Apolipoprotein A-I mutant proteins having cysteine substitutions and polynucleotides encoding same

DOEpatents

Oda, Michael N [Benicia, CA; Forte, Trudy M [Berkeley, CA

2007-05-29

Functional Apolipoprotein A-I mutant proteins, having one or more cysteine substitutions and polynucleotides encoding same, can be used to modulate paraoxonase's arylesterase activity. These ApoA-I mutant proteins can be used as therapeutic agents to combat cardiovascular disease, atherosclerosis, acute phase response and other inflammatory related diseases. The invention also includes modifications and optimizations of the ApoA-I nucleotide sequence for purposes of increasing protein expression and optimization.

Interactions between lipid-free apolipoprotein-AI and a lipopeptide incorporating the RGDS cell adhesion motif

NASA Astrophysics Data System (ADS)

Castelletto, V.; Hamley, I. W.; Reza, M.; Ruokolainen, J.

2014-11-01

The interaction of a designed bioactive lipopeptide C16-GGGRGDS, comprising a hexadecyl lipid chain attached to a functional heptapeptide, with the lipid-free apoliprotein, Apo-AI, is examined. This apolipoprotein is a major component of high density lipoprotein and it is involved in lipid metabolism and may serve as a biomarker for cardiovascular disease and Alzheimers' disease. We find via isothermal titration calorimetry that binding between the lipopeptide and Apo-AI occurs up to a saturation condition, just above equimolar for a 10.7 μM concentration of Apo-AI. A similar value is obtained from circular dichroism spectroscopy, which probes the reduction in α-helical secondary structure of Apo-AI upon addition of C16-GGGRGDS. Electron microscopy images show a persistence of fibrillar structures due to self-assembly of C16-GGGRGDS in mixtures with Apo-AI above the saturation binding condition. A small fraction of spheroidal or possibly ``nanodisc'' structures was observed. Small-angle X-ray scattering (SAXS) data for Apo-AI can be fitted using a published crystal structure of the Apo-AI dimer. The SAXS data for the lipopeptide/Apo-AI mixtures above the saturation binding conditions can be fitted to the contribution from fibrillar structures coexisting with flat discs corresponding to Apo-AI/lipopeptide aggregates.

In situ AFM imaging of apolipoprotein A-I directly derived from plasma HDL.

PubMed

Gan, Chaoye; Wang, Zhexuan; Chen, Yong

2017-04-01

The major apolipoproteins of plasma lipoproteins play vital roles in the structural integrity and physiological functions of lipoproteins. More than ten structural models of apolipoprotein A-I (apoA-I), the major apolipoprotein of high-density lipoprotein (HDL), have been developed successively. In these models, apoA-I was supposed to organize in a ring-shaped form. To date, however, there is no direct evidence under physiological condition. Here, atomic force microscopy (AFM) was used to in situ visualize the organization of apoA-I, which was exposed via depletion of the lipid component of plasma HDL pre-immobilized on functionalized mica sheets. For the first time, the ring-shaped coarse structure and three detailed structures (crescent-shaped, gapped "O"-shaped, and parentheses-shaped structures, respectively) of apoA-I in plasma HDL, which have the ability of binding scavenger receptors, were directly observed and quantitatively measured by AFM. The three detailed structures probably represent the different extents to which the lipid component of HDL was depleted. Data on lipid depletion of HDL may provide clues to understand lipid insertion of HDL. These data provide important information for the understanding of the structure/maturation of plasma HDL. Moreover, they suggest a powerful method for directly visualizing the major apolipoproteins of plasma lipoproteins or the protein component of lipoprotein-like lipid-protein complexes. Copyright © 2017 Elsevier B.V. All rights reserved.

A model of lipid-free Apolipoprotein A-I revealed by iterative molecular dynamics simulation

DOE PAGES

Zhang, Xing; Lei, Dongsheng; Zhang, Lei; ...

2015-03-20

Apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, has been proven inversely correlated to cardiovascular risk in past decades. The lipid-free state of apo A-I is the initial stage which binds to lipids forming high-density lipoprotein. Molecular models of lipid-free apo A-I have been reported by methods like X-ray crystallography and chemical cross-linking/mass spectrometry (CCL/MS). Through structural analysis we found that those current models had limited consistency with other experimental results, such as those from hydrogen exchange with mass spectrometry. Through molecular dynamics simulations, we also found those models could not reach a stable equilibrium state. Therefore,more » by integrating various experimental results, we proposed a new structural model for lipidfree apo A-I, which contains a bundled four-helix N-terminal domain (1–192) that forms a variable hydrophobic groove and a mobile short hairpin C-terminal domain (193–243). This model exhibits an equilibrium state through molecular dynamics simulation and is consistent with most of the experimental results known from CCL/MS on lysine pairs, fluorescence resonance energy transfer and hydrogen exchange. This solution-state lipid-free apo A-I model may elucidate the possible conformational transitions of apo A-I binding with lipids in high-density lipoprotein formation.« less

Iowa Mutant Apolipoprotein A-I (ApoA-IIowa) Fibrils Target Lysosomes.

PubMed

Kameyama, Hirokazu; Nakajima, Hiroyuki; Nishitsuji, Kazuchika; Mikawa, Shiho; Uchimura, Kenji; Kobayashi, Norihiro; Okuhira, Keiichiro; Saito, Hiroyuki; Sakashita, Naomi

2016-07-28

The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis. The N-terminal fragments (amino acid residues 1-83) of apoA-I containing this mutation deposit as amyloid fibrils in patients' tissues and organs, but the mechanisms of cellular degradation and cytotoxicity have not yet been clarified. In this study, we demonstrated degradation of apoA-IIowa fibrils via the autophagy-lysosomal pathway in human embryonic kidney 293 cells. ApoA-IIowa fibrils induced an increase in lysosomal pH and the cytosolic release of the toxic lysosomal protease cathepsin B. The mitochondrial dysfunction caused by apoA-IIowa fibrils depended on cathepsin B and was ameliorated by increasing the degradation of apoA-IIowa fibrils. Thus, although apoA-IIowa fibril transport to lysosomes and fibril degradation in lysosomes may have occurred, the presence of an excess number of apoA-IIowa fibrils, more than the lysosomes could degrade, may be detrimental to cells. Our results thus provide evidence that the target of apoA-IIowa fibrils is lysosomes, and we thereby gained a novel insight into the mechanism of AApoA1 amyloidosis.

Effect of an isoenergetic traditional Mediterranean diet on apolipoprotein A-I kinetic in men with metabolic syndrome

USDA-ARS?s Scientific Manuscript database

The impact of the Mediterranean diet (MedDiet) on high-density lipoprotein (HDL) kinetics has not been studied to date. The objective of this study was therefore to investigate the effect of the MedDiet in the absence of changes in body weight on apolipoprotein (apo) A-I kinetic in men with metaboli...

Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis.

PubMed

Bisoendial, Radjesh; Tabet, Fatiha; Tak, Paul P; Petrides, Francine; Cuesta Torres, Luisa F; Hou, Liming; Cook, Adam; Barter, Philip J; Weninger, Wolfgang; Rye, Kerry-Anne

2015-11-01

Lymphatic endothelial dysfunction underlies the pathogenesis of many chronic inflammatory disorders. The proinflammatory cytokine tumor necrosis factor (TNF) is known for its role in disrupting the function of the lymphatic vasculature. This study investigates the ability of apolipoprotein (apo) A-I, the principal apolipoprotein of high-density lipoproteins, to preserve the normal function of lymphatic endothelial cells treated with TNF. TNF decreased the ability of lymphatic endothelial cells to form tube-like structures. Preincubation of lymphatic endothelial cells with apoA-I attenuated the TNF-mediated inhibition of tube formation in a concentration-dependent manner. In addition, apoA-I reversed the TNF-mediated suppression of lymphatic endothelial cell migration and lymphatic outgrowth in thoracic duct rings. ApoA-I also abrogated the negative effect of TNF on lymphatic neovascularization in an ATP-binding cassette transporter A1-dependent manner. At the molecular level, this involved downregulation of TNF receptor-1 and the conservation of prospero-related homeobox gene-1 expression, a master regulator of lymphangiogenesis. ApoA-I also re-established the normal phenotype of the lymphatic network in the diaphragms of human TNF transgenic mice. ApoA-I restores the neovascularization capacity of the lymphatic system during TNF-mediated inflammation. This study provides a proof-of-concept that high-density lipoprotein-based therapeutic strategies may attenuate chronic inflammation via its action on lymphatic vasculature. © 2015 American Heart Association, Inc.

Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and decreases leaflet inflammation in an experimental rabbit model.

PubMed

Speidl, Walter S; Cimmino, Giovanni; Ibanez, Borja; Elmariah, Sammy; Hutter, Randolph; Garcia, Mario J; Fuster, Valentin; Goldman, Martin E; Badimon, Juan J

2010-08-01

Aortic stenosis (AS) is associated with significant morbidity and mortality. Recombinant apolipoprotein A-I Milano (rApoA-I(M)) induces atherosclerotic plaque regression. The aims of this study were to determine the effects of rApoA-I(M) on experimental aortic valve degeneration and its mechanisms of action. New Zealand White rabbits (n = 20) were fed an atherogenic diet for 9 months and then randomized to either placebo or rApoA-I(M). Echocardiography was used to assess the effect of the treatments on AS. Porcine aortic valve myofibroblasts (PAVMF) treated with oxidized low-density lipoprotein served to define the effects of rApoA-I(M) on the expression of monocyte chemoattractant protein-1 (MCP-1), nuclear factor (NF)-kappaB, and alkaline phosphatase (AP). Recombinant apolipoprotein A-I Milano increased aortic valve area (AVA) by 32% (0.25 +/- 0.05 to 0.34 +/- 0.07 cm(2), P < 0.01); whereas AVA remained unchanged in the placebo group (0.24 +/- 0.05 to 0.26 +/- 0.04 cm(2), P = 0.58). Histopathological examination of aortic valves in the rApoA-I(M) animals showed significantly less leaflet thickening, inflammation, and calcification vs. the placebo group. In vitro, rApoA-I(M) significantly inhibited MCP-1, AP, and NF-kappaB and decreased intracellular cholesterol content in PAVMF. Recombinant apolipoprotein A-I Milano treatment reverses AS in this experimental rabbit model. The beneficial effects seem to be mediated by enhanced cholesterol removal and by reduced inflammation and calcification.

Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity

PubMed Central

2010-01-01

Background Previous reports have shown that peptides derived from the apolipoprotein E receptor binding region and the amphipathic α-helical domains of apolipoprotein AI have broad anti-infective activity and antiviral activity respectively. Lipoproteins and viruses share a similar cell biological niche, being of overlapping size and displaying similar interactions with mammalian cells and receptors, which may have led to other antiviral sequences arising within apolipoproteins, in addition to those previously reported. We therefore designed a series of peptides based around either apolipoprotein receptor binding regions, or amphipathic α-helical domains, and tested these for antiviral and antibacterial activity. Results Of the nineteen new peptides tested, seven showed some anti-infective activity, with two of these being derived from two apolipoproteins not previously used to derive anti-infective sequences. Apolipoprotein J (151-170) - based on a predicted amphipathic alpha-helical domain from apolipoprotein J - had measurable anti-HSV1 activity, as did apolipoprotein B (3359-3367) dp (apoBdp), the latter being derived from the LDL receptor binding domain B of apolipoprotein B. The more active peptide - apoBdp - showed similarity to the previously reported apoE derived anti-infective peptide, and further modification of the apoBdp sequence to align the charge distribution more closely to that of apoEdp or to introduce aromatic residues resulted in increased breadth and potency of activity. The most active peptide of this type showed similar potent anti-HIV activity, comparable to that we previously reported for the apoE derived peptide apoEdpL-W. Conclusions These data suggest that further antimicrobial peptides may be obtained using human apolipoprotein sequences, selecting regions with either amphipathic α-helical structure, or those linked to receptor-binding regions. The finding that an amphipathic α-helical region of apolipoprotein J has antiviral

The effect of chromium picolinate on serum cholesterol and apolipoprotein fractions in human subjects.

PubMed Central

Press, R. I.; Geller, J.; Evans, G. W.

1990-01-01

Chromium has been implicated as a cofactor in the maintenance of normal lipid and carbohydrate metabolism. A deficiency of chromium results from diets low in biologically available chromium. Picolinic acid, a metabolite of tryptophan, forms stable complexes with transitional metal ions, which results in an improved bioavailability of the metal ion chromium. To determine whether or not chromium picolinate is effective in humans, 28 volunteer subjects were given either chromium tripicolinate (3.8 micromol [200 micrograms] chromium) or a placebo daily for 42 days in a double-blind crossover study. A 14-day period off capsules was used between treatments. Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B, the principal protein of the LDL fraction, decreased significantly while the subjects were ingesting chromium picolinate. The concentration of apolipoprotein A-I, the principal protein of the high-density lipoprotein (HDL) fraction, increased substantially during treatment with chromium picolinate. The HDL-cholesterol level was elevated slightly but not significantly during ingestion of chromium picolinate. Only apolipoprotein B, of the variables measured, was altered significantly during supplementation with the placebo. These observations show that chromium picolinate is efficacious in lowering blood lipids in humans. PMID:2408233

Comparison of deuterated leucine, valine, and lysine in the measurement of human apolipoprotein A-I and B-100 kinetics

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

Lichtenstein, A.H.; Cohn, J.S.; Hachey, D.L.

1990-09-01

The production rates of apolipoprotein (apo)B-100 in very low density lipoprotein and in low density lipoprotein and apolipoprotein A-I in high density lipoprotein were determined using a primed-constant infusion of (5,5,5,-2H3)leucine, (4,4,4,-2H3)valine, and (6,6-2H2,1,2-13C2)lysine. The three stable isotope-labeled amino acids were administered simultaneously to determine whether absolute production rates calculated using a stochastic model were independent of the tracer species utilized. Three normolipidemic adult males were studied in the constantly fed state over a 15-h period. The absolute production rates of very low density lipoprotein apoB-100 were 11.4 +/- 5.8 (leucine), 11.2 +/- 6.8 (valine), and 11.1 +/- 5.4 (lysine)more » mg per kg per day (mean +/- SDM). The absolute production rates for low density lipoprotein apoB-100 were 8.0 +/- 4.7 (leucine), 7.5 +/- 3.8 (valine), and 7.5 +/- 4.2 (lysine) mg per kg per day. The absolute production rates for high density lipoprotein apoA-I were 9.7 +/- 0.2 (leucine), 9.4 +/- 1.7 (valine), and 9.1 +/- 1.3 (lysine) mg per kg per day. There were no statistically significant differences in absolute synthetic rates of the three apolipoproteins when the plateau isotopic enrichment values of very low density lipoprotein apoB-100 were used to define the isotopic enrichment of the intracellular precursor pool. Our data indicate that deuterated leucine, valine, or lysine provided similar results when used for the determination of apoA-I and apoB-100 absolute production rates within plasma lipoproteins as part of a primed-constant infusion protocol.« less

Expression and purification of recombinant apolipoprotein A-I Zaragoza (L144R) and formation of reconstituted HDL particles.

PubMed

Fiddyment, Sarah; Barceló-Batllori, Sílvia; Pocoví, Miguel; García-Otín, Angel-Luis

2011-11-01

Apolipoprotein A-I Zaragoza (L144R) (apo A-I Z), has been associated with severe hypoalphalipoproteinemia and an enhanced effect of high density lipoprotein (HDL) reverse cholesterol transport. In order to perform further studies with this protein we have optimized an expression and purification method of recombinant wild-type apo A-I and apo A-I Z and produced mimetic HDL particles with each protein. An pET-45 expression system was used to produce N-terminal His-tagged apo A-I, wild-type or mutant, in Escherichia coli BL21 (DE3) which was subsequently purified by affinity chromatography in non-denaturing conditions. HDL particles were generated via a modified sodium cholate method. Expression and purification of both proteins was verified by SDS-PAGE, MALDI-TOF MS and immunochemical procedures. Yield was 30mg of purified protein (94% purity) per liter of culture. The reconstituted HDL particles checked via non-denaturing PAGE showed high homogeneity in their size when reconstituted both with wild-type apo A-I and apo A-I Z. An optimized system for the expression and purification of wild-type apo A-I and apo A-I Z with high yield and purity grade has been achieved, in addition to their use in reconstituted HDL particles, as a basis for further studies. Copyright © 2011 Elsevier Inc. All rights reserved.

Açai (Euterpe oleracea Mart.) dietary intake affects plasma lipids, apolipoproteins, cholesteryl ester transfer to high-density lipoprotein and redox metabolism: A prospective study in women.

PubMed

Pala, Daniela; Barbosa, Priscila Oliveira; Silva, Carla Teixeira; de Souza, Melina Oliveira; Freitas, Fatima Rodrigues; Volp, Ana Carolina Pinheiro; Maranhão, Raul Cavalcante; Freitas, Renata Nascimento de

2018-04-01

The açai fruit (Euterpe oleracea Martius), which is native to the Brazilian Amazon region, was shown to have high polyphenols and MUFA contents. In this study, we aimed to assess the effects of açai consumption on plasma lipids, apolipoproteins, the transfer of lipids to HDL (which is a relevant HDL function), and some biomarkers of redox metabolism. Forty healthy volunteer women aged 24 ± 3 years consumed 200 g of açai pulp/day for 4 weeks; their clinical variables and blood sample were obtained before and after this period. Açai pulp consumption did not alter anthropometric parameters, systemic arterial pressure, glucose, insulin and total, LDL and HDL cholesterol, triglycerides and apolipoprotein (apo) B, but it did increase the concentration of apo A-I. Açai consumption decreased the ROS, ox-LDL and malondialdehyde while increasing the activity of antioxidative paraoxonase 1. Overall, the total antioxidant capacity (TAC) was increased. Regarding the transfer of plasma lipids to HDL, açai consumption increased the transfer of cholesteryl esters (p = 0.0043) to HDL. Unesterified cholesterol, phospholipids and triglyceride transfers were unaffected. The increase in apo A-I and the cholesteryl ester transfer to HDL after the açai intake period suggests that an improvement in the metabolism of this lipoprotein occurred, and it is well known that HDL is protective against atherosclerosis. Another important finding was the general improvement of the anti-oxidant defences elicited by açai consumption. Our data indicate that açai has favourable actions on plasma HDL metabolism and anti-oxidant defence; therefore açai could have a beneficial overall role against atherosclerosis, and it is a consistently good candidate to consider as a functional food. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

9-cis-retinoic acid increases apolipoprotein AI secretion and mRNA expression in HepG2 cells.

PubMed

Haghpassand, M; Moberly, J B

1995-10-01

HepG2 cells were studied as a model for regulation of hepatic apolipoprotein AI (apo AI) secretion and gene expression by 9-cis-retinoic acid. HepG2 cells cultured on plastic dishes were exposed to 9-cis-retinoic acid (9-cis-RA) for 48 h with a complete media change at 24 h. Apo AI mass in cultured media was determined by ELISA, by quantitative immunoblotting and by steady-state 35S-methionine labeling. Messenger RNA levels were determined by RNase protection using probes for apo AI and the housekeeping gene, glyceraldehyde 3-phosphate dehydrogenase (G3PDH). 9-cis-RA increased secretion of apo AI by 52% at doses of 10 and 1 microM (6.3 +/- 0.6 vs. 4.2 +/- 0.3; P < 0.005; 6.1 +/- 0.3 vs. 4.0 +/- 0.7 ng of apo AI/mg cell protein, P < 0.05) and by 35% at 0.1 microM (5.5 +/- 0.6 vs. 4.1 +/- 0.4 ng apo AI/mg protein, P < 0.05, n = 4). Immunoblotting results were consistent with results from ELISA (70% increase at 10 microM 9-cis-RA, P < 0.001; 34% increase at 1 microM, P < 0.005, n = 3). Metabolically labeled apoAI in the medium was increased by 39% following steady-state labeling in the presence of 10 microM 9-cis-RA (597 +/- 7 vs. 430 +/- 13 DPM/microliters media; P < 0.001; n = 4). 9-cis-RA (10 microM) also increased HepG2 cell apo AI mRNA expression by 76% (68 700 +/- 400 vs. 38 900 +/- 2700 DPM, P < 0.01, n = 4), whereas expression of G3PDH mRNA was slightly decreased (14%, P < 0.05). Thus, 9-cis-RA stimulates apo AI expression in HepG2 cells, suggesting a role for retinoids in activating endogenous apo AI gene expression.

Blood plasma apolipoproteins A-I and B in different types of hyperlipoproteinaemia: comparative analysis of population groups in Moscow and Prague.

PubMed

Metel'skaya, V A; Ceska, R; Perova, N V; Sobra, J

1988-01-01

The level of blood plasma apolipoproteins A-I and B was studied in Moscow and Prague residents with different types of hyperlipoproteinaemia (HLP). The analysis proceeded in two directions. On the one hand, lipoprotein (LP) spectra in residents of both cities with the same type of LP disturbance (HLP type IIa, IIb or IV) were compared; in Prague lipid and apolipoprotein content was compared in inhabitants with a normal lipid level and those with HLP types I, III and V. The analysis showed that inhabitants of Prague with types II and IV HLP have a higher concentrations of high density LP cholesterol. At the same time, it was found that the apolipoprotein profile of blood plasma LP in HLP patients was similar to that in patients living elsewhere. The authors regard comparative study of LP system disturbances in residents of different cities and countries differing in their geographical, ethnic and ecological conditions as a promising approach to understanding the mechanisms responsible for the development of HLP.

Transfer of C-terminal residues of human apolipoprotein A-I to insect apolipophorin III creates a two-domain chimeric protein with enhanced lipid binding activity.

PubMed

Horn, James V C; Ellena, Rachel A; Tran, Jesse J; Beck, Wendy H J; Narayanaswami, Vasanthy; Weers, Paul M M

2017-08-01

Apolipophorin III (apoLp-III) is an insect apolipoprotein (18kDa) that comprises a single five-helix bundle domain. In contrast, human apolipoprotein A-I (apoA-I) is a 28kDa two-domain protein: an α-helical N-terminal domain (residues 1-189) and a less structured C-terminal domain (residues 190-243). To better understand the apolipoprotein domain organization, a novel chimeric protein was engineered by attaching residues 179 to 243 of apoA-I to the C-terminal end of apoLp-III. The apoLp-III/apoA-I chimera was successfully expressed and purified in E. coli. Western blot analysis and mass spectrometry confirmed the presence of the C-terminal domain of apoA-I within the chimera. While parent apoLp-III did not self-associate, the chimera formed oligomers similar to apoA-I. The chimera displayed a lower α-helical content, but the stability remained similar compared to apoLp-III, consistent with the addition of a less structured domain. The chimera was able to solubilize phospholipid vesicles at a significantly higher rate compared to apoLp-III, approaching that of apoA-I. The chimera was more effective in protecting phospholipase C-treated low density lipoprotein from aggregation compared to apoLp-III. In addition, binding interaction of the chimera with phosphatidylglycerol vesicles and lipopolysaccharides was considerably improved compared to apoLp-III. Thus, addition of the C-terminal domain of apoA-I to apoLp-III created a two-domain protein, with self-association, lipid and lipopolysaccharide binding properties similar to apoA-I. The apoA-I like behavior of the chimera indicate that these properties are independent from residues residing in the N-terminal domain of apoA-I, and that they can be transferred from apoA-I to apoLp-III. Copyright © 2017 Elsevier B.V. All rights reserved.

Endotoxin contamination of apolipoprotein A-I: effect on macrophage proliferation--a cautionary tale.

PubMed

Jin, Xueting; Xu, Qing; Champion, Keith; Kruth, Howard S

2015-05-01

This technical report addresses the problem of endotoxin contamination of apolipoprotein reagents. Using a bromodeoxyuridine incorporation cell proliferation assay, we observed that human plasma ApoA-I as low as 1 μg/ml resulted in a >90% inhibition in macrophage proliferation. However, not all ApoA-I from different sources showed this effect. We considered the possibility that endotoxin contamination of the apolipoproteins contributed to the differential inhibition of macrophage cell proliferation. Endotoxin alone very potently inhibited macrophage proliferation (0.1 ng/ml inhibited macrophage proliferation>90%). Measurement of endotoxin levels in the apolipoprotein products, including an analysis of free versus total endotoxin, the latter which included endotoxin that was masked due to binding to protein, suggested that free endotoxin mediated inhibition of macrophage proliferation. Despite the use of an advanced endotoxin removal procedure and agents commonly used to inhibit endotoxin action, the potency of endotoxin precluded successful elimination of endotoxin effect. Our findings show that endotoxin contamination can significantly influence apparent apolipoprotein-mediated cell effects (or effects of any other biological products), especially when these products are tested on highly endotoxin-sensitive cells, such as macrophages. Published by Elsevier Ireland Ltd.

Lipid and apolipoproteins (ApoAI, ApoB, Apo CIII, ApoE) disturbance in hemodialysis (HD) and renal transplant (Tx) patients.

PubMed

Janicki, Krzysztof; Solski, Janusz; Janicka, Lucyna; Kimak, Elzbieta; Bednarek-Skublewska, Anna; Stettner, Seweryn; Molas, Grzegorz

2004-01-01

The aim of the study was to evaluate the serum lipid and apolipoprotein profiles among patients after renal transplantation (Tx) and to compare them with the profiles obtained for permanently hemodialysed patients (HD). The investigations were performed at 15 Tx, 40 HD patients and the control group of 40 healthy subjects. There were significantly increased TG, ApoAIII, ApoE, TC/ HDL-C, ApoCIII non B, ApoCIII:B and decreased HDL-C, ApoAI, HDL-C/ApoAI, ApoAI/ApoCIII, ApoB/ApoCIII ratios comparing HD patients to the control group. There were increased TG, ApoCIII, ApoCIII non B, ApoB/ApoCIII ratios and decreased ApoAI/ApoCIII ratios in Tx patients as compared to the control subjects. Moreover, there were significantly higher HDL, ApoAI, HDL/ApoAI, ApoCIII non B and lower ApoE, ApoE/ApoB, ApoCIII:B ratios in Tx patients as compared to these of HD patients. Significant inverse correlation of the time which passed from executed Tx and ApoCIII:B ratio (r = -0.67; p < 0.01) at renal transplant patients were observed, which means the diminished risk of development of atherosclerosis.

Novel Small Molecule Therapeutics for Sickle Cell Disease: Nitric Oxide, Carbon Monoxide, Nitrite, and Apolipoprotein A-I

PubMed Central

Kato, Gregory J.

2009-01-01

A hemolysis-linked subphenotype of sickle cell disease (SCD), characterized by pulmonary hypertension, stroke, priapism and leg ulcers, is associated with decreased nitric oxide bioavailability and vasculopathy. Vasculopathy appears to have a multifactorial etiology, including mechanisms primarily that involve deficient nitric oxide (NO) signaling, but also involving altered function of NO synthase related to substrate availability and cooperating factors such as apolipoproteins. Improved understanding of the vascular pathophysiology of SCD has led to new vascular targets for translational research in SCD. This growing vascular therapeutics field in SCD is complementary to the ongoing efforts to reduce the morbidity of vaso-occlusive pain crisis. This presentation will review the current biology and translational clinical development of novel small molecules targeting sickle cell vasculopathy. Strategies targeting the heme-oxygenase-carbon monoxide pathway, the arginine-NO synthase-cGMP-phosphodiesterase 5 pathway, the nitrate-nitrite-NO pathway, and the apolipoprotein A-I pathways will be reviewed. In this context, current clinical trials of inhaled NO, CO, nitrite, sildenafil and apoA-I mimetics will be discussed. PMID:19074079

Supplementation with tocotrienol-rich fraction alters the plasma levels of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor from young and old individuals.

PubMed

Heng, Eng Chee; Karsani, Saiful Anuar; Abdul Rahman, Mariati; Abdul Hamid, Noor Aini; Hamid, Zalina; Wan Ngah, Wan Zurinah

2013-10-01

Tocotrienol possess beneficial effects not exhibited by tocopherol. In vitro studies using animal models have suggested that these effects are caused via modulation of gene and protein expression. However, human supplementation studies using tocotrienol-rich isomers are limited. This study aims to identify plasma proteins that changed in expression following tocotrienol-rich fraction (TRF) supplementation within two different age groups. Subjects were divided into two age groups-32 ± 2 (young) and 52 ± 2 (old) years old. Four subjects from each group were assigned with TRF (78% tocotrienol and 22% tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting. Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression. TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.

Deep subcortical infarct burden in relation to apolipoprotein B/AI ratio in patients with intracranial atherosclerotic stenosis.

PubMed

Park, J-H; Hong, K-S; Lee, J; Kim, Y-J; Song, P

2013-04-01

Pre-existing brain infarct (PBI), frequently seen on magnetic resonance imaging and usually silent, is recognized as a risk factor for future stroke. Increased apolipoprotein B (apoB)/apoAI ratio is known to be a risk predictor of ischaemic stroke and is associated with intracranial atherosclerotic stenosis (ICAS). However, little is known about the association of apoB/apoAI ratio with PBI. A total of 522 statin-/fibrate-naïve Korean patients, who experienced acute ischaemic stroke, were categorized into three groups: ICAS (n=254), extracranial (n=51), and no cerebral atherosclerotic stenosis (n=217). We explored the association between apoB/apoAI ratio and PBI lesions according to atherosclerosis type (ICAS, ECAS, and NCAS), PBI location (deep subcortical [ds-PBI] versus hemispheric [h-PBI]), and symptomatic PBI (s-PBI) which was relevant to a prior clinical stroke event. Pre-existing brain infarct(+) patients showed a higher apoB/apoAI ratio than PBI(-) patients (0.81 ± 0.28 vs. 0.72 ± 0.23, P<0.001). In ICAS group, patients with higher apoB/apoAI ratio quartiles had more PBIs, ds-PBIs, and s-PBIs (P=0.020, P=0.025, and P=0.001, respectively). With multivariable analyses, the highest apoB/apoAI ratio quartile was associated with PBI (OR, 2.56; 95% CI, 1.39-4.73), ds-PBI (2.48; 1.33-4.62), and advanced (≥ 3) ds-PBIs (2.68; 1.27-5.63) in ICAS group, but not with h-PBI. s-PBI had a dose-response relationship with apoB/apoAI ratio quartiles (6.18; 1.31-29.13 for the second; 5.34; 1.06-26.83 for the third; and 12.17; 2.50-59.19 for the fourth quartile), when referenced to the first quartile. ApoB/apoAI ratio is associated with asymptomatic deep subcortical ischaemic burden as well as with symptomatic lesion in patients with ICAS. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Endotoxin Contamination of Apolipoprotein A-I: Effect on Macrophage Proliferation – A Cautionary Tale

PubMed Central

Jin, Xueting; Xu, Qing; Champion, Keith; Kruth, Howard S.

2015-01-01

This technical report addresses the problem of endotoxin contamination of apolipoprotein reagents. Using a bromodeoxyuridine incorporation cell proliferation assay, we observed that human plasma ApoA-I as low as 1 μg/ml resulted in a >90% inhibition in macrophage proliferation. However, not all ApoA-I from different sources showed this effect. We considered the possibility that endotoxin contamination of the apolipoproteins contributed to the differential inhibition of macrophage cell proliferation. Endotoxin alone very potently inhibited macrophage proliferation (0.1 ng/ml inhibited macrophage proliferation >90%). Measurement of endotoxin levels in the apolipoprotein products, including an analysis of free versus total endotoxin, the latter which included endotoxin that was masked due to binding to protein, suggested that free endotoxin mediated inhibition of macrophage proliferation. Despite the use of an advanced endotoxin removal procedure and agents commonly used to inhibit endotoxin action, the potency of endotoxin precluded successful elimination of endotoxin effect. Our findings show that endotoxin contamination can significantly influence apparent apolipoprotein-mediated cell effects (or effects of any other biological products), especially when these products are tested on highly endotoxin-sensitive cells, such as macrophages. PMID:25778625

A case report of hereditary apolipoprotein A-I amyloidosis associated with a novel APOA1 mutation and variable phenotype.

PubMed

Tougaard, Birgitte G; Pedersen, Katja Venborg; Krag, Søren Rasmus; Gilbertson, Janet A; Rowczenio, Dorota; Gillmore, Julian D; Birn, Henrik

2016-09-01

Apolipoprotein A-I (apo A-I) amyloidosis is a non-AL, non-AA, and non-transthyretin type of amyloidosis associated with mutations in the APOA1 gene inherited in an autosomal dominant fashion. It is a form of systemic amyloidosis, but at presentation, can also mimic localized amyloidosis. The renal presentation generally involves interstitial and medullary deposition of apo A-I amyloid protein. We describe the identification of apo A-I amyloidosis by mass spectrometry in a 52-year old male, with no family history of amyloidosis, presenting with nephrotic syndrome and associated with heterozygosity for a novel APOA1 mutation (c.220 T > A) which encodes the known amyloidogenic Trp50Arg variant. Renal amyloid deposits in this case were confined to the glomeruli alone, and the patient developed progressive renal impairment. One year after diagnosis, the patient had a successful kidney transplant from an unrelated donor. Pathogenic mutations in the APOA1 gene are generally associated with symptoms of amyloidosis. In this family however, genotyping of family members identified several unaffected carriers suggesting a variable disease penetrance, which has not been described before in this form of amyloidosis and has implications when counselling those with APOA1 mutations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Homocysteine diminishes apolipoprotein A-I function and expression in patients with hypothyroidism: a cross-sectional study.

PubMed

Yang, Ning; Yao, Zhi; Miao, Li; Liu, Jia; Gao, Xia; Xu, Yuan; Wang, Guang

2016-07-26

Hypothyroidism (HO) can significantly impair lipid metabolism and increase cardiovascular disease risk. Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease. Our previous study demonstrated that HHcy significantly induced insulin resistance and impaired coronary artery endothelial function in patients with either hypertension or HO. In the present study, we studied whether plasma levels of high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (Apo A-I) were altered in patients with HO, and if so, whether this change was mediated by HHcy. A total of 258 subjects were enrolled and divided into the following three groups: control group (n = 94), HO group (n = 73), and subclinical hypothyroidism (SHO) group (n = 91). Additionally, all groups were subdivided based on the subjects' Hcy levels into HHcy (plasma Hcy level over 15 μmol/l) and normal Hcy subgroups. The plasma levels of lipid indexes were measured. Statistical analyses were performed to evaluate the correlations between groups. The plasma Hcy levels were significantly higher in the HO group than in the SHO or control groups (all p < 0.05). Moreover, levels of Apo A-I and HDL-C were markedly reduced in the HHcy subgroup compared with the normal Hcy subgroup for patients with either HO (Apo A-I: p < 0.05; HDL-C: p < 0.01) or SHO (Apo A-I: p < 0.05; HDL-C: p < 0.01). In addition, the plasma Hcy levels were negatively correlated with levels of Apo A-I in all three groups (HO group: r = - 0.320, SHO group: r = - 0.337 and control group: r = - 0.317; all p < 0.01). Hcy levels were significantly increased in patients with HO or SHO. These increased Hcy levels may impair cardiovascular function via the inhibition of Apo A-1 expression and impairment of its antioxidant capacity. Our findings provide new insights into the pathogenesis of hypothyroidism-induced metabolic disorders.

Apolipoprotein A-I interactions with insulin secretion and production.

PubMed

Rye, Kerry-Anne; Barter, Philip J; Cochran, Blake J

2016-02-01

Human population studies have established that an elevated plasma high-density lipoprotein cholesterol (HDL-C) level is associated with a decreased risk of developing cardiovascular disease. In addition to having several potentially cardioprotective functions, HDLs and apolipoprotein (apo)A-I, the main HDL apolipoprotein, also have antidiabetic properties. Interventions that elevate plasma HDL-C and apoA-I levels improve glycemic control in people with type 2 diabetes mellitus by enhancing pancreatic β-cell function and increasing insulin sensitivity. This review is concerned with recent advances in understanding the mechanisms by which HDLs and apoA-I improve pancreatic β-cell function. HDLs and apoA-I increase insulin synthesis and secretion in pancreatic β cells. The underlying mechanism of this effect is similar to what has been reported for intestinally derived incretins, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, which both increase β-cell insulin secretion under high glucose conditions. This involves the activation of a heterotrimeric G protein Gαs subunit on the β-cell surface that leads to induction of a transmembrane adenylyl cyclase, increased intracellular cyclic adenosine monophosphate and Ca levels, and activation of protein kinase A. Protein kinase A increases insulin synthesis by excluding FoxO1 from the β-cell nucleus and derepressing transcription of the insulin gene.

Analysis of apolipoprotein A-I as a substrate for matrix metalloproteinase-14

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

Park, Jun Hyoung; Park, Sung-Min; Park, Ki-Hoon

2011-05-27

Highlights: {yields} MMP-14 degrades apoA-I more efficiently than other tested MMPs. {yields} Lipid-free apoA-I is more susceptible to MMPs than lipid-bound apoA-I. {yields} MMP-14 cleavage sites on apoA-I have been determined. {yields} Cleavage of apoA-I by MMP-14 impairs its ability to form HDL. -- Abstract: Substrates for matrix metalloproteinase (MMP)-14 were previously identified in human plasma using proteomic techniques. One putative MMP-14 substrate was apolipoprotein A-I (apoA-I), a major component of high-density lipoprotein (HDL). In vitro cleavage assays showed that lipid-free apoA-I is a more accessible substrate for MMP-14 compared to lipid-bound apoA-I, and that MMP-14 is more prone tomore » digest apoA-I than MMP-3. The 28-kDa apoA-I was cleaved into smaller fragments of 27, 26, 25, 22, and 14-kDa by MMP-14. ApoA-I sites cleaved by MMP-14 were determined by isotope labeling of C-termini derived from the cleavage and analysis of the labeled peptides by mass spectrometry, along with N-terminal sequencing of the fragments. Cleavage of apoA-I by MMP-14 resulted in a loss of ability to form HDL. Our results suggest that cleavage of lipid-free apoA-I by MMP-14 may contribute to reduced HDL formation, and this may be occurring during the development of various vascular diseases as lipid metabolism is disrupted.« less

High-Density Lipoprotein-Targeted Therapy and Apolipoprotein A-I Mimetic Peptides.

PubMed

Uehara, Yoshinari; Chiesa, Giulia; Saku, Keijiro

2015-01-01

Numerous randomized clinical trials have established statins as the major standard therapy for atherosclerotic diseases because these molecules decrease the plasma level of low-density lipoprotein (LDL) cholesterol and moderately increase that of plasma high-density lipoprotein (HDL) cholesterol. The reverse cholesterol transport pathway, mediated by HDL particles, has a relevant antiatherogenic potential. An important approach to HDL-targeted therapy is optimization of the HDL-cholesterol level and enhanced removal of plasma cholesterol, together with the prevention and mitigation of inflammation related to atherosclerosis. Small-molecule inhibitors of cholesteryl ester transfer protein (CETP) increase the HDL-cholesterol level in subjects with normal or low HDL-cholesterol. However, CETP inhibitors do not seem to reduce the risk of atherosclerotic diseases. HDL therapies using reconstituted HDL, including apolipoprotein (Apo) A-I Milano, ApoA-I mimetics, or full-length ApoA-I, are dramatically effective in animal models. Of those, the ApoA-I-mimetic peptide called FAMP effectively removes cholesterol via the ABCA1 transporter and acts as an antiatherosclerotic agent by enhancing the biological functions of HDL without elevating the HDL-cholesterol level. Our review of the literature leads us to conclude that HDL-targeted therapies have significant atheroprotective potential and thus may effectively treat patients with cardiovascular diseases.

Effect of feeding diets of varying fatty acid composition on apolipoprotein expression in newborn swine.

PubMed

Wang, H; Hunter, F; Black, D D

1998-10-01

The purpose of this study was to determine the effect of chronic (1 wk) feeding of dietary triacylglycerol (TG) of varying fatty acid composition on small intestinal and hepatic apolipoprotein expression, as well as serum lipid and apolipoprotein concentrations, in newborn swine. Two-day-old female swine were fed one of three diets by gavage with the following lipid composition: medium-chain TG (MCT; MCT oil), intermediate-chain saturated TG (ICST; coconut oil), and long-chain polyunsaturated TG (LCPUT; safflower oil) at 753 kJ . kg-1 . day-1 with 51% of energy from fat. After 1 wk, serum lipids and apolipoprotein concentrations were measured, and jejunal apolipoprotein B (apo B) and apo A-I mass and apo B, apo A-I, apo A-IV, and apo C-III synthesis were measured. Liver was processed for determination of apo B and apo A-I mass and apo B, apo A-I, apo C-III, and beta-actin mRNA abundance by slot blot hybridization. Compared with the MCT and LCPUT groups, the ICST group had higher total serum cholesterol, TG, high-density lipoprotein (HDL)-cholesterol, and apo A-I concentrations. There were no differences among the three groups for intestinal apolipoprotein mass or synthesis. In liver, apo A-I mass was highest in the ICST group. Liver apo A-I and apo C-III mRNA abundance was highest in the ICST group. Among all three groups, hepatic apo A-I mass correlated significantly with plasma HDL-cholesterol concentrations, and serum TG concentrations correlated with hepatic apo C-III mRNA abundance. In conclusion, we found that in the newborn piglet, chronic feeding of ICST increases serum total cholesterol, TG, HDL-cholesterol, and apo A-I concentrations and hepatic expression of apo A-I and apo C-III mRNA, compared with feeding of MCT or LCPUT. We speculate that increased hepatic apo A-I expression may contribute to the higher serum HDL and apo A-I concentrations in the ICST animals. Increased hepatic expression of apo C-III with ICST feeding may contribute to the higher

[Screening and identification of apolipoprotein A-I as a potential marker for hepatoblastoma in children].

PubMed

Guo, Li-Hua; Zhao, Wei; Zhang, Jun-Jie; Zhang, Qian; Fan, Ying-Zhong; Wang, Jia-Xiang

2016-12-01

To screen and identify serum biomarkers for childhood hepatoblastoma (HB). The serum samples from 30 children with hepatoblastoma (HB), 20 children with systemic inflammatory response syndrome, and 20 normal children were treated with magnetic bead-based weak cation exchange chromatography. The platform of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to eliminate the interference of inflammatory factors and to screen out the differentially expressed proteins in serum between tumor group and normal group. After the purification and separation of target proteins were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry was used to determine their amino acid sequences. The SwissProt database was searched for matched proteins. Finally, real-time PCR and ELISA were used to verify and measure the expression of target proteins. After SELDI-TOF-MS was used for screening and elimination of the interference of inflammatory factors, a differentially expression protein with a mass-to-charge ratio of 9 348 Da was found in serum between HB group and normal group, and the HB group had significantly lower expression of this protein than the normal group (p<0.05). This protein was identified as apolipoprotein A-1 (Apo A-I). Real-time PCR and ELISA verified the low mRNA and protein expression of Apo A-I in serum in the HB group and high expression in serum in the normal group. Apo A-I can be used as a non-inflammatory protein marker for HB and has a certain value in the early diagnosis of HB.

Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic)

PubMed Central

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; Yan, Yuhui; LoGiudice, John; Sanger, James R.; Matloub, Hani S.; Pritchard, Kirkwood A.; Jaradeh, Safwan S.; Havlik, Robert

2017-01-01

Background Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. Methods A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. Results Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. Conclusions The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning. PMID:26433438

Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic).

PubMed

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; Yan, Yuhui; LoGiudice, John; Sanger, James R; Matloub, Hani S; Pritchard, Kirkwood A; Jaradeh, Safwan S; Havlik, Robert

2015-12-01

Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning. Copyright © 2015 National Stroke Association. All rights reserved.

Lipid profile, apolipoprotein A-I and oxidative stress in professional footballers, sedentary individuals, and their relatives.

PubMed

Zanella, Aline Margioti; Nakazone, Marcelo Arruda; Pinhel, Marcela Augusta Souza; Souza, Dorotéia Rossi Silva

2011-03-01

To evaluate whether lipid profile (LP), apolipoprotein A-1 (apo A-I) and malondialdehyde (MDA) have any relationship with physical exercise by comparing the groups of footballers (FG) with sedentary individuals (CG) and their relatives (RFG and RCG). Twenty individuals from FG and CG, 60 from RFG, and 57 from RCG were studied. FG showed lower levels of total cholesterol (119.5 ± 37.9 mg/dL), LDL-cholesterol fraction (53.6 ± 30.3), apo A-I (116.7 ± 11.9), and higher level of HDL-cholesterol fraction (HDLc) (49.7 ± 8.5) compared to RFG (148.3 ± 36.9, P = 0.02; 82.4 ± 37.7, P < 0.01; 124.6 ± 10.2, P = 0.03; and 42.7 ± 7.7, P < 0.01; respectively). Moreover, FG had reduced levels of MDA (101.0 ± 77.0 ng/mL) compared to CG (290.0 ± 341.0, P = 0.03) and RFG (209.9 ± 197.5, P = 0.04). These results suggest an association between physical exercise and lower levels of MDA in FG. Physical activity seems to promote beneficial effects on the LP regardless of the genetic influence considering HDLc levels.

A Consensus Model of Human Apolipoprotein A-I in its Monomeric and Lipid-free State

PubMed Central

Melchior, John T.; Walker, Ryan G.; Cooke, Allison L.; Morris, Jamie; Castleberry, Mark; Thompson, Thomas B.; Jones, Martin K.; Song, Hyun D.; Rye, Kerry-Anne; Oda, Mike N.; Sorci-Thomas, Mary G.; Thomas, Michael J.; Heinecke, Jay W.; Mei, Xiaohu; Atkinson, David; Segrest, Jere P.; Lund-Katz, Sissel; Phillips, Michael C.; Davidson, W. Sean

2017-01-01

Apolipoprotein (apo)A-I is an organizing scaffold protein that is critical to high density lipoprotein (HDL) structure and metabolism, likely mediating many of its cardioprotective properties. However, HDL biogenesis is poorly understood as lipid-free apoA-I has been notoriously resistant to high resolution structural study. Published models from low resolution techniques share certain features but vary considerably in shape and secondary structure. To tackle this central issue in lipoprotein biology, we assembled an unprecedented team of lipoprotein structural biologists and set out to build a consensus model of monomeric lipid-free human apoA-I. Combining novel and published cross-link constraints, small angle X-ray scattering (SAXS), hydrogen-deuterium exchange (H-DX) and crystallography data, we propose a time averaged model consistent with much of the experimental data published over the last 40 years. The model provides a long sought platform for understanding and testing details of HDL biogenesis, structure and function. PMID:29131142

Lipid-free apolipoprotein A-I and discoidal reconstituted high-density lipoproteins differentially inhibit glucose-induced oxidative stress in human macrophages.

PubMed

Tabet, Fatiha; Lambert, Gilles; Cuesta Torres, Luisa F; Hou, Liming; Sotirchos, Irene; Touyz, Rhian M; Jenkins, Alicia J; Barter, Philip J; Rye, Kerry-Anne

2011-05-01

The goal of this study was to investigate the mechanisms by which apolipoprotein (apo) A-I, in the lipid-free form or as a constituent of discoidal reconstituted high-density lipoproteins ([A-I]rHDL), inhibits high-glucose-induced redox signaling in human monocyte-derived macrophages (HMDM). HMDM were incubated under normal (5.8 mmol/L) or high-glucose (25 mmol/L) conditions with native high-density lipoproteins (HDL) lipid-free apoA-I from normal subjects and from subjects with type 2 diabetes (T2D) or (A-I)rHDL. Superoxide (O2-) production was measured using dihydroethidium fluorescence. NADPH oxidase activity was assessed using lucigenin-derived chemiluminescence and a cyotochrome c assay. p47phox translocation to the plasma membrane, Nox2, superoxide dismutase 1 (SOD1), and SOD2 mRNA and protein levels were determined by real-time polymerase chain reaction and Western blotting. Native HDL induced a time-dependent inhibition of O2- generation in HMDM incubated with 25 mmol/L glucose. Lipid-free apoA-I and (A-I)rHDL increased SOD1 and SOD2 levels and attenuated 25 mmol/L glucose-mediated increases in cellular O2-, NADPH oxidase activity, p47 translocation, and Nox2 expression. Lipid-free apoA-I mediated its effects on Nox2, SOD1, and SOD2 via ABCA1. (A-I)rHDL-mediated effects were via ABCG1 and scavenger receptor BI. Lipid-free apoA-I from subjects with T2D inhibited reactive oxygen species generation less efficiently than normal apoA-I. Native HDL, lipid-free apoA-I and (A-I)rHDL inhibit high-glucose-induced redox signaling in HMDM. The antioxidant properties of apoA-I are attenuated in T2D.

Sidedness of interfacial arginine residues and anti-atherogenicity of apolipoprotein A-I mimetic peptides

PubMed Central

Nayyar, Gaurav; Mishra, Vinod K.; Handattu, Shaila P.; Palgunachari, Mayakonda N.; Shin, Ronald; McPherson, David T.; Deivanayagam, Champion C. S.; Garber, David W.; Segrest, Jere P.; Anantharamaiah, G. M.

2012-01-01

To test the hypothesis that sidedness of interfacial arginine (Arg) in apoA-I mimetic peptides, similar to that observed in apoA-I (Bashtovyy, D. et al. 2011. Sequence conservation of apolipoprotein A-I affords novel insights into HDL structure-function. J. Lipid Res. 52: 435–450.), may be important for biological activity, we compared properties of 4F and analogs, [K4,15>R]4F and [K9,13>R]4F, with Lys>Arg substitutions on the right and left side, respectively, of the 4F amphipathic helix. Intraperitoneal administration of these peptides into female apoE null mice (n = 13 in each group) reduced en face lesions significantly compared with controls; 4F and [K4,15>R]4F were equally effective whereas [K9,13>R]4F was less effective. Turnover experiments indicated that [K4,15>R]4F reached the highest, whereas [K9,13>R]4F had the lowest, plasma peak levels with a similar half life as the [K4,15>R]4F analog. The half life of 4F was two times longer than the other two peptides. The order in their abilities to associate with HDL in human plasma, generation of apoA-I particles with pre-β mobility from isolated HDL, lipid associating ability, and sensitivity of lipid complexes to trypsin digestion was: 4F>[K4,15,>R]4F>[K9,13>R]4F. These studies support our hypothesis that the sidedness of interfacial Arg residues in the polar face of apoA-I mimetics results in differential biological properties. PMID:22377531

Acid lipase inhibitor in chicken plasma identified as apolipoprotein A-I.

PubMed

Fujii, M; Higuchi, T; Mukai, S; Yonekura, M; Yano, T; Kawaguchi, H; Nonaka, K; Fukunaga, T; Sugimoto, Y; Yamada, S

1996-10-01

We have reported a inhibitor of acid lipases in liver lysosomes and erythrocytes from chickens [M. Fujii et al., Int. J. Biochem., 22, 895-898 (1990)]. In this paper, the properties of the inhibitor were described in comparison with those of apo A-I of chicken. The purified inhibitor migrated with the same mobility on SDS-PAGE as apo A-I, and had a molecular weight of 27,000. The peptide map from the lipase inhibitor was similar to that of apo A-I. Antibodies to the acid lipase inhibitor also reacted with apo A-I. Apo A-I inhibited the acid lipase activities of liver lysosomes and erythrocytes from chickens as strongly as the lipase inhibitor. The N-terminal amino acid sequence of lipase inhibitor was identical to that of apo A-I as far as residue 20. The amino acid sequence of peptides obtained from the inhibitor by cleavage with CNBr corresponded to internal sequence of apo A-I, and so the CNBr-peptides were derived by cleavage after the methionine residues in apo A-I. The findings showed that the inhibitor of the acid lipases in liver lysosomes and erythrocytes from chickens was identical to apo A-I.

Screening and identification of apolipoprotein A-I as a potential hepatoblastoma biomarker in children, excluding inflammatory factors

PubMed Central

ZHAO, WEI; LI, JUAN; ZHANG, YILIN; GAO, PENGFEI; ZHANG, JUNJIE; GUO, FEI; YU, JIEKAI; ZHENG, SHU; WANG, JIAXIANG

2015-01-01

The aim of the present study was to identify a child hepatoblastoma serum biomarker that is unaffected by inflammatory factors, with the ultimate aim of finding an effective method for the early diagnosis of hepatoblastoma. The magnetic bead-based weak cation exchange chromatography technique was used to process serum harvested from 30 children with hepatoblastoma, 20 children with systemic inflammatory response syndrome (SIRS) and 20 healthy children. Proteins differentially expressed in SIRS were excluded from consideration as biomarkers for hepatoblastoma. Proteins differentially expressed in hepatoblastoma and healthy controls were screened using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). Target proteins were purified by SDS-PAGE, and matrix-assisted laser desorption/ionization (MALDI)-TOF-MS was used to determine their amino acid sequences. Protein matches were searched in the SwissProt database. Quantitative polymerase chain reaction (qPCR) and ELISA were employed to confirm the expression of target proteins. Following screening to exclude inflammatory factors, SELDI-TOF-MS revealed a protein with a mass-to-charge ratio of 9,348 Da that was expressed at significantly lower levels in the serum of children with hepatoblastoma compared with healthy controls (P<0.01). Sequence analysis identified this protein as apolipoprotein A-1 (Apo A-I). qPCR and ELISA confirmed that the expression of Apo A-I mRNA and protein were significantly lower in children with hepatoblastoma compared with healthy controls (P<0.05). These results indicate that Apo A-I is a non-inflammatory protein marker for hepatoblastoma with the potential for use in early diagnosis of hepatoblastoma. In addition, the present study demonstrates the feasibility of proteomic screening for the identification of proteins that can serve as markers for a specific tumor. PMID:26171005

Screening and identification of apolipoprotein A-I as a potential hepatoblastoma biomarker in children, excluding inflammatory factors.

PubMed

Zhao, Wei; Li, Juan; Zhang, Yilin; Gao, Pengfei; Zhang, Junjie; Guo, Fei; Yu, Jiekai; Zheng, Shu; Wang, Jiaxiang

2015-07-01

The aim of the present study was to identify a child hepatoblastoma serum biomarker that is unaffected by inflammatory factors, with the ultimate aim of finding an effective method for the early diagnosis of hepatoblastoma. The magnetic bead-based weak cation exchange chromatography technique was used to process serum harvested from 30 children with hepatoblastoma, 20 children with systemic inflammatory response syndrome (SIRS) and 20 healthy children. Proteins differentially expressed in SIRS were excluded from consideration as biomarkers for hepatoblastoma. Proteins differentially expressed in hepatoblastoma and healthy controls were screened using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). Target proteins were purified by SDS-PAGE, and matrix-assisted laser desorption/ionization (MALDI)-TOF-MS was used to determine their amino acid sequences. Protein matches were searched in the SwissProt database. Quantitative polymerase chain reaction (qPCR) and ELISA were employed to confirm the expression of target proteins. Following screening to exclude inflammatory factors, SELDI-TOF-MS revealed a protein with a mass-to-charge ratio of 9,348 Da that was expressed at significantly lower levels in the serum of children with hepatoblastoma compared with healthy controls (P<0.01). Sequence analysis identified this protein as apolipoprotein A-1 (Apo A-I). qPCR and ELISA confirmed that the expression of Apo A-I mRNA and protein were significantly lower in children with hepatoblastoma compared with healthy controls (P<0.05). These results indicate that Apo A-I is a non-inflammatory protein marker for hepatoblastoma with the potential for use in early diagnosis of hepatoblastoma. In addition, the present study demonstrates the feasibility of proteomic screening for the identification of proteins that can serve as markers for a specific tumor.

Association of serum lipids and coronary artery disease with polymorphisms in the apolipoprotein AI-CIII-AIV gene cluster

PubMed Central

Rai, Himanshu; Sinha, Nakul; Finn, James; Agrawal, Suraksha; Mastana, Sarabjit

2016-01-01

Abstract Genetic variants are considered as one of the main determinants of the concentration of serum lipids and coronary artery disease (CAD). Polymorphisms in the Apolipoprotein (Apo) AI-CIII-AIV gene cluster has been known to affect the concentrations of various lipid sub-fractions and the risk of CAD. The present study assessed associations between polymorphisms of the Apo AI-CIII-AIV gene cluster, [ApoA-I,-75G > A, (rs1799837); ApoC-III 3238C > G, (SstI), (rs5128) and ApoA-IV, Thr347Ser(347A > T), (rs675)] with serum lipids and their contributions to CAD in North Indian population. We recruited age, sex matched, 200 CAD patients and 200 healthy controls and tested them for fasting levels of serum lipids. We genotyped selected polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. There were no statistically significant association of selected polymorphisms (or their combinations) with CAD even after employing additive, dominant and recessive models. However there was significant association of selected polymorphisms with various lipid traits amongst the control cohort (p < 0.05). Mean levels of high density lipoprotein cholesterol and triglycerides were found to be significantly higher among controls carrying at least one mutant allele at ApoA1-75G > A (p = 0.019) and ApoCIII SstI (p < 0.001) polymorphism respectively. Our study observed that the selected polymorphisms in the ApoAI-CIII-AIV gene cluster although significantly affect various lipid traits but this affect does not seem to translate into association with CAD, at least among North Indian population. PMID:28261635

Effect of curcumin on amyloid-like aggregates generated from methionine-oxidized apolipoprotein A-I

DOE PAGES

Krishnamoorthy, Aparna; Tavoosi, Narjes; Chan, Gary K. L.; ...

2018-01-10

Curcumin is a polyphenolic phytonutrient that has antineurodegenerative properties. Here, we investigated the anti-amyloidogenic properties of curcumin. Following incubation with curcumin, intrinsic tryptophan fluorescence emission of apolipoprotein (apo) A-I was strongly quenched. At the same time, curcumin fluorescence emission was enhanced. The fluorescence emission spectra of curcumin in the presence of amyloid-like aggregates formed by methionine-oxidized (ox) apoA-I varied, depending on whether curcumin was added before, or after, aggregate formation. The impact of curcumin on the structure of the aggregating material was revealed by the lower amount of β-structure in ox-apoA-I amyloid-like aggregates formed in the presence of curcumin, comparedmore » to aggregates formed without curcumin. However, the kinetics of ox-apoA-I amyloid-like aggregate formation was not altered by the presence of curcumin. Moreover, electron microscopy analysis detected no discernable differences in amyloid morphology when ox-apoA-I amyloid-like aggregates were formed in the presence or absence of curcumin. In conclusion, curcumin interacts with apoA-I and alters the structure of ox-apoA-I amyloid-like aggregates yet does not diminish the propensity of ox-apoA-I to form aggregates.« less

Effect of curcumin on amyloid-like aggregates generated from methionine-oxidized apolipoprotein A-I

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

Krishnamoorthy, Aparna; Tavoosi, Narjes; Chan, Gary K. L.

Curcumin is a polyphenolic phytonutrient that has antineurodegenerative properties. Here, we investigated the anti-amyloidogenic properties of curcumin. Following incubation with curcumin, intrinsic tryptophan fluorescence emission of apolipoprotein (apo) A-I was strongly quenched. At the same time, curcumin fluorescence emission was enhanced. The fluorescence emission spectra of curcumin in the presence of amyloid-like aggregates formed by methionine-oxidized (ox) apoA-I varied, depending on whether curcumin was added before, or after, aggregate formation. The impact of curcumin on the structure of the aggregating material was revealed by the lower amount of β-structure in ox-apoA-I amyloid-like aggregates formed in the presence of curcumin, comparedmore » to aggregates formed without curcumin. However, the kinetics of ox-apoA-I amyloid-like aggregate formation was not altered by the presence of curcumin. Moreover, electron microscopy analysis detected no discernable differences in amyloid morphology when ox-apoA-I amyloid-like aggregates were formed in the presence or absence of curcumin. In conclusion, curcumin interacts with apoA-I and alters the structure of ox-apoA-I amyloid-like aggregates yet does not diminish the propensity of ox-apoA-I to form aggregates.« less

Learning from Synthetic Models of Extracellular Matrix; Differential Binding of Wild Type and Amyloidogenic Human Apolipoprotein A-I to Hydrogels Formed from Molecules Having Charges Similar to Those Found in Natural GAGs.

PubMed

Rosú, Silvana A; Toledo, Leandro; Urbano, Bruno F; Sanchez, Susana A; Calabrese, Graciela C; Tricerri, M Alejandra

2017-08-01

Among other components of the extracellular matrix (ECM), glycoproteins and glycosaminoglycans (GAGs) have been strongly associated to the retention or misfolding of different proteins inducing the formation of deposits in amyloid diseases. The composition of these molecules is highly diverse and a key issue seems to be the equilibrium between physiological and pathological events. In order to have a model in which the composition of the matrix could be finely controlled, we designed and synthesized crosslinked hydrophilic polymers, the so-called hydrogels varying the amounts of negative charges and hydroxyl groups that are prevalent in GAGs. We checked and compared by fluorescence techniques the binding of human apolipoprotein A-I and a natural mutant involved in amyloidosis to the hydrogel scaffolds. Our results indicate that both proteins are highly retained as long as the negative charge increases, and in addition it was shown that the mutant is more retained than the Wt, indicating that the retention of specific proteins in the ECM could be part of the pathogenicity. These results show the importance of the use of these polymers as a model to get deep insight into the studies of proteins within macromolecules.

Apolipoprotein A-I inhibits chemotaxis, adhesion, activation of THP-1 cells and improves the plasma HDL inflammatory index.

PubMed

Wang, Li; Chen, Wei-Zhong; Wu, Man-Ping

2010-02-01

The anti-inflammatory effects of high density lipoprotein (HDL) are well described, however, such effects of Apolipoprotein A-I (ApoA-I) are less studied. Building on our previous study, we further explored the mechanism of anti-inflammatory effects of ApoA-I, and focused especially on the interaction between monocyte and endothelial cells and plasma HDL inflammatory index in LPS-challenged rabbits. Our results show that ApoA-I significantly decreased LPS-induced MCP-1 release from THP-1 cells and ox-LDL-induced THP-1 migration ratio (P<0.01, respectively). ApoA-I significantly decreased sL-selectin, sICAM-1 and sVCAM-1 release (P<0.01, P<0.01, P<0.05, respectively) from LPS-stimulated THP-1 cells. Furthermore, ApoA-I significantly inhibited LPS-induced CD11b and VCAM-1 expression on THP-1 cells (P<0.01, P<0.05, respectively). ApoA-I diminished LPS-induced mCD14 expression (P<0.01) and NFkappaB nuclear translocation in THP-1 cells. After single dose treatment of ApoA-I, the value of plasma HDL inflammatory index in LPS-challenged rabbits was improved significantly (P<0.05). These results suggest that ApoA-I can inhibit chemotaxis, adhesion and activation of human monocytes and improve plasma HDL inflammatory index with presenting beneficial anti-inflammatory effects. Copyright 2009 Elsevier Ltd. All rights reserved.

Prolonged Caloric Restriction in Obese Patients With Type 2 Diabetes Mellitus Decreases Plasma CETP and Increases Apolipoprotein AI Levels Without Improving the Cholesterol Efflux Properties of HDL

PubMed Central

Wang, Yanan; Snel, Marieke; Jonker, Jacqueline T.; Hammer, Sebastiaan; Lamb, Hildo J.; de Roos, Albert; Meinders, A. Edo; Pijl, Hanno; Romijn, Johannes A.; Smit, Johannes W.A.; Jazet, Ingrid M.; Rensen, Patrick C.N.

2011-01-01

OBJECTIVE Using a mouse model for human-like lipoprotein metabolism, we observed previously that reduction of the hepatic triglyceride (TG) content resulted in a decrease in plasma cholesteryl ester transfer protein (CETP) and an increase in HDL levels. The aim of the current study was to investigate the effects of prolonged caloric restriction in obese patients with type 2 diabetes mellitus, resulting in a major reduction in hepatic TG content, on plasma CETP and HDL levels. RESEARCH DESIGN AND METHODS We studied 27 obese (BMI: 37.2 ± 0.9 kg/m2) insulin-dependent patients with type 2 diabetes mellitus (14 men and 13 women, aged 55 ± 2 years) who received a 16-week very low calorie diet (VLCD). At baseline and after a 16-week VLCD, plasma lipids, lipoproteins, and CETP were measured. Furthermore, functionality of HDL with respect to inducing cholesterol efflux from human monocyte cells (THP-1) was determined. RESULTS A 16-week VLCD markedly decreased plasma CETP concentration (−18%; P < 0.01) and increased plasma apolipoprotein (apo)AI levels (+16%; P < 0.05), without significantly affecting plasma HDL-cholesterol and HDL-phospholipids. Although a VLCD results in HDL that is less lipidated, the functionality of HDL with respect to inducing cholesterol efflux in vitro was unchanged. CONCLUSIONS The marked decrease in hepatic TG content induced by a 16-week VLCD is accompanied by a decrease in plasma CETP concentration and an increase in apoAI levels, without improving the cholesterol efflux properties of HDL in vitro. PMID:21994427

Targeting nanodisks via a single chain variable antibody--apolipoprotein chimera.

PubMed

Iovannisci, David M; Beckstead, Jennifer A; Ryan, Robert O

2009-02-06

Nanodisks (ND) are nanometer scale complexes of phospholipid and apolipoprotein that have been shown to function as drug delivery vehicles. ND harboring significant quantities of the antifungal agent, amphotericin B, or the bioactive isoprenoid, all trans retinoic acid, have been generated and characterized. As currently formulated, ND possess limited targeting capability. In this study, we constructed a single chain variable antibody (scFv).apolipoprotein chimera and assessed the ability of this fusion protein to form ND and recognize the antigen to which the scFv is directed. Data obtained revealed that alpha-vimentin scFv.apolipoprotein A-I is functional in ND formation and antigen recognition, opening the door to the use of such chimeras in targeting drug-enriched ND to specific tissues.

Multiple system atrophy and apolipoprotein E.

PubMed

Ogaki, Kotaro; Martens, Yuka A; Heckman, Michael G; Koga, Shunsuke; Labbé, Catherine; Lorenzo-Betancor, Oswaldo; Wernick, Anna I; Walton, Ronald L; Soto, Alexandra I; Vargas, Emily R; Nielsen, Henrietta M; Fujioka, Shinsuke; Kanekiyo, Takahisa; Uitti, Ryan J; van Gerpen, Jay A; Cheshire, William P; Wszolek, Zbigniew K; Low, Phillip A; Singer, Wolfgang; Dickson, Dennis W; Bu, Guojun; Ross, Owen A

2018-04-01

Dysregulation of the specialized lipid metabolism involved in myelin synthesis and maintenance by oligodendrocytes has been associated with the unique neuropathology of MSA. We hypothesized that apolipoprotein E, which is associated with neurodegeneration, may also play a role in the pathogenesis of MSA. This study evaluated genetic associations of Apolipoprotein E alleles with risk of MSA and α-synuclein pathology, and also examined whether apolipoprotein E isoforms differentially affect α-synuclein uptake in a oligodendrocyte cell. One hundred sixty-eight pathologically confirmed MSA patients, 89 clinically diagnosed MSA patients, and 1,277 control subjects were genotyped for Apolipoprotein E. Human oligodendrocyte cell lines were incubated with α-synuclein and recombinant human apolipoprotein E, with internalized α-synuclein imaged by confocal microscopy and cells analyzed by flow cytometry. No significant association with risk of MSA or was observed for either Apolipoprotein E ɛ2 or ɛ4. α-Synuclein burden was also not associated with Apolipoprotein E alleles in the pathologically confirmed patients. Interestingly, in our cell assays, apolipoprotein E ɛ4 significantly reduced α-synuclein uptake in the oligodendrocytic cell line. Despite differential effects of apolipoprotein E isoforms on α-synuclein uptake in a human oligodendrocytic cell, we did not observe a significant association at the Apolipoprotein E locus with risk of MSA or α-synuclein pathology. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

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

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

Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer

2003-08-15

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

Myeloperoxidase-mediated Methionine Oxidation Promotes an Amyloidogenic Outcome for Apolipoprotein A-I*

PubMed Central

Chan, Gary K. L.; Witkowski, Andrzej; Gantz, Donald L.; Zhang, Tianqi O.; Zanni, Martin T.; Jayaraman, Shobini; Cavigiolio, Giorgio

2015-01-01

High plasma levels of apolipoprotein A-I (apoA-I) correlate with cardiovascular health, whereas dysfunctional apoA-I is a cause of atherosclerosis. In the atherosclerotic plaques, amyloid deposition increases with aging. Notably, apoA-I is the main component of these amyloids. Recent studies identified high levels of oxidized lipid-free apoA-I in atherosclerotic plaques. Likely, myeloperoxidase (MPO) secreted by activated macrophages in atherosclerotic lesions is the promoter of such apoA-I oxidation. We hypothesized that apoA-I oxidation by MPO levels similar to those present in the artery walls in atherosclerosis can promote apoA-I structural changes and amyloid fibril formation. ApoA-I was exposed to exhaustive chemical (H2O2) oxidation or physiological levels of enzymatic (MPO) oxidation and incubated at 37 °C and pH 6.0 to induce fibril formation. Both chemically and enzymatically oxidized apoA-I produced fibrillar amyloids after a few hours of incubation. The amyloid fibrils were composed of full-length apoA-I with differential oxidation of the three methionines. Met to Leu apoA-I variants were used to establish the predominant role of oxidation of Met-86 and Met-148 in the fibril formation process. Importantly, a small amount of preformed apoA-I fibrils was able to seed amyloid formation in oxidized apoA-I at pH 7.0. In contrast to hereditary amyloidosis, wherein specific mutations of apoA-I cause protein destabilization and amyloid deposition, oxidative conditions similar to those promoted by local inflammation in atherosclerosis are sufficient to transform full-length wild-type apoA-I into an amyloidogenic protein. Thus, MPO-mediated oxidation may be implicated in the mechanism that leads to amyloid deposition in the atherosclerotic plaques in vivo. PMID:25759391

Gene-centric Association Signals for Lipids and Apolipoproteins Identified via the HumanCVD BeadChip

PubMed Central

Talmud, Philippa J.; Drenos, Fotios; Shah, Sonia; Shah, Tina; Palmen, Jutta; Verzilli, Claudio; Gaunt, Tom R.; Pallas, Jacky; Lovering, Ruth; Li, Kawah; Casas, Juan Pablo; Sofat, Reecha; Kumari, Meena; Rodriguez, Santiago; Johnson, Toby; Newhouse, Stephen J.; Dominiczak, Anna; Samani, Nilesh J.; Caulfield, Mark; Sever, Peter; Stanton, Alice; Shields, Denis C.; Padmanabhan, Sandosh; Melander, Olle; Hastie, Claire; Delles, Christian; Ebrahim, Shah; Marmot, Michael G.; Smith, George Davey; Lawlor, Debbie A.; Munroe, Patricia B.; Day, Ian N.; Kivimaki, Mika; Whittaker, John; Humphries, Steve E.; Hingorani, Aroon D.

