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Sample records for accumulated reduced levels

  1. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta.

    PubMed

    Visiedo, Francisco; Bugatto, Fernando; Sánchez, Viviana; Cózar-Castellano, Irene; Bartha, Jose L; Perdomo, Germán

    2013-07-15

    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides. PMID:23673156

  2. A mutant of the Arabidopsis thaliana TOC159 gene accumulates reduced levels of linolenic acid and monogalactosyldiacylglycerol.

    PubMed

    Afitlhile, Meshack; Workman, Samantha; Duffield, Kayla; Sprout, Danielle; Berhow, Mark

    2013-12-01

    Previous studies have shown that a mutant of Arabidopsis that lacks the Toc159 receptor is impaired in chloroplast biogenesis. The mutant is referred as plastid protein import 2 or ppi2 and has an albino phenotype due to its inability to import the photosynthetic proteins. In this study, we measured fatty acid composition and transcript levels of plastid-localized fatty acid desaturases in the wild type and ppi2 mutant. The objective was to evaluate whether the Toc159 receptor was critical in the import of lipid-synthesizing enzymes. The ppi2 mutant accumulated decreased levels of oleic acid (18:1) and α-linolenic acid (18:3). The mutant accumulated drastically reduced amounts of the chloroplast lipid monogalactosyldiacylglycerol (MGDG), which contains more than 80% of 18:3. The expression of genes that encode stearoyl-ACP desaturase and MGD1 synthase were down-regulated in the ppi2 mutant, and this corresponded to decreased levels of 18:1 and MGDG, respectively. We conclude that in the ppi2 mutant the impaired synthesis of MGDG resulted in decreased amounts of 18:3. The mutant however, had a 30-fold increase in fad5 transcript levels; this increase was mirrored by a 16- to 50-fold accumulation of hexadecatrienoic acid (16:3), a fatty acid found exclusively in MGDG. Taken together, these data suggest that the Toc159 receptor is required in the import of stearoyl-ACP desaturase and MGD1 synthase into the chloroplasts. Since the expression of fad5 gene was up-regulated in the ppi2 mutant, we propose that fad5 desaturase is imported into plastids through the atToc132/atToc120 protein import pathway. PMID:24184455

  3. Proline accumulation protects Saccharomyces cerevisiae cells in stationary phase from ethanol stress by reducing reactive oxygen species levels.

    PubMed

    Takagi, Hiroshi; Taguchi, Junpei; Kaino, Tomohiro

    2016-08-01

    During fermentation processes, Saccharomyces cerevisiae cells are exposed to multiple stresses, including a high concentration of ethanol that represents toxicity through intracellular reactive oxygen species (ROS) generation. We previously reported that proline protected yeast cells from damage caused by various stresses, such as freezing and ethanol. As an anti-oxidant, proline is suggested to scavenge intracellular ROS. In this study, we examined the role of intracellular proline during ethanol treatment in S. cerevisiae strains that accumulate different concentrations of proline. When cultured in YPD medium, there was a significant accumulation of proline in the put1 mutant strain, which is deficient in proline oxidase, in the stationary phase. Expression of the mutant PRO1 gene, which encodes the γ-glutamyl kinase variant (Asp154Asn or Ile150Thr) with desensitization to feedback inhibition by proline in the put1 mutant strain, showed a prominent increase in proline content as compared with that of the wild-type strain. The oxidation level was clearly increased in wild-type cells after exposure to ethanol, indicating that the generation of ROS occurred. Interestingly, proline accumulation significantly reduces the ROS level and increases the survival rate of yeast cells in the stationary phase under ethanol stress conditions. However, there was not a clear correlation between proline content and survival rate in yeast cells. An appropriate level of intracellular proline in yeast might be important for its stress-protective effect. Hence, the engineering of proline metabolism could be promising for breeding stress-tolerant industrial yeast strains. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26833688

  4. Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice.

    PubMed

    Ejaz, Asma; Martinez-Guino, Laura; Goldfine, Allison B; Ribas-Aulinas, Francesc; De Nigris, Valeria; Ribó, Sílvia; Gonzalez-Franquesa, Alba; Garcia-Roves, Pablo M; Li, Elizabeth; Dreyfuss, Jonathan M; Gall, Walt; Kim, Jason K; Bottiglieri, Teodoro; Villarroya, Francesc; Gerszten, Robert E; Patti, Mary-Elizabeth; Lerin, Carles

    2016-04-01

    Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21(-/-) mice, demonstrating that Fgf21 is necessary for betaine's beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans. PMID:26858359

  5. Can mercury in fish be reduced by water level management? Evaluating the effects of water level fluctuation on mercury accumulation in yellow perch (Perca flavescens)

    USGS Publications Warehouse

    Larson, James H.; Maki, Ryan P.; Knights, Brent C.; Gray, Brian R.

    2014-01-01

    Mercury (Hg) contamination of fisheries is a major concern for resource managers of many temperate lakes. Anthropogenic Hg contamination is largely derived from atmospheric deposition within a lake’s watershed, but its incorporation into the food web is facilitated by bacterial activity in sediments. Temporal variation in Hg content of fish (young-of-year yellow perch) in the regulated lakes of the Rainy–Namakan complex (on the border of the United States and Canada) has been linked to water level (WL) fluctuations, presumably through variation in sediment inundation. As a result, Hg contamination of fish has been linked to international regulations of WL fluctuation. Here we assess the relationship between WL fluctuations and fish Hg content using a 10-year dataset covering six lakes. Within-year WL rise did not appear in strongly supported models of fish Hg, but year-to-year variation in maximum water levels (∆maxWL) was positively associated with fish Hg content. This WL effect varied in magnitude among lakes: In Crane Lake, a 1 m increase in ∆maxWL from the previous year was associated with a 108 ng increase in fish Hg content (per gram wet weight), while the same WL change in Kabetogama was associated with only a 5 ng increase in fish Hg content. In half the lakes sampled here, effect sizes could not be distinguished from zero. Given the persistent and wide-ranging extent of Hg contamination and the large number of regulated waterways, future research is needed to identify the conditions in which WL fluctuations influence fish Hg content.

  6. Reduced cytosolic carboxypeptidase 6 (CCP6) level leads to accumulation of serum polyglutamylated DNAJC7 protein: A potential biomarker for renal cell carcinoma early detection

    PubMed Central

    Li, Yi; Zhu, Xiaoxiao; Ding, Juan; Ren, Shuangchun; Zhao, Heping; Wu, Song; Tian, Yong; Wang, Guo-Qing

    2016-01-01

    Renal cell carcinoma (RCC) is frequently diagnosed at advanced stages of disease, although early diagnosis has much favorable prognosis. This study assessed aberrant expression of cytosolic carboxypeptidase 6 (CCP6) leading to accumulation of serum polyglutamylated DNAJC7 as a biomarker for early RCC detection. A total of 835 RCCs, 143 chronic nephritis, 170 kidney stones and 415 health controls were collected for qRT-PCR, immunohistochemistry and Western blot analysis of CCP6 expression and mass spectrometry of DNAJC7 and polyglutamylated DNAJC7. The data showed that CCP6 expression was significantly decreased in 30 RCC tissues and that mass spectrometric and pull-down analysis identified DNAJC7 as a substrate of CCP6 and showed upregulated polyglutamylated-DNAJC7 (polyE-DNAJC7) in sera of RCC patients. The electrochemiluminescence immunoassay of large-scale serum samples from multi-institutes further confirmed the remarkable increase of polyE-DNAJC7 in 805 RCCs compared to that of 385 healthy controls (p < 0.001), 128 patients with chronic nephritis (p < 0.001), and 153 with kidney stone (p < 0.001). Serum level of DNAJC7-polyE protein was also associated with advanced RCC stage and grade in 805 patients. The data from the current study for the first time demonstrated increased serum polyglutamylated DNAJC7 as a potential biomarker for RCC early detection and association with advanced tumor stages and grade, which provides support of further polyglutamylation research in RCC. PMID:26993597

  7. Reduced cytosolic carboxypeptidase 6 (CCP6) level leads to accumulation of serum polyglutamylated DNAJC7 protein: A potential biomarker for renal cell carcinoma early detection.

    PubMed

    Li, Chong; Wang, Jihan; Hao, Junfeng; Dong, Baijun; Li, Yi; Zhu, Xiaoxiao; Ding, Juan; Ren, Shuangchun; Zhao, Heping; Wu, Song; Tian, Yong; Wang, Guo-Qing

    2016-04-19

    Renal cell carcinoma (RCC) is frequently diagnosed at advanced stages of disease, although early diagnosis has much favorable prognosis. This study assessed aberrant expression of cytosolic carboxypeptidase 6 (CCP6) leading to accumulation of serum polyglutamylated DNAJC7 as a biomarker for early RCC detection. A total of 835 RCCs, 143 chronic nephritis, 170 kidney stones and 415 health controls were collected for qRT-PCR, immunohistochemistry and Western blot analysis of CCP6 expression and mass spectrometry of DNAJC7 and polyglutamylated DNAJC7. The data showed that CCP6 expression was significantly decreased in 30 RCC tissues and that mass spectrometric and pull-down analysis identified DNAJC7 as a substrate of CCP6 and showed upregulated polyglutamylated-DNAJC7 (polyE-DNAJC7) in sera of RCC patients. The electrochemiluminescence immunoassay of large-scale serum samples from multi-institutes further confirmed the remarkable increase of polyE-DNAJC7 in 805 RCCs compared to that of 385 healthy controls (p < 0.001), 128 patients with chronic nephritis (p < 0.001), and 153 with kidney stone (p < 0.001). Serum level of DNAJC7-polyE protein was also associated with advanced RCC stage and grade in 805 patients. The data from the current study for the first time demonstrated increased serum polyglutamylated DNAJC7 as a potential biomarker for RCC early detection and association with advanced tumor stages and grade, which provides support of further polyglutamylation research in RCC. PMID:26993597

  8. Reducing synuclein accumulation improves neuronal survival after spinal cord injury.

    PubMed

    Fogerson, Stephanie M; van Brummen, Alexandra J; Busch, David J; Allen, Scott R; Roychaudhuri, Robin; Banks, Susan M L; Klärner, Frank-Gerrit; Schrader, Thomas; Bitan, Gal; Morgan, Jennifer R

    2016-04-01

    Spinal cord injury causes neuronal death, limiting subsequent regeneration and recovery. Thus, there is a need to develop strategies for improving neuronal survival after injury. Relative to our understanding of axon regeneration, comparatively little is known about the mechanisms that promote the survival of damaged neurons. To address this, we took advantage of lamprey giant reticulospinal neurons whose large size permits detailed examination of post-injury molecular responses at the level of individual, identified cells. We report here that spinal cord injury caused a select subset of giant reticulospinal neurons to accumulate synuclein, a synaptic vesicle-associated protein best known for its atypical aggregation and causal role in neurodegeneration in Parkinson's and other diseases. Post-injury synuclein accumulation took the form of punctate aggregates throughout the somata and occurred selectively in dying neurons, but not in those that survived. In contrast, another synaptic vesicle protein, synaptotagmin, did not accumulate in response to injury. We further show that the post-injury synuclein accumulation was greatly attenuated after single dose application of either the "molecular tweezer" inhibitor, CLR01, or a translation-blocking synuclein morpholino. Consequently, reduction of synuclein accumulation not only improved neuronal survival, but also increased the number of axons in the spinal cord proximal and distal to the lesion. This study is the first to reveal that reducing synuclein accumulation is a novel strategy for improving neuronal survival after spinal cord injury. PMID:26854933

  9. Rice koji reduced body weight gain, fat accumulation, and blood glucose level in high-fat diet-induced obese mice

    PubMed Central

    Yoshizaki, Yumiko; Kawasaki, Chihiro; Cheng, Kai-Chun; Ushikai, Miharu; Amitani, Haruka; Asakawa, Akihiro; Okutsu, Kayu; Sameshima, Yoshihiro; Takamine, Kazunori

    2014-01-01

    Rice koji is considered a readily accessible functional food that may have health-promoting effects. We investigated whether white, yellow, and red koji have the anti-obesity effect in C57BL/6J mice fed a high-fat diet (HFD), which is a model for obesity. Mice were fed HFD containing 10% (w/w) of rice koji powder or steamed rice for 4 weeks. Weight gain, epididymal white adipose tissue, and total adipose tissue weight were significantly lower in all rice koji groups than in the HFD-rice group after 4 weeks. Feed efficiency was significantly reduced in the yellow koji group. Blood glucose levels were significantly lower in the white and red koji groups with HOMA-R and leptin levels being reduced in the white koji group. White and red koji increased glucose uptake and GLUT4 protein expression in L6 myotube cells. These results showed that all rice koji have the anti-obesity or anti-diabetes effects although the mechanisms may differ depending on the type of rice koji consumed. PMID:25237599

  10. Biochar amendment reduced methylmercury accumulation in rice plants.

    PubMed

    Shu, Rui; Wang, Yongjie; Zhong, Huan

    2016-08-01

    There is growing concern about methylmercury (MeHg) accumulation in rice grains and thus enhanced dietary exposure to MeHg in Asian countries. Here, we explored the possibility of reducing grain MeHg levels by biochar amendment, and the underlying mechanisms. Pot (i.e., rice cultivation in biochar amended soils) and batch experiments (i.e., incubation of amended soils under laboratory conditions) were carried out, to investigate MeHg dynamics (i.e., MeHg production, partitioning and phytoavailability in paddy soils, and MeHg uptake by rice) under biochar amendment (1-4% of soil mass). We demonstrate for the first time that biochar amendment could evidently reduce grain MeHg levels (49-92%). The declines could be attributed to the combined effects of: (1) increased soil MeHg concentrations, probably explained by the release of sulfate from biochar and thus enhanced microbial production of MeHg (e.g., by sulfate-reducing bacteria), (2) MeHg immobilization in soils, facilitated by the large surface areas and high organosulfur content of biochar, and (3) biodilution of MeHg in rice grains, due to the increased grain biomass under biochar amendment (35-79%). These observations together with mechanistic explanations improve understanding of MeHg dynamics in soil-rice systems, and support the possibility of reducing MeHg phytoaccumulation under biochar amendment. PMID:27045620

  11. Reducing arsenic accumulation in rice grain through iron oxide amendment.

    PubMed

    Farrow, Eric M; Wang, Jianmin; Burken, Joel G; Shi, Honglan; Yan, Wengui; Yang, John; Hua, Bin; Deng, Baolin

    2015-08-01

    Effects of soil-arsenic (As), phosphorus and iron oxide on As accumulation in rice grain were investigated. Cultivars that have significantly different sensitivity to As, straighthead-resistant Zhe 733 and straighthead-susceptible Cocodrie, were used to represent different cultivar varieties. The grain accumulation of other elements of concern, selenium (Se), molybdenum (Mo), and cadmium (Cd) was also monitored. Results demonstrated that high soil-As not only resulted in high grain-As, but could also result in high grain-Se, and Zhe 733 had significantly less grain-As than Cocodrie did. However, soil-As did not impact grain-Mo and Cd. Among all elements monitored, iron oxide amendment significantly reduced grain-As for both cultivars, while the phosphate application only reduced grain-Se for Zhe 733. Results also indicated that cultivar type significantly impacted grain accumulation of all monitored trace elements. Therefore, applying iron oxide to As-contaminated land, in addition to choosing appropriate rice cultivar, can effectively reduce the grain accumulation of As. PMID:25910688

  12. Targeting acid sphingomyelinase reduces cardiac ceramide accumulation in the post-ischemic heart.

    PubMed

    Klevstig, Martina; Ståhlman, Marcus; Lundqvist, Annika; Scharin Täng, Margareta; Fogelstrand, Per; Adiels, Martin; Andersson, Linda; Kolesnick, Richard; Jeppsson, Anders; Borén, Jan; Levin, Malin C

    2016-04-01

    Ceramide accumulation is known to accompany acute myocardial ischemia, but its role in the pathogenesis of ischemic heart disease is unclear. In this study, we aimed to determine how ceramides accumulate in the ischemic heart and to determine if cardiac function following ischemia can be improved by reducing ceramide accumulation. To investigate the association between ceramide accumulation and heart function, we analyzed myocardial left ventricle biopsies from subjects with chronic ischemia and found that ceramide levels were higher in biopsies from subjects with reduced heart function. Ceramides are produced by either de novo synthesis or hydrolysis of sphingomyelin catalyzed by acid and/or neutral sphingomyelinase. We used cultured HL-1 cardiomyocytes to investigate these pathways and showed that acid sphingomyelinase activity rather than neutral sphingomyelinase activity or de novo sphingolipid synthesis was important for hypoxia-induced ceramide accumulation. We also used mice with a partial deficiency in acid sphingomyelinase (Smpd1(+/-) mice) to investigate if limiting ceramide accumulation under ischemic conditions would have a beneficial effect on heart function and survival. Although we showed that cardiac ceramide accumulation was reduced in Smpd1(+/-) mice 24h after an induced myocardial infarction, this reduction was not accompanied by an improvement in heart function or survival. Our findings show that accumulation of cardiac ceramides in the post-ischemic heart is mediated by acid sphingomyelinase. However, targeting ceramide accumulation in the ischemic heart may not be a beneficial treatment strategy. PMID:26930027

  13. Dissolved organic matter reduces algal accumulation of methylmercury

    USGS Publications Warehouse

    Luengen, Allison C.; Fisher, Nicholas S.; Bergamaschi, Brian A.

    2012-01-01

    Dissolved organic matter (DOM) significantly decreased accumulation of methylmercury (MeHg) by the diatom Cyclotella meneghiniana in laboratory experiments. Live diatom cells accumulated two to four times more MeHg than dead cells, indicating that accumulation may be partially an energy-requiring process. Methylmercury enrichment in diatoms relative to ambient water was measured by a volume concentration factor (VCF). Without added DOM, the maximum VCF was 32 x 104, and the average VCF (from 10 to 72 h) over all experiments was 12.6 x 104. At very low (1.5 mg/L) added DOM, VCFs dropped by approximately half. At very high (20 mg/L) added DOM, VCFs dropped 10-fold. Presumably, MeHg was bound to a variety of reduced sulfur sites on the DOM, making it unavailable for uptake. Diatoms accumulated significantly more MeHg when exposed to transphilic DOM extracts than hydrophobic ones. However, algal lysate, a labile type of DOM created by resuspending a marine diatom in freshwater, behaved similarly to a refractory DOM isolate from San Francisco Bay. Addition of 67 μM L-cysteine resulted in the largest drop in VCFs, to 0.28 x 104. Although the DOM composition influenced the availability of MeHg to some extent, total DOM concentration was the most important factor in determining algal bioaccumulation of MeHg.

  14. SOD1 nanozyme with reduced toxicity and MPS accumulation.

    PubMed

    Jiang, Yuhang; Arounleut, Phonepasong; Rheiner, Steven; Bae, Younsoo; Kabanov, Alexander V; Milligan, Carol; Manickam, Devika S

    2016-06-10

    We previously developed a "cage"-like nano-formulation (nanozyme) for copper/Zinc superoxide dismutase (SOD1) by polyion condensation with a conventional block copolymer poly(ethylene glycol)-b-poly(L-lysine) (PEG-PLL) followed by chemical cross-linking. Herein we report a new SOD1 nanozyme based on PEG-b-poly(aspartate diethyltriamine) (PEG-PAsp(DET), or PEG-DET for short) engineered for chronic dosing. This new nanozyme was spherical (Rg/Rh=0.785), and hollow (60% water composition) nanoparticles with colloidal properties similar to PLL-based nanozyme. It was better tolerated by brain microvessel endothelial/neuronal cells, and accumulated less in the liver and spleen. This formulation reduced the infarct volumes by more than 50% in a mouse model of ischemic stroke. However, it was not effective at preventing neuromuscular junction denervation in a mutant SOD1(G93A) mouse model of amyotrophic lateral sclerosis (ALS). To our knowledge, this work is the first report of using PEG-DET for protein delivery and a direct comparison between two cationic block copolymers demonstrating the effect of polymer structure in modulating the mononuclear phagocyte system (MPS) accumulation of polyion complexes. PMID:26928528

  15. Arrhythmia causes lipid accumulation and reduced glucose uptake.

    PubMed

    Lenski, Matthias; Schleider, Gregor; Kohlhaas, Michael; Adrian, Lucas; Adam, Oliver; Tian, Qinghai; Kaestner, Lars; Lipp, Peter; Lehrke, Michael; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

    2015-01-01

    Atrial fibrillation (AF) is characterized by irregular contractions of atrial cardiomyocytes and increased energy demand. The aim of this study was to characterize the influence of arrhythmia on glucose and fatty acid (FA) metabolism in cardiomyocytes, mice and human left atrial myocardium. Compared to regular pacing, irregular (pseudo-random variation at the same number of contractions/min) pacing of neonatal rat cardiomyocytes induced shorter action potential durations and effective refractory periods and increased diastolic [Ca(2+)]c. This was associated with the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and AMP-activated protein kinase (AMPK). Membrane expression of fatty acid translocase (FAT/CD36) and (14)C-palmitic acid uptake were augmented while membrane expression of glucose transporter subtype 4 (GLUT-4) as well as (3)H-glucose uptake were reduced. Inhibition of AMPK and CaMKII prevented these arrhythmia-induced metabolic changes. Similar alterations of FA metabolism were observed in a transgenic mouse model (RacET) for spontaneous AF. Consistent with these findings samples of left atrial myocardium of patients with AF compared to matched samples of patients with sinus rhythm showed up-regulation of CaMKII and AMPK and increased membrane expression of FAT/CD36, resulting in lipid accumulation. These changes of FA metabolism were accompanied by decreased membrane expression of GLUT-4, increased glycogen content and increased expression of the pro-apoptotic protein bax. Irregular pacing of cardiomyocytes increases diastolic [Ca(2+)]c and activation of CaMKII and AMPK resulting in lipid accumulation, reduced glucose uptake and increased glycogen synthesis. These metabolic changes are accompanied by an activation of pro-apoptotic signalling pathways. PMID:26018791

  16. Reduced Antimony Accumulation in ARM58-Overexpressing Leishmania infantum

    PubMed Central

    Schäfer, Carola; Tejera Nevado, Paloma; Zander, Dorothea

    2014-01-01

    Antimony-based drugs are still the mainstay of chemotherapy against Leishmania infections in many countries where the parasites are endemic. The efficacy of antimonials has been compromised by increasing numbers of resistant infections, the basis of which is not fully understood and likely involves multiple factors. By using a functional cloning strategy, we recently identified a novel antimony resistance marker, ARM58, from the parasite Leishmania braziliensis that protects the parasites against antimony-based antileishmanial compounds. Here we show that the Leishmania infantum homologue also confers resistance against antimony but not against other antileishmanial drugs and that its function depends critically on one of four conserved domains of unknown function. This critical domain requires at least two hydrophobic amino acids and is predicted to form a transmembrane structure. Overexpression of ARM58 in antimony-exposed parasites reduces the intracellular Sb accumulation by over 70%, indicating a role for ARM58 in Sb extrusion pathways, but without involvement of energy-dependent transporter proteins. PMID:24366738

  17. Reducing Unnecessary Accumulation of Incomplete Grades: A Quality Improvement Project

    ERIC Educational Resources Information Center

    Domocmat, Maria Carmela L.

    2015-01-01

    It has been noted that there is an increasing percentage of students accumulating incomplete (INC) grades. This paper aims to identify the factors that contribute to the accumulation of incomplete grades of students and, utilizing the best practices of various universities worldwide, it intends to recommend solutions in limiting the number of…

  18. Advanced Glycation End-Product Accumulation Reduces Vitreous Permeability

    PubMed Central

    Lee, On-Tat; Good, Samuel D.; Lamy, Ricardo; Kudisch, Max; Stewart, Jay M.

    2015-01-01

    Purpose. To evaluate the effect of nonenzymatic cross-linking (glycation) upon the permeability of the vitreous to small- and large-solute diffusion. Methods. Vitreous from freshly excised porcine eyes was treated for 30 minutes with control or 0.01%, 0.1%, or 1% methylglyoxal (MG) solution. The efficacy of the glycation regimen was verified by measuring nonenzymatic cross-link density by fluorescence in the vitreous samples. Resistance to collagenase digestion as well as Nε-(carboxyethyl) lysine (CEL) content were also measured. The permeability coefficient for fluorescein and fluorescein isothiocyanate (FITC)-IgG diffusion through 3 mL of the vitreous samples was determined by using a custom permeability tester. Results. Vitreous cross-linking with MG treatment was confirmed by increased fluorescence, increased CEL concentration, and increased resistance to collagenase digestion. Vitreous glycation resulted in a statistically significant decrease in the permeability coefficient for fluorescein diffusion when either 0.1% or 1% MG solution was used (5.36 ± 5.24 × 10−5 cm s−1, P = 0.04; and 4.03 ± 2.1 × 10−5 cm s−1, P = 0.001; respectively, compared with control, 9.77 ± 5.45 × 10−5 cm s−1). The permeability coefficient for diffusion of FITC-IgG between control (9.9 ± 6.37 × 10−5 cm s−1) and treatment groups was statistically significant at all MG concentrations (0.01% MG: 3.95 ± 3.44 × 10−5 cm s−1, P = 0.003; 0.1% MG: 4.27 ± 1.32 × 10−5 cm s−1, P = 0.004; and 0.1% MG: 3.72 ± 2.49 × 10−5 cm s−1, P = 0.001). Conclusions. Advanced glycation end-product (AGE) accumulation reduces vitreous permeability when glycation is performed in ex vivo porcine vitreous. The permeability change was more pronounced for the larger solute, suggesting a lower threshold for AGE-induced permeability changes to impact the movement of proteins through the vitreous when compared with smaller molecules. PMID:26024075

  19. Sea level controls carbon accumulation in the Everglades

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Atreyee

    2012-10-01

    How much carbon is stored in the organic soils of tropical wetlands is becoming an important question as erosion, agriculture, and global climate change slowly set into motion a series of processes that could potentially release carbon locked up in these wetlands. In a recent study, Glaser et al. reconstructed a complete, carbon-14 dated 4000-year history of both organic and inorganic matter accumulation in the Everglades of south Florida. The authors found that despite the fact that erosion, fires, and similar processes may have removed as much as 2 meters of soil from the Everglades, there is a remarkable consistency in the accumulation rates of both organic and inorganic matter in the Everglades over the past 4000 years. They speculate that processes such as sea level rise that operate on time scales of centuries or even millennia may be ultimately controlling the rates of formation and accumulation of organic matter in the Everglades.

  20. Reducing arsenic accumulation in rice grain through iron oxide amendment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this research, we investigated the accumulation of arsenic (As), selenium (Se), molybdenum (Mo), and cadmium (Cd) in rice grain under different soil conditions in standard straighthead-resistant and straighthead-susceptible cultivars, Zhe 733 and Cocodrie, respectively. Results demonstrated that,...

  1. Nickel accumulation by Streptanthus polygaloides (Brassicaceae) reduces floral visitation rate.

    PubMed

    Meindl, George A; Ashman, Tia-Lynn

    2014-02-01

    Hyperaccumulation is the phenomenon whereby plants take up and sequester in high concentrations elements that generally are excluded from above-ground tissues. It largely is unknown whether the metals taken up by these plants are transferred to floral rewards (i.e., nectar and pollen) and, if so, whether floral visitation is affected. We grew Streptanthus polygaloides, a nickel (Ni) hyperaccumulator, in short-term Ni supplemented soils and control soils to determine whether Ni is accumulated in floral rewards and whether floral visitation is affected by growth in Ni-rich soils. We found that while supplementation of soils with Ni did not alter floral morphology or reward quantity (i.e., anther size or nectar volume), Ni did accumulate in the nectar and pollen-filled anthers-providing the first demonstration that Ni is accumulated in pollinator rewards. Further, S. polygaloides grown in Ni-supplemented soils received fewer visits per flower per hour from both bees and flies (both naïve to Ni-rich floral resources in the study area) relative to plants grown in control soils, although the probability a plant was visited initially was unaffected by Ni treatment. Our findings show that while Ni-rich floral rewards decrease floral visitation, floral visitors are not completely deterred, so some floral visitors may collect and ingest potentially toxic resources from metal-hyperaccumulating plants. In addition to broadening our understanding of the effects of metal accumulation on ecological interactions in natural populations, these results have implications for the use of insect-pollinated plants in phytoremediation. PMID:24477333

  2. Inactivation of Plin4 downregulates Plin5 and reduces cardiac lipid accumulation in mice.

    PubMed

    Chen, Weiqin; Chang, Benny; Wu, Xinyu; Li, Lan; Sleeman, Mark; Chan, Lawrence

    2013-04-01

    Plin4 is a lipid droplet protein (LDP) found predominantly in white adipose tissue (WAT). The Plin4 gene is immediately downstream of the Plin5 gene; the two genes exhibit distinct though overlapping tissue expression patterns. Plin4 is absent in brown adipose tissue (BAT) and liver and expressed at low levels in heart and skeletal muscle, whereas Plin5 is highly expressed in these oxidative tissues but at a low level in WAT. The physiological role of Plin4 remains unclear. We have generated Plin4(-/-) mice by gene targeting. Loss of Plin4 has no effect on body weight or composition or on adipose mass or development. However, the triacylglycerol (TAG) content in heart, but not other oxidative tissues such as BAT, soleus muscle, and liver, is markedly reduced in Plin4(-/-) mice. The heart of Plin4(-/-) mice displays reduced Plin5 mRNA and protein levels (by ~38 and 87%, respectively, vs. wild-type) but unchanged mRNA levels of other perilipin family genes (Plin2 and Plin3) or genes involved in glucose and lipid metabolism. Despite reduced cardiac TAG level, both young and aged Plin4(-/-) mice maintain normal heart function as wild-type mice, as measured by echocardiography. Interestingly, Plin4 deficiency prevents the lipid accumulation in the heart that normally occurs after a prolonged (48-h) fast. It also protects the heart from cardiac steatosis induced by high-fat diet or when Plin4(-/-) mice are bred into Lep(-/-) obese background. In conclusion, inactivation of Plin4 downregulates Plin5 and reduces cardiac lipid accumulation in mice. PMID:23423172

  3. Lianas reduce carbon accumulation and storage in tropical forests

    PubMed Central

    van der Heijden, Geertje M. F.; Powers, Jennifer S.; Schnitzer, Stefan A.

    2015-01-01

    Tropical forests store vast quantities of carbon, account for one-third of the carbon fixed by photosynthesis, and are a major sink in the global carbon cycle. Recent evidence suggests that competition between lianas (woody vines) and trees may reduce forest-wide carbon uptake; however, estimates of the impact of lianas on carbon dynamics of tropical forests are crucially lacking. Here we used a large-scale liana removal experiment and found that, at 3 y after liana removal, lianas reduced net above-ground carbon uptake (growth and recruitment minus mortality) by ∼76% per year, mostly by reducing tree growth. The loss of carbon uptake due to liana-induced mortality was four times greater in the control plots in which lianas were present, but high variation among plots prevented a significant difference among the treatments. Lianas altered how aboveground carbon was stored. In forests where lianas were present, the partitioning of forest aboveground net primary production was dominated by leaves (53.2%, compared with 39.2% in liana-free forests) at the expense of woody stems (from 28.9%, compared with 43.9%), resulting in a more rapid return of fixed carbon to the atmosphere. After 3 y of experimental liana removal, our results clearly demonstrate large differences in carbon cycling between forests with and without lianas. Combined with the recently reported increases in liana abundance, these results indicate that lianas are an important and increasing agent of change in the carbon dynamics of tropical forests. PMID:26460031

  4. Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4

    SciTech Connect

    Song, Jun; Ren, Pingping; Zhang, Lin; Wang, Xing Li; Chen, Li; Shen, Ying H.

    2010-02-26

    Objective: The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Strategies to reduce lipid accumulation in macrophages may have therapeutic potential for preventing and treating atherosclerosis and cardiovascular complications. The antidiabetic drug metformin has been reported to reduce lipid accumulation in adipocytes. In this study, we examined the effects of metformin on lipid accumulation in macrophages and investigated the mechanisms involved. Methods and results: We observed that metformin significantly reduced palmitic acid (PA)-induced intracellular lipid accumulation in macrophages. Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4) which was involved in PA-induced lipid accumulation. Quantitative real-time PCR showed that metformin regulates FABP4 expression at the transcriptional level. We identified forkhead transcription factor FOXO1 as a positive regulator of FABP4 expression. Inhibiting FOXO1 expression with FOXO1 siRNA significantly reduced basal and PA-induced FABP4 expression. Overexpression of wild-type FOXO1 and constitutively active FOXO1 significantly increased FABP4 expression, whereas dominant negative FOXO1 dramatically decreased FABP4 expression. Metformin reduced FABP4 expression by promoting FOXO1 nuclear exclusion and subsequently inhibiting its activity. Conclusions: Taken together, these results suggest that metformin reduces lipid accumulation in macrophages by repressing FOXO1-mediated FABP4 transcription. Thus, metformin may have a protective effect against lipid accumulation in macrophages and may serve as a therapeutic agent for preventing and treating atherosclerosis in metabolic syndrome.

  5. Effects of biochar amendment on relieving cadmium stress and reducing cadmium accumulation in pepper.

    PubMed

    Xu, Dongyu; Zhao, Ye; Zhou, Huaidong; Gao, Bo

    2016-06-01

    Biochar is widely used in agricultural soils or heavy metal-polluted soils to improve the quality of the soils, which would affect the growth of the plant. However, the information of biochars' effect on the plant growth was still lacking, especially for the physiological response of the plant. Pot experiments were used to examine the effect of willow-derived biochars at two temperatures (450 and 600 °C) on cadmium (Cd) accumulation in pepper and to reveal the response of physiological parameters to exogenous Cd stress (1 and 5 mg/kg). The results showed that the accumulation of Cd in pepper roots was higher than that in pepper shoots. For low level of Cd treatments, high additional rates of the biochars could obviously reduce the accumulation of Cd in the pepper roots. Moreover, there was a negative correlation between the C content of the biochar-amended soils and the Cd content of the pepper root, suggesting that the application of biochar to the soil decreased the Cd accumulation in the root. A positive relationship between the H/C ratios of biochar-amended soils and their corresponding Cd concentrations in pepper root indicated that low thermal temperature-derived biochar could play an important role in immobilizing Cd in the soil. Furthermore, on the condition of low Cd level of treatments, the malondialdehyde content decreased in biochar-amended soils, especially at high biochar application rate. The chlorophyll content increased with increasing the rates of the biochar application. The physiological parameters indirectly proved that the application of biochar did not always alleviate the toxic effects of Cd on pepper leaves at high Cd concentration. PMID:26976015

  6. Salicylic acid reduces napropamide toxicity by preventing its accumulation in rapeseed (Brassica napus L.).

    PubMed

    Cui, Jing; Zhang, Rui; Wu, Guo Lin; Zhu, Hong Mei; Yang, Hong

    2010-07-01

    Napropamide is a widely used herbicide for controlling weeds in crop production. However, extensive use of the herbicide has led to its accumulation in ecosystems, thus causing toxicity to crops and reducing crop production and quality. Salicylic acid (SA) plays multiple roles in regulating plant adaptive responses to biotic and environmental stresses. However, whether SA regulates plant response to herbicides (or pesticides) was unknown. In this study, we investigated the effect of SA on herbicide napropamide accumulation and biological processes in rapeseed (Brassica napus). Plants exposed to 8 mg kg(-1) napropamide showed growth stunt and oxidative damage. Treatment with 0.1 mM SA improved growth and reduced napropamide levels in plants. Treatment with SA also decreased the abundance of O (2) (-.) and H(2)O(2) as well as activities of superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX), and increased activities of guaiacol peroxidase (POD) and glutathione-S-transferase (GST) in napropamide-exposed plants. Analysis of SOD, CAT, and POD activities using nondenaturing polyacrylamide gel electrophoresis (PAGE) confirmed the results. These results may help to understand how SA regulates plant response to organic contaminants and provide a basis to control herbicide/pesticide contamination in crop production. PMID:19967348

  7. Tyramine accumulation in rice cells caused a dwarf phenotype via reduced cell division.

    PubMed

    Kim, Young Soon; Park, Sangkyu; Kang, Kiyoon; Lee, Kyungjin; Back, Kyoungwhan

    2011-02-01

    Transgenic rice plants overexpressing a rice tyrosine decarboxylase (TyDC) exhibited a dwarf phenotype with a high level of tyramine accumulation. The height of transgenic rice was reduced on average to 35% of the wild-type height, whereas the number of tillers increased to 190% that of wild type. When judged by cellular distribution of tyramine and tyramine derivatives, the level of tyramine in soluble and insoluble fractions was higher than that of tyramine derivatives such as 4-coumaroyltyramine (CT) in the transgenic rice plants, suggesting that tyramine rather than its derivatives was a causative compound triggering the dwarf phenotype. Microscopic observation revealed that cell size in the transgenic lines was maintained, with a slightly irregular arrangement in the leaf mesophyll cells. When wild-type rice seeds were grown in the presence of tyramine, rice seedlings also showed stunted phenotypes in a dose-dependent manner. When these stunted seedlings were employed to measure the degree of cellular proliferation by bromodeoxyuridine incorporation, only small numbers of cells were found to retain labeled nuclei in shoot tips compared with the untreated control. These results show that the dwarf phenotype associated with tyramine accumulation in transgenic rice plants is attributable to a reduction in cell number rather than cell size. In addition, our dwarf phenotype caused by tyramine was not closely associated with known dwarf genes such as D88. PMID:20978800

  8. Celastrus Orbiculatus Thunb. Reduces Lipid Accumulation by Promoting Reverse Cholesterol Transport in Hyperlipidemic Mice.

    PubMed

    Zhang, Ying; Si, Yanhong; Zhai, Lei; Guo, Shoudong; Zhao, Jilong; Sang, Hui; Pang, Xiaofei; Zhang, Xue; Chen, Anbin; Qin, Shucun

    2016-06-01

    Previously, we found that Celastrus orbiculatus Thunb. (COT) decreases athero-susceptibility in lipoproteins and the aorta of guinea pigs fed a high-fat diet, and increases high-density lipoprotein (HDL). In the present study, we investigated the effect of COT in reducing lipid accumulation and promoting reverse cholesterol transport (RCT) in vivo and vitro. Healthy male mice were treated with high-fat diet alone, high-fat diet with COT (10.0 g/kg/d), or general fodder for 6 weeks. Serum levels of total cholesterol (TC), triglyceride (TG), HDL-C, non-HDL-C, and (3)H-cholesterol in plasma, liver, bile, and feces were determined. Pathological changes and the levels of TC and TG in liver were examined. The expression of hepatic genes and protein associated with RCT were analyzed. COT administration reduced lipid accumulation in the liver, ameliorated the pathological changes, and lessened liver injury, the levels of TG, TC, and non-HDL-C in plasma were decreased significantly, and COT led to a significant increase in plasma HDL-C and apolipoprotein A (apoA1). (3)H-cholesterol in plasma, liver, bile, and feces was also significantly increased in COT-treated mice compared to controls. Both mRNA and protein expression of SRB1, CYP7A1, LDLR, ATP-binding cassette transporters ABCA1, ABCG5, and LXRα were improved in COT-treated mice. An in vitro isotope tracing experiment showed that COT and its bioactive ingredients, such as celastrol, ursolic acid, oleanolic acid, and quercetin, significantly increased the efflux of (3)H-cholesterol. They also increased the expression of SRB1, ABCA1, and ABCG1 significantly in macrophages. Our findings provided a positive role of COT in reducing lipid accumulation by promoting RCT. These effects may be achieved by activating the SRB1 and ABC transporter pathway and promoting cholesterol metabolism via the CYP7A1 pathway in vivo. The effective ingredients in vitro are celastrol, ursolic acid, oleanolic acid, and quercetin. PMID

  9. Lead accumulation reduces photosynthesis in the lead hyper-accumulator Salvinia minima Baker by affecting the cell membrane and inducing stomatal closure.

    PubMed

    Leal-Alvarado, Daniel A; Espadas-Gil, Francisco; Sáenz-Carbonell, Luis; Talavera-May, Carlos; Santamaría, Jorge M

    2016-02-01

    Salvinia minima Baker accumulates a fair amount of lead in its tissues; however, no studies have investigated the effect of lead on the physiological processes that affect photosynthesis in this species. The objective of the present study was to assess whether the high amounts of lead accumulated by S. minima can affect its photosynthetic apparatus. The physiological changes in the roots and leaves in response to lead accumulation were analyzed. An exposure to 40 μM Pb(NO3)2 for 24 h (first stage) was sufficient to reduce the photosynthetic rate (Pn) by 44%. This reduction in Pn was apparently the result of processes at various levels, including damage to the cell membranes (mainly in roots). Interestingly, although the plants were transferred to fresh medium without lead for an additional 24 h (second stage), Pn not only remained low, but was reduced even further, which was apparently related to stomatal closure, and may have led to reduced CO2 availability. Therefore, it can be concluded that lead exposure first decreases the photosynthetic rate by damaging the root membrane and then induces stomatal closure, resulting in decreased CO2 availability. PMID:26742090

  10. Levels of Lycopene β-Cyclase 1 Modulate Carotenoid Gene Expression and Accumulation in Daucus carota

    PubMed Central

    Moreno, Juan Camilo; Pizarro, Lorena; Fuentes, Paulina; Handford, Michael; Cifuentes, Victor; Stange, Claudia

    2013-01-01

    Plant carotenoids are synthesized and accumulated in plastids through a highly regulated pathway. Lycopene β-cyclase (LCYB) is a key enzyme involved directly in the synthesis of α-carotene and β-carotene through the cyclization of lycopene. Carotenoids are produced in both carrot (Daucus carota) leaves and reserve roots, and high amounts of α-carotene and β-carotene accumulate in the latter. In some plant models, the presence of different isoforms of carotenogenic genes is associated with an organ-specific function. D. carota harbors two Lcyb genes, of which DcLcyb1 is expressed in leaves and storage roots during carrot development, correlating with an increase in carotenoid levels. In this work, we show that DcLCYB1 is localized in the plastid and that it is a functional enzyme, as demonstrated by heterologous complementation in Escherichia coli and over expression and post transcriptional gene silencing in carrot. Transgenic plants with higher or reduced levels of DcLcyb1 had incremented or reduced levels of chlorophyll, total carotenoids and β-carotene in leaves and in the storage roots, respectively. In addition, changes in the expression of DcLcyb1 are accompanied by a modulation in the expression of key endogenous carotenogenic genes. Our results indicate that DcLcyb1 does not possess an organ specific function and modulate carotenoid gene expression and accumulation in carrot leaves and storage roots. PMID:23555569

  11. Reducing methylmercury accumulation in the food webs of San Francisco Bay and its local watersheds.

    PubMed

    Davis, J A; Looker, R E; Yee, D; Marvin-Di Pasquale, M; Grenier, J L; Austin, C M; McKee, L J; Greenfield, B K; Brodberg, R; Blum, J D

    2012-11-01

    from urban runoff. Atmospheric deposition is a lower priority for source control in the Bay Area due to a combination of a lack of major local sources. Internal net production of MeHg is the dominant source of MeHg that enters the food web. Controlling internal net production is the second primary management approach, and has the potential to reduce food web MeHg in some habitats more effectively and within a much shorter time-frame. Controlling net MeHg production and accumulation in the food web of upstream reservoirs and ponds is very promising due to the many features of these ecosystems that can be manipulated. The most feasible control options in tidal marshes relate to the design of flow patterns and subhabitats in restoration projects. Options for controlling MeHg production in open Bay habitat are limited due primarily to the highly dispersed distribution of Hg throughout the ecosystem. Other changes in these habitats may also have a large influence on food web MeHg, including temperature changes due to global warming, sea level rise, food web alterations due to introduced species and other causes, and changes in sediment supply. Other options for reducing or mitigating exposure and risk include controlling bioaccumulation, cleanup of contaminated sites, and reducing other factors (e.g., habitat availability) that limit at-risk wildlife populations. PMID:23122771

  12. Reducing Methylmercury Accumulation in the Food Webs of San Francisco Bay and Its Local Watersheds

    PubMed Central

    Davis, J.A.; Looker, R.E.; Yee, D.; Marvin-DiPasquale, M.; Grenier, J.L.; Austin, C.M.; McKee, L.J.; Greenfield, B.K.; Brodberg, R.; Blum, J.D.

