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Sample records for net endogenous acid

  1. Net Endogenous Acid Production (NEAP) and Bone Mineral Density in Men and Women: The Framingham Offspring Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the short term, bone may buffer excess acid by releasing calcium. It has been proposed that diets high in protein, which have high potential renal acid load, may contribute to low BMD. In contrast, some evidence indicates higher protein intake may be beneficial for bone health, possibly by enhanc...

  2. Higher estimates of daily dietary net endogenous acid production (NEAP) in the elderly as compared to the young in a healthy, free-living elderly population of Pakistan.

    PubMed

    Alam, Iftikhar; Alam, Ibrar; Paracha, Parvez I; Pawelec, Graham

    2012-01-01

    Dietary intake has been shown to influence the acid-base balance in human subjects; however, this phenomenon is poorly understood and rarely reported for the least well-studied segment of older people in a developing country. The aims of the present study were to: (1) quantify estimates of daily net endogenous acid production (NEAP) (mEq/d) in a sample of otherwise healthy elderly aged 50 years and above; and (2) compare NEAP between the elderly and young to determine the effects of aging, which could contribute to changes in the acid-base balance. Analyses were carried out among 526 elderly and 131 young participants (aged 50-80 and 23-28 years, respectively), all of whom were free of discernible disease, nonsmokers, and not on any chronic medication. Selected anthropometric factors were measured and 24-hour dietary recall was recorded. We used two measures to characterize dietary acid load: (1) NEAP estimated as the dietary potential renal acid load plus organic acid excretion, the latter as a multiple of estimated body surface area; and (2) estimated NEAP based on protein and K. For the young and elderly, the ranges of NEAP were 12.1-67.8 mEq/d and 2.0-78.3 mEq/d, respectively. Regardless of the method used, the mean dietary acid-base balance (NEAP) was significantly higher for the elderly than the young (P = 0.0035 for NEAP [elderly, 44.1 mEq/d versus young 40.1 mEq/d]; and P = 0.0035 for the protein:potassium ratio [elderly, 1.4 mEq/d versus young 1.1 mEq/d]). A positive and significant correlation was found between NEAP and energy, protein, and phosphorus (P < 0.05 for all trends). The findings from this study provide evidence of the relatively higher production of NEAP in older people, possibly as an effect of higher consumption of certain acid-producing foods by the elderly.

  3. The Cannabinoid Acids, Analogs and Endogenous Counterparts

    PubMed Central

    Burstein, Sumner H.

    2015-01-01

    The cannabinoid acids are a structurally heterogeneous group of compounds some of which are endogenous molecules and others that are metabolites of phytocannabinoids. The prototypic endogenous substance is N-arachidonoyl glycine (NAgly) that is closely related in structure to the cannabinoid agonist anandamide. The most studied phytocannabinoid is Δ9–THC-11-oic acid, the principal metabolite of Δ9–THC. Both types of acids have in common several biological actions such as low affinity for CB1, anti-inflammatory activity and analgesic properties. This suggests that there may be similarities in their mechanism of action, a point that is discussed in this review. Also presented are reports on analogs of the acids that provide opportunities for the development of novel therapeutic agents, such as ajulemic acid. PMID:24731541

  4. Net alkalinity and net acidity 2: Practical considerations

    USGS Publications Warehouse

    Kirby, C.S.; Cravotta, C.A.

    2005-01-01

    The pH, alkalinity, and acidity of mine drainage and associated waters can be misinterpreted because of the chemical instability of samples and possible misunderstandings of standard analytical method results. Synthetic and field samples of mine drainage having various initial pH values and concentrations of dissolved metals and alkalinity were titrated by several methods, and the results were compared to alkalinity and acidity calculated based on dissolved solutes. The pH, alkalinity, and acidity were compared between fresh, unoxidized and aged, oxidized samples. Data for Pennsylvania coal mine drainage indicates that the pH of fresh samples was predominantly acidic (pH 2.5-4) or near neutral (pH 6-7); ??? 25% of the samples had pH values between 5 and 6. Following oxidation, no samples had pH values between 5 and 6. The Standard Method Alkalinity titration is constrained to yield values >0. Most calculated and measured alkalinities for samples with positive alkalinities were in close agreement. However, for low-pH samples, the calculated alkalinity can be negative due to negative contributions by dissolved metals that may oxidize and hydrolyze. The Standard Method hot peroxide treatment titration for acidity determination (Hot Acidity) accurately indicates the potential for pH to decrease to acidic values after complete degassing of CO2 and oxidation of Fe and Mn, and it indicates either the excess alkalinity or that required for neutralization of the sample. The Hot Acidity directly measures net acidity (= -net alkalinity). Samples that had near-neutral pH after oxidation had negative Hot Acidity; samples that had pH < 6.3 after oxidation had positive Hot Acidity. Samples with similar pH values before oxidation had dissimilar Hot Acidities due to variations in their alkalinities and dissolved Fe, Mn, and Al concentrations. Hot Acidity was approximately equal to net acidity calculated based on initial pH and dissolved concentrations of Fe, Mn, and Al minus the

  5. Net alkalinity and net acidity 1: Theoretical considerations

    USGS Publications Warehouse

    Kirby, C.S.; Cravotta, C.A.

    2005-01-01

    Net acidity and net alkalinity are widely used, poorly defined, and commonly misunderstood parameters for the characterization of mine drainage. The authors explain theoretical expressions of 3 types of alkalinity (caustic, phenolphthalein, and total) and acidity (mineral, CO2, and total). Except for rarely-invoked negative alkalinity, theoretically defined total alkalinity is closely analogous to measured alkalinity and presents few practical interpretation problems. Theoretically defined "CO 2-acidity" is closely related to most standard titration methods with an endpoint pH of 8.3 used for determining acidity in mine drainage, but it is unfortunately named because CO2 is intentionally driven off during titration of mine-drainage samples. Using the proton condition/mass- action approach and employing graphs to illustrate speciation with changes in pH, the authors explore the concept of principal components and how to assign acidity contributions to aqueous species commonly present in mine drainage. Acidity is defined in mine drainage based on aqueous speciation at the sample pH and on the capacity of these species to undergo hydrolysis to pH 8.3. Application of this definition shows that the computed acidity in mg L -1 as CaCO3 (based on pH and analytical concentrations of dissolved FeII, FeIII, Mn, and Al in mg L -1):aciditycalculated=50{1000(10-pH)+[2(FeII)+3(FeIII)]/56+2(Mn)/ 55+3(Al)/27}underestimates contributions from HSO4- and H+, but overestimates the acidity due to Fe3+ and Al3+. However, these errors tend to approximately cancel each other. It is demonstrated that "net alkalinity" is a valid mathematical construction based on theoretical definitions of alkalinity and acidity. Further, it is shown that, for most mine-drainage solutions, a useful net alkalinity value can be derived from: (1) alkalinity and acidity values based on aqueous speciation, (2) measured alkalinity minus calculated acidity, or (3) taking the negative of the value obtained in a

  6. Lunularic acid, a common endogenous growth inhibitor of liverworts.

    PubMed

    Pryce, R J

    1971-12-01

    By gas-liquid chromotography and thin layer chromatography, an endogenous growth inhibitor of Lunularia cruciata has been detected in seven other representatives of the class of liverworts. All liverworts so far examined have been found to contain lunularic acid. Evidence for the identity of the previously isolated, but unidentified, endogenous growth inhibitor of Marchantia polymorpha and lunularic acid is presented.

  7. Endogenous molecules stimulating N-acylethanolamine-hydrolyzing acid amidase (NAAA).

    PubMed

    Tai, Tatsuya; Tsuboi, Kazuhito; Uyama, Toru; Masuda, Kim; Cravatt, Benjamin F; Houchi, Hitoshi; Ueda, Natsuo

    2012-05-16

    Fatty acid amide hydrolase (FAAH) plays the central role in the degradation of bioactive N-acylethanolamines such as the endocannabinoid arachidonoylethanolamide (anandamide) in brain and peripheral tissues. A lysosomal enzyme referred to as N-acylethanolamine-hydrolyzing acid amidase (NAAA) catalyzes the same reaction with preference to palmitoylethanolamide, an endogenous analgesic and neuroprotective substance, and is therefore expected as a potential target of therapeutic drugs. In the in vitro assays thus far performed, the maximal activity of NAAA was achieved in the presence of both nonionic detergent (Triton X-100 or Nonidet P-40) and the SH reagent dithiothreitol. However, endogenous molecules that might substitute for these synthetic compounds remain poorly understood. Here, we examined stimulatory effects of endogenous phospholipids and thiol compounds on recombinant NAAA. Among different phospholipids tested, choline- or ethanolamine-containing phospholipids showed potent effects, and 1 mM phosphatidylcholine increased NAAA activity by 6.6-fold. Concerning endogenous thiol compounds, dihydrolipoic acid at 0.1-1 mM was the most active, causing 8.5-9.0-fold stimulation. These results suggest that endogenous phospholipids and dihydrolipoic acid may contribute in keeping NAAA active in lysosomes. Even in the presence of phosphatidylcholine and dihydrolipoic acid, however, the preferential hydrolysis of palmitoylethanolamide was unaltered. We also investigated a possible compensatory induction of NAAA mRNA in brain and other tissues of FAAH-deficient mice. However, NAAA expression levels in all the tissues examined were not significantly altered from those in wild-type mice.

  8. Endogenous Molecules Stimulating N-Acylethanolamine-Hydrolyzing Acid Amidase (NAAA)

    PubMed Central

    2012-01-01

    Fatty acid amide hydrolase (FAAH) plays the central role in the degradation of bioactive N-acylethanolamines such as the endocannabinoid arachidonoylethanolamide (anandamide) in brain and peripheral tissues. A lysosomal enzyme referred to as N-acylethanolamine-hydrolyzing acid amidase (NAAA) catalyzes the same reaction with preference to palmitoylethanolamide, an endogenous analgesic and neuroprotective substance, and is therefore expected as a potential target of therapeutic drugs. In the in vitro assays thus far performed, the maximal activity of NAAA was achieved in the presence of both nonionic detergent (Triton X-100 or Nonidet P-40) and the SH reagent dithiothreitol. However, endogenous molecules that might substitute for these synthetic compounds remain poorly understood. Here, we examined stimulatory effects of endogenous phospholipids and thiol compounds on recombinant NAAA. Among different phospholipids tested, choline- or ethanolamine-containing phospholipids showed potent effects, and 1 mM phosphatidylcholine increased NAAA activity by 6.6-fold. Concerning endogenous thiol compounds, dihydrolipoic acid at 0.1–1 mM was the most active, causing 8.5–9.0-fold stimulation. These results suggest that endogenous phospholipids and dihydrolipoic acid may contribute in keeping NAAA active in lysosomes. Even in the presence of phosphatidylcholine and dihydrolipoic acid, however, the preferential hydrolysis of palmitoylethanolamide was unaltered. We also investigated a possible compensatory induction of NAAA mRNA in brain and other tissues of FAAH-deficient mice. However, NAAA expression levels in all the tissues examined were not significantly altered from those in wild-type mice. PMID:22860206

  9. Diet-dependent net acid load and risk of incident hypertension in United States women.

    PubMed

    Zhang, Luxia; Curhan, Gary C; Forman, John P

    2009-10-01

    Animal and human studies suggest a potential link between acid-base status and blood pressure. Contemporary Western diets yield a daily systemic acid load of varying amounts, yet the association with hypertension has never been explored. We prospectively examined the association between the diet-dependent net acid load (also known as the estimated net endogenous acid production) and the risk of incident hypertension among 87 293 women without a history of hypertension in the Nurses' Health Study II. We also used the ratio of animal protein intake to potassium intake as an alternative evaluation of diet-dependent net acid load. We identified 15 385 incident cases of hypertension during 995 239 person-years of follow-up. After adjusting for potential confounders, women in the top decile of estimated diet-dependent net acid load had an increased risk of hypertension (relative risk: 1.14; 95% CI: 1.05 to 1.24; P for trend=0.01) compared with women in the bottom decile. To test whether the association between estimated diet-dependent net acid load and hypertension is independent of its individual components, an additional adjustment for intakes of protein and potassium was made and resulted in a relative risk of 1.23 (95% CI: 1.08 to 1.41; P for trend=0.003) for the top decile of estimated diet-dependent net acid load. Results of the ratio of animal protein intake to potassium intake were similar with those of estimated diet-depend net acid load. In conclusion, a high diet-dependent net acid load is independently associated with a higher risk of incident hypertension.

  10. Inhibition of endogenous dentin matrix metalloproteinases by ethylenediaminetetraacetic acid

    PubMed Central

    Thompson, J.M.; Agee, K.; Sidow, S.; McNally, K.; Lindsey, K.; Borke, J.; Elsalanty, M.; Tay, F.R.; Pashley, D.H.

    2011-01-01

    Introduction Endogenous dentin matrix metalloproteinases (MMPs) contribute to extracellular collagen matrix degradation in hybrid layers following adhesive dentin bonding procedures. Endodontic irrigants, including chlorhexidine (CHX) and ethylenediaminetetraacetic acid (EDTA) may help protect the hybrid layer from this process. The objective of the present study was to determine the exposure time necessary for EDTA to inactivate endogenous MMP activity in human dentin. Methods Dentin beams (2×1×3 mm) were prepared from mid-coronal dentin of extracted third molars. The beams were demineralized in 10 wt% phosphoric acid which also activated endogenous MMPs, and were divided into four experimental groups based on exposure time to 17% EDTA (0, 1, 2 or 5 min). A generic colorimetric MMP assay measured MMP activity via absorbance at 412 nm. Data were evaluated by Kruskal Wallis ANOVA, followed by Dunn’s pair-wise comparisons at α = 0.05. Results All exposure times resulted in significant inhibition (P<0.001) compared to unexposed controls. Specifically, percent inhibition for 1-, 2-, and 5-minute exposure times were 55.1±21.5%, 72.8±11.7%, and 74.7±19.7%, respectively. Conclusions 17% EDTA significantly inhibits endogenous MMP activity of human dentin within 1–2 min. This may minimize hybrid layer degradation following resin bonding procedures in the root canal space. PMID:22152622

  11. Phytic acid increases mucin and endogenous amino acid losses from the gastrointestinal tract of chickens.

    PubMed

    Onyango, Edward M; Asem, Elikplimi K; Adeola, Olayiwola

    2009-03-01

    The influence of the form of phytic acid on the regulation of mucin and endogenous losses of amino acids, nitrogen and energy in chickens was investigated. Forty-eight 10-week-old male broilers were grouped by weight into eight blocks of six cages with one bird per cage. Birds received by intubation six dextrose-based combinations of phytic acid and phytase arranged in a 3 x 2 factorial consisting of phytic acid form (no phytic acid, 1.0 g free phytic acid or 1.3 g magnesium-potassium phytate) and phytase (0 or 1000 units). Each bird received the assigned combination added to 25 g dextrose at each of the two feedings on the first day of experimentation. All excreta were collected continuously for 54 h following feeding and frozen until analysed. Frozen excreta were thawed, pooled for each bird, lyophilised, ground, and analysed for DM, energy, nitrogen, amino acids, mucin, and sialic and uric acids. Chickens fed either magnesium-potassium phytate or free phytic acid showed increased (P < 0.05) loss of crude mucin and sialic acid. The amount of crude mucin lost was significantly greater (P < 0.05) with magnesium-potassium phytate than with free phytic acid treatment. Both phytic acid treatments also increased (P < 0.05) endogenous loss of threonine, proline and serine. In conclusion, the form of phytic acid fed to chickens affects the extent of mucin and endogenous amino acid losses from the gastrointestinal tract.

  12. Visualization of an endogenous retinoic acid gradient across embryonic development.

    PubMed

    Shimozono, Satoshi; Iimura, Tadahiro; Kitaguchi, Tetsuya; Higashijima, Shin-Ichi; Miyawaki, Atsushi

    2013-04-18

    In vertebrate development, the body plan is determined by primordial morphogen gradients that suffuse the embryo. Retinoic acid (RA) is an important morphogen involved in patterning the anterior-posterior axis of structures, including the hindbrain and paraxial mesoderm. RA diffuses over long distances, and its activity is spatially restricted by synthesizing and degrading enzymes. However, gradients of endogenous morphogens in live embryos have not been directly observed; indeed, their existence, distribution and requirement for correct patterning remain controversial. Here we report a family of genetically encoded indicators for RA that we have termed GEPRAs (genetically encoded probes for RA). Using the principle of fluorescence resonance energy transfer we engineered the ligand-binding domains of RA receptors to incorporate cyan-emitting and yellow-emitting fluorescent proteins as fluorescence resonance energy transfer donor and acceptor, respectively, for the reliable detection of ambient free RA. We created three GEPRAs with different affinities for RA, enabling the quantitative measurement of physiological RA concentrations. Live imaging of zebrafish embryos at the gastrula and somitogenesis stages revealed a linear concentration gradient of endogenous RA in a two-tailed source-sink arrangement across the embryo. Modelling of the observed linear RA gradient suggests that the rate of RA diffusion exceeds the spatiotemporal dynamics of embryogenesis, resulting in stability to perturbation. Furthermore, we used GEPRAs in combination with genetic and pharmacological perturbations to resolve competing hypotheses on the structure of the RA gradient during hindbrain formation and somitogenesis. Live imaging of endogenous concentration gradients across embryonic development will allow the precise assignment of molecular mechanisms to developmental dynamics and will accelerate the application of approaches based on morphogen gradients to tissue engineering and

  13. Do polyunsaturated fatty acids behave like an endogenous "polypill"?

    PubMed

    Das, Undurti N

    2008-01-01

    Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin - called as polypill - was estimated to reduce cardiovascular events by approximately 80%. Essential fatty acids (EFAs) and their long-chain metabolites and other products prevent platelet aggregation, lower blood pressure, reduce LDL-C, and ameliorate the adverse actions of homocysteine. Thus, EFAs and their metabolites show all the actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules, have no significant side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and children; and have been shown to reduce the incidence cardiovascular diseases. I propose that a rational combination of omega-3 and omega-6 fatty acids is as beneficial as that of the "polypill"; and may even show additional benefit in the prevention of depression, schizophrenia, Alzheimer's disease, and enhance cognitive function.

  14. The effect of dietary methionine levels on endogenous nitrogen and endogenous amino acids flows in growing goats.

    PubMed

    Zhou, C S; Tan, Z L; Tang, S X; Sun, Z H; Han, X F; Wang, M; Tayo, G O

    2010-10-01

    The effect of dietary methionine (Met) levels on endogenous N and amino acids (AA) flows at different part of the digestive tract of growing goats was determined using a (15)N isotope dilution technique. Three goats (25 ± 2.5 kg) were fitted with the ruminal, duodenal and ileal cannulae and allocated to three dietary treatments in a 3 × 3 Latin square design. The dietary treatments consisted of a total mixed ration containing three levels of Met (0.15%, 0.25% and 0.35%) respectively. It was found that at 0.15% Met level, the lowest flow in endogenous N and total AA at the duodenum and ileum occurred. The endogenous N secretion contributed to 26% and 23% of the duodenal and ileal total N flows, respectively, and the proportions were not affected by the dietary Met levels. The duodenal and ileal flows of endogenous total AA were 11.1, 11.8, 11.3 g/d and 2.9, 3.9, 4.1 g/d respectively. The average real digestibility of N was 65%, 87% and 95% in the forestomach, intestine and whole digestive tract respectively.

  15. Influence of dietary phytic acid and source of microbial phytase on ileal endogenous amino acid flows in broiler chickens.

    PubMed

    Cowieson, A J; Ravindran, V; Selle, P H

    2008-11-01

    The effects of phytic acid and 2 sources of exogenous phytase (bacterial vs. fungal) on the flow of endogenous amino acids at the terminal ileum of broilers were assessed using the enzyme-hydrolyzed casein method. Phytic acid (as the sodium salt) was included in a purified diet at 8.5 and 14.5 g/kg, and each diet was fed without or with a fungal (Aspergillus niger-derived) or a bacterial (Escherichia coli-derived) microbial phytase at 500 phytase units/kg of diet. Increasing the concentration of phytic acid in the diet from 8.5 to 14.5 g/kg increased (P < 0.001) the flow of all measured amino acids by an average of 68%, with a range from 17% for proline to 145% for phenylalanine. The flow of endogenous aspartic acid, serine, glutamic acid, glycine, leucine, tyrosine, phenylalanine, and histidine were increased by more than the mean, indicating changes in the composition of endogenous protein in response to the presence of higher concentrations of phytic acid. Supplementation of both phytases reduced (P < 0.001) the flow of endogenous amino acids, but the reduction (P = 0.06) was greater for the bacterial phytase compared with the fungal phytase. These data suggest that a substantial part of the amino acid and energy responses observed following phytase supplementation in broiler chickens stems from reduced endogenous amino acid flows and that the capacity of different phytases to counteract the antinutritive properties of phytic acid vary.

  16. Dietary and endogenous amino acids are the main contributors to microbial protein in the upper gut of normally nourished pigs.

    PubMed

    Libao-Mercado, Aileen Joy O; Zhu, Cuilan L; Cant, John P; Lapierre, Hélène; Thibault, Jean-Noël; Sève, Bernard; Fuller, Malcolm F; de Lange, Cornelis F M

    2009-06-01

    Although amino acids (AA) synthesized by enteric microbiota in the upper gut of nonruminants can be absorbed, they do not necessarily make a net contribution to the host's AA supply. That depends on whether protein or nonprotein nitrogen sources are used for microbial protein production. We determined the contributions of urea, endogenous protein (EP), and dietary protein (DP) to microbial valine (M.VAL) at the distal ileum of growing pigs, based on isotope dilutions after a 4-d continuous infusion of l-[1-(13)C]valine to label EP and of [(15)N(15)N]urea. Eight barrows were assigned to either a cornstarch and soybean meal-based diet with or without 12% added fermentable fiber from pectin. Dietary pectin did not affect (P > 0.10) the contributions of the endogenous and DP to M.VAL. More than 92% of valine in microbial protein in the upper gut was derived from preformed AA from endogenous and DP, suggesting that de novo synthesis makes only a small contribution to microbial AA.

  17. Fatty acids are potential endogenous regulators of aldosterone secretion.

    PubMed

    Goodfriend, T L; Ball, D L; Elliott, M E; Morrison, A R; Evenson, M A

    1991-05-01

    Adrenal glomerulosa cells washed with delipidated albumin produced increased amounts of aldosterone in response to angiotensin-II (AII) or (Bu)2cAMP. Albumin treatment also increased binding of 125I-labeled AII to high affinity binding sites on adrenal cells. Lipid extracts of albumin solutions that were used to wash cells inhibited AII binding and aldosterone responses by washed glomerulosa cells. Chromatographic fractionation and mass spectroscopic analysis indicated that the inhibitors removed from cells by albumin were long chain fatty acids. Exogenous fatty acids not only inhibited AII binding, but they inhibited basal aldosterone production and increments in aldosterone caused by AII or dbcAMP, suggesting an effect on postreceptor steps in aldosteronogenesis. The most potent and most abundant fatty acids removed from adrenal cells were oleic, linoleic, and arachidonic. These fatty acids inhibited at micromolar concentrations in the absence of albumin and at somewhat higher concentrations in its presence. Cells that had been washed, then inhibited by exogenous oleic acid in vitro, were restored to their enhanced responsiveness by a second albumin wash, making it unlikely that cell damage is the mechanism of inhibition by fatty acids. Responses of fasciculata cells were not potentiated by albumin washes, and cortisol production was less sensitive than aldosterone production to exogenous fatty acids. Binding of ANP to glomerulosa cells was not affected by albumin or fatty acids. These results combined with clinical correlations make it plausible that unesterified fatty acids are naturally occurring regulators of the adrenal glomerulosa. Insulin's ability to lower plasma levels of fatty acids may be one way that it causes sodium retention.

  18. Multicriteria optimization of gluconic acid production using net flow.

    PubMed

    Halsall-Whitney, H; Taylor, D; Thibault, J

    2003-03-01

    The biochemical process industry is often confronted with the challenge of making decisions in an atmosphere of multiple and conflicting objectives. Recent innovations in the field of operations research and systems science have yielded rigorous multicriteria optimization techniques that can be successfully applied to the field of biochemical engineering. These techniques incorporate the expert's experience into the optimization routine and provide valuable information about the zone of possible solutions. This paper presents a multicriteria optimization strategy that generates a Pareto domain, given a set of conflicting objective criteria, and determines the optimal operating region for the production of gluconic acid using the net flow method (NFM). The objective criteria include maximizing the productivity and concentration of gluconic acid, while minimizing the residual substrate. Three optimization strategies are considered. The first two strategies identify the optimal operating region for the process inputs. The results yielded an acceptable compromise between productivity, gluconic acid concentration and residual substrate concentration. Fixing the process inputs representing the batch time, initial substrate concentration and initial biomass equal to their optimal values, the remaining simulations were used to study the sensitivity of the optimum operating region to changes in the oxygen mass transfer coefficient, K(L) a, by utilizing a multi-level K(L) a strategy. The results show that controlling K(L) a during the reaction reduced the production of biomass, which in turn resulted in increased productivity and concentration of gluconic acid above that of a fixed K(L) a.

  19. Quantitative measurement of endogenous amino acid absorption in unanaesthetized pigs.

    PubMed

    Rerat, A; Vaissade, P; Vaugelade, P

    1988-06-01

    The present experiment was carried out with 11 pigs (mean body weight: 53.9 +/- 1.3 kg) fitted with permanent catheters in the portal vein and carotid artery and with an electromagnetic flow probe around the portal vein. They were each subjected to 2 or 3 trials at 3 to 4-day intervals. During each trial the animals received after a previous fasting of 20 h a given amount of a protein-free diet (200 to 1200 g). The blood was collected either continuously for a quantitative determination of amino nitrogen, reducing sugars, urea and ammonia (number of meals 12, mean intake: 727 +/- 60 g) or discontinuously every 30 min between 0 and 8 h after the meal for amino acid analysis (number of meals 8; mean intake 709 +/- 105 g). A rather constant appearance (2 g/h) of amino acids in the portal blood was observed throughout the postprandial period. The intestinal absorption of each amino acid was however variable and represented between 10 and 50% of the daily requirements of the animal during the measuring period (8 h). Glutamine and to a less extent glutamic acid were exceptions as they were taken up by the gut wall from the arterial blood. There was also a marked synthesis of ornithine and citrulline by the latter. Because of the low blood level of urea, there were no apparent exchanges of urea between the blood and the intestine; in contrast, the ammonia absorption represented about 70% of that observed after ingestion of normal protein diets. Most amino acids are largely taken up by the liver and peripheral tissues, but in the case of alanine the syntheses exceed the uptake.

  20. STANDARDIZING TERMINOLOGY FOR ESTIMATING THE DIET-DEPENDENT NET ACID LOAD TO THE METABOLIC SYSTEM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Contemporary Western diets contain acid precursors in excess of base precursors, yielding a daily systemic net acid load of varying amounts, depending on the specific composition of the diet. Increasing evidence suggests that differences in daily net acid load, resulting predominantly from differen...

  1. Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts

    SciTech Connect

    Guo, Lei; Xiao, Yongsheng; Wang, Yinsheng

    2014-05-15

    Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ∼ 6500 unique proteins quantified, ∼ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. - Highlights: • MMA(III)-induced perturbation of the entire proteome of GM00637 cells is studied. • Quantitative proteomic approach revealed alterations of multiple cellular pathways. • MMA(III) inhibits de novo cholesterol biosynthesis. • MMA

  2. Transcriptomic Analysis of Murine Embryos Lacking Endogenous Retinoic Acid Signaling

    PubMed Central

    Paschaki, Marie; Schneider, Carole; Rhinn, Muriel; Thibault-Carpentier, Christelle; Dembélé, Doulaye; Niederreither, Karen; Dollé, Pascal

    2013-01-01

    Retinoic acid (RA), an active derivative of the liposoluble vitamin A (retinol), acts as an important signaling molecule during embryonic development, regulating phenomenons as diverse as anterior-posterior axial patterning, forebrain and optic vesicle development, specification of hindbrain rhombomeres, pharyngeal arches and second heart field, somitogenesis, and differentiation of spinal cord neurons. This small molecule directly triggers gene activation by binding to nuclear receptors (RARs), switching them from potential repressors to transcriptional activators. The repertoire of RA-regulated genes in embryonic tissues is poorly characterized. We performed a comparative analysis of the transcriptomes of murine wild-type and Retinaldehyde Dehydrogenase 2 null-mutant (Raldh2−/−) embryos — unable to synthesize RA from maternally-derived retinol — using Affymetrix DNA microarrays. Transcriptomic changes were analyzed in two embryonic regions: anterior tissues including forebrain and optic vesicle, and posterior (trunk) tissues, at early stages preceding the appearance of overt phenotypic abnormalities. Several genes expected to be downregulated under RA deficiency appeared in the transcriptome data (e.g. Emx2, Foxg1 anteriorly, Cdx1, Hoxa1, Rarb posteriorly), whereas reverse-transcriptase-PCR and in situ hybridization performed for additional selected genes validated the changes identified through microarray analysis. Altogether, the affected genes belonged to numerous molecular pathways and cellular/organismal functions, demonstrating the pleiotropic nature of RA-dependent events. In both tissue samples, genes upregulated were more numerous than those downregulated, probably due to feedback regulatory loops. Bioinformatic analyses highlighted groups (clusters) of genes displaying similar behaviors in mutant tissues, and biological functions most significantly affected (e.g. mTOR, VEGF, ILK signaling in forebrain tissues; pyrimidine and purine metabolism

  3. Accelerating biodegradation of a monoazo dye Acid Orange 7 by using its endogenous electron donors.

    PubMed

    Sun, Weihua; Zhang, Chengji; Chen, Jun; Zhang, Bingbing; Zhang, Hongzhuan; Zhang, Yongming; Chen, Lujun

    2017-02-15

    Biodegradation of a monoazo dye - Acid Orange 7 (AO7) was investigated by using an internal circulation baffled biofilm reactor. For accelerating AO7 biodegradation, endogenous electron donors produced from AO7 by UV photolysis were added into the reactor. The result shows that AO7 removal rate can be accelerated by using its endogenous electron donors, such as sulfanilic and aniline. When initial AO7 concentration was 13.6mg/L, electron donors generated by 8h UV photolysis were added into the same system. The biodegradation rate 0.4mg(0.05)h(-1) was enhanced 60% than that without adding electron donor. Furthermore, sulfanilic and aniline were found to be the main endogenous electron carriers, which could accelerate the steps of the azo dye biodegradation.

  4. Endogenous Bioactive Jasmonate Is Composed of a Set of (+)-7-iso-JA-Amino Acid Conjugates.

    PubMed

    Yan, Jianbin; Li, Suhua; Gu, Min; Yao, Ruifeng; Li, Yuwen; Chen, Juan; Yang, Mai; Tong, Jianhua; Xiao, Langtao; Nan, Fajun; Xie, Daoxin

    2016-12-01

    Jasmonates (JAs) regulate a wide range of plant defense and development processes. The bioactive JA is perceived by its receptor COI1 to trigger the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins and subsequently derepress the JAZ-repressed transcription factors for activation of expression of JA-responsive genes. So far, (+)-7-iso-JA-l-Ile has been the only identified endogenous bioactive JA molecule. Here, we designed coronafacic acid (CFA) conjugates with all the amino acids (CFA-AA) to mimic the JA amino acid conjugates, and revealed that (+)-7-iso-JA-Leu, (+)-7-iso-JA-Val, (+)-7-iso-JA-Met, and (+)-7-iso-JA-Ala are new endogenous bioactive JA molecules. Furthermore, our studies uncover the general characteristics for all the bioactive JA molecules, and provide a new strategy to synthetically generate novel active JA molecules.

  5. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    SciTech Connect

    Marion, Tracy L.; Perry, Cassandra H.; St Claire, Robert L.; Brouwer, Kim L.R.

    2012-05-15

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR{sup ®} technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na{sup +}-taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA

  6. Effect of phytic acid and microbial phytase on the flow and amino acid composition of endogenous protein at the terminal ileum of growing broiler chickens.

    PubMed

    Cowieson, A J; Ravindran, V

    2007-10-01

    The effects of phytic acid and microbial phytase on the flow and composition of endogenous protein at the terminal ileum of broiler chickens were investigated using the peptide alimentation method. Phytic acid (fed as the sodium salt) was included in a synthetic diet at 8.5, 11.5 and 14.5 g/kg (or 2.4, 3.2 and 4.0 g/kg phytate-phosphorus) and each diet was fed without or with an Escherichia coli-derived microbial phytase at 500 phytase units/kg diet. A control containing no phytate was fed as a comparison to estimate basal endogenous flows. Ingestion of phytic acid increased (P < 0.05) the flow of endogenous amino acids and N by an average of 47 % at the lowest phytic acid concentration and 87 % at the highest. The addition of microbial phytase reduced (P < 0.05) the inimical effects of phytic acid on endogenous amino acid flow at all dietary phytic acid levels. The composition of endogenous protein was also influenced (P < 0.10-0.001) by increasing phytic acid concentrations and phytase addition. The effects of phytic acid and phytase on endogenous flow and composition of endogenous protein, however, varied depending on the amino acid. It is concluded that the effects of phytase on amino acid digestibility may be mediated, in part, through a route of reduced endogenous loss.

  7. Determination of Endogenous Indole-3-Acetic Acid in Plagiochila arctica (Hepaticae) 1

    PubMed Central

    Law, David M.; Basile, Dominick V.; Basile, Margaret R.

    1985-01-01

    Endogenous indole-3-acetic acid (IAA) was found in axenically cultured gametophytes of the leafy liverwort, Plagiochila arctica Bryhn and Kaal., by high-performance liquid chromatography with electrochemical detection. Identification of the methylated auxin was confirmed by gas chromatography-mass spectrometry. Addition of 57 micromolar IAA to cultures increased relative production of ethylene. This is the first definitive (gas chromatography-mass spectrometry) demonstration of the natural occurrence of IAA in a bryophyte. PMID:16664164

  8. Imitation of biomembranes on the basis of cholic acid and endogenic thermostable protein complex in biopartitioning micellar chromatography.

    PubMed

    Rukhadze, Marina; Dzidziguri, Diana; Giorgobiani, Nana; Kerkenjia, Salome

    2011-12-01

    The structure of biomembranes was imitated by introducing nonionic surfactant polyoxyethylene (23) dodecylether, cholic acid and endogenic thermostable protein complex (14-65 kDa) into the mobile phase. The influence of concentration of these additives on the retention of the model compounds was studied. The competing interaction of cholic acid and endogenic thermostable protein complex in the lipid bilayer model was revealed on the basis of chromatographic data. The values of efficiency of the chromatographic column regarding solutes were increased by addition of endogenic thermostable protein complex to the mobile phase containing Brij-35 and cholic acid.

  9. Ileal digestibility and endogenous flow of minerals and amino acids: responses to dietary phytic acid in piglets.

    PubMed

    Woyengo, Tofuko A; Cowieson, Aaron J; Adeola, Olayiwola; Nyachoti, Charles M

    2009-08-01

    Effects of phytic acid (PA) on ileal mineral and amino acid (AA) digestibilities and ileal endogenous AA flow in piglets were investigated. Seven ileal-cannulated weanling pigs were fed a casein-maize starch-based diet with PA (as sodium phytate) at 0, 5, 10 or 20 g/kg in 4 x 4 Latin square design with three added columns to give seven observations per treatment. The basal diet was formulated to meet National Research Council energy and AA requirements for piglets. The respective digestibility and endogenous lysine loss were determined by indicator and homoarginine methods. The apparent ileal digestibility (AID) of Na, K and P was linearly and quadratically reduced (P < 0.05) by increased dietary PA concentration, whereas that of Ca and Mg was only linearly reduced (P < 0.05) by the dietary PA. The AID values for Mg and Na were negative ( - 0.03 and - 0.18, respectively) when PA was supplemented at 20 g/kg. The AID of isoleucine, leucine and valine responded quadratically to dietary PA concentration, though the differences between the AID values of the AA due to change in dietary PA concentration were marginal (at most by 1.8 percentage units). Furthermore, dietary PA did not affect (P>0.05) endogenous AA losses. The results suggest that PA has limited effect on the digestibility and endogenous losses of AA in piglets, but can reduce AID of Mg and Na partly by increasing endogenous losses of these minerals as evidenced by their negative AID values.

  10. Stimulation by surangin B of endogenous amino acid release from synaptosomes.

    PubMed

    Deng, Yanshen; Nicholson, Russell A

    2003-09-15

    The effect of surangin B, an insecticidal natural product coumarin, on presynaptic release of endogenous amino acids was investigated using a purified synaptosomal fraction isolated from mouse brain. Surangin B stimulated the release of glutamic acid (GLU), gamma-aminobutyric acid (GABA), serine, alanine and the aminosulfonic acid taurine from synaptosomes at micromolar concentrations. In all cases, these responses were reduced by removing calcium from the saline and surangin B-evoked release of GLU, GABA, aspartic acid (ASP) and alanine was significantly inhibited by the sodium channel blocker tetrodotoxin. Rotenone (a complex I inhibitor) and carbonyl cyanide chlorophenylhydrazone (CCCP; an uncoupler), were more potent releasers of amino acids from synaptosomes than surangin B, however, carboxin (a complex II-selective inhibitor), was extremely weak to ineffective in this regard. The stimulatory effect of surangin B and complex III-selective inhibitors on release of GLU, GABA, ASP and alanine by synaptosomes was significantly reduced by N,N,N',N'-tetramethyl-p-phenylenediamine, suggesting that blockade of complex III in intraterminal mitochondria is an important effect of this coumarin. Our results demonstrate that surangin B, in common with CCCP and inhibitors of complex I and III, cause release of both neurotransmitter and non-neurotransmitter amino acids from nerve endings in vitro. However, in contrast to most classical agents which interfere selectively with mitochondrial function, the release of endogenous amino acids from synaptosomes by surangin B also involves a moderate extracellular calcium ion-dependent component and relies partially on sodium ion entry into the nerve ending.

  11. Endogenous salicylic acid accumulation is required for chilling tolerance in cucumber (Cucumis sativus L.) seedlings.

    PubMed

    Dong, Chun-Juan; Li, Liang; Shang, Qing-Mao; Liu, Xin-Yan; Zhang, Zhi-Gang

    2014-10-01

    Salicylic acid (SA) is an important plant hormone, and its exogenous application can induce tolerance to multiple environmental stresses in plants. In this study, we examine the potential involvement of endogenous SA in response to chilling in cucumber (Cucumis sativus L.) seedlings. A low temperature of 8 °C induces a moderate increase in endogenous SA levels. Chilling stimulates the enzymatic activities and the expression of genes for phenylalanine ammonia-lyase (PAL) and benzoic acid-2-hydroxylase rather than isochorismate synthase. This indicates that the PAL enzymatic pathway contributes to chilling-induced SA production. Cucumber seedlings pretreated with SA biosynthesis inhibitors accumulate less endogenous SA and suffer more from chilling damage. The expression of cold-responsive genes is also repressed by SA inhibitors. The reduction in stress tolerance and in gene expression can be restored by the exogenous application of SA, confirming the critical roles of SA in chilling responses in cucumber seedlings. Furthermore, the inhibition of SA biosynthesis under chilling stress results in a prolonged and enhanced hydrogen peroxide (H2O2) accumulation. The application of exogenous SA and the chemical scavenger of H2O2 reduces the excess H2O2 and alleviates chilling injury. In contrast, the protective effects of SA are negated by foliar spraying with high concentrations of H2O2 and an inhibitor of the antioxidant enzyme. These results suggest that endogenous SA is required in response to chilling stress in cucumber seedlings, by modulating the expression of cold-responsive genes and the precise induction of cellular H2O2 levels.

  12. Endogenous Levels of Abscisic Acid and Decanoic Acid in Dutch Iris Bulbs and the Influence of Abscisic Acid and Decanoic Acid on Iris Meristems Cultured In Vitro1

    PubMed Central

    Doss, Robert P.; Kimura, Yosh; Christian, James K.

    1983-01-01

    Abscisic acid (ABA) and decanoic acid inhibited shoot elongation and floral development of Dutch iris (Iris hollandica Hoog. cv Ideal) meristems cultured in vitro. No synergism with respect to inhibition of leaf growth between ABA and decanoic acid was observed. With monthly harvest dates, from July 10, 1981 to October 10, 1981, there was a progressive decrease in endogenous level of free ABA in `Ideal' iris bulbs. Bulbs subjected to a full set of the usual preplanting storage conditions flowered, on average, 46 days after planting versus 194 days after planting for bulbs planted directly after harvest. ABA levels at harvest were 4- to 5-fold those after the preplanting storage treatment. In general, ABA levels did not correlate well with the length of time from planting until flowering of iris bulbs. Endogenous decanoic acid levels did not follow any pattern with respect to harvest date or postharvest treatment. After the postharvest high temperature treatment, there was about a 3-fold increase in nonscale decanoic acid concentration. Decanoic acid levels, in nonscale tissue, remained high after each of the other postharvest treatments. It is concluded that there is no good evidence to support the contention that either ABA or decanoic acid is directly involved in iris bulb dormancy. PMID:16663072

  13. A search for endogenous amino acids in martian meteorite ALH84001

    NASA Technical Reports Server (NTRS)

    Bada, J. L.; Glavin, D. P.; McDonald, G. D.; Becker, L.

    1998-01-01

    Trace amounts of glycine, serine, and alanine were detected in the carbonate component of the martian meteorite ALH84001 by high-performance liquid chromatography. The detected amino acids were not uniformly distributed in the carbonate component and ranged in concentration from 0.1 to 7 parts per million. Although the detected alanine consists primarily of the L enantiomer, low concentrations (<0.1 parts per million) of endogenous D-alanine may be present in the ALH84001 carbonates. The amino acids present in this sample of ALH84001 appear to be terrestrial in origin and similar to those in Allan Hills ice, although the possibility cannot be ruled out that minute amounts of some amino acids such as D-alanine are preserved in the meteorite.

  14. Fern and Lycophyte Guard Cells Do Not Respond to Endogenous Abscisic Acid

    PubMed Central

    McAdam, Scott A.M.; Brodribb, Timothy J.

    2012-01-01

    Stomatal guard cells regulate plant photosynthesis and transpiration. Central to the control of seed plant stomatal movement is the phytohormone abscisic acid (ABA); however, differences in the sensitivity of guard cells to this ubiquitous chemical have been reported across land plant lineages. Using a phylogenetic approach to investigate guard cell control, we examined the diversity of stomatal responses to endogenous ABA and leaf water potential during water stress. We show that although all species respond similarly to leaf water deficit in terms of enhanced levels of ABA and closed stomata, the function of fern and lycophyte stomata diverged strongly from seed plant species upon rehydration. When instantaneously rehydrated from a water-stressed state, fern and lycophyte stomata rapidly reopened to predrought levels despite the high levels of endogenous ABA in the leaf. In seed plants under the same conditions, high levels of ABA in the leaf prevented rapid reopening of stomata. We conclude that endogenous ABA synthesized by ferns and lycophytes plays little role in the regulation of transpiration, with stomata passively responsive to leaf water potential. These results support a gradualistic model of stomatal control evolution, offering opportunities for molecular and guard cell biochemical studies to gain further insights into stomatal control. PMID:22517320

  15. Fern and lycophyte guard cells do not respond to endogenous abscisic acid.

    PubMed

    McAdam, Scott A M; Brodribb, Timothy J

    2012-04-01

    Stomatal guard cells regulate plant photosynthesis and transpiration. Central to the control of seed plant stomatal movement is the phytohormone abscisic acid (ABA); however, differences in the sensitivity of guard cells to this ubiquitous chemical have been reported across land plant lineages. Using a phylogenetic approach to investigate guard cell control, we examined the diversity of stomatal responses to endogenous ABA and leaf water potential during water stress. We show that although all species respond similarly to leaf water deficit in terms of enhanced levels of ABA and closed stomata, the function of fern and lycophyte stomata diverged strongly from seed plant species upon rehydration. When instantaneously rehydrated from a water-stressed state, fern and lycophyte stomata rapidly reopened to predrought levels despite the high levels of endogenous ABA in the leaf. In seed plants under the same conditions, high levels of ABA in the leaf prevented rapid reopening of stomata. We conclude that endogenous ABA synthesized by ferns and lycophytes plays little role in the regulation of transpiration, with stomata passively responsive to leaf water potential. These results support a gradualistic model of stomatal control evolution, offering opportunities for molecular and guard cell biochemical studies to gain further insights into stomatal control.

  16. Endogenous fatty acids in olfactory hairs influence pheromone binding protein structure and function in Lymantria dispar.

    PubMed

    Nardella, Jason; Terrado, Mailyn; Honson, Nicolette S; Plettner, Erika

    2015-08-01

    The gypsy moth utilizes a pheromone, (7R,8S)-2-methyl-7,8-epoxyoctadecane, for mate location. The pheromone is detected by sensory hairs (sensilla) on the antennae of adult males. Sensilla contain the dendrites of olfactory neurons bathed in lymph, which contains pheromone binding proteins (PBPs). We have extracted and identified free fatty acids from lymph of sensory hairs, and we demonstrate that these function as endogenous ligands for gypsy moth PBP1 and PBP2. Homology modeling of both PBPs, and docking of fatty acids reveal multiple binding sites: one internal, the others external. Pheromone binding assays suggest that these fatty acids increase PBP-pheromone binding affinity. We show that fatty acid binding causes an increase in α-helix content in the N-terminal domain, but not in the C-terminal peptide of both proteins. The C-terminal peptide was shown to form a α-helix in a hydrophobic, homogeneous environment, but not in the presence of fatty acid micelles. Through partition assays we show that the fatty acids prevent adsorption of the pheromone on hydrophobic surfaces and facilitate pheromone partition into an aqueous phase. We propose that lymph is an emulsion of fatty acids and PBP that influence each other and thereby control the partition equilibria of hydrophobic odorants.

  17. Desaturase and elongase limiting endogenous long chain polyunsaturated fatty acid biosynthesis

    PubMed Central

    Zhang, Ji Yao; Kothapalli, Kumar S.D.; Brenna, J. Thomas

    2016-01-01

    Purpose of Review Endogenous synthesis of the long chain polyunsaturated fatty acids (LCPUFA) is mediated by the fatty acid desaturase (FADS) gene cluster (11q12-13.1) and elongation of very long chain fatty acids 2 (ELOVL2) (6p24.2) and ELOVL5 (6p12.1). Though older biochemical work identified the product of one gene, FADS2, rate limiting for LCPUFA synthesis, recent studies suggest that polymorphisms in any of these genes can limit accumulation of product LCPUFA. Recent findings Genome-wide association study (GWAS) of Greenland Inuit show strong adaptation signals within FADS gene cluster, attributed to high omega-3 fatty acid intake, while GWAS found ELOVL2 associated with sleep duration, age and DNA methylation. ELOVL5 coding mutations cause spinocerebellar ataxia 38, and epigenetic marks were associated with depression and suicide risk. Two sterol response element binding sites were found on ELOVL5, a SREBP-1c target gene. Minor allele carriers of a 3 single nucleotide polymorphism (SNP) haplotype in ELOVL2 have decreased 22:6n-3 levels. Unequivocal molecular evidence shows mammalian FADS2 catalyzes direct Δ4-desaturation to yield 22:6n-3 and 22:5n-6. A SNP near FADS1 influences the levels of 5-lipoxygenase products and epigenetic alteration. Summary Genetic polymorphisms within FADS and ELOVL can limit LCPUFA product accumulation at any step of the biosynthetic pathway. PMID:26828581

  18. Taurine Bromamine: Reactivity of an Endogenous and Exogenous Anti-Inflammatory and Antimicrobial Amino Acid Derivative

    PubMed Central

    Bertozo, Luiza De Carvalho; Morgon, Nelson Henrique; De Souza, Aguinaldo Robinson; Ximenes, Valdecir Farias

    2016-01-01

    Taurine bromamine (Tau-NHBr) is produced by the reaction between hypobromous acid (HOBr) and the amino acid taurine. There are increasing number of applications of Tau-NHBr as an anti-inflammatory and microbicidal drug for topical usage. Here, we performed a comprehensive study of the chemical reactivity of Tau-NHBr with endogenous and non-endogenous compounds. Tau-NHBr reactivity was compared with HOBr, hypochlorous acid (HOCl) and taurine chloramine (Tau-NHCl). The second-order rate constants (k2) for the reactions between Tau-NHBr and tryptophan (7.7 × 102 M−1s−1), melatonin (7.3 × 103 M−1s−1), serotonin (2.9 × 103 M−1s−1), dansylglycine (9.5 × 101 M−1s−1), tetramethylbenzidine (6.4 × 102 M−1s−1) and H2O2 (3.9 × M−1s−1) were obtained. Tau-NHBr demonstrated the following selectivity regarding its reactivity with free amino acids: tryptophan > cysteine ~ methionine > tyrosine. The reactivity of Tau-NHBr was strongly affected by the pH of the medium (for instance with dansylglycine: pH 5.0, 1.1 × 104 M−1s−1, pH 7.0, 9.5 × 10 M−1s−1 and pH 9.0, 1.7 × 10 M−1s−1), a property that is related to the formation of the dibromamine form at acidic pH (Tau-NBr2). The formation of singlet oxygen was observed in the reaction between Tau-NHBr and H2O2. Tau-NHBr was also able to react with linoleic acid, but with low efficiency compared with HOBr and HOCl. Compared with HOBr, Tau-NHBr was not able to react with nucleosides. In conclusion, the following reactivity sequence was established: HOBr > HOCl > Tau-NHBr > Tau-NHCl. These findings can be very helpful for researchers interested in biological applications of taurine haloamines. PMID:27110829

  19. Taurine Bromamine: Reactivity of an Endogenous and Exogenous Anti-Inflammatory and Antimicrobial Amino Acid Derivative.

    PubMed

    De Carvalho Bertozo, Luiza; Morgon, Nelson Henrique; De Souza, Aguinaldo Robinson; Ximenes, Valdecir Farias

    2016-04-21

    Taurine bromamine (Tau-NHBr) is produced by the reaction between hypobromous acid (HOBr) and the amino acid taurine. There are increasing number of applications of Tau-NHBr as an anti-inflammatory and microbicidal drug for topical usage. Here, we performed a comprehensive study of the chemical reactivity of Tau-NHBr with endogenous and non-endogenous compounds. Tau-NHBr reactivity was compared with HOBr, hypochlorous acid (HOCl) and taurine chloramine (Tau-NHCl). The second-order rate constants (k₂) for the reactions between Tau-NHBr and tryptophan (7.7 × 10² M(-1)s(-1)), melatonin (7.3 × 10³ M(-1)s(-1)), serotonin (2.9 × 10³ M(-1)s(-1)), dansylglycine (9.5 × 10¹ M(-1)s(-1)), tetramethylbenzidine (6.4 × 10² M(-1)s(-1)) and H₂O₂ (3.9 × M(-1)s(-1)) were obtained. Tau-NHBr demonstrated the following selectivity regarding its reactivity with free amino acids: tryptophan > cysteine ~ methionine > tyrosine. The reactivity of Tau-NHBr was strongly affected by the pH of the medium (for instance with dansylglycine: pH 5.0, 1.1 × 10⁴ M(-1)s(-1), pH 7.0, 9.5 × 10 M(-1)s(-1) and pH 9.0, 1.7 × 10 M(-1)s(-1)), a property that is related to the formation of the dibromamine form at acidic pH (Tau-NBr₂). The formation of singlet oxygen was observed in the reaction between Tau-NHBr and H₂O₂. Tau-NHBr was also able to react with linoleic acid, but with low efficiency compared with HOBr and HOCl. Compared with HOBr, Tau-NHBr was not able to react with nucleosides. In conclusion, the following reactivity sequence was established: HOBr > HOCl > Tau-NHBr > Tau-NHCl. These findings can be very helpful for researchers interested in biological applications of taurine haloamines.

  20. Endogenous Generation and Signaling Actions of Omega-3 Fatty Acid Electrophilic Derivatives

    PubMed Central

    Cipollina, Chiara

    2015-01-01

    Dietary omega-3 polyunsaturated fatty acids (PUFAs) are beneficial for a number of conditions ranging from cardiovascular disease to chronic airways disorders, neurodegeneration, and cancer. Growing evidence has shown that bioactive oxygenated derivatives are responsible for transducing these salutary effects. Electrophilic oxo-derivatives of omega-3 PUFAs represent a class of oxidized derivatives that can be generated via enzymatic and nonenzymatic pathways. Inflammation and oxidative stress favor the formation of these signaling species to promote the resolution of inflammation within a fine autoregulatory loop. Endogenous generation of electrophilic oxo-derivatives of omega-3 PUFAs has been observed in in vitro and ex vivo human models and dietary supplementation of omega-3 PUFAs has been reported to increase their formation. Due to the presence of an α,β-unsaturated ketone moiety, these compounds covalently and reversibly react with nucleophilic residues on target proteins triggering the activation of cytoprotective pathways, including the Nrf2 antioxidant response, the heat shock response, and the peroxisome proliferator activated receptor γ (PPARγ) and suppressing the NF-κB proinflammatory pathway. The endogenous nature of electrophilic oxo-derivatives of omega-3 PUFAs combined with their ability to simultaneously activate multiple cytoprotective pathways has made these compounds attractive for the development of new therapies for the treatment of chronic disorders and acute events characterized by inflammation and oxidative stress. PMID:26339618

  1. Enriched endogenous omega-3 fatty acids in mice protect against global ischemia injury

    PubMed Central

    Luo, Chuanming; Ren, Huixia; Wan, Jian-Bo; Yao, Xiaoli; Zhang, Xiaojing; He, Chengwei; So, Kwok-Fai; Kang, Jing X.; Pei, Zhong; Su, Huanxing

    2014-01-01

    Transient global cerebral ischemia, one of the consequences of cardiac arrest and cardiovascular surgery, usually leads to delayed death of hippocampal cornu Ammonis1 (CA1) neurons and cognitive deficits. Currently, there are no effective preventions or treatments for this condition. Omega-3 (ω-3) PUFAs have been shown to have therapeutic potential in a variety of neurological disorders. Here, we report that the transgenic mice that express the fat-1 gene encoding for ω-3 fatty acid desaturase, which leads to an increase in endogenous ω-3 PUFAs and a concomitant decrease in ω-6 PUFAs, were protected from global cerebral ischemia injury. The results of the study show that the hippocampal CA1 neuronal loss and cognitive deficits induced by global ischemia insult were significantly less severe in fat-1 mice than in WT mice controls. The protection against global cerebral ischemia injury was closely correlated with increased production of resolvin D1, suppressed nuclear factor-kappa B activation, and reduced generation of pro-inflammatory mediators in the hippocampus of fat-1 mice compared with WT mice controls. Our study demonstrates that fat-1 mice with high endogenous ω-3 PUFAs exhibit protective effects on hippocampal CA1 neurons and cognitive functions in a global ischemia injury model. PMID:24875538

  2. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

    PubMed Central

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

    2013-01-01

    In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  3. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid.

    PubMed

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E; Redhi, Godfrey H; Panlilio, Leigh V; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R

    2013-11-01

    In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse.

  4. Modulation of endogenous indole-3-acetic acid biosynthesis in bacteroids within Medicago sativa nodules.

    PubMed

    Bianco, C; Senatore, B; Arbucci, S; Pieraccini, G; Defez, R

    2014-07-01

    To evaluate the dose-response effects of endogenous indole-3-acetic acid (IAA) on Medicago plant growth and dry weight production, we increased the synthesis of IAA in both free-living and symbiosis-stage rhizobial bacteroids during Rhizobium-legume symbiosis. For this purpose, site-directed mutagenesis was applied to modify an 85-bp promoter sequence, driving the expression of iaaM and tms2 genes for IAA biosynthesis. A positive correlation was found between the higher expression of IAA biosynthetic genes in free-living bacteria and the increased production of IAA under both free-living and symbiotic conditions. Plants nodulated by RD65 and RD66 strains, synthetizing the highest IAA concentration, showed a significant (up to 73%) increase in the shoot fresh weight and upregulation of nitrogenase gene, nifH, compared to plants nodulated by the wild-type strain. When these plants were analyzed by confocal microscopy, using an anti-IAA antibody, the strongest signal was observed in bacteroids of Medicago sativa RD66 (Ms-RD66) plants, even when they were located in the senescent nodule zone. We show here a simple system to modulate endogenous IAA biosynthesis in bacteria nodulating legumes suitable to investigate which is the maximum level of IAA biosynthesis, resulting in the maximal increase of plant growth.

  5. Involvement of endogenous salicylic acid in iron-deficiency responses in Arabidopsis.

    PubMed

    Shen, Chenjia; Yang, Yanjun; Liu, Kaidong; Zhang, Lei; Guo, Hong; Sun, Tao; Wang, Huizhong

    2016-07-01

    Several phytohormones have been demonstrated to be involved in iron (Fe) homeostasis. We took advantage of a salicylic acid (SA) biosynthesis defective mutant phytoalexin deficient 4 (pad4: T-DNA Salk_089936) to explore the possible effects of endogenous SA on the morphological and physiological responses to Fe deprivation. The morphological and physiological analysis was carried out between Col-0 and the pad4 mutant. Under an Fe-deficiency treatment, Col-0 showed more severe leaf chlorosis and root growth inhibition compared with the pad4 mutant. The soluble Fe concentrations were significantly higher in pad4 than in Col-0 under the Fe-deficiency treatment. Fe deficiency significantly induced SA accumulation in Col-0 and the loss-of-function of PAD4 blocked this process. The requirement of endogenous SA accumulation for Fe-deficiency responses was confirmed using a series of SA biosynthetic mutants and transgenic lines. Furthermore, a comparative RNA sequencing analysis of the whole seedling transcriptomes between Col-0 and the pad4 mutant was also performed. Based on the transcriptome data, the expression levels of many auxin- and ethylene-response genes were altered in pad4 compared with Col-0. Fe deficiency increases SA contents which elevates auxin and ethylene signalling, thereby activating Fe translocation via the bHLH38/39-mediated transcriptional regulation of downstream Fe genes.

  6. Evaluation of endogenous acidic metabolic products associated with carbohydrate metabolism in tumor cells

    PubMed Central

    Mazzio, Elizabeth A.; Smith, Bruce

    2010-01-01

    Tumor cells have a high tolerance for acidic and hypoxic microenvironments, also producing abundant lactic acid through accelerated glycolysis in the presence or absence of O2. While the accumulation of lactate is thought to be a major contributor to the reduction of pH-circumscribing aggressive tumors, it is not known if other endogenous metabolic products contribute this acidity. Furthermore, anaerobic metabolism in cancer cells bears similarity to homo-fermentative lactic acid bacteria, however very little is known about an alternative pathway that may drive adenosine triphosphate (ATP) production independent of glycolysis. In this study, we quantify over 40 end-products (amines, acids, alcohols, aldehydes, or ketones) produced by malignant neuroblastoma under accelerated glycolysis (+glucose (GLU) supply 1–10 mM) ± mitochondrial toxin; 1-methyl-4-phenyl-pyridinium (MPP+) to abate aerobic respiration to delineate differences between anaerobic vs. aerobic cell required metabolic pathways. The data show that an acceleration of anaerobic glycolysis prompts an expected reduction in extracellular pH (pHex) from neutral to 6.7±0.006. Diverse metabolic acids associated with this drop in acidity were quantified by ionic exchange liquid chromatography (LC), showing concomitant rise in lactate (Ctrls 7.5±0.5 mM; +GLU 12.35±1.3 mM; +GLU + MPP 18.1±1.8 mM), acetate (Ctrl 0.84±0.13 mM: +GLU 1.3±0.15 mM; +GLU + MPP 2.7±0.4 mM), fumarate, and a-ketoglutarate (<10μM) while a range of other metabolic organic acids remained undetected. Amino acids quantified by o-phthalaldehyde precolumn derivatization/electrochemical detection–LC show accumulation of L-alanine (1.6±.052 mM), L-glutamate (285±9.7μM), L-asparagine (202±2.1μM), and L-aspartate (84.2±4.9μM) produced during routine metabolism, while other amino acids remain undetected. In contrast, the data show no evidence for accumulation of acetaldehyde, aldehydes, or ketones (Purpald/2

  7. Spherical Oligo-Silicic Acid SOSA Disclosed as Possible Endogenous Digitalis-Like Factor

    PubMed Central

    Kerek, Franz; Voicu, Victor A.

    2015-01-01

    The Na+/K+-ATPase is a membrane ion-transporter protein, specifically inhibited by digitalis glycosides used in cardiac therapy. The existence in mammals of some endogenous digitalis-like factors (EDLFs) as presumed ATPase ligands is generally accepted. But the chemical structure of these factors remained elusive because no weighable amounts of pure EDLFs have been isolated. Recent high-resolution crystal structure data of Na+/K+-ATPase have located the hydrophobic binding pocket of the steroid glycoside ouabain. It remained uncertain if the EDLF are targeting this steroid-receptor or another specific binding site(s). Our recently disclosed spherical oligo-silicic acids (SOSA) fulfill the main criteria to be identified with the presumed EDL factors. SOSA was found as a very potent inhibitor of the Na+/K+-ATPase, Ca2+-ATPase, H+/K+-ATPase, and of K-dp-ATPase, with IC50 values between 0.2 and 0.5 μg/mL. These findings are even more astonishing while so far, neither monosilicic acid nor its poly-condensed forms have been remarked biologically active. With the diameter ϕ between 1 and 3 nm, SOSA still belong to molecular species definitely smaller than silica nano-particles with ϕ > 5 nm. In SOSA molecules, almost all Si-OH bonds are displayed on the external shell, which facilitates the binding to hydrophilic ATPase domains. SOSA is stable for long term in solution but is sensitive to freeze-drying, which could explain the failure of countless attempts to isolate pure EDLF. There is a strong resemblance between SOSA and vanadates, the previously known general inhibitors of P-type ATPases. SOSA may be generated endogenously by spherical oligomerization of the ubiquitously present monosilicic acid in animal fluids. The structure of SOSA is sensitive to the concentration of Na+, K+, Ca2+, Mg2+, and other ions suggesting a presumably archaic mechanism for the regulation of the ATPase pumps. PMID:25667581

  8. Spherical Oligo-Silicic Acid SOSA Disclosed as Possible Endogenous Digitalis-Like Factor.

    PubMed

    Kerek, Franz; Voicu, Victor A

    2014-01-01

    The Na(+)/K(+)-ATPase is a membrane ion-transporter protein, specifically inhibited by digitalis glycosides used in cardiac therapy. The existence in mammals of some endogenous digitalis-like factors (EDLFs) as presumed ATPase ligands is generally accepted. But the chemical structure of these factors remained elusive because no weighable amounts of pure EDLFs have been isolated. Recent high-resolution crystal structure data of Na(+)/K(+)-ATPase have located the hydrophobic binding pocket of the steroid glycoside ouabain. It remained uncertain if the EDLF are targeting this steroid-receptor or another specific binding site(s). Our recently disclosed spherical oligo-silicic acids (SOSA) fulfill the main criteria to be identified with the presumed EDL factors. SOSA was found as a very potent inhibitor of the Na(+)/K(+)-ATPase, Ca(2+)-ATPase, H(+)/K(+)-ATPase, and of K-dp-ATPase, with IC50 values between 0.2 and 0.5 μg/mL. These findings are even more astonishing while so far, neither monosilicic acid nor its poly-condensed forms have been remarked biologically active. With the diameter ϕ between 1 and 3 nm, SOSA still belong to molecular species definitely smaller than silica nano-particles with ϕ > 5 nm. In SOSA molecules, almost all Si-OH bonds are displayed on the external shell, which facilitates the binding to hydrophilic ATPase domains. SOSA is stable for long term in solution but is sensitive to freeze-drying, which could explain the failure of countless attempts to isolate pure EDLF. There is a strong resemblance between SOSA and vanadates, the previously known general inhibitors of P-type ATPases. SOSA may be generated endogenously by spherical oligomerization of the ubiquitously present monosilicic acid in animal fluids. The structure of SOSA is sensitive to the concentration of Na(+), K(+), Ca(2+), Mg(2+), and other ions suggesting a presumably archaic mechanism for the regulation of the ATPase pumps.

  9. Endogenous Polysialic Acid Based Micelles for Calmodulin Antagonist Delivery against Vascular Dementia.

    PubMed

    Wang, Xiao-Juan; Gao, Yin-Ping; Lu, Nan-Nan; Li, Wei-Shuo; Xu, Ji-Fang; Ying, Xiao-Ying; Wu, Gang; Liao, Mei-Hua; Tan, Chao; Shao, Ling-Xiao; Lu, Ying-Mei; Zhang, Chen; Fukunaga, Kohji; Han, Feng; Du, Yong-Zhong

    2016-12-28

    Clinical treatment for vascular dementia still remains a challenge mainly due to the blood-brain barrier (BBB). Here, a micelle based on polysialic acid (PSA), which is a hydrophilic and endogenous carbohydrate polymer, was designed to deliver calmodulin antagonist for therapy of vascular dementia. PSA was first chemically conjugated with octadecylamine (ODA), and the obtained PSA-ODA copolymer could self-assemble into micelle in aqueous solution with a 120.0 μg/mL critical micelle concentration. The calmodulin antagonist loaded PSA-ODA micelle, featuring sustained drug release behavior over a period of 72 h with a 3.6% (w/w) drug content and a 107.0 ± 4.0 nm size was then fabricated. The PSA-ODA micelle could cross the BBB mainly via active endocytosis by brain endothelial cells followed by transcytosis. In a water maze test for spatial learning, calmodulin antagonist loaded PSA-ODA micelle significantly reduced the escape latencies of right unilateral common carotid arteries occlusion (rUCCAO) mice with dosage significantly reduced versus free drug. The decrease of hippocampal phospho-CaMKII (Thr286/287) and phospho-synapsin I (Ser603) was partially restored in rUCCAO mice following calmodulin antagonist loaded PSA-ODA micelle treatment. Consistent with the restored CaMKII phosphorylation, the elevation of BrdU/NeuN double-positive cells in the same context was also observed. Overall, the PSA-ODA micelle developed from the endogenous material might promote the development of therapeutic approaches for improving the efficacy of brain-targeted drug delivery and have great potential for vascular dementia treatment.