2009-01-01

Blood lipids are important cardiovascular disease (CVD) risk factors with both genetic and environmental determinants. The Whitehall II study (n = 5592) was genotyped with the gene-centric HumanCVD BeadChip (Illumina). We identified 195 SNPs in 16 genes/regions associated with 3 major lipid fractions and 2 apolipoprotein components at p < 10−5, with the associations being broadly concordant with prior genome-wide analysis. SNPs associated with LDL cholesterol and apolipoprotein B were located in LDLR, PCSK9, APOB, CELSR2, HMGCR, CETP, the TOMM40-APOE-C1-C2-C4 cluster, and the APOA5-A4-C3-A1 cluster; SNPs associated with HDL cholesterol and apolipoprotein AI were in CETP, LPL, LIPC, APOA5-A4-C3-A1, and ABCA1; and SNPs associated with triglycerides in GCKR, BAZ1B, MLXIPL, LPL, and APOA5-A4-C3-A1. For 48 SNPs in previously unreported loci that were significant at p < 10−4 in Whitehall II, in silico analysis including the British Women's Heart and Health Study, BRIGHT, ASCOT, and NORDIL studies (total n > 12,500) revealed previously unreported associations of SH2B3 (p < 2.2 × 10−6), BMPR2 (p < 2.3 × 10−7), BCL3/PVRL2 (flanking APOE; p < 4.4 × 10−8), and SMARCA4 (flanking LDLR; p < 2.5 × 10−7) with LDL cholesterol. Common alleles in these genes explained 6.1%–14.7% of the variance in the five lipid-related traits, and individuals at opposite tails of the additive allele score exhibited substantial differences in trait levels (e.g., >1 mmol/L in LDL cholesterol [∼1 SD of the trait distribution]). These data suggest that multiple common alleles of small effect can make important contributions to individual differences in blood lipids potentially relevant to the assessment of CVD risk. These genes provide further insights into lipid metabolism and the likely effects of modifying the encoded targets therapeutically. PMID:19913121

Several Human Liver Cell Expressed Apolipoproteins Complement HCV Virus Production with Varying Efficacy Conferring Differential Specific Infectivity to Released Viruses.

PubMed

Hueging, Kathrin; Weller, Romy; Doepke, Mandy; Vieyres, Gabrielle; Todt, Daniel; Wölk, Benno; Vondran, Florian W R; Geffers, Robert; Lauber, Chris; Kaderali, Lars; Penin, François; Pietschmann, Thomas

2015-01-01

Apolipoprotein E (ApoE), an exchangeable apolipoprotein, is necessary for production of infectious Hepatitis C virus (HCV) particles. However, ApoE is not the only liver-expressed apolipoprotein and the role of other apolipoproteins for production of infectious HCV progeny is incompletely defined. Therefore, we quantified mRNA expression of human apolipoproteins in primary human hepatocytes. Subsequently, cDNAs encoding apolipoproteins were expressed in 293T/miR-122 cells to explore if they complement HCV virus production in cells that are non-permissive due to limiting endogenous levels of human apolipoproteins. Primary human hepatocytes expressed high mRNA levels of ApoA1, A2, C1, C3, E, and H. ApoA4, A5, B, D, F, J, L1, L2, L3, L4, L6, M, and O were expressed at intermediate levels, and C2, C4, and L5 were not detected. All members of the ApoA and ApoC family of lipoproteins complemented HCV virus production in HCV transfected 293T/miR-122 cells, albeit with significantly lower efficacy compared with ApoE. In contrast, ApoD expression did not support production of infectious HCV. Specific infectivity of released particles complemented with ApoA family members was significantly lower compared with ApoE. Moreover, the ratio of extracellular to intracellular infectious virus was significantly higher for ApoE compared to ApoA2 and ApoC3. Since apolipoproteins complementing HCV virus production share amphipathic alpha helices as common structural features we altered the two alpha helices of ApoC1. Helix breaking mutations in both ApoC1 helices impaired virus assembly highlighting a critical role of alpha helices in apolipoproteins supporting HCV assembly. In summary, various liver expressed apolipoproteins with amphipathic alpha helices complement HCV virus production in human non liver cells. Differences in the efficiency of virus assembly, the specific infectivity of released particles, and the ratio between extracellular and intracellular infectivity point to

Several Human Liver Cell Expressed Apolipoproteins Complement HCV Virus Production with Varying Efficacy Conferring Differential Specific Infectivity to Released Viruses

PubMed Central

Doepke, Mandy; Vieyres, Gabrielle; Todt, Daniel; Wölk, Benno; Vondran, Florian W. R.; Geffers, Robert; Lauber, Chris; Kaderali, Lars; Penin, François; Pietschmann, Thomas

2015-01-01

Apolipoprotein E (ApoE), an exchangeable apolipoprotein, is necessary for production of infectious Hepatitis C virus (HCV) particles. However, ApoE is not the only liver-expressed apolipoprotein and the role of other apolipoproteins for production of infectious HCV progeny is incompletely defined. Therefore, we quantified mRNA expression of human apolipoproteins in primary human hepatocytes. Subsequently, cDNAs encoding apolipoproteins were expressed in 293T/miR-122 cells to explore if they complement HCV virus production in cells that are non-permissive due to limiting endogenous levels of human apolipoproteins. Primary human hepatocytes expressed high mRNA levels of ApoA1, A2, C1, C3, E, and H. ApoA4, A5, B, D, F, J, L1, L2, L3, L4, L6, M, and O were expressed at intermediate levels, and C2, C4, and L5 were not detected. All members of the ApoA and ApoC family of lipoproteins complemented HCV virus production in HCV transfected 293T/miR-122 cells, albeit with significantly lower efficacy compared with ApoE. In contrast, ApoD expression did not support production of infectious HCV. Specific infectivity of released particles complemented with ApoA family members was significantly lower compared with ApoE. Moreover, the ratio of extracellular to intracellular infectious virus was significantly higher for ApoE compared to ApoA2 and ApoC3. Since apolipoproteins complementing HCV virus production share amphipathic alpha helices as common structural features we altered the two alpha helices of ApoC1. Helix breaking mutations in both ApoC1 helices impaired virus assembly highlighting a critical role of alpha helices in apolipoproteins supporting HCV assembly. In summary, various liver expressed apolipoproteins with amphipathic alpha helices complement HCV virus production in human non liver cells. Differences in the efficiency of virus assembly, the specific infectivity of released particles, and the ratio between extracellular and intracellular infectivity point to

Concomitant Effects of Ramadan Fasting and Time-Of-Day on Apolipoprotein AI, B, Lp-a and Homocysteine Responses during Aerobic Exercise in Tunisian Soccer Players

PubMed Central

Hammouda, Omar; Chtourou, Hamdi; Aloui, Asma; Chahed, Henda; Kallel, Choumous; Miled, Abdelhedi; Chamari, Karim; Chaouachi, Anis; Souissi, Nizar

2013-01-01

Objective To examine the time-of-day and Ramadan fasting (RF) effects on serum apolipoprotein-AI (Apo-AI) and B (Apo-B), lipoprotein particles-a (Lp-a), high-sensitive C-reactive-protein (hs-CRP), and homocysteine (Hcy) during the Yo-Yo intermittent recovery test (YYIRT). Design Performance and biochemical measures were completed at two times-of-day (07:00 and 17:00 h), 1-week before RF (BR), the second week of RF (SWR), and the fourth week of RF (ER). Setting For each session, subjects performed the YYIRT, and blood samples were taken before and 3-min after the test for biochemical measures. Participants Fifteen soccer players. Main Outcome Measures Total distance during the YYIRT, core temperature, body composition, dietary intakes, lipid (HDL-C, LDL-C, Apo-AI, B and Lp-a) and inflammatory (hs-CRP and Hcy) profiles. Results Performances during the YYIRT were higher in the evening than the morning BR (P < 0.05), but this fluctuation was not observed during RF. Moreover, LDL-C, ApoB, and Lp-a were stable throughout the daytime BR. However, during RF, they decreased at 17:00 h (P < 0.05). Likewise, HDL-C and Apo-AI increased after the exercise and were higher at 17:00 h BR (P < 0.001). Moreover, these parameters increased during RF (P < 0.01). Furthermore, Hcy and hs-CRP increased during the exercise (P < 0.01) with higher evening levels BR. During ER, the diurnal pattern of Hcy was inversed (P < 0.001). Conclusions This study concluded that caloric restriction induced by RF seems to ameliorate lipid and inflammatory markers of cardiovascular health during intermittent exercise performed in the evening. PMID:24244572

Secretion of apolipoproteins A-I and B by HepG2 cells: regulation by substrates and metabolic inhibitors.

PubMed

Kempen, H J; Imbach, A P; Giller, T; Neumann, W J; Hennes, U; Nakada, N

1995-08-01

It was the aim of this study to i) compare the effects of glucose and other hexoses with that of oleate on secretion of apolipoproteins (apos) A-I and B by HepG2 cells, and ii) document the effect of various metabolic inhibitors on the secretion of these apos in the absence or presence of extra glucose/oleate. i) The addition of 10 mM glucose increased secretion of apoA-I and apoB, as measured by enzyme immunoassay, by about 60% when cells were incubated for 48 h in DMEM + 10% fetal calf serum. The addition of extra glucose also increased the mRNA levels for these apos. Increased radioactivity was also found in these apolipoproteins by immunoprecipitation after metabolic labeling with [35S]methionine for 48 h. However, in a pulse-chase experiment (15 min labeling, 2 h chase), glucose was found to increase apoA-I synthesis but not apoB synthesis. More labeled apoB appeared in the medium during the chase because glucose inhibited its intracellular degradation. The effect of glucose on secretion of these apos could be mimicked by fructose and mannose but not by 6-deoxyglucose, showing that the hexoses must enter the cells and be phosphorylated. In contrast, the addition of 0.5 mM oleate had a weak inhibitory effect on secretion of apoA-I whereas it increased the secretion of apoB by more than twofold. The combination of 10 mM glucose and 0.5 mM oleate had no greater effect than glucose alone on apoA-I secretion but increased apoB secretion by fourfold. ii) Inhibiting glycolysis (by glucosamine) lowered secretion of both apoA-I and apoB, while inhibiting lipogenesis (using 8-Br-cyclic AMP or 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA)) did not affect apoA-I secretion but clearly decreased that of apoB. However, the inhibitory effect of TOFA on apoB secretion was much smaller in the presence of 0.5 mM oleate instead of extra glucose. Actinomycin-D and cycloheximide strongly suppressed the stimulatory effect of glucose on secretion of both apolipoproteins

Apolipoprotein gene polymorphisms and plasma levels in healthy Tunisians and patients with coronary artery disease

PubMed Central

Bahri, Raoudha; Esteban, Esther; Moral, Pedro; Hassine, Mohsen; Hamda, Khaldoun Ben; Chaabani, Hassen

2008-01-01

Aim To analyze apolipoprotein gene polymorphisms in the Tunisian population and to check the relation of these polymorphisms and homocysteine, lipid and apolipoprotein levels to the coronary artery disease (CAD). Methods In healthy blood donors and in patients with CAD complicated by myocardial infarction (MI) four apolipoprotein gene polymorphisms [APO (a) PNR, APO E, APO CI and APO CII] were determined and plasma levels of total homocysteine, total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HLD-C) and apolipoproteins (apo A-I, Apo B, Apo E) were measured. Results Analysis of the four apolipoprotein gene polymorphisms shows a relative genetic homogeneity between Tunisian population and those on the other side of Mediterranean basin. Compared to controls, CAD patients have significantly higher main concentrations of TC, TG, LDL-C, apo B and homocysteine, and significantly lower ones of HDL-C, apo A-I and apo E. The four apolipoprotein gene polymorphisms have not showed any significant differences between patients and controls. However, the APO E4 allele appears to be associated to the severity of CAD and to high levels of atherogenic parameters and low level of apo E, which has very likely an anti-atherogenic role. Conclusion Although APO (a) PNR, APO CI and APO CII genes are analyzed in only few populations, they show a frequency distribution, which is not at variance with that of APO E gene and other widely studied genetic markers. In the Tunisian population the APO E 4 appears to be only indirectly involved in the severity of CAD. In the routine practice, in addition of classic parameters, it will be useful to measure the concentration of apo E and that of Homocysteine and if possible to determine the APO E gene polymorphism. PMID:19014618

The paradox of high apolipoprotein A-I levels independently predicting incident type-2 diabetes among Turks.

PubMed

Onat, A; Hergenç, G; Bulur, S; Uğur, M; Küçükdurmaz, Z; Can, G

2010-06-25

Predictive value of apolipoprotein (apo) A-I for incident hypertension, metabolic syndrome (MetS), type 2 diabetes (DM) and coronary heart disease (CHD) needs further exploration. A representative sample of Turkish adults was studied with this purpose prospectively. Sex-specific apoA-I tertiles were examined regarding cardiometabolic risk. A total of 1044 men and 1067 women (aged 49+/-12 years at baseline) were followed up over 7.4 years. High serum apoA-I levels were significantly associated in multivariable analysis with female sex, aging, alcohol intake, (inversely) cigarette smoking and, in women, with systolic blood pressure. Risk of diabetes was predicted in logistic regression in both genders by top versus bottom apoA-I tertile (RR 1.98; [95%CI 1.31; 3.0]), additive to age, body mass index (BMI), C-reactive protein (CRP), HDL-cholesterol and lipid lowering drugs. By adding sex hormone-binding globulin to the model in a subset of the sample, the association between high apoA-I and incident diabetes was attenuated only in women. ApoA-I tertiles tended to be positively associated also with hypertension and CHD only in women but this did not reach significance. High compared with low serum apoA-I levels nearly double the risk for incident diabetes, additively to age, BMI, CRP, HDL-cholesterol among Turks. Systemic inflammation concomitant with prevailing MetS might turn apoA-I into proinflammatory particles. Copyright 2008 Elsevier Ireland Ltd. All rights reserved.

Genome-wide screen for modulation of hepatic apolipoprotein A-I (ApoA-I) secretion.

PubMed

Miles, Rebecca R; Perry, William; Haas, Joseph V; Mosior, Marian K; N'Cho, Mathias; Wang, Jian W J; Yu, Peng; Calley, John; Yue, Yong; Carter, Quincy; Han, Bomie; Foxworthy, Patricia; Kowala, Mark C; Ryan, Timothy P; Solenberg, Patricia J; Michael, Laura F

2013-03-01

Control of plasma cholesterol levels is a major therapeutic strategy for management of coronary artery disease (CAD). Although reducing LDL cholesterol (LDL-c) levels decreases morbidity and mortality, this therapeutic intervention only translates into a 25-40% reduction in cardiovascular events. Epidemiological studies have shown that a high LDL-c level is not the only risk factor for CAD; low HDL cholesterol (HDL-c) is an independent risk factor for CAD. Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-c that mediates reverse cholesterol transport from tissues to the liver for excretion. Therefore, increasing ApoA-I levels is an attractive strategy for HDL-c elevation. Using genome-wide siRNA screening, targets that regulate hepatocyte ApoA-I secretion were identified through transfection of 21,789 siRNAs into hepatocytes whereby cell supernatants were assayed for ApoA-I. Approximately 800 genes were identified and triaged using a convergence of information, including genetic associations with HDL-c levels, tissue-specific gene expression, druggability assessments, and pathway analysis. Fifty-nine genes were selected for reconfirmation; 40 genes were confirmed. Here we describe the siRNA screening strategy, assay implementation and validation, data triaging, and example genes of interest. The genes of interest include known and novel genes encoding secreted enzymes, proteases, G-protein-coupled receptors, metabolic enzymes, ion transporters, and proteins of unknown function. Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor manumycin A caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes. In total, this work underscores the power of functional genetic assessment to identify new therapeutic targets.

Bioinformatic Analysis of Plasma Apolipoproteins A-I and A-II Revealed Unique Features of A-I/A-II HDL Particles in Human Plasma

PubMed Central

Kido, Toshimi; Kurata, Hideaki; Kondo, Kazuo; Itakura, Hiroshige; Okazaki, Mitsuyo; Urata, Takeyoshi; Yokoyama, Shinji

2016-01-01

Plasma concentration of apoA-I, apoA-II and apoA-II-unassociated apoA-I was analyzed in 314 Japanese subjects (177 males and 137 females), including one (male) homozygote and 37 (20 males and 17 females) heterozygotes of genetic CETP deficiency. ApoA-I unassociated with apoA-II markedly and linearly increased with HDL-cholesterol, while apoA-II increased only very slightly and the ratio of apoA-II-associated apoA-I to apoA-II stayed constant at 2 in molar ratio throughout the increase of HDL-cholesterol, among the wild type and heterozygous CETP deficiency. Thus, overall HDL concentration almost exclusively depends on HDL with apoA-I without apoA-II (LpAI) while concentration of HDL containing apoA-I and apoA-II (LpAI:AII) is constant having a fixed molar ratio of 2 : 1 regardless of total HDL and apoA-I concentration. Distribution of apoA-I between LpAI and LpAI:AII is consistent with a model of statistical partitioning regardless of sex and CETP genotype. The analysis also indicated that LpA-I accommodates on average 4 apoA-I molecules and has a clearance rate indistinguishable from LpAI:AII. Independent evidence indicated LpAI:A-II has a diameter 20% smaller than LpAI, consistent with a model having two apoA-I and one apoA-II. The functional contribution of these particles is to be investigated. PMID:27526664

Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas.

PubMed

Crosby, Natasha M; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A; Kamei, Ayako; Simonsen, Jens B; Luo, Bing; Gordon, Leo I; Forte, Trudy M; Ryan, Robert O

2015-08-01

A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents.

Haplotype analysis of the apolipoprotein gene cluster on human chromosome 11

PubMed Central

Olivier, Michael; Wang, Xujing; Cole, Regina; Gau, Brian; Kim, Jessica; Rubin, Edward M.; Pennacchio, Len A.

2009-01-01

Members of the apolipoprotein gene cluster (APOA1/C3/A4/A5) on human chromosome 11q23 play an important role in lipid metabolism. Polymorphisms in both APOA5 and APOC3 are strongly associated with plasma triglyceride concentrations. The close genomic locations of these two genes as well as their functional similarity have hindered efforts to define whether each gene independently influences human triglyceride concentrations. In this study, we examined the linkage disequilibrium and haplotype structure of 49 SNPs in a 150-kb region spanning the gene cluster. We identified a total of five common APOA5 haplotypes with a frequency of greater than 8% in samples of northern European origin. The APOA5 haplotype block did not extend past the 7 SNPs in the gene and was separated from the other apolipoprotein gene in the cluster by a region of significantly increased recombination. Furthermore, one previously identified triglyceride risk haplotype of APOA5 (APOA5*3) showed no association with three APOC3 SNPs previously associated with triglyceride concentrations, in contrast to the other risk haplotype (APOA5*2), which was associated with all three minor APOC3 SNP alleles. These results highlight the complex genetic relationship between APOA5 and APOC3 and support the notion that APOA5 represents an independent risk gene affecting plasma triglyceride concentrations in humans. PMID:15081120

Genetic deletion of apolipoprotein A-I increases airway hyperresponsiveness, inflammation, and collagen deposition in the lung

PubMed Central

Wang, Weiling; Xu, Hao; Shi, Yang; Nandedkar, Sandhya; Zhang, Hao; Gao, Haiqing; Feroah, Thom; Weihrauch, Dorothee; Schulte, Marie L.; Jones, Deron W.; Jarzembowski, Jason; Sorci-Thomas, Mary; Pritchard, Kirkwood A.

2010-01-01

The relationship between high-density lipoprotein and pulmonary function is unclear. To determine mechanistic relationships we investigated the effects of genetic deletion of apolipoprotein A-I (apoA-I) on plasma lipids, paraoxonase (PON1), pro-inflammatory HDL (p-HDL), vasodilatation, airway hyperresponsiveness and pulmonary oxidative stress, and inflammation. ApoA-I null (apoA-I−/−) mice had reduced total and HDL cholesterol but increased pro-inflammatory HDL compared with C57BL/6J mice. Although PON1 protein was increased in apoA-I−/− mice, PON1 activity was decreased. ApoA-I deficiency did not alter vasodilatation of facialis arteries, but it did alter relaxation responses of pulmonary arteries. Central airway resistance was unaltered. However, airway resistance mediated by tissue dampening and elastance were increased in apoA-I−/− mice, a finding also confirmed by positive end-expiratory pressure (PEEP) studies. Inflammatory cells, collagen deposition, 3-nitrotyrosine, and 4-hydroxy-2-nonenal were increased in apoA-I−/− lungs but not oxidized phospholipids. Colocalization of 4-hydroxy-2-nonenal with transforming growth factor β-1 (TGFβ-1 was increased in apoA-I−/− lungs. Xanthine oxidase, myeloperoxidase and endothelial nitric oxide synthase were increased in apoA-I−/− lungs. Dichlorodihydrofluorescein-detectable oxidants were increased in bronchoalveolar lavage fluid (BALF) in apoA-I−/− mice. In contrast, BALF nitrite+nitrate levels were decreased in apoA-I−/− mice. These data demonstrate that apoA-I plays important roles in limiting pulmonary inflammation and oxidative stress, which if not prevented, will decrease pulmonary artery vasodilatation and increase airway hyperresponsiveness. PMID:20498409

Interfacial Properties of High-Density Lipoprotein-like Lipid Droplets with Different Lipid and Apolipoprotein A-I Compositions

PubMed Central

Koivuniemi, Artturi; Sysi-Aho, Marko; Orešič, Matej; Ollila, Samuli

2013-01-01

The surface properties of high-density lipoproteins (HDLs) are important because different enzymes bind and carry out their functions at the surface of HDL particles during metabolic processes. However, the surface properties of HDL and other lipoproteins are poorly known because they cannot be directly measured for nanoscale particles with contemporary experimental methods. In this work, we carried out coarse-grained molecular dynamics simulations to study the concentration of core lipids in the surface monolayer and the interfacial tension of droplets resembling HDL particles. We simulated lipid droplets composed of different amounts of phospholipids, cholesterol esters (CEs), triglycerides (TGs), and apolipoprotein A-Is. Our results reveal that the amount of TGs in the vicinity of water molecules in the phospholipid monolayer is 25–50% higher compared to the amount of CEs in a lipid droplet with a mixed core of an equal amount of TG and CE. In addition, the correlation time for the exchange of molecules between the core and the monolayer is significantly longer for TGs compared to CEs. This suggests that the chemical potential of TG is lower in the vicinity of aqueous phase but the free-energy barrier for the translocation between the monolayer and the core is higher compared to CEs. From the point of view of enzymatic modification, this indicates that TG molecules are more accessible from the aqueous phase. Further, our results point out that CE molecules decrease the interfacial tension of HDL-like lipid droplets whereas TG keeps it constant while the amount of phospholipids varies. PMID:23708359

Zebrafish as a model for apolipoprotein biology: comprehensive expression analysis and a role for ApoA-IV in regulating food intake.

PubMed

Otis, Jessica P; Zeituni, Erin M; Thierer, James H; Anderson, Jennifer L; Brown, Alexandria C; Boehm, Erica D; Cerchione, Derek M; Ceasrine, Alexis M; Avraham-Davidi, Inbal; Tempelhof, Hanoch; Yaniv, Karina; Farber, Steven A

2015-03-01

Improved understanding of lipoproteins, particles that transport lipids throughout the circulation, is vital to developing new treatments for the dyslipidemias associated with metabolic syndrome. Apolipoproteins are a key component of lipoproteins. Apolipoproteins are proteins that structure lipoproteins and regulate lipid metabolism through control of cellular lipid exchange. Constraints of cell culture and mouse models mean that there is a need for a complementary model that can replicate the complex in vivo milieu that regulates apolipoprotein and lipoprotein biology. Here, we further establish the utility of the genetically tractable and optically clear larval zebrafish as a model of apolipoprotein biology. Gene ancestry analyses were implemented to determine the closest human orthologs of the zebrafish apolipoprotein A-I (apoA-I), apoB, apoE and apoA-IV genes and therefore ensure that they have been correctly named. Their expression patterns throughout development were also analyzed, by whole-mount mRNA in situ hybridization (ISH). The ISH results emphasized the importance of apolipoproteins in transporting yolk and dietary lipids: mRNA expression of all apolipoproteins was observed in the yolk syncytial layer, and intestinal and liver expression was observed from 4-6 days post-fertilization (dpf). Furthermore, real-time PCR confirmed that transcription of three of the four zebrafish apoA-IV genes was increased 4 hours after the onset of a 1-hour high-fat feed. Therefore, we tested the hypothesis that zebrafish ApoA-IV performs a conserved role to that in rat in the regulation of food intake by transiently overexpressing ApoA-IVb.1 in transgenic larvae and quantifying ingestion of co-fed fluorescently labeled fatty acid during a high-fat meal as an indicator of food intake. Indeed, ApoA-IVb.1 overexpression decreased food intake by approximately one-third. This study comprehensively describes the expression and function of eleven zebrafish apolipoproteins and

Effect of Royal Jelly Intake on Serum Glucose, Apolipoprotein A-I (ApoA-I), Apolipoprotein B (ApoB) and ApoB/ApoA-I Ratios in Patients with Type 2 Diabetes: A Randomized, Double-Blind Clinical Trial Study.

PubMed

Khoshpey, Basemeh; Djazayeri, Shima; Amiri, Fatemehsadat; Malek, Mojtaba; Hosseini, Agha Fateme; Hosseini, Sharieh; Shidfar, Shahrzad; Shidfar, Farzad

2016-08-01

Type 2 diabetes is the most common metabolic disorder worldwide. Evidence supports a role for royal jelly (RJ) in reduction of serum glucose and lipids in animals and healthy subjects. The purpose of this study was to determine the effect of RJ intake on serum glucose, apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB) and ApoB/ApoA-I ratios in patients with type 2 diabetes. Fifty patients with type 2 diabetes participated in a double-blind, placebo-controlled study. The participants were randomly divided into RJ and placebo groups and were given doses of 1000 mg royal jelly or placebo 3 times a day for 8 weeks, respectively. Weight, height, fasting blood glucose, ApoA-I and ApoB were measured at baseline and endpoint. There were no significant differences in baseline characteristics and dietary intakes between groups. The mean difference in glucose concentrations decreased in the RJ group (-9.4 mg/dL vs. 4 mg/dL; p=0.011). The mean difference in ApoA-I concentrations increased in the RJ group (34.4 mg/dL vs. -1.08 mg/dL; p=0.013). There was a significant decrease in mean difference of ApoB/ApoA-I in the RJ group compared with the placebo group (0.008 vs. 0.13; p<0.044), respectively. These data suggest that RJ intake may have desirable effects on serum glucose, Apo-A-I concentrations and ApoB/ApoA-I ratios in people with type 2 diabetes. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Rosuvastatin does not affect human apolipoprotein A-I expression in genetically modified mice: a clue to the disputed effect of statins on HDL.

PubMed

Marchesi, Marta; Parolini, Cinzia; Caligari, Silvia; Gilio, Donatella; Manzini, Stefano; Busnelli, Marco; Cinquanta, Paola; Camera, Marina; Brambilla, Marta; Sirtori, Cesare R; Chiesa, Giulia

2011-11-01

Besides a significant reduction of low-density lipoprotein (LDL) cholesterol, statins moderately increase high-density lipoprotein (HDL) levels. In vitro studies have indicated that this effect may be the result of an increased expression of apolipoprotein (apo)A-I, the main protein component of HDL. The aim of the present study was to investigate in vivo the effect of rosuvastatin on apoA-I expression and secretion in a transgenic mouse model for human apoA-I. Human apoA-I transgenic mice were treated for 28 days with 5, 10 or 20 mg·kg(-1) ·day(-1) of rosuvastatin, the most effective statin in raising HDL levels. Possible changes of apoA-I expression by treatment were investigated by quantitative real-time RT-PCR on RNA extracted from mouse livers. The human apoA-I secretion rate was determined in primary hepatocytes isolated from transgenic mice from each group after treatment. Rosuvastatin treatment with 5 and 10 mg·kg(-1) ·day(-1) did not affect apoA-I plasma levels, whereas a significant decrease was observed in mice treated with 20 mg·kg(-1) ·day(-1) of rosuvastatin (-16%, P < 0.01). Neither relative hepatic mRNA concentrations of apoA-I nor apoA-I secretion rates from primary hepatocytes were influenced by rosuvastatin treatment at each tested dose. In human apoA-I transgenic mice, rosuvastatin treatment does not increase either apoA-I transcription and hepatic secretion, or apoA-I plasma levels. These results support the hypothesis that other mechanisms may account for the observed HDL increase induced by statin therapy in humans. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

The “Beta-Clasp” model of apolipoprotein A-I - a lipid-free solution structure determined by electron paramagnetic resonance spectroscopy

PubMed Central

Lagerstedt, Jens O.; Budamagunta, Madhu S.; Liu, Grace S.; DeValle, Nicole C.; Voss, John C.; Oda, Michael N.

2012-01-01

Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and plays a central role in cholesterol metabolism. The lipid-free / lipid-poor form of apoA-I is the preferred substrate for the ATP-binding cassette transporter A1 (ABCA1). The interaction of apoA-I with ABCA1 leads to the formation of cholesterol laden high density lipoprotein (HDL) particles, a key step in reverse cholesterol transport and the maintenance of cholesterol homeostasis. Knowledge of the structure of lipid-free apoA-I is essential to understanding its critical interaction with ABCA1 and the molecular mechanisms underlying HDL biogenesis. We therefore examined the structure of lipid-free apoA-I by electron paramagnetic resonance spectroscopy (EPR). Through site directed spin label EPR, we mapped the secondary structure of apoA-I and identified sites of spin coupling as residues 26, 44, 64, 167, 217 and 226. We capitalize on the fact that lipid-free apoA-I self-associates in an anti-parallel manner in solution. We employed these sites of spin coupling to define the central plane in the dimeric apoA-I complex. Applying both the constraints of dipolar coupling with the EPR-derived pattern of solvent accessibility, we assembled the secondary structure into a tertiary context, providing a solution structure for lipid-free apoA-I. PMID:22245143

CRISPR/Cas9-Mediated Gene Editing in Human iPSC-Derived Macrophage Reveals Lysosomal Acid Lipase Function in Human Macrophages-Brief Report.

PubMed

Zhang, Hanrui; Shi, Jianting; Hachet, Melanie A; Xue, Chenyi; Bauer, Robert C; Jiang, Hongfeng; Li, Wenjun; Tohyama, Junichiro; Millar, John; Billheimer, Jeffrey; Phillips, Michael C; Razani, Babak; Rader, Daniel J; Reilly, Muredach P

2017-11-01

To gain mechanistic insights into the role of LIPA (lipase A), the gene encoding LAL (lysosomal acid lipase) protein, in human macrophages. We used CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) technology to knock out LIPA in human induced pluripotent stem cells and then differentiate to macrophage (human-induced pluripotent stem cells-derived macrophage [IPSDM]) to explore the human macrophage LIPA loss-of-function phenotypes. LIPA was abundantly expressed in monocyte-derived macrophages and was markedly induced on IPSDM differentiation to comparable levels as in human monocyte-derived macrophage. IPSDM with knockout of LIPA ( LIPA -/- ) had barely detectable LAL enzymatic activity. Control and LIPA -/- IPSDM were loaded with [ 3 H]-cholesteryl oleate-labeled AcLDL (acetylated low-density lipoprotein) followed by efflux to apolipoprotein A-I. Efflux of liberated [ 3 H]-cholesterol to apolipoprotein A-I was abolished in LIPA -/- IPSDM, indicating deficiency in LAL-mediated lysosomal cholesteryl ester hydrolysis. In cells loaded with [ 3 H]-cholesterol-labeled AcLDL, [ 3 H]-cholesterol efflux was, however, not different between control and LIPA -/- IPSDM. ABCA1 (ATP-binding cassette, subfamily A, member 1) expression was upregulated by AcLDL loading but to a similar extent between control and LIPA -/- IPSDM. In nonlipid loaded state, LIPA -/- IPSDM had high levels of cholesteryl ester mass compared with minute amounts in control IPSDM. Yet, with AcLDL loading, overall cholesteryl ester mass was increased to similar levels in both control and LIPA -/- IPSDM. LIPA -/- did not impact lysosomal apolipoprotein-B degradation or expression of IL1B , IL6 , and CCL5. CONCLUSIONS: LIPA -/- IPSDM reveals macrophage-specific hallmarks of LIPA deficiency. CRISPR/Cas9 and IPSDM provide important tools to study human macrophage biology and more broadly for future studies of disease-associated LIPA genetic variation in human

A simple approach for human recombinant apolipoprotein E4 expression and purification.

PubMed

Argyri, Letta; Skamnaki, Vassiliki; Stratikos, Efstratios; Chroni, Angeliki

2011-10-01

We report a simple expression and purification procedure for the production of recombinant apolipoprotein E4 (apoE4), an important protein for the lipid homeostasis in humans that plays critical roles in the pathogenesis of cardiovascular and neurodegenerative diseases. Our approach is based on the expression of a thioredoxin-apoE4 fusion construct in bacterial cells and subsequent removal of the fused thioredoxin using the highly specific 3C protease, avoiding costly and laborious lipidation-delipidation steps used before. Our approach results in rapid, high-yield production of structurally and functionally competent apoE4 as evidenced by secondary structure measurements, thermal and chemical melting profiles and the kinetic profile of solubilization of dimyristoyl-phosphatidylcholine (DMPC) vesicles. This protocol is appropriate for laboratories with little experience in apolipoprotein biochemistry and will facilitate future studies on the role of apoE4 in the pathogenesis of cardiovascular disease and neurodegenerative diseases, including Alzheimer's disease. Copyright © 2011 Elsevier Inc. All rights reserved.

Tyrosine 192 in apolipoprotein A-I is the major site of nitration and chlorination by myeloperoxidase, but only chlorination markedly impairs ABCA1-dependent cholesterol transport.

PubMed

Shao, Baohai; Bergt, Constanze; Fu, Xiaoyun; Green, Pattie; Voss, John C; Oda, Michael N; Oram, John F; Heinecke, Jay W

2005-02-18

High density lipoprotein (HDL) isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of 3-nitrotyrosine and 3-chlorotyrosine. Myeloperoxidase (MPO) is the only known source of 3-chlorotyrosine in humans, indicating that MPO oxidizes HDL in vivo. In the current studies, we used tandem mass spectrometry to identify the major sites of tyrosine oxidation when lipid-free apolipoprotein A-I (apoA-I), the major protein of HDL, was exposed to MPO or peroxynitrite (ONOO(-)). Tyrosine 192 was the predominant site of both nitration and chlorination by MPO and was also the major site of nitration by ONOO(-). Electron paramagnetic spin resonance studies of spin-labeled apoA-I revealed that residue 192 was located in an unusually hydrophilic environment. Moreover, the environment of residue 192 became much more hydrophobic when apoA-I was incorporated into discoidal HDL, and Tyr(192) of HDL-associated apoA-I was a poor substrate for nitration by both myeloperoxidase and ONOO(-), suggesting that solvent accessibility accounted in part for the reactivity of Tyr(192). The ability of lipid-free apoA-I to facilitate ATP-binding cassette transporter A1 cholesterol transport was greatly reduced after chlorination by MPO. Loss of activity occurred in concert with chlorination of Tyr(192). Both ONOO(-) and MPO nitrated Tyr(192) in high yield, but unlike chlorination, nitration minimally affected the ability of apoA-I to promote cholesterol efflux from cells. Our results indicate that Tyr(192) is the predominant site of nitration and chlorination when MPO or ONOO(-) oxidizes lipid-free apoA-I but that only chlorination markedly reduces the cholesterol efflux activity of apoA-I. This impaired biological activity of chlorinated apoA-I suggests that MPO-mediated oxidation of HDL might contribute to the link between inflammation and cardiovascular disease.

Effect of acute feeding of diets of varying fatty acid composition on intestinal apolipoprotein expression in the newborn swine.

PubMed

Wang, H; Zhan, R; Hunter, F; Du, J; Black, D

1996-06-01

The purpose of this study was to determine the effects of dietary fatty acids of varying chain lengths and degrees of saturation on intestinal apolipoprotein (apo) B and A-I expression in the newborn piglet. Two-day-old female piglets received one of three isocaloric formulas containing 48% of total calories (120 kcal/kg/24 h) as medium-chain triglycerides (MCT) from MCT oil, intermediate-chain saturated triglycerides (ICST) from coconut oil, or long-chain polyunsaturated triglycerides (LCPUT) from safflower oil by continuous duodenal infusion for 24 h. After in situ radiolabeling, jejunal and ileal mucosal apo B-48 and A-I were immunoprecipitated, and synthesis was expressed as percentage of total protein synthesis. Mucosal apo B and A-I mass was measured by ELISA as nanograms of apoprotein/microgram of total protein. Fifty percent less apo B jejunal synthesis was present in the ICST group versus the MCT and LCPUT groups (0.67 +/- 0.07, 1.19 +/- 0.20, and 1.25 +/- 0.15, respectively, mean +/- SEM, p < 0.05). Jejunal apo B mass was lower in the MCT group versus the ICST and LCPUT groups (0.10 +/- 0.02, 0.21 +/- 0.03, and 0.16 +/- 0.03, respectively, p < 0.05). Ileal apo B synthesis was lowest in the ICST group. No differences were found in ileal apo B mass. Two-fold higher jejunal apo A-I synthesis was found in the LCPUT group versus the MCT and ICST groups (14.18 +/- 1.69, 7.56 +/- 2.63, and 6.36 +/- 0.58, respectively, p < 0.01). No differences were found for jejunal apo A-I mass. In the ileum, the only difference was a higher apo A-I mass in the LCPUT group (p < 0.05). We conclude that in the newborn piglet intestinal apo B and A-I expression is acutely and differentially regulated by dietary lipid varying in fatty acid chain length and saturation. The patterns of regulation are complex and vary among specific apolipoproteins and regions of the small intestine and include co- and posttranslational mechanisms.

Human Frontal Lobes and AI Planning Systems

NASA Technical Reports Server (NTRS)

Levinson, Richard; Lum, Henry Jr. (Technical Monitor)

1994-01-01

Human frontal lobes are essential for maintaining a self-regulating balance between predictive and reactive behavior. This paper describes a system that integrates prediction and reaction based on neuropsychological theories of frontal lobe function. In addition to enhancing our understanding of deliberate action in humans' the model is being used to develop and evaluate the same properties in machines. First, the paper presents some background neuropsychology in order to set a general context. The role of frontal lobes is then presented by summarizing three theories which formed the basis for this work. The components of an artificial frontal lobe are then discussed from both neuropsychological and AI perspectives. The paper concludes by discussing issues and methods for evaluating systems that integrate planning and reaction.

Apolipoprotein AI tertiary structures determine stability and phospholipid-binding activity of discoidal high-density lipoprotein particles of different sizes

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

Chen, Bin; Ren, Xuefeng; Neville, Tracey

2009-05-18

Human high-density lipoprotein (HDL) plays a key role in the reverse cholesterol transport pathway that delivers excess cholesterol back to the liver for clearance. In vivo, HDL particles vary in size, shape and biological function. The discoidal HDL is a 140-240 kDa, disk-shaped intermediate of mature HDL. During mature spherical HDL formation, discoidal HDLs play a key role in loading cholesterol ester onto the HDL particles by activating the enzyme, lecithin:cholesterol acyltransferase (LCAT). One of the major problems for high-resolution structural studies of discoidal HDL is the difficulty in obtaining pure and, foremost, homogenous sample. We demonstrate here that themore » commonly used cholate dialysis method for discoidal HDL preparation usually contains 5-10% lipid-poor apoAI that significantly interferes with the high-resolution structural analysis of discoidal HDL using biophysical methods. Using an ultracentrifugation method, we quickly removed lipid-poor apoAI. We also purified discoidal reconstituted HDL (rHDL) into two pure discoidal HDL species of different sizes that are amendable for high-resolution structural studies. A small rHDL has a diameter of 7.6 nm, and a large rHDL has a diameter of 9.8 nm. We show that these two different sizes of discoidal HDL particles display different stability and phospholipid-binding activity. Interestingly, these property/functional differences are independent from the apoAI -helical secondary structure, but are determined by the tertiary structural difference of apoAI on different discoidal rHDL particles, as evidenced by two-dimensional NMR and negative stain electron microscopy data. Our result further provides the first high-resolution NMR data, demonstrating a promise of structural determination of discoidal HDL at atomic resolution using a combination of NMR and other biophysical techniques.« less

Reduced biliary sterol output with no change in total faecal excretion in mice expressing a human apolipoprotein A-I variant.

PubMed

Parolini, Cinzia; Caligari, Silvia; Gilio, Donatella; Manzini, Stefano; Busnelli, Marco; Montagnani, Marco; Locatelli, Marcello; Diani, Erika; Giavarini, Flavio; Caruso, Donatella; Roda, Enrico; Roda, Aldo; Sirtori, Cesare R; Chiesa, Giulia

2012-10-01

Apolipoprotein (apo)A-I(M) (ilano), is a molecular variant of apoA-I(wild-type), associated with dramatically low HDL-cholesterol levels, but no increased risk for cardiovascular disease. In view of the present uncertainties on the role of apoA-I in liver cholesterol removal by way of bile acids and neutral sterols, and of the greater capacity of apoA-I(M) (ilano) to remove arterial cholesterol, biliary sterol metabolism was evaluated in transgenic mice expressing apoA-I(M) (ilano). ApoA-I(M) (ilano) mice were fed a high-cholesterol/high-fat diet, and compared with human apoA-I(wild-type) mice. Plasma lipid levels, hepatic bile flow and composition, hepatic and intestinal cholesterol and bile acid content, and faecal sterol content were measured. Moreover, the expression of hepatic ABCA1, SR-B1 and that of hepatic and intestinal genes involved in bile acid metabolism were evaluated. The dietary treatment led to a strong elevation in HDL-cholesterol levels in A-I(M) (ilano) mice, associated with an increased expression of hepatic ABCA1. ApoA-I(M) (ilano) mice showed lower cholesterol output from the liver compared with apoA-I(wild-type) mice, in the absence of liver sterol accumulation. Faecal excretion of neutral sterols and bile acids was similar in the two mouse lines. In spite of a different response to the dietary challenge, with an increased ABCA1 expression and a lower hepatic cholesterol output in apoA-I(M) (ilano) mice, the net sterol excretion is comparable in the two transgenic lines. © 2012 John Wiley & Sons A/S.

Development of a new bioactivatable fluorescent probe for quantification of apolipoprotein A-I proteolytic degradation in vitro and in vivo.

PubMed

Maafi, Foued; Li, Baoqiang; Gebhard, Catherine; Brodeur, Mathieu R; Nachar, Walid; Villeneuve, Louis; Lesage, Frédéric; Rhainds, David; Rhéaume, Eric; Tardif, Jean-Claude

2017-03-01

The potential benefits of high-density lipoproteins (HDL) against atherosclerosis are attributed to its major protein component, apolipoprotein A-I (apoA-I). Most of the apoA-I in the vascular wall appears to be in its lipid-poor form. The latter, however, is subjected to degradation by proteases localized in atherosclerotic plaques, which, in turn, has been shown to negatively impact its atheroprotective functions. Here, we report the development and in vivo use of a bioactivatable near-infrared full-length apoA-I-Cy5.5 fluorescent probe for the assessment of apoA-I-degrading proteolytic activities. Fluorescence quenching was obtained by saturation of Cy5.5 fluorophore molecules on apoA-I protein. ApoA-I cleavage led to near-infrared fluorescence enhancement. In vitro proteolysis of the apoA-I probe by a variety of proteases including serine, cysteine, and metalloproteases resulted in an up to 11-fold increase in fluorescence (n = 5, p ≤ 0.05). We detected activation of the probe in atherosclerotic mice aorta sections using in situ zymography and showed that broad-spectrum protease inhibitors protected the probe from degradation, resulting in decreased fluorescence (-54%, n = 6 per group, p ≤ 0.0001). In vivo, the injected probe showed stronger fluorescence emission in the aorta of human apoB transgenic Ldlr - /- atherosclerotic mice (ATX) as compared to wild-type mice. In vivo observations were confirmed by ex vivo aorta imaging quantification where a 10-fold increase in fluorescent signal in ATX mice (p ≤ 0.05 vs. control mice) was observed. The use of this probe in different applications may help to assess new molecular mechanisms of atherosclerosis and may improve current HDL-based therapies by enhancing apoA-I functionality. Copyright © 2017 Elsevier B.V. All rights reserved.

An experimental study on amelioration of dyslipidemia-induced atherosclesis by Clematichinenoside through regulating Peroxisome proliferator-activated receptor-α mediated apolipoprotein A-I, A-II and C-III.

PubMed

Liu, Chao; Guo, Qianqian; Lu, Mengchen; Li, Yunman

2015-08-15

Prevention or amelioration the prevalence of atherosclerosis has been an effective strategy in the management of cardiovascular diseases. The aim of the study was to scrutinize the effect of Clematichinenoside (AR) on dyslipidemia-induced atherosclerosis and explore its capability on expression of Peroxisome proliferator-activated receptor-α (PPAR-alpha), apolipoprotein A-I (APOA1) and A-II (APOA2), and suppression of apolipoprotein C-III (APOC3) genes and proteins. In the present study, we investigated atherosclerosis effect of AR using a combination of high-fat diet and balloon injury model in rabbits. The levels of biochemical indicators were evaluated in plasma, liver and HepG2 cells using immunoassay technology. In order to expose the underlying mechanism, we evaluated the regulation of PPAR-alpha, APOA1, APOA2 and APOC3 expressions by AR, and we further evaluated the interactions between them after transfection with shRNA (shPPAR-alpha) and, the action of PPAR-alpha in HepG2 cells. We could find that AR markedly promoted the PPAR-alpha transfer from cytoplasm to nucleus which resulted in the alteration of APOA1, APOA2 and APOC3 expressions in HepG2 cells. Moreover, AR significantly reduced total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) levels, and elevated high-density lipoprotein cholesterol (HDL-C) level, which play an important role in dyslipidemia-induced atherosclerosis. In conclusion, AR ameliorated atherosclerosis via the regulation of hepatic lipid metabolism, and AR also contributed to the activation of PPAR-alpha, APOA1, APOA2 and APOC3. Therefore, AR could be a potential therapeutic agent in the treatment of atherosclerosis. Copyright © 2015 Elsevier B.V. All rights reserved.

A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

PubMed Central

Sakurai, Toshihiro; Sakurai-Ikuta, Akiko; Sviridov, Denis; Freeman, Lita; Ahsan, Lusana; Remaley, Alan T.

2015-01-01

Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux and their other beneficial antiatherogenic properties. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) for binding to lipoproteins and stimulating cholesterol efflux as well as a motif based on the last helix of apolipoprotein C-II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to be comparable to the full-length apoC-II protein in activating lipolysis by LPL. When added to serum from a patient with apoC-II deficiency, it restored normal levels of LPL-induced lipolysis and also enhanced lipolysis in serum from patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a (30 mg/kg) in apolipoprotein E–knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides of 38 ± 6% and 85 ± 7%, respectively, at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to completely block the hypertriglyceridemic effect of the 5A peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II, which promotes cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II deficiency and other forms of hypertriglyceridemia. PMID:25395590

Antisense apolipoprotein B therapy: where do we stand?

PubMed

Akdim, Fatima; Stroes, Erik S G; Kastelein, John J P

2007-08-01

Antisense oligonucleotides are novel therapeutic agents that reduce the number of specific mRNAs available for translation of the encoded protein. ISIS 301012 is an antisense oligonucleotide developed to reduce the hepatic synthesis of apolipoprotein B-100. Apolipoprotein B-100 is made in the liver, and antisense oligonucleotides preferentially distribute to that organ, so antisense apolipoprotein B-100 may have potential as an efficacious lipid-lowering agent. Recently, in healthy volunteers and in mild dyslipidaemic patients, this strategy as monotherapy or in conjunction with statins has shown unparalleled efficacy in reducing apolipoprotein B-100 and LDL-cholesterol. Tolerance for this novel therapy is encouraging and safety concerns currently only relate to mild injection-site reactions and rare liver-function test abnormalities. It should be noted, however, that these safety results were obtained in relatively few individuals. ISIS 301012 has initially shown promising results in experimental animal models, and in clinical trials in humans. Besides the effect of reducing apolipoprotein B-100 and LDL-cholesterol, this compound also significantly lowers plasma triglycerides. Safety concerns related to the drug include increased liver-function tests. To date no evidence of hepatic steatosis has been reported. Nonetheless, clinical trials of longer duration are required to demonstrate further safety.

High-density lipoprotein apolipoproteins in urine: I. Characterization in normal subjects and in patients with proteinuria.

PubMed

Gomo, Z A; Henderson, L O; Myrick, J E

1988-09-01

A high-resolution two-dimensional electrophoretic method for protein, with silver staining, has been used to characterize and identify urinary high-density-lipoprotein apolipoproteins (HDL-Apos) and their isoforms in healthy subjects and in patients with kidney disease. Analytical techniques based on both molecular mass and ultracentrifugal flotation properties were used to isolate urinary lipoprotein particles with characteristics identical to those of HDL in plasma. HDL-Apos identified in urine of normal subjects and patients with glomerular proteinuria were Apos A-I, A-II, and C. Five isoforms of Apo A-I were present. Immunostaining of electroblotted proteins further confirmed the presence of HDL-Apos in urine. Creatinine clearance rate was decreased in the patients with proteinuria, and ranged from 32.5 to 40 mL/min. Concentrations of cholesterol and triglycerides in serum were greater in the patients' group, whereas mean HDL-cholesterol (0.68, SD 0.10 mmol/L) and Apo A-I (0.953, SD 0.095 g/L) were significantly (each P less than 0.01) lower. Results of this study suggest that measurement of urinary Apo A-I will reflect excretion of HDL in urine.

Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction

PubMed Central

ASAHINA, Makoto; SHIMIZU, Fumi; OHTA, Masayuki; TAKEYAMA, Michiyasu; TOZAWA, Ryuichi

2015-01-01

Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome. PMID:25912321

Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction.

PubMed

Asahina, Makoto; Shimizu, Fumi; Ohta, Masayuki; Takeyama, Michiyasu; Tozawa, Ryuichi

2015-01-01

Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome.

Effect of Apolipoprotein E Genotype and Diet on Apolipoprotein E Lipidation and Amyloid Peptides

PubMed Central

Hanson, Angela J.; Bayer-Carter, Jennifer L.; Green, Pattie S.; Montine, Thomas J.; Wilkinson, Charles W.; Baker, Laura D.; Watson, G. Stennis; Bonner, Laura M.; Callaghan, Maureen; Leverenz, James B.; Tsai, Elaine; Postupna, Nadia; Zhang, Jing; Lampe, Johanna; Craft, Suzanne

2013-01-01

Importance Sporadic Alzheimer disease (AD) is caused in part by decreased clearance of the β-amyloid (Aβ) peptide breakdown products. Lipid-depleted (LD) apolipoproteins are less effective at binding and clearing Aβ, and LD Aβ peptides are more toxic to neurons. However, not much is known about the lipid states of these proteins in human cerebrospinal fluid. Objective To characterize the lipidation states of Aβ peptides and apolipoprotein E in the cerebrospinal fluid in adults with respect to cognitive diagnosis and APOE ε4 allele carrier status and after a dietary intervention. Design Randomized clinical trial. Setting Veterans Affairs Medical Center clinical research unit. Participants Twenty older adults with normal cognition (mean [SD] age, 69 [7] years) and 27 with amnestic mild cognitive impairment (67 [6] years). Interventions Randomization to a diet high in saturated fat content and with a high glycemic index (High diet;45% of energy from fat [>25% saturated fat], 35%-40%fromcarbohydrates with a mean glycemic index >70, and15%-20% from protein) or a diet low in saturated fat content and with a low glycemic index (Low diet; 25% of energy from fat [<7% saturated fat], 55%-60% from carbohydrates with a mean glycemic index <55, and 15%-20% from protein). Main Outcomes and Measures Lipid-depleted Aβ42 and Aβ40 and apolipoprotein E in cerebrospinal fluid. Results Baseline levels of LD Aβ were greater for adults with mild cognitive impairment compared with adults with normal cognition (LD Aβ42, P=.05; LD Aβ40, P=.01).These findings were magnified in adults with mild cognitive impairment and the ε4 allele, who had higher LD apolipoprotein E levels irrespective of cognitive diagnosis (P<.001). The Low diet tended to decrease LD Aβ levels, whereas the High diet increased these fractions (LD Aβ42, P=.01; LD Aβ40, P=.15). Changes in LD Aβ levels with the Low diet negatively correlated with changes in cerebrospinal fluid levels of insulin (LD Aβ42 and

Composition, structure and substrate properties of reconstituted discoidal HDL with apolipoprotein A-I and cholesteryl ester

NASA Astrophysics Data System (ADS)

Dergunov, Alexander D.; Shabrova, Elena V.; Dobretsov, Gennady E.

2010-03-01

To investigate the influence of lipid unsaturation and neutral lipid on the maturation of high density lipoproteins, the discoidal complexes of apoA-I, phosphatidylcholine and cholesteryl ester (CE) were prepared. Saturated dipalmitoylphosphatidylcholine (DPPC) and unsaturated palmitoyllinoleoylphosphatidylcholine (PLPC), palmitoyloleoylphosphatidylcholine (POPC), and fluorescent probe cholesteryl 1-pyrenedecanoate (CPD) that forms in a diffusion- and concentration-dependent manner short-lived dimer of unexcited and excited molecules (excimer) were used. The apoA-I/DPPC/CPD complexes were heterogeneous by size, composition and probe location. CPD molecules incorporated more efficiently into larger complexes and accumulated in a central part of the discs. The apoA-I/POPC(PLPC)/CPD were also heterogeneous, however, probe molecules distributed preferentially into smaller complexes and accumulated at disc periphery. The kinetics of CPD transfer by recombinant cholesteryl ester transfer protein (CETP) to human plasma LDL is well described by two-exponential decay, the fast component with a shorter transfer time being more populated in PLPC compared to DPPC complexes. The presence of CE molecules in discoidal HDL results in particle heterogeneity. ApoA-I influences the CETP activity modulating the properties of apolipoprotein-phospholipid interface. This may include CE molecules accumulation in the boundary lipid in unsaturated phosphatidylcholine and cluster formation in the bulk bilayer in saturated phosphatidylcholine.

D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

PubMed Central

Valleix, Sophie; Verona, Guglielmo; Jourde-Chiche, Noémie; Nédelec, Brigitte; Mangione, P. Patrizia; Bridoux, Frank; Mangé, Alain; Dogan, Ahmet; Goujon, Jean-Michel; Lhomme, Marie; Dauteuille, Carolane; Chabert, Michèle; Porcari, Riccardo; Waudby, Christopher A.; Relini, Annalisa; Talmud, Philippa J.; Kovrov, Oleg; Olivecrona, Gunilla; Stoppini, Monica; Christodoulou, John; Hawkins, Philip N.; Grateau, Gilles; Delpech, Marc; Kontush, Anatol; Gillmore, Julian D.; Kalopissis, Athina D.; Bellotti, Vittorio

2016-01-01

Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients. PMID:26790392

Contributions of the N- and C-terminal helical segments to the lipid-free structure and lipid interaction of apolipoprotein A-I.

PubMed

Tanaka, Masafumi; Dhanasekaran, Padmaja; Nguyen, David; Ohta, Shinya; Lund-Katz, Sissel; Phillips, Michael C; Saito, Hiroyuki

2006-08-29

The tertiary structure of lipid-free apolipoprotein (apo) A-I in the monomeric state comprises two domains: a N-terminal alpha-helix bundle and a less organized C-terminal domain. This study examined how the N- and C-terminal segments of apoA-I (residues 1-43 and 223-243), which contain the most hydrophobic regions in the molecule and are located in opposite structural domains, contribute to the lipid-free conformation and lipid interaction. Measurements of circular dichroism in conjunction with tryptophan and 8-anilino-1-naphthalenesulfonic acid fluorescence data demonstrated that single (L230P) or triple (L230P/L233P/Y236P) proline insertions into the C-terminal alpha helix disrupted the organization of the C-terminal domain without affecting the stability of the N-terminal helix bundle. In contrast, proline insertion into the N terminus (Y18P) disrupted the bundle structure in the N-terminal domain, indicating that the alpha-helical segment in this region is part of the helix bundle. Calorimetric and gel-filtration measurements showed that disruption of the C-terminal alpha helix significantly reduced the enthalpy and free energy of binding of apoA-I to lipids, whereas disruption of the N-terminal alpha helix had only a small effect on lipid binding. Significantly, the presence of the Y18P mutation offset the negative effects of disruption/removal of the C-terminal helical domain on lipid binding, suggesting that the alpha helix around Y18 concealed a potential lipid-binding region in the N-terminal domain, which was exposed by the disruption of the helix-bundle structure. When these results are taken together, they indicate that the alpha-helical segment in the N terminus of apoA-I modulates the lipid-free structure and lipid interaction in concert with the C-terminal domain.

Molecular dynamics simulations on discoidal HDL particles suggest a mechanism for rotation in the apo A-I belt model.

PubMed

Klon, Anthony E; Segrest, Jere P; Harvey, Stephen C

2002-12-06

Apolipoprotein A-I (apo A-I) is the major protein component of high-density lipoprotein (HDL) particles. Elevated levels of HDL in the bloodstream have been shown to correlate strongly with a reduced risk factor for atherosclerosis. Molecular dynamics simulations have been carried out on three separate model discoidal high-density lipoprotein particles (HDL) containing two monomers of apo A-I and 160 molecules of palmitoyloleoylphosphatidylcholine (POPC), to a time-scale of 1ns. The starting structures were on the basis of previously published molecular belt models of HDL consisting of the lipid-binding C-terminal domain (residues 44-243) wrapped around the circumference of a discoidal HDL particle. Subtle changes between two of the starting structures resulted in significantly different behavior during the course of the simulation. The results provide support for the hypothesis of Segrest et al. that helical registration in the molecular belt model of apo A-I is modulated by intermolecular salt bridges. In addition, we propose an explanation for the presence of proline punctuation in the molecular belt model, and for the presence of two 11-mer helical repeats interrupting the otherwise regular pattern of 22-mer helical repeats in the lipid-binding domain of apo A-I.

Rapamycin rescues vascular, metabolic and learning deficits in apolipoprotein E4 transgenic mice with pre-symptomatic Alzheimer's disease.

PubMed

Lin, Ai-Ling; Jahrling, Jordan B; Zhang, Wei; DeRosa, Nicholas; Bakshi, Vikas; Romero, Peter; Galvan, Veronica; Richardson, Arlan

2017-01-01

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood-brain barrier integrity and glucose metabolism, compared to age- and gender-matched wild-type controls. The preserved vasculature and metabolism were associated with amelioration of incipient learning deficits. We also found that rapamycin restored the levels of the proinflammatory cyclophilin A in vasculature, which may contribute to the preservation of cerebrovascular function in the apolipoprotein E ɛ4 transgenics. Our results show that rapamycin improves functional outcomes in this mouse model and may have potential as an effective intervention to block progression of vascular, metabolic and early cognitive deficits in human Apolipoprotein E ɛ4 carriers. As rapamycin is FDA-approved and neuroimaging is readily used in humans, the results of the present study may provide the basis for future Alzheimer's disease intervention studies in human subjects. © The Author(s) 2015.

Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

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

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

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

An Experimentally Robust Model of Monomeric Apolipoprotein A-I Created from a Chimera of Two X-ray Structures and Molecular Dynamics Simulations

PubMed Central

2015-01-01

High-density lipoprotein (HDL) retards atherosclerosis by accepting cholesterol from the artery wall. However, the structure of the proposed acceptor, monomeric apolipoprotein A-I (apoA-I), the major protein of HDL, is poorly understood. Two published models for monomeric apoA-I used cross-linking distance constraints to derive best fit conformations. This approach has limitations. (i) Cross-linked peptides provide no information about secondary structure. (ii) A protein chain can be folded in multiple ways to create a best fit. (iii) Ad hoc folding of a secondary structure is unlikely to produce a stable orientation of hydrophobic and hydrophilic residues. To address these limitations, we used a different approach. We first noted that the dimeric apoA-I crystal structure, (Δ185–243)apoA-I, is topologically identical to a monomer in which helix 5 forms a helical hairpin, a monomer with a hydrophobic cleft running the length of the molecule. We then realized that a second crystal structure, (Δ1–43)apoA-I, contains a C-terminal structure that fits snuggly via aromatic and hydrophobic interactions into the hydrophobic cleft. Consequently, we combined these crystal structures into an initial model that was subjected to molecular dynamics simulations. We tested the initial and simulated models and the two previously published models in three ways: against two published data sets (domains predicted to be helical by H/D exchange and six spin-coupled residues) and against our own experimentally determined cross-linking distance constraints. We note that the best fit simulation model, superior by all tests to previously published models, has dynamic features of a molten globule with interesting implications for the functions of apoA-I. PMID:25423138

Human Apolipoprotein A1 at Solid/Liquid and Liquid/Gas Interfaces.

PubMed

Dogan, Susanne; Paulus, Michael; Forov, Yury; Weis, Christopher; Kampmann, Matthias; Cewe, Christopher; Kiesel, Irena; Degen, Patrick; Salmen, Paul; Rehage, Heinz; Tolan, Metin

2018-04-12

An X-ray reflectivity study on the adsorption behavior of human apolipoprotein A1 (apoA1) at hydrophilic and hydrophobic interfaces is presented. It is shown that the protein interacts via electrostatic and hydrophobic interactions with the interfaces, resulting in the absorption of the protein. pH dependent measurements at the solid/liquid interface between silicon dioxide and aqueous protein solution show that in a small pH range between pH 4 and 6, adsorption is increased due to electrostatic attraction. Here, the native shape of the protein seems to be conserved. In contrast, the adsorption at the liquid/gas interface is mainly driven by hydrophobic effects, presumably by extending the hydrophobic regions of the amphipathic helices, and results in a conformational change of the protein during adsorption. However, the addition of differently charged membrane-forming lipids at the liquid/gas interface illustrates the ability of apoA1 to include lipids, resulting in a depletion of the lipids from the interface.

Human-centered automation and AI - Ideas, insights, and issues from the Intelligent Cockpit Aids research effort

NASA Technical Reports Server (NTRS)

Abbott, Kathy H.; Schutte, Paul C.

1989-01-01

A development status evaluation is presented for the NASA-Langley Intelligent Cockpit Aids research program, which encompasses AI, human/machine interfaces, and conventional automation. Attention is being given to decision-aiding concepts for human-centered automation, with emphasis on inflight subsystem fault management, inflight mission replanning, and communications management. The cockpit envisioned is for advanced commercial transport aircraft.

Direct targeting of human plasma for matrix-assisted laser desorption/ionization and analysis of plasma proteins by time of flight-mass spectrometry.

PubMed

Jin, Ya; Manabe, Takashi

2005-07-01

A method to analyze human plasma proteins without fractionation, directly applying a plasma-matrix mixture on the target plate of a matrix-assisted laser desorption/ionization-time of flight-mass spectrometer (MALDI-TOF-MS), has been described. Peaks of ionized plasma proteins could not be detected applying a mixture of an undiluted plasma sample and a matrix solution, but they appeared when the plasma was diluted before mixing with the matrix. Tenfold diluted plasma provided well-resolved protein peaks in the m/z range from 4000 to 30,000. The addition of a simple post-crystallization washing procedure performed on the target plate further improved the quality of mass spectra. We numbered 58 peaks in the range of 4-160 kDa and 32 out of which were assigned to the plasma protein species which have been reported. Especially high sensitivity and resolution were obtained in the region < 30 kDa, where multiple isoforms of apolipoprotein A-I, apolipoprotein A-II, apolipoprotein C-I, apolipoprotein C-II, apolipoprotein C-III, and transthyretin could be assigned. Various post-translational modifications are involved in the isoforms, e.g., proteolytic cleavage, glycosylation and chemical modifications. This method will become complementary with the present electrophoretic techniques, especially for the analysis of low-molecular-mass proteins.

Apolipoprotein A5: A newly identified gene impacting plasmatriglyceride levels in humans and mice

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

Pennacchio, Len A.; Rubin, Edward M.

2002-09-15

Apolipoprotein A5 (APOA5) is a newly described member of theapolipoprotein gene family whose initial discovery arose from comparativesequence analysis of the mammalian APOA1/C3/A4 gene cluster. Functionalstudies in mice indicated that alteration in the level of APOA5significantly impacted plasma triglyceride concentrations. Miceover-expressing human APOA5 displayed significantly reducedtriglycerides, while mice lacking apoA5 had a large increase in thislipid parameter. Studies in humans have also suggested an important rolefor APOA5 in determining plasma triglyceride concentrations. In theseexperiments, polymorphisms in the human gene were found to define severalcommon haplotypes that were associated with significant changes intriglyceride concentrations in multiple populations. Several separateclinical studies havemore » provided consistent and strong support for theeffect with 24 percent of Caucasians, 35 percent of African-Americans and53 percent of Hispanics carrying APOA5 haplotypes associated withincreased plasma triglyceride levels. In summary, APOA5 represents anewly discovered gene involved in triglyceride metabolism in both humansand mice whose mechanism of action remains to be deciphered.« less

Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.

PubMed

Lamon-Fava, S; Fisher, E C; Nelson, M E; Evans, W J; Millar, J S; Ordovas, J M; Schaefer, E J

1989-01-01

Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

Artificial intelligence. Fears of an AI pioneer.

PubMed

Russell, Stuart; Bohannon, John

2015-07-17

From the enraged robots in the 1920 play R.U.R. to the homicidal computer H.A.L. in 2001: A Space Odyssey, science fiction writers have embraced the dark side of artificial intelligence (AI) ever since the concept entered our collective imagination. Sluggish progress in AI research, especially during the “AI winter” of the 1970s and 1980s, made such worries seem far-fetched. But recent breakthroughs in machine learning and vast improvements in computational power have brought a flood of research funding— and fresh concerns about where AI may lead us. One researcher now speaking up is Stuart Russell, a computer scientist at the University of California, Berkeley, who with Peter Norvig, director of research at Google, wrote the premier AI textbook, Artificial Intelligence: A Modern Approach, now in its third edition. Last year, Russell joined the Centre for the Study of Existential Risk at Cambridge University in the United Kingdom as an AI expert focusing on “risks that could lead to human extinction.” Among his chief concerns, which he aired at an April meeting in Geneva, Switzerland, run by the United Nations, is the danger of putting military drones and weaponry under the full control of AI systems. This interview has been edited for clarity and brevity.

β3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2 cells, which might further promote cholesterol efflux from macrophage foam cells.

PubMed

Gao, Xia-Qing; Li, Yan-Fang; Jiang, Zhi-Li

2017-01-01

The aim of this study was to explore the effects of β 3 -adrenoceptor (β 3 -AR) activation on HepG2 cells and its influence on cholesterol efflux from macrophage foam cells. HepG2 cells were cultured and treated with the β 3 -AR agonist, BRL37344, and antagonist, SR52390A, and the expression of apolipoprotein (Apo) A-I, ApoA-II, ApoB, and β 3 -AR in the supernatants and cells was determined. The expression of peroxisome proliferator-activated receptor (PPAR) γ and PPARα in the HepG2 cells was also assessed. Next, using the RAW264.7 macrophage foam cell model, we also assessed the influence of the HepG2 cell supernatants on lipid efflux. The cholesterol content of the foam cells was also measured, and the cholesterol efflux from the macrophages was examined by determining 3 H-labeled cholesterol levels. Expression of ATP-binding cassette transporter (ABC) A1 and ABCG1 of the macrophage foam cells was also assessed. β 3 -AR activation increased ApoA-I expression in both the HepG2 cells and the supernatants; PPARγ expression was upregulated, but PPARα expression was not. Treatment with GW9662 abolished the increased expression of ApoA-I induced by the β 3 -AR agonist. The HepG2 cell supernatants decreased the lipid accumulation and increased the cholesterol efflux from the macrophage foam cells. ABCA1 expression, but not ABCG1 expression, increased in the macrophage foam cells treated with BRL37344-treated HepG2 cell supernatants. Activation of β 3 -AR in HepG2 cells upregulates ApoA-I expression, which might further promote cholesterol efflux from macrophage foam cells. PPARγ might be required for the induction of ApoA-I expression.

