with de novo peptide sequencing.

PubMed

Peng, Qisheng; Wang, Zijian; Wu, Donglin; Li, Xiaoou; Liu, Xiaofeng; Sun, Wanchun; Liu, Ning

2016-08-01

Amino acid substitutions in the neuraminidase of the influenza virus are the main cause of the emergence of resistance to zanamivir or oseltamivir during seasonal influenza treatment; they are the result of non-synonymous mutations in the viral genome that can be successfully detected by polymer chain reaction (PCR)-based approaches. There is always an urgent need to detect variation in amino acid sequences directly at the protein level. Mass spectrometry coupled with de novo sequencing has been explored as an alternative and straightforward strategy for detecting amino acid substitutions, as well - this approach is the primary focus of the present study. Influenza virus (A/Puerto Rico/8/1934 H1N1) propagated in embryonated chicken eggs was purified by ultracentrifugation, followed by PNGase F treatment. The deglycosylated virion was lysed and separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The gel band corresponding to neuraminidase was picked up and subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. LC-MS/MS analyses, coupled with manual de novo sequencing, allowed the determination of three amino acid substitutions: R346K, S349 N, and S370I/L, in the neuraminidase from the influenza virus (A/Puerto Rico/8/1934 H1N1), which were located in three mutated peptides of the neuraminidase: YGNGVWIGK, TKNHSSR, and PNGWTETDI/LK, respectively. We found that the amino acid substitutions in the proteins of RNA viruses (including influenza A virus) resulting from non-synonymous gene mutations can indeed be directly analyzed via mass spectrometry, and that manual interpretation of the MS/MS data may be beneficial. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of dicyandiamide and dolomite application on N2O emission from an acidic soil.

PubMed

Shaaban, Muhammad; Wu, Yupeng; Peng, Qi-an; Lin, Shan; Mo, Yongliang; Wu, Lei; Hu, Ronggui; Zhou, Wei

2016-04-01

Soil acidification is a major problem for sustainable agriculture since it limits productivity of several crops. Liming is usually adopted to ameliorate soil acidity that can trigger soil processes such as nitrification, denitrification, and loss of nitrogen (N) as nitrous oxide (N2O) emissions. The loss of N following liming of acidic soils can be controlled by nitrification inhibitors (such as dicyandiamide). However, effects of nitrification inhibitors following liming of acidic soils are not well understood so far. Here, we conducted a laboratory study using an acidic soil to examine the effects of dolomite and dicyandiamide (DCD) application on N2O emissions. Three levels of DCD (0, 10, and 20 mg kg(-1); DCD0, DCD10, and DCD20, respectively) were applied to the acidic soil under two levels of dolomite (0 and 1 g kg(-1)) which were further treated with two levels of N fertilizer (0 and 200 mg N kg(-1)). Results showed that N2O emissions were highest at low soil pH levels in fertilizer-treated soil without application of DCD and dolomite. Application of DCD and dolomite significantly (P ≤ 0.001) reduced N2O emissions through decreasing rates of NH4 (+)-N oxidation and increasing soil pH, respectively. Total N2O emissions were reduced by 44 and 13% in DCD20 and dolomite alone treatments, respectively, while DCD20 + dolomite reduced N2O emissions by 54% when compared with DCD0 treatment. The present study suggests that application of DCD and dolomite to acidic soils can mitigate N2O emissions.

Acidic 1,3-propanediaminetetraacetato lanthanides with luminescent and catalytic ester hydrolysis properties

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

Chen, Mao-Long; Shi, Yan-Ru; Yang, Yu-Chen

2014-11-15

In acidic solution, a serials of water-soluble coordination polymers (CPs) were isolated as zonal 1D-CPs 1,3-propanediaminetetraacetato lanthanides [Ln(1,3-H{sub 3}pdta)(H{sub 2}O){sub 5}]{sub n}·2Cl{sub n}·3nH{sub 2}O [Ln=La, 1; Ce, 2; Pr, 3; Nd, 4; Sm, 5] (1,3-H{sub 4}pdta=1,3-propanediaminetetraacetic acid, C{sub 11}H{sub 18}N{sub 2}O{sub 8}) in high yields. When 1 eq. mol potassium hydroxide was added to the solutions of 1D-CPs, respectively, two 1D-CPs [Ln(1,3-H{sub 2}pdta)(H{sub 2}O){sub 3}]{sub n}·Cl{sub n}·2nH{sub 2}O [Ln=Sm, 6; Gd, 7] were isolated at room temperature and seven 2D-CPs [Ln(1,3-H{sub 2}pdta)(H{sub 2}O){sub 2}]{sub n}·Cl{sub n}·2nH{sub 2}O [Ln=La, 8; Ce, 9; Pr, 10; Nd, 11; Sm, 12; Eu, 13; Gd,more » 14] were isolated at 70 °C. When the crystals of 1–4 were hydrothermally heated at 180 °C with 1–2 eq. mol potassium hydroxide, four 3D-CPs [Ln(1,3-Hpdta)]{sub n}·nH{sub 2}O [Ln=La, 15; Ce, 16; Pr, 17; Nd, 18] were obtained. The two 2D-CPs [Ln(1,3-Hpdta)(H{sub 2}O)]{sub n}·4nH{sub 2}O (Sm, 19; Eu, 20) were isolated in similar reaction conditions. With the increments of pH value in the solution and reaction temperature, the structure becomes more complicated. 1–5 are soluble in water and 1 was traced by solution {sup 13}C({sup 1}H) NMR technique, the water-soluble lanthanides 1 and 5 show catalytic activity to ester hydrolysis reaction respectively, which indicate their important roles in the hydrolytic reaction. The europium complexes 13 and 20 show visible fluorescence at an excitation of 394 nm. The structure diversity is mainly caused by the variation of coordinated ligand in different pH values and lanthanide contraction effect. Acidic conditions are favorable for the isolations of lanthanide complexes in different structures and this may helpful to separate different lanthanides. The thermal stability investigations reveal that acidic condition is favorable to obtain the oxides at a lower temperature. - Graphical abstract: A

Phthalazin-1(2H)-one–picric acid (1/1)

PubMed Central

Yathirajan, H. S.; Narayana, B.; Swamy, M. T.; Sarojini, B. K.; Bolte, Michael

2008-01-01

The geometric parameters of the title compound, C8H6N2O·C6H3N3O7, are in the usual ranges. The three nitro groups are almost coplanar with the aromatic picrate ring [dihedral angles 10.2 (2)°, 7.62 (16) and 8.08 (17)°]. The mol­ecular conformation of the picric acid is stabilized by an intra­molecular O—H⋯O hydrogen bond. The phthalazin-1(2H)-one mol­ecules are connected via N—H⋯O hydrogen bonds, forming centrosymmetric dimers. PMID:21200682

Overexpression of the protein phosphatase 2A regulatory subunit a gene ZmPP2AA1 improves low phosphate tolerance by remodeling the root system architecture of maize

PubMed Central

Wang, Jiemin; Pei, Laming; Jin, Zhe; Zhang, Kewei; Zhang, Juren

2017-01-01

Phosphate (Pi) limitation is a constraint for plant growth and development in many natural and agricultural ecosystems. In this study, a gene encoding Zea mays L. protein phosphatase 2A regulatory subunit A, designated ZmPP2AA1, was induced in roots by low Pi availability. The function of the ZmPP2AA1 gene in maize was analyzed using overexpression and RNA interference. ZmPP2AA1 modulated root gravitropism, negatively regulated primary root (PR) growth, and stimulated the development of lateral roots (LRs). A detailed characterization of the root system architecture (RSA) in response to different Pi concentrations with or without indole-3-acetic acid and 1-N-naphthylphthalamic acid revealed that auxin was involved in the RSA response to low Pi availability. Overexpression of ZmPP2AA1 enhanced tolerance to Pi starvation in transgenic maize in hydroponic and soil pot experiments. An increased dry weight (DW), root-to-shoot ratio, and total P content and concentration, along with a delayed and reduced accumulation of anthocyanin in overexpressing transgenic maize plants coincided with their highly branched root system and increased Pi uptake capability under low Pi conditions. Inflorescence development of the ZmPP2AA1 overexpressing line was less affected by low Pi stress, resulting in higher grain yield per plant under Pi deprivation. These data reveal the biological function of ZmPP2AA1, provide insights into a linkage between auxin and low Pi responses, and drive new strategies for the efficient utilization of Pi by maize. PMID:28448624

Echium oil is better than rapeseed oil in enriching poultry meat with n-3 polyunsaturated fatty acids, including eicosapentaenoic acid and docosapentaenoic acid.

PubMed

Kitessa, Soressa M; Young, Paul

2009-03-01

alpha-Linolenic acid (ALA; 18 : 3n-3) and stearidonic acid (SDA; 18 : 4n-3) are on the biosynthetic pathway of EPA (20 : 5n-3) and DHA (22 : 6n-3). The n-3 fatty acid in rapeseed oil is ALA while Echium oil contains both ALA and SDA. To determine the comparative efficacy of ALA- and SDA-rich oils in enriching broiler meat with n-3 PUFA, we offered diets supplemented with rapeseed oil (rapeseed group) or Echium oil (Echium group) for 35 d to two groups of chicks (age 21 d). There were no differences in carcass weight (2.20 (sem 0.06) v. 2.23 (sem 0.05) kg), boned, skinless thigh muscle (494 (sem 20.5) v. 507 (sem 16.7) g), boned, skinless breast muscle (553 (sem 13.4) v. 546 (sem 11.6) g) or organ weights (heart, liver and gizzard) between the two groups. The total intramuscular fat (IMF) percentage of thigh (8.0 (sem 0.64) v. 8.1 (sem 0.62) %) and breast muscles (2.3 (sem 0.24) v. 2.0 (sem 0.19) %) were also similar between the groups. In contrast, the concentrations of most of the individual n-3 fatty acids (ALA, SDA, EPA and docosapentaenoic acid) were all higher in the Echium than the rapeseed group (P < 0.05). However, differences in DHA concentrations were significant in breast but not thigh muscle IMF. The total n-3 yields/100 g serve thigh muscle were 265 and 676 mg for the rapeseed and Echium groups, respectively (P < 0.0001). The corresponding values for equivalent breast muscles were 70 and 137 mg, respectively (P < 0.01). We conclude that Echium oil is a better lipid supplement than rapeseed oil in changing the concentration and yield of n-3 fatty acids, except DHA, in broiler meat.

Fatty acids of pulmonary surfactant phosphatidylcholine from fetal rabbit lung tissue in culture. Biosynthesis of n-10 monoenoic fatty acids.

PubMed

Longmuir, K J; Resele-Tiden, C; Rossi, M E

1988-08-01

of the unusual n-10 fatty acids was observed from the start of culture throughout the entire 7-day culture period, and was observed in incubations of tissue slices of day 23 fetal rabbit lung. This is the first report of the biosynthesis of n-10 fatty acids (16:1 cis-6 and 18:1 cis-8) in a mammalian tissue other than skin, where these fatty acids are found in the secretory product (sebum) of sebaceous glands.

Presence and inter-individual variability of carboxylesterases (CES1 and CES2) in human lung.

PubMed

Gabriele, Morena; Puccini, Paola; Lucchi, Marco; Vizziello, Anna; Gervasi, Pier Giovanni; Longo, Vincenzo

2018-04-01

Lungs are pharmacologically active organs and the pulmonary drug metabolism is of interest for inhaled drugs design. Carboxylesterases (CESs) are enzymes catalyzing the hydrolysis of many structurally different ester, amide and carbamate chemicals, including prodrugs. For the first time, the presence, kinetics, inhibition and inter-individual variations of the major liver CES isozymes (CES1 and CES2) were investigated in cytosol and microsomes of human lungs from 20 individuals using 4-nitrophenyl acetate (pNPA), 4-methylumbelliferyl acetate (4-MUA), and fluorescein diacetate (FD) as substrates the rates of hydrolysis (V max ) for pNPA and 4-MUA, unlike FD, were double in microsomes than in cytosol. In these cellular fractions, the V max of pNPA, as CES1 marker, were much greater (30-50-fold) than those of FD, as a specific CES2 marker. Conversely, the K m values were comparable suggesting the involvement of the same enzymes. Inhibition studies revealed that the FD hydrolysis was inhibited by bis-p-nitrophenylphosphate, phenylmethanesulfonyl fluoride, and loperamide (specific for CES2), whereas the pNPA and 4-MUA hydrolysis inhibition was limited. Inhibitors selective for other esterases missed having any effect on above-mentioned activities. In cytosol and microsomes of 20 lung samples, inter-individual variations were found for the hydrolysis of pNPA (2.5-5-fold), FD or 4-MUA (8-15-fold). Similar variations were also observed in CES1 and CES2 gene expression, although determined in a small number (n = 9) of lung samples. The identification of CES1 and CES2 and their variability in human lungs are important for drug metabolism and design of prodrugs which need to be activated in this organ. Copyright © 2018 Elsevier Inc. All rights reserved.

Hydrogen bonded binary molecular adducts derived from exobidentate N-donor ligand with dicarboxylic acids: Acid⋯imidazole hydrogen-bonding interactions in neutral and ionic heterosynthons

NASA Astrophysics Data System (ADS)

Kathalikkattil, Amal Cherian; Damodaran, Subin; Bisht, Kamal Kumar; Suresh, Eringathodi

2011-01-01

Four new binary molecular compounds between a flexible exobidentate N-heterocycle and a series of dicarboxylic acids have been synthesized. The N-donor 1,4-bis(imidazol-1-ylmethyl)benzene (bix) was reacted with flexible and rigid dicarboxylic acids viz., cyclohexane-1,4-dicarboxylic acid (H 2chdc), naphthalene-1,4-dicarboxylic acid (H 2npdc) and 1H-pyrazole-3,5-dicarboxylic acid (H 2pzdc), generating four binary molecular complexes. X-ray crystallographic investigation of the molecular adducts revealed the primary intermolecular interactions carboxylic acid⋯amine (via O-H⋯N) as well as carboxylate⋯protonated amine (via N-H +⋯O -) within the binary compounds, generating layered and two-dimensional sheet type H-bonded networks involving secondary weak interactions (C-H⋯O) including the solvent of crystallization. Depending on the differences in p Ka values of the selected base/acid (Δp Ka), diverse H-bonded supramolecular assemblies could be premeditated. This study demonstrates the H-bonding interactions between imidazole/imidazolium cation and carboxylic acid/carboxylate anion in providing sufficient driving force for the directed assembly of binary molecular complexes. In the two-component solid form of hetero synthons involving bix and dicarboxylic acid, only H 2chdc exist as cocrystal with bix, while all the other three compounds crystallized exclusively as salt, in agreement with the Δp Ka values predicted for the formation of salts/cocrystals from the base and acid used in the synthesis of supramolecular solids.

Calcium-loaded 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid blocks cell-to-cell diffusion of carboxyfluorescein in staminal hairs of Setcreasea purpurea.

PubMed

Tucker, E B

1990-08-01

The effect of microinjected calcium-loaded 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (CaBAPTA) on cell-to-cell diffusion of carboxyfluorescein (CF) was examined in staminal hairs of S. purpurea Boom. The CaBAPTA was microinjected into the cytoplasm of the staminal hairs either with CF or prior to a subsequent microinjection of CF. The cell-to-cell diffusion of CF along the hair was monitored using enhanced-fluorescence video microscopy. Cytoplasmic streaming stopped in cells treated with CaBAPTA, indicating that intracellular Ca(2+) had increased. Cell-to-cell diffusion of CF was blocked in cells treated with Ca-BAPTA. An inhibition of cytoplasmic streaming and cell-to-cell diffusion was observed in the cells adjoining the CaBAPTA-microinjected cell, indicating that the Ca-BAPTA appeared to pass through plasmodesmata. While cytoplasmic streaming resumed 5-10 min after CaBAPTA treatment, cell-to-cell diffusion did not resume until 30-120 min later. These data support an involvement of calcium in the regulation of cell-to-cell communication in plants.

Genetic diversity of HA1 domain of heammaglutinin gene of influenza A(H1N1)pdm09 in Tunisia

PubMed Central

2013-01-01

We present major results concerning isolation and determination of the nucleotide sequence of hemagglutinin (HA1) of the pandemic (H1N1)pdm09 influenza viruses found in Tunisia. Amino acid analysis revealed minor amino acid changes in the antigenic or receptor-binding domains. We found mutations that were also present in 1918 pandemic virus, which includes S183P in 4 and S185T mutation in 19 of 27 viruses analyzed from 2011, while none of the 2009 viruses carried these mutations. Also two specific amino acid differences into N-glycosylation sites (N288T and N276H) were detected. The phylogenetic analysis revealed that the majority of the Tunisian isolates clustered with clade A/St. Petersburg/27/2011 viruses characterized by D97N and S185T mutations. However it also reveals a trend of 2010 strains to accumulate amino acid variation and form new phylogenetic clade with three specific amino acid substitutions: V47I, E172K and K308E. PMID:23679923

Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation.

PubMed

Barden, Anne; Mas, Emilie; Croft, Kevin D; Phillips, Michael; Mori, Trevor A

2014-11-01

Resolution of inflammation is an active process involving specialized proresolving mediators (SPM) formed from the n-3 fatty acids. This study examined the effect of n-3 fatty acid supplementation and aspirin on plasma SPMs in healthy humans. Healthy volunteers (n = 21) were supplemented with n-3 fatty acids (2.4g/day) for 7 days with random assignment to take aspirin (300 mg/day) or placebo from day 5 to day 7. Blood was collected at baseline (day 0), day 5, and day 7. Plasma 18R/S-HEPE, E-series resolvins, 17R/S-HDHA, D-series resolvins, 14R/S-HDHA, and MaR-1 were measured by LC/MS/MS. At baseline concentrations of E- and D- series resolvins and the upstream precursors 18R/S-HEPE, 17R/S-HDHA ranged from 0.1nM to 0.2nM. 14R/S-HDHA was 3-fold higher than the other SPMs at baseline but MaR-1 was below the limit of detection. Supplementation with n-3 fatty acids significantly increased RvE1, 18R/S-HEPE, 17R/S-HDHA, and 14R/S-HDHA but not other SPMs. The addition of aspirin after 5 days of n-3 fatty acids did not affect concentrations of any SPM. N-3 fatty acid supplementation for 5 days results in concentrations of SPMs that are biologically active in healthy humans. Aspirin administered after n-3 fatty acids did not offer any additional benefit in elevating the levels of SPMs. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

[Effect of humic acids on migration and transformation of NH4(+) -N in saturated aquifer].

PubMed

Meng, Qing-Jun; Zhang, Yan; Feng, Qi-Yan; Zhang, Shuang-Sheng

2011-11-01

Isothermal adsorption experiment was used to study the adsorbing process of NH4(+) -N in quartz sands under the conditions with and without humic acid; the Langmuir and Freundlich equations were used to fit the absorption result and the maximum adsorption capacity of NH4(+) -N by quarts sands was calculated. Through the soil column experiments, the concentration of NH4(+) -N, NO3(-) -N and NO2(-) -N in effluent water in the tested soil column was investigated, and the effect of humic acid on migration and transformation of NH4(+) -N in saturated aquifer was analyzed, and Pseudo-second-order Kinetics Equation and Two-step Adsorption Kinetics Rate Equation were applied to fit the kinetic processes. The results showed that both Langmuir and Freundlich models can well describe the isothermal adsorption process of NH4(+) -N on the surface of quartz sands, which means that NH4(+) -N adsorbed by the quartz sand was mainly in the form of monolayer adsorption. The humic acid could increase the adsorption capacity of NH4(+) -N on quartz sand, and the saturated adsorption capacity was 0.354 mg x g(-1) under the condition with humic acid and 0.205 mg x g(-1) with the absence of humic acid. The experiment indicated that humic acid increased the adsorption capacity of NH4(+) -N on the surface of quartz sand by increasing adsorption space in the initial stage. After saturation, humic acid influenced the migration and transformation of NH4(+) -N to NO3(-) -N and NO2(-) -N probably through providing carbon source and energy for microorganisms such as nitrifying bacteria and then resulting in lower NH4(+) -N concentration in effluent water. Both Pseudo-second-order Kinetics Equation and Two-step Adsorption Kinetics Rate Equations can well describe the process of NH4(+) -N adsorption kinetics on quartz sand (R2 = 0.997 7 and R2 = 0.998 1 with humic acid; R2 = 0.992 3 and R2 = 0.994 4 without humic acid), indicating that this process was chemical adsorption. By comparing the

6-Methyl-1,2,4-benzenetriol, a new intermediate in penicillic acid biosynthesis in Penicillium cyclopium

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

Sekiguchi, J.; Katayama, S.; Yamada, Y.

1987-07-01

Penicillic acid-negative mutants were obtained from a color mutant derived from Penicillium cyclopium NRRL 1888 through N-methyl-N'-nitro-N-nitrosoguanidine treatment. One mutant (SK2N6) accumulated 6-methyl-1,2,4-benzenetriol, which was not previously known to be a metabolite of P. cyclopium, in addition to orsellinic acid and orcinol. The radioactivity of (1-/sup 14/C)acetic acid was rapidly incorporated into 6-methyl-1,2,4-benzenetriol in a culture of P. cyclopium SK2N6. Moreover, the radioactivity of (/sup 14/C)6-methyl-1,2,4-benzenetriol was efficiently incorporated into penicillic acid in a culture of P. cyclopium NRRL 1888. These data indicate that 6-methyl-1,2,4-benzenetriol is a precursor for penicillic acid biosynthesis. The results on the addition of 1,4-dihydroxy-6-methoxy-2-methylbenzene, 6-methoxy-2-methylbenzoquinonemore » (1,4), and 1-O-methylorcinol to a culture of P. cyclopium SK2N6 indicated that only the former two compounds are converted to penicillic acid. Thus, a new portion of the penicillic acid biosynthetic pathway is proposed.« less

Pork as a Source of Omega-3 (n-3) Fatty Acids

PubMed Central

Dugan, Michael E.R.; Vahmani, Payam; Turner, Tyler D.; Mapiye, Cletos; Juárez, Manuel; Prieto, Nuria; Beaulieu, Angela D.; Zijlstra, Ruurd T.; Patience, John F.; Aalhus, Jennifer L.