  10. Dual Role of Endogenous Serotonin in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis

    PubMed Central

    Rapalli, Alberto; Bertoni, Simona; Arcaro, Valentina; Saccani, Francesca; Grandi, Andrea; Vivo, Valentina; Cantoni, Anna M.; Barocelli, Elisabetta

    2016-01-01

    Background and Aims: Changes in gut serotonin (5-HT) content have been described in Inflammatory Bowel Disease (IBD) and in different experimental models of colitis: the critical role of this monoamine in the pathogenesis of chronic gastrointestinal inflammation is gradually emerging. Aim of the present study was to evaluate the contribution of endogenous 5-HT through the activation of its specific receptor subtypes to the local and systemic inflammatory responses in an experimental model of IBD. Materials and Methods: Colitis was induced by intrarectal 2,4,6-TriNitroBenzene Sulfonic acid in mice subacutely treated with selective antagonists of 5-HT1A (WAY100135), 5-HT2A (Ketanserin), 5-HT3 (Ondansetron), 5-HT4 (GR125487), 5-HT7 (SB269970) receptors and with 5-HT1A agonist 8-Hydroxy-2-(di-n-propylamino)tetralin. Results: Blockade of 5-HT1A receptors worsened TNBS-induced local and systemic neutrophil recruitment while 5-HT1A agonist delayed and mitigated the severity of colitis, counteracting the increase in colonic 5-HT content. On the contrary, blockade of 5-HT2A receptors improved global health conditions, reduced colonic morphological alterations, down-regulated neutrophil recruitment, inflammatory cytokines levels and colonic apoptosis. Antagonism of 5-HT3, 5-HT4, and 5-HT7 receptor sites did not remarkably affect the progression and outcome of the pathology or only slightly improved it. Conclusion: The prevailing deleterious contribution given by endogenous 5-HT to inflammation in TNBS-induced colitis is seemingly mediated by 5-HT2A and, to a lesser extent, by 5-HT4 receptors and coexists with the weak beneficial effect elicited by 5-HT1A stimulation. These findings suggest how only a selective interference with 5-HT pro-inflammatory actions may represent an additional potential therapeutic option for intestinal inflammatory disorders. PMID:27047383

  11. Enriched Endogenous Omega-3 Polyunsaturated Fatty Acids Protect Cortical Neurons from Experimental Ischemic Injury.

    PubMed

    Shi, Zhe; Ren, Huixia; Luo, Chuanming; Yao, Xiaoli; Li, Peng; He, Chengwei; Kang, Jing-X; Wan, Jian-Bo; Yuan, Ti-Fei; Su, Huanxing

    2016-11-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential in a variety of neurological disorders, including ischemic stroke. However, the underlying mechanisms still lack investigation. Here, we report that cultured cortical neurons isolated from fat-1 mice with high endogenous n-3 PUFAs were tolerant to oxygen-glucose deprivation/reperfusion (OGD/R) injury. Fat-1 neurons exhibited significantly attenuated reactive oxygen species (ROS) activation induced by OGD/R injury, upregulated antiapoptotic proteins Bcl-2 and Bcl-xL, and reduced cleaved caspase-3. Exogenous administration of docosahexaenoic acid (DHA), a major component of the n-3 PUFA family, resulted in similar protective effects on cultured cortex neurons. We further verified the protective effects of n-3 PUFAs in vivo, using a mini ischemic model with a reproducible cortical infarct and manifest function deficits by occlusion of the distal branch of the middle cerebral artery with focused femtosecond laser pulses. The Fat-1 animals showed decreased ROS expression and higher level of glutathione in the injured brain, associated with improved functional recovery. We therefore provide evidence that n-3 PUFAs exert their protective effects against ischemic injury both in vitro and in vivo, partly through inhibiting ROS activation.

  12. Neutral detergent fiber increases endogenous ileal losses but has no effect on ileal digestibility of amino acids in growing pigs.

    PubMed

    Mariscal-Landín, Gerardo; Reis de Souza, Tércia Cesária; Bayardo Uribe, Alejandro

    2017-02-01

    Two experiments were conducted to determine the effect of neutral detergent fiber (NDF) on endogenous amino acids and protein ileal losses; and also apparent ileal digestibility (AID), and standardized ileal digestibility (SID) of amino acids and crude protein. Sixteen barrows were fed four protein-free diets containing graded NDF levels in Experiment 1. NDF was a mixture of sugarcane bagasse and corn leaves (SBCL). Twenty-four barrows were fed diets with soybean protein concentrate (SPC) or casein as protein sources and SBCL or corncobs (CC) as NDF sources in Experiment 2. In Experiment 1, a linear increase (P < 0.05) in endogenous amino acid and protein ileal losses was observed with increased NDF levels, except for arginine, histidine, methionine and proline. In Experiment 2, protein (P < 0.001) and NDF (P < 0.01) sources significantly affected AID of dry matter, which was higher in casein diets (71.7%) and CC diets (70.7%). Protein and NDF sources significantly affected (P < 0.05) SID of crude protein, which was higher in casein diets (92.8%) and CC diets (92.7%). NDF source had no effect (P > 0.05) on SID of amino acids. Overall, this study showed that NDF increased endogenous amino acid and protein ileal losses, but did not affect ileal digestibility of amino acids.

  13. Osmotic stress, endogenous abscisic acid and the control of leaf morphology in Hippuris vulgaris L

    NASA Technical Reports Server (NTRS)

    Goliber, T. E.; Feldman, L. J.

    1989-01-01

    Previous reports indicate that heterophyllous aquatic plants can be induced to form aerial-type leaves on submerged shoots when they are grown in exogenous abscisic acid (ABA). This study reports on the relationship between osmotic stress (e.g. the situation encountered by a shoot tip when it grows above the water surface), endogenous ABA (as measured by gas chromatography-electron capture detector) and leaf morphology in the heterophyllous aquatic plant, Hippuris vulgaris. Free ABA could not be detected in submerged shoots of H. vulgaris but in aerial shoots ABA occurred at ca. 40 ng (g fr wt)-1. When submerged shoots were osmotically stressed ABA appeared at levels of 26 to 40 ng (g fr wt)-1. These and other data support two main conclusions: (1) Osmotically stressing a submerged shoot causes the appearance of detectable levels of ABA. (2) The rise of ABA in osmotically stressed submerged shoots in turn induces a change in leaf morphology from the submerged to the aerial form. This corroborates the hypothesis that, in the natural environment, ABA levels rise in response to the osmotic stress encountered when a submerged shoot grows up through the water/air interface and that the increased ABA leads to the production of aerial-type leaves.

  14. Quinolinic Acid, an endogenous molecule combining excitotoxicity, oxidative stress and other toxic mechanisms.

    PubMed

    Pérez-De La Cruz, Verónica; Carrillo-Mora, Paul; Santamaría, Abel

    2012-01-01

    Quinolinic acid (QUIN), an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington's disease, Alzheimer's disease, schizophrenia, HIV associated dementia (HAD) etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS) has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca(2+) concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity.

  15. Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

    PubMed Central

    Pérez-De La Cruz, Verónica; Carrillo-Mora, Paul; Santamaría, Abel

    2012-01-01

    Quinolinic acid (QUIN), an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington’s disease, Alzheimer’s disease, schizophrenia, HIV associated dementia (HAD) etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS) has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca2+ concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity. PMID:22408367

  16. Endogenously elevated n-3 polyunsaturated fatty acids alleviate acute ethanol-induced liver steatosis.

    PubMed

    Huang, Wei; Wang, Bin; Li, Xiangyong; Kang, Jing X

    2015-01-01

    Effective means for the prevention of alcohol-induced liver disease, a global health problem, have yet to be developed. We evaluated whether the high endogenous levels of omega-3 polyunsaturated acids (n-3 PUFA) in fat-1 transgenic mice could protect them against acute ethanol-induced liver steatosis. We induced alcoholic liver steatosis in 9-week-old male heterozygous fat-1 mice and their wild-type (WT) male littermates through three oral gavages of 60% ethanol at 4.7 g/kg body weight. Hepatic lipid accumulation was significantly increased in both alcohol treatment groups, but by much less in the fat-1 group compared with the WT group. Fat-1 mice exhibited significantly lower levels of total hepatic/plasma TG and plasma alanine aminotransferase activity. Accordingly, hepatic expression of lipogenesis-related genes (e.g., SREBP-1c, FAS, and SCD-1) and plasma levels of inflammatory cytokines (e.g., IL-6, TNF-α, and MCP-1) were reduced in the fat-1 mice. Furthermore, decreased hepatic expression of cytochrome P450 2E1 (CYP2E1) and increased hepatic levels of PPAR-α and HO-1 were observed in the fat-1 mice, compared to the WT mice. These findings show that elevated tissue n-3 PUFA protect against acute ethanol-induced liver steatosis in fat-1 mice, possibly through the down-regulation of hepatic lipogenesis, inflammatory response, and oxidative stress.

  17. Chenodeoxycholic acid, an endogenous FXR ligand alters adipokines and reverses insulin resistance.

    PubMed

    Shihabudeen, Mohamed Sham; Roy, Debasish; James, Joel; Thirumurugan, Kavitha

    2015-10-15

    Adipose tissue secretes adipokines that regulate insulin sensitivity in adipocytes and other peripheral tissues critical to glucose metabolism. Insulin resistance is associated with severe alterations in adipokines characterized by release of increased pro-inflammatory cytokines and decreased anti-inflammatory cytokines from adipose tissue. The role of Farnesoid X receptor (FXR) activation on adipokines in relation to adipose tissue inflammation and insulin resistance is not completely explored. For the first time, we have evaluated the ability of Chenodeoxycholic acid (CDCA), an endogenous FXR ligand, in restoring the disturbance in adipokine secretion and insulin resistance in palmitate treated 3T3-L1 cells and adipose tissues of High fat diet (HFD) rats. CDCA suppressed several of the tested pro-inflammatory adipokines (TNF-α, MCP-1, IL-6, Chemerin, PAI, RBP4, resistin, vaspin), and enhanced the major anti-inflammatory and insulin sensitizing adipokines (adiponectin, leptin). CDCA suppressed the activation of critical inflammatory regulators such as NF-κB and IKKβ which are activated by palmitate treatment in differentiated cells and HFD in rats. We show the altered adipokines in insulin resistance, its association with inflammatory regulators, and the role of CDCA in amelioration of insulin resistance by modulation of adipokines.

  18. Glutamate-evoked release of endogenous brain dopamine: inhibition by an excitatory amino acid antagonist and an enkephalin analogue.

    PubMed Central

    Jhamandas, K.; Marien, M.

    1987-01-01

    The present study examined the effect of a selective delta-opioid receptor agonist [D-Ala2-D-Leu5] enkephalin (DADL) on the spontaneous and the L-glutamic acid (L-Glu)-evoked release of endogenous dopamine from superfused slices of rat caudate-putamen. The amount of dopamine in slice superfusates was measured by a sensitive method employing high-performance liquid chromatography with electrochemical detection (h.p.l.c.-e.d.) after a two-step separation procedure. The spontaneous release of endogenous dopamine was partially dependent on Ca2+, enhanced in Mg2+-free superfusion medium, partially reduced by tetrodotoxin (TTX, 0.3 microM), partially reduced by the putative excitatory amino acid receptor antagonist DL-2-amino-7-phosphonoheptanoic acid (DL-APH, 1 mM), and increased 10 fold by the dopamine uptake blocker, nomifensine (10 microM). DADL (5 and 50 nM) did not significantly affect spontaneous dopamine release. L-Glu (0.1-10 mM) produced a concentration-dependent release of endogenous dopamine from slices of caudate-putamen. This effect was Ca2+-dependent, strongly inhibited by 1.2 mM Mg2+, attenuated by DL-APH (1 mM), attenuated by TTX (0.3 microM), and enhanced by nomifensine (10 microM). In the presence of nomifensine DADL (50 nM) reduced significantly the L-Glu-evoked release of endogenous dopamine by 20%. The inhibitory effect of DADL was blocked by 10 microM naloxone. These results indicate that L-Glu stimulates the Ca2+-dependent release of endogenous dopamine in the caudate-putamen by activation of N-methy-D-aspartate-type of excitatory amino acid receptors. This release can be selectively modified by the delta-opioid agonist DADL in a naloxone-sensitive manner. PMID:2884003

  19. Nitration of endogenous para-hydroxyphenylacetic acid and the metabolism of nitrotyrosine.

    PubMed Central

    Mani, Ali R; Pannala, Ananth S; Orie, Nelson N; Ollosson, Richard; Harry, David; Rice-Evans, Catherine A; Moore, Kevin P

    2003-01-01

    Reactive nitrogen species, such as peroxynitrite, can nitrate tyrosine in proteins to form nitrotyrosine. Nitrotyrosine is metabolized to 3-nitro-4-hydroxyphenylacetic acid (NHPA), which is excreted in the urine. This has led to the notion that measurement of urinary NHPA may provide a time-integrated index of nitrotyrosine formation in vivo. However, it is not known whether NHPA is derived exclusively from metabolism of nitrotyrosine, or whether it can be formed by nitration of circulating para -hydroxyphenylacetic acid (PHPA), a metabolite of tyrosine. In the present study, we have developed a gas chromatography MS assay for NHPA and PHPA to determine whether or not NHPA can be formed directly by nitration of PHPA. Following the injection of nitrotyrosine, 0.5+/-0.16% of injected dose was recovered unchanged as nitrotyrosine, and 4.3+/-0.2% as NHPA in the urine. To determine whether or not NHPA could be formed by the nitration of PHPA, deuterium-labelled PHPA ([(2)H(6)]PHPA) was injected, and the formation of deuterated NHPA ([(2)H(5)]NHPA) was measured. Of the infused [(2)H(6)]PHPA, 78+/-2% was recovered in the urine unchanged, and approx. 0.23% was recovered as [(2)H(5)]NHPA. Since the plasma concentration of PHPA is markedly higher than free nitrotyrosine (approx. 400-fold), the nitration of high-circulating endogenous PHPA to form NHPA becomes very significant and accounts for the majority of NHPA excreted in urine. This is the first study to demonstrate that NHPA can be formed by nitration of PHPA in vivo, and that this is the major route for its formation. PMID:12797864

  20. Increased dietary sodium chloride concentrations reduce endogenous amino acid flow and influence the physiological response to the ingestion of phytic acid by broiler chickens.

    PubMed

    Cowieson, A J; Bedford, M R; Ravindran, V; Selle, P H

    2011-10-01

    A total of 240 Ross 308 broilers were used to investigate the effect of sodium (1·5 or 2·5 g/kg), phytate-P (0 or 3·2 g/kg), and phytase (0 or 1000 FTU/kg; 2x2x2 factorial) on endogenous amino acid flow using the enzyme-hydrolysed casein method. The ingestion of phytate increased endogenous amino acid flow (∼30%) compared with the phytate-free control diets. Phytase reduced endogenous amino acid flow only when fed in concert with phytate, resulting in a significant phytate x phytase interaction. Increasing dietary sodium concentration from 1·5 to 2·5 g/kg reduced endogenous amino acid flow by around 10%. This reduction of endogenous flow was particularly evident in diets which contained phytate, resulting in a significant sodium x phytate interaction for several amino acids, including Thr and Ser. Further, high sodium concentrations muted the effect of phytase resulting in a significant sodium x phytase interaction for some amino acids. The concentration of Asp, Thr, Ser and some other amino acids was increased in the endogenous protein in response to the ingestion of phytate. Both sodium and phytase essentially restored the composition of endogenous protein to that of the phytate-free control. Further, as both sodium and phytase had similar effects there were significant interactions between sodium and phytase for most amino acids, such that one was only effective in the absence of the other. These data confirm previous reports that phytate is a nutritional aggressor, causing quantitative and qualitative changes in endogenous protein flow. However, this is the first report which has shown that dietary sodium concentrations play a role in the severity of this antinutritional effect and consequently may blunt the efficacy of exogenous phytase. The mechanism is obscure, though it has been previously demonstrated that sodium can disrupt phytate:protein complexes, thus mitigating one of the mechanisms by which phytate exerts its antinutritional effect.

  1. Exogenous amino acids stimulate net muscle protein synthesis in the elderly.

    PubMed Central

    Volpi, E; Ferrando, A A; Yeckel, C W; Tipton, K D; Wolfe, R R

    1998-01-01

    We have investigated the response of amino acid transport and protein synthesis in healthy elderly individuals (age 71+/-2 yr) to the stimulatory effect of increased amino acid availability. Muscle protein synthesis and breakdown, and amino acid transport were measured in the postabsorptive state and during the intravenous infusion of an amino acid mixture. Muscle-free amino acid kinetics were calculated by means of a three compartment model using data obtained by femoral arterio-venous catheterization and muscle biopsies from the vastus lateralis during the infusion of stable isotope tracers of amino acids. In addition, muscle protein fractional synthetic rate (FSR) was measured. Peripheral amino acid infusion significantly increased amino acid delivery to the leg, amino acid transport, and muscle protein synthesis when measured either with the three compartment model (P < 0.05) or with the traditional precursor-product approach (FSR increased from 0. 0474+/-0.0054 to 0.0940+/-0.0143%/h, P < 0.05). Because protein breakdown did not change during amino acid infusion, a positive net balance of amino acids across the muscle was achieved. We conclude that, although muscle mass is decreased in the elderly, muscle protein anabolism can nonetheless be stimulated by increased amino acid availability. We thus hypothesize that muscle mass could be better maintained with an increased intake of protein or amino acids. PMID:9576765

  2. Acute supplementation of amino acids increases net protein accretion in IUGR fetal sheep.

    PubMed

    Brown, Laura D; Rozance, Paul J; Thorn, Stephanie R; Friedman, Jacob E; Hay, William W

    2012-08-01

    Placental insufficiency decreases fetal amino acid uptake from the placenta, plasma insulin concentrations, and protein accretion, thus compromising normal fetal growth trajectory. We tested whether acute supplementation of amino acids or insulin into the fetus with intrauterine growth restriction (IUGR) would increase net fetal protein accretion rates. Late-gestation IUGR and control (CON) fetal sheep received acute, 3-h infusions of amino acids (with euinsulinemia), insulin (with euglycemia and euaminoacidemia), or saline. Fetal leucine metabolism was measured under steady-state conditions followed by a fetal muscle biopsy to quantify insulin signaling. In CON, increasing amino acid delivery rates to the fetus by 100% increased leucine oxidation rates by 100%. In IUGR, amino acid infusion completely suppressed fetal protein breakdown rates but increased leucine oxidation rate by only 25%, resulting in increased protein accretion rates by 150%. Acute insulin infusion, however, had very little effect on amino acid delivery rates, fetal leucine disposal rates, or fetal protein accretion rates in CON or IUGR fetuses despite robust signaling of the fetal skeletal muscle insulin-signaling cascade. These results indicate that, when amino acids are given directly into the fetal circulation independently of changes in insulin concentrations, IUGR fetal sheep have suppressed protein breakdown rates, thus increasing net fetal protein accretion.

  3. The release of endogenous amino acids from the rat visual cortex.

    PubMed

    Clark, R M; Collins, G G

    1976-11-01

    The release of endogenous taurine, GABA, glycine, aspartate, glutamate, glutamine and alanine from the rat visual cortex was measured using a cortical cup technique. The electrocorticogram (ECoG) was monitored throughout most experiments. 2. Spreading depression, evoked by the dropwise placement of 10% KCl solution on to the brain outside the cup was associated with a significant increase in the release of GABA and glutamine but a marked fall in that of glutamate. The evoked release of GABA and glutamate but not of glutamine was Ca2+ dependent. 3. A solution containing 50 mM-K+ placed within the cup elicited a significant increase in the release of taurine and GABA, whereas 100 mM-K+ additionally released aspartate and glutamate. The K+-evoked release of these amino acids with the exceptions of taurine and glutamine was Ca2+-dependent. 4. Three series of experiments were carried out in which the preparations were stimulated electrically. Bipolar stimulation (100 Hz, 1 msec pulse width, 2-5 mA for 5 min) with the electrode within the cup was followed by significant increases in taurine, GABA and glutamate release; using a 5 mA current, there was an additional release of aspartate and alanine. Only the evoked release of GABA and glutamate was Ca2+ dependent. 5. In the second and third series of experiments, the electrode was sited adjacent to the cup or on the contralateral cortex respectively. Following stimulation (100 Hz, 1 msec pulse width, 2-5 mA for 5 min) there was a significant increase in taurine and GABA release and a significant fall in the release of aspartate and glutamate. With the exception of taurine, these changes in release were Ca2+ dependent. Reducing the stimulus current to 1-5 mA or the period of stimulation to 2-5 min initiated similar but statistically insignificant changes in release. A range (10-100 Hz) of stimulation frequencies was examined: the evoked release of GABA was linearly related to frequency whereas that of taurine was frequency

  4. Exogenous γ-aminobutyric Acid (GABA) Application Improved Early Growth, Net Photosynthesis, and Associated Physio-Biochemical Events in Maize

    PubMed Central

    Li, Wu; Liu, Jianhua; Ashraf, Umair; Li, Gaoke; Li, Yuliang; Lu, Wenjia; Gao, Lei; Han, Fuguang; Hu, Jianguang

    2016-01-01

    γ-aminobutyric acid (GABA) is an endogenous signaling molecule and involved in growth regulations and plant development, however, a little information is available on the consequences of exogenous GABA application on growth, development, and associated physio-biochemical processes in maize. The present study examined the GABA-induced regulations in early growth, net photosynthetic rate, gas exchange, osmoregulation, and enzymatic activities in three maize cultivars, i.e., Yuecainuo 6, Zhengtian 68, and Yuecainuo 2. Two levels of GABA, i.e., 0 mg L-1 and 50 mg L-1, in solution form, with total application volume of 100 ml per pot containing 15 maize seedlings were exogenously applied. Results revealed that exogenous GABA application improved seedling growth in terms of seedling length and biomass accumulation in all maize cultivars at both 3 and 7 days after treatment (DAT). It also promoted net photosynthesis and variably affected gas exchange attributes, i.e., stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr), as well as leaves SPAD value. Furthermore, lipid peroxidation [in terms of malondialdehyde (MDA)] under GABA treated maize seedlings were also remained variable; however, osmolyte accumulation (protein and proline) and activities of anti-oxidants enzymes, i.e., super-oxide dismutase and peroxidase were also affected differently at both 3 and 7 DAT in all maize cultivars. Furthermore, enzymes involved in nitrogen metabolism, e.g., nitrate reductase and glutamine synthetase were improved. These results suggest the involvement of GABA in various physio-metablical mechanisms which might lead to improvement in morphological growth of maize. In future, research is still needed at molecular and genetic levels to unravel the involvement of GABA-mediated regulations in growth and its associated physio-biochemical mechanisms. PMID:27446149

  5. Exogenous γ-aminobutyric Acid (GABA) Application Improved Early Growth, Net Photosynthesis, and Associated Physio-Biochemical Events in Maize.

    PubMed

    Li, Wu; Liu, Jianhua; Ashraf, Umair; Li, Gaoke; Li, Yuliang; Lu, Wenjia; Gao, Lei; Han, Fuguang; Hu, Jianguang

    2016-01-01

    γ-aminobutyric acid (GABA) is an endogenous signaling molecule and involved in growth regulations and plant development, however, a little information is available on the consequences of exogenous GABA application on growth, development, and associated physio-biochemical processes in maize. The present study examined the GABA-induced regulations in early growth, net photosynthetic rate, gas exchange, osmoregulation, and enzymatic activities in three maize cultivars, i.e., Yuecainuo 6, Zhengtian 68, and Yuecainuo 2. Two levels of GABA, i.e., 0 mg L(-1) and 50 mg L(-1), in solution form, with total application volume of 100 ml per pot containing 15 maize seedlings were exogenously applied. Results revealed that exogenous GABA application improved seedling growth in terms of seedling length and biomass accumulation in all maize cultivars at both 3 and 7 days after treatment (DAT). It also promoted net photosynthesis and variably affected gas exchange attributes, i.e., stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr), as well as leaves SPAD value. Furthermore, lipid peroxidation [in terms of malondialdehyde (MDA)] under GABA treated maize seedlings were also remained variable; however, osmolyte accumulation (protein and proline) and activities of anti-oxidants enzymes, i.e., super-oxide dismutase and peroxidase were also affected differently at both 3 and 7 DAT in all maize cultivars. Furthermore, enzymes involved in nitrogen metabolism, e.g., nitrate reductase and glutamine synthetase were improved. These results suggest the involvement of GABA in various physio-metablical mechanisms which might lead to improvement in morphological growth of maize. In future, research is still needed at molecular and genetic levels to unravel the involvement of GABA-mediated regulations in growth and its associated physio-biochemical mechanisms.

  6. Endogenous excitatory amino acid neurotransmission regulates thyroid-stimulating hormone and thyroid hormone secretion in conscious freely moving male rats.

    PubMed

    Arufe, M C; Durán, R; Perez-Vences, D; Alfonso, M

    2002-04-01

    The role of neurotransmission of endogenous excitatory amino acid (EAA) on serum thyroid hormones and thyroid-stimulating hormone (TSH) levels was examined in conscious and freely moving adult male Sprague-Dawley rats. The rats were cannulated at the third ventricle 2 d before the experiments. Several glutamate receptor agonists, such as kainic acid and domoic acid, and antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and dizocilpine (MK-801) were administered into the third ventricle. Serum TSH levels were assesed by radioimmunoassay, and serum thyroid hormone levels were assessed by enzyme immunoassay. The results showed that the administration of CNQX and MK-801 produced a decrease in serum levels of TSH and thyroid hormones. The administration of kainic acid and domoic acid increased TSH concentrations, whereas CNQX completely blocked the release of TSH induced by kainic acid and domoic acid. These results suggest the importance of endogenous EAA in the regulation of hormone secretion from the pituitary-thyroid axis, as well as the role of the N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the stimulatory effect of EAAs on the pituitary-thyroid axis.

  7. Endogenous Synthesis of Amino Acids Limits Growth, Lactation, and Reproduction in Animals12

    PubMed Central

    Hou, Yongqing; Yao, Kang; Yin, Yulong; Wu, Guoyao

    2016-01-01

    Amino acids (AAs) are building blocks of protein. Eight AAs (Ala, Asn, Asp, Glu, Gln, Gly, Pro, and Ser) are formed by all animals, whereas de novo synthesis of Arg occurs in a species-specific manner in most mammals (e.g., humans, pigs, and rats). Synthesizable AAs were traditionally classified as nutritionally nonessential for animals, because they were thought to be formed in sufficient amounts. However, this assumption is not supported by evidence showing that 1) rats grow slowly when their diets do not contain Arg, Glu, or Gln despite adequate provision of all other proteinogenous AAs; 2) pigs cannot achieve maximum growth, lactation, or reproduction performance when fed corn- and soybean meal-based diets meeting National Research Council–recommended requirements of protein and AAs without supplemental Arg, Glu, Gln, Gly, or Pro; 3) chickens exhibit increases in lean tissue gain and feed efficiency when their diets are supplemented with Glu, Gln, Gly, and Pro; 4) lactating cows cannot obtain maximum milk protein production without a postruminal supply of Gln or Pro; 5) fish cannot achieve maximum growth when diets do not contain Gln or Pro; and 6) men fail to sustain spermatogenesis when fed an Arg-deficient diet. Quantitative analysis of nitrogen metabolism showed that AA synthesis in animals is constrained by both precursor availability and enzyme activity. Taken together, these findings support the conclusion that the endogenous synthesis of AAs limits growth, lactation, and reproduction in animals. This new knowledge can guide the optimization of human nutrition for improving health and well-being. PMID:26980816

  8. Endogenous Synthesis of Amino Acids Limits Growth, Lactation, and Reproduction in Animals.

    PubMed

    Hou, Yongqing; Yao, Kang; Yin, Yulong; Wu, Guoyao

    2016-03-01

    Amino acids (AAs) are building blocks of protein. Eight AAs (Ala, Asn, Asp, Glu, Gln, Gly, Pro, and Ser) are formed by all animals, whereas de novo synthesis of Arg occurs in a species-specific manner in most mammals (e.g., humans, pigs, and rats). Synthesizable AAs were traditionally classified as nutritionally nonessential for animals, because they were thought to be formed in sufficient amounts. However, this assumption is not supported by evidence showing that 1) rats grow slowly when their diets do not contain Arg, Glu, or Gln despite adequate provision of all other proteinogenous AAs; 2) pigs cannot achieve maximum growth, lactation, or reproduction performance when fed corn- and soybean meal-based diets meeting National Research Council-recommended requirements of protein and AAs without supplemental Arg, Glu, Gln, Gly, or Pro; 3) chickens exhibit increases in lean tissue gain and feed efficiency when their diets are supplemented with Glu, Gln, Gly, and Pro; 4) lactating cows cannot obtain maximum milk protein production without a postruminal supply of Gln or Pro; 5) fish cannot achieve maximum growth when diets do not contain Gln or Pro; and 6) men fail to sustain spermatogenesis when fed an Arg-deficient diet. Quantitative analysis of nitrogen metabolism showed that AA synthesis in animals is constrained by both precursor availability and enzyme activity. Taken together, these findings support the conclusion that the endogenous synthesis of AAs limits growth, lactation, and reproduction in animals. This new knowledge can guide the optimization of human nutrition for improving health and well-being.

  9. Endogenous n-3 Polyunsaturated Fatty Acids Attenuate T Cell-Mediated Hepatitis via Autophagy Activation

    PubMed Central

    Li, Yanli; Tang, Yuan; Wang, Shoujie; Zhou, Jing; Zhou, Jia; Lu, Xiao; Bai, Xiaochun; Wang, Xiang-Yang; Chen, Zhengliang; Zuo, Daming

    2016-01-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A) was administered intravenously to wild-type (WT) and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase activity, and inhibited production of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-17A, and IFN-γ). In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n-3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism and could be exploited as a new therapeutic approach for autoimmune hepatitis. PMID:27679638

  10. A Novel Synthetic Pathway Enables Microbial Production of Polyphenols Independent from the Endogenous Aromatic Amino Acid Metabolism.

    PubMed

    Kallscheuer, Nicolai; Vogt, Michael; Marienhagen, Jan

    2016-12-14

    Numerous plant polyphenols have potential applications as pharmaceuticals or nutraceuticals. Stilbenes and flavonoids as most abundant polyphenols are synthesized from phenylpropanoids, which are exclusively derived from aromatic amino acids in nature. Several microorganisms were engineered for the synthesis of biotechnologically interesting plant polyphenols; however, low activity of heterologous ammonia lyases, linking endogenous microbial aromatic amino acid biosynthesis to phenylpropanoid synthesis, turned out to be the limiting step during microbial synthesis. We here developed an alternative strategy for polyphenol production from cheap benzoic acids by reversal of a β-oxidative phenylpropanoid degradation pathway avoiding any ammonia lyase activity. The synthetic pathway running in the non-natural direction is feasible with respect to thermodynamics and involved reaction mechanisms. Instantly, product titers of 5 mg/L resveratrol could be achieved in recombinant Corynebacterium glutamicum strains indicating that phenylpropanoid synthesis from 4-hydroxybenzoic acid can in principle be implemented independently from aromatic amino acids and ammonia lyase activity.

  11. Cut-off net acid generation pH in predicting acid-forming potential in mine spoils.

    PubMed

    Liao, B; Huang, L N; Ye, Z H; Lan, C Y; Shu, W S

    2007-01-01

    Acidification of mine wastes can lead to a series of environmental problems, such as acid drainage, heavy metal mobilization, and ecosystem degradation. Prediction of acid-forming potential is one of the key steps in management of sulfide-bearing mine wastes. In this paper, the acid-forming potential of 180 mine waste samples collected from 17 mine sites in China were studied using a net acid generation (NAG) method. The samples contained different contents of total sulfur (ranging from 0.6 to 200 g kg(-1)), pyritic sulfur (ranging from 0 to 100 g kg(-1)), and acid neutralization capacity (ANC, ranging from -41 to 274 kg H2SO4 t(-1)). Samples with high acid-forming potential are generally due to their high sulfur content or low acid neutralization capacity. After the samples were oxidized by H2O2, the amounts of acid generation and the final NAG pH were measured. Results indicated that the final NAG pH gave a well-defined demarcation between acid-forming and non-acid-forming materials. Samples with final NAG pH >or= 5 could be classified as non-acid-forming materials, while those with NAG pH acid-forming materials. Materials with NAG pH > 2.5, but < 5, had low risk of being acid-forming. The confirmation of cut-off NAG pH will be used as a rapid and cost-effective operational monitoring tool for the in-pit prediction of acid-forming potential of mine wastes and classification of waste types.

  12. The First Observation of Domoic Acid in Plankton Net Samples from the Sea of Marmara, Turkey.

    PubMed

    Dursun, Fuat; Yurdun, Türkan; Ünlü, Selma

    2016-01-01

    This study reports the first evidence of domoic acid (DA), an algal neurotoxin produced by the genus Pseudo-nitzschia, from plankton net samples collected in the Sea of Marmara in December, 2010 and February, 2011. DA concentrations of plankton net samples were analyzed by high-performance liquid chromatography (HPLC), using the fluorenylmethoxycarbonyl fluorescence derivatization technique (detection limit 0.2 ng DA). The biotoxin concentrations in samples from coastal waters varied between 0.96 and 5.25 µg DA/mL. We also investigated possible correlations between physicochemical parameters and DA concentration. The DA levels appear to be correlated negatively with silica and nitrite concentrations for both sampling periods. These data may be used to evaluate the probability of finding similar conditions in coastal waters of the Sea of Marmara in order to determine the potential risks to local aquaculture and fisheries.

  13. Dietary starch sources affect net portal appearance of amino acids and glucose in growing pigs.

    PubMed

    Li, T-J; Dai, Q-Z; Yin, Y-L; Zhang, J; Huang, R-L; Ruan, Z; Deng, Z; Xie, M

    2008-05-01

    Four male pigs (Duroc × Landrace × Yorkshire; average initial (mean ± SEM) BW = 22.5 ± 1.1 kg), fitted with permanent catheters in the portal vein, ileal vein and carotid artery, were used in a 4 × 4 Latin square experimental design to measure the effect of dietary starch sources on the net portal appearance of glucose and amino acids. Dietary starch sources were resistant starch (RS), maize, sticky rice and brown rice. Diets were provided at 0730, 1530 and 2330 h during a 6-day adjustment period and 1-day collection period. On day 7 of each period, blood samples were collected from the portal vein and carotid artery at 0730 h (prior to feeding) and hourly up to 8 h after meal. Blood samples were used to determine glucose, amino acid, packed cell volume and partial pressure of oxygen (pO2). When calculated per 100 g feed intake, cumulative portal glucose appearance was lower (P < 0.05) for resistant starch than for maize, sticky rice or brown rice up to 8 h after the meal. Cumulative portal glucose appearance was higher (P < 0.05) for sticky rice and brown rice than for other diets until 4 h after the meal, but maize had higher cumulative glucose appearance after 4 h. Net cumulative portal concentrations of most amino acids for resistant starch were also reduced (P < 0.05) than for the other starch sources. Cumulative portal appearance of amino acid represented 48.39%, 63.76%, 61.80% and 59.18% of dietary intake for resistant starch, maize, sticky rice and brown rice, respectively. Collectively, our results indicate that dietary starch sources substantially affect the appearance of amino acids and glucose in the portal circulation.

  14. Endogenous salicylic acid protects rice plants from oxidative damage caused by aging as well as biotic and abiotic stress.

    PubMed

    Yang, Yinong; Qi, Min; Mei, Chuansheng

    2004-12-01

    Salicylic acid (SA) is a key endogenous signal that mediates defense gene expression and disease resistance in many dicotyledonous species. In contrast to tobacco and Arabidopsis, which contain low basal levels of SA, rice has two orders of magnitude higher levels of SA and appears to be insensitive to exogenous SA treatment. To determine the role of SA in rice plants, we have generated SA-deficient transgenic rice by expressing the bacterial salicylate hydroxylase that degrades SA. Depletion of high levels of endogenous SA in transgenic rice does not measurably affect defense gene expression, but reduces the plant's capacity to detoxify reactive oxygen intermediates (ROI). SA-deficient transgenic rice contains elevated levels of superoxide and H2O2, and exhibits spontaneous lesion formation in an age- and light-dependent manner. Exogenous application of SA analog benzothiadiazole complements SA deficiency and suppresses ROI levels and lesion formation. Although an increase of conjugated catechol was detected in SA-deficient rice, catechol does not appear to significantly affect ROI levels based on the endogenous catechol data and exogenous catechol treatment. When infected with the blast fungus (Magnaporthe grisea), SA-deficient rice exhibits increased susceptibility to oxidative bursts elicited by avirulent isolates. Furthermore, SA-deficient rice is hyperresponsive to oxidative damage caused by paraquat treatment. Taken together, our results strongly suggest that SA plays an important role to modulate redox balance and protect rice plants from oxidative stress.

  15. Endogenous n-3 Fatty Acids Alleviate Carbon-Tetrachloride-Induced Acute Liver Injury in Fat-1 Transgenic Mice

    PubMed Central

    Feng, Ruibing; Wang, Meng; Yan, Chunyan

    2016-01-01

    n-3 polyunsaturated fatty acids (PUFAs) are beneficial for numerous models of liver diseases. The probable protective effects of n-3 PUFA against carbon-tetrachloride- (CCl4-) induced acute liver injury were evaluated in a fat-1 transgenic mouse that synthesizes endogenous n-3 from n-6 PUFA. Fat-1 mice and their WT littermates were fed a modified AIN93 diet containing 10% corn oil and were injected intraperitoneally with a single dose of CCl4 or vehicle. CCl4 challenge caused severe liver injury in WT mice, as indicated by serum parameters and histopathological changes, which were remarkably ameliorated in fat-1 mice. Endogenous n-3 PUFA decreased the elevation of oxidative stress induced by CCl4 challenge, which might be attributed to the activation of Nrf2/keap1 pathway. Additionally, endogenous n-3 PUFA reduces hepatocyte apoptosis via suppressing MAPK pathway. These findings indicate that n-3 PUFA has potent protective effects against acute liver injury induced by CCl4 in mice, suggesting that n-3 PUFA can be used for the prevention and treatment of liver injury. PMID:27891208

  16. Atlantic salmon (Salmo salar L.) as a net producer of long-chain marine ω-3 fatty acids.

    PubMed

    Sanden, Monica; Stubhaug, Ingunn; Berntssen, Marc H G; Lie, Øyvind; Torstensen, Bente E

    2011-12-14

    The objective of the present study was to investigate the effects of replacing high levels of marine ingredients with vegetable raw materials and with emphasis on lipid metabolism and net production of long-chain polyunsaturated ω-3 fatty acids (EPA + DHA). Atlantic salmon were fed three different replacement vegetable diets and one control marine diet before sensory attributes, β-oxidation capacity, and fatty acid productive value (FAPV) of ingested fatty acids (FAs) were evaluated. Fish fed the high replacement diet had a net production of 0.8 g of DHA and a FAPV of 142%. Fish fed the marine diet had a net loss of DHA. The present work shows that Atlantic salmon can be a net producer of marine DHA when dietary fish oil is replaced by vegetable oil with minor effects on sensory attributes and lipid metabolism.

  17. Spatio-temporal changes in endogenous abscisic acid contents during etiolated growth and photomorphogenesis in tomato seedlings

    PubMed Central

    Humplík, Jan F; Turečková, Veronika; Fellner, Martin; Bergougnoux, Véronique

    2015-01-01

    The role of abscisic acid (ABA) during early development was investigated in tomato seedlings. The endogenous content of ABA in particular organs was analyzed in seedlings grown in the dark and under blue light. Our results showed that in dark-grown seedlings, the ABA accumulation was maximal in the cotyledons and elongation zone of hypocotyl, whereas under blue-light, the ABA content was distinctly reduced. Our data are consistent with the conclusion that ABA promotes the growth of etiolated seedlings and the results suggest that ABA plays an inhibitory role in de-etiolation and photomorphogenesis in tomato. PMID:26322576

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

    PubMed Central

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

    2011-01-01

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

  19. Effect of baking process on added folic acid and endogenous folates stability in wheat and rye breads.

    PubMed

    Gujska, Elzbieta; Majewska, Katarzyna

    2005-06-01

    In Poland bread as a staple food both made from wheat and rye flour can be a potential product for future fortification with folic acid. The objective of the study was to examine the effect of fermentation and baking on added folic acid and some endogenous folates stability during breadmaking of rye and wheat breads. Breads were produced using the formulation containing enriched flour with 0.2 mg folic acid/100 g product, baker's yeast and additionally ascorbic acid for wheat bread and lactic acid for rye bread. Folates were extracted with Hepes/Ches buffer (pH = 7.85) followed by destruction of matrix by amylase and protease and deconjugation with rat serum conjugase. Affinity chromatography (FBP bovine milk) was used to purify and concentrate samples. The folates were separated by HPLC with C18 column and with a combination of fluorescence and UV detection. For both rye and wheat breads there was a decrease of folic acid from flour to bread stage. The total losses depend on baking process and ranged from 12 to 21%. Some changes in the level of different native folate forms during the stage of baking process were also observed.

  20. Effect of heat stress on the endogenous intestinal loss of amino acids in growing pigs.

    PubMed

    Morales, A; Hernández, L; Buenabad, L; Avelar, E; Bernal, H; Baumgard, L H; Cervantes, M

    2016-01-01

    Heat stress (HS) increases the death of intestinal cells in pigs, which, in turn, may elevate the endogenous intestinal loss (EIL) of proteins and AA. An experiment was conducted to analyze the effect of HS on the AA composition of intestinal endogenous proteins and the EIL of AA in pigs. Eight pigs (25.2 ± 1.2 kg initial BW) were surgically implanted with T-type cannulas at the end of the small intestine. After surgery recovery, during the subsequent 7 d, all pigs were adapted to a protein- and AA-free diet and trained to consume the same amount of feed twice a day. All pigs were housed under thermoneutral (TN) conditions (22 ± 2°C) during this time. The following day, all pigs were still under TN conditions and ileal content was collected during 12 consecutive hours, at the end of which and for the following 8 d the pigs were exposed to natural HS conditions (31 to 37°C). Ileal content was collected again on d 2 (HS at d 2 [HSd2]) and 8 (HS at d 8 [HSd8]). Body temperature (BT) was measured in another group of 8 pigs every 15 min during the whole study. The average BT at HSd2 (39.6°C) was higher ( < 0.05) compared with both TN conditions (38.6°C) and HSd8 (38.8°C), but it did not differ between TN conditions and HSd8. The AA composition of endogenous intestinal protein was not affected by HS. The EIL of Arg and His were greater ( < 0.05) and the EIL of Thr and Phe tended to be greater ( ≤ 0.10) at HSd2 than in TN conditions; the EIL of Pro was greater ( = 0.01) at HSd8. The EIL of the remaining AA was not affected by HS. Although HS increased the EIL of Arg and His within the first 2 d, it appeared that normal EIL was shortly reestablished. These data show that acute HS does not affect the AA composition of intestinal endogenous proteins in growing pigs and that the EIL of AA may not be critical in growing pigs acclimated to high ambient temperature. Nevertheless, the increased EIL of Arg and Thr at HSd2 indicate that HS might affect the integrity of the

  1. Myo-inositol esters of indole-3-acetic acid are endogenous components of Zea mays L. shoot tissue

    NASA Technical Reports Server (NTRS)

    Chisnell, J. R.

    1984-01-01

    Indole-3-acetyl-myo-inositol esters have been demonstrated to be endogenous components of etiolated Zea mays shoots tissue. This was accomplished by comparison of the putative compounds with authentic, synthetic esters. The properties compared were liquid and gas-liquid chromatographic retention times and the 70-ev mass spectral fragmentation pattern of the pentaacetyl derivative. The amount of indole-3-acetyl-myo-inositol esters in the shoots was determined to be 74 nanomoles per kilogram fresh weight as measured by isotope dilution, accounting for 19% of the ester indole-3-acetic acid of the shoot. This work is the first characterization of an ester conjugate of indole-3-acetate acid from vegetative shoot tissue using multiple chromatographic properties and mass spectral identification. The kernel and the seedling shoot both contain indole-3-acetyl-myo-inositol esters, and these esters comprise approximately the same percentage of the total ester content of the kernel and of the shoot.

  2. Magnetic properties, acid neutralization capacity, and net acid production of rocks in the Animas River Watershed Silverton, Colorado

    USGS Publications Warehouse

    McCafferty, Anne E.; Yager, Douglas B.; Horton, Radley M.; Diehl, Sharon F.

    2006-01-01

    Federal land managers along with local stakeholders in the Upper Animas River watershed near Silverton, Colorado are actively designing and implementing mine waste remediation projects to mitigate the effects of acid mine drainage from several abandoned hard rock metal mines and mills. Local source rocks with high acid neutralization capacity (ANC) within the watershed are of interest to land managers for use in these remediation projects. A suite of representative samples was collected from propylitic to weakly sericitic-altered volcanic and plutonic rocks exposed in outcrops throughout the watershed. Acid-base accounting laboratory methods coupled with mineralogic and geochemical characterization provide insight into lithologies that have a range of ANC and net acid production (NAP). Petrophysical lab determinations of magnetic susceptibility converted to estimates for percent magnetite show correlation with the environmental properties of ANC and NAP for many of the lithologies. A goal of our study is to interpret watershed-scale airborne magnetic data for regional mapping of rocks that have varying degrees of ANC and NAP. Results of our preliminary work are presented here.

  3. Positive Selection on a Regulatory Insertion–Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid

    PubMed Central

    Kothapalli, Kumar S. D.; Ye, , Kaixiong; Gadgil, Maithili S.; Carlson, Susan E.; O’Brien, Kimberly O.; Zhang, Ji Yao; Park, Hui Gyu; Ojukwu, Kinsley; Zou, James; Hyon, Stephanie S.; Joshi, Kalpana S.; Gu, Zhenglong; Keinan, Alon; Brenna, J.Thomas

    2016-01-01

    Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22-bp insertion–deletion within FADS2, is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here, we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the US. A much higher I/I genotype frequency was found in Indians (68%) than in the US (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum, and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African, and some East Asian populations. Basal plasma phospholipid arachidonic acid (ARA) status was 8% greater in I/I compared with D/D individuals. The biochemical pathway product–precursor difference, ARA minus linoleic acid, was 31% and 13% greater for I/I and I/D compared with D/D, respectively. This study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice. PMID:27188529

  4. Positive Selection on a Regulatory Insertion-Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid.

    PubMed

    Kothapalli, Kumar S D; Ye, Kaixiong; Gadgil, Maithili S; Carlson, Susan E; O'Brien, Kimberly O; Zhang, Ji Yao; Park, Hui Gyu; Ojukwu, Kinsley; Zou, James; Hyon, Stephanie S; Joshi, Kalpana S; Gu, Zhenglong; Keinan, Alon; Brenna, J Thomas

    2016-07-01

    Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22-bp insertion-deletion within FADS2, is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here, we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the US. A much higher I/I genotype frequency was found in Indians (68%) than in the US (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum, and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African, and some East Asian populations. Basal plasma phospholipid arachidonic acid (ARA) status was 8% greater in I/I compared with D/D individuals. The biochemical pathway product-precursor difference, ARA minus linoleic acid, was 31% and 13% greater for I/I and I/D compared with D/D, respectively. This study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice.

  5. Colored petri nets to model gene mutation and amino acids classification.

    PubMed

    Yang, Jinliang; Gao, Rui; Meng, Max Q-H; Tarn, Tzyh-Jong

    2012-05-07

    The genetic code is the triplet code based on the three-letter codons, which determines the specific amino acid sequences in proteins synthesis. Choosing an appropriate model for processing these codons is a useful method to study genetic processes in Molecular Biology. As an effective modeling tool of discrete event dynamic systems (DEDS), colored petri net (CPN) has been used for modeling several biological systems, such as metabolic pathways and genetic regulatory networks. According to the genetic code table, CPN is employed to model the process of genetic information transmission. In this paper, we propose a CPN model of amino acids classification, and further present the improved CPN model. Based on the model mentioned above, we give another CPN model to classify the type of gene mutations via contrasting the bases of DNA strands and the codons of amino acids along the polypeptide chain. This model is helpful in determining whether a certain gene mutation will cause the changes of the structures and functions of protein molecules. The effectiveness and accuracy of the presented model are illustrated by the examples in this paper.

  6. 2-buten-4-olide, an endogenous feeding suppressant, improves spatial performance through brain acidic fibroblast growth factor in mice.

    PubMed

    Li, X L; Aou, S; Li, A J; Hori, T; Tooyama, I; Oomura, Y

    2001-12-01

    Endogenous sugar acid 2-buten-4-olide, a satiety substance, has been shown to increase the blood glucose, norepinephrine, and glucocorticoid concentrations that are known to modulate learning and memory processes. The glucose-induced release of acidic fibroblast growth factor facilitated the hippocampus-dependent memory function. In the present study, we investigated the effect of 2-buten-4-olide on the spatial performance of male DDY mice undergoing the water maze task. The intraperitoneal injection of 2-buten-4-olide (5 mg/kg) facilitated the spatial performance, which was indicated by a reduction in the escape latency in which the mouse finds and climbs the goal platform in comparison to the vehicle-injected control mice. In the probe test after removing the platform, the 2-buten-4-olide-treated mice stayed a longer time in the quadrant where the platform was originally located and crossed more frequently at the platform location than did the control mice. The pretreatment of acidic fibroblast growth factor antibody injected into the lateral ventricle eliminated the effect of 2-buten-4-olide both during the training sessions and during the probe test. Therefore, 2-buten-4-olide was found to improve the spatial performance, and this effect is mediated, at least in part, by acidic fibroblast growth factor.

  7. Characterization and quantification of endogenous fatty acid nitroalkene metabolites in human urine.

    PubMed

    Salvatore, Sonia R; Vitturi, Dario A; Baker, Paul R S; Bonacci, Gustavo; Koenitzer, Jeffrey R; Woodcock, Steven R; Freeman, Bruce A; Schopfer, Francisco J

    2013-07-01

    The oxidation and nitration of unsaturated fatty acids transforms cell membrane and lipoprotein constituents into mediators that regulate signal transduction. The formation of 9-NO2-octadeca-9,11-dienoic acid and 12-NO2-octadeca-9,11-dienoic acid stems from peroxynitrite- and myeloperoxidase-derived nitrogen dioxide reactions as well as secondary to nitrite disproportionation under the acidic conditions of digestion. Broad anti-inflammatory and tissue-protective responses are mediated by nitro-fatty acids. It is now shown that electrophilic fatty acid nitroalkenes are present in the urine of healthy human volunteers (9.9 ± 4.0 pmol/mg creatinine); along with electrophilic 16- and 14-carbon nitroalkenyl β-oxidation metabolites. High resolution mass determinations and coelution with isotopically-labeled metabolites support renal excretion of cysteine-nitroalkene conjugates. These products of Michael addition are in equilibrium with the free nitroalkene pool in urine and are displaced by thiol reaction with mercury chloride. This reaction increases the level of free nitroalkene fraction >10-fold and displays a K(D) of 7.5 × 10(-6) M. In aggregate, the data indicates that formation of Michael adducts by electrophilic fatty acids is favored under biological conditions and that reversal of these addition reactions is critical for detecting both parent nitroalkenes and their metabolites. The measurement of this class of mediators can constitute a sensitive noninvasive index of metabolic and inflammatory status.

  8. Hypoxia suppresses Kv 2.1 channel expression through endogenous 15-hydroxyeicosatetraenoic acid in rat pulmonary artery.

    PubMed

    Guo, Lei; Qiu, Zhaoping; Zhang, Lei; Chen, Shuo; Zhu, Daling

    2010-09-01

    We have previously reported that hypoxia activates lung 15-lipoxygenase (15-LOX), which catalyzes arachidonic acid to produce 15-HETE, leading to constriction of neonatal rabbit pulmonary arteries. Hypoxia suppresses Kv2.1 channel expression. Although the Kv channel inhibition by hypoxia is likely to be mediated through 15-HETE, direct evidence is still lacking. To explore whether 15-LOX/15-HETE pathway contributes to the hypoxia-induced down-regulation of Kv2.1 channel, we performed studies using 15-LOX blockers, semi-quantitative PCR and western blot analysis. We found that Kv2.1 channel expression at the mRNA and protein levels was greatly up-regulated in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary artery (PA) after blockade of endogenous 15-HETE under hypoxic condition. 15-HETE further decreased Kv2.1 channel expression in comparison with 12-HETE and 5-HETE in cultured PASMCs and PA under normoxic conditions. These data indicate that hypoxia suppresses Kv2.1 channel expression through endogenous 15-HETE in PA.

  9. Evidences for Chlorogenic Acid — A Major Endogenous Polyphenol Involved in Regulation of Ripening and Senescence of Apple Fruit

    PubMed Central

    Xi, Yu; Cheng, Dai; Zeng, Xiangquan; Cao, Jiankang; Jiang, Weibo

    2016-01-01

    To learn how the endogenous polyphenols may play a role in fruit ripening and senescence, apple pulp discs were used as a model to study the influences of chlorogenic acid (CHA, a major polyphenol in apple pulp) on fruit ripening and senescence. Apple (‘Golden Delicious’) pulp discs prepared from pre-climacteric fruit were treated with 50 mg L-1 CHA and incubated in flasks with 10 mM MES buffer (pH 6.0, 11% sorbitol). Compared to the control samples, treatment with CHA significantly reduced ethylene production and respiration rate, and enhanced levels of firmness and soluble solids content of the pulp discs during incubation at 25°C. These results suggested that CHA could retard senescence of the apple pulp discs. Proteomics analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry (MALDI-TOF/TOF) revealed that the expressions of several key proteins correlated to fruit ripening and senescence were affected by the treatment with CHA. Further study showed that treating the pulp discs with CHA remarkably reduced levels of lipoxygenase, β-galactosidase, NADP-malic enzyme, and enzymatic activities of lipoxygenase and UDP-glucose pyrophosphorylase, all of which are known as promoters of fruit ripening and senescence. These results could provide new insights into the functions of endogenous phenolic compounds in fruit ripening and senescence. PMID:26756813

  10. Endogenous lysophosphatidic acid participates in vascularisation and decidualisation at the maternal?fetal interface in the rat.

    PubMed

    Sordelli, Micaela S; Beltrame, Jimena S; Zotta, Elsa; Gomez, Natalia; Dmytrenko, Ganna; Sales, María Elena; Blois, Sandra M; Davio, Carlos; Martinez, Silvina Perez; Franchi, Ana M; Ribeiro, María L

    2017-04-05

    Lysophosphatidic acid (LPA) affects several female reproductive functions through G-protein-coupled receptors. LPA contributes to embryo implantation via the lysophospholipid LPA3 receptor. In the present study we investigated the participation of endogenous LPA signalling through the LPA3 receptor in vascularisation and decidualisation, two crucial events at the maternal-fetal interface. Pregnant rats were treated with diacylglycerol pyrophosphate (DGPP), a highly selective antagonist of LPA3 receptors, on Day 5 of gestation. Pregnant rats received intrauterine (i.u.) injections of single doses of DGPP (0.1mgkg-1) in a total volume of 2μL in the left horn (treated horn) in the morning of GD5. DGPP treatment produced aberrant embryo spacing and increased embryo resorption. The LPA3 receptor antagonist decreased the cross-sectional length of the uterine and arcuate arteries and induced histological anomalies in the decidua and placentas. Marked haemorrhagic processes, infiltration of immune cells and tissue disorganisation were observed in decidual and placental tissues from sites of resorption. The mRNA expression of three vascularisation markers, namely interleukin 10 (Il10), vascular endothelial growth factor (Vegfa) and vascular endothelial growth factor receptor 1 (Vegfr1), was reduced at sites of resorption from Day 8. The results show that the disruption of endogenous LPA signalling by blocking the LPA3 receptor modified the development of uterine vessels with consequences in the formation of the decidua and placenta and in the growth of embryos.

  11. Increase of hypoxic tolerance in rat hippocampal slices following 3-nitropropionic acid is not mediated by endogenous nerve growth factor.

    PubMed

    Riepe, M W; Kasischke, K; Gericke, C A; Löwe, A; Hellweg, R

    1996-06-14

    Chemical preconditioning with low dose inhibition of succinic dehydrogenase by 3-nitropropionic acid (3-np) increases tolerance against succeeding hypoxia. Supraphysiological doses of nerve growth factor (NGF) repeatedly were shown to protect against ischemic damage. We investigated whether increased tolerance against hypoxia results from increased or accelerated production of endogenous NGF. Average recovery of population spike amplitude after 15 min of hypoxia and 45 min of reoxygenation was 31 +/- 9% (mean +/- SE) in control hippocampal slices. After pretreatment with 3-np (single i.p. injection of 20 mg/kg body weight 1 h to 3 days prior to slice preparation), recovery exceeded 90% (P < 0.01). However, NGF content did not increase upon slice preparation, hypoxia in vitro, and pretreatment with 3-np in vivo 1 h to 1 day prior to slice preparation with and without additional hypoxia in vitro. We conclude that early-onset tolerance to hypoxia induced by 3-np treatment is not caused by induction of endogenous NGF production.

  12. Evidences for Chlorogenic Acid--A Major Endogenous Polyphenol Involved in Regulation of Ripening and Senescence of Apple Fruit.

    PubMed

    Xi, Yu; Cheng, Dai; Zeng, Xiangquan; Cao, Jiankang; Jiang, Weibo

    2016-01-01

    To learn how the endogenous polyphenols may play a role in fruit ripening and senescence, apple pulp discs were used as a model to study the influences of chlorogenic acid (CHA, a major polyphenol in apple pulp) on fruit ripening and senescence. Apple ('Golden Delicious') pulp discs prepared from pre-climacteric fruit were treated with 50 mg L(-1) CHA and incubated in flasks with 10 mM MES buffer (pH 6.0, 11% sorbitol). Compared to the control samples, treatment with CHA significantly reduced ethylene production and respiration rate, and enhanced levels of firmness and soluble solids content of the pulp discs during incubation at 25°C. These results suggested that CHA could retard senescence of the apple pulp discs. Proteomics analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry (MALDI-TOF/TOF) revealed that the expressions of several key proteins correlated to fruit ripening and senescence were affected by the treatment with CHA. Further study showed that treating the pulp discs with CHA remarkably reduced levels of lipoxygenase, β-galactosidase, NADP-malic enzyme, and enzymatic activities of lipoxygenase and UDP-glucose pyrophosphorylase, all of which are known as promoters of fruit ripening and senescence. These results could provide new insights into the functions of endogenous phenolic compounds in fruit ripening and senescence.

  13. Effects of the dietary ratio of ruminal degraded to undegraded protein and feed intake on intestinal flows of endogenous nitrogen and amino acids in goats.

    PubMed

    Zhou, Chuanshe; Chen, Liang; Tan, Zhiliang; Tang, Shaoxun; Han, Xuefeng; Wang, Min; Kang, Jinhe; Yan, Qiongxian

    2015-01-01

    This study was conducted to evaluate the effects of the dietary ratio of ruminal degraded protein (RDP) to ruminal undegraded protein (RUP) and the dry matter intake (DMI) on the intestinal flows of endogenous nitrogen (N) and amino acids (AA) in goats. The experiment was designed as a 4×4 Latin square using four ruminally, duodenally and ileally cannulated goats. The treatments were arranged in a 2×2 factorial design; two ratios of RDP to RUP (65:35 and 45:55, RDP1 and RDP2, respectively) and two levels at 95% and 75% of voluntary feed intake (DMI1 and DMI2, respectively) were fed to the goats. There were no significant differences in the N intake, duodenal flow of total N, undegraded feed N, microbial N, endogenous N or ileal flow of endogenous N, but the duodenal and ileal flow of endogenous N numerically decreased by approximately 22% and 9%, respectively, when the feed intake changed from DMI1 (0.63 kg/d) to DMI2 (0.50 kg/d). The dietary ratio of RDP to RUP had significant effects (p<0.05) on the ileal flows of endogenous leucine, phenylalanine and cysteine. The present results implied that the duodenal flows of endogenous N and AA decreased when the dietary RDP to RUP ratio and DMI decreased, and the flow of endogenous AA at the ileum also decreased when the DMI decreased but increased with decreasing RDP to RUP ratios.

  14. Lipidomic analyses of the mouse brain after antidepressant treatment: evidence for endogenous release of long-chain fatty acids?

    PubMed

    Lee, Lynette Hui-Wen; Shui, Guanghou; Farooqui, Akhlaq A; Wenk, Markus R; Tan, Chay-Hoon; Ong, Wei-Yi

    2009-08-01

    Recently, there has been considerable interest in a possible link between changes in brain polyunsaturated fatty acids, neural membrane phospholipid degradation, serotonergic neurotransmission, and depression. The present study aims to examine effects of antidepressants on lipids in different regions of the brain at individual molecular species level, using the novel technique of lipidomics. Balb/C mice received daily intraperitoneal (i.p.) injections of 10 mg/kg of the antidepressants maprotiline, fluoxetine and paroxetine for 4 wk. The prefrontal cortex, hippocampus, striatum and cerebellum were harvested, and lipid profiles compared to those of saline-injected mice. Treatment with maprotiline and paroxetine, but not fluoxetine, resulted in significant decreases in phosphatidylcholine (PC) species, PC36:1, PC38:3, PC40:2p, PC40:6, PC40:5, PC42:7p, PC42:6p and PC42:5p in the prefrontal neocortex. The decreases in phospholipids were accompanied by increases in lysophospholipid species, lysoPC16:0, lysoPC18:2 and lysoPC18:0 in the prefrontal cortex, indicating increase in phospholipase A2 activity and possible release of long-chain fatty acids. Maprotiline and paroxetine treatment also resulted in decreases in sphingomyelin and increases in several ceramide species in the prefrontal cortex. It is postulated that endogenous release of long-chain fatty acids may be related to the mechanism of action of maprotiline and paroxetine.

  15. A high-resolution mitochondria-targeting ratiometric fluorescent probe for detection of the endogenous hypochlorous acid

    NASA Astrophysics Data System (ADS)

    Zhou, Liyi; Lu, Dan-Qing; Wang, Qianqian; Hu, Shunqin; Wang, Haifei; Sun, Hongyan; Zhang, Xiaobing

    2016-09-01

    Hypochlorite anion, one of the biologically important reactive oxygen species, plays an essential role in diverse normal biochemical functions and abnormal pathological processes. Herein, an efficient high-resolution mitochondria-targeting ratiometric fluorescent probe for hypochlorous acid detection has been designed, synthesized and characterized. It is easily synthesized by the condensation reaction (Cdbnd C) of a 2-(2-hydroxyphenyl) quinazolin-4(3H)-one fluorophore and a cyanine group (mitochondria-targeting), which made the whole molecular a large Stokes shift (210 nm) and the two well-resolved emission peaks separated by 140 nm. As a result, it is considered as a good candidate for high resolution hypochlorous acid imaging in live cells. The ratiometric fluorescent probe exhibited outstanding features of high sensitivity, high selectivity, rapid response time (within 50 s), and excellent mitochondria-targeting ability. Moreover, the probe can also be successfully applied to imaging endogenously hypochlorous acid in the mitochondria of living cells with low cytotoxicity, and high resolution.

  16. Acid rain mitigation experiment shifts a forested watershed from a net sink to a net source of nitrogen

    PubMed Central

    Rosi-Marshall, Emma J.; Bernhardt, Emily S.; Buso, Donald C.; Driscoll, Charles T.; Likens, Gene E.

    2016-01-01

    Decades of acid rain have acidified forest soils and freshwaters throughout montane forests of the northeastern United States; the resulting loss of soil base cations is hypothesized to be responsible for limiting rates of forest growth throughout the region. In 1999, an experiment was conducted that reversed the long-term trend of soil base cation depletion and tested the hypothesis that calcium limits forest growth in acidified soils. Researchers added 1,189 kg Ca2+ ha−1 as the pelletized mineral wollastonite (CaSiO3) to a 12-ha forested watershed within the Hubbard Brook Experimental Forest in the White Mountains of New Hampshire. Significant increases in the pH and acid-neutralizing capacity of soils and streamwater resulted, and the predicted increase in forest growth occurred. An unanticipated consequence of this acidification mitigation experiment began to emerge a decade later, with marked increases in dissolved inorganic nitrogen (DIN) exports in streamwater from the treated watershed. By 2013, 30-times greater DIN was exported from this base-treated watershed than from adjacent reference watersheds, and DIN exports resulting from this experiment match or exceed earlier reports of inorganic N losses after severe ice-storm damage within the study watershed. The discovery that CaSiO3 enrichment can convert a watershed from a sink to a source of N suggests that numerous potential mechanisms drive watershed N dynamics and provides new insights into the influence of acid deposition mitigation strategies for both carbon cycling and watershed N export. PMID:27335456

  17. Acid rain mitigation experiment shifts a forested watershed from a net sink to a net source of nitrogen.

    PubMed

    Rosi-Marshall, Emma J; Bernhardt, Emily S; Buso, Donald C; Driscoll, Charles T; Likens, Gene E

    2016-07-05

    Decades of acid rain have acidified forest soils and freshwaters throughout montane forests of the northeastern United States; the resulting loss of soil base cations is hypothesized to be responsible for limiting rates of forest growth throughout the region. In 1999, an experiment was conducted that reversed the long-term trend of soil base cation depletion and tested the hypothesis that calcium limits forest growth in acidified soils. Researchers added 1,189 kg Ca(2+) ha(-1) as the pelletized mineral wollastonite (CaSiO3) to a 12-ha forested watershed within the Hubbard Brook Experimental Forest in the White Mountains of New Hampshire. Significant increases in the pH and acid-neutralizing capacity of soils and streamwater resulted, and the predicted increase in forest growth occurred. An unanticipated consequence of this acidification mitigation experiment began to emerge a decade later, with marked increases in dissolved inorganic nitrogen (DIN) exports in streamwater from the treated watershed. By 2013, 30-times greater DIN was exported from this base-treated watershed than from adjacent reference watersheds, and DIN exports resulting from this experiment match or exceed earlier reports of inorganic N losses after severe ice-storm damage within the study watershed. The discovery that CaSiO3 enrichment can convert a watershed from a sink to a source of N suggests that numerous potential mechanisms drive watershed N dynamics and provides new insights into the influence of acid deposition mitigation strategies for both carbon cycling and watershed N export.