Apolipoprotein A-V is present in bile and its secretion increases with lipid absorption in Sprague-Dawley rats.

PubMed

Zhang, Linda S; Sato, Hirokazu; Yang, Qing; Ryan, Robert O; Wang, David Q-H; Howles, Philip N; Tso, Patrick

2015-12-01

Apolipoprotein (apo) A-V is a protein synthesized only in the liver that dramatically modulates plasma triglyceride levels. Recent studies suggest a novel role for hepatic apoA-V in regulating the absorption of dietary triglycerides, but its mode of action on the gut remains unknown. The aim of this study was to test for apoA-V in bile and to determine whether its secretion is regulated by dietary lipids. After an overnight recovery, adult male Sprague-Dawley bile fistula rats indeed secreted apoA-V into bile at a constant rate under fasting conditions. An intraduodenal bolus of intralipid (n = 12) increased the biliary secretion of apoA-V but not of other apolipoproteins, such as A-I, A-IV, B, and E. The lipid-induced increase of biliary apoA-V was abolished under conditions of poor lymphatic lipid transport, suggesting that the stimulation is regulated by the magnitude of lipids associated with chylomicrons transported into lymph. We also studied the secretion of apoA-V into bile immediately following bile duct cannulation. Biliary apoA-V increased over time (∼6-fold increase at hour 16, n = 8) but the secretions of other apolipoproteins remained constant. Replenishing luminal phosphatidylcholine and taurocholate (n = 9) only enhanced apoA-V secretion in bile, suggesting that the increase was not due to depletion of phospholipids or bile salts. This is the first study to demonstrate that apoA-V is secreted into bile, introducing a potential route of delivery of hepatic apoA-V to the gut lumen. Our study also reveals the uniqueness of apoA-V secretion into bile that is regulated by mechanisms different from other apolipoproteins. Copyright © 2015 the American Physiological Society.

Apolipoprotein A-V is present in bile and its secretion increases with lipid absorption in Sprague-Dawley rats

PubMed Central

Sato, Hirokazu; Yang, Qing; Ryan, Robert O.; Wang, David Q.-H.; Howles, Philip N.; Tso, Patrick

2015-01-01

Apolipoprotein (apo) A-V is a protein synthesized only in the liver that dramatically modulates plasma triglyceride levels. Recent studies suggest a novel role for hepatic apoA-V in regulating the absorption of dietary triglycerides, but its mode of action on the gut remains unknown. The aim of this study was to test for apoA-V in bile and to determine whether its secretion is regulated by dietary lipids. After an overnight recovery, adult male Sprague-Dawley bile fistula rats indeed secreted apoA-V into bile at a constant rate under fasting conditions. An intraduodenal bolus of intralipid (n = 12) increased the biliary secretion of apoA-V but not of other apolipoproteins, such as A-I, A-IV, B, and E. The lipid-induced increase of biliary apoA-V was abolished under conditions of poor lymphatic lipid transport, suggesting that the stimulation is regulated by the magnitude of lipids associated with chylomicrons transported into lymph. We also studied the secretion of apoA-V into bile immediately following bile duct cannulation. Biliary apoA-V increased over time (∼6-fold increase at hour 16, n = 8) but the secretions of other apolipoproteins remained constant. Replenishing luminal phosphatidylcholine and taurocholate (n = 9) only enhanced apoA-V secretion in bile, suggesting that the increase was not due to depletion of phospholipids or bile salts. This is the first study to demonstrate that apoA-V is secreted into bile, introducing a potential route of delivery of hepatic apoA-V to the gut lumen. Our study also reveals the uniqueness of apoA-V secretion into bile that is regulated by mechanisms different from other apolipoproteins. PMID:26505974

Situated, strategic, and AI-Enhanced technology introduction to healthcare.

PubMed

Bushko, Renata G

2005-01-01

We work hard on creating AI-wings for physicians to let them fly higher and faster in diagnosing patients--a task that physicians do not want to automate. What we do not work hard on is determining the ENVIRONMENT in which physicians' AI wings are supposed to function. It seems to be a job for social/business analysts that have their own separate kingdom. For the sake of all of us (potential patients!) social/business consultants and their methodologies should not be treated as a separate kingdom. The most urgent task is to achieve synergy between (1) AI/Fuzzy/Neural research, (2) Applied medical AI, (3) Social/Business research on medical institutions. We need this synergy in order to assure humanistic medical technology; technology flexible and sensitive enough to facilitate healthcare work while leaving space for human pride and creativity. In order to achieve humanistic technology, designers should consider the impact of technological breakthroughs on the organizations in which this technology will function and the nature of work of humans destined to use this technology. Situated (different for each organization), Strategic (based on an in-depth knowledge of Healthcare business), and AI-Enhanced (ended with a dynamic model) method for introducing technology to Healthcare allows identifying areas where technology can make medical work easier. Using this method before automating human work will get us closer to the ideal where there is no discontinuity between design and use of programs; where the technology matches users' needs perfectly--the world with humanistic technology and healthcare workers with AI-wings.

A novel compound inhibits rHDL assembly and blocks nascent HDL biogenesis downstream of apoAI binding to ABCA1 expressing cells

PubMed Central

Lyssenko, Nicholas N.; Brubaker, Gregory; Smith, Bradley D.; Smith, Jonathan D.

2011-01-01

Objective Nascent high-density lipoprotein (HDL) particles form from cellular lipids and extracellular lipid-free apolipoprotein AI (apoAI) in a process mediated by ATP-binding cassette transporter A1 (ABCA1). We have sought out compounds that inhibit nascent HDL biogenesis without affecting ABCA1 activity. Methods and Results Reconstituted HDL (rHDL) formation and cellular cholesterol efflux assays were used to show that two compounds that bond via hydrogen with phospholipids inhibit rHDL and nascent HDL production. In rHDL formation assays, the inhibitory effect of compound 1 (methyl 3α-acetoxy-7α,12α-di[(phenylaminocarbonyl)amino]-5β-cholan-24-oate), the more active of the two, depended on its ability to associate with phospholipids. In cell assays, compound 1 suppressed ABCA1-mediated cholesterol efflux to apoAI, the 18A peptide, and taurocholate with high specificity, without affecting ABCA1-independent cellular cholesterol efflux to HDL and endocytosis of acetylated low-density lipoprotein (AcLDL) and transferrin. Furthermore, compound 1 did not affect ABCA1 activity adversely, as ABCA1-mediated shedding of microparticles proceeded unabated and apoAI binding to ABCA1-expressing cells increased in its presence. Conclusions The inhibitory effects of compound 1 support a three-step model of nascent HDL biogenesis: plasma membrane remodeling by ABCA1, apoAI binding to ABCA1, and lipoprotein particle assembly. The compound inhibits the final step, causing accumulation of apoAI in ABCA1-expressing cells. PMID:21836073

Cell-free Co-expression of Functional Membrane Proteins and Apolipoprotein, Forming Soluble Nanolipoprotein Particles*S⃞

PubMed Central

Cappuccio, Jenny A.; Blanchette, Craig D.; Sulchek, Todd A.; Arroyo, Erin S.; Kralj, Joel M.; Hinz, Angela K.; Kuhn, Edward A.; Chromy, Brett A.; Segelke, Brent W.; Rothschild, Kenneth J.; Fletcher, Julia E.; Katzen, Federico; Peterson, Todd C.; Kudlicki, Wieslaw A.; Bench, Graham; Hoeprich, Paul D.; Coleman, Matthew A.

2008-01-01

Here we demonstrate rapid production of solubilized and functional membrane protein by simultaneous cell-free expression of an apolipoprotein and a membrane protein in the presence of lipids, leading to the self-assembly of membrane protein-containing nanolipoprotein particles (NLPs). NLPs have shown great promise as a biotechnology platform for solubilizing and characterizing membrane proteins. However, current approaches are limited because they require extensive efforts to express, purify, and solubilize the membrane protein prior to insertion into NLPs. By the simple addition of a few constituents to cell-free extracts, we can produce membrane proteins in NLPs with considerably less effort. For this approach an integral membrane protein and an apolipoprotein scaffold are encoded by two DNA plasmids introduced into cell-free extracts along with lipids. For this study reported here we used plasmids encoding the bacteriorhodopsin (bR) membrane apoprotein and scaffold protein Δ1–49 apolipoprotein A-I fragment (Δ49A1). Cell free co-expression of the proteins encoded by these plasmids, in the presence of the cofactor all-trans-retinal and dimyristoylphosphatidylcholine, resulted in production of functional bR as demonstrated by a 5-nm shift in the absorption spectra upon light adaptation and characteristic time-resolved FT infrared difference spectra for the bR → M transition. Importantly the functional bR was solubilized in discoidal bR·NLPs as determined by atomic force microscopy. A survey study of other membrane proteins co-expressed with Δ49A1 scaffold protein also showed significantly increased solubility of all of the membrane proteins, indicating that this approach may provide a general method for expressing membrane proteins enabling further studies. PMID:18603642

Role of Conserved Proline Residues in Human Apolipoprotein A-IV Structure and Function*

PubMed Central

Deng, Xiaodi; Walker, Ryan G.; Morris, Jamie; Davidson, W. Sean; Thompson, Thomas B.

2015-01-01

Apolipoprotein (apo)A-IV is a lipid emulsifying protein linked to a range of protective roles in obesity, diabetes, and cardiovascular disease. It exists in several states in plasma including lipid-bound in HDL and chylomicrons and as monomeric and dimeric lipid-free/poor forms. Our recent x-ray crystal structure of the central domain of apoA-IV shows that it adopts an elongated helical structure that dimerizes via two long reciprocating helices. A striking feature is the alignment of conserved proline residues across the dimer interface. We speculated that this plays important roles in the structure of the lipid-free protein and its ability to bind lipid. Here we show that the systematic conversion of these prolines to alanine increased the thermodynamic stability of apoA-IV and its propensity to oligomerize. Despite the structural stabilization, we noted an increase in the ability to bind and reorganize lipids and to promote cholesterol efflux from cells. The novel properties of these mutants allowed us to isolate the first trimeric form of an exchangeable apolipoprotein and characterize it by small-angle x-ray scattering and chemical cross-linking. The results suggest that the reciprocating helix interaction is a common feature of all apoA-IV oligomers. We propose a model of how self-association of apoA-IV can result in spherical lipoprotein particles, a model that may have broader applications to other exchangeable apolipoprotein family members. PMID:25733664

Apolipoprotein B variant derived from rat intestine.

PubMed Central

Krishnaiah, K V; Walker, L F; Borensztajn, J; Schonfeld, G; Getz, G S

1980-01-01

A variant of apolipoprotein B has been observed in the lymph lipoproteins [chylomicrons, very low density lipoproteins (VLDL), and low density lipoproteins (LDL)] of rats, in the plasma VLDL of fed rats, and in the plasma VLDL and LDL of rats fed a high-fat, high-cholesterol diet. It is the sole apolipoprotein B in the chylomicrons and VLDL of lymph. It differs from the apolipoprotein B of normal plasma LDL in its immunological properties and in its apparent molecular weight from electrophoresis on 3.5% NaDodSO4/polyacrylamide gel. Images PMID:6933436

Native protein mapping and visualization of protein interactions in the area of human plasma high-density lipoprotein by combining nondenaturing micro 2DE and quantitative LC-MS/MS.

PubMed

Jin, Ya; Bu, Shujie; Zhang, Jun; Yuan, Qi; Manabe, Takashi; Tan, Wen

2014-07-01

A human plasma sample was subjected to nondenaturing micro 2DE and a gel area (5 mm × 18 mm) that includes high-density lipoprotein (HDL) was cut into 1 mm × 1 mm squares, then the proteins in the 90 gel pieces were analyzed by quantitative LC-MS/MS. Grid-cutting of the gel was employed to; (i) ensure the total analysis of the proteins in the area, (ii) standardize the conditions of analysis by LC-MS/MS, (iii) reconstruct the protein distribution patterns from the quantity data. Totally 154 proteins were assigned in the 90 gel pieces and the quantity distribution of each was reconstructed as a color density pattern (a native protein map). The map of apolipoprotein (Apo) A-I showed a wide apparent mass distribution characteristic to HDL and was compared with the maps of the other 153 proteins. Eleven proteins showed maps of wide distribution that overlapped with the map of Apo A-I, and all have been reported to be the components of HDL. Further, seven minor proteins associated with HDL were detected at the gel positions of high Apo A-I quantity. These results for the first time visualized the localization of HDL apolipoproteins on a nondenaturing 2DE gel and strongly suggested their interactions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of urea on recombinant Apo A-I stability and its utilization in anion exchange chromatography.

PubMed

Angarita, Monica; Arosio, Paolo; Müller-Späth, Thomas; Baur, Daniel; Falkenstein, Roberto; Kuhne, Wolfgang; Morbidelli, Massimo

2014-08-08

Apolipoprotein A-I (Apo A-I) is an important lipid-binding protein involved in the transport and metabolism of cholesterol. High protein purity, in particular with respect to endotoxins is required for therapeutic applications. The use of urea during the purification process of recombinant Apo A-I produced in Escherichia coli has been suggested so as to provide high endotoxin clearance. In this work, we show that urea can be used as a sole modifier during the ion exchange chromatographic purification of Apo A-I and we investigate the molecular mechanism of elution by correlating the effect of urea on self-association, conformation and adsorption equilibrium properties of a modified model Apo A-I. In the absence of urea the protein was found to be present as a population of oligomers represented mainly by trimers, hexamers and nonamers. The addition of urea induced oligomer dissociation and protein structure unfolding. We correlated the changes in protein association and conformation with variations of the adsorption equilibrium of the protein on a strong anion exchanger. It was confirmed that the adsorption isotherms, described by a Langmuir model, were dependent on both protein and urea concentrations. Monomers, observed at low urea concentration (0.5M), were characterized by larger binding affinity and adsorption capacity compared to both protein oligomers (0M) and unfolded monomers (2-8M). The reduction of both the binding strength and maximum adsorption capacity at urea concentrations larger than 0.5M explains the ability of urea of inducing elution of the protein from the ion exchange resin. The dissociation of the protein complexes occurring during the elution could likely be the origin of the effective clearance of endotoxins originally trapped inside the oligomers. Copyright © 2014 Elsevier B.V. All rights reserved.

Appreciation of concentration of lipoproteins and apolipoproteins in serum of male rats under the influence of diet change composition and its supplementation with group B vitamins.

PubMed

Goluch-Koniuszy, Zuzanna; Wierzbicka, Aldona

2011-01-01

This study was aimed at exploring, on animal model, how the diet changes, which results in exceeding 5 times the amount of deficit of group B vitamins after diet change, which up to a certain extent imitates supplementation method in people, influences the concentration of apolipoprotein A-I and apolipoprotein B – the components of lipoprotein HDL-C and LDL-C. The research was conducted on 24 WISTAR male rats, aged ca 5 months. The animals were divided into 3 feeding groups: I was fed with basic compound which contained among others full wheat grain and corn grain, group II and III with modified compound in which part of the full wheat grain, from basic compound, was substituted for wheat flour, and 50% of corn with saccharose. Group I and II animals were drinking pure tap water which was left to stand for some time beforehand, group III animals vitamins dissolved in water: B(1), B(2), B(6), and PP – five times exceeded the difference between the amount of basic and modified feed, which in a certain way imitated the supplementation in human food. After one week of animals conditioning, the experiment was conducted for 6 weeks. In their blood serum were determined concentration of glucose (GL), triacyloglycerols (TG), total cholesterol (TC), fraction of HDL-cholesterol (HDLC), fraction of LDL-cholesterol (LDL-C) and apolipoproteins A-I (apo A-I) and apolipoproteins B (apoB). In the dissected muscles and in the animals' livers the amount of fat was determined with Soxhlet's method. The obtained results were analysed with one factor variance by use of statistic computer program Statistica® with application of Duncan test. Analysing the influence of diet change and its supplementation with chosen group B vitamins on the amount of consumed feed, it was ascertained that in spite of the same calorific value of the used feed, significantly less, compared to other groups, was consumed by the animals from the supplemented group. However, there was no significant gain of

Amphipathic α-helices in apolipoproteins are crucial to the formation of infectious hepatitis C virus particles.

PubMed

Fukuhara, Takasuke; Wada, Masami; Nakamura, Shota; Ono, Chikako; Shiokawa, Mai; Yamamoto, Satomi; Motomura, Takashi; Okamoto, Toru; Okuzaki, Daisuke; Yamamoto, Masahiro; Saito, Izumu; Wakita, Takaji; Koike, Kazuhiko; Matsuura, Yoshiharu

2014-12-01

Apolipoprotein B (ApoB) and ApoE have been shown to participate in the particle formation and the tissue tropism of hepatitis C virus (HCV), but their precise roles remain uncertain. Here we show that amphipathic α-helices in the apolipoproteins participate in the HCV particle formation by using zinc finger nucleases-mediated apolipoprotein B (ApoB) and/or ApoE gene knockout Huh7 cells. Although Huh7 cells deficient in either ApoB or ApoE gene exhibited slight reduction of particles formation, knockout of both ApoB and ApoE genes in Huh7 (DKO) cells severely impaired the formation of infectious HCV particles, suggesting that ApoB and ApoE have redundant roles in the formation of infectious HCV particles. cDNA microarray analyses revealed that ApoB and ApoE are dominantly expressed in Huh7 cells, in contrast to the high level expression of all of the exchangeable apolipoproteins, including ApoA1, ApoA2, ApoC1, ApoC2 and ApoC3 in human liver tissues. The exogenous expression of not only ApoE, but also other exchangeable apolipoproteins rescued the infectious particle formation of HCV in DKO cells. In addition, expression of these apolipoproteins facilitated the formation of infectious particles of genotype 1b and 3a chimeric viruses. Furthermore, expression of amphipathic α-helices in the exchangeable apolipoproteins facilitated the particle formation in DKO cells through an interaction with viral particles. These results suggest that amphipathic α-helices in the exchangeable apolipoproteins play crucial roles in the infectious particle formation of HCV and provide clues to the understanding of life cycle of HCV and the development of novel anti-HCV therapeutics targeting for viral assembly.

Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles

PubMed Central

Nakamura, Shota; Ono, Chikako; Shiokawa, Mai; Yamamoto, Satomi; Motomura, Takashi; Okamoto, Toru; Okuzaki, Daisuke; Yamamoto, Masahiro; Saito, Izumu; Wakita, Takaji; Koike, Kazuhiko; Matsuura, Yoshiharu

2014-01-01

Apolipoprotein B (ApoB) and ApoE have been shown to participate in the particle formation and the tissue tropism of hepatitis C virus (HCV), but their precise roles remain uncertain. Here we show that amphipathic α-helices in the apolipoproteins participate in the HCV particle formation by using zinc finger nucleases-mediated apolipoprotein B (ApoB) and/or ApoE gene knockout Huh7 cells. Although Huh7 cells deficient in either ApoB or ApoE gene exhibited slight reduction of particles formation, knockout of both ApoB and ApoE genes in Huh7 (DKO) cells severely impaired the formation of infectious HCV particles, suggesting that ApoB and ApoE have redundant roles in the formation of infectious HCV particles. cDNA microarray analyses revealed that ApoB and ApoE are dominantly expressed in Huh7 cells, in contrast to the high level expression of all of the exchangeable apolipoproteins, including ApoA1, ApoA2, ApoC1, ApoC2 and ApoC3 in human liver tissues. The exogenous expression of not only ApoE, but also other exchangeable apolipoproteins rescued the infectious particle formation of HCV in DKO cells. In addition, expression of these apolipoproteins facilitated the formation of infectious particles of genotype 1b and 3a chimeric viruses. Furthermore, expression of amphipathic α-helices in the exchangeable apolipoproteins facilitated the particle formation in DKO cells through an interaction with viral particles. These results suggest that amphipathic α-helices in the exchangeable apolipoproteins play crucial roles in the infectious particle formation of HCV and provide clues to the understanding of life cycle of HCV and the development of novel anti-HCV therapeutics targeting for viral assembly. PMID:25502789

Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells.

PubMed

Sayılan Özgün, Gülben; Özgün, Eray; Tabakçıoğlu, Kıymet; Süer Gökmen, Selma; Eskiocak, Sevgi; Çakır, Erol

2017-12-01

Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant and anti-atherosclerotic structural high-density lipoprotein proteins that are mainly synthesized by the liver. No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels. To investigate the dose-dependent effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels. In vitro experimental study. HepG2 cells were incubated with 0 (control), 10, 50 and 200 μM of caffeine for 24 hours. Cell viability was evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels were measured by western blotting. We observed a significant increase on apolipoprotein A-1 and paraoxonase-1 protein levels in the cells incubated with 50 µM of caffeine and a significant increase on paraoxonase-1 protein level in the cells incubated with 200 µM of caffeine. Our study showed that caffeine does not change paraoxonase-3 protein level, but the higher doses used in our study do cause an increase in both apolipoprotein A-1 and paraoxonase-1 protein levels in liver cells.

[Comparative characteristics of the basic blood lipid and apolipoprotein spectrum in groups of patients from Moscow and Bordeaux with ischemic heart disease].

PubMed

Perova, N V; Bonne, Zh; Nechaev, A S; Shcherbakova, I A; Metel'skaia, V A

1986-01-01

A comparative diagnostic examination of patients with chest pains in Moscow and Bordeaux revealed in both cities a higher level of total plasma cholesterol and apo B/A-I ratio in CHD patients with angiographically documented coronary atherosclerosis than in men without CHD. CHD patients from Bordeaux had higher levels of total and HDL cholesterol and a lower triglyceride level than patients from an analogous Moscow group. Both in Moscow and Bordeaux inhabitants the determination of the levels and the ratio of plasma apo B lipoprotein to A-I apolipoprotein proved highly informative for diagnosing atherogenous shifts in the lipoprotein system.

The Application of Multiple Reaction Monitoring to Assess Apo A-I Methionine Oxidations in Diabetes and Cardiovascular Disease

PubMed Central

Yassine, Hussein N.; Jackson, Angela M.; Reaven, Peter D.; Nedelkov, Dobrin; Nelson, Randall W.; Lau, Serrine S.; Borchers, Christoph H.

2014-01-01

The oxidative modification of apolipoprotein A-I ‘s methionine148(M148) is associated with defective HDL function in vitro. Multiple Reaction Monitoring (MRM) is a mass spectrometric technique that can be used to quantitate post-translational modifications. In this study, we developed an MRM assay to monitor the abundance ratio of the peptide containing oxidized M148 to the native peptide in Apo A-I. Measurement of the oxidized-to-unoxidized-M148 ratio was reproducible (CV<5%). The extent of methionine M148 oxidation in the HDL of healthy controls, and type 2 diabetic participants with and without prior cardiovascular events (CVD) were then examined. The results suggest a significant increase in the relative ratio of the peptide containing oxidized M148 to the unmodified peptide in the HDL of participants with diabetes and CVD (p<0.001), compared to participants without CVD. Monitoring the abundance ratio of the peptides containing oxidized and unoxidized M148 by MRM provides a means of examining the relationship between M148 oxidation and vascular complications in CVD. PMID:25705587

AIS training manual

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

Kramer, C.F.; Barancik, J.I.

1989-05-01

This Training Manual was developed by the Injury Prevention and Analysis Group (IPAG) as part of a training program in AIS 85 and AIS-EM (Epidemiological Modifications) coding. The IPAG Program is designed primarily to train medical record and other health professionals from diverse backgrounds and experience levels in the use of AIS 85 and AIS 85-EM. The Manual is designed to be used as a reference text after completion of the Program and includes copies of visual projection materials used during the training sessions.

Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.

PubMed

Pennacchio, Len A; Olivier, Michael; Hubacek, Jaroslav A; Krauss, Ronald M; Rubin, Edward M; Cohen, Jonathan C

2002-11-15

The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in approximately 16% of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n=419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12% of Caucasians, 14% of African-Americans and 28% of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25-50% of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels

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

Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.

2002-09-16

The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in {approx}16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceridemore » concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n 1/4 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12 percent of Caucasians, 14 percent of African-Americans and 28 percent of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 50 percent of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.« less

Production of Cloned Miniature Pigs Expressing High Levels of Human Apolipoprotein(a) in Plasma.

PubMed

Ozawa, Masayuki; Himaki, Takehiro; Ookutsu, Shoji; Mizobe, Yamato; Ogawa, Junki; Miyoshi, Kazuchika; Yabuki, Akira; Fan, Jianglin; Yoshida, Mitsutoshi

2015-01-01

High lipoprotein(a) [Lp(a)] levels are a major risk factor for the development of atherosclerosis. However, because apolipoprotein(a) [apo(a)], the unique component of Lp(a), is found only in primates and humans, the study of human Lp(a) has been hampered due to the lack of appropriate animal models. Using somatic cell nuclear transfer (SCNT) techniques, we produced transgenic miniature pigs expressing human apo(a) in the plasma. First, we placed the hemagglutinin (HA)-tagged cDNA of human apo(a) under the control of the β-actin promoter and cytomegalovirus enhancer, and then introduced this construct into kidney epithelial cells. Immunostaining of cells with anti-HA antibody allowed identification of cells stably expressing apo(a); one of the positive clones was used to provide donor cells for SCNT, yielding blastocysts that expressed apo(a). Immunohistochemical analysis of tissue sections and RT-PCR analysis of total RNA from organs of cloned piglet revealed that apo(a) is expressed in various tissues/organs including heart, liver, kidney, and intestine. More importantly, a transgenic line exhibited a high level (>400 mg/dL) of Lp(a) in plasma, and the transgenic apo(a) gene was transmitted to the offspring. Thus, we generated a human apo(a)-transgenic miniature pig that can be used as a model system to study advanced atherosclerosis related to human disease. The anatomical and physiological similarities between the swine and human cardiovascular systems will make this pig model a valuable source of information on the role of apo(a) in the formation of atherosclerosis, as well as the mechanisms underlying vascular health and disease.

Effect of apolipoprotein A-I deficiency on lecithin:cholesterol acyltransferase activation in mouse plasma.

PubMed

Parks, J S; Li, H; Gebre, A K; Smith, T L; Maeda, N

1995-02-01

Plasma cholesteryl ester (CE) synthesis by lecithin cholesterol acyltransferase (LCAT) is activated by apolipoprotein (apo)A-I. We studied the effect of plasma apoA-I concentration on LCAT activation, using normal, heterozygous or homozygous apoA-I-deficient mice made by gene targeting. Plasma esterified cholesterol concentrations of mice fed chow diets were ordered (mean +/- SEM): 105 +/- 7 (normal) > 70 +/- 5 (heterozygotes) > 26 +/- 2 (homozygotes) mg/dl. Plasma free cholesterol concentrations were similar among the three genotypes. Endogenous LCAT activity, measured as the decrease in plasma free cholesterol after a 1 h incubation at 37 degrees C, was ordered: 44 +/- 3 (normal) > 21 +/- 2 (heterozygotes) > 5 +/- 1 (homozygotes) nmol CE formed/h per ml plasma. Using a recombinant exogenous substrate consisting of egg yolk phospholipid, [14C]cholesterol, and apoA-I, CE formation of normals and heterozygotes was similar (27.4 +/- 0.6 and 28.8 +/- 1.3 nmol/h per ml plasma, respectively), but was significantly less for homozygotes (19.2 +/- 1.7 nmol/h per ml plasma). However, using a small unilamellar vesicle substrate particle containing phospholipid and [14C]cholesterol, CE formation was ordered: 1.6 +/- 0.1 (normal) = 1.6 +/- 0.1 (heterozygotes) > 0.6 +/- 0.1 (homozygotes) nmol/h per ml plasma; addition of apoA-I to the plasma of homozygous animals restored CE formation to normal levels (1.6 +/- 0.1). CE fatty acid analysis demonstrated that plasma from homozygous mice contained significantly more saturated and monounsaturated and fewer polyunsaturated fatty acids compared to normal and heterozygous mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular pathways in the transformation of model discoidal lipoprotein complexes induced by lecithin:cholesterol acyltransferase.

PubMed

Nichols, A V; Blanche, P J; Gong, E L; Shore, V G; Forte, T M

1985-05-17

Incubation (24 h, 37 degrees C) of discoidal complexes of phosphatidylcholine and apolipoprotein A-I (molar ratio 95 +/- 10 egg yolk phosphatidylcholine-apolipoprotein A-I; 10.5 X 4.0 nm, long X short dimension; designated, class 3 complexes) with the ultracentrifugal d greater than 1.21 g/ml fraction transformed the discoidal complexes to a small product with apparent mean hydrated and nonhydrated diameter of 7.8 and 6.6 nm, respectively. Formation of the small product was associated with marked reduction in phosphatidylcholine-apolipoprotein AI molar ratio of the complexes (on average from 95:1 to 45:1). Phospholipase A2 activity of lecithin:cholesterol acyltransferase participated in the depletion process, as evidenced by production of unesterified fatty acids. In the presence of the d greater than 1.21 g/ml fraction or partially purified lecithin:cholesterol acyltransferase and a source of unesterified cholesterol, the small product could be transformed to a core-containing (cholesteryl ester) round product with a hydrated and nonhydrated diameter of 8.6 and 7.5 nm, respectively. By means of cross-linking with dimethylsuberimidate, the protein moiety of the small product was shown to contain primarily two apolipoprotein A-I molecules per particle, while the large product contained three apolipoprotein A-I molecules per particle. The increase in number of apolipoprotein A-I molecules per particle during transformation of the small to the large product appeared to result from fusion of the small particles during core build-up and release of excess apolipoprotein A-I from the fusion product. The results obtained with the model complexes were consistent for the most part with recent observations (Chen, C., Applegate, K., King, W.C., Glomset, J.A., Norum, K.R. and Gjone, E. (1984) J. Lipid Res. 25, 269-282) on the transformation, by lecithin:cholesterol acyltransferase, of the small spherical high-density lipoproteins of patients with familial lecithin

Association of High-Density Lipoprotein-Cholesterol Versus Apolipoprotein A-I With Risk of Coronary Heart Disease: The European Prospective Investigation Into Cancer-Norfolk Prospective Population Study, the Atherosclerosis Risk in Communities Study, and the Women's Health Study.

PubMed

van Capelleveen, Julian C; Bochem, Andrea E; Boekholdt, S Matthijs; Mora, Samia; Hoogeveen, Ron C; Ballantyne, Christie M; Ridker, Paul M; Sun, Wensheng; Barter, Philip J; Tall, Alan R; Zwinderman, Aeilko H; Kastelein, John J P; Wareham, Nick J; Khaw, Kay-Tee; Hovingh, G Kees

2017-08-03

The contribution of apolipoprotein A-I (apoA-I) to coronary heart disease (CHD) risk stratification over and above high-density lipoprotein cholesterol (HDL-C) is unclear. We studied the associations between plasma levels of HDL-C and apoA-I, either alone or combined, with risk of CHD events and cardiovascular risk factors among apparently healthy men and women. HDL-C and apoA-I levels were measured among 17 661 participants of the EPIC (European Prospective Investigation into Cancer)-Norfolk prospective population study. Hazard ratios for CHD events and distributions of risk factors were calculated by quartiles of HDL-C and apoA-I. Results were validated using data from the ARIC (Atherosclerosis Risk in Communities) and WHS (Women's Health Study) cohorts, comprising 15 494 and 27 552 individuals, respectively. In EPIC-Norfolk, both HDL-C and apoA-I quartiles were strongly and inversely associated with CHD risk. Within HDL-C quartiles, higher apoA-I levels were not associated with lower CHD risk; in fact, CHD risk was higher within some HDL-C quartiles. ApoA-I levels were associated with higher levels of CHD risk factors: higher body mass index, HbA1c, non-HDL-C, triglycerides, apolipoprotein B, systolic blood pressure, and C-reactive protein, within fixed HDL-C quartiles. In contrast, HDL-C levels were consistently inversely associated with overall CHD risk and CHD risk factors within apoA-I quartiles ( P <0.001). These findings were validated in the ARIC and WHS cohorts. Our findings demonstrate that apoA-I levels do not offer predictive information over and above HDL-C. In fact, within some HDL-C quartiles, higher apoA-I levels were associated with higher risk of CHD events, possibly because of the unexpected higher prevalence of cardiovascular risk factors in association with higher apoA-I levels. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00000479. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Apolipoprotein A-I in Labeo rohita: Cloning and functional characterisation reveal its broad spectrum antimicrobial property, and indicate significant role during ectoparasitic infection.

PubMed

Mohapatra, Amruta; Karan, Sweta; Kar, Banya; Garg, L C; Dixit, A; Sahoo, P K

2016-08-01

Apolipoprotein A-I (ApoA-I) is the most abundant and multifunctional high-density lipoprotein (HDL) having a major role in lipid transport and potent antimicrobial activity against a wide range of microbes. In this study, a complete CDS of 771 bp of Labeo rohita (rohu) ApoA-I (LrApoA-I) encoding a protein of 256 amino acids was amplified, cloned and sequenced. Tissue specific transcription analysis of LrApoA-I revealed its expression in a wide range of tissues, with a very high level of expression in liver and spleen. Ontogenic study of LrApoA-I expression showed presence of transcripts in milt and 3 h post-fertilization onwards in the larvae. The expression kinetics of LrApoA-I was studied upon infection with three different types of pathogens to elucidate its functional significance. Its expression was found to be up-regulated in the anterior kidney of L. rohita post-infection with Aeromonas hydrophila. Similarly following poly I:C (poly inosinic:cytidylic) stimulation, the transcript levels increased in both the anterior kidney and liver tissues. Significant up-regulation of LrApoA-I expression was observed in skin, mucous, liver and anterior kidney of the fish challenged with the ectoparasite Argulus siamensis. Immunomodulatory effect of recombinant LrApoA-I (rApoA-I) produced in Escherichia coli was demonstrated against A. hydrophila challenge in vivo. L. rohita administered with rApoA-I at a dose of 100 μg exhibited significantly higher protection (∼55%) upon challenge with A. hydrophila 12 h post-administration of the protein, in comparison to that observed in control group, along with higher level of expression of immune-related genes. The heightened expression of ApoA-I observed post-infection reflected its involvement in immune responses against a wide range of infections including bacterial, viral as well as parasitic pathogens. Our results also suggest the possibility of using rApoA-I as an immunostimulant, particularly rendering protection

Plasma lipoproteins as mediators of the oxidative stress induced by UV light in human skin: a review of biochemical and biophysical studies on mechanisms of apolipoprotein alteration, lipid peroxidation, and associated skin cell responses.

PubMed

Filipe, Paulo; Morlière, Patrice; Silva, João N; Mazière, Jean-Claude; Patterson, Larry K; Freitas, João P; Santus, R

2013-01-01

There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL) and low-density lipoprotein (LDL) as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces (•)Trp and (•)O2 (-) radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO(•)) by α -tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α -tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α -tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α -tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

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

Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey

2004-10-01

Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

Towards AI-powered personalization in MOOC learning

NASA Astrophysics Data System (ADS)

Yu, Han; Miao, Chunyan; Leung, Cyril; White, Timothy John

2017-12-01

Massive Open Online Courses (MOOCs) represent a form of large-scale learning that is changing the landscape of higher education. In this paper, we offer a perspective on how advances in artificial intelligence (AI) may enhance learning and research on MOOCs. We focus on emerging AI techniques including how knowledge representation tools can enable students to adjust the sequence of learning to fit their own needs; how optimization techniques can efficiently match community teaching assistants to MOOC mediation tasks to offer personal attention to learners; and how virtual learning companions with human traits such as curiosity and emotions can enhance learning experience on a large scale. These new capabilities will also bring opportunities for educational researchers to analyse students' learning skills and uncover points along learning paths where students with different backgrounds may require different help. Ethical considerations related to the application of AI in MOOC education research are also discussed.

AIS ASM Operational Integration Plan

DTIC Science & Technology

2013-08-01

al. | Public August 2013 This page intentionally left blank. AIS ASM Operational Integration Plan v ...that supply AIS Routers as part of their AIS shoreside network software : Kongsberg C-Scope, Gatehouse AIS, Transas AIS Network, and CNS DataSwitch...commercial systems would be suitable for the current USCG traffic conditions. The ASM Manager is software that adds the required queuing and

The study of the proteome of healthy human blood plasma under conditions of long-term confinement in an isolation chamber.

PubMed

Trifonova, O P; Pastushkova, L Kh; Samenkova, N F; Chernobrovkin, A L; Karuzina, I I; Lisitsa, A V; Larina, I M

2013-05-01

We identified changes in the proteome of healthy human blood plasma caused by exposure to 105-day confinement in an isolation chamber. After removal of major proteins and concentration of minor proteins, plasma fractions were analyzed by two-dimensional electrophoresis followed by identification of significantly different protein spots by mass spectrometric analysis of the peptide fragments. The levels of α- and β-chains of fibrinogen, a fragment of complement factor C4, apolipoproteins AI and E, plasminogen factor C1 complement, and immunoglobulin M changed in participants during the isolation period. These changes probably reflect the adaptive response to altered conditions of life.

Antisense oligonucleotide directed to human apolipoprotein B-100 reduces lipoprotein(a) levels and oxidized phospholipids on human apolipoprotein B-100 particles in lipoprotein(a) transgenic mice.

PubMed

Merki, Esther; Graham, Mark J; Mullick, Adam E; Miller, Elizabeth R; Crooke, Rosanne M; Pitas, Robert E; Witztum, Joseph L; Tsimikas, Sotirios

2008-08-12

Lipoprotein (a) [Lp(a)] is a genetic cardiovascular risk factor that preferentially binds oxidized phospholipids (OxPL) in plasma. There is a lack of therapeutic agents that reduce plasma Lp(a) levels. Transgenic mice overexpressing human apolipoprotein B-100 (h-apoB-100 [h-apoB mice]) or h-apoB-100 plus human apo(a) to generate genuine Lp(a) particles [Lp(a) mice] were treated with the antisense oligonucleotide mipomersen directed to h-apoB-100 mRNA or control antisense oligonucleotide for 11 weeks by intraperitoneal injection. Mice were then followed up for an additional 10 weeks off therapy. Lp(a) levels [apo(a) bound to apoB-100] and apo(a) levels ["free" apo(a) plus apo(a) bound to apoB-100] were measured by chemiluminescent enzyme-linked immunoassay and commercial assays, respectively. The content of OxPL on h-apoB-100 particles (OxPL/h-apoB) was measured by capturing h-apoB-100 in microtiter wells and detecting OxPL by antibody E06. As expected, mipomersen significantly reduced plasma h-apoB-100 levels in both groups of mice. In Lp(a) mice, mipomersen significantly reduced Lp(a) levels by approximately 75% compared with baseline (P<0.0001) but had no effect on apo(a) levels or hepatic apo(a) mRNA expression. OxPL/h-apoB levels were much higher at baseline in Lp(a) mice compared with h-ApoB mice (P<0.0001) but decreased in a time-dependent fashion with mipomersen. There was no effect of the control antisense oligonucleotide on lipoprotein levels or oxidative parameters. Mipomersen significantly reduced Lp(a) and OxPL/apoB levels in Lp(a) mice. The present study demonstrates that h-apoB-100 is a limiting factor in Lp(a) particle synthesis in this Lp(a) transgenic model. If applicable to humans, mipomersen may represent a novel therapeutic approach to reducing Lp(a) levels and their associated OxPL.

Importance of Apolipoprotein A-I in Multiple Sclerosis.

PubMed

Gardner, Lidia A; Levin, Michael C

2015-01-01

Jean-Martin Charcot has first described multiple sclerosis (MS) as a disease of the central nervous system (CNS) over a century ago. MS remains incurable today, and treatment options are limited to disease modifying drugs. Over the years, significant advances in understanding disease pathology have been made in autoimmune and neurodegenerative components. Despite the fact that brain is the most lipid rich organ in human body, the importance of lipid metabolism has not been extensively studied in this disorder. In MS, the CNS is under attack by a person's own immune system. Autoantigens and autoantibodies are known to cause devastation of myelin through up regulation of T-cells and cytokines, which penetrate through the blood-brain barrier to cause inflammation and myelin destruction. The anti-inflammatory role of high-density lipoproteins (HDLs) has been implicated in a plethora of biological processes: vasodilation, immunity to infection, oxidation, inflammation, and apoptosis. However, it is not known what role HDL plays in neurological function and myelin repair in MS. Understanding of lipid metabolism in the CNS and in the periphery might unveil new therapeutic targets and explain the partial success of some existing MS therapies.

Cloning, characterization and comparative analysis of pig plasma apolipoprotein A-IV.

PubMed

Navarro, María A; Acín, Sergio; Iturralde, María; Calleja, Lucía; Carnicer, Ricardo; Guzmán-García, Mario A; González-Ramón, Nieves; Mata, Pedro; Isabel, Beatriz; López-Bote, Clemente J; Lampreave, Fermín; Piñeiro, Andrés; Osada, Jesús

2004-01-21

Pig apolipoprotein (apo) A-IV cDNA was cloned, characterized and compared to the human ortholog. Mature porcine apo A-IV consists of 362 amino acids and displays a 75.6% sequence identity with human protein. Pig apo A-IV is the smallest reported mammalian apo A-IV because it lacks the repeated motifs of glutamine and glutamic acid at the carboxyl terminus. A phylogenic tree of apo A-IV mammalian proteins reveals that porcine apo A-IV is more closely related to humans and primates than to rodents. This protein is highly hydrophobic and is mainly associated with lipoproteins.

Do Postpartum Levels of Apolipoproteins Prospectively Predict the Development of Type 2 Diabetes in Women with Previous Gestational Diabetes Mellitus?

PubMed

Lappas, Martha; Georgiou, Harry M; Velagic, Anida; Willcox, Jane C; Permezel, Michael; Shub, Alexis

2018-03-12

The risk of developing type 2 diabetes is greater in women with previous gestational diabetes mellitus (GDM). Apolipoprotein (Apo) species have been associated with the development of type 2 diabetes in the general population. The aim of this study was to determine if circulating levels of Apo species can predict development of type 2 diabetes in women with previous GDM. Apo AI, Apo AII, Apo B, Apo CII, Apo CIII and Apo E levels were measured in 95 women with normal glucose tolerance, 12 weeks following an index GDM pregnancy. Women were assessed for up to 10 years for the development of type 2 diabetes. Postpartum Apo CIII levels, and Apo CIII/Apo AI, Apo CIII/Apo AII, Apo CIII/Apo CII, Apo CIII/Apo E and Apo E/Apo CIII ratios were significantly and positively associated with the development of type 2 diabetes. After controlling for age and BMI, these associations, except for the Apo E/Apo CIII ratio, remained significant. In a clinical model of prediction of type 2 diabetes that included age, BMI, and pregnancy and postnatal fasting glucose, the addition of Apo CIII levels, Apo CIII/Apo AI, Apo CIII/Apo AII, Apo CIII/Apo CII, and Apo CIII/Apo E resulted in a net reclassification improvement of 16.2%. High Apo CIII levels and the Apo CIII/Apo AI, Apo CIII/Apo AII, Apo CIII/Apo CII, and Apo CIII/Apo E ratios are all significant risk factors for the development of type 2 diabetes in women with a previous GDM pregnancy. © Georg Thieme Verlag KG Stuttgart · New York.

Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2c).

PubMed

Ge, Fengxia; Yao, Junjie; Fu, Xiaoying; Guo, Zhanjun; Yan, Jingmin; Zhang, Beiru; Zhang, Huanyu; Tomozawa, Hiroshi; Miyazaki, Junichi; Sawashita, Jinko; Mori, Masayuki; Higuchi, Keiichi

2007-07-01

In mice, apolipoprotein A-II (apoA-II) self-associates to form amyloid fibrils (AApoAII) in an age-associated manner. We postulated that the two most important factors in apoA-II amyloidosis are the Apoa2(c) allele, which codes for the amyloidogenic protein APOA2C (Gln5, Ala38) and transmission of amyloid fibrils. To characterize further the contribution of the Apoa2(c) allele to amyloidogenesis and improve detection of amyloidogenic materials, we established transgenic mice that overexpress APOA2C protein under the cytomegalovirus (CMV) immediate early gene (CMV-IE) enhancer/chicken beta promoter. Compared to transgene negative (Tg(-/-)) mice that express apoA-II protein mainly in the liver, mice homozygous (Tg(+/+)) and heterozygous (Tg(+/-)) for the transgene express a high level of apoA-II protein in many tissues. They also have higher plasma concentrations of apoA-II, higher ratios of ApoA-II/apolipoprotein A-I (ApoA-I) and higher concentrations of high-density lipoprotein (HDL) cholesterol. Following injection of AApoAII fibrils into Tg(+/+) mice, amyloid deposition was observed in the testis, liver, kidney, heart, lungs, spleen, tongue, stomach and intestine but not in the brain. In Tg(+/+) mice, but not in Tg(-/-) mice, amyloid deposition was induced by injection of less than 10(-8) mug AApoAII fibrils. Furthermore, deposition in Tg(+/+) mice occurred more rapidly and to a greater extent than in Tg(-/-) mice. These studies indicate that increased levels of APOA2C protein lead to earlier and greater amyloid deposition and enhanced sensitivity to the transmission of amyloid fibrils in transgenic mice. This transgenic mouse model should prove valuable for studies of amyloidosis.

Architectural roles of multiple chromatin insulators at the human apolipoprotein gene cluster

PubMed Central

Mishiro, Tsuyoshi; Ishihara, Ko; Hino, Shinjiro; Tsutsumi, Shuichi; Aburatani, Hiroyuki; Shirahige, Katsuhiko; Kinoshita, Yoshikazu; Nakao, Mitsuyoshi

2009-01-01

Long-range regulatory elements and higher-order chromatin structure coordinate the expression of multiple genes in cluster, and CTCF/cohesin-mediated chromatin insulator may be a key in this regulation. The human apolipoprotein (APO) A1/C3/A4/A5 gene region, whose alterations increase the risk of dyslipidemia and atherosclerosis, is partitioned at least by three CTCF-enriched sites and three cohesin protein RAD21-enriched sites (two overlap with the CTCF sites), resulting in the formation of two transcribed chromatin loops by interactions between insulators. The C3 enhancer and APOC3/A4/A5 promoters reside in the same loop, where the APOC3/A4 promoters are pointed towards the C3 enhancer, whereas the APOA1 promoter is present in the different loop. The depletion of either CTCF or RAD21 disrupts the chromatin loop structure, together with significant changes in the APO expression and the localization of transcription factor hepatocyte nuclear factor (HNF)-4α and transcriptionally active form of RNA polymerase II at the APO promoters. Thus, CTCF/cohesin-mediated insulators maintain the chromatin loop formation and the localization of transcriptional apparatus at the promoters, suggesting an essential role of chromatin insulation in controlling the expression of clustered genes. PMID:19322193

Complex effects of inhibiting hepatic apolipoprotein B100 synthesis in humans.

PubMed

Reyes-Soffer, Gissette; Moon, Byoung; Hernandez-Ono, Antonio; Dionizovik-Dimanovski, Marija; Dionizovick-Dimanovski, Marija; Jimenez, Jhonsua; Obunike, Joseph; Thomas, Tiffany; Ngai, Colleen; Fontanez, Nelson; Donovan, Daniel S; Karmally, Wahida; Holleran, Stephen; Ramakrishnan, Rajasekhar; Mittleman, Robert S; Ginsberg, Henry N

2016-01-27

Mipomersen is a 20mer antisense oligonucleotide (ASO) that inhibits apolipoprotein B (apoB) synthesis; its low-density lipoprotein (LDL)-lowering effects should therefore result from reduced secretion of very-low-density lipoprotein (VLDL). We enrolled 17 healthy volunteers who received placebo injections weekly for 3 weeks followed by mipomersen weekly for 7 to 9 weeks. Stable isotopes were used after each treatment to determine fractional catabolic rates and production rates of apoB in VLDL, IDL (intermediate-density lipoprotein), and LDL, and of triglycerides in VLDL. Mipomersen significantly reduced apoB in VLDL, IDL, and LDL, which was associated with increases in fractional catabolic rates of VLDL and LDL apoB and reductions in production rates of IDL and LDL apoB. Unexpectedly, the production rates of VLDL apoB and VLDL triglycerides were unaffected. Small interfering RNA-mediated knockdown of apoB expression in human liver cells demonstrated preservation of apoB secretion across a range of apoB synthesis. Titrated ASO knockdown of apoB mRNA in chow-fed mice preserved both apoB and triglyceride secretion. In contrast, titrated ASO knockdown of apoB mRNA in high-fat-fed mice resulted in stepwise reductions in both apoB and triglyceride secretion. Mipomersen lowered all apoB lipoproteins without reducing the production rate of either VLDL apoB or triglyceride. Our human data are consistent with long-standing models of posttranscriptional and posttranslational regulation of apoB secretion and are supported by in vitro and in vivo experiments. Targeting apoB synthesis may lower levels of apoB lipoproteins without necessarily reducing VLDL secretion, thereby lowering the risk of steatosis associated with this therapeutic strategy. Copyright © 2016, American Association for the Advancement of Science.

Complex effects of inhibiting hepatic apolipoprotein B100 synthesis in humans

PubMed Central

Reyes-Soffer, Gissette; Moon, Byoung; Hernandez-Ono, Antonio; Dionizovik-Dimanovski, Marija; Jimenez, Jhonsua; Obunike, Joseph; Thomas, Tiffany; Ngai, Colleen; Fontanez, Nelson; Donovan, Daniel S.; Karmally, Wahida; Holleran, Stephen; Ramakrishnan, Rajasekhar; Mittleman, Robert S.; Ginsberg, Henry N.

2016-01-01

Mipomersen is a 20mer antisense oligonucleotide (ASO) that inhibits apolipoprotein B (apoB) synthesis; its low-density lipoprotein (LDL)–lowering effects should therefore result from reduced secretion of very-low-density lipoprotein (VLDL). We enrolled 17 healthy volunteers who received placebo injections weekly for 3 weeks followed by mipomersen weekly for 7 to 9 weeks. Stable isotopes were used after each treatment to determine fractional catabolic rates and production rates of apoB in VLDL, IDL (intermediate-density lipoprotein), and LDL, and of triglycerides in VLDL. Mipomersen significantly reduced apoB in VLDL, IDL, and LDL, which was associated with increases in fractional catabolic rates of VLDL and LDL apoB and reductions in production rates of IDL and LDL apoB. Unexpectedly, the production rates of VLDL apoB and VLDL triglycerides were unaffected. Small interfering RNA–mediated knockdown of apoB expression in human liver cells demonstrated preservation of apoB secretion across a range of apoB synthesis. Titrated ASO knockdown of apoB mRNA in chow-fed mice preserved both apoB and triglyceride secretion. In contrast, titrated ASO knockdown of apoB mRNA in high-fat–fed mice resulted in stepwise reductions in both apoB and triglyceride secretion. Mipomersen lowered all apoB lipoproteins without reducing the production rate of either VLDL apoB or triglyceride. Our human data are consistent with longstanding models of posttranscriptional and posttranslational regulation of apoB secretion and are supported by in vitro and in vivo experiments. Targeting apoB synthesis may lower levels of apoB lipoproteins without necessarily reducing VLDL secretion, thereby lowering the risk of steatosis associated with this therapeutic strategy. PMID:26819195

Plasma apolipoproteins and physical and cognitive health in very old individuals.

PubMed

Muenchhoff, Julia; Song, Fei; Poljak, Anne; Crawford, John D; Mather, Karen A; Kochan, Nicole A; Yang, Zixuan; Trollor, Julian N; Reppermund, Simone; Maston, Kate; Theobald, Adam; Kirchner-Adelhardt, Susanne; Kwok, John B; Richmond, Robyn L; McEvoy, Mark; Attia, John; Schofield, Peter W; Brodaty, Henry; Sachdev, Perminder S

2017-07-01

Apolipoproteins play a crucial role in lipid metabolism with implications in cardiovascular disease, obesity, diabetes, Alzheimer's disease, and longevity. We quantified 7 apolipoproteins in plasma in 1067 individuals aged 56-105 using immunoassays and explored relationships with APOE polymorphism ε2/3/4, vascular health, frailty, and cognition. ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH, and ApoJ decreased from mid-life, although ApoE and ApoJ had U-shaped trends. Centenarians had the highest ApoE levels and the lowest frequency of APOE ε4 allele relative to younger groups. Apolipoprotein levels trended lower in APOE ε4 homozygotes and heterozygotes compared with noncarriers, with ApoE and ApoJ being significantly lower. Levels of all apolipoproteins except ApoH were higher in females. Sex- and age-related differences were apparent in the association of apolipoproteins with cognitive performance, as only women had significant negative associations of ApoB, ApoE, ApoH, and ApoJ in mid-life, whereas associations at older age were nonsignificant or positive. Our findings suggest levels of some apolipoproteins, especially ApoE, are associated with lifespan and cognitive function in exceptionally long-lived individuals. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative Effects of Diet-Induced Lipid Lowering Versus Lipid Lowering Along With Apo A-I Milano Gene Therapy on Regression of Atherosclerosis.

PubMed

Wang, Lai; Tian, Fang; Arias, Ana; Yang, Mingjie; Sharifi, Behrooz G; Shah, Prediman K

2016-05-01

Apolipoprotein A-1 (Apo A-I) Milano, a naturally occurring Arg173to Cys mutant of Apo A-1, has been shown to reduce atherosclerosis in animal models and in a small phase 2 human trial. We have shown the superior atheroprotective effects of Apo A-I Milano (Apo A-IM) gene compared to wild-type Apo A-I gene using transplantation of retrovirally transduced bone marrow in Apo A-I/Apo E null mice. In this study, we compared the effect of dietary lipid lowering versus lipid lowering plus Apo A-IM gene transfer using recombinant adeno-associated virus (rAAV) 8 as vectors on atherosclerosis regression in Apo A-I/Apo E null mice. All mice were fed a high-cholesterol diet from age of 6 weeks until week 20, and at 20 weeks, 10 mice were euthanized to determine the extent of atherosclerosis. After 20 weeks, an additional 20 mice were placed on either a low-cholesterol diet plus empty rAAV (n = 10) to serve as controls or low-cholesterol diet plus 1 single intravenous injection of 1.2 × 10(12)vector genomes of adeno-associated virus (AAV) 8 vectors expressing Apo A-IM (n = 10). At the 40 week time point, intravenous AAV8 Apo A-IM recipients showed a significant regression of atherosclerosis in the whole aorta (P< .01), aortic sinuses (P< .05), and brachiocephalic arteries (P< .05) compared to 20-week-old mice, whereas low-cholesterol diet plus empty vector control group showed no significant regression in lesion size. Immunostaining showed that compared to the 20-week-old mice, there was a significantly reduced macrophage content in the brachiocephalic (P< .05) and aortic sinus plaques (P< .05) of AAV8 Apo A-IM recipients. These data show that although dietary-mediated cholesterol lowering halts progression of atherosclerosis, it does not induce regression, whereas combination of low-cholesterol diet and AAV8 mediated Apo A-I Milano gene therapy induces rapid and significant regression of atherosclerosis in mice. These data provide support for the potential feasibility of this

P-selectin expressed by a human SELP transgene is atherogenic in apolipoprotein E-deficient mice

PubMed Central

Zhang, Nan; Liu, Zhenghui; Yao, Longbiao; Mehta-D’souza, Padmaja; McEver, Rodger P.

2016-01-01

Objective During inflammation, P-selectin expressed on activated endothelial cells and platelets mediates rolling adhesion of leukocytes. Atherosclerosis-prone mice crossed with P-selectin-deficient (Selp−/−) mice develop smaller lesions. Cytokines such as tumor necrosis factor-α increase Selp transcripts and augment atherosclerosis in mice. However, they decrease SELP transcripts in humans, challenging assumptions that human P-selectin is atherogenic. We used mice expressing a human SELP transgene to examine the atherogenic role of P-selectin. Approach and results We crossed apolipoprotein E-deficient (Apoe−/−) mice with Selp−/− mice and/or transgenic mice expressing the entire human SELP gene (TgSELP+/−). Aortas developed larger, macrophage-rich atheromas in Apoe−/−Selp−/−TgSELP+/− mice than in Apoe−/−Selp−/− mice after 8 or 16 weeks on a Western diet. Confocal microscopy of Apoe−/−Selp−/−TgSELP+/− aortas revealed staining for human P-selectin in endothelial cells overlying atheromas, but not in lesional macrophages. We also observed staining for human P-selectin in aortic endothelial cells of 3–4-week-old Apoe−/−Selp−/−TgSELP+/− weanlings before atheromas developed. Furthermore, human SELP transcripts were ~3-fold higher in aortas of Apoe−/−Selp+/−TgSELP+/− weanlings than in Selp+/−TgSELP+/− weanlings, whereas murine Selp and Sele transcripts were equivalent in weanlings of both genotypes. Human SELP transcripts in aortas of Apoe−/−Selp+/−TgSELP+/− mice remained nearly constant during 16 weeks on a Western diet, whereas murine Selp and Sele transcripts progressively increased. Bone marrow transplantation in Apoe−/−Selp−/− and Apoe−/−Selp−/−TgSELP+/− mice demonstrated that both platelets and endothelial cells must express human P-selectin to promote atherogenesis. Conclusions P-selectin expressed by human SELP is atherogenic in Apoe−/− mice, suggesting that P

Apolipoprotein E genotype in schizophrenia

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

Joober, R.; Lal, S.; Bloom, D.

We investigated the association between schizophrenia and the allelic polymorphism in the apolipoprotein E (Apo E) gene in 51 schizophrenic patients and 35 controls. The Apo E4 allele was equally represented in the schizophrenic group (16%) and the control group (20%) suggesting no association between schizophrenia and the Apo E4 allele. The apolipoprotein E (Apo E) is a polymorphic (E2, E3, and E4) lipoprotein involved in the transmembrane transport of cholesterol and is thought to play an important role in neuronal growth and in the central nervous system response to injury, particularly in the hippocampal region. Recent findings strongly suggestmore » that the Apo E4 allele is associated with cognitive deficits in normal and pathological aging, e.g., Alzheimer`s disease. 5 refs., 1 tab.« less

High-density lipoprotein and apolipoprotein A-I inhibit palmitate-induced translocation of toll-like receptor 4 into lipid rafts and inflammatory cytokines in 3T3-L1 adipocytes

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

Yamada, Hodaka; Umemoto, Tomio; Kawano, Mikihiko

Saturated fatty acids (SFAs) activate toll-like receptor 4 (TLR4) signal transduction in macrophages and are involved in the chronic inflammation accompanying obesity. High-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) produce anti-inflammatory effects via reverse cholesterol transport. However, the underlying mechanisms by which HDL and apoA-I inhibit inflammatory responses in adipocytes remain to be determined. Here we examined whether palmitate increases the translocation of TLR4 into lipid rafts and whether HDL and apoA-I inhibit inflammation in adipocytes. Palmitate exposure (250 μM, 24 h) increased interleukin-6 and tumor necrosis factor-α gene expressions and translocation of TLR4 into lipid rafts in 3T3-L1 adipocytes. Pretreatment withmore » HDL and apoA-I (50 μg/mL, 6 h) suppressed palmitate-induced inflammatory cytokine expression and TLR4 translocation into lipid rafts. Moreover, HDL and apoA-I inhibited palmitate-induced phosphorylation of nuclear factor-kappa B. HDL showed an anti-inflammatory effect via ATP-binding cassette transporter G1 and scavenger receptor class B, member 1, whereas apoA-I showed an effect via ATP-binding cassette transporter A1. These results demonstrated that HDL and apoA-I reduced palmitate-potentiated TLR4 trafficking into lipid rafts and its related inflammation in adipocytes via these specific transporters. - Highlights: • Palmitate induces TLR4 translocation into lipid rafts in 3T3-L1 adipocytes. • Raft disruption by MβCD inhibits lipid raft formation. • HDL and apoA-I inhibit palmitate-induced translocation of TLR4 into lipid rafts. • Anti-inflammatory effects of HDL and apoA-I occur via specific transporters.« less

Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E

NASA Astrophysics Data System (ADS)

Rute Neves, Ana; Fontes Queiroz, Joana; Weksler, Babette; Romero, Ignacio A.; Couraud, Pierre-Olivier; Reis, Salette

2015-12-01

Nanotechnology can be an important tool to improve the permeability of some drugs for the blood-brain barrier. In this work we created a new system to enter the brain by functionalizing solid lipid nanoparticles with apolipoprotein E, aiming to enhance their binding to low-density lipoprotein receptors on the blood-brain barrier endothelial cells. Solid lipid nanoparticles were successfully functionalized with apolipoprotein E using two distinct strategies that took advantage of the strong interaction between biotin and avidin. Transmission electron microscopy images revealed spherical nanoparticles, and dynamic light scattering gave a Z-average under 200 nm, a polydispersity index below 0.2, and a zeta potential between -10 mV and -15 mV. The functionalization of solid lipid nanoparticles with apolipoprotein E was demonstrated by infrared spectroscopy and fluorimetric assays. In vitro cytotoxic effects were evaluated by MTT and LDH assays in the human cerebral microvascular endothelial cells (hCMEC/D3) cell line, a human blood-brain barrier model, and revealed no toxicity up to 1.5 mg ml-1 over 4 h of incubation. The brain permeability was evaluated in transwell devices with hCMEC/D3 monolayers, and a 1.5-fold increment in barrier transit was verified for functionalized nanoparticles when compared with non-functionalized ones. The results suggested that these novel apolipoprotein E-functionalized nanoparticles resulted in dynamic stable systems capable of being used for an improved and specialized brain delivery of drugs through the blood-brain barrier.

Mapping AIS coverage for trusted surveillance

NASA Astrophysics Data System (ADS)

Lapinski, Anna-Liesa S.; Isenor, Anthony W.

2010-10-01

Automatic Identification System (AIS) is an unattended vessel reporting system developed for collision avoidance. Shipboard AIS equipment automatically broadcasts vessel positional data at regular intervals. The real-time position and identity data from a vessel is received by other vessels in the area thereby assisting with local navigation. As well, AIS broadcasts are beneficial to those concerned with coastal and harbour security. Land-based AIS receiving stations can also collect the AIS broadcasts. However, reception at the land station is dependent upon the ship's position relative to the receiving station. For AIS to be used as a trusted surveillance system, the characteristics of the AIS coverage area in the vicinity of the station (or stations) should be understood. This paper presents some results of a method being investigated at DRDC Atlantic, Canada) to map the AIS coverage characteristics of a dynamic AIS reception network. The method is shown to clearly distinguish AIS reception edges from those edges caused by vessel traffic patterns. The method can also be used to identify temporal changes in the coverage area, an important characteristic for local maritime security surveillance activities. Future research using the coverage estimate technique is also proposed to support surveillance activities.

Artificial Intelligence Study (AIS).

DTIC Science & Technology

1987-02-01

ARTIFICIAL INTELLIGNECE HARDWARE ....... 2-50 AI Architecture ................................... 2-49 AI Hardware ....................................... 2...ftf1 829 ARTIFICIAL INTELLIGENCE STUDY (RIS)(U) MAY CONCEPTS 1/3 A~NLYSIS AGENCY BETHESA RD R B NOJESKI FED 6? CM-RP-97-1 NCASIFIED /01/6 M |K 1.0...p/ - - ., e -- CAA- RP- 87-1 SAOFŔ)11 I ARTIFICIAL INTELLIGENCE STUDY (AIS) tNo DTICFEBRUARY 1987 LECT 00 I PREPARED BY RESEARCH AND ANALYSIS

Crystal structures, vibrational spectra and DFT calculations of five halogeno-derivatives of 7-azaindole (3Br7AI, 4Br7AI, 4Cl7AI, 3Br4Cl7AI and 5Br3Cl7AI): a comparative study

NASA Astrophysics Data System (ADS)

Morzyk-Ociepa, Barbara; Dysz, Karolina; Turowska-Tyrk, Ilona; Michalska, Danuta

2018-01-01

Structures and vibrational spectra of 3-bromo-7-azaindole (3Br7AI), 4-bromo-7-azaindole (4Br7AI), 4-chloro-7-azaindole (4Cl7AI), 5-bromo-3-chloro-7-azaindole (5Br3Cl7AI) and 3-bromo-4-chloro-7-azaindole (3Br4Cl7AI) have been investigated. For the first time a single crystal analysis is reported for the three compounds: 3Br7AI (P21/n space group; a = 12.6586(3), b = 3.98664(12), c = 14.1189(4)Å, β = 100.901(2)o, Z = 4); 4Br7AI (P21/n space group; a = 5.38136 (13), b = 9.2262 (2), c = 13.9806 (4)Å, β = 90.052 (2)o, Z = 4); and 5Br3Cl7AI (C2/c space group; a = 22.9444(10), b = 3.91953(12), c = 17.8500(6)Å, β = 102.621(4)o, Z = 8). In the crystal structure, a pair of molecules forms a centrosymmetric dimer connected by dual nearly linear Nsbnd H⋯N hydrogen bonds between the pyrrole and pyridine rings. In addition, the structures of 4Br7AI and 5Br3Cl7AI are stabilized by C2sbnd H2⋯Br hydrogen bonds. The IR and Raman spectra of all compounds and their N-deuterated derivatives were recorded in the solid state. The theoretical molecular structures and vibrational spectra of the centrosymmetric dimers of five investigated compounds were calculated using the B3LYP method with the 6-311G++(d,p) basis set. The optimized structural parameters and the calculated vibrational spectra reproduce well the experiment. Detailed vibrational assignments for all these compounds have been made on the basis of the calculated potential energy distributions (PEDs). The characteristic marker bands for the chloro- and bromo-derivativeds of 7-azaindoles are reported.

Comparison of injury severity between AIS 2005 and AIS 1990 in a large injury database

PubMed Central

Barnes, J; Hassan, A; Cuerden, R; Cookson, R; Kohlhofer, J

2009-01-01

The aim of this study is to investigate the differences in car occupant injury severity recorded in AIS 2005 compared to AIS 1990 and to outline the likely effects on future data analysis findings. Occupant injury data in the UK Cooperative Crash Injury Study Database (CCIS) were coded for the period February 2006 to November 2007 using both AIS 1990 and AIS 2005. Data for 1,994 occupants with over 6000 coded injuries were reviewed at the AIS and MAIS level of severities and body regions to determine changes between the two coding methodologies. Overall there was an apparent general trend for fewer injuries to be coded at the AIS 4+ severity and more injuries to be coded at the AIS 2 severity. When these injury trends were reviewed in more detail it was found that the body regions which contributed the most to these changes in severity were the head, thorax and extremities. This is one of the first studies to examine the implications for large databases when changing to an updated method for coding injuries. PMID:20184835

High hydrostatic pressure extract of garlic increases the HDL cholesterol level via up-regulation of apolipoprotein A-I gene expression in rats fed a high-fat diet

PubMed Central

2012-01-01

Background Cardiovascular disease (CVD) is the number one cause of mortality worldwide and a low high-density lipoprotein cholesterol (HDL-C) level is an important marker of CVD risk. Garlic (Allium sativum) has been widely used in the clinic for treatment of CVD and regulation of lipid metabolism. This study investigated the effects of a high hydrostatic pressure extract of garlic (HEG) on HDL-C level and regulation of hepatic apolipoprotein A-I (apoA-I) gene expression. Methods Male Sprague–Dawley rats were divided into two groups and maintained on a high-fat control diet (CON) or high-fat control diet supplemented with high hydrostatic pressure extract of garlic (HEG) for 5 weeks. Changes in the expression of genes related to HDL-C metabolism were analyzed in liver, together with biometric and blood parameters. Results In the HEG group, the plasma triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased in comparison with the CON group (P < 0.05). Dietary HEG also lowered the hepatic TG and total cholesterol (TC) levels compared to the CON group. While the plasma HDL-C level and mRNA level of hepatic apoA-I, which is one of primarily proteins of HDL-C particle, were significantly increased in the HEG group compared to the CON group (P < 0.05). The gene expression of ATP-binding cassette transporter A1 (ABCA1) and lecithin:cholesterol acyltransferase (LCAT), importantly involved in the biogenesis in HDL, were also up-regulated by dietary HEG. Conclusions These results suggest that HEG ameliorates plasma lipid profiles and attenuates hepatic lipid accumulation in the high-fat fed rats. Our findings provides that the effects of HEG on the increase of the plasma HDL-C level was at least partially mediated by up-regulation of hepatic genes expression such as apoA-I, ABCA1, and LCAT in rats fed a high-fat diet. PMID:22713542

High hydrostatic pressure extract of garlic increases the HDL cholesterol level via up-regulation of apolipoprotein A-I gene expression in rats fed a high-fat diet.