    2013-01-01

    from urban runoff. Atmospheric deposition is a lower priority for source control in the Bay Area due to a combination of a lack of major local sources and Hg isotope data indicating it is a secondary contributor to food web MeHg. Internal net production of MeHg is the dominant source of MeHg that enters the food web. Controlling internal net production is the second primary management approach, and has the potential to reduce food web MeHg more effectively and within a much shorter time-frame. MeHg cycling and control opportunities vary by habitat. Controlling net MeHg production and accumulation in the food web of upstream reservoirs and ponds is very promising due to the many features of these ecosystems that can be manipulated. The most feasible control options in tidal marshes relate to the design of flow patterns and subhabitats in restoration projects. Options for controlling MeHg production in open Bay habitat are limited due primarily to the highly dispersed distribution of Hg throughout the ecosystem. Other changes in these habitats may also have a large influence on food web MeHg, including temperature changes due to global warming, sea level rise, food web alterations due to introduced species and other causes, and changes in sediment supply. Other options for reducing or mitigating exposure and risk include controlling bioaccumulation, cleanup of contaminated sites, and reducing other factors (e.g., habitat availability) that limit at risk wildlife populations. PMID:23122771

  13. Reducing methylmercury accumulation in the food webs of San Francisco Bay and its local watersheds

    SciTech Connect

    Davis, J.A.; Looker, R.E.; Yee, D.; Marvin-Di Pasquale, M.; Austin, C.M.; McKee, L.J.; Greenfield, B.K.; Brodberg, R.; Blum, J.D.

    2012-11-15

    from urban runoff. Atmospheric deposition is a lower priority for source control in the Bay Area due to a combination of a lack of major local sources. Internal net production of MeHg is the dominant source of MeHg that enters the food web. Controlling internal net production is the second primary management approach, and has the potential to reduce food web MeHg in some habitats more effectively and within a much shorter time-frame. Controlling net MeHg production and accumulation in the food web of upstream reservoirs and ponds is very promising due to the many features of these ecosystems that can be manipulated. The most feasible control options in tidal marshes relate to the design of flow patterns and subhabitats in restoration projects. Options for controlling MeHg production in open Bay habitat are limited due primarily to the highly dispersed distribution of Hg throughout the ecosystem. Other changes in these habitats may also have a large influence on food web MeHg, including temperature changes due to global warming, sea level rise, food web alterations due to introduced species and other causes, and changes in sediment supply. Other options for reducing or mitigating exposure and risk include controlling bioaccumulation, cleanup of contaminated sites, and reducing other factors (e.g., habitat availability) that limit at-risk wildlife populations.

  14. Effects of high ammonium level on biomass accumulation of common duckweed Lemna minor L.

    PubMed

    Wang, Wenguo; Yang, Chuang; Tang, Xiaoyu; Gu, Xinjiao; Zhu, Qili; Pan, Ke; Hu, Qichun; Ma, Danwei

    2014-12-01

    Growing common duckweed Lemna minor L. in diluted livestock wastewater is an alternative option for pollutants removal and consequently the accumulated duckweed biomass can be used for bioenergy production. However, the biomass accumulation can be inhibited by high level of ammonium (NH4 (+)) in non-diluted livestock wastewater and the mechanism of ammonium inhibition is not fully understood. In this study, the effect of high concentration of NH4 (+) on L. minor biomass accumulation was investigated using NH4 (+) as sole source of nitrogen (N). NH4 (+)-induced toxicity symptoms were observed when L. minor was exposed to high concentrations of ammonium nitrogen (NH4 (+)-N) after a 7-day cultivation. L. minor exposed to the NH4 (+)-N concentration of 840 mg l(-1) exhibited reduced relative growth rate, contents of carbon (C) and photosynthetic pigments, and C/N ratio. Ammonium irons were inhibitory to the synthesis of photosynthetic pigments and caused C/N imbalance in L. minor. These symptoms could further cause premature senescence of the fronds, and restrain their reproduction, growth and biomass accumulation. L. minor could grow at NH4 (+)-N concentrations of 7-84 mg l(-1) and the optimal NH4 (+)-N concentration was 28 mg l(-1). PMID:25056754

  15. Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration

    PubMed Central

    Kuszczyk, Magdalena A.; Sanchez, Sandrine; Pankiewicz, Joanna; Kim, Jungsu; Duszczyk, Malgorzata; Guridi, Maitea; Asuni, Ayodeji A.; Sullivan, Patrick M.; Holtzman, David M.; Sadowski, Martin J.

    2014-01-01

    Accumulation of β-amyloid (Aβ) in the brain is a key event in Alzheimer disease pathogenesis. Apolipoprotein (Apo) E is a lipid carrier protein secreted by astrocytes, which shows inherent affinity for Aβ and has been implicated in the receptor-mediated Aβ uptake by neurons. To characterize ApoE involvement in the intraneuronal Aβ accumulation and to investigate whether blocking the ApoE/Aβ interaction could reduce intraneuronal Aβ buildup, we used a noncontact neuronal-astrocytic co-culture system, where synthetic Aβ peptides were added into the media without or with cotreatment with Aβ12-28P, which is a nontoxic peptide antagonist of ApoE/Aβ binding. Compared with neurons cultured alone, intraneuronal Aβ content was significantly increased in neurons co-cultured with wild-type but not with ApoE knockout (KO) astrocytes. Neurons co-cultured with astrocytes also showed impaired intraneuronal degradation of Aβ, increased level of intraneuronal Aβ oligomers, and marked down-regulation of several synaptic proteins. Aβ12-28P treatment significantly reduced intraneuronal Aβ accumulation, including Aβ oligomer level, and inhibited loss of synaptic proteins. Furthermore, we showed significantly reduced intraneuronal Aβ accumulation in APPSW/PS1dE9/ApoE KO mice compared with APPSW/PS1dE9/ApoE targeted replacement mice that expressed various human ApoE isoforms. Data from our co-culture and in vivo experiments indicate an essential role of ApoE in the mechanism of intraneuronal Aβ accumulation and provide evidence that ApoE/Aβ binding antagonists can effectively prevent this process. PMID:23499462

  16. Nonsteroidal anti-inflammatory drug reduces neutrophil and macrophage accumulation but does not improve tendon regeneration.

    PubMed

    Marsolais, David; Côté, Claude H; Frenette, Jérôme

    2003-07-01

    Whether nonsteroidal anti-inflammatory drugs have a beneficial effect on tendon regeneration is still a matter of debate. Given that inflammatory cells are thought to induce nonspecific damage following an injury, we tested the hypothesis that a 3-day treatment with diclofenac would protect tendons from inflammatory cell injury and would promote healing. Neutrophil and ED1(+) macrophage concentrations were determined in the paratenon and the core of the rat Achilles tendon following collagenase-induced injury. Hydroxyproline content, edema, and mechanical properties were also evaluated at 1, 3, 7, 14, and 28 days post-trauma. Collagenase injections induced a 70% decrease in the ultimate rupture point at Day 3. Diclofenac treatments (1 mg/kg bid) selectively decreased the accumulation of neutrophils and ED1(+) macrophages by 59% and 35%, respectively, in the paratenon, where blood vessels are numerous, but did not reduce the accumulation of neutrophils and ED1(+) macrophages in the core of the tendon. Edema was significantly reduced on Day 3 but persisted during the remodeling phase in the diclofenac-treated group only. The inhibition of leukocyte accumulation by diclofenac did not translate into a reduction of tissue damage or a promotion of tissue healing, because the mechanical properties of injured Achilles tendons were identical in placebo and diclofenac-treated groups. These results indicate that diclofenac reduced both edema and the accumulation of inflammatory cells within the paratenon but provided no biochemical or functional benefits for the Achilles tendon. PMID:12861039

  17. Reduced plasma pyrophosphate levels in hemodialysis patients.

    PubMed

    Lomashvili, Koba A; Khawandi, Wassim; O'Neill, W Charles

    2005-08-01

    Pyrophosphate (PPi) is a known inhibitor of hydroxyapatite formation and has been shown to inhibit medial vascular calcification in vitamin D-toxic rats. It was demonstrated recently that endogenous production of PPi prevents calcification of rat aorta that are cultured in high concentrations of calcium and phosphate. For determining whether PPi metabolism is altered in hemodialysis patients, plasma levels and dialytic clearance of PPi were measured in stable hemodialysis patients. Predialysis plasma [PPi] was 2.26 +/- 0.19 microM in 38 clinically stable hemodialysis patients compared with 3.26 +/- 0.17 in 36 normal subjects (P < 0.01). Approximately 30% of plasma PPi was protein bound, and this was not altered in dialysis patients. There was a weak inverse correlation with age in normal individuals but not in dialysis patients. Plasma [PPi] in dialysis patients was correlated with plasma [PO4(3-)] (r = 0.56) but not with [Ca2+], parathyroid hormone, or the dose of dialysis, and levels did not vary between interdialytic periods of 2 and 3 d. Plasma [PPi] decreased 32 +/- 5% after standard hemodialysis in 17 patients. In vitro clearance of PPi by a 2.1-m2 cellulose acetate dialyzer was 36%, and the mean PPi removal in five patients was 43 +/- 5 micromol, consistent with a similar in vivo clearance. Cleared PPi was greater than the plasma pool but less than the estimated extracellular fluid pool. Erythrocyte PPi content decreased 24 +/- 4%, indicating that intracellular PPi is removed as well. It is concluded that plasma [PPi] is reduced in hemodialysis patients and that PPi is cleared by dialysis. Plasma levels in some patients were below those that have previously been shown to prevent calcification of vessels in culture, suggesting that altered PPi metabolism could contribute to vascular calcification in hemodialysis patients. PMID:15958726

  18. Soluble Moringa oleifera leaf extract reduces intracellular cadmium accumulation and oxidative stress in Saccharomyces cerevisiae.

    PubMed

    Kerdsomboon, Kittikhun; Tatip, Supinda; Kosasih, Sattawat; Auesukaree, Choowong

    2016-05-01

    Moringa oleifera leaves are a well-known source of antioxidants and traditionally used for medicinal applications. In the present study, the protective action of soluble M. oleifera leaf extract (MOLE) against cadmium toxicity was investigated in the model eukaryote Saccharomyces cerevisiae. The results showed that this extract exhibited a protective effect against oxidative stress induced by cadmium and H2O2 through the reduction of intracellular reactive oxygen species. Interestingly, not only the co-exposure of soluble MOLE with cadmium but also pretreatment of this extract prior to cadmium exposure significantly reduced the cadmium uptake through an inhibition of Fet4p, a low-affinity iron(II) transporter. In addition, the supplementation of soluble MOLE significantly reduced intracellular iron accumulation in a Fet4p-independent manner. Our findings suggest the potential use of soluble extract from M. oleifera leaves as a dietary supplement for protection against cadmium accumulation and oxidative stress. PMID:26675819

  19. Apoplastic Nucleoside Accumulation in Arabidopsis Leads to Reduced Photosynthetic Performance and Increased Susceptibility Against Botrytis cinerea

    PubMed Central

    Daumann, Manuel; Fischer, Marietta; Niopek-Witz, Sandra; Girke, Christopher; Möhlmann, Torsten

    2015-01-01

    Interactions between plant and pathogen often occur in the extracellular space and especially nucleotides like ATP and NAD have been identified as key players in this scenario. Arabidopsis mutants accumulating nucleosides in the extracellular space were generated and studied with respect to susceptibility against Botrytis cinerea infection and general plant fitness determined as photosynthetic performance. The mutants used are deficient in the main nucleoside uptake system ENT3 and the extracellular nucleoside hydrolase NSH3. When grown on soil but not in hydroponic culture, these plants markedly accumulate adenosine and uridine in leaves. This nucleoside accumulation was accompanied by reduced photosystem II efficiency and altered expression of photosynthesis related genes. Moreover, a higher susceptibility toward Botrytis cinerea infection and a reduced induction of pathogen related genes PR1 and WRKY33 was observed. All these effects did not occur in hydroponically grown plants substantiating a contribution of extracellular nucleosides to these effects. Whether reduced general plant fitness, altered pathogen response capability or more direct interactions with the pathogen are responsible for these observations is discussed. PMID:26779190

  20. Accumulation of metals in GOLD4 COPD lungs is associated with decreased CFTR levels

    PubMed Central

    2014-01-01

    Background The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that primarily resides in airway epithelial cells. Decreased CFTR expression and/or function lead to impaired airway surface liquid (ASL) volume homeostasis, resulting in accumulation of mucus, reduced clearance of bacteria, and chronic infection and inflammation. Methods Expression of CFTR and the cigarette smoke metal content were assessed in lung samples of controls and COPD patients with established GOLD stage 4. CFTR protein and mRNA were quantified by immunohistochemistry and quantitative RT-PCR, respectively. Metals present in lung samples were quantified by ICP-AES. The effect of cigarette smoke on down-regulation of CFTR expression and function was assessed using primary human airway epithelial cells. The role of leading metal(s) found in lung samples of GOLD 4 COPD patients involved in the alteration of CFTR was confirmed by exposing human bronchial epithelial cells 16HBE14o- to metal-depleted cigarette smoke extracts. Results We found that CFTR expression is reduced in the lungs of GOLD 4 COPD patients, especially in bronchial epithelial cells. Assessment of metals present in lung samples revealed that cadmium and manganese were significantly higher in GOLD 4 COPD patients when compared to control smokers (GOLD 0). Primary human airway epithelial cells exposed to cigarette smoke resulted in decreased expression of CFTR protein and reduced airway surface liquid height. 16HBE14o-cells exposed to cigarette smoke also exhibited reduced levels of CFTR protein and mRNA. Removal and/or addition of metals to cigarette smoke extracts before exposure established their role in decrease of CFTR in airway epithelial cells. Conclusions CFTR expression is reduced in the lungs of patients with severe COPD. This effect is associated with the accumulation of cadmium and manganese suggesting a role for these metals in the pathogenesis of COPD. PMID:24957904

  1. Angiotensinogen Gene Silencing Reduces Markers of Lipid Accumulation and Inflammation in Cultured Adipocytes

    PubMed Central

    Carroll, Wenting X.; Kalupahana, Nishan S.; Booker, Suzanne L.; Siriwardhana, Nalin; LeMieux, Monique; Saxton, Arnold M.; Moustaid-Moussa, Naima

    2013-01-01

    Inflammatory adipokines secreted from adipose tissue are major contributors to obesity-associated inflammation and other metabolic dysfunctions. We and others have recently documented the contribution of adipose tissue renin-angiotensin system to the pathogenesis of obesity, inflammation, and insulin resistance. We hypothesized that adipocyte-derived angiotensinogen (Agt) plays a critical role in adipogenesis and/or lipogenesis as well as inflammation. This was tested using 3T3-L1 adipocytes, stably transfected with Agt-shRNA or scrambled Sc-shRNA as a control. Transfected preadipocytes were differentiated and used to investigate the role of adipose Agt through microarray and PCR analyses and adipokine profiling. As expected, Agt gene silencing significantly reduced the expression of Agt and its hormone product angiotensin II (Ang II), as well as lipid accumulation in 3T3-L1 adipocytes. Microarray studies identified several genes involved in lipid metabolism and inflammatory pathways which were down-regulated by Agt gene inactivation, such as glycerol-3-phosphate dehydrogenase 1 (Gpd1), serum amyloid A 3 (Saa3), nucleotide-binding oligomerization domain containing 1 (Nod1), and signal transducer and activator of transcription 1 (Stat1). Mouse adipogenesis PCR arrays revealed lower expression levels of adipogenic/lipogenic genes such as peroxisome proliferator activated receptor gamma (PPARγ), sterol regulatory element binding transcription factor 1 (Srebf1), adipogenin (Adig), and fatty acid binding protein 4 (Fabp4). Further, silencing of Agt gene significantly lowered expression of pro-inflammatory adipokines including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and monocyte chemotactic protein-1 (MCP-1). In conclusion, this study directly demonstrates critical effects of Agt in adipocyte metabolism and inflammation and further support a potential role for adipose Agt in the pathogenesis of obesity-associated metabolic alterations. PMID:23483012

  2. Reducing ethylene levels along the food supply chain: a key to reducing food waste?

    PubMed

    Blanke, Michael M

    2014-09-01

    Excessive waste along the food supply chain of 71 (UK, Netherlands) to 82 (Germany) kg per head per year sparked widespread criticism of the agricultural food business and provides a great challenge and task for all its players and stakeholders. Origins of this food waste include private households, restaurants and canteens, as well as supermarkets, and indicate that 59-65% of this food waste can be avoided. Since ∼50% of the food waste is fruit and vegetables, monitoring and control of their natural ripening gas - ethylene - is suggested here as one possible key to reducing food waste. Ethylene accelerates ripening of climacteric fruits, and accumulation of ethylene in the supply chain can lead to fruit decay and waste. While ethylene was determined using a stationary gas chromatograph with gas cylinders, the new generation of portable sensor-based instruments now enables continuous in situ determination of ethylene along the food chain, a prerequisite to managing and maintaining the quality and ripeness of fruits and identifying hot spots of ethylene accumulation along the supply chain. Ethylene levels were measured in a first trial, along the supply chain of apple fruit from harvest to the consumer, and ranged from 10 ppb in the CA fruit store with an ethylene scrubber, 70 ppb in the fruit bin, to 500 ppb on the sorting belt in the grading facility, to ppm levels in perforated plastic bags of apples. This paper also takes into account exogenous ethylene originating from sources other than the fruit itself. Countermeasures are discussed, such as the potential of breeding for low-ethylene fruit, applications of ethylene inhibitors (e.g. 1-MCP) and absorber strips (e.g. 'It's Fresh', Ryan'), packages (e.g. 'Peakfresh'), both at the wholesale and retail level, vents and cooling for the supply chain, sale of class II produce ('Wunderlinge'), collection (rather than waste) of produce on the 'sell by' date ('Die Tafel') and whole crop purchase (WCP) to aid reducing

  3. Tau accumulation impairs mitophagy via increasing mitochondrial membrane potential and reducing mitochondrial Parkin

    PubMed Central

    Wang, Zhi-hao; Luo, Yu; Zhang, Xiangnan; Liu, Xiu-Ping; Feng, Qiong; Wang, Qun; Yue, Zhenyu; Chen, Zhong; Ye, Keqiang; Wang, Jian-Zhi; Liu, Gong-Ping

    2016-01-01

    Intracellular accumulation of wild type tau is a hallmark of sporadic Alzheimer's disease (AD). However, the molecular mechanisms underlying tau toxicity is not fully understood. Here, we detected mitophagy deficits evidenced by the increased levels of mitophagy markers, including COX IV, TOMM20, and the ratio of mtDNA to genomic DNA indexed as mt-Atp6/Rpl13, in the AD brains and in the human wild type full-length tau (htau) transgenic mice. More interestingly, the mitophagy deficit was only shown in the AD patients who had an increased total tau level. Further studies demonstrated that overexpression of htau induced mitophagy deficits in HEK293 cells, the primary hippocampal neurons and in the brains of C57 mice. Upon overexpression of htau, the mitochondrial membrane potential was increased and the levels of PTEN-induced kinase 1 (PINK1) and Parkin decreased in the mitochondrial fraction, while upregulation of Parkin attenuated the htau-induced mitophagy deficits. Finally, we detected a dose-dependent allocation of tau proteins into the mitochondrial outer membrane fraction along with its cytoplasmic accumulation. These data suggest that intracellular accumulation of htau induces mitophagy deficits by direct inserting into the mitochondrial membrane and thus increasing the membrane potential, which impairs the mitochondrial residence of PINK1/Parkin. Our findings reveal a novel mechanism underlying the htau-induced neuronal toxicities in AD and other tauopathies. PMID:26943044

  4. Oregonin reduces lipid accumulation and proinflammatory responses in primary human macrophages.

    PubMed

    Lundqvist, Annika; Magnusson, Lisa U; Ullström, Christina; Krasilnikova, Jelena; Telysheva, Galina; Dizhbite, Tatjana; Hultén, Lillemor Mattsson

    2015-03-13

    Inflammation in the vascular wall is important for the development of atherosclerosis. We have previously shown that inflammatory macrophages are more abundant in human atherosclerotic lesions than in healthy arteries. Activated macrophages produce reactive oxygen species (ROS) that promote local inflammation in atherosclerotic lesions. Here, we investigated the role of oregonin, a diarylheptanoid, on proinflammatory responses in primary human macrophages and found that oregonin decreased cellular lipid accumulation and proinflammatory cytokine secretion. We also found that oregonin decreased ROS production in macrophages. Additionally, we observed that treatment of lipopolysaccharide-exposed macrophages with oregonin significantly induced the expression of antioxidant-related genes, including Heme oxygenase-1 and NADPH dehydrogenase quinone 1. In summary, we have shown that oregonin reduces lipid accumulation, inflammation and ROS production in primary human macrophages, indicating that oregonin has anti-inflammatory bioactivities. PMID:25686497

  5. Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

    PubMed

    Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

    2016-05-01

    Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss. PMID:26758875

  6. Accumulation of particulate matter and trace elements on vegetation as affected by pollution level, rainfall and the passage of time.

    PubMed

    Przybysz, A; Sæbø, A; Hanslin, H M; Gawroński, S W

    2014-05-15

    Particulate matter is harmful to human health. To reduce its concentration in air, plants could be used as biological filters, accumulating particulate matter on their foliage. In a study carried out at three sites with differing pollution levels and exposure to precipitation, the capacity of evergreen species (Taxus baccata L., Hedera helix L. and Pinus sylvestris L.) to accumulate particulate matter and trace elements from ambient air in urban areas was investigated. The effects of rainfall and the passage of time on particulate matter deposition on foliage were also determined. The results showed that foliage accumulated an increasing quantity of particulate matter in successive months, but the actual amount of particulate matter and trace elements accumulated differed considerably between sites and plant species. The greatest accumulation of air pollutants occurred on the foliage of plants protected from the rain at a site exposed to traffic related pollution and the smallest accumulation at a rural site. Among the species analysed, the deposited mass of particulate matter and trace elements was the greatest on P. sylvestris. In all species, precipitation removed a considerable proportion of particles accumulated on foliage. Most of the removed particulate matter was large size fraction, but little belong to the smallest size fraction. These results showed that both, the dynamics of deposition and leaf washing by rain during the season need to be considered when evaluating the total effect of vegetation in pollutant remediation. PMID:24607629

  7. Exogenous malic and acetic acids reduce cadmium phytotoxicity and enhance cadmium accumulation in roots of sunflower plants.

    PubMed

    Hawrylak-Nowak, Barbara; Dresler, Sławomir; Matraszek, Renata

    2015-09-01

    There is increasing evidence showing that low molecular weight organic acids (LMWOA) are involved in heavy metal resistance mechanisms in plants. The aim of this study was to investigate the effects of exogenous malic (MA) or acetic (AA) acids on the toxicity and accumulation of cadmium (Cd) in sunflower (Helianthus annuus L.). For this purpose, plants were grown in hydroponics under controlled conditions. Single Cd stress (5 μM Cd for 14 days) induced strong phytotoxic effects, as indicated by a decrease in all growth parameters, concentration of photosynthetic pigments, and root activity, as well as a high level of hydrogen peroxide (H2O2) accumulation. Exogenous MA or AA (250 or 500 μM) applied to the Cd-containing medium enhanced the accumulation of Cd by the roots and limited Cd translocation to the shoots. Moreover, the MA or AA applied more or less reduced Cd phytotoxicity by increasing the growth parameters, photosynthetic pigment concentrations, decreasing accumulation of H2O2, and improving the root activity. Of the studied organic acids, MA was much more efficient in mitigation of Cd toxicity than AA, probably by its antioxidant effects, which were stronger than those of AA. Plant response to Cd involved decreased production of endogenous LMWOA, probably as a consequence of severe Cd toxicity. The addition of MA or AA to the medium increased endogenous accumulation of LMWOA, especially in the roots, which could be beneficial for plant metabolism. These results imply that especially MA may be involved in the processes of Cd uptake, translocation, and tolerance in plants. PMID:26115548

  8. TNF Neutralization Results in the Delay of Transplantable Tumor Growth and Reduced MDSC Accumulation

    PubMed Central

    Atretkhany, Kamar-Sulu N.; Nosenko, Maxim A.; Gogoleva, Violetta S.; Zvartsev, Ruslan V.; Qin, Zhihai; Nedospasov, Sergei A.; Drutskaya, Marina S.

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells (IMCs) that, under normal conditions, may differentiate into mature macrophages, granulocytes, and dendritic cells. However, under pathological conditions associated with inflammation, cancer, or infection, such differentiation is inhibited leading to IMC expansion. Under the influence of inflammatory cytokines, these cells become MDSCs, acquire immunosuppressive phenotype, and accumulate in the affected tissue, as well as in the periphery. Immune suppressive activity of MDSCs is partly due to upregulation of arginase 1, inducible nitric oxide synthase, and anti-inflammatory cytokines, such as IL-10 and TGF-β. These suppressive factors can enhance tumor growth by repressing T-cell-mediated anti-tumor responses. TNF is a critical factor for the induction, expansion, and suppressive activity of MDSCs. In this study, we evaluated the effects of systemic TNF ablation on tumor-induced expansion of MDSCs in vivo using TNF humanized (hTNF KI) mice. Both etanercept and infliximab treatments resulted in a delayed growth of MCA 205 fibrosarcoma in hTNF KI mice, significantly reduced tumor volume, and also resulted in less accumulated MDSCs in the blood 3 weeks after tumor cell inoculation. Thus, our study uncovers anti-tumor effects of systemic TNF ablation in vivo. PMID:27148266

  9. TNF Neutralization Results in the Delay of Transplantable Tumor Growth and Reduced MDSC Accumulation.

    PubMed

    Atretkhany, Kamar-Sulu N; Nosenko, Maxim A; Gogoleva, Violetta S; Zvartsev, Ruslan V; Qin, Zhihai; Nedospasov, Sergei A; Drutskaya, Marina S

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells (IMCs) that, under normal conditions, may differentiate into mature macrophages, granulocytes, and dendritic cells. However, under pathological conditions associated with inflammation, cancer, or infection, such differentiation is inhibited leading to IMC expansion. Under the influence of inflammatory cytokines, these cells become MDSCs, acquire immunosuppressive phenotype, and accumulate in the affected tissue, as well as in the periphery. Immune suppressive activity of MDSCs is partly due to upregulation of arginase 1, inducible nitric oxide synthase, and anti-inflammatory cytokines, such as IL-10 and TGF-β. These suppressive factors can enhance tumor growth by repressing T-cell-mediated anti-tumor responses. TNF is a critical factor for the induction, expansion, and suppressive activity of MDSCs. In this study, we evaluated the effects of systemic TNF ablation on tumor-induced expansion of MDSCs in vivo using TNF humanized (hTNF KI) mice. Both etanercept and infliximab treatments resulted in a delayed growth of MCA 205 fibrosarcoma in hTNF KI mice, significantly reduced tumor volume, and also resulted in less accumulated MDSCs in the blood 3 weeks after tumor cell inoculation. Thus, our study uncovers anti-tumor effects of systemic TNF ablation in vivo. PMID:27148266

  10. Altered cell wall properties are responsible for ammonium-reduced aluminium accumulation in rice roots.

    PubMed

    Wang, Wei; Zhao, Xue Qiang; Chen, Rong Fu; Dong, Xiao Ying; Lan, Ping; Ma, Jian Feng; Shen, Ren Fang

    2015-07-01

    The phytotoxicity of aluminium (Al) ions can be alleviated by ammonium (NH4(+)) in rice and this effect has been attributed to the decreased Al accumulation in the roots. Here, the effects of different nitrogen forms on cell wall properties were compared in two rice cultivars differing in Al tolerance. An in vitro Al-binding assay revealed that neither NH4(+) nor NO3(-) altered the Al-binding capacity of cell walls, which were extracted from plants not previously exposed to N sources. However, cell walls extracted from NH4(+)-supplied roots displayed lower Al-binding capacity than those from NO3(-)-supplied roots when grown in non-buffered solutions. Fourier-transform infrared microspectroscopy analysis revealed that, compared with NO3(-)-supplied roots, NH4(+)-supplied roots possessed fewer Al-binding groups (-OH and COO-) and lower contents of pectin and hemicellulose. However, when grown in pH-buffered solutions, these differences in the cell wall properties were not observed. Further analysis showed that the Al-binding capacity and properties of cell walls were also altered by pHs alone. Taken together, our results indicate that the NH4(+)-reduced Al accumulation was attributed to the altered cell wall properties triggered by pH decrease due to NH4(+) uptake rather than direct competition for the cell wall binding sites between Al(3+) and NH4(+). PMID:25444246

  11. Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation

    PubMed Central

    Fu, Ming; Sato, Yoshiharu; Lyons-Warren, Ariel; Zhang, Bin; Kane, Maureen A.; Napoli, Joseph L.; Heuckeroth, Robert O.

    2010-01-01

    Hirschsprung disease is a serious disorder of enteric nervous system (ENS) development caused by the failure of ENS precursor migration into the distal bowel. We now demonstrate that retinoic acid (RA) is crucial for GDNF-induced ENS precursor migration, cell polarization and lamellipodia formation, and that vitamin A depletion causes distal bowel aganglionosis in serum retinol-binding-protein-deficient (Rbp4–/–) mice. Ret heterozygosity increases the incidence and severity of distal bowel aganglionosis induced by vitamin A deficiency in Rbp4–/– animals. Furthermore, RA reduces phosphatase and tensin homolog (Pten) accumulation in migrating cells, whereas Pten overexpression slows ENS precursor migration. Collectively, these data support the hypothesis that vitamin A deficiency is a non-genetic risk factor that increases Hirschsprung disease penetrance and expressivity, suggesting that some cases of Hirschsprung disease might be preventable by optimizing maternal nutrition. PMID:20110328

  12. The HSP terminator of Arabidopsis thaliana induces a high level of miraculin accumulation in transgenic tomatoes.

    PubMed

    Hirai, Tadayoshi; Kurokawa, Natsuko; Duhita, Narendra; Hiwasa-Tanase, Kyoko; Kato, Kazuhisa; Kato, Ko; Ezura, Hiroshi

    2011-09-28

    High-level accumulation of the target recombinant protein is a significant issue in heterologous protein expression using transgenic plants. Miraculin, a taste-modifying protein, was accumulated in transgenic tomatoes using an expression cassette in which the miraculin gene was expressed by the cauliflower mosaic virus (CaMV) 35S promoter and the heat shock protein (HSP) terminator (MIR-HSP). The HSP terminator was derived from heat shock protein 18.2 in Arabidopsis thaliana . Using this HSP-containing cassette, the miraculin concentration in T0 transgenic tomato lines was 1.4-13.9% of the total soluble protein (TSP), and that in the T1 transgenic tomato line homozygous for the miraculin gene reached 17.1% of the TSP. The accumulation level of the target protein was comparable to levels observed with chloroplast transformation. The high-level accumulation of miraculin in T0 transgenic tomato lines achieved by the HSP terminator was maintained in the successive T1 generation, demonstrating the genetic stability of this accumulation system. PMID:21861502

  13. Iron-reducing bacteria accumulate ferric oxyhydroxide nanoparticle aggregates that may support planktonic growth

    SciTech Connect

    Luef, Birgit; Fakra, Sirine C.; Csencsits, Roseann; Wrighton, Kelly C.; Williams, Kenneth H.; Wilkins, Michael J.; Downing, Kenneth H.; Long, Philip E.; Comolli, Luis R.; Banfield, Jillian F.

    2013-02-04

    Iron-reducing bacteria (FeRB) play key roles in anaerobic metal and carbon cycling and carry out biogeochemical transformations that can be harnessed for environmental bioremediation. A subset of FeRB require direct contact with Fe(III) bearing minerals for dissimilatory growth, yet these bacteria must move between mineral particles. Further, they proliferate in planktonic consortia during biostimulation experiments. Thus, a key question is how such organisms can sustain growth under these conditions. Here we characterized planktonic microbial communities sampled from an aquifer in Rifle, Colorado, USA close to the peak of iron reduction following in situ acetate amendment. Samples were cryo-plunged on site and subsequently examined using correlated 2- and 3- dimensional cryogenic transmission electron microscopy (cryo-TEM) and scanning transmission X-ray microscopy (STXM). Most cells had their outer membranes decorated with up to 150 nm diameter aggregates composed of a few nm wide amorphous, Fe-rich nanoparticles. Fluorescent in situ hybridization of lineage-specific probes applied to rRNA of cells subsequently imaged via cryo-TEM identified Geobacter spp., a well studied group of FeRB. STXM results at the Fe L2,3 absorption edges indicate that nanoparticle aggregates contain a variable mixture of Fe(II)-Fe(III), and are generally enriched in Fe(III). Geobacter bemidjiensis cultivated anaerobically in the laboratory on acetate and hydrous ferric oxyhydroxides also accumulated mixed valence nanoparticle aggregates. In field-collected samples, FeRB with a wide variety of morphologies were associated with nano-aggregates, indicating that cell-surface Fe(III) accumulation may be a general mechanism by which FeRB can grow while in planktonic suspension.

  14. Iron-reducing bacteria accumulate ferric oxyhydroxide nanoparticle aggregates that may support planktonic growth

    PubMed Central

    Luef, Birgit; Fakra, Sirine C; Csencsits, Roseann; Wrighton, Kelly C; Williams, Kenneth H; Wilkins, Michael J; Downing, Kenneth H; Long, Philip E; Comolli, Luis R; Banfield, Jillian F

    2013-01-01

    Iron-reducing bacteria (FeRB) play key roles in anaerobic metal and carbon cycling and carry out biogeochemical transformations that can be harnessed for environmental bioremediation. A subset of FeRB require direct contact with Fe(III)-bearing minerals for dissimilatory growth, yet these bacteria must move between mineral particles. Furthermore, they proliferate in planktonic consortia during biostimulation experiments. Thus, a key question is how such organisms can sustain growth under these conditions. Here we characterized planktonic microbial communities sampled from an aquifer in Rifle, Colorado, USA, close to the peak of iron reduction following in situ acetate amendment. Samples were cryo-plunged on site and subsequently examined using correlated two- and three-dimensional cryogenic transmission electron microscopy (cryo-TEM) and scanning transmission X-ray microscopy (STXM). The outer membranes of most cells were decorated with aggregates up to 150 nm in diameter composed of ∼3 nm wide amorphous, Fe-rich nanoparticles. Fluorescent in situ hybridization of lineage-specific probes applied to rRNA of cells subsequently imaged via cryo-TEM identified Geobacter spp., a well-studied group of FeRB. STXM results at the Fe L2,3 absorption edges indicate that nanoparticle aggregates contain a variable mixture of Fe(II)–Fe(III), and are generally enriched in Fe(III). Geobacter bemidjiensis cultivated anaerobically in the laboratory on acetate and hydrous ferric oxyhydroxides also accumulated mixed-valence nanoparticle aggregates. In field-collected samples, FeRB with a wide variety of morphologies were associated with nano-aggregates, indicating that cell surface Fe(III) accumulation may be a general mechanism by which FeRB can grow while in planktonic suspension. PMID:23038172

  15. Reducing Isozyme Competition Increases Target Fatty Acid Accumulation in Seed Triacylglycerols of Transgenic Arabidopsis1[OPEN

    PubMed Central

    van Erp, Harrie; Shockey, Jay; Zhang, Meng; Adhikari, Neil D.; Browse, John

    2015-01-01

    One goal of green chemistry is the production of industrially useful fatty acids (FAs) in crop plants. We focus on hydroxy fatty acids (HFAs) and conjugated polyenoic FAs (α-eleostearic acids [ESAs]) using Arabidopsis (Arabidopsis thaliana) as a model. These FAs are found naturally in seed oils of castor (Ricinus communis) and tung tree (Vernicia fordii), respectively, and used for the production of lubricants, nylon, and paints. Transgenic oils typically contain less target FA than that produced in the source species. We hypothesized that competition between endogenous and transgenic isozymes for substrates limits accumulation of unique FAs in Arabidopsis seeds. This hypothesis was tested by introducing a mutation in Arabidopsis diacylglycerol acyltransferase1 (AtDGAT1) in a line expressing castor FA hydroxylase and acyl-Coenzyme A:RcDGAT2 in its seeds. This led to a 17% increase in the proportion of HFA in seed oil. Expression of castor phospholipid:diacylglycerol acyltransferase 1A in this line increased the proportion of HFA by an additional 12%. To determine if our observations are more widely applicable, we investigated if isozyme competition influenced production of ESA. Expression of tung tree FA conjugase/desaturase in Arabidopsis produced approximately 7.5% ESA in seed lipids. Coexpression of VfDGAT2 increased ESA levels to approximately 11%. Overexpression of VfDGAT2 combined with suppression of AtDGAT1 increased ESA accumulation to 14% to 15%. Our results indicate that isozyme competition is a limiting factor in the engineering of unusual FAs in heterologous plant systems and that reduction of competition through mutation and RNA suppression may be a useful component of seed metabolic engineering strategies. PMID:25739701

  16. Exogenous rhTRX reduces lipid accumulation under LPS-induced inflammation

    PubMed Central

    Han, Gi-Yeon; Lee, Eun-Kyung; Park, Hey-won; Kim, Hyun-Jung; Kim, Chan-Wha

    2014-01-01

    Redox-regulating molecule, recombinant human thioredoxin (rhTRX) which shows anti-inflammatory, and anti-oxidative effects against lipopolysaccharide (LPS)-stimulated inflammation and regulate protein expression levels. LPS-induced reactive oxygen intermediates (ROI) and NO production were inhibited by exogenous rhTRX. We identified up/downregulated intracellular proteins under the LPS-treated condition in exogenous rhTRX-treated A375 cells compared with non-LPS-treated cells via 2-DE proteomic analysis. Also, we quantitatively measured cytokines of in vivo mouse inflammation models using cytometry bead array. Exogenous rhTRX inhibited LPS-stimulated production of ROI and NO levels. TIP47 and ATP synthase may influence the inflammation-related lipid accumulation by affecting lipid metabolism. The modulation of skin redox environments during inflammation is most likely to prevent alterations in lipid metabolism through upregulation of TIP47 and ATP synthase and downregulation of inflammatory cytokines. Our results demonstrate that exogenous rhTRX has anti-inflammatory properties and intracellular regulatory activity in vivo and in vitro. Monitoring of LPS-stimulated pro-inflammatory conditions treated with rhTRX in A375 cells could be useful for diagnosis and follow-up of inflammation reduction related with candidate proteins. These results have a therapeutic role in skin inflammation therapy. PMID:24406320

  17. Specific accumulation of organochlorines in human breast milk from Indonesia: levels, distribution, accumulation kinetics and infant health risk.

    PubMed

    Sudaryanto, Agus; Kunisue, Tatsuya; Kajiwara, Natsuko; Iwata, Hisato; Adibroto, Tussy A; Hartono, Phillipus; Tanabe, Shinsuke

    2006-01-01

    This study determined concentrations of polychlorinated biphenyls (PCBs) and organochlorine compound (OC) pesticides in the milk samples of women from the general population in four locations of Indonesia. The most prevalent residues of OCs were DDTs, PCBs and hexachlorocyclohexane isomers (HCHs), whereas other OCs such as chlordane compounds (CHLs), tris(4-chlorophenyl)methane and hexachlorobenzene were lower. The levels of OCs varied between locations and individuals, with DDTs higher in suburban and rural areas than urban localities, may be due to the differences in food habits and sources between the individuals and locations. Data from Purwakarta site indicated continuing DDT exposure, which may confirm recent usage of DDT in Indonesia. A positive correlation was observed between concentration of OCs in human milk and age of mothers, primiparas women having higher OCs than multiparas, suggesting these parameters play an important role influencing the OC burdens in lactating women. Some individuals accumulated DDTs and HCHs in breast milk close to or even higher than the TDI (tolerable daily intake) guidelines proposed by Health Canada. PMID:15992976

  18. Olive Leaf Extract from Sicilian Cultivar Reduced Lipid Accumulation by Inducing Thermogenic Pathway during Adipogenesis.

    PubMed

    Palmeri, Rosa; Monteleone, Julieta I; Spagna, Giovanni; Restuccia, Cristina; Raffaele, Marco; Vanella, Luca; Li Volti, Giovanni; Barbagallo, Ignazio

    2016-01-01

    Olive leaves contain a wide variety of phenolic compounds belonging to phenolic acids, phenolic alcohols, flavonoids, and secoiridoids, and include also many other pharmacological active compounds. They could play an important role in human diet and health because of their ability to lower blood pressure, increase coronary arteries blood flow and decrease the risk of cardiovascular diseases. The aim of this study was to investigate the effect of olive leaf extract (OLE) from Sicilian cultivar on adipogenic differentiation of human adipose derived mesenchymal stem cells and its impact on lipid metabolism. We showed that OLE treatment during adipogenic differentiation reduces inflammation, lipid accumulation and induces thermogenesis by activation of uncoupling protein uncoupling protein 1, sirtuin 1, peroxisome proliferator-activated receptor alpha, and coactivator 1 alpha. Furthermore, OLE significantly decreases the expression of molecules involved in adipogenesis and upregulates the expression of mediators involved in thermogenesis and lipid metabolism. Taken together, our results suggest that OLE may promote the brown remodeling of white adipose tissue inducing thermogenesis and improving metabolic homeostasis. PMID:27303302

  19. Olive Leaf Extract from Sicilian Cultivar Reduced Lipid Accumulation by Inducing Thermogenic Pathway during Adipogenesis

    PubMed Central

    Palmeri, Rosa; Monteleone, Julieta I.; Spagna, Giovanni; Restuccia, Cristina; Raffaele, Marco; Vanella, Luca; Li Volti, Giovanni; Barbagallo, Ignazio

    2016-01-01

    Olive leaves contain a wide variety of phenolic compounds belonging to phenolic acids, phenolic alcohols, flavonoids, and secoiridoids, and include also many other pharmacological active compounds. They could play an important role in human diet and health because of their ability to lower blood pressure, increase coronary arteries blood flow and decrease the risk of cardiovascular diseases. The aim of this study was to investigate the effect of olive leaf extract (OLE) from Sicilian cultivar on adipogenic differentiation of human adipose derived mesenchymal stem cells and its impact on lipid metabolism. We showed that OLE treatment during adipogenic differentiation reduces inflammation, lipid accumulation and induces thermogenesis by activation of uncoupling protein uncoupling protein 1, sirtuin 1, peroxisome proliferator-activated receptor alpha, and coactivator 1 alpha. Furthermore, OLE significantly decreases the expression of molecules involved in adipogenesis and upregulates the expression of mediators involved in thermogenesis and lipid metabolism. Taken together, our results suggest that OLE may promote the brown remodeling of white adipose tissue inducing thermogenesis and improving metabolic homeostasis. PMID:27303302

  20. Cadmium-Induced Hydrogen Accumulation Is Involved in Cadmium Tolerance in Brassica campestris by Reestablishment of Reduced Glutathione Homeostasis

    PubMed Central

    Chen, Qin; Shen, Wenbiao; Shen, Zhenguo; Xia, Yan; Cui, Jin

    2015-01-01

    Hydrogen gas (H2) was recently proposed as a therapeutic antioxidant and signaling molecule in clinical trials. However, the underlying physiological roles of H2 in plants remain unclear. In the present study, hydrogen-rich water (HRW) was used to characterize the physiological roles of H2 in enhancing the tolerance of Brassica campestris against cadmium (Cd). The results showed that both 50 μM CdCl2 and 50%-saturated HRW induced an increase of endogenous H2 in Brassica campestris seedlings, and HRW alleviated Cd toxicity related to growth inhibition and oxidative damage. Seedlings supplied with HRW exhibited increased root length and reduced lipid peroxidation, similar to plants receiving GSH post-treatment. Additionally, seedlings post-treated with HRW accumulated higher levels of reduced glutathione (GSH) and ascorbic acid (AsA) and showed increased GST and GPX activities in roots. Molecular evidence illustrated that the expression of genes such as GS, GR1 and GR2, which were down-regulated following the addition of Cd, GSH or BSO, could be reversed to varying degrees by the addition of HRW. Based on these results, it could be proposed that H2 might be an important regulator for enhancing the tolerance of Brassica campestris seedlings against Cd, mainly by governing reduced glutathione homeostasis. PMID:26445361

  1. Emodin ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle.

    PubMed

    Cao, Yanni; Chang, Shufang; Dong, Jie; Zhu, Shenyin; Zheng, Xiaoying; Li, Juan; Long, Rui; Zhou, Yuanda; Cui, Jianyu; Zhang, Ye

    2016-06-01

    Emodin, an anthraquinone derivative isolated from root and rhizome of Rheum palmatum, has been reported to have promising anti-diabetic activity. The present study was to explore the possible mechanism of emodin to ameliorate insulin resistance. Insulin resistance was induced by feeding a high fat diet to Sprague-Dawley rats. The blood glucose and lipid profiles in serum were measured by an enzymatic method, and a hyperinsulinaemic-euglycaemic clamp was used to evaluate insulin resistance. L6 cells were cultured and treated with palmitic acid and emodin. The lipid content was assayed in the soleus muscle and L6 cells by Oil Red O staining. Western blot, qRT-PCR, and immunohistochemical staining were used to detect the following in the rat soleus muscle and L6 cells: protein levels, mRNA levels of FATP1, FATP4, transporter fatty acid translocase (FAT/CD36), and plasma membrane-associated fatty acid protein (FABPpm). We found that blood glucose, triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly decreased in the emodin group. Oil Red O staining and the level of TG in skeletal muscle and L6 cells confirmed that lipid deposition decreased after treatment with emodin. Furthermore, the protein levels and mRNA levels of FATP1 in skeletal muscle and in L6 cells of rats were significantly decreased, yet the protein levels and mRNA levels of FATP4, FAT/CD36 and FABPpm did not drop off significantly. The study suggest that emodin ameliorates insulin resistance by reducing FATP1-mediated skeletal muscle lipid accumulation in rats fed a high fat diet. PMID:27020550

  2. Ezetimibe Reduces Plant Sterol Accumulation and Favorably Increases Platelet Count in Sitosterolemia

    PubMed Central

    Othman, Rgia A.; Myrie, Semone B.; Mymin, David; Merkens, Louise S.; Roullet, Jean-Baptiste; Steiner, Robert D.; Jones, Peter J.H.