  18. Transcription of exogenous and endogenous deoxyribonucleic acid templates in cold-shocked Bacillus subtilis.

    PubMed Central

    Kuhl, S J; Brown, L R

    1980-01-01

    Ribonucleic acid (RNA) synthesis was examined in cold-shocked Bacillus subtilis cells. The cells were grown to mid-log stage, harvested, and cold shocked. RNA synthesis was monitored by the incorporation of [3H]uridine triphosphate or [alpha 32P]adenosine triphosphate into trichloroacetic acid-precipitable material in the presence of all four nucleoside triphosphates. The inhibition of RNA synthesis in cold-shocked cells by lipiarmycin, ethidium bromide, rifampin. or streptolydigin was analyzed using mutant or wild-type cells. Also examined were the effects of temperature, salt concentration, and the addition of polyamines or highly phosphorylated nucleotides. In ultraviolet-irradiated and cold-shocked cells, RNA wynthesis decreased to low levels. The addition of exogenous phi 29 or TSP-1 template to these cells caused a 13- to 20-fold increase in RNA synthesis, as monitored by trichloroacetic acid-precipitable counts. RNA synthesized in the presence of phi 29 deoxyribonucleic acid (DNA) hybridizes mainly to EcoRI fragments A and C of phi 29 DBA, These two fragments direct transcription by purified RNA polymerase in vitro and hybridize to early phi 29 DNA produced in vivo. Our results with TSP-1 DNA in this system indicated that the RNA produced hybridizes to the same fragments as early RNA produced in vivo. Plasmic pUB110 DNA was not transcribed in this system. Images PMID:6157674

  19. Dietary linoleic acid elevates endogenous 2-AG and anandamide and induces obesity.

    PubMed

    Alvheim, Anita R; Malde, Marian K; Osei-Hyiaman, Douglas; Lin, Yu Hong; Pawlosky, Robert J; Madsen, Lise; Kristiansen, Karsten; Frøyland, Livar; Hibbeln, Joseph R

    2012-10-01

    Suppressing hyperactive endocannabinoid tone is a critical target for reducing obesity. The backbone of both endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) is the ω-6 fatty acid arachidonic acid (AA). Here we posited that excessive dietary intake of linoleic acid (LA), the precursor of AA, would induce endocannabinoid hyperactivity and promote obesity. LA was isolated as an independent variable to reflect the dietary increase in LA from 1 percent of energy (en%) to 8 en% occurring in the United States during the 20th century. Mice were fed diets containing 1 en% LA, 8 en% LA, and 8 en% LA + 1 en% eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) in medium-fat diets (35 en% fat) and high-fat diets (60 en%) for 14 weeks from weaning. Increasing LA from 1 en% to 8 en% elevated AA-phospholipids (PL) in liver and erythrocytes, tripled 2-AG + 1-AG and AEA associated with increased food intake, feed efficiency, and adiposity in mice. Reducing AA-PL by adding 1 en% long-chain ω-3 fats to 8 en% LA diets resulted in metabolic patterns resembling 1 en% LA diets. Selectively reducing LA to 1 en% reversed the obesogenic properties of a 60 en% fat diet. These animal diets modeled 20th century increases of human LA consumption, changes that closely correlate with increasing prevalence rates of obesity. In summary, dietary LA increased tissue AA, and subsequently elevated 2-AG + 1-AG and AEA resulting in the development of diet-induced obesity. The adipogenic effect of LA can be prevented by consuming sufficient EPA and DHA to reduce the AA-PL pool and normalize endocannabinoid tone.

  20. Simultaneous determination of the endogenous free α-lipoic acid and dihydrolipoic acid in human plasma and erythrocytes by RP-HPLC coupled with electrochemical detector.

    PubMed

    Khan, Muhammad Imran; Iqbal, Zafar; Khan, Abad

    2015-01-01

    A highly sensitive, precise, and accurate reversed-phase high performance liquid-chromatography/electrochemical detection method for simultaneous determination of the endogenous free α-lipoic acid and dihydrolipoic acid in biological matrices is presented. The two analytes are extracted from samples with acetonitrile-10% m-phosphoric acid solution(aqueous) (50:50 v/v). To determine the total lipoic acid, samples are treated with tris(2-carboxyethyl)phosphine solution in phosphate buffer: pH 2.5 with 85% o-phosphoric acid prior to deproteination. The two analytes are separated on a C18 (150 × 4.6 mm, 5 μm) analytical column using acetonitrile-50 mM phosphate buffer: pH 2.5 with 85% o-phosphoric acid (35:65 v/v) as the isocratic mobile phase pumped at a flow rate of 2.0 ml/min at the column oven temperature of 35 °C. The column eluents are monitored at a potential of 0.9 V. These analytes are efficiently resolved in <7 min.

  1. Comparison of different methods for determination of the duodenal and ileal flows of endogenous nitrogen and amino acids in growing goats.

    PubMed

    Zhou, Chuanshe; Tan, Zhiliang; Pan, Yafei; Tang, Shaoxun; Sun, Zhihong; Han, Xuefeng; Wang, Min

    2009-01-01

    The objective of the present study was to compare the isotope dilution, the difference and the amino acid profile (AAP) methods for the quantification of duodenal and ileal flows of endogenous nitrogen (N) and amino acids (AA) in growing goats. Nine growing goats were fed the same diet containing maize stover, ground corn and soybean meal. The duodenal flow of endogenous N determined by the isotope dilution method was significantly (p < 0.01) higher than that determined by the difference and AAP methods, while there was no difference between the difference and the AAP methods. The duodenal flows of individual endogenous AA determined by the isotope dilution method exceed those determined by the difference and the AAP method by 10 to 106%. The endogenous flow at the ileum determined by the isotope dilution method was not significantly different to those determined by the water-soluble method, but tended to be lower for N and all amino acids. It is concluded that the difference method and AAP method underestimate the duodenal flow of endogenous N and AA compared to the isotope dilution method.

  2. Abnormal endogenous amino acid release in brain slices from vitamin B-6 restricted neonatal rats.

    PubMed

    Guilarte, T R

    1991-01-02

    The basal and potassium-evoked efflux of glutamate, glycine, taurine, and gamma-aminobutyric acid (GABA) was measured in brain slices from vitamin B-6 restricted and sufficient 14-day-old rats. The results indicate a reduced level of basal glutamate, taurine, and GABA efflux in hippocampal slices and taurine and GABA in cortical slices from vitamin B-6 restricted animals. In the presence of depolarizing potassium concentrations, there was a reduced level of GABA efflux in hippocampal and cortical slices, and a marked reduction in the release of glutamate in cortical slices from B-6 restricted rats. The abnormalities in the secretion process of these neuroactive amino acids may be related to the neurological sequelae associated with neonatal vitamin B-6 restriction.

  3. Analysis of Endogenous D-Amino Acid-Containing Peptides in Metazoa

    PubMed Central

    Bai, Lu; Sheeley, Sarah; Sweedler, Jonathan V.

    2010-01-01

    Peptides are chiral molecules with their structure determined by the composition and configuration of their amino acid building blocks. The naturally occurring amino acids, except glycine, possess two chiral forms. This allows the formation of multiple peptide diastereomers that have the same sequence. Although living organisms use L-amino acids to make proteins, a group of D-amino acid-containing peptides (DAACPs) has been discovered in animals that have at least one of their residues isomerized to the D-form via an enzyme-catalyzed process. In many cases, the biological functions of these peptides are enhanced due to this structural conversion. These DAACPs are different from those known to occur in bacterial cell wall and antibiotic peptides, the latter of which are synthesized in a ribosome-independent manner. DAACPs have now also been identified in a number of distinct groups throughout the Metazoa. Their serendipitous discovery has often resulted from discrepancies observed in bioassays or in chromatographic behavior between natural peptide fractions and peptides synthesized according to a presumed all-L sequence. Because this L-to-D post-translational modification is subtle and not detectable by most sequence determination approaches, it is reasonable to suspect that many studies have overlooked this change; accordingly, DAACPs may be more prevalent than currently thought. Although diastereomer separation techniques developed with synthetic peptides in recent years have greatly aided in the discovery of natural DAACPs, there is a need for new, more robust methods for naturally complex samples. In this review, a brief history of DAACPs in animals is presented, followed by discussion of a variety of analytical methods that have been used for diastereomeric separation and detection of peptides. PMID:20490347

  4. The Tryptophan Conjugates of Jasmonic and Indole-3-Acetic Acids Are Endogenous Auxin Inhibitors1[W][OA

    PubMed Central

    Staswick, Paul E.

    2009-01-01

    Most conjugates of plant hormones are inactive, and some function to reduce the active hormone pool. This study characterized the activity of the tryptophan (Trp) conjugate of jasmonic acid (JA-Trp) in Arabidopsis (Arabidopsis thaliana). Unexpectedly, JA-Trp caused agravitropic root growth in seedlings, unlike JA or nine other JA-amino acid conjugates. The response was dose dependent from 1 to100 μm, was independent of the COI1 jasmonate signaling locus, and unlike the jasmonate signal JA-isoleucine, JA-Trp minimally inhibited root growth. The Trp conjugate with indole-3-acetic acid (IAA-Trp) produced a similar response, while Trp alone and conjugates with benzoic and cinnamic acids did not. JA-Trp and IAA-Trp at 25 μm nearly eliminated seedling root inhibition caused by 2 μm IAA. The TIR1 auxin receptor is required for activity because roots of tir1-1 grew only approximately 60% of wild-type length on IAA plus JA-Trp, even though tir1-1 is auxin resistant. However, neither JA-Trp nor IAA-Trp interfered with IAA-dependent interaction between TIR1 and Aux/IAA7 in cell-free assays. Trp conjugates inhibited IAA-stimulated lateral root production and DR5-β-glucuronidase gene expression. JA-deficient mutants were hypersensitive to IAA and a Trp-overaccumulating mutant was less sensitive, suggesting endogenous conjugates affect auxin sensitivity. Conjugates were present at 5.8 pmol g−1 fresh weight or less in roots, seedlings, leaves, and flowers, and the values increased approximately 10-fold in roots incubated in 25 μm Trp and IAA or JA at 2 μm. These results show that JA-Trp and IAA-Trp constitute a previously unrecognized mechanism to regulate auxin action. PMID:19458116

  5. Ursolic acid sensitizes radioresistant NSCLC cells expressing HIF-1α through reducing endogenous GSH and inhibiting HIF-1α

    PubMed Central

    Song, Bing; Zhang, Qian; Yu, Maohu; Qi, Xinrong; Wang, Gang; Xiao, Linlin; Yi, Qiyi; Jin, Wensen

    2017-01-01

    In previous studies, the present authors demonstrated that effective sensitization of ionizing radiation-induced death of tumor cells, including non-small cell lung cancer (NSCLC) cells, could be produced by oleanolic acid (OA), a pentacyclic triterpenoid present in plants. In the present study, it was investigated whether ursolic acid (UA), an isomer of OA, had also the capacity of sensitizing radioresistant NSCLC cells. The radioresistant cell line H1299/M-hypoxia inducible factor-1α (HIF-1α) was established by transfection with a recombinant plasmid expressing mutant HIF-1α (M-HIF-1α). Compared with parental H1299 cells and H1299 cells transfected with empty plasmid, H1299/M-HIF-1α cells had lower radiosensitivity. Following the use of UA to treat NSCLC cells, elevation of the radiosensitivity of cells was observed by MTT assay. The irradiated H1299/M-HIF-1α cells were more sensitive to UA pretreatment than the irradiated cells with empty plasmid and control. The alteration of DNA damage in the irradiated cells was further measured using micronucleus (MN) assay. The combination of UA treatment with radiation could induce the increase of cellular MN frequencies, in agreement with the change in the tendency observed in the cell viability assay. It was further shown that the endogenous glutathione (GSH) contents were markedly attenuated in the differently irradiated NSCLC cells with UA (80 µmol/l) pretreatment through glutathione reductase/5,5′-dithiobis-(2-nitrob-enzoic acid) (DTNB) recycling assay. The results revealed that UA treatment alone could effectively decrease the GSH content in H1299/M-HIF-1α cells. In addition, the inhibition of HIF-1α expression in radioresistant cells was confirmed by western blotting. It was then concluded that UA could upregulate the radiosensitivity of NSCLC cells, and in particular reduce the refractory response of cells expressing HIF-1α to ionizing radiation. The primary mechanism is associated with reduction of

  6. Absorption and lymphatic transport of exogenous and endogenous arachidonic and linoleic acid in the rat

    SciTech Connect

    Nilsson, A.; Landin, B.; Jensen, E.; Akesson, B.

    1987-06-01

    (/sup 3/H)Arachidonic (20:4) and (/sup 14/C)linoleic acid (18:2) were fed to thoracic duct-cannulated rats in test meals of either tracers alone, cream, Intralipid, pure arachidonic acid, or pure linoleic acid. Less (/sup 3/H)20:4 than (/sup 14/C)18:2 was recovered in chyle during the first 5 h. After cream feeding, the proportion of radioactivity found in phospholipids was high and increased during the first 3 h. After the meal 61 +/- 6% of the /sup 3/H and 57 +/- 10% of the /sup 14/C was in phosphatidylcholine, and 11 +/- 3% of the /sup 3/H and 3.0 +/- 4% of the /sup 14/C was in phosphatidylethanolamine. Changing the fat vehicle to Intralipid or pure 18:2 decreased the proportion of label in the phospholipds and increased the /sup 3/H and /sup 14/C radioactivity in the triacylglycerol fraction, the distribution of /sup 14/C radioactivity in the triacylglycerol fraction, the distribution of /sup 14/C being influenced more than that of /sup 3/H. After feeding the tracers in 200 ..mu..l of pure 20:4, >90% of both isotopes was in triacylglycerol. During fasting, triacylglycerol transported 56% (0.7 ..mu..mol/h), phosphatidylethanolamine transported 10% (0.1 ..mu..mol/h) of the 20:4 mass. After cream or Intralipid feeding, the output of 20:4-containing phosphatidylcholine and phosphatidylethanolamine increased 2.1- to 2.8-fold, whereas the transport of 20:4 with triacylglycerol remained constant. Phospholipids thus became the predominant transport form for 20:4. After feeding 200 ..mu..l of 20:4, the intestine produced, however, 20:4-rich triacylglycerols that transported 80% of the chyle 20:4.

  7. Detection of in vivo genotoxicity of endogenously formed N-nitroso compounds and suppression by ascorbic acid, teas and fruit juices.

    PubMed

    Ohsawa, Koh-ichi; Nakagawa, Shin-ya; Kimura, Masaaki; Shimada, Chihiro; Tsuda, Shuji; Kabasawa, Kazumi; Kawaguchi, Satomi; Sasaki, Yu F

    2003-08-05

    The genotoxicity of endogenously formed N-nitrosamines from secondary amines and sodium nitrite (NaNO(2)) was evaluated in multiple organs of mice, using comet assay. Groups of four male mice were orally given dimethylamine, proline, and morpholine simultaneously with NaNO(2). The stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow were sampled 3 and 24 h after these compounds had been ingested. Although secondary amines and the NaNO(2) tested did not yield DNA damage in any of the organs tested, DNA damage was observed mainly in the liver following simultaneous oral ingestion of these compounds. The administration within a 60 min interval also yielded hepatic DNA damage. It is considered that DNA damage induced in mouse organs with the coexistence of amines and nitrite in the acidic stomach is due to endogenously formed nitrosamines. Ascorbic acid reduced the liver DNA damage induced by morpholine and NaNO(2). Reductions in hepatic genotoxicity of endogenously formed N-nitrosomorpholine by tea polyphenols, such as catechins and theaflavins, and fresh apple, grape, and orange juices were more effective than was by ascorbic acid. In contrast with the antimutagenicity of ascorbic acid in the liver, ascorbic acid yielded stomach DNA damage in the presence of NaNO(2) (in the presence and absence of morpholine). Even if ascorbic acid acts as an antimutagen in the liver, nitric oxide (NO) formed from the reduction of NaNO(2) by ascorbic acid damaged stomach DNA.

  8. Ascorbic acid, carotenoids, and visual quality of baby spinach as affected by shade netting and postharvest storage.

    PubMed

    Bergquist, Sara A M; Gertsson, Ulla E; Nordmark, Lotta Y G; Olsson, Marie E

    2007-10-17

    Baby spinach ( Spinacia oleracea L.) was grown under three types of shade netting (high transmittance, spectrum-altering, and low transmittance) to study the effect on the concentrations of vitamin C (ascorbic acid and dehydroascorbic acid), carotenoids, and chlorophyll and on the visual quality of the leaves. The spinach was sown in April and August and harvested at two growth stages. After harvest, leaves were stored in polypropylene bags at 2 and 10 degrees C. Shading significantly decreased the ascorbic acid concentration of April-sown spinach by 12-33%, but in the August-sown spinach, the response was inconsistent. Concentrations of total carotenoids and total chlorophylls were significantly higher under the nettings in many cases, especially under the spectrum-altering and low-transmittance nettings. Postharvest visual quality and postharvest persistence of the compounds analyzed were not greatly affected by shading. We conclude that these shade nettings are acceptable to use in baby spinach production when it comes to the studied aspects of internal and external quality of the produce.

  9. Sink limitation induces the expression of multiple soybean vegetative lipoxygenase mRNAs while the endogenous jasmonic acid level remains low.

    PubMed

    Bunker, T W; Koetje, D S; Stephenson, L C; Creelman, R A; Mullet, J E; Grimes, H D

    1995-08-01

    The response of individual members of the lipoxygenase multigene family in soybeans to sink deprivation was analyzed. RNase protection assays indicated that a novel vegetative lipoxygenase gene, vlxC, and three other vegetative lipoxygenase mRNAs accumulated in mature leaves in response to a variety of sink limitations. These data suggest that several members of the lipoxygenase multigene family are involved in assimilate partitioning. The possible involvement of jasmonic acid as a signaling molecule regulating assimilate partitioning into the vegetative storage proteins and lipoxygenases was directly assessed by determining the endogenous level of jasmonic acid in leaves from plants with their pods removed. There was no rise in the level of endogenous jasmonic acid coincident with the strong increase in both vlxC and vegetative storage protein VspB transcripts in response to sink limitation. Thus, expression of the vegetative lipoxygenases and vegetative storage proteins is not regulated by jasmonic acid in sink-limited leaves.

  10. Synthesis of medium chain length fatty acid ethyl esters in engineered Escherichia coli using endogenously produced medium chain fatty acids.

    PubMed

    Fan, Liping; Liu, Junfeng; Nie, Kaili; Liu, Luo; Wang, Fang; Tan, Tianwei; Deng, Li

    2013-07-10

    Microbial biosynthesis of fatty acid-derived biofuels from renewable carbon sources has attracted significant attention in recent years. Free fatty acids (FFAs) can be used as precursors for the production of micro-diesel. The expression of codon optimized two plants (Umbellularia californica and Cinnamomum camphora) medium-chain acyl-acyl carrier protein (ACP) thioesterase genes (ucFatB and ccFatB) in Escherichia coli resulted in a very high level of extractable medium-chain-specific hydrolytic activity and caused large accumulation of medium-chain free fatty acids. By heterologous co-expression of acyl-coenzyme A:diacylglycerol acyltransferase from Acinetobacter baylyi ADP1, specific plant thioesterases in E. coli, with supplementation of exogenous ethanol, resulted in drastic changes in fatty acid ethyl esters (FAEEs) composition ranging from 12:0 to 18:1. Through an optimized microbial shake-flask fermentation of two modified E. coli strains, yielded FFAs and FAEEs in the concentration of approximately 500 mg L(-1)/250 mg L(-1) and 2.01 mg g(-1)/1.99 mg g(-1), respectively. The optimal ethanol level for FAEEs yield in the two recombinant strains was reached at the 3% ethanol concentration, which was about 5.4-fold and 1.93-fold higher than that of 1% ethanol concentration.

  11. Stimulation of insulin release by phospholipase D. A potential role for endogenous phosphatidic acid in pancreatic islet function.

    PubMed

    Metz, S A; Dunlop, M

    1990-09-01

    Although exogenous phosphatidic acid (PA) has been shown to promote insulin release, the effects of endogenous PA on endocrine function are largely unexplored. In order to generate PA in situ, intact adult-rat islets were treated with exogenous phospholipases of the D type (PLD), and their effects on phospholipid metabolism and on insulin release were studied in parallel. Chromatographically purified PLD from Streptomyces chromofuscus stimulated the accumulation of PA in [14C]arachidonate- or [14C]myristate-prelabelled islets, and also promoted insulin secretion over an identical concentration range. During 30 min incubations, insulin release correlated closely with the accumulation of [14C]arachidonate-labelled PA (r2 = 0.98; P less than 0.01) or [14C]myristate-labelled PA (r2 = 0.97; P less than 0.01). Similar effects were seen both in freshly isolated and in overnight-cultured intact islets. In contrast, PLDs (from cabbage or peanut) which do not support phospholipid hydrolysis at the pH of the extracellular medium also did not promote insulin release. The effects on secretion of the active PLD preparation were inhibited by modest cooling (to 30 degrees C); dantrolene or Co2+ also inhibited PLD-induced secretion without decreasing PLD-induced PA formation. Additionally, the removal of PLD left the subsequent islet responsiveness to glucose intact, further supporting an exocytotic non-toxic mechanism. PLD-induced insulin release did not appear to require influx of extracellular Ca2+, nor could the activation of protein kinase C clearly be implicated. During incubations of 30 min, PLD selectively generated PA; however, more prolonged incubations (60 min) also led to production of some diacyglycerol and free arachidonic acid concomitant with progressive insulin release. These data suggest that PLD activation has both rapid and direct effects (via PA) and more delayed, secondary, effects (via other effects of PA or the generation of other lipid signals). Taken in

  12. Estimation of endogenous protein and amino acid ileal losses in weaned piglets by regression analysis using diets with graded levels of casein

    PubMed Central

    2013-01-01

    Background Many studies have investigated endogenous loss of proteins and amino acids (AAs) at the ileal level in growing pigs. However, only a few studies have researched this subject in piglets. Knowledge regarding AA ileal digestibility in piglets would be helpful during the formulation of diets for weaning piglets, rather than just using coefficients obtained in growing pigs. Therefore, in this study, we sought to estimate endogenous protein and AA ileal losses in piglets. Furthermore, apparent and true ileal digestibility (AID and TID) of protein and AAs from casein were measured. Results The average flow of protein was 20.8 g/kg of dry matter intake (DMI). Basal protein loss, as estimated by regression, was 16.9 g/kg DMI. Glutamic acid, arginine, and aspartic acid (2.2, 1.4, and 1.2 g/kg DMI, respectively) were the AAs for which greater losses were seen. The AID of protein and AAs increased as the protein level in the diet increased. A higher increment in AID was observed between diets with 80 and160 g CP/kg of feed; this finding was mainly attributable to increases in glycine and arginine (46.1% and 18%, respectively). The TID of protein was 97.8, and the TID of AAs varied from 93.9 for histidine to 100.2 for phenylalanine. Conclusions The basal endogenous protein loss in piglets was 16.9 g/kg DMI. Endogenous protein was rich in glutamic acid, aspartic acid, and arginine, which represented 32.7% of endogenous protein loss in weaning piglets. The TID of casein was high and varied from 93.0 for histidine to 100.2 for phenylalanine. PMID:24053636

  13. [Endogenous hypertriglyceridemia].

    PubMed

    Tsukamoto, Kazuhisa

    2013-09-01

    Endogenous hypertriglyceridemia, which includes familial hypertriglyceridemia and idiopathic hypertriglyceridemia, is characterized by the increased level of VLDL-triglycerides in the blood. Increased production of VLDL from the liver and the decreased catabolism of VLDL-TG in the vessel, which are also the main metabolic features of insulin resistance, have been proposed to be the causes of endogenous hypertriglyceridemia. Genetic factors responsible for endogenous hypertriglyceridemia have been elucidated in several studies, however, these factors have so far not been clearly identified yet; thus the causes of endogenous hypertriglyceridemia would be polygenic. Recent advances in the genetic analytical methods like genome-wide association study would hopefully unveil the whole pictures of endogenous hypertriglyceridemia.

  14. Effects of Endogenous Salicylic Acid on Nodulation in the Model Legumes Lotus japonicus and Medicago truncatula1[W

    PubMed Central

    Stacey, Gary; McAlvin, Crystal Bickley; Kim, Sung-Yong; Olivares, José; Soto, María José

    2006-01-01

    The exogenous addition of salicylic acid (SA) was previously shown to inhibit indeterminate but not determinate-type nodulation. We sought to extend these results by modulating endogenous levels of SA through the transgenic expression of salicylate hydroxylase (NahG) in both stably transformed Lotus japonicus and composite Medicago truncatula plants. NahG expression in L. japonicus resulted in a marked reduction of SA levels. This reduction correlated with an increase in the number of infections and mean nodule number when compared to controls. However, a complicating factor was that NahG-expressing plants had greater root growth. Spot inoculations of NahG-expressing L. japonicus plants confirmed increased nodulation in these plants. Consistent with the reported inhibitory effects of exogenous SA on indeterminate-type nodulation, NahG expression in M. truncatula plants led to enhanced nodulation and infection. These data point to an important role for SA-mediated plant defense pathways in controlling nodule formation on both determinate and indeterminate nodule-forming hosts. PMID:16798946

  15. Dormancy in somatic embryos and seeds ofVitis: changes in endogenous abscisic acid during embryogeny and germination.

    PubMed

    Rajasekaran, K; Vine, J; Mullins, M G

    1982-03-01

    Abscisic acid (ABA) in extracts of somatic embryos and seeds of Gloryvine (Vitis vinifera L.xV. rupestris Scheele) was measured by gas chromatography-mass spectrometry-selected ion monitoring using deuterated ABA, (±)-[C-3Me-(2)H3]ABA, ([(2)H3]ABA) as internal standard. The ABA content increased rapidly during embryogeny (0.035 ng/embryo at the globular stage to 0.22 ng/embryo at the mature stage). The level of ABA in the tissues of somatic embryos, expressed in ng/mg dry weight, decreased from the globular stage (0.76 ng/mg) to the mature stage (0.25 ng/mg). Chilling (4° C) induced normal germination of seeds and mature somatic embryos and precocious germination of globular, heart-shaped and torpedoshaped somatic embryos. In all cases chilling led to a marked reduction in endogenous ABA. Exogenous (±)-ABA inhibited the germination of chilled somatic embryos.

  16. Endogenous abscisic acid promotes hypocotyl growth and affects endoreduplication during dark-induced growth in tomato (Solanum lycopersicum L.).

    PubMed

    Humplík, Jan F; Bergougnoux, Véronique; Jandová, Michaela; Šimura, Jan; Pěnčík, Aleš; Tomanec, Ondřej; Rolčík, Jakub; Novák, Ondřej; Fellner, Martin

    2015-01-01

    Dark-induced growth (skotomorphogenesis) is primarily characterized by rapid elongation of the hypocotyl. We have studied the role of abscisic acid (ABA) during the development of young tomato (Solanum lycopersicum L.) seedlings. We observed that ABA deficiency caused a reduction in hypocotyl growth at the level of cell elongation and that the growth in ABA-deficient plants could be improved by treatment with exogenous ABA, through which the plants show a concentration dependent response. In addition, ABA accumulated in dark-grown tomato seedlings that grew rapidly, whereas seedlings grown under blue light exhibited low growth rates and accumulated less ABA. We demonstrated that ABA promotes DNA endoreduplication by enhancing the expression of the genes encoding inhibitors of cyclin-dependent kinases SlKRP1 and SlKRP3 and by reducing cytokinin levels. These data were supported by the expression analysis of the genes which encode enzymes involved in ABA and CK metabolism. Our results show that ABA is essential for the process of hypocotyl elongation and that appropriate control of the endogenous level of ABA is required in order to drive the growth of etiolated seedlings.

  17. Fatty acid labeling from glutamine in hypoxia can be explained by isotope exchange without net reductive isocitrate dehydrogenase (IDH) flux.

    PubMed

    Fan, Jing; Kamphorst, Jurre J; Rabinowitz, Joshua D; Shlomi, Tomer

    2013-10-25

    Acetyl-CoA is an important anabolic precursor for lipid biosynthesis. In the conventional view of mammalian metabolism, acetyl-CoA is primarily derived by the oxidation of glucose-derived pyruvate in mitochondria. Recent studies have employed isotope tracers to show that in cancer cells grown in hypoxia or with defective mitochondria, a major fraction of acetyl-CoA is produced via another route, reductive carboxylation of glutamine-derived α-ketoglutarate (catalyzed by reverse flux through isocitrate dehydrogenase, IDH). Here, we employ a quantitative flux model to show that in hypoxia and in cells with defective mitochondria, oxidative IDH flux persists and may exceed the reductive flux. Therefore, IDH flux may not be a net contributor to acetyl-CoA production, although we cannot rule out net reductive IDH flux in some compartments. Instead of producing large amounts of net acetyl-CoA reductively, the cells adapt by reducing their demand for acetyl-CoA by importing rather than synthesizing fatty acids. Thus, fatty acid labeling from glutamine in hypoxia can be explained by spreading of label without net reductive IDH flux.

  18. The effect of trinitrobenzene sulfonic acid on gut-derived smooth muscle cell arachidonic acid metabolism: role of endogenous prostanoids.

    PubMed

    Longo, W E; Smith, G S; Deshpande, Y; Reickenberg, C; Kaminski, D L

    1997-01-01

    The contribution of smooth muscle cells as a potential source of eicosanoid production during inflammatory states remains to be elucidated. We investigated the effect of trinitrobenzene sulfonic acid (TNB), a known pro-inflammatory agent, on jejunal smooth muscle cell eicosanoid production. Human gut-derived smooth muscle cells (HISM) were incubated with TNB for 1 hour. Additionally, some cells were preincubated with either dimethylthiourea, or indomethacin for 1 hour before exposure to identical concentrations of TNB. Incubation with TNB led to significant increases in PGE(2) and 6-keto PGF-1(alpha) release, but not leukotriene B(4) release; responses which were both inhibited by dimethylthiourea and indomethacin treatment. Our results suggest that gutderived smooth muscle cells may represent an important source of proinflammatory prostanoids but not leukotrienes during inflammatory states of the intestine. The inhibition of prostanoid activity by thiourea may be mediated by suppression of cyclooxygenase activity in this cell line.

  19. Mitochondrial impairment induced by 3-nitropropionic acid is enhanced by endogenous metalloprotease activity inhibition in cultured rat striatal neurons.

    PubMed

    de Oca Balderas, Pavel Montes; Ospina, Gabriel Gutiérrez; Del Ángel, Abel Santamaría

    2013-06-24

    Metalloproteases from the metzincin family mediate molecule processing at the cell membrane termed ectodomain shedding (ES). This mechanism enables the generation of intracellular and extracellular fragments from cell membrane molecules that exert additional functions involved in cell processes including cell death, beyond those of full length molecules. Micotoxin 3-nitropropionic acid (3-NP) induces striatal neuronal degeneration in vivo and in vitro through mitochondrial complex II inhibition. In this study, we hypothesized that metalloproteases regulate mitochondrial activity in cultured rat striatal neurons undergoing degeneration. To test this idea, striatal neuronal cultures characterized by NeuN and GAD-67 expression were treated with 3-NP together with the metalloprotease inhibitor GM6001 and their mitochondrial activity was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Our results showed that metalloprotease inhibition potentiated mitochondrial activity impairment induced by 3-NP whereas the inhibitor alone had no effect. These results indicate that metalloproteases regulate and promote mitochondrial functionality in striatal neurons undergoing degeneration induced by 3-NP. Since NMDA receptor is involved in the excitotoxic neuronal death triggered by 3-NP and is known to undergo ES, we analyzed NMDAR subunit NR1 phenotypic distribution by immunofluorescence. 3-NP and GM6001 induced abnormal perinuclear NR1 accumulation that was not observed with 3-NP or GM6001 alone. This observation suggests that metalloproteases are involved in NR1 cellular reorganization induced by 3-NP, and that their inhibition results in abnormal NR1 distribution. Together results indicate that endogenous metalloproteases are activated during striatal neurodegeneration induced by 3-NP eliciting an adaptative or compensatory response that protects mitochondrial functionality.

  20. Endogenous salicylic acid levels correlate with accumulation of pathogenesis-related proteins and virus resistance in tobacco

    SciTech Connect

    Yalpani, N.; Shulaev, V.; Raskin, I. )

    1993-07-01

    Salicylic acid (SA) is hypothesized to be an endogenous regulator of local and systemic disease resistance and an inducer of pathogenesis-related (PR) proteins among plants. High levels of PR proteins have been observed in an uninoculated amphidiploid hybrid of Nicotiana glutinosa [times] N. debneyi, which is highly resistant to tobacco mosaic virus (TMV). Fluoresence, UV, and mass spectral analysis established that the levels of SA in healthy N. glutinosa [times] N. debneyi leaves were 30 times greater than in N. tabacum [open quotes]Xanthi-nc[close quotes] tobacco, which does not constitutively express PR proteins and is less resistant to TMV. Upon TMV-inoculation SA levels increased at least 70-fold leaves of Xanthi-nc but role only slightly in the hybrid. Phloem exudates of N. glutinosa [times] N. debneyi contained at least 500 times more SA than those of Xanthi-nc. SA treatment caused the appearance of PR-1 protein in Xanthi-nc but did not affect constitutively high levels of PR-1 protein in N. glutinosa [times] N. debneyi. In contrast to Xanthi-nc tobacco, TMV-inoculated N. glutinosa [times] N. debneyi kept at 32 C accumulated more than 0.5 [mu]g SA/g fresh weight, maintained high levels of PR proteins, and developed a hypersensitive response to TMV. PR proteins have previously been shown to accumulate in the lower leaves of healthy, flowering Xanthi-nc tobacco, which exhibited increased resistance to TMV. These developmentally induced increases in resistance and PR-1 proteins positively correlated with tissue levels of SA. These results affirm the regulatory role of SA in disease resistance and PR protein production. 31 refs., 9 figs., 1 tab.

  1. Effect of insulin in conjunction with glucose, amino acids and potassium on net metabolism of glucose and amino acids in the goat mammary gland.

    PubMed

    Tesseraud, S; Grizard, J; Makarski, B; Debras, E; Bayle, G; Champredon, C

    1992-05-01

    The hyperinsulinaemic euglycaemic insulin clamp technique was used to study the effect of insulin on the arterio-venous concentration differences of glucose and amino acids across the mammary gland in dairy goats. Insulin was given in conjunction with K to prevent insulin hypokalaemia. Appropriate amino acid infusion was used to blunt insulin-induced hypoaminoacidaemia or to create hyperaminoacidaemia and maintain this state under insulin treatment. Hyperaminoacidaemia alone only stimulated mammary leucine uptake but did not significantly modify the net metabolism of other amino acids and glucose. Insulin infusion at physiological level in conjunction with glucose, KCl-NaCl and amino acids failed to alter mammary uptake of glucose and essential amino acids; occasional increase in arginine extraction and decrease in tyrosine extraction were exceptions. Thus these new experimental conditions did not reveal any galactopoietic effect of insulin.

  2. Endogenous gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens and further recommendation for interpretative cut-offs.

    PubMed

    Andresen-Streichert, Hilke; Jensen, P; Kietzerow, J; Schrot, M; Wilke, N; Vettorazzi, E; Mueller, A; Iwersen-Bergmann, S

    2015-01-01

    When interpreting gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens, a possible increase in GHB concentrations because of post-mortem generation must be considered. In this study, endogenous GHB concentrations in post-mortem biological fluids were investigated. Additionally, we review post-mortem GHB concentrations already published in the literature. Heart and peripheral blood samples, cerebrospinal fluid, urine, and vitreous humor were collected from 64 autopsies in subjects where the cause of death excluded GHB exposure. Sample analysis was carried out either on the day of autopsy or later after immediate freezing and storage at -20 °C. GHB concentrations in venous blood samples (n = 61) were <0.6-28.7 mg/L (mean 11.9 mg/L; median 10.6 mg/L), <0.6-65.3 mg/L (mean 15.2 mg/L; median 12.8 mg/L) in heart blood (n = 56), <0.6-25.1 mg/L (mean 6.0 mg/L; median 3.8 mg/L) in urine (n = 50), <0.6-39.0 mg/L (mean 9.6 mg/L; median 7.5 mg/L), in vitreous humor (n = 54), and <0.6-24.0 mg/L (mean 4.2 mg/L; median 3.2 mg/L) in cerebrospinal fluid (n = 52). There was no significant difference between GHB concentrations in cases where there were signs of beginning putrefaction at the time of autopsy (n = 9) and cases without obvious signs of putrefaction. In one case with advanced putrefaction, the GHB concentration in venous blood was 32.7 mg/L. In conclusion, for post-mortem venous blood, urine, and cerebrospinal fluid, an interpretative cut-off of 30 mg/L for GHB concentrations is suggested in cases where GHB analysis is conducted on the day of sample collection at autopsy or if samples have been stored at -20 °C immediately after collection.

  3. Glutathione and abscisic acid supplementation influences somatic embryo maturation and hormone endogenous levels during somatic embryogenesis in Podocarpus lambertii Klotzsch ex Endl.

    PubMed

    Fraga, Hugo Pacheco de Freitas; Vieira, Leila do Nascimento; Puttkammer, Catarina Corrêa; Dos Santos, Henrique Pessoa; Garighan, Julio de Andrade; Guerra, Miguel Pedro

    2016-12-01

    Here we propose a protocol for embryogenic cultures induction, proliferation and maturation for the Brazilian conifer Podocarpus lambertii, and investigated the effect of abscisic acid (ABA) and glutathione (GSH) supplementation on the maturation phase. ABA, zeatin (Z) and salicylic acid (SA) endogenous levels were quantified. Number of somatic embryos obtained in ABA-supplemented treatment was significant higher than in ABA-free treatment, showing the relevance of ABA supplementation during somatic embryos maturation. Histological analysis showed the stereotyped sequence of developmental stages in conifer somatic embryos, reaching the late torpedo-staged embryo. GSH supplementation in maturation culture medium improved the somatic embryos number and morphological features. GSH 0mM and GSH 0.1mM treatments correlated with a decreased ABA endogenous level during maturation, while GSH 0.5mM treatment showed constant levels. All treatments resulted in decreased Z endogenous levels, supporting the concept that cytokinins are important during the initial cell division but not for the later stages of embryo development. The lowest SA levels found in GSH 0.5mM treatment were coincident with early embryonic development, and this treatment resulted in the highest development of somatic embryos. Thus, a correlation between lower SA levels and improved somatic embryo formation can be hypothesized.

  4. Evaluation of net acid generation pH as a single indicator for acid forming potential of rocks using geochemical properties.

    PubMed

    Oh, Chamteut; Ji, Sangwoo; Yim, Giljae; Cheong, Youngwook

    2017-04-01

    The main purpose of this research was to evaluate the geochemical properties of rocks for a single indicator of acid-forming potential. The indicators, such as net acid generation (NAG), NAG pH and total S, were applied to 312 rock samples of various geological characteristics. Additional indicators, such as a Modified NAG pH, paste pH and available acid neutralizing capacity (ANC), were applied to 22 selected samples. Among them, NAG pH was considered the most plausible single indicator in evaluating acid-forming potential, as it is simple to measure, widely applicable to various samples and can be used to estimate the NAG value. The acid-forming potential of 287 samples (92% of samples examined in this research) was classified as either non-acid forming (NAF) or potentially acid forming (PAF) by NAG pH, with an NAF criteria of <3.21 and PAF of >4.52. The NAG pH was also a good estimate of the risk of short-term acid release when combined with paste pH information. However, application of NAG pH to coal mine wastes, with high organic carbon contents, produced erroneous results due to the generation of organic acid during the NAG test. In this research, a Modified NAG pH was assessed as an alternative to NAG pH in such situations.

  5. Environment or development? Lifetime net CO2 exchange and control of the expression of Crassulacean acid metabolism in Mesembryanthemum crystallinum.

    PubMed

    Winter, Klaus; Holtum, Joseph A M

    2007-01-01

    The relative influence of plant age and environmental stress signals in triggering a shift from C(3) photosynthesis to Crassulacean acid metabolism (CAM) in the annual halophytic C(3)-CAM species Mesembryanthemum crystallinum was explored by continuously monitoring net CO(2) exchange of whole shoots from the seedling stage until seed set. Plants exposed to high salinity (400 mm NaCl) in hydroponic culture solution or grown in saline-droughted soil acquired between 11% and 24% of their carbon via net dark CO(2) uptake involving CAM. In contrast, plants grown under nonsaline, well-watered conditions were capable of completing their life cycle by operating in the C(3) mode without ever exhibiting net CO(2) uptake at night. These observations are not consistent with the widely expressed view that the induction of CAM by high salinity in M. crystallinum represents an acceleration of preprogrammed developmental processes. Rather, our study demonstrates that the induction of the CAM pathway for carbon acquisition in M. crystallinum is under environmental control.

  6. Content and in vitro release of endogenous amino acids in the area of the nucleus of the solitary tract of the rat.

    PubMed

    Meeley, M P; Underwood, M D; Talman, W T; Reis, D J

    1989-12-01

    We sought to identify amino acid neurotransmitter candidates within the nucleus of the solitary tract in rats. Twenty endogenous amino acids were quantified by reverse-phase HPLC with fluorescence detection (30-fmol limit). Micropunches (1 mm) of the intermediate area of the solitary nucleus were prepared, and the amino acid content determined. Of all the components measured, the putative transmitters Glu, Gly, gamma-aminobutyric acid, taurine, Asp, and Ala appeared in greatest concentrations. Bilateral micropunches superfused in vitro with buffered medium containing 56 mM potassium released Glu, gamma-aminobutyric acid, and Gly in a significant manner (p less than 0.05) compared with basal levels. With Glu, 78% was calcium-dependent and, therefore, presumably from nerve endings; 99% of gamma-aminobutyric acid and 42% of Gly were dependent on calcium. After removal of the nodose ganglion, a bilateral decrease in the calcium-dependent release of Glu and gamma-aminobutyric acid, but not Gly, was observed; decreases were significant ipsilateral to the site of ablation. We conclude that (a) Glu is a transmitter of primary afferents in the nucleus of the solitary tract; (b) glutamatergic afferents may interact with gamma-aminobutyric acid system(s) in this region; (c) Gly also may participate in the mediation and/or modulation of cardiovascular or other visceral reflexes; and (d) amino acid neurotransmission may play an integral role in the neurogenic control of arterial pressure.

  7. Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: Involvement of endogenous copper and a putative mechanism for anticancer properties

    SciTech Connect

    Bhat, S.H.; Azmi, A.S.; Hadi, S.M. . E-mail: smhadi@vsnl.com

    2007-02-01

    Plant-derived dietary material contains several classes of polyphenols such as flavonoids, curcuminoids, stilbenes and hydroxycinnamic acids. They are recognized as naturally occurring antioxidants but also act as prooxidants catalyzing cellular DNA degradation in the presence of transition metal ions such as copper. Earlier we have shown that the stilbene resveratrol is able to mobilize endogenous copper ions leading to oxidative breakage of cellular DNA. In this paper, we show that caffeic acid (a hydroxycinnamic acid), which is a major constituent of coffee, is also capable of DNA breakage in human peripheral lymphocytes. Incubation of lymphocytes with neocuproine inhibited the DNA degradation confirming that Cu(I) is an intermediate in the DNA cleavage reaction. Further, we have also shown that caffeic acid generates oxidative stress in lymphocytes, which is inhibited by scavengers of reactive oxygen species and neocuproine. These results are in further support of our hypothesis that anticancer mechanism of plant polyphenols involves mobilization of endogenous copper, possibly chromatin bound copper, and the consequent prooxidant action.

  8. Endogenous abscisic acid is involved in methyl jasmonate-induced reactive oxygen species and nitric oxide production but not in cytosolic alkalization in Arabidopsis guard cells.

    PubMed

    Ye, Wenxiu; Hossain, Mohammad Anowar; Munemasa, Shintaro; Nakamura, Yoshimasa; Mori, Izumi C; Murata, Yoshiyuki

    2013-09-01

    We recently demonstrated that endogenous abscisic acid (ABA) is involved in methyl jasmonate (MeJA)-induced stomatal closure in Arabidopsis thaliana. In this study, we investigated whether endogenous ABA is involved in MeJA-induced reactive oxygen species (ROS) and nitric oxide (NO) production and cytosolic alkalization in guard cells using an ABA-deficient Arabidopsis mutant, aba2-2, and an inhibitor of ABA biosynthesis, fluridon (FLU). The aba2-2 mutation impaired MeJA-induced ROS and NO production. FLU inhibited MeJA-induced ROS production in wild-type guard cells. Pretreatment with 0.1 μM ABA, which does not induce stomatal closure in the wild type, complemented the insensitivity to MeJA of the aba2-2 mutant. However, MeJA induced cytosolic alkalization in both wild-type and aba2-2 guard cells. These results suggest that endogenous ABA is involved in MeJA-induced ROS and NO production but not in MeJA-induced cytosolic alkalization in Arabidopsis guard cells.

  9. In vivo visualization of endogenous miR-21 using hyaluronic acid-coated graphene oxide for targeted cancer therapy.

    PubMed

    Hwang, Do Won; Kim, Han Young; Li, Fangyuan; Park, Ji Yong; Kim, Dohyun; Park, Jae Hyung; Han, Hwa Seung; Byun, Jung Woo; Lee, Yun-Sang; Jeong, Jae Min; Char, Kookheon; Lee, Dong Soo

    2017-03-01

    Oncogene-targeted nucleic acid therapy has been spotlighted as a new paradigm for cancer therapeutics. However, in vivo delivery issues and uncertainty of therapeutic antisense drug reactions remain critical hurdles for a successful targeted cancer therapy. In this study, we developed a fluorescence-switchable theranostic nanoplatform using hyaluronic acid (HA)-conjugated graphene oxide (GO), which is capable of both sensing oncogenic miR-21 and inhibiting its tumorigenicity simultaneously. Cy3-labeled antisense miR-21 peptide nucleic acid (PNA) probes loaded onto HA-GO (HGP21) specifically targeted CD44-positive MBA-MB231 cells and showed fluorescence recovery by interacting with endogenous miR-21 in the cytoplasm of the MBA-MB231 cells. Knockdown of endogenous miR-21 by HGP21 led to decreased proliferation and reduced migration of cancer cells, as well as the induction of apoptosis, with enhanced PTEN levels. Interestingly, in vivo fluorescence signals markedly recovered 3 h after the intravenous delivery of HGP21 and displayed signals more than 5-fold higher than those observed in the HGPscr-treated group of tumor-bearing mice. These findings demonstrate the possibility of using the HGP nanoplatform as a cancer theranostic tool in miRNA-targeted therapy.

  10. Dietary sodium chloride intake independently predicts the degree of hyperchloremic metabolic acidosis in healthy humans consuming a net acid-producing diet.

    PubMed

    Frassetto, Lynda A; Morris, R Curtis; Sebastian, Anthony

    2007-08-01

    We previously demonstrated that typical American net acid-producing diets predict a low-grade metabolic acidosis of severity proportional to the diet net acid load as indexed by the steady-state renal net acid excretion rate (NAE). We now investigate whether a sodium (Na) chloride (Cl) containing diet likewise associates with a low-grade metabolic acidosis of severity proportional to the sodium chloride content of the diet as indexed by the steady-state Na and Cl excretion rates. In the steady-state preintervention periods of our previously reported studies comprising 77 healthy subjects, we averaged in each subject three to six values of blood hydrogen ion concentration ([H]b), plasma bicarbonate concentration ([HCO(3)(-)]p), the partial pressure of carbon dioxide (Pco(2)), the urinary excretion rates of Na, Cl, NAE, and renal function as measured by creatinine clearance (CrCl), and performed multivariate analyses. Dietary Cl strongly correlated positively with dietary Na (P < 0.001) and was an independent negative predictor of [HCO(3)(-)]p after adjustment for diet net acid load, Pco(2) and CrCl, and positive and negative predictors, respectively, of [H]b and [HCO(3)(-)]p after adjustment for diet acid load and Pco(2). These data provide the first evidence that, in healthy humans, the diet loads of NaCl and net acid independently predict systemic acid-base status, with increasing degrees of low-grade hyperchloremic metabolic acidosis as the loads increase. Assuming a causal relationship, over their respective ranges of variation, NaCl has approximately 50-100% of the acidosis-producing effect of the diet net acid load.

  11. Modeled dosage-response relationship on the net photosynthetic rate for the sensitivity to acid rain of 21 plant species.

    PubMed

    Deng, Shihuai; Gou, Shuzhen; Sun, Baiye; Lv, Wenlin; Li, Yuanwei; Peng, Hong; Xiao, Hong; Yang, Gang; Wang, Yingjun

    2012-08-01

    This study investigated the sensitivity of plant species to acid rain based on the modeled dosage-response relationship on the net photosynthetic rate (P (N)) of 21 types of plant species, subjected to the exposure of simulated acid rain (SAR) for 5 times during a period of 50 days. Variable responses of P (N) to SAR occurred depending on the type of plant. A majority (13 species) of the dosage-response relationship could be described by an S-shaped curve and be fitted with the Boltzmann model. Model fitting allowed quantitative evaluation of the dosage-response relationship and an accurate estimation of the EC(10), termed as the pH of the acid rain resulting in a P (N) 10 % lower than the reference value. The top 9 species (Camellia sasanqua, Cinnamomum camphora, etc. EC(10) ≤ 3.0) are highly endurable to very acid rain. The rare, relict plant Metasequoia glyptostroboides was the most sensitive species (EC(10) = 5.1) recommended for protection.

  12. Endogenous level of acetic acid in yellowfin tuna (Thunnus albacares): a pilot study about a possible controversy on its residue nature.

    PubMed

    Chiesa, Luca Maria; Pasquale, Elisa; Panseri, Sara; Britti, Domenico; Malandra, Renato; Villa, Roberto; Arioli, Francesco

    2017-03-01

    A method based on headspace solid-phase microextraction (HS-SPME) followed by GC-MS analysis was developed for the determination of underivatised acetic acid in fresh tuna fish muscle. Parameters such as the fibre selected and the extraction time and temperature were optimised and the linearity, detection limits and precision of the whole analytical procedure were assessed. The method was then applied to determine the acetic acid concentration in fresh yellowfin tuna muscles (Thunnus albacares) in order to evaluate the endogenous level and its variations during the shelf life under different storage conditions. A qualitative comparison was also made with variations in histamine levels to evaluate the possibility of the joint monitoring of acetic acid and histamine to identify fish stored in poor conditions. The caudal area always had a lower content of acetic acid than the ventral area, independent of the storage time and temperature. A difference was found between the 6- and 3-day time points and day 0 at a storage temperature of 8°C and between the 6-day time point and day 0 at a storage temperature of 0°C, independent of the anatomical area of the sampled tissue. The evaluation of acetic acid could represent an important approach in the field of food safety to detect the illicit use of acetic acid as an antibacterial preservative treatment or to eliminate the unpleasant smell of trimethylamine.

  13. Acetaldehyde stimulation of net gluconeogenic carbon movement from applied malic acid in tomato fruit pericarp tissue

    SciTech Connect

    Halinska, A.; Frenkel, C. )

    1991-03-01

    Applied acetaldehyde is known to lead to sugar accumulation in fruit including tomatoes (Lycopersicon esculentum) presumably due to stimulation of gluconeogenesis. This conjecture was examined using tomato fruit pericarp discs as a test system and applied l-(U-{sup 14}C)malic acid as the source for gluconeogenic carbon mobilization. Results indicate that malic and perhaps other organic acids are carbon sources for gluconeogenesis occurring normally in ripening tomatoes. The process is stimulated by acetaldehyde apparently by attenuating the fructose-2,6-biphosphate levels. The mode of the acetaldehyde regulation of fructose-2,6-biphosphate metabolism awaits clarification.

  14. NMR identification of endogenous metabolites interacting with fatted and non-fatted human serum albumin in blood plasma: Fatty acids influence the HSA-metabolite interaction

    NASA Astrophysics Data System (ADS)

    Jupin, Marc; Michiels, Paul J.; Girard, Frederic C.; Spraul, Manfred; Wijmenga, Sybren S.

    2013-03-01

    Metabolites and their concentrations are direct reporters on body biochemistry. Thanks to technical developments metabolic profiling of body fluids, such as blood plasma, by for instance NMR has in the past decade become increasingly accurate enabling successful clinical diagnostics. Human Serum Albumin (HSA) is the main plasma protein (∼60% of all plasma protein) and responsible for the transport of endogenous (e.g. fatty acids) and exogenous metabolites, which it achieves thanks to its multiple binding sites and its flexibility. HSA has been extensively studied with regard to its binding of drugs (exogenous metabolites), but only to a lesser extent with regard to its binding of endogenous (non-fatty acid) metabolites. To obtain correct NMR measured metabolic profiles of blood plasma and/or potentially extract information on HSA and fatty acids content, it is necessary to characterize these endogenous metabolite/plasma protein interactions. Here, we investigate these metabolite-HSA interactions in blood plasma and blood plasma mimics. The latter contain the roughly twenty metabolites routinely detected by NMR (also most abundant) in normal relative concentrations with fatted or non-fatted HSA added or not. First, we find that chemical shift changes are small and seen only for a few of the metabolites. In contrast, a significant number of the metabolites display reduced resonance integrals and reduced free concentrations in the presence of HSA or fatted HSA. For slow-exchange (or strong) interactions, NMR resonance integrals report the free metabolite concentration, while for fast exchange (weak binding) the chemical shift reports on the binding. Hence, these metabolites bind strongly to HSA and/or fatted HSA, but to a limited degree because for most metabolites their concentration is smaller than the HSA concentration. Most interestingly, fatty acids decrease the metabolite-HSA binding quite significantly for most of the interacting metabolites. We further find

  15. NMR identification of endogenous metabolites interacting with fatted and non-fatted human serum albumin in blood plasma: Fatty acids influence the HSA-metabolite interaction.

    PubMed

    Jupin, Marc; Michiels, Paul J; Girard, Frederic C; Spraul, Manfred; Wijmenga, Sybren S

    2013-03-01

    Metabolites and their concentrations are direct reporters on body biochemistry. Thanks to technical developments metabolic profiling of body fluids, such as blood plasma, by for instance NMR has in the past decade become increasingly accurate enabling successful clinical diagnostics. Human Serum Albumin (HSA) is the main plasma protein (∼60% of all plasma protein) and responsible for the transport of endogenous (e.g. fatty acids) and exogenous metabolites, which it achieves thanks to its multiple binding sites and its flexibility. HSA has been extensively studied with regard to its binding of drugs (exogenous metabolites), but only to a lesser extent with regard to its binding of endogenous (non-fatty acid) metabolites. To obtain correct NMR measured metabolic profiles of blood plasma and/or potentially extract information on HSA and fatty acids content, it is necessary to characterize these endogenous metabolite/plasma protein interactions. Here, we investigate these metabolite-HSA interactions in blood plasma and blood plasma mimics. The latter contain the roughly twenty metabolites routinely detected by NMR (also most abundant) in normal relative concentrations with fatted or non-fatted HSA added or not. First, we find that chemical shift changes are small and seen only for a few of the metabolites. In contrast, a significant number of the metabolites display reduced resonance integrals and reduced free concentrations in the presence of HSA or fatted HSA. For slow-exchange (or strong) interactions, NMR resonance integrals report the free metabolite concentration, while for fast exchange (weak binding) the chemical shift reports on the binding. Hence, these metabolites bind strongly to HSA and/or fatted HSA, but to a limited degree because for most metabolites their concentration is smaller than the HSA concentration. Most interestingly, fatty acids decrease the metabolite-HSA binding quite significantly for most of the interacting metabolites. We further find

  16. Circadian changes in endogenous concentrations of indole-3-acetic acid, melatonin, serotonin, abscisic acid and jasmonic acid in Characeae (Chara australis Brown)

    PubMed Central

    Beilby, Mary J; Turi, Christina E; Baker, Teesha C; Tymm, Fiona JM; Murch, Susan J

    2015-01-01

    Giant-celled Characeae (Chara australis Brown), grown for 4 months on 12/12 hr day/night cycle and summer/autumn temperatures, exhibited distinct concentration maxima in auxin (indole-3-acetic acid; IAA), melatonin and serotonin about 4 hr after subjective daybreak. These concentration peaks persisted after 3 day pretreatment in continuous darkness: confirming a circadian rhythm, rather than a response to “light on.” The plants pretreated for 3 d in continuous light exhibited several large IAA concentration maxima throughout the 24 hr. The melatonin and serotonin concentrations decreased and were less synchronized with IAA. Chara plants grown on 9/15 hr day/night cycle for 4 months and winter/spring temperatures contained much smaller concentrations of IAA, melatonin and serotonin. The IAA concentration maxima were observed in subjective dark phase. Serotonin concentration peaks were weakly correlated with those of IAA. Melatonin concentration was low and mostly independent of circadian cycle. The “dark” IAA concentration peaks persisted in plants treated for 3 d in the dark. The plants pretreated for 3 d in the light again developed more IAA concentration peaks. In this case the concentration maxima in melatonin and serotonin became more synchronous with those in IAA. The abscisic acid (ABA) and jasmonic acid (JA) concentrations were also measured in plants on winter regime. The ABA concentration did not exhibit circadian pattern, while JA concentration peaks were out of phase with those of IAA. The data are discussed in terms of crosstalk between metabolic pathways. PMID:26382914

  17. Contribution of the net charge to the regulatory effects of amino acids and epsilon-poly(L-lysine) on the gelatinization behavior of potato starch granules.

    PubMed

    Ito, Azusa; Hattori, Makoto; Yoshida, Tadashi; Takahashi, Koji

    2006-01-01

    The effects of lysine (Lys), monosodium glutamate (GluNa), glycine, alanine and epsilon-poly(L-lysine) (PL) with different degrees of polymerization on the gelatinization behavior of potato starch granules were investigated by DSC, viscosity and swelling measurements, microscopic observation, and measurement of the retained amino acid amount to clarify the contribution of the net charge to their regulatory effects on the gelatinization behavior. The amino acids and PL each contributed to an increase in the gelatinization temperature, and a decrease in the peak viscosity and swelling. These effects strongly depended on the absolute value of their net charge. The disappearance of a negative or positive net charge by adjusting the pH value weakened the contribution. The swelling index and size of the potato starch granules changed according to replacement of the swelling medium. The amino acids and PL were easily retained by the swollen potato starch granules according to replacement of the outer solution of the starch granules.

  18. Concerted action of endogenous and heterologous phytase on phytic acid degradation in seed of transgenic wheat (Triticum aestivum L.).

    PubMed

    Brinch-Pedersen, Henrik; Hatzack, Frank; Sørensen, Lisbeth D; Holm, Preben B

    2003-12-01

    Expression of heterologous phytases in crops offers a great potential for improving phosphate and mineral bioavailability in food and feed. In this context it is of relevance to describe the concerted action of endogenous and hetrologous phytases on the transgenic seed inositol phosphate profile. Here we report metal-dye detection HPLC analysis of inositol phosphate degradation in flour from transgenic wheat materials possessing wheat endogenous 6-phytase [EC 3.1.3.26] and Aspergillus 3-phytase [EC 3.1.3.8] activities under the control of the maize ubiquitin-1 promoter and the wheat high molecular weight glutenin subunit 1DX5 promoter respectively. During 50 min incubation there is an accumulation of InsP5 to InsP2 breakdown products in non-transgenic material. Aspergillus niger phytase specific breakdown products are transiently detected in transgenic material but after 50 min incubation virtually all InsP5, InsP4 and InsP3 isomers are hydrolysed.

  19. Neuronal gamma-aminobutyric acid (GABA) type A receptors undergo cognate ligand chaperoning in the endoplasmic reticulum by endogenous GABA

    PubMed Central

    Wang, Ping; Eshaq, Randa S.; Meshul, Charles K.; Moore, Cynthia; Hood, Rebecca L.; Leidenheimer, Nancy J.

    2015-01-01

    GABAA receptors mediate fast inhibitory neurotransmission in the brain. Dysfunction of these receptors is associated with various psychiatric/neurological disorders and drugs targeting this receptor are widely used therapeutic agents. Both the efficacy and plasticity of GABAA receptor-mediated neurotransmission depends on the number of surface GABAA receptors. An understudied aspect of receptor cell surface expression is the post-translational regulation of receptor biogenesis within the endoplasmic reticulum (ER). We have previously shown that exogenous GABA can act as a ligand chaperone of recombinant GABAA receptors in the early secretory pathway leading us to now investigate whether endogenous GABA facilitates the biogenesis of GABAA receptors in primary cerebral cortical cultures. In immunofluorescence labeling experiments, we have determined that neurons expressing surface GABAA receptors contain both GABA and its degradative enzyme GABA transaminase (GABA-T). Treatment of neurons with GABA-T inhibitors, a treatment known to increase intracellular GABA levels, decreases the interaction of the receptor with the ER quality control protein calnexin, concomittantly increasing receptor forward-trafficking and plasma membrane insertion. The effect of GABA-T inhibition on the receptor/calnexin interaction is not due to the activation of surface GABAA or GABAB receptors. Consistent with our hypothesis that GABA acts as a cognate ligand chaperone in the ER, immunogold-labeling of rodent brain slices reveals the presence of GABA within the rough ER. The density of this labeling is similar to that present in mitochondria, the organelle in which GABA is degraded. Lastly, the effect of GABA-T inhibition on the receptor/calnexin interaction was prevented by pretreatment with a GABA transporter inhibitor. Together, these data indicate that endogenous GABA acts in the rough ER as a cognate ligand chaperone to facilitate the biogenesis of neuronal GABAA receptors. PMID

  20. Near Infrared Graphene Quantum Dots-Based Two-Photon Nanoprobe for Direct Bioimaging of Endogenous Ascorbic Acid in Living Cells.

    PubMed

    Feng, Li-Li; Wu, Yong-Xiang; Zhang, Dai-Liang; Hu, Xiao-Xiao; Zhang, Jing; Wang, Peng; Song, Zhi-Ling; Zhang, Xiao-Bing; Tan, Weihong

    2017-04-04

    Ascorbic acid (AA), as one of the most important vitamins, participates in various physiological reactions in the human body and is implicated with many diseases. Therefore, the development of effective methods for monitoring the AA level in living systems is of great significance. Up to date, various technologies have been developed for the detection of AA. However, few methods can realize the direct detection of endogenous AA in living cells. In this work, we for the first time reported that near-infrared (NIR) graphene quantum dots (GQD) possessed good two-photon fluorescence properties with a NIR emission at 660 nm upon exciting with 810 nm femtosecond pulses and a two-photon (TP) excitation action cross-section (δΦ) of 25.12 GM. They were then employed to construct a TP nanoprobe for detection and bioimaging of endogenous AA in living cells. In this nanosystem, NIR GQDs (NGs), which exhibited lower fluorescence background in living system to afford improved fluorescence imaging resolution, were acted as fluorescence reporters. Also CoOOH nanoflakes were chosen as fluorescence quenchers by forming on the surface of NGs. Once AA was introduced, CoOOH was reduced to Co(2+), which resulted in a "turn-on" fluorescence signal of NGs. The proposed nanoprobe demonstrated high sensitivity toward AA, with the observed LOD of 270 nM. It also showed high selectivity to AA with excellent photostability. Moreover, the nanoprobe was successfully used for TP imaging of endogenous AA in living cells as well as deep tissue imaging.

  1. The site of net absorption of Ca from the intestinal tract of growing pigs and effect of phytic acid, Ca level and Ca source on Ca digestibility.

    PubMed

    González-Vega, J Caroline; Walk, Carrie L; Liu, Yanhong; Stein, Hans H

    2014-01-01

    An experiment was conducted to test the hypothesis that the standardised digestibility of Ca in calcium carbonate and Lithothamnium calcareum Ca is not different regardless of the level of dietary Ca, and that phytic acid affects the digestibility of Ca in these two ingredients to the same degree. The objectives were to determine where in the intestinal tract Ca absorption takes place and if there are measurable quantities of basal endogenous Ca fluxes in the stomach, small intestine or large intestine. Diets contained calcium carbonate or L. calcareum Ca as the sole source of Ca, 0% or 1% phytic acid and 0.4% or 0.8% Ca. A Ca-free diet was also formulated and used to measure endogenous fluxes and losses of Ca. Nine growing pigs (initial body weight 23.8 ± 1.3 kg) were cannulated in the duodenum and in the distal ileum, and faecal, ileal and duodenal samples were collected. Duodenal endogenous fluxes of Ca were greater (p < 0.05) than ileal endogenous fluxes and total tract endogenous losses of Ca, but ileal endogenous fluxes were less (p < 0.05) than total tract endogenous losses. Standardised digestibility of Ca was not affected by the level of phytic acid, but decreased (p < 0.05) as Ca level increased in L. calcareum Ca diets, but that was not the case if calcium carbonate was the source of Ca (interaction, p < 0.05). The standardised duodenal digestibility (SDD), standardised ileal digestibility (SID) and standardised total tract digestibility (STTD) of Ca were not different if calcium carbonate was the source of dietary Ca. However, the STTD of Ca in L. calcareum Ca was greater (p < 0.05) than the SID and SDD of Ca. The SDD, SID and STTD of Ca in calcium carbonate were greater (p < 0.05) than those of L. calcareum Ca. In conclusion, under the conditions of this experiment, standardised digestibility of Ca is not affected by the level of phytic acid, but may be affected by dietary Ca level depending on the Ca source. Calcium from calcium carbonate is mostly

  2. Role of Toll-like receptors and retinoic acid inducible gene I in endogenous production of type I interferon in dermatomyositis.

    PubMed

    Li, Ling; Dai, Tingjun; Lv, Jingwei; Ji, Kunqian; Liu, Junling; Zhang, Bin; Yan, Chuanzhu

    2015-08-15

    To explore the possible mechanisms implicated in the endogenous production of type I interferons within the muscle tissue of dermatomyositis (DM) patients. We detected the co-localization of plasmacytoid dendritic cells (pDCs) with Toll-like receptors (TLRs) and retinoic acid inducible gene (RIG)-I by immunohistochemistry and immunofluorescence. Western blotting confirmed the expression of TLRs and RIG-I. TLR-3 and RIG-I was preferentially expressed in the perifascicular atrophy fibers of DM. TLR-7 was only in inflammatory infiltrates of a few DM patients. TLR-4 and TLR-9 was expressed mainly in inflammatory infiltrates. Immunofluorescence showed extensive co-localization of BDCA-2 with TLR-9 and little co-localization with TLR-7. Western blotting showed upregulation of expression of TLRs and RIG-I in DM compared with the controls. Our findings indicate that endogenous production of type I IFN in DM is generated by pDCs, mainly through the TLR-9 pathway and in part by TLR-7. TLR-3 and RIG-I are implicated in the formation of perifascicular atrophy in DM.