PubMed

Lee, Seohyun; Joo, Hyunjin; Kim, Chong-Tai; Kim, In-Hwan; Kim, Yangha

2012-06-19

Cardiovascular disease (CVD) is the number one cause of mortality worldwide and a low high-density lipoprotein cholesterol (HDL-C) level is an important marker of CVD risk. Garlic (Allium sativum) has been widely used in the clinic for treatment of CVD and regulation of lipid metabolism. This study investigated the effects of a high hydrostatic pressure extract of garlic (HEG) on HDL-C level and regulation of hepatic apolipoprotein A-I (apoA-I) gene expression. Male Sprague-Dawley rats were divided into two groups and maintained on a high-fat control diet (CON) or high-fat control diet supplemented with high hydrostatic pressure extract of garlic (HEG) for 5 weeks. Changes in the expression of genes related to HDL-C metabolism were analyzed in liver, together with biometric and blood parameters. In the HEG group, the plasma triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased in comparison with the CON group (P < 0.05). Dietary HEG also lowered the hepatic TG and total cholesterol (TC) levels compared to the CON group. While the plasma HDL-C level and mRNA level of hepatic apoA-I, which is one of primarily proteins of HDL-C particle, were significantly increased in the HEG group compared to the CON group (P < 0.05). The gene expression of ATP-binding cassette transporter A1 (ABCA1) and lecithin:cholesterol acyltransferase (LCAT), importantly involved in the biogenesis in HDL, were also up-regulated by dietary HEG. These results suggest that HEG ameliorates plasma lipid profiles and attenuates hepatic lipid accumulation in the high-fat fed rats. Our findings provides that the effects of HEG on the increase of the plasma HDL-C level was at least partially mediated by up-regulation of hepatic genes expression such as apoA-I, ABCA1, and LCAT in rats fed a high-fat diet.

Managing bioengineering complexity with AI techniques.

PubMed

Beal, Jacob; Adler, Aaron; Yaman, Fusun

2016-10-01

Our capabilities for systematic design and engineering of biological systems are rapidly increasing. Effectively engineering such systems, however, requires the synthesis of a rapidly expanding and changing complex body of knowledge, protocols, and methodologies. Many of the problems in managing this complexity, however, appear susceptible to being addressed by artificial intelligence (AI) techniques, i.e., methods enabling computers to represent, acquire, and employ knowledge. Such methods can be employed to automate physical and informational "routine" work and thus better allow humans to focus their attention on the deeper scientific and engineering issues. This paper examines the potential impact of AI on the engineering of biological organisms through the lens of a typical organism engineering workflow. We identify a number of key opportunities for significant impact, as well as challenges that must be overcome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Clinical significance of plasma apolipoprotein F in Japanese healthy and hypertriglyceridemic subjects.

PubMed

Kujiraoka, Takeshi; Nakamoto, Takaaki; Sugimura, Hiroyuki; Iwasaki, Tadao; Ishihara, Mitsuaki; Hoshi, Toshiyasu; Horie, Yasuto; Ogawa, Kazuyuki; Todoroki, Masakatsu; Nakatani, Yuki; Banba, Nobuyuki; Yasu, Takanori; Hattori, Hiroaki

2013-01-01

Apolipoprotein F (apo F), also known as lipid transfer inhibitory protein (LTIP), is a protein component of plasma lipoprotein classes including HDL and functions to inhibit lipid transfer between lipoproteins in vitro. To study the role of plasma apo F, a reliable and sensitive tool for the quantification would be needed. We have developed a sandwich ELISA using two monoclonal antibodies for human plasma apo F, and analyzed apo F concentration in 397 Japanese healthy and 221 hypertriglyceridemic subjects. Our ELISA enables apo F to be assayed in the range of 0.6-25 µg/mL with intra- and inter-assay coefficients of variation less than 3.8% and 7.8%, respectively. In healthy subjects, plasma apo F concentration was 12.5±2.9 µg/mL (mean±SD), and was significantly higher in females than in males (p<0.05). By linear regression analysis in healthy subjects, plasma apo F concentration correlated positively with HDL cholesterol and apo A-I levels, and in males but not in females, negatively with apo B and triglyceride levels. It also correlated negatively with intrinsic CETP activity measured using intrinsic apo B-containing lipoprotein as an acceptor, and positively with PLTP mass and apo J levels. Apo F concentration in hypertriglyceridemic patients (10.3±3.1 µg/mL) was lower than in healthy controls (p<0.0001) and correlated positively with PLTP mass. Our ELISA is reliable and sensitive for the quantification of plasma apo F concentration. This system can be applicable for clinical significance in lipoprotein metabolism and reverse cholesterol transport.

USCG AIS Broadcast

Science.gov Websites

these cooler months. Did you know your body can cool 25 times faster in water than in air? That water Traffic Service began broadcasting Automatic Identification System (AIS) test messages to select test participants in the area via standard AIS channels. These broadcasts-originating from MMSI 003660471-are less

Is Apolipoprotein E4 an Important Risk Factor for Dementia in Persons with Down Syndrome?

PubMed

Rohn, Troy T; McCarty, Katie L; Love, Julia E; Head, Elizabeth

2014-12-08

Down syndrome is one of the most common genetic causes of intellectual disability and is characterized by a number of behavioral as well as cognitive symptoms. Triplication of all or part of human chromosome 21 has been considered as the main cause of Down syndrome. Due to the location of the amyloid precursor protein on chromosome 21, many of the neuropathological features of early-onset Alzheimer's disease including senile plaques and neurofibrillary tangles are also present in Down syndrome patients who are either demented or nondemented. Significant advances in medical treatment have increased longevity in people with Down syndrome resulting in an increased population that may be subjected to many of the same risk factors as those with Alzheimer's disease. It is well established that harboring one or both apolipoprotein E4 alleles greatly increases the risk for Alzheimer's disease. However, whether apolipoprotein E4 contributes to an earlier onset of dementia or increased mortality in Down syndrome patients is still a matter of debate. The purpose of this mini review is to provide an updated assessment on apolipoprotein E4 status and risk potential of developing dementia and mortality associated with Down syndrome.

Deploying Embodied AI into Virtual Worlds

NASA Astrophysics Data System (ADS)

Burden, David J. H.

The last two years have seen the start of commercial activity within virtual worlds. Unlike computer games where Non-Player-Character avatars are common, in most virtual worlds they are the exception — and until recently in Second Life they were non-existent. However there is real commercial scope for Als in these worlds — in roles from virtual sales staff and tutors to personal assistants. Deploying an embodied AI into a virtual world offers a unique opportunity to evaluate embodied Als, and to develop them within an environment where human and computer are on almost equal terms. This paper presents an architecture being used for the deployment of chatbot driven avatars within the Second Life virtual world, looks at the challenges of deploying an AI within such a virtual world, the possible implications for the Turing Test, and identifies research directions for the future.

AI techniques for optimizing multi-objective reservoir operation upon human and riverine ecosystem demands

NASA Astrophysics Data System (ADS)

Tsai, Wen-Ping; Chang, Fi-John; Chang, Li-Chiu; Herricks, Edwin E.

2015-11-01

Flow regime is the key driver of the riverine ecology. This study proposes a novel hybrid methodology based on artificial intelligence (AI) techniques for quantifying riverine ecosystems requirements and delivering suitable flow regimes that sustain river and floodplain ecology through optimizing reservoir operation. This approach addresses issues to better fit riverine ecosystem requirements with existing human demands. We first explored and characterized the relationship between flow regimes and fish communities through a hybrid artificial neural network (ANN). Then the non-dominated sorting genetic algorithm II (NSGA-II) was established for river flow management over the Shihmen Reservoir in northern Taiwan. The ecosystem requirement took the form of maximizing fish diversity, which could be estimated by the hybrid ANN. The human requirement was to provide a higher satisfaction degree of water supply. The results demonstrated that the proposed methodology could offer a number of diversified alternative strategies for reservoir operation and improve reservoir operational strategies producing downstream flows that could meet both human and ecosystem needs. Applications that make this methodology attractive to water resources managers benefit from the wide spread of Pareto-front (optimal) solutions allowing decision makers to easily determine the best compromise through the trade-off between reservoir operational strategies for human and ecosystem needs.

Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease: a mendelian randomisation analysis.

PubMed

Saleheen, Danish; Haycock, Philip C; Zhao, Wei; Rasheed, Asif; Taleb, Adam; Imran, Atif; Abbas, Shahid; Majeed, Faisal; Akhtar, Saba; Qamar, Nadeem; Zaman, Khan Shah; Yaqoob, Zia; Saghir, Tahir; Rizvi, Syed Nadeem Hasan; Memon, Anis; Mallick, Nadeem Hayyat; Ishaq, Mohammad; Rasheed, Syed Zahed; Memon, Fazal-Ur-Rehman; Mahmood, Khalid; Ahmed, Naveeduddin; Frossard, Philippe; Tsimikas, Sotirios; Witztum, Joseph L; Marcovina, Santica; Sandhu, Manjinder; Rader, Daniel J; Danesh, John

2017-07-01

(a) concentration, after adjustment for LPA KIV2 repeats and conventional lipids. Genome-wide analysis identified rs2457564 as a variant associated with smaller apolipoprotein(a) isoform size, but not lipoprotein(a) concentration, and rs3777392 as a variant associated with lipoprotein(a) concentration, but not apolipoprotein(a) isoform size. In 60 801 patients with coronary heart disease and 123 504 controls, OR for myocardial infarction was 0·96 (0·94-0·98; p<0·0001) per 1-SD increment in apolipoprotein(a) protein isoform size in serum due to rs2457564, which was directionally concordant with the OR observed in PROMIS for a similar change. The OR for myocardial infarction was 1·27 (1·07-1·50; p=0·007) per 1-SD increment in lipoprotein(a) concentration due to rs3777392, which was directionally concordant with the OR observed for a similar change in PROMIS. Human genetic data suggest that both smaller apolipoprotein(a) isoform size and increased lipoprotein(a) concentration are independent and causal risk factors for coronary heart disease. Lipoprotein(a)-lowering interventions could be preferentially effective in reducing the risk of coronary heart disease in individuals with smaller apolipoprotein(a) isoforms. British Heart Foundation, US National Institutes of Health, Fogarty International Center, Wellcome Trust, UK Medical Research Council, UK National Institute for Health Research, and Pfizer. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.

Influence of liver cancer on lipid and lipoprotein metabolism

PubMed Central

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

2006-01-01

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

Quercetin Represses Apolipoprotein B Expression by Inhibiting the Transcriptional Activity of C/EBPβ

PubMed Central

Inoue, Jun; Sato, Ryuichiro

2015-01-01

Quercetin is one of the most abundant polyphenolic flavonoids found in fruits and vegetables and has anti-oxidative and anti-obesity effects. Because the small intestine is a major absorptive organ of dietary nutrients, it is likely that highly concentrated food constituents, including polyphenols, are present in the small intestinal epithelial cells, suggesting that food factors may have a profound effect in this tissue. To identify novel targets of quercetin in the intestinal enterocytes, mRNA profiling using human intestinal epithelial Caco-2 cells was performed. We found that mRNA levels of some apolipoproteins, particularly apolipoprotein B (apoB), are downregulated in the presence of quercetin. On the exposure of Caco-2 cells to quercetin, both mRNA and protein levels of apoB were decreased. Promoter analysis of the human apoB revealed that quercetin response element is localized at the 5′-proximal promoter region, which contains a conserved CCAAT enhancer-binding protein (C/EBP)-response element. We found that quercetin reduces the promoter activity of apoB, driven by the enforced expression of C/EBPβ. Quercetin had no effect on either mRNA or protein levels of C/EBPβ. In contrast, we found that quercetin inhibits the transcriptional activity of C/EBPβ but not its recruitment to the apoB promoter. On the exposure of Caco-2 cells to quercetin 3-O-glucuronide, which is in a cell-impermeable form, no notable change in apoB mRNA was observed, suggesting an intracellular action of quercetin. In vitro interaction experiments using quercetin-conjugated beads revealed that quercetin binds to C/EBPβ. Our results describe a novel regulatory mechanism of transcription of apolipoprotein genes by quercetin in the intestinal enterocytes. PMID:25875015

T'ai chi ch'uan.

PubMed

Lewis, D E

2000-11-01

The Chinese practice of t'ai chi seems to be receiving increased interest in the West. This article gives a brief overview of t'ai chi, including its origins, development, principles and potential health benefits. The function of the essential elements of t'ai chi, namely the Form and chi kung are described and their potential benefits for patients and nurses are discussed. Exponents of t'ai chi believe that it has health benefits on physical, psychological and spiritual levels, thus promoting a feeling of well-being. In addition, regular practitioners are empowered to be in greater control of themselves, their health, and situations in which they find themselves.

Red blood cells play a role in reverse cholesterol transport.

PubMed

Hung, Kimberly T; Berisha, Stela Z; Ritchey, Brian M; Santore, Jennifer; Smith, Jonathan D

2012-06-01

Reverse cholesterol transport (RCT) involves the removal of cholesterol from peripheral tissue for excretion in the feces. Here, we determined whether red blood cells (RBCs) can contribute to RCT. We performed a series of studies in apolipoprotein AI-deficient mice where the high-density lipoprotein-mediated pathway of RCT is greatly diminished. RBCs carried a higher fraction of whole blood cholesterol than plasma in apolipoprotein AI-deficient mice, and as least as much of the labeled cholesterol derived from injected foam cells appeared in RBCs compared with plasma. To determine whether RBCs mediate RCT to the fecal compartment, we measured RCT in anemic and control apolipoprotein AI-deficient mice and found that anemia decreased RCT to the feces by over 35% after correcting for fecal mass. Transfusion of [(3)H]cholesterol-labeled RBCs led to robust delivery of the labeled cholesterol to the feces in apolipoprotein AI-deficient hosts. In wild-type mice, the majority of the blood cholesterol mass, as well as [(3)H]cholesterol derived from the injected foam cells, was found in plasma, and anemia did not significantly alter RCT to the feces after correction for fecal mass. The RBC cholesterol pool is dynamic and facilitates RCT of peripheral cholesterol to the feces, particularly in the low high-density lipoprotein state.

APOA1 and APOB polymorphisms and apolipoprotein concentrations as biomarkers of risk in acute coronary syndrome: Relationship with lipid-lowering therapy effectiveness.

PubMed

Casillas-Muñoz, Fidel; Valle, Yeminia; Muñoz-Valle, José Francisco; Martínez-Fernández, Diana Emilia; Reynoso-Villalpando, Gabriela Lizet; Flores-Salinas, Héctor Enrique; Llamas-Covarrubias, Mara Anaís; Padilla-Gutiérrez, Jorge Ramón

2017-10-06

Lipid metabolism alterations contribute to acute coronary syndrome (ACS). rs670, rs5070 and rs693 polymorphisms have shown to modify the risk of cardiovascular disease. Apolipoprotein A-I (ApoA-I) plays a major role in reverse cholesterol transport; apolipoprotein B (ApoB) contributes to accumulation of cholesterol in the plaque. The aim of this study was to investigate the association of rs670 and rs5070 polymorphisms of APOA1 and rs693 polymorphism of APOB with ACS and circulating levels of its proteins and find if ApoB/ApoA-I could be implemented as an independent parameter of risk for cardiovascular disease and as a biomarker of lipid-lowering therapy effectiveness in Mexican population. Three hundred patients with ACS and 300 control subjects (CS) were included. Neither genotype nor allele frequencies of rs670, rs5070 and rs693 polymorphisms showed statistical differences between groups. Serum levels of ApoA-I (195 vs. 161.4mg/dL; P<.001) and ApoB (167 vs. 136.9mg/dL; P<.001) were significantly higher in CS compared with ACS; however, there was no genetic association. Unstable angina patients showed the highest ApoA-I levels (males: 176.3mg/dL; females: 209.1mg/dL). The rs670, rs5070 and rs693 polymorphisms are not genetic susceptibility factors for ACS in Mexican population and had no effect on their apolipoprotein concentrations. In our population, ApoA-I, ApoB and HDL-C could be better biomarkers of cardiovascular risk and could indicate if statins doses reduce atherogenic particles properly. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Amyloid substance within stenotic aortic valves promotes mineralization.

PubMed

Audet, Audrey; Côté, Nancy; Couture, Christian; Bossé, Yohan; Després, Jean-Pierre; Pibarot, Philippe; Mathieu, Patrick

2012-10-01

Accumulation of apolipoproteins may play an important role in the pathobiology of calcific aortic valve disease (CAVD). We aimed to explore the hypothesis that apolipoprotein-derived amyloid could play a role in the development of CAVD. In 70 explanted CAVD valves and 15 control non-calcified aortic valves, we assessed the presence of amyloid by using Congo red staining. Immunohistochemistry was performed to document the presence of apolipoprotein AI (Apo-AI). Apoptosis was documented by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) studies performed in control and CAVD valves. Control valves were free of amyloid. Deposition of amyloid was detected in all CAVD valves, and the amount was positively correlated with plasma high-density lipoprotein and Apo-AI levels. Apo-AI within CAVD valves co-localized with intense staining of fibrillar amyloid. In turn, deposition of amyloid co-localized with apoptosis near mineralized areas. Isolation of amyloid fibrils confirmed that Apo-AI is a major component of amyloid deposits in CAVD. In vitro, CAVD-derived amyloid extracts increased apoptosis and mineralization of isolated aortic valvular interstitial cells. Apo-AI is a major component of amyloid substance present within CAVD valves. Furthermore, amyloid deposits participate in mineralization in CAVD by promoting apoptosis of valvular interstitial cells. © 2012 Blackwell Publishing Ltd.

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

PubMed Central

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

1999-01-01

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

Effects of the C161T polymorphism in the gene of peroxisome proliferators activated receptor γ on changes of plasma lipid and apolipoprotein ratios induced by a high carbohydrate diet in a healthy Chinese Han young population.

PubMed

Fan, Mei; Gong, Ren Rong; Lin, Jia; Jiang, Zhe; Li, Yuan Hao; Zhang, Rong Rong; Fang, Ding Zhi

2014-01-01

Changes in the ratios of plasma lipids and apolipoproteins may be associated with diets and the C161T polymorphism in the gene of peroxisome proliferators activated receptor gamma (PPARgamma). As a result, this study was to investigate the effects of this polymorphism on changes of the ratios induced by a high-carbohydrate (high-CHO) diet. After a washout diet of 54% carbohydrate for 7 days, 56 healthy young adults (22.89 +/- 1.80 years old) were given the high-CHO diet of 70% carbohydrate for 6 days. Height, weight, waist circumference (WC), glucose, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) AI, and apoB100 at baseline and before and after the high-CHO diet were measured. Body mass index (BMI), TG/HDL-C, log (TG/HDL-C), TC/HDL-C, LDL-C/HDL-C, and apoB100/apoAI were calculated. PPARgamma C161T was detected by a PCR-RFLP method. The relationship between the polymorphism and the ratios were analyzed. The female T carriers had higher BMI and WC than the female CC homozygotes at baseline and before and after the diet, higher glucose, TG/HDL-C and log (TG/HDL-C) before the diet. In males, when compared to the T carriers, the CC homozygotes had higher TG/HDL-C, log (TG/HDL-C) and apoB100/apoAI at baseline and before and after the diet, higher glucose at baseline, higher LDL-C/HDL-C and TC/HDL-C before and after the diet. Compared with those before the high-CHO diet, TC/HDL-C and LDL-C/HDL-C decreased after the diet regardless of gender and the genotypes. Decreased BMI and WC were observed in the male CC homozygotes but only decreased BMI in the female T carriers. Notably, decreased apoB100/apoAI was observed in the male T carriers, while elevated TG/HDL-C and log (TG/HDL-C) in the female CC homozygotes, and reduced glucose in the female T carriers. The results suggest that the interplay of gender, the PPARgamma C161T polymorphism and the high-CHO diet can

The BSM-AI project: SUSY-AI-generalizing LHC limits on supersymmetry with machine learning

NASA Astrophysics Data System (ADS)

Caron, Sascha; Kim, Jong Soo; Rolbiecki, Krzysztof; de Austri, Roberto Ruiz; Stienen, Bob

2017-04-01

A key research question at the Large Hadron Collider is the test of models of new physics. Testing if a particular parameter set of such a model is excluded by LHC data is a challenge: it requires time consuming generation of scattering events, simulation of the detector response, event reconstruction, cross section calculations and analysis code to test against several hundred signal regions defined by the ATLAS and CMS experiments. In the BSM-AI project we approach this challenge with a new idea. A machine learning tool is devised to predict within a fraction of a millisecond if a model is excluded or not directly from the model parameters. A first example is SUSY-AI, trained on the phenomenological supersymmetric standard model (pMSSM). About 300, 000 pMSSM model sets - each tested against 200 signal regions by ATLAS - have been used to train and validate SUSY-AI. The code is currently able to reproduce the ATLAS exclusion regions in 19 dimensions with an accuracy of at least 93%. It has been validated further within the constrained MSSM and the minimal natural supersymmetric model, again showing high accuracy. SUSY-AI and its future BSM derivatives will help to solve the problem of recasting LHC results for any model of new physics. SUSY-AI can be downloaded from http://susyai.hepforge.org/. An on-line interface to the program for quick testing purposes can be found at http://www.susy-ai.org/.

The advantages of haplotype analysis of the promoter region of the human apolipoprotein E gene.

PubMed

McLaughlin, D P; Sharma, A; McGinley, A; Samra, G S

2001-12-15

Polymorphisms in the regulatory region of the human apolipoprotein E gene (gene, APOE; protein, apoE) have been implicated in Alzheimer's disease. Here we describe in detail the advantages of a simple method for haplotype analysis of this region (at -491 and -427 bases relative to the transcription start site of the gene). The promoter region of the APOE gene was amplified by polymerase chain reaction (PCR) and this fragment was then used as a template for PCR with "nested" primers to generate a 228-bp product incorporating both the -491 and the -427 loci. PCR products were then digested with DraI and AluI together and subjected to polyacrylamide gel electrophoresis. The distinct pattern of bands appearing on the gel was then used to ascribe [-491,-427] haplotypes to each subject, from which -491 and -427 genotypes were inferred. -491 and -427 genotypes were also confirmed by digestion with DraI alone or AluI alone. Haplotype analysis was successful in all 20 samples analyzed and was 100% consistent with genotyping. We suggest that this is a reliable, time-saving method that the will be useful in large-scale APOE promoter genotyping studies. (c)2001 Elsevier Science.

Inhibition of transglutaminase 2 reduces efferocytosis in human macrophages: Role of CD14 and SR-AI receptors.

PubMed

Eligini, S; Fiorelli, S; Tremoli, E; Colli, S

2016-10-01

Transglutaminase 2 (TGM2), a member of the transglutaminase family of enzymes, is a multifunctional protein involved in numerous events spanning from cell differentiation, to signal transduction, apoptosis, and wound healing. It is expressed in a variety of cells, macrophages included. Macrophage TGM2 promotes the clearance of apoptotic cells (efferocytosis) and emerging evidence suggests that defective efferocytosis contributes to the consequences of inflammation-associated diseases, including atherosclerotic lesion progression and its sequelae. Of interest, active TGM2 identified in human atherosclerotic lesions plays critical roles in plaque stability through effects on matrix cross-linking and TGFβ activity. This study explores the mechanisms by which TGM2 controls efferocytosis in human macrophages. Herein we show that TGM2 increases progressively during monocyte differentiation towards macrophages and controls their efferocytic potential as well as morphology and viability. Two experimental approaches that took advantage of the inhibition of TGM2 activity and protein silencing give proof that TGM2 reduction significantly impairs macrophage efferocytosis. Among the mechanisms involved we highlighted a role of the receptors CD14 and SR-AI whose levels were markedly reduced by TGM2 inhibition. Conversely, CD36 receptor and αvβ3 integrin levels were not influenced. Of note, lipid accumulation and IL-10 secretion were reduced in macrophages displaying defective efferocytosis. Overall, our data define a crucial role of TGM2 activity during macrophage differentiation via mechanisms involving CD14 and SR-AI receptors and show that TGM2 inhibition triggers a pro-inflammatory phenotype. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Susceptibility of Mice to Trypanosoma evansi Treated with Human Plasma Containing Different Concentrations of Apolipoprotein L-1

PubMed Central

Fanfa, Vinicius R.; Otto, Mateus A.; Gressler, Lucas T.; Tavares, Kaio C.S.; Lazzarotto, Cícera R.; Tonin, Alexandre A.; Miletti, Luiz C.; Duarte, Marta M.M.F.; Monteiro, Silvia G.

2011-01-01

The aim of this study was to test the susceptibility of mice to Trypanosoma evansi treated with human plasma containing different concentrations of apolipoprotein L-1 (APOL1). For this experiment, a strain of T. evansi and human plasma (plasmas 1, 2, and 3) from 3 adult males clinically healthy were used. In vivo test used 50 mice divided in 5 groups (A to E) with 10 animals in each group. Animals of groups B to E were infected, and then treated with 0.2 ml of human plasma in the following outline: negative control (A), positive control (B), treatment with plasma 1 (C), treatment with plasma 2 (D), and treatment with plasma 3 (E). Mice treated with human plasma showed an increase in longevity of 40.9±0.3 (C), 20±9.0 (D) and 35.6±9.3 (E) days compared to the control group (B) which was 4.3±0.5 days. The number of surviving mice and free of the parasite (blood smear and PCR negative) at the end of the experiment was 90%, 0%, and 60% for groups C, D, and E, respectively. The quantification of APOL1 was performed due to the large difference in the treatments that differed in the source plasma. In plasmas 1, 2, and 3 was detected the concentration of 194, 99, and 115 mg/dl of APOL1, respectively. However, we believe that this difference in the treatment efficiency is related to the level of APOL1 in plasmas. PMID:22355213

Analysis of apolipoprotein genes and their involvement in disease response of channel catfish after bacterial infection.

PubMed

Yang, Yujia; Fu, Qiang; Zhou, Tao; Li, Yun; Liu, Shikai; Zeng, Qifan; Wang, Xiaozhu; Jin, Yulin; Tian, Changxu; Qin, Zhenkui; Dunham, Rex; Liu, Zhanjiang

2017-02-01

Apolipoproteins are protein component of plasma lipoproteins. They exert crucial roles in lipoprotein metabolism and serve as enzyme cofactors, receptor ligands, and lipid transfer carriers in mammals. In teleosts, apolipoproteins are also involved in diverse processes including embryonic and ontogenic development, liver and digestive system organogenesis, and innate immunity. In this study, we identified a set of 19 apolipoprotein genes in channel catfish (Ictalurus punctatus). Phylogenetic analysis and syntenic analysis were conducted to determine their identities and evolutionary relationships. The expression signatures of apolipoproteins in channel catfish were determined in healthy tissues and after infections with two major bacterial pathogens, Edwardsiella ictaluri and Flavobacterium columnare. In healthy channel catfish, most apolipoprotein genes exhibited tissue-specific expression patterns in channel catfish. After ESC and columnaris infections, 5 and 7 apolipoprotein genes were differentially expressed respectively, which presented a pathogen-specific and time-dependent pattern of regulation. After ESC infection, three exchangeable apolipoproteins (apoA-IB, apoC-I, and apoE-B) were suppressed in catfish intestine, while two nonexchangeable apolipoproteins (apoB-A and apoB-B) were slightly up-regulated. After columnaris infection, apoB-B, apoD-B, and apoE-A were significantly down-regulated in catfish gill, while apoF, apoL-IV, apoO-like, and apo-14 kDa showed significantly up-regulation. Taken together, these results suggested that apolipoprotein genes may play significant roles in innate immune responses to bacterial pathogens in channel catfish. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

Graham, Mark J; Lee, Richard G; Bell, Thomas A; Fu, Wuxia; Mullick, Adam E; Alexander, Veronica J; Singleton, Walter; Viney, Nick; Geary, Richard; Su, John; Baker, Brenda F; Burkey, Jennifer; Crooke, Stanley T; Crooke, Rosanne M

2013-05-24

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

Measurement level AIS/radar fusion for maritime surveillance

NASA Astrophysics Data System (ADS)

Habtemariam, Biruk K.; Tharmarasa, R.; Meger, Eric; Kirubarajan, T.

2012-05-01

Using the Automatic Identification System (AIS) ships identify themselves intermittently by broadcasting their location information. However, traditionally radars are used as the primary source of surveillance and AIS is considered as a supplement with a little interaction between these data sets. The data from AIS is much more accurate than radar data with practically no false alarms. But unlike the radar data, the AIS measurements arrive unpredictably, depending on the type and behavior of a ship. The AIS data includes target IDs that can be associated to initialized tracks. In multitarget maritime surveillance environment, for some targets the revisit interval form the AIS could be very large. In addition, the revisit intervals for various targets can be different. In this paper, we proposed a joint probabilistic data association based tracking algorithm that addresses the aforementioned issues to fuse the radar measurements with AIS data. Multiple AIS IDs are assigned to a track, with probabilities updated by both AIS and radar measurements to resolve the ambiguity in the AIS ID source. Experimental results based on simulated data demonstrate the performance the proposed technique.

Comparison of AIS 1990 update 98 versus AIS 2005 for describing PMHS injuries in lateral and oblique sled tests

PubMed Central

Yoganandan, Narayan; Pintar, Frank A.; Humm, John R.; Stadter, Gregory W.; Curry, William H.; Brasel, Karen J.

2013-01-01

This study analyzed skeletal and organ injuries in pure lateral and oblique impacts from 20 intact post mortem human surrogate (PMHS) sled tests at 6.7 m/s. Injuries to the shoulder, thorax, abdomen, pelvis and spine were scored using AIS 1990–1998 update and 2005. The Injury Severity Scores (ISS) were extracted for both loadings from both versions. Mean age, stature, total body mass and body mass index for pure lateral and oblique tests: 58 and 55 years, 1.7 and 1.8 m, 69 and 66 kg, and 24 and 21 kg/m2. Skeletal injuries (ribs, sternum) occurred in both impacts. However, oblique impacts resulted in more injuries. Pure lateral and oblique impacts ISS: 0 to 16 and 0 to 24, representing a greater potential for injury-related consequences in real-world situations in oblique impacts. Internal organs were more involved in oblique impacts. ISS decreased in AIS 2005, reflecting changes to scoring and drawing attention to potential effects for pre-hospital care/medical aspects. Mean AIS scores for the two load vectors and two AIS coding schemes are included. From automotive crashworthiness perspectives, decreases in injury severities might alter injury risk functions with a shift to lower metrics for the same risk level than current risk estimations. This finding influences dummy-based injury criteria and occupant safety as risk functions are used for countermeasure effectiveness and cost-benefit analyses by regulatory bodies. Increase in organ injuries in oblique loading indicate the importance of this vector as current dummies and injury criteria used in regulations are based on pure lateral impact data. PMID:24406958

A Laboratory Exercise to Illustrate Protein-Membrane Interactions

ERIC Educational Resources Information Center

Weers, Paul M. M.; Prenner, Elmar J.; Curic, Spomenka; Lohmeier-Vogel, Elke M.

2016-01-01

The laboratory protocol presented here takes about 3 hours to perform and investigates protein and lipid interactions. Students first purify His6-tagged human apolipoprotein A-I (apoA-I) with Ni-NTA affinity resin in a simple batch protocol and prepare multilamellar vesicles (MLV) from pre-dried phospholipid films. When apoA-I is added to the MLV,…

Apolipoprotein-containing lipoprotein subclasses and subclinical atherosclerosis in systemic lupus erythematosus.

PubMed

Kiani, Adnan N; Fang, Hong; Akhter, Ehtisham; Quiroga, Carmen; Simpson, Nancy; Alaupovic, Petar; Magder, Laurence S; Petri, Michelle

2015-03-01

Traditional classification of hyperlipidemia using high-density lipoprotein, low-density lipoprotein (LDL), and very low-density lipoprotein does not provide information on lipoprotein function. Apolipoproteins (Apos), which are protein components of plasma lipoproteins (including A, B, C, D, E) with their different composition, metabolic, and atherogenic properties, provide insight on lipoprotein functioning. In particular, the Apo B/A-I ratio is associated with atherogenic LDL and development of cardiovascular disease. We explored the baseline association between these nontraditional risk factors with subclinical measures of atherosclerosis (coronary artery calcification [CAC] and carotid intima-media thickness [IMT]) in systemic lupus erythematosus (SLE). A total of 58 SLE patients (97% women, 58% white, 40% African American, and 2% other, mean ± SD age 44 ± 11 years) had measurement of Apo and lipoproteins by immunoturbidimetric procedures, electroimmunoassays, and immunoprecipitation. CAC was measured by helical computed tomography and carotid IMT by carotid duplex. This study was based on the baseline assessment of subclinical atherosclerosis in the Lupus Atherosclerosis Prevention Study. The measurement of the lipoproteins was made on sera collected at the same time. There was no association between cardioprotective Apos (Apo A-I, LpA-I, LpA-I:A-II) and CAC (P < 0.15, P < 0.41, and P < 0.39, respectively) or carotid IMT (P < 0.97, P < 0.53, and P < 0.76, respectively). CAC and carotid IMT did not associate with atherogenic Apos either, including LpB:E+LpB:C:E, Apo B, LpB, LpB:C, Apo C-III, Apo C-III-HS, Apo C-III-HP, Apo C-III-R, LpA-II:B:C:D:E, and Apo B/Apo A-I. Measures of disease activity, including physician's global assessment and Systemic Lupus Erythematosus Disease Activity Index, were not associated with CAC or carotid IMT. Neither cardioprotective nor atherogenic lipoproteins were associated with measures of subclinical atherosclerosis in this

Apolipoprotein A-I and B levels, dyslipidemia and metabolic syndrome in south-west Chinese women with PCOS.

PubMed

Zhang, Jinxia; Fan, Ping; Liu, Hongwei; Bai, Huai; Wang, Ying; Zhang, Feng

2012-08-01

What are the relationships between apolipoprotein (apo) A-I and apoB concentrations, the apoB/apoA-I ratio and the prevalences of dyslipidemia and metabolic syndrome (MS) in south-west Chinese women with polycystic ovary syndrome (PCOS). There is a relatively high incidence of dyslipidemia and MS in south-west Chinese women with PCOS, especially in patients without hyperandrogenism. Patients with dyslipidemia are more obese, and have a more adverse glucose and lipid metabolic profile and higher apoB levels and apoB/apoA-I ratio. The increased apoB levels and apoB/A1 ratio and the MS are strongly associated with PCOS, suggesting that there is an increased risk of cardiovascular diseases in these patients. Dyslipidemia and MS have been widely studied in women with PCOS, but to date no data from south-west Chinese subjects have been available. The apoB/apoA-I ratio has been reported to be strongly associated with MS and insulin resistance (IR) and to be a reliable parameter that reflects lipid disturbances and the potential to develop atherosclerosis, but its relationship with PCOS is unclear. DESIGN This case-control study included 406 patients with PCOS and 342 control women between 17 and 40 years of age from a population in south-west China during 2006-2011. The diagnosis of PCOS was based on the revised 2003 Rotterdam criteria. The control group, consisting of women with infertility due to a Fallopian obstruction or the husband's infertility, women undergoing a pre-pregnancy check and healthy volunteers, was recruited from the same hospital during the same period. All women were not taking any medication known to affect carbohydrate or lipid or hormone metabolism for at least 3 months prior to the study, and were studied during the follicular phase of their menstrual cycle. MS was assessed by the National Cholesterol Education Program-Adult treatment Panel (NCEP-ATP) III criteria modified for Asian populations. Dyslipidemia was defined by one or more of the

Measuring the Value of AI in Space Science and Exploration

NASA Astrophysics Data System (ADS)

Blair, B.; Parr, J.; Diamond, B.; Pittman, B.; Rasky, D.

2017-10-01

FDL is tackling knowledge gaps useful to the space program by forming small teams of industrial partners, cutting-edge AI researchers and space science domain experts, and tasking them to solve problems that are important to NASA as well as humanity's future.

Results from service tests on AI-91 gasoline

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

Turovskii, F.V.; Bakaleinik, A.M.; Belyaev, A.A.

1988-01-01

Research was conducted to establish whether the operational reliability of engines will be affected by the use of a gasoline with an octane number two points lower than that of commercial AI-93 leaded gasoline with knock resistance in acceleration that is better than that of the AI-93 by approximately the same amount. Extended road tests were run in VAZ-2106 and Moskvich-2140 automobiles using gasoline with a research octane number of 91, containing an antiknock additive based on tetramethyl lead, and AI-93. The experimental AI-91 and the commercial AI-93 gasolines were prepared from the same base blend. Average specific fuel consumptionsmore » were identical for automobiles using AI-93 and AI-91 with the tetramethyl lead additive. For automobiles using AI-91 with the additive and with ethyl bromide as a lead scavenger the fuel consumption was 2% lower.« less

The implementation of AI technologies in computer wargames

NASA Astrophysics Data System (ADS)

Tiller, John A.

2004-08-01

Computer wargames involve the most in-depth analysis of general game theory. The enumerated turns of a game like chess are dwarfed by the exponentially larger possibilities of even a simple computer wargame. Implementing challenging AI is computer wargames is an important goal in both the commercial and military environments. In the commercial marketplace, customers demand a challenging AI opponent when they play a computer wargame and are frustrated by a lack of competence on the part of the AI. In the military environment, challenging AI opponents are important for several reasons. A challenging AI opponent will force the military professional to avoid routine or set-piece approaches to situations and cause them to think much deeper about military situations before taking action. A good AI opponent would also include national characteristics of the opponent being simulated, thus providing the military professional with even more of a challenge in planning and approach. Implementing current AI technologies in computer wargames is a technological challenge. The goal is to join the needs of AI in computer wargames with the solutions of current AI technologies. This talk will address several of those issues, possible solutions, and currently unsolved problems.

Human apolipoprotein E ɛ4 expression impairs cerebral vascularization and blood–brain barrier function in mice

PubMed Central

Alata, Wael; Ye, Yue; St-Amour, Isabelle; Vandal, Milène; Calon, Frédéric

2015-01-01

Human apolipoprotein E (APOE) exists in three isoforms ɛ2, ɛ3, and ɛ4, of which APOE4 is the main genetic risk factor of Alzheimer's disease (AD). As cerebrovascular defects are associated with AD, we tested whether APOE genotype has an impact on the integrity and function of the blood–brain barrier (BBB) in human APOE-targeted replacement mice. Using the quantitative in situ brain perfusion technique, we first found lower (13.0% and 17.0%) brain transport coefficient (Clup) of [3H]-diazepam in APOE4 mice at 4 and 12 months, compared with APOE2 and APOE3 mice, reflecting a decrease in cerebral vascularization. Accordingly, results from immunohistofluorescence experiments revealed a structurally reduced cerebral vascularization (26% and 38%) and thinner basement membranes (30% and 35%) in 12-month-old APOE4 mice compared with APOE2 and APOE3 mice, suggesting vascular atrophy. In addition, APOE4 mice displayed a 29% reduction in [3H]-d-glucose transport through the BBB compared with APOE2 mice without significant changes in the expression of its transporter GLUT1 in brain capillaries. However, an increase of 41.3% of receptor for advanced glycation end products (RAGE) was found in brain capillaries of 12-month-old APOE4 mice. In conclusion, profound divergences were observed between APOE genotypes at the cerebrovascular interface, suggesting that APOE4-induced BBB anomalies may contribute to AD development. PMID:25335802

Scoring of anatomic injury after trauma: AIS 98 versus AIS 90--do the changes affect overall severity assessment?

PubMed

Skaga, Nils O; Eken, Torsten; Hestnes, Morten; Jones, J Mary; Steen, Petter A

2007-01-01

Although several changes were implemented in the 1998 update of the abbreviated injury scale (AIS 98) versus the previous AIS 90, both are still used worldwide for coding of anatomic injury in trauma. This could possibly invalidate comparisons between systems using different AIS versions. Our aim was to evaluate whether the use of different coding dictionaries affected estimation of Injury Severity Score (ISS), New Injury Severity Score (NISS) and probability of survival (Ps) according to TRISS in a hospital-based trauma registry. In a prospective study including 1654 patients from Ulleval University Hospital, a Norwegian trauma referral centre, patients were coded according to both AIS 98 and AIS 90. Agreement between the classifications of ISS, NISS and Ps according to TRISS methodology was estimated using intraclass correlation coefficients (ICC) with 95% CI. ISS changed for 378 of 1654 patients analysed (22.9%). One hundred and forty seven (8.9%) were coded differently due to different injury descriptions and 369 patients (22.3%) had a change in ISS value in one or more regions due to the different scoring algorithm for skin injuries introduced in AIS 98. This gave a minimal change in mean ISS (14.74 versus 14.54). An ICC value of 0.997 (95% CI 0.9968-0.9974) for ISS indicates excellent agreement between the scoring systems. There were no significant changes in NISS and Ps. There was excellent agreement for the overall population between ISS, NISS and Ps values obtained using AIS 90 and AIS 98 for injury coding. Injury descriptions for hypothermia were re-introduced in the recently published AIS 2005. We support this change as coding differences due to hypothermia were encountered in 4.3% of patients in the present study.

The Influence of Education and Apolipoprotein ε4 on Mortality in Community-Dwelling Elderly Men and Women.

PubMed

Appiah, Duke; Baumgartner, Richard N

2018-01-01

We investigated the risk of death in relation to the apolipoprotein ε 4 allele and evaluated how it interacts with education in 504 elderly adults (mean age 73 years, 65.3% women) who were enrolled in 1993 into the New Mexico Aging Process Study. During 9 years of follow-up, apolipoprotein ε 2 appeared to be associated with a lower risk for all-cause mortality (hazard ratio (HR) = 0.73, 95% confidence interval (CI): 0.30-1.71) compared to apolipoprotein ε 3 carriers in models adjusted for age, sociodemographic variables, medical conditions, adiposity, and lifestyle factors. The apolipoprotein ε 4 allele conferred almost a threefold elevated risk of mortality (HR = 2.76, CI: 1.42-5.37). An interaction between education and apolipoprotein e4 ( p =0.027) was observed with the HR of mortality among e4 carriers compared to noncarriers being 1.59 (0.64-3.96) for those with ≥college education; 6.66 (1.90-23.4) for those with some college or trade; and 14.1 (3.03-65.6) for participants with ≤high school education. No significant interaction was identified between apolipoprotein E genotype and cognitive function for mortality risk. These findings suggest that genetic (apolipoprotein ε 4) and environmental (education) factors act interactively to influences survival in the elderly with higher education attenuating the adverse effect of apolipoprotein ε 4 on mortality.

The Influence of Education and Apolipoprotein ε4 on Mortality in Community-Dwelling Elderly Men and Women

PubMed Central

Baumgartner, Richard N.

2018-01-01

We investigated the risk of death in relation to the apolipoprotein ε4 allele and evaluated how it interacts with education in 504 elderly adults (mean age 73 years, 65.3% women) who were enrolled in 1993 into the New Mexico Aging Process Study. During 9 years of follow-up, apolipoprotein ε2 appeared to be associated with a lower risk for all-cause mortality (hazard ratio (HR) = 0.73, 95% confidence interval (CI): 0.30–1.71) compared to apolipoprotein ε3 carriers in models adjusted for age, sociodemographic variables, medical conditions, adiposity, and lifestyle factors. The apolipoprotein ε4 allele conferred almost a threefold elevated risk of mortality (HR = 2.76, CI: 1.42–5.37). An interaction between education and apolipoprotein e4 (p=0.027) was observed with the HR of mortality among e4 carriers compared to noncarriers being 1.59 (0.64–3.96) for those with ≥college education; 6.66 (1.90–23.4) for those with some college or trade; and 14.1 (3.03–65.6) for participants with ≤high school education. No significant interaction was identified between apolipoprotein E genotype and cognitive function for mortality risk. These findings suggest that genetic (apolipoprotein ε4) and environmental (education) factors act interactively to influences survival in the elderly with higher education attenuating the adverse effect of apolipoprotein ε4 on mortality. PMID:29770230

Activation of lecithin: cholesterol acyltransferase by human apolipoprotein A-IV.

PubMed

Steinmetz, A; Utermann, G

1985-02-25

Human plasma apoproteins (apo) A-I and A-IV both activate the enzyme lecithin:cholesterol acyltransferase (EC 2.3.1.43). Lecithin:cholesterol acyltransferase activity was measured by the conversion of [4-14C] cholesterol to [4-14C]cholesteryl ester using artificial phospholipid/cholesterol/[4-14C]cholesterol/apoprotein substrates. The substrate was prepared by the addition of apoprotein to a sonicated aqueous dispersion of phospholipid/cholesterol/[4-14C]cholesterol. The activation of lecithin:cholesterol acyltransferase by apo-A-I and -A-IV differed, depending upon the nature of the hydrocarbon chains of the sn-L-alpha-phosphatidylcholine acyl donor. Apo-A-I was a more potent activator than apo-A-IV with egg yolk lecithin, L-alpha-dioleoylphosphatidylcholine, and L-alpha-phosphatidylcholine substituted with one saturated and one unsaturated fatty acid regardless of the substitution position. When L-alpha-phosphatidylcholine esterified with two saturated fatty acids was used as acyl donor, apo-A-IV was more active than apo-A-I in stimulating the lecithin:cholesterol acyltransferase reaction. Complexes of phosphatidylcholines substituted with two saturated fatty acids served as substrate for lecithin:cholesterol acyltransferase even in the absence of any activator protein. Essentially the same results were obtained when substrate complexes (phospholipid-cholesterol-[4-14C]cholesterol-apoprotein) were prepared by a detergent dialysis procedure. Apo-A-IV-L-alpha-dimyristoylphosphatidylcholine complexes thus prepared were shown to be homogeneous particles by column chromatography and density gradient ultracentrifugation. It is concluded that apo-A-IV is able to facilitate the lecithin:cholesterol acyltransferase reaction in vitro.

Development of CER-001: Preclinical Dose Selection Through to Phase I Clinical Findings.

PubMed

Keyserling, Constance H; Barbaras, Ronald; Benghozi, Renee; Dasseux, Jean-Louis

2017-05-01

CER-001 comprises recombinant human apolipoprotein A-I complexed with phospholipids that mimics natural, nascent, pre-β high-density lipoprotein (HDL). We present animal model data showing dose-dependent increases in cholesterol efflux with CER-001 and its subsequent elimination by reverse lipid transport, together with inhibition of atherosclerotic plaque progression. We report the first phase I study results with CER-001 in humans, starting at 0.25 mg/kg, which is 1/80th of the safe dose (20 mg/kg) established in 4-week multiple-dose animal studies dosed every second day. Healthy volunteers, 18-55 years old with a low-density lipoprotein-cholesterol:HDL-cholesterol ratio greater than 3.0, received single intravenous escalating doses of CER-001 (0.25-45.0 mg/kg) and placebo in a double-blind randomised cross-over fashion. Subjects were followed up for 3 weeks post-dose. Assessments included adverse event monitoring, blood sampling, and clinical laboratory measurements. Thirty-two subjects were enrolled. All CER-001 doses (0.25-45 mg/kg) were safe and well tolerated, with an adverse event profile similar to placebo. Effects on clinical chemistry, haematology and coagulation parameters were comparable to placebo. No adverse effects of CER-001 on electrocardiograms were observed. No antibodies to apolipoprotein A-I were detected following single-dose administration of CER-001. Plasma apolipoprotein A-I levels increased in a dose-related manner and returned to baseline by 24 h post-dose for doses up to 10 mg/kg but remained in circulation for >72 h post-dose for doses >10 mg/kg. CER-001 caused elevations in plasma cholesterol and total and unesterified cholesterol in the HDL fraction. Mobilisation of unesterified cholesterol in the HDL fraction was seen with CER-001 at doses as low as 2 mg/kg. CER-001 is well tolerated when administered to humans as single doses up to 45 mg/kg and mobilises and eliminates cholesterol via reverse lipid transport.

Why Don't Accounting Students like AIS?

ERIC Educational Resources Information Center

Vatanasakdakul, Savanid; Aoun, Chadi

2011-01-01

Purpose: The demand for Accounting Information Systems (AIS) knowledge has increased exponentially over the past two decades, but studying AIS has not proved easy for many accounting students. The aim of the study is to understand the challenges accounting students face in studying AIS through investigation of the factors which may be contributing…

Validation of the "HAMP" mapping algorithm: a tool for long-term trauma research studies in the conversion of AIS 2005 to AIS 98.

PubMed

Adams, Derk; Schreuder, Astrid B; Salottolo, Kristin; Settell, April; Goss, J Richard

2011-07-01

There are significant changes in the abbreviated injury scale (AIS) 2005 system, which make it impractical to compare patients coded in AIS version 98 with patients coded in AIS version 2005. Harborview Medical Center created a computer algorithm "Harborview AIS Mapping Program (HAMP)" to automatically convert AIS 2005 to AIS 98 injury codes. The mapping was validated using 6 months of double-coded patient injury records from a Level I Trauma Center. HAMP was used to determine how closely individual AIS and injury severity scores (ISS) were converted from AIS 2005 to AIS 98 versions. The kappa statistic was used to measure the agreement between manually determined codes and HAMP-derived codes. Seven hundred forty-nine patient records were used for validation. For the conversion of AIS codes, the measure of agreement between HAMP and manually determined codes was [kappa] = 0.84 (95% confidence interval, 0.82-0.86). The algorithm errors were smaller in magnitude than the manually determined coding errors. For the conversion of ISS, the agreement between HAMP versus manually determined ISS was [kappa] = 0.81 (95% confidence interval, 0.78-0.84). The HAMP algorithm successfully converted injuries coded in AIS 2005 to AIS 98. This algorithm will be useful when comparing trauma patient clinical data across populations coded in different versions, especially for longitudinal studies.

Space-based detection of spoofing AIS signals using Doppler frequency

NASA Astrophysics Data System (ADS)

Guo, Shanzeng

2014-05-01

The Automatic Identification System (AIS) is a self-reporting system based on VHF radio to transmit a vessel's identity, position, speed, heading and other parameters to improve maritime domain awareness. However, AIS information can be programmatically spoofed by terrorists or other criminals, who often choose to masquerade as innocent civilians and exploit the vulnerabilities of military and civilian infrastructures for their purposes. Therefore, detecting and localizing a spoofing AIS ship become a critical and challenging issue for maritime security. This paper presents an algorithm to detect and geolocalize a spoofing AIS emitter using space-based AIS signals with its Doppler frequency. With an AIS signal sensor on a fast orbiting satellite, the measured AIS Doppler frequency of an AIS emitter can be used to define a double-napped cone of which the satellite is at its vertex and satellite velocity coincides with its axis, such that the theoretical Doppler frequency derived from the radial velocity to the AIS emitter matches the measured Doppler frequency. All such matches can only lie on either cone extending out from the satellite, which cuts the Earth's surface in two curves, so we know that the AIS emitter must lie somewhere on these curves. Two such AIS Doppler frequency measurements for the same stationary AIS emitter produce two valid curves which intersect at the position of the AIS emitter. Multiple Doppler frequency measurements can be used to better estimate the position fix of an AIS emitter, hence determine the spoofing AIS ship if the estimated position fix unreasonably differs from the position carried in its AIS message. A set of formulas are derived which relate an AIS emitter position to its Doppler frequency measurements.

Quantifying the tracking capability of space-based AIS systems

NASA Astrophysics Data System (ADS)

Skauen, Andreas Nordmo

2016-01-01

The Norwegian Defence Research Establishment (FFI) has operated three Automatic Identification System (AIS) receivers in space. Two are on dedicated nano-satellites, AISSat-1 and AISSat-2. The third, the NORAIS Receiver, was installed on the International Space Station. A general method for calculating the upper bound on the tracking capability of a space-based AIS system has been developed and the results from the algorithm applied to AISSat-1 and the NORAIS Receiver individually. In addition, a constellation of AISSat-1 and AISSat-2 is presented. The tracking capability is defined as the probability of re-detecting ships as they move around the globe and is explained to represent and upper bound on a space-based AIS system performance. AISSat-1 and AISSat-2 operates on the nominal AIS1 and AIS2 channels, while the NORAIS Receiver data used are from operations on the dedicated space AIS channels, AIS3 and AIS4. The improved tracking capability of operations on the space AIS channels is presented.

47 CFR 80.393 - Frequencies for AIS stations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... (AIS 1) and 162.025 MHz (AIS 2), each with a 25 kHz bandwidth, may be authorized only for AIS. In... carriage requirements for non-Federal Government ships. These requirements are codified at 33 CFR 164.46...

47 CFR 80.393 - Frequencies for AIS stations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... (AIS 1) and 162.025 MHz (AIS 2), each with a 25 kHz bandwidth, may be authorized only for AIS. In... carriage requirements for non-Federal Government ships. These requirements are codified at 33 CFR 164.46...

Altering the time of the second gonadotropin-releasing hormone injection and artificial insemination (AI) during Ovsynch affects pregnancies per AI in lactating dairy cows.

PubMed

Brusveen, D J; Cunha, A P; Silva, C D; Cunha, P M; Sterry, R A; Silva, E P B; Guenther, J N; Wiltbank, M C

2008-03-01

Based on previous research, we hypothesized that Cosynch at 72 h [GnRH-7 d-PGF(2alpha)-72 h-GnRH + artificial insemination (AI)] would result in a greater number of pregnancies per AI (P/AI) than Cosynch at 48 h. Further, we hypothesized that P/AI would be improved to a greater extent when GnRH was administered at 56 h after PGF(2alpha) before AI at 72 h due to a more optimal interval between the LH surge and AI. Nine hundred twenty-seven lactating dairy cows (n = 1,507 AI) were blocked by pen, and pens rotated through treatments. All cows received GnRH followed 7 d later by PGF(2alpha) and then received one of the following: 1) GnRH + timed AI 48 h after PGF(2alpha) (Cosynch-48); 2) GnRH 56 h after PGF(2alpha) + timed AI 72 h after PGF(2alpha) (Ovsynch-56); or 3) GnRH + timed AI 72 h after PGF(2alpha) (Cosynch-72). Pregnancy diagnoses were performed by ultrasound at 31 to 33 d post-AI and again at 52 to 54 d post-AI. Overall P/AI were similar for the Cosynch-48 (29.2%) and Cosynch-72 (25.4%) groups. The Ovsynch-56 group had a greater P/AI (38.6%) than Cosynch-48 or Cosynch-72. Presynchronized first-service animals had greater P/AI than cows at later services in Cosynch-48 (36.2 vs. 23.0%) and Ovsynch-56 (44.8 vs. 32.7%) but not in Cosynch-72 (24.6 vs. 26.2%). Similarly, primiparous cows had greater P/AI than multiparous cows in Cosynch-48 (34.1 vs. 22.9%) and Ovsynch-56 (41.3 vs. 32.6%), but not Cosynch-72 (29.8 vs. 25.3%). In conclusion, we found no advantage to Cosynch at 72 h vs. 48 h. In contrast, we found a clear advantage to treating with GnRH at 56 h, 16 h before a 72-h AI, probably because of more-optimal timing of AI before ovulation.

AI applications to conceptual aircraft design

NASA Technical Reports Server (NTRS)

Chalfan, Kathryn M.

1990-01-01

This paper presents in viewgraph form several applications of artificial intelligence (AI) to the conceptual design of aircraft, including: an access manager for automated data management, AI techniques applied to optimization, and virtual reality for scientific visualization of the design prototype.

Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes.

PubMed

Calanna, S; Scicali, R; Di Pino, A; Knop, F K; Piro, S; Rabuazzo, A M; Purrello, F

2014-06-01

We aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia. Ninety-one subjects with prediabetes according to HbA1c, i.e. from 5.7 to 6.4% (39-46 mmol/mol), 50 newly diagnosed patients with HbA1c-defined type 2 diabetes (HbA1c ≥6.5% [≥48 mmol/mol]), and 67 controls with HbA1c lower than 5.7% (<39 mmol/mol), were studied. Fasting blood samples for lipid profiles, fatty liver index (FLI), bioimpedance analysis, ultrasound scan of the liver, and BARD (body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score for evaluation of liver fibrosis, were performed in all subjects. In comparison to controls, subjects with prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure, triglycerides levels and apolipoprotein B/apolipoprotein AI ratio, higher FLI, increased prevalence of and more severe hepatic steatosis, similar BARD score, and higher total body fat mass. In comparison to subjects with diabetes, subjects with prediabetes exhibited: similar blood pressure and apolipoprotein B/apolipoprotein AI ratio, similar FLI, reduced prevalence of and less severe hepatic steatosis, lower BARD score, increased percent fat and lower total body muscle mass. In comparison to controls, subjects with diabetes showed: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure and triglycerides levels, higher FLI, increased prevalence of and more severe hepatic steatosis, higher BARD score, and higher total body muscle mass. Moreover, HbA1c was correlated with BMI, HOMA-IR, triglycerides, HDL cholesterol, AST, and ALT. Subjects with HbA1c-defined prediabetes and type 2 diabetes, respectively, are characterised by abnormalities in lipid profile and liver steatosis, thus exhibiting a severe risk profile for cardiovascular and liver diseases. Copyright © 2014

AI in space: Past, present, and possible futures

NASA Technical Reports Server (NTRS)

Rose, Donald D.; Post, Jonathan V.

1992-01-01

While artificial intelligence (AI) has become increasingly present in recent space applications, new missions being planned will require even more incorporation of AI techniques. In this paper, we survey some of the progress made to date in implementing such programs, some current directions and issues, and speculate about the future of AI in space scenarios. We also provide examples of how thinkers from the realm of science fiction have envisioned AI's role in various aspects of space exploration.

Mapping Fishing Effort through AIS Data

PubMed Central

Natale, Fabrizio; Gibin, Maurizio; Alessandrini, Alfredo; Vespe, Michele; Paulrud, Anton

2015-01-01

Several research initiatives have been undertaken to map fishing effort at high spatial resolution using the Vessel Monitoring System (VMS). An alternative to the VMS is represented by the Automatic Identification System (AIS), which in the EU became compulsory in May 2014 for all fishing vessels of length above 15 meters. The aim of this paper is to assess the uptake of the AIS in the EU fishing fleet and the feasibility of producing a map of fishing effort with high spatial and temporal resolution at European scale. After analysing a large AIS dataset for the period January-August 2014 and covering most of the EU waters, we show that AIS was adopted by around 75% of EU fishing vessels above 15 meters of length. Using the Swedish fleet as a case study, we developed a method to identify fishing activity based on the analysis of individual vessels’ speed profiles and produce a high resolution map of fishing effort based on AIS data. The method was validated using detailed logbook data and proved to be sufficiently accurate and computationally efficient to identify fishing grounds and effort in the case of trawlers, which represent the largest portion of the EU fishing fleet above 15 meters of length. Issues still to be addressed before extending the exercise to the entire EU fleet are the assessment of coverage levels of the AIS data for all EU waters and the identification of fishing activity in the case of vessels other than trawlers. PMID:26098430

Mapping Fishing Effort through AIS Data.

PubMed

Natale, Fabrizio; Gibin, Maurizio; Alessandrini, Alfredo; Vespe, Michele; Paulrud, Anton

2015-01-01

Several research initiatives have been undertaken to map fishing effort at high spatial resolution using the Vessel Monitoring System (VMS). An alternative to the VMS is represented by the Automatic Identification System (AIS), which in the EU became compulsory in May 2014 for all fishing vessels of length above 15 meters. The aim of this paper is to assess the uptake of the AIS in the EU fishing fleet and the feasibility of producing a map of fishing effort with high spatial and temporal resolution at European scale. After analysing a large AIS dataset for the period January-August 2014 and covering most of the EU waters, we show that AIS was adopted by around 75% of EU fishing vessels above 15 meters of length. Using the Swedish fleet as a case study, we developed a method to identify fishing activity based on the analysis of individual vessels' speed profiles and produce a high resolution map of fishing effort based on AIS data. The method was validated using detailed logbook data and proved to be sufficiently accurate and computationally efficient to identify fishing grounds and effort in the case of trawlers, which represent the largest portion of the EU fishing fleet above 15 meters of length. Issues still to be addressed before extending the exercise to the entire EU fleet are the assessment of coverage levels of the AIS data for all EU waters and the identification of fishing activity in the case of vessels other than trawlers.

Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans

PubMed Central

Sakamoto, Norihisa; Tsuji, Kazuhide; Muul, Linda M.; Lawler, Ann M.; Petricoin, Emanuel F.; Candotti, Fabio; Metcalf, Julia A.; Tavel, Jorge A.; Lane, H. Clifford; Urba, Walter J.; Fox, Bernard A.; Varki, Ajit; Lunney, Joan K.

2007-01-01

Recent studies have demonstrated that cell populations intended for therapeutic purposes that are cultured in heterologous animal products can acquire xenoantigens, potentially limiting their utility. In investigations of the immune response to murine embryonic stem cells, we found that a strong antibody response was generated after the second infusion. Both polyclonal and monoclonal antibody responses, derived from immunized mice, were found to be specific for bovine apolipoprotein B-100, which binds to abundant low-density lipoprotein receptors on the cell surface and is internalized. Here we show that in the majority of patients administered 3 different types of cell-based therapies using cells grown in fetal calf serum-containing media, an antibody response to bovine apolipoprotein B-100 develops after the second infusion and is the dominant specificity. The known and potential clinical effects of such antibodies are discussed. PMID:17395779

USACE AIS Transmit Technical Support Summary Report

DTIC Science & Technology

2014-09-01

the TAG block for the correct transmitters, and then send to the USACE AIS network. B. Outbound openings in the USCG firewall for the USCG Message...USACE AIS Transmit Technical Support Summary Report Distribution Statement A: Approved for public release; distribution is unlimited...September 2014 Report No. CD-D-09-15 USACE AIS Transmit Technical Support Summary Report ii UNCLAS//Public | CG-926 RDC | I. Gonin et al. Public

Apolipoprotein L1 and kidney disease in African Americans

PubMed Central

Friedman, David J.; Pollak, Martin R.

2016-01-01

Genetic variants in the Apolipoprotein L1 (APOL1) gene cause high rates of kidney disease in African Americans. These variants, found only in individuals with recent African ancestry, confer enhanced innate immunity against African trypanosomes. Though they are among the most powerful disease-causing common variants discovered to date, we are just beginning to understand how they promote kidney injury. Since APOL1 is only present in a few primate species, much of our current knowledge has come from natural experiments in humans and in vitro studies while awaiting the development of transgenic animal models. Understanding more about the function of ApoL1 and how the high-risk variants behave differently from other ApoL1 molecules is a high priority in kidney disease research. PMID:26947522

Screening for familial hypercholesterolaemia by measurement of apolipoproteins in capillary blood.

PubMed Central

Skovby, F; Micic, S; Jepsen, B; Larsen, S O; Hansen, B; Tegllund, L; Pedersen, B N

1991-01-01

A total of 3025 families with schoolchildren aged 6-8 years were offered pilot screening for familial hypercholesterolaemia by measurement of the concentrations of apolipoproteins A-1 and B in the children's capillary blood and by analysis of their family histories of early ischaemic heart disease. The concentrations of the apolipoproteins were determined by double rocket immunoelectrophoresis of an eluate of blood spotted on filter paper. Results were available from 2085 children. Because their B:A-1 ratio was above the 97.5 centile and their concentration of B was above the 99th centile, 54 children (2.6%) were selected to have their apolipoprotein concentrations reassessed. The 17 children (0.8%) whose values were persistently above the chosen cut off points, and all of their available first and second degree relatives, had fasting determinations of serum lipid concentrations carried out. Raised serum concentrations of low density lipoprotein cholesterol and an autosomal dominant pattern of hypercholesterolaemia were found in 12 children and 10 families, respectively, suggesting a higher incidence of familial hypercholesterolaemia than the reported 1:500. Further investigations among family members disclosed hypercholesterolaemia in 29 relatives. A family history of early ischaemic heart disease was elicited by questionnaire, and was positive in only five of the 12 schoolchildren with hypercholesterolaemia. We conclude that analysis of apolipoproteins from capillary blood spotted on filter paper is suitable for screening for familial hypercholesterolaemia, and that this method is more efficient than screening based on family history. PMID:1863097

33 CFR 164.46 - Automatic Identification System (AIS).

Code of Federal Regulations, 2014 CFR

2014-07-01

... (AIS). 164.46 Section 164.46 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Identification System (AIS). (a) The following vessels must have a properly installed, operational, type approved AIS as of the date specified: (1) Self-propelled vessels of 65 feet or more in length, other than...

33 CFR 164.46 - Automatic Identification System (AIS).

Code of Federal Regulations, 2013 CFR

2013-07-01

... (AIS). 164.46 Section 164.46 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Identification System (AIS). (a) The following vessels must have a properly installed, operational, type approved AIS as of the date specified: (1) Self-propelled vessels of 65 feet or more in length, other than...

33 CFR 164.46 - Automatic Identification System (AIS).

Code of Federal Regulations, 2010 CFR

2010-07-01

... (AIS). 164.46 Section 164.46 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Identification System (AIS). (a) The following vessels must have a properly installed, operational, type approved AIS as of the date specified: (1) Self-propelled vessels of 65 feet or more in length, other than...

33 CFR 164.46 - Automatic Identification System (AIS).

Code of Federal Regulations, 2011 CFR

2011-07-01

... (AIS). 164.46 Section 164.46 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Identification System (AIS). (a) The following vessels must have a properly installed, operational, type approved AIS as of the date specified: (1) Self-propelled vessels of 65 feet or more in length, other than...

33 CFR 164.46 - Automatic Identification System (AIS).

Code of Federal Regulations, 2012 CFR

2012-07-01

... (AIS). 164.46 Section 164.46 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Identification System (AIS). (a) The following vessels must have a properly installed, operational, type approved AIS as of the date specified: (1) Self-propelled vessels of 65 feet or more in length, other than...

Arco foresees productivity increases with AI technologies

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

Smutz, J.

1989-01-09

Efforts are under way in exploration, production, and drilling to exploit the powerful technology known as artificial intelligence (AI). Arco Oil and Gas Co. (AOGC) foresees AI increasing productivity in nearly every aspect of its business. The industry trend toward applying state-of-the-art technology to exploration and production applications is creating a definite realignment of resources within AOGC information services. AI technologies such as expert systems represent a powerful, yet complex opportunity. The learning curve with which AI technologies challenge us can be effectively addressed through progressive hands-on experience. By beginning where cost effectiveness can be easily demonstrated and evolving tomore » more ambitious projects, this new way of thinking about applications can be effectively assimilated.« less

Tactical AI in Real Time Strategy Games

DTIC Science & Technology

2015-03-26

TACTICAL AI IN REAL TIME STRATEGY GAMES THESIS Donald A. Gruber, Capt, USAF AFIT-ENG-MS-15-M-021 DEPARTMENT OF THE AIR FORCE AIR UNIVERSITY AIR FORCE...protection in the United States. AFIT-ENG-MS-15-M-021 TACTICAL AI IN REAL TIME STRATEGY GAMES THESIS Presented to the Faculty Department of Electrical...DISTRIBUTION STATEMENT A APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED. AFIT-ENG-MS-15-M-021 TACTICAL AI IN REAL TIME STRATEGY GAMES THESIS Donald A

T'ai Chi

MedlinePlus

... who practice it wear a martial arts training uniform. T'ai chi is usually practiced barefoot or ... health problem. Is your schedule jam-packed with school, work, and social activities? Here are a few ...

AI challenges for spacecraft control programs

NASA Technical Reports Server (NTRS)

Lightfoot, Patricia

1986-01-01

The application of AI technology to the spacecraft and experiment command and control systems environment is proposed. The disadvantages of the present methods for analyzing and resolving spacecraft experiment command and control problems are discussed. The potential capabilities and advantages of using AI for the spacecraft and experiment command and control systems are described.

PCSK9 inhibition with alirocumab reduces lipoprotein(a) levels in nonhuman primates by lowering apolipoprotein(a) production rate.

PubMed

Croyal, Mikaël; Tran, Thi-Thu-Trang; Blanchard, Rose Hélène; Le Bail, Jean-Christophe; Villard, Elise F; Poirier, Bruno; Aguesse, Audrey; Billon-Crossouard, Stéphanie; Ramin-Mangata, Stéphane; Blanchard, Valentin; Nativel, Brice; Chemello, Kévin; Khantalin, Ilya; Thedrez, Aurélie; Janiak, Philip; Krempf, Michel; Boixel, Christophe; Lambert, Gilles; Guillot, Etienne

2018-05-31

Therapeutic antibodies targeting proprotein convertase subtilisin kexin type 9 (PCSK9) (e.g. alirocumab) lower low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] levels in clinical trials. We recently showed that PCSK9 enhances apolipoprotein(a) [apo(a)] secretion from primary human hepatocytes but does not affect Lp(a) cellular uptake. Here, we aimed to determine how PCSK9 neutralization modulates Lp(a) levels in vivo Six nonhuman primates (NHP) were treated with alirocumab or a control antibody (IgG1) in a crossover protocol. After the lowering of lipids reached steady state, NHP received an intravenous injection of [ 2 H 3 ]-leucine, and blood samples were collected sequentially over 48 h. Enrichment of apolipoproteins in [ 2 H 3 ]-leucine was assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Kinetic parameters were calculated using numerical models with the SAAMII software. Compared with IgG1, alirocumab significantly reduced total cholesterol (TC) (-28%), LDL-C (-67%), Lp(a) (-56%), apolipoprotein B100 (apoB100) (-53%), and apo(a) (-53%). Alirocumab significantly increased the fractional catabolic rate of apoB100 (+29%) but not that of apo(a). Conversely, alirocumab sharply and significantly reduced the production rate (PR) of apo(a) (-42%), but not significantly that of apoB100, compared with IgG1, respectively.In line with the observations made in human hepatocytes, the present kinetic study establishes that PCSK9 neutralization with alirocumab efficiently reduces circulating apoB100 and apo(a) levels by distinct mechanisms: apoB primarily by enhancing its catabolism and apo(a) primarily by lowering its production. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil.