    2014-01-01

    Objective To assess if ezetimibe (EZE), a sterol-absorption inhibitor, improves platelet (PLT) count and size relative to its effect on plasma plant sterol (PS) in patients with sitosterolemia (STSL). Study design Patients with STSL (5 males, 3 females, 16 to 56 years of age) receiving EZE intervention as part of their routine care participated in this study. EZE was discontinued for 14 weeks (off) and then resumed for another 14 weeks (on). Hematology variables along with plasma and red blood cells (RBC) PS and total cholesterol (TC) levels were measured at the end of each phase. Results EZE increased PLT count (23 ± 9%) and decreased mean PLT volume (MPV; 10 ± 3%, all P < .05). In patients off EZE, PLT counts inversely correlated (r = − 0.96 and r = − 0.91, all P < .01) with plasma and RBC PS to TC ratio (PS/TC), and MPV positively correlated (r = 0.91, P = .03 and r = 0.93, P = .02) with plasma and RBC PS/TC. EZE reduced plasma and RBC sitosterol (−35 ± 4 and −28 ± 3%), total PS (−37 ± 4 and −28 ± 3%, all P < .0001) levels and PS/TC (−27 ± 4 and −28 ± 4%, P < .01). Conclusion EZE reduces plasma and RBC PS levels, and increasing PLT count and decreasing MPV, and thereby may reduce the risk for bleeding in STSL. Plasma PS levels and ABCG5/ABCG8 genes should be analyzed in patients with unexplained hematologic abnormalities. PMID:25444527

  3. Fluid-phase pinocytosis of LDL by macrophages: a novel target to reduce macrophage cholesterol accumulation in atherosclerotic lesions.

    PubMed

    Kruth, Howar S

    2013-01-01

    Circulating low-density lipoprotein (LDL) that enters the blood vessel wall is the main source of cholesterol that accumulates within atherosclerotic plaques. Much of the deposited cholesterol accumulates within plaque macrophages converting these macrophages into cholesterol-rich foamy looking cells. Cholesterol accumulation in macrophages contributes to cholesterol retention within the vessel wall, and promotes vessel wall inflammation and thrombogenicity. Thus, how macrophages accumulate cholesterol and become foam cells has been the subject of intense investigation. It is generally believed that macrophages accumulate cholesterol only through scavenger receptor-mediated uptake of modified LDL. However, an alternative mechanism for macrophage foam cell formation that does not depend on LDL modification or macrophage receptors has been elucidated. By this alternative mechanism, macrophages show receptor-independent uptake of unmodified native LDL that is mediated by fluid-phase pinocytosis. In receptor-independent, fluid-phase pinocytosis, macrophages take up LDL as part of the fluid that they ingest during micropinocytosis within small vesicles called micropinosomes, and by macropinocytosis within larger vacuoles called macropinosomes. This produces cholesterol accumulation in macrophages to levels characteristic of macrophage foam cells in atherosclerotic plaques. Fluid-phase pinocytosis of LDL is a plausible mechanism that can explain how macrophages accumulate cholesterol and become disease-causing foam cells. Fluid-phase pinocytosis of LDL is a relevant pathway to target for modulating macrophage cholesterol accumulation in atherosclerosis. Recent studies show that phosphoinositide 3-kinase (PI3K), liver X receptors (LXRs), the macrophage colony-stimulating factor (M-CSF) receptor, and protein kinase C (PKC) mediate macrophage macropinocytosis of LDL, and thus, these may be relevant targets to inhibit macrophage cholesterol accumulation in atherosclerosis

  4. Overexpression of rice glutaredoxins (OsGrxs) significantly reduces arsenite accumulation by maintaining glutathione pool and modulating aquaporins in yeast.

    PubMed

    Verma, Pankaj Kumar; Verma, Shikha; Meher, Alok Kumar; Pande, Veena; Mallick, Shekhar; Bansiwal, Amit Kumar; Tripathi, Rudra Deo; Dhankher, Om Parkash; Chakrabarty, Debasis

    2016-09-01

    Arsenic (As) is an acute poison and class I carcinogen, can cause a serious health risk. Staple crops like rice are the primary source of As contamination in human food. Rice grown on As contaminated areas accumulates higher As in their edible parts. Based on our previous transcriptome data, two rice glutaredoxins (OsGrx_C7 and OsGrx_C2.1) were identified that showed up-regulated expression during As stress. Here, we report OsGrx_C7 and OsGrx_C2.1 from rice involved in the regulation of intracellular arsenite (AsIII). To elucidate the mechanism of OsGrx mediated As tolerance, both OsGrxs were cloned and expressed in Escherichia coli (Δars) and Saccharomyces cerevisiae mutant strains (Δycf1, Δacr3). The expression of OsGrxs increased As tolerance in E. coli (Δars) mutant strain (up to 4 mM AsV and up to 0.6 mM AsIII). During AsIII exposure, S. cerevisiae (Δacr3) harboring OsGrx_C7 and OsGrx_C2.1 have lower intracellular AsIII accumulation (up to 30.43% and 24.90%, respectively), compared to vector control. Arsenic accumulation in As-sensitive S. cerevisiae mutant (Δycf1) also reduced significantly on exposure to inorganic As. The expression of OsGrxs in yeast maintained intracellular GSH pool and increased extracellular GSH concentration. Purified OsGrxs displays in vitro GSH-disulfide oxidoreductase, glutathione reductase and arsenate reductase activities. Also, both OsGrxs are involved in AsIII extrusion by altering the Fps1 transcripts in yeast and protect the cell by maintaining cellular GSH pool. Thus, our results strongly suggest that OsGrxs play a crucial role in the maintenance of the intracellular GSH pool and redox status of the cell during both AsV and AsIII stress and might be involved in regulating intracellular AsIII levels by modulation of aquaporin expression and functions. PMID:27174139

  5. Walnut diet reduces accumulation of polyubiquitinated proteins and inflammation in the brain of aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An increase in the aggregation of misfolded/damaged polyubiquitinated proteins has been the hallmark of many age-related neurodegenerative diseases. The accumulation of these potentially toxic proteins in brain increases with age, in part due to increased oxidative and inflammatory stresses. Walnuts...

  6. RNA interference reduces aflatoxin accumulation by Aspergillus flavus in peanut seeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aflatoxins are among the most powerful carcinogens in nature. They are produced by the fungal pathogen Aspergillus flavus Link and other Aspergillus species. Aflatoxins accumulate in many crops, including rice, wheat, oats, pecans, pistachios, soybean, cassava, almonds, peanuts, beans, corn and cot...

  7. Low levels of astroglial markers in Parkinson's disease: relationship to α-synuclein accumulation.

    PubMed

    Tong, Junchao; Ang, Lee-Cyn; Williams, Belinda; Furukawa, Yoshiaki; Fitzmaurice, Paul; Guttman, Mark; Boileau, Isabelle; Hornykiewicz, Oleh; Kish, Stephen J

    2015-10-01

    Although gliosis is a normal response to brain injury, reports on the extent of astrogliosis in the degenerating substantia nigra in Parkinson's disease (PD) are conflicting. It has also been recently suggested that accumulation of nigral α-synuclein in this disorder might suppress astrocyte activation which in turn could exacerbate the degenerative process. This study examined brain protein levels (intact protein, fragments, and aggregates, if any) of astroglial markers and their relationship to α-synuclein in PD and in the positive control parkinson-plus conditions multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Autopsied brain homogenates of patients with PD (n=10), MSA (n=11), PSP (n=11) and matched controls (n=10) were examined for the astroglial markers glial fibrillary acidic protein (GFAP), vimentin, and heat shock protein-27 (Hsp27) by quantitative immunoblotting. As expected, both MSA (putamen>substantia nigra>caudate>frontal cortex) and PSP (substantia nigra>caudate>putamen, frontal cortex) showed widespread but regionally specific pattern of increased immunoreactivity of the markers, in particular for the partially proteolyzed fragments (all three) and aggregates (GFAP). In contrast, immunoreactivity of the three markers was largely normal in PD in brain regions examined with the exception of trends for variably increased levels of cleaved vimentin in substantia nigra and frontal cortex. In patients with PD, GFAP levels in the substantia nigra correlated inversely with α-synuclein accumulation whereas the opposite was true for MSA. Our biochemical findings of generally normal protein levels of astroglial markers in substantia nigra of PD, and negative correlation with α-synuclein concentration, are consistent with some recent neuropathology reports of mild astroglial response and with the speculation that astrogliosis might be suppressed in this disorder by excessive α-synuclein accumulation. Should astrogliosis protect, to

  8. Reduced uptake and accumulation of norfloxacin in resistant strains of Neisseria gonorrhoeae isolated in Japan.

    PubMed Central

    Tanaka, M; Fukuda, H; Hirai, K; Hosaka, M; Matsumoto, T; Kumazawa, J

    1994-01-01

    OBJECTIVE--To investigate the alteration of cell permeability toward fluoroquinolones in Neisseria gonorrhoeae, which is a major quinolone-resistance mechanism along with the alteration of DNA gyrase in gram-negative bacteria. The prevalence of fluoroquinolone-resistant N gonorrhoeae strains is rapidly increasing in Japan. MATERIALS AND METHODS--The uptake and accumulation of norfloxacin by gonococcal cells, including six clinical and five World Health Organization (WHO) reference strains, were measured. Of the six clinical strains, two were highly resistant to norfloxacin (MIC 8.0 and 4.0 micrograms/ml), two were moderately resistant (MIC 1.0 and 0.5 microgram/ml), and two were sensitive (MIC 0.063 and 0.004 microgram/ml). All five WHO reference strains were sensitive to norfloxacin (MIC < or = 0.001 to 0.063 microgram/ml). RESULTS--Mean initial norfloxacin uptake in the four resistant strains (104 ng/mg of dry cells) was significantly lower than that in the seven sensitive strains (158 ng/mg of dry cells) (p < 0.05). The mean uptake after 20 minutes was also significantly lower in the four resistant strains (130 ng/mg of dry cells) than in the seven sensitive strains (194 ng/mg of dry cells) (p < 0.05). However, there was no significant difference in mean norfloxacin accumulation after 20 minutes between the four resistant strains (26 ng/mg of dry cells) and the seven sensitive strains (36 ng/mg of dry cells). The accumulation of norfloxacin after 20 minutes was almost zero in two of the four resistant strains, while the remaining two strains accumulated norfloxacin as well as the sensitive strains. CONCLUSIONS--These findings suggest that alteration of bacterial cell permeability is a quinolone-resistance mechanism in N gonorrhoeae isolated in Japan, and that this bacteria may exhibit other mechanisms such as alteration of DNA gyrase. PMID:7959709

  9. An Adaptive Method for Reducing Clock Skew in an Accumulative Z-Axis Interconnect System

    NASA Technical Reports Server (NTRS)

    Bolotin, Gary; Boyce, Lee

    1997-01-01

    This paper will present several methods for adjusting clock skew variations that occur in a n accumulative z-axis interconnect system. In such a system, delay between modules in a function of their distance from one another. Clock distribution in a high-speed system, where clock skew must be kept to a minimum, becomes more challenging when module order is variable before design.

  10. Docosahexaenoic acid reduces ER stress and abnormal protein accumulation and improves neuronal function following traumatic brain injury.

    PubMed

    Begum, Gulnaz; Yan, Hong Q; Li, Liaoliao; Singh, Amneet; Dixon, C Edward; Sun, Dandan

    2014-03-01

    In this study, we investigated the development of endoplasmic reticulum (ER) stress after traumatic brain injury (TBI) and the efficacy of post-TBI administration of docosahexaenoic acid (DHA) in reducing ER stress. TBI was induced by cortical contusion injury in Sprague-Dawley rats. Either DHA (16 mg/kg in DMSO) or vehicle DMSO (1 ml/kg) was administered intraperitoneally at 5 min after TBI, followed by a daily dose for 3-21 d. TBI triggered sustained expression of the ER stress marker proteins including phosphorylated eukaryotic initiation factor-2α, activating transcription factor 4, inositol requiring kinase 1, and C/EBP homologous protein in the ipsilateral cortex at 3-21 d after TBI. The prolonged ER stress was accompanied with an accumulation of abnormal ubiquitin aggregates and increased expression of amyloid precursor protein (APP) and phosphorylated tau (p-Tau) in the frontal cortex after TBI. The ER stress marker proteins were colocalized with APP accumulation in the soma. Interestingly, administration of DHA attenuated all ER stress marker proteins and reduced the accumulation of both ubiquitinated proteins and APP/p-Tau proteins. In addition, the DHA-treated animals exhibited early recovery of their sensorimotor function after TBI. In summary, our study demonstrated that TBI induces a prolonged ER stress, which is positively correlated with abnormal APP accumulation. The sustained ER stress may play a role in chronic neuronal damage after TBI. Our findings illustrate that post-TBI administration of DHA has therapeutic potentials in reducing ER stress, abnormal protein accumulation, and neurological deficits. PMID:24599472

  11. Characterization of cadmium-resistant bacteria and their potential for reducing accumulation of cadmium in rice grains.

    PubMed

    Lin, Xiaoyan; Mou, Renxiang; Cao, Zhaoyun; Xu, Ping; Wu, Xiaoliang; Zhu, Zhiwei; Chen, Mingxue

    2016-11-01

    Cadmium (Cd) pollution is a serious widespread environmental problem that not only destroys the microbial ecology of soil and decreases crop production, but also poses a serious risk to human health. Many methods have been used for the remediation of Cd pollution but none of these is totally satisfactory. Microbial remediation strategies have attracted increasing interest since they are environmentally friendly and cost-effective. In the present study, three Cd-resistant bacteria were isolated and evaluated for potential application in Cd bioremediation. Based on their morphological, physiological and biochemical characteristics, together with 16S rDNA gene sequence analyses, bacteria were identified as Stenotrophomonas acidaminiphila (2#), Pseudomonas aeruginosa (9#) and Delftia tsuruhatensis (12#). Pseudomonas aeruginosa showed very high tolerance to metals, especially Cd (2200mg/L), Zn (1800mg/L) and Pb (1200mg/L), and is thought to be a multi-metal-resistant bacterium. Pseudomonas aeruginosa was also sensitive to 13 different antibiotics. The effects of the bacterial strains on the growth of rice plants and their ability to reduce Cd accumulation from Cd-contaminated soils in pot experiments were also evaluated. For Oryza sativa L. A grown in contaminated soil (3mg/kg Cd), the accumulation of Cd was decreased by 31.2 and 25.5% in brown rice and polished rice, respectively, by strain 9#; Pseudomonas aeruginosa was more effective in reducing Cd accumulation in rice grains than a mixture of strains. For Oryza sativa L. B, a mixture of strains acting synergistically was more effective than a single strain in reducing Cd accumulation; treatment with mixed strains (strains+3mg/kg Cd) resulted in 41.3, 35.9, and 32.6% reductions in Cd accumulation in unhulled rice, brown rice and polished rice, respectively. Although different results were obtained for two rice varieties, it can still be concluded that Cd-resistant bacteria are suitable for reducing Cd accumulation in

  12. Comparative study on the efficacy of Garcinia kola in reducing some heavy metal accumulation in liver of Wistar rats.

    PubMed

    Nwokocha, C R; Owu, D U; Ufearo, C S; Iwuala, M O E

    2011-05-17

    Garcinia kola is regarded as an antidote and anti-hepatotoxic agent. We examined its protection ability against mercury (Hg), lead (Pb) and cadmium (Cd) accumulation in the liver. The ground seed was mixed with rat feed (5%, w/w) and fed to rats while Hg (10 ppm), Cd (200 ppm) and Pb (100 ppm) was given in drinking water. Garcinia kola was administered either at the same time with the metals (group 2), a week after exposure to heavy metals (group 3) or given a week before heavy metal exposure (group 4) for six weeks. The heavy metal accumulations in the liver were determined using AAS. Garcinia kola could not reverse the weight reduction in the heavy metal exposed groups although it offers more protection and aid greater elimination of heavy metals from the liver. There was a significant (P<0.01) increase in protection by Garcinia kola to Cd (72.4%) and Pb (56.2%) accumulation when compared to Hg (40%) at week 2 which was significantly (P<0.01) decreased at week 4 when compared to week 2. At week 6, the percentage protection to both Hg (64.2%) and Cd (62.2%) were comparable to each other while protection to Pb (49.9%) accumulation was significantly (P<0.01) reduced. The percentage protection was time-dependent in some groups but treatment during and after the exposure provided a greater protection. Garcinia kola has the highest hepatoprotective effect to Cd followed by Hg and least protection against Pb toxicity in rats and its administration is beneficial in reducing heavy metal accumulation in the liver. PMID:21458555

  13. Dietary saturated fatty acids reduce hepatic lipid accumulation but induce fibrotic change in alcohol-fed rats

    PubMed Central

    Chen, Ya-Ling; Peng, Hsiang-Chi; Wang, Xiang-Dong

    2015-01-01

    Background In this study, we evaluated the influence of an ethanol-containing diet with high saturated fatty acids (SFAs) on alcoholic liver disease (ALD) in rats. Methods Male Wistar rats weighing about 160 g were divided into four groups: an ethanol (E) group fed an ethanol-containing liquid diet with 36% total calories as fat (corn oil, olive oil and safflower oil); a control (C) group pair-fed an isoenergetic diet without ethanol; an ethanol with saturated fat (EHS) group fed an ethanol-containing diet which contained 40% total calories as fat (90% lard); and a control with saturated fat (CHS) group fed an isoenergetic diet without ethanol, which contained 40% total calories as fat. Results After 8 weeks of treatment, the liver weight and plasma aspartate aminotransferase (AST) activities in E and EHS groups were significantly higher than those of C group. Significantly higher scores of inflammation, necrosis, and fatty changes were found in E group, whereas significantly higher scores of necrosis, bile duct hyperplasia, and fibrosis were found in EHS group. Although significantly lower plasma adiponectin concentrations were observed in both E and EHS groups, compared to C group, plasma adiponectin in EHS group was significantly higher than that in E group. There was no change in hepatic peroxisome proliferator activated receptor (PPAR)-α expression between E and C groups, and rats in EHS group showed a significantly elevated level compared to the other groups. A lower hepatic sirtuins (SIRT)-1 level was found in E group, but it did not reach statistical significance. Moreover, the highest plasma TGF-β1 level was found in EHS group. Compared to C group, the hepatic reduced glutathione/oxidized glutathione ratio and thiobarbituric acid (TBA)-reactive substance level were significantly increased in E and EHS groups; however, there was no significant difference between E and EHS groups. Significantly increased hepatic CYP2E1 expression was observed in both E and

  14. Disruption of adenosine-5'-phosphosulfate kinase in Arabidopsis reduces levels of sulfated secondary metabolites.

    PubMed

    Mugford, Sarah G; Yoshimoto, Naoko; Reichelt, Michael; Wirtz, Markus; Hill, Lionel; Mugford, Sam T; Nakazato, Yoshimi; Noji, Masaaki; Takahashi, Hideki; Kramell, Robert; Gigolashvili, Tamara; Flügge, Ulf-Ingo; Wasternack, Claus; Gershenzon, Jonathan; Hell, Rüdiger; Saito, Kazuki; Kopriva, Stanislav

    2009-03-01

    Plants can metabolize sulfate by two pathways, which branch at the level of adenosine 5'-phosphosulfate (APS). APS can be reduced to sulfide and incorporated into Cys in the primary sulfate assimilation pathway or phosphorylated by APS kinase to 3'-phosphoadenosine 5'-phosphosulfate, which is the activated sulfate form for sulfation reactions. To assess to what extent APS kinase regulates accumulation of sulfated compounds, we analyzed the corresponding gene family in Arabidopsis thaliana. Analysis of T-DNA insertion knockout lines for each of the four isoforms did not reveal any phenotypical alterations. However, when all six combinations of double mutants were compared, the apk1 apk2 plants were significantly smaller than wild-type plants. The levels of glucosinolates, a major class of sulfated secondary metabolites, and the sulfated 12-hydroxyjasmonate were reduced approximately fivefold in apk1 apk2 plants. Although auxin levels were increased in the apk1 apk2 mutants, as is the case for most plants with compromised glucosinolate synthesis, typical high auxin phenotypes were not observed. The reduction in glucosinolates resulted in increased transcript levels for genes involved in glucosinolate biosynthesis and accumulation of desulfated precursors. It also led to great alterations in sulfur metabolism: the levels of sulfate and thiols increased in the apk1 apk2 plants. The data indicate that the APK1 and APK2 isoforms of APS kinase play a major role in the synthesis of secondary sulfated metabolites and are required for normal growth rates. PMID:19304933

  15. The relative contribution of intramyocellular lipid to whole body fat oxidation is reduced with age, but subsarcolemmal lipid accumulation and insulin resistance are only associated with overweight individuals

    PubMed Central

    Chee, Carolyn; Shannon, Chris E.; Burns, Aisling; Selby, Anna L.; Wilkinson, Daniel; Smith, Kenneth; Greenhaff, Paul L.; Stephens, Francis B.

    2016-01-01

    , 7). Of note, intramyocellular lipid (IMCL) accumulates with age, particularly in subsarcolemmal (SSL) regions (8), and has been strongly associated with insulin resistance (9, 10, 11, 12). Indeed, SSL lipid accumulation has been linked to the accumulation of metabolites, such as diacylglycerol (DAG) and ceramide, thought by some (13, 14, 15), but not others (16), to contribute to impaired insulin-stimulated muscle glucose uptake. Nevertheless, it remains contentious as to which factors associated with age influence IMCL accumulation. The accumulation of IMCL and associated metabolites likely result from an imbalance between muscle lipid delivery and oxidation. Indeed, studies have demonstrated reduced free fatty acid (FFA) oxidation in older people compared to young, despite whole-body lipolysis and plasma FFA availability being greater at rest and during exercise at the same absolute and relative intensities (17, 18). Linked to this, several studies have suggested age related blunting of FFA oxidation and increased IMCL accumulation are a result of reduced muscle mitochondrial content (8) and function (3, 19, 20) with age. However, increased adiposity and reduced habitual levels of physical activity also affect FFA flux and oxidation in older individuals (21), and studies to date have not controlled for these factors when investigating changes in muscle IMCL metabolism with age. Therefore, we investigated the effect of ageing on whole-body and skeletal muscle lipid metabolism, with parallel characterization of muscle insulin sensitivity, in lean young and older individuals matched for estimated habitual physical activity levels and body composition. To determine the effect of adiposity and reduced physical activity on the ageing process, the older lean individuals were also compared to a group of older overweight individuals matched for lean mass. We hypothesized that an age-associated imbalance between FFA delivery and oxidation in skeletal muscle during exercise

  16. TRMM Version 7 Level 3 Gridded Monthly Accumulations of GPROF Precipitation Retrievals

    NASA Technical Reports Server (NTRS)

    Stocker, E. F.; Kelley, O. A.

    2012-01-01

    In July 2011, improved versions of the retrieval algorithms were approved for TRMM. All data starting with June 2011 are produced only with the version 7 code. At the same time, version 7 reprocessing of all TRMM mission data was started. By the end of August 2011, the 14+ years of the reprocessed mission data became available online to users. This reprocessing provided the opportunity to redo and enhance upon an analysis of V7 impacts on L3 data accumulations that was presented at the 2010 EGU General Assembly. This paper will discuss the impact of algorithm changes made in th GPROF retrieval on the Level 2 swath products. Perhaps the most important change in that retrieval was to replacement of a model based a priori database with one created from Precipitation Radar (PR) and TMI brightness temperature (Tb) data. The radar pays a major role in the V7 GPROF (GPROF2010) in determining existence of rain. The level 2 retrieval algorithm also introduced a field providing the probability of rain. This combined use of the PR has some impact on the retrievals and created areas, particularly over ocean, where many areas of low-probability precipitation are retrieved whereas in version 6, these areas contained zero rain rates. This paper will discuss how these impacts get translated to the space/time averaged monthly products that use the GPROF retrievals. The level 3 products discussed are the gridded text product 3G68 and the standard 3A12 and 3B31 products. The paper provides an overview of the changes and explanation of how the level 3 products dealt with the change in the retrieval approach. Using the .25 deg x .25 degree grid, the paper will show that agreement between the swath product and the level 3 remains very high. It will also present comparisons of V6 and V7 GPROF retrievals as seen both at the swath level and the level 3 time/space gridded accumulations. It will show that the various L3 products based on GPROF level 2 retrievals are in close agreement. The

  17. δ-Tocopherol reduces lipid accumulation in Niemann-Pick type C1 and Wolman cholesterol storage disorders.

    PubMed

    Xu, Miao; Liu, Ke; Swaroop, Manju; Porter, Forbes D; Sidhu, Rohini; Firnkes, Sally; Finkes, Sally; Ory, Daniel S; Marugan, Juan J; Xiao, Jingbo; Southall, Noel; Pavan, William J; Davidson, Cristin; Walkley, Steven U; Remaley, Alan T; Baxa, Ulrich; Sun, Wei; McKew, John C; Austin, Christopher P; Zheng, Wei

    2012-11-16

    Niemann-Pick disease type C (NPC) and Wolman disease are two members of a family of storage disorders caused by mutations of genes encoding lysosomal proteins. Deficiency in function of either the NPC1 or NPC2 protein in NPC disease or lysosomal acid lipase in Wolman disease results in defective cellular cholesterol trafficking. Lysosomal accumulation of cholesterol and enlarged lysosomes are shared phenotypic characteristics of both NPC and Wolman cells. Utilizing a phenotypic screen of an approved drug collection, we found that δ-tocopherol effectively reduced lysosomal cholesterol accumulation, decreased lysosomal volume, increased cholesterol efflux, and alleviated pathological phenotypes in both NPC1 and Wolman fibroblasts. Reduction of these abnormalities may be mediated by a δ-tocopherol-induced intracellular Ca(2+) response and subsequent enhancement of lysosomal exocytosis. Consistent with a general mechanism for reduction of lysosomal lipid accumulation, we also found that δ-tocopherol reduces pathological phenotypes in patient fibroblasts from other lysosomal storage diseases, including NPC2, Batten (ceroid lipofuscinosis, neuronal 2, CLN2), Fabry, Farber, Niemann-Pick disease type A, Sanfilippo type B (mucopolysaccharidosis type IIIB, MPSIIIB), and Tay-Sachs. Our data suggest that regulated exocytosis may represent a potential therapeutic target for reduction of lysosomal storage in this class of diseases. PMID:23035117

  18. Anaerobic granule-based biofilms formation reduces propionate accumulation under high H2 partial pressure using conductive carbon felt particles.

    PubMed

    Xu, Heng; Wang, Cuiping; Yan, Kun; Wu, Jing; Zuo, Jiane; Wang, Kaijun

    2016-09-01

    Syngas based co-digestion is not only more economically attractive than separate syngas methanation but also able to upgrade biogas and increase overall CH4 amount simultaneously. However, high H2 concentration in the syngas could inhibit syntrophic degradation of propionate, resulting in propionate accumulation and even failure of the co-digestion system. In an attempt to reduce propionate accumulation via enhancing both H2 interspecies transfer (HIT) and direct interspecies electron transfer (DIET) pathways, layered granule-based biofilms induced by conductive carbon felt particles (CCFP) was employed. The results showed that propionate accumulation was effectively reduced with influent COD load up to 7gL(-1)d(-1). Two types of granule-based biofilms, namely biofilm adhered to CCFP (B-CCFP) and granules formed by self-immobilization (B-SI) were formed in the reactor. Clostridium, Syntrophobacter, Methanospirillum were possibly involved in HIT and Clostridium, Geobacter, Anaerolineaceae, Methanosaeta in DIET, both of which might be responsible for the high-rate propionate degradation. PMID:27289059

  19. Identification of genes and physiological factors that reduce accumulation of arsenic in rice grain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The arsenic (As) levels in rice grains and food products can reach toxic levels when produced under certain growing conditions. The World Health Organization (WHO) recently set a CODEX limit of 0.2 ppm inorganic As in milled white rice, and lower limits may be set for baby food products. While studi...

  20. Moderate physical activity from childhood contributes to metabolic health and reduces hepatic fat accumulation in adult rats

    PubMed Central

    2013-01-01

    Background Obesity, oxidative stress and inflammation, by triggering insulin resistance, may contribute to the accumulation of hepatic fat, and this accumulation by lipotoxicity can lead the organ to fail. Because obesity is growing at an alarming rate and, worryingly, in a precocious way, the present study aimed to investigate the effects of moderate physical training performed from childhood to adulthood on liver fat metabolism in rats. Methods Twenty rats that were 28 days old were divided into two groups: control (C) and trained (T). The C Group was kept in cages without exercise, and the T group was submitted to swimming exercise for 1 hour/day, 5 days/week from 28 to 90 days of age (8 weeks) at 80% of the anaerobic threshold determined by the lactate minimum test. At the end of the experiment, the body weight gain, insulin sensitivity (glucose disappearance rate during the insulin tolerance test), concentrations of free fatty acids (FFA) and triglycerides (TG) and hepatic lipogenic rate were analyzed. For the statistical analysis, the Student t-test was used with the level of significance preset at 5%. Results The T group showed lower body weight gain, FFA concentrations, fat accumulation, hepatic lipogenic rate and insulin resistance. Conclusion The regular practice of moderate physical exercise from childhood can contribute to the reduction of obesity and insulin resistance and help prevent the development of accumulation of hepatic fat in adulthood. PMID:23496920

  1. Low level laser therapy reduces inflammation in activated Achilles tendinitis

    NASA Astrophysics Data System (ADS)

    Bjordal, Jan M.; Iversen, Vegard; Lopes-Martins, Rodrigo Alvaro B.

    2006-02-01

    Objective: Low level laser therapy (LLLT) has been forwarded as therapy for osteoarthritis and tendinopathy. Results in animal and cell studies suggest that LLLT may act through a biological mechanism of inflammatory modulation. The current study was designed to investigate if LLLT has an anti-inflammatory effect on activated tendinitis of the Achilles tendon. Methods: Seven patients with bilateral Achilles tendonitis (14 tendons) who had aggravated symptoms by pain-inducing activity immediately prior to the study. LLLT (1.8 Joules for each of three points along the Achilles tendon with 904nm infrared laser) and placebo LLLT were administered to either Achilles tendons in a random order to which patients and therapist were blinded. Inflammation was examined by 1) mini-invasive microdialysis for measuring the concentration of inflammatory marker PGE II in the peritendinous tissue, 2) ultrasound with Doppler measurement of peri- and intratendinous blood flow, 3) pressure pain algometry and 4) single hop test. Results: PGE 2- levels were significantly reduced at 75, 90 and 105 minutes after active LLLT compared both to pre-treatment levels (p=0.026) and to placebo LLLT (p=0.009). Changes in pressure pain threshold (PPT) were significantly different (P=0.012) between groups. PPT increased by a mean value of 0.19 kg/cm2 [95%CI:0.04 to 0.34] after treatment in the active LLLT group, while pressure pain threshold was reduced by -0.20 kg/cm2 [95%CI:-0.45 to 0.05] after placebo LLLT. Conclusion: LLLT can be used to reduce inflammatory musculskeletal pain as it reduces inflammation and increases pressure pain threshold levels in activity-induced pain episodes of Achilles tendinopathy.

  2. Accumulation and localization of cadmium in potato (Solanum tuberosum) under different soil Cd levels.

    PubMed

    Chen, Zhifan; Zhao, Ye; Gu, Lei; Wang, Shuifeng; Li, Yongliang; Dong, Fangli

    2014-06-01

    Phytoavailability and uptake mechanism of Cd in edible plant tissues grown on metal polluted agricultural soils has become a growing concern worldwide. Uptake, transport, accumulation and localization of cadmium in potato organs under different soil Cd levels were investigated using inductively-coupled plasma mass spectrometry and energy dispersive X-ray microanalysis. Results indicated that Cd contents in potato organs increased with increasing soil Cd concentrations, and the order of Cd contents in different organs was leaves > stems/roots > tubers. Root-to-stem Cd translocation coefficients ranged from 0.89 to 1.81. Cd localization in potato tissues suggested that leaves and stems should be the main compartment of Cd storage and uptake. Although low concentrations of Cd migrated from the root to tuber, Cd accumulation in the tuber exceeded the standard for food security. Therefore, the planting of potato plants in farmland containing Cd should be closely evaluated due to its potential to present health risks. PMID:24682567

  3. Deciphering maize genetics and ecology to reduce insect damage and aflatoxin accumulation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ear-colonizing insects and diseases, which reduce yield and impose health threats via mycotoxin contaminations, are critical impediments for maize production in the southern US states. To address this problem a combination of basic and applied research approaches are being conducted by the interdis...

  4. Low stimulus environments: reducing noise levels in continuing care.

    PubMed

    Brown, Juliette; Fawzi, Waleed; Shah, Amar; Joyce, Margaret; Holt, Genevieve; McCarthy, Cathy; Stevenson, Carmel; Marange, Rosca; Shakes, Joy; Solomon-Ayeh, Kwesi

    2016-01-01

    In the low stimulus environment project, we aimed to reduce the levels of intrusive background noise on an older adult mental health ward, combining a very straightforward measure on decibel levels with a downstream measure of reduced distress and agitation as expressed in incidents of violence. This project on reducing background noise levels on older adult wards stemmed from work the team had done on reducing levels of violence and aggression. We approached the problem using quality improvement methods. Reducing harm to patients and staff is a strategic aim of our Trust and in our efforts we were supported by the Trust's extensive programme of quality improvement, including training and support provided by the Institute for Healthcare Improvement and the trust's own Quality Improvement team. Prior to the project we were running a weekly multi-disciplinary quality improvement group on the ward. We established from this a sub-group to address the specific problem of noise levels and invited carers of people with dementia on our ward to the group. The project was led by nursing staff. We used a noise meter app readily downloadable from the internet to monitor background noise levels on the ward and establish a baseline measure. As a group we used a driver diagram to identify an overall aim and a clear understanding of the major factors that would drive improvements. We also used a staff and carer survey to identify further areas to work on. Change ideas that came from staff and carers included the use of the noise meter to track and report back on noise levels, the use of posters to remind staff about noise levels, the introduction of a visual indication of current noise levels (the Yacker Tracker), the addition of relaxing background music, and adaptations to furniture and environment. We tested many of these over the course of nine months in 2015, using the iterative learning gained from multiple PDSA cycles. The specific aim was a decrease from above 60dB to

  5. Low stimulus environments: reducing noise levels in continuing care

    PubMed Central

    Brown, Juliette; Fawzi, Waleed; Shah, Amar; Joyce, Margaret; Holt, Genevieve; McCarthy, Cathy; Stevenson, Carmel; Marange, Rosca; Shakes, Joy; Solomon-Ayeh, Kwesi

    2016-01-01

    In the low stimulus environment project, we aimed to reduce the levels of intrusive background noise on an older adult mental health ward, combining a very straightforward measure on decibel levels with a downstream measure of reduced distress and agitation as expressed in incidents of violence. This project on reducing background noise levels on older adult wards stemmed from work the team had done on reducing levels of violence and aggression. We approached the problem using quality improvement methods. Reducing harm to patients and staff is a strategic aim of our Trust and in our efforts we were supported by the Trust's extensive programme of quality improvement, including training and support provided by the Institute for Healthcare Improvement and the trust's own Quality Improvement team. Prior to the project we were running a weekly multi-disciplinary quality improvement group on the ward. We established from this a sub-group to address the specific problem of noise levels and invited carers of people with dementia on our ward to the group. The project was led by nursing staff. We used a noise meter app readily downloadable from the internet to monitor background noise levels on the ward and establish a baseline measure. As a group we used a driver diagram to identify an overall aim and a clear understanding of the major factors that would drive improvements. We also used a staff and carer survey to identify further areas to work on. Change ideas that came from staff and carers included the use of the noise meter to track and report back on noise levels, the use of posters to remind staff about noise levels, the introduction of a visual indication of current noise levels (the Yacker Tracker), the addition of relaxing background music, and adaptations to furniture and environment. We tested many of these over the course of nine months in 2015, using the iterative learning gained from multiple PDSA cycles. The specific aim was a decrease from above 60dB to

  6. Endogenous macrophage migration inhibitory factor reduces the accumulation and toxicity of misfolded SOD1 in a mouse model of ALS.

    PubMed

    Leyton-Jaimes, Marcel F; Benaim, Clara; Abu-Hamad, Salah; Kahn, Joy; Guetta, Amos; Bucala, Richard; Israelson, Adrian

    2016-09-01

    Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons in the brain and spinal cord. It has been suggested that the toxicity of mutant SOD1 results from its misfolding and accumulation on the cytoplasmic faces of intracellular organelles, including the mitochondria and endoplasmic reticulum (ER) of ALS-affected tissues. Recently, macrophage migration inhibitory factor (MIF) was shown to directly inhibit the accumulation of misfolded SOD1 and its binding to intracellular membranes, but the role of endogenous MIF in modulating SOD1 misfolding in vivo remains unknown. To elucidate this role, we bred MIF-deficient mice with SOD1(G85R) mice, which express a dismutase-inactive mutant of SOD1 and are considered a model of familial ALS. We found that the accumulation of misfolded SOD1, its association with mitochondrial and ER membranes, and the levels of sedimentable insoluble SOD1 aggregates were significantly higher in the spinal cords of SOD1(G85R)-MIF(-/-) mice than in their SOD1(G85R)-MIF(+/+) littermates. Moreover, increasing MIF expression in neuronal cultures inhibited the accumulation of misfolded SOD1 and rescued from mutant SOD1-induced cell death. In contrast, the complete elimination of endogenous MIF accelerated disease onset and late disease progression and shortened the lifespan of the SOD1(G85R) mutant mice. These findings indicate that MIF plays a significant role in the folding and misfolding of SOD1 in vivo, and they have implications for the potential therapeutic role of up-regulating MIF within the nervous system to modulate the selective accumulation of misfolded SOD1. PMID:27551074

  7. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels.

    PubMed

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W; Riebesell, Ulf; Gao, Kunshan

    2015-01-01

    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46-212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130-160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28-48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes. PMID:26503801

  8. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

    PubMed Central

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W.; Riebesell, Ulf; Gao, Kunshan

    2015-01-01

    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46–212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130–160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28–48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes. PMID:26503801

  9. Localizing Organomercury Uptake And Accumulation in Zebrafish Larvae at the Tissue And Cellular Level

    SciTech Connect

    Korbas, M.; Blechinger, S.R.; Krone, P.H.; Pickering, I.J.; George, G.N.

    2009-05-20

    Using synchrotron x-ray fluorescence mapping, we have examined the uptake and localization of organic mercury in zebrafish larvae. Strikingly, the greatest accumulation of methyl and ethyl mercury compounds was highly localized in the rapidly dividing lens epithelium, with lower levels going to brain, optic nerve, and various other organs. The data suggest that the reported impairment of visual processes by mercury may arise not only from previously reported neurological effects, but also from direct effects on the ocular tissue. This novel approach is a powerful tool for directly investigating the molecular toxicology of heavy metals, and should be equally applicable to the study of a wide range of elements in developing embryos.

  10. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

    NASA Astrophysics Data System (ADS)

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W.; Riebesell, Ulf; Gao, Kunshan

    2015-10-01

    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46-212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130-160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28-48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

  11. Localizing organomercury uptake and accumulation in zebrafish larvae at the tissue and cellular level

    PubMed Central

    Korbas, Malgorzata; Blechinger, Scott R.; Krone, Patrick H.; Pickering, Ingrid J.; George, Graham N.

    2008-01-01

    Using synchrotron x-ray fluorescence mapping, we have examined the uptake and localization of organic mercury in zebrafish larvae. Strikingly, the greatest accumulation of methyl and ethyl mercury compounds was highly localized in the rapidly dividing lens epithelium, with lower levels going to brain, optic nerve, and various other organs. The data suggest that the reported impairment of visual processes by mercury may arise not only from previously reported neurological effects, but also from direct effects on the ocular tissue. This novel approach is a powerful tool for directly investigating the molecular toxicology of heavy metals, and should be equally applicable to the study of a wide range of elements in developing embryos. PMID:18719123

  12. Surface hole accumulation and Fermi level stabilization energy in SnTe

    NASA Astrophysics Data System (ADS)

    Nishitani, Junichi; Detert, Douglas; Beeman, Jeffrey; Yu, Kin Man; Walukiewicz, Wladek

    2014-09-01

    SnTe films were deposited by RF magnetron sputtering. The thickness dependence of the sheet hole concentration indicated the presence of a high hole density surface accumulation layer. Irradiation of SnTe by Ne+ ions led to the saturation of the hole concentration corresponding to a Fermi energy that is 0.5 eV below the valence band edge. The stabilized Fermi energy on the surface and in the heavily damaged bulk is in agreement with the amphoteric native defect model. These results show that SnTe is a unique semiconductor with an extremely high valence band edge located at 4.4 eV below the vacuum level.

  13. Expressing ScACR3 in rice enhanced arsenite efflux and reduced arsenic accumulation in rice grains.

    PubMed

    Duan, Guilan; Kamiya, Takehiro; Ishikawa, Satoru; Arao, Tomohito; Fujiwara, Toru

    2012-01-01

    Arsenic (As) accumulation in rice grain poses a serious health risk to populations with high rice consumption. Extrusion of arsenite [As(III)] by ScAcr3p is the major arsenic detoxification mechanism in Saccharomyces cerevisiae. However, ScAcr3p homolog is absent in higher plants, including rice. In this study, ScACR3 was introduced into rice and expressed under the control of the Cauliflower mosaic virus (CaMV) 35S promoter. In the transgenic lines, As concentrations in shoots and roots were about 30% lower than in the wild type, while the As translocation factors were similar between transgenic lines and the wild type. The roots of transgenic plants exhibited significantly higher As efflux activities than those of the wild type. Within 24 h exposure to 10 μM arsenate [As(V)], roots of ScACR3-expressing plants extruded 80% of absorbed As(V) to the external solution as As(III), while roots of the wild type extruded 50% of absorbed As(V). Additionally, by exposing the As-containing rice plants to an As-lacking solution for 24 h, about 30% of the total As derived from pre-treatment was extruded to the external solution by ScACR3-expressing plants, while about 15% of As was extruded by wild-type plants. Importantly, ScACR3 expression significantly reduced As accumulation in rice straws and grains. When grown in flooded soil irrigated with As(III)-containing water, the As concentration in husk and brown rice of the transgenic lines was reduced by 30 and 20%, respectively, compared with the wild type. This study reports a potential strategy to reduce As accumulation in the food chain by expressing heterologous genes in crops. PMID:22107880

  14. Copepods in Turbid Shallow Soda Lakes Accumulate Unexpected High Levels of Carotenoids

    PubMed Central

    Schneider, Tobias; Herzig, Alois; Koinig, Karin A.; Sommaruga, Ruben

    2012-01-01

    Carotenoids are protective pigments present in many aquatic organisms that reduce the photooxidative stress induced by short-wavelenght solar radiation, yet increase their susceptibility to predators. Arctodiaptomus spinosus, a calanoid copepod typically found in many fishless shallow soda lakes, shows large between-lake differences in pigmentation. Here, we attribute these differences to the environmental state of these ecosystems, namely, ‘dark water’ lakes with submersed vegetation and turbid ‘white’ lakes lacking macrophytes. Copepod carotenoid concentration in the turbid ‘white’ lakes was significantly (about 20-fold) higher than in the ‘dark water’ ones, although the latter systems were characterized by higher transparency. In addition, males had on a dry weight basis around three times higher carotenoid concentrations than females. Mycosporine-like amino acids (direct UV screening substances) were found in all cases, but in low concentration. The environmental conditions in these ecosystems were largely shaped by the presence/absence of submersed macrophytes Thus, in the turbid lakes, the strong wind-driven mixis allows for copepods to be brought to the surface and being exposed to solar radiation, whereas in ‘dark water’ ones, macrophytes reduce water turbulence and additionally provide shelter. Our results explain the counter-intuitive notion of strong red pigmentation in copepods from a turbid ecosystem and suggest that factors other than high UV transparency favor carotenoid accumulation in zooplankton. PMID:22916208

  15. Inhibition of citric acid accumulation by manganese ions in Aspergillus niger mutants with reduced citrate control of phosphofructokinase

    SciTech Connect

    Schreferl, G.; Kubicek, C.P.; Roehr, M.