2015-01-01

Pork is the most widely eaten meat in the world, but typical feeding practices give it a high omega-6 (n-6) to omega-3 (n-3) fatty acid ratio and make it a poor source of n-3 fatty acids. Feeding pigs n-3 fatty acids can increase their contents in pork, and in countries where label claims are permitted, claims can be met with limited feeding of n-3 fatty acid enrich feedstuffs, provided contributions of both fat and muscle are included in pork servings. Pork enriched with n-3 fatty acids is, however, not widely available. Producing and marketing n-3 fatty acid enriched pork requires regulatory approval, development costs, quality control costs, may increase production costs, and enriched pork has to be tracked to retail and sold for a premium. Mandatory labelling of the n-6/n-3 ratio and the n-3 fatty acid content of pork may help drive production of n-3 fatty acid enriched pork, and open the door to population-based disease prevention polices (i.e., food tax to provide incentives to improve production practices). A shift from the status-quo, however, will require stronger signals along the value chain indicating production of n-3 fatty acid enriched pork is an industry priority. PMID:26694475

Pork as a Source of Omega-3 (n-3) Fatty Acids.

PubMed

Dugan, Michael E R; Vahmani, Payam; Turner, Tyler D; Mapiye, Cletos; Juárez, Manuel; Prieto, Nuria; Beaulieu, Angela D; Zijlstra, Ruurd T; Patience, John F; Aalhus, Jennifer L

2015-12-16

Pork is the most widely eaten meat in the world, but typical feeding practices give it a high omega-6 (n-6) to omega-3 (n-3) fatty acid ratio and make it a poor source of n-3 fatty acids. Feeding pigs n-3 fatty acids can increase their contents in pork, and in countries where label claims are permitted, claims can be met with limited feeding of n-3 fatty acid enrich feedstuffs, provided contributions of both fat and muscle are included in pork servings. Pork enriched with n-3 fatty acids is, however, not widely available. Producing and marketing n-3 fatty acid enriched pork requires regulatory approval, development costs, quality control costs, may increase production costs, and enriched pork has to be tracked to retail and sold for a premium. Mandatory labelling of the n-6/n-3 ratio and the n-3 fatty acid content of pork may help drive production of n-3 fatty acid enriched pork, and open the door to population-based disease prevention polices (i.e., food tax to provide incentives to improve production practices). A shift from the status-quo, however, will require stronger signals along the value chain indicating production of n-3 fatty acid enriched pork is an industry priority.

Erythrocyte stearidonic acid and other n-3 fatty acids and CHD in the Physicians’ Health Study

USDA-ARS?s Scientific Manuscript database

Intake of marine-based n-3 fatty acids (EPA, docosapentaenoic acid and DHA) is recommended to prevent CHD. Stearidonic acid (SDA), a plant-based n-3 fatty acid, is a precursor of EPA and may be more readily converted to EPA than a-linolenic acid (ALA). While transgenic soyabeans might supply SDA at ...

Combined effects of π-π stacking and hydrogen bonding on the (N1) acidity of uracil and hydrolysis of 2'-deoxyuridine.

PubMed

Kellie, Jennifer L; Navarro-Whyte, Lex; Carvey, Matthew T; Wetmore, Stacey D

2012-03-01

M06-2X/6-31+G(d,p) is used to study the simultaneous effects of π-π stacking interactions with phenylalanine (modeled as benzene) and hydrogen bonding with small molecules (HF, H(2)O, and NH(3)) on the N1 acidity of uracil and the hydrolytic deglycosylation of 2'-deoxyuridine (dU) (facilitated by fully (OH(-)) or partially (HCOO(-)···H(2)O) activated water). When phenylalanine is complexed with isolated uracil, the proton affinity of all acceptor sites significantly increases (by up to 28 kJ mol(-1)), while the N1 acidity slightly decreases (by ~6 kJ mol(-1)). When small molecules are hydrogen bound to uracil, addition of the phenylalanine ring can increase or decrease the acidity of uracil depending on the number and nature (acidity) of the molecules bound. Furthermore, a strong correlation between the effects of π-π stacking on the acidity of U and the dU deglycosylation reaction energetics is found, where the hydrolysis barrier can increase or decrease depending on the nature and number of small molecules bound, the nucleophile considered (which dictates the negative charge on U in the transition state), and the polarity of the (bulk) environment. These findings emphasize that the catalytic (or anticatalytic) role of the active-site aromatic amino acid residues is highly dependent on the situation under consideration. In the case of uracil-DNA glycosylase (UNG), which catalyzes the hydrolytic excision of uracil from DNA, the type of discrete hydrogen-bonding interactions with U, the nature of the nucleophile, and the anticipated weak, nonpolar environment in the active site suggest that phenylalanine will be slightly anticatalytic in the chemical step, and therefore experimentally observed contributions to catalysis may entirely result from associated structural changes that occur prior to deglycosylation.

Thermodynamic, Spectroscopic, and Computational Studies of f -Element Complexation by N -Hydroxyethyl-diethylenetriamine- N,N ', N ", N"-tetraacetic Acid

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

Grimes, Travis S.; Heathman, Colt R.; Jansone-Popova, Santa

Potentiometric and spectroscopic techniques were combined with DFT calculations to probe the coordination environment and determine thermodynamic features of trivalent f-element complexation by N-hydroxyethyl-diethylenetriamine-N,N',N",N"-tetraacetic acid, HEDTTA. Ligand protonation constants and lanthanide stability constants were determined using potentiometry. Five protonation constants were accessible in I = 2.0 M (H +/Na +)ClO 4. UV–vis spectroscopy was used to determine stability constants for Nd 3+ and Am 3+ complexation with HEDTTA. Luminescence spectroscopy indicates two water molecules in the inner coordination sphere of the Eu/HEDTTA complex, suggesting HEDTTA is heptadentate. Luminescence data was supported by DFT calculations, which demonstrate that substitution of themore » acetate pendant arm by a N-hydroxyethyl group weakens the metal–nitrogen bond. This bond elongation is reflected in HEDTTA’s ability to differentiate trivalent actinides from trivalent lanthanides. The trans-lanthanide Ln/HEDTTA complex stability trend is analogous to Ln/DTPA complexation; however, the loss of one chelate ring resulting from structural substitution weakens the complexation by ~3 orders of magnitude. Successful separation of trivalent americium from trivalent lanthanides was demonstrated when HEDTTA was utilized as aqueous holdback complexant in a liquid–liquid system. Time-dependent extraction studies for HEDTTA were compared to diethylenetriamine-N,N,N',N",N"-pentaacetic acid (DTPA) and N-hydroxyethyl-ethylenediamine-N,N',N'-triacetic acid (HEDTA). The results presented here indicate substantially enhanced phase-transfer kinetic rates for mixtures containing HEDTTA.« less

Thermodynamic, Spectroscopic, and Computational Studies of f -Element Complexation by N -Hydroxyethyl-diethylenetriamine- N,N ', N ", N"-tetraacetic Acid

DOE PAGES

Grimes, Travis S.; Heathman, Colt R.; Jansone-Popova, Santa; ...

2017-01-24

Potentiometric and spectroscopic techniques were combined with DFT calculations to probe the coordination environment and determine thermodynamic features of trivalent f-element complexation by N-hydroxyethyl-diethylenetriamine-N,N',N",N"-tetraacetic acid, HEDTTA. Ligand protonation constants and lanthanide stability constants were determined using potentiometry. Five protonation constants were accessible in I = 2.0 M (H +/Na +)ClO 4. UV–vis spectroscopy was used to determine stability constants for Nd 3+ and Am 3+ complexation with HEDTTA. Luminescence spectroscopy indicates two water molecules in the inner coordination sphere of the Eu/HEDTTA complex, suggesting HEDTTA is heptadentate. Luminescence data was supported by DFT calculations, which demonstrate that substitution of themore » acetate pendant arm by a N-hydroxyethyl group weakens the metal–nitrogen bond. This bond elongation is reflected in HEDTTA’s ability to differentiate trivalent actinides from trivalent lanthanides. The trans-lanthanide Ln/HEDTTA complex stability trend is analogous to Ln/DTPA complexation; however, the loss of one chelate ring resulting from structural substitution weakens the complexation by ~3 orders of magnitude. Successful separation of trivalent americium from trivalent lanthanides was demonstrated when HEDTTA was utilized as aqueous holdback complexant in a liquid–liquid system. Time-dependent extraction studies for HEDTTA were compared to diethylenetriamine-N,N,N',N",N"-pentaacetic acid (DTPA) and N-hydroxyethyl-ethylenediamine-N,N',N'-triacetic acid (HEDTA). The results presented here indicate substantially enhanced phase-transfer kinetic rates for mixtures containing HEDTTA.« less

Springback in root gravitropism

NASA Technical Reports Server (NTRS)

Leopold, A. C.; Wettlaufer, S. H.

1989-01-01

Conditions under which a gravistimulus of Merit corn roots (Zea mays L.) is withdrawn result in a subsequent loss of gravitropic curvature, an effect which we refer to as springback.' This loss of curvature begins within 1 to 10 minutes after removal of the gravistimulus. It occurs regardless of the presence or absence of the root cap. It is insensitive to inhibitors of auxin transport (2,3,5-triiodobenzoic acid, naphthylphthalamic [correction of naphthylphthalmaic] acid) or to added auxin (2,4-dichlorophenoxyacetic acid). Springback is prevented if a clinostat treatment is interjected to neutralize gravistimulation during germination, which suggests that the change in curvature is a response to a memory' effect carried over from a prior gravistimulation.

Partial replacement of dietary linoleic acid with long chain n-3 polyunsaturated fatty acids protects against dextran sulfate sodium-induced colitis in rats.

PubMed

Tyagi, Anupama; Kumar, Uday; Santosh, Vadakattu Sai; Reddy, Suryam; Mohammed, Saazida Bhanu; Ibrahim, Ahamed

2014-12-01

Imbalances in the dietary n-6 and n-3 polyunsaturated fatty acids have been implicated in the increased prevalence of inflammatory bowel disease. This study investigated the effects of substitution of linoleic acid with long chain n-3 polyunsaturated fatty acids and hence decreasing n-6:n-3 fatty acid ratio on inflammatory response in dextran sulfate sodium induced colitis. Male weanling Sprague Dawley rats were fed diets with n-6:n-3 fatty acid in the ratios of 215,50,10 or 5 for 3 months and colitis was induced by administration of dextran sulfate sodium in drinking water during last 11 days. Decreasing the dietary n-6:n-3 fatty acid ratio to 10 and 5 significantly attenuated the severity of colitis as evidenced by improvements in clinical symptoms, reversal of shortening of colon length, reduced severity of anemia, preservation of colonic architecture as well as reduced colonic mucosal myeloperoxidase activity. This protection was associated with suppression of colonic mucosal proinflammatory mediators such as TNFα, IL-1β and nitric oxide. These findings suggest that long chain n-3 polyunsaturated fatty acids at a level of 3.0 g/kg diet (n-6:n-3 ratio of 10) prevents dextran sulfate sodium induced colitis by suppressing the proinflammatory mediators. Copyright © 2014 Elsevier Ltd. All rights reserved.

An efficient synthesis of the constrained peptidomimetic 2-oxo-3-(N-9-fluorenyloxycarbonylamino)-1-azabicyclo[4.3.0]nonane-9-carboxylic acid from pyroglutamic acid.

PubMed

Mandal, Pijus Kumar; Kaluarachchi, Kumar K; Ogrin, Douglas; Bott, Simon G; McMurray, John S

2005-11-25

[reaction: see text] Azabicyclo[X.Y.0]alkane amino acids are rigid dipeptide mimetics that are useful tools for structure-activity studies in peptide-based drug discovery. Herein, we report an efficient synthesis of three diastereomers of 9-tert-butoxycarbonyl-2-oxo-3-(N-tert-butoxycarbonylamino)-1-azabicyclo[4.3.0]nonane (3S,6S,9S, 3S,6R,9R, and 3S,6R,9S). Methyl N-Boc-pyroglutamate is cleaved with vinylmagnesium bromide to produce an acyclic gamma-vinyl ketone. Michael addition of N-diphenylmethyleneglycine tert-butyl ester produces the N-Boc-delta-oxo-alpha,omega-diaminoazelate intermediate, which, on hydrogenloysis, gives the fused ring system. Acidolytic deprotection followed by Fmoc-protection provided building blocks suitable for solid-phase synthesis.

Supramolecular architectures in two 1:1 cocrystals of 5-fluorouracil with 5-bromothiophene-2-carboxylic acid and thiophene-2-carboxylic acid.

PubMed

Mohana, Marimuthu; Thomas Muthiah, Packianathan; McMillen, Colin D

2017-06-01

In solid-state engineering, cocrystallization is a strategy actively pursued for pharmaceuticals. Two 1:1 cocrystals of 5-fluorouracil (5FU; systematic name: 5-fluoro-1,3-dihydropyrimidine-2,4-dione), namely 5-fluorouracil-5-bromothiophene-2-carboxylic acid (1/1), C 5 H 3 BrO 2 S·C 4 H 3 FN 2 O 2 , (I), and 5-fluorouracil-thiophene-2-carboxylic acid (1/1), C 4 H 3 FN 2 O 2 ·C 5 H 4 O 2 S, (II), have been synthesized and characterized by single-crystal X-ray diffraction studies. In both cocrystals, carboxylic acid molecules are linked through an acid-acid R 2 2 (8) homosynthon (O-H...O) to form a carboxylic acid dimer and 5FU molecules are connected through two types of base pairs [homosynthon, R 2 2 (8) motif] via a pair of N-H...O hydrogen bonds. The crystal structures are further stabilized by C-H...O interactions in (II) and C-Br...O interactions in (I). In both crystal structures, π-π stacking and C-F...π interactions are also observed.

Inhibitory activity and mechanism of inhibition of the N-[[(4-benzoylamino)phenyl]sulfonyl]amino acid aldose reductase inhibitors.

PubMed

DeRuiter, J; Mayfield, C A

1990-11-15

A series of substituted N-[[(4-benzoylamino)phenyl]sulfonyl]amino acids (BAPS-amino acids) were synthesized by established methods, and the stereochemistry of the products was confirmed by HPLC analysis after chiral derivatization. When tested against aldose reductase (alditol:NADP+ oxidoreductase; EC 1.1.1.21; ALR2) isolated from rat lens, all of the BAPS-amino acids were determined to be significantly more inhibitory than the corresponding N-(phenylsulfonyl)amino acids. Structure-inhibition and enzyme kinetic analyses suggest that the BAPS-amino acids inhibit ALR2 by a mechanism similar to the N-(phenylsulfonyl)amino acids. However, multiple inhibition analyses indicate that the increased inhibitory activity of the BAPS-amino acids is a result of interaction with multiple sites present on ALR2. Enzyme specificity studies with several of the BAPS-amino acids demonstrated that these compounds do not produce significant inhibition of other nucleotide-requiring enzymes including aldehyde reductase (alcohol: NADP+ oxidoreductase; EC 1.1.1.2; ALR1).

Thermodynamic and Spectroscopic Studies of Trivalent f -element Complexation with Ethylenediamine- N,N '-di(acetylglycine)- N,N '-diacetic Acid

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

Heathman, Colt R.; Grimes, Travis S.; Zalupski, Peter R.

In this study, the coordination behavior and thermodynamic features of complexation of trivalent lanthanides and americium by ethylenediamine- N,N'-di(acetylglycine)- N,N'-diacetic acid (EDDAG-DA) (bisamide-substituted-EDTA) were investigated by potentiometric and spectroscopic techniques. Acid dissociation constants (K a) and complexation constants (β) of lanthanides (except Pm) were determined by potentiometric analysis. Absorption spectroscopy was used to determine stability constants for the binding of trivalent americium and neodymium by EDDAG-DA under similar conditions. The potentiometry revealed 5 discernible protonation constants and 3 distinct metal–ligand complexes (identified as ML –, MHL, and MH 2L +). Time-resolved fluorescence studies of Eu-(EDDAG-DA) solutions (at varying pH) identifiedmore » a constant inner-sphere hydration number of 3, suggesting that glycine functionalities contained in the amide pendant arms are not involved in metal complexation and are protonated under more acidic conditions. The thermodynamic studies identified that f-element coordination by EDDAG-DA is similar to that observed for ethylenediamine- N,N,N',N'-tetraacetic acid (EDTA). However, coordination via two amidic oxygens of EDDAG-DA lowers its trivalent f-element complex stability by roughly 3 orders of magnitude relative to EDTA.« less

Thermodynamic and Spectroscopic Studies of Trivalent f -element Complexation with Ethylenediamine- N,N '-di(acetylglycine)- N,N '-diacetic Acid

DOE PAGES

Heathman, Colt R.; Grimes, Travis S.; Zalupski, Peter R.

2016-03-21

In this study, the coordination behavior and thermodynamic features of complexation of trivalent lanthanides and americium by ethylenediamine- N,N'-di(acetylglycine)- N,N'-diacetic acid (EDDAG-DA) (bisamide-substituted-EDTA) were investigated by potentiometric and spectroscopic techniques. Acid dissociation constants (K a) and complexation constants (β) of lanthanides (except Pm) were determined by potentiometric analysis. Absorption spectroscopy was used to determine stability constants for the binding of trivalent americium and neodymium by EDDAG-DA under similar conditions. The potentiometry revealed 5 discernible protonation constants and 3 distinct metal–ligand complexes (identified as ML –, MHL, and MH 2L +). Time-resolved fluorescence studies of Eu-(EDDAG-DA) solutions (at varying pH) identifiedmore » a constant inner-sphere hydration number of 3, suggesting that glycine functionalities contained in the amide pendant arms are not involved in metal complexation and are protonated under more acidic conditions. The thermodynamic studies identified that f-element coordination by EDDAG-DA is similar to that observed for ethylenediamine- N,N,N',N'-tetraacetic acid (EDTA). However, coordination via two amidic oxygens of EDDAG-DA lowers its trivalent f-element complex stability by roughly 3 orders of magnitude relative to EDTA.« less

Brown algae hydrolysis in 1-n-butyl-3-methylimidazolium chloride with mineral acid catalyst system.

PubMed

Malihan, Lenny B; Nisola, Grace M; Chung, Wook-Jin

2012-08-01

The amenability of three brown algal species, Sargassum fulvellum, Laminaria japonica and Undaria pinnatifida, to hydrolysis were investigated using the ionic liquid (IL), 1-n-butyl-3-methylimidazolium chloride ([BMIM]Cl). Compositional analyses of the brown algae reveal that sufficient amounts of sugars (15.5-29.4 wt.%) can be recovered. Results from hydrolysis experiments show that careful selection of the type of mineral acid as catalyst and control of acid loading could maximize the recovery of sugars. Optimal reaction time and temperature were determined from the kinetic studies on the sequential reducing sugar (TRS) formation and degradation. Optimal reaction times were determined based on the extent of furfurals formation as TRS degradation products. X-ray diffraction and environmental scanning electron microscopy confirmed the suitability of [BMIM]Cl as solvent for the hydrolysis of the three brown algae. Overall results show the potential of brown algae as renewable energy resources for the production of valuable chemicals and biofuels. Copyright © 2012 Elsevier Ltd. All rights reserved.

Benzamide–picric acid (1/1)

PubMed Central

Sivaramkumar, M. S.; Velmurugan, R.; Sekar, M.; Ramesh, P.; Ponnuswamy, M. N.

2010-01-01

In the title compound, C7H7NO·C6H3N3O7, one of the nitro groups of the picric acid mol­ecule lies in the plane of the attached benzene ring [dihedral angle = 1.4 (1)°] while the other two are twisted away by 9.9 (1) and 30.3 (1)°. In the benzamide mol­ecule, the amide group is almost coplanar with the benzene ring [dihedral angle = 4.4 (1)°]. An intra­molecular O—H⋯O hydrogen bond generates an S6 ring motif. In the crystal, mol­ecules are linked into a ribbon-like structure along the b axis by O—H⋯O and N—H⋯O inter­molecular hydrogen bonds. In addition, C—H⋯O hydrogen bonds and short O⋯O contacts [2.828 (2) Å] are observed. PMID:21588027

A structural insight into the P1S1 binding mode of diaminoethylphosphonic and phosphinic acids, selective inhibitors of alanine aminopeptidases

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

Węglarz-Tomczak, Ewelina; Berlicki, Łukasz; Pawełczak, Małgorzata

N0 -substituted 1,2-diaminoethylphosphonic acids and 1,2-diaminoethylphosphinic dipeptides were explored to unveil the structural context of the unexpected selectivity of these inhibitors of M1 alanine aminopeptidases (APNs) versus M17 leucine aminopeptidase (LAP). The diaminophosphonic acids were obtained via aziridines in an improved synthetic procedure that was further expanded for the phosphinic pseudodipeptide system. The inhibitory activity, measured for three M1 and one M17 metalloaminopeptidases of different sources (bacterial, human and porcine), revealed several potent compounds (e.g., Ki ¼ 65 nM of 1u for HsAPN). Two structures of an M1 representative (APN from Neisseria meningitidis) in complex with N-benzyl-1,2-diaminoethylphosphonic acid and N-cyclohexyl-1,2-more » diaminoethylphosphonic acid were determined by the X-ray crystallography. The analysis of these structures and the models of the phosphonic acid complexes of the human ortholog provided an insight into the role of the additional amino group and the hydrophobic substituents of the ligands within the S1 active site region.« less

SIZ1 Regulation of Phosphate Starvation-Induced Root Architecture Remodeling Involves the Control of Auxin Accumulation1[C][W][OA

PubMed Central

Miura, Kenji; Lee, Jiyoung; Gong, Qingqiu; Ma, Shisong; Jin, Jing Bo; Yoo, Chan Yul; Miura, Tomoko; Sato, Aiko; Bohnert, Hans J.; Hasegawa, Paul M.