  3. A smart sealed nucleic acid biosensor based on endogenous reference gene detection to screen and identify mammals on site

    PubMed Central

    Xu, Yuancong; Xiang, Wenjin; Wang, Qin; Cheng, Nan; Zhang, Li; Huang, Kunlun; Xu, Wentao

    2017-01-01

    The identification of meat adulteration is a hotspot for food research worldwide. In this paper, a smart and sealed biosensor that combines loop-mediated isothermal amplification (LAMP) with a lateral flow device (LFD) was developed, resulting in the universal mammalian assessment on site. First, the highly specific chromosomal Glucagon gene (Gcg) was chosen as the endogenous reference gene, and the LAMP approach provided double-labeled duplex DNA products using FITC- and BIO- modified primers. Then, an LFD strategy was used for specific signal recognition through an immunoassay. Meanwhile, LFD-LAMP was compared to LAMP and real-time LAMP, the results showed consistent high specificity and sensitivity but in a more convenient and easy-to-use system. In addition, the detection limit was as low as 10 pg, which was equivalent to 3~5 copies in mammals. All of the reactions were performed in a sealed system regardless of the amplification process or products recognized. Therefore, the smart design demonstrated significantly high specificity and the ability to detect trace amounts of DNA in complex and processed foods with mammalian meat. As a universal and specific platform for the detection of mammalian DNA, this smart biosensor is an excellent prospect for species identification and meat adulteration. PMID:28233849

  4. Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status

    NASA Astrophysics Data System (ADS)

    Marcus, Stuart L.; Sobel, Russel S.; Golub, Allyn L.; Carroll, Ronald L.; Lundahl, Scott L.; Shulman, D. Geoffrey

    1996-04-01

    Exogenous provision of ALA to many tissues results in the accumulation of sufficient quantities of the endogenous photosensitizer protoporphyrin IX, (PpIX), to produce a photodynamic effect. Therefore, ALA may be considered the only current PDT agent in clinical development which is a biochemical precursor of a photosensitizer. Topical ALA application, followed by exposure to activating light (ALA PDT), has been reported effective for the treatment of a variety of dermatologic diseases including cutaneous T-cell lymphoma, superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses, and is also being examined for treatment of acne and hirsutism. PpIX induced by ALA application also may serve as a fluorescence detection marker for photodiagnosis (PD) of malignant and pre- malignant conditions of the urinary bladder and other organs. Local internal application of ALA has also been used for selective endometrial ablation in animal model systems and is beginning to be examined in human clinical studies. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer, various gastrointestinal cancers, and the condition known as Barrett's esophagus. This brief paper reviews the current clinical and development status of ALA PDT.

  5. A smart sealed nucleic acid biosensor based on endogenous reference gene detection to screen and identify mammals on site.

    PubMed

    Xu, Yuancong; Xiang, Wenjin; Wang, Qin; Cheng, Nan; Zhang, Li; Huang, Kunlun; Xu, Wentao

    2017-02-24

    The identification of meat adulteration is a hotspot for food research worldwide. In this paper, a smart and sealed biosensor that combines loop-mediated isothermal amplification (LAMP) with a lateral flow device (LFD) was developed, resulting in the universal mammalian assessment on site. First, the highly specific chromosomal Glucagon gene (Gcg) was chosen as the endogenous reference gene, and the LAMP approach provided double-labeled duplex DNA products using FITC- and BIO- modified primers. Then, an LFD strategy was used for specific signal recognition through an immunoassay. Meanwhile, LFD-LAMP was compared to LAMP and real-time LAMP, the results showed consistent high specificity and sensitivity but in a more convenient and easy-to-use system. In addition, the detection limit was as low as 10 pg, which was equivalent to 3~5 copies in mammals. All of the reactions were performed in a sealed system regardless of the amplification process or products recognized. Therefore, the smart design demonstrated significantly high specificity and the ability to detect trace amounts of DNA in complex and processed foods with mammalian meat. As a universal and specific platform for the detection of mammalian DNA, this smart biosensor is an excellent prospect for species identification and meat adulteration.

  6. Inhibition of gastric mucosal prostaglandin synthetase activity by mercaptomethylimidazole, an inducer of gastric acid secretion--plausible involvement of endogenous H2O2.

    PubMed

    Bhattacharjee, M; Chakraborty, T; Ganguly, C; Banerjee, R K

    1998-10-01

    We have reported earlier that mercaptomethylimidazole (MMI), an antithyroid drug of thionamide group, induces gastric acid secretion at least partially through the liberation of histamine, sensitive to cimetidine. Now, we show that the drug has a significant inhibitory effect on the cyclooxygenase and peroxidase activity of the prostaglandin (PG) synthetase of the gastric mucosal microsomal preparation. The effect can also be mimicked by low concentrations of H2O2. While studying the possible intracellular effect of MMI on acid secretion, a cell fraction (F3) enriched in parietal cell was isolated by controlled digestion of the mucosa with protease. This cell fraction is activated by MMI as measured by increased O2 consumption. The activation is sensitive to omeprazole, a proton-pump inhibitor, indicating that the activation is due to increased acid secretion by MMI. MMI was also found to directly inhibit the peroxidase activity of the F3 cell fraction and may thus increase the intracellular level of H2O2. The cyclooxygenase activity of the PG synthetase of the F3 cell fraction is also inhibited by MMI and the effect can be reproduced by low concentrations of H2O2. Both MMI and H2O2 can also inhibit the peroxidase activity of the PG synthetase. We suggest that in addition to the activation of the parietal cell by MMI possibly through endogenous H2O2, MMI induces acid secretion in vivo by inactivating the PG synthetase thereby inhibiting the biosynthesis of PG and removing its inhibitory influence on acid secretion so that the histamine released by MMI can stimulate acid secretion with maximum efficiency.

  7. Development of a Medium-Throughput Targeted LCMS Assay to Detect Endogenous Cellular Levels of Malonyl-CoA to Screen Fatty Acid Synthase Inhibitors.

    PubMed

    Hopcroft, Philip J; Fisher, David I

    2016-02-01

    The fatty acid synthase (FAS) enzyme in mammalian cells is a large multidomain protein responsible for de novo synthesis of fatty acids. The steps catalyzed by FAS involve the condensation of acetyl-CoA and malonyl-CoA moieties in the presence of NADPH until palmitate is formed. Inhibition of FAS causes an accumulation of intracellular malonyl-CoA, as this metabolite is essentially committed to fatty acid synthesis once formed. Detection of intracellular metabolites for screening can be problematic due to a lack of appropriate tools, but here we describe a targeted liquid chromatography-mass spectroscopy (LCMS) method to directly measure endogenous levels of malonyl-CoA to drive a drug development structure-activity relationship (SAR) screening cascade. Our process involves preparation of samples at 96-well scale, normalization postpermeabilization via use of a whole-well imaging platform, and the LCMS detection methodology. The assay is amenable to multiplexing cellular endpoints, has a typical Z' of >0.6, and has high reproducibility of EC50 values.

  8. On-Tissue Derivatization via Electrospray Deposition for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging of Endogenous Fatty Acids in Rat Brain Tissues

    PubMed Central

    2016-01-01

    Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is used for the multiplex detection and characterization of diverse analytes over a wide mass range directly from tissues. However, analyte coverage with MALDI MSI is typically limited to the more abundant compounds, which have m/z values that are distinct from MALDI matrix-related ions. On-tissue analyte derivatization addresses these issues by selectively tagging functional groups specific to a class of analytes, while simultaneously changing their molecular masses and improving their desorption and ionization efficiency. We evaluated electrospray deposition of liquid-phase derivatization agents as a means of on-tissue analyte derivatization using 2-picolylamine; we were able to detect a range of endogenous fatty acids with MALDI MSI. When compared with airbrush application, electrospray led to a 3-fold improvement in detection limits and decreased analyte delocalization. Six fatty acids were detected and visualized from rat cerebrum tissue using a MALDI MSI instrument operating in positive mode. MALDI MSI of the hippocampal area allowed targeted fatty acid analysis of the dentate gyrus granule cell layer and the CA1 pyramidal layer with a 20-μm pixel width, without degrading the localization of other lipids during liquid-phase analyte derivatization. PMID:27181709

  9. Net Acid Production, Acid Neutralizing Capacity, and Associated Mineralogical and Geochemical Characteristics of Animas River Watershed Igneous Rocks Near Silverton, Colorado

    USGS Publications Warehouse

    Yager, Douglas B.; Choate, LaDonna; Stanton, Mark R.

    2008-01-01

    This report presents results from laboratory and field studies involving the net acid production (NAP), acid neutralizing capacity (ANC), and magnetic mineralogy of 27 samples collected in altered volcanic terrain in the upper Animas River watershed near Silverton, Colo., during the summer of 2005. Sampling focused mainly on the volumetrically important, Tertiary-age volcanic and plutonic rocks that host base- and precious-metal mineralization in the study area. These rocks were analyzed to determine their potential for neutralization of acid-rock drainage. Rocks in the study area have been subjected to a regional propylitic alteration event, which introduced calcite, chlorite (clinochlore), and epidote that have varying amounts and rates of acid neutralizing capacity (ANC). Locally, hydrothermal alteration has consumed any ANC and introduced minerals, mainly pyrite, that have a high net acid production (NAP). Laboratory studies included hydrogen pyroxide (H2O2) acid digestion and subsequent sodium hydroxide (NaOH) titration to determine NAP, and sulfuric acid (H2SO4) acid titration experiments to determine ANC. In addition to these environmental rock-property determinations, mineralogical, chemical, and petrographic characteristics of each sample were determined through semiquantitative X-ray diffractometry (Rietveld method), optical mineralogy, wavelength dispersive X-ray fluorescence, total carbon-carbonate, and inductively coupled plasma?mass spectrometric analysis. An ANC ranking was assigned to rock samples based on calculated ANC quantity in kilograms/ton (kg/t) calcium carbonate equivalent and ratios of ANC to NAP. Results show that talus near the southeast Silverton caldera margin, composed of andesite clasts of the Burns Member of the Silverton Volcanics, has the highest ANC (>100 kg/t calcium carbonate equivalent) with little to no NAP. The other units found to have moderate to high ANC include (a) andesite lavas and volcaniclastic rocks of the San Juan

  10. Hydrokolloid occlusive dressings for photodynamic therapy (PDT) of cutaneous lesions with endogenous porphyrins induced by 5-aminolevulinic acid

    NASA Astrophysics Data System (ADS)

    Gahlen, Johannes; Stern, Josef; Herfarth, Christian

    1995-03-01

    Protoporphyrin (Pp IX) is the final intermediate product before haem and can be stimulated to a phototoxic reaction with light. The presence of 5-aminolevulinic acid can increase the intracellular biosynthesis of Pp IX in certain types of tumor cells. The photosensitizing concentrations of Pp IX make laser light induced fluorescence diagnostics (LIFD) and photodynamic therapy possible. A topical application of a 5-aminolevulinic acid solution requires a waterproof occlusive dressing for several hours. We developed a simple technique for a practical preparation for PDT using a hydrocolloid dressing. The normal surrounding skin can be spared. We present our first therapeutic experience with a case of cutaneous breast cancer in a 65-year-old female patient. Six hours after topical application of 10% isotonic 5- aminolevulinic acid under the hydrocolloid dressing PDT was performed (Ar-Dye Laser, 630 nm wavelength). Twenty four hours after PDT a superficial tumor necrosis could be observed with a maximum depth of tumor necrosis of 2 - 3 mm. The surrounding normal skin was without any inflammation.

  11. Detection in vivo of a Novel Endogenous Etheno DNA Adduct Derived from Arachidonic Acid and the Effects of Antioxidants on Its Formation

    PubMed Central

    Cruz, Idalia M.; Pondicherry, Sharanya R.; Fernandez, Aileen; Schultz, Casey L.; Yang, Peiying; Pan, Jishen; Desai, Dhimant; Krzeminski, Jacek; Amin, Shantu; Christov, Plamen P.; Hara, Yukihiko; Chung, Fung-Lung

    2014-01-01

    Previous studies showed that the 7-(1′,2′-dihydroxyheptyl) substituted etheno DNA adducts are products from reactions with epoxide of (E)-4-hydroxy-2-nonenal (HNE), an oxidation product of ω-6 polyunsaturated fatty acids (PUFAs). In this work, we report the detection of 7-(1′,2′-dihydroxyheptyl)-1,N6-ethenodeoxyadenosine (DHHedA) in rodent and human tissues by two independent methods: a 32P-postlabeling/HPLC method and an isotope dilution liquid chromatography electrospray ionization tandem mass spectrometry method (ID-LC-ESI-MS/MS), demonstrating for the first time that DHHedA is a background DNA lesion in vivo. We showed that DHHedA can be formed upon incubation of arachidonic acid (AA) with deoxyadenosine (dA), supporting the notion that ω-6 PUFAs are the endogenous source of DHHedA formation. Because cyclic adducts are derived from the oxidation of PUFAs, we subsequently examined the effects of antioxidants, α-lipoic acid, Polyphenon E and vitamin E, on the formation of DHHedA and γ-hydroxy-1,N2-propanodeoxyguanosine (γ-OHPdG), a widely studied acrolein-derived adduct arising from oxidized PUFAs, in the livers of Long Evans Cinnamon (LEC) rats. LEC rats are inflicted with elevated lipid peroxidation and prone to the development of hepatocellular carcinomas. The results showed that while the survival of LEC rats increased significantly by α-lipoic acid, none of the antioxidants inhibited the formation of DHHedA and only Polyphenon E decreased the formation of γ-OHPdG. In contrast, vitamin E caused a significant increase in the formation of both γ-OHPdG and DHHedA in the livers of LEC rats. PMID:24816294

  12. Effect of endogenous ascorbic acid oxidase activity and stability on vitamin C in carrots (Daucus carota subsp. sativus) during thermal treatment.

    PubMed

    Leong, Sze Ying; Oey, Indrawati

    2012-10-15

    The purpose of this research was to study the effect of endogenous ascorbic acid oxidase (AAO) on vitamin C in carrots (Daucus carota subsp. sativus), namely Nantes, Egmont Gold and baby carrots during thermal treatment. Enzyme-substrate reaction kinetics of AAO were described using Michaelis-Menten equation. The estimated K(m) and V(max) values of AAO ranged from 50.34 to 63.54 μM and 23.70 to 26.82 μmol/min, respectively. Nantes carrots had the lowest AAO activity. On the other hand, Egmont Gold had the highest V(max). AAO activity in all carrot cultivars was stable up to 50 °C and inactivated above 50 °C. Irreversible thermal inactivation of AAO followed first order kinetics (55-70 °C) and the estimated activation energy of the three carrot cultivars situated between 114.33 and 191.45 kJ/mol. Regarding vitamin C stability, thermal treatment at 60-70 °C has resulted in total conversion of l-AA to DHAA due to residual AAO activity; a complete AAO inactivation was found in 80 °C-treated carrots with high vitamin C retention predominantly in l-AA form, up to 90%. On average, the carrots had a total vitamin C content amounting from 368.24 to 379.87 μg/g dry matter and the Nantes carrots had the highest vitamin C content. The effectiveness of rapid inactivation of endogenous AAO via heating (>80 °C, 10 min) prior to matrix disruption gave protection to l-AA towards enzymatic oxidation, thus resulted in a higher vitamin C content and stability in carrots.

  13. Effect of pulsed electric field treatment on enzyme kinetics and thermostability of endogenous ascorbic acid oxidase in carrots (Daucus carota cv. Nantes).

    PubMed

    Leong, Sze Ying; Oey, Indrawati

    2014-03-01

    The objective of this research was to study the enzyme kinetics and thermostability of endogenous ascorbic acid oxidase (AAO) in carrot purée (Daucus carota cv. Nantes) after being treated with pulsed electric field (PEF) processing. Various PEF treatments using electric field strength between 0.2 and 1.2kV/cm and pulsed electrical energy between 1 and 520kJ/kg were conducted. The enzyme kinetics and the kinetics of AAO thermal inactivation (55-70°C) were described using Michaelis-Menten model and first order reaction model, respectively. Overall, the estimated Vmax and KM values were situated in the same order of magnitude as the untreated carrot purée after being exposed to pulsed electrical energy between 1 and 400kJ/kg, but slightly changed at pulsed electrical energy above 500kJ/kg. However, AAO presented different thermostability depending on the electric field strength applied. After PEF treatment at the electric field strength between 0.2 and 0.5kV/cm, AAO became thermolabile (i.e. increase in inactivation rate (k value) at reference temperature) but the temperature dependence of k value (Ea value) for AAO inactivation in carrot purée decreased, indicating that the changes in k values were less temperature dependent. It is obvious that PEF treatment affects the temperature stability of endogenous AAO. The changes in enzyme kinetics and thermostability of AAO in carrot purée could be related to the resulting carrot purée composition, alteration in intracellular environment and the effective concentration of AAO released after being subjected to PEF treatment.

  14. Nitrooleic acid, an endogenous product of nitrative stress, activates nociceptive sensory nerves via the direct activation of TRPA1.

    PubMed

    Taylor-Clark, Thomas E; Ghatta, Srinivas; Bettner, Weston; Undem, Bradley J

    2009-04-01

    Transient Receptor Potential A1 (TRPA1) is a nonselective cation channel, preferentially expressed on a subset of nociceptive sensory neurons, that is activated by a variety of reactive irritants via the covalent modification of cysteine residues. Excessive nitric oxide during inflammation (nitrative stress), leads to the nitration of phospholipids, resulting in the formation of highly reactive cysteine modifying agents, such as nitrooleic acid (9-OA-NO(2)). Using calcium imaging and electrophysiology, we have shown that 9-OA-NO(2) activates human TRPA1 channels (EC(50), 1 microM), whereas oleic acid had no effect on TRPA1. 9-OA-NO(2) failed to activate TRPA1 in which the cysteines at positions 619, 639, and 663 and the lysine at 708 had been mutated. TRPA1 activation by 9-OA-NO(2) was not inhibited by the NO scavenger carboxy-PTIO. 9-OA-NO(2) had no effect on another nociceptive-specific ion channel, TRPV1. 9-OA-NO(2) activated a subset of mouse vagal and trigeminal sensory neurons, which also responded to the TRPA1 agonist allyl isothiocyanate and the TRPV1 agonist capsaicin. 9-OA-NO(2) failed to activate neurons derived from TRPA1(-/-) mice. The action of 9-OA-NO(2) at nociceptive nerve terminals was investigated using an ex vivo extracellular recording preparation of individual bronchopulmonary C fibers in the mouse. 9-OA-NO(2) evoked robust action potential discharge from capsaicin-sensitive fibers with slow conduction velocities (0.4-0.7 m/s), which was inhibited by the TRPA1 antagonist AP-18. These data demonstrate that nitrooleic acid, a product of nitrative stress, can induce substantial nociceptive nerve activation through the selective and direct activation of TRPA1 channels.

  15. Post mortem concentrations of endogenous gamma hydroxybutyric acid (GHB) and in vitro formation in stored blood and urine samples.

    PubMed

    Busardò, Francesco Paolo; Bertol, Elisabetta; Vaiano, Fabio; Baglio, Giovanni; Montana, Angelo; Barbera, Nunziata; Zaami, Simona; Romano, Guido

    2014-10-01

    Gamma-hydroxybutyrate (GHB) is a central nervous system depressant, primarily used as a recreational drug of abuse with numerous names. It has also been involved in various instances of drug-facilitated sexual assault due to its potential incapacitating effects. The first aim of this paper is to measure the post-mortem concentration of endogenous GHB in whole blood and urine samples of 30 GHB free-users, who have been divided according to the post-mortem interval (PMI) in three groups (first group: 24-36h; second group: 37-72h; third group: 73-192h), trying to evaluate the role of PMI in affecting post mortem levels. Second, the Authors have evaluated the new formation of GHB in vitro in blood and urine samples of the three groups, which have been stored at -20°C, 4°C and 20°C over a period of one month. The concentrations were measured by GC-MS after liquid-liquid extraction according to the method validated and published by Elliot (For. Sci. Int., 2003). For urine samples, GHB concentrations were creatinine-normalized. In the first group the GHB mean concentration measured after autopsy was: 2.14mg/L (range 0.54-3.21mg/L) in blood and 3.90mg/g (range 0.60-4.81mg/g) in urine; in the second group it was: 5.13mg/L (range 1.11-9.60mg/L) in blood and 3.93mg/g (range 0.91-7.25mg/g) in urine; in the third group it was: 11.8mg/L (range 3.95-24.12mg/L) in blood and 9.83mg/g (range 3.67-21.90mg/g) in urine. The results obtained in blood and urine samples showed a statistically significant difference among groups (p<0.001) in the first analysis performed immediately after autopsy. Throughout the period of investigation up to 4 weeks, the comparison of storage temperatures within each group showed in blood and urine samples a mean difference at 20°C compared to -20°C not statistically significant at the 10% level. These findings allow us to affirm that the PMI strongly affects the post mortem production of GHB in blood and urine samples. Regarding the new formation of

  16. Endogenous Levels of Five Fatty Acid Metabolites in Exhaled Breath Condensate to Monitor Asthma by High-Performance Liquid Chromatography: Electrospray Tandem Mass Spectrometry

    PubMed Central

    Nording, Malin L.; Yang, Jun; Hegedus, Christine M.; Bhushan, Abhinav; Kenyon, Nicholas J.; Davis, Cristina E.; Hammock, Bruce D.

    2010-01-01

    Airway inflammation characterizing asthma and other airway diseases may be monitored through biomarker analysis of exhaled breath condensate (EBC). In an attempt to discover novel EBC biomarkers, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was used to analyze EBC from ten control non-asthmatics and one asthmatic individual for five fatty acid metabolites: 9,12,13-trihydroxyoctadecenoic acid (9,12,13-TriHOME), 9,10,13-TriHOME, 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME), 12-hydroxyeicosatetraenoic acid (12-HETE), and 12(13)-epoxyoctadecenoic acid (12(13)-EpOME). The method was shown to be sensitive, with an on-column limit of quatitation (LOQ) in the pg range (corresponding to pM concentrations in EBC), and linear over several orders of magnitude for each analyte in the calibrated range. Analysis of EBC spiked with the five fatty acid metabolites was within 81%–119% with only a few exceptions. Endogenous levels in EBC exhibited intra- and inter-assay precision of 10%–22%, and 12%–36%, respectively. EBC from the healthy subjects contained average analyte levels between 15 and 180 pM with 12-HETE present above the LOQ in only one of the subjects at a concentration of 240 pM. Exposure of the asthmatic subject to allergen led to increased EBC concentrations of 9,12,13-TriHOME, 9,10,13-TriHOME, 12,13-DiHOME, and 12(13)-EpOME when compared to levels in EBC collected prior to allergen exposure (range =40–510 pM). 12,13-DiHOME was significantly increased (Student's t-test, p < 0.05). In conclusion, we have developed a new HPLC-ESI-MS/MS method for the analysis of five fatty acid metabolites in EBC, which are potential biomarkers for asthma monitoring and diagnosis. PMID:21103452

  17. Phosphate Solubilizing Bacillus megaterium mj1212 Regulates Endogenous Plant Carbohydrates and Amino Acids Contents to Promote Mustard Plant Growth.

    PubMed

    Kang, Sang-Mo; Radhakrishnan, Ramalingam; You, Young-Hyun; Joo, Gil-Jae; Lee, In-Jung; Lee, Ko-Eun; Kim, Jin-Ho

    2014-12-01

    The current study was conducted to explore the potential of a phosphate solubilizing soil bacterium, Bacillus megaterium mj1212 for enhancing the growth of mustard plants. The newly isolated bacterial strain mj1212 was identified as B. megaterium using phylogenetic analysis and, its phosphate solubilization ability was shown by the clear zone formation on National Botanical Research Institute's Phosphate medium. Moreover, the phosphate solubilization ability of B. megaterium mj1212 was enhanced by optimal culture conditions at pH 7.0 and 35 °C which might be due to the presence of malic and quinic acid in the culture medium. The beneficial effect of B. megaterium mj1212 in mustard plants was determined by an increasing shoot length, root length and fresh weight of plants. In the biochemical analysis revealed that chlorophyll, sucrose, glucose, fructose and amino acids (Asp, Thr, Ser, Glu, Gly, Ala, Cys, Val, Met, Ilu, Leu, Tyr, Phe, Lys, His, Arg and Pro) were higher in B. megaterium mj1212 treated plants, when compared to their control. The result of present study suggests that B. megaterium mj1212 treatment could be act as phosphate biofertilizer to improve the plant growth.

  18. Naringin ameliorates acetic acid induced colitis through modulation of endogenous oxido-nitrosative balance and DNA damage in rats

    PubMed Central

    Kumar, Venkatashivam Shiva; Rajmane, Anuchandra Ramchandra; Adil, Mohammad; Kandhare, Amit Dattatraya; Ghosh, Pinaki; Bodhankar, Subhash Laxman

    2014-01-01

    The aim of this study was to evaluate the effect of naringin on experimentally induced inflammatory bowel disease in rats. Naringin (20, 40 and 80 mg/kg) was given orally for 7 days to Wistar rats before induction of colitis by intrarectal instillation of 2 mL of 4% (v/v) acetic acid solution. The degree of colonic mucosal damage was analyzed by examining mucosal damage, ulcer area, ulcer index and stool consistency. Intrarectal administration of 4% acetic acid resulted in significant modulation of serum alkaline phosphatase, lactate dehydrogenase, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) content along with colonic nitric oxide (NO), xanthine oxidase (XO) level and protein carbonyl content in the colonic tissue as well as in blood. Naringin (40 and 80 mg/kg) exerted a dose dependent (P < 0.05) ameliorative effect, as it significantly increased hematological parameter as well as colonic SOD and GSH. There was a significant (P < 0.05) and dose dependant inhibition of macroscopical score, ulcer area along with colonic MDA, MPO activity by the 7 days of pretreatment of naringin (40 and 80 mg/kg). Biochemical studies revealed a significant (P < 0.05) dose dependant inhibition in serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels by pretreatment of naringin. Increased levels of colonic NO, XO, protein carbonyl content and DNA damage were also significantly decreased by naringin pretreatment. The findings of the present investigation propose that naringin has an anti-inflammatory, anti-oxidant and anti-apoptotic potential effect at colorectal sites as it modulates the production and expression of oxidative mediators such as MDA, MPO, NO and XO, thus reducing DNA damage. PMID:24683411

  19. Suppressed Helicobacter pylori-associated gastric tumorigenesis in Fat-1 transgenic mice producing endogenous ω-3 polyunsaturated fatty acids

    PubMed Central

    Jeong, Migyeung; Park, Jong-Min; Go, Eun-Jin; Kang, Jing X; Hong, Sung Pyo; Hahm, Ki Baik

    2016-01-01

    Dietary approaches to preventing Helicobacter pylori (H. pylori)-associated gastric carcinogenesis are widely accepted because surrounding break-up mechanisms are mandatory for cancer prevention, however, eradication alone has been proven to be insufficient. Among these dietary interventions, omega-3-polyunsaturated-fatty acids (ω-3 PUFAs) are often the first candidate selected. However, there was no trial of fatty acids in preventing H. pylori-associated carcinogenesis and inconclusive results have been reported, likely based on inconsistent dietary administration. In this study, we developed an H. pylori initiated-, high salt diet promoted-gastric tumorigenesis model and conducted a comparison between wild-type (WT) and Fat-1-transgenic (TG)-mice. Gross and pathological lesions in mouse stomachs were evaluated at 16, 24, 32, and 45 weeks after H. pylori infection, and the underlying molecular changes to explain the cancer preventive effects were investigated. Significant changes in: i) ameliorated gastric inflammations at 16 weeks of H. pylori infection, ii) decreased angiogenic growth factors at 24 weeks, iii) attenuated atrophic gastritis and tumorigenesis at 32 weeks, and iv) decreased gastric cancer at 45 weeks were all noted in Fat-1-TG-mice compared to WT-mice. While an increase in the expression of Cyclooxygenase (COX)-2, and reduced expression of the tumor suppressive 15-PGDH were observed in WT-mice throughout the experimental periods, the expression of Hydroxyprostaglandin dehydrogenase (15-PGDH) was preserved in Fat-1-TG-mice. Using a comparative protein array, attenuated expressions of proteins implicated in proliferation and inflammation were observed in Fat-1-TG-mice compared to WT-mice. Conclusively, long-term administration of ω-3 PUFAs can suppress H. pylori-induced gastric tumorigenesis through a dampening of inflammation and reduced proliferation in accordance with afforded rejuvenation. PMID:27528223

  20. Lactic acid microbiota identification in water, raw milk, endogenous starter culture, and fresh Minas artisanal cheese from the Campo das Vertentes region of Brazil during the dry and rainy seasons.

    PubMed

    Castro, R D; Oliveira, L G; Sant'Anna, F M; Luiz, L M P; Sandes, S H C; Silva, C I F; Silva, A M; Nunes, A C; Penna, C F A M; Souza, M R

    2016-08-01

    Minas artisanal cheese, produced in the Campo das Vertentes region of Brazil, is made from raw milk and endogenous starter cultures. Although this cheese is of great historical and socioeconomic importance, little information is available about its microbiological and physical-chemical qualities, or about its beneficial microbiota. This work was aimed at evaluating the qualities of the cheese and the components used for its production, comparing samples collected during the dry and rainy seasons. We also conducted molecular identification and isolated 50 samples of lactic acid bacteria from cheese (n=21), water (n=3), raw milk (n=9), and endogenous starter culture (n=17). The microbiological quality of the cheese, water, raw milk, and endogenous starter culture was lower during the rainy period, given the higher counts of coagulase-positive Staphylococcus and total and thermotolerant coliforms. Enterococcus faecalis was the lactic acid bacteria isolated most frequently (42.86%) in cheese samples, followed by Lactococcus lactis (28.57%) and Lactobacillus plantarum (14.29%). Lactobacillus brevis (5.88%), Enterococcus pseudoavium (5.88%), Enterococcus durans (5.88%), and Aerococcus viridans (5.88%) were isolated from endogenous starter cultures and are described for the first time in the literature. The lactic acid bacteria identified in the analyzed cheeses may inhibit undesirable microbiota and contribute to the safety and flavor of the cheese, but this needs to be evaluated in future research.

  1. A Method for Activation of Endogenous Acid-sensing Ion Channel 1a (ASIC1a) in the Nervous System with High Spatial and Temporal Precision

    PubMed Central

    Li, Tianbo; Yang, Youshan; Canessa, Cecilia M.

    2014-01-01

    Protons activate acid-sensing ion channel 1a (ASIC1a) in the central nervous system (CNS) although the impact of such activation on brain outputs remains elusive. Progress elucidating the functional roles of ASIC1a in the CNS has been hindered by technical difficulties of achieving acidification with spatial and temporal precision. We have implemented a method to control optically the opening of ASIC1a in brain slices and also in awake animals. The light-driven H+ pump ArchT was expressed in astrocytes of mouse cortex by injection of adenoviral vectors containing a strong and astrocyte-specific promoter. Illumination with amber light acidified the surrounding interstitium and led to activation of endogenous ASIC1a channels and firing of action potentials in neurons localized in close proximity to ArchT-expressing astrocytes. We conclude that this optogenetic method offers a minimally invasive approach that enables examining the biological consequences of ASIC1a currents in any structure of the CNS and in the modulation of animal behaviors. PMID:24727474

  2. Effects of the Indole-3-Acetic Acid (IAA) Transport Inhibitors N-1-Naphthylphthalamic Acid and Morphactin on Endogenous IAA Dynamics in Relation to Compression Wood Formation in 1-Year-Old Pinus sylvestris (L.) Shoots.

    PubMed Central

    Sundberg, B.; Tuominen, H.; Little, CHA.

    1994-01-01

    Both N-1-naphthylphthalamic acid (NPA) and methyl-2-chloro-9-hydroxyfluorene-9-carboxylic acid (CF) inhibit the polar transport of indole-3-acetic acid (IAA) and, therefore, are attractive tools for investigating IAA's role in the regulation of plant growth. Ringing an intact conifer shoot with lanolin containing NPA or CF induces the formation of compression wood above the ring. This induction has been attributed to a postulated accumulation of IAA above the application site of the IAA transport inhibitor, but the validity of this postulation has never been confirmed. Using gas chromatography-selected ion monitoring-mass spectroscopy with [13C6]IAA as an internal standard, we measured the levels of endogenous free and conjugated IAA in 1-year-old Pinus sylvestris (L.) shoots ringed with NPA or CF. The level of free IAA was dramatically decreased below the ring, indicating that the polar transport of endogenous IAA was inhibited by the treatment. However, the free IAA level above the ring, where compression wood was formed, was also slightly lower than in control shoots. The lack of IAA accumulation above the site of the IAA transport inhibitor could not be explained by an increase in IAA conjugation. Furthermore, the turnover of [2-14C]IAA, measured using high-performance liquid chromatography with on-line radioactivity monitoring, was the same in NPA-treated and control shoots. The decrease in IAA level above a NPA or CF ring is attributed to these substances being transported acropetally and interfering with polar IAA transport along the shoot. It is concluded that compression wood formation above a NPA or CF ring is not associated with an overall increase in cambial region IAA level or increased IAA turnover. Instead, we suggest that acropetally transported NPA and CF induce compression wood formation by interacting with the NPA receptor in differentiating tracheids, thereby locally increasing IAA in these cells. PMID:12232343

  3. A multi-matrix HILIC-MS/MS method for the quantitation of endogenous small molecule neurological biomarker N-acetyl aspartic acid (NAA).

    PubMed

    Sangaraju, Dewakar; Shahidi-Latham, Sheerin K; Burgess, Braydon L; Dean, Brian; Ding, Xiao

    2017-03-14

    A multi-matrix hydrophilic interaction liquid chromatography tandem mass spectrometric method (HILIC-MS/MS) was developed for the quantitation of N-Acetyl Aspartic acid (NAA) using stable isotope labeled internal standard, D3-NAA in various biological matrices such as human plasma, human CSF, mouse plasma, brain and spinal cord. A high throughput 96-well plate format supported liquid extraction (SLE) procedure was developed and used for sample preparation. Mass spectrometric analysis of NAA was performed using selected reaction monitoring transitions in positive electrospray ionization mode. As NAA is endogenously present, a surrogate matrix approach was used for quantitation of NAA and the method was qualified over linear calibration curve range of 0.01-10μg/mL. Intra and inter assay precision indicated by percent relative standard deviation (%RSD) was less than 7.1% for low, medium, medium high and high QCs. The accuracy of the method ranged from 92.6-107.0% of nominal concentration for within-run and between-run for the same QCs. Extraction recovery of NAA and D3-NAA was greater than 76%. Stability of NAA was established in the above biological matrices under bench top (RT, 5h), freeze thaw (-20±10°C, 3 cycles) and moues/human plasma sample collection (Wet ice, RT) conditions. HILIC-MS/MS method was then used to quantify and compare the NAA levels in human plasma and CSF of ALS patients versus control human subjects. NAA CSF levels in control human subjects (73.3±31.0ng/mL,N=10) were found to be slightly higher than ALS patients (46.1±22.6ng/mL, N=10) (P=0.04). No differences were observed in NAA plasma levels in human control subjects (49.7±13.8ng/mL,N=9) as compared to ALS patients (49.6±8.1ng/mL, N=10) (P=0.983). NAA endogenous concentrations in mouse plasma, brain and spinal cord were found to be 243.8±56.8ng/mL (N=6), 1029.8±115.2μg/g tissue weight (N=5) and 487.6±178.4μg/g tissue weight (N=5) respectively.

  4. Comparison of the endogenous ileal and faecal amino acid excretion in the dog (Canis familiaris) and the rat (Rattus rattus) determined under protein-free feeding and peptide alimentation.

    PubMed

    Hendriks, W H; Sritharan, K; Hodgkinson, S M

    2002-10-01

    The aim of the study was to determine and compare the endogenous ileal excretions of nitrogen and amino acids under protein-free and peptide alimentation by the dog and rat. Two diets were prepared, one that was devoid of protein and the other containing 23% enzyme hydrolysed casein. Chromic oxide was included in the diets as an indigestible marker. A total of 10 mixed breed dogs were fed hourly either a protein-free or enzymatically hydrolysed casein diet for a total of 10 days. A faecal sample was obtained from each dog on day 9 while digesta was obtained from the terminal 20 cm of the ileum directly after euthanasia on day 10. A total of 12 8-week-old Sprague-Dawley rats received the same diets as the dogs. A faecal sample from each rat was obtained on day 7 while ileal digesta samples were obtained on day 8. The endogenous ileal excretions of most amino acids were greater in the dogs and rats that received the enzymatically hydrolysed casein diet compared with those receiving the protein free diet. Whereas the pattern of endogenous amino acid excretion was similar in the rats and dogs, the dogs excreted a significantly greater amount of nitrogen (1.91 vs. 2.27 and 1.63 vs. 4.12 g/kg dry matter intake for the protein-free and peptide alimentation method, respectively) and all amino acids except for glycine, isoleucine and leucine. Endogenous ileal amino acid excretions are higher in dogs compared to omnivorous animals such as rats and pigs but similar to the carnivorous cat.

  5. Net Gains

    ERIC Educational Resources Information Center

    Fielker, David

    2008-01-01

    The Easter conference 2008 had several activities which for the author raised the same questions on cube nets in some work with eight-year-olds some time ago. In this article, the author muses on some problems from the Easter conference regarding nets of shapes. (Contains 1 note.)

  6. Endogenous activation of nAChRs and NMDA receptors contributes to the excitability of CA1 stratum radiatum interneurons in rat hippocampal slices: effects of kynurenic acid.

    PubMed

    Alkondon, Manickavasagom; Pereira, Edna F R; Albuquerque, Edson X

    2011-10-15

    CA1 stratum radiatum interneurons (SRIs) express α7 nicotinic receptors (nAChRs) and receive inputs from glutamatergic neurons/axons that express α3β4β2 nAChRs. To test the hypothesis that endogenously active α7 and/or α3β4β2 nAChRs control the excitability of CA1 SRIs in the rat hippocampus, we examined the effects of selective receptor antagonists on spontaneous fast current transients (CTs) recorded from these interneurons under cell-attached configuration. The frequency of CTs, which represent action potentials, increased in the absence of extracellular Mg(2+) and decreased in the presence of the α3β4β2 nAChR antagonist mecamylamine (3 μM) or the NMDA receptor antagonist APV (50 μM). However, it was unaffected by the α7 nAChR antagonist MLA (10 nM) or the AMPA receptor antagonist CNQX (10 μM). Thus, in addition to synaptically and tonically activated NMDA receptors, α3β4β2 nAChRs that are present on glutamatergic axons/neurons synapsing onto SRIs and are activated by basal levels of acetylcholine contribute to the maintenance of the excitability of these interneurons. Kynurenic acid (KYNA), an astrocyte-derived kynurenine metabolite whose levels are increased in the brains of patients with schizophrenia, also controls the excitability of SRIs. At high micromolar concentrations, KYNA, acting primarily as an NMDA receptor antagonist, decreased the CT frequency recorded from the interneurons. At 2 μM, KYNA reduced the CA1 SRI excitability via mechanisms independent of NMDA receptor block. KYNA-induced reduction of excitability of SRIs may contribute to sensory gating deficits that have been attributed to deficient hippocampal GABAergic transmission and high levels of KYNA in the brain of patients with schizophrenia.

  7. α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology.

    PubMed

    Piermartiri, Tetsade; Pan, Hongna; Figueiredo, Taiza H; Marini, Ann M

    2015-11-12

    α-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP) nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE) that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders.

  8. Endogenous n-3 Polyunsaturated Fatty Acids Delay Progression of Pancreatic Ductal Adenocarcinoma in Fat-1-p48Cre/+-LSL-KrasG12D/+ Mice12

    PubMed Central

    Mohammed, Altaf; Janakiram, Naveena B; Brewer, Misty; Duff, Ashley; Lightfoot, Stan; Brush, Richard S; Anderson, Robert E; Rao, Chinthalapally V

    2012-01-01

    Preclinical studies suggest that diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for prevention of pancreatic cancer. Nutritional intervention studies are often complex, and there is no clear evidence, without potential confounding factors, on whether conversion of n-6 PUFAs to n-3 PUFAs in pancreatic tissues would provide protection. Experiments were designed using n-3 fatty acid desaturase (Fat-1) transgenic mice, which can convert n-6 PUFA to n-3 FAs endogenously, to determine the impact of n-3 PUFAs on pancreatic intraepithelial neoplasms (PanINs) and their progression to pancreatic ductal adenocarcinoma (PDAC). Six-weekold female p48Cre/+-LSL-KrasG12D/+ andcompoundFat-1-p48Cre/+-LSL-KrasG12D/+ mice were fed (AIN-76A) diets containing 10% safflower oil for 35 weeks. Pancreata were evaluated histopathologically for PanINs and PDAC. Results showed a dramatic reduction in incidence of PDAC (84%; P < .02) in Fat-1-p48Cre/+-LSL-KrasG12D/+ mice compared to p48Cre/+-LSL-KrasG12D/+ mice. Importantly, significant reductions of pancreatic ducts with carcinoma (90%; P < .0001) and PanIN 3 (∼50%; P < .001) lesions were observed in the compound transgenic mice. The levels of n-3 PUFA were much higher (>85%; P < .05–0.01) in pancreas of compound transgenic mice than in those of p48Cre/+-LSL-KrasG12D/+ mice. Molecular analysis of the pancreas showed a significant down-regulation of proliferating cell nuclear antigen, cyclooxygenase-2, 5-lipoxygenase (5-LOX), 5-LOX-activating protein, Bcl-2, and cyclin D1 expression levels in Fat-1-p48Cre/+-LSL-KrasG12D/+ mice compared to p48Cre/+-LSL-KrasG12D/+ mice. These data highlight the promise of dietary n-3 FAs for chemoprevention of pancreatic cancer in high-risk individuals. PMID:23308056

  9. Endogenous respiration of Polyporus sulphureus

    SciTech Connect

    Li, S.M.W.; Siehr, D.J.

    1980-01-01

    Thirty percent of the dry weight of the basidiomycete Polyporus sulphureus is triterpenoid acid. The endogenous respiratory quotient of this organism is 0.8 indicating that the triterpenoid is being used as an endogenous storage material. Monosaccharides did not seem to be utilized as exogenous substrates but Krebs-cycle intermediates stimulated oxygen uptake. Pyruvic acid inhibited oxygen uptake. Studies with /sup 14/C-labeled glucose indicated that 27% of the glucose was metabolized by way of glycolysis. The hexose-monophosphate pathway was the major metabolic path for the utilization of glucose. Despite the fact that P. sulphureus is associated with brown rot, its carbon metabolism suggests that it utilizes substances associated with the degradation of lignin more readily than it does glucose.

  10. Ileal Endogenous Amino Acid Flow Response to Nitrogen-free Diets with Differing Ratios of Corn Starch to Dextrose in Pigs

    PubMed Central

    Kong, C.; Ragland, D.; Adeola, O.

    2014-01-01

    The objective of this study was to determine the responses in the digestibility of dry matter (DM) and amino acid (AA) composition of ileal endogenous flow (IEF) of pigs (initial body weight, 69.1±6.46 kg) fed N-free diets (NFD) formulated with different ratios of corn starch to dextrose. Fifteen pigs fitted with a T-cannula at the distal ileum were fed 5 diets according to a triplicated 5×2 incomplete Latin-square design. Each period consisted of a 5-d adjustment period and 2 d of ileal digesta collection for 12 h on each of d 6 and 7 and between each period, there was a 5-d recovery period to avoid abnormal weight loss. The ratios of corn starch to dextrose investigated were 0:879, 293:586, 586:293, 779:100, and 879:0 for diet numbers 1, 2, 3, 4 and 5, respectively, and chromic oxide (5 g/kg) was used as an indigestible index. Ileal DM digestibility was greater in Diet 1 than that in Diet 4 (89.5% vs 87.3%, p<0.01) but they were not different from Diet 2, 3, or 5. The IEF for most of indispensable AA were not different among diets with the exception of Met, in which a lack of corn starch or dextrose gave lower (p = 0.028) IEF of Met than diets containing corn starch and dextrose. Likewise, the dispensable AA and total AA in the IEF did not differ among diets. The respective IEF of AA (mg/kg of dry matter intake) in pigs fed Diets 1, 2, 3, 4, or 5 were 301, 434, 377, 477,or 365 for Lys, 61, 89, 71, 87, or 61 for Met, and 477, 590, 472, 520, or 436 for Thr. Proline was the most abundant AA in the IEF followed by Gly, Glu, and Asp and together accounted for approximately 50% of the total ileal AA flows of pigs fed NFD. In conclusion, the variation in proportion of corn starch and dextrose in a NFD does not largely affect estimates of IEF of N and AA for growing-finishing pigs. PMID:25083106

  11. Whole body acid-base modeling revisited.

    PubMed

    Ring, Troels; Nielsen, Søren

    2017-04-01

    The textbook account of whole body acid-base balance in terms of endogenous acid production, renal net acid excretion, and gastrointestinal alkali absorption, which is the only comprehensive model around, has never been applied in clinical practice or been formally validated. To improve understanding of acid-base modeling, we managed to write up this conventional model as an expression solely on urine chemistry. Renal net acid excretion and endogenous acid production were already formulated in terms of urine chemistry, and we could from the literature also see gastrointestinal alkali absorption in terms of urine excretions. With a few assumptions it was possible to see that this expression of net acid balance was arithmetically identical to minus urine charge, whereby under the development of acidosis, urine was predicted to acquire a net negative charge. The literature already mentions unexplained negative urine charges so we scrutinized a series of seminal papers and confirmed empirically the theoretical prediction that observed urine charge did acquire negative charge as acidosis developed. Hence, we can conclude that the conventional model is problematic since it predicts what is physiologically impossible. Therefore, we need a new model for whole body acid-base balance, which does not have impossible implications. Furthermore, new experimental studies are needed to account for charge imbalance in urine under development of acidosis.

  12. Phosphoric acid functionalized mesoporous organo-silica (EPO) as the adsorbent for in situ enrichment and isotope labeling of endogenous phosphopeptides.

    PubMed

    Qin, Hongqiang; Wang, Fangjun; Wang, Peiyuan; Zhao, Liang; Zhu, Jun; Yang, Qihua; Wu, Ren'an; Ye, Mingliang; Zou, Hanfa

    2012-01-25

    Ti(4+)-EPO nanoparticles were adopted as the adsorbent for in situ solid phase enrichment and isotope labeling of endogenous phosphopeptides, which has great potential application in high-throughput analyses of biological samples for screening and discovery of disease-specific biomarkers.

  13. Methane Suppression: The Impacts of Fe(III) and Humic Acids on Net Methane Flux from Arctic Tundra Wetlands in Alaska and Finland (Invited)

    NASA Astrophysics Data System (ADS)

    Lipson, D.; Miller, K.; Lai, C.

    2013-12-01

    Arctic soils contain large reservoirs of carbon (C) that are vulnerable to loss from climatic warming. However the potential global impacts of this C depend on whether it is lost primarily in the form of methane (CH4) or carbon dioxide (CO2), two gases with very different greenhouse warming potentials. In anaerobic environments, the relative production of CH4 vs. CO2 may be controlled by the presence of alternative terminal electron acceptors, which allow more thermodynamically favorable anaerobic respiratory pathways to dominate over methanogenesis. This work investigated how the addition of terminal electron acceptors, ferric iron (Fe(III)) and humic acids, affected net CH4 fluxes from high-latitude wetland ecosystems. We conducted two manipulative field experiments in Barrow, Alaska (71° N) and Finnish Lapland (69° N). The ecosystem in Barrow was known from previous studies to be rich in Fe(III) and to harbor a microbial community that is dominated by Fe(III)- and humic acid-reducing microorganisms. The role of these alternative electron acceptors had not previously been studied at the Finnish site. CH4 and CO2 fluxes were measured using a portable trace gas analyzer from experimental plots, before and after amendments with Fe(III) (in the chelated form, ferric nitrilotriacetic acid), humic acids, or water as a control. Both in the ecosystem with permafrost and naturally high levels of soil Fe (Barrow, AK) and in the ecosystem with no permafrost and naturally low levels of soil Fe (Petsikko, Finland), the addition of the alternative electron acceptors Fe(III) and humic acids significantly reduced net CH4 flux. CO2 fluxes were not significantly altered by the treatments. The reduction in CH4 flux persisted for at least several weeks post-treatment. There was no significant difference between the reduction caused by humic acids versus that from Fe(III). These results show that the suppression of CH4 flux by Fe(III) and humic acids is a widespread phenomenon that

  14. Net release of individual fatty acids from white adipose tissue during lipolysis in vitro: evidence for selective fatty acid re-uptake.

    PubMed Central

    Raclot, T; Oudart, H

    2000-01-01

    During lipolysis, adipose tissue triacylglycerols (TAG) undergo concurrent breakdown and synthesis because some of the newly hydrolysed and released non-esterified ('free') fatty acids (NEFA) can subsequently be taken up and re-esterified. The present study examines whether and how the release of individual fatty acids is affected by the re-uptake of some of the newly hydrolysed fatty acids in vitro during lipolysis. To alter fatty acid release and re-uptake, adipose tissue fragments and isolated adipocytes from rats were incubated under various conditions, i.e. several cell concentrations or adipose fragment quantities, with or without glucose. In the various conditions tested, the NEFA/glycerol molar ratio ranged from 1.5 to 2.9. Whatever the incubation conditions, including those resulting in very low, medium or high fatty acid re-uptake (as assessed by the NEFA/glycerol ratio), the percentage weight of fatty acids in NEFA was significantly different from that in TAG for 20-24 of the 35 fatty acids that were considered. Thus the greater the fatty acid re-uptake, the higher the proportion of polyunsaturated fatty acids and the lower the proportion of long-chain saturated and monounsaturated fatty acids in NEFA. Moreover, the relative mobilization (%NEFA/%TAG) of the least readily mobilized fatty acid (C(22:1,n-11)) was 6.2-fold lower than that of the most readily mobilized fatty acid (C(20:5,n-3)) under conditions of very low fatty acid re-uptake, and 14.8-fold lower under conditions of high fatty acid re-uptake, indicating a widening of the range of relative mobilizations. We conclude that the composition of the NEFA pool is affected by the rate of fatty acid re-uptake. This provides strong evidence for the selective re-uptake of adipose tissue fatty acids during lipolysis. PMID:10794723

  15. Long-term oxandrolone treatment increases muscle protein net deposition via improving amino acid utilization in pediatric patients 6 months after burn injury

    PubMed Central

    Tuvdendorj, D.; Chinkes, DL.; Zhang, XJ.; Suman, OE.; Aarsland, A.; Ferrando, A.; Kulp, GA; Jeschke, MG.; Wolfe, RR.; Herndon, DN.

    2011-01-01

    Background We recently showed that mechanisms of protein turnover in skeletal muscle are unresponsive to amino acid (AA) infusion in severely burned pediatric patients at 6 months postinjury. In the current study, we evaluated if oxandrolone treatment affects mechanisms of protein turnover in skeletal muscle and whole-body protein breakdown in pediatric burn patients 6 months postinjury. Methods At the time of admission, patients were randomized to control or oxandrolone treatments. The treatment regimens were continued until 6 months postinjury, at which time patients (n = 26) underwent study with a stable isotope tracer infusion to measure muscle and whole-body protein turnover. Results Protein kinetics in leg muscle were expressed in nmol/min/100 ml leg volume (mean±SE). During AA infusion, rates of protein synthesis in leg muscle were increased (p < .05) in both groups (Basal vs. AA: control, 51±8 vs. 86±21; oxandrolone, 56±7 vs. 96±12). In the control group, there was also a simultaneous increase in breakdown (Basal vs. AA: 65±10 vs. 89±25), which resulted in no change in the net balance of leg muscle protein (Basal vs. AA: − 15±4 vs. − 2±10). In the oxandrolone group, protein breakdown did not change (Basal vs. AA: 80±12 vs. 77±9), leading to increased net balance (Basal vs. AA: − 24±7 vs. 19±7, p < .05). Protein breakdown at the whole-body level was not different between the groups. Conclusion Long-term oxandrolone treatment increased net deposition of leg muscle protein during AA infusion by attenuating protein breakdown, but did not affect whole-body protein breakdown. PMID:21333314

  16. Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts: Multi-Pollutant Models Based on Elastic Net Regression

    PubMed Central

    Lenters, Virissa; Portengen, Lützen; Rignell-Hydbom, Anna; Jönsson, Bo A.G.; Lindh, Christian H.; Piersma, Aldert H.; Toft, Gunnar; Bonde, Jens Peter; Heederik, Dick; Rylander, Lars; Vermeulen, Roel

    2015-01-01

    Background Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures. Objectives We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight. Methods We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´-DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models. Results Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL). Conclusions This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts. Citation Lenters V, Portengen L, Rignell-Hydbom A, Jönsson BA, Lindh CH, Piersma AH, Toft G, Bonde JP

  17. Immediate and delayed effects of gill-net capture on acid-base balance and intramuscular lactate concentration of gummy sharks, Mustelus antarcticus.

    PubMed

    Frick, Lorenz H; Walker, Terence I; Reina, Richard D

    2012-06-01

    Many sharks are captured as untargeted by-catch during commercial fishing operations and are subsequently discarded. A reliable assessment of the proportion of discarded sharks that die post-release as a result of excessive physiological stress is important for fisheries management and conservation purposes, but a reliable physiological predictor of post-release mortality has not been identified. To investigate effects of gill-net capture on the acid-base balance of sharks, we exposed gummy sharks, Mustelus antarcticus, to 60 min of gill-net capture in a controlled setting, and obtained multiple blood and muscle tissue samples during a 72-h recovery period following the capture event. Overall mortality of gummy sharks was low (9%). Blood pH was significantly depressed immediately after the capture event due to a combination of respiratory and metabolic acidosis. Maximum concentrations of plasma lactate (9.9 ± 1.5 mmol L(-1)) were measured 3h after the capture event. Maximum intramuscular lactate concentrations (37.0 ± 4.6 μmol g(-1)) were measured immediately after the capture event, and intramuscular lactate concentrations were substantially higher than plasma lactate concentrations at all times. Sharks in poor condition had low blood pH and high intramuscular lactate concentration, but blood pH does not appear to be a reliable predictor of survival. Suitability of intramuscular lactate concentration as predictor of delayed mortality deserves further investigation.

  18. Acetaldehyde Stimulation of Net Gluconeogenic Carbon Movement from Applied Malic Acid in Tomato Fruit Pericarp Tissue 12

    PubMed Central

    Halinska, Anna; Frenkel, Chaim

    1991-01-01

    Applied acetaldehyde is known to lead to sugar accumulation in fruit including tomatoes (Lycopersicon esculentum) (O Paz, HW Janes, BA Prevost, C Frenkel [1982] J Food Sci 47: 270-274) presumably due to stimulation of gluconeogenesis. This conjecture was examined using tomato fruit pericarp discs as a test system and applied i-[U-14C]malic acid as the source for gluconeogenic carbon mobilization. The label from malate was recovered in respiratory CO2, in other organic acids, in ethanol insoluble material, and an appreciable amount in the ethanol soluble sugar fraction. In Rutgers tomatoes, the label recovery in the sugar fraction and an attendant label reduction in the organic acids fraction intensified with fruit ripening. In both Rutgers and in the nonripening tomato rin, these processes were markedly stimulated by 4000 ppm acetaldehyde. The onset of label apportioning from malic acids to sugars coincided with decreased levels of fructose-2,6-biphosphate, the gluconeogenesis inhibitor. In acetaldehyde-treated tissues, with enhanced label mobilization, this decline reached one-half to one third of the initial fructose-2,6-biphosphate levels. Application of 30 micromolar fructose-2,6-biphosphate or 2,5-anhydro-d-mannitol in turn led to a precipitous reduction in the label flow to sugars presumably due to inhibition of fructose-1,6-biphosphatase by the compounds. We conclude that malic and perhaps other organic acids are carbon sources for gluconeogenesis occurring normally in ripening tomatoes. The process is stimulated by acetaldehyde apparently by attenuating the fructose-2,6-biphosphate levels. The mode of the acetaldehyde regulation of fructose-2,6-biphosphate metabolism awaits clarification. PMID:16668078

  19. Downflow limestone beds for treatment of net-acidic, oxic, iron-laden drainage from a flooded anthracite mine, Pennsylvania, USA: 2. Laboratory evaluation

    USGS Publications Warehouse

    Cravotta, C.A.; Ward, S.J.; Hammarstrom, J.M.

    2008-01-01

    Acidic mine drainage (AMD) containing elevated concentrations of dissolved iron and other metals can be neutralized to varying degrees by reactions with limestone in passive treatment systems. We evaluated the chemical and mineralogical characteristics and the effectiveness of calcitic and dolomitic limestone for the neutralization of net-acidic, oxic, iron-laden AMD from a flooded anthracite mine. The calcitic limestone, with CaCO3 and MgCO3 contents of 99.8 and <0.1 wt%, respectively, and the dolomitic limestone, with CaCO3 and MgCO3 contents of 60.3 and 40.2 wt%, were used to construct a downflow treatment system in 2003 at the Bell Mine, a large source of AMD and baseflow to the Schuylkill River in the Southern Anthracite Coalfield, in east-central Pennsylvania. In the winter of 2002-2003, laboratory neutralization-rate experiments evaluated the evolution of effluent quality during 2 weeks of continuous contact between AMD from the Bell Mine and the crushed calcitic or dolomitic limestone in closed, collapsible containers (cubitainers). The cubitainer tests showed that: (1) net-alkaline effluent could be achieved with detention times greater than 3 h, (2) effluent alkalinities and associated dissolution rates were equivalent for uncoated and Fe(OH)3-coated calcitic limestone, and (3) effluent alkalinities and associated dissolution rates for dolomitic limestone were about half those for calcitic limestone. The dissolution rate data for the cubitainer tests were used with data on the volume of effuent and surface area of limestone in the treatment system at the Bell Mine to evaluate the water-quality data for the first 1.5 years of operation of the treatment system. These rate models supported the interpretation of field results and indicated that treatment benefits were derived mainly from the dissolution of calcitic limestone, despite a greater quantity of dolomitic limestone within the treatment system. The dissolution-rate models were extrapolated on a

  20. Endogenous Pyrogen Physiology.

    ERIC Educational Resources Information Center

    Beisel, William R.

    1980-01-01

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

  1. NET Confusion

    PubMed Central

    Malachowa, Natalia; Kobayashi, Scott D.; Quinn, Mark T.; DeLeo, Frank R.

    2016-01-01

    Neutrophils are arguably the most important white blood cell for defense against bacterial and fungal infections. These leukocytes are produced in high numbers on a daily basis in humans and are recruited rapidly to injured/infected tissues. Phagocytosis and subsequent intraphagosomal killing and digestion of microbes have historically been the accepted means by which neutrophils carry out their role in innate host defense. Indeed, neutrophils contain and produce numerous cytotoxic molecules, including antimicrobial peptides, proteases, and reactive oxygen species, that are highly effective at killing the vast majority of ingested microbes. On the other hand, it is these characteristics – high numbers and toxicity – that endow neutrophils with the potential to injure and destroy host tissues. This potential is borne out by many inflammatory processes and diseases. Therefore, it is not surprising that host mechanisms exist to control virtually all steps in the neutrophil activation process and to prevent unintended neutrophil activation and/or lysis during the resolution of inflammatory responses or during steady-state turnover. The notion that neutrophil extracellular traps (NETs) form by cytolysis as a standard host defense mechanism seems inconsistent with these aforementioned neutrophil “containment” processes. It is with this caveat in mind that we provide perspective on the role of NETs in human host defense and disease. PMID:27446089

  2. Effects of forage intake level on nitrogen net flux by portal-drained viscera of mature sheep with abomasal infusion of an amino acid mixture.

    PubMed

    EL-Sabagh, M; Sugino, T; Obitsu, T; Taniguchi, K

    2013-10-01

    This study aimed to investigate the pattern of nitrogen (N) metabolites flux across the portal-drained viscera (PDV) of mature sheep over a wide range of forage intake, and to determine the effect of dry matter intake (DMI) on the PDV recovery of an abomasally infused amino acids (AA) mixture. Four Suffolk mature sheep (61.4 ± 3.6 kg BW) surgically fitted with abomasal cannulae and multi-catheters were fed four levels of DMI of lucerne hay cubes ranging from 0.4 to 1.6 fold the metabolizable energy requirements for maintenance. Each period lasted for 17 days: 7 days for diet adaptation, 5 days for measurement of N balance and N metabolites flux under basal pre-infusion conditions (basal phase) and 5 days for determining the recovery of the infused AA (584 mmol/day) across the PDV (infusion phase). Six sets of blood samples were collected on the last day of both basal and infusion phases. Increasing DMI increased portal release of AA and enhanced N retention. At 0.4 M and as a proportion of digested N, there was a marked drop in total AA-N release accompanied by greater ammonia-N release and urea-N uptake across the PDV. The incremental recovery ratio of infused AA across the PDV was altered with increasing DMI accounting for 0.88, 1.12, 1.23 and 1.31 at 0.4, 0.8, 1.2 and 1.6 M, respectively. In addition, across the individual AA, the net portal recovery ratio of infused methionine and valine increased linearly (P < 0.05) while that of phenylalanine, branched-chain AA and total essential AA tended to increase linearly (P < 0.10) with increasing DMI. These results indicated that DMI affects the net portal recovery of AA available in the small intestine of mature sheep.

  3. The Endogenous Exposome

    PubMed Central

    Nakamura, Jun; Mutlu, Esra; Sharma, Vyom; Collins, Leonard; Bodnar, Wanda; Yu, Rui; Lai, Yongquan; Moeller, Benjamin; Lu, Kun; Swenberg, James

    2014-01-01

    The concept of the Exposome, is a compilation of diseases and one’s lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the Endogenous Exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions. PMID:24767943

  4. Laboratory and field evaluation of a flushable oxic limestone drain for treatment of net-acidic drainage from a flooded anthracite mine, Pennsylvania, USA

    USGS Publications Warehouse

    Cravotta, C.A.

    2008-01-01

    This paper demonstrates the use of dissolution-rate data obtained in the laboratory to indicate the potential quality of effluent from a field-scale oxic limestone drain (OLD) treatment system for neutralization of dilute acidic mine drainage (AMD). Effluent from the Reevesdale Mine South Dip Tunnel, a large source of AMD and base flow to the Wabash Creek and Little Schuylkill River in the Southern Anthracite Coalfield of east-central Pennsylvania, is representative of AMD with low concentrations but high loadings of dissolved Fe, Al and other metals because of a high flow rate. In January 2003, rapid neutralization of the AMD from the Reevesdale Mine was achieved in laboratory tests of its reaction rate with crushed limestone in closed, collapsible containers (Cubitainers). The tests showed that net-alkaline effluent could be achieved with retention times greater than 3 h and that effluent alkalinities and associated dissolution rates were equivalent for Fe(OH)3-coated and uncoated limestone. On the basis of the laboratory results, a flushable OLD containing 1450 metric tons of high-purity calcitic limestone followed by two 0.7-m deep wetlands were constructed at the Reevesdale Mine. During the first year of operation, monthly data at the inflow, outflow and intermediate points within the treatment system were collected (April 2006-2007). The inflow to the treatment system ranged from 6.8 to 27.4 L/s, with median pH of 4.7, net acidity of 9.1 mg/L CaCO3, and concentrations of dissolved Al, Fe and Mn of 1.0, 1.9 and 0.89 mg/L, respectively. The corresponding effluent from the OLD had computed void-volume retention times of 4.5-18 h, with median pH of 6.6, net acidity of -93.2 mg/L CaCO3, and concentrations of dissolved Al, Fe and Mn of <0.1, 0.08 and 0.52 mg/L, respectively. The wetlands below the OLD were effective for retaining metal-rich solids flushed at monthly or more frequent intervals from the OLD, but otherwise had little effect on the effluent quality

  5. Downflow limestone beds for treatment of net-acidic, oxic, iron-laden drainage from a flooded Anthracite Mine, Pennsylvania, USA: 1. Field evaluation

    USGS Publications Warehouse

    Cravotta, C.A.; Ward, S.J.