    1986-03-01

    Mutant strains of Aspergillus niger with reduced citrate control of carbohydrate catabolism (cic mutants) grow faster than the parent strain on media containing 5% (wt/vol) citrate. The mutants tolerated a higher intracellular citrate concentration than the parent strain. One mutant (cic-7/3) contained phosphofructokinase activity significantly less sensitive towards citrate than the enzyme from the parent strain. When this mutant was grown under citrate accumulating conditions, acidogenesis was far less sensitive to inhibition by Mn/sup 2 +/ than in the parent strain. Some of the cic mutants also showed altered citrate inhibition of NADP-specific isocitrate dehydrogenase.

  16. Unsaturated fatty acids supplementation reduces blood lead level in rats.

    PubMed

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: "super lecithin" (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

  17. Unsaturated Fatty Acids Supplementation Reduces Blood Lead Level in Rats

    PubMed Central

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: “super lecithin” (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

  18. High level accumulation of soluble diphtheria toxin mutant (CRM197) with co-expression of chaperones in recombinant Escherichia coli.

    PubMed

    Mahamad, Pornpimol; Boonchird, Chuenchit; Panbangred, Watanalai

    2016-07-01

    CRM197 is the diphtheria toxin mutant used in many conjugate vaccines. A fusion CRM197 (fCRM197) containing all the tags conferred by the pET32a vector was produced as a soluble protein in Escherichia coli co-expressing several chaperone proteins in conjunction with low temperature cultivation. Trigger factor (Tf) enhanced formation of soluble fCRM197 (150.69 ± 8.95 μg/mL) to a greater degree than other chaperones when fCRM197 expression was induced at 25 °C for 12 h. However, prolonged cultivation resulted in a progressive reduction of fCRM197 accumulation. In contrast, at 15 °C cells, with or without Tf, fCRM197 accumulated to the highest level at 48 h (153.70 ± 13.14 μg/mL and 150.07 ± 8.13 μg/mL, respectively). Transmission electron microscopy (TEM) demonstrated that the formation of inclusion protein as well as cell lysis was reduced in cultures grown at 15 °C. Cell viability was substantially reduced in cells expressing Tf, compared to cultures without Tf, when fCRM197 was induced at 25 °C. The viability of Tf-expressing cells was enhanced when cultured at 15 °C. Both purified fCRM197 and CRM197 efficiently digested lambda DNA (λDNA) at 37 °C (92.78 and 97.45 %, respectively). Digestion efficiency of fCRM197 and CRM197 was reduced at 25 °C (80.80 and 62.73 %, respectively) and at 15 °C (7.34 and 24.79 %, respectively). These results demonstrating nuclease activity, enhanced cell lysis, and reduced cell viability are consistent with the finding of lower fCRM197 yield when cultivation and induction times were prolonged at 25 °C. The present work provides a procedure for the high-level production of soluble fCRM197 using E. coli as a heterologous host. PMID:27020286

  19. Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes.

    PubMed

    Nanthirudjanar, Tharnath; Furumoto, Hidehiro; Zheng, Jiawen; Kim, Young-Il; Goto, Tsuyoshi; Takahashi, Nobuyuki; Kawada, Teruo; Park, Si-Bum; Hirata, Akiko; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

    2015-11-01

    Hydroxy and oxo fatty acids were recently found to be produced as intermediates during gut microbial fatty acid metabolism. Lactobacillus plantarum produces these fatty acids from unsaturated fatty acids such as linoleic acid. In this study, we investigated the effects of these gut microbial fatty acid metabolites on the lipogenesis in liver cells. We screened their effect on sterol regulatory element binding protein-1c (SREBP-1c) expression in HepG2 cells treated with a synthetic liver X receptor α (LXRα) agonist (T0901317). The results showed that 10-hydroxy-12(Z)-octadecenoic acid (18:1) (HYA), 10-hydroxy-6(Z),12(Z)-octadecadienoic acid (18:2) (γHYA), 10-oxo-12(Z)-18:1 (KetoA), and 10-oxo-6(Z),12(Z)-18:2 (γKetoA) significantly decreased SREBP-1c mRNA expression induced by T0901317. These fatty acids also downregulated the mRNA expression of lipogenic genes by suppressing LXRα activity and inhibiting SREBP-1 maturation. Oral administration of KetoA, which effectively reduced triacylglycerol accumulation and acetyl-CoA carboxylase 2 (ACC2) expression in HepG2 cells, for 2 weeks significantly decreased Srebp-1c, Scd-1, and Acc2 expression in the liver of mice fed a high-sucrose diet. Our findings suggest that the hypolipidemic effect of the fatty acid metabolites produced by L. plantarum can be exploited in the treatment of cardiovascular diseases or dyslipidemia. PMID:26399511

  20. Tadalafil reduces visceral adipose tissue accumulation by promoting preadipocytes differentiation towards a metabolically healthy phenotype: Studies in rabbits.

    PubMed

    Maneschi, Elena; Cellai, Ilaria; Aversa, Antonio; Mello, Tommaso; Filippi, Sandra; Comeglio, Paolo; Bani, Daniele; Guasti, Daniele; Sarchielli, Erica; Salvatore, Giulia; Morelli, Annamaria; Mazzanti, Benedetta; Corcetto, Francesca; Corno, Chiara; Francomano, Davide; Galli, Andrea; Vannelli, Gabriella Barbara; Lenzi, Andrea; Mannucci, Edoardo; Maggi, Mario; Vignozzi, Linda

    2016-03-15

    Development of metabolically healthy adipocytes within dysfunctional adipose tissue may represent an attractive way to counteract metabolic syndrome (MetS). In an experimental animal model of high fat diet (HFD)-induced MetS, in vivo, long- and short-term tadalafil treatments were able to reduce visceral adipose tissue (VAT) accumulation and hypertriglyceridemia, and to induce the expression in VAT of the brown fat-specific marker, uncoupling protein 1 (UCP1). VAT preadipocytes (PAD), isolated from the tadalafil-treated HFD rabbits, showed: i) a multilocular morphology; ii) an increased expression of brown fat-specific genes (such as UCP1 and CIDEA); iii) improved mitochondrial structure and dynamic and reduced superoxide production; iv) improved insulin sensitivity. Similar effects were obtained after in vitro tadalafil treatment in HFD rPAD. In conclusion, tadalafil counteracted HFD-associated VAT alterations, by restoring insulin-sensitivity and prompting preadipocytes differentiation towards a metabolically healthy phenotype. PMID:26805634

  1. Gibberellic acid alleviates cadmium toxicity by reducing nitric oxide accumulation and expression of IRT1 in Arabidopsis thaliana.

    PubMed

    Zhu, Xiao Fang; Jiang, Tao; Wang, Zhi Wei; Lei, Gui Jie; Shi, Yuan Zhi; Li, Gui Xin; Zheng, Shao Jian

    2012-11-15

    Gibberellic acid (GA) is involved in not only plant growth and development but also plant responses to abiotic stresses. Here it was found that treating the plants with GA concentrations from 0.1 to 5 μM for 24 h had no obvious effect on root elongation in the absence of cadmium (Cd), whereas in the presence of Cd2+, GA at 5 μM improved root growth, reduced Cd content and lipid peroxidation in the roots, indicating that GA can partially alleviate Cd toxicity. Cd2+ increased nitric oxide (NO) accumulation in the roots, but GA remarkably reduced it, and suppressed the up-regulation of the expression of IRT1. In contrary, the beneficial effect of GA on alleviating Cd toxicity was not observed in an IRT1 knock-out mutant irt1, suggesting the involvement of IRT1 in Cd2+ absorption. Furthermore, the GA-induced reduction of NO and Cd content can also be partially reversed by the application of a NO donor (S-nitrosoglutathione [GSNO]). Taken all these together, the results showed that GA-alleviated Cd toxicity is mediated through the reduction of the Cd-dependent NO accumulation and expression of Cd2+ uptake related gene-IRT1 in Arabidopsis. PMID:23021314

  2. Dual Mode NOx Sensor: Measuring Both the Accumulated Amount and Instantaneous Level at Low Concentrations

    PubMed Central

    Groß, Andrea; Beulertz, Gregor; Marr, Isabella; Kubinski, David J.; Visser, Jaco H.; Moos, Ralf

    2012-01-01

    The accumulating-type (or integrating-type) NOx sensor principle offers two operation modes to measure low levels of NOx: The direct signal gives the total amount dosed over a time interval and its derivative the instantaneous concentration. With a linear sensor response, no baseline drift, and both response times and recovery times in the range of the gas exchange time of the test bench (5 to 7 s), the integrating sensor is well suited to reliably detect low levels of NOx. Experimental results are presented demonstrating the sensor’s integrating properties for the total amount detection and its sensitivity to both NO and to NO2. We also show the correlation between the derivative of the sensor signal and the known gas concentration. The long-term detection of NOx in the sub-ppm range (e.g., for air quality measurements) is discussed. Additionally, a self-adaption of the measurement range taking advantage of the temperature dependency of the sensitivity is addressed. PMID:22736980

  3. Retinoids regulate TGFβ signaling at the level of Smad2 phosphorylation and nuclear accumulation

    PubMed Central

    Hoover, Loretta L.; Burton, Elizabeth G.; O'Neill, Megan L.; Brooks, Bonnie A.; Sreedharan, Shilpa; Dawson, Nineveh A.; Kubalak, Steven W.

    2008-01-01

    Indirect regulation of transforming growth factor (TGF)-β signaling by retinoids occurs on a long-term timescale, secondary to transcriptional events. Studies by our group show loss of retinoid X receptor (RXR) alpha results in increased TGFβ2 in the midgestational heart, which may play a role in the cardiac defects seen in this model[1]. Acute and direct interactions between retinoid and TGFβ signaling, however, are not clearly understood. Treatment of dispersed hearts and NIH3T3 cells for one-hour with TGFβ and retinoids (dual treatment) resulted in increased phosphorylated Smad2 and Smad3 when compared to treatment with TGFβ alone. Of all dual treatments, those with the RXR agonist Bexarotene, resulted in the highest level of phosphorylated Smad2, a 7-fold increase over TGFβ2 alone. Additionally, during dual treatment phosphorylation of Smad2 occurs via the TGFβ type I receptor but not by increased activation of the receptor. As loss of RXRα results in increased levels of Smad2 phosphorylation in response to TGFβ treatment and since nuclear accumulation of phosphorylated Smad2 is decreased during dual treatment, we propose that RXRα directly regulates the activities of Smad2. These data show retinoid signaling influences the TGFβ pathway in an acute and direct manner that has been unappreciated until now. PMID:18773928

  4. Salt Stress Reduces Root Meristem Size by Nitric Oxide-Mediated Modulation of Auxin Accumulation and Signaling in Arabidopsis1[OPEN

    PubMed Central

    Liu, Wen; Li, Rong-Jun; Han, Tong-Tong; Cai, Wei; Fu, Zheng-Wei

    2015-01-01

    The development of the plant root system is highly plastic, which allows the plant to adapt to various environmental stresses. Salt stress inhibits root elongation by reducing the size of the root meristem. However, the mechanism underlying this process remains unclear. In this study, we explored whether and how auxin and nitric oxide (NO) are involved in salt-mediated inhibition of root meristem growth in Arabidopsis (Arabidopsis thaliana) using physiological, pharmacological, and genetic approaches. We found that salt stress significantly reduced root meristem size by down-regulating the expression of PINFORMED (PIN) genes, thereby reducing auxin levels. In addition, salt stress promoted AUXIN RESISTANT3 (AXR3)/INDOLE-3-ACETIC ACID17 (IAA17) stabilization, which repressed auxin signaling during this process. Furthermore, salt stress stimulated NO accumulation, whereas blocking NO production with the inhibitor Nω-nitro-l-arginine-methylester compromised the salt-mediated reduction of root meristem size, PIN down-regulation, and stabilization of AXR3/IAA17, indicating that NO is involved in salt-mediated inhibition of root meristem growth. Taken together, these findings suggest that salt stress inhibits root meristem growth by repressing PIN expression (thereby reducing auxin levels) and stabilizing IAA17 (thereby repressing auxin signaling) via increasing NO levels. PMID:25818700

  5. Enzymatic treatment of peanut kernels to reduce allergen levels.

    PubMed

    Yu, Jianmei; Ahmedna, Mohamed; Goktepe, Ipek; Cheng, Hsiaopo; Maleki, Soheila

    2011-08-01

    This study investigated the use of enzymatic treatment to reduce peanut allergens in peanut kernels as affected by processing conditions. Two major peanut allergens, Ara h 1 and Ara h 2, were used as indicators of process effectiveness. Enzymatic treatment effectively reduced Ara h 1 and Ara h 2 in roasted peanut kernels by up to 100% under optimal conditions. For instance, treatment of roasted peanut kernels with α-chymotrypsin and trypsin for 1-3h significantly increased the solubility of peanut protein while reducing Ara h 1 and Ara h 2 in peanut kernel extracts by 100% and 98%, respectively, based on ELISA readings. Ara h 1 and Ara h 2 levels in peanut protein extracts were inversely correlated with protein solubility in roasted peanut. Blanching of kernels enhanced the effectiveness of enzyme treatment in roasted peanuts but not in raw peanuts. The optimal concentration of enzyme was determined by response surface to be in the range of 0.1-0.2%. No consistent results were obtained for raw peanut kernels since Ara h 1 and Ara h 2 increased in peanut protein extracts under some treatment conditions and decreased in others. PMID:25214091

  6. Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

    SciTech Connect

    Malur, Anagha; Huizar, Isham; Wells, Greg; Barna, Barbara P.; Malur, Achut G.; Thomassen, Mary Jane

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by

  7. Kissing reduces allergic skin wheal responses and plasma neurotrophin levels.

    PubMed

    Kimata, Hajime

    2003-11-01

    The effect of kissing on allergen-induced skin wheal responses and plasma neurotrophin levels were studied in 30 normal subjects, 30 patients with allergic rhinitis (AR), and 30 patients with atopic dermatitis (AD). All of the patients with AR or AD are allergic to house dust mite (HDM) and Japanese cedar pollen (JCP). They are all Japanese and they do not kiss habitually. The subject kissed freely during 30 min with their lover or spouse alone in a room with closed doors while listening to soft music. Before and after kissing, skin prick tests were performed using commercial HDM allergen, JCP allergen, as well as histamine and control solution, and wheal responses were measured. Simultaneously, plasma levels of neurotrophin, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and -4 (NT-4) were measured. Kissing significantly reduced wheal responses induced by HDM and JCP, but not by histamine, and decreased plasma levels of NGF, BDNF, NT-3, and NT-4 in patients with AR or AD, while it failed to do so in normal subjects. These finding indicate that kissing have some implication in the study of neuroimmunology in allergic patients. PMID:14637240

  8. Inactivation of two newly identified tobacco heavy metal ATPases leads to reduced Zn and Cd accumulation in shoots and reduced pollen germination

    PubMed Central

    Hermand, Victor; Julio, Emilie; Dorlhac de Borne, François; Punshon, Tracy; Ricachenevsky, Felipe K; Bellec, Arnaud; Gosti, Françoise; Berthomieu, Pierre

    2015-01-01

    Cadmium (Cd) is a non-essential heavy metal, which is classified as a “known human carcinogen” by the International Agency for Research on Cancer (IARC). Understanding the mechanisms controlling Cd distribution in planta is essential to develop phytoremediation approaches as well as for food safety. Unlike most other plants, tobacco (Nicotiana tabacum) plants translocate most of the Cd taken up from the soil, out of the roots and into the shoots, leading to high Cd accumulation in tobacco shoots. Two orthologs to the Arabidopsis thaliana HMA2 and HMA4 Zn and Cd ATPases that are responsible for zinc (Zn) and Cd translocation from roots to shoots were identified in tobacco and sequenced. These genes, named NtHMAα and NtHMAβ, were more highly expressed in roots than in shoots. NtHMAα was expressed in the vascular tissues of both roots and leaves as well as in anthers. No visual difference was observed between wild-type plants and plants in which the NtHMAα and NtHMAβ genes were either mutated or silenced. These mutants showed reduced Zn and Cd accumulation in shoots as well as increased Cd tolerance. When both NtHMA genes were silenced, plant development was altered and pollen germination was severely impaired due to Zn deficiency. Interestingly, seeds from these lines also showed decreased Zn concentration but increased iron (Fe) concentration. PMID:24760325

  9. Inactivation of two newly identified tobacco heavy metal ATPases leads to reduced Zn and Cd accumulation in shoots and reduced pollen germination.

    PubMed

    Hermand, Victor; Julio, Emilie; Dorlhac de Borne, François; Punshon, Tracy; Ricachenevsky, Felipe K; Bellec, Arnaud; Gosti, Françoise; Berthomieu, Pierre

    2014-08-01

    Cadmium (Cd) is a non-essential heavy metal, which is classified as a "known human carcinogen" by the International Agency for Research on Cancer (IARC). Understanding the mechanisms controlling Cd distribution in planta is essential to develop phytoremediation approaches as well as for food safety. Unlike most other plants, tobacco (Nicotiana tabacum) plants translocate most of the Cd taken up from the soil, out of the roots and into the shoots, leading to high Cd accumulation in tobacco shoots. Two orthologs of the Arabidopsis thaliana HMA2 and HMA4 Zn and Cd ATPases that are responsible for zinc (Zn) and Cd translocation from roots to shoots were identified in tobacco and sequenced. These genes, named NtHMAα and NtHMAβ, were more highly expressed in roots than in shoots. NtHMAα was expressed in the vascular tissues of both roots and leaves as well as in anthers. No visual difference was observed between wild-type plants and plants in which the NtHMAα and NtHMAβ genes were either mutated or silenced. These mutants showed reduced Zn and Cd accumulation in shoots as well as increased Cd tolerance. When both NtHMA genes were silenced, plant development was altered and pollen germination was severely impaired due to Zn deficiency. Interestingly, seeds from these lines also showed decreased Zn concentration but increased iron (Fe) concentration. PMID:24760325

  10. Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice.

    PubMed

    Zhang, Xilin; Hu, Jin; Zhong, Li; Wang, Na; Yang, Longyu; Liu, Chia-Chen; Li, Huifang; Wang, Xin; Zhou, Ying; Zhang, Yunwu; Xu, Huaxi; Bu, Guojun; Zhuang, Jiangxing

    2016-09-01

    Apolipoprotein E (apoE) is a major cholesterol carrier that regulates lipid homeostasis by mediating lipid transport from one tissue or cell type to another. In the central neural system (CNS), apoE is mainly produced by astrocytes, and transports cholesterol to neurons via apoE receptors, which are members of the low-density lipoprotein receptor family. The APOEε4 gene is a strong genetic risk factor for late-onset sporadic Alzheimer's disease (AD), likely through its strong effect on the accumulation of amyloid-β (Aβ) peptide. ApoE protein levels in cerebrospinal fluid (CSF) and plasma are reduced in APOEε4 carriers and in patients with AD. Furthermore, altered cholesterol levels are also associated with the risk of AD. Aβ accumulation, oligomerization and deposition in the brain are central to the pathogenesis of AD. Mounting evidence demonstrates that apoE and apoE receptors play important roles in these processes. Astrocyte-derived apoE is pivotal for cerebral cholesterol metabolism and clearance of Aβ. Thus, we hypothesized that increased apoE in the brain may be an effective therapeutic strategy for AD. We report here that quercetin can significantly increase apoE levels by inhibiting apoE degradation in immortalized astrocytes. Importantly, we show that oral administration of quercetin significantly increased brain apoE and reduced insoluble Aβ levels in the cortex of 5xFAD amyloid model mice. Our results demonstrate that quercetin increases apoE levels through a novel mechanism and can be explored as a novel class of drug for AD therapy. PMID:27114256

  11. Expression of a constitutively active nitrate reductase variant in tobacco reduces tobacco-specific nitrosamine accumulation in cured leaves and cigarette smoke.

    PubMed

    Lu, Jianli; Zhang, Leichen; Lewis, Ramsey S; Bovet, Lucien; Goepfert, Simon; Jack, Anne M; Crutchfield, James D; Ji, Huihua; Dewey, Ralph E

    2016-07-01

    Burley tobaccos (Nicotiana tabacum) display a nitrogen-use-deficiency phenotype that is associated with the accumulation of high levels of nitrate within the leaf, a trait correlated with production of a class of compounds referred to as tobacco-specific nitrosamines (TSNAs). Two TSNA species, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), have been shown to be strong carcinogens in numerous animal studies. We investigated the potential of molecular genetic strategies to lower nitrate levels in burley tobaccos by overexpressing genes encoding key enzymes of the nitrogen-assimilation pathway. Of the various constructs tested, only the expression of a constitutively active nitrate reductase (NR) dramatically decreased free nitrate levels in the leaves. Field-grown tobacco plants expressing this NR variant exhibited greatly reduced levels of TSNAs in both cured leaves and mainstream smoke of cigarettes made from these materials. Decreasing leaf nitrate levels via expression of a constitutively active NR enzyme represents an exceptionally promising means for reducing the production of NNN and NNK, two of the most well-documented animal carcinogens found in tobacco products. PMID:26800860

  12. High-Level Accumulation of Triacylglycerol and Starch in Photoautotrophically Grown Chlamydomonas debaryana NIES-2212.

    PubMed

    Toyoshima, Masakazu; Sato, Naoki

    2015-12-01

    Microalgae have the potential to produce triacylglycerol (TAG) and starch, which provide alternative sources of biofuel. A problem in using Chlamydomonas reinhardtii as a model for TAG production has been that this alga lacks phosphatidylcholine (PC), which is thought to be important for TAG synthesis in plants. We found that C. debaryana is one of the rare species of Chlamydomonas having PC. Here we show that this strain, grown under complete photoautotrophic conditions, accumulated TAG and starch up to 20 and 250 pg per cell, respectively, during the stationary phase without nutrient deprivation. Addition of nutrients in this state did not cause loss of TAG, which was found in dilution with fresh medium. The photosynthetically produced TAG contained a high level of monounsaturated fatty acids, which is a preferred property as a material for biodiesel. The oil bodies were present in the cytoplasm, either between the cytoplasmic membrane and the chloroplast or between the chloroplast and the nucleus, whereas the starch granules were present within the chloroplast. Oil bodies were also deposited as a broad layer in the peripheral space of the cytoplasm outside the chloroplast, and might be easily released from the cells by genetic, chemical or mechanical manipulation. These results suggest that C. debaryana is a promising seed organism for developing a good biofuel producer. PMID:26542110

  13. Cadmium accumulation in Panax notoginseng: levels, affecting factors and the non-carcinogenic health risk.

    PubMed

    Zhu, Meilin; Jiang, Yang; Cui, Bin; Jiang, Yanxue; Cao, Hongbin; Zhang, Wensheng

    2016-04-01

    Cadmium (Cd) contamination has been reported to be a problem for the safe usage of Panax notoginseng (Sanchi); thus, it is necessary to elucidate the Cd accumulation in Sanchi and to assess its associated health risk. Samples were collected from major producing areas in Yunnan, China. The average concentration of Cd in Sanchi was 0.43 mg/kg, which exceeds the standard level for herbal medicine in China (0.3 mg/kg). A stepwise regression analysis showed that zinc and the pH were the related factors that most significantly impacted Cd in Sanchi roots. The hazard quotient values were estimated as 0.0010 (men) and 0.0012 (women) for consumers taking preparations and were 0.011 (men) and 0.013 (women) for consumers taking health products, implying that there is no non-carcinogenic hazard associated with Sanchi consumption. However, a Monte Carlo simulation showed that approximately 0.80 % of male and 1.02 % of female consumers via drug consumption and 36.28 % of male and 41.87 % of female consumers via health product consumption had an exposure exceeding the acceptable daily intake (ADI) of Cd from drugs (1 % of the total oral ADI as suggested by the World Health Organization). These people should control their oral Cd intake from both Sanchi consumption and diet as a whole. PMID:26070861

  14. A glutathione reductase mutant of yeast accumulates high levels of oxidized glutathione and requires thioredoxin for growth.

    PubMed Central

    Muller, E G

    1996-01-01

    A glutathione reductase null mutant of Saccharomyces cerevisiae was isolated in a synthetic lethal genetic screen for mutations which confer a requirement for thioredoxin. Yeast mutants that lack glutathione reductase (glr1 delta) accumulate high levels of oxidized glutathione and have a twofold increase in total glutathione. The disulfide form of glutathione increases 200-fold and represents 63% of the total glutathione in a glr1 delta mutant compared with only 6% in wild type. High levels of oxidized glutathione are also observed in a trx1 delta, trx2 delta double mutant (22% of total), in a glr1 delta, trx1 delta double mutant (71% of total), and in a glr1 delta, trx2 delta double mutant (69% of total). Despite the exceptionally high ratio of oxidized/reduced glutathione, the glr1 delta mutant grows with a normal cell cycle. However, either one of the two thioredoxins is essential for growth. Cells lacking both thioredoxins and glutathione reductase are not viable under aerobic conditions and grow poorly anaerobically. In addition, the glr1 delta mutant shows increased sensitivity to the thiol oxidant diamide. The sensitivity to diamide was suppressed by deletion of the TRX2 gene. The genetic analysis of thioredoxin and glutathione reductase in yeast runs counter to previous studies in Escherichia coli and for the first time links thioredoxin with the redox state of glutathione in vivo. Images PMID:8930901

  15. Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves

    NASA Astrophysics Data System (ADS)

    Dixit, Garima; Singh, Amit Pal; Kumar, Amit; Dwivedi, Sanjay; Deeba, Farah; Kumar, Smita; Suman, Shankar; Adhikari, Bijan; Shukla, Yogeshwar; Trivedi, Prabodh Kumar; Pandey, Vivek; Tripathi, Rudra Deo

    2015-11-01

    Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress.

  16. Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves

    PubMed Central

    Dixit, Garima; Singh, Amit Pal; Kumar, Amit; Dwivedi, Sanjay; Deeba, Farah; Kumar, Smita; Suman, Shankar; Adhikari, Bijan; Shukla, Yogeshwar; Trivedi, Prabodh Kumar; Pandey, Vivek; Tripathi, Rudra Deo

    2015-01-01

    Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress. PMID:26552588

  17. Calcium Deficiency Reduces Circulating Levels of FGF23

    PubMed Central

    Rodriguez-Ortiz, María E.; Lopez, Ignacio; Muñoz-Castañeda, Juan R.; Martinez-Moreno, Julio M.; Ramírez, Alan Peralta; Pineda, Carmen; Canalejo, Antonio; Jaeger, Philippe; Aguilera-Tejero, Escolastico; Felsenfeld, Arnold; Almaden, Yolanda

    2012-01-01

    Fibroblast growth factor (FGF) 23 inhibits calcitriol production, which could exacerbate calcium deficiency or hypocalcemia unless calcium itself modulates FGF23 in this setting. In Wistar rats with normal renal function fed a diet low in both calcium and vitamin D, the resulting hypocalcemia was associated with low FGF23 despite high parathyroid hormone (PTH) and high calcitriol levels. FGF23 correlated positively with calcium and negatively with PTH. Addition of high dietary phosphorus to this diet increased FGF23 except in rats with hypocalcemia despite high PTH levels. In parathyroidectomized rats, an increase in dietary calcium for 10 days increased serum calcium, with an associated increase in FGF23, decrease in calcitriol, and no change in phosphorus. Also in parathyroidectomized rats, FGF23 increased significantly 6 hours after administration of calcium gluconate. Taken together, these results suggest that hypocalcemia reduces the circulating concentrations of FGF23. This decrease in FGF23 could be a response to avoid a subsequent reduction in calcitriol, which could exacerbate hypocalcemia. PMID:22581996

  18. Population Characteristics May Reduce the Levels of Individual Call Identity

    PubMed Central

    Delgado, María del Mar; Caferri, Eleonora; Méndez, Maria; Godoy, José A.; Campioni, Letizia; Penteriani, Vincenzo

    2013-01-01

    Individual variability influences the demographic and evolutionary dynamics of spatially structured populations, and conversely ecological and evolutionary dynamics provide the context under which variations at the individual level occur. Therefore, it is essential to identify and characterize the importance of the different factors that may promote or hinder individual variability. Animal signaling is a prime example of a type of behavior that is largely dependent on both the features of individuals and the characteristics of the population to which they belong. After 10 years studying the dynamics of a population of a long-lived species, the eagle owl (Bubo bubo), we investigated the emergence and maintenance of traits that reveal individual identity by focusing on vocal features. We found that individuals inhabiting a high density population characterized by a relative lack of heterogeneity (in terms of prey availability and breeding success) among breeding sites might be selected for reducing the levels of identity. Two non-mutually exclusive hypotheses may explain the structural call patterns we detected: (1) similarity in calls may be principally a consequence of the particular characteristics of the population; and (2) high density may encourage individuals to mimic each other’s vocalizations in a cascade effect, leading to a widespread and unique communication network. PMID:24204869

  19. Reduced arsenic accumulation in rice (Oryza sativa L.) shoot involves sulfur mediated improved thiol metabolism, antioxidant system and altered arsenic transporters.

    PubMed

    Dixit, Garima; Singh, Amit Pal; Kumar, Amit; Mishra, Seema; Dwivedi, Sanjay; Kumar, Smita; Trivedi, Prabodh Kumar; Pandey, Vivek; Tripathi, Rudra Deo

    2016-02-01

    Arsenic (As) contamination in rice is at alarming level as majority of rice growing regions are As contaminated such as South East Asia. Restricting the As in aerial parts of rice plant may be an effective strategy to reduce As contamination in food chain. Sulfur (S), an essential element for plant growth and development, plays a crucial role in diminishing heavy metal toxicity. Current study is designed to investigate the role of S to mitigate As toxicity in rice under different S regimes. High S (5 mM) treatment resulted in enhanced root As accumulation as well as prevented its entry in to shoot. Results of thiol metabolism indicate that As was complexed in plant roots through enhanced synthesis of phytochelatins. High S treatment also reduced the expression of OsLsi1 and OsLsi2, the potent transporters of As in rice. High S treatment enhanced the activities of antioxidant enzymes and mitigated the As induced oxidative stress. Thus from present study it is evident that proper supply of S nutrition may be helpful in prevention of As accumulation in aerial parts of plant as well as As induced toxicity. PMID:26741538

  20. Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin.

    PubMed

    Khan, Sabbir; Jena, Gopabandhu

    2016-07-25

    Recent evidences highlighted that histone deacetylases (HDACs) can deacetylate the histone, various transcription factors and regulatory proteins, which directly or indirectly affect glucose metabolism. The present study aimed to evaluate the comparative effects of sodium butyrate (NaB) and metformin on the glucose homeostasis, insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet (HFD) and low dose streptozotocin (STZ, 35 mg/kg). NaB at the doses of 200 and 400 mg/kg twice daily as well as metformin (as a positive control) 150 mg/kg twice daily for 10 consecutive weeks were administered by i.p. and oral route, respectively. NaB treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, dyslipidemia and gluconeogenesis, which are comparable to metformin treatment. Further, NaB treatment ameliorated the micro- and macro-vesicular steatosis in liver and fat deposition in brown adipose tissue, white adipose tissue (adipocytes hypertrophy) as well as pancreatic beta-cell damage. In the present study, both NaB and metformin inhibited the diabetes-associated increased HDACs activity, thereby increased the acetylation of histone H3 in liver. The present findings demonstrated that NaB and metformin reduced insulin-resistance, dyslipidemia, fat accumulation and gluconeogenesis thereby improved the glucose homeostasis in rat. Thus, NaB might be a promising molecule for the prevention and treatment of type-2 diabetes and dyslipidemia. PMID:27270450

  1. Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis

    PubMed Central

    2011-01-01

    Background Numerous evidences suggest that diabetic heart is characterized by compromised ventricular contraction and prolonged relaxation attributable to multiple causative factors including calcium accumulation, oxidative stress and apoptosis. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under diabetic condition. Methods This study was designed to examine the effect of long-acting calcium channel blocker (CCB), Azelnidipine (AZL) on contractile dysfunction, intracellular calcium (Ca2+) cycling proteins, stress-activated signaling molecules and apoptosis on cardiomyocytes in diabetes. Adult male Wistar rats were made diabetic by a single intraperitoneal (IP) injection of streptozotocin (STZ). Contractile functions were traced from live diabetic rats to isolated individual cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-relengthening (TR90), maximal velocity of shortening/relengthening (± dL/dt) and intracellular Ca2+ fluorescence. Results Diabetic heart showed significantly depressed PS, ± dL/dt, prolonged TPS, TR90 and intracellular Ca2+ clearing and showed an elevated resting intracellular Ca2+. AZL itself exhibited little effect on myocyte mechanics but it significantly alleviated STZ-induced myocyte contractile dysfunction. Diabetes increased the levels of superoxide, enhanced expression of the cardiac damage markers like troponin I, p67phox NADPH oxidase subunit, restored the levels of the mitochondrial superoxide dismutase (Mn-SOD), calcium regulatory proteins RyR2 and SERCA2a, and suppressed the levels of the anti-apoptotic Bcl-2 protein. All of these STZ-induced alterations were reconciled by AZL treatment. Conclusion Collectively, the data suggest beneficial effect of AZL in diabetic cardiomyopathy via altering intracellular Ca2+ handling proteins and preventing apoptosis by its antioxidant property. PMID:22054019

  2. Reduced expression of fumarate hydratase in clear cell renal cancer mediates HIF-2α accumulation and promotes migration and invasion.

    PubMed

    Sudarshan, Sunil; Shanmugasundaram, Karthigayan; Naylor, Susan L; Lin, Shu; Livi, Carolina B; O'Neill, Christine F; Parekh, Dipen J; Yeh, I-Tien; Sun, Lu-Zhe; Block, Karen

    2011-01-01

    Germline mutations of FH, the gene that encodes for the tricarboxylic acid TCA (TCA) cycle enzyme fumarate hydratase, are associated with an inherited form of cancer referred to as Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). Individuals with HLRCC are predisposed to the development of highly malignant and lethal renal cell carcinoma (RCC). The mechanisms of tumorigenesis proposed have largely focused on the biochemical consequences of loss of FH enzymatic activity. While loss of the tumor suppressor gene von Hippel Lindau (VHL) is thought to be an initiating event for the majority of RCCs, a role for FH in sporadic renal cancer has not been explored. Here we report that FH mRNA and protein expression are reduced in clear cell renal cancer, the most common histologic variant of kidney cancer. Moreover, we demonstrate that reduced FH leads to the accumulation of hypoxia inducible factor- 2α (HIF-2α), a transcription factor known to promote renal carcinogenesis. Finally, we demonstrate that overexpression of FH in renal cancer cells inhibits cellular migration and invasion. These data provide novel insights into the tumor suppressor functions of FH in sporadic kidney cancer. PMID:21695080

  3. Development of a novel transgenic rice with hypocholesterolemic activity via high-level accumulation of the α' subunit of soybean β-conglycinin.

    PubMed

    Cabanos, Cerrone; Kato, Naoki; Amari, Yoshiki; Fujiwara, Keigo; Ohno, Tomoki; Shimizu, Kousuke; Goto, Tsuyoshi; Shimada, Masaya; Kuroda, Masaharu; Masuda, Taro; Takaiwa, Fumio; Utsumi, Shigeru; Nagaoka, Satoshi; Maruyama, Nobuyuki

    2014-08-01

    Soybean 7S globulin, known as β-conglycinin, has been shown to regulate human plasma cholesterol and triglyceride levels. Furthermore, the α' subunit of β-conglycinin has specifically been shown to possess low-density lipoprotein (LDL)-cholesterol-lowering activity. Therefore, accumulation of the α' subunit of β-conglycinin in rice seeds could lead to the production of new functional rice that could promote human health. Herein, we used the low-glutelin rice mutant 'Koshihikari' (var. a123) and suppressed its glutelins and prolamins, the major seed storage proteins of rice, by RNA interference. The accumulation levels of the α' subunit in the lines with suppressed glutelin and prolamin levels were >20 mg in 1 g of rice seeds, which is considerably higher than those in previous studies. Oral administration of the transgenic rice containing the α' subunit exhibited a hypocholesterolemic activity in rats; the serum total cholesterol and LDL cholesterol levels were significantly reduced when compared to those of the control rice (var. a123). The cholesterol-lowering action by transgenic rice accumulating the α' subunit induces a significant increase in fecal bile acid excretion and a tendency to increase in fecal cholesterol excretion. This is the first report that transgenic rice exhibits a hypocholesterolemic activity in rats in vivo by using the β-conglycinin α' subunit. PMID:24676962

  4. 5 CFR 630.301 - Annual leave accrual and accumulation-Senior Executive Service, Senior-Level, and Scientific and...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Annual leave accrual and accumulation-Senior Executive Service, Senior-Level, and Scientific and Professional Employees. 630.301 Section 630.301 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS ABSENCE AND LEAVE Annual Leave § 630.301 Annual leave...

  5. Reduced cadmium levels in human kidney cortex in sweden.

    PubMed Central

    Friis, L; Petersson, L; Edling, C

    1998-01-01

    Environmental pollution with the nephrotoxic metal cadmium is considered a potential health risk for the general population. In 1976 it was reported that the cadmium concentration in human kidney cortex in Sweden had increased in parallel with increasing levels in soil and grain during the twentieth century. Since the cadmium concentration in farming lands is still increasing, the present study was undertaken to further elucidate whether the cadmium concentration in the kidney is still increasing. Kidney cortex biopsies were collected at 171 autopsies of victims to sudden and accidental death during 1995 and 1996, and the cadmium concentrations were determined and compared with previously published Swedish data obtained from forensic autopsies. The geometric mean cadmium concentration in kidney cortex in subjects 40 years of age and younger was about 40% of the concentration found in the 1970s, while the reduction was less pronounced among older people. The highest individual concentration of cadmium was 41.5 microg/g wet weight (ww). The geometric mean concentration was less than 14 microg/g ww at ages around 50 years of age, when the cadmium concentration in kidney cortex is highest, as compared with approximately 20 microg/g ww in the 1970s. There was also a reduction in cadmium concentrations among nonsmokers; thus, a decrease in tobacco smoking in Sweden during the last decades is not the only explanation for the reduction of cadmium in the kidney cortex. Other reasons for this reduction could be changes in dietary habits and reduced cadmium contamination from Swedish industries. Images Figure 1 PMID:9485480

  6. Short-term fasting induces intra-hepatic lipid accumulation and decreases intestinal mass without reduced brush-border enzyme activity in mink (Mustela vison) small intestine.

    PubMed

    Bjornvad, C R; Elnif, J; Sangild, P T

    2004-11-01

    For many mammalian species short-term fasting is associated with intestinal atrophy and decreased digestive capacity. Under natural conditions, strictly carnivorous animals often experience prey scarcity during winter, and they may therefore be particularly well adapted to short-term food deprivation. To examine how the carnivorous gastrointestinal tract is affected by fasting, small-intestinal structure, brush-border enzyme activities and hepatic structure and function were examined in fed mink (controls) and mink that had been fasted for 1-10 days. During the first 1-2 days of fasting, intestinal mass decreased more rapidly than total body mass and villus heights were reduced 25-40%. In contrast, tissue-specific activity of the brush-border enzymes sucrase, maltase, lactase, aminopeptidase A and dipeptidylpeptidase IV increased 0.5- to 1.5-fold at this time, but returned to prefasting levels after 6 days of fasting. After 6-10 days of fasting there was a marked increase in the activity of hepatic enzymes and accumulation of intra-hepatic lipid vacuoles. Thus, mink may be a useful model for studying fasting-induced intestinal atrophy and adaptation as well as mechanisms involved in accumulation of intra-hepatic lipids following food deprivation in strictly carnivorous domestic mammals, such as cats and ferrets. PMID:15503054

  7. Carotenoid accumulation in orange-pigmented Capsicum annuum fruit, regulated at multiple levels

    PubMed Central

    Rodriguez-Uribe, Laura; Guzman, Ivette; Rajapakse, Wathsala; Richins, Richard D.; O’Connell, Mary A.

    2012-01-01

    The pericarp of Capsicum fruit is a rich dietary source of carotenoids. Accumulation of these compounds may be controlled, in part, by gene transcription of biosynthetic enzymes. The carotenoid composition in a number of orange-coloured C. annuum cultivars was determined using HPLC and compared with transcript abundances for four carotenogenic enzymes, Psy, LcyB, CrtZ-2, and Ccs determined by qRT-PCR. There were unique carotenoid profiles as well as distinct patterns of transcription of carotenogenic enzymes within the seven orange-coloured cultivars. In one cultivar, ‘Fogo’, carrying the mutant ccs-3 allele, transcripts were detected for this gene, but no CCS protein accumulated. The premature stop termination in ccs-3 prevented expression of the biosynthetic activity to synthesize the capsanthin and capsorubin forms of carotenoids. In two other orange-coloured cultivars, ‘Orange Grande’ and ‘Oriole’, both with wild-type versions of all four carotenogenic enzymes, no transcripts for Ccs were detected and no red pigments accumulated. Finally, in a third case, the orange-coloured cultivar, Canary, transcripts for all four of the wild-type carotenogenic enzymes were readily detected yet no CCS protein appeared to accumulate and no red carotenoids were synthesized. In the past, mutations in Psy and Ccs have been identified as the loci controlling colour in the fruit. Now there is evidence that a non-structural gene may control colour development in Capsicum. PMID:21948863

  8. ISOLATED MEDICAGO TRUNCATULA MUTANTS WITH INCREASED CALCIUM OXALATE CRYSTAL ACCUMULATION HAVE DECREASED ASCORBIC ACID LEVELS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mechanisms controlling oxalate biosynthesis and calcium oxalate formation in plants remains largely unknown. As an initial step toward gaining insight into these regulatory mechanisms we initiated a mutant screen to identify plants that over-accumulate crystals of calcium oxalate. Four new mut...

  9. BIOMASS ACCUMULATION AND PARTITIONING OF EASTERN GAMMAGRASS GROWN UNDER DIFFERENT TEMPERATURE AND CO2 LEVELS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eastern gamagrass has been reported to have one of the highest photosynthetic rates of any C4 species but data on temperature x CO2 interactions are lacking. This study was conducted to determine the potential effects of future increases of atmospheric carbon dioxide on growth, biomass accumulation...

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

    PubMed Central

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

    2014-01-01

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

  11. Reduced cholesterol levels impair Smoothened activation in Smith–Lemli–Opitz syndrome

    PubMed Central

    Blassberg, Robert; Macrae, James I.; Briscoe, James; Jacob, John

    2016-01-01

    Smith–Lemli–Opitz syndrome (SLOS) is a common autosomal-recessive disorder that results from mutations in the gene encoding the cholesterol biosynthetic enzyme 7-dehydrocholesterol reductase (DHCR7). Impaired DHCR7 function is associated with a spectrum of congenital malformations, intellectual impairment, epileptiform activity and autism spectrum disorder. Biochemically, there is a deficit in cholesterol and an accumulation of its metabolic precursor 7-dehydrocholesterol (7DHC) in developing tissues. Morphological abnormalities in SLOS resemble those seen in congenital Sonic Hedgehog (SHH)-deficient conditions, leading to the proposal that the pathogenesis of SLOS is mediated by aberrant SHH signalling. SHH signalling is transduced through the transmembrane protein Smoothened (SMO), which localizes to the primary cilium of a cell on activation and is both positively and negatively regulated by sterol molecules derived from cholesterol biosynthesis. One proposed mechanism of SLOS involves SMO dysregulation by altered sterol levels, but the salient sterol species has not been identified. Here, we clarify the relationship between disrupted cholesterol metabolism and reduced SHH signalling in SLOS by modelling the disorder in vitro. Our results indicate that a deficit in cholesterol, as opposed to an accumulation of 7DHC, impairs SMO activation and its localization to the primary cilium. PMID:26685159

  12. Effects of reduced coronary flow on thallium-201 accumulation and release in an in vitro rat heart preparation

    SciTech Connect

    Goldhaber, S.Z.; Newell, J.B.; Ingwall, J.S.; Pohost, G.M.; Alpert, N.M.; Fossel, E.T.

    1983-03-01

    To study the relation between myocardial thallium-201 (TI-201) uptake, TI-201 release, and reduced coronary flow, isolated Langendorff rat hearts (n . 8) were perfused for 3 hours at constant flows ranging from physiologic (12 ml/min) to severely ischemic (1.5 ml/min); thallium activity was monitored with a scintillation probe. Each heart was perfused for 1 hour with thallium buffer, followed by 2 hours with thallium-free buffer at the same flow rate. Accumulation curves for all 4 flows were monoexponential. However, release curves during the 2 hours of washout with thallium-free buffer demonstrated a biexponential configuration. The early fast release component decreased with reductions in coronary flow, and the later slow release component did not vary significantly with flow. These data show that thallium clearance has at least 2 components: a rapid (possibly extracellular) component related to coronary flow and a slow (possibly intracellular) component independent of coronary flow. These findings should be useful in providing a better understanding of thallium redistribution observed clinically.