2011-01-01

Phosphate (Pi) limitation causes plants to modulate the architecture of their root systems to facilitate the acquisition of Pi. Previously, we reported that the Arabidopsis (Arabidopsis thaliana) SUMO E3 ligase SIZ1 regulates root architecture remodeling in response to Pi limitation; namely, the siz1 mutations cause the inhibition of primary root (PR) elongation and the promotion of lateral root (LR) formation. Here, we present evidence that SIZ1 is involved in the negative regulation of auxin patterning to modulate root system architecture in response to Pi starvation. The siz1 mutations caused greater PR growth inhibition and LR development of seedlings in response to Pi limitation. Similar root phenotypes occurred if Pi-deficient wild-type seedlings were supplemented with auxin. N-1-Naphthylphthalamic acid, an inhibitor of auxin efflux activity, reduced the Pi starvation-induced LR root formation of siz1 seedlings to a level equivalent to that seen in the wild type. Monitoring of the auxin-responsive reporter DR5::uidA indicated that auxin accumulates in PR tips at early stages of the Pi starvation response. Subsequently, DR5::uidA expression was observed in the LR primordia, which was associated with LR elongation. The time-sequential patterning of DR5::uidA expression occurred earlier in the roots of siz1 as compared with the wild type. In addition, microarray analysis revealed that several other auxin-responsive genes, including genes involved in cell wall loosening and biosynthesis, were up-regulated in siz1 relative to wild-type seedlings in response to Pi starvation. Together, these results suggest that SIZ1 negatively regulates Pi starvation-induced root architecture remodeling through the control of auxin patterning. PMID:21156857

Chronic sucrose intake decreases concentrations of n6 fatty acids, but not docosahexaenoic acid in the rat brain phospholipids.

PubMed

Mašek, Tomislav; Starčević, Kristina

2017-07-13

We investigated the influence of high sucrose intake, administered in drinking water, on the lipid profile of the brain and on the expression of SREBP1c and Δ-desaturase genes. Adult male rats received 30% sucrose solution for 20 weeks (Sucrose group), or plain water (Control group). After the 20th week of sucrose treatment, the Sucrose group showed permanent hyperglycemia. Sucrose treatment also increased the amount of total lipids and fatty acids in the brain. The brain fatty acid profile of total lipids as well as phosphatidylethanolamine, phosphatidylcholine and cardiolipin of the Sucrose group was extensively changed. The most interesting change was a significant decrease in n6 fatty acids, including the important arachidonic acid, whereas the content of oleic and docosahexaenoic acid remained unchanged. RT-qPCR revealed an increase in Δ-5-desaturase and SREBP1c gene expression. In conclusion, high sucrose intake via drinking water extensively changes rat brain fatty acid profile by decreasing n6 fatty acids, including arachidonic acid. In contrast, the content of docosahexaenoic acid remains constant in the brain total lipids as well as in phospholipids. Changes in the brain fatty acid profile reflect changes in the lipid metabolism of the rat lipogenic tissues and concentrations in the circulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Conformational characterization of the 1-aminocyclobutane-1-carboxylic acid residue in model peptides.

PubMed

Gatos, M; Formaggio, F; Crisma, M; Toniolo, C; Bonora, G M; Benedetti, Z; Di Blasio, B; Iacovino, R; Santini, A; Saviano, M; Kamphuis, J

1997-01-01

A series of N- and C-protected, monodispersed homo-oligopeptides (to the dodecamer level) from the small-ring alicyclic C alpha, alpha-dialkylated glycine 1-aminocyclobutane-1-carboxylic acid (Ac4c) and two Ala/Ac4c tripeptides were synthesized by solution methods and fully characterized. The conformational preferences of all the model peptides were determined in deuterochloroform solution by FT-IR absorption and 1H-NMR. The molecular structures of the amino acid derivatives Z-Ac4c-OH and Z2-Ac4c-OH, the tripeptides Z-(Ac4c)3-OtBu, Z-Ac4c-(L-Ala)2-OMe and Z-L-Ala-Ac4c-L-Ala-OMe, and the tetrapeptide Z-(Ac4c)4-OtBu were determined in the crystal state by X-ray diffraction. The average geometry of the cyclobutyl moiety of the Ac4c residue was assessed and the tau(N-C alpha-C') bond angle was found to be significantly expanded from the regular tetrahedral value. The conformational data are strongly in favour of the conclusion that the Ac4c residue is an effective beta-turn and helix former. A comparison with the structural propensities of alpha-aminoisobutyric acid, the prototype of C alpha, alpha-dialkylated glycines, and the other extensively investigated members of the family of 1-aminocycloalkane-1-carboxylic acids (Acnc, with n = 3, 5-8) is made and the implications for the use of the Ac4c residue in conformationally constrained peptide analogues are briefly examined.

Incorporation of N-amidino-pyroglutamic acid into peptides using intramolecular cyclization of alpha-guanidinoglutaric acid.

PubMed

Burov, Sergey; Moskalenko, Yulia; Dorosh, Marina; Shkarubskaya, Zoya; Panarin, Evgeny

2009-11-01

N-terminal modification of peptides by unnatural amino acids significantly affects their enzymatic stability, conformational properties and biological activity. Application of N-amidino-amino acids, positively charged under physiological conditions, can change peptide conformation and its affinity to the corresponding receptor. In this article, we describe synthesis of short peptides, containing a new building block-N-amidino-pyroglutamic acid. Although direct guanidinylation of pyroglutamic acid and oxidation of N-amidino-proline using RuO(4) did not produce positive results, N-amidino-Glp-Phe-OH was synthesized on Wang polymer by cyclization of alpha-guanidinoglutaric acid residue. In the course of synthesis, it was found that literature procedure of selective Boc deprotection using TMSOTf/TEA reagent is accompanied by concomitant side reaction of triethylamine alkylation by polymer linker fragment. It should be mentioned that independently from cyclization time and coupling agent (DIC or HCTU), the lactam formation was incomplete. Separation of the cyclic product from the linear precursor was achieved by HPLC in ammonium formate buffer at pH 6. HPLC analysis showed N-amidino-Glp-Phe-OH stability at acidic and physiological pH and fast ring opening in water solution at pH 9. The suggested method of N-amidino-Glp residue formation can be applied in the case of short peptide chains, whereas synthesis of longer ones will require fragment condensation approach.

Sulfuric acid and hydrogen peroxide surface passivation effects on AlGaN/GaN high electron mobility transistors

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

Zaidi, Z. H., E-mail: zaffar.zaidi@sheffield.ac.uk; Lee, K. B.; Qian, H.

2014-12-28

In this work, we have compared SiN{sub x} passivation, hydrogen peroxide, and sulfuric acid treatment on AlGaN/GaN HEMTs surface after full device fabrication on Si substrate. Both the chemical treatments resulted in the suppression of device pinch-off gate leakage current below 1 μA/mm, which is much lower than that for SiN{sub x} passivation. The greatest suppression over the range of devices is observed with the sulfuric acid treatment. The device on/off current ratio is improved (from 10{sup 4}–10{sup 5} to 10{sup 7}) and a reduction in the device sub-threshold (S.S.) slope (from ∼215 to 90 mV/decade) is achieved. The sulfuric acid ismore » believed to work by oxidizing the surface which has a strong passivating effect on the gate leakage current. The interface trap charge density (D{sub it}) is reduced (from 4.86 to 0.90 × 10{sup 12 }cm{sup −2} eV{sup −1}), calculated from the change in the device S.S. The gate surface leakage current mechanism is explained by combined Mott hopping conduction and Poole Frenkel models for both untreated and sulfuric acid treated devices. Combining the sulfuric acid treatment underneath the gate with the SiN{sub x} passivation after full device fabrication results in the reduction of D{sub it} and improves the surface related current collapse.« less

Azido and tetrazolo 1,2,4,5-tetrazine N-oxides

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

Chavez, David E.; Parrish, Damon A.; Mitchell, Lauren

2017-02-23

This paper presents the synthesis and characterization of the oxidation products of 3,6-diazido-1,2,4,5-tetrazine (1) and 6-amino-[1,5-b]tetrazolo-1,2,4,5-tetrazine (2). 3,6-Diazido-1,2,4,5-tetrazine-1,4-dioxide was produced from oxidation with peroxytrifluoroacetic acid, and more effectively using hypofluorous acid, and 2 can be oxidized to two different products, 6-amino-[1,5-b]tetrazolo-1,2,4,5-tetrazine mono-N-oxide and di-N-oxide. These N-oxide compounds display promising performance properties as energetic materials.

Effects of dietary n-3 fatty acids on the phospholipid molecular species of monkey brain.

PubMed

Lin, D S; Connor, W E; Anderson, G J; Neuringer, M

1990-10-01

We examined the changes in the molecular species of brain ethanolamine glycerophospholipids of monkeys fed diets containing widely ranging amounts of n-3 fatty acids. Two groups of rhesus monkeys were fed pre- and postnatally either a control diet (soy oil; containing 8% of fatty acids as 18:3n-3) or a deficient diet (safflower oil; containing less than 0.3% 18:3n-3). The brains of these animals were analyzed at 22 months of age. A third group of monkeys was fed the safflower oil diet to 22 months of age and then switched to a fish oil diet (28% long-chain n-3 fatty acids) for 1-2 years before autopsy. The molecular species of the diacyl, alkylacyl, and alkenylacyl ethanolamine glycerophospholipids from frontal cortex were separated by HPLC. A total of 24 molecular species were identified. Fatty acids in the sn-2 position differed markedly among the diet groups, but the sn-1 position always contained only 16:0, 18:0, or 18:1. In the diacyl subclass of the control brain, the n-3 molecular species represented 41% of total and the n-6 species 45%, whereas in the deficient brain the n-3 molecular species decreased to 9% and n-6 molecular species increased to 77%. The fatty acid 22:5n-6 did not replace 22:6n-3 in a symmetrical fashion in the molecular species of the deficient brain. In the brains of the fish oil-fed monkeys, the n-3 molecular species amounted to 61% and n-6 molecular species were reduced to 25%. The species 18:1-22:6, 16:0-22:6, and 18:0-22:6 generally changed proportionally in response to diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Shaken not stirred: a facile synthesis of 1,4-bis(furo[2,3-d]-pyrimidine-2,4(1H,3H)-dione-5-yl)benzenes by one-pot reaction of isocyanides, N,N'-dimethylbarbituric acid, and terephthaldialdehyde.

PubMed

Teimouri, Mohammad Bagher; Bazhrang, Reihaneh

2006-07-15

A simple and efficient synthesis of 1,4-bis(furo[2,3-d]pyrimidine-2,4(1H,3H)-dione-5-yl)benzene derivatives was achieved via a one-pot three-component reaction of isocyanides, N,N'-dimethylbarbituric acid, and terephthaldialdehyde in DMF at room temperature for 30 min. These improved reaction conditions allow the preparation of highly substituted furopyrimidinones in high yields and purity under mild reaction conditions.

Combination of tauroursodeoxycholic acid and N-acetylcysteine exceeds standard treatment for acetaminophen intoxication.

PubMed

Paridaens, Annelies; Raevens, Sarah; Colle, Isabelle; Bogaerts, Eliene; Vandewynckel, Yves-Paul; Verhelst, Xavier; Hoorens, Anne; van Grunsven, Leo A; Van Vlierberghe, Hans; Geerts, Anja; Devisscher, Lindsey

2017-05-01

Acetaminophen overdose in mice is characterized by hepatocyte endoplasmic reticulum stress, which activates the unfolded protein response, and centrilobular hepatocyte death. We aimed at investigating the therapeutic potential of tauroursodeoxycholic acid, a hydrophilic bile acid known to have anti-apoptotic and endoplasmic reticulum stress-reducing capacities, in experimental acute liver injury induced by acetaminophen overdose. Mice were injected with 300 mg/kg acetaminophen, 2 hours prior to receiving tauroursodeoxycholic acid, N-acetylcysteine or a combination therapy, and were euthanized 24 hours later. Liver damage was assessed by serum transaminases, liver histology, terminal deoxynucleotidyl transferase dUTP nick end labelling staining, expression profiling of inflammatory, oxidative stress, unfolded protein response, apoptotic and pyroptotic markers. Acetaminophen overdose resulted in a significant increase in serum transaminases, hepatocyte cell death, unfolded protein response activation, oxidative stress, NLRP3 inflammasome activation, caspase 1 and pro-inflammatory cytokine expressions. Standard of care, N-acetylcysteine and, to a lesser extent, tauroursodeoxycholic treatment were associated with significantly lower transaminase levels, hepatocyte death, unfolded protein response activation, oxidative stress markers, caspase 1 expression and NLRP3 levels. Importantly, the combination of N-acetylcysteine and tauroursodeoxycholic acid improved serum transaminase levels, reduced histopathological liver damage, UPR-activated CHOP, oxidative stress, caspase 1 expression, NLRP3 levels, IL-1β levels and the expression of pro-inflammatory cytokines and this to a greater extend than N-acetylcysteine alone. These findings indicate that a combination strategy of N-acetylcysteine and tauroursodeoxycholic acid surpasses the standard of care in acetaminophen-induced liver injury in mice and might represent an attractive therapeutic opportunity for acetaminophen

Effect of n-3 fatty acids on free tryptophan and exercise fatigue.

PubMed

Huffman, Derek M; Altena, Thomas S; Mawhinney, Thomas P; Thomas, Tom R

2004-08-01

Free tryptophan (Trp), which is augmented by liberated free fatty acids (FFA) from adipose tissue, can induce mental fatigue via serotonin during exercise. Since an attenuation in FFA has been observed with omega-3 fatty acid (n-3fa) use, our purpose was to examine the effect of n-3fa supplementation on free Trp availability and exercise fatigue. Ten recreationally trained men ( n=5) and women ( n=5), with maximal oxygen consumption (VO(2max))of 51.6 (3.0) and 44.3 (1.4) ml kg(-1) min(-1), respectively, were studied on two occasions following an overnight fast, before and after n-3fa supplementation (4 g day(-1) for 4 weeks). The exercise trials consisted of a 75-min treadmill run at 60% VO(2max) followed immediately by a high-intensity incremental bout to fatigue. Measurements included exercise monitors, plasma volume (PV), triglycerides (TG), FFA, glycerol, lactate, and glucose. Free Trp and branched-chain amino acids (BCAA) were measured and correlated with time to fatigue; all blood variables were corrected for PV. Free Trp, lactate, glucose, FFA, and glycerol were not significantly different between trials, but TG ( P<0.001) and the free Trp/BCAA ratio were significantly lower after n-3fa use [1.76 (0.18)x10(-2) microg ml(-1)] versus before supplementation [2.17 (0.22), P=0.033]. There was a non-significant increase in time to fatigue after supplementation [10.2 (0.3) min] versus before n-3fa use [9.7 (0.2), P=0.068], and a tendency for higher BCAA levels after supplementation, P=0.068. However, neither free Trp nor the free Trp/BCAA ratio significantly predicted time to fatigue. In conclusion, n-3fa supplementation did not diminish free Trp concentrations or significantly improve endurance performance during a maximal bout of exercise.

A 2:1 co-crystal of 2-methyl-benzoic acid and N,N'-bis-(pyridin-4-ylmeth-yl)ethanedi-amide: crystal structure and Hirshfeld surface analysis.

PubMed

Syed, Sabrina; Jotani, Mukesh M; Halim, Siti Nadiah Abdul; Tiekink, Edward R T

2016-03-01

The asymmetric unit of the title 2:1 co-crystal, 2C8H8O2·C14H14N4O2, comprises an acid mol-ecule in a general position and half a di-amide mol-ecule, the latter being located about a centre of inversion. In the acid, the carb-oxy-lic acid group is twisted out of the plane of the benzene ring to which it is attached [dihedral angle = 28.51 (8)°] and the carbonyl O atom and methyl group lie approximately to the same side of the mol-ecule [hy-droxy-O-C-C-C(H) torsion angle = -27.92 (17)°]. In the di-amide, the central C4N2O2 core is almost planar (r.m.s. deviation = 0.031 Å), and the pyridyl rings are perpendicular, lying to either side of the central plane [central residue/pyridyl dihedral angle = 88.60 (5)°]. In the mol-ecular packing, three-mol-ecule aggregates are formed via hy-droxy-O-H⋯N(pyrid-yl) hydrogen bonds. These are connected into a supra-molecular layer parallel to (12[Formula: see text]) via amide-N-H⋯O(carbon-yl) hydrogen bonds, as well as methyl-ene-C-H⋯O(amide) inter-actions. Significant π-π inter-actions occur between benzene/benzene, pyrid-yl/benzene and pyrid-yl/pyridyl rings within and between layers to consolidate the three-dimensional packing.

Degradation of bromamine acid by nanoscale zero-valent iron (nZVI) supported on sepiolite.

PubMed

Fei, Xuening; Cao, Lingyun; Zhou, Lifeng; Gu, Yingchun; Wang, Xiaoyang

2012-01-01

Sepiolite, a natural nano-material, was chosen as a carrier to prepare supported nanoscale zero-valent iron (nZVI). The effects of preparation conditions, including mass ratio of nZVI and activated sepiolite and preparation pH value, on properties of the supported nZVI were investigated. The results showed that the optimal mass ratio of nZVI and sepiolite was 1.12:1 and the optimal pH value was 7. The supported nZVI was characterized by X-ray diffraction (XRD), transmission electron microscope (TEM) and energy dispersive spectrometer (EDS), and furthermore an analogy model of the supported nZVI was set up. Compared with the nZVI itself, the supported nZVI was more stable in air and possessed better water dispersibility, which were beneficial for the degradation of bromamine acid aqueous solution. The degradation characteristics, such as effects of supported nZVI dosage, initial concentration and initial pH value of the solution on the decolorization efficiency were also investigated. The results showed that in an acidic environment the supported nZVI with a dosage of 2 g/L showed high activity in the degradation of bromamine acid with an initial concentration of 1,000 mg/L, and the degree of decolorization could reach up to 98%.

DFT Study of Small Gold Clusters, Au n (2≤ n ≤ 6): Stability and Charge Distribution Using M08-SO Functional

NASA Astrophysics Data System (ADS)

Carvalho, F. S.; Braga, J. P.

2018-05-01

We have investigated the more stable structures for small gold clusters, Aun (2≤ n ≤ 6), using the density functional theory method. Two functionals used in the literature, the well-known B3LYP and M06-L, were compared with the one that has not been used for this system yet, M08-SO, and the results for dimer were compared with experimental data. It was found that M08-SO gives the best results for the effective core potential and basis set tested. Therefore, the functional M08-SO was used for other structures. The planar geometries were found to have the lowest energies. After the geometry optimization, Mulliken populational analysis (MPA) and natural populational analysis (NPA) were carried out and the results for charge distribution in gold trimer and tetramer were compared with data found in literature. The MPA calculation does not give results in agreement with the literature. On the other hand, the NPA calculation gives coherent data. The results showed that the charge distribution will not always predict the more favorable site of interaction.

Supra-molecular architecture in a co-crystal of the N(7)-H tautomeric form of N (6)-benzoyl-adenine with adipic acid (1/0.5).

PubMed

Swinton Darious, Robert; Thomas Muthiah, Packianathan; Perdih, Franc

2016-06-01

The asymmetric unit of the title co-crystal, C12H9N5O·0.5C6H10O4, consists of one mol-ecule of N (6)-benzoyl-adenine (BA) and one half-mol-ecule of adipic acid (AA), the other half being generated by inversion symmetry. The dihedral angle between the adenine and phenyl ring planes is 26.71 (7)°. The N (6)-benzoyl-adenine mol-ecule crystallizes in the N(7)-H tautomeric form with three non-protonated N atoms. This tautomeric form is stabilized by intra-molecular N-H⋯O hydrogen bonding between the carbonyl (C=O) group and the N(7)-H hydrogen atom on the Hoogsteen face of the purine ring, forming an S(7) ring motif. The two carboxyl groups of adipic acid inter-act with the Watson-Crick face of the BA mol-ecules through O-H⋯N and N-H⋯O hydrogen bonds, generating an R 2 (2)(8) ring motif. The latter units are linked by N-H⋯N hydrogen bonds, forming layers parallel to (10-5). A weak C-H⋯O hydrogen bond is also present, linking adipic acid mol-ecules in neighbouring layers, enclosing R (2) 2(10) ring motifs and forming a three-dimensional structure. C=O⋯π and C-H⋯π inter-actions are also present in the structure.

Transcriptional Analysis of Lactobacillus brevis to N-Butanol and Ferulic Acid Stress Responses

PubMed Central

Winkler, James; Kao, Katy C.

2011-01-01

Background The presence of anti-microbial phenolic compounds, such as the model compound ferulic acid, in biomass hydrolysates pose significant challenges to the widespread use of biomass in conjunction with whole cell biocatalysis or fermentation. Currently, these inhibitory compounds must be removed through additional downstream processing or sufficiently diluted to create environments suitable for most industrially important microbial strains. Simultaneously, product toxicity must also be overcome to allow for efficient production of next generation biofuels such as n-butanol, isopropanol, and others from these low cost feedstocks. Methodology and Principal Findings This study explores the high ferulic acid and n-butanol tolerance in Lactobacillus brevis, a lactic acid bacterium often found in fermentation processes, by global transcriptional response analysis. The transcriptional profile of L. brevis reveals that the presence of ferulic acid triggers the expression of currently uncharacterized membrane proteins, possibly in an effort to counteract ferulic acid induced changes in membrane fluidity and ion leakage. In contrast to the ferulic acid stress response, n-butanol challenges to growing cultures primarily induce genes within the fatty acid synthesis pathway and reduced the proportion of 19∶1 cyclopropane fatty acid within the L. brevis membrane. Both inhibitors also triggered generalized stress responses. Separate attempts to alter flux through the Escherichia coli fatty acid synthesis by overexpressing acetyl-CoA carboxylase subunits and deleting cyclopropane fatty acid synthase (cfa) both failed to improve n-butanol tolerance in E. coli, indicating that additional components of the stress response are required to confer n-butanol resistance. Conclusions Several promising routes for understanding both ferulic acid and n-butanol tolerance have been identified from L. brevis gene expression data. These insights may be used to guide further engineering of

Perinatal n-3 fatty acid deficiency selectively reduces myo-inositol levels in the adult rat PFC: an in vivo (1)H-MRS study.