    2008-01-01

    Passive-treatment systems that route acidic mine drainage (AMD) through crushed limestone and/or organic-rich substrates have been used to remove the acidity and metals from various AMD sources, with a wide range of effects. This study evaluates treatment of net-acidic, oxic, iron-laden AMD with limestone alone, and with organic-rich compost layered with the limestone. In the fall of 2003, a treatment system consisting of two parallel, 500-m2 downflow cells followed by a 400-m2 aerobic settling pond and wetland was installed to neutralize the AMD from the Bell Mine, a large source of AMD and baseflow to the Schuylkill River in the Southern Anthracite Coalfield, in east-central Pennsylvania. Each downflow cell consisted of a lower substrate layer of 1,090 metric tons (t) of dolomitic limestone (60 wt% CaCO3) and an upper layer of 300 t of calcitic limestone (95 wt% CaCO3); one of the downflow cells also included a 0.3 m thick layer of mushroom compost over the limestone. AMD with pH of 3.5-4.3, dissolved oxygen of 6.6-9.9 mg/L, iron of 1.9-5.4 mg/L, and aluminum of 0.8-1.9 mg/L flooded each cell to a depth 0.65 m above the treatment substrates, percolated through the substrates to underlying, perforated outflow pipes, and then flowed through the aerobic pond and wetland before discharging to the Schuylkill River. Data on the flow rates and chemistry of the effluent for the treatment system indicated substantial neutralization by the calcitic limestone but only marginal effects from the dolomitic limestone or compost. Because of its higher transmissivity, the treatment cell containing only limestone neutralized greater quantities of acidity than the cell containing compost and limestone. On average, the treatment system removed 62% of the influent acidity, 47% of the dissolved iron, 34% of the dissolved aluminum, and 8% of the dissolved manganese. Prior to treatment of the Bell Discharge, the Schuylkill River immediately below its confluence with the discharge had p

  6. Tau Pathology Promotes the Reorganization of the Extracellular Matrix and Inhibits the Formation of Perineuronal Nets by Regulating the Expression and the Distribution of Hyaluronic Acid Synthases

    PubMed Central

    Li, Yin; Li, Ze-Xu; Jin, Tan; Wang, Zhan-You; Zhao, Pu

    2017-01-01

    Hyaluronic acid (HA) is the backbone of the extracellular matrix (ECM) and provides biochemical and physical support to aggrecan-based perineuronal nets (PNNs), which are associated with the selective vulnerability of neurons in Alzheimer’s disease (AD). Here, we showed that HA synthases (HASs), including Has1, Has2, and Has3, were widely expressed in murine central nervous system. All types of HASs were localized to cell bodies of neurons; only Has1 existed in the membranes of neural axons. By using TauP301S transgenic (Tg) mouse model, we found that the axonal-localization of Has1 was abolished in TauP301S overexpressed mouse brain, and the redistribution of Has1 was also observed in human AD brains, suggesting that the localization of Has1 is dependent on intact microtubules which are regulated partially by the phosphorylation and dephosphorylation cycles of tau proteins. Furthermore, Has1 was reduced and Has3 was increased in TauP301S Tg mouse brain, resulting in the upregulation of shorter-chain HA in the ECM. These findings suggest that by abolishing the axonal-localization of Has1 and promoting the expression of Has3 and the synthesis of shorter-chain HA, the tau pathology breaks the balance of ECM components, promotes the reorganization of the ECM, and inhibits the formation of PNNs in the hippocampus, and then regulates neuronal plasticity during the progression of AD. PMID:28234253

  7. A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding

    PubMed Central

    Ko, Emily Ray; Ko, Dennis; Chen, Carolyn; Lipsick, Joseph S

    2008-01-01

    The c-Myb protein is a transcriptional regulator initially identified by homology to the v-Myb oncoprotein, and has since been implicated in human cancer. The most highly conserved portion of the c-Myb protein is the DNA-binding domain which consists of three imperfect repeats. Many other proteins contain one or more Myb-related domains, including a number of proteins that do not bind directly to DNA. We performed a phylogenetic analysis of diverse classes of Myb-related domains and discovered a highly conserved patch of acidic residues common to all Myb-related domains. These acidic residues are positioned in the first of three alpha-helices within each of the three repeats that comprise the c-Myb DNA-binding domain. Interestingly, these conserved acidic residues are present on a surface of the protein which is distinct from that which binds to DNA. Alanine mutagenesis revealed that the acidic patch of the third c-Myb repeat is essential for transcriptional activity, but neither for nuclear localization nor DNA-binding. Instead, these acidic residues are required for efficient chromatin binding and interaction with the histone H4 N-terminal tail. PMID:18840288

  8. Effects of collection time on flow of chromium and dry matter and on basal ileal endogenous losses of amino acids in growing pigs.

    PubMed

    Kim, B G; Liu, Y; Stein, H H

    2016-10-01

    The objectives of this experiment were to examine the diurnal patterns of chromium and DM flow at the distal ileum of pigs and to determine the effect of collection time on basal ileal endogenous losses (BEL) of CP and AA. Eight barrows with an initial BW of 34.6kg (SD = 2.1) were individually fitted with a T-cannula in the distal ileum and randomly allotted to a replicated 4× 4 Latin square design with 4 diets and 4 periods in each square. Three diets contained either corn, soybean meal, or distillers dried grains with solubles as the sole source of CP and AA. An N-free diet was also prepared. All diets contained 0.5% chromic oxide as an indigestible marker. Equal meals were provided at 0800 and 2000 h. Ileal digesta samples were collected in 2-h intervals from 0800 to 2000 h during the last 3 d of each 7-d period. The concentration of Cr in ileal digesta samples collected in each of the six 2-h periods exhibited a quadratic effect ( < 0.01) that increased and then decreased in pigs fed the CP containing diets. However, the concentration of Cr in ileal digesta collected in each of the six 2-h periods from pigs fed the N-free diet increased (linear, < 0.01). These differences were possibly related to differences in DM flow, because DM flow to the distal ileum had a pattern that was opposite of that observed for the concentration of Cr in the ileal digesta samples. The BEL of all indispensable AA and the sum of indispensable AA from pigs fed the N-free diet decreased (linear, < 0.05) in each of the six 2-h periods, with the exception that the BEL of Arg increased and then decreased (quadratic, < 0.05). The BEL of Asp, Cys, Glu, Ser, and Tyr also decreased (linear, < 0.05) during each of the six 2-h periods, whereas the BEL of Pro and the sum of dispensable AA increased and then decreased (quadratic, < 0.05) over the 12 h. Collection time did not affect BEL of CP. No differences were observed in the concentration of Cr, flow of DM, or basal endogenous loss of all AA

  9. Effects of particle size and dry matter content of a total mixed ration on intraruminal equilibration and net portal flux of volatile fatty acids in lactating dairy cows.

    PubMed

    Storm, A C; Kristensen, N B

    2010-09-01

    Effects of physical changes in consistency of ruminal contents on intraruminal equilibration and net portal fluxes of volatile fatty acids (VFA) in dairy cows were studied. Four Danish Holstein cows (121+/-17 d in milk, 591+/-24 kg of body weight, mean+/-SD) surgically fitted with a ruminal cannula and permanent indwelling catheters in the major splanchnic blood vessels were used. The experimental design was a 4x4 Latin square with a 2x2 factorial design of treatments. Treatments differed in forage (grass hay) particle size (FPS; 3.0 and 30 mm) and feed dry matter (DM) content of the total mixed ration (44.3 and 53.8%). The feed DM did not affect chewing time, ruminal variables, or net portal flux of VFA. However, decreasing the FPS decreased the overall chewing and rumination times by 151+/-55 and 135+/-29 min/d, respectively. No effect of the reduced chewing time was observed on ruminal pH or milk fat percentage. Cows maintained average ventral ruminal pH of 6.65+/-0.02, medial ruminal pH of 5.95+/-0.04, and milk fat of 4.42+/-0.12% with chewing time of 28.0+/-2.1 min/kg of DM when fed short particles. The medial ruminal pool of wet particulate matter was decreased by 10.53+/-2.29 kg with decreasing FPS, thereby decreasing the medial pool of total VFA, acetate, propionate, butyrate, isobutyrate, and isovalerate by 1,143+/-333, 720+/-205, 228+/-69, 140+/-51, 8.0+/-2.3, and 25.2+/-5.6 mmol, respectively. Ventral pool variables were not affected by treatments. Relatively large intraruminal differences of VFA concentrations and pH between the ventral and medial pools were observed, VFA concentrations being largest and pH being the lowest medially. This indicates that the ruminal mat acts as a barrier retaining VFA. The effects of reduced FPS were limited to the VFA pool sizes of the mat, leaving ruminal pH, ruminal VFA concentrations, and net portal flux of VFA unaffected. Consequently reduced FPS affected the intraruminal equilibration of VFA between mat and ventral

  10. Endogenous BDNF protein is increased in adult rat hippocampus after a kainic acid induced excitotoxic insult but exogenous BDNF is not neuroprotective.

    PubMed

    Rudge, J S; Mather, P E; Pasnikowski, E M; Cai, N; Corcoran, T; Acheson, A; Anderson, K; Lindsay, R M; Wiegand, S J

    1998-02-01

    Systemic administration of the excitotoxin kainic acid to adult rats results in a well defined pattern of loss of the CA1 and CA3 pyramidal neurons of the hippocampus. Prior to this neuronal loss, brain-derived neurotrophic factor (BDNF) mRNA is substantially increased. We show here that BDNF protein is increased after excitotoxic insult in specific areas of the hippocampus, reaching maximal levels 24 h after the insult. BDNF protein levels in the hippocampus increase in direct relation to the severity of seizure. Up to 7 days after injection of kainic acid, levels of full-length TrkB protein were unchanged, whereas levels of truncated TrkB protein were significantly increased by 12 h. To determine whether elevations in BDNF protein levels are potentially beneficial to hippocampal neurons exposed to an excitotoxic stress, we infused exogenous BDNF prior to and during the period of neuronal death caused by kainic acid. We find that administration of high levels of exogenous BDNF does not affect severity of seizure, but does in fact, exacerbate the injury caused by kainic acid, specifically to CA3 pyramidal neurons. Although there was a trend toward sparing of CA1 pyramidal neurons on the side infused with BDNF, this was not significant. In the same paradigm, infusion of exogenous NT-3 had no effect.

  11. Exogenous leukotriene B4 (LTB4) inhibits human neutrophil generation of LTB4 from endogenous arachidonic acid during opsonized zymosan phagocytosis.

    PubMed

    Fiedler, J; Wheelan, P; Henson, P M; Murphy, R C

    1998-10-01

    The effect of exogenous leukotriene B4 (LTB4) on opsonized zymosan-stimulated human neutrophil formation of 5-lipoxygenase products and arachidonic acid release was directly assessed using reverse-phase HPLC/tandem mass spectrometric methods for quantitation. Stable isotopically labeled LTB4, [1,2-13C2]LTB4, caused a dose-dependent inhibition of LTB4 production in isolated human neutrophils with significant inhibition (60 +/- 7% of control levels) when 0.12 nM [13C2]LTB4 was present. Production of 5-hydroxy-6,8,11,14-eicosatetraenoic acid and release of free arachidonic acid were also dose-dependently inhibited by exogenous LTB4. Metabolites of LTB4, 20-hydroxy-LTB4 and 3(S)-hydroxy-LTB4, also significantly reduced LTB4 production to levels as low as 10 +/- 6% and 10 +/- 7% of control levels, respectively, when present exogenously at 10 nM. Exogenous 5-hydroxy-6,8,11,14-eicosatetraenoic acid at concentrations as high as 10 nM produced no significant reduction in LTB4 biosynthesis during zymosan-stimulated human neutrophil production of LTB4. The inhibitory effect of LTB4 could be partially reversed by the LTB4 receptor antagonist U 75302. Furthermore, an alternative stimulus, N-formyl-methionyl-leucyl-phenylalanine (100 nM), did not inhibit the production of LTB4 in opsonized zymosan-stimulated human neutrophils. These results suggest that activation of the LTB4 receptor on the human neutrophil during phagocytosis limits the ultimate biosynthesis of LTB4. This autocrine effect is opposite to that observed when neutrophils have much of the signal transduction pathways bypassed when stimulated with calcium ionophore A23187 or treated with exogenous free arachidonic acid.

  12. Stimulating endogenous cardiac repair

    PubMed Central

    Finan, Amanda; Richard, Sylvain

    2015-01-01

    The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration, a combination of these approaches could ameliorate the overall repair process to incorporate the participation of multiple cellular players. PMID:26484341

  13. Endogenous Pyrogen Physiology

    DTIC Science & Technology

    1980-01-01

    Intracerebroventricular injection of rats: a sensitive directed to the photoreceptor system for phototaxis of the proto- assay method for endogenous...spinal heating and cooling and photobiologists. The remainder of the book is devoted to the eye. intracerebroventricular injections of monoamines and...photobehavior and vision discussed, such as histamine /antihistamines, cough remedies, of invertebrates. h i e nd slep-aids and laxatives. The few citations

  14. Expression of a Flax Allene Oxide Synthase cDNA Leads to Increased Endogenous Jasmonic Acid (JA) Levels in Transgenic Potato Plants but Not to a Corresponding Activation of JA-Responding Genes.

    PubMed Central

    Harms, K.; Atzorn, R.; Brash, A.; Kuhn, H.; Wasternack, C.; Willmitzer, L.; Pena-Cortes, H.

    1995-01-01

    Both jasmonic acid (JA) and its methyl ester, methyl jasmonate (MeJA), are thought to be significant components of the signaling pathway regulating the expression of plant defense genes in response to various stresses. JA and MeJA are plant lipid derivatives synthesized from [alpha]-linolenic acid by a lipoxygenase-mediated oxygenation leading to 13-hydroperoxylinolenic acid, which is subsequently transformed by the action of allene oxide synthase (AOS) and additional modification steps. AOS converts lipoxygenase-derived fatty acid hydroperoxide to allene epoxide, which is the precursor for JA formation. Overexpression of flax AOS cDNA under the regulation of the cauliflower mosaic virus 35S promoter in transgenic potato plants led to an increase in the endogenous level of JA. Transgenic plants had six- to 12-fold higher levels of JA than the nontransformed plants. Increased levels of JA have been observed when potato and tomato plants are mechanically wounded. Under these conditions, the proteinase inhibitor II (pin2) genes are expressed in the leaves. Despite the fact that the transgenic plants had levels of JA similar to those found in nontransgenic wounded plants, pin2 genes were not constitutively expressed in the leaves of these plants. Transgenic plants with increased levels of JA did not show changes in water state or in the expression of water stress-responsive genes. Furthermore, the transgenic plants overexpressing the flax AOS gene, and containing elevated levels of JA, responded to wounding or water stress by a further increase in JA and by activating the expression of either wound- or water stress-inducible genes. Protein gel blot analysis demonstrated that the flax-derived AOS protein accumulated in the chloroplasts of the transgenic plants. PMID:12242357

  15. Targeted deletion of the kynurenine aminotransferase ii gene reveals a critical role of endogenous kynurenic acid in the regulation of synaptic transmission via alpha7 nicotinic receptors in the hippocampus.

    PubMed

    Alkondon, Manickavasagon; Pereira, Edna F R; Yu, Ping; Arruda, Emerson Z; Almeida, Luis E F; Guidetti, Paolo; Fawcett, William P; Sapko, Michael T; Randall, William R; Schwarcz, Robert; Tagle, Danilo A; Albuquerque, Edson X

    2004-05-12

    It has been postulated that endogenous kynurenic acid (KYNA) modulates alpha7* nicotinic acetylcholine receptor (nAChR) and NMDA receptor activities in the brain.a To test this hypothesis, alpha7* nAChR and NMDA receptor functions were studied in mice with a targeted null mutation in the gene encoding kynurenine aminotransferase II (mKat-2-/- mice), an enzyme responsible for brain KYNA synthesis. At 21 postnatal days, mKat-2-/- mice had lower hippocampal KYNA levels and higher spontaneous locomotor activity than wild-type (WT) mice. At this age, alpha7* nAChR activity induced by exogenous application of agonists to CA1 stratum radiatum interneurons was approximately 65% higher in mKat-2-/- than WT mice. Binding studies indicated that the enhanced receptor activity may not have resulted from an increase in alpha7* nAChR number. In 21-d-old mKat-2-/- mice, endogenous alpha7* nAChR activity in the hippocampus was also increased, leading to an enhancement of GABAergic activity impinging onto CA1 pyramidal neurons that could be reduced significantly by acute exposure to KYNA (100 nM). The activities of GABA(A) and NMDA receptors in the interneurons and of alpha3beta4* nAChRs regulating glutamate release onto these neurons were comparable between mKat-2-/- and WT mice. By 60 d of age, KYNA levels and GABAergic transmission in the hippocampus and locomotor activity were similar between mKat-2-/- and WT mice. Our findings that alpha7* nAChRs are major targets for KYNA in the brain may provide insights into the pathophysiology of schizophrenia and Alzheimer's disease, disorders in which brain KYNA levels are increased and alpha7* nAChR functions are impaired.

  16. Epileptiform activity in the CA1 region of the hippocampus becomes refractory to attenuation by cannabinoids in part because of endogenous γ-aminobutyric acid type B receptor activity.

    PubMed

    Messer, Ricka D; Levine, Eric S

    2012-07-01

    The anticonvulsant properties of marijuana have been known for centuries. The recently characterized endogenous cannabinoid system thus represents a promising target for novel anticonvulsant agents; however, administration of exogenous cannabinoids has shown mixed results in both human epilepsy and animal models. The ability of cannabinoids to attenuate release of both excitatory and inhibitory neurotransmitters may explain the variable effects of cannabinoids in different models of epilepsy, but this has not been well explored. Using acute mouse brain slices, we monitored field potentials in the CA1 region of the hippocampus to characterize systematically the effects of the cannabinoid agonist WIN55212-2 (WIN) on evoked basal and epileptiform activity. WIN, acting presynaptically, significantly reduced the amplitude and slope of basal field excitatory postsynaptic potentials as well as stimulus-evoked epileptiform responses induced by omission of magnesium from the extracellular solution. In contrast, the combination of omission of magnesium plus elevation of potassium induced an epileptiform response that was refractory to attenuation by WIN. The effect of WIN in this model was partially restored by blocking γ-aminobutyric acid type B (GABA(B) ), but not GABA(A) , receptors. Subtle differences in models of epileptiform activity can profoundly alter the efficacy of cannabinoids. Endogenous GABA(B) receptor activation played a role in the decreased cannabinoid sensitivity observed for epileptiform activity induced by omission of magnesium plus elevation of potassium. These results suggest that interplay between presynaptic G protein-coupled receptors with overlapping downstream targets may underlie the variable efficacy of cannabinoids in different models of epilepsy.

  17. Increased renal net acid excretion in prematures below 1,600 g body weight compared with prematures and small-for-date newborns above 2,100 g on alimentation with a commercial preterm formula.

    PubMed

    Kalhoff, H; Wiese, B; Kunz, C; Diekmann, L; Stock, G J; Manz, F

    1994-01-01

    In 76 low birth weight infants with an actual body weight ranging from 1,210 to 2,540 g and fed a commercial preterm formula, urine samples were collected and blood acid base status was measured on day 38 (+/- 17, mean +/- SD) of life. Infants with an actual body weight below 1,600 g demonstrated a higher daily weight gain (22 +/- 3 vs. 14 +/- 5 g/kg/day), lower blood pCO2 (35.4 +/- 5.0 vs. 38.9 +/- 3.8 mm Hg), lower urine pH (5.8 +/- 0.5 vs. 6.5 +/- 0.3), higher renal net acid (1.86 +/- 0.38 vs. 1.28 +/- 0.55 mmol/kg/day) and higher phosphorus excretion (0.67 vs. 0.52 mmol/kg/day) than infants with an actual body weight above 2,100 g. Urinary ionogram data of these 2 groups of infants show that the increased renal net acid excretion of the smaller prematures is the result of a lower urinary excretion of sodium, potassium and chloride, due to a higher daily weight gain, probably a higher retention of these minerals, and a higher urinary phosphorus excretion probably due to an age-specific lower intestinal calcium absorption, and therefore a lower rate of calcium and phosphorus retention. Considering the low renal capacity for hydrogen ion excretion, very low birth weight infants still run a considerable risk for disturbances of acid base metabolism due to the high mean level of net acid excretion in nutrition with preterm formulas and an additional age-specific augmentation of renal acid load.

  18. Stress enhances the gene expression and enzyme activity of phenylalanine ammonia-lyase and the endogenous content of salicylic acid to induce flowering in pharbitis.

    PubMed

    Wada, Kaede C; Mizuuchi, Kaori; Koshio, Aya; Kaneko, Kentaro; Mitsui, Toshiaki; Takeno, Kiyotoshi

    2014-07-01

    The involvement of salicylic acid (SA) in the regulation of stress-induced flowering in the short-day plant pharbitis (also called Japanese morning glory) Ipomoea nil (formerly Pharbitis nil) was studied. Pharbitis cv. Violet was induced to flower when grown in 1/100-strength mineral nutrient solution under non-inductive long-day conditions. All fully expanded true leaves were removed from seedlings, leaving only the cotyledons, and flowering was induced under poor-nutrition stress conditions. This indicates that cotyledons can play a role in the regulation of poor-nutrition stress-induced flowering. The expression of the pharbitis homolog of PHENYLALANINE AMMONIA-LYASE, the enzyme activity of phenylalanine ammonia-lyase (PAL; E.C. 4.3.1.5) and the content of SA in the cotyledons were all up-regulated by the stress treatment. The Violet was also induced to flower by low-temperature stress, DNA demethylation and short-day treatment. Low-temperature stress enhanced PAL activity, whereas non-stress factors such as DNA demethylation and short-day treatment decreased the activity. The PAL enzyme activity was also examined in another cultivar, Tendan, obtaining similar results to Violet. The exogenously applied SA did not induce flowering under non-stress conditions but did promote flowering under weak stress conditions in both cultivars. These results suggest that stress-induced flowering in pharbitis is induced, at least partly, by SA, and the synthesis of SA is promoted by PAL.

  19. Real-time analysis of endogenous protoporphyrin IX fluorescence from δ-aminolevulinic acid and its derivatives reveals distinct time- and dose-dependent characteristics in vitro

    NASA Astrophysics Data System (ADS)

    Kiesslich, Tobias; Helander, Linda; Illig, Romana; Oberdanner, Christian; Wagner, Andrej; Lettner, Herbert; Jakab, Martin; Plaetzer, Kristjan

    2014-08-01

    Photodynamic therapy (PDT) and photodiagnosis based on the intracellular production of the photosensitizer protoporphyrin IX (PPIX) by administration of its metabolic precursor δ-aminolevulinic acid (ALA) achieved their breakthrough upon the clinical approval of MAL (ALA methyl ester) and HAL (ALA hexyl ester). For newly developed ALA derivatives or application in new tumor types, in vitro determination of PPIX formation involves multiparametric experiments covering variable pro-drug concentrations, medium composition, time points of analysis, and cell type(s). This study uses a fluorescence microplate reader with a built-in temperature and atmosphere control to investigate the high-resolution long-term kinetics (72 h) of cellular PPIX fueled by administration of either ALA, MAL, or HAL for each 10 different concentrations. For simultaneous proliferation correction, A431 cells were stably transfected with green fluorescent protein. The results indicate that the peak PPIX level is a function of both, incubation concentration and period: maximal PPIX is generated with 1 to 2-mM ALA/MAL or 0.125-mM HAL; also, the PPIX peak shifts to longer incubation periods with increasing pro-drug concentrations. The results underline the need for detailed temporal analysis of PPIX formation to optimize ALA (derivative)-based PDT or photodiagnosis and highlight the value of environment-controlled microplate readers for automated in vitro analysis.

  20. Subacute hypoxia suppresses Kv3.4 channel expression and whole-cell K+ currents through endogenous 15-hydroxyeicosatetraenoic acid in pulmonary arterial smooth muscle cells.

    PubMed

    Guo, Lei; Tang, Xiaobo; Tian, Hua; Liu, Ye; Wang, Zhigang; Wu, Hong; Wang, Jing; Guo, Sholi; Zhu, Daling

    2008-06-10

    We have previously reported that subacute hypoxia activates lung 15-lipoxygenase (15-LOX), which catalyzes arachidonic acid to produce 15-HETE, leading to constriction of neonatal rabbit pulmonary arteries. Subacute hypoxia suppresses Kv3.4 channel expression and results in an inhibition of whole-cell K(+) currents (I(K)). Although the Kv channel inhibition is likely to be mediated through 15-HETE, direct evidence is still lacking. To reveal the role of the 15-LOX/15-HETE pathway in the hypoxia-induced down-regulation of Kv3.4 channel expression and inhibition of I(K), we performed studies using 15-LOX blockers, whole-cell patch-clamp, semi-quantitative PCR, ELISA and Western blot analysis. We found that Kv3.4 channel expression at the mRNA and protein levels was greatly up-regulated in pulmonary arterial smooth muscle cells after blockade of 15-LOX by CDC or NDGA. The 15-LOX blockade also partially restored I(K). In comparison, 15-HETE had a stronger effect than 12-HETE on the expression of Kv3.4 channels. 5-HETE had no noticeable effect on Kv3.4 channel expression. These data indicate that the 15-LOX pathway via its metabolite, 15-HETE, seems to play a role in the down-regulation of Kv3.4 expression and I(K) inhibition after subacute hypoxia.

  1. Analysis of plant-bacteria interactions in their native habitat: bacterial communities associated with wild tobacco are independent of endogenous jasmonic acid levels and developmental stages.

    PubMed

    Santhanam, Rakesh; Groten, Karin; Meldau, Dorothea G; Baldwin, Ian T

    2014-01-01

    Jasmonic acid (JA) mediates defense responses against herbivores and necrotrophic pathogens but does it influence the recruitment of bacterial communities in the field? We conducted field and laboratory experiments with transformed Nicotiana attenuata plants deficient in jasmonate biosynthesis (irAOC) and empty vector controls (EV) to answer this question. Using both culture-dependent and independent techniques, we characterized root and leaf-associated bacterial communities over five developmental stages, from rosette through flowering of plants grown in their natural habitat. Based on the pyrosequencing results, alpha and beta diversity did not differ among EV and irAOC plants or over ontogeny, but some genera were more abundant in one of the genotypes. Furthermore, bacterial communities were significantly different among leaves and roots. Taxa isolated only from one or both plant genotypes and hence classified as 'specialists' and 'generalists' were used in laboratory tests to further evaluate the patterns observed from the field. The putative specialist taxa did not preferentially colonize the jasmonate-deficient genotype, or alter the plant's elicited phytohormone signaling. We conclude that in N. attenuata, JA signaling does not have a major effect on structuring the bacterial communities and infer that colonization of plant tissues is mainly shaped by the local soil community in which the plant grows.

  2. Diabetes-linked transcription factor HNF4α regulates metabolism of endogenous methylarginines and β-aminoisobutyric acid by controlling expression of alanine-glyoxylate aminotransferase 2

    PubMed Central

    Burdin, Dmitry V.; Kolobov, Alexey A.; Brocker, Chad; Soshnev, Alexey A.; Samusik, Nikolay; Demyanov, Anton V.; Brilloff, Silke; Jarzebska, Natalia; Martens-Lobenhoffer, Jens; Mieth, Maren; Maas, Renke; Bornstein, Stefan R.; Bode-Böger, Stefanie M.; Gonzalez, Frank; Weiss, Norbert; Rodionov, Roman N.

    2016-01-01

    Elevated levels of circulating asymmetric and symmetric dimethylarginines (ADMA and SDMA) predict and potentially contribute to end organ damage in cardiovascular diseases. Alanine-glyoxylate aminotransferase 2 (AGXT2) regulates systemic levels of ADMA and SDMA, and also of beta-aminoisobutyric acid (BAIB)-a modulator of lipid metabolism. We identified a putative binding site for hepatic nuclear factor 4 α (HNF4α) in AGXT2 promoter sequence. In a luciferase reporter assay we found a 75% decrease in activity of Agxt2 core promoter after disruption of the HNF4α binding site. Direct binding of HNF4α to Agxt2 promoter was confirmed by chromatin immunoprecipitation assay. siRNA-mediated knockdown of Hnf4a led to an almost 50% reduction in Agxt2 mRNA levels in Hepa 1–6 cells. Liver-specific Hnf4a knockout mice exhibited a 90% decrease in liver Agxt2 expression and activity, and elevated plasma levels of ADMA, SDMA and BAIB, compared to wild-type littermates. Thus we identified HNF4α as a major regulator of Agxt2 expression. Considering a strong association between human HNF4A polymorphisms and increased risk of type 2 diabetes our current findings suggest that downregulation of AGXT2 and subsequent impairment in metabolism of dimethylarginines and BAIB caused by HNF4α deficiency might contribute to development of cardiovascular complications in diabetic patients. PMID:27752141

  3. Diabetes-linked transcription factor HNF4α regulates metabolism of endogenous methylarginines and β-aminoisobutyric acid by controlling expression of alanine-glyoxylate aminotransferase 2.

    PubMed

    Burdin, Dmitry V; Kolobov, Alexey A; Brocker, Chad; Soshnev, Alexey A; Samusik, Nikolay; Demyanov, Anton V; Brilloff, Silke; Jarzebska, Natalia; Martens-Lobenhoffer, Jens; Mieth, Maren; Maas, Renke; Bornstein, Stefan R; Bode-Böger, Stefanie M; Gonzalez, Frank; Weiss, Norbert; Rodionov, Roman N

    2016-10-18

    Elevated levels of circulating asymmetric and symmetric dimethylarginines (ADMA and SDMA) predict and potentially contribute to end organ damage in cardiovascular diseases. Alanine-glyoxylate aminotransferase 2 (AGXT2) regulates systemic levels of ADMA and SDMA, and also of beta-aminoisobutyric acid (BAIB)-a modulator of lipid metabolism. We identified a putative binding site for hepatic nuclear factor 4 α (HNF4α) in AGXT2 promoter sequence. In a luciferase reporter assay we found a 75% decrease in activity of Agxt2 core promoter after disruption of the HNF4α binding site. Direct binding of HNF4α to Agxt2 promoter was confirmed by chromatin immunoprecipitation assay. siRNA-mediated knockdown of Hnf4a led to an almost 50% reduction in Agxt2 mRNA levels in Hepa 1-6 cells. Liver-specific Hnf4a knockout mice exhibited a 90% decrease in liver Agxt2 expression and activity, and elevated plasma levels of ADMA, SDMA and BAIB, compared to wild-type littermates. Thus we identified HNF4α as a major regulator of Agxt2 expression. Considering a strong association between human HNF4A polymorphisms and increased risk of type 2 diabetes our current findings suggest that downregulation of AGXT2 and subsequent impairment in metabolism of dimethylarginines and BAIB caused by HNF4α deficiency might contribute to development of cardiovascular complications in diabetic patients.

  4. Release of GLP-1 and PYY in response to the activation of G protein-coupled bile acid receptor TGR5 is mediated by Epac/PLC-ε pathway and modulated by endogenous H2S.

    PubMed

    Bala, Vanitha; Rajagopal, Senthilkumar; Kumar, Divya P; Nalli, Ancy D; Mahavadi, Sunila; Sanyal, Arun J; Grider, John R; Murthy, Karnam S

    2014-01-01

    Activation of plasma membrane TGR5 receptors in enteroendocrine cells by bile acids is known to regulate gastrointestinal secretion and motility and glucose homeostasis. The endocrine functions of the gut are modulated by microenvironment of the distal gut predominantly by sulfur-reducing bacteria of the microbiota that produce H2S. However, the mechanisms involved in the release of peptide hormones, GLP-1 and PYY in response to TGR5 activation by bile acids and the effect of H2S on bile acid-induced release of GLP-1 and PYY are unclear. In the present study, we have identified the signaling pathways activated by the bile acid receptor TGR5 to mediate GLP-1 and PYY release and the mechanism of inhibition of their release by H2S in enteroendocrine cells. The TGR5 ligand oleanolic acid (OA) stimulated Gαs and cAMP formation, and caused GLP-1 and PYY release. OA-induced cAMP formation and peptide release were blocked by TGR5 siRNA. OA also caused an increase in PI hydrolysis and intracellular Ca(2+). Increase in PI hydrolysis was abolished in cells transfected with PLC-ε siRNA. 8-pCPT-2'-O-Me-cAMP, a selective activator of Epac, stimulated PI hydrolysis, and GLP-1 and PYY release. L-Cysteine, which activates endogenous H2S producing enzymes cystathionine-γ-lyase and cystathionine-β-synthase, and NaHS and GYY4137, which generate H2S, inhibited PI hydrolysis and GLP-1 and PYY release in response to OA or 8-pCPT-2'-O-Me-cAMP. Propargylglycine, an inhibitor of CSE, reversed the effect of L-cysteine on PI hydrolysis and GLP-1 and PYY release. We conclude: (i) activation of Gαs-coupled TGR5 receptors causes stimulation of PI hydrolysis, and release of GLP-1 and PYY via a PKA-independent, cAMP-dependent mechanism involving Epac/PLC-ε/Ca(2+) pathway, and (ii) H2S has potent inhibitory effects on GLP-1 and PYY release in response to TGR5 activation, and the mechanism involves inhibition of PLC-ε/Ca(2+) pathway.

  5. Endogenous ethanol--its metabolic, behavioral and biomedical significance.

    PubMed

    Ostrovsky YuM

    1986-01-01

    Ethanol is constantly formed endogenously from acetaldehyde, and level of the former can be measured in both human beings and animals. Acetaldehyde can be generated in situ from the metabolism of pyruvate, threonine, deoxyribose-5-phosphate, phosphoethanolamine, alanine and presumably from other substrates. The levels of blood and tissue endogenous ethanol change as a function of various physiologic and experimental conditions such as starvation, aging, stress, cooling, adrenalectomy, etc. and are regulated by many exogenous compounds such as antimetabolites, derivatives of amino acids, lithium salts, disulfiram, cyanamide, etc. Under free choice alcohol selection situations, the levels of endogenous ethanol in rat blood and alcohol preference by the animals are negatively correlated. Similar negative correlations have been found between the levels of blood endogenous ethanol and the frequency of delirium in alcoholic patients undergoing alcohol withdrawal. Endogenous ethanol and acetaldehyde can therefore be regarded as compounds which fulfil substrate, regulatory and modulator functions.

  6. NA-NET numerical analysis net

    SciTech Connect

    Dongarra, J. . Dept. of Computer Science Oak Ridge National Lab., TN ); Rosener, B. . Dept. of Computer Science)

    1991-12-01

    This report describes a facility called NA-NET created to allow numerical analysts (na) an easy method of communicating with one another. The main advantage of the NA-NET is uniformity of addressing. All mail is addressed to the Internet host na-net.ornl.gov'' at Oak Ridge National Laboratory. Hence, members of the NA-NET do not need to remember complicated addresses or even where a member is currently located. As long as moving members change their e-mail address in the NA-NET everything works smoothly. The NA-NET system is currently located at Oak Ridge National Laboratory. It is running on the same machine that serves netlib. Netlib is a separate facility that distributes mathematical software via electronic mail. For more information on netlib consult, or send the one-line message send index'' to netlib{at}ornl.gov. The following report describes the current NA-NET system from both a user's perspective and from an implementation perspective. Currently, there are over 2100 members in the NA-NET. An average of 110 mail messages pass through this facility daily.

  7. NA-NET numerical analysis net

    SciTech Connect

    Dongarra, J. |; Rosener, B.

    1991-12-01

    This report describes a facility called NA-NET created to allow numerical analysts (na) an easy method of communicating with one another. The main advantage of the NA-NET is uniformity of addressing. All mail is addressed to the Internet host ``na-net.ornl.gov`` at Oak Ridge National Laboratory. Hence, members of the NA-NET do not need to remember complicated addresses or even where a member is currently located. As long as moving members change their e-mail address in the NA-NET everything works smoothly. The NA-NET system is currently located at Oak Ridge National Laboratory. It is running on the same machine that serves netlib. Netlib is a separate facility that distributes mathematical software via electronic mail. For more information on netlib consult, or send the one-line message ``send index`` to netlib{at}ornl.gov. The following report describes the current NA-NET system from both a user`s perspective and from an implementation perspective. Currently, there are over 2100 members in the NA-NET. An average of 110 mail messages pass through this facility daily.

  8. Determination of endogenous concentration of γ-hydroxybutyric acid (GHB) in hair through an ad hoc GC-MS analysis: A study on a wide population and influence of gender and age.

    PubMed

    Vaiano, Fabio; Serpelloni, Giovanni; Furlanetto, Sandra; Palumbo, Diego; Mari, Francesco; Fioravanti, Alessia; Bertol, Elisabetta

    2016-01-25

    γ-Hydroxybutyric acid (GHB) spread for recreational purposes or as "rape drug" represents a hard issue for forensic toxicologists due to its endogenous nature. It is clear that an actual and reliable discrimination between basal and exogenous levels is mandatory to achieve a correct evaluation of conscious/unconscious administration. This research aimed to study the GHB baseline in hair samples, collected from 150 volunteers, non-consumers of any drugs of abuse, in order to evaluate if a generic cut-off value could be accepted, also focusing on potential influences of gender and age. The analysis consisted of an overnight incubation with NaOH at 56 °C, liquid-liquid extraction with ethylacetate and trimethylsylil derivatization. Detection was carried out through gas chromatography-mass spectrometry in single ion monitoring (m/z 233, 234, 147 for GHB; m/z 239, 240 and 147 for GHB-d6). The endogenous amount in "blank" hair was estimated by the standard addition method. Concentration range was 0.279-2.839 ng/mg. In males, the average GHB levels were higher than in females (0.829 vs 0.596 ng/mg, respectively), especially in the first age category (<30 years, 1.008 vs 0.606 ng/mg, respectively). Age influences on GHB levels seemed to be different among the two sexes: in male population concentrations were higher <30 (1.008 ng/mg) and similar in the other age ranges (0.762 ng/mg, 30-50; 0.763 ng/mg, >50); in female, quite similar levels were registered throughout all the age categories (0.606 ng/mg, <30; 0.536 ng/mg, 30-50; 0.691 ng/mg, >50). Further study should be performed on GHB physiology in order to better understand these differences among ages and genders. Moreover, we demonstrated that for hair analysis a cut-off reference value is not strictly mandatory, underlining the great interpretative valence of segmental analysis.

  9. Pushing the endogenous envelope

    PubMed Central

    Henzy, Jamie E.; Johnson, Welkin E.

    2013-01-01

    The majority of retroviral envelope glycoproteins characterized to date are typical of type I viral fusion proteins, having a receptor binding subunit associated with a fusion subunit. The fusion subunits of lentiviruses and alpha-, beta-, delta- and gammaretroviruses have a very conserved domain organization and conserved features of secondary structure, making them suitable for phylogenetic analyses. Such analyses, along with sequence comparisons, reveal evidence of numerous recombination events in which retroviruses have acquired envelope glycoproteins from heterologous sequences. Thus, the envelope gene (env) can have a history separate from that of the polymerase gene (pol), which is the most commonly used gene in phylogenetic analyses of retroviruses. Focusing on the fusion subunits of the genera listed above, we describe three distinct types of retroviral envelope glycoproteins, which we refer to as gamma-type, avian gamma-type and beta-type. By tracing these types within the ‘fossil record’ provided by endogenous retroviruses, we show that they have surprisingly distinct evolutionary histories and dynamics, with important implications for cross-species transmissions and the generation of novel lineages. These findings validate the utility of env sequences in contributing phylogenetic signal that enlarges our understanding of retrovirus evolution. PMID:23938755

  10. Endogenous Cooperation Network Formation

    NASA Astrophysics Data System (ADS)

    Angus, S.

    This paper employs insights from Complex Systems literature to develop a computational model of endogenous strategic network formation. Artificial Adaptive Agents (AAAs), implemented as finite state automata, play a modified two-player Iterated Prisoner's Dilemma game with an option to further develop the interaction space as part of their strategy. Several insights result from this relatively minor modification: first, I find that network formation is a necessary condition for cooperation to be sustainable but that both the frequency of interaction and the degree to which edge formation impacts agent mixing are both necessary conditions for cooperative networks. Second, within the FSA-modified IPD frame-work, a rich ecology of agents and network topologies is observed, with consequent payoff symmetry and network 'purity' seen to be further contributors to robust cooperative networks. Third, the dynamics of the strategic system under network formation show that initially simple dynamics with small interaction length between agents gives way to complex, a-periodic dynamics when interaction lengths are increased by a single step.

  11. Endogenous Cooperation Network Formation

    NASA Astrophysics Data System (ADS)

    Angus, S.

    This paper employs insights from Complex Systems literature to develop a computational model of endogenous strategic network formation. Artificial Adaptive Agents (AAAs), implemented as finite state automata, play a modified two-player Iterated Prisoner's Dilemma game with an option to further develop the interaction space as part of their strategy. Several insights result from this relatively minor modification: first, I find that network formation is a necessary condition for cooperation to be sustainable but that both the frequency of interaction and the degree to which edge formation impacts agent mixing are both necessary conditions for cooperative networks. Second, within the FSA-modified IPD frame-work, a rich ecology of agents and network topologies is observed, with consequent payoff symmetry and network `purity' seen to be further contributors to robust cooperative networks. Third, the dynamics of the strategic system under network formation show that initially simple dynamics with small interaction length between agents gives way to complex, a-periodic dynamics when interaction lengths are increased by a single step.

  12. No Safety Net Required

    ERIC Educational Resources Information Center

    Benigni, Mark D.; Moylan, Maureen

    2009-01-01

    This article discusses the Berlin (Connecticut) High School's NET (Non-Traditional Educational Training) program. NET is a self-contained program that is composed of three components: academics, social and emotional support, and vocational training. Rather than treat students alike, the NET program tailors their high school experience to meet…

  13. Net Making = Kuvrinialiq.

    ERIC Educational Resources Information Center

    Pulu, Tupou L.; And Others

    Presented in English and Upper Kobuk Inupiaq Eskimo, the booklet describes and illustrates the skills necessary for the construction and the hanging of the fishing nets used by Eskimos. Description of net making includes gathering the bark; willow twine making; kinds of implements used in net construction (twine, shuttle, gauge, forked stick,…

  14. The endogenous cannabinoid anandamide produces delta-9-tetrahydrocannabinol-like discriminative and neurochemical effects that are enhanced by inhibition of fatty acid amide hydrolase but not by inhibition of anandamide transport.

    PubMed

    Solinas, Marcello; Tanda, Gianluigi; Justinova, Zuzana; Wertheim, Carrie E; Yasar, Sevil; Piomelli, Daniele; Vadivel, Subramanian K; Makriyannis, Alexandros; Goldberg, Steven R

    2007-04-01

    Anandamide is an endogenous ligand for brain cannabinoid CB(1) receptors, but its behavioral effects are difficult to measure due to rapid inactivation. Here we used a drug-discrimination procedure to test the hypothesis that anandamide, given i.v. or i.p., would produce discriminative effects like those of delta-9-tetrahydrocannabinol (THC) in rats when its metabolic inactivation was inhibited. We also used an in vivo microdialysis procedure to investigate the effects of anandamide, given i.v. or i.p., on dopamine levels in the nucleus accumbens shell in rats. When injected i.v., methanandamide (AM-356), a metabolically stable anandamide analog, produced clear dose-related THC-like discriminative effects, but anandamide produced THC-like discriminative effects only at a high 10-mg/kg dose that almost eliminated lever-press responding. Cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester (URB-597), an inhibitor of fatty acid amide hydrolase (FAAH), the main enzyme responsible for metabolic inactivation of anandamide, produced no THC-like discriminative effects alone but dramatically potentiated discriminative effects of anandamide, with 3 mg/kg anandamide completely substituting for the THC training dose. URB-597 also potentiated the ability of anandamide to increase dopamine levels in the accumbens shell. The THC-like discriminative-stimulus effects of anandamide after URB-597 and methanandamide were blocked by the CB1 receptor antagonist rimonabant, but not the vanilloid VR1 receptor antagonist capsazepine. Surprisingly, the anandamide transport inhibitors N-(4-hydroxyphenyl)-eicosa-5,8,11,14-tetraenamide (AM-404) and N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide (UCM-707) did not potentiate THC-like discriminative effects of anandamide or its dopamine-elevating effects. Thus, anandamide has THC-like discriminative and neurochemical effects that are enhanced after treatment with a FAAH inhibitor but not after treatment with transport inhibitors, suggesting

  15. Cannabinoid receptors and their endogenous agonist, anandamide.

    PubMed

    Axelrod, J; Felder, C C

    1998-05-01

    Cannabinoids are a class of compound found in marijuana which have been known for their therapeutic and psychoactive properties for at least 4000 years. Isolation of the active principle in marijuana, delta9-THC, provided the lead structure in the development of highly potent congeners which were used to probe for the mechanism of marijuana action. Cannabinoids were shown to bind to selective binding sites in brain tissue thereby regulating second messenger formation. Such studies led to the cloning of three cannabinoid receptor subtypes, CB1, CB2, and CB1A all of which belong to the superfamily of G protein-coupled plasma membrane receptors. Analogous to the discovery of endogenous opiates, isolation of cannabinoid receptors provided the appropriate tool to isolate an endogenous cannabimimetic eicosanoid, anandamide, from porcine brain. Recent studies indicate that anandamide is a member of a family of fatty acid ethanolamides that may represent a novel class of lipid neurotransmitters. This review discusses recent progress in cannabinoid research with a focus on the receptors for delta9-THC, their coupling to second messenger responses, and the endogenous lipid cannabimimetic, anandamide.

  16. Endogenous Antibodies for Tumor Detection

    PubMed Central

    Rich, Barrie S.; Honeyman, Joshua N.; Darcy, David G.; Smith, Peter T.; Williams, Andrew R.; Lim, Irene Isabel P.; Johnson, Linda K.; Gönen, Mithat; Simon, Joel S.; LaQuaglia, Michael P.; Simon, Sanford M.

    2014-01-01

    The study of cancer immunology has provided diagnostic and therapeutic instruments through serum autoantibody biomarkers and exogenous monoclonal antibodies. While some endogenous antibodies are found within or surrounding transformed tissue, the extent to which this exists has not been entirely characterized. We find that in transgenic and xenograft mouse models of cancer, endogenous gamma immunoglobulin (IgG) is present at higher concentration in malignantly transformed organs compared to non-transformed organs in the same mouse or organs of cognate wild-type mice. The enrichment of endogenous antibodies within the malignant tissue provides a potential means of identifying and tracking malignant cells in vivo as they mutate and diversify. Exploiting these antibodies for diagnostic and therapeutic purposes is possible through the use of agents that bind endogenous antibodies. PMID:24875800

  17. Association of endogenous substrate with solubilized bovine brain sialidase.

    PubMed

    Schengrund, C L; Repman, M A

    1986-01-01

    Nonidet P40 solubilized up to 90% of the sialidase, active towards added ganglioside substrate, that was associated with the total membrane fraction prepared from gray matter of bovine brains. Solubilized sialidase acted upon endogenous substrate (sialic acid containing compounds solubilized with the enzyme), hydrolyzing approximately 50% of the readily available sialosyl residues within 20 min. During a 2-hr reaction time 80% of the polysialylated gangliosides solubilized with the enzyme were acted upon. A 20-min lag was observed before sialidase acted upon added ganglioside substrate. The lag could be reduced to less than 2 min when the enzyme was allowed to act on endogenous substrate prior to exposure to exogenous substrate, suggesting that the solubilized enzyme acted preferentially on endogenous substrate. A protease inhibitor prevented much of the 86% loss of activity towards added substrate that was seen when the enzyme was stored at 4 degrees C for 6 days; activity towards endogenous substrate decreased only 34%.

  18. Relationship between bradykinin-induced relaxation and endogenous epoxyeicosanoid synthesis in human bronchi.

    PubMed

    Tabet, Yacine; Sirois, Marco; Sirois, Chantal; Rizcallah, Edmond; Rousseau, Éric

    2013-04-15

    Epoxyeicosanoids (EETs) are produced by cytochrome P-450 epoxygenase; however, it is not yet known what triggers their endogenous production in epithelial cells. The relaxing effects of bradykinin are known to be related to endogenous production of epithelial-derived hyperpolarizing factors (EpDHF). Because of their effects on membrane potential, EETs have been reported to be EpDHF candidates (Benoit C, Renaudon B, Salvail D, Rousseau E. Am J Physiol Lung Cell Mol Physiol 280: L965-L973, 2001.). Thus, we hypothesized that bradykinin (BK) may stimulate endogenous EET production in human bronchi. To test this hypothesis, the relaxing and hyperpolarizing effects of BK and 14,15-EET were quantified on human bronchi, as well as the effects of various enzymatic inhibitors on these actions. One micromolar BK or 1 μM 14,15-EET induced a 45% relaxation on the tension induced by 30 nM U-46619 [a thromboxane-prostanoid (TP)-receptor agonist]. These BK-relaxing effects were reduced by 42% upon addition of 10 nM iberiotoxin [a large-conductance Ca(2+)-sensitive K(+) (BK(Ca)) channel blocker], by 27% following addition of 3 μM 14,15-epoxyeicosa-5(Z)-enoic acid (an EET antagonist), and by 32% with 3 μM N-methanesulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH, an epoxygenase inhibitor). Hence, BK and 14,15-EET display net hyperpolarizing effects on airway smooth muscle cells that are related to the activation of BK(Ca) channels and ultimately yielding to relaxation. Data also indicate that 3 μM MS-PPOH reduced the hyperpolarizing effects of BK by 43%. Together, the present data support the current hypothesis suggesting a direct relationship between BK and the production of EET regioisomers. Because of its potent anti-inflammatory and relaxing properties, epoxyeicosanoid signaling may represent a promising target in asthma and chronic obstructive pulmonary disease.

  19. Non-invasive quantification of endogenous root auxin transport using an integrated flux microsensor technique.

    PubMed

    McLamore, Eric S; Diggs, Alfred; Calvo Marzal, Percy; Shi, Jin; Blakeslee, Joshua J; Peer, Wendy A; Murphy, Angus S; Porterfield, D Marshall

    2010-09-01

    Indole-3-acetic acid (IAA) is a primary phytohormone that regulates multiple aspects of plant development. Because polar transport of IAA is an essential determinant of organogenesis and dynamic tropic growth, methods to monitor IAA movement in vivo are in demand. A self-referencing electrochemical microsensor was optimized to non-invasively measure endogenous IAA flux near the surface of Zea mays roots without the addition of exogenous IAA. Enhanced sensor surface modification, decoupling of acquired signals, and integrated flux analyses were combined to provide direct, real time quantification of endogenous IAA movement in B73 maize inbred and brachytic2 (br2) auxin transport mutant roots. BR2 is localized in epidermal and hypodermal tissues at the root apex. br2 roots exhibit reduced shootward IAA transport at the root apex in radiotracer experiments and reduced gravitropic growth. IAA flux data indicates that maximal transport occurs in the distal elongation zone of maize roots, and net transport in/out of br2 roots was decreased compared to B73. Integration of short term real time flux data in this zone revealed oscillatory patterns, with B73 exhibiting shorter oscillatory periods and greater amplitude than br2. IAA efflux and influx were inhibited using 1-N-naphthylphthalamic acid (NPA), and 2-naphthoxyacetic acid (NOA), respectively. A simple harmonic oscillation model of these data produced a correlation between modeled and measured values of 0.70 for B73 and 0.69 for br2. These results indicate that this technique is useful for real-time IAA transport monitoring in surface tissues and that this approach can be performed simultaneously with current live imaging techniques.

  20. Pull-Up Nets

    ERIC Educational Resources Information Center

    Meenan, Liz

    2008-01-01

    When the author began teaching, she always hit a problem when it came to 3D shapes. She wanted the pupils to get a feel for them, and she would get them to make the shapes from their nets. The pupils would first try to visualize how the 2D nets could become 3D shapes and then they would physically fold the nets into the shapes for themselves.…

  1. Quantification of endogenous retinoids.

    PubMed

    Kane, Maureen A; Napoli, Joseph L

    2010-01-01

    Numerous physiological processes require retinoids, including development, nervous system function, immune responsiveness, proliferation, differentiation, and all aspects of reproduction. Reliable retinoid quantification requires suitable handling and, in some cases, resolution of geometric isomers that have different biological activities. Here we describe procedures for reliable and accurate quantification of retinoids, including detailed descriptions for handling retinoids, preparing standard solutions, collecting samples and harvesting tissues, extracting samples, resolving isomers, and detecting with high sensitivity. Sample-specific strategies are provided for optimizing quantification. Approaches to evaluate assay performance also are provided. Retinoid assays described here for mice also are applicable to other organisms including zebrafish, rat, rabbit, and human and for cells in culture. Retinoid quantification, especially that of retinoic acid, should provide insight into many diseases, including Alzheimer's disease, type 2 diabetes, obesity, and cancer.

  2. Protein turnover and proliferation. Turnover kinetics associated with the elevation of 3T3-cell acid-proteinase activity and cessation of net protein gain.

    PubMed Central

    Lockwood, T D; Minassian, I A; Roux, L

    1982-01-01

    1. At least 95% of the total protein of A31-3T3 cell cultures undergoes turnover. 2. First-order exponential kinetics were used to provide a crude approximation of averaged protein synthesis, Ks, degradation, Kd, and net accumulation, Ka, as cells ceased growth at near-confluent density in unchanged Dulbecco's medium containing 10% serum. The values of the relationship Ka = Ks - Kd were : 5%/h = 6%/h - 1%/h in growing cells, and 0%/h = 3%/h - 3%/h in steady-state resting cells. 3. As determined by comparison of the progress of protein synthesis and net protein accumulation, the time course of increase in protein degradation coincided with the onset of an increase in lysosomal proteinase activity and decrease in thymidine incorporation after approx. 2 days of exponential growth. 4. After acute serum deprivation, rapid increases in protein degradation of less than 1%/h could be superimposed on the prevailing degradation rate in either growing or resting cells. The results indicate that two proteolytic mechanisms can be distinguished on the basis of the kinetics of their alterations. A slow mechanism changes in relation to proliferative status and lysosomal enzyme elevation. A prompt mechanism, previously described by others, changes before changes in cell-cycle distribution or lysosomal proteinase activity. 5. When the serum concentration of growing cultures was decreased to 1% or 0.25%, then cessation of growth was accompanied by a lower steady-state protein turnover rate of 2.0%/h or 1.5%/h respectively. When growth ceased under conditions of overcrowded cultures, or severe nutrient insufficiency, protein turnover did not attain a final steady state, but declined continually into the death of the culture. PMID:6756389

  3. Electro-netting: Fabrication of two-dimensional nano-nets for highly sensitive trimethylamine sensing

    NASA Astrophysics Data System (ADS)

    Wang, Xianfeng; Ding, Bin; Yu, Jianyong; Si, Yang; Yang, Shangbin; Sun, Gang

    2011-03-01

    Two-dimensional (2D) polyacrylic acid (PAA) nano-nets that comprise interlinked ultrathin nanowires with diameters of 10-30 nm are successfully prepared by a facile electro-netting process. Nano-nets feature a clear geometric characteristic with ideal and weighted Steiner networks due to the rapid phase separation process and its obeyed minimal energy principle. The versatile nano-nets create enhanced interconnectivity and additional surface area and facilitate the diffusion of analytes into the membranes, which significantly boost the gas diffusion coefficient and sensing properties. As one example, PAA membranes containing fibers and nano-nets used as sensing materials are deposited by electrospinning/electro-netting on an electrode of a quartz crystal microbalance (QCM) for trimethylamine (TMA) detection, which exhibits a quick response (~180 s), low detection limit (1 ppm) and ideal selectivity at room temperature.Two-dimensional (2D) polyacrylic acid (PAA) nano-nets that comprise interlinked ultrathin nanowires with diameters of 10-30 nm are successfully prepared by a facile electro-netting process. Nano-nets feature a clear geometric characteristic with ideal and weighted Steiner networks due to the rapid phase separation process and its obeyed minimal energy principle. The versatile nano-nets create enhanced interconnectivity and additional surface area and facilitate the diffusion of analytes into the membranes, which significantly boost the gas diffusion coefficient and sensing properties. As one example, PAA membranes containing fibers and nano-nets used as sensing materials are deposited by electrospinning/electro-netting on an electrode of a quartz crystal microbalance (QCM) for trimethylamine (TMA) detection, which exhibits a quick response (~180 s), low detection limit (1 ppm) and ideal selectivity at room temperature. Electronic supplementary information (ESI) available: Experimental details; Fig. S1 and S2. See DOI: 10.1039/c0nr00783h

  4. Endogenous rhythms influence interpersonal synchrony.

    PubMed

    Zamm, Anna; Wellman, Chelsea; Palmer, Caroline

    2016-05-01

    Interpersonal synchrony, the temporal coordination of actions between individuals, is fundamental to social behaviors from conversational speech to dance and music-making. Animal models indicate constraints on synchrony that arise from endogenous rhythms: Intrinsic periodic behaviors or processes that continue in the absence of change in external stimulus conditions. We report evidence for a direct causal link between endogenous rhythms and interpersonal synchrony in a music performance task, which places high demands on temporal coordination. We first establish that endogenous rhythms, measured by spontaneous rates of individual performance, are stable within individuals across stimulus materials, limb movements, and time points. We then test a causal link between endogenous rhythms and interpersonal synchrony by pairing each musician with a partner who is either matched or mismatched in spontaneous rate and by measuring their joint behavior up to 1 year later. Partners performed melodies together, using either the same or different hands. Partners who were matched for spontaneous rate showed greater interpersonal synchrony in joint performance than mismatched partners, regardless of hand used. Endogenous rhythms offer potential to predict optimal group membership in joint behaviors that require temporal coordination.

  5. Possibilistic Petri nets.

    PubMed

    Cardoso, J; Valette, R; Dubois, D

    1999-01-01

    This paper presents the possibilistic Petri net model which combines possibility logic with Petri nets with objects. The main feature of this model is to allow one to reason about the aspects of uncertainty and change in dynamic discrete event systems. The paper presents relevant concepts of Petri nets with objects and possibility logic and how imprecision and vagueness are introduced in the marking of a Petri net with objects. The marking of a net is imprecise, or in a more general way, fuzzy, in order to represent an ill-known knowledge about a system state. A new marking updating according to the fuzzy marking such defined is also discussed. An example of shop door monitoring is presented that illustrates our approach.

  6. A NET Outcome

    PubMed Central

    Lu, Thea; Kobayashi, Scott D.; Quinn, Mark T.; DeLeo, Frank R.

    2012-01-01

    Neutrophils constitute a critical part of innate immunity and are well known for their ability to phagocytose and kill invading microorganisms. The microbicidal processes employed by neutrophils are highly effective at killing most ingested bacteria and fungi. However, an alternative non-phagocytic antimicrobial mechanism of neutrophils has been proposed whereby microorganisms are eliminated by neutrophil extracellular traps (NETs). NETs are comprised of DNA, histones, and antimicrobial proteins extruded by neutrophils during NETosis, a cell death pathway reported to be distinct from apoptosis, phagocytosis-induced cell death, and necrosis. Although multiple laboratories have reported NETs using various stimuli in vitro, the molecular mechanisms involved in this process have yet to be definitively elucidated, and many questions regarding the formation and putative role or function of NETs in innate host defense remain unanswered. It is with these questions in mind that we provide some reflection and perspective on NETs and NETosis. PMID:23227026

  7. Environment and phenology: CO2 net ecosystem exchange and CO2 flux partitioning at an acid and oligotrophic mire system in northern Sweden

    NASA Astrophysics Data System (ADS)

    Gažovič, Michal; Peichl, Matthias; Vermeij, Ilse; Limpens, Juul; Nilsson, Mats. B.

    2015-04-01

    Static chamber and environmental measurements in combination with vegetation indices (i.e. vascular green area (VGA) and the greenness chromatic color index (gcc) derived from digital camera images) were used to investigate effects of environment and phenology on the CO2 net ecosystem exchange (NEE) and CO2 flux partitioning at the Degerö Stormyr site in northern Sweden (64°11' 23.565" N, 19°33' 55.291 E) during two environmentally different years. Our measurement design included a control plot, a moss plot (where vascular plants were removed by clipping) and four heterotrophic respiration (RH) collars (where all green moss and vascular plant biomass were removed) to partition between soil heterotrophic and plant autotrophic (moss and vascular plants) respiration (RA), as well as between moss and vascular plant gross primary production (GPP). Environmental conditions, especially the shallow snow cover, peat soil frost and cold spring in 2014 caused delayed onset of spring green up, reduced soil respiration flux and reduced GPP of vascular plants. Soil temperature measured in 26 cm depth started to rise from spring temperatures of ~ 0.6 °C in 2013 and 0.15 °C in 2014 about 20 days earlier in 2013 compared to 2014. With earlier onset of the growing season and higher soil temperatures in 2013, heterotrophic soil respiration was higher in year 2013 than in year 2014. In 2013, RH dominated the total ecosystem respiration in all months but June and August. On contrary, autotrophic respiration dominated ecosystem respiration in all months of 2014. In both years, vascular plants and mosses were more or less equally contributing to autotrophic respiration. We measured higher GPP in year 2013 compared to year 2014. Also VGA and gcc were higher in spring and throughout the rest of 2013 compared to 2014. The onset of VGA was delayed by ~ 10 days in 2014. In general, total GPP was dominated by GPP of vascular plants in both years, although moss GPP had substantial

  8. Nematode endogenous small RNA pathways

    PubMed Central

    Hoogstrate, Suzanne W; Volkers, Rita JM; Sterken, Mark G; Kammenga, Jan E; Snoek, L Basten

    2014-01-01

    The discovery of small RNA silencing pathways has greatly extended our knowledge of gene regulation. Small RNAs have been presumed to play a role in every field of biology because they affect many biological processes via regulation of gene expression and chromatin remodeling. Most well-known examples of affected processes are development, fertility, and maintenance of genome stability. Here we review the role of the three main endogenous small RNA silencing pathways in Caenorhabditis elegans: microRNAs, endogenous small interfering RNAs, and PIWI-interacting RNAs. After providing an entry-level overview on how these pathways function, we discuss research on other nematode species providing insight into the evolution of these small RNA pathways. In understanding the differences between the endogenous small RNA pathways and their evolution, a more comprehensive picture is formed of the functions and effects of small RNAs. PMID:25340013

  9. Quantitative analysis of endogenous compounds.

    PubMed

    Thakare, Rhishikesh; Chhonker, Yashpal S; Gautam, Nagsen; Alamoudi, Jawaher Abdullah; Alnouti, Yazen

    2016-09-05

    Accurate quantitative analysis of endogenous analytes is essential for several clinical and non-clinical applications. LC-MS/MS is the technique of choice for quantitative analyses. Absolute quantification by LC/MS requires preparing standard curves in the same matrix as the study samples so that the matrix effect and the extraction efficiency for analytes are the same in both the standard and study samples. However, by definition, analyte-free biological matrices do not exist for endogenous compounds. To address the lack of blank matrices for the quantification of endogenous compounds by LC-MS/MS, four approaches are used including the standard addition, the background subtraction, the surrogate matrix, and the surrogate analyte methods. This review article presents an overview these approaches, cite and summarize their applications, and compare their advantages and disadvantages. In addition, we discuss in details, validation requirements and compatibility with FDA guidelines to ensure method reliability in quantifying endogenous compounds. The standard addition, background subtraction, and the surrogate analyte approaches allow the use of the same matrix for the calibration curve as the one to be analyzed in the test samples. However, in the surrogate matrix approach, various matrices such as artificial, stripped, and neat matrices are used as surrogate matrices for the actual matrix of study samples. For the surrogate analyte approach, it is required to demonstrate similarity in matrix effect and recovery between surrogate and authentic endogenous analytes. Similarly, for the surrogate matrix approach, it is required to demonstrate similar matrix effect and extraction recovery in both the surrogate and original matrices. All these methods represent indirect approaches to quantify endogenous compounds and regardless of what approach is followed, it has to be shown that none of the validation criteria have been compromised due to the indirect analyses.

  10. Net Flux of Amino Acids Across the Portal-drained Viscera and Liver of the Ewe During Abomasal Infusion of Protein and Glucose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Decreasing the fraction of amino acids metabolized by the mucosal cells may increase the fraction of AA being released into the blood. A potential mechanism to reduce AA catabolism by mucosal cells is to provide an alternative source of energy. We hypothesized that increasing glucose flow to the s...

  11. A population of endogenous pararetrovirus genomes in carrizo citrange

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The complete genomes of three related endogenous pararetroviruses (EPRVs) were obtained by 454 sequencing of nucleic acid extracts from ‘Carrizo’citrange, used as a citrus rootstock. Numerous homologous sequences have been found in the sweet orange genome. The new EPRVs are most closely related to...

  12. Apparent posttranscriptional block to anaerobic induction of endogenous leukemia virus.

    PubMed Central

    Whitaker-Dowling, P A; Marotti, K R; Anderson, G R

    1979-01-01

    Uninfected Fischer rat cells were induced by anaerobic stress to transcribe high levels of endogenous type C leukemia virus RNA. Complete 35S virus RNA with attached polyadenylic acid sequences was found associated with polysomes, indicating functional mRNA. Since no mature virus was released under these conditions, the presence of a posttranscriptional block to complete virus synthesis is strongly indicated. PMID:232174

  13. Getting to Net Zero

    SciTech Connect

    2016-09-01

    The technology necessary to build net zero energy buildings (NZEBs) is ready and available today, however, building to net zero energy performance levels can be challenging. Energy efficiency measures, onsite energy generation resources, load matching and grid interaction, climatic factors, and local policies vary from location to location and require unique methods of constructing NZEBs. It is recommended that Components start looking into how to construct and operate NZEBs now as there is a learning curve to net zero construction and FY 2020 is just around the corner.

  14. SpawnNet

    SciTech Connect

    2014-12-23

    SpawnNet provides a networking interface similar to Linux sockets that runs natively on High-performance network interfaces. It is intended to be used to bootstrap parallel jobs and communication libraries like MPI.

  15. TrialNet

    MedlinePlus

    ... If you have T1D in your family, your participation can be the difference. A simple blood test ... through a TrialNet screening and explains how their participation can make a difference in type 1 diabetes ...

  16. NetState

    SciTech Connect

    Durgin, Nancy; Mai, Yuqing; Hutchins, James

    2005-09-01

    NetState is a distributed network monitoring system. It uses passive sensors to develop status information on a target network. Two major features provided by NetState are version and port tracking. Version tracking maintains information about software and operating systems versions. Port tracking identifies information about active TOP and UDP ports. Multiple NetState sniffers can be deployed, one at each entry point of the target network. The sniffers monitor network traffic, then send the information to the NetState server. The information is stored in centralized database which can then be accessed via standard SQL database queries or this web-based GUI, for further analysis and display.

  17. NASA's Software Bank (NETS)

    NASA Technical Reports Server (NTRS)

    1992-01-01

    NETS (A Neural Network Development Tool) is a software system for mimicking the human brain. It is used in a University of Arkansas project in pattern matching of chemical systems. If successful, chemists would be able to identify mixtures of compounds without long and costly separation procedures. Using NETS, the group has trained the computer to recognize pattern relationships in a known compound and associate the results to an unknown compound. The research appears to be promising.