  13. Chronic administration of palmitoleic acid reduces insulin resistance and hepatic lipid accumulation in KK-Ay Mice with genetic type 2 diabetes

    PubMed Central

    2011-01-01

    Background Studies have demonstrated the beneficial effect of palmitoleic acid (C16:1 n-7) on reducing muscle insulin resistance and preventing beta-cell apoptosis. However, the effect of palmitoleic acid on diabetes remains to be elucidated. The aim of this study was to examine the antidiabetic effect of palmitoleic acid in KK-Ay mice, a spontaneous model for studies of obese type 2 diabetes with low insulin sensitivity. Methods KK-Ay mice were orally administered vehicle, 300 mg/kg of palmitoleic acid, or 300 mg/kg of palmitic acid (C16:0) on a daily basis for 4 weeks. Results Palmitoleic acid reduced body weight increase, ameliorated the development of hyperglycemia and hypertriglyceridemia, and improved insulin sensitivity. In addition, hepatic characteristics were significantly affected, as weight of the liver and hepatic triglyceride levels were lower in the palmitoleic acid group when compared to the control (vehicle and palmitic acid groups). Oil red O staining clearly indicated reduced hepatic lipid accumulation in response to palmitoleic acid. Furthermore, palmitoleic acid down-regulated mRNA expressions of proinflammatory adipocytokine genes (TNFα and resistin) in white adipose tissue and lipogenic genes (SREBP-1, FAS, and SCD-1) in liver. Conclusions These results suggest that palmitoleic acid improves hyperglycemia and hypertriglyceridemia by increasing insulin sensitivity, in part owing to suppressing proinflammatory gene expressions and improving hepatic lipid metabolism in diabetic mice. PMID:21774832

  14. Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

    SciTech Connect

    Kay, Steve A.

    2013-05-02

    Several breakthroughs have been recently made in our understanding of plant growth and biomass accumulation. It was found that plant growth is rhythmically controlled throughout the day by the circadian clock through a complex interplay of light and phytohormone signaling pathways. While plants such as the C4 energy crop sorghum (Sorghum bicolor (L.) Moench) and possibly the C3 grass (Brachypodium distachyon) also exhibit daily rhythms in growth rate, the molecular details of its regulation remain to be explored. A better understanding of diurnally regulated growth behavior in grasses may lead to species-specific mechanisms highly relevant to future strategies to optimize energy crop biomass yield. Here we propose to devise a systems approach to identify, in parallel, regulatory hubs associated with rhythmic growth in C3 and C4 plants. We propose to use rhythmicity in daily growth patterns to drive the discovery of regulatory network modules controlling biomass accumulation.

  15. Enzymatic treatment of peanut kernels to reduce allergen levels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study investigated the use of enzymatic treatment to reduce peanut allergens in peanut kernel by processing conditions, such as, pretreatment with heat and proteolysis at different enzyme concentrations and treatment times. Two major peanut allergens, Ara h 1 and Ara h 2, were used as indicator...

  16. Identification of Leaf Proteins Differentially Accumulated between Wheat Cultivars Distinct in Their Levels of Drought Tolerance.

    PubMed

    Cheng, Zhiwei; Dong, Kun; Ge, Pei; Bian, Yanwei; Dong, Liwei; Deng, Xiong; Li, Xiaohui; Yan, Yueming

    2015-01-01

    The drought-tolerant 'Ningchun 47' (NC47) and drought-sensitive 'Chinese Spring' (CS) wheat (Triticum aestivum L.) cultivars were treated with different PEG6000 concentrations at the three-leaf stage. An analysis on the physiological and proteomic changes of wheat seedling in response to drought stress was performed. In total, 146 differentially accumulated protein (DAP) spots were separated and recognised using two-dimensional gel electrophoresis. In total, 101 DAP spots representing 77 unique proteins were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. These proteins were allocated to 10 groups according to putative functions, which were mainly involved in carbon metabolism (23.4%), photosynthesis/respiration (22.1%) and stress/defence/detoxification (18.2%). Some drought stress-related proteins in NC47, such as enolase, 6-phosphogluconate dehydrogenase, Oxygen-evolving enhancer protein 2, fibrillin-like protein, 2-Cys peroxiredoxin BAS1 and 70-kDa heat shock protein, were more upregulated than those in CS. Multivariate principal components analysis revealed obvious differences between the control and treatments in both NC47 and CS, while cluster analysis showed that the DAPs displayed five and six accumulation patterns in NC47 and CS, respectively. Protein-protein interaction network analysis showed that some key DAPs, such as 2-Cys peroxiredoxin BAS1, RuBisCO large subunit-binding protein, 50S ribosomal protein L1, 6-phosphogluconate dehydrogenase, glyceraldehyde 3-phosphate dehydrogenase isoenzyme and 70-kDa heat shock protein, with upregulated accumulation in NC47, had complex interactions with other proteins related to amino acid metabolism, carbon metabolism, energy pathway, signal transduction, stress/defence/detoxification, protein folding and nucleotide metabolism. These proteins could play important roles in drought-stress tolerance and contribute to the relatively stronger drought tolerance of NC47. PMID

  17. Identification of Leaf Proteins Differentially Accumulated between Wheat Cultivars Distinct in Their Levels of Drought Tolerance

    PubMed Central

    Bian, Yanwei; Dong, Liwei; Deng, Xiong; Li, Xiaohui; Yan, Yueming

    2015-01-01

    The drought-tolerant ‘Ningchun 47’ (NC47) and drought-sensitive ‘Chinese Spring’ (CS) wheat (Triticum aestivum L.) cultivars were treated with different PEG6000 concentrations at the three-leaf stage. An analysis on the physiological and proteomic changes of wheat seedling in response to drought stress was performed. In total, 146 differentially accumulated protein (DAP) spots were separated and recognised using two-dimensional gel electrophoresis. In total, 101 DAP spots representing 77 unique proteins were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. These proteins were allocated to 10 groups according to putative functions, which were mainly involved in carbon metabolism (23.4%), photosynthesis/respiration (22.1%) and stress/defence/detoxification (18.2%). Some drought stress-related proteins in NC47, such as enolase, 6-phosphogluconate dehydrogenase, Oxygen-evolving enhancer protein 2, fibrillin-like protein, 2-Cys peroxiredoxin BAS1 and 70-kDa heat shock protein, were more upregulated than those in CS. Multivariate principal components analysis revealed obvious differences between the control and treatments in both NC47 and CS, while cluster analysis showed that the DAPs displayed five and six accumulation patterns in NC47 and CS, respectively. Protein–protein interaction network analysis showed that some key DAPs, such as 2-Cys peroxiredoxin BAS1, RuBisCO large subunit-binding protein, 50S ribosomal protein L1, 6-phosphogluconate dehydrogenase, glyceraldehyde 3-phosphate dehydrogenase isoenzyme and 70-kDa heat shock protein, with upregulated accumulation in NC47, had complex interactions with other proteins related to amino acid metabolism, carbon metabolism, energy pathway, signal transduction, stress/defence/detoxification, protein folding and nucleotide metabolism. These proteins could play important roles in drought-stress tolerance and contribute to the relatively stronger drought tolerance of NC47

  18. Impaired clearance of accumulated lysosomal glycogen in advanced Pompe disease despite high-level vector-mediated transgene expression

    PubMed Central

    Sun, Baodong; Zhang, Haoyue; Bird, Andrew; Li, Songtao; Young, Sarah P.; Koeberl, Dwight D.

    2013-01-01

    Background Infantile-onset glycogen storage disease type II (GSD-II; Pompe disease; MIM 232300) causes death early in childhood from cardiorespiratory failure in absence of effective treatment, whereas late-onset Pompe disease causes a progressive skeletal myopathy. The limitations of enzyme replacement therapy could potentially be addressed with adeno-associated virus (AAV) vector-mediated gene therapy. Methods AAV vectors containing tissue-specific regulatory cassettes, either liver-specific or muscle-specific, were administered to 12 and 17 month old Pompe disease mice to evaluate the efficacy of gene therapy in advanced Pompe disease. Biochemical correction was evaluated through GAA activity and glycogen content analyses of the heart and skeletal muscle. Western blotting, urinary biomarker, and Rotarod performance were evaluated following vector administration. Results The AAV vector containing the liver-specific regulatory cassette secreted high-level hGAA into the blood and corrected glycogen storage in the heart and diaphragm. The biochemical correction of the heart and diaphragm was associated with efficacy, as reflected by increased Rotarod performance; however, the clearance of glycogen from skeletal muscles was relatively impaired, in comparison with younger Pompe disease mice. An alternative vector containing a muscle-specific regulatory cassette transduced skeletal muscle with high efficiency, but also failed to achieve complete clearance of accumulated glycogen. Decreased transduction of the heart and liver in older mice, especially in females, was implicated as a cause for reduced efficacy in advanced Pompe disease. Conclusion The impaired efficacy of AAV vector-mediated gene therapy in old Pompe disease mice emphasized the need for early treatment to achieve full efficacy. PMID:19621331

  19. Demise of reef-flat carbonate accumulation with late Holocene sea-level fall: Evidence from Molokai, Hawaii

    USGS Publications Warehouse

    Engels, M.S.; Fletcher, C.H.; Field, M.; Conger, C.L.; Bochicchio, C.

    2008-01-01

    Twelve cores from the protected reef-flat of Molokai revealed that carbonate sediment accumulation, ranging from 3 mm year-1 to less than 1 mm year-1, ended on average 2,500 years ago. Modern sediment is present as a mobile surface veneer but is not trapped within the reef framework. This finding is consistent with the arrest of deposition at the end of the mid-Holocene highstand, known locally as the "Kapapa Stand of the Sea," ???2 m above the present datum ca. 3,500 years ago in the main Hawaiian Islands. Subsequent erosion, non-deposition, and/or a lack of rigid binding were probable factors leading to the lack of reef-flat accumulation during the late Holocene sea-level fall. Given anticipated climate changes, increased sedimentation of reef-flat environments is to be expected as a consequence of higher sea level. ?? 2008 Springer-Verlag.

  20. Accumulation of secondary metabolites in healthy and diseased barley, grown under future climate levels of CO2, ozone and temperature.

    PubMed

    Mikkelsen, B L; Olsen, C E; Lyngkjær, M F

    2015-10-01

    Plants produce secondary metabolites promoting adaptation to changes in the environment and challenges by pathogenic microorganisms. A future climate with increased temperature and CO2 and ozone levels will likely alter the chemical composition of plants and thereby plant-pathogen interactions. To investigate this, barley was grown at elevated CO2, temperature and ozone levels as single factors or in combination resembling future climatic conditions. Increased basal resistance to the powdery mildew fungus was observed when barley was grown under elevated CO2, temperature and ozone as single factors. However, this effect was neutralized in the combination treatments. Twenty-five secondary metabolites were putatively identified in healthy and diseased barley leaves, including phenylpropanoids, phenolamides and hydroxynitrile glucosides. Accumulation of the compounds was affected by the climatic growth conditions. Especially elevated temperature, but also ozone, showed a strong impact on accumulation of many compounds, suggesting that these metabolites play a role in adaptation to unfavorable growth conditions. Many compounds were found to increase in powdery mildew diseased leaves, in correlation with a strong and specific influence of the climatic growth conditions. The observed disease phenotypes could not be explained by accumulation of single compounds. However, decreased accumulation of the powdery mildew associated defense compound p-coumaroylhydroxyagmatine could be implicated in the increased disease susceptibility observed when barley was grown under combination of elevated CO2, temperature and ozone. The accumulation pattern of the compounds in both healthy and diseased leaves from barley grown in the combination treatments could not be deduced from the individual single factor treatments. This highlights the complex role and regulation of secondary metabolites in plants' adaptation to unfavorable growth conditions. PMID:26343414

  1. Glycine betaine accumulation, ionic and water relations of red-beet at contrasting levels of sodium supply

    NASA Technical Reports Server (NTRS)

    Subbarao, G. V.; Wheeler, R. M.; Levine, L. H.; Stutte, G. W.; Sager, J. C. (Principal Investigator)

    2001-01-01

    Exposure of plants to sodium (Na) and salinity may increase glycine betaine accumulation in tissues. To study this, red-beet cvs. Scarlet Supreme and Ruby Queen, were grown for 42 days in a growth chamber using a re-circulating nutrient film technique with 0.25 mmol/L K and either 4.75 mmol/L (control) or 54.75 mmol/L (saline) Na (as NaCl). Plants were harvested at weekly intervals and measurements were taken on leaf water relations, leaf photosynthetic rates, chlorophyll fluorescence, chlorophyll levels, glycine betaine levels, and tissue elemental composition. Glycine betaine accumulation increased under salinity and this accumulation correlated with higher tissue levels of Na in both cultivars. Na accounted for 80 to 90% of the total cation uptake under the saline treatment. At final harvest (42 days), K concentrations in laminae ranged from approximately 65-95 micromoles g-1 dry matter (DM), whereas Na in shoot tissue ranged from approximately 3000-4000 micromoles g-1. Leaf sap osmotic potential at full turgor [psi(s100)] increased as lamina Na content increased. Glycine betaine levels of leaf laminae showed a linear relationship with leaf sap [psi(s100)]. Chlorophyll levels, leaf photosynthetic rates, and chlorophyll fluorescence were not affected by Na levels. These results suggest that the metabolic tolerance to high levels of tissue Na in red-beet could be due to its ability to synthesize and regulate glycine betaine production, and to control partitioning of Na and glycine betaine between the vacuole and the cytoplasm.

  2. Total arsenic accumulation in yabbies (Cherax destructor Clark) exposed to elevated arsenic levels in Victorian gold mining areas, Australia.

    PubMed

    Williams, Gemma; West, Jan M; Snow, Elizabeth T

    2008-06-01

    Arsenic is a proven carcinogen often found at high concentrations in association with gold and other heavy metals. The freshwater yabby, Cherax destructor Clark (Decapoda, Parastacidae), is a ubiquitous species native to Australia's central and eastern regions, with a growing international commercial market. However, in this region of Australia, yabby farmers often harvest organisms from old mine tailings dams with elevated environmental arsenic levels. Yabbies exposed to elevated environmental arsenic were found to accumulate and store as much as 100 microg/g arsenic in their tissues. The accumulation is proportional to the concentration of arsenic in the sediment and is high enough to be of concern for people who eat the yabbies. A comparison of arsenic levels in wild and lab-fed animals also was performed. Although there was no significant difference in the level of arsenic in the various organs of the wild animals, the animals purchased from a yabby farm showed a significantly higher arsenic concentration in their hepatopancreas (3.7 +/- 0.9 microg/g) compared to other organs (0.6-1.8 microg/g). Furthermore, after a 40-d exposure to food containing 200 to 300 microg/g inorganic arsenic, arsenate (As[V])-exposed animals showed a significant increase in tissue-specific arsenic accumulation, whereas arsenite (As[III])-exposed animals showed a lower, nonsignificant increase in As uptake, primarily in the hepatopancreas. These results have important implications for yabby growers and consumers alike. PMID:18198937

  3. Health Promotion to Reduce Blood Pressure Level among Older Blacks.

    ERIC Educational Resources Information Center

    Haber, David

    1986-01-01

    Low-income Black elders completed a 10-week health promotion program for the purpose of lowering or stabilizing blood pressure levels. Comparisons were made between classes that met weekly versus three times a week, and between yoga and aerobics formats. A peer-led program was developed that continued for 10 months after the professionally-led…

  4. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    PubMed

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type. PMID:25198797

  5. Disruption of Adenosine-5′-Phosphosulfate Kinase in Arabidopsis Reduces Levels of Sulfated Secondary Metabolites[W

    PubMed Central

    Mugford, Sarah G.; Yoshimoto, Naoko; Reichelt, Michael; Wirtz, Markus; Hill, Lionel; Mugford, Sam T.; Nakazato, Yoshimi; Noji, Masaaki; Takahashi, Hideki; Kramell, Robert; Gigolashvili, Tamara; Flügge, Ulf-Ingo; Wasternack, Claus; Gershenzon, Jonathan; Hell, Rüdiger; Saito, Kazuki; Kopriva, Stanislav

    2009-01-01

    Plants can metabolize sulfate by two pathways, which branch at the level of adenosine 5′-phosphosulfate (APS). APS can be reduced to sulfide and incorporated into Cys in the primary sulfate assimilation pathway or phosphorylated by APS kinase to 3′-phosphoadenosine 5′-phosphosulfate, which is the activated sulfate form for sulfation reactions. To assess to what extent APS kinase regulates accumulation of sulfated compounds, we analyzed the corresponding gene family in Arabidopsis thaliana. Analysis of T-DNA insertion knockout lines for each of the four isoforms did not reveal any phenotypical alterations. However, when all six combinations of double mutants were compared, the apk1 apk2 plants were significantly smaller than wild-type plants. The levels of glucosinolates, a major class of sulfated secondary metabolites, and the sulfated 12-hydroxyjasmonate were reduced approximately fivefold in apk1 apk2 plants. Although auxin levels were increased in the apk1 apk2 mutants, as is the case for most plants with compromised glucosinolate synthesis, typical high auxin phenotypes were not observed. The reduction in glucosinolates resulted in increased transcript levels for genes involved in glucosinolate biosynthesis and accumulation of desulfated precursors. It also led to great alterations in sulfur metabolism: the levels of sulfate and thiols increased in the apk1 apk2 plants. The data indicate that the APK1 and APK2 isoforms of APS kinase play a major role in the synthesis of secondary sulfated metabolites and are required for normal growth rates. PMID:19304933

  6. Different palm oil preparations reduce plasma cholesterol concentrations and aortic cholesterol accumulation compared to coconut oil in hypercholesterolemic hamsters.

    PubMed

    Wilson, Thomas A; Nicolosi, Robert J; Kotyla, Timothy; Sundram, Kalyana; Kritchevsky, David

    2005-10-01

    in the coconut oil-fed hamsters compared to the hamsters fed the RPO (60%), RBD-PO (42%) and the reconstituted RBD-PO (49%), while for plasma alpha-tocopherol concentrations, the coconut oil-fed hamsters were significantly higher than only the RPO-fed hamsters (21%). The coconut oil-fed hamsters also had significantly higher plasma lipid hydroperoxide concentrations compared to RBD-PO (112%) and the reconstituted RBD-PO (485%). The hamsters fed the coconut oil diet excreted significantly more fecal total neutral sterols and cholesterol compared to the hamsters fed the RBD-PO (158% and 167%, respectively). The coconut oil-fed hamsters had significantly higher levels of aortic total, free and esterified cholesterol compared to the hamsters fed the RPO (74%, 50% and 225%, respectively), RBD-PO (57%, 48% and 92%, respectively) and the reconstituted RBD-PO (111%, 94% and 94%, respectively). Also, aortic free/ester cholesterol ratio in the aortas of hamsters fed RPO was significantly higher than in those fed the coconut oil (124%). In conclusion, hamsters fed the three palm oil preparations had lower plasma TC and non-HDL-C and higher HDL-C concentrations while accumulating less aortic cholesterol concentrations compared to hamsters fed coconut oil. PMID:16081272

  7. Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52

    NASA Astrophysics Data System (ADS)

    Jo, Chulman; Gundemir, Soner; Pritchard, Susanne; Jin, Youngnam N.; Rahman, Irfan; Johnson, Gail V. W.

    2014-03-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor in the defence against oxidative stress. Here we provide evidence that activation of the Nrf2 pathway reduces the levels of phosphorylated tau by induction of an autophagy adaptor protein NDP52 (also known as CALCOCO2) in neurons. The expression of NDP52, which we show has three antioxidant response elements (AREs) in its promoter region, is strongly induced by Nrf2, and its overexpression facilitates clearance of phosphorylated tau in the presence of an autophagy stimulator. In Nrf2-knockout mice, phosphorylated and sarkosyl-insoluble tau accumulates in the brains concurrent with decreased levels of NDP52. Moreover, NDP52 associates with phosphorylated tau from brain cortical samples of Alzheimer disease cases, and the amount of phosphorylated tau in sarkosyl-insoluble fractions is inversely proportional to that of NDP52. These results suggest that NDP52 plays a key role in autophagy-mediated degradation of phosphorylated tau in vivo.

  8. Changes in Metabolite Levels in Kalanchoë daigremontiana and the Regulation of Malic Acid Accumulation in Crassulacean Acid Metabolism.

    PubMed

    Cockburn, W; McAulay, A

    1977-03-01

    Changes in glucose-6-P, fructose-6-P, fructose-1,6-diP, 6-phospho-gluconate, phosphoenolpyruvate, 3-phosphoglycerate, and pyruvate levels in the leaves of the Crassulacean plant Kalanchoë daigremontiana Hammet et Perrier were measured enzymically during transitions from CO(2)-free air to air, air to CO(2)-free air, and throughout the course of acid accumulation in darkness. The data are discussed in terms of the involvement of phosphoenolpyruvate carboxylase in malic acid synthesis and in terms of the regulation of the commencement of malic acid synthesis and accumulation through the effects of CO(2) on storage carbohydrate mobilization and its termination through the effects of malic acid on phosphoenolpyruvate carboxylase activity. PMID:16659872

  9. Reflectance of litter accumulation levels at five wavelengths within the 0.5- to 2.5 micron waveband

    NASA Technical Reports Server (NTRS)

    Gerbermann, A. H.; Everitt, J. H.; Gausman, H. W. (Principal Investigator)

    1982-01-01

    Reflectance was measured for 1-m2 range grass plots with two canopy treatments (standing and clipped) and four levels of litter accumulation and for grain sorghum with two canopy treatments. Reflectance was significantly higher at the 0.65- to 1.65-, and 2.20-micrometer. Wavelengths for both grass and grain sorghum canopies when the canopies were clipped and the resulting litter was removed. The natural accumulation of litter under the grass canopy did not significantly affect reflectance. The 1.65- and 2.20-micrometer wavelength reflectances of the live grass and the intact litter were 21.8% and 16.2%, respectively, and those of grain sorghum were 21.8% and 16.5%, respectively.

  10. Reducing nursing students' anxiety level and increasing retention of materials.

    PubMed

    Phillips, A P

    1988-01-01

    The purpose of this descriptive study is to examine the effects active learning, collaboration and modified group testing have on reducing students' anxiety and increasing learning and retention of material. Subjects consist of 34 associate degree nursing students enrolled in the Advanced Adult Health nursing class at North Georgia College. Most of the students are married, have children and work part time. A self-reporting questionnaire suggests a reduction of the students' anxiety during the quarter. The attitudinal questionnaire reveals an atmosphere of collaboration among peers. Data evaluating learning and retention of material were analyzed using the parametric (T-test) and nonparametric (Wiley Rank Sum test) methods. Examination of the Null Hypotheses I and II suggests there were increased learning and retention of material as evidenced by higher grades on the comprehensive final examination than on the quizzes given after presentation of content. Principles of andragogy as defined by Knowles (1980) and cooperation with peers as described by Johnson, Johnson, Holabec, and Roy (1984), Johnson, Johnson, and Maruyama (1983), and Johnson and Johnson (1975) form the theoretical foundation. PMID:2828575

  11. Pathogenic VCP Mutations Induce Mitochondrial Uncoupling and Reduced ATP Levels

    PubMed Central

    Bartolome, Fernando; Wu, Hsiu-Chuan; Burchell, Victoria S.; Preza, Elisavet; Wray, Selina; Mahoney, Colin J.; Fox, Nick C.; Calvo, Andrea; Canosa, Antonio; Moglia, Cristina; Mandrioli, Jessica; Chiò, Adriano; Orrell, Richard W.; Houlden, Henry; Hardy, John; Abramov, Andrey Y.; Plun-Favreau, Helene

    2013-01-01

    Summary Valosin-containing protein (VCP) is a highly expressed member of the type II AAA+ ATPase family. VCP mutations are the cause of inclusion body myopathy, Paget’s disease of the bone, and frontotemporal dementia (IBMPFD) and they account for 1%–2% of familial amyotrophic lateral sclerosis (ALS). Using fibroblasts from patients carrying three independent pathogenic mutations in the VCP gene, we show that VCP deficiency causes profound mitochondrial uncoupling leading to decreased mitochondrial membrane potential and increased mitochondrial oxygen consumption. This mitochondrial uncoupling results in a significant reduction of cellular ATP production. Decreased ATP levels in VCP-deficient cells lower their energy capacity, making them more vulnerable to high energy-demanding processes such as ischemia. Our findings propose a mechanism by which pathogenic VCP mutations lead to cell death. PMID:23498975

  12. Argonaute Proteins Affect siRNA Levels and Accumulation of a Novel Extrachromosomal DNA from the Dictyostelium Retrotransposon DIRS-1*

    PubMed Central

    Boesler, Benjamin; Meier, Doreen; Förstner, Konrad U.; Friedrich, Michael; Hammann, Christian; Sharma, Cynthia M.; Nellen, Wolfgang

    2014-01-01

    The retrotransposon DIRS-1 is the most abundant retroelement in Dictyostelium discoideum and constitutes the pericentromeric heterochromatin of the six chromosomes in D. discoideum. The vast majority of cellular siRNAs is derived from DIRS-1, suggesting that the element is controlled by RNAi-related mechanisms. We investigated the role of two of the five Argonaute proteins of D. discoideum, AgnA and AgnB, in DIRS-1 silencing. Deletion of agnA resulted in the accumulation of DIRS-1 transcripts, the expression of DIRS-1-encoded proteins, and the loss of most DIRS-1-derived secondary siRNAs. Simultaneously, extrachromosomal single-stranded DIRS-1 DNA accumulated in the cytoplasm of agnA− strains. These DNA molecules appear to be products of reverse transcription and thus could represent intermediate structures before transposition. We further show that transitivity of endogenous siRNAs is impaired in agnA− strains. The deletion of agnB alone had no strong effect on DIRS-1 transposon regulation. However, in agnA−/agnB− double mutant strains strongly reduced accumulation of extrachromosomal DNA compared with the single agnA− strains was observed. PMID:25352599

  13. Glycine propionyl-L-carnitine produces enhanced anaerobic work capacity with reduced lactate accumulation in resistance trained males

    PubMed Central

    Jacobs, Patrick L; Goldstein, Erica R; Blackburn, Will; Orem, Ihsan; Hughes, John J

    2009-01-01

    Background Recent research has indicated that short term administration of glycine propionyl-L-carnitine (GPLC) significantly elevates levels of nitric oxide metabolites at rest and in response to reactive hyperaemia. However, no scientific evidence exists that suggests such supplementation enhances exercise performance in healthy, trained individuals. The purpose of this study was to examine the effects of GPLC on the performance of repeated high intensity stationary cycle sprints with limited recovery periods in resistance trained male subjects. Methods In a double-blind, placebo-controlled, cross-over design, twenty-four male resistance trained subjects (25.2 ± 3.6 years) participated in two test sessions separated by one week. Testing was performed 90 minutes following oral ingestion of either 4.5 grams GPLC or 4.5 grams cellulose (PL), in randomized order. The exercise testing protocol consisted of five 10-second Wingate cycle sprints separated by 1-minute active recovery periods. Peak (PP) and mean values (MP) of sprint power output and percent decrement of power (DEC) were determined per bout and standardized relative to body masss. Heart rate (HR) and blood lactate (LAC) were measured prior to, during and following the five sprint bouts. Results Significant main effects (p < 0.001) were observed for sprint bout order in values of PP, MP, DEC, and HR. There were significant main effects detected for condition in PP and MP (p < 0.05), with values across the five sprint bouts 2.6 – 15% greater with GPLC. Significant statistical interactions were detected between bout order and condition for both PP and MP (p < 0.05). There was a significant main effect of condition for LAC, LAC values 15.7% lower 4 min post-exercise with GPLC (p = 0.09) and with GPLC resulting in 16.2% less LAC at 14 min post-exercise (p < 0.05). Conclusion These findings indicate that short-term oral supplementation of GPLC can enhance peak power production in resistance trained males with

  14. Rising Level of Public Exposure to Mobile Phones: Accumulation through Additivity and Reflectivity

    NASA Astrophysics Data System (ADS)

    Hondou, Tsuyoshi

    2002-02-01

    A dramatic development occurring in our daily life is the increasing use of mobile equipment including mobile phones and wireless access to the Internet. They enable us to access several types of information more easily than in the past. Simultaneously, the density of mobile users is rapidly increasing. When hundreds of mobile phones emit radiation, their total power is found to be comparable to that of a microwave oven or a satellite broadcasting station. Thus, the question arises: what is the public exposure level in an area with many sources of electromagnetic wave emission? We show that this level can reach the reference level for general public exposure (ICNIRP Guideline) in daily life. This is caused by the fundamental properties of electromagnetic field, namely, reflection and additivity. The level of exposure is found to be much higher than that estimated by the conventional framework of analysis that assumes that the level rapidly decreases with the inverse square distance between the source and the affected person. A simple formula for the exposure level is derived by applying energetics to the electromagnetic field. The formula reveals a potential risk of intensive exposure.

  15. A 12-week aerobic exercise program reduces hepatic fat accumulation and insulin resistance in obese, Hispanic adolescents.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The rise in obesity-related morbidity in children and adolescents requires urgent prevention and treatment strategies. Currently, only limited data are available on the effects of exercise programs on insulin resistance, and visceral, hepatic, and intramyocellular fat accumulation. We hypothesized t...

  16. Trehalose accumulation induced during the oxidative stress response is independent of TPS1 mRNA levels in Candida albicans.

    PubMed

    Zaragoza, Oscar; González-Párraga, Pilar; Pedreño, Yolanda; Alvarez-Peral, Francisco J; Argüelles, Juan-Carlos

    2003-06-01

    Growing cells of the Candida albicans trehalose-deficient mutant tps1/tps1 were extremely sensitive to severe oxidative stress exposure (H2O2). However, their viability was not affected after saline stress or heat-shock treatments, being roughly equivalent to that of the parental strain. In wild-type cells, these adverse conditions induced the intracellular accumulation of trehalose together with activation of trehalose-6P synthase, whereas the endogenous trehalose content and the corresponding biosynthetic activity were barely detectable in the tps1/tps1 mutant. The addition of cycloheximide did not prevent the marked induction of trehalose-6P synthase activity. Furthermore, the presence of H2O2 decreased the level of TPS1 mRNA expression. Hence, the conspicuous trehalose accumulation in response to oxidative stress is not induced by increased transcription of TPS1. Our results are consistent with a specific requirement of trehalose in order to withstand a severe oxidative stress in C. albicans, and suggest that trehalose accumulation observed under these conditions is a complex process that most probably involves post-translational modifications of the trehalose synthase complex. PMID:12783274

  17. Regulatory control of high levels of carotenoid accumulation in potato tubers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potato (Solanum tuberosum L.) tubers contain a wide range of carotenoid content. To decipher the key factors controlling carotenoid levels in tubers, four potato lines (Atlantic, Désirée, 91E22, and POR03) were examined by a combination of biochemical, molecular, and genomics approaches. These lines...

  18. An examination of the southern California field test for the systematic accumulation of the optical refraction error in geodetic leveling.

    USGS Publications Warehouse

    Castle, R.O.; Brown, B.W., Jr.; Gilmore, T.D.; Mark, R.K.; Wilson, R.C.

    1983-01-01

    Appraisals of the two levelings that formed the southern California field test for the accumulation of the atmospheric refraction error indicate that random error and systematic error unrelated to refraction competed with the systematic refraction error and severely complicate any analysis of the test results. If the fewer than one-third of the sections that met less than second-order, class I standards are dropped, the divergence virtually disappears between the presumably more refraction contaminated long-sight-length survey and the less contaminated short-sight-length survey. -Authors

  19. Contemporary deposition and long-term accumulation of sediment and nutrients by tidal freshwater forested wetlands impacted by sea level rise

    USGS Publications Warehouse

    Noe, Gregory; Hupp, Cliff R.; Bernhardt, Christopher E.; Krauss, Ken W.

    2016-01-01

    Contemporary deposition (artificial marker horizon, 3.5 years) and long-term accumulation rates (210Pb profiles, ~150 years) of sediment and associated carbon (C), nitrogen (N), and phosphorus (P) were measured in wetlands along the tidal Savannah and Waccamaw rivers in the southeastern USA. Four sites along each river spanned an upstream-to-downstream salinification gradient, from upriver tidal freshwater forested wetland (TFFW), through moderately and highly salt-impacted forested wetlands, to oligohaline marsh downriver. Contemporary deposition rates (sediment, C, N, and P) were greatest in oligohaline marsh and lowest in TFFW along both rivers. Greater rates of deposition in oligohaline and salt-stressed forested wetlands were associated with a shift to greater clay and metal content that is likely associated with a change from low availability of watershed-derived sediment to TFFW and to greater availability of a coastal sediment source to oligohaline wetlands. Long-term accumulation rates along the Waccamaw River had the opposite spatial pattern compared to contemporary deposition, with greater rates in TFFW that declined to oligohaline marsh. Long-term sediment and elemental mass accumulation rates also were 3–9× lower than contemporary deposition rates. In comparison to other studies, sediment and associated nutrient accumulation in TFFW are lower than downriver/estuarine freshwater, oligohaline, and salt marshes, suggesting a reduced capacity for surface sedimentation (short-term) as well as shallow soil processes (long-term sedimentation) to offset sea level rise in TFFW. Nonetheless, their potentially large spatial extent suggests that TFFW have a large impact on the transport and fate of sediment and nutrients in tidal rivers and estuaries.

  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. Methylene blue reduceslevels and rescues early cognitive deficit by increasing proteasome activity

    PubMed Central

    Medina, David X.; Caccamo, Antonella; Oddo, Salvatore

    2010-01-01

    Promising results have emerged from a phase II clinical trial testing Methylene blue (MB) as a potential therapeutic for Alzheimer disease (AD), where improvements in cognitive functions of AD patients after 6 months of MB administration have been reported. Despite these reports, no preclinical testing of MB in mammals has been published, and thus its mechanism of action in relation to AD pathology remains unknown. In order to elucidate the effects of MB on AD pathology and to determine its mechanism of action, we used a mouse model (3xTg-AD) that develops age-dependent accumulation of Aβ and tau and cognitive decline. Here, we report that chronic dietary MB treatment reduceslevels and improves learning and memory deficits in the 3xTg-AD mice. The mechanisms underlying the effects of MB on Aβ pathology appears to be mediated by an increase in Aβ clearance as we show that MB increases the chymotrypsin-and trypsin-like activities of the proteasome in the brain. To our knowledge, this is the first report showing that MB increases proteasome function and ameliorates AD-like pathology in vivo. Overall, the data presented here support the use of MB for the treatment of AD and offer a possible mechanism of action. PMID:20731659

  2. Red mud (RM)-Induced enhancement of iron plaque formation reduces arsenic and metal accumulation in two wetland plant species.

    PubMed

    Yang, J X; Guo, Q J; Yang, J; Zhou, X Y; Ren, H Y; Zhang, H Z; Xu, R X; Wang, X D; Peters, M; Zhu, G X; Wei, R F; Tian, L Y; Han, X K

    2016-01-01

    Human activities have resulted in arsenic (As) and heavy metals accumulation in paddy soils in China. Phytoremediation has been suggested as an effective and low-cost method to clean up contaminated soils. A combined soil-sand pot experiment was conducted to investigate the influence of red mud (RM) supply on iron plaque formation and As and heavy metal accumulation in two wetland plant species (Cyperus alternifolius Rottb., Echinodorus amazonicus Rataj), using As and heavy metals polluted paddy soil combined with three rates of RM application (0, 2%, 5%). The results showed that RM supply significantly decreased As and heavy metals accumulation in shoots of the two plants due to the decrease of As and heavy metal availability and the enhancement of the formation of iron plaque on the root surface and in the rhizosphere. Both wetland plants supplied with RM tended to have more Fe plaque, higher As and heavy metals on roots and in their rhizospheres, and were more tolerant of As and heavy metal toxicity. The results suggest that RM-induced enhancement of the formation of iron plaque on the root surface and in the rhizosphere of wetland plants may be significant for remediation of soils contaminated with As and heavy metals. PMID:26505322

  3. Elevated Plasma Level of Interferon-λ1 in Chronic Spontaneous Urticaria: Upregulated Expression in CD8+ and Epithelial Cells and Induction of Inflammatory Cell Accumulation

    PubMed Central

    Wang, S. F.; Gao, X. Q.; Xu, Y. N.; Li, D. N.; Wang, H. Y.

    2016-01-01

    Interferon- (IFN-) λ1 is regarded as a potent bio-active molecule in innate immunity. However, little is known about its role in chronic spontaneous urticaria (CSU). We therefore investigated expression of IFN-λ1 in CSU, its cellular location, and its influence on inflammatory cell accumulation by using flow cytometry analysis, skin tissue dispersion, immunohistochemical stain, and a mouse peritoneal inflammation model. The results showed that level of IFN-λ1 was 2.0-fold higher in plasma of the patients with CSU than the level in healthy control (HC) subjects. Among leukocytes examined, only CD8+ T cells expressed more IFN-λ1 in CSU blood. Double labeling immunohistochemical staining revealed that IFN-λ1+ inflammatory cells such as mast cells, eosinophils, B cells, neutrophils, and macrophages were mainly located in dermis, whereas epidermis tissue highly expressed IFN-λ1. IFN-λ1 induced a dose-dependent increase in number of eosinophils, lymphocytes, mast cells, macrophages, and neutrophils in the peritoneum of mice at 6 h following injection, which was inhibited by pretreatment of the animals with anti-intercellular adhesion molecule- (ICAM-) 1 and/or anti-L-selectin antibodies. In conclusion, IFN-λ1 is likely to play a role in the pathogenesis of CSU. Blocking IFN-λ1 production may help to reduce the accumulation of inflammatory cells in the involved CSU skin. PMID:27445435

  4. Voluntary running in young adult mice reduces anxiety-like behavior and increases the accumulation of bioactive lipids in the cerebral cortex.

    PubMed

    Santos-Soto, Iván J; Chorna, Nataliya; Carballeira, Néstor M; Vélez-Bartolomei, José G; Méndez-Merced, Ana T; Chornyy, Anatoliy P; Peña de Ortiz, Sandra

    2013-01-01

    Combinatorial therapies using voluntary exercise and diet supplementation with polyunsaturated fatty acids have synergistic effects benefiting brain function and behavior. Here, we assessed the effects of voluntary exercise on anxiety-like behavior and on total FA accumulation within three brain regions: cortex, hippocampus, and cerebellum of running versus sedentary young adult male C57/BL6J mice. The running group was subjected to one month of voluntary exercise in their home cages, while the sedentary group was kept in their home cages without access to a running wheel. Elevated plus maze (EPM), several behavioral postures and two risk assessment behaviors (RABs) were then measured in both animal groups followed immediately by blood samplings for assessment of corticosterone levels. Brains were then dissected for non-targeted lipidomic analysis of selected brain regions using gas chromatography coupled to mass spectrometry (GC/MS). Results showed that mice in the running group, when examined in the EPM, displayed significantly lower anxiety-like behavior, higher exploratory and risky behaviors, compared to sedentary mice. Notably, we found no differences in blood corticosterone levels between the two groups, suggesting that the different EPM and RAB behaviors were not related to reduced physiological stress in the running mice. Lipidomics analysis revealed a region-specific cortical decrease of the saturated FA: palmitate (C16:0) and a concomitant increase of polyunsaturated FA, arachidonic acid (AA, omega 6-C20: 4) and docosahexaenoic acid (DHA, omega 3-C22: 6), in running mice compared to sedentary controls. Finally, we found that running mice, as opposed to sedentary animals, showed significantly enhanced cortical expression of phospholipase A2 (PLA2) protein, a signaling molecule required in the production of both AA and DHA. In summary, our data support the anxiolytic effects of exercise and provide insights into the molecular processes modulated by

  5. Low Level Chlorpyrifos Exposure Increases Anandamide Accumulation in Juvenile Rat Brain in the Absence of Brain Cholinesterase Inhibition

    PubMed Central

    Carr, Russell L.; Graves, Casey A.; Mangum, Lee C.; Nail, Carole A.; Ross, Matthew K.

    2014-01-01

    The prevailing dogma is that chlorpyrifos (CPF) mediates its toxicity through inhibition of cholinesterase (ChE). However, in recent years, the toxicological effects of developmental CPF exposure have been attributed to an unknown non-cholinergic mechanism of action. We hypothesize that the endocannabinoid system may be an important target because of its vital role in nervous system development. We have previously reported that repeated exposure to CPF results in greater inhibition of fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide (AEA), than inhibition of either forebrain ChE or monoacylglycerol lipase (MAGL), the enzyme that metabolizes the endocannabinoid 2-arachidonylglycerol (2-AG). This exposure resulted in the accumulation of 2-AG and AEA in the forebrain of juvenile rats; however, even at the lowest dosage level used (1.0 mg/kg), forebrain ChE inhibition was still present. Thus, it is not clear if FAAH activity would be inhibited at dosage levels that do not inhibit ChE. To determine this, 10 day old rat pups were exposed daily for 7 days to either corn oil or 0.5 mg/kg CPF by oral gavage. At 4 and 12 h post-exposure on the last day of administration, the activities of serum ChE and carboxylesterase (CES) and forebrain ChE, MAGL, and FAAH were determined as well as the forebrain AEA and 2-AG levels. Significant inhibition of serum ChE and CES was present at both 4 and 12 h. There was no significant inhibition of the activities of forebrain ChE or MAGL and no significant change in the amount of 2-AG at either time point. On the other hand, while no statistically significant effects were observed at 4 h, FAAH activity was significantly inhibited at 12 h resulting in a significant accumulation of AEA. Although it is not clear if this level of accumulation impacts brain maturation, this study demonstrates that developmental CPF exposure at a level that does not inhibit brain ChE can alter components of

  6. Redirection of metabolic flux for high levels of omega-7 monounsaturated fatty acid accumulation in camelina seeds.

    PubMed

    Nguyen, Huu Tam; Park, Hyunwoo; Koster, Karen L; Cahoon, Rebecca E; Nguyen, Hanh T M; Shanklin, John; Clemente, Thomas E; Cahoon, Edgar B

    2015-01-01

    Seed oils enriched in omega-7 monounsaturated fatty acids, including palmitoleic acid (16:1∆9) and cis-vaccenic acid (18:1∆11), have nutraceutical and industrial value for polyethylene production and biofuels. Existing oilseed crops accumulate only small amounts (<2%) of these novel fatty acids in their seed oils. We demonstrate a strategy for enhanced production of omega-7 monounsaturated fatty acids in camelina (Camelina sativa) and soybean (Glycine max) that is dependent on redirection of metabolic flux from the typical ∆9 desaturation of stearoyl (18:0)-acyl carrier protein (ACP) to ∆9 desaturation of palmitoyl (16:0)-acyl carrier protein (ACP) and coenzyme A (CoA). This was achieved by seed-specific co-expression of a mutant ∆9-acyl-ACP and an acyl-CoA desaturase with high specificity for 16:0-ACP and CoA substrates, respectively. This strategy was most effective in camelina where seed oils with ~17% omega-7 monounsaturated fatty acids were obtained. Further increases in omega-7 fatty acid accumulation to 60-65% of the total fatty acids in camelina seeds were achieved by inclusion of seed-specific suppression of 3-keto-acyl-ACP synthase II and the FatB 16:0-ACP thioesterase genes to increase substrate pool sizes of 16:0-ACP for the ∆9-acyl-ACP desaturase and by blocking C18 fatty acid elongation. Seeds from these lines also had total saturated fatty acids reduced to ~5% of the seed oil versus ~12% in seeds of nontransformed plants. Consistent with accumulation of triacylglycerol species with shorter fatty acid chain lengths and increased monounsaturation, seed oils from engineered lines had marked shifts in thermotropic properties that may be of value for biofuel applications. PMID:25065607

  7. Higher transcription levels in ascorbic acid biosynthetic and recycling genes were associated with higher ascorbic acid accumulation in blueberry.

    PubMed

    Liu, Fenghong; Wang, Lei; Gu, Liang; Zhao, Wei; Su, Hongyan; Cheng, Xianhao

    2015-12-01

    In our preliminary study, the ripe fruits of two highbush blueberry (Vaccinium corymbosum L.) cultivars, cv 'Berkeley' and cv 'Bluecrop', were found to contain different levels of ascorbic acid. However, factors responsible for these differences are still unknown. In the present study, ascorbic acid content in fruits was compared with expression profiles of ascorbic acid biosynthetic and recycling genes between 'Bluecrop' and 'Berkeley' cultivars. The results indicated that the l-galactose pathway was the predominant route of ascorbic acid biosynthesis in blueberry fruits. Moreover, higher expression levels of the ascorbic acid biosynthetic genes GME, GGP, and GLDH, as well as the recycling genes MDHAR and DHAR, were associated with higher ascorbic acid content in 'Bluecrop' compared with 'Berkeley', which indicated that a higher efficiency ascorbic acid biosynthesis and regeneration was likely to be responsible for the higher ascorbic acid accumulation in 'Bluecrop'. PMID:26041210

  8. Protective effect of panax notoginseng saponins on acute ethanol-induced liver injury is associated with ameliorating hepatic lipid accumulation and reducing ethanol-mediated oxidative stress.