PubMed

McNamara, Robert K; Able, Jessica; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lindquist, Diana M

2009-03-01

To investigate the effects of omega-3 fatty acid deficiency on phosphatidylinositol signaling in brain, myo-inositol (mI) concentrations were determined in the prefrontal cortex (PFC) of omega-3 fatty acid deficient rats by in vivo proton magnetic resonance spectroscopy ((1)H-MRS). To generate graded deficits in PFC docosahexaenoic acid (22:6n-3) (DHA) composition, perinatal and postweaning alpha-linolenic acid (18:3n-3) (ALA) deficiency models were used. Adult male rats were scanned in a 7T Bruker Biospec system and a (1)H-MRS spectrum acquired from the bilateral medial PFC. Rats were then challenged with SKF83959, a selective agonist at phosphoinositide (PI)-coupled dopamine D(1) receptors. Postmortem PFC fatty acid composition was determined by gas chromatography. Relative to controls, PFC DHA composition was significantly reduced in adult postweaning (-27%) and perinatal (-65%) ALA-deficiency groups. Basal PFC mI concentrations were significantly reduced in the perinatal deficiency group (-21%, P = 0.001), but not in the postweaning deficiency group (-1%, P = 0.86). Among all rats, DHA composition was positively correlated with mI concentrations and the mI/creatine (Cr) ratio. SKF83959 challenge significantly increased mI concentrations only in the perinatal deficiency group (+16%, P = 0.02). These data demonstrate that perinatal deficits in cortical DHA accrual significantly and selectively reduce mI concentrations and augment receptor-generated mI synthesis.

Effects of Dietary n-6:n-3 PUFA Ratios on Lipid Levels and Fatty Acid Profile of Cherry Valley Ducks at 15-42 Days of Age.

PubMed

Li, Mengmeng; Zhai, Shuangshuang; Xie, Qiang; Tian, Lu; Li, Xiaocun; Zhang, Jiaming; Ye, Hui; Zhu, Yongwen; Yang, Lin; Wang, Wence

2017-11-22

The objective of this study was to investigate the effects of dietary n-6:n-3 PUFA ratio on growth performance, serum and tissue lipid levels, fatty acid profile, and hepatic expression of fatty acid synthesis genes in ducks. A total of 3168 15-day old ducks were fed different n-6:n-3 PUFA ratios: 13:1 (control), 10:1, 8:1, 6:1, 4:1, and 2:1. The feeding trial lasted 4 weeks. Our results revealed that dietary n-6:n-3 PUFA ratios had no effects on growth performance. The 2:1 group had the highest serum triglyceride levels. Serum total cholesterol and HDL levels were higher in the 13:1 and 8:1 groups than in the 6:1 and 2:1 groups. The concentration of C18:3n-3 in serum and tissues (liver and muscle) increased with decreasing dietary n-6:n-3 PUFA ratios. The hepatic expression of FADS2, ELOVL5, FADS1, and ELOVL2 increased on a quadratic function with decreasing dietary n-6:n-3 PUFA ratios. These results demonstrate that lower dietary n-6:n-3 PUFA ratios had strong effects on the fatty acid profile of edible parts and the deposition of n-3 PUFAs in adipose tissue of ducks.

Therapeutic potential of n-3 polyunsaturated fatty acids in disease.

PubMed

Fetterman, James W; Zdanowicz, Martin M

2009-07-01

The potential therapeutic benefits of supplementation with n-3 polyunsaturated fatty acids (PUFAs) in various diseases are reviewed, and the antiinflammatory actions, activity, and potential drug interactions and adverse effects of n-3 PUFAs are discussed. Fish oils are an excellent source of long-chain n-3 PUFAs, such as eicosapentaenoic acid and docosahexaenoic acid. After consumption, n-3 PUFAs can be incorporated into cell membranes and reduce the amount of arachidonic acid available for the synthesis of proinflammatory eicosanoids (e.g., prostaglandins, leukotrienes). Likewise, n-3 PUFAs can also reduce the production of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1, and interleukin-6. Considerable research has been conducted to evaluate the potential therapeutic effects of fish oils in numerous conditions, including arthritis, coronary artery disease, inflammatory bowel disease, asthma, and sepsis, all of which have inflammation as a key component of their pathology. Additional investigations into the use of supplementation with fish oils in patients with neural injury, cancer, ocular diseases, and critical illness have recently been conducted. The most commonly reported adverse effects of fish oil supplements are a fishy aftertaste and gastrointestinal upset. When recommending an n-3 PUFA, clinicians should be aware of any possible adverse effect or drug interaction that, although not necessarily clinically significant, may occur, especially for patients who may be susceptible to increased bleeding (e.g., patients taking warfarin). The n-3 PUFAs have been shown to be efficacious in treating and preventing various diseases. The wide variation in dosages and formulations used in studies makes it difficult to recommend dosages for specific treatment goals.

40 CFR 721.3152 - Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

Code of Federal Regulations, 2013 CFR

2013-07-01

...-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates (salts). 721.3152 Section 721... Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates... ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates...

40 CFR 721.3152 - Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

Code of Federal Regulations, 2014 CFR

2014-07-01

...-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates (salts). 721.3152 Section 721... Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates... ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates...

40 CFR 721.3152 - Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

Code of Federal Regulations, 2012 CFR

2012-07-01

...-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates (salts). 721.3152 Section 721... Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates... ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates...

40 CFR 721.3152 - Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

Code of Federal Regulations, 2011 CFR

2011-07-01

...-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates (salts). 721.3152 Section 721... Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates... ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates...

Crystal structure of 1-(3-chloro-phen-yl)piperazin-1-ium picrate-picric acid (2/1).

PubMed

Kavitha, Channappa N; Jasinski, Jerry P; Kaur, Manpreet; Anderson, Brian J; Yathirajan, H S

2014-11-01

The title salt {systematic name: bis-[1-(3-chloro-phen-yl)piperazinium 2,4,6-tri-nitro-phenolate]-picric acid (2/1)}, 2C10H14ClN2 (+)·2C6H5N3O7 (-)·C6H6N3O7, crystallized with two independent 1-(3-chloro-phen-yl)piperazinium cations, two picrate anions and a picric acid mol-ecule in the asymmetric unit. The six-membered piperazine ring in each cation adopts a slightly distorted chair conformation and contains a protonated N atom. In the picric acid mol-ecule, the mean planes of the nitro groups in the ortho-, meta-, and para-positions are twisted from the benzene ring by 31.5 (3), 7.7 (1), and 3.8 (2)°, respectively. In the anions, the dihedral angles between the benzene ring and the ortho-, meta-, and para-nitro groups are 36.7 (1), 5.0 (6), 4.8 (2)°, and 34.4 (9), 15.3 (8), 4.5 (1)°, respectively. The nitro group in one anion is disordered and was modeled with two sites for one O atom with an occupancy ratio of 0.627 (7):0.373 (7). In the crystal, the picric acid mol-ecule inter-acts with the picrate anion through a trifurcated O-H⋯O four-centre hydrogen bond involving an intra-molecular O-H⋯O hydrogen bond and a weak C-H⋯O inter-action. Weak inter-molecular C-H⋯O inter-actions are responsible for the formation of cation-anion-cation trimers resulting in a chain along [010]. In addition, weak C-H⋯Cl and weak π-π inter-actions [centroid-centroid distances of 3.532 (3), 3.756 (4) and 3.705 (3) Å] are observed and contribute to the stability of the crystal packing.

Atypical cleavage of protonated N-fatty acyl amino acids derived from aspartic acid evidenced by sequential MS3 experiments.

PubMed

Boukerche, Toufik Taalibi; Alves, Sandra; Le Faouder, Pauline; Warnet, Anna; Bertrand-Michel, Justine; Bouchekara, Mohamed; Belbachir, Mohammed; Tabet, Jean-Claude

2016-12-01

Lipidomics calls for information on detected lipids and conjugates whose structural elucidation by mass spectrometry requires to rationalization of their gas phase dissociations toward collision-induced dissociation (CID) processes. This study focused on activated dissociations of two lipoamino acid (LAA) systems composed of N-palmitoyl acyl coupled with aspartic and glutamic acid mono ethyl esters (as LAA (*D) and LAA (*E) ). Although in MS/MS, their CID spectra show similar trends, e.g., release of water and ethanol, the [(LAA (*D/*E) +H)-C 2 H 5 OH] + product ions dissociate via distinct pathways in sequential MS 3 experiments. The formation of all the product ions is rationalized by charge-promoted cleavages often involving stepwise processes with ion isomerization into ion-dipole prior to dissociation. The latter explains the maleic anhydride or ketene neutral losses from N-palmitoyl acyl aspartate and glutamate anhydride fragment ions, respectively. Consequently, protonated palmitoyl acid amide is generated from LAA (*D), whereas LAA (*E) leads to the [*E+H-H 2 O] + anhydride. The former releases ammonia to provide acylium, which gives the C n H (2n-1) and C n H (2n-3) carbenium series. This should offer structural information, e.g., to locate either unsaturation(s) or alkyl group branching present on the various fatty acyl moieties of lipo-aspartic acid in further studies based on MS n experiments.

The lathyrus toxin, {beta}-N-oxalyl-L-{alpha},{beta}-diaminopropionic acid (ODAP), and homocysteic acid sensitize CA1 pyramidal neurons to cystine and L-2-amino-6-phosphonohexanoic acid

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

Chase, L.A.; Peterson, N.L.; Koerner, J.F.

2007-02-15

A brief exposure of hippocampal slices to L-quisqualic acid (QUIS) sensitizes CA1 pyramidal neurons 30- to 250-fold to depolarization by certain excitatory amino acids analogues, e.g., L-2-amino-6-phosphonohexanoic acid (L-AP6), and by the endogenous compound, L-cystine. This phenomenon has been termed QUIS sensitization. A mechanism similar to that previously described for QUIS neurotoxicity has been proposed to describe QUIS sensitization. Specifically, QUIS has been shown to be sequestered into GABAergic interneurons by the System x{sub c} {sup -} and subsequently released by heteroexchange with cystine or L-AP6, resulting in activation of non-NMDA receptors. We now report two additional neurotoxins, the Lathyrusmore » excitotoxin, {beta}-N-oxalyl-L-{alpha},{beta}-diaminopropionic acid (ODAP), and the endogenous compound, L-homocysteic acid (HCA), sensitize CA1 hippocampal neurons > 50-fold to L-AP6 and > 10-fold to cystine in a manner similar to QUIS. While the cystine- or L-AP6-mediated depolarization can be inhibited by the non-NMDA receptor antagonist CNQX in ODAP- or QUIS-sensitized slices, the NMDA antagonist D-AP5 inhibits depolarization by cystine or L-AP6 in HCA-sensitized slices. Thus, HCA is the first identified NMDA agonist that induces phosphonate or cystine sensitization. Like QUIS sensitization, the sensitization evoked by either ODAP or HCA can be reversed by a subsequent exposure to 2 mM {alpha}-aminoadipic acid. Finally, we have demonstrated that there is a correlation between the potency of inducers for triggering phosphonate or cystine sensitivity and their affinities for System x{sub c} {sup -} and either the non-NMDA or NMDA receptor. Thus, the results of this study support our previous model of QUIS sensitization and have important implications for the mechanisms of neurotoxicity, neurolathyrism and hyperhomocystinemia.« less

n-3 fatty acids reduce plasma 20-hydroxyeicosatetraenoic acid and blood pressure in patients with chronic kidney disease.

PubMed

Barden, Anne E; Burke, Valerie; Mas, Emilie; Beilin, Lawrence J; Puddey, Ian B; Watts, Gerald F; Irish, Ashley B; Mori, Trevor A

2015-09-01

Metabolism of arachidonic acid by cytochrome P450 ω-hydroxylase leads to the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) that regulates vascular function, sodium homeostasis and blood pressure (BP). Supplementation with n-3 fatty acids is known to alter arachidonic acid metabolism and reduce the formation of the lipid peroxidation products F2-isoprostanes, but the effect of n-3 fatty acids on 20-HETE has not been studied. We previously reported a significant effect of n-3 fatty acids but not coenzyme Q10 (CoQ) to reduce BP in a double-blind, placebo-controlled intervention, wherein patients with chronic kidney disease (CKD) were randomized to n-3 fatty acids (4 g), CoQ (200 mg), both supplements or control (4 g olive oil), daily for 8 weeks. This study examined the effect of n-3 fatty acids on plasma and urinary 20-HETE in the same study, as well as plasma and urinary F2-isoprostanes, and relate these to changes in BP. Seventy-four patients completed the 8-week intervention. n-3 fatty acids but not CoQ significantly reduced plasma 20-HETE (P = 0.001) and F2-isoprostanes (P < 0.001). In regression models adjusted for BP at baseline, postintervention plasma 20-HETE was a significant predictor of the fall in SBP (P < 0.0001) and DBP (P < 0.0001) after n-3 fatty acids. This is the first report that n-3 fatty acid supplementation reduces plasma 20-HETE in humans and that this associates with reduced BP. These results provide a plausible mechanism for the reduction in BP observed in patients with CKD following n-3 fatty acid supplementation.

Is vaccenic acid (18:1t n-7) associated with an increased incidence of hip fracture? An explanation for the calcium paradox.

PubMed

Hamazaki, Kei; Suzuki, Nobuo; Kitamura, Kei-Ichiro; Hattori, Atsuhiko; Nagasawa, Tetsuro; Itomura, Miho; Hamazaki, Tomohito

2016-06-01

High calcium intake may increase hip fracture (HF) incidence. This phenomenon, known as the calcium paradox, might be explained by vaccenic acid (18:1t n-7, VA), the highly specific trans fatty acid (TFA) present in dairy products. First, we ecologically investigated the relationship between 18:1 TFA intake and HF incidence using data from 12 to 13 European countries collected before 2000; then we measured the effects of VA and elaidic acid (18:1t n-9, EA) on osteoblasts from goldfish scales (tissues very similar to mammalian bone), with alkaline phosphatase as a marker; and finally we measured the effect of VA on mRNA expression in the scales for the major bone proteins type I collagen and osteocalcin. HF incidence was significantly correlated with 18:1 TFA intake in men (r=0.57) and women (r=0.65). Incubation with 1μmol/L VA and EA for 48h significantly decreased alkaline phosphatase activity by 25% and 21%, respectively. Incubation of scales with 10μmol/L VA for 48h significantly decreased mRNA expression for type I collagen and osteocalcin (by about 50%). In conclusion, VA may be causatively related to HF and could explain the calcium paradox. It may be prudent to reduce 18:1 TFA intake, irrespective of trans positions, to prevent HF. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the influenza A virus subtypes responsible for the 20th‐century pandemics

PubMed Central

Pasricha, Gunisha; Mishra, Akhilesh C.; Chakrabarti, Alok K.

2012-01-01

Please cite this paper as: Pasricha et al. (2012) Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the Influenza A virus subtypes responsible for the 20th‐century pandemics. Influenza and Other Respiratory Viruses 7(4), 497–505. Background  PB1F2 is the 11th protein of influenza A virus translated from +1 alternate reading frame of PB1 gene. Since the discovery, varying sizes and functions of the PB1F2 protein of influenza A viruses have been reported. Selection of PB1 gene segment in the pandemics, variable size and pleiotropic effect of PB1F2 intrigued us to analyze amino acid sequences of this protein in various influenza A viruses. Methods  Amino acid sequences for PB1F2 protein of influenza A H5N1, H1N1, H2N2, and H3N2 subtypes were obtained from Influenza Research Database. Multiple sequence alignments of the PB1F2 protein sequences of the aforementioned subtypes were used to determine the size, variable and conserved domains and to perform mutational analysis. Results  Analysis showed that 96·4% of the H5N1 influenza viruses harbored full‐length PB1F2 protein. Except for the 2009 pandemic H1N1 virus, all the subtypes of the 20th‐century pandemic influenza viruses contained full‐length PB1F2 protein. Through the years, PB1F2 protein of the H1N1 and H3N2 viruses has undergone much variation. PB1F2 protein sequences of H5N1 viruses showed both human‐ and avian host‐specific conserved domains. Global database of PB1F2 protein revealed that N66S mutation was present only in 3·8% of the H5N1 strains. We found a novel mutation, N84S in the PB1F2 protein of 9·35% of the highly pathogenic avian influenza H5N1 influenza viruses. Conclusions  Varying sizes and mutations of the PB1F2 protein in different influenza A virus subtypes with pandemic potential were obtained. There was genetic divergence of the protein in various hosts which highlighted the host‐specific evolution of the virus

Production of Structured Triacylglycerols Containing Palmitic Acids at sn-2 Position and Docosahexaenoic Acids at sn-1, 3 Positions.

PubMed

Liu, Yanjun; Guo, Yongli; Sun, Zhaomin; Jie, Xu; Li, Zhaojie; Wang, Jingfeng; Wang, Yuming; Xue, Changhu

2015-01-01

Docosahexaenoic acid supplementation has been shown well-established health benefits that justify their use as functional ingredients in healthy foods and nutraceutical products. Structured triacylglycerols rich in 1,3-docosahexenoyl-2-palmitoyl-sn-glycerol were produced from algal oil (Schizochytrium sp) which was prepared by a two-step process. Novozym 435 lipase was used to produce tripalmitin. Tripalmitin was then used to produce the final structured triacylglycerol (STAG) through interesterification reactions using Lipozyme RM IM. The optimum conditions for the enzymatic reaction were a mole ratio of tripalmitin/fatty acid ethyl esters 1:9, 60°C, 10% enzyme load (wt % of substrates), 10 h; the enzymatic product contained 51.6% palmitic acid (PA), 30.13% docosahexaenoic acid (DHA, C22:6 n-3) and 5.33% docosapentanoic acid (DPA, C22:5 n-3), 12.15% oleic acid (OLA). This STAG can be used as a functional ingredient in dietary supplementation to provide the benefits of DHA.

Direct N-alkylation of unprotected amino acids with alcohols

PubMed Central

Yan, Tao; Feringa, Ben L.; Barta, Katalin

2017-01-01

N-alkyl amino acids find widespread application as highly valuable, renewable building blocks. However, traditional synthesis methodologies to obtain these suffer from serious limitations, providing a major challenge to develop sustainable alternatives. We report the first powerful catalytic strategy for the direct N-alkylation of unprotected α-amino acids with alcohols. This method is highly selective, produces water as the only side product leading to a simple purification procedure, and a variety of α-amino acids are mono- or di-N-alkylated, in most cases with excellent retention of optical purity. The hydrophobicity of the products is tunable, and even simple peptides are selectively alkylated. An iron-catalyzed route to mono-N-alkyl amino acids using renewable fatty alcohols is also described that represents an ideal green transformation for obtaining fully bio-based surfactants. PMID:29226249

Olfactory discrimination ability and brain expression of c-fos, Gir and Glut1 mRNA are altered in n-3 fatty acid-depleted rats.

PubMed

Hichami, Aziz; Datiche, Frédérique; Ullah, Sana; Liénard, Fabienne; Chardigny, Jean-Michel; Cattarelli, Martine; Khan, Naim Akhtar

2007-11-22

The long-chain polyunsaturated n-3 fatty acids (n-3 PUFA), particularly docosahexaenoic acid (DHA), are abundantly present in the central nervous system and play an important role in cognitive functions such as learning and memory. We, therefore, investigated the effects of n-3 PUFA-depletion in rats (F2 generation) on the learning of an olfactory discrimination task, progressively acquired within a four-arm maze, and on the mRNA expression of some candidate genes, i.e., c-fos, Gir and glucose transporter (Glut1), which could reflect the level of cerebral activity. We observed that DHA contents were dramatically decreased in the olfactory bulb, the piriform cortex and the neocortex of n-3-depleted rats. Furthermore, the n-3 deficiency resulted in a mild olfactory learning impairment as these rats required more days to master the olfactory task compared to control rats. Real-time RT-PCR experiments revealed that the training induced the expression of c-fos mRNA in all the three regions of the brain whereas Gir and Glut1 mRNA were induced only in olfactory bulb and neocortex. However, such an increase was less marked in the n-3-deficient rats. Taken together, these results allow us to assume that the behavioural impairment in n-3-deficient rats is linked to the depletion of n-3 fatty acids in brain regions processing olfactory cues. Data are discussed in view of the possible role of some of these genes in learning-induced neuronal olfactory plasticity.

Dietary n-3 fatty acid restriction during gestation in rats: neuronal cell body and growth-cone fatty acids.

PubMed

Auestad, N; Innis, S M

2000-01-01

Growth cones are membrane-rich structures found at the distal end of growing axons and are the predecessors of the synaptic membranes of nerve endings. This study examined whether n-3 fatty acid restriction during gestation in rats alters the composition of growth cone and neuronal cell body membrane fatty acids in newborns. Female rats were fed a standard control diet containing soy oil (8% of fatty acids as 18:3n-3 by wt) or a semisynthetic n-3 fatty acid-deficient diet with safflower oil (0.3% of fatty acids as 18:3n-3 by wt) throughout normal pregnancy. Experiments were conducted on postnatal day 2 to minimize the potential for contamination from synaptic membranes and glial cells. Dietary n-3 fatty acid restriction resulted in lower docosahexaenoic acid (DHA) concentrations and a corresponding higher docosapentaenoic acid concentration in neuronal growth cones, but had no effects on neuronal cell body fatty acid concentrations. These studies suggest that accretion of DHA in growth cones, but not neuronal cell bodies, is affected by n-3 fatty acid restriction during gestation. Differences in other fatty acids or components between the semisynthetic and the standard diet, however, could have been involved in the effects on growth-cone DHA content. The results also provide evidence to suggest that the addition of new membrane fatty acids to neurons during development occurs along the shaft of the axon or at the growth cone, rather than originating at the cell body.

Docosahexaneoic acid (22:6,n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26S proteasome-dependent pathways

PubMed Central

Botolin, Daniela; Wang, Yun; Christian, Barbara; Jump, Donald B.