  18. TideNet

    DTIC Science & Technology

    2014-10-27

    mapping tools to query sources of tide data in a desired geographic region of the U.S. and its territories. Users can select a tide data source...produce tables and figures, and prepare input files for numerical models used in USACE projects. TideNet can fetch tide data, including plots and...tables from the source, or process tide data downloaded from any source site to perform additional analyses. The home page of the TideNet map in

  19. WaveNet

    DTIC Science & Technology

    2014-10-27

    Studies (WIS), Coastal Data Information Program (CDIP), Great Lakes Observing System (GLOS), Great Lakes Coastal Forecasting System (GLCFS), and...Army Engineer Research and Development Center,CIRP - The Coastal Inlets Research Program,3909 Halls Ferry Road,Vicksburg,MS,39180 8. PERFORMING... Coastal Inlets Research Program WaveNet WaveNet is a web-based, Graphical-User-Interface (GUI) data management tool developed for the Corps’ coastal

  20. WetNet operations

    NASA Technical Reports Server (NTRS)

    Goodman, H. Michael; Smith, Matt; Lafontaine, Vada; Lafontaine, Frank; Moss, Don

    1991-01-01

    WetNet is an interdisciplinary Earth science data analysis and research project with an emphasis on the study of the global hydrological cycle. The project goals are to facilitate scientific discussion, collaboration, and interaction among a selected group of investigators by providing data access and data analysis software on a personal computer. The WetNet system fulfills some of the functionality of a prototype Product Generation System (PGS), Data Archive and Distribution System (DADS), and Information Management System for the Distributed Active Archive Center. The PGS functionality is satisfied in WetNet by processing the Special Sensor Microwave/Imager (SSM/I) data into a standard format (McIDAS) data sets and generating geophysical parameter Level II browse data sets. The DADS functionality is fulfilled when the data sets are archived on magneto optical cartridges and distributed to the WetNet investigators. The WetNet data sets on the magneto optical cartridges contain the complete WetNet processing, catalogue, and menu software in addition to SSM/I orbit data for the respective two week time period.

  1. Endogenous opiates and behavior: 2014.

    PubMed

    Bodnar, Richard J

    2016-01-01

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

  2. [Memory processes in endogenous depression].

    PubMed

    Radziwiłłowicz, W; Radziwiłłowicz, P

    1998-01-01

    The thesis aims to answer the questions about the profile of mental ability in endogenous depression and to decide whether self-estimation of depressive symptoms influences the results achieved by patients in memory tests. Fifty six patients suffering from endogenous depression have been examined. The following methods have been applied: Mini Mental State Examination, Benton Visual Retention Test, Beck Depression Inventory, hold tests: Vocabulary, Information, Comprehension and Digit Span of Wechsler Adult Intelligence Scale (WAIS), Rey-Osterrieth Complex Figure, Auditory Verbal Learning Test, DCS Weidlich. General status of cognitive functions correlates with the profile of specific kinds of memory results, particularly with delayed memory. Self-estimation of depressive symptoms intensity is mostly influenced by memory capacity, visuomotorial factor, functions of perception and lingual factor. High correlation between verbal and non verbal learning shows uniform influence of depression on the process of learning.

  3. Endogenous Interleukin-1β in Neuropathic Rats Enhances Glutamate Release from the Primary Afferents in the Spinal Dorsal Horn through Coupling with Presynaptic N-Methyl-d-aspartic Acid Receptors*♦

    PubMed Central

    Yan, Xisheng; Weng, Han-Rong

    2013-01-01

    Excessive activation of glutamate receptors and overproduction of proinflammatory cytokines, including interleukin-1β (IL-1β) in the spinal dorsal horn, are key mechanisms underlying the development and maintenance of neuropathic pain. In this study, we investigated the mechanisms by which endogenous IL-1β alters glutamatergic synaptic transmission in the spinal dorsal horn in rats with neuropathic pain induced by ligation of the L5 spinal nerve. We demonstrated that endogenous IL-1β in neuropathic rats enhances glutamate release from the primary afferent terminals and non-NMDA glutamate receptor activities in postsynaptic neurons in the spinal dorsal horn. Myeloid differentiation primary response protein 88 (MyD88) is a mediator used by IL-1β to enhance non-NMDA glutamate receptor activities in postsynaptic neurons in the spinal dorsal horn. Presynaptic NMDA receptors are effector receptors used by the endogenous IL-1β to enhance glutamate release from the primary afferents in neuropathic rats. This is further supported by the fact that NMDA currents recorded from small neurons in the dorsal root ganglion of normal rats are potentiated by exogenous IL-1β. Furthermore, we provided evidence that functional coupling between IL-1β receptors and presynaptic NMDA receptors at the primary afferent terminals is mediated by the neutral sphingomyelinase/ceramide signaling pathway. Hence, functional coupling between IL-1β receptors and presynaptic NMDA receptors at the primary afferent terminals is a crucial mechanism leading to enhanced glutamate release and activation of non-NMDA receptors in the spinal dorsal horn neurons in neuropathic pain conditions. Interruption of such functional coupling could be an effective approach for the treatment of neuropathic pain. PMID:24003233

  4. WhaleNet/environet

    SciTech Connect

    Williamson, J.M.

    1994-12-31

    WhaleNet has established a network where students, educators, and scientists can interact and share data for use in interdisciplinary curricular and student research activities in classrooms around the world by utilizing telecommunication. This program enables students to participate in marine/whale research programs in real-time with WhaleNet data and supplementary curriculum materials regardless of their geographic location. Systems have been established with research organizations and whale watch companies whereby research data is posted by scientists and students participating in whale watches on the WhaleNet bulletin board and shared with participating classrooms. WhaleNet presently has contacts with classrooms across the nation, and with research groups, whale watch organizations, science museums, and universities from Alaska to North Carolina, Hawaii to Maine, and Belize to Norway. WhaleNet has plans to make existing whale and fisheries research databases available for classroom use and to have research data from satellite tagging programs on various species of whales available for classroom access in real-time.

  5. Endogenous endophthalmitis caused by Citrobacter koseri.

    PubMed

    Chiu, Chun-Hsiang; Peng, Ming-Yieh; Wang, Ying-Chuan; Chang, Feng-Yee

    2009-12-01

    Endogenous endophthalmitis occurs when organisms are hematogenously disseminated in to the eye from a distant focus of infection. The most common isolated organisms that cause endogenous endophthalmitis are Klebsiella pneumoniae and Escherichia coli. Previous reports on endophthalmitis caused by Citrobacter species are limited. We present the first case of endogenous endophthalmitis caused by Citrobacter koseri bacteremia and renal abscesses.

  6. The acid-ash hypothesis revisited: a reassessment of the impact of dietary acidity on bone.

    PubMed

    Nicoll, Rachel; McLaren Howard, John

    2014-09-01

    The acid-ash hypothesis states that when there are excess blood protons, bone is eroded to provide alkali to buffer the net acidity and maintain physiologic pH. There is concern that with the typical Western diet, we are permanently in a state of net endogenous acid production, which is gradually reducing bone. While it is clear that a high acid-producing diet generates increased urinary acid and calcium excretion, the effect of diet does not always have the expected results on BMD, fracture risk and markers of bone formation and resorption, suggesting that other factors are influencing the effect of acid/alkali loading on bone. High dietary protein, sodium and phosphorus intake, all of which are necessary for bone formation, were thought to be net acid forming and contribute to low BMD and fracture risk, but appear under certain conditions to be beneficial, with the effect of protein being driven by calcium repletion. Dietary salt can increase short-term markers of bone resorption but may also trigger 1,25(OH)2D synthesis to increase calcium absorption; with low calcium intake, salt intake may be inversely correlated with BMD but with high calcium intake, salt intake was positively correlated with BMD. With respect to the effect of phosphorus, the data are conflicting. Inclusion of an analysis of calcium intake may help to reconcile the contradictory results seen in many of the studies of bone. The acid-ash hypothesis could, therefore, be amended to state that with an acid-producing diet and low calcium intake, bone is eroded to provide alkali to buffer excess protons but where calcium intake is high the acid-producing diet may be protective.

  7. Net Zero Water Update

    DTIC Science & Technology

    2011-05-12

    Windturbine at McKinney, Texas store • Leadership in Net Zero Water (Seattle, WA): net- zero office building - Cascadia Center for Sustainable Design and... concepts are not new and they work! • In many industries and government organizations, sustainability practices are becoming the norm rather than...Zero – General • http://www.asaie.army.mil/Public/IE/ • http://www.army.mil/standto/archive/2011/01/31/ • http://www.nrel.gov/docs/fy06osti/39833.pdf

  8. NET23/STING promotes chromatin compaction from the nuclear envelope.

    PubMed

    Malik, Poonam; Zuleger, Nikolaj; de las Heras, Jose I; Saiz-Ros, Natalia; Makarov, Alexandr A; Lazou, Vassiliki; Meinke, Peter; Waterfall, Martin; Kelly, David A; Schirmer, Eric C

    2014-01-01

    Changes in the peripheral distribution and amount of condensed chromatin are observed in a number of diseases linked to mutations in the lamin A protein of the nuclear envelope. We postulated that lamin A interactions with nuclear envelope transmembrane proteins (NETs) that affect chromatin structure might be altered in these diseases and so screened thirty-one NETs for those that promote chromatin compaction as determined by an increase in the number of chromatin clusters of high pixel intensity. One of these, NET23 (also called STING, MITA, MPYS, ERIS, Tmem173), strongly promoted chromatin compaction. A correlation between chromatin compaction and endogenous levels of NET23/STING was observed for a number of human cell lines, suggesting that NET23/STING may contribute generally to chromatin condensation. NET23/STING has separately been found to be involved in innate immune response signaling. Upon infection cells make a choice to either apoptose or to alter chromatin architecture to support focused expression of interferon genes and other response factors. We postulate that the chromatin compaction induced by NET23/STING may contribute to this choice because the cells expressing NET23/STING eventually apoptose, but the chromatin compaction effect is separate from this as the condensation was still observed when cells were treated with Z-VAD to block apoptosis. NET23/STING-induced compacted chromatin revealed changes in epigenetic marks including changes in histone methylation and acetylation. This indicates a previously uncharacterized nuclear role for NET23/STING potentially in both innate immune signaling and general chromatin architecture.

  9. NET23/STING Promotes Chromatin Compaction from the Nuclear Envelope

    PubMed Central

    de las Heras, Jose I.; Saiz-Ros, Natalia; Makarov, Alexandr A.; Lazou, Vassiliki; Meinke, Peter; Waterfall, Martin; Kelly, David A.; Schirmer, Eric C.

    2014-01-01

    Changes in the peripheral distribution and amount of condensed chromatin are observed in a number of diseases linked to mutations in the lamin A protein of the nuclear envelope. We postulated that lamin A interactions with nuclear envelope transmembrane proteins (NETs) that affect chromatin structure might be altered in these diseases and so screened thirty-one NETs for those that promote chromatin compaction as determined by an increase in the number of chromatin clusters of high pixel intensity. One of these, NET23 (also called STING, MITA, MPYS, ERIS, Tmem173), strongly promoted chromatin compaction. A correlation between chromatin compaction and endogenous levels of NET23/STING was observed for a number of human cell lines, suggesting that NET23/STING may contribute generally to chromatin condensation. NET23/STING has separately been found to be involved in innate immune response signaling. Upon infection cells make a choice to either apoptose or to alter chromatin architecture to support focused expression of interferon genes and other response factors. We postulate that the chromatin compaction induced by NET23/STING may contribute to this choice because the cells expressing NET23/STING eventually apoptose, but the chromatin compaction effect is separate from this as the condensation was still observed when cells were treated with Z-VAD to block apoptosis. NET23/STING-induced compacted chromatin revealed changes in epigenetic marks including changes in histone methylation and acetylation. This indicates a previously uncharacterized nuclear role for NET23/STING potentially in both innate immune signaling and general chromatin architecture. PMID:25386906

  10. Game Theory .net.

    ERIC Educational Resources Information Center

    Shor, Mikhael

    2003-01-01

    States making game theory relevant and accessible to students is challenging. Describes the primary goal of GameTheory.net is to provide interactive teaching tools. Indicates the site strives to unite educators from economics, political and computer science, and ecology by providing a repository of lecture notes and tests for courses using…

  11. MASTER Net: optical transients

    NASA Astrophysics Data System (ADS)

    Gress, O.; Shumkov, V.; Pogrosheva, T.; Shurpakov, S.; Lipunov, V.; Buckley, D.; Lopez, R. Rebolo; Ricart, M. Serra; Podesta, R.; Levato, H. O.; Gorbovskoy, E.; Tiurina, N.; Balanutsa, P.; Kuznetsov, A.; Chazov, V.; Kornilov, V.; Ivanov, K.; Vladimirov, V.; Potter, S.; Lopez, C.; Podesta, F.; Saffe, C.

    2016-10-01

    MASTER-SAAO auto-detection system ( Lipunov et al., "MASTER Global Robotic Net", Advances in Astronomy, 2010, 30L ) discovered OT source at (RA, Dec) = 14h 38m 49.60s -44d 37m 24.5s on 2016-10-01.73438 UT with unfiltered m_OT=16.4m (mlim=19.7m).

  12. Nonmetro Net Outmigration Stops.

    ERIC Educational Resources Information Center

    Cromartie, John B.

    1992-01-01

    Annual population losses from net migration for nonmetro areas declined from 0.38-0.20 percent during the period of 1988-91. However, annual inmigration and outmigration flows were consistently above 1.5 million (about 3 percent of nonmetro population). During the three-year period, nonmetro areas consistently lost young adults and those with…

  13. Conjugate Silhouette Nets

    DTIC Science & Technology

    2000-01-01

    19) dv vEI 2 . Calling these curves the projective hodographs of p and q respectively, we can state Corollary. The Laplace transforms of a conjugate...silhouette net £ are the projective hodographs of the generating curves C1, C2 of L (considered as a projective translation surface). §3. Axial

  14. Mobile robot sense net

    NASA Astrophysics Data System (ADS)

    Konolige, Kurt G.; Gutmann, Steffen; Guzzoni, Didier; Ficklin, Robert W.; Nicewarner, Keith E.

    1999-08-01

    Mobile robot hardware and software is developing to the point where interesting applications for groups of such robots can be contemplated. We envision a set of mobots acting to map and perform surveillance or other task within an indoor environment (the Sense Net). A typical application of the Sense Net would be to detect survivors in buildings damaged by earthquake or other disaster, where human searchers would be put a risk. As a team, the Sense Net could reconnoiter a set of buildings faster, more reliably, and more comprehensibly than an individual mobot. The team, for example, could dynamically form subteams to perform task that cannot be done by individual robots, such as measuring the range to a distant object by forming a long baseline stereo sensor form a pari of mobots. In addition, the team could automatically reconfigure itself to handle contingencies such as disabled mobots. This paper is a report of our current progress in developing the Sense Net, after the first year of a two-year project. In our approach, each mobot has sufficient autonomy to perform several tasks, such as mapping unknown areas, navigating to specific positions, and detecting, tracking, characterizing, and classifying human and vehicular activity. We detail how some of these tasks are accomplished, and how the mobot group is tasked.

  15. Endogenous Zinc in Neurological Diseases

    PubMed Central

    2005-01-01

    The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized. PMID:20396459

  16. Endogenous fertility, mortality and growth.

    PubMed

    Blackburn, K; Cipriani, G P

    1998-01-01

    This paper presents a model that illustrates the joint determination of population and development. "Economic and demographic outcomes are determined jointly in a choice-theoretic model of fertility, mortality and capital accumulation.... In addition to choosing savings and births, parents may reduce (infant) deaths by incurring expenditures on health-care which is also provided by the government. A generalised production technology accounts for long-run endogenous growth with short-run transitional dynamics. The analysis yields testable time series and cross-section implications which accord with the empirical evidence on the relationship between demography and development."

  17. Endogenous Inhibitors of Kidney Inflammation

    PubMed Central

    Trostel, Jessica; Garcia, Gabriela E.

    2015-01-01

    Although inflammation is the physiological response to pathogen invasion and tissue damage, it can also be responsible for significant tissue damage. Therefore, the inflammatory response must be carefully regulated to prevent critical inflammatory damage to vital organs. Typically, local endogenous regulatory mechanisms adjust the magnitude of the response such that the injurious condition is resolved and homeostasis is mantained. Humoral mechanisms that restrain or inhibit inflammation include glucocorticoid hormones, anti-inflammatory cytokines such as IL-10 and transforming growth factor-β (TGF-β), and soluble cytokine receptors; other mediators facilitate tissue healing, like lipoxins and resolvins. There is growing evidence that inflammation plays a critical role in the development and progression of heart disease, cancer, stroke, diabetes, kidney diseases, sepsis, and several fibroproliferative disorders. Consequently, understanding the mechanisms that regulate inflammation may offer therapeutic targets for inhibiting the progression of several diseases. In this article, we review the significance of several novel endogenous anti-inflammatory mediators in the protection from kidney injury and the potential of these regulatory molecules as therapeutic targets for treatment of kidney inflammatory diseases. PMID:26779569

  18. Human endogenous retroviruses and cancer

    PubMed Central

    Gonzalez-Cao, María; Iduma, Paola; Karachaliou, Niki; Santarpia, Mariacarmela; Blanco, Julià; Rosell, Rafael

    2016-01-01

    Human endogenous retroviruses (HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K (HML6) and HERV-K (HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K (HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are two-edged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors. PMID:28154780

  19. Endogeneity in prison risk classification.

    PubMed

    Shermer, Lauren O'Neill; Bierie, David M; Stock, Amber

    2013-10-01

    Security designation tools are a key feature of all prisons in the United States, intended as objective measures of risk that funnel inmates into security levels-to prison environments varying in degree of intrusiveness, restriction, dangerousness, and cost. These tools are mostly (if not all) validated by measuring inmates on a set of characteristics, using scores from summations of that information to assign inmates to prisons of varying security level, and then observing whether inmates assumed more risky did in fact offend more. That approach leaves open the possibility of endogeneity--that the harsher prisons are themselves bringing about higher misconduct and thus biasing coefficients assessing individual risk. The current study assesses this potential bias by following an entry cohort of inmates to more than 100 facilities in the Federal Bureau of Prisons (BOP) and exploiting the substantial variation in classification scores within a given prison that derive from systematic overrides of security-level designations for reasons not associated with risk of misconduct. By estimating pooled models of misconduct along with prison-fixed effects specifications, the data show that a portion of the predictive accuracy thought associated with the risk-designation tool used in BOP was a function of facility-level contamination (endogeneity).

  20. HMGB1: Endogenous Danger Signaling

    PubMed Central

    Klune, John R; Dhupar, Rajeev; Cardinal, Jon; Billiar, Timothy R; Tsung, Allan

    2008-01-01

    While foreign pathogens and their products have long been known to activate the innate immune system, the recent recognition of a group of endogenous molecules that serve a similar function has provided a framework for understanding the overlap between the inflammatory responses activated by pathogens and injury. These endogenous molecules, termed alarmins, are normal cell constituents that can be released into the extracellular milieu during states of cellular stress or damage and subsequently activate the immune system. One nuclear protein, High mobility group box-1 (HMGB1), has received particular attention as fulfilling the functions of an alarmin by being involved in both infectious and non-infectious inflammatory conditions. Once released, HMGB1 signals through various receptors to activate immune cells involved in the immune process. Although initial studies demonstrated HMGB1 as a late mediator of sepsis, recent findings indicate HMGB1 to have an important role in models of non-infectious inflammation, such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. Furthermore, in contrast to its pro-inflammatory functions, there is evidence that HMGB1 also has restorative effects leading to tissue repair and regeneration. The complex functions of HMGB1 as an archetypical alarmin are outlined here to review our current understanding of a molecule that holds the potential for treatment in many important human conditions. PMID:18431461

  1. Endogenous Opiates and Behavior: 2006

    PubMed Central

    Bodnar, Richard J.

    2009-01-01

    This paper is the twenty-ninth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning thirty years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:17949854

  2. Endogenous retroviruses in domestic animals.

    PubMed

    Garcia-Etxebarria, Koldo; Sistiaga-Poveda, Maialen; Jugo, Begoña Marina

    2014-08-01

    Endogenous retroviruses (ERVs) are genomic elements that are present in a wide range of vertebrates. Although the study of ERVs has been carried out mainly in humans and model organisms, recently, domestic animals have become important, and some species have begun to be analyzed to gain further insight into ERVs. Due to the availability of complete genomes and the development of new computer tools, ERVs can now be analyzed from a genome-wide viewpoint. In addition, more experimental work is being carried out to analyze the distribution, expression and interplay of ERVs within a host genome. Cats, cattle, chicken, dogs, horses, pigs and sheep have been scrutinized in this manner, all of which are interesting species in health and economic terms. Furthermore, several studies have noted differences in the number of endogenous retroviruses and in the variability of these elements among different breeds, as well as their expression in different tissues and the effects of their locations, which, in some cases, are near genes. These findings suggest a complex, intriguing relationship between ERVs and host genomes. In this review, we summarize the most important in silico and experimental findings, discuss their implications and attempt to predict future directions for the study of these genomic elements.

  3. NetB and necrotic enteritis: the hole movable story.

    PubMed

    Rood, Julian I; Keyburn, Anthony L; Moore, Robert J

    2016-06-01

    Clostridium perfringens is the primary causative agent of avian necrotic enteritis. Our understanding of the pathogenesis of this economically important disease has been enhanced by the discovery of C. perfringens NetB toxin, which belongs to the α-haemolysin family of β-pore-forming toxins. In a chicken disease model, the analysis of an isogenic set of strains comprising the wild type, a netB mutant, and its complemented derivative, fulfilled molecular Koch's postulates and revealed that NetB was essential for disease. These results were consistent with epidemiological surveys, which generally found that there was a higher prevalence of netB carriage in C. perfringens isolates from diseased poultry compared to healthy birds. The netB gene has been shown to be located on large conjugative plasmids that are closely related to other toxin plasmids from C. perfringens, which has potential implications for the epidemiology of necrotic enteritis infections. The crystal structures of both monomeric NetB and the heptameric NetB pore have been determined, the latter revealed a central pore diameter of approximately 26 Å. Finally, it has been shown that vaccine preparations that include NetB can protect chickens against disease and a series of single amino acid substitution derivatives of NetB that have potential value for vaccine formulations have been isolated and analysed. It is likely that NetB will be an important antigen to include in an effective, commercially viable, necrotic enteritis vaccine.

  4. Lower vegetable protein intake and higher dietary acid load associated with lower carbohydrate intake are risk factors for metabolic syndrome in patients with type 2 diabetes: Post-hoc analysis of a cross-sectional study

    PubMed Central

    Iwase, Hiroya; Tanaka, Muhei; Kobayashi, Yukiko; Wada, Sayori; Kuwahata, Masashi; Kido, Yasuhiro; Hamaguchi, Masahide; Asano, Mai; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto; Fukui, Michiaki

    2015-01-01

    Aims/Introduction A low-carbohydrate diet based on animal sources is associated with higher all-cause mortality, whereas a vegetable-based low-carbohydrate diet is associated with lower cardiovascular disease mortality. It has been suggested that acid/base imbalance might play an important role in some cardiometabolic abnormalities. The aims of the present study were to evaluate whether carbohydrate intake is associated with quality of dietary protein and acid load, and whether these are related to metabolic syndrome in patients with type 2 diabetes. Materials and Methods The present cross-sectional study involved 149 patients with type 2 diabetes. Dietary intake was assessed using a validated self-administered diet history questionnaire. Dietary acid load was assessed by potential renal acid load and net endogenous acid production. Results Mean daily total energy intake, carbohydrate intake, animal protein intake and vegetable protein intake were 1821.5 kcal, 248.8 g, 36.1 g and 31.1 g, respectively. Carbohydrate energy/total energy was negatively correlated with animal protein energy/total energy, potential renal acid load or net endogenous acid production score, and was positively correlated with vegetable protein energy/total energy. Logistic regression analyses showed that the subgroup of patients with a lower vegetable protein energy/total energy or higher potential renal acid load or net endogenous acid production score was significantly associated with the prevalence of metabolic syndrome. Conclusions The present study showed that carbohydrate intake was associated with the quality of dietary protein and dietary acid load. Furthermore, decreased vegetable protein intake and increased dietary acid load were associated with the prevalence of metabolic syndrome. PMID:26221526

  5. Quantum Neural Nets

    NASA Technical Reports Server (NTRS)

    Zak, Michail; Williams, Colin P.

    1997-01-01

    The capacity of classical neurocomputers is limited by the number of classical degrees of freedom which is roughly proportional to the size of the computer. By Contrast, a Hypothetical quantum neurocomputer can implement an exponentially large number of the degrees of freedom within the same size. In this paper an attempt is made to reconcile linear reversible structure of quantum evolution with nonlinear irreversible dynamics for neural nets.

  6. WaveNet

    DTIC Science & Technology

    2015-10-30

    modeling and planning missions which require metocean data ( winds , waves, tides, water levels). It allows users to access, process, and analyze wave...and wind data from different data sources (Figure 1), and provides a combination of analysis and graphical capabilities to minimize the complexity and...employs techniques to minimize complexity and uncertainty of data processing. WaveNet is a decision-support tool that provides wave and wind data

  7. Characteristics of injury and recovery of net NO3- transport of barley seedlings from treatments of NaCl

    NASA Technical Reports Server (NTRS)

    Klobus, G.; Ward, M. R.; Huffaker, R. C.

    1988-01-01

    The nature of the injury and recovery of nitrate uptake (net uptake) from NaCl stress in young barley (Hordeum vulgare L, var CM 72) seedlings was investigated. Nitrate uptake was inhibited rapidly by NaCl, within 1 minute after exposure to 200 millimolar NaCl. The duration of exposure to saline conditions determined the time of recovery of NO3- uptake from NaCl stress. Recovery was dependent on the presence of NO3- and was inhibited by cycloheximide, 6-methylpurine, and cerulenin, respective inhibitors of protein, RNA, and sterol/fatty acid synthesis. These inhibitors also prevented the induction of the NO3- uptake system in uninduced seedlings. Uninduced seedlings exhibited endogenous NO3- transport activity that appeared to be constitutive. This constitutive activity was also inhibited by NaCl. Recovery of constitutive NO3- uptake did not require the presence of NO3-.

  8. Horizontal ichthyoplankton tow-net system with unobstructed net opening

    USGS Publications Warehouse

    Nester, Robert T.

    1987-01-01

    The larval fish sampler described here consists of a modified bridle, frame, and net system with an obstruction-free net opening and is small enough for use on boats 10 m or less in length. The tow net features a square net frame attached to a 0.5-m-diameter cylinder-on-cone plankton net with a bridle designed to eliminate all obstructions forward of the net opening, significantly reducing currents and vibrations in the water directly preceding the net. This system was effective in collecting larvae representing more than 25 species of fish at sampling depths ranging from surface to 10 m and could easily be used at greater depths.

  9. Annotating WordNet

    DTIC Science & Technology

    2004-01-01

    the subject of long de- bate (see the Hanks and Kilgarriff papers for two recent contributions). These are topics in need of serious con- sideration...classic example, its unrelated senses being “river bank” and “financial institution.” WordNet does not make a distinction between homonymy and polysemy ...Prescribed by ANSI Std Z39-18 a manual sense-tagging system, and it is these we will concentrate on here. The difficulties inherent in the sense

  10. Helminth.net: expansions to Nematode.net and an introduction to Trematode.net.

    PubMed

    Martin, John; Rosa, Bruce A; Ozersky, Philip; Hallsworth-Pepin, Kymberlie; Zhang, Xu; Bhonagiri-Palsikar, Veena; Tyagi, Rahul; Wang, Qi; Choi, Young-Jun; Gao, Xin; McNulty, Samantha N; Brindley, Paul J; Mitreva, Makedonka

    2015-01-01

    Helminth.net (http://www.helminth.net) is the new moniker for a collection of databases: Nematode.net and Trematode.net. Within this collection we provide services and resources for parasitic roundworms (nematodes) and flatworms (trematodes), collectively known as helminths. For over a decade we have provided resources for studying nematodes via our veteran site Nematode.net (http://nematode.net). In this article, (i) we provide an update on the expansions of Nematode.net that hosts omics data from 84 species and provides advanced search tools to the broad scientific community so that data can be mined in a useful and user-friendly manner and (ii) we introduce Trematode.net, a site dedicated to the dissemination of data from flukes, flatworm parasites of the class Trematoda, phylum Platyhelminthes. Trematode.net is an independent component of Helminth.net and currently hosts data from 16 species, with information ranging from genomic, functional genomic data, enzymatic pathway utilization to microbiome changes associated with helminth infections. The databases' interface, with a sophisticated query engine as a backbone, is intended to allow users to search for multi-factorial combinations of species' omics properties. This report describes updates to Nematode.net since its last description in NAR, 2012, and also introduces and presents its new sibling site, Trematode.net.

  11. Erbium-doped yttrium aluminium garnet ablative laser treatment for endogenous ochronosis.

    PubMed

    Chaptini, Cassandra; Huilgol, Shyamala C

    2015-08-01

    Ochronosis is a rare disease characterised clinically by bluish-grey skin discolouration and histologically by yellow-brown pigment deposits in the dermis. It occurs in endogenous and exogenous forms. Endogenous ochronosis, also known as alkaptonuria, is an autosomal recessive disease of tyrosine metabolism, resulting in the accumulation and deposition of homogentisic acid in connective tissue. We report a case of facial endogenous ochronosis and coexistent photodamage, which was successfully treated with erbium-doped yttrium aluminium garnet laser resurfacing and deep focal point treatment to remove areas of residual deep pigment.

  12. Endogenous Peer Effects: Fact or Fiction?

    ERIC Educational Resources Information Center

    Yeung, Ryan; Nguyen-Hoang, Phuong

    2016-01-01

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

  13. Endogenous timing factors in bird migration

    NASA Technical Reports Server (NTRS)

    Gwinner, E. G.

    1972-01-01

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

  14. Approaches towards endogenous pancreatic regeneration.

    PubMed

    Banerjee, Meenal; Kanitkar, Meghana; Bhonde, Ramesh R

    2005-01-01

    The phenomenon of pancreatic regeneration in mammals has been well documented. It has been shown that pancreatic tissue is able to regenerate in several species of mammal after surgical insult. This tissue is also known to have the potential to maintain or increase its beta-cell mass in response to metabolic demands during pregnancy and obesity. Since deficiency in beta-cell mass is the hallmark of most forms of diabetes, it is worthwhile understanding pancreatic regeneration in the context of this disease. With this view in mind, this article aims to discuss the potential use in clinical strategies of knowledge that we obtained from studies carried out in animal models of diabetes. Approaches to achieve this goal involve the use of biomolecules, adult stem cells and gene therapy. Various molecules, such as glucagon-like peptide-1, beta-cellulin, nicotinamide, gastrin, epidermal growth factor-1 and thyroid hormone, play major roles in the initiation of endogenous islet regeneration in diabetes. The most accepted hypothesis is that these molecules stimulate islet precursor cells to undergo neogenesis or to induce replication of existing beta-cells, emphasizing the importance of pancreas-resident stem/progenitor cells in islet regeneration. Moreover, the potential of adult stem cell population from bone marrow, umbilical cord blood, liver, spleen, or amniotic membrane, is also discussed with regard to their potential to induce pancreatic regeneration.

  15. Xenotransplantation and pig endogenous retroviruses.

    PubMed

    Magre, Saema; Takeuchi, Yasuhiro; Bartosch, Birke

    2003-01-01

    Xenotransplantation, in particular transplantation of pig cells, tissues and organs into human patients, may alleviate the current shortage of suitable allografts available for human transplantation. This overview addresses the physiological, immunological and virological factors considered with regard to xenotransplantation. Among the issues reviewed are the merits of using pigs as xenograft source species, the compatibility of pig and human organ physiology and the immunological hindrances with regard to the various types of rejection and attempts at abrogating rejection. Advances in the prevention of pig organ rejection by creating genetically modified pigs that are more suited to the human microenvironment are also discussed. Finally, with regard to virology, possible zoonotic infections emanating from pigs are reviewed, with special emphasis on the pig endogenous retrovirus (PERV). An in depth account of PERV studies, comprising their discovery as well as recent knowledge of the virus, is given. To date, all retrospective studies on patients with pig xenografts have shown no evidence of PERV transmission, however, many factors make us interpret these results with caution. Although the lack of PERV infection in xenograft recipients up to now is encouraging, more basic research and controlled animal studies that mimic the pig to human xenotransplantation setting more closely are required for safety assessment.

  16. Endogenous Auxin and Ethylene in Pellia (Bryophyta) 1

    PubMed Central

    Thomas, Robert J.; Harrison, Marcia A.; Taylor, Jane; Kaufman, Peter B.

    1983-01-01

    The occurrence of endogenous indole-3-acetic acid and ethylene in bryophyte tissue was tentatively demonstrated using gas chromatography, high performance liquid chromatography, and double-standard isotope dilution techniques. Rapidly elongating stalks (or setae) of Pellia epiphylla (L.) Corda sporophytes contain approximately 2.5 to 2.9 micrograms per gram fresh weight of putative free IAA. Ethylene released by setae increases during growth from 0.027 to 0.035 nanoliter per seta per hour. Application of 5 microliters per liter ethylene inhibits auxin-stimulated elongation growth of this tissue, a result which suggests that both endogenously produced compounds act in tandem as natural growth modulators. Images Fig. 1 PMID:16663227

  17. The Equivalency between Logic Petri Workflow Nets and Workflow Nets

    PubMed Central

    Wang, Jing; Yu, ShuXia; Du, YuYue

    2015-01-01

    Logic Petri nets (LPNs) can describe and analyze batch processing functions and passing value indeterminacy in cooperative systems. Logic Petri workflow nets (LPWNs) are proposed based on LPNs in this paper. Process mining is regarded as an important bridge between modeling and analysis of data mining and business process. Workflow nets (WF-nets) are the extension to Petri nets (PNs), and have successfully been used to process mining. Some shortcomings cannot be avoided in process mining, such as duplicate tasks, invisible tasks, and the noise of logs. The online shop in electronic commerce in this paper is modeled to prove the equivalence between LPWNs and WF-nets, and advantages of LPWNs are presented. PMID:25821845

  18. The equivalency between logic Petri workflow nets and workflow nets.

    PubMed

    Wang, Jing; Yu, ShuXia; Du, YuYue

    2015-01-01

    Logic Petri nets (LPNs) can describe and analyze batch processing functions and passing value indeterminacy in cooperative systems. Logic Petri workflow nets (LPWNs) are proposed based on LPNs in this paper. Process mining is regarded as an important bridge between modeling and analysis of data mining and business process. Workflow nets (WF-nets) are the extension to Petri nets (PNs), and have successfully been used to process mining. Some shortcomings cannot be avoided in process mining, such as duplicate tasks, invisible tasks, and the noise of logs. The online shop in electronic commerce in this paper is modeled to prove the equivalence between LPWNs and WF-nets, and advantages of LPWNs are presented.

  19. [Nutrition, acid-base metabolism, cation-anion difference and total base balance in humans].

    PubMed

    Mioni, R; Sala, P; Mioni, G

    2008-01-01

    The relationship between dietary intake and acid-base metabolism has been investigated in the past by means of the inorganic cation-anion difference (C(+)(nm)-A(-)(nm)) method based on dietary ash-acidity titration after the oxidative combustion of food samples. Besides the inorganic components of TA (A(-)(nm)-C(+)(nm)), which are under renal control, there are also metabolizable components (A(-)(nm)-C(+)(nm)) of TA, which are under the control of the intermediate metabolism. The whole body base balance, NBb(W), is obtained only by the application of C(+)(nm)-A(-)(nm) to food, feces and urine, while the metabolizable component (A(-)(nm)-C(+)(nm)) is disregarded. A novel method has been subsequently suggested to calculate the net balance of fixed acid, made up by the difference between the input of net endogenous acid production: NEAP = SO(4)(2-)+A(-)(m)-(C(+)(nm)-A(-)(nm)), and the output of net acid excretion: NAE = TA + NH(4)(+) - HCO(3)(-). This approach has been criticized because 1) it includes metabolizable acids, whose production cannot be measured independently; 2) the specific control of metabolizable acid and base has been incorrectly attributed to the kidney; 3) the inclusion of A-m in the balance input generates an acid overload; 4) the object of measurement in making up a balance has to be the same, a condition not fulfilled as NEAP is different from NAE. Lastly, by rearranging the net balance of the acid equation, the balance of nonmetabolizable acid equation is obtained. Therefore, any discrepancy between these two equations is due to the inaccuracy in the urine measurement of metabolizable cations and/or anions.

  20. Army Net Zero Prove Out. Net Zero Waste Best Practices

    DTIC Science & Technology

    2014-11-20

    Assistant Secretary of the Army for Energy & Sustainability POP Period of Performance QRP Qualified Recycling Program iii Task 0818, “Army Net...policy that all installations will implement Net Zero Waste to the maximum extent practical and fiscally prudent by reducing, reusing, recycling ...Waste 32 U.S. ARMY Fort Hood Recycling Center Introduction To date, the Army has made substantial progress in the areas of Net Zero Energy, Water

  1. Gravity effects on endogenous movements

    NASA Astrophysics Data System (ADS)

    Johnsson, Anders; Antonsen, Frank

    Gravity effects on endogenous movements A. Johnsson * and F. Antonsen *+ * Department of Physics, Norwegian University of Science and Technology,NO-7491, Trond-heim, Norway, E-mail: anders.johnsson@ntnu.no + Present address: Statoil Research Center Trondheim, NO-7005, Trondheim, Norway Circumnutations in stems/shoots exist in many plants and often consists of more or less regular helical movements around the plumb line under Earth conditions. Recent results on circumnu-tations of Arabidopsis in space (Johnsson et al. 2009) showed that minute amplitude oscilla-tions exist in weightlessness, but that centripetal acceleration (mimicking the gravity) amplified and/or created large amplitude oscillations. Fundamental mechanisms underlying these results will be discussed by modeling the plant tissue as a cylinder of cells coupled together. As a starting point we have modeled (Antonsen 1998) standing waves on a ring of biological cells, as first discussed in a classical paper (Turing 1952). If the coupled cells can change their water content, an `extension' wave could move around the ring. We have studied several, stacked rings of cells coupled into a cylinder that together represent a cylindrical plant tissue. Waves of extensions travelling around the cylinder could then represent the observable circumnutations. The coupling between cells can be due to cell-to-cell diffusion, or to transport via channels, and the coupling can be modeled to vary in both longitudinal and transversal direction of the cylinder. The results from ISS experiments indicate that this cylindrical model of coupled cells should be able to 1) show self-sustained oscillations without the impact of gravity (being en-dogenous) and 2) show how an environmental factor like gravity can amplify or generate the oscillatory movements. Gravity has been introduced in the model by a negative, time-delayed feed-back transport across the cylinder. This represents the physiological reactions to acceler

  2. Enhancing tolerance of rice (Oryza sativa) to simulated acid rain by exogenous abscisic acid.

    PubMed

    Wu, Xi; Liang, Chanjuan

    2017-02-01

    Abscisic acid (ABA) regulates much important plant physiological and biochemical processes and induces tolerance to different stresses. Here, we studied the regulation of exogenous ABA on adaptation of rice seedlings to simulated acid rain (SAR) stress by measuring biomass dry weight, stomatal conductance, net photosynthesis rate, nutrient elements, and endogenous hormones. The application of 10 μM ABA alleviated the SAR-induced inhibition on growth, stomatal conductance, net photosynthesis rate, and decreases in contents of nutrient (K, Mg, N, and P) and hormone (auxin, gibberellins, and zeatin). Moreover, 10 μM ABA could stimulate the Ca content as signaling molecules under SAR stress. Contrarily, the application of 100 μM ABA aggravated the SAR-induced inhibition on growth, stomatal conductance, net photosynthesis rate, and contents of nutrient and hormone. The results got after a 5-day recovery (without SAR) show that exogenous 10 μM ABA can promote self-restoration process in rice whereas 100 μM ABA hindered the restoration by increasing deficiency of nutrients and disturbing the balance of hormones. These results confirmed that exogenous ABA at proper concentration could enhance the tolerance of rice to SAR stress.

  3. Net Catches Debris From Explosion

    NASA Technical Reports Server (NTRS)

    Kahn, Jon B.; Schneider, William C.

    1992-01-01

    Device restrains fragments and absorbs their kinetic energy. Net of stitched webbing folds compactly over honeycomb plug. Attaches to frame mounted on wall around rectangular area to be cut out by explosion. Honeycomb panel absorbs debris from explosion and crumples into net. Dissipates energy by ripping about 9 in. of stitched net. Developed for emergency escape system in Space Shuttle, adaptable to restraint belts for vehicles; subjecting passengers to more gradual deceleration and less shock.

  4. NetView technical research

    NASA Technical Reports Server (NTRS)

    1993-01-01

    This is the Final Technical Report for the NetView Technical Research task. This report is prepared in accordance with Contract Data Requirements List (CDRL) item A002. NetView assistance was provided and details are presented under the following headings: NetView Management Systems (NMS) project tasks; WBAFB IBM 3090; WPAFB AMDAHL; WPAFB IBM 3084; Hill AFB; McClellan AFB AMDAHL; McClellan AFB IBM 3090; and Warner-Robins AFB.

  5. AdaNET executive summary

    NASA Technical Reports Server (NTRS)

    Digman, R. Michael

    1988-01-01

    The goal of AdaNET is to transfer existing and emerging software engineering technology from the Federal government to the private sector. The views and perspectives of the current project participants on long and short term goals for AdaNET; organizational structure; resources and returns; summary of identified AdaNET services; and the summary of the organizational model currently under discussion are presented.

  6. Endogenous, Spontaneous Formation of Beta-Lactamase in Staphylococcus aureus

    PubMed Central

    Sachithanandam, S.; Lowery, D. L.; Saz, A. K.

    1974-01-01

    In a β-lactamase-inducible strain of Staphylococcus aureus, the enzyme appears spontaneously in the absence of added inducer during lag and early log phases of growth and then declines rapidly to low levels. The endogenous inducer responsible for appearance of the enzyme has been isolated and purified and characterized as a peptidoglycan, containing muramic acid, glucosamine, glutamic acid, alanine, lysine, and glycine. The inducing compound could be isolated from the cells only during the lag and early log phases and from no other later periods. The data obtained are consistent with the thesis advanced earlier from this laboratory that β-lactamase serves a cellular function in the producing cell more important and beyond its capability of hydrolyzing certain penicillins to the antibiotically inactive penicilloic acids. PMID:4451348

  7. Endogenous synthesis of taurine and GABA in rat ocular tissues.

    PubMed

    Heinämäki, A A

    1988-01-01

    The endogenous production of taurine and gamma-aminobutyric acid (GABA) in rat ocular tissues was investigated. The activities of taurine-producing enzyme, cysteine sulfinic acid decarboxylase (CSAD), and GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), were observed in the retina, lens, iris-ciliary body and cornea. The highest specific activity of CSAD was in the cornea and that of GAD in the retina. The discrepancy between CSAD activity and taurine content within the ocular tissues indicates that intra- or extraocular transport processes may regulate the concentration of taurine in the rat eye. The GAD activity and the content of GABA were distributed in parallel within the rat ocular tissues. The quantitative results suggest that the GAD/GABA system has functional significance only in the retina of the rat eye.

  8. Regulation of carbohydrate metabolism in lymphoid tissue. Nature of the endogenous substrates and their contribution to the respiratory fuel of the sliced rat spleen in vitro.

    PubMed

    Suter, D; Weidemann, M J

    1976-04-15

    1. Tissue glycogen contributes, maximally, only 10% of the respiratory fuel of the rat spleen slice in the absence of an added carbon source, and makes no significant contribution when glucose (3mM) is added. 2. The reserves of fatty acid in the form of triglyceride (35.5mumol of fatty acid/g dry wt. of tissue) fall by approx. 25% after incubation of spleen slices with or without added glucose for 2h, and , on this basis, account for 32% of the oxidative fuel. 3. In contrast, the total oxidative contribution of fatty acid reserves to the respiratory fuel, determined on the basis of inhibiton of respiration by 2-bromostearate, is 42-52%. This range includes tissue from both starved and well-fed animals and is not significantly altered by the presence of added glycose (3mM). 4. Large quantities of NH3 (31-35mumol//h per g dry wt. of tissue) are produced by spleen slices incubated in the absence of added substrates, and this value is suppressed by approx. 50% on incubation with glucose (3mM). Adenine nucleotide breakdown can account for only 17% of the total ammonia produced. 5. Individual free amino acid concentrations in spleen were determined, both in vivo and in slices before and after 60 min of incubation. Although the total free amino acid pool size increases by 45% during incubation, owing to protein breakdown, the tissue concentrations of aspartate, glutamate, glutamine and alanine do not increase. It is suggested that these amino acids areoxidized in a net sense to CO2 and water with the liberation of free NH3 via transamination reactions, glutaminase, the purine nucleotide cycle and the tricarboxylic acid cycle. 6. It is concluded that the normal endogenous metabolism of sliced rat spleen (43-52% due to lipids, 30% due to amino acids and 10% due to glycogen) is modified by added glycose only to the extent that glycogen oxidation and 50% of the contribtion made by ino acids are suppressed; endogenous lipid metabolism is unaffected.

  9. Neural nets on the MPP

    NASA Technical Reports Server (NTRS)

    Hastings, Harold M.; Waner, Stefan

    1987-01-01

    The Massively Parallel Processor (MPP) is an ideal machine for computer experiments with simulated neural nets as well as more general cellular automata. Experiments using the MPP with a formal model neural network are described. The results on problem mapping and computational efficiency apply equally well to the neural nets of Hopfield, Hinton et al., and Geman and Geman.

  10. KM3NeT

    SciTech Connect

    Jong, M. de; Collaboration: KM3NeT Collaboration

    2015-07-15

    KM3NeT is a large research infrastructure, that will consist of a network of deep-sea neutrino telescopes in the Mediterranean Sea. The main objective of KM3NeT is the discovery and subsequent observation of high-energy neutrino sources in the Universe. A further physics perspective is the measurement of the mass hierarchy of neutrinos. A corresponding study, ORCA, is ongoing within KM3NeT. A cost effective technology for (very) large water Cherenkov detectors has been developed based on a new generation of low price 3-inch photo-multiplier tubes. Following the successful deployment and operation of two prototypes, the construction of the KM3NeT research infrastructure has started. The prospects of the different phases of the implementation of KM3NeT are summarised.

  11. TacNet Tracker Software

    SciTech Connect

    WISEMAN, JAMES; & STEVENS, JAMES

    2008-08-04

    The TacNet Tracker will be used for the monitoring and real-time tracking of personnel and assets in an unlimited number of specific applications. The TacNet Tracker software is a VxWorks Operating System based programming package that controls the functionality for the wearable Tracker. One main use of the TacNet Tracker is in Blue Force Tracking, the ability to track the good guys in an adversarial situation or in a force-on-force or real battle conditions. The purpose of blue force tracking is to provide situational awareness to the battlefield commanders and personnel. There are practical military applications with the TacNet Tracker.The mesh network is a wireless IP communications network that moves data packets from source IP addresses to specific destination IP addresses. Addresses on the TacNet infrastructure utilize an 8-bit network mask (255.0.0.0). In other words, valid TacNet addresses range from 10.0.0.1 to 10.254.254.254. The TacNet software design uses uni-cast transmission techniques because earlier mesh network software releases did not provide for the ability to utilize multi-cast data movement. The TacNet design employs a list of addresses to move information within the TacNet infrastructure. For example, a convoy text file containing the IP addresses of all valid receivers of TacNet information could be used for transmitting the information and for limiting transmission to addresses on the list.

  12. Endogenous conversion of ω-6 to ω-3 polyunsaturated fatty acids in fat-1 mice attenuated intestinal polyposis by either inhibiting COX-2/β-catenin signaling or activating 15-PGDH/IL-18.

    PubMed

    Han, Young-Min; Park, Jong-Min; Cha, Ji-Young; Jeong, Migyeong; Go, Eun-Jin; Hahm, Ki Baik

    2016-05-01

    Omega-3 polyunsaturated fatty acids (ω-3PUFAs) have inhibitory effects in various preclinical cancer models, but their effects in intestinal polyposis have never been examined. As attempts have been made to use nutritional intervention to counteract colon cancer development, in this study we evaluated the effects of ω-3 PUFAs on intestinal polyposis in the Apc(Min/+) mouse model. The experimental groups included wild-type C56BL/6 mice, Apc(Min/+) mice, fat-1 transgenic mice expressing an n-3 desaturase to enable ω-3 PUFA synthesis, and Apc(Min/+) × fat-1 double-transgenic mice; all mice were 20 weeks of age. Small intestines were collected for gross and pathologic evaluation, including assessment of polyp number and size, followed by immunohistochemical staining and Western blotting. After administration of various concentrations of ω-3 PUFAs, PUFA levels were measured in small intestine tissue by GC/MS/MS analysis to compare with PUFA synthesis of between C57BL6 and fat-1mice. As a result, ω-3 PUFAs significantly attenuated Apc mutation-induced intestinal polyposis accompanied with significant inhibition of Wnt/β-catenin signaling, COX-2 and PGE2, but induced significant levels of 15-PGDH. In addition, significant induction of the inflammasome-related substrates as IL-1β and IL-18 and activation of caspase-1 was observed in Apc(Min/+) × fat-1 mice. Administration of at least 3 g/60 kg ω-3 PUFAs was equivalent to ω-3 PUFAs produced in fat-1 mice and resulted in significant increase in the expression of IL-1β, caspase-3 and IL-18, as seen in Apc(Min/+) × fat-1 mice. We conclude that ω-3PUFAs can prevent intestinal polyp formation by inhibition of Wnt/β-catenin signaling, but increased levels of 15-PGDH and IL-18.

  13. Sulphonic acid strong cation-exchange restricted access columns in sample cleanup for profiling of endogenous peptides in multidimensional liquid chromatography. Structure and function of strong cation-exchange restricted access materials.

    PubMed

    Machtejevas, E; Denoyel, R; Meneses, J M; Kudirkaite, V; Grimes, B A; Lubda, D; Unger, K K

    2006-08-04

    In this work, the pore structural parameters and size exclusion properties of LiChrospher strong cation-exchange and reverse phase restricted access materials (RAM) are analysed. The molecular weight size exclusion limit for polystyrenes was found to be about 17.7 kDa, while for standard proteins, the molecular weight size exclusion limit was higher, at approximately 25 kDa. The average pore diameter on a volume basis calculated from the pore network model changes from 8.5 nm (native LiChrospher) to 8.6 nm (diol derivative) to 8.2 nm (sulphonic acid derivative) to 6.9 nm (n-octadecyl derivative). Additional characterisations were performed on restricted access materials with nitrogen sorption at 77 K, water adsorption at 25 degrees C, intrusion-extrusion of water (in order to evaluate the hydrophobic properties of the pores of the hydrophobic RAM), and zeta potential measurements by microelectrophoresis. For peptide analysis out of the biofluids, the strong cation-exchange functionality seems to be particularly suitable mainly because of the high loadability of the strong cation-exchange restricted access material (SCX-RAM) and the fact that one can work under non-denaturing conditions to perform effective chromatographic separations. For bacitracin, the dynamic capacity of the SCX-RAM columns does not reach its maximum value in the analysed range. For lysozyme, the dynamic capacity reaches a value of 0.08 mg/ml of column volume before column is overloaded. Additionally, the proper column operating conditions that lead to the total effective working time of the RAM column to be equal to approximately 500 injections (depending on the type of sample), is comprehensively described. The SCX-RAM column was used in the same system analysing urine samples for the period of 1 month (approximately 150 injections) with run-to-run reproducibility below 5% RSD and below 10% RSD for the relative fractions.

  14. Endogenous Epoxygenases Are Modulators of Monocyte/Macrophage Activity

    PubMed Central

    Sugden, Mary C.; Holness, Mark J.; Swales, Karen E.; Warner, Timothy D.; Edin, Matthew L.; Zeldin, Darryl C.; Gilroy, Derek W.; Bishop-Bailey, David

    2011-01-01

    Background Arachidonic acid is metabolized through three major metabolic pathways, the cyclooxygenase, lipoxygenase and CYP450 enzyme systems. Unlike cyclooxygenase and lipoxygenases, the role of CYP450 epoxygenases in monocyte/macrophage-mediated responses is not known. Methodology/Principal Findings When transfected in vitro, CYP2J2 is an efficient activator of anti-inflammatory pathways through the nuclear receptor peroxisome proliferator-activated receptor (PPAR) α. Human monocytes and macrophages contain PPARα and here we show they express the epoxygenases CYP2J2 and CYP2C8. Inhibition of constitutive monocyte epoxygenases using the epoxygenase inhibitor SKF525A induces cyclooxygenase (COX)-2 expression and activity, and the release of TNFα, and can be reversed by either add back of the endogenous epoxygenase products and PPARα ligand 11,12- epoxyeicosatrienoic acid (EET) or the addition of the selective synthetic PPARα ligand GW7647. In alternatively activated (IL-4-treated) monocytes, in contrast to classically activated cells, epoxygenase inhibition decreased TNFα release. Epoxygenases can be pro-inflammatory via superoxide anion production. The suppression of TNFα by SKF525A in the presence of IL-4 was associated with a reduction in superoxide anion generation and reproduced by the superoxide dismutase MnCl2. Similar to these acute activation studies, in monocyte derived macrophages, epoxygenase inhibition elevates M1 macrophage TNFα mRNA and further decreases M2 macrophage TNFα. Conclusions/Significance In conclusion, epoxygenase activity represents an important endogenous pathway which limits monocyte activation. Moreover endogenous epoxygenases are immuno-modulators regulating monocyte/macrophage activation depending on the underlying activation state. PMID:22028915

  15. Army Net Zero Prove Out. Net Zero Waster Best Practices

    DTIC Science & Technology

    2014-11-18

    sustainable water supply for years to come. This concept is of increasing importance because water scarcity is a serious and growing issue in many parts of...concept is of increasing importance because water scarcity is a serious and growing issue in many parts of the United States and around the world. Honorable Katherine Hammack ...ARMY NET ZERO PROVE OUT Final Net Zero Water Best Practices November 18, 2014 Distribution A Approved for public release

  16. Conformal Nets II: Conformal Blocks

    NASA Astrophysics Data System (ADS)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-03-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  17. AdaNET research project

    NASA Technical Reports Server (NTRS)

    Digman, R. Michael

    1988-01-01

    The components necessary for the success of the commercialization of an Ada Technology Transition Network are reported in detail. The organizational plan presents the planned structure for services development and technical transition of AdaNET services to potential user communities. The Business Plan is the operational plan for the AdaNET service as a commercial venture. The Technical Plan is the plan from which the AdaNET can be designed including detailed requirements analysis. Also contained is an analysis of user fees and charges, and a proposed user fee schedule.

  18. Silent no more: Endogenous small RNA pathways promote gene expression.

    PubMed

    Wedeles, Christopher J; Wu, Monica Z; Claycomb, Julie M

    2014-01-01

    Endogenous small RNA pathways related to RNA interference (RNAi) play a well-documented role in protecting host genomes from the invasion of foreign nucleic acids. In C. elegans, the PIWI type Argonaute, PRG-1, through an association with 21U-RNAs, mediates a genome surveillance process by constantly scanning the genome for potentially deleterious invading elements. Upon recognition of foreign nucleic acids, PRG-1 initiates a cascade of cytoplasmic and nuclear events that results in heritable epigenetic silencing of these transcripts and their coding genomic loci. If the PRG-1/21U-RNA genome surveillance pathway has the capacity to target most of the C. elegans transcriptome, what mechanisms exist to protect endogenous transcripts from being silenced by this pathway? In this commentary, we discuss three recent publications that implicate the CSR-1 small RNA pathway in the heritable activation of germline transcripts, propose a model as to why not all epialleles behave similarly, and touch on the practical implications of these findings.

  19. Endogenous production of hydrogen sulfide in isolated bovine eye.

    PubMed

    Kulkarni, Madhura; Njie-Mbye, Ya Fatou; Okpobiri, Ikechukwu; Zhao, Min; Opere, Catherine A; Ohia, Sunny E

    2011-08-01

    Hydrogen sulfide (H(2)S) is a novel gasotransmitter with physiological and pathological functions in vascular homeostasis, cardiovascular system and central nervous system. In the present study, we determined the endogenous levels of H(2)S in various tissues of the bovine eye. We also examined the basal levels of H(2)S in response to donors (sodium hydrosulfide, NaHS and sodium sulfide, Na(2)S), substrate (L: -cysteine), inhibitors (propargylglycine, PAG and aminooxyacetic acid, AOA) and activator (S-adenosyl-L: -methionine, SAM) of this gas in the bovine retina. H(2)S was measured using a well established spectrophotometric method. The highest concentration of endogenous H(2)S was detected in cornea (19 ± 2.85 nmoles/mg protein, n = 6) and retina (17 ± 2.1 nmoles/mg protein, n = 6). Interestingly, H(2)S was not present in vitreous humor. The inhibitors of CSE and CBS; PAG (1 mM) and AOA (1 mM), significantly attenuated the production of H(2)S in the bovine retina by 56.8 and 42%, respectively. On the other hand the activator of CBS; SAM (100 μM), H(2)S donors; NaHS (1 μM) and Na(2)S (100 μM), significantly increased endogenous levels of H(2)S in bovine retina. L: -cysteine (10-300 μM) produced a significant (P < 0.05) concentration-dependent increase in H(2)S levels reaching a maximal at 300 μM. We conclude that H(2)S is endogenously produced in various tissues of the isolated bovine eye. Moreover, endogenous levels of H(2)S are enhanced in the presence of substrate (L: -cysteine), an activator of CBS (SAM) and H(2)S donors but are blocked by inhibitors of enzymes that synthesize this gas in neural retina.

  20. Digestion and nutrient net fluxes across the rumen, and the mesenteric- and portal-drained viscera in sheep fed with fresh forage twice daily: net balance and dynamic aspects.

    PubMed

    Rémond, Didier; Bernard, Laurence; Chauveau, Béatrice; Nozière, Pierre; Poncet, Claude

    2003-05-01

    Digestion and portal net flux of nutrients were studied in sheep fed twice daily with fresh orchard-grass. Digestive flows were measured in six fistulated sheep using the double-marker technique. Three sheep were fitted with catheters and blood-flow probes, allowing nutrient net flux measurements across the portal-drained viscera (PDV), the mesenteric-drained viscera (MDV) and the rumen. Total tract apparent digestion of N was similar to portal net appearance of N, calculated as the sum of free amino acids (FAA), peptide amino acids (PAA), NH3, and urea net fluxes. PAA accounted for 25 % of non-protein amino acid net release across the PDV. With the exception of glycine and glutamate, the small intestine was the main contributor to this PAA net release. The essential amino acid (EAA) apparent disappearance between the duodenum and the ileum was lower than the net appearance of EAA (FAA + PAA) across the MDV. The value of PDV:MDV flux of free EAA was, on average, 78 %. The rumen accounted for 30 % of the net uptake of EAA by the PDV tissues not drained by the mesenteric vein. Rumen net release of acetate, propionate, butyrate, 3-hydroxybutyrate, and lactate accounted for 70, 55, 46, 77 and 52 %, respectively, of their portal net releases. Conversely, the small intestine was a net consumer of arterial acetate and 3-hydroxybutyrate. Dynamic study of nutrient net fluxes across the PDV showed that throughout a feeding cycle, the liver faced a constant flux of amino acids (AA), whereas volatile fatty acid and NH3 net fluxes varied in response to the meal. The present study specified, in forage-fed sheep, the partitioning of nutrient net fluxes across the PDV and the role of peptides in portal net release of AA.

  1. Endogenous versus Exogenous Origins of Crises

    NASA Astrophysics Data System (ADS)

    Sornette, Didier

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

  2. Support Net for Frontline Providers

    DTIC Science & Technology

    2016-03-01

    2-0153 TITLE: SupportNet for Frontline Behavioral Health Providers PRINCIPAL INVESTIGATOR: Dr. Charles Benight CONTRACTING ORGANIZATION: Regents...military behavioral health providers who are continually exposed to extensive traumatic material on an on-going basis. Job burnout and STS potentially...readiness for soldiers. SupportNet aimed to assess the level of secondary trauma and job burnout among military behavioral health providers and to

  3. An endogenous model of the credit network

    NASA Astrophysics Data System (ADS)

    He, Jianmin; Sui, Xin; Li, Shouwei

    2016-01-01

    In this paper, an endogenous credit network model of firm-bank agents is constructed. The model describes the endogenous formation of firm-firm, firm-bank and bank-bank credit relationships. By means of simulations, the model is capable of showing some obvious similarities with empirical evidence found by other scholars: the upper-tail of firm size distribution can be well fitted with a power-law; the bank size distribution can be lognormally distributed with a power-law tail; the bank in-degrees of the interbank credit network as well as the firm-bank credit network fall into two-power-law distributions.

  4. 29 CFR 4204.13 - Net income and net tangible assets tests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 4204(a)(1)(B); or (2) Net tangible assets test. The purchaser's net tangible assets at the end of the... 29 Labor 9 2012-07-01 2012-07-01 false Net income and net tangible assets tests. 4204.13 Section....13 Net income and net tangible assets tests. (a) General. The criteria under this section are...

  5. 29 CFR 4204.13 - Net income and net tangible assets tests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 4204(a)(1)(B); or (2) Net tangible assets test. The purchaser's net tangible assets at the end of the... 29 Labor 9 2010-07-01 2010-07-01 false Net income and net tangible assets tests. 4204.13 Section....13 Net income and net tangible assets tests. (a) General. The criteria under this section are...

  6. 26 CFR 1.904(f)-3 - Allocation of net operating losses and net capital losses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 9 2014-04-01 2014-04-01 false Allocation of net operating losses and net... States § 1.904(f)-3 Allocation of net operating losses and net capital losses. For rules relating to the allocation of net operating losses and net capital losses, see § 1.904(g)-3T....

  7. 29 CFR 4204.13 - Net income and net tangible assets tests.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Net income and net tangible assets tests. 4204.13 Section....13 Net income and net tangible assets tests. (a) General. The criteria under this section are that either— (1) Net income test. The purchaser's average net income after taxes for its three most...

  8. 26 CFR 1.904(f)-3 - Allocation of net operating losses and net capital losses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 9 2013-04-01 2013-04-01 false Allocation of net operating losses and net... States § 1.904(f)-3 Allocation of net operating losses and net capital losses. For rules relating to the allocation of net operating losses and net capital losses, see § 1.904(g)-3T....

  9. 26 CFR 1.172-4 - Net operating loss carrybacks and net operating loss carryovers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 3 2014-04-01 2014-04-01 false Net operating loss carrybacks and net operating... and Corporations (continued) § 1.172-4 Net operating loss carrybacks and net operating loss carryovers... net operating loss deduction the taxpayer must first determine the part of any net operating...

  10. 26 CFR 1.904(f)-3 - Allocation of net operating losses and net capital losses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Allocation of net operating losses and net....904(f)-3 Allocation of net operating losses and net capital losses. For rules relating to the allocation of net operating losses and net capital losses, see § 1.904(g)-3T....

  11. 26 CFR 1.172-4 - Net operating loss carrybacks and net operating loss carryovers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 3 2012-04-01 2012-04-01 false Net operating loss carrybacks and net operating... and Corporations (continued) § 1.172-4 Net operating loss carrybacks and net operating loss carryovers... net operating loss deduction the taxpayer must first determine the part of any net operating...

  12. 26 CFR 1.904(f)-3 - Allocation of net operating losses and net capital losses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 9 2011-04-01 2011-04-01 false Allocation of net operating losses and net... States § 1.904(f)-3 Allocation of net operating losses and net capital losses. For rules relating to the allocation of net operating losses and net capital losses, see § 1.904(g)-3T....

  13. 26 CFR 1.172-4 - Net operating loss carrybacks and net operating loss carryovers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 3 2011-04-01 2011-04-01 false Net operating loss carrybacks and net operating... and Corporations (continued) § 1.172-4 Net operating loss carrybacks and net operating loss carryovers... net operating loss deduction the taxpayer must first determine the part of any net operating...

  14. 26 CFR 1.172-4 - Net operating loss carrybacks and net operating loss carryovers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 3 2013-04-01 2013-04-01 false Net operating loss carrybacks and net operating... and Corporations (continued) § 1.172-4 Net operating loss carrybacks and net operating loss carryovers... net operating loss deduction the taxpayer must first determine the part of any net operating...

  15. 29 CFR 4204.13 - Net income and net tangible assets tests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Net income and net tangible assets tests. 4204.13 Section....13 Net income and net tangible assets tests. (a) General. The criteria under this section are that either— (1) Net income test. The purchaser's average net income after taxes for its three most...

  16. 26 CFR 1.904(f)-3 - Allocation of net operating losses and net capital losses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 9 2012-04-01 2012-04-01 false Allocation of net operating losses and net... States § 1.904(f)-3 Allocation of net operating losses and net capital losses. For rules relating to the allocation of net operating losses and net capital losses, see § 1.904(g)-3T....

  17. 29 CFR 4204.13 - Net income and net tangible assets tests.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Net income and net tangible assets tests. 4204.13 Section....13 Net income and net tangible assets tests. (a) General. The criteria under this section are that either— (1) Net income test. The purchaser's average net income after taxes for its three most...

  18. Nicotine effects and the endogenous opioid system.

    PubMed

    Kishioka, Shiroh; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro

    2014-01-01

    Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor (nAChR), and it influences various functions in the central nervous system. Systemic administration of NIC elicits the release of endogenous opioids (endorphins, enkephalins, and dynorphins) in the supraspinal cord. Additionally, systemic NIC administration induces the release of methionine-enkephalin in the spinal dorsal horn. NIC has acute neurophysiological actions, including antinociceptive effects, and the ability to activate the hypothalamic-pituitary-adrenal (HPA) axis. The endogenous opioid system participates in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception is mediated by α4β2 and α7 nAChRs, while NIC-induced HPA axis activation is mediated by α4β2, not α7, suggesting that the effects of NIC on the endogenous opioid system are mediated by α7, not α4β2. NIC has substantial physical dependence liability. The opioid-receptor antagonist naloxone (NLX) elicits NIC withdrawal after repeated NIC administration, and NLX-induced NIC withdrawal is inhibited by concomitant administration of an opioid-receptor antagonist. NLX-induced NIC withdrawal is also inhibited by concomitant administration of an α7 antagonist, but not an α4β2 antagonist. Taken together, these findings suggest that NIC-induced antinociception and the development of physical dependence are mediated by the endogenous opioid system, via the α7 nAChR.