    PubMed

    Ding, Ren-Bo; Tian, Ke; Cao, Yi-Wei; Bao, Jiao-Lin; Wang, Meng; He, Chengwei; Hu, Yuanjia; Su, Huanxing; Wan, Jian-Bo

    2015-03-11

    The aim of present study was to evaluate the effects of Panax notoginseng saponins (PNS) against acute ethanol-induced liver injury and further to elucidate its probable mechanisms. Mice were treated with PNS (100 or 300 mg/kg) once daily for seven consecutive days priors to ethanol gavage (4.7 g/kg) every 12 h for a total of three doses. Acute alcohol gavage dramatically significantly increased serum activities of alanine aminotransferase (ALT) (23.4 ± 5.0 IU/L vs 11.7 ± 4.1 IU/L) and aspartate aminotransferase (AST) (52.6 ± 14.9 IU/L vs 31.1 ± 12.9 IU/L), and hepatic triglyceride level (4.04 ± 0.64 mg/g vs 1.92 ± 0.34 mg/g), these elevations were significantly diminished by pretreatment with PNS at dose of 100 mg/kg or 300 mg/kg. Alcohol exposure markedly induced the lipolysis of white adipose tissue (WAT), up-regulated protein expression of the phosphorylated hormone-sensitive lipase (p-HSL, p < 0.01), and total HSL (p < 0.01), and enhanced fatty acid uptake capacity in liver as indicated by increasing hepatic CD36 expression (p < 0.01), these effects were attenuated by PNS treatment. Additionally, PNS suppressed the elevation of reactive oxygen species (ROS) production and malondialdehyde (MDA) content, reduced TNF-α and IL-6 levels, restored glutathione (GSH) level, enhanced the superoxide dismutase (SOD) activity in liver, and abrogated cytochrome P450 2E1 (CYP2E1) induction. These data demonstrated that pretreatment with PNS protected against acute ethanol-induced liver injury, possibly through ameliorating hepatic lipid accumulation and reducing CYP2E1-mediated oxidative stress. Our findings also suggested that PNS may be potential to be developed as an effective agent for acute ethanol-induced liver injury. PMID:25665731

  9. Enhanced levels of nicotianamine promote iron accumulation and tolerance to calcareous soil in soybean.

    PubMed

    Nozoye, Tomoko; Kim, Suyoen; Kakei, Yusuke; Takahashi, Michiko; Nakanishi, Hiromi; Nishizawa, Naoko K

    2014-01-01

    Iron (Fe) is an essential nutrient in both plants and humans. Fe deficiency on calcareous soil with low Fe availability is a major agricultural problem. Nicotianamine (NA) is one of the Fe chelator in plants, which is involved in metal translocation into seeds, and serves as an antihypertensive substance in humans. In this study, soybean plants overexpressing the barley NA synthase 1 (HvNAS1) gene driven by the constitutive CaMV 35S promoter were produced using Agrobacterium-mediated transformation. The transgenic soybean showed no growth defect and grew normally. The NA content of transgenic soybean seeds was up to four-fold greater than that of non-transgenic (NT) soybean seeds. The level of HvNAS1 expression was positively correlated with the amount of NA, and a high concentration of NA was maintained in the seeds in succeeding generations. The Fe concentration was approximately two-fold greater in transgenic soybean seeds than in NT soybean seeds. Furthermore, the transgenic soybeans showed tolerance to low Fe availability in calcareous soil. Our results suggested that increasing the NA content in soybean seeds by the overexpression of HvNAS1 offers potential benefits for both human health and agricultural productivity. PMID:25047240

  10. Pallidal Index as Biomarker of Manganese Brain Accumulation and Associated with Manganese Levels in Blood: A Meta-Analysis

    PubMed Central

    Huang, Shuang; Huang, Yan-Ni; Li, Xiang-Rong; Chen, Jing-Wen; Li, Yong; Luo, Hai-Lan; Wang, Fang; Ou, Shi-Yan; Jiang, Yue-Ming

    2014-01-01

    Objective The current study was designed to evaluate the sensitivity, feasibility, and effectiveness of the pallidal index (PI) serving as a biomarker of brain manganese (Mn) accumulation, which would be used as an early diagnosis criteria for Mn neurotoxicity. Methods The weighted mean difference (WMD) of the PI between control and Mn-exposed groups was estimated by using a random-effects or fixed-effects meta-analysis with 95% confidence interval (CI) performed by STATA software version 12.1. Moreover, the R package “metacor” was used to estimate correlation coefficients between PI and blood Mn (MnB). Results A total of eight studies with 281 occupationally Mn-exposed workers met the inclusion criteria. Results were pooled and performed with the Meta-analysis. Our data indicated that the PI of the exposed group was significantly higher than that of the control (WMD: 7.76; 95% CI: 4.86, 10.65; I2 = 85.7%, p<0.0001). A random effects model was used to perform meta-analysis. These findings were remarkably robust in the sensitivity analysis, and publication bias was shown in the included studies. Seven out of the eight studies reported the Pearson correlation (r) values. Significantly positive correlation between PI and MnB was observed (r = 0.42; 95% CI, 0.31, 0.52). Conclusions PI can be considered as a sensitive, feasible, effective and semi-quantitative index in evaluating brain Mn accumulation. MnB can also augment the evaluation of brain Mn accumulation levels in the near future. However, the results should be interpreted with caution. PMID:24718592

  11. Macrophage depletion reduces cell proliferation and extracellular matrix accumulation but increases the ultimate tensile strength of injured Achilles tendons.

    PubMed

    de la Durantaye, Mélissa; Piette, Antoine Boulanger; van Rooijen, Nico; Frenette, Jérôme

    2014-02-01

    Macrophages are present in large numbers and display specific and distinct phenotypes during the various phases of tissue repair. However, their role following tendon injury and during repair has never been investigated. We injected C57BL/6 mice daily for 4 days with liposome-encapsulated clodronate to deplete circulating monocytes/macrophages. Placebo mice were injected with PBS. The left Achilles tendons of the mice were transversely sectioned and sutured using the 8-strand technique. Macrophage accumulation and cell proliferation were significantly lower in the tendons of clodronate-treated mice than in those of PBS-treated mice on days 3 and 7 post-injury. TGF-β1 staining was significantly more intense in the tendons of PBS-treated mice on day 7 post-injury. Edema and the dry mass of the Achilles tendons were also higher in the PBS-treated mice on days 7 and 14 post-injury. No differences in absolute strength and stiffness were observed, but Young's modulus and maximal stress were significantly greater for tendons from the clodronate-treated mice than those from PBS-treated mice after 14 days of tendon repair. Overall, our findings showed that macrophages promote cell proliferation and extracellular matrix accumulation but their presence leads to inferior ultimate tensile strength of the Achilles tendons. PMID:24307236

  12. Dietary supplementation with phytosterol and ascorbic acid reduces body mass accumulation and alters food transit time in a diet-induced obesity mouse model

    PubMed Central

    2011-01-01

    Previous research indicates that animals fed a high fat (HF) diet supplemented with disodium ascorbyl phytostanyl phosphate (DAPP) exhibit reduced mass accumulation when compared to HF control. This compound is a water-soluble phytostanol ester and consists of a hydrophobic plant stanol covalently bonded to ascorbic acid (Vitamin C). To provide insight into the mechanism of this response, we examined the in vivo effects of a high fat diet supplemented with ascorbic acid (AA) in the presence and absence of unesterified phytosterols (PS), and set out to establish whether the supplements have a synergistic effect in a diet-induced obesity mouse model. Our data indicate that HF diet supplementation with a combination of 1% w/w phytosterol and 1% w/w ascorbic acid results in reduced mass accumulation, with mean differences in absolute mass between PSAA and HF control of 10.05%; and differences in mass accumulation of 21.6% (i.e. the PSAA group gained on average 21% less mass each week from weeks 7-12 than the HF control group). In our previous study, the absolute mass difference between the 2% DAPP and HF control was 41%, while the mean difference in mass accumulation between the two groups for weeks 7-12 was 67.9%. Mass loss was not observed in animals supplemented with PS or AA alone. These data suggest that the supplements are synergistic with respect to mass accumulation, and the esterification of the compounds further potentiates the response. Our data also indicate that chronic administration of PS, both in the presence and absence of AA, results in changes to fecal output and food transit time, providing insight into the possibility of long-term changes in intestinal function related to PS supplementation. PMID:21711516

  13. SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario

    SciTech Connect

    Almeida, Luciana O.; Goto, Renata N.; Neto, Marinaldo P.C.; Sousa, Lucas O.; Curti, Carlos; Leopoldino, Andréia M.

    2015-03-06

    We hypothesized that SET, a protein accumulated in some cancer types and Alzheimer disease, is involved in cell death through mitochondrial mechanisms. We addressed the mRNA and protein levels of the mitochondrial uncoupling proteins UCP1, UCP2 and UCP3 (S and L isoforms) by quantitative real-time PCR and immunofluorescence as well as other mitochondrial involvements, in HEK293 cells overexpressing the SET protein (HEK293/SET), either in the presence or absence of oxidative stress induced by the pro-oxidant t-butyl hydroperoxide (t-BHP). SET overexpression in HEK293 cells decreased UCP1 and increased UCP2 and UCP3 (S/L) mRNA and protein levels, whilst also preventing lipid peroxidation and decreasing the content of cellular ATP. SET overexpression also (i) decreased the area of mitochondria and increased the number of organelles and lysosomes, (ii) increased mitochondrial fission, as demonstrated by increased FIS1 mRNA and FIS-1 protein levels, an apparent accumulation of DRP-1 protein, and an increase in the VDAC protein level, and (iii) reduced autophagic flux, as demonstrated by a decrease in LC3B lipidation (LC3B-II) in the presence of chloroquine. Therefore, SET overexpression in HEK293 cells promotes mitochondrial fission and reduces autophagic flux in apparent association with up-regulation of UCP2 and UCP3; this implies a potential involvement in cellular processes that are deregulated such as in Alzheimer's disease and cancer. - Highlights: • SET, UCPs and autophagy prevention are correlated. • SET action has mitochondrial involvement. • UCP2/3 may reduce ROS and prevent autophagy. • SET protects cell from ROS via UCP2/3.

  14. Targeting of the polyhydroxybutyrate biosynthetic pathway to the plastids of Arabidopsis thaliana results in high levels of polymer accumulation

    SciTech Connect

    Nawrath, C.; Poirier, Y.; Somerville, C. )

    1994-12-20

    In the bacterium Alcaligenes eutrophus, three genes encode the enzymes necessary to catalyze the synthesis of poly[(R)-(-)-3-hydroxybutyrate] (PHB) from acetyl-CoA. In order to target these enzymes into the plastids of higher plants, the genes were modified by addition of DNA fragments encoding a pea chloroplast transit peptide, a constitutive plant promoter, and a poly(A) addition sequence. Each of the modified bacterial genes was introduced into Arabidopsis thaliana by Agrobacterium-mediated transformation, and plants containing all three genes were obtained by sexual crosses. These plans accumulated PHB up to 14% of the dry weight as 0.2- to 0.7-[mu]m granules within plastids. In contrast to earlier experiments in which expression of the PHB biosynthetic pathway in the cytoplasm led to a deleterious effect on growth, expression of the PHB biosynthetic pathway in plastids had no obvious effect on the growth or fertility of the transgenic plants and resulted in a 100-fold increase in the amount of PHB in higher plants. The high level of PHB accumulation also suggests that the synthesis of plastid acetyl-CoA is regulated by a mechanism which responds to metabolic demand. 20 refs., 6 figs.

  15. Silencing of WIPK and SIPK mitogen-activated protein kinases reduces tobacco mosaic virus accumulation but permits systemic viral movement in tobacco possessing the N resistance gene.

    PubMed

    Kobayashi, Michie; Seo, Shigemi; Hirai, Katsuyuki; Yamamoto-Katou, Ayako; Katou, Shinpei; Seto, Hideharu; Meshi, Tetsuo; Mitsuhara, Ichiro; Ohashi, Yuko

    2010-08-01

    Infection of tobacco cultivars possessing the N resistance gene with Tobacco mosaic virus (TMV) results in confinement of the virus by necrotic lesions at the infection site. Although the mitogen-activated protein kinases WIPK and SIPK have been implicated in TMV resistance, evidence linking them directly to disease resistance is, as yet, insufficient. Viral multiplication was reduced slightly in WIPK- or SIPK-silenced plants but substantially in WIPK/SIPK-silenced plants, and was correlated with an increase in salicylic acid (SA) and a decrease in jasmonic acid (JA). Silencing of WIPK and SIPK in a tobacco cultivar lacking the N gene did not inhibit viral accumulation. The reduction in viral accumulation was attenuated by expressing a gene for an SA-degrading enzyme or by exogenously applying JA. Inoculation of lower leaves resulted in the systemic spread of TMV and formation of necrotic lesions in uninoculated upper leaves. These results suggested that WIPK and SIPK function to negatively regulate local resistance to TMV accumulation, partially through modulating accumulation of SA and JA in an N-dependent manner, but positively regulate systemic resistance. PMID:20615114

  16. Moderate hypothermia induces marked increase in levels and nuclear accumulation of SUMO2/3-conjugated proteins in neurons

    PubMed Central

    Wang, Liangli; Ma, Qing; Yang, Wei; Mackensen, G. Burkhard; Paschen, Wulf

    2012-01-01

    Deep hypothermia protects the brain from ischemic damage and is therefore used during major cardiovascular surgeries requiring cardiopulmonary bypass and a period of circulatory arrest. Here, we demonstrated that small ubiquitin-like modifier (SUMO1-3) conjugation is markedly activated in the brain during deep to moderate hypothermia. Animals were subjected to normothermic (37°C) or deep to moderate (18°C, 24°C, 30°C) hypothermic cardiopulmonary bypass, and the effects of hypothermia on SUMO conjugation were evaluated by Western blot and immunohistochemistry. Exposure to moderate 30°C hypothermia was sufficient to markedly increased levels and nuclear accumulation of SUMO2/3-conjugated proteins in these cells. Deep hypothermia induced nuclear translocation of the SUMO conjugating enzyme Ubc9, suggesting that the increase in nuclear levels of SUMO2/3-conjugated proteins observed in brains of hypothermic animals is an active process. Exposure of primary neuronal cultures to deep hypothermia induced only a moderate rise in levels of SUMO2/3-conjugated proteins. This suggests that neurons in vivo have a higher capacity than neurons in vitro to activate this endogenous potentially neuroprotective pathway upon exposure to hypothermia. Identifying proteins that are SUMO2/3 conjugated during hypothermia could help to design new strategies for preventive and therapeutic interventions to make neurons more resistant to a transient interruption of blood supply. PMID:22891650

  17. Marine CDOM accumulation during a coastal Arctic mesocosm experiment: No response to elevated pCO2 levels

    NASA Astrophysics Data System (ADS)

    Pavlov, Alexey K.; Silyakova, Anna; Granskog, Mats A.; Bellerby, Richard G. J.; Engel, Anja; Schulz, Kai G.; Brussaard, Corina P. D.

    2014-06-01

    A large-scale multidisciplinary mesocosm experiment in an Arctic fjord (Kongsfjorden, Svalbard; 78°56.2'N) was used to study Arctic marine food webs and biogeochemical elements cycling at natural and elevated future carbon dioxide (CO2) levels. At the start of the experiment, marine-derived chromophoric dissolved organic matter (CDOM) dominated the CDOM pool. Thus, this experiment constituted a convenient case to study production of autochthonous CDOM, which is typically masked by high levels of CDOM of terrestrial origin in the Arctic Ocean proper. CDOM accumulated during the experiment in line with an increase in bacterial abundance; however, no response was observed to increased pCO2 levels. Changes in CDOM absorption spectral slopes indicate that bacteria were most likely responsible for the observed CDOM dynamics. Distinct absorption peaks (at ~ 330 and ~ 360 nm) were likely associated with mycosporine-like amino acids (MAAs). Due to the experimental setup, MAAs were produced in absence of ultraviolet exposure providing evidence for MAAs to be considered as multipurpose metabolites rather than simple photoprotective compounds. We showed that a small increase in CDOM during the experiment made it a major contributor to total absorption in a range of photosynthetically active radiation (PAR, 400-700 nm) and, therefore, is important for spectral light availability and may be important for photosynthesis and phytoplankton groups composition in a rapidly changing Arctic marine ecosystem.

  18. THE BIOCIDE TRIBUTYLTIN REDUCES THE ACCUMULATION OF TESTOSTERONE AS FATTY ACID ESTERS IN THE MUD SNAIL (ILYANASSA OBSOLETA)

    EPA Science Inventory

    Imposex, the development of male sex characteristics by female gonochoristic snails, has been documented globally and is causally associated with exposure to the ubiquitous environmental contaminant tributyltin (TBT). Elevated testosterone levels in snails also are associated wit...

  19. Accumulate repeat accumulate codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative channel coding scheme called 'Accumulate Repeat Accumulate codes' (ARA). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes, thus belief propagation can be used for iterative decoding of ARA codes on a graph. The structure of encoder for this class can be viewed as precoded Repeat Accumulate (RA) code or as precoded Irregular Repeat Accumulate (IRA) code, where simply an accumulator is chosen as a precoder. Thus ARA codes have simple, and very fast encoder structure when they representing LDPC codes. Based on density evolution for LDPC codes through some examples for ARA codes, we show that for maximum variable node degree 5 a minimum bit SNR as low as 0.08 dB from channel capacity for rate 1/2 can be achieved as the block size goes to infinity. Thus based on fixed low maximum variable node degree, its threshold outperforms not only the RA and IRA codes but also the best known LDPC codes with the dame maximum node degree. Furthermore by puncturing the accumulators any desired high rate codes close to code rate 1 can be obtained with thresholds that stay close to the channel capacity thresholds uniformly. Iterative decoding simulation results are provided. The ARA codes also have projected graph or protograph representation that allows for high speed decoder implementation.

  20. An Arabidopsis Mutant Tolerant to Lethal Ultraviolet-B Levels Shows Constitutively Elevated Accumulation of Flavonoids and Other Phenolics1

    PubMed Central

    Bieza, Kim; Lois, Rodrigo

    2001-01-01

    The isolation and characterization of mutants hypersensitive to ultraviolet (UV) radiation has been a powerful tool to learn about the mechanisms that protect plants against UV-induced damage. To increase our understanding of the various mechanisms of defense against UVB radiation, we searched for mutations that would increase the level of tolerance of Arabidopsis plants to UV radiation. We describe a single gene dominant mutation (uvt1) that leads to a remarkable tolerance to UVB radiation conditions that would kill wild-type plants. Pigment analyses show a constitutive increase in accumulation of UV-absorbing compounds in uvt1 that increases the capacity of the leaves to block UVB radiation and therefore is likely to be responsible for the elevated resistance of this mutant to UVB radiation. These increases in absorption in the UV region are due, at least in part, to increases in flavonoid and sinapate accumulation. Expression of chalcone synthase (CHS) mRNA was shown to be constitutively elevated in uvt1 plants, suggesting that the increases in absorption may be a consequence of changes in gene expression. Expression of CHS in uvt1 was shown to be still inducible by UV, indicating that the uvt1 lesion may not affect the UV-mediated regulation of CHS gene expression. Our data support an important role for UV screens in the overall protection of plants to UVB radiation. The uvt1 mutant could prove to be an important tool to elucidate further the exact role of UV-absorbing pigments in UV protection as well as the relative contribution of other mechanisms to the overall tolerance of plants to UV radiation. PMID:11457961

  1. Reduced hnRNPA3 increases C9orf72 repeat RNA levels and dipeptide-repeat protein deposition.

    PubMed

    Mori, Kohji; Nihei, Yoshihiro; Arzberger, Thomas; Zhou, Qihui; Mackenzie, Ian R; Hermann, Andreas; Hanisch, Frank; Kamp, Frits; Nuscher, Brigitte; Orozco, Denise; Edbauer, Dieter; Haass, Christian

    2016-09-01

    Intronic hexanucleotide (G4C2) repeat expansions in C9orf72 are genetically associated with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The repeat RNA accumulates within RNA foci but is also translated into disease characterizing dipeptide repeat proteins (DPR). Repeat-dependent toxicity may affect nuclear import. hnRNPA3 is a heterogeneous nuclear ribonucleoprotein, which specifically binds to the G4C2 repeat RNA We now report that a reduction of nuclear hnRNPA3 leads to an increase of the repeat RNA as well as DPR production and deposition in primary neurons and a novel tissue culture model that reproduces features of the C9orf72 pathology. In fibroblasts derived from patients carrying extended C9orf72 repeats, nuclear RNA foci accumulated upon reduction of hnRNPA3. Neurons in the hippocampus of C9orf72 patients are frequently devoid of hnRNPA3. Reduced nuclear hnRNPA3 in the hippocampus of patients with extended C9orf72 repeats correlates with increased DPR deposition. Thus, reduced hnRNPA3 expression in C9orf72 cases leads to increased levels of the repeat RNA as well as enhanced production and deposition of DPR proteins and RNA foci. PMID:27461252

  2. Accumulate Repeat Accumulate Coded Modulation

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative coded modulation scheme called 'Accumulate Repeat Accumulate Coded Modulation' (ARA coded modulation). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes that are combined with high level modulation. Thus at the decoder belief propagation can be used for iterative decoding of ARA coded modulation on a graph, provided a demapper transforms the received in-phase and quadrature samples to reliability of the bits.

  3. Mature-stem expression of a silencing-resistant sucrose isomerase gene drives isomaltulose accumulation to high levels in sugarcane.

    PubMed

    Mudge, Stephen R; Basnayake, Shiromi W V; Moyle, Richard L; Osabe, Kenji; Graham, Michael W; Morgan, Terence E; Birch, Robert G

    2013-05-01

    Isomaltulose (IM) is a natural isomer of sucrose. It is widely approved as a food with properties including slower digestion, lower glycaemic index and low cariogenicity, which can benefit consumers. Availability is currently limited by the cost of fermentative conversion from sucrose. Transgenic sugarcane plants with developmentally-controlled expression of a silencing-resistant gene encoding a vacuole-targeted IM synthase were tested under field conditions typical of commercial sugarcane cultivation. High yields of IM were obtained, up to 483 mm or 81% of total sugars in whole-cane juice from plants aged 13 months. Using promoters from sugarcane to drive expression preferentially in the sugarcane stem, IM levels were consistent between stalks and stools within a transgenic line and across consecutive vegetative field generations of tested high-isomer lines. Germination and early growth of plants from setts were unaffected by IM accumulation, up to the tested level around 500 mm in flanking stem internodes. These are the highest yields ever achieved of value-added materials through plant metabolic engineering. The sugarcane stem promoters are promising for strategies to achieve even higher IM levels and for other applications in sugarcane molecular improvement. Silencing-resistant transgenes are critical to deliver the potential of these promoters in practical sugarcane improvement. At the IM levels now achieved in field-grown sugarcane, direct production of IM in plants is feasible at a cost approaching that of sucrose, which should make the benefits of IM affordable on a much wider scale. PMID:23297683

  4. Transcript level coordination of carbon pathways during silicon starvation-induced lipid accumulation in the diatom Thalassiosira pseudonana.

    PubMed

    Smith, Sarah R; Glé, Corine; Abbriano, Raffaela M; Traller, Jesse C; Davis, Aubrey; Trentacoste, Emily; Vernet, Maria; Allen, Andrew E; Hildebrand, Mark

    2016-05-01

    Diatoms are one of the most productive and successful photosynthetic taxa on Earth and possess attributes such as rapid growth rates and production of lipids, making them candidate sources of renewable fuels. Despite their significance, few details of the mechanisms used to regulate growth and carbon metabolism are currently known, hindering metabolic engineering approaches to enhance productivity. To characterize the transcript level component of metabolic regulation, genome-wide changes in transcript abundance were documented in the model diatom Thalassiosira pseudonana on a time-course of silicon starvation. Growth, cell cycle progression, chloroplast replication, fatty acid composition, pigmentation, and photosynthetic parameters were characterized alongside lipid accumulation. Extensive coordination of large suites of genes was observed, highlighting the existence of clusters of coregulated genes as a key feature of global gene regulation in T. pseudonana. The identity of key enzymes for carbon metabolic pathway inputs (photosynthesis) and outputs (growth and storage) reveals these clusters are organized to synchronize these processes. Coordinated transcript level responses to silicon starvation are probably driven by signals linked to cell cycle progression and shifts in photophysiology. A mechanistic understanding of how this is accomplished will aid efforts to engineer metabolism for development of algal-derived biofuels. PMID:26844818

  5. Regulation of S-like ribonuclease levels in Arabidopsis. Antisense inhibition of RNS1 or RNS2 elevates anthocyanin accumulation

    SciTech Connect

    Bariola, P.A.; MacIntosh, G.C.; Green, P.J.

    1999-01-01

    The S-like ribonucleases (RNases) RNS1 and RNS2 of Arabidopsis are members of the widespread T{sub 2} ribonuclease family, whose members also include the S-RNases, involved in gametophytic self-incompatibility in plants. Both RNS1 and RNS2 mRNAs have been shown previously to be induced by inorganic phosphate (Pi) starvation. In this study the authors examined this regulation at the protein level and determined the effects of diminishing RNS1 and RNS2 expression using antisense techniques. The Pi-starvation control of RNS1 and RNS2 was confirmed using antibodies specific for each protein. These specific antibodies also demonstrated that RNS1 is secreted, whereas RNS2 is intracellular. By introducing antisense constructs, mRNA accumulation was inhibited by up to 90% for RNS1 and up to 65% for NS2. These plants contained abnormally high levels of anthocyanins, the production of which is often associated with several forms of stress, including Pi starvation. This effect demonstrates that diminishing the amounts of either RNS1 or RNS2 leads to effects that cannot be compensated for by the actions of other RNases, even though Arabidopsis contains a large number of different RNase activities. These results, together with the differential localization of the proteins, imply that RNS1 and RNS2 have distinct functions in the plant.

  6. Basal and adenosine receptor-stimulated levels of cAMP are reduced in lymphocytes from alcoholic patients

    SciTech Connect

    Diamond, I.; Wrubel, B.; Estrin, W.; Gordon, A.

    1987-03-01

    Alcoholism causes serious neurologic disease that may be due, in part, to the ability of ethanol to interact with neural cell membranes and change neuronal function. Adenosine receptors are membrane-bound proteins that appear to mediate some of the effects of ethanol in the brain. Human lymphocytes also have adenosine receptors, and their activation causes increases in cAMP levels. To test the hypothesis that basal and adenosine receptor-stimulated cAMP levels in lymphocytes might be abnormal in alcoholism, the authors studied lymphocytes from 10 alcoholic subjects, 10 age- and sex-matched normal individuals, and 10 patients with nonalcoholic liver disease. Basal and adenosine receptor-stimulated cAMP levels were reduced 75% in lymphocytes from alcoholic subjects. Also, there was a 76% reduction in ethanol stimulation of cAMP accumulation in lymphocytes from alcoholics. Similar results were demonstrable in isolated T cells. Unlike other laboratory tests examined, these measurements appeared to distinguish alcoholics from normal subjects and from patients with nonalcoholic liver disease. Reduced basal and adenosine receptor-stimulated levels of cAMP in lymphocytes from alcoholics may reflect a change in cell membranes due either to chronic alcohol abuse or to a genetic predisposition unique to alcoholic subjects.

  7. Medium-chain fatty acid reduces lipid accumulation by regulating expression of lipid-sensing genes in human liver cells with steatosis.

    PubMed

    Wang, Baogui; Fu, Jing; Li, Lumin; Gong, Deming; Wen, Xuefang; Yu, Ping; Zeng, Zheling

    2016-05-01

    Accumulation of lipids in the liver can lead to cell dysfunction and steatosis, an important factor in pathogenesis causing non-alcoholic fatty liver disease. The mechanisms related to lipid deposition in the liver, however, remain poorly understood. This study was aimed to investigate the effects of medium-chain fatty acid (MCFA) on the lipolysis and expression of lipid-sensing genes in human liver cells with steatosis. A cellular steatosis model, which is suitable to experimentally investigate the impact of fat accumulation in the liver, was established in human normal liver cells (LO2 cells) with a mixture of free fatty acids (oleate/palmitate, 2:1) at 200 μm for 24 h incubation. MCFA was found to down-regulate expression of liver X receptor-α, sterol regulatory element binding protein-1, acetyl-CoA carboxylase, fatty acid synthase, CD 36 and lipoprotein lipase in this cellular model, and have positive effects on adipose triglyceride lipase and hormone-sensitive lipase. These results suggest that MCFA may reduce lipid accumulation by regulating key lipid-sensing genes in human liver cells with steatosis. PMID:26932533

  8. Loss of Reelin protects against atherosclerosis by reducing leukocyte-endothelial cell adhesion and lesion macrophage accumulation.

    PubMed

    Ding, Yinyuan; Huang, Linzhang; Xian, Xunde; Yuhanna, Ivan S; Wasser, Catherine R; Frotscher, Michael; Mineo, Chieko; Shaul, Philip W; Herz, Joachim

    2016-01-01

    The multimodular glycoprotein Reelin controls neuronal migration and synaptic transmission by binding to apolipoprotein E receptor 2 (Apoer2) and very low density lipoprotein receptor (Vldlr) on neurons. In the periphery, Reelin is produced by the liver, circulates in blood, and promotes thrombosis and hemostasis. To investigate if Reelin influences atherogenesis, we studied atherosclerosis-prone low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice in which we inducibly deleted Reelin either ubiquitously or only in the liver, thus preventing the production of circulating Reelin. In both types of Reelin-deficient mice, atherosclerosis progression was markedly attenuated, and macrophage content and endothelial cell staining for vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were reduced at the sites of atherosclerotic lesions. Intravital microscopy revealed decreased leukocyte-endothelial adhesion in the Reelin-deficient mice. In cultured human endothelial cells, Reelin enhanced monocyte adhesion and increased ICAM1, VCAM1, and E-selectin expression by suppressing endothelial nitric oxide synthase (eNOS) activity and increasing nuclear factor κB (NF-κB) activity in an Apoer2-dependent manner. These findings suggest that circulating Reelin promotes atherosclerosis by increasing vascular inflammation, and that reducing or inhibiting circulating Reelin may present a novel approach for the prevention of cardiovascular disease. PMID:26980442

  9. Hepatic oxidative stress and catalyst metals accumulation in goldfish exposed to carbon nanotubes under different pH levels.

    PubMed

    Wang, Xinghao; Qu, Ruijuan; Huang, Qingguo; Wei, Zhongbo; Wang, Zunyao

    2015-03-01

    Experiments were conducted to investigate the effect of three different carbon nanotubes [single-walled carbon nanotubes (SWCNTs), hydroxylated multi-walled carbon nanotubes (OH-MWCNTs), and carboxylated multi-walled carbon nanotubes (COOH-MWCNTs)] on antioxidant parameters and metals accumulation in the liver of Carassius auratus. A semi-static test system was used to expose C. auratus to either a freshwater control, 0.1, or 0.5mg/L CNTs at three pH levels (5.0, 7.25, and 9.0) for 3 and 12 days. The activities of three antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), together with the level of glutathione (GSH) and malondialdehyde (MDA) were determined in liver on the 3rd and 12th day. The results showed that there was a significant increase in MDA concentration and SOD activity in fish exposed to CNTs, indicating that CNTs exposure induces an oxidative stress response in fish. According to integrated biomarker response (IBR) index, the effect of these three CNTs on liver can be ordered as SWCNTs>OH-MWCNTs>COOH-MWCNTs and they are more toxic to fish in an alkaline environment. Moreover, the concentrations of catalyst metals (Co, Ni, and Mo) and bioelements (Cu, Fe, Zn, and Se) in liver were changed, depending on the CNTs concentration, the pH level, and the exposure duration. Generally, all CNTs groups showed that catalyst metals could be concentrated significantly into the liver of fish, and changes in hepatic Cu, Zn, Fe, and Se contents are consistent with the activity of antioxidant enzymes. PMID:25625523

  10. A School-Level Proxy Measure for Individual-level Poverty Using School-Level Eligibility for Free and Reduced-Price Meals

    ERIC Educational Resources Information Center

    Day, Sophia E.; Hinterland, Kinjia; Myers, Christa; Gupta, Leena; Harris, Tiffany G.; Konty, Kevin J.

    2016-01-01

    Background: Socioeconomic status (SES) impacts health outcomes. The Youth Risk Behavior Survey (YRBS), like many school-based data sources, lacks individual-level poverty information. We propose using school-level percentages of student eligibility for free/reduced-price meals (%FRPM) as a proxy for individual-level poverty. Methods: Using the New…

  11. Reduced progesterone levels explain the reduced risk of breast cancer in obese premenopausal women: a new hypothesis.

    PubMed

    Dowsett, Mitch; Folkerd, Elizabeth

    2015-01-01

    Understanding the complex relationship between obesity and breast cancer is fundamental to our knowledge of the etiology of this malignancy; changes in the composition of the hormonal milieu are implicit in this process. Estrogens are synthesized from androgens by aromatase in the gonads and in peripheral tissues, principally, adipose tissue. Obesity in women, regardless of their age, leads to more aromatase and more extra-glandular estrogen production. In postmenopausal women, in whom ovarian estrogen production is absent, the increased incidence of breast cancer in women with high body mass index has been attributed to the relatively high plasma levels of estradiol from subcutaneous fat. In contrast, obesity in premenopausal women is associated with a previously unexplained reduced incidence of breast cancer. In obese premenopausal women, the cumulative effect of higher levels of estrogens synthesized in the peripheral tissues, together with ovarian estrogen production, results in a negative feedback on the hypothalamic pituitary controlled release of gonadotrophins and a resultant diminution in ovarian steroid production. As a consequence, the normal balance of estrogen and progesterone levels is disrupted: while estrogen levels are normalized, progesterone production is markedly decreased. Progesterone is a promoter of proliferation in the breast. The low levels of progesterone in obese premenopausal women are consistent with, and we propose, are responsible for, the reduction in breast cancer incidence in these women. PMID:25414027

  12. High-sucrose diet increases ROS generation, FFA accumulation, UCP2 level, and proton leak in liver mitochondria.

    PubMed

    Ruiz-Ramírez, Angélica; Chávez-Salgado, Monserrath; Peñeda-Flores, José Antonio; Zapata, Estrella; Masso, Felipe; El-Hafidi, Mohammed

    2011-12-01

    Obesity, a risk factor for insulin resistance, contributes to the development of type 2 diabetes and cardiovascular diseases. The relationship between increased levels of free fatty acids in the liver mitochondria, mitochondrial function, and ROS generation in rat model of obesity induced by a high-sucrose diet was not sufficiently established. We determined how the bioenergetic functions and ROS generation of the mitochondria respond to a hyperlipidemic environment. Mitochondria from sucrose-fed rats generated H(2)O(2) at a higher rate than the control mitochondria. Adding fatty acid-free bovine serum albumin to mitochondria from sucrose-fed rats significantly reduced the rate of H(2)O(2) generation. In contrast, adding exogenous oleic or linoleic acid exacerbated the rate of H(2)O(2) generation in both sucrose-fed and control mitochondria, and the mitochondria from sucrose-fed rats were more sensitive than the control mitochondria. The increased rate of H(2)O(2) generation in sucrose-fed mitochondria corresponded to decreased levels of reduced GSH and vitamin E and increased levels of Cu/Zn-SOD in the intermembrane space. There was no difference between the levels of lipid peroxidation and protein carbonylation in the two types of mitochondria. In addition to the normal activity of Mn-SOD, GPX and catalase detected an increased activity of complex II, and upregulation of UCP2 was observed in mitochondria from sucrose-fed rats, all of which may accelerate respiration rates and reduce generation of ROS. In turn, these effects may protect the mitochondria of sucrose-fed rats from oxidative stress and preserve their function and integrity. However, in whole liver these adaptive mechanisms of the mitochondria were inefficient at counteracting redox imbalances and inhibiting oxidative stress outside of the mitochondria. PMID:21917631

  13. The Prolonged Intake of L-Arginine-L-Aspartate Reduces Blood Lactate Accumulation and Oxygen Consumption During Submaximal Exercise

    PubMed Central

    Burtscher, Martin; Brunner, Fritz; Faulhaber, Martin; Hotter, Barbara; Likar, Rudolf

    2005-01-01

    L-arginine-L-aspartate is widely used by athletes for its potentially ergogenic properties. However, only little information on its real efficacy is available from controlled studies. Therefore, we evaluated the effects of prolonged supplementation with L-arginine-L-aspartate on metabolic and cardiorespiratory responses to submaximal exercise in healthy athletes by a double blind placebo-controlled trial. Sixteen healthy male volunteers (22 ± 3 years) performed incremental cycle spiroergometry up to 150 watts before and after intake of L-arginine-L-aspartate (3 grams per day) or placebo for a period of 3 weeks. After intake of L-arginine-L-aspartate, blood lactate at 150 watts dropped from 2.8 ± 0.8 to 2.0 ± 0.9 mmol·l-1 (p < 0.001) and total oxygen consumption during the 3-min period at 150 watts from 6.32 ± 0.51 to 5.95 ± 0.40 l (p = 0.04) compared to placebo (2.7 ± 1.1 to 2.7 ± 1.4 mmol·l-1; p = 0.9 and 6.07 ± 0.51 to 5.91 ± 0.50 l; p = 0.3). Additionally, L-arginine-L-aspartate supplementation effected an increased fat utilisation at 50 watts. L-arginine and L-aspartate seem to have induced synergistic metabolic effects. L-arginine might have reduced lactic acid production by the inhibition of glycolysis and L-aspartate may have favoured fatty acid oxidation. Besides, the results indicate improved work efficiency after L-arginine-L-aspartate intake. The resulting increases of submaximal work capacity and exercise tolerance may have important implications for athletes as well as patients. Key Points Amino acids are among the most common nutritional supplements taken by athletes. They are involved in numerous metabolic pathways that affect exercise metabolism. Three weeks of L-arginine-L-aspartate supplementation resulted in lower blood lactate concentrations and oxygen consumption, diminished glucose and enhanced fat oxidation, and reduced heart rate and ventilation during submaximal cycle exercise. This implies increased submaximal work capacity and

  14. Development of Superoxide Dismutase Mimetic Surfaces to Reduce Accumulation of Reactive Oxygen Species for Neural Interfacing Applications

    PubMed Central

    Potter-Baker, Kelsey A.; Nguyen, Jessica K.; Kovach, Kyle M.; Gitomer, Martin M.; Srail, Tyler W.; Stewart, Wade G.; Skousen, John L.; Capadona, Jeffrey R.

    2014-01-01

    Despite successful initial recording, neuroinflammatory-mediated oxidative stress products can contribute to microelectrode failure by a variety of mechanisms including: inducing microelectrode corrosion, degrading insulating/passivating materials, promoting blood-brain barrier breakdown, and directly damaging surrounding neurons. We have shown that a variety of anti-oxidant treatments can reduce intracortical microelectrode-mediated oxidative stress, and preserve neuronal viability. Unfortunately, short-term soluble delivery of anti-oxidant therapies may be unable to provide sustained therapeutic benefits due to low bio-availability and fast clearance rates. In order to develop a system to provide sustained neuroprotection, we investigated modifying the microelectrode surface with an anti-oxidative coating. For initial proof of concept, we chose the superoxide dismutase (SOD) mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP). Our system utilizes a composite coating of adsorbed and immobilized MnTBAP designed to provide an initial release followed by continued presentation of an immobilized layer of the antioxidant. Surface modification was confirmed by XPS and QCMB-D analysis. Antioxidant activity of composite surfaces was determined using a Riboflavin/NitroBlue Tetrazolium (RF/NBT) assay. Our results indicate that the hybrid modified surfaces provide several days of anti-oxidative activity. Additionally, in vitro studies with BV-2 microglia cells indicated a significant reduction of intracellular and extracellular reactive oxygen species when cultured on composite MnTBAP surfaces. PMID:25132966

  15. α-Tocopherol Supplementation Reduces 5-Nitro-γ-Tocopherol Accumulation By Decreasing γ-Tocopherol In Young Adult Smokers1

    PubMed Central

    Leonard, Scott W; Traber, Maret G; Bruno, Richard S

    2016-01-01

    γ-Tocopherol (γ-T) scavenges reactive nitrogen species (RNS) to form 5-NO2-γ-tocopherol (NGT). However, α-T supplementation decreases circulating γ-T, which could limit its RNS scavenging activities. We hypothesized that α-T supplementation would mitigate NGT accumulation by impairing γ-T status. Healthy smokers (21±1 y, n=11) and non-smokers (21±2 y, n=10) ingested 75 mg/d each of RRR- and all rac-α-tocopheryl acetate for 6 d. Plasma α-T, γ-T, γ-carboxyethyl-hydroxychromanol (CEHC), NGT, and nitrate/nitrite were measured prior to supplementation (Pre), the morning after 6 consecutive evenings of supplementation (Post 1), and on the mornings of d 6 (Post 6) and d 14 (Post 14) during the post-supplementation period. α-T supplementation increased plasma α-T, and decreased γ-T, in both groups and these returned to Pre concentrations on Post 6 regardless of smoking status. Plasma γ-CEHC increased after the first dose of supplementation in both groups, suggesting that α-T supplementation decreased plasma γ-T in part by increasing its metabolism. Plasma NGT and nitrate/nitrite at Pre were greater in smokers, indicating greater nitrative stress due to cigarette smoking. Plasma NGT was lowered only in smokers on Post 1 and Post 6 and was restored to Pre levels on Post 14. Plasma nitrate/nitrite tended (P=0.07) to increase post-supplementation only in smokers, supporting decreases in RNS scavenging by γ-T. Plasma NGT was more strongly correlated (P<0.05) with γ-T in smokers (R=0.83) compared to non-smokers (R=0.50), supporting that α-T-mediated decreases in γ-T reduces NGT formation. These data indicate that α-T supplementation limits γ-T scavenging of RNS in smokers by decreasing γ-T availability. PMID:25966030

  16. Overexpression of hydroxynitrile lyase in cassava roots elevates protein and free amino acids while reducing residual cyanogen levels.

    PubMed

    Narayanan, Narayanan N; Ihemere, Uzoma; Ellery, Claire; Sayre, Richard T

    2011-01-01

    Cassava is the major source of calories for more than 250 million Sub-Saharan Africans, however, it has the lowest protein-to-energy ratio of any major staple food crop in the world. A cassava-based diet provides less than 30% of the minimum daily requirement for protein. Moreover, both leaves and roots contain potentially toxic levels of cyanogenic glucosides. The major cyanogen in cassava is linamarin which is stored in the vacuole. Upon tissue disruption linamarin is deglycosylated by the apolplastic enzyme, linamarase, producing acetone cyanohydrin. Acetone cyanohydrin can spontaneously decompose at pHs >5.0 or temperatures >35°C, or is enzymatically broken down by hydroxynitrile lyase (HNL) to produce acetone and free cyanide which is then volatilized. Unlike leaves, cassava roots have little HNL activity. The lack of HNL activity in roots is associated with the accumulation of potentially toxic levels of acetone cyanohydrin in poorly processed roots. We hypothesized that the over-expression of HNL in cassava roots under the control of a root-specific, patatin promoter would not only accelerate cyanogenesis during food processing, resulting in a safer food product, but lead to increased root protein levels since HNL is sequestered in the cell wall. Transgenic lines expressing a patatin-driven HNL gene construct exhibited a 2-20 fold increase in relative HNL mRNA levels in roots when compared with wild type resulting in a threefold increase in total root protein in 7 month old plants. After food processing, HNL overexpressing lines had substantially reduced acetone cyanohydrin and cyanide levels in roots relative to wild-type roots. Furthermore, steady state linamarin levels in intact tissues were reduced by 80% in transgenic cassava roots. These results suggest that enhanced linamarin metabolism contributed to the elevated root protein levels. PMID:21799761

  17. A one-dimensional biomorphodynamic model of tidal flats: Sediment sorting, marsh distribution, and carbon accumulation under sea level rise

    NASA Astrophysics Data System (ADS)

    Zhou, Zeng; Ye, Qinghua; Coco, Giovanni

    2016-07-01

    We develop a biomorphodynamic model to investigate sediment and vegetation dynamics on a schematic intertidal flat characterized by an initially well-mixed sand-mud mixture. Major interactions between tides, wind waves, salt marshes, sediment transport and sea level rise (SLR) are taken into account. For a bare flat under only tidal action, the model predicts a convex cross-shore profile with the surficial distribution of mud and sand on the upper and lower part of the intertidal flat, respectively. When wind waves are strong, the intertidal flat is highly eroded resulting in a concave profile near the high water mark. This behavior is pronouncedly altered when the intertidal flat is vegetated with the presence of salt marshes. Numerical results suggest that a considerable amount of mud can still remain in the vegetated region even when wave action is strong. A steeper transition zone forms at the boundary between salt marshes and bare flats because of the differential sediment deposition in the two neighboring regions. The inclusion of wind waves is found to considerably enhance the size of the marsh-edge transition zone. For the numerical experiments designed in this study, the profile shape and sediment sorting behavior of tidal flats are not significantly modified by a gradual rising sea level. However, the impacts of SLR on vegetated tidal flats are still manifold: (a) driving the landward migration of intertidal zone and salt marshes; (b) enhancing sediment erosion on intertidal flats; and (c) drowning salt marshes under limited sediment supply with the constrain of seawalls. Finally, model results suggest that organic carbon accumulation on marshlands may be enhanced with an increasing SLR rate provided that salt marshes are not drowned.