2009-01-01

Insulin induces and dietary n-3 PUFAs suppress hepatic de novo lipogenesis by controlling sterol-regulatory element binding protein-1 nuclear abundance (nSREBP-1). Our goal was to define the mechanisms involved in this regulatory process. Insulin treatment of rat primary hepatocytes rapidly augments nSREBP-1 and mRNASREBP-1c while suppressing mRNAInsig-2 but not mRNAInsig-1. These events are preceded by rapid but transient increases in Akt and Erk phosphorylation. Removal of insulin from hepatocytes leads to a rapid decline in nSREBP-1 [half-time (T1/2) ~ 10 h] that is abrogated by inhibitors of 26S proteasomal degradation. 22:6,n-3, the major n-3 PUFA accumulating in livers of fish oil-fed rats, suppresses hepatocyte levels of nSREBP-1, mRNASREBP-1c, and mRNAInsig-2 but modestly and transiently induces mRNAInsig-1. More importantly, 22:6,n-3 accelerates the disappearance of hepatocyte nSREBP-1 (T1/2 ~ 4 h) through a 26S proteasome-dependent process. 22:6,n-3 has minimal effects on microsomal SREBP-1 and sterol-regulatory element binding protein cleavage-activating protein or nuclear SREBP-2. 22:6,n-3 transiently inhibits insulin-induced Akt phosphorylation but induces Erk phosphorylation. Inhibitors of Erk phosphorylation, but not overexpressed constitutively active Akt, rapidly attenuate 22:6,n-3 suppression of nSREBP-1. Thus, 22:6,n-3 suppresses hepatocyte nSREBP-1 through 26S proteasome- and Erk-dependent pathways. These studies reveal a novel mechanism for n-3 PUFA regulation of hepatocyte nSREBP-1 and lipid metabolism.—Botolin, D., Y. Wang, B. Christian, and D. B. Jump. Docosahexaneoic acid (22:6,n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26S proteasome-dependent pathways. PMID:16222032

Low n-6:n-3 fatty acid ratio, with fish- or flaxseed oil, in a high fat diet improves plasma lipids and beneficially alters tissue fatty acid composition in mice.

PubMed

Riediger, Natalie D; Othman, Rgia; Fitz, Evelyn; Pierce, Grant N; Suh, Miyoung; Moghadasian, Mohammed H

2008-04-01

Health benefits from low n-6:n-3 fatty acid (FA) ratio on cardiovascular risk have been shown. However, the impact of the source of n-3 FAs has not been fully investigated. Our purpose was to investigate cardiovascular benefits of oils with a low ratio of n-6:n-3 FAs, but different sources of n-3 FAs in C57BL/6 mice. Twenty-one mice were divided into 3 groups (n=7) and fed a diet supplemented with either a fish or flaxseed oil-based 'designer oils' with an approximate n-6:n-3 FA ratio of 2/1 or with a safflower-oil-based diet with a ratio of 25/1, for 16 weeks. Plasma lipids and fatty acid profile of the liver tissue were characterized. Compared to baseline, plasma triacylglycerol levels declined (>50%) in all groups by week 4. Plasma cholesterol levels were reduced in both fish and flax groups by 27% and 36%, respectively, as compared to controls at endpoint. The levels of EPA and DHA in liver phospholipids were significantly increased in both fish and flax groups as compared to the control group, with more profound increases in the fish group. Arachidonic acid levels were similarly decreased in the liver tissues from both fish and flax groups as compared to controls. Our data suggest that health benefits may be achieved by lowering dietary n-6:n-3 FA even in a high fat diet medium.

Plasma free amino acid kinetics in rainbow trout (Oncorhynchus mykiss) using a bolus injection of 15N-labeled amino acids.

PubMed

Robinson, Jacob William; Yanke, Dan; Mirza, Jeff; Ballantyne, James Stuart

2011-02-01

To gain insight into the metabolic design of the amino acid carrier systems in fish, we injected a bolus of (15)N amino acids into the dorsal aorta in mature rainbow trout (Oncorhynchus mykiss). The plasma kinetic parameters including concentration, pool size, rate of disappearance (R(d)), half-life and turnover rate were determined for 15 amino acids. When corrected for metabolic rate, the R(d) values obtained for trout for most amino acids were largely comparable to human values, with the exception of glutamine (which was lower) and threonine (which was higher). R(d) values ranged from 0.9 μmol 100 g(-1) h(-1) (lysine) to 22.1 μmol 100 g(-1) h(-1) (threonine) with most values falling between 2 and 6 μmol 100 g(-1) h(-1). There was a significant correlation between R(d) and the molar proportion of amino acids in rainbow trout whole body protein hydrolysate. Other kinetic parameters did not correlate significantly with whole body amino acid composition. This indicates that an important design feature of the plasma-free amino acids system involves proportional delivery of amino acids to tissues for protein synthesis.

Ruminal fermentation of anti-methanogenic nitrate- and nitro-containing forages in vitro

USDA-ARS?s Scientific Manuscript database

Nitrate, 3-nitro-1-propionic acid (NPA), and 3-nitro-1-propanol (NPOH) can accumulate in forages and be poisonous to animals if fed at high enough amounts. These chemicals are also recognized as potent anti-methanogenic compounds, but plants naturally containing these chemicals have been studied li...

N-Docosahexaenoyl Dopamine, an Endocannabinoid-like Conjugate of Dopamine and the n-3 Fatty Acid Docosahexaenoic Acid, Attenuates Lipopolysaccharide-Induced Activation of Microglia and Macrophages via COX-2.

PubMed

Wang, Ya; Plastina, Pierluigi; Vincken, Jean-Paul; Jansen, Renate; Balvers, Michiel; Ten Klooster, Jean Paul; Gruppen, Harry; Witkamp, Renger; Meijerink, Jocelijn

2017-03-15

Several studies indicate that the n-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) contributes to an attenuated inflammatory status in the development of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. To explain these effects, different mechanisms are being proposed, including those involving endocannabinoids and related signaling molecules. Many of these compounds belong to the fatty acid amides, conjugates of fatty acids with biogenic amines. Conjugates of DHA with ethanolamine or serotonin have previously been shown to possess anti-inflammatory and potentially neuroprotective properties. Here, we synthesized another amine conjugate of DHA, N-docosahexaenoyl dopamine (DHDA), and tested its immune-modulatory properties in both RAW 264.7 macrophages and BV-2 microglial cells. N-Docosahexaenoyl dopamine significantly suppressed the production of nitric oxide (NO), the cytokine interleukin-6 (IL-6), and the chemokines macrophage-inflammatory protein-3α (CCL20) and monocyte chemoattractant protein-1 (MCP-1), whereas its parent compounds, dopamine and DHA, were ineffective. Further exploration of potential effects of DHDA on key inflammatory mediators revealed that cyclooxygenase-2 (COX-2) mRNA level and production of prostaglandin E 2 (PGE 2 ) were concentration-dependently inhibited in macrophages. In activated BV-2 cells, PGE 2 production was also reduced, without changes in COX-2 mRNA levels. In addition, DHDA did not affect NF-kB activity in a reporter cell line. Finally, the immune-modulatory activities of DHDA were compared with those of N-arachidonoyl dopamine (NADA) and similar potencies were found in both cell types. Taken together, our data suggest that DHDA, a potentially endogenous endocannabinoid, may be an additional member of the group of immune-modulating n-3 fatty acid-derived lipid mediators.

Cinnamic acid hydrogen bonds to isoniazid and N'-(propan-2-ylidene)isonicotinohydrazide, an in situ reaction product of isoniazid and acetone.

PubMed

Sarcevica, Inese; Orola, Liana; Veidis, Mikelis V; Belyakov, Sergey

2014-04-01

A new polymorph of the cinnamic acid-isoniazid cocrystal has been prepared by slow evaporation, namely cinnamic acid-pyridine-4-carbohydrazide (1/1), C9H8O2·C6H7N3O. The crystal structure is characterized by a hydrogen-bonded tetrameric arrangement of two molecules of isoniazid and two of cinnamic acid. Possible modification of the hydrogen bonding was investigated by changing the hydrazide group of isoniazid via an in situ reaction with acetone and cocrystallization with cinnamic acid. In the structure of cinnamic acid-N'-(propan-2-ylidene)isonicotinohydrazide (1/1), C9H8O2·C9H11N3O, carboxylic acid-pyridine O-H···N and hydrazide-hydrazide N-H···O hydrogen bonds are formed.

Potential of ethylenediaminedi(o-hydroxyphenylacetic acid) and N,N'-bis(hydroxybenzyl)ethylenediamine-N,N'-diacetic acid for the determination of metal ions by capillary electrophoresis.

PubMed

Krokhin, O V; Kuzina, O V; Hoshino, H; Shpigun, O A; Yotsuyanagi, T

2000-08-25

Two aromatic polyaminocarboxylate ligands, ethylenediaminedi(o-hydroxyphenylacetic acid) (EDDHA) and N,N'-bis(hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED), were applied for the separation of transition and heavy metal ions by the ion-exchange variant of electrokinetic chromatography. EDDHA structure contains two chiral carbon centers. It makes it impossible to use the commercially available ligand. All the studied metal ions showed two peaks, which correspond to meso and rac forms of the ligand. The separation of metal-HBED chelates was performed using poly(diallyldimethylammonium) polycations in mixed acetate-hydroxide form. Simultaneous separation of nine single- and nine double-charged HBED chelates, including In(III), Ga(III), Co(II)-(III) and Mn(II)-(III) pairs demonstrated the efficiency of 40,000-400,000 theoretical plates. The separation of Co(III), Fe(III) complexes with different arrangements of donor groups and oxidation of Co(II), Mn(H), Fe(II) ions in reaction with HBED have been discussed.

A theoretical and experimental study on isonitrosoacetophenone nicotinoyl hydrazone: Crystal structure, spectroscopic properties, NBO, NPA and NLMO analyses and the investigation of interaction with some transition metals

NASA Astrophysics Data System (ADS)

Zülfikaroğlu, Ayşin; Batı, Hümeyra; Dege, Necmi

2018-06-01

A new hydrazone oxime compound, isonitrosoacetophenone nicotinoyl hydrazone (inapNH2), was synthesized and characterized by spectroscopic techniques (FT-IR, 1H-NMR and 13C-NMR) and single-crystal X-ray diffraction. The molecular geometry, NMR chemical shift values and vibrational frequencies of the inapNH2 in the ground state have been calculated by using the Density Functional Method (DFT/B3LYP) with 6-31G(d) and 6-311++G(d,p) basis sets. The computational results obtained were in agreement with the experimental results. The thermodynamic parameters of the inapNH2 were calculated at different temperatures, and the changes in thermodynamic properties were studied with increasing temperature. The molecular stability originating from charge transfer and hyperconjugative interactions in the title compound was analyzed using Natural Bond Orbital (NBO) and Natural Localized Molecular Orbital (NLMO) analyzes. The Natural Population Analysis (NPA) charges obtained from NBO analysis were used in order to find out the possible coordination modes of the inapNH2 compound with metal ions. To predict the chemical reactivity of the molecule, the molecular electrostatic potential (MEP) surface map of inapNH2 was investigated and some of its global reactivity descriptors (chemical potential μ, electronegativity χ, hardness η and electrophilicity index ω) were calculated using DFT. Furthermore, the strength of metal-ligand interaction between chlorides of Co(II), Ni(II), Cu(II), Zn(II) and inapNH2, in both aqueous and ethanol phases, was elucidated by using the values of Charge Transfer (ΔN) and Energy Lowering (ΔE). The results indicated that the best interaction in both solvents is between CuCl2 and inapNH2.

Functional Evolution of Influenza Virus NS1 Protein in Currently Circulating Human 2009 Pandemic H1N1 Viruses.

PubMed

Clark, Amelia M; Nogales, Aitor; Martinez-Sobrido, Luis; Topham, David J; DeDiego, Marta L

2017-09-01

In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein. Notably, these 6 residue changes restore the ability of pH1N1 NS1 to inhibit general host gene expression, mainly by their ability to restore binding to the cellular factor CPSF30. This is the first report describing the ability of the pH1N1 NS1 protein to naturally acquire mutations that restore this function. Importantly, a recombinant pH1N1 virus containing these 6 amino acid changes in the NS1 protein (pH1N1/NSs-6mut) inhibited host IFN and proinflammatory responses to a greater extent than that with the parental virus (pH1N1/NS1-wt), yet virus titers were not significantly increased in cell cultures or in mouse lungs, and the disease was partially attenuated. The pH1N1/NSs-6mut virus grew similarly to pH1N1/NSs-wt in mouse lungs, but infection with pH1N1/NSs-6mut induced lower levels of proinflammatory cytokines, likely due to a general inhibition of gene expression mediated by the mutated NS1 protein. This lower level of inflammation induced by the pH1N1/NSs-6mut virus likely accounts for the attenuated disease phenotype and may represent a host-virus adaptation affecting influenza virus pathogenesis. IMPORTANCE Seasonal influenza A viruses (IAVs) are among the most common causes of respiratory infections in humans. In addition, occasional pandemics are caused when IAVs circulating in other species emerge in the human population. In 2009, a swine-origin H1N1 IAV (pH1N1) was transmitted to humans, infecting people then and up

Functional Evolution of Influenza Virus NS1 Protein in Currently Circulating Human 2009 Pandemic H1N1 Viruses

PubMed Central

Clark, Amelia M.; Nogales, Aitor; Martinez-Sobrido, Luis

2017-01-01

ABSTRACT In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein. Notably, these 6 residue changes restore the ability of pH1N1 NS1 to inhibit general host gene expression, mainly by their ability to restore binding to the cellular factor CPSF30. This is the first report describing the ability of the pH1N1 NS1 protein to naturally acquire mutations that restore this function. Importantly, a recombinant pH1N1 virus containing these 6 amino acid changes in the NS1 protein (pH1N1/NSs-6mut) inhibited host IFN and proinflammatory responses to a greater extent than that with the parental virus (pH1N1/NS1-wt), yet virus titers were not significantly increased in cell cultures or in mouse lungs, and the disease was partially attenuated. The pH1N1/NSs-6mut virus grew similarly to pH1N1/NSs-wt in mouse lungs, but infection with pH1N1/NSs-6mut induced lower levels of proinflammatory cytokines, likely due to a general inhibition of gene expression mediated by the mutated NS1 protein. This lower level of inflammation induced by the pH1N1/NSs-6mut virus likely accounts for the attenuated disease phenotype and may represent a host-virus adaptation affecting influenza virus pathogenesis. IMPORTANCE Seasonal influenza A viruses (IAVs) are among the most common causes of respiratory infections in humans. In addition, occasional pandemics are caused when IAVs circulating in other species emerge in the human population. In 2009, a swine-origin H1N1 IAV (pH1N1) was transmitted to humans, infecting people

Plasma fatty acid changes following consumption of dietary oils containing n-3, n-6, and n-9 fatty acids at different proportions: preliminary findings of the Canola Oil Multicenter Intervention Trial (COMIT).

PubMed

Senanayake, Vijitha K; Pu, Shuaihua; Jenkins, David A; Lamarche, Benoît; Kris-Etherton, Penny M; West, Sheila G; Fleming, Jennifer A; Liu, Xiaoran; McCrea, Cindy E; Jones, Peter J

2014-04-23

The Canola Oil Multicenter Intervention Trial (COMIT) was a randomized controlled crossover study designed to evaluate the effects of five diets that provided different oils and/or oil blends on cardiovascular disease (CVD) risk factors in individuals with abdominal obesity. The present objective is to report preliminary findings on plasma fatty acid profiles in volunteers with abdominal obesity, following the consumption of diets enriched with n-3, n-6 and n-9 fatty acids. COMIT was conducted at three clinical sites, Winnipeg, Manitoba, Canada, Québec City, Québec, Canada and University Park, Pennsylvania, United States. Inclusion criteria were at least one of the followings: waist circumference (≥90 cm for males and ≥84 cm for females), and at least one other criterion: triglycerides ≥1.7 mmol/L, high density lipoprotein cholesterol <1 mmol/L (males) or <1.3 mmol/L (females), blood pressure ≥130 mmHg (systolic) and/or ≥85 mmHg (diastolic), and glucose ≥5.5 mmol/L. Weight-maintaining diets that included shakes with one of the dietary oil blends were provided during each of the five 30-day dietary phases. Dietary phases were separated by four-week washout periods. Treatment oils were canola oil, high oleic canola oil, high oleic canola oil enriched with docosahexaenoic acid (DHA), flax oil and safflower oil blend, and corn oil and safflower oil blend. A per protocol approach with a mixed model analysis was decided to be appropriate for data analysis. One hundred and seventy volunteers were randomized and 130 completed the study with a dropout rate of 23.5%. The mean plasma total DHA concentrations, which were analyzed among all participants as a measure of adherence, increased by more than 100% in the DHA-enriched phase, compared to other phases, demonstrating excellent dietary adherence. Recruitment and retention strategies were effective in achieving a sufficient number of participants who completed the study protocol to enable sufficient

Crystal and molecular structures of sixteen charge-assisted hydrogen bond-mediated diisopropylammonium salts from different carboxylic acids

NASA Astrophysics Data System (ADS)

Lin, Zhihao; Hu, Kaikai; Jin, Shouwen; Ding, Aihua; Wang, Yining; Dong, Lingfeng; Gao, Xingjun; Wang, Daqi

2017-10-01

Cocrystallization of the commonly available organic amine, diisopropylamine, with a series of carboxylic acids gave a total of sixteen molecular salts with the compositions: diisopropylaminium 2-methyl-2-phenoxypropanate [(Hdpa)+ · (mpa-), mpa- = 2-methyl-2-phenoxypropanoate] (1), diisopropylaminium 2-methyl-2-(naphthalen-2-yloxy)-propionate [(Hdpa)+ · (npa-), npa- = 2-methyl-2-(naphthalen-2-yloxy)-propionate] (2), diisopropylaminium indole-3-acetate [(Hdpa)+ · (iaa-), iaa- = indole-3-acetate] (3), diisopropylaminium 4-chlorophenoxyacetate [(Hdpa)+ · (cpa-), cpa- = 4-chlorophenoxyacetate] (4), diisopropylaminium 2,4-dichlorophenoxyacetate [(Hdpa)+ · (dcpa-), dcpa- = 2,4-dichlorophenoxyacetate] (5), diisopropylaminium 4-hydroxybenzoate [(Hdpa)+ · (hba-), hba- = 4-hydroxybenzoate] (6), diisopropylaminium 4-aminobenzoate [(Hdpa)+ · (aba-), aba- = 4-aminobenzoate] (7), tetra(diisopropylaminium) tetra(1-hydroxy-2-naphthoate) trihydrate [(Hdpa)44+ · (2-hnpa)44- · 3H2O, 2-hnpa = 1-hydroxy-2-naphthoate] (8), diisopropylaminium 2-hydroxy-3-naphthoate [(Hdpa)+ · (3-hnpa-), 3-hnpa- = 2-hydroxy-3-naphthoate] (9), diisopropylaminium 5-bromosalicylate [(Hdpa)+ · (bsa-), bsa- = 5-bromosalicylate] (10), diisopropylaminium 3,5-dinitrobenzoate [(Hdpa)+ · (dna-), dna- = 3,5-dinitrobenzoate] (11), diisopropylaminium 3,5-dinitrosalicylate [(Hdpa)+ · (3,5-dns-), 3,5-dns- = 3,5-dinitrosalicylate] (12), tetra(diisopropylaminium) bis(m-phthalate) monohydrate [(Hdpa+)4 · (mpta2-)2 · H2O, mpta2- = m-phthalate] (13), bis(diisopropylaminium) dihydrogen 1,2,3,4-butane tetracarboxylate [(Hdpa+)2 · (H2Bta2-), H2Bta2- = dihydrogen 1,2,3,4-butane tetracarboxylate] (14), bis(diisopropylaminium) mucate [(Hdpa+)2 · (muc2-), muc2- = mucate] (15), and diisopropylaminium hydrogen 1,2-phenylenediacetate [(Hdpa) · (Hpda-), Hpda- = hydrogen 1,2-phenylenediacetate] (16). The sixteen salts have been characterised by XRD technique, IR, and elemental analysis, and the melting points of all the

The dietary n6:n3 fatty acid ratio during pregnancy is inversely associated with child neurodevelopment in the EDEN mother-child cohort.

PubMed

Bernard, Jonathan Y; De Agostini, Maria; Forhan, Anne; de Lauzon-Guillain, Blandine; Charles, Marie-Aline; Heude, Barbara

2013-09-01

Long-chain polyunsaturated fatty acids (LC-PUFAs) of the n6 (ω6) and n3 series are essential for the development of a child's brain. Fetal LC-PUFA exposure as well as infant exposure via breast milk depend on the maternal intake of these LC-PUFAs and of their respective dietary precursors (PUFAs). We aimed to investigate the associations between maternal LC-PUFA and PUFA [(LC)PUFA] dietary intake during pregnancy and child neurodevelopment at ages 2 and 3 y. In 1335 mother-child pairs from the EDEN cohort, we evaluated associations between daily maternal (LC)PUFA intake during the last 3 months of pregnancy with the child's language at age 2 y and with different assessments of development at age 3 y. Associations were investigated separately in breastfed and never-breastfed children. We examined interactions between the ratios of n6 and n3 (LC)PUFA intakes (n6:n3 fatty acid ratio) and duration of breastfeeding. Breastfeeding mothers had a lower n6:n3 fatty acid ratio (8.4 vs. 8.8; P = 0.02). Among never-breastfed children (n = 338), we found negative associations between maternal dietary n6:n3 fatty acid ratios and neurodevelopment, as reflected by the child's language at age 2 y (β ± SE = -2.1 ± 0.7; P = 0.001) and development assessed with the Ages and Stages Questionnaire at age 3 y (-1.5 ± 0.8; P = 0.05). Among mothers with a high n6:n3 fatty acid ratio only, breastfeeding duration was positively associated with language at age 2 y (P-interaction < 0.05). This suggests that the ratio between maternal dietary n6 and n3 (LC)PUFA intake possibly influences the child's brain development during fetal life but not during or by breastfeeding. However, breastfeeding might compensate for prenatal imbalance in maternal dietary n6:n3 fatty acid ratio.

Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids

PubMed Central

2011-01-01

Background The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]). Results Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic low density lipoprotein (LDL) receptor, sterol regulatory element binding protein (SREBP)-1c and acyl-CoA: cholesterol acyl transferase-2 (ACAT) mRNA and protein (p < 0.05), and higher hepatic apolipoprotein (apo) B-100 and apo E protein levels. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower non-HDL cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic SREBP-1c (p < 0.05) but not apo B-100, apo E or ACAT-2 mRNA or protein levels. Independent of cholesterol status, fish oil fed hamsters had lower HDL cholesterol concentrations (p < 0.001), which were associated with lower hepatic apoA-I protein levels (p < 0.05). Conclusion These data suggest disturbing cholesterol homeostasis in F1B hamsters alters their response to dietary fatty acids, which is reflected in altered plasma lipoprotein patterns and regulation of genes associated with their metabolism. PMID:22018327

Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids.