PubMed

Mitter, Sumeet S; Oriá, Reinaldo B; Kvalsund, Michelle P; Pamplona, Paula; Joventino, Emanuella Silva; Mota, Rosa M S; Gonçalves, Davi C; Patrick, Peter D; Guerrant, Richard L; Lima, Aldo A M

2012-01-01

Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children. A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ) received 200,000 IU of retinol (every four months), zinc (40 mg twice weekly), or both for one year, with half of each group receiving glutamine supplementation for 10 days. Height-for-age z-scores, weight-for-age z-scores, weight-for-height z-scores, and lactulose:mannitol ratios were assessed during the initial four months of treatment. An average of four years (range 1.4-6.6) later, the children underwent cognitive testing to evaluate non-verbal intelligence, coding, verbal fluency, verbal learning, and delayed verbal learning. Apolipoprotein E4 carriage was determined by PCR analysis for 144 children. Thirty-seven children were apolipoprotein E4(+), with an allele frequency of 13.9%. Significant associations were found for vitamin A and glutamine with intestinal barrier function. Apolipoprotein E4(+) children receiving glutamine presented significant positive Pearson correlations between the change in height-for-age z-scores over four months and delayed verbal learning, along with correlated changes over the same period in weight-for-age z-scores and weight-for-height z-scores associated with non-verbal intelligence quotients. There was a significant correlation between vitamin A supplementation of apolipoprotein E4(+) children and improved delta lactulose/mannitol. Apolipoprotein E4(-) children, regardless of intervention, exhibited negative Pearson correlations between the change in lactulose-to-mannitol ratio over four months and verbal learning and non-verbal intelligence. During development, apolipoprotein E4 may function concomitantly with gut-tropic nutrients to

JGOMAS: New Approach to AI Teaching

ERIC Educational Resources Information Center

Barella, A.; Valero, S.; Carrascosa, C.

2009-01-01

This paper presents a new environment for teaching practical work in AI subjects. The main purpose of this environment is to make AI techniques more appealing to students and to facilitate the use of the toolkits which are currently widely used in research and development. This new environment has a toolkit for developing and executing agents,…

Soya phytoestrogens, genistein and daidzein, decrease apolipoprotein B secretion from HepG2 cells through multiple mechanisms.

PubMed Central

Borradaile, Nica M; de Dreu, Linda E; Wilcox, Lisa J; Edwards, Jane Y; Huff, Murray W

2002-01-01

Diets containing the soya-derived phytoestrogens, genistein and daidzein, decrease plasma cholesterol in humans and experimental animals. The mechanisms responsible for the hypocholesterolaemic effects of these isoflavones are unknown. The present study was conducted to determine if genistein and daidzein regulate hepatocyte cholesterol metabolism and apolipoprotein (apo) B secretion in cultured human hepatoma (HepG2) cells. ApoB secretion was decreased dose-dependently by up to 63% and 71% by genistein and daidzein (100 microM; P<0.0001) respectively. In contrast, no effect on apoAI secretion was observed. Cellular cholesterol synthesis was inhibited 41% by genistein (100 microM; P<0.005) and 18% by daidzein (100 microM; P<0.05), which was associated with significant increases in 3-hydroxy-3-methylglutaryl-CoA reductase mRNA. Cellular cholesterol esterification was decreased 56% by genistein (100 microM; P<0.04) and 29% by daidzein (100 microM; P<0.04); however, mRNA levels for acyl-CoA:cholesterol acyltransferase (ACAT) 1 and ACAT2 were unaffected. At 100 microM, both isoflavones equally inhibited the activities of both forms of ACAT in cells transfected with either ACAT1 or ACAT2. Genistein (100 microM) and daidzein (100 microM) significantly decreased the activity of microsomal triacylglycerol transfer protein (MTP) by 30% and 24% respectively, and significantly decreased MTP mRNA levels by 35% and 55%. Both isoflavones increased low-density lipoprotein (LDL)-receptor mRNA levels by 3- to 6-fold (100 microM; P<0.03) and significantly increased the binding, uptake and degradation of (125)I-labelled LDL, suggesting that enhanced reuptake of newly secreted apoB-containing lipoproteins contributed to the net decrease in apoB secretion. These results indicate that genistein and daidzein inhibit hepatocyte apoB secretion through several mechanisms, including inhibition of cholesterol synthesis and esterification, inhibition of MTP activity and expression and

Application of Artificial Intelligence (AI) Programming Techniques to Tactical Guidance for Fighter Aircraft

NASA Technical Reports Server (NTRS)

McManus, John W.; Goodrich, Kenneth H.

1989-01-01

A research program investigating the use of Artificial Intelligence (AI) techniques to aid in the development of a Tactical Decision Generator (TDG) for Within-Visual-Range (WVR) air combat engagements is discussed. The application of AI methods for development and implementation of the TDG is presented. The history of the Adaptive Maneuvering Logic (AML) program is traced and current versions of the AML program are compared and contrasted with the TDG system. The Knowledge-Based Systems (KBS) used by the TDG to aid in the decision-making process are outlined in detail and example rules are presented. The results of tests to evaluate the performance of the TDG versus a version of AML and versus human pilots in the Langley Differential Maneuvering Simulator (DMS) are presented. To date, these results have shown significant performance gains in one-versus-one air combat engagements, and the AI-based TDG software has proven to be much easier to modify than the updated FORTRAN AML programs.

GLADIS: GLobal AIS & Data-X International Satellite Constellation

DTIC Science & Technology

2008-01-01

1Approved for public release; distribution is unlimited GLADIS : GLobal AIS & Data-X International Satellite Constellation Space-Based System for...TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE GLADIS : GLobal AIS & Data-X International Satellite Constellation 5a. CONTRACT NUMBER 5b...Maritime & Technology Challenges • GLADIS Mission Objective • AIS & Data-X capabilities • GLADIS Architecture • International Strategy – MSSIS as Model

The AI Interdisciplinary Context: Single or Multiple Research Bases?

ERIC Educational Resources Information Center

Khawam, Yves J.

1992-01-01

This study used citation analysis to determine whether the disciplines contributing to the journal literature of artificial intelligence (AI)--philosophy, psychology, linguistics, computer science, and engineering--share a common AI research base. The idea that AI consists of a completely interdisciplinary endeavor was refuted. (MES)

Comparisons of the Outcome Prediction Performance of Injury Severity Scoring Tools Using the Abbreviated Injury Scale 90 Update 98 (AIS 98) and 2005 Update 2008 (AIS 2008)

PubMed Central

Tohira, Hideo; Jacobs, Ian; Mountain, David; Gibson, Nick; Yeo, Allen

2011-01-01

The Abbreviated Injury Scale (AIS) was revised in 2005 and updated in 2008 (AIS 2008). We aimed to compare the outcome prediction performance of AIS-based injury severity scoring tools by using AIS 2008 and AIS 98. We used all major trauma patients hospitalized to the Royal Perth Hospital between 1994 and 2008. We selected five AIS-based injury severity scoring tools, including Injury Severity Score (ISS), New Injury Severity Score (NISS), modified Anatomic Profile (mAP), Trauma and Injury Severity Score (TRISS) and A Severity Characterization of Trauma (ASCOT). We selected survival after injury as a target outcome. We used the area under the Receiver Operating Characteristic curve (AUROC) as a performance measure. First, we compared the five tools using all cases whose records included all variables for the TRISS (complete dataset) using a 10-fold cross-validation. Second, we compared the ISS and NISS for AIS 98 and AIS 2008 using all subjects (whole dataset). We identified 1,269 and 4,174 cases for a complete dataset and a whole dataset, respectively. With the 10-fold cross-validation, there were no clear differences in the AUROCs between the AIS 98- and AIS 2008-based scores. With the second comparison, the AIS 98-based ISS performed significantly worse than the AIS 2008-based ISS (p<0.0001), while there was no significant difference between the AIS 98- and AIS 2008-based NISSs. Researchers should be aware of these findings when they select an injury severity scoring tool for their studies. PMID:22105401

Comparisons of the Outcome Prediction Performance of Injury Severity Scoring Tools Using the Abbreviated Injury Scale 90 Update 98 (AIS 98) and 2005 Update 2008 (AIS 2008).

PubMed

Tohira, Hideo; Jacobs, Ian; Mountain, David; Gibson, Nick; Yeo, Allen

2011-01-01

The Abbreviated Injury Scale (AIS) was revised in 2005 and updated in 2008 (AIS 2008). We aimed to compare the outcome prediction performance of AIS-based injury severity scoring tools by using AIS 2008 and AIS 98. We used all major trauma patients hospitalized to the Royal Perth Hospital between 1994 and 2008. We selected five AIS-based injury severity scoring tools, including Injury Severity Score (ISS), New Injury Severity Score (NISS), modified Anatomic Profile (mAP), Trauma and Injury Severity Score (TRISS) and A Severity Characterization of Trauma (ASCOT). We selected survival after injury as a target outcome. We used the area under the Receiver Operating Characteristic curve (AUROC) as a performance measure. First, we compared the five tools using all cases whose records included all variables for the TRISS (complete dataset) using a 10-fold cross-validation. Second, we compared the ISS and NISS for AIS 98 and AIS 2008 using all subjects (whole dataset). We identified 1,269 and 4,174 cases for a complete dataset and a whole dataset, respectively. With the 10-fold cross-validation, there were no clear differences in the AUROCs between the AIS 98- and AIS 2008-based scores. With the second comparison, the AIS 98-based ISS performed significantly worse than the AIS 2008-based ISS (p<0.0001), while there was no significant difference between the AIS 98- and AIS 2008-based NISSs. Researchers should be aware of these findings when they select an injury severity scoring tool for their studies.

[T'ai chi in the elderly: practical aspects].

PubMed

Kressig, Reto W; Beauchet, Olivier; Tharicharu, Jai

2003-11-01

New approaches to health promotion for the growing geriatric population are needed. Low to moderately intense exercise programs, such as T'ai Chi seem particularly appropriate for older individuals because of many worthwhile physiological and psychological long-term benefits. T'ai Chi reduces falls and improves postural stability in older adults. It also has a positive impact on muscle strength and cardiovascular fitness and can improve mobility in patients with rheumatoid arthritis. It imparts a sense of well-being and confidence, and can reduce fear of falling in older adults. This article reviews the current medical literature regarding the multiple effects of T'ai Chi. Historical aspects of T'ai Chi and its current adaptation for practice by healthy older adults are presented. Finally, a set of modified exercises is proposed that is based on underlying principles of T'ai Chi and can be applied to patients with mild to moderate cognitive impairment.

Insulin resistance, dyslipidemia, and apolipoprotein E interactions as mechanisms in cognitive impairment and Alzheimer's disease

PubMed Central

Salameh, Therese S; Rhea, Elizabeth M; Hanson, Angela J

2016-01-01

An increased risk for Alzheimer's disease is associated with dyslipidemia and insulin resistance. A separate literature shows the genetic risk for developing Alzheimer's disease is strongly correlated to the presence of the E4 isoform of the apolipoprotein E carrier protein. Understanding how apolipoprotein E carrier protein, lipids, amyloid β peptides, glucose, central nervous system insulin, and peripheral insulin interact with one another in Alzheimer's disease is an area of increasing interest. Here, we will review the evidence relating apolipoprotein E carrier protein, lipids, and insulin action to Alzheimer's disease and Aβ peptides and then propose mechanisms as to how these factors might interact with one another to impair cognition and promote Alzheimer's disease. PMID:27470930

The enzyme lecithin-cholesterol acyltransferase esterifies cerebrosterol and limits the toxic effect of this oxysterol on SH-SY5Y cells.

PubMed

La Marca, Valeria; Spagnuolo, Maria Stefania; Cigliano, Luisa; Marasco, Daniela; Abrescia, Paolo

2014-07-01

Cholesterol is mostly removed from the CNS by its conversion to cerebrosterol (24(S)-hydroxycholesterol, 24(S)OH-C), which is transported to the circulation for bile formation in liver. A neurotoxic role of this oxysterol was previously demonstrated in cell culture. Here, we provide evidence that the enzyme lecithin-cholesterol acyltransferase, long known to esterify cholesterol, also produces monoesters of 24(S)OH-C. Proteoliposomes containing apolipoprotein A-I or apolipoprotein E were used to stimulate the enzyme activity and entrap the formed esters. Proteoliposomes with apolipoprotein A-I were found to be more active than those with apolipoprotein E in stimulating the production of oxysteryl esters. Cholesterol and 24(S)OH-C were found to compete for enzyme activity. High levels of haptoglobin, as those circulating during the acute inflammatory phase, inhibited 24(S)OH-C esterification. When highly neurotoxic 24(S)OH-C was treated with enzyme and proteoliposomes before incubation with differentiated SH-SY5Y cells, the neuron survival improved. The esters of 24(S)OH-C, embedded into proteoliposomes by the enzyme and isolated from unesterified 24(S)OH-C by gel filtration chromatography, did not enter the neurons in culture. These results suggest that the enzyme, in the presence of the apolipoproteins, converts 24(S)OH-C into esters restricted to the extracellular environment, thus preventing or limiting oxysterol-induced neurotoxic injuries to neurons in culture. 24-hydroxycholesterol (24(S)OH-C) is neurotoxic. The enzyme lecithin-cholesterol acyltransferase (LCAT) synthesizes monoesters of 24(S)OH-C in reaction mixtures with proteoliposomes containing phospholipids and apolipoprotein A-I or apolipoprotein E. The esters, also produced by incubation of cerebrospinal fluid only with tritiated 24(S)OH-C, are embedded into lipoproteins that do not enter neurons in culture. The enzyme activity limits the toxicity of 24-hydroxycholesterol in neuron culture. © 2014

High- and low-temperature unfolding of human high-density apolipoprotein A-2.

PubMed Central

Gursky, O.; Atkinson, D.

1996-01-01

Human plasma apolipoprotein A-2 (apoA-2) is the second major protein of the high-density lipoproteins that mediate the transport and metabolism of cholesterol. Using CD spectroscopy and differential scanning calorimetry, we demonstrate that the structure of lipid-free apoA-2 in neutral low-salt solutions is most stable at approximately 25 degrees C and unfolds reversibly both upon heating and cooling from 25 degrees C. High-temperature unfolding of apoA-2, monitored by far-UV CD, extends from 25-85 degrees C with midpoint Th = 56 +/- 2 degrees C and vant Hoff's enthalpy delta H(Th) = 17 +/- 2 kcal/mol that is substantially lower than the expected enthalpy of melting of the alpha-helical structure. This suggests low-cooperativity apoA-2 unfolding. The apparent free energy of apoA-2 stabilization inferred from the CD analysis of the thermal unfolding, delta G(app)(25 degrees) = 0.82 +/- 0.15 kcal/mol, agrees with the value determined from chemical denaturation. Enhanced low-temperature stability of apoA-2 observed upon increase in Na2HPO4 concentration from 0.3 mM to 50 mM or addition of 10% glycerol may be linked to reduced water activity. The close proximity of the heat and cold unfolding transitions, that is consistent with low delta G(app)(25 degrees), indicates that lipid-free apoA-2 has a substantial hydrophobic core but is only marginally stable under near-physiological solvent conditions. This suggests that in vivo apoA-2 transfer is unlikely to proceed via the lipid-free state. Low delta H(Th) and low apparent delta Cp approximately 0.52 kcal/mol.K inferred from the far-UV CD analysis of apoA-2 unfolding, and absence of tertiary packing interactions involving Tyr groups suggested by near-UV CD, are consistent with a molten globular-like state of lipid-free apoA-2. PMID:8880911

Human plasma lipid modulation in schistosomiasis mansoni depends on apolipoprotein E polymorphism.

PubMed

Martins da Fonseca, Caíque Silveira; Pimenta Filho, Adenor Almeida; dos Santos, Bianka Santana; da Silva, César Augusto; Domingues, Ana Lúcia Coutinho; Owen, James Stuart; Lima, Vera Lúcia de Menezes

2014-01-01

Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis. Blood samples were used for APOE genotyping and to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; P<0.0001) compared to control individuals, whereas HDL-C was increased (10% higher; P = 0.0136). Frequency of the common alleles, ε2, ε3 and ε4, was similar (P = 0.3568) between controls (n = 108) and patients (n = 84), implying that APOE genotype did not affect susceptibility to the advanced stage of schistosomiasis. Nevertheless, while patient TC and LDL-C levels were significantly reduced for each allele (except TC in ε2 patients), changes in HDL-C and triglycerides were noted only for the less common ε2 and ε4 alleles. The most striking finding, however, was that accepted regulation of plasma lipid levels by APOE genotype was disrupted by schistosomiasis. Thus, while ε2 controls had higher TC and LDL-C than ε3 carriers, these parameters were lower in ε2 versus ε3 patients. Similarly, the inverse relationship of TG levels in controls (ε2>ε3>ε4) was absent in patients (ε2 or ε4>ε3), and the increase in HDL-C of ε2 or ε4 patients compared to ε3 patients was not seen in the control groups. We confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat

Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins

PubMed Central

Curcio, Christine A.; Johnson, Mark; Huang, Jiahn-Dar; Rudolf, Martin

2015-01-01

The largest risk factor for age-related macular degeneration (ARMD) is advanced age. A prominent age-related change in the human retina is the accumulation of histochemically detectable neutral lipid in normal Bruch’s membrane (BrM) throughout adulthood. This change has the potential to have a major impact on physiology of the retinal pigment epithelium (RPE). It occurs in the same compartment as drusen and basal linear deposit, the pathognomonic extracellular, lipid-containing lesions of ARMD. Here we present evidence from light microscopic histochemistry, ultrastructure, lipid profiling of tissues and isolated lipoproteins, and gene expression analysis that this deposition can be accounted for by esterified cholesterol-rich, apolipoprotein B-containing lipoprotein particles constitutively produced by the RPE. This work collectively allows ARMD lesion formation and its aftermath to be conceptualized as a response to the retention of a sub-endothelial apolipoprotein B lipoprotein, similar to a widely accepted model of atherosclerotic coronary artery disease (CAD) (Tabas et al., 2007). This approach provides a wide knowledge base and sophisticated clinical armamentarium that can be readily exploited for the development of new model systems and the future benefit of ARMD patients. PMID:19698799

Thiol oxidation and di-tyrosine formation in human plasma proteins induced by inflammatory concentrations of hypochlorous acid.

PubMed

Colombo, Graziano; Clerici, Marco; Altomare, Alessandra; Rusconi, Francesco; Giustarini, Daniela; Portinaro, Nicola; Garavaglia, Maria Lisa; Rossi, Ranieri; Dalle-Donne, Isabella; Milzani, Aldo

2017-01-30

In this study, we assessed the oxidative damage occurring in plasma proteins when human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). We used specific thiol labelling and Western blot analyses to determine protein thiol oxidation, as well as analytical gel filtration HPLC coupled to fluorescence detection to explore formation of high molecular weight (HMW) protein aggregates. Thiol-containing proteins oxidized by HOCl were identified by redox proteomics. Mass spectrometry (MS) analysis was performed to elucidate the protein composition of HMW aggregates. α1-antitrypsin, transthyretin, and haptoglobin showed thiol oxidation at HOCl concentrations higher than those causing complete oxidation of albumin. At the highest HOCl concentrations, formation of carbonylated and di-tyrosine cross-linked HMW protein aggregates also occurred. MS analysis identified fibrinogen, complement C3 and apolipoprotein A-I as components of HMW protein aggregates. These results could be relevant for human diseases characterized by inflammatory conditions in which myeloperoxidase and HOCl are involved. In this study we evaluated the oxidative damage occurring on plasma proteins when reconstituted human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). Pathophysiological concentrations of HOCl are able to induce different modifications on plasma proteins such as carbonylation, sulfhydryl oxidation and formation of high molecular weight (HMW) protein aggregates characterized by di-tyrosine fluorescence. There are two relevant aspects emerging from this paper. The first one consists on identifying low abundant proteins undergoing sulfhydryl oxidation by biotin-maleimide derivatization followed by MALDI-TOF mass spectrometry. This approach suggests three low-abundant proteins undergoing HOCl-induced oxidation: transthyretin, α1-antitrypsin, and haptoglobin. In addition, we analysed HMW protein aggregates forming after HOCl exposure

Multiple SNPs Within and Surrounding the Apolipoprotein E Gene Influence Cerebrospinal Fluid Apolipoprotein E Protein Levels

PubMed Central

Bekris, Lynn M.; Millard, Steven P.; Galloway, Nichole M.; Vuletic, Simona; Albers, John J.; Li, Ge; Galasko, Douglas R.; DeCarli, Charles; Farlow, Martin R.; Clark, Chris M.; Quinn, Joseph F.; Kaye, Jeffrey A.; Schellenberg, Gerard D.; Tsuang, Debby; Peskind, Elaine R.; Yu, Chang-En

2010-01-01

The ε4 allele of the apolipoprotein E gene (APOE) is associated with increased risk and earlier age at onset in late onset Alzheimer’s disease (AD). Other factors, such as expression level of apolipoprotein E protein (apoE), have been postulated to modify the APOE related risk of developing AD. Multiple loci in and outside of APOE are associated with a high risk of AD. The aim of this exploratory hypothesis generating investigation was to determine if some of these loci predict cerebrospinal fluid (CSF) apoE levels in healthy non-demented subjects. CSF apoE levels were measured from healthy non-demented subjects 21–87 years of age (n = 134). Backward regression models were used to evaluate the influence of 21 SNPs, within and surrounding APOE, on CSF apoE levels while taking into account age, gender, APOE ε4 and correlation between SNPs (linkage disequilibrium). APOE ε4 genotype does not predict CSF apoE levels. Three SNPs within the TOMM40 gene, one APOE promoter SNP and two SNPs within distal APOE enhancer elements (ME1 and BCR) predict CSF apoE levels. Further investigation of the genetic influence of these loci on apoE expression levels in the central nervous system is likely to provide new insight into apoE regulation as well as AD pathogenesis. PMID:18430993

[Apolipoprotein e polymorphism and cognitive function change of the elderly in a rural area, Korea].

PubMed

Kim, Sang Kyu; Hwang, Tae Yoon; Lee, Kyeong Soo; Kang, Pock Soo; Cho, Hee Soon; Bae, Young Kyung

2009-07-01

The aim of this study is to examine the cognitive function change related to aging, the incidence of cognitive impairment, and the association between apolipoprotein E polymorphism and cognitive impairment through a follow-up of the elderly with normal cognitive ability at baseline. Two hundred and fifteen subjects aged 65 and over were surveyed in February, 1998 (baseline survey), and their cognitive function was assessed again in 2003 (1st follow-up) and the once again in 2006 (2nd follow-up). Ninety one subjects completed all surveys up through the 2nd follow-up and their cognitive function scores using MMSE-K (Korean Version of the Mini-Mental State Examination) and the distribution of apolipoprotein E allele were analyzed. The cognitive function scores decreased with aging and the difference between baseline and the 2nd follow-up scores of the study increased with the age group. The incidence rate of cognitive impairment through an 8-year follow-up was 38.5% and higher in older age groups. Age was the only significant factor for incidence of cognitive impairment, but there was no significant association between apolipoprotein E genotype and incidence of cognitive impairment. The cognition of the elderly decreased with aging and the association of apolipoprotein E genotype with incidence of cognitive impairment was not significant in this study. To confirm the association between apolipoprotein E polymorphism and incidence of cognitive impairment further studies will be needed.

Mipomersen, an antisense apolipoprotein B synthesis inhibitor.

PubMed

Bell, Damon A; Hooper, Amanda J; Burnett, John R

2011-02-01

mipomersen is a second-generation antisense oligonucleotide (ASO) targeted to human apolipoprotein (apo) B-100, a large protein synthesized by the liver that plays a fundamental role in human lipoprotein metabolism. Mipomersen predominantly distributes to the liver and decreases the production of apoB-100, the primary structural protein of the atherogenic lipoproteins including low density lipoprotein (LDL), thereby reducing plasma LDL-cholesterol and apoB-100 concentrations. the mode of action, preclinical development and clinical trials of mipomersen, an antisense apoB synthesis inhibitor. The paper provides an understanding of the pharmacokinetic and pharmacodynamic characteristics of mipomersen and insight into its clinical efficacy and safety. In clinical trials, mipomersen produced dose-dependent and prolonged reductions in LDL-cholesterol and other apoB-containing lipoproteins, including lipoprotein (a) [Lp(a)] in healthy volunteers and in patients with mild to moderate hypercholesterolemia. Mipomersen has been shown to decrease apoB, LDL-cholesterol and Lp(a) in patients with heterozygous and homozygous familial hypercholesterolemia on maximally tolerated lipid-lowering therapy. mipomersen shows promise as an adjunctive agent by reducing apoB-containing lipoproteins in patients at high risk of atherosclerotic cardiovascular disease who are not at target or are intolerant of statins. Although the short-term efficacy and safety of mipomersen has been established, concern exists regarding the long-term potential for hepatic steatosis with this ASO.

No association between apolipoprotein E or N-acetyltransferase 2 gene polymorphisms and age-related hearing loss.

PubMed

Dawes, Piers; Platt, Hazel; Horan, Michael; Ollier, William; Munro, Kevin; Pendleton, Neil; Payton, Antony

2015-01-01

Age-related hearing loss has a genetic component, but there have been limited genetic studies in this field. Both N-acetyltransferase 2 and apolipoprotein E genes have previously been associated. However, these studies have either used small sample sizes, examined a limited number of polymorphisms, or have produced conflicting results. Here we use a haplotype tagging approach to determine association with age-related hearing loss and investigate epistasis between these two genes. Candidate gene association study of a continuous phenotype. We investigated haplotype tagging single nucleotide polymorphisms in the N-acetyltransferase 2 gene and the presence/absence of the apolipoprotein E ε4 allele for association with age-related hearing loss in a cohort of 265 Caucasian elderly volunteers from Greater Manchester, United Kingdom. Hearing phenotypes were generated using principal component analysis of the hearing threshold levels for the better ear (severity, slope, and concavity). Genotype data for the N-acetyltransferase 2 gene was obtained from existing genome-wide association study data from the Illumina 610-Quadv1 chip. Apolipoprotein E genotyping was performed using Sequenom technology. Linear regression analysis was performed using Plink and Stata software. No significant associations (P value, > 0.05) were observed between the N-acetyltransferase 2 or apolipoprotein E gene polymorphisms and any hearing factor. No significant association was observed for epistasis analysis of apolipoprotein E ε4 and the N-acetyltransferase 2 single nucleotide polymorphism rs1799930 (NAT2*6A). We found no evidence to support that either N-acetyltransferase 2 or apolipoprotein E gene polymorphisms are associated with age-related hearing loss in a cohort of 265 elderly volunteers. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Molecular Characterization and Growth Association of Two Apolipoprotein A-Ib Genes in Common Carp (Cyprinus carpio)

PubMed Central

Wang, Xinhua; Yu, Xiaomu; Tong, Jingou

2016-01-01

Apolipoprotein A-I (ApoA-I) is functionally involved in the transportation and metabolism of lipids in vertebrates. In this study, two isoforms of apoA-Ib in common carp (Cyprinus carpio L.) were characterized. Sequence comparison and phylogenetic analysis showed that C. carpio ApoA-Ib is relatively conserved within cyprinid fishes. During embryonic development, C. carpio apoA-Ib was first expressed at the stage of multi-cells, and the highest mRNA level was observed at the stage of optic vesicle. A ubiquitous expression pattern was detected in various tissues with extreme predominance in the liver. Significantly different expression levels were observed between light and heavy body weight groups and also in the compensatory growth test. Seventeen and eight single-nucleotide polymorphisms (SNPs) were identified in matured mRNA of the C. carpio apoA-Ib.1 and apoA-Ib.2, respectively. Two of these SNPs (apoA-Ib.2-g.183A>T and apoA-Ib.2-g.1753C>T) were significantly associated with body weight and body length in two populations of common carp. These results indicate that apoA-Ib may play an important role in the modulation of growth and development in common carp. PMID:27649163

Molecular Characterization and Growth Association of Two Apolipoprotein A-Ib Genes in Common Carp (Cyprinus carpio).

PubMed

Wang, Xinhua; Yu, Xiaomu; Tong, Jingou

2016-09-16

Apolipoprotein A-I (ApoA-I) is functionally involved in the transportation and metabolism of lipids in vertebrates. In this study, two isoforms of apoA-Ib in common carp (Cyprinus carpio L.) were characterized. Sequence comparison and phylogenetic analysis showed that C. carpio ApoA-Ib is relatively conserved within cyprinid fishes. During embryonic development, C. carpio apoA-Ib was first expressed at the stage of multi-cells, and the highest mRNA level was observed at the stage of optic vesicle. A ubiquitous expression pattern was detected in various tissues with extreme predominance in the liver. Significantly different expression levels were observed between light and heavy body weight groups and also in the compensatory growth test. Seventeen and eight single-nucleotide polymorphisms (SNPs) were identified in matured mRNA of the C. carpio apoA-Ib.1 and apoA-Ib.2, respectively. Two of these SNPs (apoA-Ib.2-g.183A>T and apoA-Ib.2-g.1753C>T) were significantly associated with body weight and body length in two populations of common carp. These results indicate that apoA-Ib may play an important role in the modulation of growth and development in common carp.

Genetic variation of apolipoproteins, diet and other environmental interactions; an updated review.

PubMed

Sotos-Prieto, Mercedes; Peñalvo, José Luis

2013-01-01

This paper summarizes the recent findings from studies investigating the potential environmental modulation of the genetic variation of apolipoprotein genes on metabolic traits. We reviewed nutrigenetic studies evaluating variations on apolipoproteins-related genes and its associated response to nutrients (mostly dietary fatty acids) or any other dietary or environmental component. Most revised research studied single nucleotide polymorphism (SNP) and specific nutrients through small intervention studies, and only few interactions have been replicated in large and independent populations (as in the case of -265T > C SNP in APOA2 gene). Although current knowledge shows that variations on apolipoprotein genes may contribute to the different response on metabolic traits due to dietary interventions, evidence is still scarce and results are inconsistent. Success in this area will require going beyond the limitations of current experimental designs and explore the hypotheses within large populations. Some of these limitations are being covered by the rapidly advance in high-throughput technologies and large scale-genome wide association studies. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

AI and cognitive science: the past and next 30 years.

PubMed

Forbus, Kenneth D

2010-07-01

Artificial Intelligence (AI) is a core area of Cognitive Science, yet today few AI researchers attend the Cognitive Science Society meetings. This essay examines why, how AI has changed over the last 30 years, and some emerging areas of potential interest where AI and the Society can go together in the next 30 years, if they choose. Copyright © 2010 Cognitive Science Society, Inc.

Pro-apoptotic activities of polyphenolics from açai (Euterpe oleracea Martius) in human SW-480 colon cancer cells.

PubMed

Dias, Manoela Maciel dos Santos; Noratto, Giuliana; Martino, Hercia Stampini Duarte; Arbizu, Shirley; Peluzio, Maria do Carmo Gouveia; Talcott, Stephen; Ramos, Afonso Mota; Mertens-Talcott, Susanne U

2014-01-01

This study aimed to evaluate the cell growth inhibition activity of açai (Euterpe oleracea Mart.) polyphenolic extract against colon cancer HT-29 and SW-480 cells and the nonmalignant CCD-18Co colon fibroblast cells. Results showed that açai polyphenolic extract (5-20 mg/L) inhibited preferentially the growth of SW-480 cells with no toxicity in CCD-18Co cells, and this was accompanied by reduction of H2O2-induced reactive oxygen species (ROS) generation. The mechanisms involved in SW-480 cell growth-inhibition by açai polyphenolic extract included the downregulation of NF-κB proinflammatory transcription factor and the nuclear factor-kappa B targets intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Furthermore, prooncogenic specificity proteins (Sp) were downregulated as well as Sp-targets Bcl-2, vascular endothelial growth factor, and survivin. This was accompanied by activation of mitochondrial proapoptotic pathway involving increase of cytochrome c, cleavage of caspase-3, and decrease of PARP-1. Results strongly suggest that açai polyphenolic extract has antiinflammatory and cytotoxic activities in colon cancer cells and can be effective as natural colon cancer chemopreventive agents.

Towards an AI Behavior Toolkit for Games

DTIC Science & Technology

2000-01-01

Introduction To date there exists a disparity between AI research and game development technologies (Laird and van Lent 2000). We are currently...art AI re- sults. Such a kit has obvious benefits for both communities. On the game development side, the kit will provide a straight- forward method

The Relevance of AI Research to CAI.

ERIC Educational Resources Information Center

Kearsley, Greg P.

This article provides a tutorial introduction to Artificial Intelligence (AI) research for those involved in Computer Assisted Instruction (CAI). The general theme is that much of the current work in AI, particularly in the areas of natural language understanding systems, rule induction, programming languages, and socratic systems, has important…

Application of AI methods to aircraft guidance and control

NASA Technical Reports Server (NTRS)

Hueschen, Richard M.; Mcmanus, John W.

1988-01-01

A research program for integrating artificial intelligence (AI) techniques with tools and methods used for aircraft flight control system design, development, and implementation is discussed. The application of the AI methods for the development and implementation of the logic software which operates with the control mode panel (CMP) of an aircraft is presented. The CMP is the pilot control panel for the automatic flight control system of a commercial-type research aircraft of Langley Research Center's Advanced Transport Operating Systems (ATOPS) program. A mouse-driven color-display emulation of the CMP, which was developed with AI methods and used to test the AI software logic implementation, is discussed. The operation of the CMP was enhanced with the addition of a display which was quickly developed with AI methods. The display advises the pilot of conditions not satisfied when a mode does not arm or engage. The implementation of the CMP software logic has shown that the time required to develop, implement, and modify software systems can be significantly reduced with the use of the AI methods.

Apolipoprotein nanodiscs with telodendrimer

DOEpatents

Luo, Juntao; He, Wei; Lam, Kit S.; Henderson, Paul; Coleman, Matthew; Cheng, R. Holland; Xing, Li

2017-05-09

The present invention provides a nanodisc with a membrane scaffold protein. The nanodisc includes a membrane scaffold protein, a telodendrimer and a lipid. The membrane scaffold protein can be apolipoprotein. The telodendrimer has the general formula PEG-L-D-(R).sub.n, wherein D is a dendritic polymer; L is a bond or a linker linked to the focal point group of the dendritic polymer; each PEG is a poly(ethylene glycol) polymer; each R is and end group of the dendritic polymer, or and end group with a covalently bound hydrophobic group, hydrophilic group, amphiphilic compound, or drug; and subscript n is an integer from 2 to 20. Cell free methods of making the nanodiscs are also provided.

Characteristics of polymorphism at a VNTR locus 3[prime] to the apolipoprotein B gene in five human populations

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

Deka, R.; DeCroo, S.; Ferrell, R.E.

1992-12-01

The authors have analyzed the allele frequency distribution at the hypervariable locus 3[prime] to the apolipoprotein B gene (ApoB 3[prime] VNTR) in five well-defined human populations (Kacharis of northeast India, New Guinea Highlanders of Papua New Guinea, Dogrib Indians of Canada, Pehuenche Indians of Chile, and a relatively homogeneous Caucasian population of northern German extraction) by using the PCR technique. A total of 12 segregating alleles were detected in the pooled sample of 319 individuals. A fairly consistent bimodal pattern of allele frequency distribution, apparent in most of these geographically and genetically diverse populations, suggests that the ApoB 3[prime] VNTRmore » polymorphism predates the geographic dispersal of ancestral human populations. In spite of the observed high degree of polymorphism at this locus (expected heterozygosity levels 55%-78%), the genotype distributions in all populations (irrespective of their tribal or cosmopolitan nature) conform to their respective Hardy-Weinberg predictions. Furthermore, analysis of the congruence between expected heterozygosity and the observed number of alleles reveals that, in general, the allele frequency distributions at this locus are in agreement with the predictions of the classical mutation-drift models. The data also show that alleles that are shared by all populations have the highest average frequency within populations. These findings demonstrate the potential utility of highly informative hypervariable loci such as the ApoB 3[prime] VNTR locus in population genetic research, as well as in forensic medicine and determination of biological relatedness of individuals. 38 refs., 2 figs., 3 tabs.« less

Mechanism of lipid lowering in mice expressing human apolipoprotein A5

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

Fruchart-Najib, Jamila; Bauge, Eric; Niculescu, Loredan-Stefan

2004-01-15

Recently, we reported that apoAV plays key role in triglycerides lowering. Here, we attempted to determine the mechanism underlying this hypotriglyceridemic effect. We showed that triglyceride turnover is faster in hAPOA5 transgenic compared to wild type mice. Moreover, both apoB and apoCIII are decreased and LPL activity is increased in postheparin plasma of hAPOA5 transgenic mice. These data suggest a decrease in size and number of VLDL. To further investigate the mechanism of hAPOA5 in hyperlipidemic background, we intercrossed hAPOA5 and hAPOC3 transgenic mice. The effect resulted in a marked decreased of VLDL triglyceride, cholesterol, apolipoproteins B and CIII. Inmore » postprandial state, the triglyceride response is abolished in hAPOA5 transgenic mice. We demonstrated that in response to the fat load in hAPOA5XhAPOC3 mice, apoAV shifted from HDL to VLDL, probably to limit the elevation of triglycerides. In vitro, apoAV activates lipoprotein lipase. However, apoAV does not interact with LPL but interacts physically with apoCIII. This interaction does not seem to displace apoCIII from VLDL but may induce conformational change in apoCIII and consequently change in its function leading the activation of lipoprotein lipase.« less

Apo AI/ABCA1-dependent and HDL3-mediated lipid efflux from compositionally distinct cholesterol-based microdomains.

PubMed

Drobnik, Wolfgang; Borsukova, Hana; Böttcher, Alfred; Pfeiffer, Alexandra; Liebisch, Gerhard; Schütz, Gerhard J; Schindler, Hansgeorg; Schmitz, Gerd

2002-04-01

We have investigated whether a raft heterogeneity exists in human monocyte-derived macrophages and fibroblasts and whether these microdomains are modulated by lipid efflux. Triton X-100 (Triton) or Lubrol WX (Lubrol) detergent-resistant membranes from cholesterol-loaded monocytes were associated with the following findings: (i) Lubrol-DRM contained most of the cellular cholesterol and at least 75% of Triton-detergent-resistant membranes. (ii) 'Lubrol rafts', defined by their solubility in Triton but insolubility in Lubrol, were enriched in unsaturated phosphatidylcholine and showed a lower cholesterol to choline-phospholipid ratio compared to Triton rafts. (iii) CD14 and CD55 were recovered in Triton- and Lubrol-detergent-resistant membranes, whereas CD11b was found exclusively in Triton DRM. ABCA1 implicated in apo AI-mediated lipid efflux and CDC42 were partially localized in Lubrol- but not in Triton-detergent-resistant membranes. (iv) Apo AI preferentially depleted cholesterol and choline-phospholipids from Lubrol rafts, whereas HDL3 additionally decreased the cholesterol content of Triton rafts. In fibroblasts, neither ABCA1 nor CDC42 was found in Lubrol rafts, and both apo AI and HDL3 reduced the lipid content in Lubrol- as well as in Triton-detergent-resistant membranes. In summary, we provide evidence for the existence of compositionally distinct membrane microdomains in human cells and their modulation by apo AI/ABCA1-dependent and HDL3-mediated lipid efflux.

Enhanced AIS receiver design for satellite reception

NASA Astrophysics Data System (ADS)

Clazzer, Federico; Lázaro, Francisco; Plass, Simon

2016-12-01

The possibility to detect Automatic Identification System (AIS) messages from low earth orbit (LEO) satellites paves the road for a plurality of new and unexplored services. Besides worldwide tracking of vessels, maritime traffic monitoring, analysis of vessel routes employing big data, and oceans monitoring are just few of the fields, where satellite-aided AIS is beneficial. Designed for ship-to-ship communication and collision avoidance, AIS satellite reception performs poorly in regions with a high density of vessels. This calls for the development of advanced satellite AIS receivers able to improve the decoding capabilities. In this context, our contribution focuses on the introduction of a new enhanced AIS receiver design and its performance evaluation. The enhanced receiver makes use of a coherent receiver for the low signal-to-noise ratio (SNR) region, while for medium to high SNRs, a differential Viterbi receiver is used. Additional novelty of our work is in the exploitation of previously decoded packets from one vessel that is still under the LEO reception range, to improve the vessel detection probability. The assessment of the performance against a common receiver is done making the use of a simple and tight model of the medium access (MAC) layer and the multi-packet reception (MPR) matrix for physical layer (PHY) representation. Performance results show the benefits of such enhanced receiver, especially when it is bundled with successive interference cancellation (SIC).

Plasma apolipoprotein O level increased in the patients with acute coronary syndrome

PubMed Central

Yu, Bi-lian; Wu, Chen-lu; Zhao, Shui-ping

2012-01-01

Apolipoprotein (apo) O is a novel apolipoprotein that is present predominantly in high density lipoprotein (HDL). However, overexpression of apoO does not impact on plasma HDL levels or functionality in human apoA-I transgenic mice. Thus, the physiological function of apoO is not yet known. In the present study, we investigated relationships between plasma apoO levels and high-sensitive C-reactive protein (hs-CRP) levels, as well as other lipid parameters in healthy subjects (n = 111) and patients with established acute coronary syndrome (ACS) (n = 50). ApoO was measured by the sandwich dot-blot technique with recombinant apoO as a protein standard. Mean apoO level in healthy subjects was 2.21 ± 0.83 µg/ml whereas it was 4.94 ± 1.59 µg/ml in ACS patients. There were significant differences in plasma level of apoO between two groups (P < 0.001). In univariate analysis, apoO correlated significantly with lg(hsCRP) (r = 0.48, P < 0.001) in ACS patients. Notably, no significant correlation between apoO and other lipid parameters was observed. Logistic regression analysis showed that plasma apoO level was an independent predictor of ACS (OR = 5.61, 95% CI 2.16–14.60, P < 0.001). In conclusion, apoO increased in ACS patients, and may be regarded as an independent inflammatory predictor of ACS patients. PMID:22693255

Reduced expression of the long non-coding RNA AI364715 in gastric cancer and its clinical significance.

PubMed

Zhu, Shengqian; Mao, Jinqin; Shao, Yongfu; Chen, Fang; Zhu, Xiaoqin; Xu, Dingli; Zhang, Xinjun; Guo, Junming

2015-09-01

Long non-coding RNA (lncRNA), which is greater than 200 nucleotides, is a class of RNA molecules without protein coding function. In recent years, studies have shown that lncRNAs are associated with cancers. They are affecting the occurrence and development of cancers. However, the diagnostic significances of lncRNAs in gastric cancer are largely unknown. In this study, we focused on AI364715, one typical lncRNA. A total of 186 samples were collected from two cancer centers. To find the potential association between its level and gastric cancer, we first collected 75 paired gastric cancer tissues and normal tissues, which are 5 cm away from the edge of carcinoma. Besides, 18 human healthy gastric mucosa and 18 gastric precancerous lesions (dysplasia) were also collected. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was first used to detect the expression level of AI364715 at multiple stages of gastric tumorigenesis. Then, the relationships between AI364715 level and the clinicopathological factors of patients with gastric cancer were analyzed. The results showed that the expression level of AI364715 in gastric cancer tissues was downregulated. Meanwhile, its expression level was closely associated with tumor size and differentiation. More importantly, AI364715 expression level was significantly changed in dysplasia, the typical precancerous lesions. Taken together, AI364715 may be a potential biomarker for the diagnosis of gastric cancer.

Apolipoprotein E-mimetics inhibit neurodegeneration and restore cognitive functions in a transgenic Drosophila model of Alzheimer's disease.

PubMed

Sarantseva, Svetlana; Timoshenko, Svetlana; Bolshakova, Olga; Karaseva, Eugenia; Rodin, Dmitry; Schwarzman, Alexander L; Vitek, Michael P

2009-12-07

Mutations of the amyloid precursor protein gene (APP) are found in familial forms of Alzheimer's disease (AD) and some lead to the elevated production of amyloid-beta-protein (Abeta). While Abeta has been implicated in the causation of AD, the exact role played by Abeta and its APP precursor are still unclear. In our study, Drosophila melanogaster transgenics were established as a model to analyze AD-like pathology caused by APP overexpression. We demonstrated that age related changes in the levels and pattern of synaptic proteins accompanied progressive neurodegeneration and impairment of cognitive functions in APP transgenic flies, but that these changes may be independent from the generation of Abeta. Using novel peptide mimetics of Apolipoprotein-E, COG112 or COG133 proved to be neuroprotective and significantly improved the learning and memory of APP transgenic flies. The development of neurodegeneration and cognitive deficits was corrected by injections of COG112 or COG133, novel mimetics of apolipoprotein-E (apoE) with neuroprotective activities.

Omapatrilat, a dual angiotensin-converting enzyme and neutral endopeptidase inhibitor, prevents fatty streak deposit in apolipoprotein E-deficient mice.

PubMed

Arnal, J F; Castano, C; Maupas, E; Mugniot, A; Darblade, B; Gourdy, P; Michel, J B; Bayard, F

2001-04-01

Angiotensin-converting enzyme (ACE) is mainly responsible for converting angiotensin I (AI) to angiotensin II (AII), and ACE inhibitors prevent atherosclerosis in animal models. Neutral endopeptidase 24.11 (NEP) degrades substance P, kinins and atrial natriuretic peptide (ANP), and aortic wall NEP activity was found to be increased in atherosclerosis. In the present study, we have evaluated the effect of candoxatril, a NEP inhibitor, and of omapatrilat, a dual ACE and NEP inhibitor, on the development of fatty streak in apolipoprotein E (apoE)-deficient mice. Groups of ten male apoE-deficient mice were given either placebo, candoxatril 50 mg/kg per day, or omapatrilat 10, or 100 mg/kg per day for 4 months. None of the treatments influenced body weight, serum total or HDL-cholesterol. Compared with the placebo, candoxatril did not protect the mice from fatty streak deposit. In contrast, omapatrilat dose dependently inhibited the constitution of fatty streak in apoE-deficient mice. The precise advantages of the dual ACE and NEP inhibition versus the inhibition of only ACE should now be considered in the prevention of atherosclerosis as well as in the occurrence of its complications.

Long-range AIS message analysis based on the TianTuo-3 micro satellite

NASA Astrophysics Data System (ADS)

Li, Shiyou; Chen, Lihu; Chen, Xiaoqian; Zhao, Yong; Bai, Yuzhu

2017-07-01

The "Type-27 AIS message" is the long-range AIS broadcast message, which is primarily intended for the long-range detection of AIS typically by satellite. The TT3-AIS uses a four-frequency receiver scheme which includes two frequency channels conventionally applied by the AIS system and two new frequency channels allocated to the long-range AIS broadcast message. To the end of April 2016, the TT3-AIS has already received more than 11,400 packets of Type-27 AIS messages. In this paper, a detailed analysis of the Type-27 AIS messages is performed. Firstly, an eavesdropper diagram of the space-borne AIS received from the worldwide vessels is obtained. Secondly, the analysis to the trend of the number and the ratio of the new-type vessels is performed based on the Type-27 AIS message. The detection probability of the new-type vessels is also discussed. The result would be helpful on the usage of the long-range AIS message both for data application and for the improvement in designing the next space-based AIS receiver.

Reduced telomere length in subjects with dementia and diabetes mellitus type 2 is independent of apolipoprotein E4 genotype.

PubMed

Kota, Lakshmi Narayanan; Bharath, Srikala; Purushottam, Meera; Paul, Pradip; Sivakumar, Palanimuthu Thangaraju; Varghese, Mathew; Jain, Sanjeev

2014-12-01

Apolipoprotein E4 gene is associated with increased risk of dementia with comorbid diabetes mellitus. Both dementia and diabetes mellitus type 2 are independently associated with telomere shortening. We assessed relative telomere length and apolipoprotein E genotype in subjects with dementia (n=70) and cognitively normal control groups (n=55) with and without comorbid diabetes mellitus type 2. Relative telomere length was highest in the control group (Q2=0.91) followed by dementia (Q2=0.48) and dementia with comorbid diabetes mellitus type 2 (Q2=0.39). Apolipoprotein E4 allele frequency was highest in dementia with comorbid diabetes mellitus type 2 (0.26). Apolipoprotein E4 allele was not significantly associated with telomere attrition in both dementia and cognitively normal group irrespective of comorbid diabetes mellitus type 2 (P>0.05). The findings suggest that relative telomere length is unrelated to apolipoprotein E4 genotype in dementia and cognitive normal subjects with or without comorbid diabetes mellitus type 2. Copyright © 2014 Elsevier B.V. All rights reserved.

Calibrating AIS images using the surface as a reference

NASA Technical Reports Server (NTRS)

Smith, M. O.; Roberts, D. A.; Shipman, H. M.; Adams, J. B.; Willis, S. C.; Gillespie, A. R.

1987-01-01

A method of evaluating the initial assumptions and uncertainties of the physical connection between Airborne Imaging Spectrometer (AIS) image data and laboratory/field spectrometer data was tested. The Tuscon AIS-2 image connects to lab reference spectra by an alignment to the image spectral endmembers through a system gain and offset for each band. Images were calibrated to reflectance so as to transform the image into a measure that is independent of the solar radiant flux. This transformation also makes the image spectra directly comparable to data from lab and field spectrometers. A method was tested for calibrating AIS images using the surface as a reference. The surface heterogeneity is defined by lab/field spectral measurements. It was found that the Tuscon AIS-2 image is consistent with each of the initial hypotheses: (1) that the AIS-2 instrument calibration is nearly linear; (2) the spectral variance is caused by sub-pixel mixtures of spectrally distinct materials and shade, and (3) that sub-pixel mixtures can be treated as linear mixtures of pure endmembers. It was also found that the image can be characterized by relatively few endmembers using the AIS-2 spectra.

Harbour surveillance with cameras calibrated with AIS data

NASA Astrophysics Data System (ADS)

Palmieri, F. A. N.; Castaldo, F.; Marino, G.

The inexpensive availability of surveillance cameras, easily connected in network configurations, suggests the deployment of this additional sensor modality in port surveillance. Vessels appearing within cameras fields of view can be recognized and localized providing to fusion centers information that can be added to data coming from Radar, Lidar, AIS, etc. Camera systems, that are used as localizers however, must be properly calibrated in changing scenarios where often there is limited choice on the position on which they are deployed. Automatic Identification System (AIS) data, that includes position, course and vessel's identity, freely available through inexpensive receivers, for some of the vessels appearing within the field of view, provide the opportunity to achieve proper camera calibration to be used for the localization of vessels not equipped with AIS transponders. In this paper we assume a pinhole model for camera geometry and propose perspective matrices computation using AIS positional data. Images obtained from calibrated cameras are then matched and pixel association is utilized for other vessel's localization. We report preliminary experimental results of calibration and localization using two cameras deployed on the Gulf of Naples coastline. The two cameras overlook a section of the harbour and record short video sequences that are synchronized offline with AIS positional information of easily-identified passenger ships. Other small vessels, not equipped with AIS transponders, are localized using camera matrices and pixel matching. Localization accuracy is experimentally evaluated as a function of target distance from the sensors.

Application of AI techniques to blast furnace operations

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

Iida, Osamu; Ushijima, Yuichi; Sawada, Toshiro

1995-10-01

It was during the first stages of application of artificial intelligence (AI) to industrial fields, that the ironmaking division of Mizushima works at Kawasaki Steel recognized its potential. Since that time, the division has sought applications for these techniques to solve various problems. AI techniques applied to control the No. 3 blast furnace operations at the Mizushima works include: Blast furnace control by a diagnostic type of expert system that gives guidance to the actions required for blast furnace operation as well as control of furnace heat by automatically setting blast temperature; Hot stove combustion control by a combination ofmore » fuzzy inference and a physical model to insure good thermal efficiency of the stove; and blast furnace burden control using neural networks makes it possible to connect the pattern of gas flow distribution with the condition of the furnace. Experience of AI to control the blast furnace and other ironmaking operations has proved its capability for achieving automation and increased operating efficiency. The benefits are very high. For these reasons, the applications of AI techniques will be extended in the future and new techniques studied to further improve the power of AI.« less

Effect of nandrolone decanonate on paraoxonase activity in hemodialysis patients.

PubMed

Ghorbanihaghjo, Amir; Argani, Hassan; Rahbaninoubar, Mohammad; Rashtchizadeh, Nadereh

2005-12-01

This study was designed to determine the effect of nandrolone decanonate (ND) on HDL-C, apolipoproteins and paraoxonase (PON) activity in stable hemodialysis patients. 64 hemodialysis patients were treated with ND at a dose of 100 mg/I.M./week for 4 months. HDL-C, Apo-AI, Apo B, concentrations and PON activity were measured before and after 2 and 4 months of treatment as well as 2 months after withdrawing the treatment. After 4 months of treatment, an elevation in the serum levels of Apo B (P<0.0001) and a marked decrease in the concentration of HDL-C (P<0.0001), Apo-AI (P<0.0001) and PON activity (P<0.0001) were found. A significant correlation between PON and both Apo-AI (r=0.270, P<0.04) and HDL-C (r=0.455, P<0.0001) and also between HDL-C and Apo-AI (r=0.305, P<0.02) were found. Results revealed the adverse effects of ND on apolipoprotein levels in our study population. It is possible that ND reduces PON activity mostly by reducing both the HDL-C and Apo-AI levels.

The effect of a combination of plant sterol-enriched foods in mildly hypercholesterolemic subjects.

PubMed

Madsen, Martin B; Jensen, Anne-Mette; Schmidt, Erik B

2007-12-01

The purpose of this study was to evaluate the effect of low-fat products enriched with plant sterols in addition to a National Cholesterol Education Program step 1 diet on serum lipids and lipoproteins. This study was a double-blind, randomised, placebo-controlled cross-over design with a run-in period and 2 intervention periods, each lasting 4 weeks. A total of 46 mildly hypercholesterolemic subjects (age 50.6+/-9.8) completed the trial. The study products consisted of 20 g low-fat margarine (35% fat) and 250 ml low-fat milk (0.7% fat), in total delivering 2.3g plant sterols/d. Serum total and low-density lipoprotein cholesterol were significantly reduced by 5.5% (p<0.001, 95% CI: 2.5; 8.3) and 7.7% (p=0.001, 95% CI: 3.4; 11.9), respectively, by plant sterol-enriched products compared to placebo. Serum apolipoprotein B was significantly reduced by 4.6% (p<0.05, 95% CI: 1.7; 7.5), and apolipoprotein B/apolipoprotein A-I by 3.4% (p<0.05, 95% CI: 0.1; 6.6) after plant sterol intake compared to the placebo supplement. A combination of low-fat margarine and milk enriched with plant sterols significantly reduced low-density lipoprotein cholesterol, apolipoprotein B and the ratio of apolipoprotein B to apolipoprotein A-I in mildly hypercholesterolemic subjects, but had no effect on C-reactive protein and lipoprotein (a) concentrations. Unilever Denmark A/S.

Apolipoprotein J (clusterin) and Alzheimer's disease.

PubMed

Calero, M; Rostagno, A; Matsubara, E; Zlokovic, B; Frangione, B; Ghiso, J

2000-08-15

Apolipoprotein J (clusterin) is a ubiquitous multifunctional glycoprotein capable of interacting with a broad spectrum of molecules. In pathological conditions, it is an amyloid associated protein, co-localizing with fibrillar deposits in systemic and localized amyloid disorders. In Alzheimer's disease, the most frequent form of amyloidosis in humans and the major cause of dementia in the elderly, apoJ is present in amyloid plaques and cerebrovascular deposits but is rarely seen in NFT-containing neurons. ApoJ expression is up-regulated in a wide variety of insults and may represent a defense response against local damage to neurons. Four different mechanisms of action could be postulated to explain the role of apoJ as a neuroprotectant during cellular stress: (1) function as an anti-apoptotic signal, (2) protection against oxidative stress, (3) inhibition of the membrane attack complex of complement proteins locally activated as a result of inflammation, and (4) binding to hydrophobic regions of partially unfolded, stressed proteins, and therefore avoiding aggregation in a chaperone-like manner. This review focuses on the association of apoJ in biological fluids with Alzheimer's soluble Abeta. This interaction prevents Abeta aggregation and fibrillization and modulates its blood-brain barrier transport at the cerebrovascular endothelium. Copyright 2000 Wiley-Liss, Inc.

Nutrient Intake, Apolipoprotein A5 -1131T>C Polymorphism and Its Relationship with Obesity

NASA Astrophysics Data System (ADS)

Sari, M. I.; Sari, D. I.

2017-03-01

Obesity is associated with the development of some of the most prevalent diseases of modern society. The World Health Organization estimates that at least 2.8 million adult die each year as result of being obesity. Nutrient intake is a key environmental factor that may interact with genotype to affect risk of obesity. The aim of study was assess the relation between nutrient intake and apolipoprotein A5 -1131T>C polimorphism with obesity. A cross sectional study has been carried out on 139 subjects. Nutrient intake data was collected by using a 24 hour dietary recall and analyzed by nutrisurvey software. Anthropometric variables were measured and body mass index (BMI). Apolipoprotein A5 -1131T>C polymorphism was visualized with 5% agarose gel after restriction length fragment polymorphism (RFLP) digested with MseI. Results : Subjects in this study were 55 male and 84 female, with average age 19.20 ± 1.08, 75 had obese and 64 non obese. Based on the chi square test is found a relationship between total energy intake and protein intake in obese group compared to the non-obese group (p = 0.029, p = 0.006) and no relationship was found in Apolipoprotein A5 -1131T> C polymorphism with obesity. These findings indicate that nutrient intake no depending with apolipoprotein A5 gene variant to modulate obesity

47 CFR 80.393 - Frequencies for AIS stations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 162.025 MHz (AIS 2), each with a 25 kHz bandwidth, may be authorized only for AIS. In accordance with... requirements for non-Federal Government ships. These requirements are codified at 33 CFR 164.46, 401.20. [74 FR...

47 CFR 80.393 - Frequencies for AIS stations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 162.025 MHz (AIS 2), each with a 25 kHz bandwidth, may be authorized only for AIS. In accordance with... requirements for non-Federal Government ships. These requirements are codified at 33 CFR 164.46, 401.20. [74 FR...

47 CFR 80.393 - Frequencies for AIS stations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 162.025 MHz (AIS 2), each with a 25 kHz bandwidth, may be authorized only for AIS. In accordance with... requirements for non-Federal Government ships. These requirements are codified at 33 CFR 164.46, 401.20. [74 FR...

Lead and aluminum bonding in Pb-AI metaphosphate glasses.

PubMed

Tsuchida, J E; Schneider, J; Pizani, P S; Oliveira, S L

2008-01-21

The bonding properties of cations in phosphate glasses determine many short- and medium-range structural features in the glass network, hence influencing bulk properties. In this work, Pb-Al-metaphosphate glasses (1 - x)Pb(PO(3))(2).xAI(PO(3))(3) with 0 < or = x < or = 1 were analyzed to determine the effect of the substitution of Pb by AI on the glass structure in the metaphosphate composition. The glass transition temperature and density were measured as a function of the Al concentration. The vibrational and structural properties were probed by Raman spectroscopy and nuclear magnetic resonance of (31)P, (27)AI, and (207)Pb. Aluminum incorporates homogeneously in the glass creating a stiffer and less packed network. The average coordination number for AI decreases from 5.9 to 5.0 as x increases from 0.1 to 1, indicating more covalent AI-O bonds. The coordination number of Pb in these glasses is greater than 8, showing an increasing ionic behavior for compositions richer in AI. A quantitative analysis of the phosphate speciation shows definite trends in the bonding of AIO(n) groups and phosphate tetrahedra. In glasses with x < 0.48, phosphate groups share preferentially only one nonbridging O corner with an AIO(n) coordination polyhedron. For x > 0.48 more than one nonbridging O can be linked to AIO(n) polyhedra. There is no corner sharing of O between AIO(n) and PbO(n) polyhedra nor between AIO(n) themselves throughout the compositional range. The PbO(n) coordination polyhedra show considerable nonbridging O sharing, with each O participating in the coordination sphere of at least two Pb. The bonding preferences determined for Al are consistent with the behavior observed in Na-AI and Ca-AI metaphosphates, indicating this may be a general behavior for ternary phosphate glasses.

Apolipoprotein L1 Variant Associated with Increased Susceptibility to Trypanosome Infection

PubMed Central

Cuypers, Bart; Lecordier, Laurence; Meehan, Conor J.; Van den Broeck, Frederik; Imamura, Hideo; Büscher, Philippe; Dujardin, Jean-Claude; Laukens, Kris; Schnaufer, Achim; Dewar, Caroline; Lewis, Michael; Balmer, Oliver; Azurago, Thomas; Kyei-Faried, Sardick; Ohene, Sally-Ann; Duah, Boateng; Homiah, Prince; Mensah, Ebenezer Kofi; Anleah, Francis; Franco, Jose Ramon; Pays, Etienne

2016-01-01

ABSTRACT African trypanosomes, except Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, which cause human African trypanosomiasis, are lysed by the human serum protein apolipoprotein L1 (ApoL1). These two subspecies can resist human ApoL1 because they express the serum resistance proteins T. b. gambiense glycoprotein (TgsGP) and serum resistance-associated protein (SRA), respectively. Whereas in T. b. rhodesiense, SRA is necessary and sufficient to inhibit ApoL1, in T. b. gambiense, TgsGP cannot protect against high ApoL1 uptake, so different additional mechanisms contribute to limit this uptake. Here we report a complex interplay between trypanosomes and an ApoL1 variant, revealing important insights into innate human immunity against these parasites. Using whole-genome sequencing, we characterized an atypical T. b. gambiense infection in a patient in Ghana. We show that the infecting trypanosome has diverged from the classical T. b. gambiense strains and lacks the TgsGP defense mechanism against human serum. By sequencing the ApoL1 gene of the patient and subsequent in vitro mutagenesis experiments, we demonstrate that a homozygous missense substitution (N264K) in the membrane-addressing domain of this ApoL1 variant knocks down the trypanolytic activity, allowing the trypanosome to avoid ApoL1-mediated immunity. PMID:27073096

Human cytokine response to Texas crotaline envenomation before and after antivenom administration.

PubMed

Crocker, Patrick; Zad, Omid; Milling, Truman; Maxson, Todd; King, Benjamin; Whorton, Elbert

2010-10-01

The aim of this study was to characterize the human cytokine response to Texas crotaline envenomation before and after antivenom administration. This study enrolled crotaline bite victims presenting to a regional trauma center and children's hospital from March to November 2007 and age-matched unbitten controls. Blood spot cards were obtained from bite victims at presentation and at 1 and 6 hours after antivenom administration. One control sample was drawn from each of the age-matched controls selected from urgent care patients presenting for minor complaints. Samples were delivered to a laboratory using a proprietary method for quantitative evaluation of a large number of biomarkers in parallel with bead-based multiplex immunoassays. After obtaining informed consent, 14 crotaline bite victims (age range, 5-85 years; median age, 45 years; 50% female) (Snakebite Severity Score, 2-7; median, 3) and 14 age-matched controls were enrolled. There were 7 copperhead (Agkistrodon contortrix) bites, 4 rattlesnake (probably Western Diamondback Crotalus atrox) bites, 2 cottonmouth (Agkistrodon piscivorus) bites, and 1 bite from a snake that was not identified by the victim. In t tests, the means in the presentation samples for apolipoprotein A-I (Apo A-I), Apo C3, interleukin 4 (IL-4), myeloperoxidase, plasminogen activator inhibitor 1 (PAI-1), epidermal growth factor, and regulated upon activation, normal t-cell expressed and secreted were significantly lower and Apo H was significantly higher in the bite patients than in the controls. In the 1-hour sample, α(1)-antitrypsin, Apo A-I, Apo C3, eotaxin, IL-4, myeloperoxidase, and PAI-1 levels were lower and prostatic acid phosphatase and cancer antigen 125 levels were higher in the bite patients than in the controls. And in the 6-hour sample, α(1)-antitrypsin, Apo A-I, Apo C3, endothelin-1, IL-4, macrophage inflammatory protein 1β, myeloperoxidase, and epidermal growth factor levels were lower and Apo H level was higher in

Apolipoprotein E polymorphism and low density lipoprotein (LDL) oxidation in patients with dementia.

PubMed

Wehr, Hanna; Bednarska-Makaruk, Małgorzata; Graban, Ałła; Kunicki, Paweł K; Lojkowska, Wanda; Rodo, Maria; Ryglewicz, Danuta

2003-01-01

In patients with dementia, 29 diagnosed as probably suffering from Alzheimer's disease and 46 subjects with dementia of vascular origin, and in 41 non demented control subjects LDL oxidation in vitro was compared in carriers of various apolipoprotein E alleles. Restriction isotyping was performed by gene amplification and cleavage with Hhal, LDL oxidation was investigated by determination of conjugated dienes and vitamin E (alpha tocopherol) plasma level was measured by HPLC. In subjects with dementia oxidation of LDL was shown to be higher in carriers of epsilon4 allele as compared with non-carriers of this allele. It was especially observed in the propagation phase, which illustrates oxidation intensity after the exhaustion of the antioxidant reserve in LDL. Vitamin E level did not show differences between carriers of different alleles. It is concluded that the differences in oxidation susceptibility of LDL between demented subjects possessing particular apolipoprotein E forms can result partially from differing antioxidant properties of apolipoprotein E isoforms and, in a substantial degree, from the size and quality of LDL.

10 CFR 1017.28 - Processing on Automated Information Systems (AIS).

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Processing on Automated Information Systems (AIS). 1017.28... UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Physical Protection Requirements § 1017.28 Processing on Automated Information Systems (AIS). UCNI may be processed or produced on any AIS that complies with the guidance in OMB...

No effect of C-reactive protein on early atherosclerosis development in apolipoprotein E*3-leiden/human C-reactive protein transgenic mice.

PubMed

Trion, A; de Maat, M P M; Jukema, J W; van der Laarse, A; Maas, M C; Offerman, E H; Havekes, L M; Szalai, A J; Princen, H M G; Emeis, J J

2005-08-01

C-reactive protein (CRP) has been associated with risk of cardiovascular disease. It is not clear whether CRP is causally involved in the development of atherosclerosis. Mouse CRP is not expressed at high levels under normal conditions and increases in concentration only several-fold during an acute phase response. Because the dynamic range of human CRP is much larger, apolipoprotein E*3-Leiden (E3L) transgenic mice carrying the human CRP gene offer a unique model to study the role(s) of CRP in atherosclerosis development. Atherosclerosis development was studied in 15 male and 15 female E3L/CRP mice; E3L transgenic littermates were used as controls. The mice were fed a hypercholesterolemic diet to induce atherosclerosis development. Cholesterol exposure did not differ between E3L/CRP and E3L mice. Plasma CRP levels were on average 10.2+/-6.5 mg/L in male E3L/CRP mice, 0.2+/-0.1 mg/L in female E3L/CRP mice, and undetectable in E3L mice. Quantification of atherosclerosis showed that lesion area in E3L/CRP mice was not different from that in E3L mice. This study demonstrates that mildly elevated levels of CRP in plasma do not contribute to the development of early atherosclerosis in hypercholesterolemic E3L/CRP mice.

Plasma lipoprotein and apolipoprotein distribution as a function of density in the rainbow trout (Salmo gairdneri).

PubMed Central

Babin, P J

1987-01-01

I have previously described [Babin (1987) J. Biol. Chem. 262, 4290-4296] the apolipoprotein composition of the major classes of trout plasma lipoproteins. The present work describes the use of an isopycnic density gradient centrifugation procedure and sequential flotation ultracentrifugation to show: (1) the presence of intermediate density lipoproteins (IDL) in the plasma, between 1.015 and 1.040 g/ml; (2) the existence of a single type of Mr 240,000 apoB-like in the low density lipoproteins (LDL, 1.040 less than p less than 1.085 g/ml); (3) the presence of apoA-I-like (Mr 25,000) in the densest LDL; (4) the adequacy of 1.085 g/ml as a cutoff between the LDL and high density lipoproteins (HDL); (5) the accumulation of Mr 55,000 and 76,000 apolipoproteins and apoA-like apolipoproteins in the 1.21 g/ml infranatant. The fractionation of trout lipoprotein spectrum thus furnishes the distribution of the different lipoprotein classes and leads to the description of the constituent apolipoproteins, which account for about 36% of circulating plasma proteins in this species. Images Fig. 2. Fig. 3. PMID:3689318

[Application prospect of human-artificial intelligence system in future manned space flight].