  18. Effects of chloride, sulfate and natural organic matter (NOM) on the accumulation and release of trace-level inorganic contaminants from corroding iron.

    PubMed

    Peng, Ching-Yu; Ferguson, John F; Korshin, Gregory V

    2013-09-15

    This study examined effects of varying levels of anions (chloride and sulfate) and natural organic matter (NOM) on iron release from and accumulation of inorganic contaminants in corrosion scales formed on iron coupons exposed to drinking water. Changes of concentrations of sulfate and chloride were observed to affect iron release and, in lesser extent, the retention of representative inorganic contaminants (vanadium, chromium, nickel, copper, zinc, arsenic, cadmium, lead and uranium); but, effects of NOM were more pronounced. DOC concentration of 1 mg/L caused iron release to increase, with average soluble and total iron concentrations being four and two times, respectively, higher than those in the absence of NOM. In the presence of NOM, the retention of inorganic contaminants by corrosion scales was reduced. This was especially prominent for lead, vanadium, chromium and copper whose retention by the scales decreased from >80% in the absence of NOM to <30% in its presence. Some of the contaminants, notably copper, chromium, zinc and nickel retained on the surface of iron coupons in the presence of DOC largely retained their mobility and were released readily when ambient water chemistry changed. Vanadium, arsenic, cadmium, lead and uranium retained by the scales were largely unsusceptible to changes of NOM and chloride levels. Modeling indicated that the observed effects were associated with the formation of metal-NOM complexes and effects of NOM on the sorption of the inorganic contaminants on solid phases that are typical for iron corrosion in drinking water. PMID:23863395

  19. Efficient photoinduced charge accumulation in reduced graphene oxide coupled with titania nanosheets to show highly enhanced and persistent conductance.

    PubMed

    Cai, Xingke; Sakai, Nobuyuki; Ozawa, Tadashi C; Funatsu, Asami; Ma, Renzhi; Ebina, Yasuo; Sasaki, Takayoshi

    2015-06-01

    Tuning of the electrical properties of graphene via photoexcitation of a heteroassembled material has started to attract attention for electronic and optoelectronic applications. Actually photoinduced carrier doping from the hexagonal boron nitride (h-BN) substrate greatly modulated the transport property of the top layer graphene, showing promising potential for this approach. However, for practical applications, the large scale production of this two-dimensional heterostructure is needed. Here, a superlattice film constructed from reduced graphene oxide (rGO) and photoactive titania nanosheets (Ti0.87O2(0.52-)) was employed as a channel to construct a field effect transistor (FET) device, and its UV light response on the electrical transport property was examined. The UV light illumination induced significant improvement of the electrical conductance by ∼7 times on the basis of simultaneous enhancements of the electron carrier concentration and its mobility in rGO. Furthermore, the polarity of the FET response changed from ambipolar to n-type unipolar. Such modulated properties persisted in vacuum even after the UV light was turned off. These interesting behaviors may be explained in terms of photomodulation effects from Ti0.87O2(0.52-) nanosheets. The photoexcited electrons in Ti0.87O2(0.52-) are injected into rGO to increase the electron carrier concentration as high as 7.6×10(13) cm(-2). On the other hand, the holes are likely trapped in the Ti0.87O2(0.52-) nanosheets. These photocarriers undergo reduction and oxidation of oxygen and water molecules adsorbed in the film, respectively, which act as carrier scattering centers, contributing to the enhancement of the carrier mobility. Since the film likely contains more water molecules than oxygen, upon extinction of UV light, a major portion of electrons (∼80% of the concentration at the UV off) survives in rGO, showing the highly enhanced conductance for days. This surpassing photomodulated FET response and

  20. Uranium Bio-accumulation and Cycling as revealed by Uranium Isotopes in Naturally Reduced Sediments from the Upper Colorado River Basin

    NASA Astrophysics Data System (ADS)

    Lefebvre, Pierre; Noël, Vincent; Jemison, Noah; Weaver, Karrie; Bargar, John; Maher, Kate

    2016-04-01

    Uranium (U) groundwater contamination following oxidized U(VI) releases from weathering of mine tailings is a major concern at numerous sites across the Upper Colorado River Basin (CRB), USA. Uranium(IV)-bearing solids accumulated within naturally reduced zones (NRZs) characterized by elevated organic carbon and iron sulfide compounds. Subsequent re-oxidation of U(IV)solid to U(VI)aqueous then controls the release to groundwater and surface water, resulting in plume persistence and raising public health concerns. Thus, understanding the extent of uranium oxidation and reduction within NRZs is critical for assessing the persistence of the groundwater contamination. In this study, we measured solid-phase uranium isotope fractionation (δ238/235U) of sedimentary core samples from four study sites (Shiprock, NM, Grand Junction, Rifle and Naturita, CO) using a multi-collector inductively coupled plasma mass spectrometer (MC-ICP-MS). We observe a strong correlation between U accumulation and the extent of isotopic fractionation, with Δ238U up to +1.8 ‰ between uranium-enriched and low concentration zones. The enrichment in the heavy isotopes within the NRZs appears to be especially important in the vadose zone, which is subject to variations in water table depth. According to previous studies, this isotopic signature is consistent with biotic reduction processes associated with metal-reducing bacteria. Positive correlations between the amount of iron sulfides and the accumulation of reduced uranium underline the importance of sulfate-reducing conditions for U(IV) retention. Furthermore, the positive fractionation associated with U reduction observed across all sites despite some variations in magnitude due to site characteristics, shows a regional trend across the Colorado River Basin. The maximum extent of 238U enrichment observed in the NRZ proximal to the water table further suggests that the redox cycling of uranium, with net release of U(VI) to the groundwater by

  1. New alleles of FATB-1A to reduce palmitic acid levels in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In wild-type soybeans, palmitic acid typically constitutes 10% of the total seed oil. Palmitic acid is a saturated fat linked to increased cholesterol levels, and reducing levels of saturated fats in soybean oil has been a breeding target. To identify novel and useful variation that could help in re...

  2. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism.

    PubMed

    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry

    2016-07-01

    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P < 0.05 vs. vehicle). A significant 20% reduction in hepatic LDL receptor protein expression was also observed with empagliflozin. Importantly, none of these parameters were changed by empagliflozin in fed conditions. Empagliflozin significantly reduced the catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P < 0.05 vs. vehicle). These data suggest that empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion. PMID:27207551

  3. Tension between reducing sea-level rise and global warming through solar-radiation management

    NASA Astrophysics Data System (ADS)

    Irvine, P. J.; Sriver, R. L.; Keller, K.

    2012-02-01

    Geoengineering using solar-radiation management (SRM) is gaining interest as a potential strategy to reduce future climate change impacts. Basic physics and past observations suggest that reducing insolation will, on average, cool the Earth. It is uncertain, however, whether SRM can reduce climate change stressors such as sea-level rise or rates of surface air temperature change. Here we use an Earth system model of intermediate complexity to quantify the possible response of sea levels and surface air temperatures to projected climate forcings and SRM strategies. We find that SRM strategies introduce a potentially strong tension between the objectives to reduce (1) the rate of temperature change and (2) sea-level rise. This tension arises primarily because surface air temperatures respond faster to radiative forcings than sea levels. Our results show that the forcing required to stop sea-level rise could cause a rapid cooling with a rate similar to the peak business-as-usual warming rate. Furthermore, termination of SRM was found to produce warming rates up to five times greater than the maximum rates under the business-as-usual CO2 scenario, whereas sea-level rise rates were only 30% higher. Reducing these risks requires a slow phase-out of many decades and thus commits future generations.

  4. Astaxanthin reduces hepatic lipid accumulations in high-fat-fed C57BL/6J mice via activation of peroxisome proliferator-activated receptor (PPAR) alpha and inhibition of PPAR gamma and Akt.

    PubMed

    Jia, Yaoyao; Wu, Chunyan; Kim, Jiyoung; Kim, Bobae; Lee, Sung-Joon

    2016-02-01

    We have previously reported that astaxanthin (AX), a dietary carotenoid, directly interacts with peroxisome proliferator-activated receptors PPARα and PPARγ, activating PPARα while inhibiting PPARγ, and thus reduces lipid accumulation in hepatocytes in vitro. To investigate the effects of AX in vivo, high-fat diet (HFD)-fed C57BL/6J mice were orally administered AX (6 or 30mg/kg body weight) or vehicle for 8weeks. AX significantly reduced the levels of triglyceride both in plasma and in liver compared with the control HFD mice. AX significantly improved liver histology and thus reduced both steatosis and inflammation scores of livers with hematoxylin and eosin staining. The number of inflammatory macrophages and Kupffer cells were reduced in livers by AX administration assessed with F4/80 staining. Hepatic PPARα-responsive genes involved in fatty acid uptake and β-oxidation were upregulated, whereas inflammatory genes were downregulated by AX administration. In vitro radiolabeled assays revealed that hepatic fatty acid oxidation was induced by AX administration, whereas fatty acid synthesis was not changed in hepatocytes. In mechanism studies, AX inhibited Akt activity and thus decreased SREBP1 phosphorylation and induced Insig-2a expression, both of which delayed nuclear translocation of SREBP1 and subsequent hepatic lipogenesis. Additionally, inhibition of the Akt-mTORC1 signaling axis by AX stimulated hepatic autophagy that could promote degradation of lipid droplets. These suggest that AX lowers hepatic lipid accumulation in HFD-fed mice via multiple mechanisms. In addition to the previously reported differential regulation of PPARα and PPARγ, inhibition of Akt activity and activation of hepatic autophagy reduced hepatic steatosis in mouse livers. PMID:26878778

  5. Salicylic acid treatment reduces the rot of postharvest citrus fruit by inducing the accumulation of H2O2, primary metabolites and lipophilic polymethoxylated flavones.

    PubMed

    Zhu, Feng; Chen, Jiajing; Xiao, Xue; Zhang, Mingfei; Yun, Ze; Zeng, Yunliu; Xu, Juan; Cheng, Yunjiang; Deng, Xiuxin

    2016-09-15

    To comprehensively analyze the effects of salicylic acid (SA) on the storability of Satsuma mandarin (Citrus unshiu), fruits were treated with 2mM SA. The disease incidence of control/SA-treated fruit at 50d and 120d after treatment was 23.3%/10% and 67.3%/23.3%, respectively, suggesting that SA treatment can significantly reduce the rot rate of postharvest citrus fruit. Fruit quality assays revealed that the treatment can maintain fruit firmness without affecting the inner quality. Furthermore, the contents of H2O2 and some defense-related metabolites, such as ornithine and threonine, in citrus pericarp, were significantly increased by SA treatment. Moreover, it was lipophilic polymethoxylated flavones, rather than flavanone glycosides, that accumulated in SA-treated fruits and these can directly inhibit pathogen development. These results suggest that the effects of SA on postharvest citrus fruit may be attributed to the accumulation of H2O2 and defense-related metabolites. PMID:27080881

  6. Overexpression of Rice Glutaredoxin OsGrx_C7 and OsGrx_C2.1 Reduces Intracellular Arsenic Accumulation and Increases Tolerance in Arabidopsis thaliana

    PubMed Central

    Verma, Pankaj K.; Verma, Shikha; Pande, Veena; Mallick, Shekhar; Deo Tripathi, Rudra; Dhankher, Om P.; Chakrabarty, Debasis

    2016-01-01

    Glutaredoxins (Grxs) are a family of small multifunctional proteins involved in various cellular functions, including redox regulation and protection under oxidative stress. Despite the high number of Grx genes in plant genomes (48 Grxs in rice), the biological functions and physiological roles of most of them remain unknown. Here, the functional characterization of the two arsenic-responsive rice Grx family proteins, OsGrx_C7 and OsGrx_C2.1 are reported. Over-expression of OsGrx_C7 and OsGrx_C2.1 in transgenic Arabidopsis thaliana conferred arsenic (As) tolerance as reflected by germination, root growth assay, and whole plant growth. Also, the transgenic expression of OsGrxs displayed significantly reduced As accumulation in A. thaliana seeds and shoot tissues compared to WT plants during both AsIII and AsV stress. Thus, OsGrx_C7 and OsGrx_C2.1 seem to be an important determinant of As-stress response in plants. OsGrx_C7 and OsGrx_C2.1 transgenic showed to maintain intracellular GSH pool and involved in lowering AsIII accumulation either by extrusion or reducing uptake by altering the transcript of A. thaliana AtNIPs. Overall, OsGrx_C7 and OsGrx_C2.1 may represent a Grx family protein involved in As stress response and may allow a better understanding of the As induced stress pathways and the design of strategies for the improvement of stress tolerance as well as decreased As content in crops. PMID:27313586

  7. Overexpression of Rice Glutaredoxin OsGrx_C7 and OsGrx_C2.1 Reduces Intracellular Arsenic Accumulation and Increases Tolerance in Arabidopsis thaliana.

    PubMed

    Verma, Pankaj K; Verma, Shikha; Pande, Veena; Mallick, Shekhar; Deo Tripathi, Rudra; Dhankher, Om P; Chakrabarty, Debasis

    2016-01-01

    Glutaredoxins (Grxs) are a family of small multifunctional proteins involved in various cellular functions, including redox regulation and protection under oxidative stress. Despite the high number of Grx genes in plant genomes (48 Grxs in rice), the biological functions and physiological roles of most of them remain unknown. Here, the functional characterization of the two arsenic-responsive rice Grx family proteins, OsGrx_C7 and OsGrx_C2.1 are reported. Over-expression of OsGrx_C7 and OsGrx_C2.1 in transgenic Arabidopsis thaliana conferred arsenic (As) tolerance as reflected by germination, root growth assay, and whole plant growth. Also, the transgenic expression of OsGrxs displayed significantly reduced As accumulation in A. thaliana seeds and shoot tissues compared to WT plants during both AsIII and AsV stress. Thus, OsGrx_C7 and OsGrx_C2.1 seem to be an important determinant of As-stress response in plants. OsGrx_C7 and OsGrx_C2.1 transgenic showed to maintain intracellular GSH pool and involved in lowering AsIII accumulation either by extrusion or reducing uptake by altering the transcript of A. thaliana AtNIPs. Overall, OsGrx_C7 and OsGrx_C2.1 may represent a Grx family protein involved in As stress response and may allow a better understanding of the As induced stress pathways and the design of strategies for the improvement of stress tolerance as well as decreased As content in crops. PMID:27313586

  8. Genetic suppression of a phosphomimic myosin II identifies system-level factors that promote myosin II cleavage furrow accumulation

    PubMed Central

    Ren, Yixin; West-Foyle, Hoku; Surcel, Alexandra; Miller, Christopher; Robinson, Douglas N.

    2014-01-01

    How myosin II localizes to the cleavage furrow in Dictyostelium and metazoan cells remains largely unknown despite significant advances in understanding its regulation. We designed a genetic selection using cDNA library suppression of 3xAsp myosin II to identify factors involved in myosin cleavage furrow accumulation. The 3xAsp mutant is deficient in bipolar thick filament assembly, fails to accumulate at the cleavage furrow, cannot rescue myoII-null cytokinesis, and has impaired mechanosensitive accumulation. Eleven genes suppressed this dominant cytokinesis deficiency when 3xAsp was expressed in wild-type cells. 3xAsp myosin II's localization to the cleavage furrow was rescued by constructs encoding rcdBB, mmsdh, RMD1, actin, one novel protein, and a 14-3-3 hairpin. Further characterization showed that RMD1 is required for myosin II cleavage furrow accumulation, acting in parallel with mechanical stress. Analysis of several mutant strains revealed that different thresholds of myosin II activity are required for daughter cell symmetry than for furrow ingression dynamics. Finally, an engineered myosin II with a longer lever arm (2xELC), producing a highly mechanosensitive motor, could also partially suppress the intragenic 3xAsp. Overall, myosin II accumulation is the result of multiple parallel and partially redundant pathways that comprise a cellular contractility control system. PMID:25318674

  9. Stochastic Analysis and Forecasts of the Patterns of Speed, Acceleration, and Levels of Material Stock Accumulation in Society.

    PubMed

    Fishman, Tomer; Schandl, Heinz; Tanikawa, Hiroki

    2016-04-01

    The recent acceleration of urbanization and industrialization of many parts of the developing world, most notably in Asia, has resulted in a fast-increasing demand for and accumulation of construction materials in society. Despite the importance of physical stocks in society, the empirical assessment of total material stock of buildings and infrastructure and reasons for its growth have been underexplored in the sustainability literature. We propose an innovative approach for explaining material stock dynamics in society and create a country typology for stock accumulation trajectories using the ARIMA (Autoregressive Integrated Moving Average) methodology, a stochastic approach commonly used in business studies and economics to inspect and forecast time series. This enables us to create scenarios for future demand and accumulation of building materials in society, including uncertainty estimates. We find that the so-far overlooked aspect of acceleration trends of material stock accumulation holds the key to explaining material stock growth, and that despite tremendous variability in country characteristics, stock accumulation is limited to only four archetypal growth patterns. The ability of nations to change their pattern will be a determining factor for global sustainability. PMID:26927731

  10. A mutant of the Arabidopsis thaliana Toc159 gene accumulates reduced levels of linolenic acid and monogalactosyldiacylglycerol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have shown that a null mutant of Arabidopsis that lacks Toc159 receptor is impaired in chloroplast biogenesis and incapable of importing photosynthetic proteins. The mutant is referred to as plastid protein import 2 or ppi2, and has an albino phenotype. In this study, we measured ...

  11. A mutant of the Arabidopsis thaliana TOC159 gene accumulates reduced levels of linolenic acid and monogalactosyldiacylglycerol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have shown that a mutant of Arabidopsis that lacks the Toc159 receptor is impaired in chloroplast biogenesis. The mutant is referred as plastid protein import 2 or ppi2 and has an albino phenotype due to its inability to import the photosynthetic proteins. In this study, we measured...

  12. Phytoene desaturase is localized exclusively in the chloroplast and up-regulated at the mRNA level during accumulation of secondary carotenoids in Haematococcus pluvialis (Volvocales, chlorophyceae).

    PubMed

    Grünewald, K; Eckert, M; Hirschberg, J; Hagen, C

    2000-04-01

    The unicellular green alga Haematococcus pluvialis Flotow is known for its massive accumulation of ketocarotenoids under various stress conditions. Therefore, this microalga is one of the favored organisms for biotechnological production of these antioxidative compounds. Astaxanthin makes up the main part of the secondary carotenoids and is accumulated mostly in an esterified form in extraplastidic lipid vesicles. We have studied phytoene desaturase, an early enzyme of the carotenoid biosynthetic pathway. The increase in the phytoene desaturase protein levels that occurs following induction is accompanied by a corresponding increase of its mRNA during the accumulation period, indicating that phytoene desaturase is regulated at the mRNA level. We also investigated the localization of the enzyme by western-blot analysis of cell fractions and by immunogold labeling of ultrathin sections for electron microscopy. In spite of the fact that secondary carotenoids accumulate outside the chloroplast, no extra pathway specific for secondary carotenoid biosynthesis in H. pluvialis was found, at least at this early stage in the biosynthesis. A transport process of carotenoids from the site of biosynthesis (chloroplast) to the site of accumulation (cytoplasmatic located lipid vesicles) is implicated. PMID:10759523

  13. Quantification of Maize Fine Streak Virus Genomic and Positive-sense RNAs in Infected Maize Reveals High Level Accumulation of ORF 3 and 4 MFSV Transcripts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Quantification of Maize fine streak virus genomic and positive-sense RNAs in infected maize reveals high level accumulation of ORF 3 and 4 MFSV transcripts. We improved methods to analyze RNA produced by Maize fine streak virus (MVSF) within infected maize tissue using real-time RT-qPCR. We designe...

  14. Diabetes and Elevated HbA1c levels are Associated with Brain Hypometabolism but not Amyloid Accumulation

    PubMed Central

    Roberts, Rosebud O.; Knopman, David S.; Cha, Ruth H.; Mielke, Michelle M.; Pankratz, V. Shane; Boeve, Bradley F.; Kantarci, Kejal; Geda, Yonas E.; Jack, Clifford R.; Petersen, Ronald C.; Lowe, Val J.

    2014-01-01

    Dysfunctional insulin signaling may affect brain metabolism or amyloid deposition. We investigated the associations of type 2 diabetes with amyloid accumulation measured using 11C-Pittsburgh Compound B (PiB) and brain hypometabolism measured using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Methods We studied a sample of non-demented participants from the population-based Mayo Clinic Study of Aging. All subjects underwent MRI, amyloid PET and FDG PET. Alzheimer’s disease (AD) signature and region of interest (ROI) measures for PiB retention ratio and FDG ratio were measured. Diabetes was assessed from the Rochester Epidemiology Project medical records-linkage system. Results Among 749 participants (median age 79.0 years; 56.5% male, 81.0% cognitively normal; 20.6% diabetics), FDG hypometabolism (FDG ratio < 1.31) in the AD signature meta-ROI was more common in diabetics (48.1%) than in non-diabetics (28.9%; p <0.001). The median FDG ratio was lower in diabetics vs. non-diabetics in the AD signature meta-ROI (1.32 vs. 1.40, p < 0.001), and in the angular (1.40 vs. 1.48, p < 0.001) and posterior cingulate gyri ROIs (1.63 vs. 1.72, p < 0.001). The odds ratio (OR [95% confidence interval]) for abnormal AD signature FDG hypometabolism was elevated (OR, 2.28 [1.56, 3.33]) in diabetics vs. non-diabetics after adjustment for age, sex, and education, and after additional adjustment for Apolipoprotein ε4 allele, glycemic level, and cognitive status (OR, 1.69 [1.10, 2.60]). However, AD signature PiB retention ratio was similar in diabetics vs. non-diabetics (OR, 1.03 [0.71, 1.51]; p = 0.87). In post-hoc analyses in non-diabetics, a 1% increase in HBA1c was associated with greater AD signature hypometabolism in cognitively normal subjects (OR, 1.93 [1.03, 3.62; p = 0.04]) and in the total cohort (OR 1.59 [0.92, 2.75; p = 0.10). Conclusion Diabetes and poor glycemic control in non-diabetics may enhance glucose hypometabolism in AD signature regions

  15. Reducing Lissencephaly-1 levels augments mitochondrial transport and has a protective effect in adult Drosophila neurons

    PubMed Central

    Vagnoni, Alessio; Hoffmann, Patrick C.; Bullock, Simon L.

    2016-01-01

    ABSTRACT Defective transport of mitochondria in axons is implicated in the pathogenesis of several age-associated neurodegenerative diseases. However, the regulation and function of axonal mitochondrial motility during normal ageing is poorly understood. Here, we use novel imaging procedures to characterise axonal transport of these organelles in the adult Drosophila wing nerve. During early adult life there is a boost and progressive decline in the proportion of mitochondria that are motile, which is not due to general changes in cargo transport. Experimental inhibition of the mitochondrial transport machinery specifically in adulthood accelerates the appearance of focal protein accumulations in ageing axons, which is suggestive of defects in protein homeostasis. Unexpectedly, lowering levels of Lissencephaly-1 (Lis1), a dynein motor co-factor, augments axonal mitochondrial transport in ageing wing neurons. Lis1 mutations suppress focal protein accumulations in ageing neurons, including those caused by interfering with the mitochondrial transport machinery. Our data provide new insights into the dynamics of mitochondrial motility in adult neurons in vivo, identify Lis1 as a negative regulator of transport of these organelles, and provide evidence of a link between mitochondrial movement and neuronal protein homeostasis. PMID:26598558

  16. Diabetes accelerates smooth muscle accumulation in lesions of atherosclerosis: lack of direct growth-promoting effects of high glucose levels.

    PubMed

    Suzuki, L A; Poot, M; Gerrity, R G; Bornfeldt, K E

    2001-04-01

    In combination with other factors, hyperglycemia may cause the accelerated progression of atherosclerosis in people with diabetes. Arterial smooth muscle cell (SMC) proliferation and accumulation contribute to formation of advanced atherosclerotic lesions. Therefore, we investigated the effects of hyperglycemia on SMC proliferation and accumulation in vivo and in isolated arteries and SMCs by taking advantage of a new porcine model of diabetes-accelerated atherosclerosis, in which diabetic animals are hyperglycemic without receiving exogenous insulin. We show that diabetic animals fed a cholesterol-rich diet, like humans, develop severe lesions of atherosclerosis characterized by SMC accumulation and proliferation, whereas lesions in nondiabetic animals contain fewer SMCs after 20 weeks. However, high glucose (25 mmol/l) does not directly stimulate the proliferation of SMCs in isolated arterial tissue from diabetic or nondiabetic animals, or of cultured SMCs from these animals or from humans. Furthermore, the mitogenic actions of platelet-derived growth factor, IGF-I, or serum are not enhanced by high glucose. High glucose increases SMC glucose metabolism through the citric acid cycle and the pentose phosphate pathway by 240 and 90%, respectively, but <10% of consumed glucose is metabolized through these pathways. Instead, most of the consumed glucose is converted into lactate and secreted by the SMCs. Thus, diabetes markedly accelerates SMC proliferation and accumulation in atherosclerotic lesions. The stimulatory effect of diabetes on SMCs is likely to be mediated by effects secondary to the hyperglycemic state. PMID:11289052

  17. T1 Relaxation Rate (R1) Indicates Nonlinear Mn Accumulation in Brain Tissue of Welders With Low-Level Exposure.

    PubMed

    Lee, Eun-Young; Flynn, Michael R; Du, Guangwei; Lewis, Mechelle M; Fry, Rebecca; Herring, Amy H; Van Buren, Eric; Van Buren, Scott; Smeester, Lisa; Kong, Lan; Yang, Qing; Mailman, Richard B; Huang, Xuemei

    2015-08-01

    Although the essential element manganese (Mn) is neurotoxic at high doses, the effects of lower exposure are unclear. MRI T1-weighted (TIW) imaging has been used to estimate brain Mn exposure via the pallidal index (PI), defined as the T1W intensity ratio in the globus pallidus (GP) versus frontal white matter (FWM). PI may not, however, be sensitive to Mn in GP because Mn also may accumulate in FWM. This study explored: (1) whether T1 relaxation rate (R1) could quantify brain Mn accumulation more sensitively; and (2) the dose-response relationship between estimated Mn exposure and T1 relaxation rate (R1). Thirty-five active welders and 30 controls were studied. Occupational questionnaires were used to estimate hours welding in the past 90 days (HrsW) and lifetime measures of Mn exposure. T1W imaging and T1-measurement were utilized to generate PI and R1 values in brain regions of interest (ROIs). PI did not show a significant association with any measure of Mn and/or welding-related exposure. Conversely, in several ROIs, R1 showed a nonlinear relationship to HrsW, with R1 signal increasing only after a critical exposure was reached. The GP had the greatest rate of Mn accumulation. Welders with higher exposure showed significantly higher R1 compared either with controls or with welders with lower exposure. Our data are additional evidence that Mn accumulation can be assessed more sensitively by R1 than by PI. Moreover, the nonlinear relationship between welding exposure and Mn brain accumulation should be considered in future studies and policies. PMID:25953701

  18. T1 Relaxation Rate (R1) Indicates Nonlinear Mn Accumulation in Brain Tissue of Welders With Low-Level Exposure

    PubMed Central

    Lee, Eun-Young; Flynn, Michael R.; Du, Guangwei; Lewis, Mechelle M.; Fry, Rebecca; Herring, Amy H.; Van Buren, Eric; Van Buren, Scott; Smeester, Lisa; Kong, Lan; Yang, Qing; Mailman, Richard B.; Huang, Xuemei

    2015-01-01

    Although the essential element manganese (Mn) is neurotoxic at high doses, the effects of lower exposure are unclear. MRI T1-weighted (TIW) imaging has been used to estimate brain Mn exposure via the pallidal index (PI), defined as the T1W intensity ratio in the globus pallidus (GP) versus frontal white matter (FWM). PI may not, however, be sensitive to Mn in GP because Mn also may accumulate in FWM. This study explored: (1) whether T1 relaxation rate (R1) could quantify brain Mn accumulation more sensitively; and (2) the dose-response relationship between estimated Mn exposure and T1 relaxation rate (R1). Thirty-five active welders and 30 controls were studied. Occupational questionnaires were used to estimate hours welding in the past 90 days (HrsW) and lifetime measures of Mn exposure. T1W imaging and T1-measurement were utilized to generate PI and R1 values in brain regions of interest (ROIs). PI did not show a significant association with any measure of Mn and/or welding-related exposure. Conversely, in several ROIs, R1 showed a nonlinear relationship to HrsW, with R1 signal increasing only after a critical exposure was reached. The GP had the greatest rate of Mn accumulation. Welders with higher exposure showed significantly higher R1 compared either with controls or with welders with lower exposure. Our data are additional evidence that Mn accumulation can be assessed more sensitively by R1 than by PI. Moreover, the nonlinear relationship between welding exposure and Mn brain accumulation should be considered in future studies and policies. PMID:25953701

  19. An Action Science Research Approach to Reducing Student Tardiness at the High School Level

    ERIC Educational Resources Information Center

    Gile, Curtis S.

    2013-01-01

    The purpose of this action research study was to design, implement, analyze, and evaluate a series of interventions to reduce student tardiness at the high school level. Another purpose of the study was to determine the underlying values, beliefs, and behaviors associated with student tardiness from a faculty and staff perspective. The study…

  20. PROLONGED FASTING AND CORTISOL REDUCE MYOSTATIN MRNA LEVELS IN TILAPIA LARVAE, SHORT-TERM FASTING ELEVATES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myostatin negatively regulates muscle growth and development and has recently been characterized in several fishes. We measured fasting myostatin mRNA levels in adult tilapia skeletal muscle and in whole larvae. Although fasting reduced some growth indices in adults, skeletal muscle myostatin mRNA...

  1. Schoolwide Intervention to Reduce Chronic Tardiness at the Middle and High School Levels

    ERIC Educational Resources Information Center

    Tyre, Ashli; Feuerborn, Laura; Pierce, Jennifer

    2011-01-01

    When many students are tardy at the secondary level, teachers must continually restart instruction or delay beginning instructional periods throughout the school day. To address the considerable amount of instructional time lost caused by high rates of tardiness, the authors investigated the results of schoolwide intervention to reduce student…

  2. Modulation of cGMP accumulation by adenosine A1 receptors at the hippocampus: influence of cGMP levels and gender.

    PubMed

    Serpa, André; Sebastião, Ana M; Cascalheira, José F

    2014-12-01

    Adenosine A1 receptor is highly expressed in hippocampus where it inhibits neurotransmitter release and has neuroprotective activity. Similar actions are obtained by increasing cGMP concentration, but a clear link between adenosine A1 receptor and cGMP levels remains to be established. The present work aims to investigate if cGMP formation is modulated by adenosine A1 receptors at the hippocampus and if this effect is gender dependent. cGMP accumulation, induced by phosphodiesterases inhibitors Zaprinast (100 μM) and Bay 60-7550 (10 μM), and cAMP accumulation, induced by Forskolin (20 μM) and Rolipram (50 μM), were quantified in rat hippocampal slices using specific enzymatic immunoassays. N6-cyclopentyladenosine (CPA, 100 nM) alone failed to modify basal cGMP accumulation. However, the presence of adenosine deaminase (ADA, 2 U/ml) unmasked a CPA (0.03-300 nM) stimulatory effect on basal cGMP accumulation (EC50: 4.2±1.4 nM; Emax: 17±0.9%). ADA influence on CPA activity was specific for cGMP, since inhibition of cAMP accumulation by CPA was not affected by the presence of ADA, though ADA inhibited cAMP accumulation in the absence of CPA. Increasing cGMP accumulation, by about four-fold, with sodium nitroprusside (SNP, 100 μM) abolished the CPA (100 nM) effect on cGMP accumulation in males but did not modify the effect of CPA in female rats. This effect was reversed by 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM), indicating an adenosine A1 receptor mediated effect on cGMP accumulation. In conclusion, adenosine A1 receptors increase intracellular cGMP formation at hippocampus both in males and females under basal conditions, but only in females when cGMP levels are increased by SNP. PMID:25300679

  3. Suppression of antiviral silencing by cucumber mosaic virus 2b protein in Arabidopsis is associated with drastically reduced accumulation of three classes of viral small interfering RNAs.

    PubMed

    Diaz-Pendon, Juan A; Li, Feng; Li, Wan-Xiang; Ding, Shou-Wei

    2007-06-01

    We investigated the genetic pathway in Arabidopsis thaliana targeted during infection by cucumber mosaic virus (CMV) 2b protein, known to suppress non-cell-autonomous transgene silencing and salicylic acid (SA)-mediated virus resistance. We show that 2b expressed from the CMV genome drastically reduced the accumulation of 21-, 22-, and 24-nucleotide classes of viral small interfering RNAs (siRNAs) produced by Dicer-like4 (DCL4), DCL2, and DCL3, respectively. The defect of a CMV 2b-deletion mutant (CMV-Delta2b) in plant infection was efficiently rescued in Arabidopsis mutants producing neither 21- nor 22-nucleotide viral siRNAs. Since genetic analysis further identifies a unique antiviral role for DCL3 upstream of DCL4, our data indicate that inhibition of the accumulation of distinct viral siRNAs plays a key role in 2b suppression of antiviral silencing. Strikingly, disease symptoms caused by CMV-Delta2b in Arabidopsis mutants defective in antiviral silencing were as severe as those caused by CMV, demonstrating an indirect role for the silencing suppressor activity in virus virulence. We found that production of CMV siRNAs without 2b interference depended largely on RNA-dependent RNA polymerase 1 (RDR1) inducible by SA. Given the known role of RDR6-dependent transgene siRNAs in non-cell-autonomous silencing, our results suggest a model in which 2b inhibits the production of RDR1-dependent viral siRNAs that confer SA-dependent virus resistance by directing non-cell-autonomous antiviral silencing. PMID:17586651

  4. Crude caffeine reduces memory impairment and amyloid β(1-42) levels in an Alzheimer's mouse model.

    PubMed

    Chu, Yi-Fang; Chang, Wen-Han; Black, Richard M; Liu, Jia-Ren; Sompol, Pradoldej; Chen, Yumin; Wei, Huilin; Zhao, Qiuyan; Cheng, Irene H

    2012-12-01

    Alzheimer's disease (AD), a chronic neurodegenerative disorder associated with the abnormal accumulations of amyloid β (Aβ) peptide and oxidative stress in the brain, is the most common form of dementia among the elderly. Crude caffeine (CC), a major by-product of the decaffeination of coffee, has potent hydrophilic antioxidant activity and may reduce inflammatory processes. Here, we showed that CC and pure caffeine intake had beneficial effects in a mouse model of AD. Administration of CC or pure caffeine for 2months partially prevented memory impairment in AD mice, with CC having greater effects than pure caffeine. Furthermore, consumption of CC, but not pure caffeine, reduced the Aβ(1-42) levels and the number of amyloid plaques in the hippocampus. Moreover, CC and caffeine protected primary neurons from Aβ-induced cell death and suppressed Aβ-induced caspase-3 activity. Our data indicate that CC may contain prophylactic agents against the cell death and the memory impairment in AD. PMID:22953961

  5. Reduced serum levels of 1 alpha,25-dihydroxyvitamin D during long-term total parenteral nutrition.

    PubMed

    Klein, G L; Horst, R L; Norman, A W; Ament, M E; Slatopolsky, E; Coburn, J W

    1981-05-01

    Painful bone disease, characterized by patchy osteomalacia and inactive bone, can develop in patients treated with total parenteral nutrition for more than 3 months. Serum levels of 1 alpha,25-dihydroxyvitamin D (1 alpha, 25(OH)2D), 24,25-dihydroxyvitamin D and 25-hydroxyvitamin D were measured in seven adults and five children treated with parenteral nutrition for 9 to 60 months. Serum levels of 1 alpha, 25(OH)2D were markedly reduced, while levels of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were normal. Serum calcium and phosphorus levels were normal or slightly increased, and immunoreactive parathyroid hormone levels were normal or low. Renal function was normal or minimally reduced. Skeletal symptoms disappeared and serum 1 alpha, 25(OH)2D levels rose to normal in one patient when nutrient infusions were discontinued for 6 weeks. Removal of calcium from the nutrient solution for 2 to 4 days was associated with no change in serum 1 alpha, 25(OH)2D in two patients. The cause of the reduction in serum levels of 1 alpha, 25(OH)2D and its role in the pathogenesis of bone disease in these patients remain uncertain. PMID:6786151

  6. The Cauliflower Or Gene Encodes a DnaJ Cysteine-Rich Domain-Containing Protein That Mediates High Levels of β-Carotene Accumulation[W

    PubMed Central

    Lu, Shan; Van Eck, Joyce; Zhou, Xiangjun; Lopez, Alex B.; O'Halloran, Diana M.; Cosman, Kelly M.; Conlin, Brian J.; Paolillo, Dominick J.; Garvin, David F.; Vrebalov, Julia; Kochian, Leon V.; Küpper, Hendrik; Earle, Elizabeth D.; Cao, Jun; Li, Li

    2006-01-01

    Despite recent progress in our understanding of carotenogenesis in plants, the mechanisms that govern overall carotenoid accumulation remain largely unknown. The Orange (Or) gene mutation in cauliflower (Brassica oleracea var botrytis) confers the accumulation of high levels of β-carotene in various tissues normally devoid of carotenoids. Using positional cloning, we isolated the gene representing Or and verified it by functional complementation in wild-type cauliflower. Or encodes a plastid-associated protein containing a DnaJ Cys-rich domain. The Or gene mutation is due to the insertion of a long terminal repeat retrotransposon in the Or allele. Or appears to be plant specific and is highly conserved among divergent plant species. Analyses of the gene, the gene product, and the cytological effects of the Or transgene suggest that the functional role of Or is associated with a cellular process that triggers the differentiation of proplastids or other noncolored plastids into chromoplasts for carotenoid accumulation. Moreover, we demonstrate that Or can be used as a novel genetic tool to induce carotenoid accumulation in a major staple food crop. We show here that controlling the formation of chromoplasts is an important mechanism by which carotenoid accumulation is regulated in plants. PMID:17172359

  7. Accumulate-Repeat-Accumulate-Accumulate-Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Sam; Thorpe, Jeremy

    2004-01-01

    Inspired by recently proposed Accumulate-Repeat-Accumulate (ARA) codes [15], in this paper we propose a channel coding scheme called Accumulate-Repeat-Accumulate-Accumulate (ARAA) codes. These codes can be seen as serial turbo-like codes or as a subclass of Low Density Parity Check (LDPC) codes, and they have a projected graph or protograph representation; this allows for a high-speed iterative decoder implementation using belief propagation. An ARAA code can be viewed as a precoded Repeat-and-Accumulate (RA) code with puncturing in concatenation with another accumulator, where simply an accumulator is chosen as the precoder; thus ARAA codes have a very fast encoder structure. Using density evolution on their associated protographs, we find examples of rate-lJ2 ARAA codes with maximum variable node degree 4 for which a minimum bit-SNR as low as 0.21 dB from the channel capacity limit can be achieved as the block size goes to infinity. Such a low threshold cannot be achieved by RA or Irregular RA (IRA) or unstructured irregular LDPC codes with the same constraint on the maximum variable node degree. Furthermore by puncturing the accumulators we can construct families of higher rate ARAA codes with thresholds that stay close to their respective channel capacity thresholds uniformly. Iterative decoding simulation results show comparable performance with the best-known LDPC codes but with very low error floor even at moderate block sizes.

  8. ATP production from adenine by a self-coupling enzymatic process: high-level accumulation under ammonium-limited conditions.

    PubMed

    Maruyama, A; Fujio, T

    2001-03-01

    To improve ATP production from adenine, we optimized cultivation and reaction conditions for the ATP producing strain, Corynebacterium ammoniagenes KY13510. In the conventional method, 28% NH4OH has been used both to adjust pH during cultivation and reaction, and to provide nitrogen for cell growth. In the ATP-producing reaction, high concentrations of inorganic phosphate and magnesium ion are needed, which form magnesium ammonium phosphate (MgNH4PO4) precipitate. To keep inorganic phosphate and magnesium ions soluble in the reaction mixture, it was indispensable to add phytic acid as a chelating agent of divalent metal ions. Under such conditions, 37 mg/ml (61.2 mM) ATP was accumulated in 13 h (Appl. Microbiol. Biotechnol. 21, 143 1985). If ammonium ion was depleted from the reaction mixture to avoid MgNH4 PO4 formation, we expected that there was no need to add phytic acid and ATP accumulation might be improved. Therefore, we obtained the cultured broth of C. ammoniagenes KY13510 strain with low ammonium ion content (less than 1 mg/ml as NH3) by the method that a part of alkali solution (28% NH4OH) for pH control was replaced with 10 N KOH. Using this culture broth, ATP producing reaction was done in 2-liter jar fermentor, controlling the pH of the reaction mixture with 10 N KOH. Under these conditions, the rate of ATP accumulation improved greatly, and 70.6 mg/ml (117 mM) ATP was accumulated in 28 h. The molar conversion ratio from adenine to ATP was about 82%. Phytic acid was slightly inhibitory to ATP formation under these ammonium-limited conditions. PMID:11330681

  9. [Pigment accumulation and functional activity of chloroplasts in common Pisum sativum L. mutants with low chlorophyll level (chlorotica)].

    PubMed

    Ladygin, V G

    2003-01-01

    Pea mutants chlorotica 2004 and 2014 with a low content of chlorophyll were studied. The mutant 2004 has light green leaves and stem, and the mutant 2014 has yellow green leaves and stem. They accumulate approximately 80 and 50% chlorophylls of the parent form of pea Torsdag cv. The content of carotene in carotenoids of the mutant 2004 was much lower, and the accumulation of lutein and violaxanthine was increased. The accumulation of all carotenoids in the mutant 2014 decreased almost proportionally to a decrease in the chlorophyll content. The rate of CO2 evolution in mutant chlorotica 2004 and 2014 was established to be lower. The quantum efficiency of photosynthesis in the mutants was 29-30% lower as compared to the control, and in hybrid plants it was 1.5-2-fold higher. It is assumed that the increase in the activity of the night-time respiration in gas exchange of chlorotica mutants and the drop of photosynthesis lead to a decrease in biomass increment. The results obtained allow us to conclude that the mutation of chlorotica 2004 and 2014 affects the genes controlling the formation and functioning of different components of the photosynthetic apparatus. PMID:12723346

  10. Increasing the maximally random jammed density with electric field to reduce the fat level in chocolate

    NASA Astrophysics Data System (ADS)

    Tao, R.; Tang, H.

    Chocolate is one of the most popular food types and flavors in the world. Unfortunately, at present, chocolate products contain too much fat, leading to obesity. For example, a typical molding chocolate has various fat up to 40% in total and chocolate for covering ice cream has fat 50 -60%. Especially, as children are the leading chocolate consumers, reducing the fat level in chocolate products to make them healthier is important and urgent. While this issue was called into attention and elaborated in articles and books decades ago and led to some patent applications, no actual solution was found unfortunately. Why is reducing fat in chocolate so difficult? What is the underlying physical mechanism? We have found that this issue is deeply related to the basic science of soft matters, especially to their viscosity and maximally random jammed (MRJ) density φx. All chocolate productions are handling liquid chocolate, a suspension with cocoa solid particles in melted fat, mainly cocoa butter. The fat level cannot be lower than 1-φxin order to have liquid chocolate to flow. Here we show that that with application of an electric field to liquid chocolate, we can aggregate the suspended particles into prolate spheroids. This microstructure change reduces liquid chocolate's viscosity along the flow direction and increases its MRJ density significantly. Hence the fat level in chocolate can be effectively reduced. We are looking forward to a new class of healthier and tasteful chocolate coming to the market soon. Dept. of Physics, Temple Univ, Philadelphia, PA 19122.