  19. Essays on Policy Evaluation with Endogenous Adoption

    ERIC Educational Resources Information Center

    Gentile, Elisabetta

    2011-01-01

    Over the last decade, experimental and quasi-experimental methods have been favored by researchers in empirical economics, as they provide unbiased causal estimates. However, when implementing a program, it is often not possible to randomly assign subjects to treatment, leading to a possible endogeneity bias. This dissertation consists of two…

  20. The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation

    PubMed Central

    De Petrocellis, Luciano; Melck, Dominique; Palmisano, Antonella; Bisogno, Tiziana; Laezza, Chiara; Bifulco, Maurizio; Di Marzo, Vincenzo

    1998-01-01

    Anandamide was the first brain metabolite shown to act as a ligand of “central” CB1 cannabinoid receptors. Here we report that the endogenous cannabinoid potently and selectively inhibits the proliferation of human breast cancer cells in vitro. Anandamide dose-dependently inhibited the proliferation of MCF-7 and EFM-19 cells with IC50 values between 0.5 and 1.5 μM and 83–92% maximal inhibition at 5–10 μM. The proliferation of several other nonmammary tumoral cell lines was not affected by 10 μM anandamide. The anti-proliferative effect of anandamide was not due to toxicity or to apoptosis of cells but was accompanied by a reduction of cells in the S phase of the cell cycle. A stable analogue of anandamide (R)-methanandamide, another endogenous cannabinoid, 2-arachidonoylglycerol, and the synthetic cannabinoid HU-210 also inhibited EFM-19 cell proliferation, whereas arachidonic acid was much less effective. These cannabimimetic substances displaced the binding of the selective cannabinoid agonist [3H]CP 55,940 to EFM-19 membranes with an order of potency identical to that observed for the inhibition of EFM-19 cell proliferation. Moreover, anandamide cytostatic effect was inhibited by the selective CB1 receptor antagonist SR 141716A. Cell proliferation was arrested by a prolactin mAb and enhanced by exogenous human prolactin, whose mitogenic action was reverted by very low (0.1–0.5 μM) doses of anandamide. Anandamide suppressed the levels of the long form of the prolactin receptor in both EFM-19 and MCF-7 cells, as well as a typical prolactin-induced response, i.e., the expression of the breast cancer cell susceptibility gene brca1. These data suggest that anandamide blocks human breast cancer cell proliferation through CB1-like receptor-mediated inhibition of endogenous prolactin action at the level of prolactin receptor. PMID:9653194

  1. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    PubMed Central

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

    Endogenous activation of μ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) that is masked by spinal MOR signaling for months, even after complete recovery from injury and re-establishment of normal pain thresholds. Disruption with MOR inverse agonists reinstates pain and precipitates cellular, somatic and aversive signs of physical withdrawal; this phenomenon requires N-methyl-D-aspartate receptor-mediated activation of calcium-sensitive adenylyl cyclase type 1 (AC1). In this review, we present a new conceptual model of the transition from acute to chronic pain, based on the delicate balance between LS and endogenous analgesia that develops after painful tissue injury. First, injury activates pain pathways. Second, the spinal cord establishes MOR constitutive activity (MORCA) as it attempts to control pain. Third, over time, the body becomes dependent on MORCA, which paradoxically sensitizes pain pathways. Stress or injury escalates opposing inhibitory and excitatory influences on nociceptive processing as a pathological consequence of increased endogenous opioid tone. Pain begets MORCA begets pain vulnerability in a vicious cycle. The final result is a silent insidious state characterized by the escalation of two opposing excitatory and inhibitory influences on pain transmission: LS mediated by AC1 (which maintains accelerator), and pain inhibition mediated by MORCA (which maintains the brake). This raises the prospect that opposing homeostatic interactions between MORCA analgesia and latent NMDAR–AC1-mediated pain sensitization create a lasting vulnerability to develop chronic pain. Thus, chronic pain syndromes may result from a failure in constitutive signaling of spinal MORs and a loss of endogenous analgesic control. An overarching long-term therapeutic goal of future research is to alleviate chronic pain by either: a) facilitating endogenous opioid

  2. Net zero building energy conservation

    NASA Astrophysics Data System (ADS)

    Kadam, Rohit

    This research deals with energy studies performed as part of a net-zero energy study for buildings. Measured data of actual energy utilization by a building for a continuous period of 33 months was collected and studied. The peak design day on which the building consumes maximum energy was found. The averages of the energy consumption for the peak month were determined. The DOE EnergyPlus software was used to simulate the energy requirements for the building and also obtain peak energy requirements for the peak month. Alternative energy sources such as ground source heat pump, solar photovoltaic (PV) panels and day-lighting modifications were applied to redesign the energy consumption for the building towards meeting net-zero energy requirements. The present energy use by the building, DOE Energy software simulations for the building as well as the net-zero model for the building were studied. The extents of the contributions of the individual energy harvesting measures were studied. For meeting Net Zero Energy requirement, it was found that the total energy load for the building can be distributed between alternative energy methods as 5.4% to daylighting modifications, 58% to geothermal and 36.6% to solar photovoltaic panels for electricity supply and thermal energy. Thus the directions to proceed towards achieving complete net-zero energy status were identified.

  3. Inhibition of endogenous human dentin MMPs by Gluma

    PubMed Central

    Sabatini, Camila; Scheffel, Débora L.S.; Scheffel, Régis H.; Agee, Kelli A.; Rouch, Katelyn; Takahashi, Masahiro; Breschi, Lorenzo; Mazzoni, Annalisa; Tjäderhane, Leo; Tay, Franklin R.; Pashley, David H.

    2014-01-01

    Objective The objective of this study was to determine if Gluma dentin desensitizer (5.0% glutaraldehyde and 35% HEMA in water) can inhibit the endogenous MMPs of dentin matrices in 60 sec. and to evaluate its effect on dentin matrix stiffness and dry mass weight. Methods Dentin beams of 2×1×6 mm were obtained from extracted human third molars coronal dentin. To measure the influence of Gluma treatment time on total MMP activity of dentin, beams were dipped in 37% phosphoric acid (PA) for 15 sec. and rinsed in water. The acid-etched beams were then dipped in Gluma for 5, 15, 30 or 60 sec., rinsed in water and incubated into SensoLyte generic MMP substrate (AnaSpec, Inc.) for 60 min. Controls were dipped in water for 60 sec. Additional beams of 1×1×6 mm were completely demineralized in 37% PA for 18 h, rinsed and used to evaluate changes on the dry weight and modulus of elasticity (E) after 60 sec. of Gluma treatment followed by incubation in simulated body fluid buffer for zero, one or four weeks. E was measured by 3-pt flexure. Results Gluma treatment inhibited total MMP activity of acid-etched dentin by 44, 50, 84, 86 % after 5, 15, 30 or 60 sec. of exposure, respectively. All completely demineralized dentin beams lost stiffness after one and four weeks, with no significant differences between the control and Gluma-treated dentin. Gluma treatment for 60 sec. yielded significantly less dry mass loss than the control after four weeks. Significance The use of Gluma may contribute to the preservation of adhesive interfaces by its cross-linking and inhibitory properties of endogenous dentin MMPs. PMID:24846803

  4. Gastric neuroendocrine tumor (NET): report of one case

    PubMed Central

    Dou, Dou; Qiu, Xudong

    2016-01-01

    In this article we reported a female patient with type 1 gastric neuroendocrine tumor (NET). Gastroscopy showed the presence of multiple polyp-like lesions sized 0.2–1.5 cm in the fundus and body of stomach. The main clinical manifestations were belching and fullness after a meal. She had a history of autoimmune atrophic gastritis and laboratory tests showed increased serum gastrin and acid deficiency, which met the diagnostic criteria of type 1 gastric NET. Treatments included endoscopic resection, sandostatin, and traditional Chinese herbs, and no relapse was noted during follow-up visits. The patient also had rectal NET. By analyzing this case, we tried to explore the diagnostic algorithm and clinical typing of type 1 gastric NET; meanwhile, along with literature review, we described the relapse rate of this disease and the value of regular follow-up (every 6–12 months). Finally, we analyzed the value of somatostatin analogue (SSA) in treating multiple type 1 gastric NET and in this case we demonstrated that SSA was effective in dissolving NET. PMID:28138650

  5. Gastric neuroendocrine tumor (NET): report of one case.

    PubMed

    Dou, Dou; Qiu, Xudong; Tan, Huangying

    2016-01-01

    In this article we reported a female patient with type 1 gastric neuroendocrine tumor (NET). Gastroscopy showed the presence of multiple polyp-like lesions sized 0.2-1.5 cm in the fundus and body of stomach. The main clinical manifestations were belching and fullness after a meal. She had a history of autoimmune atrophic gastritis and laboratory tests showed increased serum gastrin and acid deficiency, which met the diagnostic criteria of type 1 gastric NET. Treatments included endoscopic resection, sandostatin, and traditional Chinese herbs, and no relapse was noted during follow-up visits. The patient also had rectal NET. By analyzing this case, we tried to explore the diagnostic algorithm and clinical typing of type 1 gastric NET; meanwhile, along with literature review, we described the relapse rate of this disease and the value of regular follow-up (every 6-12 months). Finally, we analyzed the value of somatostatin analogue (SSA) in treating multiple type 1 gastric NET and in this case we demonstrated that SSA was effective in dissolving NET.

  6. Preoperative Endogenous Ouabain Predicts Acute Kidney Injury in Cardiac Surgery Patients

    PubMed Central

    Bignami, Elena; Casamassima, Nunzia; Frati, Elena; Lanzani, Chiara; Corno, Laura; Alferi, Ottavio; Gottlieb, Stephen; Simonini, Marco; Shah, Keyur B.; Mizzi, Anna; Messaggio, Elisabetta; Zangrillo, Alberto; Ferrandi, Mara; Ferrari, Patrizia; Bianchi, Giuseppe; Hamlyn, John M.; Manunta, Paolo

    2013-01-01

    Objectives Acute kidney injury is a frequent complication of cardiac surgery and increases morbidity and mortality. As preoperative biomarkers predicting the development of acute kidney injury are not available, we have tested the hypothesis that preoperative plasma levels of endogenous ouabain may function as this type of biomarker. Rationale and Design Endogenous ouabain is an adrenal stress hormone associated with adverse cardiovascular outcomes. Its involvement in acute kidney injury is unknown. With studies in patients and animal settings, including isolated podocytes, we tested the above mentioned hypothesis. Patients Preoperative endogenous ouabain was measured in 407 patients admitted for elective cardiac surgery and in a validation population of 219 other patients. We also studied the effect of prolonged elevations of circulating exogenous ouabain on renal parameters in rats and the influence of ouabain on podocyte proteins both “in vivo” and “in vitro.” Main Results In the first group of patients, acute kidney injury (2.8%, 8.3%, 20.3%, p < 0.001) and ICU stay (1.4 ± 0.38, 1.7 ± 0.41, 2.4 ± 0.59 days, p = 0.014) increased with each incremental preoperative endogenous ouabain tertile. In a linear regression analysis, the circulating endogenous ouabain value before surgery was the strongest predictor of acute kidney injury. In the validation cohort, acute kidney injury (0%, 5.9%, 8.2%, p < 0.0001) and ICU stay (1.2 ± 0.09, 1.4 ± 0.23, 2.2 ± 0.77 days, p = 0.003) increased with the preoperative endogenous ouabain tertile. Values for preoperative endogenous ouabain significantly improved (area under curve: 0.85) risk prediction over the clinical score alone as measured by integrate discrimination improvement and net reclassification improvement. Finally, in the rat model, elevated circulating ouabain reduced creatinine clearance (–18%, p < 0.05), increased urinary protein excretion (+ 54%, p < 0.05), and reduced expression of podocyte nephrin

  7. 10 CFR 436.20 - Net savings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Net savings. 436.20 Section 436.20 Energy DEPARTMENT OF... Life Cycle Cost Analyses § 436.20 Net savings. For a retrofit project, net savings may be found by... new building design, net savings is the difference between the life cycle costs of an...

  8. 47 CFR 65.450 - Net income.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Net income. 65.450 Section 65.450... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Exchange Carriers § 65.450 Net income. (a) Net... these services. The calculation of expenses entering into the determination of net income shall...

  9. 10 CFR 436.20 - Net savings.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Net savings. 436.20 Section 436.20 Energy DEPARTMENT OF... Life Cycle Cost Analyses § 436.20 Net savings. For a retrofit project, net savings may be found by... new building design, net savings is the difference between the life cycle costs of an...

  10. 47 CFR 65.450 - Net income.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 false Net income. 65.450 Section 65.450... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Exchange Carriers § 65.450 Net income. (a) Net... these services. The calculation of expenses entering into the determination of net income shall...

  11. 47 CFR 65.450 - Net income.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 false Net income. 65.450 Section 65.450... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Exchange Carriers § 65.450 Net income. (a) Net... these services. The calculation of expenses entering into the determination of net income shall...

  12. 7 CFR 51.489 - Well netted.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Well netted. 51.489 Section 51.489 Agriculture... Standards for Grades of Cantaloups 1 Definitions § 51.489 Well netted. Well netted means that to an extent characteristic of the variety the cantaloup is well covered with fully developed, well raised netting,...

  13. 7 CFR 51.489 - Well netted.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Well netted. 51.489 Section 51.489 Agriculture... Standards for Grades of Cantaloups 1 Definitions § 51.489 Well netted. Well netted means that to an extent characteristic of the variety the cantaloup is well covered with fully developed, well raised netting,...

  14. 7 CFR 51.489 - Well netted.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Well netted. 51.489 Section 51.489 Agriculture... Standards for Grades of Cantaloups 1 Definitions § 51.489 Well netted. Well netted means that to an extent characteristic of the variety the cantaloup is well covered with fully developed, well raised netting,...

  15. HIV infection en route to endogenization: two cases

    PubMed Central

    Colson, P; Ravaux, I; Tamalet, C; Glazunova, O; Baptiste, E; Chabriere, E; Wiedemann, A; Lacabaratz, C; Chefrour, M; Picard, C; Stein, A; Levy, Y; Raoult, D

    2014-01-01

    The long-term spontaneous evolution of humans and the human immunodeficiency virus (HIV) is not well characterized; many vertebrate species, including humans, exhibit remnants of other retroviruses in their genomes that question such possible endogenization of HIV. We investigated two HIV-infected patients with no HIV-related disease and no detection with routine tests of plasma HIV RNA or cell-associated HIV DNA. We used Sanger and deep sequencing to retrieve HIV DNA sequences integrated in the human genome and tested the host humoral and cellular immune responses. We noticed that viruses from both patients were inactivated by the high prevalence of the transformation of tryptophan codons into stop codons (25% overall (3–100% per gene) and 24% overall (0–50% per gene)). In contrast, the humoral and/or cellular responses were strong for one patient and moderate for the other, indicating that a productive infection occurred at one stage of the infection. We speculate that the stimulation of APOBEC, the enzyme group that exchanges G for A in viral nucleic acids and is usually inhibited by the HIV protein Vif, has been amplified and made effective from the initial stage of the infection. Furthermore, we propose that a cure for HIV may occur through HIV endogenization in humans, as observed for many other retroviruses in mammals, rather than clearance of all traces of HIV from human cells, which defines viral eradication. PMID:25366539

  16. Surfactant treatments alter endogenous surfactant metabolism in rabbit lungs

    SciTech Connect

    Oetomo, S.B.; Lewis, J.; Ikegami, M.; Jobe, A.H. )

    1990-04-01

    The effect of exogenous surfactant on endogenous surfactant metabolism was evaluated using a single-lobe treatment strategy to compare effects of treated with untreated lung within the same rabbit. Natural rabbit surfactant, Survanta, or 0.45% NaCl was injected into the left main stem bronchus by use of a Swan-Ganz catheter. Radiolabeled palmitic acid was then given by intravascular injection at two times after surfactant treatment, and the ratios of label incorporation and secretion in the left lower lobe to label incorporation and secretion in the right lung were compared. The treatment procedure resulted in a reasonably uniform surfactant distribution and did not disrupt lobar pulmonary blood flow. Natural rabbit surfactant increased incorporation of palmitate into saturated phosphatidylcholine (Sat PC) approximately 2-fold (P less than 0.01), and secretion of labeled Sat PC increased approximately 2.5-fold in the surfactant-treated left lower lobe relative to the right lung (P less than 0.01). Although Survanta did not alter incorporation, it did increase secretion but not to the same extent as rabbit surfactant (P less than 0.01). Alteration of endogenous surfactant Sat PC metabolism in vivo by surfactant treatments was different from that which would have been predicted by previous in vitro studies.

  17. Identifying and quantifying contaminants contributing to endogenous analytes in gas chromatography/mass spectrometry.

    PubMed

    Tsikas, Dimitrios

    2010-09-15

    Contaminants from various sources including medical devices, laboratory materials and the environment, and analytical apparatus may contribute to their endogenous congeners at different stages of the analytical process. Here, an approach is reported for the identification and quantification of contaminating analytes in biological fluids by stable-isotope dilution gas chromatography/mass spectrometry (GC/MS) and gas chromatography/tandem mass spectrometry (GC/MS/MS) methods. This approach is based on the analysis of different sample volumes and determination of the peak area ratio (PAR) of the endogenous analyte to the stable-isotope labeled analogue serving as the internal standard. The PAR is obtained by selected-ion monitoring or selected-reaction monitoring of appropriate ions. Generation of PAR values that correlate inversely with the sample volume subjected to analysis reveals the existence of contamination. The extent of contamination is obtained by plotting the PAR of endogenous analyte to internal standard versus the reciprocal of the sample volume analyzed. Examples are given for uncontaminated and contaminated endogenous analytes in biological samples, including nitrite and nitrate analyzed by GC/MS, and the fatty acid metabolites oleic acid oxide, oleic acid ethanol amide, and arachidonic acid ethanol amide analyzed by GC/MS/MS. Dependence of the PAR of endogenous analyte to its internal standard upon derivatization time reveals a unique kind of contamination that was identified in the GC/MS analysis of nitrate in plasma as pentafluorobenzyl ester. This kind of contamination occurs at the latest stage of GC/MS analysis and cannot be controlled by reference to the internal standard.

  18. Videotutoring via AppalNet.

    ERIC Educational Resources Information Center

    Buchanan, Harriette C.

    The Videotutoring via AppalNet project at Appalachian State University in North Carolina offers supplementary, tutorial assistance to students in certain high risk courses such as history, biology, and mathematics. This program enables instructors to tape test review sessions which are broadcast live and then later rebroadcast at other times on…

  19. SophiNet Version 12

    SciTech Connect

    2012-08-09

    SophiNet Version 12 is part of the code contained in the application ‘oglnet’ and comprises the portions that make ‘oglnet’ receive and display Sophia data from the Sophia Daemon ‘sophiad’. Specifically this encompasses the channel, host and alert receiving and the treeview HUD widget.

  20. Neural Network Development Tool (NETS)

    NASA Technical Reports Server (NTRS)

    Baffes, Paul T.

    1990-01-01

    Artificial neural networks formed from hundreds or thousands of simulated neurons, connected in manner similar to that in human brain. Such network models learning behavior. Using NETS involves translating problem to be solved into input/output pairs, designing network configuration, and training network. Written in C.

  1. The power of neural nets

    NASA Technical Reports Server (NTRS)

    Ryan, J. P.; Shah, B. H.

    1987-01-01

    Implementation of the Hopfield net which is used in the image processing type of applications where only partial information about the image may be available is discussed. The image classification type of algorithm of Hopfield and other learning algorithms, such as the Boltzmann machine and the back-propagation training algorithm, have many vital applications in space.

  2. Endogenous gas gangrene after laparoscopic cholecystectomy.

    PubMed

    Zelić, M; Kunisek, L; Mendrila, D; Gudelj, M; Abram, M; Uravić, M

    2011-01-01

    Clostridial gas gangrene of the abdominal wall is rare, and it is usually associated with organ perforation, immunosuppression or gastrointestinal malignancies. In this paper we present a case of fulminant, endogenous gas gangrene in a 58-year old diabetic female with arterial hypertension and atherosclerosis, following uneventful laparoscopic cholecystectomy. She developed gas gangrene of the abdominal wall 12-hours after cholecystectomy and died 24-hours after the onset of the first symptoms, in spite of treatment.

  3. 26 CFR 1.172-4 - Net operating loss carrybacks and net operating loss carryovers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Net operating loss carrybacks and net operating... Corporations (continued) § 1.172-4 Net operating loss carrybacks and net operating loss carryovers. (a) General provisions—(1) Years to which loss may be carried—(i) In general. In order to compute the net operating...

  4. Endogenous Viral Elements in Animal Genomes

    PubMed Central

    Katzourakis, Aris; Gifford, Robert J.

    2010-01-01

    Integration into the nuclear genome of germ line cells can lead to vertical inheritance of retroviral genes as host alleles. For other viruses, germ line integration has only rarely been documented. Nonetheless, we identified endogenous viral elements (EVEs) derived from ten non-retroviral families by systematic in silico screening of animal genomes, including the first endogenous representatives of double-stranded RNA, reverse-transcribing DNA, and segmented RNA viruses, and the first endogenous DNA viruses in mammalian genomes. Phylogenetic and genomic analysis of EVEs across multiple host species revealed novel information about the origin and evolution of diverse virus groups. Furthermore, several of the elements identified here encode intact open reading frames or are expressed as mRNA. For one element in the primate lineage, we provide statistically robust evidence for exaptation. Our findings establish that genetic material derived from all known viral genome types and replication strategies can enter the animal germ line, greatly broadening the scope of paleovirological studies and indicating a more significant evolutionary role for gene flow from virus to animal genomes than has previously been recognized. PMID:21124940

  5. [Endogenous persistent hypoglicemia of adult: case report].

    PubMed

    Costa, Raquel R; Maia, Frederico F R; Araújo, Levimar R

    2007-02-01

    Persistent Hyperinsulinemic Endogenous hypoglycemia in adults is, in most cases, due to Insulinoma. Nesidioblastosis, a peculiar functional hyperinsulinemia from hypertrophic beta cells, has been described mainly in newborns. This article describes a 34-year-old patient who presented hyperinsulinemic endogenous hypoglycemia clinical and laboratorial situation (Fasting glycemia: 54 mg/dl / Reference Interval (RI): 60-99 mg/dl; Serum insulin: 70.9 mcU/ml / RI: < 29.1 mcU/ml; e C peptide: 7.1 ng/ml / RI: 1.1-5.0 ng/ml). It was suspected Insulinoma. Because of the lack of typical images in radiologic exams (ultrasonography and computerized tomography) it had been decided to do laparotomy, but it was not found any macroscopic pancreatic tumor. Histological and histochemistry examination of a distal pancreatic segment showed alteration suitable to nesidioblastosis. The patient presented clinical stability during the next two months, however, after that, there was a recurrence of a hypoglycemia crisis, refractory to Octreotide administration. It was done "octreoscan", which showed expanded nesidioblastosis, being done extensive partial pancreatectomy. Octreotide was used again, with a good control of the hypoglycemia crisis. As it is an uncommon diagnosis in an adult, the objective of this article is to describe the diagnostic and therapeutic aspects in cases of hyperinsulinemic endogenous hypoglicemia.

  6. Biomarkers of exposure to endogenous oxidative and aldehyde stress.

    PubMed

    Bruce, W Robert; Lee, Owen; Liu, Zhen; Marcon, Norman; Minkin, Salomon; O'Brien, Peter J

    2011-08-01

    We observed an unexpectedly strong association of three different endogenous aldehydes and noted that the association could be explained by multiple reactions in which oxidative stress increased the formation of endogenous aldehydes and endogenous aldehydes increased oxidative stress. These interactions make it reasonable to assess multiple exposures to endogenous oxidative and aldehyde stress with less specific measures such as advanced glycation end-products or protein carbonyls.

  7. Caught in the Net: Perineuronal Nets and Addiction

    PubMed Central

    Slaker, Megan; Blacktop, Jordan M.; Sorg, Barbara A.

    2016-01-01

    Exposure to drugs of abuse induces plasticity in the brain and creates persistent drug-related memories. These changes in plasticity and persistent drug memories are believed to produce aberrant motivation and reinforcement contributing to addiction. Most studies have explored the effect drugs of abuse have on pre- and postsynaptic cells and astrocytes; however, more recently, attention has shifted to explore the effect these drugs have on the extracellular matrix (ECM). Within the ECM are unique structures arranged in a net-like manner, surrounding a subset of neurons called perineuronal nets (PNNs). This review focuses on drug-induced changes in PNNs, the molecules that regulate PNNs, and the expression of PNNs within brain circuitry mediating motivation, reward, and reinforcement as it pertains to addiction. PMID:26904301

  8. Army Net Zero Prove Out. Integrated Net Zero Best Practices

    DTIC Science & Technology

    2014-11-18

    comprehensive perspective for the institutionalization of NZ across the Army and aid in the transition of the NZ Pilot Installation Initiative concepts to a wider... transition and institutionalize Net Zero concepts, responsibility, methods, and implementation activities from the pilot installations to the appropriate...Army Commands (ACOMs)/Direct Reporting Units (DRUs) and all Army installations. The purpose of this task was to support that transition by documenting

  9. [Progress in endogenous plasmid curing of bacteria--a review].

    PubMed

    Feng, Jun; Zhang, Wei; Song, Cunjiang

    2013-11-04

    To investigate the functions of the bacteria endogenous plasmid, which include bacterial drug resistance, symbiosis, capsular formation and heavy metal resistance, the endogenous plasmid needs to be cured first. We reviewed physical, chemical and molecular biological methods of endogenous plasmid curing, clarified the curing principles. The prospective of research on plasmid curing was also discussed, based on our own studies.

  10. Capturing birds with mist nets: A review

    USGS Publications Warehouse

    Keyes, B.E.; Grue, C.E.

    1982-01-01

    Herein we have tried to provide a comprehensive review of mist-netting techniques suitable for both novice and experienced netters. General mist-netting procedures and modifications developed by netters for particular bird species and habitats are included. Factors which influence capture success, including site selection, net specifications and placement, weather, and time of day, are discussed. Guidelines are presented for the care of netted birds and the use of mist-net data in the study of bird communities. The advantages of the use of mist nets over other methods of capturing birds are also discussed.

  11. Petri net controllers for distributed robotic systems

    NASA Technical Reports Server (NTRS)

    Lefebvre, D. R.; Saridis, George N.

    1992-01-01

    Petri nets are a well established modelling technique for analyzing parallel systems. When coupled with an event-driven operating system, Petri nets can provide an effective means for integrating and controlling the functions of distributed robotic applications. Recent work has shown that Petri net graphs can also serve as remarkably intuitive operator interfaces. In this paper, the advantages of using Petri nets as high-level controllers to coordinate robotic functions are outlined, the considerations for designing Petri net controllers are discussed, and simple Petri net structures for implementing an interface for operator supervision are presented. A detailed example is presented which illustrates these concepts for a sensor-based assembly application.

  12. AdaNET research plan

    NASA Technical Reports Server (NTRS)

    Mcbride, John G.

    1990-01-01

    The mission of the AdaNET research effort is to determine how to increase the availability of reusable Ada components and associated software engineering technology to both private and Federal sectors. The effort is structured to define the requirements for transfer of Federally developed software technology, study feasible approaches to meeting the requirements, and to gain experience in applying various technologies and practices. The overall approach to the development of the AdaNET System Specification is presented. A work breakdown structure is presented with each research activity described in detail. The deliverables for each work area are summarized. The overall organization and responsibilities for each research area are described. The schedule and necessary resources are presented for each research activity. The estimated cost is summarized for each activity. The project plan is fully described in the Super Project Expert data file contained on the floppy disk attached to the back cover of this plan.

  13. 1990 Joint Military Net Assessment

    DTIC Science & Technology

    2007-11-02

    the Office of Net Assessment 6 Deputy Director for Theater Assessments and Planning, Office of the Assistant Secretary of Defense for Program Analysis ...countermeasures electronic countermeasures European Economic Community electronic warfare -F- FOFA FY follow-on-forces attack fiscal year -G... analysis of current and projected capabilities of US forces, assisted by allies where appropriate, to deter war and, if deterrence fails, to terminate the

  14. Net sustainable buildings: Approaching future

    NASA Astrophysics Data System (ADS)

    Bojić, Milorad

    2012-11-01

    For a net sustainable building (NSB), the paper develops its definition, and gives its characteristics. The NSB should provide the maximum thermal comfort were its energy consumption is totally covered by energy of renewable origin during its life cycle. The covered energy consumption should be operational and embodied. The used renewable energy may be that of sun and of anergy. The building may be furthermore evaluated regarding its status with regard to the mismatch, primary energy, emergy, exergy, fossil energy, carbon and dissemination.

  15. Software reuse issues affecting AdaNET

    NASA Technical Reports Server (NTRS)

    Mcbride, John G.

    1989-01-01

    The AdaNet program is reviewing its long-term goals and strategies. A significant concern is whether current AdaNet plans adequately address the major strategic issues of software reuse technology. The major reuse issues of providing AdaNet services that should be addressed as part of future AdaNet development are identified and reviewed. Before significant development proceeds, a plan should be developed to resolve the aforementioned issues. This plan should also specify a detailed approach to develop AdaNet. A three phased strategy is recommended. The first phase would consist of requirements analysis and produce an AdaNet system requirements specification. It would consider the requirements of AdaNet in terms of mission needs, commercial realities, and administrative policies affecting development, and the experience of AdaNet and other projects promoting the transfer software engineering technology. Specifically, requirements analysis would be performed to better understand the requirements for AdaNet functions. The second phase would provide a detailed design of the system. The AdaNet should be designed with emphasis on the use of existing technology readily available to the AdaNet program. A number of reuse products are available upon which AdaNet could be based. This would significantly reduce the risk and cost of providing an AdaNet system. Once a design was developed, implementation would proceed in the third phase.

  16. Independent effects of endogenous and exogenous spatial cueing: inhibition of return at endogenously attended target locations.

    PubMed

    Lupiáñez, Juan; Decaix, Caroline; Siéroff, Eric; Chokron, Sylvie; Milliken, Bruce; Bartolomeo, Paolo

    2004-12-01

    Inhibition of return (IOR) is thought to reflect a bias against returning attention to previously attended locations. According to this view, IOR should occur only if attention is withdrawn from the target location prior to target appearance. In the present study, endogenous attention and exogenous cueing were manipulated orthogonally. IOR was observed both when a target appeared at an unexpected location, and when a target appeared at the expected location. A similar pattern of results was obtained in a reanalysis of data from a study with Neglect patients. These results suggest that IOR is independent of endogenous orienting.

  17. Copper and endogenous mediators of estradiol action.

    PubMed

    Fishman, J H; Fishman, J

    1988-04-29

    Divalent copper increases by severalfold specific estradiol binding in rat uterine cytosol at 37 degrees C. Two endogenous substances have now been isolated from the cytosol one of which sharply inhibits the copper effect while the other sharply promotes it. The inhibitor is thermostable, it is adsorbed by dextran coated charcoal and elutes from Sephadex columns with water. The promoter is thermolabile at 60 degrees C, it is not readily adsorbed by the charcoal and elutes from Sephadex columns with KCl. The two substances are thought to be mediators of estradiol action.

  18. Distribution of endogenous retroviruses in crocodilians.

    PubMed

    Jaratlerdsiri, Weerachai; Rodríguez-Zárate, Clara J; Isberg, Sally R; Damayanti, Chandramaya Siska; Miles, Lee G; Chansue, Nantarika; Moran, Chris; Melville, Lorna; Gongora, Jaime

    2009-10-01

    Knowledge of endogenous retroviruses (ERVs) in crocodilians (Crocodylia) is limited, and their distribution among extant species is unclear. Here we analyzed the phylogenetic relationships of these retroelements in 20 species of crocodilians by studying the pro-pol gene. The results showed that crocodilian ERVs (CERVs) cluster into two major clades (CERV 1 and CERV 2). CERV 1 clustered as a sister group of the genus Gammaretrovirus, while CERV 2 clustered distantly with respect to all known ERVs. Interestingly, CERV 1 was found only in crocodiles (Crocodylidae). The data generated here could assist future studies aimed at identifying orthologous and paralogous ERVs among crocodilians.

  19. Diverging patterns with endogenous labor migration.

    PubMed

    Reichlin, P; Rustichini, A

    1998-05-05

    "The standard neoclassical model cannot explain persistent migration flows and lack of cross-country convergence when capital and labor are mobile. Here we present a model where both phenomena may take place.... Our model is based on the Arrow-Romer approach to endogenous growth theory. We single out the importance of a (however weak) scale effect from the size of the workforce.... The main conclusion of this simple model is that lack of convergence, or even divergence, among countries is possible, even with perfect capital mobility and labor mobility."

  20. 29 CFR 1926.105 - Safety nets.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Safety nets. (a) Safety nets shall be provided when workplaces are more than 25 feet above the ground or... shall provide a minimum breaking strength of 5,000 pounds. (e) Forged steel safety hooks or...

  1. 29 CFR 1926.105 - Safety nets.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Safety nets. (a) Safety nets shall be provided when workplaces are more than 25 feet above the ground or... shall provide a minimum breaking strength of 5,000 pounds. (e) Forged steel safety hooks or...

  2. 47 CFR 65.500 - Net income.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Interexchange Carriers § 65.500 Net income. The net income methodology specified in § 65.450 shall be utilized by all interexchange carriers that...

  3. 29 CFR 1926.105 - Safety nets.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... be hung with sufficient clearance to prevent user's contact with the surfaces or structures below... nets be required for bridge construction. (d) The mesh size of nets shall not exceed 6 inches by...

  4. 10 CFR 436.20 - Net savings.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Life Cycle Cost Analyses § 436.20 Net savings. For a retrofit project, net savings may be found by subtracting life cycle costs based on the proposed project from life cycle costs based on not having it. For a new building design, net savings is the difference between the life cycle costs of an...

  5. 10 CFR 436.20 - Net savings.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Life Cycle Cost Analyses § 436.20 Net savings. For a retrofit project, net savings may be found by subtracting life cycle costs based on the proposed project from life cycle costs based on not having it. For a new building design, net savings is the difference between the life cycle costs of an...

  6. 47 CFR 69.302 - Net investment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Net investment. 69.302 Section 69.302... Apportionment of Net Investment § 69.302 Net investment. (a) Investment in Accounts 2001, 1220 and Class B Rural...) Investment in Accounts 2002, 2003 and to the extent such inclusions are allowed by this Commission,...

  7. 47 CFR 69.302 - Net investment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Net investment. 69.302 Section 69.302... Apportionment of Net Investment § 69.302 Net investment. (a) Investment in Accounts 2001, 1220 and Class B Rural...) Investment in Accounts 2002, 2003 and to the extent such inclusions are allowed by this Commission,...

  8. 27 CFR 4.37 - Net contents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Net contents. 4.37 Section 4.37 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.37 Net contents. (a) Statement of net contents. The...

  9. 27 CFR 7.27 - Net contents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Net contents. 7.27 Section 7.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF MALT BEVERAGES Labeling Requirements for Malt Beverages § 7.27 Net contents. (a) Net contents...

  10. 27 CFR 7.27 - Net contents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Net contents. 7.27 Section 7.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF MALT BEVERAGES Labeling Requirements for Malt Beverages § 7.27 Net contents. (a) Net contents...

  11. 27 CFR 4.37 - Net contents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Net contents. 4.37 Section 4.37 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.37 Net contents. (a) Statement of net contents. The...

  12. 27 CFR 4.37 - Net contents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Net contents. 4.37 Section 4.37 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.37 Net contents. (a) Statement of net contents. The...

  13. 27 CFR 7.27 - Net contents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Net contents. 7.27 Section 7.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF MALT BEVERAGES Labeling Requirements for Malt Beverages § 7.27 Net contents. (a) Net contents...

  14. 27 CFR 7.27 - Net contents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Net contents. 7.27 Section 7.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF MALT BEVERAGES Labeling Requirements for Malt Beverages § 7.27 Net contents. (a) Net contents...

  15. 27 CFR 4.37 - Net contents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Net contents. 4.37 Section 4.37 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.37 Net contents. (a) Statement of net contents. The...

  16. 47 CFR 65.500 - Net income.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Net income. 65.500 Section 65.500... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Interexchange Carriers § 65.500 Net income. The net income methodology specified in § 65.450 shall be utilized by all interexchange carriers that...

  17. 47 CFR 65.450 - Net income.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Net income. 65.450 Section 65.450... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Exchange Carriers § 65.450 Net income. (a) Net income shall consist of all revenues derived from the provision of interstate telecommunications...

  18. 47 CFR 65.500 - Net income.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 false Net income. 65.500 Section 65.500... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Interexchange Carriers § 65.500 Net income. The net income methodology specified in § 65.450 shall be utilized by all interexchange carriers that...

  19. 47 CFR 65.500 - Net income.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Net income. 65.500 Section 65.500... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Interexchange Carriers § 65.500 Net income. The net income methodology specified in § 65.450 shall be utilized by all interexchange carriers that...

  20. 46 CFR 69.63 - Net tonnage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Net tonnage. 69.63 Section 69.63 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS Convention Measurement System § 69.63 Net tonnage. Net tonnage (NT) is determined by the formula:...

  1. 25 CFR 502.16 - Net revenues.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Net revenues. 502.16 Section 502.16 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS OF THIS CHAPTER § 502.16 Net revenues. Net revenues means gross gaming revenues of an Indian gaming operation less—...

  2. 47 CFR 69.302 - Net investment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 false Net investment. 69.302 Section 69.302 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Apportionment of Net Investment § 69.302 Net investment. (a) Investment in Accounts 2001, 1220 and Class B...

  3. 46 CFR 69.63 - Net tonnage.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Net tonnage. 69.63 Section 69.63 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS Convention Measurement System § 69.63 Net tonnage. Net tonnage (NT) is determined by the formula:...

  4. 25 CFR 502.16 - Net revenues.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Net revenues. 502.16 Section 502.16 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS OF THIS CHAPTER § 502.16 Net revenues. Net revenues means gross gaming revenues of an Indian gaming operation less—...

  5. 25 CFR 502.16 - Net revenues.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Net revenues. 502.16 Section 502.16 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS OF THIS CHAPTER § 502.16 Net revenues. Net revenues means gross gaming revenues of an Indian gaming operation less—...

  6. 25 CFR 502.16 - Net revenues.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Net revenues. 502.16 Section 502.16 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS OF THIS CHAPTER § 502.16 Net revenues. Net revenues means gross gaming revenues of an Indian gaming operation less—...

  7. 47 CFR 69.302 - Net investment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 false Net investment. 69.302 Section 69.302 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Apportionment of Net Investment § 69.302 Net investment. (a) Investment in Accounts 2001, 1220 and Class B...

  8. 25 CFR 502.16 - Net revenues.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Net revenues. 502.16 Section 502.16 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GENERAL PROVISIONS DEFINITIONS OF THIS CHAPTER § 502.16 Net revenues. Net revenues means gross gaming revenues of an Indian gaming operation less—...

  9. 47 CFR 65.500 - Net income.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 false Net income. 65.500 Section 65.500... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Interexchange Carriers § 65.500 Net income. The net income methodology specified in § 65.450 shall be utilized by all interexchange carriers that...

  10. 46 CFR 69.63 - Net tonnage.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Net tonnage. 69.63 Section 69.63 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS Convention Measurement System § 69.63 Net tonnage. Net tonnage (NT) is determined by the formula:...

  11. 46 CFR 69.63 - Net tonnage.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Net tonnage. 69.63 Section 69.63 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS Convention Measurement System § 69.63 Net tonnage. Net tonnage (NT) is determined by the formula:...

  12. 46 CFR 69.63 - Net tonnage.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Net tonnage. 69.63 Section 69.63 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS Convention Measurement System § 69.63 Net tonnage. Net tonnage (NT) is determined by the formula:...

  13. 47 CFR 69.302 - Net investment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Net investment. 69.302 Section 69.302 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Apportionment of Net Investment § 69.302 Net investment. (a) Investment in Accounts 2001, 1220 and Class B...

  14. 7 CFR 51.489 - Well netted.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Well netted. 51.489 Section 51.489 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Cantaloups 1 Definitions § 51.489 Well netted. Well netted means that to an extent characteristic of the variety the cantaloup is well...

  15. 7 CFR 51.489 - Well netted.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Well netted. 51.489 Section 51.489 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Grades of Cantaloups 1 Definitions § 51.489 Well netted. Well netted means that to an extent characteristic of the variety the cantaloup is well...

  16. Zero-Net-Charge Air Ionizer

    NASA Technical Reports Server (NTRS)

    Woods, W. R., Jr.

    1985-01-01

    Instrument monitors air supplied by air ionizer and regulates ionizer to ensure net charge neutral. High-impedance electrometer and nulling control amplifier regulate output of air ionizer. Primarily intended to furnish ionized air having no net charge, instrument adaptable to generating air with positive or negative net charge is so desired. Useful where integrated circuit chips are manufactured, inspected, tested or assembled.

  17. Revisiting tolerance from the endogenous morphine perspective.

    PubMed

    Stefano, George B; Kream, Richard M; Esch, Tobias

    2009-09-01

    Tolerance represents a dynamic mechanism that can be used to temper various regulatory processes regardless of whether they mediate excitation or inhibition. Tolerance operationally directs state-dependent attenuation of the action of endogenous and exogenous morphine. For example, tolerance ensures that immuno-inhibition induced by morphine does not compromise a requisite functional system over an extended period of time. In the nervous system, tolerance to inhibitory action insures that excitatory tone is resumed. Thus, desensitization sets in and allows various essential processes to be operational once again. Clearly, the temporal rebound of diverse immune and nervous processes involved with opiate actions provides a self-contained operational mechanism to ensure survival of the organism. Furthermore, love and/or pleasure, and satiety, are complex neurobiological phenomena linked to limbic brain reward circuitry. These processes are critically dependent on oxytocin, vasopressin, dopamine, endogenous morphine and serotoninergic signaling. Naturally rewarding and/or pleasurable activities are usually governed by beneficial biological behaviors like eating, sex, and reproduction. It is our contention that critically important tolerance mechanisms extend to behaviors mediated by CNS reward systems. In other words, we become satisfied with sex, food, pleasure for the moment and disinterest creeps in until the "urges" return.

  18. Ubiquitously expressed Human Beta Defensin 1 (hBD1) forms bacteria-entrapping nets in a redox dependent mode of action

    PubMed Central

    Raschig, Judith; Mailänder-Sánchez, Daniela; Berscheid, Anne; Berger, Jürgen; Malek, Nisar P.; Brötz-Oesterhelt, Heike

    2017-01-01

    Ever since the discovery of endogenous host defense antimicrobial peptides it has been discussed how these evolutionary conserved molecules avoid to induce resistance and to remain effective. Human ß-defensin 1 (hBD1) is an ubiquitously expressed endogenous antimicrobial peptide that exhibits qualitatively distinct activities between its oxidized and reduced forms. Here, we explore these antimicrobial mechanisms. Surprisingly, using electron microscopy we detected a so far unknown net-like structure surrounding bacteria, which were treated with the reduced but not the oxidized form of hBD1. A transmigration assay demonstrated that hBD1-derived nets capture bacteria and inhibit bacterial transmigration independent of bacterial killing. The presence of nets could completely prevent migration of hBD1 resistant pathogens and are stable in the presence of human duodenal secretion with a high amount of proteases. In contrast to HD6, cysteins are necessary for net formation. This redox-dependent function serves as an additional mechanism of action for hBD1 and differs from net formation by other defensins such as Paneth cell-derived human α-defensin 6 (HD6). While hBD1red and hBD1ox have distinct antimicrobial profiles and functions, only the reduced form provides additional host protection by entrapping bacteria in extracellular net structures preventing bacterial invasion. Better understanding of the modes of action of endogenous host peptides will help to find new antimicrobial strategies. PMID:28323883

  19. Discovery and Characterization of Mammalian Endogenous Parvoviruses▿ †

    PubMed Central

    Kapoor, Amit; Simmonds, Peter; Lipkin, W. Ian

    2010-01-01

    Public databases of nucleotide sequences contain exponentially increasing amounts of sequence data from mammalian genomes. Through the use of large-scale bioinformatic screening for sequences homologous to exogenous mammalian viruses, we found several sequences related to human and animal parvoviruses (PVs) in the Parvovirus and Dependovirus genera within genomes of several mammals, including rats, wallabies, opossums, guinea pigs, hedgehogs, African elephants, and European rabbits. However, phylogenetic analysis of these endogenous parvovirus (EnPV) sequences demonstrated substantial genetic divergence from exogenous mammalian PVs characterized to date. Entire nonstructural and capsid gene sequences of a novel EnPV were amplified and genetically characterized from rat (Rattus norvegicus) genomic DNA. Rat EnPV sequences were most closely related to members of the genus Parvovirus, with >70% and 65% amino acid identities to nonstructural and capsid proteins of canine parvovirus, respectively. Integration of EnPV into chromosome 5 of rats was confirmed by PCR cloning and sequence analysis of the viral and chromosomal junctions. Using inverse PCR, we determined that the rat genome contains a single copy of rat EnPV. Considering mammalian phylogeny, we estimate that EnPV integrated into the rat genome less than 30 million years ago. Comparative phylogenetic analysis done using all known representative exogenous parvovirus (ExPV) and EnPV sequences showed two major genetic groups of EnPVs, one genetically more similar to genus Parvovirus and the other genetically more similar to the genus Dependovirus. The full extent of the genetic diversity of parvoviruses that have undergone endogenization during evolution of mammals and other vertebrates will be recognized only once complete genomic sequences from a wider range of classes, orders, and species of animals become available. PMID:20943964

  20. Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis.

    PubMed

    Theofilopoulos, Spyridon; Wang, Yuqin; Kitambi, Satish Srinivas; Sacchetti, Paola; Sousa, Kyle M; Bodin, Karl; Kirk, Jayne; Saltó, Carmen; Gustafsson, Magnus; Toledo, Enrique M; Karu, Kersti; Gustafsson, Jan-Åke; Steffensen, Knut R; Ernfors, Patrik; Sjövall, Jan; Griffiths, William J; Arenas, Ernest

    2013-02-01

    Liver X receptors (Lxrα and Lxrβ) are ligand-dependent nuclear receptors critical for ventral midbrain neurogenesis in vivo. However, no endogenous midbrain Lxr ligand has so far been identified. Here we used LC/MS and functional assays to identify cholic acid as a new Lxr ligand. Moreover, 24(S),25-epoxycholesterol (24,25-EC) was found to be the most potent and abundant Lxr ligand in the developing mouse midbrain. Both Lxr ligands promoted neural development in an Lxr-dependent manner in zebrafish in vivo. Notably, each ligand selectively regulated the development of distinct midbrain neuronal populations. Whereas cholic acid increased survival and neurogenesis of Brn3a-positive red nucleus neurons, 24,25-EC promoted dopaminergic neurogenesis. These results identify an entirely new class of highly selective and cell type-specific regulators of neurogenesis and neuronal survival. Moreover, 24,25-EC promoted dopaminergic differentiation of embryonic stem cells, suggesting that Lxr ligands may thus contribute to the development of cell replacement and regenerative therapies for Parkinson's disease.

  1. Biofortification of rice with lysine using endogenous histones.

    PubMed

    Wong, H W; Liu, Q; Sun, S S M

    2015-02-01

    Rice is the most consumed cereal grain in the world, but deficient in the essential amino acid lysine. Therefore, people in developing countries with limited food diversity who rely on rice as their major food source may suffer from malnutrition. Biofortification of stable crops by genetic engineering provides a fast and sustainable method to solve this problem. In this study, two endogenous rice lysine-rich histone proteins, RLRH1 and RLRH2, were over-expressed in rice seeds to achieve lysine biofortification. Their protein sequences passed an allergic sequence-based homology test. Their accumulations in rice seeds were raised to a moderate level by the use of a modified rice glutelin 1 promoter with lowered expression strength to avoid the occurrence of physiological abnormalities like unfolded protein response. The expressed proteins were further targeted to protein storage vacuoles for stable storage using a glutelin 1 signal peptide. The lysine content in the transgenic rice seeds was enhanced by up to 35 %, while other essential amino acids remained balanced, meeting the nutritional standards of the World Health Organization. No obvious unfolded protein response was detected. Different degrees of chalkiness, however, were detected in the transgenic seeds, and were positively correlated with both the levels of accumulated protein and lysine enhancement. This study offered a solution to the lysine deficiency in rice, while at the same time addressing concerns about food safety and physiological abnormalities in biofortified crops.

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

    PubMed Central

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

    2014-01-01

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

  3. Biological redundancy of endogenous GPCR ligands in the gut and the potential for endogenous functional selectivity

    PubMed Central

    Thompson, Georgina L.; Canals, Meritxell; Poole, Daniel P.

    2014-01-01

    This review focuses on the existence and function of multiple endogenous agonists of the somatostatin and opioid receptors with an emphasis on their expression in the gastrointestinal tract. These agonists generally arise from the proteolytic cleavage of prepropeptides during peptide maturation or from degradation of peptides by extracellular or intracellular endopeptidases. In other examples, endogenous peptide agonists for the same G protein-coupled receptors can be products of distinct genes but contain high sequence homology. This apparent biological redundancy has recently been challenged by the realization that different ligands may engender distinct receptor conformations linked to different intracellular signaling profiles and, as such the existence of distinct ligands may underlie mechanisms to finely tune physiological responses. We propose that further characterization of signaling pathways activated by these endogenous ligands will provide invaluable insight into the mechanisms governing biased agonism. Moreover, these ligands may prove useful in the design of novel therapeutic tools to target distinct signaling pathways, thereby favoring desirable effects and limiting detrimental on-target effects. Finally we will discuss the limitations of this area of research and we will highlight the difficulties that need to be addressed when examining endogenous bias in tissues and in animals. PMID:25506328

  4. [Tribulin--a novel endogenous monoaminoxidase inhibitor (dedicated to the memory of Merton Sandler)].

    PubMed

    Medvedev, A R

    1996-01-01

    Tribulin is endogenous monoamine oxidase and benzidiazepine binding inhibitory activity extractable from biological tissues and body fluids into ethyl acetate. Tribulin output is increased in conditions of stress and anxiety. Several chemical components of tribulin have recently been identified. Isatin is a selective inhibitor of monoamine oxidase B. Esters of indoleacetic and 4-hydroxyphenylacetic acids and 4-hydroxyphenyletanol selectively inhibit monoamine oxidase A. Biomedical importance of tribulin and its components is discussed.

  5. 29 CFR 4062.4 - Determinations of net worth and collective net worth.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Determinations of net worth and collective net worth. 4062... CORPORATION LIABILITY LIABILITY FOR TERMINATION OF SINGLE-EMPLOYER PLANS § 4062.4 Determinations of net worth and collective net worth. (a) General rules. When a contributing sponsor, or member(s) of...

  6. 29 CFR 4062.4 - Determinations of net worth and collective net worth.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Determinations of net worth and collective net worth. 4062... CORPORATION LIABILITY LIABILITY FOR TERMINATION OF SINGLE-EMPLOYER PLANS § 4062.4 Determinations of net worth and collective net worth. (a) General rules. When a contributing sponsor, or member(s) of...

  7. Speech Generation from Semantic Nets

    DTIC Science & Technology

    1975-09-01

    Speech Generation from Semantic Nets Page 2 (inPUt and output) is monitored bY a "discourse module" ( Deutsch , 1975) to maintain an accurate...in the Phrase, HEURISTIC RULES Hornby describes three basic positions for adverbs in the c1ause1 "front" position, "mid" position, and "end...34 position, Front position adverbs occur before the subject: •YesterdaY he went home, from there he took a taxi," The interrogative adverbs (e,g, how, when

  8. Artificial nets from superconducting nanogranules

    NASA Astrophysics Data System (ADS)

    Ovchinnikov, Yu. N.; Kresin, V. Z.

    2012-06-01

    We show that a large transport current can flow through superconducting nets composed of nano-clusters. Although thermal and quantum fluctuations lead to a finite value of dissipation, this value can be very small in one- and two-dimensional systems for realistic parameters of the nanoclusters and distances between them. The value of the action for vortex tunneling at zero temperature can be made sufficiently large to make the dissipation negligibly small. We estimate the temperature T 0 of the transition from the thermal activation to quantum tunneling.

  9. Isomorphisms between Petri nets and dataflow graphs

    NASA Technical Reports Server (NTRS)

    Kavi, Krishna M.; Buckles, Billy P.; Bhat, U. Narayan

    1987-01-01

    Dataflow graphs are a generalized model of computation. Uninterpreted dataflow graphs with nondeterminism resolved via probabilities are shown to be isomorphic to a class of Petri nets known as free choice nets. Petri net analysis methods are readily available in the literature and this result makes those methods accessible to dataflow research. Nevertheless, combinatorial explosion can render Petri net analysis inoperative. Using a previously known technique for decomposing free choice nets into smaller components, it is demonstrated that, in principle, it is possible to determine aspects of the overall behavior from the particular behavior of components.

  10. Endogenous Gibberellins and Inhibitors in Relation to Flower Induction and Inflorescence Development in the Olive

    PubMed Central

    Badr, Sayed A.; Hartmann, Hudson T.; Martin, George C.

    1970-01-01

    Comparative analyses of reproductive and vegetative tissues of the olive (Olea europaea L. cv. Manzanillo) for endogenous hormones, particularly inhibitors and gibberellin like substances, were made to study the relation between such hormones and thermoinduction of flowering. Qualitative and quantitative changes in gibberellin-like subtance(s) were observed in lateral buds (potential flower buds) but not in leaves or terminal buds (potential vegetative buds) sampled from orchard trees at intervals during the winter and spring. At least two types of gibberellin-like substances were found in extracts of lateral buds; their levels increased progressively during the low temperature induction period, reaching a maximum shortly before floral initiation. Two types of inhibitors were extracted from buds and leaves. A nonacidic type did not change during the induction stage but decreased considerably during the initiation period. An acidic inhibitor, which was identified as an abscisic acid-like substance, was present at a relatively lower level in lateral (flower) buds than in terminal (vegetative) buds during the induction period. It was concluded that winter chilling induces flowering in the olive possibly by altering a balance between endogenous gibberellins and inhibitors, including abscisic acid. Inflorescence development following the winter chilling period was associated with an increase in the level of endogenous inhibitors and gibberellins. Shoot growth, however, was correlated with a decrease in the inhibitor(s) level. A rise in gibberellin-like activity is believed to be a result, not a cause, of shoot growth. Images PMID:16657528

  11. Fuzzy multimodel of timed Petri nets.

    PubMed

    Hennequin, S; Lefebvre, D; El Moudni, A

    2001-01-01

    This paper deals with discrete event systems (DES) modeled either by discrete timed Petri nets without conflict or by continuous Petri nets. A fuzzy rule-based multimodel is developed for this kind of system. The behavior of each Petri net transition is described by the combination of two linear local fuzzy models. Using the Takagi-Sugemo model in a systematic way, we define the exact modeling for both classes of timed Petri nets. As a result, we notice that classical sets result in the exact description of discrete timed Petri nets. On the contrary, only fuzzy sets are suitable to describe continuous Petri nets exactly. The proposed fuzzy multimodels are very interesting from a control point of view. In that sense, general results such as convergence for timed Petri nets are given.

  12. Digestion of fat and fatty acids along the gastrointestinal tract of broiler chickens.

    PubMed

    Tancharoenrat, P; Ravindran, V; Zaefarian, F; Ravindran, G

    2014-02-01

    Two experiments were conducted. The first experiment investigated the digestion of fat and fatty acids (FA) from soybean oil and tallow along the gastrointestinal tract of broiler chickens. The second experiment was conducted to determine endogenous fat and FA losses and the FA profile of chicken bile. In experiment 1, 2-wk-old broilers were fed corn-soy diets supplemented with 50 g/kg of soybean oil or tallow for 7 d and digesta were collected from the duodenum, upper jejunum, upper ileum, and lower ileum. Apparent digestibility coefficients were calculated using the titanium marker ratio in diets, and digesta. Digestibility of fat was determined to be negative in the duodenum, indicating marked net secretion of fat into this segment. Fat was rapidly digested in the jejunum, with digestibility coefficients of 0.60 to 0.64 being determined at the end of the jejunum. The digestion of fat continued in the upper ileum. The apparent digestibility coefficient of fat determined at lower ileum in soybean oil diets was higher (P < 0.05) than that in tallow diets (0.82 vs. 0.74). Linoleic acid was digested throughout the intestinal tract, whereas the digestion of palmitic, stearic, and oleic acids started only in the jejunum. Measurements at the lower ileal level showed that the unsaturated FA (linoleic and oleic acids) were well digested (0.90 to 0.94), irrespective of the source of fat. In contrast, the digestibility of saturated FA (palmitic and stearic acids) was influenced (P < 0.05) by the fat source. Digestibility coefficients of palmitic and stearic acids at lower ileum were markedly higher (P < 0.05) in the diet containing soybean oil (0.77 to 0.85) compared with that containing tallow (0.58 to 0.68). In experiment 2, ileal endogenous fat loss was determined to be 1,714 mg/kg of DM intake. Endogenous fat was composed mainly of palmitic (75 g/kg), stearic (131 g/kg), oleic (73 g/kg), linoleic (133 g/kg), and arachidonic (60 g/kg) acids. Fatty acid profile of

  13. Pro-Nets versus No-Nets: Differences in Urban Older Adults' Predilections for Internet Use

    ERIC Educational Resources Information Center

    Cresci, M. Kay; Yarandi, Hossein N.; Morrell, Roger W.

    2010-01-01

    Enthusiasm for information technology (IT) is growing among older adults. Many older adults enjoy IT and the Internet (Pro-Nets), but others have no desire to use it (No-Nets). This study found that Pro-Nets and No-Nets were different on a number of variables that might predict IT use. No-Nets were older, had less education and income, were…

  14. NetLander thermal control

    NASA Astrophysics Data System (ADS)

    Romberg, O.; Bodendieck, F.; Block, J.; Nadalini, R.; Schneider, N.

    2003-11-01

    The first mission to establish a network of stations on the surface of Mars will be the NetLander mission, which is planned for the near future. Four identical surface modules are equipped with science payloads dedicated to study the atmosphere and geosphere of Mars at four different landing locations spread over the two hemispheres. The mission duration will be one Martian year. The surface modules and their sensitive electronics compartments have to withstand a wide range of hostile conditions on Mars. Further constraints are given during flight, where heat can be exchanged only across small interfaces. The purpose of the NetLander thermal control system is to maintain the electronics and battery temperatures within a narrow band. Contrasting demands of reduced heat leaks and effective dump of surplus heat require new technologies and advanced design concepts to be satisfied under strict mass limits imposed. Recently the first thermal test model with the original thermal equipment has been completed and tested. The model includes a high performance insulation combined with an innovative Loop Heat Pipe system integrated into a one-to-one lander-structure. The paper describes the design and development activities as well as the ground test campaign performed in simulated Martian environment.

  15. Involvement of Endogenous Retroviruses in Prion Diseases

    PubMed Central

    Lee, Yun-Jung; Jeong, Byung-Hoon; Choi, Eun-Kyung; Kim, Yong-Sun

    2013-01-01

    For millions of years, vertebrates have been continuously exposed to infection by retroviruses. Ancient retroviral infection of germline cells resulted in the formation and accumulation of inherited retrovirus sequences in host genomes. These inherited retroviruses are referred to as endogenous retroviruses (ERVs), and recent estimates have revealed that a significant portion of animal genomes is made up of ERVs. Although various host factors have suppressed ERV activation, both positive and negative functions have been reported for some ERVs in normal and abnormal physiological conditions, such as in disease states. Similar to other complex diseases, ERV activation has been observed in prion diseases, and this review will discuss the potential involvement of ERVs in prion diseases. PMID:25437206

  16. Endogenous GABAA receptor activity suppresses glioma growth.

    PubMed

    Blanchart, A; Fernando, R; Häring, M; Assaife-Lopes, N; Romanov, R A; Andäng, M; Harkany, T; Ernfors, P

    2017-02-09

    Although genome alterations driving glioma by fueling cell malignancy have largely been resolved, less is known of the impact of tumor environment on disease progression. Here, we demonstrate functional GABAA receptor-activated currents in human glioblastoma cells and show the existence of a continuous GABA signaling within the tumor cell mass that significantly affects tumor growth and survival expectancy in mouse models. Endogenous GABA released by tumor cells, attenuates proliferation of the glioma cells with enriched expression of stem/progenitor markers and with competence to seed growth of new tumors. Our results suggest that GABA levels rapidly increase in tumors impeding further growth. Thus, shunting chloride ions by a maintained local GABAA receptor activity within glioma cells has a significant impact on tumor development by attenuating proliferation, reducing tumor growth and prolonging survival, a mechanism that may have important impact on therapy resistance and recurrence following tumor resection.

  17. Endogenous Group Formation via Unproductive Costs

    PubMed Central

    Aimone, Jason A.; Iannaccone, Laurence R.; Makowsky, Michael D.; Rubin, Jared

    2013-01-01

    Sacrifice is widely believed to enhance cooperation in churches, communes, gangs, clans, military units, and many other groups. We find that sacrifice can also work in the lab, apart from special ideologies, identities, or interactions. Our subjects play a modified VCM game—one in which they can voluntarily join groups that provide reduced rates of return on private investment. This leads to both endogenous sorting (because free-riders tend to reject the reduced-rate option) and substitution (because reduced private productivity favours increased club involvement). Seemingly unproductive costs thus serve to screen out free-riders, attract conditional cooperators, boost club production, and increase member welfare. The sacrifice mechanism is simple and particularly useful where monitoring difficulties impede punishment, exclusion, fees, and other more standard solutions. PMID:24808623

  18. Chitin is endogenously produced in vertebrates.

    PubMed

    Tang, W Joyce; Fernandez, Javier G; Sohn, Joel J; Amemiya, Chris T

    2015-03-30

    Chitin, a biopolymer of N-acetylglucosamine, is abundant in invertebrates and fungi and is an important structural molecule [1, 2]. There has been a longstanding belief that vertebrates do not produce chitin; however, we have obtained compelling evidence to the contrary. Chitin synthase genes are present in numerous fishes and amphibians, and chitin is localized in situ to the lumen of the developing zebrafish gut, in epithelial cells of fish scales, and in at least three different cell types in larval salamander appendages. Chitin synthase gene knockdowns and various histochemical experiments in zebrafish further authenticated our results. Finally, a polysaccharide was extracted from scales of salmon that exhibited all the chemical hallmarks of chitin. Our data and analyses demonstrate the existence of endogenous chitin in vertebrates and suggest that it serves multiple roles in vertebrate biology.

  19. Chitin is endogenously produced in vertebrates

    PubMed Central

    Sohn, Joel J.; Amemiya, Chris T.

    2015-01-01

    Chitin, a biopolymer of N-acetylglucosamine, is abundant in invertebrates and fungi, and is an important structural molecule. There has been a longstanding belief that vertebrates do not produce chitin, however, we have obtained compelling evidence to the contrary. Chitin synthase genes are present in numerous fishes and amphibians, and chitin is localized in situ to the lumen of the developing zebrafish gut, in epithelial cells of fish scales, and in at least three different cell types in larval salamander appendages. Chitin synthase gene knockdowns and various histochemical experiments in zebrafish further authenticated our results. Finally, a polysaccharide was extracted from scales of salmon that exhibited all the chemical hallmarks of chitin. Our data and analyses demonstrate the existence of endogenous chitin in vertebrates and suggest that it serves multiple roles in vertebrate biology. PMID:25772447

  20. [Endogenous retroviruses are associated with autoimmune diseases].

    PubMed

    Nexø, Bjørn A; Jensen, Sara B; Hansen, Bettina; Laska, Magdalena J

    2016-06-13

    Retroviruses can be transmitted in two fundamentally different ways: 1) They can be horizontally transmitted as infectious virus, or 2) they can integrate in the germ line and be transmitted to offspring and the offsprings' offspring as DNA. The latter is called endogenous viruses. The mode of transmission is called vertical. Viral variants of importance for development of disease must be more frequent among diseased persons than among healthy individuals. Multiple sclerosis, diabetes and rheumatoid arthritis are all associated with sets of endogenouos retroviruses but not the same sets. If a virus grows and this contributes to disease, one should be able to alleviate disease with antiretroviral drugs. We call for clinical trials to elucidate this issue.

  1. Dynamic option pricing with endogenous stochastic arbitrage

    NASA Astrophysics Data System (ADS)

    Contreras, Mauricio; Montalva, Rodrigo; Pellicer, Rely; Villena, Marcelo

    2010-09-01

    Only few efforts have been made in order to relax one of the key assumptions of the Black-Scholes model: the no-arbitrage assumption. This is despite the fact that arbitrage processes usually exist in the real world, even though they tend to be short-lived. The purpose of this paper is to develop an option pricing model with endogenous stochastic arbitrage, capable of modelling in a general fashion any future and underlying asset that deviate itself from its market equilibrium. Thus, this investigation calibrates empirically the arbitrage on the futures on the S&P 500 index using transaction data from September 1997 to June 2009, from here a specific type of arbitrage called “arbitrage bubble”, based on a t-step function, is identified and hence used in our model. The theoretical results obtained for Binary and European call options, for this kind of arbitrage, show that an investment strategy that takes advantage of the identified arbitrage possibility can be defined, whenever it is possible to anticipate in relative terms the amplitude and timespan of the process. Finally, the new trajectory of the stock price is analytically estimated for a specific case of arbitrage and some numerical illustrations are developed. We find that the consequences of a finite and small endogenous arbitrage not only change the trajectory of the asset price during the period when it started, but also after the arbitrage bubble has already gone. In this context, our model will allow us to calibrate the B-S model to that new trajectory even when the arbitrage already started.

  2. How Active Are Porcine Endogenous Retroviruses (PERVs)?

    PubMed Central

    Denner, Joachim

    2016-01-01

    Porcine endogenous retroviruses (PERVs) represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs), which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (CRISPR/Cas) technology. PMID:27527207

  3. Optimization and characterization of the endogenous production of protoporphyrin IX in a yeast model

    NASA Astrophysics Data System (ADS)

    Joniová, Jaroslava; Gerelli, Emmanuel; Zellweger, Matthieu; Wagnières, Georges

    2016-12-01

    The availability of reproducible, convenient, and inexpensive model organisms able to generate predictable levels of endogenous porphyrins, including protoporphyrin IX (PpIX), is essential in photomedicine research. Saccharomyces cerevisiae produces endogenous PpIX and was used as a model organism for this study with the aim to maximize endogenous PpIX fluorescence intensity. It was found that PpIX fluorescence was significantly enhanced by administration of 5-aminolevulinic acid (ALA) and 2,2‧-bipyridyl. Fluorescence intensity and spectroscopy of PpIX produced endogenously were measured in diluted yeast solutions under various conditions. The optimal protocol was: 5 μM ALA and 1 mM 2,2‧-bipyridyl administered synchronously at 32°C. After 3 h, PpIX in yeast demonstrated similar steady-state and time-resolved spectroscopy as that of PpIX in DMSO. Moreover, under hypoxic conditions, the reciprocal lifetime of PpIX delayed fluorescence measured in real time was correlated to the partial pressure of oxygen (pO2) measured concomitantly with a commercially available pO2 probe. These data show that yeast can, in optimal conditions, reproducibly generate PpIX. This is of interest in various fields such as photodiagnosis, photodynamic therapy, and photobiomodulation. Use of this model organism focuses on essential mechanisms, without the complexity of a multicellular organism.