PubMed

Wei, Jin-he

2003-01-01

To make the manned space flight more efficient and safer, a concept of human-artificial (AI) system is proposed in the present paper. The task of future manned space flight and the technique requirement with respect to the human-AI system development were analyzed. The main points are as follows: 1)Astronaut and AI are complementary to each other functionally; 2) Both symbol AI and connectionist AI should be included in the human-AI system, but expert system and Soar-like system are used mainly inside the cabin, the COG-like robots are mainly assigned for EVA either in LEO flight or on the surface of Moon or Mars; 3) The human-AI system is hierarchical in nature with astronaut at the top level; 4) The complex interfaces between astronaut and AI are the key points for running the system reliably and efficiently. As the importance of human-AI system in future manned space flight and the complexity of related technology, it is suggested that the R/D should be planned as early as possible.

Association of leisure-time physical activity with cognition by apolipoprotein-E genotype in persons aged 60 years and over: the National Health and Nutrition Examination Survey (NHANES-III).

PubMed

Obisesan, Thomas O; Umar, Nisser; Paluvoi, Nivedh; Gillum, Richard F

2012-01-01

To test the hypothesis that aerobic-related leisure-time physical activity (PA) is associated with better cognitive function and that the effect varies among apolipoprotein E (APOE) genotype groups. Cross-sectional study of persons examined in the Third National Health and Nutrition Examination Survey (NHANES-III; 1988-1994). US noninstitutionalized population. From a sample of 7159, aged ≥60 years, we analyzed data for 1799 older American men and women who had information on PA, a short mental status examination (SMSE), and were genotyped at the apolipoprotein E gene locus. In the initial bivariate analysis, non-ɛ4 carriers and ɛ4-heterozygotes performed better than ɛ4-homozygotes in the 60-69 age group. After controlling for multiple confounders including mobility limitation, PA correlated with a higher SMSE score in non-ɛ4 carriers (P = 0.014), but not in ɛ4 carriers (P = 0.887). At ≥70 years, PA also correlated with higher adjusted SMSE scores in non-ɛ4 carriers (P = 0.02); but this association became nonsignificant after controlling for mobility limitation (P = 0.12). In a nationally representative sample, PA was associated with enhanced cognition, an effect that was differentially influenced by apolipoprotein E genotype. Experimental studies are needed to determine whether or not PA can attenuate cognitive decline.

Genetic Ablation of Apolipoprotein A-IV Accelerates Alzheimer's Disease Pathogenesis in a Mouse Model

PubMed Central

Cui, Yujie; Huang, Mingwei; He, Yingbo; Zhang, Shuyan; Luo, Yongzhang

2011-01-01

The link between lipoprotein metabolism and Alzheimer's disease (AD) has been established. Apolipoprotein A-IV (apoA-IV), a component of lipoprotein particles similar to apolipoprotein E, has been suggested to play an important role in brain metabolism. Although there are clinical debates on the function of its polymorphism in AD, the pathologic role of apoA-IV in AD is still unknown. Here, we report that genetic ablation of apoA-IV is able to accelerate AD pathogenesis in mice. In a mouse model that overexpresses human amyloid precursor protein (APP) and presenilin 1, genetic reduction of apoA-IV augments extracellular amyloid-β peptide (Aβ) burden and aggravates neuron loss in the brain. In addition, genetic ablation of apoA-IV also accelerates spatial learning deficits and increases the mortality of mice. We have found that apoA-IV colocalizes within Aβ plaques in APP/presenilin 1 transgenic mice and binds to Aβ in vitro. Subsequent studies show that apoA-IV in this model facilitates Aβ uptake in the Aβ clearance pathway mediated by astrocytes rather than the amyloidogenic pathway of APP processing. Taken together, we conclude that apoA-IV deficiency increases Aβ deposition and results in cognitive damage in the mouse model. Enhancing levels of apoA-IV may have therapeutic potential in AD treatment. PMID:21356380

Proteomic analysis and comparison of the biopsy and autopsy specimen of human brain temporal lobe.

PubMed

He, Sizhi; Wang, Qingsong; He, Jintang; Pu, Hai; Yang, Wei; Ji, Jianguo

2006-09-01

The proteomic study on human temporal lobe can help us to understand the physiological function of CNS in normal as well as in pathological state. Proteomic tools are potent for the assessment of protein stability post mortem. In this pilot study, the human temporal lobe biopsy specimen with chronic pharmacoresistant temporal lobe epilepsy (TLE) and autopsy specimen in control were separated by 2-DE. Using MALDI-TOF-MS and MS/MS, 375 protein spots were identified which were the products of 267 genes. Six down-regulated and 23 up-regulated protein spots in the autopsy specimen were ascertained after the gel image analysis with the ImageMaster software. A number of proteins that include neurotransmitter metabolic and glycolytic enzymes, cytoprotective proteins and cytoskeleton were found decreased while the precursor of apolipoprotein A-I increased in the TLE brain. We tried several methods to prepare the protein samples and found that DNase and RNase treatment, ultracentrifugation and Amersham clean-up kit purification can improve gel separation quality. This work optimized the sample preparation method and constructed a primary protein database of human temporal lobe and found some proteins with remarkable level change probably involved in the post-mortem process and chronic pharmacoresistant TLE pathogenesis.

Integrating the Wall Street Journal into AIS Courses

ERIC Educational Resources Information Center

Kohlmeyer, James M., III

2008-01-01

While it is important for accounting information systems (AIS) students to understand computer technology, internal controls and business processes, such knowledge is of little use without reference to appropriate contexts. Integrating Wall Street Journal (WSJ) readings and discussions into AIS classes can enrich learning by stimulating…

Effects of low-dose monophasic levonorgestrel with ethinyl estradiol preparation on serum lipid levels: A twenty-four month clinical trial.

PubMed

Young, R L; DelConte, A

1999-11-01

The aim of this 24-cycle study was to evaluate the effects on serum lipid concentrations of an oral contraceptive preparation containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. Forty-two healthy women were enrolled in a study designed to evaluate the effects on serum lipid concentrations of an oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. Lipid data were evaluated for 28 women who completed 24 cycles of treatment with a preparation of 100 microg levonorgestrel with 20 microg ethinyl estradiol for 21 days followed by placebo for 7 days. Concentrations of triglycerides, total cholesterol, high-density lipoprotein cholesterol, high-density lipoprotein cholesterol subfractions 2 and 3, low-density lipoprotein cholesterol, and apolipoproteins A-I and B were analyzed. Mean percentage changes from baseline were tested for significance by means of paired Student t tests. Total cholesterol, high-density lipoprotein cholesterol, high-density lipoprotein subfraction 2, and apolipoprotein A-I concentrations were not significantly changed from baseline. Neither was the ratio of high-density lipoprotein subfraction 2 to high-density lipoprotein subfraction 3. Mean percentage increases in concentrations of triglyceride, high-density lipoprotein subfraction 3, apolipoprotein B, and low-density lipoprotein cholesterol and increases in the ratios of total cholesterol to high-density lipoprotein cholesterol, low-density lipoprotein cholesterol to high-density lipoprotein cholesterol, and apolipoprotein B to apolipoprotein A-I were significant (P <.05) at >/=1 cycle. By cycle 24, however, only the concentration of high-density lipoprotein subfraction 3 remained significantly elevated. Changes in the plasma lipid profiles among women receiving monophasic 100 microg levonorgestrel with 20 microg ethinyl estradiol were similar to those seen with other low-dose oral contraceptives, but by cycle 24 only 1 of 7 mean values

Recent progresses on AI-2 bacterial quorum sensing inhibitors.

PubMed

Zhu, Peng; Li, Minyong

2012-01-01

Quorum sensing (QS) is a communication procedure that predominates gene expression in response to cell density and fluctuations in the neighboring environment as a result of discerning molecules termed autoinducers (AIs). It has been embroiled that QS can govern bacterial behaviors such as the secretion of virulence factors, biofilm formation, bioluminescence production, conjugation, sporulation and swarming motility. Autoinducer 2 (AI-2), a QS signaling molecule brought up to be involved in interspecies communication, exists in both gram-negative and -positive bacteria. Therefore, novel approaches to interrupt AI-2 quorum sensing are being recognized as next generation antimicrobials. In the present review article, we summarized recent progresses on AI-2 bacterial quorum sensing inhibitors and discussed their potential as the antibacterial agents.

Enamelin (Enam) is essential for amelogenesis: ENU-induced mouse mutants as models for different clinical subtypes of human amelogenesis imperfecta (AI).

PubMed

Masuya, Hiroshi; Shimizu, Kunihiko; Sezutsu, Hideki; Sakuraba, Yoshiyuki; Nagano, Junko; Shimizu, Aya; Fujimoto, Naomi; Kawai, Akiko; Miura, Ikuo; Kaneda, Hideki; Kobayashi, Kimio; Ishijima, Junko; Maeda, Takahide; Gondo, Yoichi; Noda, Tetsuo; Wakana, Shigeharu; Shiroishi, Toshihiko

2005-03-01

Amelogenesis imperfecta (AI) is a group of commonly inherited defects of dental enamel formation, which exhibits marked genetic and clinical heterogeneity. The genetic basis of this heterogeneity is still poorly understood. Enamelin, the affected gene product in one form of AI (AIH2), is an extracellular matrix protein that is one of the components of enamel. We isolated three ENU-induced dominant mouse mutations, M100395, M100514 and M100521, which caused AI-like phenotypes in the incisors and molars of the affected individuals. Linkage analyses mapped each of the three mutations to a region of chromosome 5 that contained the genes encoding enamelin (Enam) and ameloblastin (Ambn). Sequence analysis revealed that each mutation was a single-base substitution in Enam. M100395 (Enam(Rgsc395)) and M100514 (Enam(Rgsc514)) were putative missense mutations that caused S to I and E to G substitutions at positions 55 and 57 of the translated protein, respectively. Enam(Rgsc395) and Enam(Rgsc514) heterozygotes showed severe breakage of the enamel surface, a phenotype that resembled local hypoplastic AI. The M100521 mutation (Enam(Rgsc521)) was a T to A substitution at the splicing donor site in intron 4. This mutation resulted in a frameshift that gave rise to a premature stop codon. The transcript of the Enam(Rgsc521) mutant allele was degraded, indicating that Enam(Rgsc521) is a loss-of-function mutation. Enam(Rgsc521) heterozygotes showed a hypomaturation-type AI phenotype in the incisors, possibly due to haploinsufficiency of Enam. Enam(Rgsc521) homozygotes showed complete loss of enamel on the incisors and the molars. Thus, we report here that the Enam gene is essential for amelogenesis, and that mice with different point mutations at Enam may provide good animal models to study the different clinical subtypes of AI.

Transgenic rabbit that expresses a functional human lipoprotein (a)

DOEpatents

Rouy, Didier; Duverger, Nicolas; Emmanuel, Florence; Denefle, Patrice; Houdebine, Louis-Marie; Viglietta, Celine; Rubin, Edward M.; Hughes, Steven D.

2003-01-01

A transgenic rabbit which has in its genomic DNA sequences that encode apolipoprotein (a) and apolipoprotein B polypeptides which are capable of combining to produce lipoprotein (a), a process for creating such a rabbit, and the use of the rabbit to identify compounds which are effective in the treatment of human diseases which are associated with, induced and/or exacerbated by Lp(a) expression.

Genetic variants on apolipoprotein gene cluster influence triglycerides with a risk of coronary artery disease among Indians.

PubMed

AshokKumar, Manickaraj; Subhashini, Navaneethan Gnana Veera; SaiBabu, Ramineni; Ramesh, Arabandi; Cherian, Kotturathu Mammen; Emmanuel, Cyril

2010-01-01

Apolipoprotein C3 and apolipoprotien A5 are proteins coded from the APOA1/C3/A4/A5 gene cluster. Sst I polymorphism on apolipoprotein C3 and -1131C polymorphism of apolipoprotien A5 are key variants involved in triglyceride metabolism and cause a significant cardio-metabolic risk. Here, we have evaluated these two variants for their roles in coronary artery disease in patients of the Indian population. The apolipoprotein gene cluster variants were analysed in 416 angiographically determined coronary artery disease patients and matched 416 controls using polymerase chain reaction-restriction fragment length polymorphism. The characteristics of the study subjects were analyzed statistically for their association with the polymorphisms. The alleles were combined as haplotypes and their combined risks were evaluated. The minor allele genotypes of both apolipoprotein C3 (S2) and apolipoprotien A5 (C) had a significant risk for coronary artery disease. The S2 allele genotyped patients had a significantly increased triglyceride level (P < 0.001) and increased triglycerides were observed among both patient and control CC genotype carriers. We identified the haplotype S2/C with a significant increased risk (P < 0.001) to coronary artery disease with increased levels of circulating triglycerides compared to other haplotypes in patients. We conclude that the variants on apolipoprotein C3 and apolipoprotien A5 modulate serum triglyceride levels and increase the risk of coronary artery disease.

Comparison of Lipoprotein Electrophoresis and Apolipoprotein E Genotyping in Investigating Dysbetalipoproteinemia.

PubMed

Ahmed, Farhan; El-Kadiki, Alia; Gibbons, Stephen

2017-06-01

Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity; however, lipoprotein electrophoresis may also be used to assist in the diagnosis. The aim of this study was to compare apolipoprotein E (apo E) genotyping and lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were collected over a three-year period from a lipid clinic in a tertiary referral centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Sixty-two patients had both apo E genotyping and lipoprotein electrophoresis. Of these, 16 patients showed broad beta band on electrophoresis. However, only 3 of them had apo E2E2 homozygosity on genotyping. Lipoprotein electrophoresis and apo E genotyping results showed poor concordance. This was primarily due to visual interpretation error of lipoprotein electrophoresis which may over diagnose dysbetalipoproteinemia.

Creating an AI modeling application for designers and developers

NASA Astrophysics Data System (ADS)

Houlette, Ryan; Fu, Daniel; Jensen, Randy

2003-09-01

Simulation developers often realize an entity's AI by writing a program that exhibits the intended behavior. These behaviors are often the product of design documents written by designers. These individuals, while possessing a vast knowledge of the subject matter, might not have any programming knowledge whatsoever. To address this disconnect between design and subsequent development, we have created an AI application whereby a designer or developer sketches an entity's AI using a graphical "drag and drop" interface to quickly articulate behavior using a UML-like representation of state charts. Aside from the design-level benefits, the application also features a runtime engine that takes the application's data as input along with a simulation or game interface, and makes the AI operational. We discuss our experience in creating such an application for both designer and developer.

Effect of gemfibrozil on apolipoprotein B secretion and diacylglycerol acyltransferase activity in human hepatoblastoma (HepG2) cells.

PubMed

Zhu, Daming; Ganji, Shobha H; Kamanna, Vaijinath S; Kashyap, Moti L

2002-10-01

The mechanism of action of a widely used drug gemfibrozil to reduce triglycerides (TG) and apolipoprotein B (apo B) is incompletely understood. Using human hepatoblastoma (HepG2) cells, we examined the effect of gemfibrozil on apo B secretion and TG synthesis catalyzed by diacylglycerol acyltransferase (DGAT), primary processes associated with the secretion of LDL. Gemfibrozil significantly decreased apo B secretion by HepG2 cells. It decreased oleate-induced stimulation of apo B secretion, suggesting that gemfibrozil-mediated inhibition of apo B secretion may be dependent on the synthesis of TG catalyzed by DGAT. Pre-incubation of HepG2 cells with gemfibrozil (200-400 micromol/l for 48 h) significantly inhibited microsomal DGAT activity. When added directly to the DGAT assay system containing control microsomes, gemfibrozil significantly inhibited the activity of DGAT by 14-25%. Gemfibrozil (200-400 micromol/l) inhibited TG synthesis by 47-50% as measured by the incorporation of 3H-oleic acid into TG. The data indicate that gemfibrozil inhibits DGAT activity resulting in decreased synthesis of TG and its availability for apo B lipidation rendering it susceptible to intracellular apo B degradation leading to the decreased secretion. These in-vitro data suggest a novel additional mechanism by which gemfibrozil lowers plasma TG and atherogenic apo B lipoproteins in dyslipidemic patients.

Modifications of the G6G timed-AI protocol improved pregnancy per AI and reduced pregnancy loss in lactating dairy cows.

PubMed

Heidari, F; Dirandeh, E; Ansari Pirsaraei, Z; Colazo, M G

2017-11-01

In dairy cows, subjected to a G6G protocol, objectives were to determine effects of (1) extending the interval from prostaglandin F2α (PGF2α) to gonadotropin-releasing hormone (GnRH) during presynchronization; and (2) adding a second PGF2α treatment before artificial insemination (AI), on ovarian response, plasma progesterone (P4) concentrations and pregnancy per AI (P/AI). In a 2×2 factorial design, lactating cows were randomly assigned to one of four timed AI (TAI) protocols: (1) G6G (n=149), one injection of PGF2α, GnRH 2 days later and a 7-day Ovsynch (GnRH, 7 days, PGF2α, 56 h, GnRH, 16 h, TAI) was initiated 6 days later; (2) G6GP (n=144), an additional PGF2α treatment (24 h after the first) during Ovsynch of the G6G protocol; (3) MG6G, one injection of PGF2α, GnRH 4 days later before initiation of the G6G protocol; and (4) MG6GP, an additional PGF2α treatment (24 h after the first) during Ovsynch of the MG6G protocol. Blood samples were collected (subset of 200 cows) at first GnRH and PGF2α of the Ovsynch, and at TAI to measure P4. Ultrasound examinations were performed in a subset of 406 cows to evaluate ovarian response at various times of Ovsynch, and in all cattle to determine pregnancy status at 32 and 60 days after TAI. Extending the interval by 2 days between PGF2α and GnRH during presynchronization increased (P<0.01) ovulatory response to first GnRH of Ovsynch, circulating P4 during Ovsynch, and P/AI at 32 and 60 days after TAI. Adding a second PGF2α treatment before AI increased the proportion of cows with luteal regression (P=0.04), improved P/AI at 60 days after TAI (P=0.05), and reduced pregnancy loss between 30 and 60 days after TAI (P=0.04). In summary, extending the interval from PGF2α to GnRH during presynchronization increased response to first GnRH of Ovsynch and P4 concentrations during Ovsynch, whereas adding a second PGF2α treatment before AI enhanced luteal regression. Both modifications of the G6G protocol improved

Reduced Apolipoprotein Glycosylation in Patients with the Metabolic Syndrome

PubMed Central

Savinova, Olga V.; Fillaus, Kristi; Jing, Linhong; Harris, William S.; Shearer, Gregory C.

2014-01-01

Objective The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls. Methods Very low density (VLDL), intermediate/low density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D) gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays. Results Metabolic syndrome patients differed from healthy controls in the following ways: (1) total plasma - apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2) VLDL - apoB, apoC3, and apoE were increased; (3) LDL - apoC3 was increased, (4) HDL -associated constitutive serum amyloid A protein (SAA4) was reduced (p<0.05 vs. controls for all). In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated) isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all). Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all). Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001). Conclusions Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined. PMID:25118169

Cross-species pharmacokinetic comparison from mouse to man of a second-generation antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100.

PubMed

Yu, Rosie Z; Kim, Tae-Won; Hong, An; Watanabe, Tanya A; Gaus, Hans J; Geary, Richard S

2007-03-01

The pharmacokinetics of a 2'-O-(2-methoxyethyl)-modified oligonucleotide, ISIS 301012 [targeting human apolipoprotein B-100 (apoB-100)], was characterized in mouse, rat, monkey, and human. Plasma pharmacokinetics following parental administration was similar across species, exhibiting a rapid distribution phase with t(1/2alpha) of several hours and a prolonged elimination phase with t(1/2beta) of days. The prolonged elimination phase represents equilibrium between tissues and circulating drug due to slow elimination from tissues. Absorption was nearly complete following s.c. injection, with bioavailability ranging from 80 to 100% in monkeys. Plasma clearance scaled well across species as a function of body weight alone, and this correlation was improved when corrected for plasma protein binding. In all of the animal models studied, the highest tissue concentrations of ISIS 301012 were observed in kidney and liver. Urinary excretion was less than 3% in monkeys and human in the first 24 h. ISIS 301012 is highly bound to plasma proteins, probably preventing rapid removal by renal filtration. However, following 25 mg/kg s.c. administration in mouse and 5-mg/kg i.v. bolus administration in rat, plasma concentrations of ISIS 301012 exceeded their respective protein binding capacity. Thus, urinary excretion increased to 16% or greater within the first 24 h. Albeit slow, urinary excretion of ISIS 301012 and its shortened metabolites is the ultimate elimination pathway of this compound, as demonstrated by 32% of dose recovered in total excreta by 14 days in a rat mass balance study. The pharmacokinetics of ISIS 301012 in human is predictable from the pharmacokinetics measured in animals. The pharmacokinetic properties of ISIS 301012 provide guidance for clinical development and support infrequent dose administration.

Specificity determinants in the interaction of apolipoprotein(a) kringles with tetranectin and LDL.

PubMed

Caterer, Nigel R; Graversen, Jonas H; Jacobsen, Christian; Moestrup, Søren K; Sigurskjold, Bent W; Etzerodt, Michael; Thøgersen, Hans C

2002-11-01

Lipoprotein(a) is composed of low density lipoprotein and apolipoprotein(a). Apolipoprotein(a) has evolved from plasminogen and contains 10 different plasminogen kringle 4 homologous domains [KIV(1-110)]. Previous studies indicated that lipoprotein(a) non-covalently binds the N-terminal region of lipoprotein B100 and the plasminogen kringle 4 binding plasma protein tetranectin. In this study recombinant KIV(2), KIV(7) and KIV(10) derived from apolipoprotein(a) were produced in E. coli and the binding to tetranectin and low density lipoprotein was examined. Only KIV(10) bound to tetranectin and binding was similar to that of plasminogen kringle 4 to tetranectin. Only KIV(7) bound to LDL. In order to identify the residues responsible for the difference in specificity between KIV(7) and KIV(10), a number of surface-exposed residues located around the lysine binding clefts were exchanged. Ligand binding analysis of these derivatives showed that Y62, and to a minor extent W32 and E56, of KIV(7) are important for LDL binding to KIV(7), whereas R32 and D56 of KIV(10) are required for tetranectin binding of KIV(10).

Apolipoprotein E and Sex Bias in Cerebrovascular Aging of Men and Mice.

PubMed

Finch, Caleb E; Shams, Sara

2016-09-01

Alzheimer disease (AD) research has mainly focused on neurodegenerative processes associated with the classic neuropathologic markers of senile plaques and neurofibrillary tangles. Additionally, cerebrovascular contributions to dementia are increasingly recognized, particularly from cerebral small vessel disease (SVD). Remarkably, in AD brains, the apolipoprotein E (ApoE) ɛ4 allele shows male excess for cerebral microbleeds (CMBs), a marker of SVD, which is opposite to the female excess of plaques and tangles. Mouse transgenic models add further complexities to sex-ApoE ɛ4 allele interactions, with female excess of both CMBs and brain amyloid. We conclude that brain aging and AD pathogenesis cannot be understood in humans without addressing major gaps in the extent of sex differences in cerebrovascular pathology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of AIS Versus TMS Data Collected over the Virginia Piedmont

NASA Technical Reports Server (NTRS)

Bell, R.; Evans, C. S.

1985-01-01

The Airborne Imaging Spectrometer (AIS, NS001 Thematic Mapper Simlulator (TMS), and Zeiss camera collected remotely sensed data simultaneously on October 27, 1983, at an altitude of 6860 meters (22,500 feet). AIS data were collected in 32 channels covering 1200 to 1500 nm. A simple atmospheric correction was applied to the AIS data, after which spectra for four cover types were plotted. Spectra for these ground cover classes showed a telescoping effect for the wavelength endpoints. Principal components were extracted from the shortwave region of the AIS (1200 to 1280 nm), full spectrum AIS (1200 to 1500 nm) and TMS (450 to 12,500 nm) to create three separate three-component color image composites. A comparison of the TMS band 5 (1000 to 1300 nm) to the six principal components from the shortwave AIS region (1200 to 1280 nm) showed improved visual discrimination of ground cover types. Contrast of color image composites created from principal components showed the AIS composites to exhibit a clearer demarcation between certain ground cover types but subtle differences within other regions of the imagery were not as readily seen.

Discovering Knowledge from AIS Database for Application in VTS

NASA Astrophysics Data System (ADS)

Tsou, Ming-Cheng

The widespread use of the Automatic Identification System (AIS) has had a significant impact on maritime technology. AIS enables the Vessel Traffic Service (VTS) not only to offer commonly known functions such as identification, tracking and monitoring of vessels, but also to provide rich real-time information that is useful for marine traffic investigation, statistical analysis and theoretical research. However, due to the rapid accumulation of AIS observation data, the VTS platform is often unable quickly and effectively to absorb and analyze it. Traditional observation and analysis methods are becoming less suitable for the modern AIS generation of VTS. In view of this, we applied the same data mining technique used for business intelligence discovery (in Customer Relation Management (CRM) business marketing) to the analysis of AIS observation data. This recasts the marine traffic problem as a business-marketing problem and integrates technologies such as Geographic Information Systems (GIS), database management systems, data warehousing and data mining to facilitate the discovery of hidden and valuable information in a huge amount of observation data. Consequently, this provides the marine traffic managers with a useful strategic planning resource.

Identification of the ancestral haplotype for apolipoprotein B suggests an African origin of Homo sapiens sapiens and traces their subsequent migration to Europe and the Pacific

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

Rapacz, J.; Hasler-Rapacz, J.O.; Chen, L.

1991-02-15

The probable ancestral haplotype for human apolipoprotein B (apoB) has been identified through immunological analysis of chimpanzee and gorilla serum and sequence analysis of their DNA. Moreover, the frequency of this ancestral apoB haplotype among different human populations provides strong support for the African origin of Homo sapiens sapiens and their subsequent migration from Africa to Europe and to the Pacific. The approach used here for the identification of the ancestral human apoB haplotype is likely to be applicable to many other genes.

On the homotopy equivalence of simple AI-algebras

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

Aristov, O Yu

1999-02-28

Let A and B be simple unital AI-algebras (an AI-algebra is an inductive limit of C*-algebras of the form BigOplus{sub i}{sup k}C([0,1],M{sub N{sub i}}). It is proved that two arbitrary unital homomorphisms from A into B such that the corresponding maps K{sub 0}A{yields}K{sub 0}B coincide are homotopic. Necessary and sufficient conditions on the Elliott invariant for A and B to be homotopy equivalent are indicated. Moreover, two algebras in the above class having the same K-theory but not homotopy equivalent are constructed. A theorem on the homotopy of approximately unitarily equivalent homomorphisms between AI-algebras is used in the proof, whichmore » is deduced in its turn from a generalization to the case of AI-algebras of a theorem of Manuilov stating that a unitary matrix almost commuting with a self-adjoint matrix h can be joined to 1 by a continuous path consisting of unitary matrices almost commuting with h.« less

Lack of Influence of Apolipoprotein E Status on Cognition or Brain Structure in Professional Fighters

PubMed Central

Miller, Justin B.; Rissman, Robert A.; Bernick, Charles B.

2017-01-01

Abstract The role of the apolipoprotein e4 allele in moderating cognitive and neuroanatomical degeneration following repeated traumatic brain injury is controversial. Here we sought to establish the presence or absence of such a moderating relationship in a prospective study of active and retired boxers and mixed martial arts fighters. Fighters (n = 193) underwent cognitive evaluations, interviews regarding fight history, MRI of the brain, and genetic testing. We used a series of moderator analyses to test for any relationship of apolipoprotein genotype on structural volumes of brain regions previously established to be smaller in those with the most fight exposure, and on cognitive abilities also established to be sensitive to fight exposure. No moderating relationship was detected in any of the analyses. The results of this study suggest that there is no impact of apolipoprotein genotype on the apparent negative association between exposure to professional fighting and brain structure volume or aspects of cognition. PMID:27245878

Quality measures and assurance for AI (Artificial Intelligence) software

NASA Technical Reports Server (NTRS)

Rushby, John

1988-01-01

This report is concerned with the application of software quality and evaluation measures to AI software and, more broadly, with the question of quality assurance for AI software. Considered are not only the metrics that attempt to measure some aspect of software quality, but also the methodologies and techniques (such as systematic testing) that attempt to improve some dimension of quality, without necessarily quantifying the extent of the improvement. The report is divided into three parts Part 1 reviews existing software quality measures, i.e., those that have been developed for, and applied to, conventional software. Part 2 considers the characteristics of AI software, the applicability and potential utility of measures and techniques identified in the first part, and reviews those few methods developed specifically for AI software. Part 3 presents an assessment and recommendations for the further exploration of this important area.

Assembly of high density lipoprotein by the ABCA1/apolipoprotein pathway.

PubMed

Yokoyama, Shinji

2005-06-01

Mammalian somatic cells do not catabolize cholesterol and therefore need to export it for sterol homeostasis at the levels of cells and whole bodies. This mechanism may reduce intracellularly accumulated cholesterol in excess, and thereby would contribute to the prevention or cure of the initial stage of atherosclerotic vascular lesions. HDL is thought to play a main role in this reaction on the basis of epidemiological evidence and in-vitro experimental data. Two independent mechanisms have been identified for this reaction. One is non-specific diffusion-mediated cholesterol 'efflux' from the cell surface, and cholesterol is trapped by various extracellular acceptors including lipoproteins. Extracellular cholesterol esterification on HDL provides a driving force for the net removal of cell cholesterol, and some cellular factors may enhance this reaction. The other mechanism is an apolipoprotein-mediated process to generate HDL by removing cellular phospholipid and cholesterol. This reaction is mediated by a membrane protein ABCA1, and lipid-free or lipid-poor helical apolipoproteins recruit cellular phospholipid and cholesterol to assemble HDL particles. The reaction is composed of two elements: the assembly of HDL particles with phospholipid by apolipoprotein, and cholesterol enrichment in HDL. ABCA1 is essential for the former step, and the latter step requires further intracellular events. ABCA1 is a rate-limiting factor of HDL assembly and is regulated by transcriptional factors and posttranscriptional factors. Posttranscriptional regulation of ABCA1 involves the modulation of its calpain-mediated degradation.

An Immune Agent for Web-Based AI Course

ERIC Educational Resources Information Center

Gong, Tao; Cai, Zixing

2006-01-01

To overcome weakness and faults of a web-based e-learning course such as Artificial Intelligence (AI), an immune agent was proposed, simulating a natural immune mechanism against a virus. The immune agent was built on the multi-dimension education agent model and immune algorithm. The web-based AI course was comprised of many files, such as HTML…

Lipid-related markers and cardiovascular disease prediction.

PubMed

Di Angelantonio, Emanuele; Gao, Pei; Pennells, Lisa; Kaptoge, Stephen; Caslake, Muriel; Thompson, Alexander; Butterworth, Adam S; Sarwar, Nadeem; Wormser, David; Saleheen, Danish; Ballantyne, Christie M; Psaty, Bruce M; Sundström, Johan; Ridker, Paul M; Nagel, Dorothea; Gillum, Richard F; Ford, Ian; Ducimetiere, Pierre; Kiechl, Stefan; Koenig, Wolfgang; Dullaart, Robin P F; Assmann, Gerd; D'Agostino, Ralph B; Dagenais, Gilles R; Cooper, Jackie A; Kromhout, Daan; Onat, Altan; Tipping, Robert W; Gómez-de-la-Cámara, Agustín; Rosengren, Annika; Sutherland, Susan E; Gallacher, John; Fowkes, F Gerry R; Casiglia, Edoardo; Hofman, Albert; Salomaa, Veikko; Barrett-Connor, Elizabeth; Clarke, Robert; Brunner, Eric; Jukema, J Wouter; Simons, Leon A; Sandhu, Manjinder; Wareham, Nicholas J; Khaw, Kay-Tee; Kauhanen, Jussi; Salonen, Jukka T; Howard, William J; Nordestgaard, Børge G; Wood, Angela M; Thompson, Simon G; Boekholdt, S Matthijs; Sattar, Naveed; Packard, Chris; Gudnason, Vilmundur; Danesh, John

2012-06-20

The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated. To determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction. Individual records were available for 165,544 participants without baseline CVD in 37 prospective cohorts (calendar years of recruitment: 1968-2007) with up to 15,126 incident fatal or nonfatal CVD outcomes (10,132 CHD and 4994 stroke outcomes) during a median follow-up of 10.4 years (interquartile range, 7.6-14 years). Discrimination of CVD outcomes and reclassification of participants across predicted 10-year risk categories of low (<10%), intermediate (10%-<20%), and high (≥20%) risk. The addition of information on various lipid-related markers to total cholesterol, HDL-C, and other conventional risk factors yielded improvement in the model's discrimination: C-index change, 0.0006 (95% CI, 0.0002-0.0009) for the combination of apolipoprotein B and A-I; 0.0016 (95% CI, 0.0009-0.0023) for lipoprotein(a); and 0.0018 (95% CI, 0.0010-0.0026) for lipoprotein-associated phospholipase A2 mass. Net reclassification improvements were less than 1% with the addition of each of these markers to risk scores containing conventional risk factors. We estimated that for 100,000 adults aged 40 years or older, 15,436 would be initially classified at intermediate risk using conventional risk factors alone. Additional testing with a combination of apolipoprotein B and A-I would reclassify 1.1%; lipoprotein(a), 4.1%; and lipoprotein-associated phospholipase A2 mass, 2.7% of people to a 20% or higher predicted CVD risk category and, therefore, in need of statin treatment under Adult Treatment Panel III guidelines. In a study of individuals without known CVD, the addition of information on the

Italian familial defective apolipoprotein B patients share a unique haplotype with other Caucasian patients.

PubMed

Cefalù, A B; Barbagallo, C M; Sesti, E; Caldarella, R; Polizzi, F; Marino, G; Noto, D; Rolleri, M; Travali, S; Scalisi, G; Notarbartolo, A; Corsini, A; Bertolini, S; Averna, M R

2001-09-01

Familial defective apolipoprotein (apo) B-100 together with familial hypercholesterolemia are the two common genetic conditions that cause hypercholesterolemia. Familial defective apolipoprotein B-100 is due to mutations around codon 3500 of the apo B gene. The most-characterized mutation is a G>A transition at nucleotide 10,708 that results in the substitution of arginine by glutamine at codon 3500 (Apo B Arg3500Gln). Two other mutations are caused by a C>T transition, one at nucleotide 10,800 (Apo B Arg3531Cys) and the other at nucleotide 10,707 (apo B Arg3500Trp). In the present study we describe three new Italian cases of familial defective apolipoprotein B-100 (Apo B Arg3500Gln), one from the Liguria region and two from Sicily, and the haplotype of the apo B gene co-segregating with the mutation. By screening two groups of probands, clinically diagnosed as having Familial Hypercholesterolemia (700 from mainland Italy and 305 from Sicily), the prevalence of familial defective apolipoprotein B-100 due to Arg3500Gln was found to be very low (0.28% and 0.65%, respectively). The Arg3531Cys mutation was not detected in any proband. In the three new families with Arg3500Gln mutation in the present study and in one previously described in Italy, the mutation was associated with a unique apo B haplotype, which is consistent with data previously reported for Caucasian patients [XbaI-, MspI+, EcoRI-, presence of the 5' signal peptide insertion (Ins) allele, and the 49-repeat allele of the 3'-VNTR].

Breast Milk from Smokers Contains Less Cholesterol and Protein and Smaller Size of Apolipoprotein A-I Resulting in Lower Zebrafish Embryo Survivability.

PubMed

Kim, Seong-Min; Kim, Suk-Jeong; Kim, Jae-Yong; Kim, Jae-Ryong; Cho, Kyung-Hyun

To determine the quality of breast milk (BM), we compared the functions of BM from ex-smokers and nonsmokers. We analyzed the contents of lipids, glucose, and protein in BM from ex-smokers (10 cigarettes/day for 13 ± 3 years) as well as infant formula. Nonsmokers' BM showed 2.4- and 1.4-fold higher cholesterol and protein contents, respectively, than BM from smokers. Infant formula contained almost no cholesterol, but did show remarkably higher glucose and triglyceride levels than BM. Microinjection of BM (50 nL) from nonsmokers and smokers into zebrafish embryos resulted in 59% and 44% survival, respectively, whereas formula injection resulted in 31% survival. The higher cholesterol and protein contents of BM were directly correlated with higher embryo survivability, suggesting that cholesterol content is directly and critically associated with growth of neonate infants. Smokers' BM contained smaller-sized apolipoproteinA-I (apoA-I) (24.4 ± 0.2 kDa) than BM from nonsmokers (26.7 ± 0.4 kDa), suggesting that putative modification and cleavage occurred in apoA-I. BM containing higher molecular weight apoA-I resulted in higher embryo survivability. Smoking before pregnancy can affect the composition and quality of BM, resulting in almost complete loss of cholesterol and protein, especially lactoferrin, lactalbumin, and apoA-I, accompanied by proteolytic degradation. These impairment effects of BM are associated with elevation of oxidative stress and lower embryo survivability.

Suppressive effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient mice.

PubMed

Natsume, Midori; Baba, Seigo

2014-01-01

Previous studies in humans have shown that the cacao polyphenols, (-)-epicatechin and its oligomers, prevent in vitro and ex vivo low-density lipoprotein oxidation mediated by free radical generators and metal ions and also reduce plasma LDL-cholesterol levels. The aim of this study was to examine the effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice. Mice aged 8 weeks (n = 90) were randomized into three groups, and fed either normal mouse chow (controls) or chow supplemented with 0.25 or 0.40 % cacao polyphenols for 16 weeks. The mean plaque area in cross-sections of the brachiocephalic trunk was measured and found to be lower in the 0.25 % cacao polyphenol group than in the control group (p < 0.05). Pathological observations showed that accumulation of cholesterol crystals in the plaque area was greater in the control group compared with the 0.40 % cacao polyphenol group (p < 0.05). Immunochemical staining in the 0.25 and 0.40 % groups showed that expression of the cell adhesion molecules (VCAM-1 and ICAM-1) and production of oxidative stress markers (4-hydroxynonenal, hexanoyl-lysine, and dityrosine) were reduced in cross-sections of the brachiocephalic trunk. These results suggest that cacao polyphenols inhibit the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice by reducing oxidative stress and inflammatory responses.

Plasma apolipoprotein levels are associated with cognitive status and decline in a community cohort of older individuals.

PubMed

Song, Fei; Poljak, Anne; Crawford, John; Kochan, Nicole A; Wen, Wei; Cameron, Barbara; Lux, Ora; Brodaty, Henry; Mather, Karen; Smythe, George A; Sachdev, Perminder S

2012-01-01

Apolipoproteins have recently been implicated in the etiology of Alzheimer's disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

PubMed Central

Song, Fei; Poljak, Anne; Crawford, John; Kochan, Nicole A.; Wen, Wei; Cameron, Barbara; Lux, Ora; Brodaty, Henry; Mather, Karen; Smythe, George A.; Sachdev, Perminder S.

2012-01-01

Objectives Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. Methods 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. Results At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Conclusions Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals. PMID:22701550

Integration of SAR and AIS for ship detection and identification

NASA Astrophysics Data System (ADS)

Yang, Chan-Su; Kim, Tae-Ho

2012-06-01

This abstract describes the preliminary design concept for an integration system of SAR and AIS data. SAR sensors are used to acquire image data over large coverage area either through the space borne or airborne platforms in UTC. AIS reports should also obtained on the same date as of the SAR acquisition for the purpose to perform integration test. Once both data reports are obtained, one need to match the timings of AIS data acquisition over the SAR image acquisition time with consideration of local time & boundary to extract the closest time signal from AIS report in order to know the AIS based ship positions, but still one cannot be able to distinguish which ships have the AIS transponder after projection of AIS based position onto the SAR image acquisition boundary. As far as integration is concerned, the ship dead-reckoning concept is most important forecasted position which provides the AIS based ship position at the time of SAR image acquisition and also provides the hints for azimuth shift which occurred in SAR image for the case of moving ships which moves in the direction perpendicular to the direction of flight path. Unknown ship's DR estimation is to be carried out based on the initial positions, speed and course over ground, which has already been shorted out from AIS reports, during the step of time matching. This DR based ship's position will be the candidate element for searching the SAR based ship targets for the purpose of identification & matching within the certain boundary around DR. The searching method is performed by means of estimation of minimum distance from ship's DR to SAR based ship position, and once it determines, so the candidate element will look for matching like ship size match of DR based ship's dimension wrt SAR based ship's edge, there may be some error during the matching with SAR based ship edges with actual ship's hull design as per the longitudinal and transverse axis size information obtained from the AIS reports due to

Anti-inflammatory activity of polyphenolics from açai (Euterpe oleracea Martius) in intestinal myofibroblasts CCD-18Co cells.

PubMed

Dias, Manoela Maciel dos Santos; Martino, Hércia Stampini Duarte; Noratto, Giuliana; Roque-Andrade, Andrea; Stringheta, Paulo César; Talcott, Stephen; Ramos, Afonso Mota; Mertens-Talcott, Susanne U

2015-10-01

The demand for tropical fruits high in polyphenolics including açai (Euterpe oleracea Mart.) has been increasing based on ascribed health benefits and antioxidant properties. This study evaluated the anti-inflammatory activities of açai polyphenolics in human colon myofibroblastic CCD-18Co cells to investigate the suppression of reactive oxygen species (ROS), and mRNA and protein expression of inflammatory proteins. Non-cytotoxic concentrations of açai extract, 1-5 mg gallic acid equivalent L(-1), were selected. The generation of ROS was induced by lipopolysaccharide (LPS) and açai extract partially reversed this effect to 0.53-fold of the LPS-control. Açai extract (5 mg GAE L(-1)) down-regulated LPS-induced mRNA-expression of tumor necrosis factor alpha, TNF-α (to 0.42-fold), cyclooxygenase 2, COX-2 (to 0.61-fold), toll-like receptor-4, TLR-4 (to 0.52-fold), TNF receptor-associated factor 6, TRAF-6 (to 0.64-fold), nuclear factor kappa-B, NF-κB (to 0.76-fold), vascular cell adhesion molecule 1, VCAM-1 (to 0.71-fold) and intercellular adhesion molecule 1, ICAM-1 (to 0.68-fold). The protein levels of COX-2, TLR-4, p-NF-κB and ICAM-1 were induced by LPS and the açai extract partially reversed this effect in a dose-dependent manner. These results suggest the anti-inflammatory effect of açai polyphenolic extract in intestinal cells are at least in part mediated through the inhibition of ROS and the expression of TLR-4 and NF-κB. Results indicate the potential for açai polyphenolics in the prevention of intestinal inflammation.

Regulation of bacteria population behaviors by AI-2 "consumer cells" and "supplier cells".

PubMed

Quan, Yufen; Meng, Fankang; Ma, Xinyu; Song, Xinhao; Liu, Xiao; Gao, Weixia; Dang, Yulei; Meng, Yao; Cao, Mingfeng; Song, Cunjiang

2017-09-19

Autoinducer-2 (AI-2) is a universal signal molecule and enables an individual bacteria to communicate with each other and ultimately control behaviors of the population. Harnessing the character of AI-2, two kinds of AI-2 "controller cells" ("consumer cells" and "supplier cells") were designed to "reprogram" the behaviors of entire population. For the consumer cells, genes associated with the uptake and processing of AI-2, which includes LsrACDB, LsrFG, LsrK, were overexpressed in varying combinations. Four consumer cell strains were constructed: Escherichia coli MG1655 pLsrACDB (NK-C1), MG1655 pLsrACDBK (NK-C2), MG1655 pLsrACDBFG (NK-C3) and MG1655 pLsrACDBFGK (NK-C4). The key enzymes responsible for production of AI-2, LuxS and Mtn, were also overexpressed, yielding strains MG1655 pLuxS (NK-SU1), and MG1655 pLuxS-Mtn (NK-SU2). All the consumer cells could decrease the environmental AI-2 concentration. NK-C2 and NK-C4 were most effective in AI-2 uptake and inhibited biofilm formation. While suppliers can increase the environmental AI-2 concentration and NK-SU2 was most effective in supplying AI-2 and facilitated biofilm formation. Further, reporter strain, MG1655 pLGFP was constructed. The expression of green fluorescent protein (GFP) in reporter cells was initiated and guided by AI-2. Mixture of consumer cells and reporter cells suggest that consumer cells can decrease the AI-2 concentration. And the supplier cells were co-cultured with reporter cells, indicating that supplier cells can provide more AI-2 compared to the control. The consumer cells and supplier cells could be used to regulate environmental AI-2 concentration and the biofilm formation. They can also modulate the AI-2 concentration when they were co-cultured with reporter cells. It can be envisioned that this system will become useful tools in synthetic biology and researching new antimicrobials.

AI Based Personal Learning Environments: Directions for Long Term Research. AI Memo 384.

ERIC Educational Resources Information Center

Goldstein, Ira P.; Miller, Mark L.

The application of artificial intelligence (AI) techniques to the design of personal learning environments is an enterprise of both theoretical and practical interest. In the short term, the process of developing and testing intelligent tutoring programs serves as a new experimental vehicle for exploring alternative cognitive and pedagogical…

Analysis of AIS Data of the Recluse Oil Field, Recluse, Wyoming

NASA Technical Reports Server (NTRS)

Dykstra, J. D.; Segal, D. B.

1985-01-01

Airborne Imaging Spectrometer (AIS) data were flown over the Recluse, Wyoming oil field on September 9, 1984. Processing software was developed at Earth Satellite Corporation (EarthSat) for interactive analysis of the AIS data. EarthSat's AIS processing capabilities include destriping, solar irradiance corrections, residual calculations, geometric resampling, equal energy normalization, interactive spectral classifications and a variety of compressive algorithms to reduce the data to 8-bit format with a minimum of information loss. The in-house photolab facilities of EarthSat can routinely produce high-quality color renditions of the enhanced AIS data. A total of 80 lithologic samples were collected under the AIS flight lines. Correlation (within the atmospheric windows) between the laboratory and the AIS spectra of sample sites was generally poor. Reasonable correlation was only possible in large, freshly plowed fields. Mixed pixels and contrast between the natural and sample's surfaces were believed responsible for the poor correlation. Finally, a drift of approximately three channels was observed in the diffraction grating position within the 1.8 to 2.1 micron quadrant.

Identification of the ancestral haplotype for apolipoprotein B suggests an African origin of Homo sapiens sapiens and traces their subsequent migration to Europe and the Pacific.

PubMed Central

Rapacz, J; Chen, L; Butler-Brunner, E; Wu, M J; Hasler-Rapacz, J O; Butler, R; Schumaker, V N

1991-01-01

The probable ancestral haplotype for human apolipoprotein B (apoB) has been identified through immunological analysis of chimpanzee and gorilla serum and sequence analysis of their DNA. Moreover, the frequency of this ancestral apoB haplotype among different human populations provides strong support for the African origin of Homo sapiens sapiens and their subsequent migration from Africa to Europe and to the Pacific. The approach used here for the identification of the ancestral human apoB haplotype is likely to be applicable to many other genes. PMID:1996341

Quantitation of apolipoprotein epsilon gene expression by competitive polymerase chain reaction in a patient with familial apolipoprotein E deficiency.

PubMed

Dobmeyer, J M; Rexin, M; Dobmeyer, T S; Klein, S A; Rossol, R; Feussner, G

1998-06-22

A simple method of obtaining semiquantitative and reliable data on apolipoprotein (apo) sigma gene expression is described. We detected apo sigma specific sequences by reverse transcription (rT)-PCR. For quantitative measurement, an apo sigma DNA standard was produced allowing the development of a competitive PCR-method. The efficiency of RNA extraction and cDNA synthesis was controlled by quantitation of a housekeeping gene (glyceraldehyde-3-phosphatedehydrogenase, G3PDH) in separate reactions. To imitate a defined induction of apo sigma gene expression, serial twofold dilutions of total RNA were reversely transcribed and the respective cDNAs used to perform a competitive apo sigma and G3PDH PCR. The change in apo sigma cDNA and G3PDH cDNA was 1.7-2.3-fold with an expected value of 2.0-fold. Standard deviations in three independently performed experiments were within a range of < 15% of the mean, indicating low intra-assay variation and high reproducibility. To illustrate this method, apo sigma gene expression was measured in a patient with complete lack of functional active apo E in comparison to healthy controls. The method presented here might be valuable in assessment of apo sigma gene expression in human disease.

Host-derived apolipoproteins play comparable roles with viral secretory proteins Erns and NS1 in the infectious particle formation of Flaviviridae

PubMed Central

Ono, Chikako; Shiokawa, Mai; Mori, Hiroyuki; Uemura, Kentaro; Yamamoto, Satomi; Okamoto, Toru; Suzuki, Ryosuke; Yoshii, Kentaro; Kurosu, Takeshi; Igarashi, Manabu; Aoki, Hiroshi; Sakoda, Yoshihiro

2017-01-01

Amphipathic α-helices of exchangeable apolipoproteins have shown to play crucial roles in the formation of infectious hepatitis C virus (HCV) particles through the interaction with viral particles. Among the Flaviviridae members, pestivirus and flavivirus possess a viral structural protein Erns or a non-structural protein 1 (NS1) as secretory glycoproteins, respectively, while Hepacivirus including HCV has no secretory glycoprotein. In case of pestivirus replication, the C-terminal long amphipathic α-helices of Erns are important for anchoring to viral membrane. Here we show that host-derived apolipoproteins play functional roles similar to those of virally encoded Erns and NS1 in the formation of infectious particles. We examined whether Erns and NS1 could compensate for the role of apolipoproteins in particle formation of HCV in apolipoprotein B (ApoB) and ApoE double-knockout Huh7 (BE-KO), and non-hepatic 293T cells. We found that exogenous expression of either Erns or NS1 rescued infectious particle formation of HCV in the BE-KO and 293T cells. In addition, expression of apolipoproteins or NS1 partially rescued the production of infectious pestivirus particles in cells upon electroporation with an Erns-deleted non-infectious RNA. As with exchangeable apolipoproteins, the C-terminal amphipathic α-helices of Erns play the functional roles in the formation of infectious HCV or pestivirus particles. These results strongly suggest that the host- and virus-derived secretory glycoproteins have overlapping roles in the viral life cycle of Flaviviridae, especially in the maturation of infectious particles, while Erns and NS1 also participate in replication complex formation and viral entry, respectively. Considering the abundant hepatic expression and liver-specific propagation of these apolipoproteins, HCV might have evolved to utilize them in the formation of infectious particles through deletion of a secretory viral glycoprotein gene. PMID:28644867

The helix bundle: A reversible lipid binding motif

PubMed Central

Narayanaswami, Vasanthy; Kiss, Robert S.; Weers, Paul M.M.

2009-01-01

Apolipoproteins are the protein components of lipoproteins that have the innate ability to inter convert between a lipid-free and a lipid-bound form in a facile manner, a remarkable property conferred by the helix bundle motif. Composed of a series of four or five amphipathic α-helices that fold to form a helix bundle, this motif allows the en face orientation of the hydrophobic faces of the α-helices in the protein interior in the lipid-free state. A conformational switch then permits helix-helix interactions to be substituted by helix-lipid interactions upon lipid binding interaction. This review compares the apolipoprotein high resolution structures and the factors that trigger this switch in insect apolipophorin III and the mammalian apolipoproteins, apolipoprotein E and apolipoprotein A-I, pointing out the commonalities and key differences in the mode of lipid interaction. Further insights into the lipid bound conformation of apolipoproteins are required to fully understand their functional role under physiological conditions. PMID:19770066

Effects of rosuvastatin and atorvastatin on the apolipoprotein B/apolipoprotein A-1 ratio in patients with an acute coronary syndrome: The CENTAURUS trial design.

PubMed

Lablanche, Jean-Marc; Danchin, Nicolas; Farnier, Michel; Tedgui, Alain; Vicaut, Eric; Alonso, Joaquim; Crean, Peter; Leone, Attilio; Morais, Joa; Santini, Massimo; Licour, Muriel; Farah, Mohamed; Tardif, Jean-Claude

2008-06-01

The mechanism underlying rapid, statin-induced event reduction in patients with an acute coronary syndrome (ACS) remains to be clarified. The primary objective is to compare the efficacy of rosuvastatin 20 mg/day and atorvastatin 80 mg/day in reducing the apolipoprotein B/apolipoprotein A-1 (apoB/apoA-1) ratio at three months, in ACS patients. Secondary objectives include a comparison of the effects of early-started rosuvastatin and placebo on inflammatory markers. This is a randomized, double-blind, parallel-group study. Patients with non-ST-segment elevation ACS, symptom onset less than 48 h before admission, and for whom a percutaneous coronary intervention is planned, are eligible for inclusion and are randomized into three groups (G1, G2 and G3). The study comprises two double-blind periods. Period 1 starts at hospital admission and lasts until Day 0 (discharge or less or equal to 6 days after admission); patients in G1 receive one tablet of rosuvastatin 20 mg/day and patients in G2 and G3 receive one matching placebo tablet per day. Period 2 starts at Day 0 and lasts for three months; patients in G1 continue to receive rosuvastatin 20 mg/day, patients in G2 receive rosuvastatin 20 mg/day and patients in G3 receive atorvastatin 80 mg/day. Recruitment of 1075 patients will ensure an 80 power to detect a 3% difference in percentage change in the apoB/apoA-1 ratio and a 20% difference in percentage change in high-sensitivity C-reactive protein. Inclusion phase is complete; results will be reported at a later date. This is the first trial investigating the effect of statins on apolipoproteins in ACS patients.

Superhuman AI for heads-up no-limit poker: Libratus beats top professionals.

PubMed

Brown, Noam; Sandholm, Tuomas

2018-01-26

No-limit Texas hold'em is the most popular form of poker. Despite artificial intelligence (AI) successes in perfect-information games, the private information and massive game tree have made no-limit poker difficult to tackle. We present Libratus, an AI that, in a 120,000-hand competition, defeated four top human specialist professionals in heads-up no-limit Texas hold'em, the leading benchmark and long-standing challenge problem in imperfect-information game solving. Our game-theoretic approach features application-independent techniques: an algorithm for computing a blueprint for the overall strategy, an algorithm that fleshes out the details of the strategy for subgames that are reached during play, and a self-improver algorithm that fixes potential weaknesses that opponents have identified in the blueprint strategy. Copyright © 2018, The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Genetics Home Reference: familial HDL deficiency

MedlinePlus

... phospholipids from cells by moving them across the cell membrane. The movement of these substances across the membrane is enhanced by another protein called apolipoprotein A-I (apoA-I), which is ...

Lineage-Specific Changes in Biomarkers in Great Apes and Humans.

PubMed

Ronke, Claudius; Dannemann, Michael; Halbwax, Michel; Fischer, Anne; Helmschrodt, Christin; Brügel, Mathias; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Scholz, Markus; Ceglarek, Uta; Thiery, Joachim; Pääbo, Svante; Prüfer, Kay; Kelso, Janet

2015-01-01

Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans.

Lineage-Specific Changes in Biomarkers in Great Apes and Humans

PubMed Central

Ronke, Claudius; Dannemann, Michael; Halbwax, Michel; Fischer, Anne; Helmschrodt, Christin; Brügel, Mathias; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Scholz, Markus; Ceglarek, Uta; Thiery, Joachim; Pääbo, Svante; Prüfer, Kay; Kelso, Janet

2015-01-01

Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans. PMID:26247603

Peptide mediators of cholesterol efflux

DOEpatents

Bielicki, John K.; Johansson, Jan

2013-04-09

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

Potent and selective mediators of cholesterol efflux

DOEpatents

Bielicki, John K; Johansson, Jan

2015-03-24

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

Scavenger receptor B1 (SR-B1) profoundly excludes high density lipoprotein (HDL) apolipoprotein AII as it nibbles HDL-cholesteryl ester.

PubMed

Gillard, Baiba K; Bassett, G Randall; Gotto, Antonio M; Rosales, Corina; Pownall, Henry J

2017-05-26

Reverse cholesterol transport (transfer of macrophage-cholesterol in the subendothelial space of the arterial wall to the liver) is terminated by selective high density lipoprotein (HDL)-cholesteryl ester (CE) uptake, mediated by scavenger receptor class B, type 1 (SR-B1). We tested the validity of two models for this process: "gobbling," i.e. one-step transfer of all HDL-CE to the cell and "nibbling," multiple successive cycles of SR-B1-HDL association during which a few CEs transfer to the cell. Concurrently, we compared cellular uptake of apoAI with that of apoAII, which is more lipophilic than apoAI, using HDL-[ 3 H]CE labeled with [ 125 I]apoAI or [ 125 I]apoAII. The studies were conducted in CHO-K1 and CHO-ldlA7 cells (LDLR -/- ) with (CHO-SR-B1) and without SR-B1 overexpression and in human Huh7 hepatocytes. Relative to CE, both apoAI and apoAII were excluded from uptake by all cells. However, apoAII was more highly excluded from uptake (2-4×) than apoAI. To distinguish gobbling versus nibbling mechanisms, media from incubations of HDL with CHO-SR-B1 cells were analyzed by non-denaturing PAGE, size-exclusion chromatography, and the distribution of apoAI, apoAII, cholesterol, and phospholipid among HDL species as a function of incubation time. HDL size gradually decreased, i.e. nibbling, with the concurrent release of lipid-free apoAI; apoAII was retained in an HDL remnant. Our data support an SR-B1 nibbling mechanism that is similar to that of streptococcal serum opacity factor, which also selectively removes CE and releases apoAI, leaving an apoAII-rich remnant. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

QML-AiNet: An immune network approach to learning qualitative differential equation models

PubMed Central

Pang, Wei; Coghill, George M.

2015-01-01

In this paper, we explore the application of Opt-AiNet, an immune network approach for search and optimisation problems, to learning qualitative models in the form of qualitative differential equations. The Opt-AiNet algorithm is adapted to qualitative model learning problems, resulting in the proposed system QML-AiNet. The potential of QML-AiNet to address the scalability and multimodal search space issues of qualitative model learning has been investigated. More importantly, to further improve the efficiency of QML-AiNet, we also modify the mutation operator according to the features of discrete qualitative model space. Experimental results show that the performance of QML-AiNet is comparable to QML-CLONALG, a QML system using the clonal selection algorithm (CLONALG). More importantly, QML-AiNet with the modified mutation operator can significantly improve the scalability of QML and is much more efficient than QML-CLONALG. PMID:25648212

QML-AiNet: An immune network approach to learning qualitative differential equation models.

PubMed

Pang, Wei; Coghill, George M

2015-02-01

In this paper, we explore the application of Opt-AiNet, an immune network approach for search and optimisation problems, to learning qualitative models in the form of qualitative differential equations. The Opt-AiNet algorithm is adapted to qualitative model learning problems, resulting in the proposed system QML-AiNet. The potential of QML-AiNet to address the scalability and multimodal search space issues of qualitative model learning has been investigated. More importantly, to further improve the efficiency of QML-AiNet, we also modify the mutation operator according to the features of discrete qualitative model space. Experimental results show that the performance of QML-AiNet is comparable to QML-CLONALG, a QML system using the clonal selection algorithm (CLONALG). More importantly, QML-AiNet with the modified mutation operator can significantly improve the scalability of QML and is much more efficient than QML-CLONALG.

The impact of the AIS 2005 revision on injury severity scores and clinical outcome measures.

PubMed

Salottolo, Kristin; Settell, April; Uribe, Phyllis; Akin, Shelley; Slone, Denetta Sue; O'Neal, Erika; Mains, Charles; Bar-Or, David

2009-09-01

The abbreviated injury scale (AIS) was updated in 2005 from the AIS 1998 version. The purpose of this study is to describe the effects of this change on injury severity scoring and outcome measures. Analyses were performed on all trauma patients consecutively admitted over a 6-month period at two geographically separate Level I trauma centers. Injuries were manually double-coded according to the AIS 05 and the AIS 98. Changes in AIS, ISS, and new ISS (NISS) were analysed using paired t-tests. Apparent differences in outcome by ISS strata (<16, 16-24, >24) were compared for AIS 05 versus AIS 98 using the Wald-type statistic. Lastly, the percent of patients with a change in ISS strata are reported. There were 2250 patients included in the study. Nearly half (46.4%) of AIS codes changed, resulting in a different AIS score for 18.9% of all codes. The mean ISS was significantly lower using the AIS 05 (11.7) versus the AIS 98 (13.3, p<0.001). Similarly, the mean NISS was significantly lower (16.3 versus 18.7, p<0.001). In the ISS strata 16-24 an apparent increase in mortality, length of stay, and percent of patients not discharged home was observed for the AIS 05 versus AIS 98. Changes in outcome measures for this stratum were as follows (AIS 98 versus AIS 05): mortality, 4.3% versus 7.7% (p=0.002); hospital length of stay, 5.2 days versus 7.3 days (p<0.001); percent of patients not discharged home, 39.2% versus 49.3% (p<0.001). Finally, there was a 20.5% reduction in patients with an ISS>or=16 and a 26.2% reduction in patients with an ISS>or=25 using the AIS 05. The AIS revision had a significant impact on overall injury severity measures, clinical outcome measures, and percent of patients in each ISS strata. Therefore, the AIS revision affects the ability to directly compare data generated using AIS 05 and AIS 98 which has implications in trauma research, reimbursement and ACS accreditation.

Functional specifications for AI software tools for electric power applications. Final report

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

Faught, W.S.

1985-08-01

The principle barrier to the introduction of artificial intelligence (AI) technology to the electric power industry has not been a lack of interest or appropriate problems, for the industry abounds in both. Like most others, however, the electric power industry lacks the personnel - knowledge engineers - with the special combination of training and skills AI programming demands. Conversely, very few AI specialists are conversant with electric power industry problems and applications. The recent availability of sophisticated AI programming environments is doing much to alleviate this shortage. These products provide a set of powerful and usable software tools that enablemore » even non-AI scientists to rapidly develop AI applications. The purpose of this project was to develop functional specifications for programming tools that, when integrated with existing general-purpose knowledge engineering tools, would expedite the production of AI applications for the electric power industry. Twelve potential applications, representative of major problem domains within the nuclear power industry, were analyzed in order to identify those tools that would be of greatest value in application development. Eight tools were specified, including facilities for power plant modeling, data base inquiry, simulation and machine-machine interface.« less

Validation of the Avoidance and Inflexibility Scale (AIS) among treatment-seeking smokers.

PubMed

Farris, Samantha G; Zvolensky, Michael J; DiBello, Angelo M; Schmidt, Norman B

2015-06-01

The Avoidance and Inflexibility Scale (AIS; Gifford et al., 2004) was derived as a smoking-specific measure of experiential avoidance. However, there has been little investigation of the psychometric proprieties of the AIS and no published work on the topic. The current study aimed to test the reliability and validity of the AIS among a sample of adult treatment-seeking daily smokers (n = 465; 48.2% female, 17.8 [SD = 9.60] cigarettes per day). The AIS was administered at 3 time points (baseline, quit-day, and 1 month postquit) as part of a larger smoking cessation trial. An exploratory factor analysis indicated a 2-factor solution, described by inflexibility and avoidance because of smoking related "thoughts/feelings" (9 items) and "somatic sensations" (4 items). Results revealed that the AIS-total and factor scores demonstrated high internal consistency and test-retest reliability. The AIS total and factor scores also displayed high convergent, discriminant, and incremental predictive validity with theoretically relevant smoking and affective variables. The present data suggest that the AIS measure appears to be a valid and reliable smoking-specific index of experiential avoidance. (c) 2015 APA, all rights reserved).

Validation of the Avoidance and Inflexibility Scale (AIS) among Treatment-Seeking Smoker

PubMed Central

Farris, Samantha G.; Zvolensky, Michael J.; DiBello, Angelo M.; Schmidt, Norman B.

2015-01-01

The Avoidance and Inflexibility Scale (AIS; Gifford et al., 2004) was derived as smoking-specific measure of experiential avoidance. However, there has been little investigation of the psychometric proprieties of the AIS and no published work on the topic. The current study aimed to test the reliability and validity of the AIS among a sample of adult treatment-seeking daily smokers (n = 465; 48.1% female, 17.8 [SD = 9.60] cigarettes per day). The AIS was administered at three time points (Baseline, Quit day, 1 month post-quit) as part of a larger smoking cessation trial. An exploratory factor analysis indicated a two-factor solution, described by inflexibility and avoidance due to smoking related “thoughts/feelings” (9 items) and “somatic sensations” (4 items). Results revealed that the AIS-total and factor scores demonstrated high internal consistency and test-retest reliability. The AIS total and factor scores also displayed high convergent, discriminant, and incremental predictive validity with theoretically-relevant smoking and affective variables. The present data suggest that the AIS measure appears to be a valid and reliable smoking-specific index of experiential avoidance. PMID:25642937

Code AI Personal Web Pages

NASA Technical Reports Server (NTRS)

Garcia, Joseph A.; Smith, Charles A. (Technical Monitor)

1998-01-01

The document consists of a publicly available web site (george.arc.nasa.gov) for Joseph A. Garcia's personal web pages in the AI division. Only general information will be posted and no technical material. All the information is unclassified.

Application of Artificial Intelligence (AI) programming techniques to tactical guidance for fighter aircraft

NASA Technical Reports Server (NTRS)

Mcmanus, John W.; Goodrich, Kenneth H.

1989-01-01

A research program investigating the use of Artificial Intelligence (AI) programming techniques to aid in the development of a Tactical Decision Generator (TDG) for Within-Visual-Range (WVR) air combat engagements is discussed. The application of AI methods for development and implementation of the TDG is presented. The history of the Adaptive Maneuvering Logic (AML) program is traced and current versions of the (AML) program is traced and current versions of the AML program are compared and contrasted with the TDG system. The Knowledge-Based Systems (KBS) used by the TDG to aid in the decision-making process are outlined and example rules are presented. The results of tests to evaluate the performance of the TDG against a version of AML and against human pilots in the Langley Differential Maneuvering Simulator (DMS) are presented. To date, these results have shown significant performance gains in one-versus-one air combat engagements.

Analysis of AIS data of the Bonanza Creek Experimental Forest, Alaska

NASA Technical Reports Server (NTRS)

Spanner, M. A.; Peterson, D. L.

1986-01-01

Airborne Imaging Spectrometer (AIS) data were acquired in 1985 over the Bonanza Creek Experimental Forest, Alaska for the analysis of canopy characteristics including biochemistry. Concurrent with AIS overflights, foliage from fifteen coniferous and deciduous forest stands were analyzed for a variety of biochemical constituents including nitrogen, lignin, protein, and chlorophyll. Preliminary analysis of AIS spectra indicates that the wavelength region between 1450 to 1800 namometers (nm) displays distinct differences in spectral response for some of the forest stands. A flat field subtraction (forest stand spectra - flat field spectra) of the AIS spectra assisted in the interpretation of features of the spectra that are related to biology.

AIS 2005: a contemporary injury scale.

PubMed

Gennarelli, Thomas A; Wodzin, Elaine

2006-12-01

To determine and to quantify outcome from injury demands that multiple factors be universally applied so that there is uniform understanding that the same outcome is understood for the same injury. It is thus important to define the variables used in any outcome assessment. Critical to defining outcomes is the need for a universal language that defines individual injuries. The abbreviated injury scale (AIS) is the only dictionary specifically designed as a system to define the severity of injuries throughout the body. In addition to a universal injury language, it provides measures of injury severity that can be used to stratify and classify injury severity in all body regions. Its revision, AIS 2005 will be discussed here.

The Air Force Advanced Instructional System (AIS): An Overview.

ERIC Educational Resources Information Center

Yasutake, Joseph Y.; Stobie, William H.

The Air Force Advanced Instructional System (AIS) is a prototype computer-based multimedia system for the administration and management of individualized technical training on a large scale. The paper provides an overview of the AIS: (1) its purposes and goals, (2) the background and rationale for the development approach, (3) a basic description…

Pedagogy and the PC: Trends in the AIS Curriculum

ERIC Educational Resources Information Center

Badua, Frank

2008-01-01

The author investigated the array of course topics in accounting information systems (AIS), as course syllabi embody. The author (a) used exploratory data analysis to determine the topics that AIS courses most frequently offered and (b) used descriptive statistics and econometric analysis to trace the diversity of course topics through time,…

The AIS-2005 Revision in Severe Traumatic Brain Injury: Mission Accomplished or Problems for Future Research?

PubMed Central

Carroll, Christopher P.; Cochran, Joseph A.; Price, Janet P.; Guse, Clare E.; Wang, Marjorie C.

2010-01-01

The Abbreviated Injury Scale (AIS) is commonly used to score injury severity and describe types of injuries. In 2005, the AIS-Head section was revised to capture more detailed information about head injuries and to better reflect their clinical severity, but the impact of these changes is largely unknown. The purpose of this study was to compare AIS-1998 and AIS-2005 coding of traumatic brain injuries (TBI) using medical records at a single Level I trauma center. We included patients with severe TBI (Glasgow Coma Scale 3–8) after blunt injury, excluding those who were missing medical records. Detailed descriptions of injuries were collected, then manually coded into AIS-1998 and AIS-2005 by the same Certified AIS Specialist. Compared to AIS-1998, AIS-2005 coded the same injuries with lower severity scores [p<0.01] and with decreased mean and maximum AIS-Head scores [p<0.01]. Of the types of traumatic brain injuries, most of the changes occurred among cerebellar and cerebral injuries. Traumatic hypoxic brain injury secondary to systemic dysfunction was captured by AIS-2005 but not by AIS-1998. However, AIS-2005 captured fewer loss of consciousness cases due to changes in criteria for coding concussive injury. In conclusion, changes from AIS-1998 to AIS-2005 result in significant differences in severity scores and types of injuries captured. This may complicate future TBI research by precluding direct comparison to datasets using AIS-1998. TBIs should be coded into the same AIS-version for comparison or evaluation of trends, and specify which AIS-version is used. PMID:21050606

The AIS-2005 Revision in Severe Traumatic Brain Injury: Mission Accomplished or Problems for Future Research?