PubMed

Lecker, Jaime L; Matthan, Nirupa R; Billheimer, Jeffrey T; Rader, Daniel J; Lichtenstein, Alice H

2011-10-21

The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]). Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic low density lipoprotein (LDL) receptor, sterol regulatory element binding protein (SREBP)-1c and acyl-CoA: cholesterol acyl transferase-2 (ACAT) mRNA and protein (p < 0.05), and higher hepatic apolipoprotein (apo) B-100 and apo E protein levels. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower non-HDL cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic SREBP-1c (p < 0.05) but not apo B-100, apo E or ACAT-2 mRNA or protein levels. Independent of cholesterol status, fish oil fed hamsters had lower HDL cholesterol concentrations (p < 0.001), which were associated with lower hepatic apoA-I protein levels (p < 0.05). These data suggest disturbing cholesterol homeostasis in F1B hamsters alters their response to dietary fatty acids, which is reflected in altered plasma lipoprotein patterns and regulation of genes associated with their metabolism.

Spectroscopic and density functional theory studies of trans-3-(trans-4-imidazolyl)acrylic acid.

PubMed

Arjunan, V; Remya, P; Sathish, U; Rani, T; Mohan, S

2014-08-14

The structural parameters, thermodynamic properties and vibrational frequencies of the optimised geometry of trans-3-(trans-4-imidazolyl)acrylic acid have been determined from B3LYP methods with 6-311++G(**) and cc-pVTZ basis sets. The effects of substituents (acrylyl group) on the imidazole vibrational frequencies are analysed. The vibrational frequencies of the fundamental modes of trans-3-(trans-4-imidazolyl)acrylic acid have been precisely assigned and analysed and the theoretical results are compared with the experimental vibrations. (1)H and (13)C NMR isotropic chemical shifts are calculated and the assignments made are compared with the experimental values. The energies of important MO's of the compound are also determined from DFT method. The total electron density and electrostatic potential of the compound are determined by natural bond orbital analysis. Various reactivity and selectivity descriptors such as chemical hardness, chemical potential, softness, electrophilicity, nucleophilicity and the appropriate local quantities employing natural population analysis (NPA) are calculated. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of the ratio of dietary n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid on broiler breeder performance, egg quality, and yolk fatty acid composition at different breeder ages.

PubMed

Koppenol, A; Delezie, E; Aerts, J; Willems, E; Wang, Y; Franssens, L; Everaert, N; Buyse, J

2014-03-01

When added to the feed of broiler breeder hens, dietary polyunsaturated fatty acids (FA) can be incorporated into the yolk and therefore become available to the progeny during their early development. The mechanism involved in lipid metabolism and deposition in the egg may be influenced by breeder age. Before the effect of an elevated concentration of certain polyunsaturated FA on the embryo can be investigated, the effect at breeder level and egg quality must be further assessed. The aim of the present experiment was to evaluate the effects of dietary n-6/n-3 ratios and dietary eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) ratios, provided to broiler breeder hens, in terms of their zoo technical performance, egg quality, and yolk FA composition. Starting at 6 wk of age, 640 Ross-308 broiler breeder hens were fed 1 of 4 different diets. The control diet was a basal diet, rich in n-6 FA. The 3 other diets were enriched in n-3 FA, formulated to obtain a different EPA/DHA ratio of 1/1 (EPA = DHA), 1/2 (DHA), or 2/1 (EPA). In fact, after analysis the EPA/DHA ratio was 0.8, 0.4, or 2.1, respectively. Dietary EPA and DHA addition did not affect the performance of the breeder hens, except for egg weight. Egg weight was lower (P < 0.001) for all n-3 treatments. Dietary EPA improved number of eggs laid in the first 2 wk of the production cycle (P = 0.029). The absolute and relative yolk weight of eggs laid by EPA = DHA fed hens was lowest (P = 0.004 and P = 0.025, respectively). The EPA and DHA concentrations in the yolk were highly dependent on dietary EPA and DHA concentrations with a regression coefficient equal to 0.89. It can be concluded that dietary EPA and DHA can be incorporated in the breeder egg yolk to become available for the developing embryo, without compromising the performance and egg quality of the flock.

Effects of dietary n-3 highly unsaturated fatty acids (HUFAs) on growth, fatty acid profiles, antioxidant capacity and immunity of sea cucumber Apostichopus japonicus (Selenka).

PubMed

Yu, Haibo; Gao, Qinfeng; Dong, Shuanglin; Zhou, Jishu; Ye, Zhi; Lan, Ying

2016-07-01

The present study was conducted to understand the effects of dietary n-3 highly unsaturated fatty acids (HUFAs) on growth, fatty acid profiles, antioxidant capacity and the immunity of sea cucumber Apostichopus japonicus (Selenka). Five experimental diets were prepared, containing graded levels of n-3 HUFAs (0.46%, 0.85%, 1.25%, 1.61% and 1.95%, respectively), and the 0.46% group was used as control group. The specific growth rates, fatty acid profiles, activities and gene expression of antioxidative enzymes and lysozyme of the sea cucumbers that were fed with the 5 experimental diets were determined. The results showed that the specific growth rate of sea cucumbers in all the treatment groups significantly increased compared to the control group (P < 0.05), indicating the positive effects of n-3 HUFAs on the growth of sea cucumbers. The contents of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in the body wall of the sea cucumbers gradually increased with the increasing levels of n-3 HUFAs in the diets. The suitable supplement of n-3 HUFAs in diets improved the activities of superoxide dismutase (SOD) and catalase (CAT) of sea cucumbers by up-regulating the expression of SOD and CAT mRNA in sea cucumbers. However, excess n-3 HUFAs in diets caused lipid peroxidation, inhibited the expression of lysozyme (LSZ) mRNA and decreased the activities of LSZ in sea cucumbers. In summary, the suitable supplement levels of n-3 HUFAs in diets of sea cucumbers A. japonicus were estimated between 0.85% and 1.25% considering the growth performance, cost and the indicators of antioxidant capacity and immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.

PubMed

Gohil, Devanshi; Kothari, Sweta; Shinde, Pramod; Meharunkar, Rhuta; Warke, Rajas; Chowdhary, Abhay; Deshmukh, Ranjana

2017-08-01

Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country. Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations. The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period. Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains. Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites. Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion. Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually. The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.

Structure of β- N-dimethylamino-4-dodecyloxypropiophenone complexes with di- and polycarboxylic acids

NASA Astrophysics Data System (ADS)

Lebedeva, Tamara L.; Shandryuk, George A.; Sycheva, Tatyana I.; Bezborodov, Vladimir S.; Talroze, Raissa V.; Platé, Nicolai A.

1995-07-01

The type of bonds responsible for the complexation of di- and polyacids with the tertiary amine β- N-dimethylamino-4-dodecyloxypropiophenone is studied by means of FTIR spectroscopy. The complexes are shown to be stable due to strong H-bonding with partial charge transfer. The characteristic composition for complexes of polyacrylic, polymethacrylic and malonic acids is calculated as 2:1 (number of carboxylic groups per number of amine molecules) whereas glutaric acid forms complexes of different composition including 1:1. The characteristic composition results from the structure of the initial acid. The structures of both the characteristic complex and "excess" acid are also discussed.

H1N1 seasonal influenza virus evolutionary rate changed over time.

PubMed

Suptawiwat, Ornpreya; Kongchanagul, Alita; Boonarkart, Chompunuch; Auewarakul, Prasert

2018-05-02

It was previously shown that the seasonal H1N1 influenza virus antigenic drift occurred at a slower rate than the seasonal H3N2 virus during the first decade of the 21th century. It was hypothesized that the slower antigenic evolution led to a decrease in average ages of infection, which in turn resulted in lower level of global viral circulation. It is unclear what caused the difference between the two viruses, but a plausible explanation may be related to the fact that the H1N1 virus had been in human population for much longer than the H3N2 virus. This would suggest that H1N1 antigenic drift in an earlier period may have been different from a more recent period. To test this hypothesis, we analyzed seasonal H1N1 influenza sequences during various time periods. In comparison to more recent H1N1 virus, the older H1N1 virus during the first half of the 20th century showed evidences of higher nonsynnonymous/synonymous ration (dN/dS) in its hemagglutinin (HA) gene. We compared amino acid sequence changes in the HA epitopes for each outbreak season and found that there were less changes in later years. Amino acid sequence diversity in the epitopes as measured by sequence entropy became smaller for each passing decade. These suggest that there might be some limit to the antigenic drift. The longer an influenza virus has drifted in human population, the less flexibility it may become. With less flexibility to adapt and escape the host immunity, the virus may have to rely more on younger naïve population. Copyright © 2018 Elsevier B.V. All rights reserved.

Human baby hair amino acid natural abundance 15N-isotope values are not related to the 15N-isotope values of amino acids in mother's breast milk protein.

PubMed

Romek, Katarzyna M; Julien, Maxime; Frasquet-Darrieux, Marine; Tea, Illa; Antheaume, Ingrid; Hankard, Régis; Robins, Richard J

2013-12-01

Since exclusively breast-suckled infants obtain their nutrient only from their mother's milk, it might be anticipated that a correlation will exist between the (15)N/(14)N isotope ratios of amino acids of protein of young infants and those supplied by their mother. The work presented here aimed to determine whether amino nitrogen transfer from human milk to infant hair protein synthesized within the first month of life conserves the maternal isotopic signature or whether post-ingestion fractionation dominates the nitrogen isotope spectrum. The study was conducted at 1 month post-birth on 100 mother-infant pairs. Isotope ratios (15)N/(14)N and (13)C/(12)C were measured using isotope ratio measurement by Mass Spectrometry (irm-MS) for whole maternal milk, and infant hair and (15)N/(14)N ratios were also measured by GC-irm-MS for the N-pivaloyl-O-isopropyl esters of amino acids obtained from the hydrolysis of milk and hair proteins. The δ(15)N and δ(13)C (‰) were found to be significantly higher in infant hair than in breast milk (δ(15)N, P < 0.001; δ(13)C, P < 0.001). Furthermore, the δ(15)N (‰) of individual amino acids in infant hair was also significantly higher than that in maternal milk (P < 0.001). By calculation, the observed shift in isotope ratio was shown not to be accounted for by the amino acid composition of hair and milk proteins, indicating that it is not simply due to differences in the composition in the proteins present. Rather, it would appear that each pool-mother and infant-turns over independently, and that fractionation in infant N-metabolism even in the first month of life dominates over the nutrient N-content.

Characterization of bovine ruminal and equine cecal microbial populations enriched for enhanced nitro-toxin metabolizing activity

USDA-ARS?s Scientific Manuscript database

The phytochemicals 3-nitro-1-propionic acid (NPA) and 3-nitro-1-propanol (NPOH) are produced by a wide variety of leguminous plants, including over 150 different species and varieties of Astragalus. These compounds are toxic to naive grazing animals, but can be safely fed to cattle and sheep that h...

Blood fatty acid changes in healthy young Americans in response to a 10-week diet that increased n-3 and reduced n-6 fatty acid consumption: a randomised controlled trial.

PubMed

Young, Andrew J; Marriott, Bernadette P; Champagne, Catherine M; Hawes, Michael R; Montain, Scott J; Johannsen, Neil M; Berry, Kevin; Hibbeln, Joseph R

2017-05-01

Military personnel generally under-consume n-3 fatty acids and overconsume n-6 fatty acids. In a placebo-controlled, double-blinded study, we investigated whether a diet suitable for implementation in military dining facilities and civilian cafeterias could benefit n-3/n-6 fatty acid status of consumers. Three volunteer groups were provided different diets for 10 weeks. Control (CON) participants consumed meals from the US Military's Standard Garrison Dining Facility Menu. Experimental, moderate (EXP-Mod) and experimental-high (EXP-High) participants consumed the same meals, but high n-6 fatty acid and low n-3 fatty acid containing chicken, egg, oils and food ingredients were replaced with products having less n-6 fatty acids and more n-3 fatty acids. The EXP-High participants also consumed smoothies containing 1000 mg n-3 fatty acids per serving, whereas other participants received placebo smoothies. Plasma and erythrocyte EPA and DHA in CON group remained unchanged throughout, whereas EPA, DHA and Omega-3 Index increased in EXP-Mod and EXP-High groups, and were higher than in CON group after 5 weeks. After 10 weeks, Omega-3 Index in EXP-High group had increased further. No participants exhibited changes in fasting plasma TAG, total cholesterol, LDL, HDL, mood or emotional reactivity. Replacing high linoleic acid (LA) containing foods in dining facility menus with similar high oleic acid/low LA and high n-3 fatty acid foods can improve n-6/n-3 blood fatty acid status after 5 weeks. The diets were well accepted and suitable for implementation in group feeding settings like military dining facilities and civilian cafeterias.

Water Permeation Across Biological Membranes: Mechanism and Dynamics of Aquaporin-1 and GlpF

NASA Astrophysics Data System (ADS)

de Groot, Bert L.; Grubmüller, Helmut

2001-12-01

``Real time'' molecular dynamics simulations of water permeation through human aquaporin-1 (AQP1) and the bacterial glycerol facilitator GlpF are presented. We obtained time-resolved, atomic-resolution models of the permeation mechanism across these highly selective membrane channels. Both proteins act as two-stage filters: Conserved fingerprint [asparagine-proline-alanine (NPA)] motifs form a selectivity-determining region; a second (aromatic/arginine) region is proposed to function as a proton filter. Hydrophobic regions near the NPA motifs are rate-limiting water barriers. In AQP1, a fine-tuned water dipole rotation during passage is essential for water selectivity. In GlpF, a glycerol-mediated ``induced fit'' gating motion is proposed to generate selectivity for glycerol over water.

Alterations in neuronal morphology and synaptophysin expression in the rat brain as a result of changes in dietary n-6: n-3 fatty acid ratios.

PubMed

Hajjar, Toktam; Goh, Yong Meng; Rajion, Mohamed Ali; Vidyadaran, Sharmili; Li, Tan Ai; Ebrahimi, Mahdi

2013-07-26

Polyunsaturated fatty acids (PUFA) play important roles in brain fatty acid composition and behavior through their effects on neuronal properties and gene expression. The hippocampus plays an important role in the formation of memory, especially spatial memory and navigation. This study was conducted to examine the effects of PUFA and specifically different dietary n-6: n-3 fatty acid ratios (FAR) on the number and size of hippocampal neurons and the expression of synaptophysin protein in the hippocampus of rats. Forty 3-week old male Sprague-Dawley rats were allotted into 4 groups. The animals received experimental diets with different n-6: n-3 FAR of either 65:1, 26.5:1, 22:1 or 4.5:1 for 14 weeks. The results showed that a lowering dietary n-6: n-3 FAR supplementation can increase the number and size of neurons. Moreover, lowering the dietary n-6: n-3 FAR led to an increase in the expression of the pre-synaptic protein synaptophysin in the CA1 hippocampal subregion of the rat brain. These findings support the notion that decreasing the dietary n-6: n-3 FAR will lead to an intensified hippocampal synaptophysin expression and increased neuron size and proliferation in the rat brain.

A combination of dietary N-3 fatty acids and a cyclooxygenase-1 inhibitor attenuates nonalcoholic fatty liver disease in mice.

PubMed

Saraswathi, Viswanathan; Perriotte-Olson, Curtis; Ganesan, Murali; Desouza, Cyrus V; Alnouti, Yazen; Duryee, Michael J; Thiele, Geoffrey M; Nordgren, Tara M; Clemens, Dahn L

2017-04-01

We sought to determine whether a combination of purified n-3 fatty acids (n-3) and SC-560 (SC), a cyclooxygenase-1-specific inhibitor, is effective in ameliorating nonalcoholic fatty liver disease in obesity. Female wild-type mice were fed a high-fat and high-cholesterol diet (HF) supplemented with n-3 in the presence or absence of SC. Mice treated with SC alone exhibited no change in liver lipids, whereas n-3-fed mice tended to have lower hepatic lipids. Mice given n-3+SC had significantly lower liver lipids compared with HF controls indicating enhanced lipid clearance. Total and sulfated bile acids were significantly higher only in n-3+SC-treated mice compared with chow diet (CD) controls. Regarding mechanisms, the level of pregnane X receptor (PXR), a nuclear receptor regulating drug/bile detoxification, was significantly higher in mice given n-3 or n-3+SC. Studies in precision-cut liver slices and in cultured hepatoma cells showed that n-3+SC enhanced not only the expression/activation of PXR and its target genes but also the expression of farnesoid X receptor (FXR), another regulator of bile synthesis/clearance, indicating that n-3+SC can induce both PXR and FXR. The mRNA level of FGFR4 which inhibits bile formation showed a significant reduction in Huh 7 cells upon n-3 and n-3+SC treatment. PXR overexpression in hepatoma cells confirmed that n-3 or SC each induced the expression of PXR target genes and in combination had an enhanced effect. Our findings suggest that combining SC with n-3 potentiates its lipid-lowering effect, in part, by enhanced PXR and/or altered FXR/FGFR4 signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of dietary long-chain n-3 fatty acids from menhaden fish oil on plasma concentrations of alpha-tocopherol in geriatric beagles.

PubMed

Hall, Jean A; Tooley, Katie A; Gradin, Joseph L; Jewell, Dennis E; Wander, Rosemary C

2002-01-01

To determine effects of dietary n-3 fatty acids from Menhaden fish oil on plasma alpha-tocopherol concentrations in Beagles. 32 female Beagles. For 82 days, dogs were fed diets that contained 1 of 2 ratios of n-6:n-3 fatty acids (40:1 [low n-3] and 1.4:1 [high n-3]) and 1 of 3 concentrations of all-rac-alpha-tocopheryl acetate (low, 17 mg/kg of diet; medium, 101 mg/kg; and high, 447 mg/kg) in a 2 X 3 factorial study. Diets high in n-3 fatty acids significantly increased total content of n-3 fatty acids in plasma (17.0 g/100 g of fatty acids), compared with low n-3 diets (2.02 g/100 g of fatty acids). Mean +/- SEM plasma concentration of cholesterol was significantly lower in dogs consuming high n-3 diets (4.59 +/- 0.48 mmol/L), compared with dogs consuming low n-3 diets (5.71 +/- 0.48 mmol/L). A significant interaction existed between the ratio for n-6 and n-3 fatty acids and amount of alpha-tocopheryl acetate in the diet (plasma alpha-tocopherol concentration expressed on a molar basis), because the plasma concentration of alpha-toco-pherol was higher in dogs consuming low n-3 diets, compared with those consuming high n-3 diets, at the 2 higher amounts of dietary alpha-tocopheryl acetate. Plasma alpha-tocopherol concentration expressed relative to total lipid content did not reveal effects of dietary n-3 fatty acids on concentration of alpha-tocopherol. Plasma alpha-tocopherol concentration is not dependent on dietary ratio of n-6 and n-3 fatty acids when alpha-tocopherol concentration is expressed relative to the total lipid content of plasma.

Kex1 protease is involved in yeast cell death induced by defective N-glycosylation, acetic acid, and chronological aging.

PubMed

Hauptmann, Peter; Lehle, Ludwig

2008-07-04

N-glycosylation in the endoplasmic reticulum is an essential protein modification and highly conserved in evolution from yeast to humans. The key step of this pathway is the transfer of the lipid-linked core oligosaccharide to the nascent polypeptide chain, catalyzed by the oligosaccharyltransferase complex. Temperature-sensitive oligosaccharyltransferase mutants of Saccharomyces cerevisiae at the restrictive temperature, such as wbp1-1, as well as wild-type cells in the presence of the N-glycosylation inhibitor tunicamycin display typical apoptotic phenotypes like nuclear condensation, DNA fragmentation, phosphatidylserine translocation, caspase-like activity, and reactive oxygen species accumulation. Since deletion of the yeast metacaspase YCA1 did not abrogate this death pathway, we postulated a different proteolytic process to be responsible. Here, we show that Kex1 protease is involved in the programmed cell death caused by defective N-glycosylation. Its disruption decreases caspase-like activity, production of reactive oxygen species, and fragmentation of mitochondria and, conversely, improves growth and survival of cells. Moreover, we demonstrate that Kex1 contributes also to the active cell death program induced by acetic acid stress or during chronological aging, suggesting that Kex1 plays a more general role in cellular suicide of yeast.

Crystal structures of the pyrazinamide-p-aminobenzoic acid (1/1) cocrystal and the transamidation reaction product 4-(pyrazine-2-carboxamido)benzoic acid in the molten state.

PubMed

Thorat, Shridhar H; Sahu, Sanjay Kumar; Gonnade, Rajesh G

2015-11-01

The synthesis of pharmaceutical cocrystals is a strategy to enhance the performance of active pharmaceutical ingredients (APIs) without affecting their therapeutic efficiency. The 1:1 pharmaceutical cocrystal of the antituberculosis drug pyrazinamide (PZA) and the cocrystal former p-aminobenzoic acid (p-ABA), C7H7NO2·C5H5N3O, (1), was synthesized successfully and characterized by relevant solid-state characterization methods. The cocrystal crystallizes in the monoclinic space group P2₁/n containing one molecule of each component. Both molecules associate via intermolecular O-H···O and N-H···O hydrogen bonds [O···O = 2.6102 (15) Å and O-H···O = 168.3 (19)°; N···O = 2.9259 (18) Å and N-H···O = 167.7 (16)°] to generate a dimeric acid-amide synthon. Neighbouring dimers are linked centrosymmetrically through N-H···O interactions [N···O = 3.1201 (18) Å and N-H···O = 136.9 (14)°] to form a tetrameric assembly supplemented by C-H···N interactions [C···N = 3.5277 (19) Å and C-H···N = 147°]. Linking of these tetrameric assemblies through N-H···O [N···O = 3.3026 (19) Å and N-H···O = 143.1 (17)°], N-H···N [N···N = 3.221 (2) Å and N-H···N = 177.9 (17)°] and C-H···O [C···O = 3.5354 (18) Å and C-H···O = 152°] interactions creates the two-dimensional packing. Recrystallization of the cocrystals from the molten state revealed the formation of 4-(pyrazine-2-carboxamido)benzoic acid, C12H9N3O3, (2), through a transamidation reaction between PZA and p-ABA. Carboxamide (2) crystallizes in the triclinic space group P1̅ with one molecule in the asymmetric unit. Molecules of (2) form a centrosymmetric dimeric homosynthon through an acid-acid O-H···O hydrogen bond [O···O = 2.666 (3) Å and O-H···O = 178 (4)°]. Neighbouring assemblies are connected centrosymmetrically via a C-H···N interaction [C···N = 3.365 (3) Å and C-H···N = 142°] engaging

EPA, DHA, and Lipoic Acid Differentially Modulate the n-3 Fatty Acid Biosynthetic Pathway in Atlantic Salmon Hepatocytes.