  4. Inhibition of Borna disease virus replication by an endogenous bornavirus-like element in the ground squirrel genome.

    PubMed

    Fujino, Kan; Horie, Masayuki; Honda, Tomoyuki; Merriman, Dana K; Tomonaga, Keizo

    2014-09-09

    Animal genomes contain endogenous viral sequences, such as endogenous retroviruses and retrotransposons. Recently, we and others discovered that nonretroviral viruses also have been endogenized in many vertebrate genomes. Bornaviruses belong to the Mononegavirales and have left endogenous fragments, called "endogenous bornavirus-like elements" (EBLs), in the genomes of many mammals. The striking features of EBLs are that they contain relatively long ORFs which have high sequence homology to the extant bornavirus proteins. Furthermore, some EBLs derived from bornavirus nucleoprotein (EBLNs) have been shown to be transcribed as mRNA and probably are translated into proteins. These features lead us to speculate that EBLs may function as cellular coopted genes. An EBLN element in the genome of the thirteen-lined ground squirrel (Ictidomys tridecemlineatus), itEBLN, encodes an ORF with 77% amino acid sequence identity to the current bornavirus nucleoprotein. In this study, we cloned itEBLN from the ground squirrel genome and investigated its involvement in Borna disease virus (BDV) replication. Interestingly, itEBLN, but not a human EBLN, colocalized with the viral factory in the nucleus and appeared to affect BDV polymerase activity by being incorporated into the viral ribonucleoprotein. Our data show that, as do certain endogenous retroviruses, itEBLN potentially may inhibit infection by related exogenous viruses in vivo.

  5. Inhibition of Borna disease virus replication by an endogenous bornavirus-like element in the ground squirrel genome

    PubMed Central

    Fujino, Kan; Horie, Masayuki; Honda, Tomoyuki; Merriman, Dana K.; Tomonaga, Keizo

    2014-01-01

    Animal genomes contain endogenous viral sequences, such as endogenous retroviruses and retrotransposons. Recently, we and others discovered that nonretroviral viruses also have been endogenized in many vertebrate genomes. Bornaviruses belong to the Mononegavirales and have left endogenous fragments, called “endogenous bornavirus-like elements” (EBLs), in the genomes of many mammals. The striking features of EBLs are that they contain relatively long ORFs which have high sequence homology to the extant bornavirus proteins. Furthermore, some EBLs derived from bornavirus nucleoprotein (EBLNs) have been shown to be transcribed as mRNA and probably are translated into proteins. These features lead us to speculate that EBLs may function as cellular coopted genes. An EBLN element in the genome of the thirteen-lined ground squirrel (Ictidomys tridecemlineatus), itEBLN, encodes an ORF with 77% amino acid sequence identity to the current bornavirus nucleoprotein. In this study, we cloned itEBLN from the ground squirrel genome and investigated its involvement in Borna disease virus (BDV) replication. Interestingly, itEBLN, but not a human EBLN, colocalized with the viral factory in the nucleus and appeared to affect BDV polymerase activity by being incorporated into the viral ribonucleoprotein. Our data show that, as do certain endogenous retroviruses, itEBLN potentially may inhibit infection by related exogenous viruses in vivo. PMID:25157155

  6. The first three-fold interpenetrated framework with two different four-connected uniform nets of 6(6) dia and new chiral 8(6) mdf networks.

    PubMed

    Wang, Zhi-Long; Fang, Wei-Hui; Yang, Guo-Yu

    2010-11-21

    Two three-fold interpenetrated frameworks, [LnCuL(4)][Ln(0.25)Cu(0.25)L] (Ln = Dy 1, Er 2; HL = 4-(pyridin-4-yl)benzoic acid), have been made. Their structures contain two kinds of four-connected uniform nets: dia and mdf nets. The mdf net is a new chiral 8(6) net with the long vertex symbol (8(1).8(3).8(4).8(4).8(4).8(4)).

  7. Predictors of mosquito net use in Ghana

    PubMed Central

    2011-01-01

    Background During the past decade the malaria control community has been successful in dramatically increasing the number of households that own mosquito nets. However, as many as half of nets already in households go unused. This study examines the factors associated with use of nets owned in Ghana. Methods The data come from an August 2008 survey in Ghana of households with a pregnant woman or a guardian of a child under five, conducted during the rainy season. 1796 households were included in this analysis, which generated a sample of 1,852 mosquito nets. Using each net owned as the unit of analysis, multivariate logistic regression was used to examine the relationship of net used last night with 23 potentially explanatory variables having to do with characteristics of the household, of the respondent, and of the net. Odds Ratios, p-values, and confidence intervals were calculated for each variable to develop an explanatory model. Results The final multivariate model consisted of 10 variables statistically associated with whether or not the net was used the prior night: rural location, lower SES, not using coils for mosquito control, fewer nets in the household, newer nets and those in better condition, light blue colour, higher level of education of the guardian of the child under five, knowing that mosquitoes transmit malaria, and paying for the net instead of obtaining it free of charge. Conclusions The results of this study suggest that net use would increase in Ghana if coloured nets were made available in mass distributions as well as in the commercial market; if programmes emphasize that malaria is caused only by night-biting mosquitoes, and that nets protect against mosquitoes better than coils and need to be used even if coils are burning; if donated nets are replaced more frequently so that households have nets that are in good condition; and if there were support for the commercial market so that those who can afford to purchase a net and want to

  8. Net-Shape HIP Powder Metallurgy Components for Rocket Engines

    NASA Technical Reports Server (NTRS)

    Bampton, Cliff; Goodin, Wes; VanDaam, Tom; Creeger, Gordon; James, Steve

    2005-01-01

    True net shape consolidation of powder metal (PM) by hot isostatic pressing (HIP) provides opportunities for many cost, performance and life benefits over conventional fabrication processes for large rocket engine structures. Various forms of selectively net-shape PM have been around for thirty years or so. However, it is only recently that major applications have been pursued for rocket engine hardware fabricated in the United States. The method employs sacrificial metallic tooling (HIP capsule and shaped inserts), which is removed from the part after HIP consolidation of the powder, by selective acid dissolution. Full exploitation of net-shape PM requires innovative approaches in both component design and materials and processing details. The benefits include: uniform and homogeneous microstructure with no porosity, irrespective of component shape and size; elimination of welds and the associated quality and life limitations; removal of traditional producibility constraints on design freedom, such as forgeability and machinability, and scale-up to very large, monolithic parts, limited only by the size of existing HIP furnaces. Net-shape PM HIP also enables fabrication of complex configurations providing additional, unique functionalities. The progress made in these areas will be described. Then critical aspects of the technology that still require significant further development and maturation will be discussed from the perspective of an engine systems builder and end-user of the technology.

  9. Bound states in string nets

    NASA Astrophysics Data System (ADS)

    Schulz, Marc Daniel; Dusuel, Sébastien; Vidal, Julien

    2016-11-01

    We discuss the emergence of bound states in the low-energy spectrum of the string-net Hamiltonian in the presence of a string tension. In the ladder geometry, we show that a single bound state arises either for a finite tension or in the zero-tension limit depending on the theory considered. In the latter case, we perturbatively compute the binding energy as a function of the total quantum dimension. We also address this issue in the honeycomb lattice where the number of bound states in the topological phase depends on the total quantum dimension. Finally, the internal structure of these bound states is analyzed in the zero-tension limit.

  10. Amino acid metabolism by perfused rat hindquarter. Effects of insulin, leucine and 2-chloro-4-methylvalerate.

    PubMed Central

    Davis, E J; Lee, S H

    1985-01-01

    Hindquarters from starved rats were perfused without substrates but in the presence of an O2- and CO2-carrying perfluorocarbon emulsion to evaluate principally the metabolism of individual endogenous and protein-derived amino acids by this muscle preparation. This experimental model was shown, by a battery of metabolite measurements, to maintain cellular homoeostasis for at least 2h. The net appearance of most amino acids closely approximated their frequency of occurrence in muscle proteins, showing that they are not significantly metabolized. Exceptions were the branched-chain amino acids, methionine and those amino acids that are interconvertible with intermediates of the citrate cycle and pyruvate through coupled transaminations. The evidence indicates that only valine, isoleucine, aspartate and probably methionine can be catabolized by skeletal muscle to provide carbon precursors for glutamate/glutamine and alanine that are formed de novo by protein-catabolic muscle. The protein-sparing effects of insulin and leucine were confirmed. Although each decreased proteolysis and the net appearance of free amino acids, they were generally without effect on the ratios of amino acids formed. 2-Chloro-4-methylvalerate selectively stimulated the removal rate for the branched-chain amino acids, confirming the idea that the branched-chain oxo acid dehydrogenase normally limits the rate of their oxidation by muscle. It is also concluded that, since alanine was not formed in excess of that found in muscle proteins when no glucose was added as substrate, the excess of alanine (carbon) released from muscles in other studies is derived to a large extent, but not exclusively, from preformed carbohydrate. PMID:3899101

  11. Role of endogenous gastric mucosal prostaglandins in the formation of acute gastric mucosal lesions induced by aspirin, ethanol, HCl and CH3COOH.

    PubMed

    Amioka, I; Arima, T; Nagashima, H

    1987-06-01

    The role of endogenous mucosal prostaglandins (PGs) in the production of acute gastric mucosal lesions (AGML) was examined in rats. Aspirin, ethanol or 0.6 N-HCl was given intragastrically and 20% acetic acid was injected into the gastric wall. Endogenous gastric mucosal PG (A + B), PGE and PGF were determined by radioimmunoassay. Their gastric contents were markedly reduced by aspirin administration (p less than 0.001). The level of gastric mucosal PGs still remained low (p less than 0.001) after the aspirin-induced AGML began to heal. Furthermore, rats with AGML induced by ethanol, HCl or acetic acid, showed no decrease in endogenous gastric mucosal PGs compared with the controls. These findings indicated that endogenous PGs are not necessary for either the induction or healing of experimental AGML.

  12. New model of cytoprotection/adaptive cytoprotection in rats: endogenous small irritants, antiulcer agents and indomethacin.

    PubMed

    Sikirić, P; Seiwerth, S; Desković, S; Grabarević, Z; Marović, A; Rucman, R; Petek, M; Konjevoda, P; Jadrijević, S; Sosa, T; Perović, D; Aralica, G; Turković, B

    1999-01-01

    .g., (increased) gastric acid secretion, duodenal reflux in gastric content in rats with termino-lateral gastrojejunal anastomosis) (endogenous irritant studies)). These factors caused modifications of agents' activities not, as initially thought, giving simple 'cytoprotection', but being only cytoprotective, or adaptive cytoprotective, or both cytoprotective and adaptive cytoprotective. Atropine (10 mg/kg i.p.) and ranitidine (10 mg) had only cytoprotective activity (exogenous irritant-studies), whereas pentadecapeptide BPC157 (10 microg or 10 ng), and omeprazole (10 mg) had mainly adaptive cytoprotective activity (endogenous/exogenous irritant studies) or both cytoprotective and adaptive cytoprotective activities (exogenous/exogenous irritant studies). Augmentation of the lesions by indomethacin (5 mg/kg s.c.), showed that only events preceding the late challenge with ethanol may be prostaglandin-dependent in both models. The second, adaptive cytoprotective part, seen after late ethanol challenge, may be either prostaglandin-dependent (exogenous/exogenous irritant studies) or non-dependent (endogenous/exogenous irritant studies). Both spontaneous lesion reduction, as an essential mechanism of adaptive cytoprotection, and the further lesion reduction by agents, such as pentadecapeptide BPC 157 and omeprazole, suggests that these agents function as an essential link between the various reactions in cytoprotection/adaptive cytoprotection.

  13. Two endogenous proteins that induce cell wall extension in plants

    NASA Technical Reports Server (NTRS)

    McQueen-Mason, S.; Durachko, D. M.; Cosgrove, D. J.

    1992-01-01

    Plant cell enlargement is regulated by wall relaxation and yielding, which is thought to be catalyzed by elusive "wall-loosening" enzymes. By employing a reconstitution approach, we found that a crude protein extract from the cell walls of growing cucumber seedlings possessed the ability to induce the extension of isolated cell walls. This activity was restricted to the growing region of the stem and could induce the extension of isolated cell walls from various dicot stems and the leaves of amaryllidaceous monocots, but was less effective on grass coleoptile walls. Endogenous and reconstituted wall extension activities showed similar sensitivities to pH, metal ions, thiol reducing agents, proteases, and boiling in methanol or water. Sequential HPLC fractionation of the active wall extract revealed two proteins with molecular masses of 29 and 30 kD associated with the activity. Each protein, by itself, could induce wall extension without detectable hydrolytic breakdown of the wall. These proteins appear to mediate "acid growth" responses of isolated walls and may catalyze plant cell wall extension by a novel biochemical mechanism.

  14. Synthetic polyphosphate inhibits endogenous coagulation and platelet aggregation in vitro

    PubMed Central

    Yang, Xiaoyang; Wan, Mengjie; Liang, Ting; Peng, Minyuan; Chen, Fangping

    2017-01-01

    Platelet-derived polyphosphate has previously been indicated to induce coagulation. However, industrially synthesized polyphosphate has been found to have different effects from those of the platelet-derived form. The present study investigated whether synthetic sodium polyphosphate inhibits coagulation using routine coagulation tests and thromboelastography. Synthetic polyphosphate was found to inhibit adenosine diphosphate-, epinephrine-, arachidonic acid-, ristocetin-, thrombin-, oxytocin- and pituitrin-induced platelet aggregation. The effects of synthetic polyphosphate in clotting inhibition were revealed by the analysis of clotting factor activity and platelet aggregation tests. Synthetic polyphosphate may inhibit platelet aggregation by reducing platelet calcium levels, as indicated by the results of flow cytometric analysis and high-throughput fluorescent screening. Furthermore, analysis of thromboxane (TX)B2 by ELISA indicated that synthetic polyphosphate reduces platelet aggregation by inhibiting the TXA2 signaling pathway. In conclusion, synthetic polyphosphate inhibits clotting factor activity and endogenous coagulation by reducing the levels of calcium ions and TXA2 to curb platelet aggregation. PMID:28123708

  15. Evidences for involvement of endogenous cAMP in Arabidopsis defense responses to Verticillium toxins.

    PubMed

    Jiang, Jing; Fan, Ling Wen; Wu, Wei Hua

    2005-08-01

    Although there were reports suggesting the involvement of endogenous cAMP in plant defense signaling cascades, there is no direct evidence supporting this notion yet and the detailed mechanism is unclear. In the present study, we have used pathogenic fungi Verticillium dahliae and Arabidopsis plants as a model system of plant-microb interaction to demonstrate the function of endogenous cAMP in Arabidopsis defense responses. Both V. dahliae inoculation and Verticillium toxins injection induced typical "wilt" symptoms in Arabidopsis seedlings. When either 8-Br-AMP (a membrane permeable cAMP analogue) or salicylic acid (SA) was applied to Arabidopsis, the plants became resistant to V. dahliae toxins. However, addition of 8-Br-AMP did not increase the resistance of Arabidopsis transgenic plants deficient in SA to the toxins, suggesting that cAMP might act upstream of SA in plant defense signaling pathway. Indeed, 8-Br-cAMP and forskolin, an activator of adenylyl cyclase, significantly stimulated the endogenous SA level in plants, whereas DDA, an inhibitor of adenylyl cyclase dramatically reduced toxin-induced SA increase. Both the endogenous cAMP and SA increased significantly in Arabidopsis seedlings treated with toxins. Furthermore, transcription level of pathogenesis-related protein 1 gene (PR1) was strongly induced by both 8-Br-cAMP and the toxin treatment. Taken together, our data demonstrate that endogenous cAMP is involved in plant defense responses against Verticillium-secreted toxins by regulating the production of the known signal SA in plant defense pathway.

  16. NASA Net Zero Energy Buildings Roadmap

    SciTech Connect

    Pless, S.; Scheib, J.; Torcellini, P.; Hendron, B.; Slovensky, M.

    2014-10-01

    In preparation for the time-phased net zero energy requirement for new federal buildings starting in 2020, set forth in Executive Order 13514, NASA requested that the National Renewable Energy Laboratory (NREL) to develop a roadmap for NASA's compliance. NASA detailed a Statement of Work that requested information on strategic, organizational, and tactical aspects of net zero energy buildings. In response, this document presents a high-level approach to net zero energy planning, design, construction, and operations, based on NREL's first-hand experience procuring net zero energy construction, and based on NREL and other industry research on net zero energy feasibility. The strategic approach to net zero energy starts with an interpretation of the executive order language relating to net zero energy. Specifically, this roadmap defines a net zero energy acquisition process as one that sets an aggressive energy use intensity goal for the building in project planning, meets the reduced demand goal through energy efficiency strategies and technologies, then adds renewable energy in a prioritized manner, using building-associated, emission- free sources first, to offset the annual energy use required at the building; the net zero energy process extends through the life of the building, requiring a balance of energy use and production in each calendar year.

  17. A case of Erysipelothrix rhusiopathiae causing bilateral endogenous endophthalmitis.

    PubMed

    Elvy, J; Hanspal, I; Simcock, P

    2008-11-01

    This report describes a case of bilateral endogenous endophthalmitis caused by Erysipelothrix rhusiopathiae, an occupational zoonotic pathogen, which was successfully treated with intravenous penicillin G followed by oral linezolid. This is believed to be the first report of E rhusiopathiae causing endogenous endophthalmitis.

  18. Endogenous opioid peptides in regulation of innate immunity cell functions.

    PubMed

    Gein, S V; Baeva, T A

    2011-03-01

    Endogenous opioid peptides comprise a group of bioregulatory factors involved in regulation of functional activity of various physiological systems of an organism. One of most important functions of endogenous opioids is their involvement in the interaction between cells of the nervous and immune systems. Summary data on the effects of opioid peptides on regulation of functions of innate immunity cells are presented.

  19. Absolute Quantification of Endogenous Ras Isoform Abundance

    PubMed Central

    Mageean, Craig J.; Griffiths, John R.; Smith, Duncan L.; Clague, Michael J.; Prior, Ian A.

    2015-01-01

    Ras proteins are important signalling hubs situated near the top of networks controlling cell proliferation, differentiation and survival. Three almost identical isoforms, HRAS, KRAS and NRAS, are ubiquitously expressed yet have differing biological and oncogenic properties. In order to help understand the relative biological contributions of each isoform we have optimised a quantitative proteomics method for accurately measuring Ras isoform protein copy number per cell. The use of isotopic protein standards together with selected reaction monitoring for diagnostic peptides is sensitive, robust and suitable for application to sub-milligram quantities of lysates. We find that in a panel of isogenic SW48 colorectal cancer cells, endogenous Ras proteins are highly abundant with ≥260,000 total Ras protein copies per cell and the rank order of isoform abundance is KRAS>NRAS≥HRAS. A subset of oncogenic KRAS mutants exhibit increased total cellular Ras abundance and altered the ratio of mutant versus wild type KRAS protein. These data and methodology are significant because Ras protein copy number is required to parameterise models of signalling networks and informs interpretation of isoform-specific Ras functional data. PMID:26560143

  20. Stem Cell Stimulation of Endogenous Myocyte Regeneration

    PubMed Central

    Weil, Brian R.; Canty, John M.

    2015-01-01

    Cell-based therapy has emerged as a promising approach to combat the myocyte loss and cardiac remodeling that characterize the progression of left ventricular dysfunction to heart failure. Several clinical trials conducted during the past decade have shown that a variety of autologous bone marrow- and peripheral blood-derived stem and progenitor cell populations can be safely administered to patients with ischemic heart disease and yield modest improvements in cardiac function. Concurrently, rapid progress has been made at the preclinical level to identify novel therapeutic cell populations, delineate the mechanisms underlying cell-mediated cardiac repair, and optimize cell-based approaches for clinical use. The following review summarizes the progress that has been made in this rapidly evolving field over the past decade and examines how our current understanding of the mechanisms involved in successful cardiac regeneration should direct future investigation in this area. Particular emphasis is placed on discussion of the general hypothesis that the benefits of cell therapy primarily result from stimulation of endogenous cardiac repair processes that have only recently been identified in the adult mammalian heart, rather than direct differentiation of exogenous cells. Continued scientific investigation in this area will guide the optimization of cell-based approaches for myocardial regeneration, with the ultimate goal of clinical implementation and substantial improvement in our ability to restore cardiac function in ischemic heart disease patients. PMID:23577634

  1. Stem cell stimulation of endogenous myocyte regeneration.

    PubMed

    Weil, Brian R; Canty, John M

    2013-08-01

    Cell-based therapy has emerged as a promising approach to combat the myocyte loss and cardiac remodelling that characterize the progression of left ventricular dysfunction to heart failure. Several clinical trials conducted over the past decade have shown that a variety of autologous bone-marrow- and peripheral-blood-derived stem and progenitor cell populations can be safely administered to patients with ischaemic heart disease and yield modest improvements in cardiac function. Concurrently, rapid progress has been made at the pre-clinical level to identify novel therapeutic cell populations, delineate the mechanisms underlying cell-mediated cardiac repair and optimize cell-based approaches for clinical use. The following review summarizes the progress that has been made in this rapidly evolving field over the past decade and examines how our current understanding of the mechanisms involved in successful cardiac regeneration should direct future investigation in this area. Particular emphasis is placed on discussion of the general hypothesis that the benefits of cell therapy primarily result from stimulation of endogenous cardiac repair processes that have only recently been identified in the adult mammalian heart, rather than direct differentiation of exogenous cells. Continued scientific investigation in this area will guide the optimization of cell-based approaches for myocardial regeneration, with the ultimate goal of clinical implementation and substantial improvement in our ability to restore cardiac function in ischaemic heart disease patients.

  2. Endogenous polyamine function—the RNA perspective

    PubMed Central

    Lightfoot, Helen L.; Hall, Jonathan

    2014-01-01

    Recent progress with techniques for monitoring RNA structure in cells such as ‘DMS-Seq’ and ‘Structure-Seq’ suggests that a new era of RNA structure-function exploration is on the horizon. This will also include systematic investigation of the factors required for the structural integrity of RNA. In this context, much evidence accumulated over 50 years suggests that polyamines play important roles as modulators of RNA structure. Here, we summarize and discuss recent literature relating to the roles of these small endogenous molecules in RNA function. We have included studies directed at understanding the binding interactions of polyamines with polynucleotides, tRNA, rRNA, mRNA and ribozymes using chemical, biochemical and spectroscopic tools. In brief, polyamines bind RNA in a sequence-selective fashion and induce changes in RNA structure in context-dependent manners. In some cases the functional consequences of these interactions have been observed in cells. Most notably, polyamine-mediated effects on RNA are frequently distinct from those of divalent cations (i.e. Mg2+) confirming their roles as independent molecular entities which help drive RNA-mediated processes. PMID:25232095

  3. Endogenous prion protein attenuates experimentally induced colitis.

    PubMed

    Martin, Gary R; Keenan, Catherine M; Sharkey, Keith A; Jirik, Frank R

    2011-11-01

    Although the cellular prion protein (PrP(C)) is expressed in the enteric nervous system and lamina propria, its function(s) in the gut is unknown. Because PrP(C) may exert a cytoprotective effect in response to various physiologic stressors, we hypothesized that PrP(C) expression levels might modulate the severity of experimental colitis. We evaluated the course of dextran sodium sulfate (DSS)-induced colitis in hemizygous Tga20 transgenic mice (approximately sevenfold overexpression of PrP(C)), Prnp(-/-) mice, and wild-type mice. On day 7, colon length, disease severity, and histologic activity indices were determined. Unlike DSS-treated wild-type and Prnp(-/-) animals, PrP(C) overexpressing mice were resistant to colitis induction, exhibited much milder histopathologic features, and did not exhibit weight loss or colonic shortening. In keeping with these results, pro-survival molecule expression and/or phosphorylation levels were elevated in DSS-treated Tga20 mice, whereas pro-inflammatory cytokine production and pSTAT3 levels were reduced. In contrast, DSS-treated Prnp(-/-) mice exhibited increased BAD protein expression and a cytokine expression profile predicted to favor inflammation and differentiation. PrP(C) expression from both the endogenous Prnp locus or the Tga20 transgene was increased in the colons of DSS-treated mice. Considered together, these findings demonstrate that PrP(C) has a previously unrecognized cytoprotective and/or anti-inflammatory function within the murine colon.

  4. Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes

    PubMed Central

    Gilbert, C.; Meik, J. M.; Dashevsky, D.; Card, D. C.; Castoe, T. A.; Schaack, S.

    2014-01-01

    We report the discovery of endogenous viral elements (EVEs) from Hepadnaviridae, Bornaviridae and Circoviridae in the speckled rattlesnake, Crotalus mitchellii, the first viperid snake for which a draft whole genome sequence assembly is available. Analysis of the draft assembly reveals genome fragments from the three virus families were inserted into the genome of this snake over the past 50 Myr. Cross-species PCR screening of orthologous loci and computational scanning of the python and king cobra genomes reveals that circoviruses integrated most recently (within the last approx. 10 Myr), whereas bornaviruses and hepadnaviruses integrated at least approximately 13 and approximately 50 Ma, respectively. This is, to our knowledge, the first report of circo-, borna- and hepadnaviruses in snakes and the first characterization of non-retroviral EVEs in non-avian reptiles. Our study provides a window into the historical dynamics of viruses in these host lineages and shows that their evolution involved multiple host-switches between mammals and reptiles. PMID:25080342

  5. Identification of receptors for pig endogenous retrovirus.

    PubMed

    Ericsson, Thomas A; Takeuchi, Yasuhiro; Templin, Christian; Quinn, Gary; Farhadian, Shelli F; Wood, James C; Oldmixon, Beth A; Suling, Kristen M; Ishii, Jennifer K; Kitagawa, Yoshinori; Miyazawa, Takayuki; Salomon, Daniel R; Weiss, Robin A; Patience, Clive

    2003-05-27

    Xenotransplantation of porcine tissues has the potential to treat a wide variety of major health problems including organ failure and diabetes. Balanced against the potential benefits of xenotransplantation, however, is the risk of human infection with a porcine microorganism. In particular, the transmission of porcine endogenous retrovirus (PERV) is a major concern [Chapman, L. E. & Bloom, E. T. (2001) J. Am. Med. Assoc. 285, 2304-2306]. Here we report the identification of two, sequence-related, human proteins that act as receptors for PERV-A, encoded by genes located on chromosomes 8 and 17. We also describe homologs from baboon and porcine cells that also are active as receptors. Conversely, activity could not be demonstrated with a syntenic murine receptor homolog. Sequence analysis indicates that PERV-A receptors [human PERV-A receptor (HuPAR)-1, HuPAR-2, baboon PERV-A receptor 2, and porcine PERV-A receptor] are multiple membrane-spanning proteins similar to receptors for other gammaretroviruses. Expression is widespread in human tissues including peripheral blood mononuclear cells, but their biological functions are unknown. The identification of the PERV-A receptors opens avenues of research necessary for a more complete assessment of the retroviral risks of pig to human xenotransplantation.

  6. Role of endogenous thiols in protection

    NASA Astrophysics Data System (ADS)

    Vos, O.

    Aminothiols represent the most important group of radioprotective compounds. The most effective compounds administered at an optimal dose and time before irradiation are able to provide a protection in mice with a dose reduction factor (DRF) of about 2-2.5. The working mechanism can partly be explained as a scavenging process of radicals induced in water and partly as a chemical repair process of injured DNA. The endogenous aminothiol which has far-out the highest intracellular concentration is glutathione (GSH). The importance of intracellular GSH in determining cellular radiosensitivity has been shown by irradiating cells that had very low GSH levels. Such cells appear to have a high radiosensitivity, especially in hypoxic conditions. On the other hand, it has been demonstrated that induction of a high GSH level (100-200% above the normal level) provides only a small protection. In vitro experiments with DNA indicate that thiols with a high positive charge condense in the vicinity of DNA and are effective protectors, whereas thiols with a negative charge are kep away from it and are poor protectors. In comparison with the most effective exogenous aminothiols like cysteamine and WR1065, GSH is not an effective radioprotector. Putative explanations for this relatively poor protective ability of GSH are presented.

  7. Endogenic modification of impact craters on Mercury

    NASA Technical Reports Server (NTRS)

    Schultz, P. H.

    1977-01-01

    The presence of internally modified impact craters on Mercury's surface may be used to evaluate the possibility of Mercurian volcanism. Such craters are similar to the floor-fractured and mare-filled craters observed on the moon. Mariner-10 images show that most such craters occur, as on the moon, near plains-filled basins. Color-ratio images have indicated that some Mercurian craters manifest red plains materials on their floors. These features may be associated with lava analogous to mare basalts in some lunar craters, or with compositionally distinct subsurface material preserved within the impact crater. Several basins manifest photometric contrasts between basin exteriors and basin-filling plains. Dark haloes are observed around some impact craters superimposed on the interior plains. This suggests the excavation of compositionally distinct material. Some possible endogenic features are discerned, despite the poor surface resolution, such as irregular rimless depressions. It is felt that volcanism may have occurred on Mercury, and that in some areas it may be similar to that of the lunar Mare Australe region.

  8. Endogenous Electric Fields May Guide Neocortical Network Activity

    PubMed Central

    Fröhlich, Flavio; McCormick, David A.

    2011-01-01

    Local field potentials and the underlying endogenous electric fields (EFs) are traditionally considered to be epiphenomena of structured neuronal network activity. Recently, however, externally applied EFs have been shown to modulate pharmacologically evoked network activity in rodent hippocampus. In contrast, very little is known about the role of endogenous EFs during physiological activity states in neocortex. Here we used the neocortical slow oscillation in vitro as a model system to show that weak sinusoidal and naturalistic EFs enhance and entrain physiological neocortical network activity with an amplitude threshold within the range of in vivo endogenous field strengths. Modulation of network activity by positive and negative feedback fields based on the network activity in real-time provide direct evidence for a feedback loop between neuronal activity and endogenous EF. This significant susceptibility of active networks to EFs that only cause small changes in membrane potential in individual neurons suggests that endogenous EFs could guide neocortical network activity. PMID:20624597

  9. Utilizing an endogenous pathway for 1-butanol production in Saccharomyces cerevisiae.

    PubMed

    Si, Tong; Luo, Yunzi; Xiao, Han; Zhao, Huimin

    2014-03-01

    Microbial production of higher alcohols from renewable feedstock has attracted intensive attention thanks to its potential as a source for next-generation gasoline substitutes. Here we report the discovery, characterization and engineering of an endogenous 1-butanol pathway in Saccharomyces cerevisiae. Upon introduction of a single gene deletion adh1Δ, S. cerevisiae was able to accumulate more than 120 mg/L 1-butanol from glucose in rich medium. Precursor feeding, ¹³C-isotope labeling and gene deletion experiments demonstrated that the endogenous 1-butanol production was dependent on catabolism of threonine in a manner similar to fusel alcohol production by the Ehrlich pathway. Specifically, the leucine biosynthesis pathway was engaged in the conversion of key 2-keto acid intermediates. Overexpression of the pathway enzymes and elimination of competing pathways achieved the highest reported 1-butanol titer in S. cerevisiae (242.8 mg/L).

  10. Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain.

    PubMed

    Roques, Bernard P; Fournié-Zaluski, Marie-Claude; Wurm, Michel

    2012-04-01

    Chronic pain remains unsatisfactorily treated, and few novel painkillers have reached the market in the past century. Increasing the levels of the main endogenous opioid peptides - enkephalins - by inhibiting their two inactivating ectopeptidases, neprilysin and aminopeptidase N, has analgesic effects in various models of inflammatory and neuropathic pain. Stemming from the same pharmacological concept, fatty acid amide hydrolase (FAAH) inhibitors have also been found to have analgesic effects in pain models by preventing the breakdown of endogenous cannabinoids. Dual enkephalinase inhibitors and FAAH inhibitors are now in early-stage clinical trials. In this Review, we compare the effects of these two potential classes of novel analgesics and describe the progress in their rational design. We also consider the challenges in their clinical development and opportunities for combination therapies.

  11. Revelation of endogenously bound Fe(2+) ions in the crystal structure of ferritin from Escherichia coli.

    PubMed

    Thiruselvam, Viswanathan; Sivaraman, Padavattan; Kumarevel, Thirumananseri; Ponnuswamy, Mondikalipudur Nanjappagounder

    2014-10-24

    Ferritin is an iron regulatory protein. It is responsible for storage and detoxification of excess iron thereby it regulates iron level in the body. Here we report the crystal structure of ferritin with two endogenously expressed Fe atoms binding in both the sites. The protein was purified and characterized by MALDI-TOF and N-terminal amino acid sequencing. The crystal belongs to I4 space group and it diffracted up to 2.5Å. The structural analysis suggested that it crystallizes as hexamer and confirmed that it happened to be the first report of endogenously expressed Fe ions incorporated in both the A and B sites, situated in between the helices.

  12. Measures of net oxidant concentration in seawater

    NASA Astrophysics Data System (ADS)

    Jackson, George A.; Williams, Peter M.

    1988-02-01

    Dissolved oxygen deficits in the ocean have been used as a measure of the organic matter oxidized in a volume of water. Such organic matter is usually assumed to be predominantly settled particles. Using dissolved oxygen concentration in this way has two problems: first, it does not differentiate between oxidant consumed by the pool of dissolved organic matter present near the ocean surface and oxidant consumed by organic matter contained by falling particles; second, it does not account for other oxidant sources, such as nitrate, which can be as important to organic matter decay as oxygen in low-oxygen water, such as off Peru or in the Southern California submarine basins. New parameters provide better measures of the net oxidant concentration in a water parcel. One such, NetOx, is changed only by gaseous exchange with the atmosphere, exchange with the benthos, or the production or consumption of sinking particles. A simplified version of NetOx, NetOx = [O2] + 1.25[NO3-] - [TOC], where TOC (total organic carbon), the dissolved organic carbon (DOC) plus the suspended particulate organic carbon (POC), provides an index based on the usually dominant variables. Calculation of NetOx and a second property, NetOC ([O2] - [TOC]), for data from GEOSECS and ourselves in the Atlantic and Pacific oceans using property-property graphs show differences from those from oxygen deficits alone. Comparison of NetOx and NetOC concentrations at high and low latitudes of the Pacific Ocean shows the difference in surface water oxidant concentrations is even larger than the difference in oxygen concentration. Vertical particle fluxes off Peru calculated from NetOx gradients are much greater than those calculated from oxygen gradients. The potential value of NetOx and NetOC as parameters to understand particle fluxes implies that determination of TOC should be a routine part of hydrographic measurements.

  13. Studies on the endogenous phospholipids of chick embryo myocardium and their in vitro hydrolysis by endogenous phospholipases during embryogenesis.

    PubMed

    Helmy, Fatma M; Aikins, Anthea; Hughes, Jeniter; Belfield, Carrie; Juracka, Amal

    2007-01-01

    The phospholipid profiles of the myocardium (from 10- and 18-day old chick embryos and 13-day old chick) and their in vitro response to the endogenous lipolytic enzymes (mainly of the phospholipase group) at pH 7.4 and 38 degrees C for 60 min were analyzed by TLC technology and densitometry. Cardiolipin (CL) was shown to be one of the major phospholipids of the chick embryo myocardium and its concentration increased as the chick embryo advanced in development. Monolysocardiolipin (MLCL) was produced subsequent to in vitro incubation of whole tissue homogenates in all myocardia studied as well as a concurrent reduction in CL. This deacylation of CL increased in magnitude as the chick embryo advanced in development indicating its age relatedness. The level of phosphatidyl ethanolamine (PE) plasmalogen was also high in all myocardia studied. Lyso alkenyl PE (LPE) was produced subsequent to in vitro incubation and its level increased as the chick embryo advanced in development, indicating PLA(2) action on the sn-2 fatty acid of PE. Phosphatidyl choline (PC) plasmalogen was also present in the chick embryo myocardium and its level increased gradually as the chick embryo advanced in development. In contrast, yolk-sac membrane contains very minute amounts of CL and PE. No PC was detected and no LPE was formed following in vitro incubation. The yolk of the unfertilized chicken egg has no CL and has very minute amounts of PE, no PC and no lysophospholipids were detected following in vitro incubation in all samples analyzed.

  14. A rooted net of life.

    PubMed

    Williams, David; Fournier, Gregory P; Lapierre, Pascal; Swithers, Kristen S; Green, Anna G; Andam, Cheryl P; Gogarten, J Peter

    2011-09-21

    Phylogenetic reconstruction using DNA and protein sequences has allowed the reconstruction of evolutionary histories encompassing all life. We present and discuss a means to incorporate much of this rich narrative into a single model that acknowledges the discrete evolutionary units that constitute the organism. Briefly, this Rooted Net of Life genome phylogeny is constructed around an initial, well resolved and rooted tree scaffold inferred from a supermatrix of combined ribosomal genes. Extant sampled ribosomes form the leaves of the tree scaffold. These leaves, but not necessarily the deeper parts of the scaffold, can be considered to represent a genome or pan-genome, and to be associated with members of other gene families within that sequenced (pan)genome. Unrooted phylogenies of gene families containing four or more members are reconstructed and superimposed over the scaffold. Initially, reticulations are formed where incongruities between topologies exist. Given sufficient evidence, edges may then be differentiated as those representing vertical lines of inheritance within lineages and those representing horizontal genetic transfers or endosymbioses between lineages.

  15. Parallelizing Timed Petri Net simulations

    NASA Technical Reports Server (NTRS)

    Nicol, David M.

    1993-01-01

    The possibility of using parallel processing to accelerate the simulation of Timed Petri Nets (TPN's) was studied. It was recognized that complex system development tools often transform system descriptions into TPN's or TPN-like models, which are then simulated to obtain information about system behavior. Viewed this way, it was important that the parallelization of TPN's be as automatic as possible, to admit the possibility of the parallelization being embedded in the system design tool. Later years of the grant were devoted to examining the problem of joint performance and reliability analysis, to explore whether both types of analysis could be accomplished within a single framework. In this final report, the results of our studies are summarized. We believe that the problem of parallelizing TPN's automatically for MIMD architectures has been almost completely solved for a large and important class of problems. Our initial investigations into joint performance/reliability analysis are two-fold; it was shown that Monte Carlo simulation, with importance sampling, offers promise of joint analysis in the context of a single tool, and methods for the parallel simulation of general Continuous Time Markov Chains, a model framework within which joint performance/reliability models can be cast, were developed. However, very much more work is needed to determine the scope and generality of these approaches. The results obtained in our two studies, future directions for this type of work, and a list of publications are included.

  16. A Rooted Net of Life

    PubMed Central

    2011-01-01

    Abstract Phylogenetic reconstruction using DNA and protein sequences has allowed the reconstruction of evolutionary histories encompassing all life. We present and discuss a means to incorporate much of this rich narrative into a single model that acknowledges the discrete evolutionary units that constitute the organism. Briefly, this Rooted Net of Life genome phylogeny is constructed around an initial, well resolved and rooted tree scaffold inferred from a supermatrix of combined ribosomal genes. Extant sampled ribosomes form the leaves of the tree scaffold. These leaves, but not necessarily the deeper parts of the scaffold, can be considered to represent a genome or pan-genome, and to be associated with members of other gene families within that sequenced (pan)genome. Unrooted phylogenies of gene families containing four or more members are reconstructed and superimposed over the scaffold. Initially, reticulations are formed where incongruities between topologies exist. Given sufficient evidence, edges may then be differentiated as those representing vertical lines of inheritance within lineages and those representing horizontal genetic transfers or endosymbioses between lineages. Reviewers W. Ford Doolittle, Eric Bapteste and Robert Beiko. PMID:21936906

  17. Endogenous neuro-protectants in ammonia toxicity in the central nervous system: facts and hypotheses.

    PubMed

    Albrecht, Jan; Wegrzynowicz, Michał

    2005-12-01

    The paper overviews experimental evidence suggestive of the engagement of three endogenous metabolites: taurine, kynurenic acid, and glutathione (GSH) in the protection of central nervous system (CNS) cells against ammonia toxicity. Intrastriatal administration of taurine via microdialysis probe attenuates ammonia-induced accumulation of extracellular cyclic guanosine monophosphate (cGMP) resulting from over-activation of the N-methyl-D: -aspartate/nitric oxide (NMDA/NO) pathway, and this effect involves agonistic effect of taurine on the GABA-A and glycine receptors. Taurine also counteracts generation of free radicals, increased release of dopamine, and its metabolism to dihydroxyphenylacetic acid (DOPAC). Taurine reduces ammonia-induced increase of cell volume (edema) in cerebrocortical slices by a mechanism involving GABA-A receptors. Massive release of radiolabeled or endogenous taurine from CNS tissues by ammonia in vivo and in vitro is thought to promote its neuroprotective action, by making the amino acid available for interaction with cell membranes and/or by driving excess water out of the CNS cells (astrocytes) that underwent ammonia-induced swelling. Ammonia in vivo and in vitro affects in variable ways the synthesis of kynurenic acid (KYNA). Since KYNA is an endogenous NMDA receptor antagonist with a high affinity towards its glycine site, changes in its content may counter over-activation or depression of glutaminergic transmission observed at the different stages of hyperammonemia. GSH is a major antioxidant in the CNS whose synthesis is partly compartmented between neurons and astrocytes: astrocytic GSH is a source of precursors for the synthesis of neuronal GSH. Ammonia in vitro stimulates GSH synthesis in cultured astrocytes, which may compensate for increased GSH consumption (decreased GSH/GSSG ratio) in neurons.

  18. 78 FR 72393 - Net Investment Income Tax

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-02

    ...This document contains final regulations under section 1411 of the Internal Revenue Code (Code). These regulations provide guidance on the general application of the Net Investment Income Tax and the computation of Net Investment Income. The regulations affect individuals, estates, and trusts whose incomes meet certain income...

  19. How is ERBE net radiation defined?

    Atmospheric Science Data Center

    2014-12-08

    ... top of the atmosphere (TOA) as the following: Net (TOA) = Solar_down (TOA) - SW_up (TOA) - LW_up (TOA) where Solar_down (TOA) is ... a net radiative energy surplus/deficit of the Earth system, respectively. ERBE: General Questions ...

  20. The Net Neutrality Debate: The Basics

    ERIC Educational Resources Information Center

    Greenfield, Rich

    2006-01-01

    Rich Greenfield examines the basics of today's net neutrality debate that is likely to be an ongoing issue for society. Greenfield states the problems inherent in the definition of "net neutrality" used by Common Cause: "Network neutrality is the principle that Internet users should be able to access any web content they choose and…

  1. 27 CFR 5.38 - Net contents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Net contents. 5.38 Section 5.38 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF DISTILLED SPIRITS Labeling Requirements for Distilled Spirits § 5.38 Net contents. (a)...

  2. 27 CFR 5.38 - Net contents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Net contents. 5.38 Section 5.38 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Labeling Requirements for Distilled Spirits § 5.38 Net contents. (a)...

  3. 27 CFR 5.38 - Net contents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Net contents. 5.38 Section 5.38 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Labeling Requirements for Distilled Spirits § 5.38 Net contents. (a)...

  4. 27 CFR 5.38 - Net contents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Net contents. 5.38 Section 5.38 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Labeling Requirements for Distilled Spirits § 5.38 Net contents. (a)...

  5. 27 CFR 5.38 - Net contents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Net contents. 5.38 Section 5.38 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF DISTILLED SPIRITS Labeling Requirements for Distilled Spirits § 5.38 Net contents. (a)...

  6. VruiNet Version 12(SOPHIA)

    SciTech Connect

    None, None

    2012-08-09

    VruiNet Version 12 is the code used exclusively by the executable ‘vruinet’. VruiNet Version 12 provides a wrapper around the code for ‘oglnet’ that makes it compatible for VRUI systems such as the CAVE at CAES.

  7. 47 CFR 65.450 - Net income.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Net income. 65.450 Section 65.450 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) INTERSTATE RATE OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Exchange Carriers § 65.450 Net income. (a)...

  8. FloriNet Handbook for Participating Libraries.

    ERIC Educational Resources Information Center

    Florida Dept. of State, Tallahassee. Div. of Library and Information Services.

    FloriNet--the Florida Library Online Resource Information Network--was first envisioned by a Florida Network Planning Task Force in 1994 as the aggregate of networked information in Florida libraries, including library networks, independent libraries, statewide databases, Free-Nets, and as-yet unimagined information resources. This document is a…

  9. 27 CFR 19.644 - Net contents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Net contents. 19.644 Section 19.644 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Liquor Bottle and Label Requirements Bottle Label Requirements § 19.644 Net contents. The...

  10. 27 CFR 4.37 - Net contents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... metric system of measure as follows: (1) If more than one liter, net contents shall be stated in liters...) Equivalent volumes of 100 fluid ounces or more will be stated in fluid ounces only, accurate to the nearest... contents need not be stated on any label if the net contents are displayed by having the same blown,...

  11. 27 CFR 7.27 - Net contents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... stated. (3) If more than 1 pint, but less than 1 quart, the net contents shall be stated in fractions of a quart, or in pints and fluid ounces. (4) If more than 1 quart, but less than 1 gallon, the net contents shall be stated in fractions of a gallon, or in quarts, pints, and fluid ounces. (5) If more...

  12. Workshop: Promoting Sustainability Through Net Zero Strategies

    EPA Science Inventory

    In 2011, EPA’s Office of Research and Development (ORD) signed an MOU with the U.S. Army to support the Army’s Net Zero initiative. The 17 Net Zero pilot installations aim to produce as much energy as used; limit freshwater use and increase water reuse; and reduce the generation ...

  13. Teaching and Learning with the Net Generation

    ERIC Educational Resources Information Center

    Barnes, Kassandra; Marateo, Raymond C.; Ferris, S. Pixy

    2007-01-01

    As the Net Generation places increasingly greater demands on educators, students and teachers must jointly consider innovative ways of teaching and learning. In this, educators are supported by the fact that the Net Generation wants to learn. However, these same educators should not fail to realize that this generation learns differently from…

  14. RadNet Sampling and Analyses Schedules

    EPA Pesticide Factsheets

    RadNet air monitors operate continuously and samples of air, precipitation and drinking water and analyzed on a routine schedule. RadNet can send deployable monitors to any U.S. location in the case of a radiological emergency.

  15. Description of SchoolNet, SchoolNet Plus, and the Ameritech Agreement.

    ERIC Educational Resources Information Center

    Ohio State Legislative Office of Education Oversight, Columbus.

    This informational memorandum is the first in a series of reports focusing on the SchoolNet initiatives. It describes SchoolNet, SchoolNet Plus, and the Ameritech Agreement, presenting background information on their funding authorities, purposes, key players, organizational structures, and statutory timeframes. The report also describes how…

  16. Endogenous neurotrophins and plasticity following spinal deafferentation.

    PubMed

    Ramer, Matt S

    2012-05-01

    Neurons intrinsic to the spinal cord dorsal horn receive input from various classes of long-distance projection systems. Two of the best known of these are primary afferent and descending monoaminergic axons. Together with intrinsic interneurons, activity in these axonal populations shapes the early part of the sensory experience before it is transmitted to supraspinal structures via ascending projection axons. Injury to dorsal roots, which contain the centrally projecting branches of primary afferent axons, results in their permanent disconnection from the spinal cord, as well as sensory dysfunction such as pain. In animals, experimental dorsal root injuries affecting a small number of roots produce dynamic behavioural changes, providing evidence for the now familiar concept that sensory processing at the level of the spinal cord is not hard-wired. Changes in behaviour following rhizotomy suggest changes in spinal sensory circuitry, and we and others have shown that the density of spinal serotonergic axons as well as processes of inhibitory interneurons increases following rhizotomy. Intact primary afferent axons are less apt to sprout into denervated territory. Recent work from our group has asked (1) what is the stimulus that induces sprouting of serotonergic (and other) axons and (2) what prevents spared primary afferent axons from occupying the territory of those lost to injury. This article will review the evidence that a single factor upregulated by dorsal root injury, brain-derived neurotrophic factor (BDNF), underpins both serotonergic sprouting and a lack of primary afferent plasticity. BDNF also differentially modulates some of the behavioural consequences of dorsal root injury: antagonizing endogenous BDNF improves spontaneous mechanosensory recovery but prevents recovery from rhizotomy-induced hypersensitivity to cold. These findings reinforce the notion that in disease states as complex and variable as spinal cord injury, single pharmacological

  17. Revelation of endogenously bound Fe{sup 2+} ions in the crystal structure of ferritin from Escherichia coli

    SciTech Connect

    Thiruselvam, Viswanathan; Sivaraman, Padavattan; Kumarevel, Thirumananseri; Ponnuswamy, Mondikalipudur Nanjappagounder

    2014-10-24

    Highlights: • Crystal structure of ferritin was determined. • Endogenously expressed iron’s were identified. • Binuclear iron sites were observed at A and B active sites. - Abstract: Ferritin is an iron regulatory protein. It is responsible for storage and detoxification of excess iron thereby it regulates iron level in the body. Here we report the crystal structure of ferritin with two endogenously expressed Fe atoms binding in both the sites. The protein was purified and characterized by MALDI-TOF and N-terminal amino acid sequencing. The crystal belongs to I4 space group and it diffracted up to 2.5 Å. The structural analysis suggested that it crystallizes as hexamer and confirmed that it happened to be the first report of endogenously expressed Fe ions incorporated in both the A and B sites, situated in between the helices.

  18. Neural Net Safety Monitor Design

    NASA Technical Reports Server (NTRS)

    Larson, Richard R.

    2007-01-01

    The National Aeronautics and Space Administration (NASA) at the Dryden Flight Research Center (DFRC) has been conducting flight-test research using an F-15 aircraft (figure 1). This aircraft has been specially modified to interface a neural net (NN) controller as part of a single-string Airborne Research Test System (ARTS) computer with the existing quad-redundant flight control system (FCC) shown in figure 2. The NN commands are passed to FCC channels 2 and 4 and are cross channel data linked (CCDL) to the other computers as shown. Numerous types of fault-detection monitors exist in the FCC when the NN mode is engaged; these monitors would cause an automatic disengagement of the NN in the event of a triggering fault. Unfortunately, these monitors still may not prevent a possible NN hard-over command from coming through to the control laws. Therefore, an additional and unique safety monitor was designed for a single-string source that allows authority at maximum actuator rates but protects the pilot and structural loads against excessive g-limits in the case of a NN hard-over command input. This additional monitor resides in the FCCs and is executed before the control laws are computed. This presentation describes a floating limiter (FL) concept1 that was developed and successfully test-flown for this program (figure 3). The FL computes the rate of change of the NN commands that are input to the FCC from the ARTS. A window is created with upper and lower boundaries, which is constantly floating and trying to stay centered as the NN command rates are changing. The limiter works by only allowing the window to move at a much slower rate than those of the NN commands. Anywhere within the window, however, full rates are allowed. If a rate persists in one direction, it will eventually hit the boundary and be rate-limited to the floating limiter rate. When this happens, a persistent counter begins and after a limit is reached, a NN disengage command is generated. The

  19. Interactions between endogenous and exogenous attention on cortical visual processing.

    PubMed

    Hopfinger, Joseph B; West, Vicki M

    2006-06-01

    Sensory processing is affected by both endogenous and exogenous mechanisms of attention, although how these mechanisms interact in the brain has remained unclear. In the present study, we recorded event-related potentials (ERPs) to investigate how multiple stages of information processing in the brain are affected when endogenous and exogenous mechanisms are concurrently engaged. We found that the earliest stage of cortical visual processing, the striate-cortex-generated C1, was immune to attentional modulation, even when endogenous and exogenous attention converged on a common location. The earliest stage of processing to be affected in this experiment was the late phase of the extrastriate-cortex-generated P1 component, which was dominated by exogenous attention. Processing at this stage was enhanced by exogenous attention, regardless of where endogenous attention had been oriented. Endogenous attention, however, dominated a later, higher-order stage of processing indexed by an enhancement of the P300 that was unaffected by exogenous attention. Critically, between these early and late stages, an interaction was found wherein endogenous and exogenous attention produced distinct, and overlapping, effects on information processing. At the same time that exogenous attention was producing an extended enhancement of the late-P1, endogenous attention was enhancing the occipital-parietal N1 component. These results provide neurophysiological support for theories suggesting that endogenous and exogenous mechanisms represent two attention systems that can affect information processing in the brain in distinct ways. Furthermore, these data provide new evidence regarding the precise stages of neural processing that are, and are not, affected when endogenous and exogenous attentions interact.

  20. [Identification of endogenous control genes for gene expression studies in peripheral blood of patients with coronary artery disease].

    PubMed

    Fong, S W; Suhairi, I; Mohamed, M S; Few, L L; Too, W C S; Khoo, B Y; Yussof, Z; Rahman, A R A; Yvonne-Tee, G B

    2013-01-01

    The selection of stable endogenous control genes is critical for normalization of quantitative real-time PCR (qPCR) data. In this study, we aimed to identify a suitable set of control genes to be used as endogenous references for gene expression evaluation in human peripheral blood samples among coronary artery disease patients. The expression levels of 12 endogenous control genes procured from TATAA Biocenter (Goteborg, Sweden) were measured in five acute coronary syndrome patients and five chronic stable angina patients. Gene expression stability was analyzed using two different software applications i.e geNorm and NormFinder. Results suggested that beta-glucuronidase is the most stable endogenous control, followed by hypoxanthine-guanine phosphoribosyltransferase. The NormFinder analysis further confirmed that beta-glucuronidase and hypoxanthine-guanine phosphoribosyltransferase were on the first rank order with the most stable expression among endogenous control genes analyzed and 60S acidic ribosomal protein P0. Besides this, the expression levels of 18S rRNA were revealed to be highly variable between coronary heart disease patients. We thus recommend the use of beta-glucuronidase and hypoxanthine-guanine phosphoribosyltransferase as reference genes for accurate normalization of relative quantities of gene expression levels in coronary artery disease patients using qPCR. Also the use of 18S rRNA as a control gene should be avoided.

  1. The endogenous plant hormones and ratios regulate sugar and dry matter accumulation in Jerusalem artichoke in salt-soil.

    PubMed

    Li, Lingling; Shao, Tianyun; Yang, Hui; Chen, Manxia; Gao, Xiumei; Long, Xiaohua; Shao, Hongbo; Liu, Zhaopu; Rengel, Zed

    2017-02-01

    The changes in content of endogenous hormones in stolons and tubers of Jerusalem artichoke (Helianthus tuberosus L.) regulate tuber growth, but the specific knowledge about the importance of balance among the endogenous hormones is lacking. Two varieties of Jerusalem artichoke (NY-1 and QY-2) were tested for the endogenous zeatin (ZT), auxins (IAA), gibberellins (GA3) and abscisic acid (ABA) in regulating sugar and dry matter accumulation in tubers. The dry matter content and sugar accumulation in tubers were correlated positively with endogenous ZT and negatively with GA3 content and GA3/ABA and IAA/ABA content ratios. Throughout the tuber formation, ZT content was higher in NY-1 than QY-2 tubers, whereas ABA content was higher in QY-2 than NY-1 tubers. The content ratios GA3/ABA and IAA/ABA were greater in NY-1 than QY-2 before tuber initiation, but QY-2 surpassed NY-1 during the tuber growth stage. The GA3/ABA and IAA/ABA content ratios declined during tuber growth. The results suggested that a dynamic balance of endogenous hormones played an important role in tuber development.

  2. CRISPR RNA-guided activation of endogenous human genes.

    PubMed

    Maeder, Morgan L; Linder, Samantha J; Cascio, Vincent M; Fu, Yanfang; Ho, Quan H; Joung, J Keith

    2013-10-01

    Short guide RNAs (gRNAs) can direct catalytically inactive CRISPR-associated 9 nuclease (dCas9) to repress endogenous genes in bacteria and human cells. Here we show that single or multiple gRNAs can direct dCas9 fused to a VP64 transcriptional activation domain to increase expression of endogenous human genes. This proof-of-principle work shows that clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems can target heterologous effector domains to endogenous sites in human cells.

  3. Strategies for the photo-control of endogenous protein activity.

    PubMed

    Brechun, Katherine E; Arndt, Katja M; Woolley, G Andrew

    2016-11-28

    Photo-controlled or 'optogenetic' effectors interfacing with endogenous protein machinery allow the roles of endogenous proteins to be probed. There are two main approaches being used to develop optogenetic effectors: (i) caging strategies using photo-controlled conformational changes, and (ii) protein relocalization strategies using photo-controlled protein-protein interactions. Numerous specific examples of these approaches have been reported and efforts to develop general methods for photo-control of endogenous proteins are a current focus. The development of improved screening and selection methods for photo-switchable proteins would advance the field.

  4. tirant, a Newly Discovered Active Endogenous Retrovirus in Drosophila simulans

    PubMed Central

    Akkouche, Abdou; Rebollo, Rita; Burlet, Nelly; Esnault, Caroline; Martinez, Sonia; Viginier, Barbara; Terzian, Christophe; Vieira, Cristina

    2012-01-01

    Endogenous retroviruses have the ability to become permanently integrated into the genomes of their host, and they are generally transmitted vertically from parent to progeny. With the exception of gypsy, few endogenous retroviruses have been identified in insects. In this study, we describe the tirant endogenous retrovirus in a subset of Drosophila simulans natural populations. By focusing on the envelope gene, we show that the entire retroviral cycle (transcription, translation, and retrotransposition) can be completed for tirant within one population of this species. PMID:22278247

  5. Demonstration of endogenous imipramine like material in rat brain

    SciTech Connect

    Rehavi, M.; Ventura, I.; Sarne, Y.

    1985-02-18

    The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits (/sup 3/H) imipramine specific binding and mimics the inhibitory effect of imipramine on (/sup 3/H) serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits (/sup 3/H) imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum.

  6. Endogenous pacemaker activity of rat tumour somatotrophs

    PubMed Central

    Kwiecien, Renata; Robert, Christophe; Cannon, Robert; Vigues, Stephan; Arnoux, Annie; Kordon, Claude; Hammond, Constance

    1998-01-01

    Cells derived from a rat pituitary tumour (GC cell line) that continuously release growth hormone behave as endogenous pacemakers. In simultaneous patch clamp recordings and cytosolic Ca2+ concentration ([Ca2+]i) imaging, they displayed rhythmic action potentials (44.7 ± 2.7 mV, 178 ± 40 ms, 0.30 ± 0.04 Hz) and concomitant [Ca2+]i transients (374 ± 57 nM, 1.0 ± 0.2 s, 0.27 ± 0.03 Hz). Action potentials and [Ca2+]i transients were reversibly blocked by removal of external Ca2+, addition of nifedipine (1 μM) or Ni2+ (40 μM), but were insensitive to TTX (1 μM). An L-type Ca2+ current activated at -33.6 ± 0.4 mV (holding potential (Vh), −40 mV), peaked at -1.8 ± 1.3 mV, was reduced by nifedipine and enhanced by S-(+)-SDZ 202 791. A T/R-type Ca2+ current activated at -41.7 ± 2.7 mV (Vh, -80 or -60 mV), peaked at -9.2 ± 3.0 mV, was reduced by low concentrations of Ni2+ (40 μM) or Cd2+ (10 μM) and was toxin resistant. Parallel experiments revealed the expression of the class E calcium channel α1-subunit mRNA. The K+ channel blockers TEA (25 mM) and charybdotoxin (10–100 nM) enhanced spike amplitude and/or duration. Apamin (100 nM) also strongly reduced the after-spike hyperpolarization. The outward K+ tail current evoked by a depolarizing step that mimicked an action potential reversed at −69.8 ± 0.3 mV, presented two components, lasted 2–3 s and was totally blocked by Cd2+ (400 μM). The slow pacemaker depolarization (3.5 ± 0.4 s) that separated consecutive spikes corresponded to a 2- to 3-fold increase in membrane resistance, was strongly Na+ sensitive but TTX insensitive. Computer simulations showed that pacemaker activity can be reproduced by a minimum of six currents: an L-type Ca2+ current underlies the rising phase of action potentials that are repolarized by a delayed rectifier and Ca2+-activated K+ currents. In between spikes, the decay of Ca2+-activated K+ currents and a persistent inward cationic current depolarize the membrane

  7. Approximation methods for stochastic petri nets

    NASA Technical Reports Server (NTRS)

    Jungnitz, Hauke Joerg

    1992-01-01

    Stochastic Marked Graphs are a concurrent decision free formalism provided with a powerful synchronization mechanism generalizing conventional Fork Join Queueing Networks. In some particular cases the analysis of the throughput can be done analytically. Otherwise the analysis suffers from the classical state explosion problem. Embedded in the divide and conquer paradigm, approximation techniques are introduced for the analysis of stochastic marked graphs and Macroplace/Macrotransition-nets (MPMT-nets), a new subclass introduced herein. MPMT-nets are a subclass of Petri nets that allow limited choice, concurrency and sharing of resources. The modeling power of MPMT is much larger than that of marked graphs, e.g., MPMT-nets can model manufacturing flow lines with unreliable machines and dataflow graphs where choice and synchronization occur. The basic idea leads to the notion of a cut to split the original net system into two subnets. The cuts lead to two aggregated net systems where one of the subnets is reduced to a single transition. A further reduction leads to a basic skeleton. The generalization of the idea leads to multiple cuts, where single cuts can be applied recursively leading to a hierarchical decomposition. Based on the decomposition, a response time approximation technique for the performance analysis is introduced. Also, delay equivalence, which has previously been introduced in the context of marked graphs by Woodside et al., Marie's method and flow equivalent aggregation are applied to the aggregated net systems. The experimental results show that response time approximation converges quickly and shows reasonable accuracy in most cases. The convergence of Marie's method and flow equivalent aggregation are applied to the aggregated net systems. The experimental results show that response time approximation converges quickly and shows reasonable accuracy in most cases. The convergence of Marie's is slower, but the accuracy is generally better. Delay

  8. 12 CFR 702.102 - Statutory net worth categories.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Statutory net worth categories. 702.102 Section... PROMPT CORRECTIVE ACTION Net Worth Classification § 702.102 Statutory net worth categories. (a) Net worth... credit union shall be classified (Table 1)— (1) Well capitalized if it has a net worth ratio of...

  9. 12 CFR 702.102 - Statutory net worth categories.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Statutory net worth categories. 702.102 Section... PROMPT CORRECTIVE ACTION Net Worth Classification § 702.102 Statutory net worth categories. (a) Net worth... credit union shall be classified (Table 1)— (1) Well capitalized if it has a net worth ratio of...

  10. 12 CFR 702.102 - Statutory net worth categories.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Statutory net worth categories. 702.102 Section... PROMPT CORRECTIVE ACTION Net Worth Classification § 702.102 Statutory net worth categories. (a) Net worth... credit union shall be classified (Table 1)— (1) Well capitalized if it has a net worth ratio of...

  11. 7 CFR 1423.7 - Net worth alternatives.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Net worth alternatives. 1423.7 Section 1423.7... WAREHOUSES § 1423.7 Net worth alternatives. Warehouse operators with net worth equal to or greater than the minimum net worth required, but less than the total net worth for the commodity involved in the...

  12. 12 CFR 702.102 - Statutory net worth categories.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 7 2014-01-01 2014-01-01 false Statutory net worth categories. 702.102 Section... PROMPT CORRECTIVE ACTION Net Worth Classification § 702.102 Statutory net worth categories. (a) Net worth... credit union shall be classified (Table 1)— (1) Well capitalized if it has a net worth ratio of...

  13. 12 CFR 702.102 - Statutory net worth categories.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Statutory net worth categories. 702.102 Section... PROMPT CORRECTIVE ACTION Net Worth Classification § 702.102 Statutory net worth categories. (a) Net worth... credit union shall be classified (Table 1)— (1) Well capitalized if it has a net worth ratio of...

  14. 7 CFR 1423.7 - Net worth alternatives.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Net worth alternatives. 1423.7 Section 1423.7... WAREHOUSES § 1423.7 Net worth alternatives. Warehouse operators with net worth equal to or greater than the minimum net worth required, but less than the total net worth for the commodity involved in the...

  15. 19 CFR 159.22 - Net weights and tares.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Net weights and tares. 159.22 Section 159.22... TREASURY (CONTINUED) LIQUIDATION OF DUTIES Weight, Gage, and Measure § 159.22 Net weights and tares. (a) Determination of net weight. The net weight of merchandise dutiable by net weight, or upon a value...

  16. 7 CFR 1423.7 - Net worth alternatives.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Net worth alternatives. 1423.7 Section 1423.7... WAREHOUSES § 1423.7 Net worth alternatives. Warehouse operators with net worth equal to or greater than the minimum net worth required, but less than the total net worth for the commodity involved in the...

  17. 7 CFR 1423.7 - Net worth alternatives.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Net worth alternatives. 1423.7 Section 1423.7... WAREHOUSES § 1423.7 Net worth alternatives. Warehouse operators with net worth equal to or greater than the minimum net worth required, but less than the total net worth for the commodity involved in the...

  18. 7 CFR 1423.7 - Net worth alternatives.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Net worth alternatives. 1423.7 Section 1423.7... WAREHOUSES § 1423.7 Net worth alternatives. Warehouse operators with net worth equal to or greater than the minimum net worth required, but less than the total net worth for the commodity involved in the...

  19. Mars MetNet Mission Payload Overview

    NASA Astrophysics Data System (ADS)

    Harri, A.-M.; Haukka, H.; Alexashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.

    2012-09-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission [1] is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide crucial scientific data about the Martian atmospheric phenomena.

  20. News from KM3NeT

    SciTech Connect

    Katz, Ulrich F.; Collaboration: KM3NeT Collaboration

    2014-11-18

    KM3NeT is a future research infrastructure in the Mediterranean Sea, hosting a multi-cubic-kilometre neutrino telescope and nodes for Earth and Sea sciences. In this report we shortly summarise the genesis of the KM3NeT project and present key elements of its technical design. The physics objectives of the KM3NeT neutrino telescope and some selected sensitivity estimates are discussed. Finally, some first results from prototype operations and the next steps towards implementation – in particular the first construction phase in 2014/15 – are described.