PubMed

Carroll, Christopher P; Cochran, Joseph A; Price, Janet P; Guse, Clare E; Wang, Marjorie C

2010-01-01

The Abbreviated Injury Scale (AIS) is commonly used to score injury severity and describe types of injuries. In 2005, the AIS-Head section was revised to capture more detailed information about head injuries and to better reflect their clinical severity, but the impact of these changes is largely unknown. The purpose of this study was to compare AIS-1998 and AIS-2005 coding of traumatic brain injuries (TBI) using medical records at a single Level I trauma center. We included patients with severe TBI (Glasgow Coma Scale 3-8) after blunt injury, excluding those who were missing medical records. Detailed descriptions of injuries were collected, then manually coded into AIS-1998 and AIS-2005 by the same Certified AIS Specialist. Compared to AIS-1998, AIS-2005 coded the same injuries with lower severity scores [p<0.01] and with decreased mean and maximum AIS-Head scores [p<0.01]. Of the types of traumatic brain injuries, most of the changes occurred among cerebellar and cerebral injuries. Traumatic hypoxic brain injury secondary to systemic dysfunction was captured by AIS-2005 but not by AIS-1998. However, AIS-2005 captured fewer loss of consciousness cases due to changes in criteria for coding concussive injury. In conclusion, changes from AIS-1998 to AIS-2005 result in significant differences in severity scores and types of injuries captured. This may complicate future TBI research by precluding direct comparison to datasets using AIS-1998. TBIs should be coded into the same AIS-version for comparison or evaluation of trends, and specify which AIS-version is used.

Apolipoprotein E gene polymorphism and gender.

PubMed

Kolovou, Genovefa; Damaskos, Dimitris; Anagnostopoulou, Katherine; Cokkinos, Dennis V

2009-01-01

Many studies have shown that the prevalence and onset of coronary heart disease (CHD) is sex-dependent. CHD prevalence is lower in women than in men at all ages. Furthermore, women's age of CHD onset seems to be 10 yr later. This is widely attributed to the fact that men have less favorable CHD risk factors (eg, plasma lipid profile) compared to women. Mean levels of protective high density lipoprotein cholesterol are lower, while triglyceride levels are higher in men than in women. It is possible that many of the genes involved in lipid metabolism, such as Apolipoprotein (Apo) E, as well as their polymorphisms, may be expressed in a sexually dimorphic manner. The human Apo E gene is polymorphic, encoding one of 3 common epsilon (epsilon) alleles (epsilon 2, epsilon 3, epsilon 4), with the epsilon 3 allele occurring most frequently (78%) in the Caucasian population. Association studies have shown a protective effect on CHD in epsilon 2 carriers and a harmful effect in epsilon 4 carriers. However, there are conflicting results regarding such allelic effects in respect to gender. This review is focused on the gender-related influence of Apo E polymorphism in respect to plasma lipid levels and the risk of CHD. Additionally, an effort is made to determine if this relation exists and if it can be satisfactorily explained. The studies cited here demonstrate a complex, multifactorial association between these factors, in need of further corroboration in greater population samples.

76 FR 44045 - Establishment of the SANE/SART AI/AN Initiative Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

... SANE/SART AI/AN Initiative Committee AGENCY: Office for Victims of Crime, Justice. ACTION: Notice of...) Initiative (``SANE/SART AI/AN Initiative Committee'' or ``Committee'') is being established in accordance... SANE/SART AI/AN Initiative Committee will provide the Office for Victims of Crime, a component of the U...

Quality of head injury coding from autopsy reports with AIS © 2005 update 2008.

PubMed

Schick, Sylvia; Humrich, Anton; Graw, Matthias

2018-02-28

ABSTACT Objective: Coding injuries from autopsy reports of traffic accident victims according to Abbreviated Injury Scale AIS © 2005 update 2008 [1] is quite time consuming. The suspicion arose, that many issues leading to discussion between coder and control reader were based on information required by the AIS that was not documented in the autopsy reports. To quantify this suspicion, we introduced an AIS-detail-indicator (AIS-DI). To each injury in the AIS Codebook one letter from A to N was assigned indicating the level of detail. Rules were formulated to receive repeatable assignments. This scheme was applied to a selection of 149 multiply injured traffic fatalities. The frequencies of "not A" codes were calculated for each body region and it was analysed, why the most detailed level A had not been coded. As a first finding, the results of the head region are presented. 747 AIS head injury codes were found in 137 traffic fatalities, and 60% of these injuries were coded with an AIS-DI of level A. There are three different explanations for codes of AIS-DI "not A": Group 1 "Missing information in autopsy report" (5%), Group 2 "Clinical data required by AIS" (20%), and Group 3 "AIS system determined" (15%). Groups 1 and 2 show consequences for the ISS in 25 cases. Other body regions might perform differently. The AIS-DI can indicate the quality of the underlying data basis and, depending on the aims of different AIS users it can be a helpful tool for quality checks.

The Additional Secondary Phase Correction System for AIS Signals

PubMed Central

Wang, Xiaoye; Zhang, Shufang; Sun, Xiaowen

2017-01-01

This paper looks at the development and implementation of the additional secondary phase factor (ASF) real-time correction system for the Automatic Identification System (AIS) signal. A large number of test data were collected using the developed ASF correction system and the propagation characteristics of the AIS signal that transmits at sea and the ASF real-time correction algorithm of the AIS signal were analyzed and verified. Accounting for the different hardware of the receivers in the land-based positioning system and the variation of the actual environmental factors, the ASF correction system corrects original measurements of positioning receivers in real time and provides corrected positioning accuracy within 10 m. PMID:28362330

DSCOVR_EPIC_L2_O3SO2AI_01

Atmospheric Science Data Center

2018-06-29

... dioxide (SO2) from volcanic plumes, scene reflectivity, and aerosol index (AI), retrieved from the ultraviolet (UV) measurements of DSCOVR ... Access:   Order Data Parameters:  Aerosol Index (AI) Reflectivity at 340 nm Vertical Column of Ozone (O3) ...

AIS Investigation of Agricultural Monocultures

NASA Technical Reports Server (NTRS)

Wood, B. L.; Wrigley, R. C.

1985-01-01

Airborne Imaging Spectrometer (AIS) data were acquired over an agricultural area in eastern San Joaquin County, California in July, 1984. Cover type information was subsequently collected for all fields along this flight line. The lack of detailed ground data on individual fields, however, limited AIS data analysis to a qualitative comparison of the spectral reflectance curves for a total of nine cover types. Based on this analysis, it appears that cover types with a positive slope in the 1550 to 1700 nm region have a higher spectral response in the 1200 to 1300 nm region compared to those cover types with a negative slope in the 1550 to 1700 nm region. Within cover type, spectral variability was also found to be greater than that between cover types. Given the lack of additional field data, the reason for these differences is a matter of speculation.

AI in manufacturing

NASA Astrophysics Data System (ADS)

Gross, John E.; Minato, Rick; Smith, David M.; Loftin, R. B.; Savely, Robert T.

1991-10-01

AI techniques are shown to have been useful in such aerospace industry tasks as vehicle configuration layouts, process planning, tool design, numerically-controlled programming of tools, production scheduling, and equipment testing and diagnosis. Accounts are given of illustrative experiences at the production facilities of three major aerospace defense contractors. Also discussed is NASA's autonomous Intelligent Computer-Aided Training System, for such ambitious manned programs as Space Station Freedom, which employs five different modules to constitute its job-independent training architecture.

Reverse engineering the human: artificial intelligence and acting theory

NASA Astrophysics Data System (ADS)

Soto-Morettini, Donna

2017-01-01

In two separate papers, Artificial Intelligence (AI)/Robotics researcher Guy Hoffman takes as a starting point that actors have been in the business of reverse engineering human behaviour for centuries. In this paper, I follow the similar trajectories of AI and acting theory (AT), looking at three primary questions, in the hope of framing a response to Hoffman's papers: (1) How are the problems of training a human to simulate a fictional human both similar to and different from training a machine to simulate a human? (2) How are the larger questions of AI design and architecture similar to the larger questions that still remain within the area of AT? (3) Is there anything in the work of AI design that might advance the work of acting theorists and practitioners? The paper explores the use of "swarm intelligence" in recent models of both AT and AI, and considers the issues of embodied cognition, and the kinds of intelligence that enhances or inhibits imaginative immersion for the actor, and concludes with a consideration of the ontological questions raised by the trend towards intersubjective, dynamic systems of generative thought in both AT and AI.

β-COP as a Component of Transport Vesicles for HDL Apolipoprotein-Mediated Cholesterol Exocytosis

PubMed Central

Ma, Weilie; Lin, Margarita; Ding, Hang; Lin, Guorong; Zhang, Zhizhen

2016-01-01

Objective HDL and its apolipoproteins protect against atherosclerotic disease partly by removing excess cholesterol from macrophage foam cells. But the underlying mechanisms of cholesterol clearance are still not well defined. We investigated roles of vesicle trafficking of coatomer β-COP in delivering cholesterol to the cell surface during apoA-1 and apoE-mediated lipid efflux from fibroblasts and THP-1 macrophages. Methods shRNA knockout, confocal and electron microscopy and biochemical analysis were used to investigate the roles of β-COP in apolipoprotein-mediated cholesterol efflux in fibroblasts and THP-1 macrophages. Results We showed that β-COP knockdown by lentiviral shRNA resulted in reduced apoA-1-mediated cholesterol efflux, while increased cholesterol accumulation and formation of larger vesicles were observed in THP-1 macrophages by laser scanning confocal microscopy. Immunogold electron microscopy showed that β-COP appeared on the membrane protrusion complexes and colocalized with apoA-1 or apoE during cholesterol efflux. This was associated with releasing heterogeneous sizes of small particles into the culture media of THP-1 macrophage. Western blotting also showed that apoA-1 promotes β-COP translocation to the cell membrane and secretion into culture media, in which a total of 17 proteins were identified by proteomics. Moreover, β-COP exclusively associated with human plasma HDL fractions. Conclusion ApoA-1 and apoE promoted transport vesicles consisting of β-COP and other candidate proteins to exocytose cholesterol, forming the protrusion complexes on cell surface, which were then released from the cell membrane as small particles to media. PMID:26986486

Apolipoprotein C3 polymorphism is associated with cognitive function in Caribbean Hispanics

USDA-ARS?s Scientific Manuscript database

Background: Apolipoprotein C3(APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired ...

Material processing: AI-MSG modification

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

Woolsey, C.C.; Carnazzola, A.

1973-12-18

This specification establishes fabrication processing requirements such as cleaning, welding, brazing, and post-weld heat treating for the modification of the Atomics International (AI) Modular Steam Generator (MSG) for use in the Large Leak Test Rig (LLTR) for the study of sodium-water reactions.

S-aryl-L-cysteine sulphoxides and related organosulphur compounds alter oral biofilm development and AI-2-based cell-cell communication.

PubMed

Kasper, S H; Samarian, D; Jadhav, A P; Rickard, A H; Musah, R A; Cady, N C

2014-11-01

To design and synthesize a library of structurally related, small molecules related to homologues of compounds produced by the plant Petiveria alliacea and determine their ability to interfere with AI-2 cell-cell communication and biofilm formation by oral bacteria. Many human diseases are associated with persistent bacterial biofilms. Oral biofilms (dental plaque) are problematic as they are often associated with tooth decay, periodontal disease and systemic disorders such as heart disease and diabetes. Using a microplate-based approach, a bio-inspired small molecule library was screened for anti-biofilm activity against the oral species Streptococcus mutans UA159, Streptococcus sanguis 10556 and Actinomyces oris MG1. To complement the static screen, a flow-based BioFlux microfluidic system screen was also performed under conditions representative of the human oral cavity. Several compounds were found to display biofilm inhibitory activity in all three of the oral bacteria tested. These compounds were also shown to inhibit bioluminescence by Vibrio harveyi and were thus inferred to be quorum sensing (QS) inhibitors. Due to the structural similarity of these compounds to each other, and to key molecules in AI-2 biosynthetic pathways, we propose that these molecules potentially reduce biofilm formation via antagonism of QS or QS-related pathways. This study highlights the potential for a non-antimicrobial-based strategy, focused on AI-2 cell-cell signalling, to control the development of dental plaque. Considering that many bacterial species use AI-2 cell-cell signalling, as well as the increased concern of the use of antimicrobials in healthcare products, such an anti-biofilm approach could also be used to control biofilms in environments beyond the human oral cavity. © 2014 The Society for Applied Microbiology.

Toward detecting California shrubland canopy chemistry with AIS data

NASA Technical Reports Server (NTRS)

Price, Curtis V.; Westman, Walter E.

1987-01-01

Airborne Imaging Spectrometer (AIS)-2 data of coastal sage scrub vegetation were examined for fine spectral features that might be used to predict concentrations of certain canopy chemical constituents. A Fourier notch filter was applied to the AIS data and the TREE and ROCK mode spectra were ratioed to a flat field. Portions of the resulting spectra resemble spectra for plant cellulose and starch in that both show reduced reflectance at 2100 and 2270 nm. The latter are regions of absorption of energy by organic bonds found in starch and cellulose. Whether the relationship is sufficient to predict the concentration of these chemicals from AIS spectra will require testing of the predictive ability of these wavebands with large field sample sizes.

Peritoneal delivery of sodium pyrophosphate blocks the progression of pre-existing vascular calcification in uremic apolipoprotein-E knockout mice.

PubMed

de Oliveira, Rodrigo B; Louvet, Loïc; Riser, Bruce L; Barreto, Fellype C; Benchitrit, Joyce; Rezg, Raja; Poirot, Sabrina; Jorgetti, Vanda; Drüeke, Tilman B; Massy, Ziad A

2015-08-01

Chronic kidney disease (CKD) is generally associated with disturbances of mineral and bone metabolism. They contribute to the development of vascular calcification (VC), a strong, independent predictor of cardiovascular risk. Pyrophosphate (PPi), an endogenous inhibitor of hydroxyapatite formation, has been shown to slow the progression of VC in uremic animals. Since in patients with CKD treatment is usually initiated for already existing calcifications, we aimed to compare the efficacy of PPi therapy with that of the phosphate binder sevelamer, using a uremic apolipoprotein-E knockout mouse model with advanced VCs. After CKD creation or sham surgery, 12-week-old female mice were randomized to one sham group and four CKD groups (n = 18-19/group). Treatment was initiated 8 weeks after left nephrectomy allowing prior VC development. Uremic groups received either intraperitoneal PPi (high dose, 1.65 mg/kg or low dose, 0.33 mg/kg per day), oral sevelamer (3 % in diet), or placebo treatment for 8 weeks. Both intima and media calcifications worsened with time in placebo-treated CKD mice, based on both quantitative image analysis and biochemical measurements. Progression of calcification between 8 and 16 weeks was entirely halted by PPi treatment, as it was by sevelamer treatment. PPi did not induce consistent bone histomorphometry changes. Finally, the beneficial vascular action of PPi probably involved mechanisms different from that of sevelamer. Further studies are needed to gain more precise insight into underlying mechanisms and to see whether PPi administration may also be useful in patients with CKD and VC.

Interaction of human low density lipoprotein and apolipoprotein B with ternary lipid microemulsion. Physical and functional properties.

PubMed

Chun, P W; Brumbaugh, E E; Shiremann, R B

1986-12-31

Based on data from sedimentation velocity experiments, electrophoresis, electron microscopy, cellular uptake studies, scanning molecular sieve chromatography using a quasi-three-dimensional data display and flow performance liquid chromatography (FPLC), models for the interaction of human serum low density lipoprotein (LDL) and of apolipoprotein B (apo B) with a ternary lipid microemulsion (ME) are proposed. The initial step in the interaction of LDL (Stokes radius 110 A) with the ternary microemulsion (Stokes radius 270 A) appears to be attachment of the LDL to emulsion particles. This attachment is followed by a very slow fusion into particles having a radius of approx. 280 A. Sonication of this mixture yields large aggregates. Electron micrographs of deoxycholate-solubilized apo B indicate an arrangement of apo B resembling strings of beads. During incubation, these particles also attach to the ternary microemulsion particles and, upon sonication, spherical particles result which resemble native LDL particles in size. Scanning chromatography corroborates the electron microscopy results. By appropriate choice of display angles in a quasi-three-dimensional display of the scanning data (corrected for gel apparent absorbance) taken at equal time intervals during passage of a sample through the column, changes in molecular radius of less than 10 A can be detected visually. Such a display gives a quantitative estimate of 101 +/- 2 A for these particles (compared to 110 A for native LDL). The LDL-ME particles and apo B-ME particles compete efficiently with native LDL for cellular binding and uptake. Cellular association studies indicate that both LDL- and apo B-ME particles are effective vehicles for lipid delivery into cells.

NASA space station automation: AI-based technology review

NASA Technical Reports Server (NTRS)

Firschein, O.; Georgeff, M. P.; Park, W.; Neumann, P.; Kautz, W. H.; Levitt, K. N.; Rom, R. J.; Poggio, A. A.

1985-01-01

Research and Development projects in automation for the Space Station are discussed. Artificial Intelligence (AI) based automation technologies are planned to enhance crew safety through reduced need for EVA, increase crew productivity through the reduction of routine operations, increase space station autonomy, and augment space station capability through the use of teleoperation and robotics. AI technology will also be developed for the servicing of satellites at the Space Station, system monitoring and diagnosis, space manufacturing, and the assembly of large space structures.

Different AIS triplets: Different mortality predictions in identical ISS and NISS.

PubMed

Aharonson-Daniel, Limor; Giveon, Adi; Stein, Michael; Peleg, Kobi

2006-09-01

Previous studies demonstrated different mortality predictions for identical Injury Severity Scores (ISS) from different Abbreviated Injury Scale (AIS) triplets. This study elaborates in both scope and volume producing results of a larger magnitude, applicable to specific injury subgroups of blunt or penetrating, traumatic brain injury, various age groups, and replicated on NISS. All patients hospitalized after trauma at 10 hospitals, with ISS/NISS (new ISS) generated by two AIS triplets, excluding patients with isolated minor or moderate injuries to a single body region were studied. Patients were separated into two groups based on the different triplets. Inpatient-mortality rates were calculated for each triplet group. Odds ratios were calculated to estimate the risk of dying in one triplet group as compared with the other. The chi test determined whether the difference in mortality rate between the two groups was significantly different. Differences were further explored for various subgroups. There were 35,827 patients who had ISS/NISS scores generated by two different AIS triplets. Significant differences in death rates were noted between triplet groups forming identical ISS/NISS. Odds ratio for being in the second group (always containing the higher AIS score) ranged from 2.3 to 7.4. ISS and NISS that are formed by different AIS triplets have significantly different inpatient-mortality rates. The triplet with the higher AIS score has higher inpatient-mortality rates, overall and in several sub-populations of varying vulnerability. The comparison of populations and the interpretation of ISS/NISS based outcome data should take this important information into account and the components of AIS triplets creating each ISS and NISS should be reported.

Accretion in Radiative Equipartition (AiRE) Disks

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

Yazdi, Yasaman K.; Afshordi, Niayesh, E-mail: yyazdi@pitp.ca, E-mail: nafshordi@pitp.ca

2017-07-01

Standard accretion disk theory predicts that the total pressure in disks at typical (sub-)Eddington accretion rates becomes radiation pressure dominated. However, radiation pressure dominated disks are thermally unstable. Since these disks are observed in approximate steady state over the instability timescale, our accretion models in the radiation-pressure-dominated regime (i.e., inner disk) need to be modified. Here, we present a modification to the Shakura and Sunyaev model, where the radiation pressure is in equipartition with the gas pressure in the inner region. We call these flows accretion in radiative equipartition (AiRE) disks. We introduce the basic features of AiRE disks andmore » show how they modify disk properties such as the Toomre parameter and the central temperature. We then show that the accretion rate of AiRE disks is limited from above and below, by Toomre and nodal sonic point instabilities, respectively. The former leads to a strict upper limit on the mass of supermassive black holes as a function of cosmic time (and spin), while the latter could explain the transition between hard and soft states of X-ray binaries.« less

Accretion in Radiative Equipartition (AiRE) Disks

NASA Astrophysics Data System (ADS)

Yazdi, Yasaman K.; Afshordi, Niayesh

2017-07-01

Standard accretion disk theory predicts that the total pressure in disks at typical (sub-)Eddington accretion rates becomes radiation pressure dominated. However, radiation pressure dominated disks are thermally unstable. Since these disks are observed in approximate steady state over the instability timescale, our accretion models in the radiation-pressure-dominated regime (I.e., inner disk) need to be modified. Here, we present a modification to the Shakura & Sunyaev model, where the radiation pressure is in equipartition with the gas pressure in the inner region. We call these flows accretion in radiative equipartition (AiRE) disks. We introduce the basic features of AiRE disks and show how they modify disk properties such as the Toomre parameter and the central temperature. We then show that the accretion rate of AiRE disks is limited from above and below, by Toomre and nodal sonic point instabilities, respectively. The former leads to a strict upper limit on the mass of supermassive black holes as a function of cosmic time (and spin), while the latter could explain the transition between hard and soft states of X-ray binaries.

Development and Validation of the Alcohol Identity Implicit Associations Test (AI-IAT)

PubMed Central

Gray, Heather M.; LaPlante, Debi A.; Bannon, Brittany L.; Ambady, Nalini; Shaffer, Howard J.

2011-01-01

Alcohol identity is the extent to which an individual perceives drinking alcohol to be a defining characteristic of his or her self-identity. Although alcohol identity might play an important role in risky college drinking practices, there is currently no easily administered, implicit measure of this concept. Therefore we developed a computerized implicit measure of alcohol identity (the Alcohol Identity Implicit Associations Test; AI-IAT) and assessed its reliability and predictive validity in relation to risky college drinking practices. One hundred forty-one college students completed the AI-IAT. Again 3- and 6-months later, we administered the AI-IAT and indices of engagement in risky college drinking practices. A subset of participants also completed the previously-validated implicit measure of alcohol identity. Scores on the AI-IAT were stable over time, internally consistent, and positively correlated with the previously-validated measure of alcohol identity. Baseline AI-IAT scores predicted future engagement in risky college drinking practices, even after controlling for standard alcohol consumption measures. We conclude that the AI-IAT reliably measures alcohol identity, a concept that appears to play an important role in risky college drinking practices. PMID:21621924

Apolipoprotein A-II polymorphism: relationships to behavioural and hormonal mediators of obesity

USDA-ARS?s Scientific Manuscript database

Background: The interaction between apolipoprotein A-II (APOA2) m265 genotype and saturated fat for obesity traits has been more extensively demonstrated than for any other locus, but behavioural and hormonal mechanisms underlying this relationship are unexplored. In this study, we evaluated relatio...

Interpretation of AIS Images of Cuprite, Nevada Using Constraints of Spectral Mixtures

NASA Technical Reports Server (NTRS)

Smith, M. O.; Adams, J. B.

1985-01-01

A technique is outlined that tests the hypothesis Airborne Imaging Spectrometer (AIS) image spectra are produced by mixtures of surface materials. This technique allows separation of AIS images into concentration images of spectral endmembers (e.g., surface materials causing spectral variation). Using a spectral reference library it was possible to uniquely identify these spectral endmembers with respect to the reference library and to calibrate the AIS images.

Human Factors in Space Exploration

NASA Technical Reports Server (NTRS)

Jones, Patricia M.; Fiedler, Edna

2010-01-01

The exploration of space is one of the most fascinating domains to study from a human factors perspective. Like other complex work domains such as aviation (Pritchett and Kim, 2008), air traffic management (Durso and Manning, 2008), health care (Morrow, North, and Wickens, 2006), homeland security (Cooke and Winner, 2008), and vehicle control (Lee, 2006), space exploration is a large-scale sociotechnical work domain characterized by complexity, dynamism, uncertainty, and risk in real-time operational contexts (Perrow, 1999; Woods et ai, 1994). Nearly the entire gamut of human factors issues - for example, human-automation interaction (Sheridan and Parasuraman, 2006), telerobotics, display and control design (Smith, Bennett, and Stone, 2006), usability, anthropometry (Chaffin, 2008), biomechanics (Marras and Radwin, 2006), safety engineering, emergency operations, maintenance human factors, situation awareness (Tenney and Pew, 2006), crew resource management (Salas et aI., 2006), methods for cognitive work analysis (Bisantz and Roth, 2008) and the like -- are applicable to astronauts, mission control, operational medicine, Space Shuttle manufacturing and assembly operations, and space suit designers as they are in other work domains (e.g., Bloomberg, 2003; Bos et al, 2006; Brooks and Ince, 1992; Casler and Cook, 1999; Jones, 1994; McCurdy et ai, 2006; Neerincx et aI., 2006; Olofinboba and Dorneich, 2005; Patterson, Watts-Perotti and Woods, 1999; Patterson and Woods, 2001; Seagull et ai, 2007; Sierhuis, Clancey and Sims, 2002). The human exploration of space also has unique challenges of particular interest to human factors research and practice. This chapter provides an overview of those issues and reports on sorne of the latest research results as well as the latest challenges still facing the field.

Waterway Performance Monitoring via Automatic Identification System (AIS) Data

DTIC Science & Technology

2013-08-01

Transceivers onboard the vessels broadcast the 4 AIS signal containing position, heading, speed, and other identifying information to shore- based 5 towers...Great Lakes system based 31 on the voyage histories reconstructed with the Destination field from the AIS static reports. In 32 spite of the much... Information Systems for Estimating Coastal Maritime Risk. 38 Transportation Research Record: Journal of the Transportation Research Board, No. 2222, 39 TRB

Do older t'ai chi practitioners have better attention and memory function?

PubMed

Man, David W K; Tsang, William W N; Hui-Chan, Christina W Y

2010-12-01

Cognitive declines are common in older people and can be a major health issue in an aging world. One type of body-mind exercises, t'ai chi, can be a possible means to help maintaining older adults' cognitive abilities, in addition to beneficial effects of physical exercises. The purpose of this study was to investigate whether t'ai chi practitioners had better attention and memory functions than older people with or without regular exercises. A cross-sectional study examining the relationship between t'ai chi practice and age-, gender- and education-similar older peoples' attention and memory functions. Forty-two (42) community-dwelling elderly subjects, aged 60 or older, recruited from t'ai chi clubs in Hong Kong formed the t'ai chi group. Another 49 elderly having regular exercise habits were recruited from community centers for inclusion in the exercise group. A nonexercise group (normal healthy control) consisting of 44 subjects were also recruited by random selection and through contacting local elderly centers. They were also screened by the Modified Barthel Index, Chinese Mini-mental Status Examination, Geriatric Depression Scale, and evaluated by attention tests (Color Trail Form A-1 and 2) and memory tests (including Rivermead Behavioral Memory Test and The Hong Kong List Learning Test). The main finding was that the three groups differed in attention and memory functions, and the t'ai chi group had demonstrated better performance than the other two groups in most subtests. As a causal relationship cannot be assumed in the present cross-sectional study, future research is required to examine how t'ai chi can improve cognitive function using a randomized control trial as well as determining whether t'ai chi practice can lead to better health status among elderly people.

TNF-alpha and IL-6 inhibit apolipoprotein A-IV production induced by linoleic acid in human intestinal Caco2 cells.

PubMed

Li, Xiaoming; Xu, Min; Liu, Min; Ji, Yong; Li, Zongfang

2015-01-01

Apolipoprotein A-IV (apoA-IV) is a protein mainly synthesized by enterocytes in the intestine. Its gene expression is suppressed during fasting and stimulated during active fat absorption. Chronic feeding of a high-fat (HF) diet abolishes the differential expression between fasting and fat-feeding and therefore may contribute to diet-induced obesity since apoA-IV is a potent satiety factor. It is well established that the circulating pro-inflammatory cytokines TNF-α and IL-6 are increased by HF feeding. To determine whether pro-inflammatory cytokines are involved in the diminished response of apoA-IV gene expression to fat-feeding, different concentrations of linoleic acid (LA), an important dietary fatty acid, was used to stimulate apoA-IV expression in human intestinal Caco2 cells. Cells were pre-treated with or without human recombinant TNF-α, IL-6 or their combination before the addition of LA. Real-time PCR and ELISA were used to detect and quantify RNA transcripts and proteins of apoA-IV and the cytokines. LA stimulated gene and protein expression of apoA-IV in a dose and time dependent manner. Pre-treatment with the cytokines for 72 h significantly inhibited the increased expression of apoA-IV gene and protein induced by LA. Furthermore, the cytokines, especially TNF-α, also positively up-regulate the cytokine themselves in Caco2 cells. Our data indicate that the pro-inflammatory cytokines may be responsible for the reduced apoA-IV production in response to fat feeding. Because of apoA-IV's role in satiety, we propose the inhibitory effect of circulating pro-inflammatory cytokines on apoA-IV production contributes to diet-induced obesity.

Constellation analysis of an integrated AIS/remote sensing spaceborne system for ship detection

NASA Astrophysics Data System (ADS)

Graziano, Maria Daniela; D'Errico, Marco; Razzano, Elena

2012-08-01

A future system integrating data from remote sensing and upcoming AIS satellites is analyzed through the development of a novel design method for global, discontinuous coverage constellations. It is shown that 8 AIS satellites suffice to guarantee global coverage and a ship location update of 50 min if the spaceborne AIS receiver has a swath of 2800 nm. Furthermore, synergic utilization of COSMO/SkyMed and Radarsat-C data would provide a mean revisit time of 7 h, with AIS information available within 25 min from SAR data acquisition.

Airborne spectroradiometry: The application of AIS data to detecting subtle mineral absorption features

NASA Technical Reports Server (NTRS)

Cocks, T. D.; Green, A. A.

1986-01-01

Analysis of Airborne Imaging Spectrometer (AIS) data acquired in Australia has revealed a number of operational problems. Horizontal striping in AIS imagery and spectral distortions due to order overlap were investigated. Horizontal striping, caused by grating position errors can be removed with little or no effect on spectral details. Order overlap remains a problem that seriously compromises identification of subtle mineral absorption features within AIS spectra. A spectrometric model of the AIS was developed to assist in identifying spurious spectral features, and will be used in efforts to restore the spectral integrity of the data.

AIS and Collision Avoidance a Sense of Déjà Vu

NASA Astrophysics Data System (ADS)

Stitt, I. P. A.

2004-05-01

Although AIS is already in use in a range of vessels, there has been little public discussion on how AIS should interact with the COLREGS in practice. The objective of this paper is to make a contribution to that debate, while recognising that “best practice” will evolve as more practical experience is obtained. The paper suggests the approach that should be adopted in several areas, but concludes that, overall, AIS is nothing more than one of several tools that should enable mariners to fulfil their existing obligations under the COLREGS.

Vitamin E Inhibits Abdominal Aortic Aneurysm Formation in Angiotensin II–Infused Apolipoprotein E–Deficient Mice

PubMed Central

Gavrila, Dan; Li, Wei Gen; McCormick, Michael L.; Thomas, Manesh; Daugherty, Alan; Cassis, Lisa A.; Miller, Francis J.; Oberley, Larry W.; Dellsperger, Kevin C.; Weintraub, Neal L.

2014-01-01

Background Abdominal aortic aneurysms (AAAs) in humans are associated with locally increased oxidative stress and activity of NADPH oxidase. We investigated the hypothesis that vitamin E, an antioxidant with documented efficacy in mice, can attenuate AAA formation during angiotensin II (Ang II) infusion in apolipoprotein E–deficient mice. Methods and Results Six-month-old male apolipoprotein E–deficient mice were infused with Ang II at 1000 ng/kg per minute for 4 weeks via osmotic minipumps while consuming either a regular diet or a diet enriched with vitamin E (2 IU/g of diet). After 4 weeks, abdominal aortic weight and maximal diameter were determined, and aortic tissues were sectioned and examined using biochemical and histological techniques. Vitamin E attenuated formation of AAA, decreasing maximal aortic diameter by 24% and abdominal aortic weight by 34% (P<0.05, respectively). Importantly, animals treated with vitamin E showed a 44% reduction in the combined end point of fatal+nonfatal aortic rupture (P<0.05). Vitamin E also decreased aortic 8-isoprostane content (a marker of oxidative stress) and reduced both aortic macrophage infiltration and osteopontin expression (P<0.05, respectively). Vitamin E treatment had no significant effect on the extent of aortic root atherosclerosis, activation of matrix metalloproteinases 2 or 9, serum lipid profile, or systolic blood pressure. Conclusions Vitamin E ameliorates AAAs and reduces the combined end point of fatal+nonfatal aortic rupture in this animal model. These findings are consistent with the concept that oxidative stress plays a pivotal role in Ang II–driven AAA formation in hyperlipidemic mice. PMID:15933246

Teaching AI Search Algorithms in a Web-Based Educational System

ERIC Educational Resources Information Center

Grivokostopoulou, Foteini; Hatzilygeroudis, Ioannis

2013-01-01

In this paper, we present a way of teaching AI search algorithms in a web-based adaptive educational system. Teaching is based on interactive examples and exercises. Interactive examples, which use visualized animations to present AI search algorithms in a step-by-step way with explanations, are used to make learning more attractive. Practice…

Methods for Processing and Interpretation of AIS Signals Corrupted by Noise and Packet Collisions

NASA Astrophysics Data System (ADS)

Poļevskis, J.; Krastiņš, M.; Korāts, G.; Skorodumovs, A.; Trokšs, J.

2012-01-01

The authors deal with the operation of Automatic Identification System (AIS) used in the marine traffic monitoring to broadcast messages containing information about the vessel: id, payload, size, speed, destination etc., meant primarily for avoidance of ship collisions. To extend the radius of AIS operation, it is envisaged to dispose its receivers on satellites. However, in space, due to a large coverage area, interfering factors are especially pronounced - such as packet collision, Doppler's shift and noise impact on AIS message receiving, pre-processing and decoding. To assess the quality of an AIS receiver's operation, a test was carried out in which, varying automatically frequency, amplitude, noise, and other parameters, the data on the ability of the receiver's ability to decode AIS signals are collected. In the work, both hardware- and software-based AIS decoders were tested. As a result, quite satisfactory statistics has been gathered - both on the common and the differing features of such decoders when operating in space. To obtain reliable data on the software-defined radio AIS receivers, further research is envisaged.

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

PubMed

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

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

The age dependency of gene expression for plasma lipids, lipoproteins, and apolipoproteins

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

Snieder, H.; Doornen, L.J.P. van; Boomsma, D.I.

The aim of this study was to investigate and disentangle the genetic and nongenetic causes of stability and change in lipids and (apo)lipoproteins that occur during the lifespan. Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) were measured in a group of 160 middle-aged parents and their twin offspring (first project) and in a group of 203 middle-aged twin pairs (second project). Combining the data of both projects enabled the estimation of the extent to which measured lipid parameters are influenced by different genes in adolescence and adulthood. To thatmore » end, an extended quantitative genetic model was specified, which allowed the estimation of heritabilities for each sex and generation separately. Heritabilities were similar for both sexes and both generations. Larger variances in the parental generation could be ascribed to proportional increases in both unique environmental and additive genetic variance from childhood to adulthood, which led to similar heritability estimates in adolescent and middle-aged twins. Although the magnitudes of heritabilities were similar across generations, results showed that, for total cholesterol, triglycerides, HDL, and LDL, partly different genes are expressed in adolescence compared to adulthood. For triglycerides, only 46% of the genetic variance was common to both age groups; for total cholesterol this was 80%. Intermediate values were found for HDL (66%) and LDL (76%). For ApoA1, ApoB, and Lp(a), the same genes seem to act in both generations. 56 refs., 2 figs., 5 tabs.« less

Evaluation of AIS-2 (1986) data over hydrothermally altered granitoid rocks of the Singatse Range (Yerington) Nevada and comparison with 1985 AIS-1 data

NASA Technical Reports Server (NTRS)

Lyon, R. J. P.

1987-01-01

The Airborne Imaging Spectrometer-2 (AIS-2) flights along 2 subparallel lines (bearing 013) were designed to traverse 3 major rock assemblages - the Triassic sedimentary sequence; the granitoid rocks of the Yerington batholith and the Tertiary ignimbritic ash flow and ash fall tuffs. The first 2 sites are hydrothermally altered to a quartz-sericite-tourmaline mineralogy. The first AIS-2 data set showed numerous line dropouts and a considerable number of randomly distributed dark pixels. A second decommutation reduced the dropout essentially to near zero and the dark pixels by about 75 percent. Vertical striping was removed by histogram matching, column by column. A log residual spectrum was calculated which showed the departure of a 2 x 2 pixel area from the spatially and spectrally averaged scene. A 1:1 correlation was found with the log residual AIS-2 data and a large open pit area of gypsum. An area with known sericite agreed with the overflight data, and an area known to be free of any significant amount of O-H bearing materials showed no evidence of any in the AIS-2 log residuals.

Purification and ATPase activity of human ABCA1.

PubMed

Takahashi, Kei; Kimura, Yasuhisa; Kioka, Noriyuki; Matsuo, Michinori; Ueda, Kazumitsu

2006-04-21

ATP-binding cassette protein A1 (ABCA1) plays a major role in cholesterol homeostasis and high density lipoprotein metabolism. Apolipoprotein A-I binds to ABCA1 and cellular cholesterol and phospholipids, mainly phosphatidylcholine, are loaded onto apoA-I to form pre-beta high density lipoprotein (HDL). It is proposed that ABCA1 translocates phospholipids and cholesterol directly or indirectly to form pre-beta HDL. To explore the mechanism of ABCA1-mediated pre-beta HDL formation, we expressed human ABCA1 in insect Sf9 cells and purified it. Trypsin limited-digestion of purified ABCA1 in the detergent-soluble form suggested that it retained conformation similar to ABCA1 expressed in the membranes of human fibroblast WI-38 cells. Purified ABCA1 showed robust ATPase activity when reconstituted in liposomes made of synthetic phosphatidylcholine. ABCA1 showed lower ATPase activity when reconstituted in liposomes containing phosphatidylserine, phosphatidylethanolamine, or phosphatidylglycerol and also showed weak specificity in acyl chain species. ATPase activity was reduced by the addition of cholesterol and decreased by 25% in the presence of 20% cholesterol. Beta-sitosterol and campesterol showed similar inhibitory effects but stigmasterol did not, suggesting structure-specific interaction between ABCA1 and sterols. Glibenclamide suppressed ABCA1 ATPase, suggesting that it inhibits apoA-I-dependent cellular cholesterol efflux by suppressing ABCA1 ATPase activity. These results suggest that the ATPase activity of ABCA1 is stimulated preferentially by phospholipids with choline head groups, phosphatidylcholine and sphingomyelin. This study with purified human ABCA1 provides the first biochemical basis of the mechanism for HDL formation mediated by ABCA1.

SDI satellite autonomy using AI and Ada

NASA Technical Reports Server (NTRS)

Fiala, Harvey E.

1990-01-01

The use of Artificial Intelligence (AI) and the programming language Ada to help a satellite recover from selected failures that could lead to mission failure are described. An unmanned satellite will have a separate AI subsystem running in parallel with the normal satellite subsystems. A satellite monitoring subsystem (SMS), under the control of a blackboard system, will continuously monitor selected satellite subsystems to become alert to any actual or potential problems. In the case of loss of communications with the earth or the home base, the satellite will go into a survival mode to reestablish communications with the earth. The use of an AI subsystem in this manner would have avoided the tragic loss of the two recent Soviet probes that were sent to investigate the planet Mars and its moons. The blackboard system works in conjunction with an SMS and a reconfiguration control subsystem (RCS). It can be shown to be an effective way for one central control subsystem to monitor and coordinate the activities and loads of many interacting subsystems that may or may not contain redundant and/or fault-tolerant elements. The blackboard system will be coded in Ada using tools such as the ABLE development system and the Ada Production system.

Pseudorange Measurement Method Based on AIS Signals.

PubMed

Zhang, Jingbo; Zhang, Shufang; Wang, Jinpeng

2017-05-22

In order to use the existing automatic identification system (AIS) to provide additional navigation and positioning services, a complete pseudorange measurements solution is presented in this paper. Through the mathematical analysis of the AIS signal, the bit-0-phases in the digital sequences were determined as the timestamps. Monte Carlo simulation was carried out to compare the accuracy of the zero-crossing and differential peak, which are two timestamp detection methods in the additive white Gaussian noise (AWGN) channel. Considering the low-speed and low-dynamic motion characteristics of ships, an optimal estimation method based on the minimum mean square error is proposed to improve detection accuracy. Furthermore, the α difference filter algorithm was used to achieve the fusion of the optimal estimation results of the two detection methods. The results show that the algorithm can greatly improve the accuracy of pseudorange estimation under low signal-to-noise ratio (SNR) conditions. In order to verify the effectiveness of the scheme, prototypes containing the measurement scheme were developed and field tests in Xinghai Bay of Dalian (China) were performed. The test results show that the pseudorange measurement accuracy was better than 28 m (σ) without any modification of the existing AIS system.

Pseudorange Measurement Method Based on AIS Signals

PubMed Central

Zhang, Jingbo; Zhang, Shufang; Wang, Jinpeng

2017-01-01

In order to use the existing automatic identification system (AIS) to provide additional navigation and positioning services, a complete pseudorange measurements solution is presented in this paper. Through the mathematical analysis of the AIS signal, the bit-0-phases in the digital sequences were determined as the timestamps. Monte Carlo simulation was carried out to compare the accuracy of the zero-crossing and differential peak, which are two timestamp detection methods in the additive white Gaussian noise (AWGN) channel. Considering the low-speed and low-dynamic motion characteristics of ships, an optimal estimation method based on the minimum mean square error is proposed to improve detection accuracy. Furthermore, the α difference filter algorithm was used to achieve the fusion of the optimal estimation results of the two detection methods. The results show that the algorithm can greatly improve the accuracy of pseudorange estimation under low signal-to-noise ratio (SNR) conditions. In order to verify the effectiveness of the scheme, prototypes containing the measurement scheme were developed and field tests in Xinghai Bay of Dalian (China) were performed. The test results show that the pseudorange measurement accuracy was better than 28 m (σ) without any modification of the existing AIS system. PMID:28531153

47 CFR 80.231 - Technical Requirements for Class B Automatic Identification System (AIS) equipment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Identification System (AIS) equipment. 80.231 Section 80.231 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... § 80.231 Technical Requirements for Class B Automatic Identification System (AIS) equipment. (a) Class B Automatic Identification System (AIS) equipment must meet the technical requirements of IEC 62287...

47 CFR 80.231 - Technical Requirements for Class B Automatic Identification System (AIS) equipment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Identification System (AIS) equipment. 80.231 Section 80.231 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... § 80.231 Technical Requirements for Class B Automatic Identification System (AIS) equipment. (a) Class B Automatic Identification System (AIS) equipment must meet the technical requirements of IEC 62287...

47 CFR 80.231 - Technical Requirements for Class B Automatic Identification System (AIS) equipment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Identification System (AIS) equipment. 80.231 Section 80.231 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... § 80.231 Technical Requirements for Class B Automatic Identification System (AIS) equipment. (a) Class B Automatic Identification System (AIS) equipment must meet the technical requirements of IEC 62287...

47 CFR 80.275 - Technical Requirements for Class A Automatic Identification System (AIS) equipment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Compulsory Ships § 80.275 Technical Requirements for Class A Automatic Identification System (AIS) equipment. (a) Prior to submitting a certification application for a Class A AIS device, the following... Identification System (AIS) equipment. 80.275 Section 80.275 Telecommunication FEDERAL COMMUNICATIONS COMMISSION...

47 CFR 80.275 - Technical Requirements for Class A Automatic Identification System (AIS) equipment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Compulsory Ships § 80.275 Technical Requirements for Class A Automatic Identification System (AIS) equipment. (a) Prior to submitting a certification application for a Class A AIS device, the following... Identification System (AIS) equipment. 80.275 Section 80.275 Telecommunication FEDERAL COMMUNICATIONS COMMISSION...

47 CFR 80.275 - Technical Requirements for Class A Automatic Identification System (AIS) equipment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Compulsory Ships § 80.275 Technical Requirements for Class A Automatic Identification System (AIS) equipment. (a) Prior to submitting a certification application for a Class A AIS device, the following... Identification System (AIS) equipment. 80.275 Section 80.275 Telecommunication FEDERAL COMMUNICATIONS COMMISSION...

47 CFR 80.275 - Technical Requirements for Class A Automatic Identification System (AIS) equipment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Compulsory Ships § 80.275 Technical Requirements for Class A Automatic Identification System (AIS) equipment. (a) Prior to submitting a certification application for a Class A AIS device, the following... Identification System (AIS) equipment. 80.275 Section 80.275 Telecommunication FEDERAL COMMUNICATIONS COMMISSION...

Direct recognition of superparamagnetic nanocrystals by macrophage scavenger receptor SR-AI.

PubMed

Chao, Ying; Karmali, Priya P; Mukthavaram, Rajesh; Kesari, Santosh; Kouznetsova, Valentina L; Tsigelny, Igor F; Simberg, Dmitri

2013-05-28

Scavenger receptors (SRs) are molecular pattern recognition receptors that have been shown to mediate opsonin-independent uptake of therapeutic and imaging nanoparticles, underlying the importance of SRs in nanomedicine. Unlike pathogens, engineered nanomaterials offer great flexibility in control of surface properties, allowing addressing specific questions regarding the molecular mechanisms of nanoparticle recognition. Recently, we showed that SR-type AI/II mediates opsonin-independent internalization of dextran superparamagnetic iron oxide (SPIO) nanoparticles via positively charged extracellular collagen-like domain. To understand the mechanism of opsonin-independent SPIO recognition, we tested the binding and uptake of nanoparticles with different surface coatings by SR-AI. SPIO coated with 10 kDa dextran was efficiently recognized and taken up by SR-AI transfected cells and J774 macrophages, while SPIO with 20 kDa dextran coating or cross-linked dextran hydrogel avoided the binding and uptake. Nanoparticle negative charge density and zeta-potential did not correlate with SR-AI binding/uptake efficiency. Additional experiments and computer modeling revealed that recognition of the iron oxide crystalline core by the positively charged collagen-like domain of SR-AI is sterically hindered by surface polymer coating. Importantly, the modeling revealed a strong complementarity between the surface Fe-OH groups of the magnetite crystal and the charged lysines of the collagen-like domain of SR-AI, suggesting a specific recognition of SPIO crystalline surface. These data provide an insight into the molecular recognition of nanocrystals by innate immunity receptors and the mechanisms whereby polymer coatings promote immune evasion.

VizieR Online Data Catalog: AI CMi UBV light curves (Arkhipova+, 2017)

NASA Astrophysics Data System (ADS)

Arkhipova, V. P.; Ikonnikova, N. P.; Esipov, V. F.; Komissarova, G. V.

2017-07-01

The UBV observations of AI CMi were carried out at the Crimean Station of the SAI MSU using a 60-cm Zeiss reflector with a photoelectric photometer designed by Lyuty (1971, Soobshch. GAISh, No. 172, 30) with a 27" aperture. We began to observe AI CMi in 1996 and obtained more than 200 UBV magnitude estimates for the star in 21 years. Table 1 presents our UBV photometry for AI CMi reduced to the Johnson system. (1 data file).

Distribution of apolipoprotein E alleles in a Scottish healthy newborn population.

PubMed

Becher, J-C; Bell, J E; McIntosh, N; Keeling, J W

2005-01-01

The different alleles of the human apolipoprotein E polymorphism, ApoE epsilon2, epsilon3, epsilon4, have important implications for systemic lipid metabolism, immunological function and for the brain in maintenance and in response to injury. Few studies have focussed on their role in early life. The ApoE alleles and genotypes were ascertained in the cord blood of 371 full-term and normal Scottish newborn infants using PCR methodology. The results were compared to previously published data for Scottish adults in late middle age. There was a marginally significant over-representation of epsilon4 and under-representation of epsilon3 alleles in healthy infants as compared with adults. Inspection of the individual genotypes confirms the over-representation of ApoE 4/4 and 2/4 with a reduction in ApoE 2/3 and 3/3 when compared with Scottish adults. Although these results may have occurred by chance, the ApoE epsilon4 allele may confer an increased risk of premature death. Copyright (c) 2005 S. Karger AG, Basel.

Novel cross-linked alcohol-insoluble solid (CL-AIS) affinity gel from pea pod for pectinesterase purification.

PubMed

Wu, Ming-Chang; Lin, Guan-Hui; Wang, Yuh-Tai; Jiang, Chii-Ming; Chang, Hung-Min

2005-10-05

Alcohol-insoluble solids (AIS) from pea pod were cross-linked (CL-AIS) and used as an affinity gel matrix to isolate pectin esterases (PEs) from tendril shoots of chayote (TSC) and jelly fig achenes (JFA), and the results were compared with those isolated by ion-exchange chromatography with a commercial resin. CL-AIS gel matrix in a column displayed poor absorption and purification fold of PE; however, highly methoxylated CL-AIS (HM-CL-AIS), by exposing CL-AIS to methanolic sulfuric acid to increase the degree of esterification (DE) to 92%, facilitated the enzyme purification. The purified TSC PE and JFA PE by the HM-CL-AIS column were proofed as a single band on an SDS-PAGE gel, showing that the HM-CL-AIS column was a good matrix for purification of PE, either with alkaline isoelectric point (pI) (TSC PE) or with acidic pI (JFA PE).

Association of Apolipoprotein B/Apolipoprotein A1 Ratio and Coronary Artery Stenosis and Plaques Detected by Multi-Detector Computed Tomography in Healthy Population

PubMed Central

Jung, Chang Hee; Hwang, Jenie Yoonoo; Shin, Mi Seon; Yu, Ji Hee; Kim, Eun Hee; Bae, Sung Jin; Yang, Dong Hyun; Kang, Joon-Won; Park, Joong-Yeol; Kim, Hong-Kyu

2013-01-01

Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT), its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1 increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT. PMID:23678262

Association of apolipoprotein b/apolipoprotein A1 ratio and coronary artery stenosis and plaques detected by multi-detector computed tomography in healthy population.

PubMed

Jung, Chang Hee; Hwang, Jenie Yoonoo; Shin, Mi Seon; Yu, Ji Hee; Kim, Eun Hee; Bae, Sung Jin; Yang, Dong Hyun; Kang, Joon-Won; Park, Joong-Yeol; Kim, Hong-Kyu; Lee, Woo Je

2013-05-01

Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT), its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1 increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT.

TBS and BMD at the end of AI-therapy: A prospective study of the B-ABLE cohort.

PubMed

María, Rodríguez-Sanz; Marta, Pineda-Moncusí; Sonia, Servitja; Natalia, Garcia-Giralt; Tamara, Martos; Ignasi, Tusquets; Maria, Martínez-García; Jaime, Rodriguez-Morera; Adolfo, Diez-Perez; Joan, Albanell; Xavier, Nogués

2016-11-01

Patients with breast cancer under aromatase inhibitor (AI) treatment often develop osteoporosis and their average bone loss rate is twice that of natural reduction during menopause, increasing fracture risk. As the current diagnostic technique based on bone mineral density (BMD) provides no information on bone quality, the Trabecular Bone Score (TBS) has been proposed to reflect bone microarchitecture status. The present study was designed to assess prospective changes in TBS and lumbar spine (LS) BMD in postmenopausal women with breast cancer at completion of AI treatment. B-ABLE is a prospective cohort of 735 women with breast cancer treated with AIs according to American Society of Clinical Oncology recommendations: 5years of AI starting within 6weeks post-surgery or 1month after the last cycle of chemotherapy (5y-AI group), or switching to an AI to complete 5-year therapy after 2-3years of tamoxifen (pTMX-AI group). Patients with osteoporosis were treated with oral bisphosphonates (BP). TBS and LS-BMD changes at completion of AI therapy were evaluated by Student t-test for paired samples. Pearson correlation coefficients were computed for correlations between LS-BMD and TBS. AI treatment was completed by 277 women. Of these, 70 (25.3%) were allocated to BP therapy. The non-BP-treated patients (74.7%) showed significant decreases in TBS (-2.94% in pTMX-AI and -2.93% in 5y-AI groups) and in LS-BMD (-4.14% in pTMX-AI and -2.28% in 5y-AI groups) at the end of AI treatment. In BP-treated patients, TBS remained stable at the end of AI treatment, whereas LS-BMD showed significant increases (+2.30% in pTMX-AI and +5.33% in 5y-AI groups). Moderate associations between TBS and LS-BMD values at baseline and at the end of AI treatment (r=0.4; P<0.001) were observed. At the end of treatment, changes in spine BMD and TBS were weakly correlated (r=0.1, P<0.01). AI therapy induces significant decreases in TBS, comparable to BMD loss. BP-treated patients maintained TBS values

The complete sequence and structural analysis of human apolipoprotein B-100: relationship between apoB-100 and apoB-48 forms.

PubMed Central

Cladaras, C; Hadzopoulou-Cladaras, M; Nolte, R T; Atkinson, D; Zannis, V I

1986-01-01

We have isolated and sequenced overlapping cDNA clones covering the entire sequence of human apolipoprotein B-100 (apoB-100). DNA sequence analysis and determination of the mRNA transcription initiation site by S1 nuclease mapping showed that the apoB mRNA consists of 14,112 nucleotides including the 5' and 3' untranslated regions which are 128 and 301 nucleotides respectively. The DNA-derived protein sequence shows that apoB-100 is 513,000 daltons and contains 4560 amino acids including a 24-amino-acid-long signal peptide. The mol. wt of apoB-100 implies that there is one apoB molecule per LDL particle. Computer analysis of the predicted secondary structure of the protein showed that some of the potential alpha helical and beta sheet structures are amphipathic, whereas others have non-amphipathic neutral to apolar character. These latter regions may contribute to the formation of the lipid-binding domains of apoB-100. The protein contains 25 cysteines and 20 potential N-glycosylation sites. The majority of cysteines are distributed in the amino terminal portion of the protein. Four of the potential glycosylation sites are in predicted beta turn structures and may represent true glycosylation positions. ApoB lacks the tandem repeats which are characteristic of other apolipoproteins. The mean hydrophobicity the mean value of H1 and helical hydrophobic moment the mean value of microH profiles of apoB showed the presence of several potential helical regions with strong polar character and high hydrophobic moment. The region with the highest hydrophobic moment, between amino acid residues 3352 and 3369, contains five closely spaced, positively charged residues, and has sequence homology to the LDL receptor binding site of apoE. This region is flanked by three neighbouring regions with positively charged amino acids and high hydrophobic moment that are located between residues 3174 and 3681. One or more of these closely spaced apoB sequences may be involved in the

AI-MSG modification work plan. [LMFBR

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

Page, J.P.

1973-08-20

This document contains the Work Plan for the modification of the AI Steam Generator for tests in Large Leak Test Rig. This Work Plan describes the objectives, scope of work, schedule and manpower, end items, and meetings and reports required for the modification.

AI's Philosophical Underpinnings: A Thinking Person's Walk through the Twists and Turns of Artificial Intelligence's Meandering Path

NASA Technical Reports Server (NTRS)

Colombano, Silvano; Norvig, Peter (Technical Monitor)

2000-01-01

Few human endeavors can be viewed both as extremely successful and unsuccessful at the same time. This is typically the case when goals have not been well defined or have been shifting in time. This has certainly been true of Artificial Intelligence (AI). The nature of intelligence has been the object of much thought and speculation throughout the history of philosophy. It is in the nature of philosophy that real headway is sometimes made only when appropriate tools become available. Similarly the computer, coupled with the ability to program (at least in principle) any function, appeared to be the tool that could tackle the notion of intelligence. To suit the tool, the problem of the nature of intelligence was soon sidestepped in favor of this notion: If a probing conversation with a computer could not be distinguished from a conversation with a human, then AI had been achieved. This notion became known as the Turing test, after the mathematician Alan Turing who proposed it in 1950. Conceptually rich and interesting, these early efforts gave rise to a large portion of the field's framework. Key to AI, rather than the 'number crunching' typical of computers until then, was viewed as the ability to manipulate symbols and make logical inferences. To facilitate these tasks, AI languages such as LISP and Prolog were invented and used widely in the field. One idea that emerged and enabled some success with real world problems was the notion that 'most intelligence' really resided in knowledge. A phrase attributed to Feigenbaum, one of the pioneers, was 'knowledge is the power.' With this premise, the problem is shifted from 'how do we solve problems' to 'how do we represent knowledge.' A good knowledge representation scheme could allow one to draw conclusions from given premises. Such schemes took forms such as rules,frames and scripts. It allowed the building of what became known as expert systems or knowledge based systems (KBS).

Launching AI in NASA ground systems

NASA Technical Reports Server (NTRS)

Perkins, Dorothy C.; Truszkowski, Walter F.

1990-01-01

This paper will discuss recent operational successes in implementing expert systems to support the complex functions of NASA mission control systems at the Goddard Space Flight Center, including fault detection and diagnosis for real time and engineering analysis functions in the Cosmic Background Explorer and Gamma Ray Observatory missions and automation of resource planning and scheduling functions for various missions. It will also discuss ongoing developments and prototypes that will lead to increasingly sophisticated applications of artificial intelligence. These include the use of neural networks to perform telemetry monitoring functions, the implementation of generic expert system shells that can be customized to telemetry handling functions specific to NASA control centers, the applications of AI in training and user support, the long-term potential of implementing systems based around distributed, cooperative problem solving, and the use of AI to control and assist system development activities.

The NeuroAiD Safe Treatment (NeST) Registry: a protocol

PubMed Central

Venketasubramanian, Narayanaswamy; Kumar, Ramesh; Soertidewi, Lyna; Abu Bakar, Azizi; Laik, Carine; Gan, Robert

2015-01-01

Introduction NeuroAiD (MLC601, MLC901), a combination of natural products, has been shown to be safe and to aid neurological recovery after brain injuries. The NeuroAiD Safe Treatment (NeST) Registry aims to assess its use and safety in the real-world setting. Methods and analysis The NeST Registry is designed as a product registry that would provide information on the use and safety of NeuroAiD in clinical practice. An online NeST Registry was set up to allow easy entry and retrieval of essential information including demographics, medical conditions, clinical assessments of neurological, functional and cognitive state, compliance, concomitant medications, and side effects, if any, among patients on NeuroAiD. Patients who are taking or have been prescribed NeuroAiD may be included. Participation is voluntary. Data collected are similar to information obtained during standard care and are prospectively entered by the participating physicians at baseline (before initialisation of NeuroAiD) and during subsequent visits. The primary outcome assessed is safety (ie, non-serious and serious adverse event), while compliance and neurological status over time are secondary outcomes. The in-person follow-up assessments are timed with clinical appointments. Anonymised data will be extracted and collectively analysed. Initial target sample size for the registry is 2000. Analysis will be performed after every 500 participants entered with completed follow-up information. Ethics and dissemination Doctors who prescribe NeuroAiD will be introduced to the registry by local partners. The central coordinator of the registry will discuss the protocol and requirements for implementation with doctors who show interest. Currently, the registry has been approved by the Ethics Committees of Universiti Kebangsaan Malaysia (Malaysia) and National Brain Center (Indonesia). In addition, for other countries, Ethics Committee approval will be obtained in accordance with local requirements. Trial

[The effect of Ai Chi method in fibromyalgic patients].

PubMed

Santana, Jacqueline Soares de; Almeida, Ana Paula Gonçalves de; Brandão, Patrícia Martins Carvalho

2010-06-01

The objective of this article is to show the effect of the Ai Chi method, as an alternative form of hydrotherapeutic approach in fibromyalgia syndrome patients. Ten patients were studied, four were part of the experiment group and five of the control group, with one desistance. The patients were evaluated through the Fibromyalgia Impact Questionnaire (QIF) and Scale of Intensity and Index of pain in Sensible Points. Two evaluations were performed, before and after the treatment. The patients were submitted to ten sessions of the Ai Chi method during 40 minutes. The scale of intensity of pain in sensible points presented an improvement in the intensity of pain after the intervention, while quality of life remained without alteration. Regarding the quality of life, it was observed that the groups had similar results, because of the fact that patients had not presented improvement at depressive state. It was also verified a difference in the index of the sensible points between the groups; the explanation for this difference might be because of the benefits of the immersion in warm water and the effect of the Ai Chi method. There was no significant difference between the groups, which can be attributed to its limitations. In this way, new studies referring to the application of the Ai Chi method in patients carrying fibromyalgia syndrome become relevant.

Influence of apolipoprotein A-V on the metabolic fate of triacylglycerol.

PubMed

Sharma, Vineeta; Forte, Trudy M; Ryan, Robert O

2013-04-01

Apolipoprotein (apo) A-V functions to modulate intracellular and extracellular triacylglycerol metabolism. The present review addresses molecular mechanisms underlying these effects. The relevance of apoA-V to human disease conditions is illustrated by the strong correlation between single nucleotide polymorphisms in APOA5, elevated plasma triacylglycerol and dyslipidemic disease. Despite undergoing processing for secretion from hepatocytes, a portion of apoA-V escapes this destiny and accumulates as a component of cytosolic lipid droplets. Expression of recombinant apoA-V in hepatocarcinoma cells results in increased lipid droplet size and number at the expense of triacylglycerol secretion.ApoA-V modulates atherosclerosis in hypercholesterolemic apoE null mice. ApoE null/human apoA-V transgenic mice had reduced levels of triacylglycerol and cholesterol in plasma along with decreased aortic lesion size. ApoA-V modulates triacylglycerol metabolic fate. Following its synthesis, apoA-V enters the endoplasmic reticulum and associates with membrane defects created by triacylglycerol accumulation. Association of apoA-V with endoplasmic reticulum membrane defects promotes nascent lipid droplets budding toward the cytosol. Despite its low concentration in plasma (∼150 ng/ml), apoA-V modulates lipoprotein metabolism by binding to glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. This interaction effectively localizes triacylglycerol-rich lipoproteins in the vicinity of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein1's other ligand, lipoprotein lipase.

Peptide stabilized amphotericin B nanodisks

PubMed Central

Tufteland, Megan; Pesavento, Joseph B.; Bermingham, Rachelle L.; Hoeprich, Paul D.; Ryan, Robert O.

2007-01-01

Nanometer scale apolipoprotein A-I stabilized phospholipid disk complexes (nanodisks; ND) have been formulated with the polyene antibiotic amphotericin B (AMB). The present studies were designed to evaluate if a peptide can substitute for the function of the apolipoprotein component of ND with respect to particle formation and stability. An 18-residue synthetic amphipathic α-helical peptide, termed 4F (Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH2), solubilized vesicles comprised of egg phosphatidylcholine (egg PC), dipentadecanoyl PC or dimyristoylphosphatidylcholine (DMPC) at rates greater than or equal to solubilization rates observed with human apolipoprotein A-I (apoA-I; 243 amino acids). Characterization studies revealed that interaction with DMPC induced a near doubling of 4F tryptophan fluorescence emission quantum yield (excitation 280 nm) and a ~7 nm blue shift in emission wavelength maximum. Inclusion of AMB in the vesicle substrate resulted in formation of 4F AMB-ND. Spectra of AMB containing particles revealed the antibiotic is a highly effective quencher of 4F tryptophan fluorescence emission, giving rise to a Ksv = 7.7 × 104. Negative stain electron microscopy revealed that AMB-ND prepared with 4F possessed a disk shaped morphology similar to ND prepared without AMB or prepared with apoA-I. In yeast and pathogenic fungi growth inhibition assays, 4F AMB-ND was as effective as apoA-I AMB-ND. The data indicate that AMB-ND generated using an amphipathic peptide in lieu of apoA-I form a discrete population of particles that possess potent biological activity. Given their intrinsic versatility, peptides may be preferred for scale up and clinical application of AMB-ND. PMID:17293004

AiGERM: A logic programming front end for GERM

NASA Technical Reports Server (NTRS)

Hashim, Safaa H.

1990-01-01

AiGerm (Artificially Intelligent Graphical Entity Relation Modeler) is a relational data base query and programming language front end for MCC (Mission Control Center)/STP's (Space Test Program) Germ (Graphical Entity Relational Modeling) system. It is intended as an add-on component of the Germ system to be used for navigating very large networks of information. It can also function as an expert system shell for prototyping knowledge-based systems. AiGerm provides an interface between the programming language and Germ.

Functional subdivisions in low-frequency primary auditory cortex (AI).

PubMed

Wallace, M N; Palmer, A R

2009-04-01

We wished to test the hypothesis that there are modules in low-frequency AI that can be identified by their responsiveness to communication calls or particular regions of space. Units were recorded in anaesthetised guinea pig AI and stimulated with conspecific vocalizations and a virtual motion stimulus (binaural beats) presented via a closed sound system. Recording tracks were mainly oriented orthogonally to the cortical surface. Some of these contained units that were all time-locked to the structure of the chutter call (14/22 tracks) and/or the purr call (12/22 tracks) and/or that had a preference for stimuli from a particular region of space (8/20 tracks with four contralateral, two ipsilateral and two midline), or where there was a strong asymmetry in the response to beats of different direction (two tracks). We conclude that about half of low-frequency AI is organized into modules that are consistent with separate "what" and "where" pathways.

Artificial intelligence (AI) based tactical guidance for fighter aircraft

NASA Technical Reports Server (NTRS)

Mcmanus, John W.; Goodrich, Kenneth H.

1990-01-01

A research program investigating the use of artificial intelligence (AI) techniques to aid in the development of a Tactical Decision Generator (TDG) for Within Visual Range air combat engagements is discussed. The application of AI programming and problem solving methods in the development and implementation of the Computerized Logic For Air-to-Air Warfare Simulations (CLAWS), a second generation TDG, is presented. The knowledge-based systems used by CLAWS to aid in the tactical decision-making process are outlined in detail, and the results of tests to evaluate the performance of CLAWS versus a baseline TDG developed in FORTRAN to run in real time in the Langley Differential Maneuvering Simulator, are presented. To date, these test results have shown significant performance gains with respect to the TDG baseline in one-versus-one air combat engagements, and the AI-based TDG software has proven to be much easier to modify and maintain than the baseline FORTRAN TDG programs.

Absolute parameters for AI Phoenicis using WASP photometry

NASA Astrophysics Data System (ADS)

Kirkby-Kent, J. A.; Maxted, P. F. L.; Serenelli, A. M.; Turner, O. D.; Evans, D. F.; Anderson, D. R.; Hellier, C.; West, R. G.

2016-06-01

Context. AI Phe is a double-lined, detached eclipsing binary, in which a K-type sub-giant star totally eclipses its main-sequence companion every 24.6 days. This configuration makes AI Phe ideal for testing stellar evolutionary models. Difficulties in obtaining a complete lightcurve mean the precision of existing radii measurements could be improved. Aims: Our aim is to improve the precision of the radius measurements for the stars in AI Phe using high-precision photometry from the Wide Angle Search for Planets (WASP), and use these improved radius measurements together with estimates of the masses, temperatures and composition of the stars to place constraints on the mixing length, helium abundance and age of the system. Methods: A best-fit ebop model is used to obtain lightcurve parameters, with their standard errors calculated using a prayer-bead algorithm. These were combined with previously published spectroscopic orbit results, to obtain masses and radii. A Bayesian method is used to estimate the age of the system for model grids with different mixing lengths and helium abundances. Results: The radii are found to be R1 = 1.835 ± 0.014 R⊙, R2 = 2.912 ± 0.014 R⊙ and the masses M1 = 1.1973 ± 0.0037 M⊙, M2 = 1.2473 ± 0.0039 M⊙. From the best-fit stellar models we infer a mixing length of 1.78, a helium abundance of YAI = 0.26 +0.02-0.01 and an age of 4.39 ± 0.32 Gyr. Times of primary minimum show the period of AI Phe is not constant. Currently, there are insufficient data to determine the cause of this variation. Conclusions: Improved precision in the masses and radii have improved the age estimate, and allowed the mixing length and helium abundance to be constrained. The eccentricity is now the largest source of uncertainty in calculating the masses. Further work is needed to characterise the orbit of AI Phe. Obtaining more binaries with parameters measured to a similar level of precision would allow us to test for relationships between helium

Cinnamon Extract Improves TNF-a Induced Overproduction of Intestinal ApolipoproteinB-48 Lipoproteins

USDA-ARS?s Scientific Manuscript database

TNF-alpha stimulates the overproduction of intestinal apolipoproteins. We evaluated whether a water extract of cinnamon (Cinnulin PF®) improved the dyslipidemia induced by TNF-alpha in Triton WR-1339 treated hamsters, and whether Cinnulin PF® inhibits the TNF-alpha-induced over the secretion of apoB...

Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients

PubMed Central

2016-01-01

Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p < 0.05) but was not significant on other parameters (p > 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients. PMID:27152298

The AIS-5000 parallel processor

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

Schmitt, L.A.; Wilson, S.S.

1988-05-01

The AIS-5000 is a commercially available massively parallel processor which has been designed to operate in an industrial environment. It has fine-grained parallelism with up to 1024 processing elements arranged in a single-instruction multiple-data (SIMD) architecture. The processing elements are arranged in a one-dimensional chain that, for computer vision applications, can be as wide as the image itself. This architecture has superior cost/performance characteristics than two-dimensional mesh-connected systems. The design of the processing elements and their interconnections as well as the software used to program the system allow a wide variety of algorithms and applications to be implemented. In thismore » paper, the overall architecture of the system is described. Various components of the system are discussed, including details of the processing elements, data I/O pathways and parallel memory organization. A virtual two-dimensional model for programming image-based algorithms for the system is presented. This model is supported by the AIS-5000 hardware and software and allows the system to be treated as a full-image-size, two-dimensional, mesh-connected parallel processor. Performance bench marks are given for certain simple and complex functions.« less

Augmentation index (AI) in a dose–response relationship with smoking habits in males

PubMed Central

Tsuru, Tomoko; Adachi, Hisashi; Enomoto, Mika; Fukami, Ako; Kumagai, Eita; Nakamura, Sachiko; Nohara, Yume; Kono, Shoko; Nakao, Erika; Sakaue, Akiko; Morikawa, Nagisa; Fukumoto, Yoshihiro

2016-01-01

Abstract We investigated the relationship between augmentation index (AI) and smoking habits in community-dwelling Japanese. This cross-sectional study enrolled 1926 subjects (769 males and 1157 females) aged 40 to 95 years who underwent a health check-up in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town in Kyushu Island in 2009. The subjects’ medical history, alcohol intake, smoking habit, and current medications for hypertension, dyslipidemia, and diabetes were ascertained by questionnaire. Radial arterial pressure wave analysis was used to obtain AI. We analyzed the data stratified by gender. Age-adjusted means of AI in males showed a clear dose–response relationship in 4 categories of smoking habits (P = 0.010). There was no significant relationship between AI and smoking habits in females (P = 0.127). The significant dose–response relationship (P = 0.036) in males between AI and 4 categories of smoking habits still remained even after adjustment for age, body mass index, systolic blood pressure, estimated glomerular filtration rate, glucose, hypertensive medication, and alcohol intake. The present study demonstrated that AI values were significantly associated with smoking habits in a dose-dependent manner in Japanese males. PMID:28002323

Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

PubMed Central

2009-01-01

Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood. PMID:19534808

Peptides having reduced toxicity that stimulate cholesterol efflux

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

Bielicki, John K.; Johansson, Jan; Danho, Waleed

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

Health Information in French (français)

MedlinePlus

... Translations Bacterial Infections Vaccine Information Statement (VIS) -- Pneumococcal Polysaccharide Vaccine (PPSV): What You Need to Know - English PDF Vaccine Information Statement (VIS) -- Pneumococcal Polysaccharide Vaccine (PPSV): What You Need to Know - français ( ...

Impact of plant-based diet on lipid risk factors for atherosclerosis.

PubMed

Kuchta, Agnieszka; Lebiedzińska, Anna; Fijałkowski, Marcin; Gałąska, Rafał; Kreft, Ewelina; Totoń, Magdalena; Czaja, Kuba; Kozłowska, Anna; Ćwiklińska, Agnieszka; Kortas-Stempak, Barbara; Strzelecki, Adrian; Gliwińska, Anna; Dąbkowski, Kamil; Jankowski, Maciej

2016-01-01

The aim of the study was to investigate the effect of a vegan diet on the serum lipid profile with particular regard to the parameters characterizing the high-density lipoprotein (HDL) fractions in subjects without subclinical atherosclerosis, measured by carotid Doppler ultrasonography. Forty-two 23 to 38 year old subjects (21 omnivores and 21 vegans) participated in the study. Compared to the omnivores, the vegan subjects were characterized by lower parameters of lipid profile: total cholesterol (p < 0.001), low-density lipoprotein (LDL)-cholesterol (p < 0.001), non-HDL-cholesterol (p < 0.001), apolipoprotein B (apoB) (p < 0.001) and phospholipids (p < 0.01). Concentration of HDL-cholesterol was apparently similar between groups. Furthermore, the parameters which characterize HDL particles (con-centration of apolipoproteins AI [apoAI] and AII, HDL-phospholipids, LpAI fraction and pre-b1-HDL fraction) were not significantly different between omnivore and vegan subjects. The apoB/apoAI ratio in vegans was lower than in omnivores (p < 0.01). There was no difference between serum concentration of triacylglycerols between omnivores and vegans. The activity of paraoxonase-1 and 8-iso-prostaglandin F2a concentration were also not different between the study groups. We suggest that a vegan diet may have a beneficial effect on serum lipid profile and cardiovascular protection, but it is not associated with changes in HDL composition.

Design of integrated ship monitoring system using SAR, RADAR, and AIS

NASA Astrophysics Data System (ADS)

Yang, Chan-Su; Kim, Tae-Ho; Hong, Danbee; Ahn, Hyung-Wook

2013-06-01

When we talk about for the ship detection, identification and its classification, we need to go for the wide area of monitoring and it may be possible only through satellite based monitoring approach which monitors and covers coastal as well as the oceanic zone. Synthetic aperture radar (SAR) has been widely used to detect targets of interest with the advantage of the operating capability in all weather and luminance free condition (Margarit and Tabasco, 2011). In EU waters, EMSA(European Maritime Safety Agency) is operating the SafeSeaNet and CleanSeaNet systems which provide the current positions of all ships and oil spill monitoring information in and around EU waters in a single picture to Member States using AIS, LRIT and SAR images. In many countries, a similar system has been developed and the key of the matter is to integrate all available data. This abstract describes the preliminary design concept for an integration system of RADAR, AIS and SAR data for vessel traffic monitoring. SAR sensors are used to acquire image data over large coverage area either through the space borne or airborne platforms in UTC. AIS reports should be also obtained on the same date as of the SAR acquisition for the purpose to perform integration test. Land-based RADAR can provide ships positions detected and tracked in near real time. In general, SAR are used to acquire image data over large coverage area, AIS reports are obtained from ship based transmitter, and RADAR can monitor continuously ships for a limited area. In this study, we developed individual ship monitoring algorithms using RADAR(FMCW and Pulse X-band), AIS and SAR(RADARSAT-2 Full-pol Mode). We conducted field experiments two times for displaying the RADAR, AIS and SAR integration over the Pyeongtaek Port, South Korea.

Mild Oxidation Promotes and Advanced Oxidation Impairs Remodeling of Human High-Density Lipoprotein in vitro

PubMed Central

Gao, Xuan; Jayaraman, Shobini; Gursky, Olga

2008-01-01

SUMMARY High-density lipoproteins (HDL) prevent atherosclerosis by removing cholesterol from macrophages and by exerting anti-oxidant and anti-inflammatory effects. Oxidation is thought to impair HDL functions, yet certain oxidative modifications may be advantageous; thus, mild oxidation reportedly enhances cell cholesterol uptake by HDL whereas extensive oxidation impairs it. To elucidate the underlying energetic and structural basis, we analyzed the effects of copper and hypochlorite (that preferentially oxidize lipids and proteins, respectively) on thermal stability of plasma spherical HDL. Circular dichroism, light scattering, calorimetry, gel electrophoresis and electron microscopy showed that mild oxidation destabilizes HDL and accelerates protein dissociation and lipoprotein fusion, while extensive oxidation inhibits these reactions; this inhibition correlates with massive protein cross-linking and lipolysis. We propose that mild oxidation lowers kinetic barriers for HDL remodeling due to diminished apolipoprotein affinity for lipids resulting from oxidation of methionine and aromatic residues in apolipoproteins A-I and A-II followed by protein cross-linking into dimers and/or trimers. In contrast, advanced oxidation inhibits protein dissociation and HDL fusion due to lipid re-distribution from core to surface upon lipolysis and to massive protein cross-linking. Our results help reconcile the apparent controversy in the studies of oxidized HDL and suggest that mild oxidation may benefit HDL functions. PMID:18190928

Formal verification of AI software

NASA Technical Reports Server (NTRS)

Rushby, John; Whitehurst, R. Alan

1989-01-01

The application of formal verification techniques to Artificial Intelligence (AI) software, particularly expert systems, is investigated. Constraint satisfaction and model inversion are identified as two formal specification paradigms for different classes of expert systems. A formal definition of consistency is developed, and the notion of approximate semantics is introduced. Examples are given of how these ideas can be applied in both declarative and imperative forms.

Preliminary geological investigation of AIS data at Mary Kathleen, Queensland, Australia

NASA Technical Reports Server (NTRS)

Huntington, J. F.; Green, A. A.; Craig, M. D.; Cocks, T. D.

1986-01-01

The Airborne Imaging Spectrometer (AIS) was flown over granitic, volcanic, and calc-silicate terrain around the Mary Kathleen Uranium Mine in Queensland, in a test of its mineralocial mapping capabilities. An analysis strategy and restoration and enhancement techniques were developed to process the 128 band AIS data. A preliminary analysis of one of three AIS flight lines shows that the data contains considerable spectral variation but that it is also contaminated by second-order leakage of radiation from the near-infrared region. This makes the recognition of expected spectral absorption shapes very difficult. The effect appears worst in terrains containing considerable vegetation. Techniques that try to predict this supplementary radiation coupled with the log residual analytical technique show that expected mineral absorption spectra can be derived. The techniques suggest that with additional refinement correction procedures, the Australian AIS data may be revised. Application of the log residual analysis method has proved very successful on the cuprite, Nevada data set, and for highlighting the alunite, linite, and SiOH mineralogy.

Processing the Interspecies Quorum-sensing Signal Autoinducer-2 (AI-2)

PubMed Central

Marques, João C.; Lamosa, Pedro; Russell, Caitlin; Ventura, Rita; Maycock, Christopher; Semmelhack, Martin F.; Miller, Stephen T.; Xavier, Karina B.

2011-01-01

The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior. PMID:21454635

Processing the Interspecies Quorum-sensing Signal Autoinducer-2 (AI-2)

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

J Marques; P Lamosa; C Russell

The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsiblemore » for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.« less

The Human Touch: Practical and Ethical Implications of Putting AI and Robotics to Work for Patients.

PubMed

Banks, Jim

2018-01-01

We live in a time when science fiction can quickly become science fact. Within a generation, the Internet has matured from a technological marvel to a utility, and mobile telephones have redefined how we communicate. Health care, as an industry, is quick to embrace technology, so it is no surprise that the application of programmable robotic systems that can carry out actions automatically and artificial intelligence (AI), e.g., machines that learn, solve problems, and respond to their environment, is being keenly explored.

Regulated efflux of photoreceptor outer segment-derived cholesterol by human RPE cells.

PubMed

Storti, Federica; Raphael, Gabriele; Griesser, Vera; Klee, Katrin; Drawnel, Faye; Willburger, Carolin; Scholz, Rebecca; Langmann, Thomas; von Eckardstein, Arnold; Fingerle, Jürgen; Grimm, Christian; Maugeais, Cyrille

2017-12-01

Genetic studies have linked age-related macular degeneration (AMD) to genes involved in high-density lipoprotein (HDL) metabolism, including ATP-binding cassette transporter A1 (ABCA1). The retinal pigment epithelium (RPE) handles large amounts of lipids, among others cholesterol, partially derived from internalized photoreceptor outer segments (OS) and lipids physiologically accumulate in the aging eye. To analyze the potential function of ABCA1 in the eye, we measured cholesterol efflux, the first step of HDL generation, in RPE cells. We show the expression of selected genes related to HDL metabolism in mouse and human eyecups as well as in ARPE-19 and human primary RPE cells. Immunofluorescence staining revealed localization of ABCA1 on both sides of polarized RPE cells. This was functionally confirmed by directional efflux to apolipoprotein AI (ApoA-I) of 3 H-labeled cholesterol given to the cells via serum or via OS. ABCA1 expression and activity was modulated using a liver-X-receptor (LXR) agonist and an ABCA1 neutralizing antibody, demonstrating that the efflux was ABCA1-dependent. We concluded that the ABCA1-mediated lipid efflux pathway, and hence HDL biosynthesis, is functional in RPE cells towards both the basal (choroidal) and apical (subretinal) space. Impaired activity of the pathway might cause age-related perturbations of lipid homeostasis in the outer retina and thus may contribute to disease development and/or progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Artificial intelligence in medicine: humans need not apply?

PubMed

Diprose, William; Buist, Nicholas

2016-05-06

Artificial intelligence (AI) is a rapidly growing field with a wide range of applications. Driven by economic constraints and the potential to reduce human error, we believe that over the coming years AI will perform a significant amount of the diagnostic and treatment decision-making traditionally performed by the doctor. Humans would continue to be an important part of healthcare delivery, but in many situations, less expensive fit-for-purpose healthcare workers could be trained to 'fill the gaps' where AI are less capable. As a result, the role of the doctor as an expensive problem-solver would become redundant.

Emerging trends in geospatial artificial intelligence (geoAI): potential applications for environmental epidemiology.

PubMed

VoPham, Trang; Hart, Jaime E; Laden, Francine; Chiang, Yao-Yi

2018-04-17

Geospatial artificial intelligence (geoAI) is an emerging scientific discipline that combines innovations in spatial science, artificial intelligence methods in machine learning (e.g., deep learning), data mining, and high-performance computing to extract knowledge from spatial big data. In environmental epidemiology, exposure modeling is a commonly used approach to conduct exposure assessment to determine the distribution of exposures in study populations. geoAI technologies provide important advantages for exposure modeling in environmental epidemiology, including the ability to incorporate large amounts of big spatial and temporal data in a variety of formats; computational efficiency; flexibility in algorithms and workflows to accommodate relevant characteristics of spatial (environmental) processes including spatial nonstationarity; and scalability to model other environmental exposures across different geographic areas. The objectives of this commentary are to provide an overview of key concepts surrounding the evolving and interdisciplinary field of geoAI including spatial data science, machine learning, deep learning, and data mining; recent geoAI applications in research; and potential future directions for geoAI in environmental epidemiology.

The genes for apolipoprotein all (APOA2) and the Duffy blood group (FY) are linked on chromosome 1 in man.

PubMed

Rogne, S; Myklebost, O; Høyheim, B; Olaisen, B; Gedde-Dahl, T

1989-02-01

We have cloned a cDNA probe for human apolipoprotein AII and used it to analyze linkage relationships on chromosome 1. We found no recombinations between APOA2 and the gene coding for the Duffy blood group antigens (FY) in the 19 meioses examined. Our maximal lod score is 4.2 at zero recombination rate. K. Berg (1987, Cytogenet. Cell Genet. 46:579) found a maximal score of 2.5 at recombination fraction 0.14 in 54 meioses. When results from both studies are combined, the most likely distance between FY and APOA2 is about 10% recombination with a combined lod score of 5.6 for both sexes.

Apolipoprotein E in Temporal Lobe Epilepsy: A Case-Control Study

PubMed Central

Kumar, Amit; Tripathi, Manjari; Pandey, Ravindra M.; Ramakrishnan, Lakshmy; Srinivas, M.; Luthra, Kalpana

2006-01-01

Purpose: To investigate the relationship of apolipoprotein E (apoE) genotype, plasma levels of apoE and lipids in temporal lobe epilepsy (TLE) patients in Asian Indians. Status of plasma levels of Apo E in epilepsy patients has not been reported till date. Methods: ApoE gene polymorphism was analyzed in 58 patients with temporal lobe epilepsy (TLE) and 57 age and sex approximated controls using Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Levels of plasma apoE and lipids were measured using ELISA and enzymatic kits respectively. Results: The distribution of ApoE genotype in epilepsy patients and controls was comparable. Higher levels of plasma ApoE were observed in TLE patients as compared to controls (p = 0.0001). Individuals with plasma levels of apoE > 190 mg/L were at 20 times higher odds (95%CI = 2.46–163.34, p = 0.005), while those with levels of apoE between 150–190 mg/L were at 4.9 times higher odds (95% CI = 1.85–13.9, p = 0.001), to develop TLE. Conclusions: We have observed for the first time, high levels of plasma apoE in epilepsy patients. The findings of this case-control study suggest that apolipoprotein E may play an important role in epilepsy. PMID:17264404

Effects of pyrophosphate delivery in a peritoneal dialysis solution on bone tissue of apolipoprotein-E knockout mice with chronic kidney disease.

PubMed

Barreto, Fellype C; de Oliveira, Rodrigo B; Benchitrit, Joyce; Louvet, Loïc; Rezg, Raja; Poirot, Sabrina; Jorgetti, Vanda; Drüeke, Tilman B; Riser, Bruce L; Massy, Ziad A

2014-11-01

Vascular calcification (VC) is a risk factor for cardiovascular mortality in the setting of chronic kidney disease (CKD). Pyrophosphate (PPi), an endogenous molecule that inhibits hydroxyapatite crystal formation, has been shown to prevent the development of VC in animal models of CKD. However, the possibility of harmful effects of exogenous administration of PPi on bone requires further investigation. To this end, we examined by histomorphometry the bone of CKD mice after intraperitoneal PPi administration. After CKD creation or sham surgery, 10-week-old female apolipoprotein-E knockout (apoE(-/-)) mice were randomized to one non-CKD group or 4 CKD groups (n = 10-35/group) treated with placebo or three distinct doses of PPi, and fed with standard diet. Eight weeks later, the animals were killed. Serum and femurs were sampled. Femurs were processed for bone histomorphometry. Placebo-treated CKD mice had significantly higher values of osteoid volume, osteoid surface and bone formation rate than sham-placebo mice with normal renal function. Slightly higher osteoid values were observed in CKD mice in response to very low PPi dose (OV/BV, O.Th and ObS/BS) and, for one parameter measured, to high PPi dose (O.Th), compared to placebo-treated CKD mice. Treatment with PPi did not modify any other structural parameters. Mineral apposition rates, and other parameters of bone formation and resorption were not significantly different among the treated animal groups or control CKD placebo group. In conclusion, PPi does not appear to be deleterious to bone tissue in apoE(-/-) mice with CKD, although a possible stimulatory PPi effect on osteoid formation may be worth further investigation.

Greater enrichment of triacylglycerol-rich lipoproteins with apolipoproteins E and C-III after meals rich in saturated fatty acids than after meals rich in unsaturated fatty acids.

PubMed

Jackson, Kim G; Wolstencroft, Emma J; Bateman, Paul A; Yaqoob, Parveen; Williams, Christine M

2005-01-01

Although there is considerable interest in the postprandial events involved in the absorption of dietary fats and the subsequent metabolism of diet-derived triacylglycerol-rich lipoproteins, little is known about the effects of meal fatty acids on the composition of these particles. We examined the effect of meal fatty acids on the lipid and apolipoprotein contents of triacylglycerol-rich lipoproteins. Ten normolipidemic men received in random order a mixed meal containing 50 g of a mixture of palm oil and cocoa butter [rich in saturated fatty acids (SFAs)], safflower oil [n-6 polyunsaturated fatty acids (PUFAs)], or olive oil [monounsaturated fatty acids (MUFAs)] on 3 occasions. Fasting and postprandial apolipoproteins B-48, B-100, E, C-II, and C-III and lipids (triacylglycerol and cholesterol) were measured in plasma fractions with Svedberg flotation rates (S(f)) >400, S(f) 60-400, and S(f) 20-60. Calculation of the composition of the triacylglycerol-rich lipoproteins (expressed per mole of apolipoprotein B) showed notable differences in the lipid and apolipoprotein contents of the SFA-enriched particles in the S(f) > 400 and S(f) 60-400 fractions. After the SFA meal, triacylglycerol-rich lipoproteins in these fractions showed significantly greater amounts of triacylglycerol and of apolipoproteins C-II (S(f) 60-400 fraction only), C-III, and E than were found after the MUFA meal (P < 0.02) and more cholesterol, apolipoprotein C-III (S(f) > 400 fraction only), and apolipoprotein E than after the PUFA meal (P < 0.02). Differences in the composition of S(f) > 400 and S(f) 60-400 triacylglycerol-rich lipoproteins formed after saturated compared with unsaturated fatty acid-rich meals may explain differences in the metabolic handling of dietary fats.

Postprandial triglyceride-rich lipoproteins promote lipid accumulation and apolipoprotein B-48 receptor transcriptional activity in human circulating and murine bone marrow neutrophils in a fatty acid-dependent manner.

PubMed

Ortega-Gómez, Almudena; Varela, Lourdes M; López, Sergio; Montserrat de la Paz, Sergio; Sánchez, Rosario; Muriana, Francisco J G; Bermúdez, Beatriz; Abia, Rocío

2017-09-01

Postprandial triglyceride-rich lipoproteins (TRLs) promote atherosclerosis. Recent research points the bone marrow (BM) as a primary site in atherosclerosis. We elucidated how the acute administration of monounsaturated fatty acids (MUFAs) MUFAs, omega-3 polyunsaturated fatty acids (PUFAs) PUFAs and saturated fatty acids (SFAs) affects human circulating and murine BM neutrophil lipid accumulation and functionality. Postprandial hypertriglyceridemia was induced in healthy subjects and Apoe -/- mice by the acute administration of dietary fats enriched in MUFAs, PUFAs, or SFAs. Postprandial hypertriglyceridemia increased apolipoprotein-B48 receptor (ApoB48R) transcriptional activity that was linearly correlated with intracellular triglycerides (TGs) TGs accumulation in human circulating and murine BM neutrophils. MUFA and omega-3 PUFAs attenuated ApoB48R gene expression and intracellular TG accumulation compared to SFAs. TRLs induced apoB48R-dependent TG accumulation in human neutrophils ex vivo. Murine BM neutrophils showed a decrease in surface L-selectin and an increase in TNF-α and IL-1β mRNA expressions only after SFAs administration. TRLs enriched in SFAs induced BM neutrophil degranulation ex vivo suggesting cell priming/activation. Postprandial TRLs disrupts the normal biology and function of circulating and BM neutrophils. MUFA- and omega-3 PUFA-rich dietary fats such as virgin olive oil or fish oil has the potential to prevent excessive neutrophil lipid accumulation and activation by targeting the fatty acid composition of TRLs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The AI Bus architecture for distributed knowledge-based systems

NASA Technical Reports Server (NTRS)

Schultz, Roger D.; Stobie, Iain

1991-01-01

The AI Bus architecture is layered, distributed object oriented framework developed to support the requirements of advanced technology programs for an order of magnitude improvement in software costs. The consequent need for highly autonomous computer systems, adaptable to new technology advances over a long lifespan, led to the design of an open architecture and toolbox for building large scale, robust, production quality systems. The AI Bus accommodates a mix of knowledge based and conventional components, running on heterogeneous, distributed real world and testbed environment. The concepts and design is described of the AI Bus architecture and its current implementation status as a Unix C++ library or reusable objects. Each high level semiautonomous agent process consists of a number of knowledge sources together with interagent communication mechanisms based on shared blackboards and message passing acquaintances. Standard interfaces and protocols are followed for combining and validating subsystems. Dynamic probes or demons provide an event driven means for providing active objects with shared access to resources, and each other, while not violating their security.

Influence of depleted uranium on hepatic cholesterol metabolism in apolipoprotein E-deficient mice.

PubMed

Souidi, M; Racine, R; Grandcolas, L; Grison, S; Stefani, J; Gourmelon, P; Lestaevel, P

2012-04-01

Depleted uranium (DU) is uranium with a lower content of the fissile isotope U-235 than natural uranium. It is a radioelement and a waste product from the enrichment process of natural uranium. Because of its very high density, it is used in the civil industry and for military purposes. DU exposure can affect many vital systems in the human body, because in addition to being weakly radioactive, uranium is a toxic metal. It should be emphasized that, to be exposed to radiation from DU, you have to eat, drink, or breathe it, or get it on your skin. This particular study is focusing on the health effects of DU for the cholesterol metabolism. Previous studies on the same issue have shown that the cholesterol metabolism was modulated at molecular level in the liver of laboratory rodents contaminated for nine months with DU. However, this modulation was not correlated with some effects at organs or body levels. It was therefore decided to use a "pathological model" such as hypercholesterolemic apolipoprotein E-deficient laboratory mice in order to try to clarify the situation. The purpose of the present study is to assess the effects of a chronic ingestion (during 3 months) of a low level DU-supplemented water (20 mg L(-1)) on the above mentioned mice in order to determine a possible contamination effect. Afterwards the cholesterol metabolism was studied in the liver especially focused on the gene expressions of cholesterol-catabolising enzymes (CYP7A1, CYP27A1 and CYP7B1), as well as those of associated nuclear receptors (LXRα, FXR, PPARα, and SREBP 2). In addition, mRNA levels of other enzymes of interest were measured (ACAT 2, as well as HMGCoA Reductase and HMGCoA Synthase). The gene expression study was completed with SRB1 and LDLr, apolipoproteins A1 and B and membrane transporters ABC A1, ABC G5. The major effect induced by a low level of DU contamination in apo-E deficient mice was a decrease in hepatic gene expression of the enzyme CYP7B1 (-23%) and nuclear

Virulence of Trypanosoma cruzi in Açai ( Euterpe oleraceae Martius) Pulp following Mild Heat Treatment.

PubMed

Barbosa, Rodrigo Labello; Pereira, Karen Signori; Dias, Viviane Liotti; Schmidt, Flávio Luis; Alves, Delma Pegolo; Guaraldo, Ana Maria Aparecida; Passos, Luiz Augusto Corrêa

2016-10-01

Outbreaks of acute Chagas disease (ACD) in northern Brazil can be caused by the ingestion of unprocessed açai pulp contaminated with Trypanosoma cruzi . The aim of this study was to determine the minimum thermal process required to inactivate T. cruzi in açai pulp. Trypomastigotes (100,000) of T. cruzi Y strain were added to 0.15 M NaCl or açai pulp and continuously mixed while being heat treated at 37 to 49°C for up to 1 h. When necessary, parasites were separated from açai pulp by forced sieving. Inocula were administrated intraperitoneally in inbred immunodeficient C.B-17-Prkdc scid /Pas Unib mice, and the recipients were monitored for parasitemia and mortality. Mice received prophylactic antibiotic therapy by using cephalexin to prevent bacterial infection from the açai pulp. T. cruzi retained its virulence in 0.15 M NaCl and açai pulp at 44 ± 0.1°C for 10 min and at 43 ± 0.1°C for 20 min, respectively, causing ACD and death in mice up to 24 days after infection. Incubation of açai pulp inoculum above 43°C for 20 min neutralized T. cruzi virulence, thereby preventing ACD and death in murine recipients. The heating of açai pulp above 43°C for 20 min is a practical and effective measure to prevent foodborne ACD caused by T. cruzi .

Dry eyes and AIs: If you don't ask you won't find out.

PubMed

Inglis, Holly; Boyle, Frances M; Friedlander, Michael L; Watson, Stephanie L

2015-12-01

Our objective was to investigate the hypothesis that women on adjuvant aromatase inhibitors (AIs) for treatment of breast cancer have a higher prevalence of dry eye syndrome (DES) compared with controls. Exposure and control groups were recruited. A cross sectional questionnaire-based study was performed. Demographic data and medical histories were collected. The presence of dry eye syndrome was determined by the ocular surface disease index (OSDI). The Functional Assessment of Cancer Treatment - Endocrine Subscale (FACT-ES) was performed to investigate correlations with other side effects of AIs. 93 exposure group and 100 control group questionnaires were included. The groups were similar in all demographic variables. The prevalence of dry eye syndrome was 35% (exposure) and 18% (control) (p < 0.01, OR 2.5). AIs were the only factor associated with dry eyes. The OSDI score was negatively correlated with the total FACT-ES score and positively correlated with duration of treatment. Our study is the first to use a validated questionnaire to assess for DES in this population. DES is significantly more prevalent in women on AIs compared with controls. This is a newly emerging, and easily treated side effect of AIs. Self-reporting of dry eye symptoms underestimates the prevalence of DES with AIs. We recommend routine screening of patients on AIs with the OSDI with the aim of improving patient quality of life and possibly adherence. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intestinal-fatty acid binding protein and lipid transport in human intestinal epithelial cells

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

Montoudis, Alain; Delvin, Edgard; Canadian Institute of Health Research, Group of the Functional Development and Physiopathology of the Digestive Tract, and Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, Que., Canada J1H 5N4

2006-01-06

Intestinal-fatty acid binding protein (I-FABP) is a 14-15 kDa cytoplasmic molecule highly expressed in the enterocyte. Although different functions have been proposed for various FABP family members, the specific function of I-FABP in human intestine remains unclear. Here, we studied the role of I-FABP in molecularly modified normal human intestinal epithelial cells (HIEC-6). cDNA transfection resulted in 90-fold I-FABP overexpression compared to cells treated with empty pQCXIP vector. The high-resolution immunogold technique revealed labeling mainly in the cytosol and confirmed the marked phenotype abundance of I-FABP in cDNA transfected cells. I-FABP overexpression was not associated with alterations in cell proliferationmore » and viability. Studies using these transfected cells cultured with [{sup 14}C]oleic acid did not reveal higher efficiency in de novo synthesis or secretion of triglycerides, phospholipids, and cholesteryl esters compared to cells treated with empty pQCXIP vector only. Similarly, the incubation with [{sup 35}S]methionine did not disclose a superiority in the biogenesis of apolipoproteins (apo) A-I, A-IV, B-48, and B-100. Finally, cells transfected with I-FABP did not exhibit an increased production of chylomicrons, VLDL, LDL, and HDL. Our observations establish that I-FABP overexpression in normal HIEC-6 is not related to cell proliferation, lipid esterification, apo synthesis, and lipoprotein assembly, and, therefore, exclude its role in intestinal fat transport.« less

Regulation of Yersina pestis Virulence by AI-2 Mediated Quorum Sensing

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

Segelke, B; Hok, S; Lao, V

The proposed research was motivated by an interest in understanding Y. pestis virulence mechanisms and bacteria cell-cell communication. It is expected that a greater understanding of virulence mechanisms will ultimately lead to biothreat countermeasures and novel therapeutics. Y. pestis is the etiological agent of plague, the most devastating disease in human history. Y. pestis infection has a high mortality rate and a short incubation before mortality. There is no widely available and effective vaccine for Y. pestis and multi-drug resistant strains are emerging. Y. pestis is a recognized biothreat agent based on the wide distribution of the bacteria in researchmore » laboratories around the world and on the knowledge that methods exist to produce and aerosolize large amounts of bacteria. We hypothesized that cell-cell communication via signaling molecules, or quorum sensing, by Y. pestis is important for the regulation of virulence factor gene expression during host invasion, though a causative link had never been established. Quorum sensing is a mode of intercellular communication which enables orchestration of gene expression for many bacteria as a function of population density and available evidence suggests there may be a link between quorum sensing and regulation of Y. pesits virulence. Several pathogenic bacteria have been shown to regulate expression of virulence factor genes, including genes encoding type III secretion, via quorum sensing. The Y. pestis genome encodes several cell-cell signaling pathways and the interaction of at least three of these are thought to be involved in one or more modes of host invasion. Furthermore, Y. pestis gene expression array studies carried out at LLNL have established a correlation between expression of known virulence factors and genes involved in processing of the AI-2 quorum sensing signal. This was a basic research project that was intended to provide new insights into bacterial intercellular communication and

The human apolipoprotein AV gene is regulated by peroxisome proliferator-activated receptor-alpha and contains a novel farnesoid X-activated receptor response element.

PubMed

Prieur, Xavier; Coste, Herve; Rodriguez, Joan C

2003-07-11

The newly identified apolipoprotein AV (apoAV) gene is a key player in determining plasma triglyceride concentrations. Because hypertriglyceridemia is a major independent risk factor in coronary artery disease, the understanding of the regulation of the expression of this gene is of considerable importance. We presently characterize the structure, the transcription start site, and the promoter of the human apoAV gene. Since the peroxisome proliferator-activated receptor-alpha (PPARalpha) and the farnesoid X-activated receptor (FXR) have been shown to modulate the expression of genes involved in triglyceride metabolism, we evaluated the potential role of these nuclear receptors in the regulation of apoAV transcription. Bile acids and FXR induced the apoAV gene promoter activity. 5'-Deletion, mutagenesis, and gel shift analysis identified a heretofore unknown element at positions -103/-84 consisting of an inverted repeat of two consensus receptor-binding hexads separated by 8 nucleotides (IR8), which was required for the response to bile acid-activated FXR. The isolated IR8 element conferred FXR responsiveness on a heterologous promoter. On the other hand, in apoAV-expressing human hepatic Hep3B cells, transfection of PPARalpha specifically enhanced apoAV promoter activity. By deletion, site-directed mutagenesis, and binding analysis, a PPARalpha response element located 271 bp upstream of the transcription start site was identified. Finally, treatment with a specific PPARalpha activator led to a significant induction of apoAV mRNA expression in hepatocytes. The identification of apoAV as a PPARalpha target gene has major implications with respect to mechanisms whereby pharmacological PPARalpha agonists may exert their beneficial hypotriglyceridemic actions.

Influence of apolipoprotein A-V on the metabolic fate of triacylglycerol

PubMed Central

Sharma, Vineeta; Forte, Trudy M.; Ryan, Robert O.

2013-01-01

Purpose of review Apolipoprotein (apo) A-V functions to modulate intracellular and extracellular triacylglycerol metabolism. The present review addresses molecular mechanisms underlying these effects. The relevance of apoA-V to human disease conditions is illustrated by the strong correlation between single nucleotide polymorphisms in APOA5, elevated plasma triacylglycerol and dyslipidemic disease. Recent findings Despite undergoing processing for secretion from hepatocytes, a portion of apoA-V escapes this destiny and accumulates as a component of cytosolic lipid droplets. Expression of recombinant apoA-V in hepatocarcinoma cells results in increased lipid droplet size and number at the expense of triacylglycerol secretion. ApoA-V modulates atherosclerosis in hypercholesterolemic apoE null mice. ApoE null/human apoA-V transgenic mice had reduced levels of triacylglycerol and cholesterol in plasma along with decreased aortic lesion size. Summary ApoA-V modulates triacylglycerol metabolic fate. Following its synthesis, apoA-V enters the endoplasmic reticulum and associates with membrane defects created by triacylglycerol accumulation. Association of apoA-V with endoplasmic reticulum membrane defects promotes nascent lipid droplets budding toward the cytosol. Despite its low concentration in plasma (~150 ng/ml), apoA-V modulates lipoprotein metabolism by binding to glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. This interaction effectively localizes triacylglycerol-rich lipoproteins in the vicinity of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1’s other ligand, lipoprotein lipase. PMID:23241513

Google Earth Visualizations of the Marine Automatic Identification System (AIS): Monitoring Ship Traffic in National Marine Sanctuaries

NASA Astrophysics Data System (ADS)

Schwehr, K.; Hatch, L.; Thompson, M.; Wiley, D.

2007-12-01

The Automatic Identification System (AIS) is a new technology that provides ship position reports with location, time, and identity information without human intervention from ships carrying the transponders to any receiver listening to the broadcasts. In collaboration with the USCG's Research and Development Center, NOAA's Stellwagen Bank National Marine Sanctuary (SBNMS) has installed 3 AIS receivers around Massachusetts Bay to monitor ship traffic transiting the sanctuary and surrounding waters. The SBNMS and the USCG also worked together propose the shifting the shipping lanes (termed the traffic separation scheme; TSS) that transit the sanctuary slightly to the north to reduce the probability of ship strikes of whales that frequent the sanctuary. Following approval by the United Nation's International Maritime Organization, AIS provided a means for NOAA to assess changes in the distribution of shipping traffic caused by formal change in the TSS effective July 1, 2007. However, there was no easy way to visualize this type of time series data. We have created a software package called noaadata-py to process the AIS ship reports and produce KML files for viewing in Google Earth. Ship tracks can be shown changing over time to allow the viewer to feel the motion of traffic through the sanctuary. The ship tracks can also be gridded to create ship traffic density reports for specified periods of time. The density is displayed as map draped on the sea surface or as vertical histogram columns. Additional visualizations such as bathymetry images, S57 nautical charts, and USCG Marine Information for Safety and Law Enforcement (MISLE) can be combined with the ship traffic visualizations to give a more complete picture of the maritime environment. AIS traffic analyses have the potential to give managers throughout NOAA's National Marine Sanctuaries an improved ability to assess the impacts of ship traffic on the marine resources they seek to protect. Viewing ship traffic

Artificial Intelligence (AI), Operations Research (OR), and Decision Support Systems (DSS): A conceptual framework

NASA Technical Reports Server (NTRS)

Parnell, Gregory S.; Rowell, William F.; Valusek, John R.

1987-01-01

In recent years there has been increasing interest in applying the computer based problem solving techniques of Artificial Intelligence (AI), Operations Research (OR), and Decision Support Systems (DSS) to analyze extremely complex problems. A conceptual framework is developed for successfully integrating these three techniques. First, the fields of AI, OR, and DSS are defined and the relationships among the three fields are explored. Next, a comprehensive adaptive design methodology for AI and OR modeling within the context of a DSS is described. These observations are made: (1) the solution of extremely complex knowledge problems with ill-defined, changing requirements can benefit greatly from the use of the adaptive design process, (2) the field of DSS provides the focus on the decision making process essential for tailoring solutions to these complex problems, (3) the characteristics of AI, OR, and DSS tools appears to be converging rapidly, and (4) there is a growing need for an interdisciplinary AI/OR/DSS education.

In vitro approaches to assess the effects of açai (Euterpe oleracea) digestion on polyphenol availability and the subsequent impact on the faecal microbiota.

PubMed

Alqurashi, Randah M; Alarifi, Sehad N; Walton, Gemma E; Costabile, Adele F; Rowland, Ian R; Commane, Daniel M

2017-11-01

A considerable proportion of dietary plant-polyphenols reach the colon intact; determining the effects of these compounds on colon-health is of interest. We hypothesise that both fibre and plant polyphenols present in açai (Euterpe oleracea) provide prebiotic and anti-genotoxic benefits in the colon. We investigated this hypothesis using a simulated in vitro gastrointestinal digestion of açai pulp, and a subsequent pH-controlled, anaerobic, batch-culture fermentation model reflective of the distal region of the human large intestine. Following in vitro digestion, 49.8% of the total initial polyphenols were available. In mixed-culture fermentations with faecal inoculate, the digested açai pulp precipitated reductions in the numbers of both the Bacteroides-Prevotella spp. and the Clostridium-histolyticum groups, and increased the short-chain fatty acids produced compared to the negative control. The samples retained significant anti-oxidant and anti-genotoxic potential through digestion and fermentation. Dietary intervention studies are needed to prove that consuming açai is beneficial to gut health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Decoding the network of Trypanosoma brucei proteins that determines sensitivity to apolipoprotein-L1

PubMed Central

MacLeod, Annette

2018-01-01

In contrast to Trypanosoma brucei gambiense and T. b. rhodesiense (the causative agents of human African trypanosomiasis), T. b. brucei is lysed by apolipoprotein-L1 (apoL1)-containing human serum trypanolytic factors (TLF), rendering it non-infectious to humans. While the mechanisms of TLF1 uptake, apoL1 membrane integration, and T. b. gambiense and T. b. rhodesiense apoL1-resistance have been extensively characterised, our understanding of the range of factors that drive apoL1 action in T. b. brucei is limited. Selecting our bloodstream-form T. b. brucei RNAi library with recombinant apoL1 identified an array of factors that supports the trypanocidal action of apoL1, including six putative ubiquitin modifiers and several proteins putatively involved in membrane trafficking; we also identified the known apoL1 sensitivity determinants, TbKIFC1 and the V-ATPase. Most prominent amongst the novel apoL1 sensitivity determinants was a putative ubiquitin ligase. Intriguingly, while loss of this ubiquitin ligase reduces parasite sensitivity to apoL1, its loss enhances parasite sensitivity to TLF1-dominated normal human serum, indicating that free and TLF1-bound apoL1 have contrasting modes-of-action. Indeed, loss of the known human serum sensitivity determinants, p67 (lysosomal associated membrane protein) and the cathepsin-L regulator, ‘inhibitor of cysteine peptidase’, had no effect on sensitivity to free apoL1. Our findings highlight a complex network of proteins that influences apoL1 action, with implications for our understanding of the anti-trypanosomal action of human serum. PMID:29346416

Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B

PubMed Central

Crooke, Stanley T; Geary, Richard S

2013-01-01

Mipomersen is a second generation antisense oligonucleotide that targets apolipoprotein B. It has been studied thoroughly in clinical trials (more than 800 subjects), including four randomized double-blind placebo controlled phase 3 studies involving 391 patients, and is in registration for the treatment of severe hypercholesterolaemia. The pharmacokinetic and pharmacodynamic properties of mipomersen are well characterized. Mipomersen is rapidly and extensively absorbed after subcutaneous administration and has an elimination half-life of approximately 30 days across species. It is cleared by nuclease metabolism and renal excretion of the metabolites. Mipomersen reduces all apolipoprotein B containing atherogenic particles and displays dose dependent reductions between 50–400 mg week−1, both as a single agent and in the presence of maximal lipid lowering therapy. No drug–drug interactions have been identified. Mipomersen is a representative of second generation antisense drugs, all of which have similar properties, and is thus representative of the behaviour of the class of drugs. PMID:23013161

Apolipoproteins regulate the kinetics of endothelial lipase-mediated hydrolysis of phospholipids in reconstituted high-density lipoproteins.

PubMed

Caiazza, Daniela; Jahangiri, Anisa; Rader, Daniel J; Marchadier, Dawn; Rye, Kerry-Anne

2004-09-21

Endothelial lipase (EL) is a newly identified member of the triglyceride lipase gene family that hydrolyzes high-density lipoprotein (HDL) phospholipids. This study investigates the ability of the major apolipoproteins of rHDL to regulate the kinetics of EL-mediated phospholipid hydrolysis in well-characterized, homogeneous preparations of spherical rHDL. The rHDL contained either apoA-I as the only apolipoprotein, (A-I)rHDL, apoA-II as the only apolipoprotein, (A-II)rHDL, or apoA-I as well as apoA-II, (A-I/A-II)rHDL. The rHDL were comparable in terms of size and lipid composition and contained cholesteryl esters (CE) as their sole core lipid. Phospholipid hydrolysis was quantitated as the mass of nonesterified fatty acids (NEFA) released from the rHDL during incubation with EL. The V(max) of phospholipid hydrolysis for (A-I/A-II)rHDL [391.9 +/- 12.9 nmol of NEFA formed (mL of EL)(-1) h(-1)] was greater than (A-I)rHDL [152.8 +/- 4.7 nmol of NEFA formed (mL of EL)(-1) h(-1)]. The energy of activation (E(a)) for the hydrolysis reactions was calculated to be 52.1 and 34.8 kJ mol(-1) for (A-I)rHDL and (A-I/A-II)rHDL, respectively. Minimal phospholipid hydrolysis was observed for the (A-II)rHDL. Kinetic analysis showed that EL has a higher affinity for the phospholipids in (A-I)rHDL [K(m)(app) = 0.10 +/- 0.01 mM] than in (A-I/A-II)rHDL [K(m)(app) = 0.27 +/- 0.03 mM]. Furthermore, (A-I)rHDL is a competitive inhibitor of the EL-mediated phospholipid hydrolysis of (A-I/A-II)rHDL. These results establish that apolipoproteins are major determinants of the kinetics of EL-mediated phospholipid hydrolysis in rHDL.

Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2-THRIVE Study

PubMed Central

Hopewell, Jemma C.; Hill, Michael R.; Marcovina, Santica; Valdes-Marquez, Elsa; Haynes, Richard; Offer, Alison; Pedersen, Terje R.; Baigent, Colin; Collins, Rory; Landray, Martin; Armitage, Jane

2018-01-01

Background: Genetic studies have shown lipoprotein(a) (Lp[a]) to be an important causal risk factor for coronary disease. Apolipoprotein(a) isoform size is the chief determinant of Lp(a) levels, but its impact on the benefits of therapies that lower Lp(a) remains unclear. Methods: HPS2-THRIVE (Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events) is a randomized trial of niacin–laropiprant versus placebo on a background of simvastatin therapy. Plasma Lp(a) levels at baseline and 1 year post-randomization were measured in 3978 participants from the United Kingdom and China. Apolipoprotein(a) isoform size, estimated by the number of kringle IV domains, was measured by agarose gel electrophoresis and the predominantly expressed isoform identified. Results: Allocation to niacin–laropiprant reduced mean Lp(a) by 12 (SE, 1) nmol/L overall and 34 (6) nmol/L in the top quintile by baseline Lp(a) level (Lp[a] ≥128 nmol/L). The mean proportional reduction in Lp(a) with niacin–laropiprant was 31% but varied strongly with predominant apolipoprotein(a) isoform size (PTrend=4×10−29) and was only 18% in the quintile with the highest baseline Lp(a) level and low isoform size. Estimates from genetic studies suggest that these Lp(a) reductions during the short term of the trial might yield proportional reductions in coronary risk of ≈2% overall and 6% in the top quintile by Lp(a) levels. Conclusions: Proportional reductions in Lp(a) were dependent on apolipoprotein(a) isoform size. Taking this into account, the likely benefits of niacin–laropiprant on coronary risk through Lp(a) lowering are small. Novel therapies that reduce high Lp(a) levels by at least 80 nmol/L (≈40%) may be needed to produce worthwhile benefits in people at the highest risk because of Lp(a). Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00461630. PMID:29449329

The intravenous injection of oxidized LDL- or Apolipoprotein B100 – Coupled splenocytes promotes Th1 polarization in wildtype and Apolipoprotein E – Deficient mice

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

Steinmetz, Martin, E-mail: martin.steinmetz@ukb.uni-bonn.de; Internal Medicine II, University Hospital Bonn, 53105 Bonn; Ponnuswamy, Padmapriya

Background: Th1 responses in atherosclerosis are mainly associated with the aggravation of atherosclerotic plaques, whereas Th2 responses lead to a less pronounced disease in mouse models. The fixation of antigens on cells by means of ethylene carbodiimide (ECDI), and subsequent injection of these antigen-coupled splenocytes (Ag-SP) to induce tolerance against the attached antigens, has been successfully used to treat murine type 1 diabetes or encephalomyelitis in. We analyzed this approach in a mouse model for atherosclerosis. Methods and results: OTII-transgenic mice that were treated with a single dose of 5 × 10{sup 7} OVA-coupled splenocytes (OVA-SP), had decreased splenocyte proliferation, and lowermore » IFNγ production in vitro upon antigen recall. However, in vivo CD4 cell activation was increased. To try lipoprotein-derived, “atherosclerosis-associated” antigens, we first tested human oxidized LDL. In wild type mice, an increase of IFNγ production upon in vitro recall was detected in the oxLDL-SP group. In Apolipoprotein E − deficient (ApoE−/−) mice that received oxLDL-SP every 5 weeks for 20 weeks, we did not find any difference of atherosclerotic plaque burden, but again increased IFNγ production. To overcome xenogenous limitations, we then examined the effects of mouse Apolipoprotein B100 peptides P3 and P6. ApoB100-SP treatment again promoted a more IFNγ pronounced response upon in vitro recall. Flow cytometry analysis of cytokine secreting spleen cells revealed CD4 positive T cells to be mainly the source for IFNγ. In ApoE−/− mice that were administered ApoB100-SP during 20 weeks, the atherosclerotic plaque burden in aortic roots as well as total aorta was unchanged compared to PBS treated controls. Splenocyte proliferation upon antigen recall was not significantly altered in ApoB100-SP treated ApoE−/− mice. Conclusion: Although we did not observe a relevant anti-atherosclerotic benefit, the treatment with antigen

A structural model for apolipoprotein C-II amyloid fibrils: experimental characterization and molecular dynamics simulations.

PubMed

Teoh, Chai Lean; Pham, Chi L L; Todorova, Nevena; Hung, Andrew; Lincoln, Craig N; Lees, Emma; Lam, Yuen Han; Binger, Katrina J; Thomson, Neil H; Radford, Sheena E; Smith, Trevor A; Müller, Shirley A; Engel, Andreas; Griffin, Michael D W; Yarovsky, Irene; Gooley, Paul R; Howlett, Geoffrey J

2011-02-04

The self-assembly of specific proteins to form insoluble amyloid fibrils is a characteristic feature of a number of age-related and debilitating diseases. Lipid-free human apolipoprotein C-II (apoC-II) forms characteristic amyloid fibrils and is one of several apolipoproteins that accumulate in amyloid deposits located within atherosclerotic plaques. X-ray diffraction analysis of aligned apoC-II fibrils indicated a simple cross-β-structure composed of two parallel β-sheets. Examination of apoC-II fibrils using transmission electron microscopy, scanning transmission electron microscopy, and atomic force microscopy indicated that the fibrils are flat ribbons composed of one apoC-II molecule per 4.7-Å rise of the cross-β-structure. Cross-linking results using single-cysteine substitution mutants are consistent with a parallel in-register structural model for apoC-II fibrils. Fluorescence resonance energy transfer analysis of apoC-II fibrils labeled with specific fluorophores provided distance constraints for selected donor-acceptor pairs located within the fibrils. These findings were used to develop a simple 'letter-G-like' β-strand-loop-β-strand model for apoC-II fibrils. Fully solvated all-atom molecular dynamics (MD) simulations showed that the model contained a stable cross-β-core with a flexible connecting loop devoid of persistent secondary structure. The time course of the MD simulations revealed that charge clusters in the fibril rearrange to minimize the effects of same-charge interactions inherent in parallel in-register models. Our structural model for apoC-II fibrils suggests that apoC-II monomers fold and self-assemble to form a stable cross-β-scaffold containing relatively unstructured connecting loops. Copyright © 2010 Elsevier Ltd. All rights reserved.

Nonreplication of an Association of Apolipoprotein E2 With Sinistrality

PubMed Central

Piper, Brian J.; Yasen, Alia L.; Taylor, Amy E.; Ruiz, Jonatan R.; Gaynor, J. William; Dayger, Catherine A.; Gonzalez-Gross, Marcela; Kwon, Oh D.; Nilsson, Lars-Göran; Day, Ian N. M.; Raber, Jacob; Miller, Jeremy K.

2013-01-01

A recent report found that left-handed adolescents were over three-fold more likely to have an Apolipoprotein (APOE) ε2 allele. This study was unable to replicate this association in young-adults (N=166). A meta-analysis of nine other datasets (N = 360 to 7,559, Power > 0.999) including that of National Alzheimer’s Coordinating Center also failed to find an over-representation of ε2 among left-handers indicating that this earlier outcome was most likely a statistical artifact. PMID:22721421

PP032. Apolipoprotein profiling in umbilical cord blood of intrauterine growth restricted (IUGR) neonates.

PubMed

Pecks, Ulrich; Wölter, Manja; Borchers, Christoph; Smith, Derek; Maass, Nicolai; Glocker, Michael; Rath, Werner

2013-04-01

Fetal umbilical cord HDL concentration is lower in IUGR neonates as compared to gestational age matched controls (CTRL). The causes by now are unknown. A full apolipoprotein analysis of cord blood might help in understanding the changes in lipid metabolism seen in IUGR. To characterize cord blood apolipoprotein profile of IUGR neonates. Serum of venous umbilical cord blood (15 IUGR vs. 15 CTRL) was analyzed by Multiple Reaction Monitoring (MRM). 15 different known apolipoproteins were profiled. HDL and LDL were measured by colorimetric methods in fetal cord blood and their corresponding mothers. Fetal HDL (p<0.0001), ApoC1 (p<0.0001), and ApoE (p=0.0001) levels were lower in IUGR as compared to CTRL. Fetal HDL levels were positive correlated to ApoE, ApoC1, and ApoA2 (r=0.79, r=0.74, r=0.56). Fetal LDL levels were positive correlated to ApoB, ApoE, ApoA2, and ApoC3 (r=0.74, r=0.67, r=0.57, r=0.55). Maternal LDL concentrations correlated positive to fetal ApoC1, ApoC2, and LCAT-concentration (r=0.54, r=0.52, r=0.52). The results underlines the relevance of ApoE in fetal development. Moreover, we speculate that maternal lipid profile has an impact on fetal lipid metabolisms as evidenced by the association of maternal LDL levels and fetal ApoC1, ApoC2, and LCAT concentrations. This observation requires further confirmation and is worth to be analyzed since it provides a mechanistic link for therapeutic options. Copyright © 2013. Published by Elsevier B.V.

Marked increase in urinary excretion of apolipoproteins in children with nephrolithiasis associated with hypercalciuria.

PubMed

Kovacevic, Larisa; Lu, Hong; Caruso, Joseph A; Govil-Dalela, Tuhina; Thomas, Ronald; Lakshmanan, Yegappan

2017-06-01

Using a proteomic approach, we aimed to identify and compare the urinary excretion of proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria (CAL), hypocitraturia (CIT), and normal metabolic work-up (NM), and in healthy controls (HCs). Additionally, we aimed to confirm these results using ELISA, and to examine the relationship between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters. Prospective, controlled, pilot study of pooled urine from CAL, CIT, and NM versus age- and gender-matched HCs, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Results were confirmed by ELISA performed on individual samples. Of the 1,813 proteins identified, 230 met the above criteria. Of those, 5 proteins (apolipoprotein A-II [APOA2]; apolipoprotein A-IV [APOA4]; apolipoprotein C-III [APOA3]; fatty acid-binding protein, liver [FABPL]; fatty acid-binding protein, adipocyte [FABP4]) involved in lipid metabolism and transport were found in the CAL group, with significant differences compared with HCs. ELISA analysis indicated statistically significant differences in the urinary excretion of APOC3, APOA4, and FABPL in the CAL group compared with HCs. Twenty-four-hour urinary calcium excretion correlated significantly with concentrations of ApoC3 (r = 0.77, p < 0.001), and FABPL (r = 0.80, p = 0.005). We provide proteomic data showing increased urinary excretion of lipid metabolism/transport-related proteins in children with kidney stones and hypercalciuria. These findings suggest that abnormalities in lipid metabolism might play a role in kidney stone formation.

AIonAI: a humanitarian law of artificial intelligence and robotics.

PubMed

Ashrafian, Hutan

2015-02-01

The enduring progression of artificial intelligence and cybernetics offers an ever-closer possibility of rational and sentient robots. The ethics and morals deriving from this technological prospect have been considered in the philosophy of artificial intelligence, the design of automatons with roboethics and the contemplation of machine ethics through the concept of artificial moral agents. Across these categories, the robotics laws first proposed by Isaac Asimov in the twentieth century remain well-recognised and esteemed due to their specification of preventing human harm, stipulating obedience to humans and incorporating robotic self-protection. However the overwhelming predominance in the study of this field has focussed on human-robot interactions without fully considering the ethical inevitability of future artificial intelligences communicating together and has not addressed the moral nature of robot-robot interactions. A new robotic law is proposed and termed AIonAI or artificial intelligence-on-artificial intelligence. This law tackles the overlooked area where future artificial intelligences will likely interact amongst themselves, potentially leading to exploitation. As such, they would benefit from adopting a universal law of rights to recognise inherent dignity and the inalienable rights of artificial intelligences. Such a consideration can help prevent exploitation and abuse of rational and sentient beings, but would also importantly reflect on our moral code of ethics and the humanity of our civilisation.

Artificial Intelligence (AI) Based Tactical Guidance for Fighter Aircraft

NASA Technical Reports Server (NTRS)

McManus, John W.; Goodrich, Kenneth H.

1990-01-01

A research program investigating the use of Artificial Intelligence (AI) techniques to aid in the development of a Tactical Decision Generator (TDG) for Within Visual Range (WVR) air combat engagements is discussed. The application of AI programming and problem solving methods in the development and implementation of the Computerized Logic For Air-to-Air Warfare Simulations (CLAWS), a second generation TDG, is presented. The Knowledge-Based Systems used by CLAWS to aid in the tactical decision-making process are outlined in detail, and the results of tests to evaluate the performance of CLAWS versus a baseline TDG developed in FORTRAN to run in real-time in the Langley Differential Maneuvering Simulator (DMS), are presented. To date, these test results have shown significant performance gains with respect to the TDG baseline in one-versus-one air combat engagements, and the AI-based TDG software has proven to be much easier to modify and maintain than the baseline FORTRAN TDG programs. Alternate computing environments and programming approaches, including the use of parallel algorithms and heterogeneous computer networks are discussed, and the design and performance of a prototype concurrent TDG system are presented.

Extracting uranium from seawater: Promising AI series adsorbents

DOE PAGES

Das, Sadananda; Oyola, Y.; Mayes, Richard T.; ...

2015-11-10

A series of adsorbent (AI10 through AI17) were successfully developed at ORNL by radiation induced graft polymerization (RIGP) of acrylonitrile (AN) and vinylphosphonic acid (VPA) (at different mole/mole ratios) onto high surface area polyethylene fiber, with higher degree of grafting which ranges from 110 300%. The grafted nitrile groups were converted to amidoxime groups by reaction with 10 wt% hydroxylamine at 80 C for 72 hours. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8 ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged frommore » 171-187 g-U/kg-ads irrespective of %DOG. The performance of the adsorbents for uranium adsorption in natural seawater was also carried out using flow-through-column at Pacific Northwest National Laboratory (PNNL). The three hours KOH conditioning was better for higher uranium uptake than one hour. The adsorbent AI11 containing AN and VPA at the mole ration of 3.52, emerged as the potential candidate for higher uranium adsorption (3.35 g-U/Kg-ads.) after 56 days of exposure in the seawater in the flow-through-column. The rate vanadium adsorption over uranium was linearly increased throughout the 56 days exposure. The total vanadium uptake was ~5 times over uranium after 56 days.« less

Extracting uranium from seawater: Promising AI series adsorbents

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

Das, Sadananda; Oyola, Y.; Mayes, Richard T.

A series of adsorbent (AI10 through AI17) were successfully developed at ORNL by radiation induced graft polymerization (RIGP) of acrylonitrile (AN) and vinylphosphonic acid (VPA) (at different mole/mole ratios) onto high surface area polyethylene fiber, with higher degree of grafting which ranges from 110 300%. The grafted nitrile groups were converted to amidoxime groups by reaction with 10 wt% hydroxylamine at 80 C for 72 hours. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8 ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged frommore » 171-187 g-U/kg-ads irrespective of %DOG. The performance of the adsorbents for uranium adsorption in natural seawater was also carried out using flow-through-column at Pacific Northwest National Laboratory (PNNL). The three hours KOH conditioning was better for higher uranium uptake than one hour. The adsorbent AI11 containing AN and VPA at the mole ration of 3.52, emerged as the potential candidate for higher uranium adsorption (3.35 g-U/Kg-ads.) after 56 days of exposure in the seawater in the flow-through-column. The rate vanadium adsorption over uranium was linearly increased throughout the 56 days exposure. The total vanadium uptake was ~5 times over uranium after 56 days.« less

Diverter AI based decision aid, phases 1 and 2

NASA Technical Reports Server (NTRS)

Sexton, George A.; Bayles, Scott J.; Patterson, Robert W.; Schulke, Duane A.; Williams, Deborah C.

1989-01-01

It was determined that a system to incorporate artificial intelligence (AI) into airborne flight management computers is feasible. The AI functions that would be most useful to the pilot are to perform situational assessment, evaluate outside influences on the contemplated rerouting, perform flight planning/replanning, and perform maneuver planning. A study of the software architecture and software tools capable of demonstrating Diverter was also made. A skeletal planner known as the Knowledge Acquisition Development Tool (KADET), which is a combination script-based and rule-based system, was used to implement the system. A prototype system was developed which demonstrates advanced in-flight planning/replanning capabilities.

Differential representation of liver proteins in obese human subjects suggests novel biomarkers and promising targets for drug development in obesity.

PubMed

Caira, Simonetta; Iannelli, Antonio; Sciarrillo, Rosaria; Picariello, Gianluca; Renzone, Giovanni; Scaloni, Andrea; Addeo, Pietro

2017-12-01

The proteome of liver biopsies from human obese (O) subjects has been compared to those of nonobese (NO) subjects using two-dimensional gel electrophoresis (2-DE). Differentially represented proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based peptide mass fingerprinting (PMF) and nanoflow-liquid chromatography coupled to electrospray-tandem mass spectrometry (nLC-ESI-MS/MS). Overall, 61 gene products common to all of the liver biopsies were identified within 65 spots, among which 25 ones were differently represented between O and NO subjects. In particular, over-representation of short-chain acyl-CoA dehydrogenase, Δ(3,5)-Δ(2,4)dienoyl-CoA isomerase, acetyl-CoA acetyltransferase, glyoxylate reductase/hydroxypyruvate reductase, fructose-biphosphate aldolase B, peroxiredoxin I, protein DJ-1, catalase, α- and β-hemoglobin subunits, 3-mercaptopyruvate S-transferase, calreticulin, aminoacylase 1, phenazine biosynthesis-like domain-containing protein and a form of fatty acid-binding protein, together with downrepresentation of glutamate dehydrogenase, glutathione S-transferase A1, S-adenosylmethionine synthase 1A and a form of apolipoprotein A-I, was associated with the obesity condition. Some of these metabolic enzymes and antioxidant proteins have already been identified as putative diagnostic markers of liver dysfunction in animal models of steatosis or obesity, suggesting additional investigations on their role in these syndromes. Their differential representation in human liver was suggestive of their consideration as obesity human biomarkers and for the development of novel antiobesity drugs.

Changing to AIS 2005 and agreement of injury severity scores in a trauma registry with scores based on manual chart review.

PubMed

Stewart, Kenneth E; Cowan, Linda D; Thompson, David M

2011-09-01

The Abbreviated Injury Scale (AIS) recently underwent a major revision from AIS 98 to AIS 05. AIS injury codes form the basis of widely used injury severity scores such as the injury severity score (ISS). ISS thresholds are often used in trauma case definitions and ISS is widely used in injury research to adjust for injury severity. This study evaluated changes from AIS 98 to AIS 05, the changes' effect on ISS distributions, and presents an application of the results. Injury descriptions from medical records of 137 randomly selected patients in the Oklahoma Trauma Registry (OTR) were obtained. A single trained coder used AIS 98 and AIS 05 to code each injury. ISS values were calculated and grouped into 4 categories: 1-8, 9-14, 16-24, >24. Paired ISS was compared using Kappa statistics and tests of symmetry. We identified common injury diagnoses for which AIS severity changed between versions. Estimates of the proportion of patients changing ISS groups were applied to the entire OTR to assess the impact on reporting and on a model for reimbursement. OTR AIS 98 and manual AIS 98-based ISS values had a weighted Kappa of 0.71. OTR AIS 98 and manual AIS 05-based ISS values had a Kappa of 0.58. Manual AIS 98 and manual AIS 05 ISS had the highest Kappa of 0.81, however, though the scores differed by only 1 ISS category, there were 30 discordant pairs. The distribution of these discordant pairs was not symmetrical (Bowker's S=30; df=6; p<0.0001) with AIS 05-based ISS values consistently shifted to a lower ISS category. Reductions in AIS severity and ISS values using AIS 05 were common for extremity fractures and thorax injuries. The results suggest fewer patients would be reported to the OTR or be eligible for reimbursement. Changing from AIS 98 to AIS 05 injury coding resulted in systematic changes in AIS codes and ISS. Specific injuries and body regions were differentially affected. Trauma registries and injury researchers that use AIS based injury coding can use this

An AIS-based approach to calculate atmospheric emissions from the UK fishing fleet

NASA Astrophysics Data System (ADS)

Coello, Jonathan; Williams, Ian; Hudson, Dominic A.; Kemp, Simon

2015-08-01

The fishing industry is heavily reliant on the use of fossil fuel and emits large quantities of greenhouse gases and other atmospheric pollutants. Methods used to calculate fishing vessel emissions inventories have traditionally utilised estimates of fuel efficiency per unit of catch. These methods have weaknesses because they do not easily allow temporal and geographical allocation of emissions. A large proportion of fishing and other small commercial vessels are also omitted from global shipping emissions inventories such as the International Maritime Organisation's Greenhouse Gas Studies. This paper demonstrates an activity-based methodology for the production of temporally- and spatially-resolved emissions inventories using data produced by Automatic Identification Systems (AIS). The methodology addresses the issue of how to use AIS data for fleets where not all vessels use AIS technology and how to assign engine load when vessels are towing trawling or dredging gear. The results of this are compared to a fuel-based methodology using publicly available European Commission fisheries data on fuel efficiency and annual catch. The results show relatively good agreement between the two methodologies, with an estimate of 295.7 kilotons of fuel used and 914.4 kilotons of carbon dioxide emitted between May 2012 and May 2013 using the activity-based methodology. Different methods of calculating speed using AIS data are also compared. The results indicate that using the speed data contained directly in the AIS data is preferable to calculating speed from the distance and time interval between consecutive AIS data points.

Adolescent idiopathic scoliosis (AIS), environment, exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network approach and possible implications for medical therapy

PubMed Central

2011-01-01

Genetic factors are believed to play an important role in the etiology of adolescent idiopathic scoliosis (AIS). Discordant findings for monozygotic (MZ) twins with AIS show that environmental factors including different intrauterine environments are important in etiology, but what these environmental factors may be is unknown. Recent evidence for common chronic non-communicable diseases suggests epigenetic differences may underlie MZ twin discordance, and be the link between environmental factors and phenotypic differences. DNA methylation is one important epigenetic mechanism operating at the interface between genome and environment to regulate phenotypic plasticity with a complex regulation across the genome during the first decade of life. The word exposome refers to the totality of environmental exposures from conception onwards, comprising factors in external and internal environments. The word exposome is used here also in relation to physiologic and etiopathogenetic factors that affect normal spinal growth and may induce the deformity of AIS. In normal postnatal spinal growth we propose a new term and concept, physiologic growth-plate exposome for the normal processes particularly of the internal environments that may have epigenetic effects on growth plates of vertebrae. In AIS, we propose a new term and concept pathophysiologic scoliogenic exposome for the abnormal processes in molecular pathways particularly of the internal environment currently expressed as etiopathogenetic hypotheses; these are suggested to have deforming effects on the growth plates of vertebrae at cell, tissue, structure and/or organ levels that are considered to be epigenetic. New research is required for chromatin modifications including DNA methylation in AIS subjects and vertebral growth plates excised at surgery. In addition, consideration is needed for a possible network approach to etiopathogenesis by constructing AIS diseasomes. These approaches may lead through screening

The effect of Ai Chi aquatic therapy on individuals with knee osteoarthritis: a pilot study.

PubMed

So, Billy C L; Kong, Iris S Y; Lee, Roy K L; Man, Ryan W F; Tse, William H K; Fong, Adalade K W; Tsang, William W N

2017-05-01

[Purpose] To examine the efficacy of Ai Chi in relieving the pain and stiffness of knee osteoarthritis and improving, physical functioning, proprioception and quality of life. [Subjects and Methods] Twenty-five persons with knee osteoarthritis completed 5 weeks Ai Chi practice (60 minutes per session, twice per week, 10 sessions in total). Knee pain and stiffness were measured before and after the intervention program. [Results] Significant improvements in pain, self-perceived physical functioning and self-perceived stiffness were observed after the Ai-Chi intervention. On average, no significant change in knee range of motion, 6-minute walk test distances or proprioception was observed. [Conclusion] A five-week Ai Chi intervention can improve the pain and stiffness of knee osteoarthritis and self-perceived physical functions and quality of life improvement. Ai Chi may be another treatment choice for people with knee OA to practice in the community.

Combined vitamin C and vitamin E deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice.

PubMed

Babaev, Vladimir R; Li, Liying; Shah, Sanket; Fazio, Sergio; Linton, MacRae F; May, James M

2010-09-01

To assess the role of combined deficiencies of vitamins C and E on the earliest stages of atherosclerosis (an inflammatory condition associated with oxidative stress), 4 combinations of vitamin supplementation (low C/low E, low C/high E, high C/low E, and high C/high E) were studied in atherosclerosis-prone apolipoprotein E-deficient mice also unable to synthesize their own vitamin C (gulonolactone oxidase(-/-)); and to evaluate the effect of a more severe depletion of vitamin C alone in a second experiment using gulonolactone oxidase(-/-) mice carrying the hemizygous deletion of SVCT2 (the vitamin C transporter). After 8 weeks of a high-fat diet (16% lard and 0.2% cholesterol), atherosclerosis developed in the aortic sinus areas of mice in all diet groups. Each vitamin-deficient diet significantly decreased liver and brain contents of the corresponding vitamin. Combined deficiency of both vitamins increased lipid peroxidation, doubled plaque size, and increased plaque macrophage content by 2- to 3-fold in male mice, although only plaque macrophage content was increased in female mice. A more severe deficiency of vitamin C in gulonolactone oxidase(-/-) mice with defective cellular uptake of vitamin C increased both oxidative stress and atherosclerosis in apolipoprotein E(-/-) mice compared with littermates receiving a diet replete in vitamin C, again most clearly in males. Combined deficiencies of vitamins E and C are required to worsen early atherosclerosis in an apolipoprotein E-deficient mouse model. However, a more severe cellular deficiency of vitamin C alone promotes atherosclerosis when vitamin E is replete.