PubMed

Bou, Marta; Østbye, Tone-Kari; Berge, Gerd M; Ruyter, Bente

2017-03-01

The aim of the present study was to investigate how EPA, DHA, and lipoic acid (LA) influence the different metabolic steps in the n-3 fatty acid (FA) biosynthetic pathway in hepatocytes from Atlantic salmon fed four dietary levels (0, 0.5, 1.0 and 2.0%) of EPA, DHA or a 1:1 mixture of these FA. The hepatocytes were incubated with [1- 14 C] 18:3n-3 in the presence or absence of LA (0.2 mM). Increased endogenous levels of EPA and/or DHA and LA exposure both led to similar responses in cells with reduced desaturation and elongation of [1- 14 C] 18:3n-3 to 18:4n-3, 20:4n-3, and EPA, in agreement with reduced expression of the Δ6 desaturase gene involved in the first step of conversion. DHA production, on the other hand, was maintained even in groups with high endogenous levels of DHA, possibly due to a more complex regulation of this last step in the n-3 metabolic pathway. Inhibition of the Δ6 desaturase pathway led to increased direct elongation to 20:3n-3 by both DHA and LA. Possibly the route by 20:3n-3 and then Δ8 desaturation to 20:4n-3, bypassing the first Δ6 desaturase step, can partly explain the maintained or even increased levels of DHA production. LA increased DHA production in the phospholipid fraction of hepatocytes isolated from fish fed 0 and 0.5% EPA and/or DHA, indicating that LA has the potential to further increase the production of this health-beneficial FA in fish fed diets with low levels of EPA and/or DHA.

Sphingomyelin-induced inhibition of the plasma membrane calcium ATPase causes neurodegeneration in type A Niemann-Pick disease.

PubMed

Pérez-Cañamás, A; Benvegnù, S; Rueda, C B; Rábano, A; Satrústegui, J; Ledesma, M D

2017-05-01

Niemann-Pick disease type A (NPA) is a rare lysosomal storage disorder characterized by severe neurological alterations that leads to death in childhood. Loss-of-function mutations in the acid sphingomyelinase (ASM) gene cause NPA, and result in the accumulation of sphingomyelin (SM) in lysosomes and plasma membrane of neurons. Using ASM knockout (ASMko) mice as a NPA disease model, we investigated how high SM levels contribute to neural pathology in NPA. We found high levels of oxidative stress both in neurons from these mice and a NPA patient. Impaired activity of the plasma membrane calcium ATPase (PMCA) increases intracellular calcium. SM induces PMCA decreased activity, which causes oxidative stress. Incubating ASMko-cultured neurons in the histone deacetylase inhibitor, SAHA, restores PMCA activity and calcium homeostasis and, consequently, reduces the increased levels of oxidative stress. No recovery occurs when PMCA activity is pharmacologically impaired or genetically inhibited in vitro. Oral administration of SAHA prevents oxidative stress and neurodegeneration, and improves behavioral performance in ASMko mice. These results demonstrate a critical role for plasma membrane SM in neuronal calcium regulation. Thus, we identify changes in PMCA-triggered calcium homeostasis as an upstream mediator for NPA pathology. These findings can stimulate new approaches for pharmacological remediation in a disease with no current clinical treatments.

Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells.

PubMed

Lajczak, Natalia K; Saint-Criq, Vinciane; O'Dwyer, Aoife M; Perino, Alessia; Adorini, Luciano; Schoonjans, Kristina; Keely, Stephen J

2017-09-01

Bile acids and epithelial-derived human β-defensins (HβDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HβD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HβD1 and HβD2 from colonic epithelial cells and mucosal tissues. DCA (10-150 µM) stimulated the release of both HβD1 and HβD2 from epithelial cell monolayers and human colonic mucosal tissue in vitro In contrast, ursodeoxycholic acid (50-200 µM) inhibited both basal and DCA-induced defensin release. Effects of DCA were mimicked by the Takeda GPCR 5 agonist, INT-777 (50 μM), but not by the farnesoid X receptor agonist, GW4064 (10 μM). INT-777 also stimulated colonic HβD1 and HβD2 release from wild-type, but not Takeda GPCR 5 -/- , mice. DCA stimulated phosphorylation of the p65 subunit of NF-κB, an effect that was attenuated by ursodeoxycholic acid, whereas an NF-κB inhibitor, BMS-345541 (25 μM), inhibited DCA-induced HβD2, but not HβD1, release. We conclude that bile acids can differentially regulate colonic epithelial HβD expression and secretion and discuss the implications of our findings for intestinal health and disease.-Lajczak, N. K., Saint-Criq, V., O'Dwyer, A. M., Perino, A., Adorini, L., Schoonjans, K., Keely, S. J. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells. © FASEB.

Microbial CH4 and N2O Consumption in Acidic Wetlands

PubMed Central

Kolb, Steffen; Horn, Marcus A.

2012-01-01

Acidic wetlands are global sources of the atmospheric greenhouse gases methane (CH4), and nitrous oxide (N2O). Consumption of both atmospheric gases has been observed in various acidic wetlands, but information on the microbial mechanisms underlying these phenomena is scarce. A substantial amount of CH4 is consumed in sub soil by aerobic methanotrophs at anoxic–oxic interfaces (e.g., tissues of Sphagnum mosses, rhizosphere of vascular plant roots). Methylocystis-related species are likely candidates that are involved in the consumption of atmospheric CH4 in acidic wetlands. Oxygen availability regulates the activity of methanotrophs of acidic wetlands. Other parameters impacting on the methanotroph-mediated CH4 consumption have not been systematically evaluated. N2O is produced and consumed by microbial denitrification, thus rendering acidic wetlands as temporary sources or sinks for N2O. Denitrifier communities in such ecosystems are diverse, and largely uncultured and/or new, and environmental factors that control their consumption activity are unresolved. Analyses of the composition of N2O reductase genes in acidic wetlands suggest that acid-tolerant Proteobacteria have the potential to mediate N2O consumption in such soils. Thus, the fragmented current state of knowledge raises open questions concerning methanotrophs and denitrifiers that consume atmospheric CH4 and N2O in acidic wetlands. PMID:22403579

Involvement of aquaporin NIP1;1 in the contrasting tolerance response to root hypoxia in Prunus rootstocks.

PubMed

Mateluna, Patricio; Salvatierra, Ariel; Solis, Simón; Nuñez, Gabriel; Pimentel, Paula

2018-05-12

Prunus species have been classified as moderately sensitive to root hypoxia, but with a certain intrageneric tolerance degree to oxygen deficiency. Previously, RNA-seq analysis described the transcriptomic reconfiguration of two Prunus rootstocks contrasting to root hypoxia, which included the shift from aerobic to anaerobic metabolism. Here, we studied the relationship between lactate accumulation and the functionality of an aquaporin differentially expressed in 'Mariana 2624', a plum-based (Prunus cerasifera x Prunus munsoniana) rootstock tolerant to root hypoxia stress, and 'Mazzard F12/1', a cherry-based (Prunus avium) rootstock sensitive to root hypoxia stress. In the root hypoxia-sensitive rootstock, higher levels of lactate and LDH1 gene expression were found in roots exposed to oxygen deprivation. Concomitantly, we detected an increase in the mRNA abundance of Prunus spp. NIP1;1, a putative lactic acid transporter. Intriguingly, the high expression of PruavNIP1;1 is not linked to a lower lactic acid content in the roots of 'Mazzard F12/1'. To study this phenomenon, we calculated the force required for the transit of a lactic acid molecule through Prunus spp. NIP1;1 channels. Comparing the calculated forces, we identified steric hindrances in PruavNIP1;1 given by the residues Phe107 and Trp88 in the NPA region and ar/R filter, respectively. The functionality of both channels was corroborated by the restoration of the lactic acid transport and the differential lactic acid sensitive-phenotypes of the yeast strain Δjen1 complemented with PruavNIP1;1 and PrucxmNIP1;1. Our findings provide new insights into the mechanisms involved in determining hypoxia tolerance between closely related species, such as plum and cherry. Copyright © 2018 Elsevier GmbH. All rights reserved.

Heat capacities and thermal diffusivities of n-alkane acid ethyl esters—biodiesel fuel components

NASA Astrophysics Data System (ADS)

Bogatishcheva, N. S.; Faizullin, M. Z.; Nikitin, E. D.

2017-09-01

The heat capacities and thermal diffusivities of ethyl esters of liquid n-alkane acids C n H2 n-1O2C2H5 with the number of carbon atoms in the parent acid n = 10, 11, 12, 14, and 16 are measured. The heat capacities are measured using a DSC 204 F1 Phoenix heat flux differential scanning calorimeter (Netzsch, Germany) in the temperature range of 305-375 K. Thermal diffusivities are measured by means of laser flash method on an LFA-457 instrument (Netzsch, Germany) at temperatures of 305-400 K. An equation is derived for the dependence of the molar heat capacities of the investigated esters on temperature. It is shown that the dependence of molar heat capacity C p,m (298.15 K) on n ( n = 1-6) is close to linear. The dependence of thermal diffusivity on temperature in the investigated temperature range is described by a first-degree polynomial, but thermal diffusivity a (298.15 K) as a function of n has a minimum at n = 5.

Acetaminophen-induced liver injury is attenuated in transgenic fat-1 mice endogenously synthesizing long-chain n-3 fatty acids.

PubMed

Feng, Ruibing; Wang, Yang; Liu, Conghui; Yan, Chunyan; Zhang, Hang; Su, Huanxing; Kang, Jing X; Shang, Chang-Zhen; Wan, Jian-Bo

2018-04-18

Acetaminophen (APAP) overdose-induced hepatotoxicity is the most commonly cause of drug-induced liver failure characterized by oxidative stress, mitochondrial dysfunction, and cell damage. Therapeutic efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFA) in several models of liver disease is well documented. However, the impacts of n-3 PUFA on APAP hepatotoxicity are not adequately addressed. In this study, the fat-1 transgenic mice that synthesize endogenous n-3 PUFA and wild type (WT) littermates were injected intraperitoneally with APAP at the dose of 400 mg/kg to induce liver injury, and euthanized at 0 h, 2 h, 4 h and 6 h post APAP injection for sampling. APAP overdose caused severe liver injury in WT mice as indicated by serum parameters, histopathological changes and hepatocyte apoptosis, which were remarkably ameliorated in fat-1 mice. These protective effects of n-3 PUFA were associated with regulation of the prolonged JNK activation via inhibition of apoptosis signal-regulating kinase 1 (ASK1)/mitogen-activated protein kinase kinase 4 (MKK4) pathway. Additionally, the augment of endogenous n-3 PUFA reduced nuclear factor kappa B (NF-κB) - mediated inflammation response induced by APAP treatment in the liver. These findings indicate that n-3 PUFA has potent protective effects against APAP-induced acute liver injury, suggesting that n-3 dietary supplement with n-3 PUFA may be a potential therapeutic strategy for the treatment of hepatotoxicity induced by APAP overdose. Copyright © 2018 Elsevier Inc. All rights reserved.

Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

PubMed

Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

2015-01-01

The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

Crystal structure of 1-(3-chloro­phen­yl)piperazin-1-ium picrate–picric acid (2/1)

PubMed Central

Kavitha, Channappa N.; Jasinski, Jerry P.; Kaur, Manpreet; Anderson, Brian J.; Yathirajan, H. S.

2014-01-01

The title salt {systematic name: bis­[1-(3-chloro­phen­yl)piperazinium 2,4,6-tri­nitro­phenolate]–picric acid (2/1)}, 2C10H14ClN2 +·2C6H5N3O7 −·C6H6N3O7, crystallized with two independent 1-(3-chloro­phen­yl)piperazinium cations, two picrate anions and a picric acid mol­ecule in the asymmetric unit. The six-membered piperazine ring in each cation adopts a slightly distorted chair conformation and contains a protonated N atom. In the picric acid mol­ecule, the mean planes of the nitro groups in the ortho-, meta-, and para-positions are twisted from the benzene ring by 31.5 (3), 7.7 (1), and 3.8 (2)°, respectively. In the anions, the dihedral angles between the benzene ring and the ortho-, meta-, and para-nitro groups are 36.7 (1), 5.0 (6), 4.8 (2)°, and 34.4 (9), 15.3 (8), 4.5 (1)°, respectively. The nitro group in one anion is disordered and was modeled with two sites for one O atom with an occupancy ratio of 0.627 (7):0.373 (7). In the crystal, the picric acid mol­ecule inter­acts with the picrate anion through a trifurcated O—H⋯O four-centre hydrogen bond involving an intra­molecular O—H⋯O hydrogen bond and a weak C—H⋯O inter­action. Weak inter­molecular C—H⋯O inter­actions are responsible for the formation of cation–anion–cation trimers resulting in a chain along [010]. In addition, weak C—H⋯Cl and weak π–π inter­actions [centroid–centroid distances of 3.532 (3), 3.756 (4) and 3.705 (3) Å] are observed and contribute to the stability of the crystal packing. PMID:25484834

Copper(II) complexes with 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid: Syntheses, crystal structures and antifungal activities

NASA Astrophysics Data System (ADS)

Xiong, Pingping; Li, Jie; Bu, Huaiyu; Wei, Qing; Zhang, Ruolin; Chen, Sanping

2014-07-01

Reaction of Cu(II) with an asymmetric semi-rigid organic ligand 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid (HL), yielded five compounds, [Cu0.5L]n (1), [Cu(HL)2Cl2]n (2), [Cu(HL)2Cl2(H2O)] (3), [Cu(L)2(H2O)]n (4) and [Cu(L)(phen)(HCO2)]n (5), which have been fully characterized by infrared spectroscopy, elemental analysis, and single-crystal X-ray diffraction. As for compounds 1, 2 and 5, Cu(II) is bridged through HL, Cl-, and formic acid, respectively, featuring 1D chain-structure. In compound 3, Cu(II) with hexahedral coordination sphere is assembled through hydrogen-bonding into 3D supramolecular framework. In compound 4, 1D chain units -Cu-O-Cu-O- are ligand-bridged into a 3D network. All compounds were tested on fungi (Fusarium graminearum, Altemaria solani, Macrophoma kawatsukai, Alternaria alternata and Colletotrichum gloeosporioides). Compound 1 exhibits a better antifungal effect compared to other compounds. An effect of structure on the antifungal activity has also been correlated.

NS1 Protein Amino Acid Changes D189N and V194I Affect Interferon Responses, Thermosensitivity, and Virulence of Circulating H3N2 Human Influenza A Viruses

PubMed Central

Nogales, Aitor; Martinez-Sobrido, Luis

2016-01-01

ABSTRACT Influenza virus NS1 protein is a nonstructural, multifunctional protein that counteracts host innate immune responses, modulating virus pathogenesis. NS1 protein variability in subjects infected with H3N2 influenza A viruses (IAVs) during the 2010/2011 season was analyzed, and amino acid changes in residues 86, 189, and 194 were found. The consequences of these mutations for the NS1-mediated inhibition of IFN responses and the pathogenesis of the virus were evaluated, showing that NS1 mutations D189N and V194I impaired the ability of the NS1 protein to inhibit general gene expression, most probably because these mutations decreased the binding of NS1 to the cleavage and polyadenylation specificity factor 30 (CPSF30). A recombinant A/Puerto Rico/8/34 (PR8) H1N1 virus encoding the H3N2 NS1-D189N protein was slightly attenuated, whereas the virus encoding the H3N2 NS1-V194I protein was further attenuated in mice. The higher attenuation of this virus could not be explained by differences in the ability of the two NS1 proteins to counteract host innate immune responses, indicating that another factor must be responsible. In fact, we showed that the virus encoding the H3N2 NS1-V194I protein demonstrated a temperature-sensitive (ts) phenotype, providing a most likely explanation for the stronger attenuation observed. As far as we know, this is the first description of a mutation in NS1 residue 194 conferring a ts phenotype. These studies are relevant in order to identify new residues important for NS1 functions and in human influenza virus surveillance to assess mutations affecting the pathogenicity of circulating viruses. IMPORTANCE Influenza viral infections represent a serious public health problem, with influenza virus causing a contagious respiratory disease that is most effectively prevented through vaccination. The multifunctional nonstructural protein 1 (NS1) is the main viral factor counteracting the host antiviral response. Therefore, influenza virus

NS1 Protein Amino Acid Changes D189N and V194I Affect Interferon Responses, Thermosensitivity, and Virulence of Circulating H3N2 Human Influenza A Viruses.

PubMed

Nogales, Aitor; Martinez-Sobrido, Luis; Topham, David J; DeDiego, Marta L

2017-03-01

Influenza virus NS1 protein is a nonstructural, multifunctional protein that counteracts host innate immune responses, modulating virus pathogenesis. NS1 protein variability in subjects infected with H3N2 influenza A viruses (IAVs) during the 2010/2011 season was analyzed, and amino acid changes in residues 86, 189, and 194 were found. The consequences of these mutations for the NS1-mediated inhibition of IFN responses and the pathogenesis of the virus were evaluated, showing that NS1 mutations D189N and V194I impaired the ability of the NS1 protein to inhibit general gene expression, most probably because these mutations decreased the binding of NS1 to the cleavage and polyadenylation specificity factor 30 (CPSF30). A recombinant A/Puerto Rico/8/34 (PR8) H1N1 virus encoding the H3N2 NS1-D189N protein was slightly attenuated, whereas the virus encoding the H3N2 NS1-V194I protein was further attenuated in mice. The higher attenuation of this virus could not be explained by differences in the ability of the two NS1 proteins to counteract host innate immune responses, indicating that another factor must be responsible. In fact, we showed that the virus encoding the H3N2 NS1-V194I protein demonstrated a temperature-sensitive (ts) phenotype, providing a most likely explanation for the stronger attenuation observed. As far as we know, this is the first description of a mutation in NS1 residue 194 conferring a ts phenotype. These studies are relevant in order to identify new residues important for NS1 functions and in human influenza virus surveillance to assess mutations affecting the pathogenicity of circulating viruses. IMPORTANCE Influenza viral infections represent a serious public health problem, with influenza virus causing a contagious respiratory disease that is most effectively prevented through vaccination. The multifunctional nonstructural protein 1 (NS1) is the main viral factor counteracting the host antiviral response. Therefore, influenza virus

Plasma n-3 and n-6 fatty acids and inflammatory markers in Chinese vegetarians.

PubMed

Yu, Xiaomei; Huang, Tao; Weng, Xiumei; Shou, Tianxing; Wang, Qiang; Zhou, Xiaoqiong; Hu, Qinxin; Li, Duo

2014-09-29

Polyunsaturated fatty acid (PUFA) intake favorably affects chronic inflammatory-related diseases such as cardiovascular disease; however, the relationship between the PUFA and inflammatory factors in the healthy vegetarians were not clear. We aimed to investigate the plasma fatty acids status, and its association with plasma inflammatory factors in Chinese vegetarians and omnivores. A total of 89 male vegetarians and 106 male omnivores were participated the study. Plasma concentrations of inflammatory factors were detected by ELISA, and as standard methods fatty acids were extracted and determined by chromatography. Compared with omnivores, vegetarians have significant higher interleukin-6 (IL-6), plasma n-6 PUFA, n-6/n-3, and 18:3n-3; while they have significant lower leukotriene B4 (LTB4), cyclo-oxygenase-2 (COX2) and prostaglandin E2 (PGE2), 20:5n-3, 22:5n-3, 22:6n-3, and n-3 PUFA. In vegetarians, plasma 20:4n-6 was significant positively related to TNF-α. LTB4 was significantly positively related to plasma 22:6n-3, and negatively associated with n-6 PUFA. Vegetarians have higher plasma n-6 PUFA and IL-6, but lower LTB4, n-3 PUFA, 22:6n-3, COX2 and PGE2 levels. It would seem appropriate for vegetarians to increase their dietary n-3 PUFA, while reduce dietary n-6 PUFA and thus reduce the risk of chronic inflammatory-related diseases.

Preference of Conjugated Bile Acids over Unconjugated Bile Acids as Substrates for OATP1B1 and OATP1B3

PubMed Central

Suga, Takahiro; Sato, Toshihiro; Maekawa, Masamitsu; Goto, Junichi; Mano, Nariyasu

2017-01-01

Bile acids, the metabolites of cholesterol, are signaling molecules that play critical role in many physiological functions. They undergo enterohepatic circulation through various transporters expressed in intestine and liver. Human organic anion-transporting polypeptides (OATP) 1B1 and OATP1B3 contribute to hepatic uptake of bile acids such as taurocholic acid. However, the transport properties of individual bile acids are not well understood. Therefore, we selected HEK293 cells overexpressing OATP1B1 and OATP1B3 to evaluate the transport of five major human bile acids (cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, lithocholic acid) together withtheir glycine and taurine conjugates via OATP1B1 and OATP1B3. The bile acids were quantified by liquid chromatography-tandem mass spectrometry. The present study revealed that cholic acid, chenodeoxyxcholic acid, and deoxycholic acid were transported by OATP1B1 and OATP1B3, while ursodeoxycholic acid and lithocholic acid were not significantly transported by OATPs. However, all the conjugated bile acids were taken up rapidly by OATP1B1 and OATP1B3. Kinetic analyses revealed the involvement of saturable OATP1B1- and OATP1B3-mediated transport of bile acids. The apparent Km values for OATP1B1 and OATP1B3 of the conjugated bile acids were similar (0.74–14.7 μM for OATP1B1 and 0.47–15.3 μM for OATP1B3). They exhibited higher affinity than cholic acid (47.1 μM for OATP1B1 and 42.2 μM for OATP1B3). Our results suggest that conjugated bile acids (glycine and taurine) are preferred to unconjugated bile acids as substrates for OATP1B1 and OATP1B3. PMID:28060902

Plasma fatty acid changes following consumption of dietary oils containing n-3, n-6, and n-9 fatty acids at different proportions: preliminary findings of the Canola Oil Multicenter Intervention Trial (COMIT)

PubMed Central

2014-01-01

Background The Canola Oil Multicenter Intervention Trial (COMIT) was a randomized controlled crossover study designed to evaluate the effects of five diets that provided different oils and/or oil blends on cardiovascular disease (CVD) risk factors in individuals with abdominal obesity. The present objective is to report preliminary findings on plasma fatty acid profiles in volunteers with abdominal obesity, following the consumption of diets enriched with n-3, n-6 and n-9 fatty acids. Methods COMIT was conducted at three clinical sites, Winnipeg, Manitoba, Canada, Québec City, Québec, Canada and University Park, Pennsylvania, United States. Inclusion criteria were at least one of the followings: waist circumference (≥90 cm for males and ≥84 cm for females), and at least one other criterion: triglycerides ≥1.7 mmol/L, high density lipoprotein cholesterol <1 mmol/L (males) or <1.3 mmol/L (females), blood pressure ≥130 mmHg (systolic) and/or ≥85 mmHg (diastolic), and glucose ≥5.5 mmol/L. Weight-maintaining diets that included shakes with one of the dietary oil blends were provided during each of the five 30-day dietary phases. Dietary phases were separated by four-week washout periods. Treatment oils were canola oil, high oleic canola oil, high oleic canola oil enriched with docosahexaenoic acid (DHA), flax oil and safflower oil blend, and corn oil and safflower oil blend. A per protocol approach with a mixed model analysis was decided to be appropriate for data analysis. Results One hundred and seventy volunteers were randomized and 130 completed the study with a dropout rate of 23.5%. The mean plasma total DHA concentrations, which were analyzed among all participants as a measure of adherence, increased by more than 100% in the DHA-enriched phase, compared to other phases, demonstrating excellent dietary adherence. Conclusions Recruitment and retention strategies were effective in achieving a sufficient number of participants who completed the study

GABAergic transmission in rat pontine reticular formation regulates the induction phase of anesthesia and modulates hyperalgesia caused by sleep deprivation.

PubMed

Vanini, Giancarlo; Nemanis, Kriste; Baghdoyan, Helen A; Lydic, Ralph

2014-07-01

The oral part of the pontine reticular formation (PnO) contributes to the regulation of sleep, anesthesia and pain. The role of PnO γ-aminobutyric acid (GABA) in modulating these states remains incompletely understood. The present study used time to loss and time to resumption of righting response (LoRR and RoRR) as surrogate measures of loss and resumption of consciousness. This study tested three hypotheses: (i) pharmacologically manipulating GABA levels in rat PnO alters LoRR, RoRR and nociception; (ii) propofol decreases GABA levels in the PnO; and (iii) inhibiting GABA synthesis in the PnO blocks hyperalgesia caused by sleep deprivation. Administering a GABA synthesis inhibitor [3-mercaptopropionic acid (3-MPA)] or a GABA uptake inhibitor [nipecotic acid (NPA)] into rat PnO significantly altered LoRR caused by propofol. 3-MPA significantly decreased LoRR for propofol (-18%). NPA significantly increased LoRR during administration of propofol (36%). Neither 3-MPA nor NPA altered RoRR following cessation of propofol or isoflurane delivery. The finding that LoRR was decreased by 3-MPA and increased by NPA is consistent with measures showing that extracellular GABA levels in the PnO were decreased (41%) by propofol. Thermal nociception was significantly decreased by 3-MPA and increased by NPA, and 3-MPA blocked the hyperalgesia caused by sleep deprivation. The results demonstrate that GABA levels in the PnO regulate the time for loss of consciousness caused by propofol, extend the concept that anesthetic induction and emergence are not inverse processes, and suggest that GABAergic transmission in the PnO mediates hyperalgesia caused by sleep loss. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

N-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth.

PubMed

Cao, Wenqing; Ma, ZhiFan; Rasenick, Mark M; Yeh, ShuYan; Yu, JiangZhou

2012-01-01

Although evidence has shown the regulating effect of n-3 poly-unsaturated fatty acid (n-3 PUFA) on cell signaling transduction, it remains unknown whether n-3 PUFA treatment modulates estrogen signaling. The current study showed that docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) shifted the pro-survival and proliferative effect of estrogen to a pro-apoptotic effect in human breast cancer (BCa) MCF-7 and T47D cells. 17 β-estradiol (E2) enhanced the inhibitory effect of n-3 PUFAs on BCa cell growth. The IC50 of DHA or EPA in MCF-7 cells decreased when combined with E2 (10 nM) treatment (from 173 µM for DHA only to 113 µM for DHA+E2, and from 187 µm for EPA only to 130 µm for EPA+E2). E2 also augmented apoptosis in n-3 PUFA-treated BCa cells. In contrast, in cells treated with stearic acid (SA, C18:0) as well as cells not treated with fatty acid, E2 promoted breast cancer cell growth. Classical (nuclear) estrogen receptors may not be involved in the pro-apoptotic effects of E2 on the n-3 PUFA-treated BCa cells because ERα agonist failed to elicit, and ERα knockdown failed to block E2 pro-apoptotic effects. Subsequent studies reveal that G protein coupled estrogen receptor 1 (GPER1) may mediate the pro-apoptotic effect of estrogen. N-3 PUFA treatment initiated the pro-apoptotic signaling of estrogen by increasing GPER1-cAMP-PKA signaling response, and blunting EGFR, Erk 1/2, and AKT activity. These findings may not only provide the evidence to link n-3 PUFAs biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, but also shed new insight into the potential application of n-3 PUFAs in BCa treatment.

n-3 Fatty Acids Attenuate the Risk of Diabetes Associated With Elevated Serum Nonesterified Fatty Acids: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Steffen, Brian T.; Steffen, Lyn M.; Zhou, Xia; Ouyang, Pamela; Weir, Natalie L.

2015-01-01

OBJECTIVE Chronically high nonesterified fatty acids (NEFAs) are a marker of metabolic dysfunction and likely increase risk of type 2 diabetes. By comparison, n-3 fatty acids (FAs) have been shown to have various health benefits and may protect against disease development. In 5,697 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we examined whether serum levels of NEFAs relate to risk of incident type 2 diabetes and further tested whether plasma n-3 FA levels may interact with this relation. RESEARCH DESIGN AND METHODS NEFAs were measured in fasting serum using an enzymatic colorimetric assay and phospholipid n-3 FAs eicosapentaenoic and docosahexaenoic acids were determined in plasma through gas chromatography-flame ionization detection in 5,697 MESA participants. Cox proportional hazards regression evaluated the association between NEFA levels and incident type 2 diabetes and whether plasma n-3 FAs modified this association adjusting for age, sex, race, education, field center, smoking, and alcohol use. RESULTS Over a mean 11.4 years of the study period, higher diabetes incidence was found across successive NEFA quartiles (Q) (hazard ratio [95% CI]): Q1, 1.0; Q2, 1.35 (1.07, 1.71); Q3, 1.58 (1.24, 2.00); and Q4, 1.86 (1.45, 2.38) (Ptrend < 0.001). A significant interaction of n-3 FAs on the relation between NEFAs and type 2 diabetes was also observed (Pinteraction = 0.03). For individuals with lower n-3 levels (<75th percentile), a higher risk of type 2 diabetes was observed across quartiles of NEFAs: Q1, 1.0; Q2, 1.41 (1.07, 1.84); Q3, 1.77 (1.35, 2.31); and Q4, 2.18 (1.65, 2.88) (Ptrend < 0.001). No significant associations were observed in those with n-3 FAs ≥75th percentile (Ptrend = 0.54). CONCLUSIONS NEFAs are a marker of type 2 diabetes and may have clinical utility for detecting risk of its development. The modifying influence of n-3 FAs suggests a protective effect against disease and/or metabolic dysfunction related to NEFAs and

Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the influenza A virus subtypes responsible for the 20th-century pandemics.

PubMed

Pasricha, Gunisha; Mishra, Akhilesh C; Chakrabarti, Alok K

2013-07-01

PB1F2 is the 11th protein of influenza A virus translated from +1 alternate reading frame of PB1 gene. Since the discovery, varying sizes and functions of the PB1F2 protein of influenza A viruses have been reported. Selection of PB1 gene segment in the pandemics, variable size and pleiotropic effect of PB1F2 intrigued us to analyze amino acid sequences of this protein in various influenza A viruses. Amino acid sequences for PB1F2 protein of influenza A H5N1, H1N1, H2N2, and H3N2 subtypes were obtained from Influenza Research Database. Multiple sequence alignments of the PB1F2 protein sequences of the aforementioned subtypes were used to determine the size, variable and conserved domains and to perform mutational analysis. Analysis showed that 96·4% of the H5N1 influenza viruses harbored full-length PB1F2 protein. Except for the 2009 pandemic H1N1 virus, all the subtypes of the 20th-century pandemic influenza viruses contained full-length PB1F2 protein. Through the years, PB1F2 protein of the H1N1 and H3N2 viruses has undergone much variation. PB1F2 protein sequences of H5N1 viruses showed both human- and avian host-specific conserved domains. Global database of PB1F2 protein revealed that N66S mutation was present only in 3·8% of the H5N1 strains. We found a novel mutation, N84S in the PB1F2 protein of 9·35% of the highly pathogenic avian influenza H5N1 influenza viruses. Varying sizes and mutations of the PB1F2 protein in different influenza A virus subtypes with pandemic potential were obtained. There was genetic divergence of the protein in various hosts which highlighted the host-specific evolution of the virus. However, studies are required to correlate this sequence variability with the virulence and pathogenicity. © 2012 John Wiley & Sons Ltd.

Installing amino acids and peptides on N-heterocycles under visible-light assistance

PubMed Central

Jin, Yunhe; Jiang, Min; Wang, Hui; Fu, Hua

2016-01-01

Readily available natural α-amino acids are one of nature’s most attractive and versatile building blocks in synthesis of natural products and biomolecules. Peptides and N-heterocycles exhibit various biological and pharmaceutical functions. Conjugation of amino acids or peptides with N-heterocycles provides boundless potentiality for screening and discovery of diverse biologically active molecules. However, it is a great challenge to install amino acids or peptides on N-heterocycles through formation of carbon-carbon bonds under mild conditions. In this article, eighteen N-protected α-amino acids and three peptides were well assembled on phenanthridine derivatives via couplings of N-protected α-amino acid and peptide active esters with substituted 2-isocyanobiphenyls at room temperature under visible-light assistance. Furthermore, N-Boc-proline residue was successfully conjugated with oxindole derivatives using similar procedures. The simple protocol, mild reaction conditions, fast reaction, and high efficiency of this method make it an important strategy for synthesis of diverse molecules containing amino acid and peptide fragments. PMID:26830014

Low n-6/n-3 PUFA Ratio Improves Lipid Metabolism, Inflammation, Oxidative Stress and Endothelial Function in Rats Using Plant Oils as n-3 Fatty Acid Source.

PubMed

Yang, Li Gang; Song, Zhi Xiu; Yin, Hong; Wang, Yan Yan; Shu, Guo Fang; Lu, Hui Xia; Wang, Shao Kang; Sun, Gui Ju

2016-01-01

Lipid metabolism, inflammation, oxidative stress and endothelial function play important roles in the pathogenesis of cardiovascular disease (CVD), which may be affected by an imbalance in the n-6/n-3 polyunsaturated fatty acid (PUFA) ratio. This study aimed to investigate the effects of the n-6/n-3 PUFA ratio on these cardiovascular risk factors in rats fed a high-fat diet using plant oils as the main n-3 PUFA source. The 1:1 and 5:1 ratio groups had significantly decreased serum levels of total cholesterol, low-density lipoprotein cholesterol, and proinflammatory cytokines compared with the 20:1 group (p < 0.05). Additionally, the 20:1 group had significantly increased serum levels of E-Selectin, von Willebrand factor (vWF), and numerous markers of oxidative stress compared with the other groups (p < 0.05). The 1:1 group had a significantly decreased lipid peroxide level compared with the other groups (p < 0.05). Serum levels of malondialdehyde, reactive oxygen species and vWF tended to increase with n-6/n-3 PUFA ratios increasing from 5:1 to 20:1. We demonstrated that low n-6/n-3 PUFA ratio (1:1 and 5:1) had a beneficial effect on cardiovascular risk factors by enhancing favorable lipid profiles, having anti-inflammatory and anti-oxidative stress effects, and improving endothelial function. A high n-6/n-3 PUFA ratio (20:1) had adverse effects. Our results indicated that low n-6/n-3 PUFA ratios exerted beneficial cardiovascular effects, suggesting that plant oils could be used as a source of n-3 fatty acids to prevent CVD. They also suggested that we should be aware of possible adverse effects from excessive n-3 PUFA.

Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012

PubMed Central

Grgić, Helena; Costa, Marcio; Friendship, Robert M.; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

2015-01-01

The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors. PMID:26030614

Cocrystals of the antimalarial drug 11-azaartemisinin with three alkenoic acids of 1:1 or 2:1 stoichiometry.

PubMed

Nisar, Madiha; Wong, Lawrence W Y; Sung, Herman H Y; Haynes, Richard K; Williams, Ian D

2018-06-01

The stoichiometry, X-ray structures and stability of four pharmaceutical cocrystals previously identified from liquid-assisted grinding (LAG) of 11-azaartemisinin (11-Aza; systematic name: 1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.0 4,13 .0 8,13 ]hexadecan-10-one) with trans-cinnamic (Cin), maleic (Mal) and fumaric (Fum) acids are herein reported. trans-Cinnamic acid, a mono acid, forms 1:1 cocrystal 11-Aza:Cin (1, C 15 H 23 NO 4 ·C 9 H 8 O 2 ). Maleic acid forms both 1:1 cocrystal 11-Aza:Mal (2, C 15 H 23 NO 4 ·C 4 H 4 O 4 ), in which one COOH group is involved in self-catenation, and 2:1 cocrystal 11-Aza 2 :Mal (3, 2C 15 H 23 NO 4 ·C 4 H 4 O 4 ). Its isomer, fumaric acid, only affords 2:1 cocrystal 11-Aza 2 :Fum (4). All cocrystal formation appears driven by acid-lactam R 2 2 (8) heterosynthons with short O-H...O=C hydrogen bonds [O...O = 2.56 (2) Å], augmented by weaker C=O...H-N contacts. Despite a better packing efficiency, cocrystal 3 is metastable with respect to 2, probably due to a higher conformational energy for the maleic acid molecule in its structure. In each case, the microcrystalline powders from LAG were useful in providing seeding for the single-crystal growth.

Improving Plant Nitrogen Use Efficiency through Alteration of Amino Acid Transport Processes1[OPEN

PubMed Central

Perchlik, Molly

2017-01-01

Improving the efficiency of nitrogen (N) uptake and utilization in plants could potentially increase crop yields while reducing N fertilization and, subsequently, environmental pollution. Within most plants, N is transported primarily as amino acids. In this study, pea (Pisum sativum) plants overexpressing AMINO ACID PERMEASE1 (AAP1) were used to determine if and how genetic manipulation of amino acid transport from source to sink affects plant N use efficiency. The modified plants were grown under low, moderate, or high N fertilization regimes. The results showed that, independent of the N nutrition, the engineered plants allocate more N via the vasculature to the shoot and seeds and produce more biomass and higher seed yields than wild-type plants. Dependent on the amount of N supplied, the AAP1-overexpressing plants displayed improved N uptake or utilization efficiency, or a combination of the two. They also showed significantly increased N use efficiency in N-deficient as well as in N-rich soils and, impressively, required half the amount of N to produce as many fruits and seeds as control plants. Together, these data support that engineering N allocation from source to sink presents an effective strategy to produce crop plants with improved productivity as well as N use efficiency in a range of N environments. PMID:28733388

Quantification of N-acetyl- and N-glycolylneuraminic acids by a stable isotope dilution assay using high-performance liquid chromatography-tandem mass spectrometry.

PubMed

Allevi, Pietro; Femia, Eti Alessandra; Costa, Maria Letizia; Cazzola, Roberta; Anastasia, Mario

2008-11-28

The present report describes a method for the quantification of N-acetyl- and N-glycolylneuraminic acids without any derivatization, using their (13)C(3)-isotopologues as internal standards and a C(18) reversed-phase column modified by decylboronic acid which allows for the first time a complete chromatographic separation between the two analytes. The method is based on high-performance liquid chromatographic coupled with electrospray ion-trap mass spectrometry. The limit of quantification of the method is 0.1mg/L (2.0ng on column) for both analytes. The calibration curves are linear for both sialic acids over the range of 0.1-80mg/L (2.0-1600ng on column) with a correlation coefficient greater than 0.997. The proposed method was applied to the quantitative determination of sialic acids released from fetuin as a model of glycoproteins.

Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats with Reflux Esophagitis.

PubMed

Zhuang, Jia-Yuan; Chen, Zhi-Yao; Zhang, Tao; Tang, Du-Peng; Jiang, Xiao-Yin; Zhuang, Ze-Hao

2017-01-30

BACKGROUND We designed this study to investigate the influence of different ratios of n-6/n-3 polyunsaturated fatty acid in the diet of reflux esophagitis (RE) rats' and the effect on the PI3K/Akt pathway. MATERIAL AND METHODS RE rats were randomly divided into a sham group and modeling groups of different concentrations of n-6/n-3 polyunsaturated fatty acid (PUFA): 12:1 group, 10:1 group, 5:1 group, and 1:1 group. RT-PCR and Western-blot were used to detect the expression of PI3K, Akt, p-Akt, NF-κBp50, and NF-κBp65 proteins in esophageal tissue. RESULTS In the n-6/n-3 PUFAs groups the expression of PI3K, Akt, p-Akt, nf-κbp50, and NF-κBp65 mRNA decreased with the decrease in n-6/n-3 ratios in the diet. The lowest expression of each indicator occurred in the 1:1 n-6/n-3 group compared with other n-6/n-3 groups, the difference was statistically significant (p<0.05). CONCLUSIONS The inhibition of n-3 PUFAs in the development of esophageal inflammation in rats with RE was attributed to the function of PI3K/Akt-NF-κB signaling pathway.

Copper(II) complexes with 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid: Syntheses, crystal structures and antifungal activities

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

Xiong, Pingping; Li, Jie; Bu, Huaiyu, E-mail: 7213792@qq.com

2014-07-01

Reaction of Cu(II) with an asymmetric semi-rigid organic ligand 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid (HL), yielded five compounds, [Cu{sub 0.5}L]{sub n} (1), [Cu(HL){sub 2}Cl{sub 2}]{sub n} (2), [Cu(HL){sub 2}Cl{sub 2}(H{sub 2}O)] (3), [Cu(L){sub 2}(H{sub 2}O)]{sub n} (4) and [Cu(L)(phen)(HCO{sub 2})]{sub n} (5), which have been fully characterized by infrared spectroscopy, elemental analysis, and single-crystal X-ray diffraction. As for compounds 1, 2 and 5, Cu(II) is bridged through HL, Cl{sup -}, and formic acid, respectively, featuring 1D chain-structure. In compound 3, Cu(II) with hexahedral coordination sphere is assembled through hydrogen-bonding into 3D supramolecular framework. In compound 4, 1D chain units –Cu–O–Cu–O–more » are ligand-bridged into a 3D network. All compounds were tested on fungi (Fusarium graminearum, Altemaria solani, Macrophoma kawatsukai, Alternaria alternata and Colletotrichum gloeosporioides). Compound 1 exhibits a better antifungal effect compared to other compounds. An effect of structure on the antifungal activity has also been correlated. - Graphical abstract: Copper(II) compounds with 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid, were prepared, structurally characterized and investigated for antifungal activity. - Highlights: • The title compounds formed by thermodynamics and thermokinetics. • The five compounds show higher inhibition percentage than reactants. • The structure effect on the antifungal activity.« less

Reevaluation of the effect of ellagic acid on N-methyl-N-nitrosourea DNA alkylation and mutagenicity

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

Lord, H.L.; Josephy, P.D.; Snieckus, V.A.

N-Methyl-N-nitrosourea (MNU) is a reactive, mutagenic methylating agent. MNU methylates DNA at various sites, including guanine N{sup 7}, guanine O{sup 6}, and adenine N{sup 3}. Dixit and Gold ((1986) Proc. Natl, Acad. Sci. U.S.A. 83, 8039-8043) reported that ellagic acid, a phenolic natural product, inhibited the mutagenicity of MNU in Salmonella typhimurium strain TA 100, inhibited salmon sperm DNA alkylation by ({sup 3}H)MNU, and also greatly reduced the ratio of guanine O{sup 6} to guanine N{sup 7} alkylation. We have examined the MNU-induced alkylation of calf thymus DNA and evaluated the effect of ellagic acid on this binding. Ellagic acidmore » had only a slight effect on total alkylation and did not alter the ratio of methylation at guanine-O{sup 6} and -N{sup 7} positions. In further experiments, ellagic acid did not significantly inhibit MNU mutagenicity. These findings do not support the potential use of ellagic acid as an inhibitor of biological damage induced by nitrosoureas.« less

Different neuraminidase inhibitor susceptibilities of human H1N1, H1N2, and H3N2 influenza A viruses isolated in Germany from 2001 to 2005/2006.

PubMed

Bauer, Katja; Richter, Martina; Wutzler, Peter; Schmidtke, Michaela

2009-04-01

In the flu season 2005/2006 amantadine-resistant human influenza A viruses (FLUAV) of subtype H3N2 circulated in Germany. This raises questions on the neuraminidase inhibitor (NAI) susceptibility of FLUAV. To get an answer, chemiluminescence-based neuraminidase inhibition assays were performed with 51 H1N1, H1N2, and H3N2 FLUAV isolated in Germany from 2001 to 2005/2006. According to the mean IC(50) values (0.38-0.91 nM for oseltamivir and 0.76-1.13 nM for zanamivir) most H1N1 and H3N2 FLUAV were NAI-susceptible. But, about four times higher zanamivir concentrations were necessary to inhibit neuraminidase activity of H1N2 viruses. Two H1N1 isolates were less susceptible to both drugs in NA inhibition as well as virus yield reduction assays. Results from sequence analysis of viral hemagglutinin and neuraminidase genes and evolutionary analysis of N2 gene revealed (i) different subclades for N2 in H1N2 and H3N2 FLUAV that could explain the differences in zanamivir susceptibility among these viruses and (ii) specific amino acid substitutions in the neuraminidase segment of the two less NAI-susceptible H1N1 isolates. One H3N2 was isolate proved to be a mixture of a NA deletion mutant and full-length NA viruses.