  11. Oxidative stress reduces levels of dysbindin-1A via its PEST domain.

    PubMed

    Yap, Mei-Yi Alicia; Lo, Yew-Long; Talbot, Konrad; Ong, Wei-Yi

    2014-12-01

    Oxidative stress resulting from the generation of reactive oxygen species has been proposed as an etiological factor in schizophrenia. The present study tests the hypothesis that oxidative stress can affect levels of dysbindin-1A, encoded by Dtnbp1, a genetic risk factor for schizophrenia, via its PEST domain. In vitro studies on SH-SY5Y cells indicate that oxidative stress triggers proteasomal degradation of dysbindin-1A, and that this requires interactions with its PEST domain, which may be a TRIM32 target. We specifically found (a) that oxidative stress induced in SH-SY5Y cells by 500 µM hydrogen peroxide reduced levels of full-length dysbindin-1, but did not reduce levels of that protein lacking its PEST domain and (b) that levels of full-length dysbindin-1, but not dysbindin-1 lacking its PEST domain, were higher in cells treated with the proteasome inhibitor MG132. Oxidative stress thus emerges as the first known cellular factor regulating dysbindin-1 isoforms with PEST domains. These findings are consistent with the previously noted fact that phosphorylation of PEST domains often marks proteins for proteasomal degradation, and raises the possibility that treatments reducing oxidative stress in the brain, especially during development, may lower schizophrenia risk. PMID:25445987

  12. Obstructive Sleep Apnea and Obesity are Associated With Reduced GPR 120 Plasma Levels in Children

    PubMed Central

    Gozal, David; Kheirandish-Gozal, Leila; Carreras, Alba; Khalyfa, Abdelnaby; Peris, Eduard

    2014-01-01

    Background: Obstructive sleep apnea (OSA) is a common health problem, particularly in obese children, in whom a vicious cycle of obesity and OSA interdependencies promotes increased food intake. G protein-coupled receptor 120 (GPR 120) is a long-chain free fatty acid (FFA) receptor that plays an important role in energy homeostasis, and protects against insulin resistance and systemic inflammation. We hypothesized that GPR 120 levels would be reduced in children with OSA, particularly among obese children. Study Design: Cross-sectional prospectively recruited cohort. Setting: Academic pediatric sleep program. Methods: Two hundred twenty-six children (mean age: 7.0 ± 2.1 y) underwent overnight polysomnographic evaluation and a fasting blood draw the morning after the sleep study. In addition to lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hsCRP) assays, monocyte GPR 120 expression, and plasma GPR 120 levels were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay kits. Results: Obese children and those with OSA had significantly lower GPR 120 monocyte expression and plasma GPR 120 levels. Furthermore, when both obesity and OSA were present, GPR 120 levels were lowest. Linear associations emerged between GPR 120 plasma levels and body mass index (BMI) z score, as well as with apnea-hypopnea index (AHI), saturation of peripheral oxygen (SpO2) nadir, and respiratory arousal index (RAI), with RAI remaining statistically significant when controlling for age, ethnicity, sex, and BMI z score (P < 0.001). Similarly, HOMA-IR was significantly associated with GPR 120 levels, but neither low density lipoprotein nor high density lipoprotein cholesterol or hsCRP levels exhibited significant correlations. Conclusions: G protein-coupled receptor 120 (GPR 120) levels are reduced in pediatric OSA and obesity (particularly when both are present) and may play a role in

  13. How Integrated Management Strategies Promote Protein Quality of Cotton Embryos: High Levels of Soil Available N, N Assimilation and Protein Accumulation Rate.

    PubMed

    Yang, HongKun; Meng, YaLi; Chen, BingLin; Zhang, XingYue; Wang, YouHua; Zhao, WenQing; Zhou, ZhiGuo

    2016-01-01

    Cottonseed is widely used as a source of ruminant feed and for industrial purposes. Therefore, there is a tremendous need to improve the nutritional value of cotton embryos. In this study, a conventional management (CM) and two integrated cotton management strategies (IMS1, IMS2) were performed at two soil fertility levels to study the relationships among soil N, N assimilation, embryonic protein accumulation and protein quality. The levels of proteins, essential amino acids, and semi-essential amino acids, especially those of glutamate, lysine, and methionine, were higher in IMS1 and IMS2 embryos than in CM embryos. These changes were significantly positively correlated with the soil-available N content, glutamine synthetase activity and peak value of protein accumulation rate and were negatively correlated with the free amino acid level. These results illustrated that integrated management strategies, especially the rates and timing of N application, raise the level of soil available N, which is beneficial for N assimilation in developing cotton embryos. The protein content was limited by the rate of protein accumulation rather than by the free amino acid content. The combination of target yield fertilization, a growth-driven N application schedule, a high plant density and the seedling raising with bio-organic fertilizer can substantially improve protein quality in cotton embryos, especially at a soil with low soil organic matter and total nitrogen. PMID:27532007

  14. How Integrated Management Strategies Promote Protein Quality of Cotton Embryos: High Levels of Soil Available N, N Assimilation and Protein Accumulation Rate

    PubMed Central

    Yang, HongKun; Meng, YaLi; Chen, BingLin; Zhang, XingYue; Wang, YouHua; Zhao, WenQing; Zhou, ZhiGuo

    2016-01-01

    Cottonseed is widely used as a source of ruminant feed and for industrial purposes. Therefore, there is a tremendous need to improve the nutritional value of cotton embryos. In this study, a conventional management (CM) and two integrated cotton management strategies (IMS1, IMS2) were performed at two soil fertility levels to study the relationships among soil N, N assimilation, embryonic protein accumulation and protein quality. The levels of proteins, essential amino acids, and semi-essential amino acids, especially those of glutamate, lysine, and methionine, were higher in IMS1 and IMS2 embryos than in CM embryos. These changes were significantly positively correlated with the soil-available N content, glutamine synthetase activity and peak value of protein accumulation rate and were negatively correlated with the free amino acid level. These results illustrated that integrated management strategies, especially the rates and timing of N application, raise the level of soil available N, which is beneficial for N assimilation in developing cotton embryos. The protein content was limited by the rate of protein accumulation rather than by the free amino acid content. The combination of target yield fertilization, a growth-driven N application schedule, a high plant density and the seedling raising with bio-organic fertilizer can substantially improve protein quality in cotton embryos, especially at a soil with low soil organic matter and total nitrogen. PMID:27532007

  15. Accumulate-Repeat-Accumulate-Accumulate Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Samuel; Thorpe, Jeremy

    2007-01-01

    Accumulate-repeat-accumulate-accumulate (ARAA) codes have been proposed, inspired by the recently proposed accumulate-repeat-accumulate (ARA) codes. These are error-correcting codes suitable for use in a variety of wireless data-communication systems that include noisy channels. ARAA codes can be regarded as serial turbolike codes or as a subclass of low-density parity-check (LDPC) codes, and, like ARA codes they have projected graph or protograph representations; these characteristics make it possible to design high-speed iterative decoders that utilize belief-propagation algorithms. The objective in proposing ARAA codes as a subclass of ARA codes was to enhance the error-floor performance of ARA codes while maintaining simple encoding structures and low maximum variable node degree.

  16. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men

    PubMed Central

    2013-01-01

    We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m2, age of 42.6 years and plasma triglycerides of 192.5 ± 96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome. PMID:23706001

  17. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men.

    PubMed

    Berge, Kjetil; Piscitelli, Fabiana; Hoem, Nils; Silvestri, Cristoforo; Meyer, Ingo; Banni, Sebastiano; Di Marzo, Vincenzo

    2013-01-01

    We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m², age of 42.6 years and plasma triglycerides of 192.5 ± 96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome. PMID:23706001

  18. Reducing bullying and victimization: student- and classroom-level mechanisms of change.

    PubMed

    Saarento, Silja; Boulton, Aaron J; Salmivalli, Christina

    2015-01-01

    This longitudinal study examines the mediating mechanisms by which the KiVa antibullying program, based on the Participant Role approach, reduces bullying and victimization among elementary school students. Both student-level mechanisms leading to reduced perpetration of bullying and classroom-level mechanisms leading to reductions in bullying and victimization are considered. Analyses are based on a sample of 7,491 students (49.5% boys) nested within 421 classrooms within 77 schools. At the beginning of program implementation, the children were in Grades 4, 5, and 6 (mean age 11.3 years). Multilevel structural equation modeling was used to analyze whether changes in the hypothesized mediators accounted for later reductions in the outcomes. At the student level, antibullying attitudes and perceptions regarding peers' defending behaviors and teacher attitudes toward bullying mediated the effects of KiVa on self-reported bullying perpetration. The effects on peer-reported bullying were only mediated by antibullying attitudes. At the classroom level, the program effects on both self- and peer-reported bullying were mediated by students' collective perceptions of teacher attitudes toward bullying. Also, perceived reinforcing behaviors predicted bullying but did not emerge as a significant mediator. Finally, bullying mediated the effects of the classroom-level factors on victimization. These findings enhance knowledge of the psychosocial developmental processes contributing to bullying and victimization and shed light on the key mechanisms by which school bullying can successfully be counteracted. PMID:24390403

  19. High intensity and reduced volume training attenuates stress and recovery levels in elite swimmers.

    PubMed

    Elbe, Anne-Marie; Rasmussen, Camilla P; Nielsen, Glen; Nordsborg, Nikolai B

    2016-04-01

    This study investigated the effect of increased high-intensity interval training (HIT) at the expense of total training volume on the stress and recovery levels of elite swimmers. Forty-one elite swimmers participated in the study and were randomly assigned to either a HIT or a control group (CON). Eleven swimmers did not complete the questionnaires. For 12 weeks both groups trained ~12 h per week. The amount of HIT was ~5 h vs. 1 h, and total distance was ~17 km vs. ~35 km per week for HIT and CON, respectively. HIT was performed as 6-10 × 10-30 s maximal effort interspersed by 2-4 min of rest. The Recovery Stress Questionnaire - Sport was used to measure the swimmers' stress and recovery levels. After the 12 week intervention, the general stress level was 16.6% (2.6-30.7%; mean and 95% CI) lower and the general recovery level was 6.5% (0.7-12.4%) higher in HIT compared to the CON, after adjusting for baseline values. No significant effects could be observed in sports-specific stress or sports-specific recovery. The results indicate that increasing training intensity and reducing training volume for 12 weeks can reduce general stress and increase general recovery levels in competitive swimmers. PMID:25867005

  20. Ascorbic acid serum levels are reduced in patients with hematological malignancies

    PubMed Central

    Huijskens, Mirelle J.A.J.; Wodzig, Will K.W.H.; Walczak, Mateusz; Germeraad, Wilfred T.V.; Bos, Gerard M.J.

    2016-01-01

    In this paper we demonstrate that patients treated with chemotherapy and/or hematopoietic stem cell transplantation (HSCT) have highly significant reduced serum ascorbic acid (AA) levels compared to healthy controls. We recently observed in in vitro experiments that growth of both T and NK cells from hematopoietic stem cells is positively influenced by AA. It might be of clinical relevance to study the function and recovery of immune cells after intensive treatment, its correlation to AA serum levels and the possible effect of AA supplementation. PMID:27014565

  1. Membrane of Functionalized Reduced Graphene Oxide Nanoplates with Angstrom-Level Channels

    PubMed Central

    Lee, Byeongho; Li, Kunzhou; Yoon, Hong Sik; Yoon, Jeyong; Mok, Yeongbong; Lee, Yan; Lee, Hong H.; Kim, Yong Hyup

    2016-01-01

    Membranes with atomic level pores or constrictions are valuable for separation and catalysis. We report a graphene-based membrane with an interlayer spacing of 3.7 angstrom (Å). When graphene oxide nanoplates are functionalized and then reduced, the laminated reduced graphene oxide (rGO) nanoplates or functionalized rGO membrane is little affected by an intercalated fluid, and the interlayer spacing of 3.7 Å increases only to 4.4 Å in wetted state, in contrast to the graphene oxide (GO) membrane whose interlayer spacing increases from 9 Å to 13 Å in wetted state. When applied to ion separation, this membrane reduced the permeation rate of small ions such as K+ and Na+ by three orders of magnitude compared to the GO membrane. PMID:27306853

  2. Membrane of Functionalized Reduced Graphene Oxide Nanoplates with Angstrom-Level Channels.

    PubMed

    Lee, Byeongho; Li, Kunzhou; Yoon, Hong Sik; Yoon, Jeyong; Mok, Yeongbong; Lee, Yan; Lee, Hong H; Kim, Yong Hyup

    2016-01-01

    Membranes with atomic level pores or constrictions are valuable for separation and catalysis. We report a graphene-based membrane with an interlayer spacing of 3.7 angstrom (Å). When graphene oxide nanoplates are functionalized and then reduced, the laminated reduced graphene oxide (rGO) nanoplates or functionalized rGO membrane is little affected by an intercalated fluid, and the interlayer spacing of 3.7 Å increases only to 4.4 Å in wetted state, in contrast to the graphene oxide (GO) membrane whose interlayer spacing increases from 9 Å to 13 Å in wetted state. When applied to ion separation, this membrane reduced the permeation rate of small ions such as K(+) and Na(+) by three orders of magnitude compared to the GO membrane. PMID:27306853

  3. Membrane of Functionalized Reduced Graphene Oxide Nanoplates with Angstrom-Level Channels

    NASA Astrophysics Data System (ADS)

    Lee, Byeongho; Li, Kunzhou; Yoon, Hong Sik; Yoon, Jeyong; Mok, Yeongbong; Lee, Yan; Lee, Hong H.; Kim, Yong Hyup

    2016-06-01

    Membranes with atomic level pores or constrictions are valuable for separation and catalysis. We report a graphene-based membrane with an interlayer spacing of 3.7 angstrom (Å). When graphene oxide nanoplates are functionalized and then reduced, the laminated reduced graphene oxide (rGO) nanoplates or functionalized rGO membrane is little affected by an intercalated fluid, and the interlayer spacing of 3.7 Å increases only to 4.4 Å in wetted state, in contrast to the graphene oxide (GO) membrane whose interlayer spacing increases from 9 Å to 13 Å in wetted state. When applied to ion separation, this membrane reduced the permeation rate of small ions such as K+ and Na+ by three orders of magnitude compared to the GO membrane.

  4. A retrospective examination of in-home educational visits to reduce childhood lead levels

    SciTech Connect

    Schultz, B. |; Pawel, D.; Murphy, A.

    1999-05-01

    A number of human health effects from lead are well known. However, the means for reducing lead exposure in children has been a subject of uncertainty. This paper presents results of a retrospective study of educational lead reduction interventions in Milwaukee, Wisconsin for children who had elevated blood lead levels between 20 and 24 {micro}g/dl. The study examined Milwaukee Health Department (MHD) records of baseline and follow-up blood lead measurements. A study group of children received an in-home educational visit by an MHD paraprofessional. The educational visits last about an hour and the importance of reducing lead exposure, nutritional suggestions, and dust clean-up practices and behavioral changes that can reduce lead exposure are discussed. After the intervention, the average observed blood lead level declined by 4.2 {micro}g/dl or by about 21%. A decline of 1.2 {micro}g/dl (6%) was also observed in a reference group of 226 children who did not receive an MHD in-home visit. The decline in the reference group may be partially due to education at the clinics taking the blood samples. The study group had a decline in blood lead levels 3.1 {micro}g/dl (15%) greater than the reference group, with the difference between groups being statistically significant with a P value of less than 0.001. Although significant exposures remained in most of the children studied, important lead reductions were observed with this relatively inexpensive and simple intervention. Education in the homes of families at risk for lead poisoning may be an effective component of programs to reduce blood lead levels.

  5. Low Level Laser Therapy Reduces the Development of Lung Inflammation Induced by Formaldehyde Exposure

    PubMed Central

    Miranda da Silva, Cristiane; Peres Leal, Mayara; Brochetti, Robson Alexandre; Braga, Tárcio; Vitoretti, Luana Beatriz; Saraiva Câmara, Niels Olsen; Damazo, Amílcar Sabino; Ligeiro-de-Oliveira, Ana Paula; Chavantes, Maria Cristina; Lino-dos-Santos-Franco, Adriana

    2015-01-01

    Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT) has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA), an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1%) or vehicle (distillated water) during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure). Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant. PMID:26569396

  6. Reducing Benzene and Cresol Levels in National Renewable Energy Laboratory's Pilot-Scale Biorefinergy Scrubber Water

    SciTech Connect

    Buzek, M.L.; Phillips, S.

    2004-01-01

    The Thermochemical Process Development Unit at the National Renewable Energy Laboratory converts biomass into energy by gasification or pyrolysis. The aqueous effluent generated in these processes must be disposed of as hazardous waste according to the Resource Conservation and Recovery Act because certain components exceed the regulatory concentration limit. Gas stripping of the scrubber water was investigated as a method of reducing benzene and cresol levels. A custom-designed packed-bed column was built and a half-factorial experimental design was implemented to determine the effects of gas flow rate, liquid flow rate, and column packing height on the final benzene concentration in the liquid. The experimental results show that packing height had a significant effect on final benzene concentration; gas flow rate and liquid flow rate had little effect. The effects of each design variable on final cresol concentration were not determined. Although the current column design did significantly reduce the benzene and cresol levels in the scrubber water, it did not reduce the concentrations below the regulatory limits. A full-factorial experimental design will be implemented with an increased packing height. Other variables, including column diameter and packing type, will be investigated to determine their effects on final benzene and cresol concentrations. Once the packed-bed column is determined to be effective in reducing contaminant concentrations below the regulatory limit, photocatalytic oxidation will be explored for remediating the benzene and cresol from the gas stream.

  7. Hepcidin bound to α2-macroglobulin reduces ferroportin-1 expression and enhances its activity at reducing serum iron levels.

    PubMed

    Huang, Michael Li-Hsuan; Austin, Christopher J D; Sari, Marie-Agnès; Rahmanto, Yohan Suryo; Ponka, Prem; Vyoral, Daniel; Richardson, Des R

    2013-08-30

    Hepcidin regulates iron metabolism by down-regulating ferroportin-1 (Fpn1). We demonstrated that hepcidin is complexed to the blood transport protein, α2-macroglobulin (α2M) (Peslova, G., Petrak, J., Kuzelova, K., Hrdy, I., Halada, P., Kuchel, P. W., Soe-Lin, S., Ponka, P., Sutak, R., Becker, E., Huang, M. L., Suryo Rahmanto, Y., Richardson, D. R., and Vyoral, D. (2009) Blood 113, 6225-6236). However, nothing is known about the mechanism of hepcidin binding to α2M or the effects of the α2M·hepcidin complex in vivo. We show that decreased Fpn1 expression can be mediated by hepcidin bound to native α2M and also, for the first time, hepcidin bound to methylamine-activated α2M (α2M-MA). Passage of high molecular weight α2M·hepcidin or α2M-MA·hepcidin complexes (≈725 kDa) through a Sephadex G-25 size exclusion column retained their ability to decrease Fpn1 expression. Further studies using ultrafiltration indicated that hepcidin binding to α2M and α2M-MA was labile, resulting in some release from the protein, and this may explain its urinary excretion. To determine whether α2M-MA·hepcidin is delivered to cells via the α2M receptor (Lrp1), we assessed α2M uptake and Fpn1 expression in Lrp1(-/-) and Lrp1(+/+) cells. Interestingly, α2M·hepcidin or α2M-MA·hepcidin demonstrated similar activities at decreasing Fpn1 expression in Lrp1(-/-) and Lrp1(+/+) cells, indicating that Lrp1 is not essential for Fpn1 regulation. In vivo, hepcidin bound to α2M or α2M-MA did not affect plasma clearance of α2M/α2M-MA. However, serum iron levels were reduced to a significantly greater extent in mice treated with α2M·hepcidin or α2M-MA·hepcidin relative to unbound hepcidin. This effect could be mediated by the ability of α2M or α2M-MA to retard kidney filtration of bound hepcidin, increasing its half-life. A model is proposed that suggests that unlike proteases, which are irreversibly bound to activated α2M, hepcidin remains labile and available to down

  8. Tinnitus is associated with reduced sound level tolerance in adolescents with normal audiograms and otoacoustic emissions

    PubMed Central

    Sanchez, Tanit Ganz; Moraes, Fernanda; Casseb, Juliana; Cota, Jaci; Freire, Katya; Roberts, Larry E.

    2016-01-01

    Recent neuroscience research suggests that tinnitus may reflect synaptic loss in the cochlea that does not express in the audiogram but leads to neural changes in auditory pathways that reduce sound level tolerance (SLT). Adolescents (N = 170) completed a questionnaire addressing their prior experience with tinnitus, potentially risky listening habits, and sensitivity to ordinary sounds, followed by psychoacoustic measurements in a sound booth. Among all adolescents 54.7% reported by questionnaire that they had previously experienced tinnitus, while 28.8% heard tinnitus in the booth. Psychoacoustic properties of tinnitus measured in the sound booth corresponded with those of chronic adult tinnitus sufferers. Neither hearing thresholds (≤15 dB HL to 16 kHz) nor otoacoustic emissions discriminated between adolescents reporting or not reporting tinnitus in the sound booth, but loudness discomfort levels (a psychoacoustic measure of SLT) did so, averaging 11.3 dB lower in adolescents experiencing tinnitus in the acoustic chamber. Although risky listening habits were near universal, the teenagers experiencing tinnitus and reduced SLT tended to be more protective of their hearing. Tinnitus and reduced SLT could be early indications of a vulnerability to hidden synaptic injury that is prevalent among adolescents and expressed following exposure to high level environmental sounds. PMID:27265722

  9. Tinnitus is associated with reduced sound level tolerance in adolescents with normal audiograms and otoacoustic emissions.

    PubMed

    Sanchez, Tanit Ganz; Moraes, Fernanda; Casseb, Juliana; Cota, Jaci; Freire, Katya; Roberts, Larry E

    2016-01-01

    Recent neuroscience research suggests that tinnitus may reflect synaptic loss in the cochlea that does not express in the audiogram but leads to neural changes in auditory pathways that reduce sound level tolerance (SLT). Adolescents (N = 170) completed a questionnaire addressing their prior experience with tinnitus, potentially risky listening habits, and sensitivity to ordinary sounds, followed by psychoacoustic measurements in a sound booth. Among all adolescents 54.7% reported by questionnaire that they had previously experienced tinnitus, while 28.8% heard tinnitus in the booth. Psychoacoustic properties of tinnitus measured in the sound booth corresponded with those of chronic adult tinnitus sufferers. Neither hearing thresholds (≤15 dB HL to 16 kHz) nor otoacoustic emissions discriminated between adolescents reporting or not reporting tinnitus in the sound booth, but loudness discomfort levels (a psychoacoustic measure of SLT) did so, averaging 11.3 dB lower in adolescents experiencing tinnitus in the acoustic chamber. Although risky listening habits were near universal, the teenagers experiencing tinnitus and reduced SLT tended to be more protective of their hearing. Tinnitus and reduced SLT could be early indications of a vulnerability to hidden synaptic injury that is prevalent among adolescents and expressed following exposure to high level environmental sounds. PMID:27265722

  10. Reduced activity-dependent protein levels in a mouse model of the fragile X premutation.

    PubMed

    von Leden, Ramona E; Curley, Lindsey C; Greenberg, Gian D; Hunsaker, Michael R; Willemsen, Rob; Berman, Robert F

    2014-03-01

    Environmental enrichment results in increased levels of Fmrp in brain and increased dendritic complexity. The present experiment evaluated activity-dependent increases in Fmrp levels in the motor cortex in response to training on a skilled forelimb reaching task in the CGG KI mouse model of the fragile X premutation. Fmrp, Arc, and c-Fos protein levels were quantified by Western blot in the contralateral motor cortex of mice following training to reach for sucrose pellets with a non-preferred paw and compared to levels in the ipsilateral motor cortex. After training, all mice showed increases in Fmrp, Arc, and c-Fos protein levels in the contralateral compared to the ipsilateral hemisphere; however, the increase in CGG KI mice was less than wildtype mice. Increases in Fmrp and Arc proteins scaled with learning, whereas this relationship was not observed with the c-Fos levels. These data suggest the possibility that reduced levels of activity-dependent proteins associated with synaptic plasticity such as Fmrp and Arc may contribute to the neurocognitive phenotype reported in the CGG KI mice and the fragile X premutation. PMID:24462720

  11. QMix® irrigant reduces lipopolysacharide (LPS) levels in an in vitro model

    PubMed Central

    GRÜNDLING, Grasiela Longhi; de MELO, Tiago André Fontoura; MONTAGNER, Francisco; SCARPARO, Roberta Kochenborger; VIER-PELISSER, Fabiana Vieira

    2015-01-01

    The presence of endotoxin inside the root canal has been associated with periapical inflammation, bone resorption and symptomatic conditions. Objectives To determine, in vitro, the effect of QMix® and other three root canal irrigants in reducing the endotoxin content in root canals. Material and Methods Root canals of single-rooted teeth were prepared. Samples were detoxified with Co-60 irradiation and inoculated with E. coli LPS (24 h, at 37°C). After that period, samples were divided into 4 groups, according to the irrigation solution tested: QMix®, 17% EDTA, 2% chlorhexidine solution (CHX), and 3% sodium hypochlorite (NaOCl). LPS quantification was determined by Limulus Amebocyte Lysate (LAL) assay. The initial counting of endotoxins for all samples, and the determination of LPS levels in non-contaminated teeth and in contaminated teeth exposed only to non-pyrogenic water, were used as controls. Results QMix® reduced LPS levels, with a median value of 1.11 endotoxins units (EU)/mL (p<0.001). NaOCl (25.50 EU/mL), chlorhexidine (44.10 EU/mL) and positive control group (26.80 EU/mL) samples had similar results. Higher levels were found with EDTA (176.00 EU/mL) when compared to positive control (p<0.001). There was no significant difference among EDTA, NaOCl and CHX groups. Negative control group (0.005 EU/mL) had statistically significant lower levels of endotoxins when compared to all test groups (p<0.001). Conclusion QMix® decreased LPS levels when compared to the other groups (p<0.001). 3% NaOCl, 2% CHX and 17% EDTA were not able to significantly reduce the root canal endotoxins load. PMID:26398517

  12. QMix® irrigant reduces lipopolysacharide (LPS) levels in an in vitro model.

    PubMed

    Gründling, Grasiela Longhi; Melo, Tiago André Fontoura de; Montagner, Francisco; Scarparo, Roberta Kochenborger; Vier-Pelisser, Fabiana Vieira

    2015-01-01

    The presence of endotoxin inside the root canal has been associated with periapical inflammation, bone resorption and symptomatic conditions.Objectives To determine, in vitro, the effect of QMix® and other three root canal irrigants in reducing the endotoxin content in root canals.Material and Methods Root canals of single-rooted teeth were prepared. Samples were detoxified with Co-60 irradiation and inoculated with E. coli LPS (24 h, at 37°C). After that period, samples were divided into 4 groups, according to the irrigation solution tested: QMix®, 17% EDTA, 2% chlorhexidine solution (CHX), and 3% sodium hypochlorite (NaOCl). LPS quantification was determined by Limulus Amebocyte Lysate (LAL) assay. The initial counting of endotoxins for all samples, and the determination of LPS levels in non-contaminated teeth and in contaminated teeth exposed only to non-pyrogenic water, were used as controls.Results QMix® reduced LPS levels, with a median value of 1.11 endotoxins units (EU)/mL (p<0.001). NaOCl (25.50 EU/mL), chlorhexidine (44.10 EU/mL) and positive control group (26.80 EU/mL) samples had similar results. Higher levels were found with EDTA (176.00 EU/mL) when compared to positive control (p<0.001). There was no significant difference among EDTA, NaOCl and CHX groups. Negative control group (0.005 EU/mL) had statistically significant lower levels of endotoxins when compared to all test groups (p<0.001).Conclusion QMix® decreased LPS levels when compared to the other groups (p<0.001). 3% NaOCl, 2% CHX and 17% EDTA were not able to significantly reduce the root canal endotoxins load. PMID:26398517

  13. Reduced striatal adenosine A2A receptor levels define a molecular subgroup in schizophrenia.

    PubMed

    Villar-Menéndez, Izaskun; Díaz-Sánchez, Sara; Blanch, Marta; Albasanz, José Luis; Pereira-Veiga, Thais; Monje, Alfonso; Planchat, Luis Maria; Ferrer, Isidre; Martín, Mairena; Barrachina, Marta

    2014-04-01

    Schizophrenia (SZ) is a mental disorder of unknown origin. Some scientific evidence seems to indicate that SZ is not a single disease entity, since there are patient groups with clear symptomatic, course and biomarker differences. SZ is characterized by a hyperdopaminergic state related to high dopamine D2 receptor activity. It has also been proposed that there is a hypoadenosynergic state. Adenosine is a nucleoside widely distributed in the organism with neuromodulative and neuroprotective activity in the central nervous system. In the brain, the most abundant adenosine receptors are A1R and A2AR. In the present report, we characterize the presence of both receptors in human postmortem putamens of patients suffering SZ with real time TaqMan PCR, western blotting and radioligand binding assay. We show that A1R levels remain unchanged with respect to age-matched controls, whereas nearly fifty percent of patients have reduced A2AR, at the transcriptional and translational levels. Moreover, we describe how DNA methylation plays a role in the pathological A2AR levels with the bisulfite-sequencing technique. In fact, an increase in 5-methylcytosine percentage in the 5' UTR region of ADORA2A was found in those SZ patients with reduced A2AR levels. Interestingly, there was a relationship between the A2A/β-actin ratio and motor disturbances as assessed with some items of the PANSS, AIMS and SAS scales. Therefore, there may be a subgroup of SZ patients with reduced striatal A2AR levels accompanied by an altered motor phenotype. PMID:24433848

  14. High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age.

    PubMed

    Mangialasche, Francesca; Kivipelto, Miia; Mecocci, Patrizia; Rizzuto, Debora; Palmer, Katie; Winblad, Bengt; Fratiglioni, Laura

    2010-01-01

    In this study we investigated the association between plasma levels of eight forms of vitamin E and incidence of Alzheimer's disease (AD) among oldest-old individuals in a population-based setting. A dementia-free sample of 232 subjects aged 80+ years, derived from the Kungsholmen Project, was followed-up to 6 years to detect incident AD. Plasma levels of vitamin E (alpha-, beta-, gamma, and delta-tocopherol; alpha-, beta-, gamma-, and delta-tocotrienol) were measured at baseline. Vitamin E forms-AD association was analyzed with Cox proportional hazard model after adjustment for several potential confounders. Subjects with plasma levels of total tocopherols, total tocotrienols, or total vitamin E in the highest tertile had a reduced risk of developing AD in comparison to persons in the lowest tertile. Multi-adjusted hazard ratios (HRs) and 95% confidence interval (CI) were 0.55 (0.32-0.94) for total tocopherols, 0.46 (0.23-0.92) for total tocotrienols, and 0.55 (0.32-0.94) for total vitamin E. When considering each vitamin E form, the risk of developing AD was reduced only in association with high plasma levels of beta-tocopherol (HR: 0.62, 95% CI 0.39-0.99), whereas alpha-tocopherol, alpha- tocotrienol, and beta-tocotrienol showed only a marginally significant effect in the multiadjusted model [HR (95% CI): alpha-tocopherol: 0.72 (0.48-1.09); alpha-tocotrienol: 0.70 (0.44-1.11); beta-tocotrienol: 0.69 (0.45-1.06)]. In conclusion, high plasma levels of vitamin E are associated with a reduced risk of AD in advanced age. The neuroprotective effect of vitamin E seems to be related to the combination of different forms, rather than to alpha-tocopherol alone, whose efficacy in interventions against AD is currently debated. PMID:20413888

  15. Critical tissue residue approach linking accumulated metals in aquatic insects to population and community-level effects

    USGS Publications Warehouse

    Schmidt, Travis S.; Clements, William H.; Zuellig, Robert E.; Mitchell, Katharine A.; Church, Stanley E.; Wanty, Richard B.; San Juan, Carma A.; Adams, Monique; Lamothe, Paul J.

    2011-01-01

    Whole body Zn concentrations in individuals (n = 825) from three aquatic insect taxa (mayflies Rhithrogena spp. and Drunella spp. and the caddisfly Arctopsyche grandis) were used to predict effects on populations and communities (n = 149 samples). Both mayflies accumulated significantly more Zn than the caddisfly. The presence/absence of Drunella spp. most reliably distinguished sites with low and high Zn concentrations; however, population densities of mayflies were more sensitive to increases in accumulated Zn. Critical tissue residues (634 (mu or u)g/g Zn for Drunella spp. and 267 (mu or u)g/g Zn for Rhithrogena spp.) caused a 20% reduction in maximum (90th quantile) mayfly densities. These critical tissue residues were associated with exposure to 7.0 and 3.9 (mu or u)g/L dissolved Zn for Drunella spp. and Rhithrogena spp., respectively. A threshold in a measure of taxonomic completeness (observed/expected) was observed at 5.4 (mu or u)g/L dissolved Zn. Dissolved Zn concentrations associated with critical tissue residues in mayflies were also associated with adverse effects in the aquatic community as a whole. These effects on populations and communities occurred at Zn concentrations below the U.S. EPA hardness-adjusted continuous chronic criterion.

  16. Modest amendment of sewage sludge biochar to reduce the accumulation of cadmium into rice(Oryza sativa L.): A field study.

    PubMed

    Zhang, Youchi; Chen, Tingting; Liao, Yongkai; Reid, Brian J; Chi, Haifeng; Hou, Yanwei; Cai, Chao

    2016-09-01

    Much research has considered the influence of biochars on the availability and phytoaccumulation of potentially toxic elements (PTEs) from soil. However, the vast majority of these studies use, what are arguably, unrealistic and unpractical amounts of biochar (10, 50 and even up to 100 t/ha). To offer a more realistic insight into the influence of biochar on PTE partitioning and phytoaccumulation, a field study, using modest rates of biochar application (1.5, 3.0 t/ha), was undertaken. Specifically, the research investigated the influence of sewage sludge biochar (SSBC) on the accumulation of Cd into rice (Oryza sativa L.) grown in Cd contaminated (0.82 ± 0.07 mg/kg) paddy soil. Results indicated, Cd concentrations in rice grains to significantly (p < 0.05) decrease from 1.35 ± 0.09 mg/kg in the control to 0.82 ± 0.07 mg/kg and 0.80 ± 0.21 mg/kg in the 1.5 t/ha and 3.0 t/ha treatments, respectively. Accordingly, the hazardous quotient (HQ) indices for Cd, associated with rice grain consumption, were also reduced by ∼40%. SSBC amendment significantly (p < 0.05) increased grain yields from 1.90 ± 0.08 g/plant in the control to 2.17 ± 0.30 g/plant and 3.40 ± 0.27 g/plant in the 1.5 t/ha and 3.0 t/ha treatments, respectively. Thus, the amendment of SSBC to contaminated paddy soils, even at low application rates, could be an effective approach to mitigate Cd accumulation into rice plants, to improve rice grain yields, and to thereby improve food security and protect public health. PMID:27368131

  17. APATHY AND APOE4 ARE ASSOCIATED WITH REDUCED BDNF LEVELS IN ALZHEIMER’S DISEASE

    PubMed Central

    Álvarez, Antón; Aleixandre, Manuel; Linares, Carlos; Masliah, Eliezer; Moessler, Herbert

    2016-01-01

    Reduced brain-derived neurotrophic factor (BDNF) signaling is considered as a pathogenic event in early Alzheimer’s disease (AD), but the influence of apathy and apolipoprotein E epsilon-4 allele (APOE4) on serum BDNF values was not previously investigated in AD. We evaluated serum BDNF levels in AD, amnestic mild cognitive impairment (MCI) and control subjects. Baseline BDNF levels were similar in AD, MCI and controls. AD patients having apathy showed lower BDNF values than patients without apathy (p<0.05). After correction for the influence of apathy, APOE4 carriers showed lower BDNF levels (p<0.01) and MMSE scores (p<0.01) than non-APOE4 carriers in the subgroup of AD females, but not in males. Significant (p<0.05) positive correlations between BDNF values and MMSE scores were only observed in subgroups of AD males and of AD patients without apathy. These results are showing the association of apathy and APOE4 with reduced serum BDNF levels in AD, and are suggesting that BDNF reductions might contribute to the worse cognitive performance exhibited by AD apathetic patients and female APOE4 carriers. PMID:25024337

  18. Preventing and reducing violence against women: innovation in community-level studies.

    PubMed

    Taft, Angela; Small, Rhonda

    2014-01-01

    Intimate partner violence is a serious global problem that damages the health and prosperity of individuals, their families, community, and society. WHO endorses an 'ecological model,' which states that there are multi-level intersecting factors enabling perpetration and victimization of violence. Intervention science to prevent or reduce the problem is in its infancy, and the few existing intervention studies have been targeted at the individual level. In a recent study published in BMC Medicine, Abramsky et al. bring innovation to the field, targeting their intervention trial "SASA!" in Kampala Uganda at all ecological levels, but particularly at the community level. Recruiting and training both male and female community leaders and activists who enabled group and media discussions, the authors focused on the beneficial and abusive detrimental uses of power rather than commencing with the central issue of gender inequality. SASA! successfully reduced community attitudes to tolerance of violence and inequality, men's sexual risk behaviors, and women's experience of physical violence. The study also improved the communities' response to victimized women. SASA! has promise for adaptation and replication in low, middle and high income countries. Please see related article: http://www.biomedcentral.com/1741-7015/12/122. PMID:25286152

  19. Helicopter far-field acoustic levels as a function of reduced rotor speeds

    NASA Technical Reports Server (NTRS)

    Mueller, Arnold W.; Lemasurier, Philip; Smith, Charles D.

    1990-01-01

    This paper will present far-field measured noise levels relative to tests conducted with a model S-76A helicopter. The project was designed to provide supplemental experimental flight data which may be used to further study reduced helicopter rotor speeds (and thus, advancing blade-tip Mach number) effects on far-field acoustic levels. The aircraft was flown in straight and level flight while operating with both the rotor speed and flight speed as test variables. The rotor speed was varied over the range of 107 percent of the main-rotor speed (NR) to 90 percent NR and with the forward flight speed varied over the range of 155 to 35 knots indicated air speed. These conditions produced a wide range of advancing blade-tip Mach numbers to which the noise data are related.

  20. Sulforaphane Restores Cellular Glutathione Levels and Reduces Chronic Periodontitis Neutrophil Hyperactivity In Vitro

    PubMed Central

    Dias, Irundika H. K.; Chapple, Ian L. C.; Milward, Mike; Grant, Melissa M.; Hill, Eric; Brown, James; Griffiths, Helen R.

    2013-01-01

    The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2. - by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients’ neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2. - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis. PMID:23826097

  1. Oral midazolam reduces cortisol levels during local anaesthesia in children: a randomised controlled trial.

    PubMed

    Gomes, Heloisa Sousa; Corrêa-Faria, Patrícia; Silva, Tarcília Aparecida; Paiva, Saul Martins; Costa, Paulo Sérgio Sucasas; Batista, Aline Carvalho; Costa, Luciane Rezende

    2015-01-01

    Little is known about whether midazolam sedation can reduce salivary cortisol levels and consequently influence children's behaviour during dental treatment. The aim of this study was to evaluate the effect of midazolam sedation on salivary cortisol and its correlation with children's behaviour during restorative dental treatment. Eighteen healthy children, aged two to five years, were randomly assigned to two dental treatment appointments, both with physical restraint: oral midazolam 1 mg/kg (MS) and placebo (PS). An observer assessed the children's behaviour (videos) using the Ohio State University Behavioral Rating Scale (OSUBRS). The children's saliva was collected just after waking up, on arrival at the dental school, 25 minutes after local anaesthesia, and 25 minutes after the end of the procedure. Salivary cortisol levels were determined using the enzyme-linked immunoabsorbent assay. The data were analysed by bivariate tests and multivariate analysis of variance (5% level). Salivary cortisol levels were lower in the MS group than in the PS group at the time of anaesthesia (p = 0.004), but did not vary during the appointment within sedation (p = 0.319) or placebo (p = 0.080) groups. Children's behaviour was negative most of the time and did not differ between MS and PS; however, the behaviour (OSUBRS) did not correlate with salivary cortisol levels. Oral midazolam is able to control salivary cortisol levels during dental treatment of pre-schoolers, which might not lead to better clinical behaviour. PMID:26892359

  2. Maintain levels of nicotine but reduce other smoke constituents: a formula for ''less-hazardous'' cigarettes

    SciTech Connect

    Robinson, J.C.; Young, J.C.; Rickert, W.S.

    1984-09-01

    Twenty-two volunteers who smoked more than 20 cigarettes with ''high'' nicotine yields (0.8 to 1.2 mg) per day participated in an 8-week study designed to test the hypothesis that smoking cigarettes with a constant level of nicotine but reduced deliveries of tar, carbon monoxide, and hydrogen cyanide leads to a decrease in smoke absorption. All subjects smoked their usual high-nicotine brand for the first 3 weeks (P1), and the absorption of smoke constituents was determined from levels of thiocyanate and cotinine in saliva and serum, levels of carbon monoxide in expired air, and levels of carboxyhemoglobin in the blood. During the final 5 weeks (P2), the treatment group (16 subjects) switched to the ''light'' version of their usual brands (similar yields of nicotine but with reduced yields of tar, carbon monoxide, and hydrogen cyanide); the control group (6 subjects) smoked their usual brands for the duration of the study. Average levels of cotinine for the subjects who switched during P2 were not significantly different from those of the control group as was expected. Slight reductions were noted in average expired-air carbon monoxide levels, blood carboxyhemoglobin, and saliva thiocyanate, but these reductions were smaller than anticipated based on brand characteristics. The results suggest that the ratio of smoke constituents is different when individuals, rather than machines, smoke cigarettes. Yields determined under subject-defined conditions are necessary in order to properly evaluate the role of nicotine in the design of ''less-hazardous'' cigarettes.

  3. Rice bran oil and oryzanol reduce plasma lipid and lipoprotein cholesterol concentrations and aortic cholesterol ester accumulation to a greater extent than ferulic acid in hypercholesterolemic hamsters.

    PubMed

    Wilson, Thomas A; Nicolosi, Robert J; Woolfrey, Benjamin; Kritchevsky, David

    2007-02-01

    plasma triglyceride concentrations compared to the control (-53% and -65%, respectively) and ferulic acid (-47% and -60%, respectively) diets. Hamsters fed the control and ferulic acid diets had significantly higher plasma vitamin E concentrations compared to the RBO (201% and 161%, respectively) and oryzanol (548% and 462%, respectively) diets; the ferulic acid and oryzanol diets had significantly lower plasma lipid hydroperoxide levels than the control (-57% and -46%, respectively) diet. The oryzanol-fed hamsters excreted significantly more coprostenol and cholesterol in their feces than the ferulic acid (127% and 120%, respectively) diet. The control diet had significantly greater aortic TC and FC accumulation compared to the RBO (115% and 89%, respectively), ferulic acid (48% and 58%, respectively) and the oryzanol (74% and 70%, respectively) diets. However, only the RBO and oryzanol diets had significantly lower aortic cholesterol ester accumulation compared to the control (-73% and -46%, respectively) diet. The present study suggests that at equal dietary levels, oryzanol has a greater effect on lowering plasma non-HDL-C levels and raising plasma HDL-C than ferulic acid, possibly through a greater extent to increase fecal excretion of cholesterol and its metabolites. However, ferulic acid may have a greater antioxidant capacity via its ability to maintain serum vitamin E levels compared to RBO and oryzanol. Thus, both oryzanol and ferulic acid may exert similar antiatherogenic properties, but through different mechanisms. PMID:16713234

  4. Comparison of Sulphate-reducing Bacterial Communities in Japanese Fish Farm Sediments with Different Levels of Organic Enrichment

    PubMed Central

    Kondo, Ryuji; Mori, Yumi; Sakami, Tomoko

    2012-01-01

    Fish farm sediments receive a large amount of organic matter from uneaten food and fecal material. This nutrient enrichment, or organic pollution, causes the accumulation of sulphide in the sediment from the action of sulphate-reducing bacteria (SRB). We investigated the effect of organic enrichment around coastal fish farms comparing the SRB community structure in these sediments. Sediment samples with different levels of organic pollution classified based upon the contents of acid-volatile sulphide and chemical oxygen demand were collected at three stations on the coast of western Japan. The SRB community composition was assessed using PCR amplification, cloning, sequencing and phylogenetic analysis of the dissimilatory sulphite reductase β-subunit gene (dsrB) fragments using directly extracted sediment DNA. Sequencing of the cloned PCR products of dsrB showed the existence of different SRB groups in the sediments. The majority of dsrB sequences were associated with the families Desulfobacteraceae and Desulfobulbaceae. Clones related to the phylum Firmicutes were also detected from all sediment samples. Statistical comparison of sequences revealed that community compositions of SRB from polluted sediments significantly differed from those of moderately polluted sediments and unpolluted sediments (LIBSHUFF, p<0.05), showing a different distribution of SRB in the fish farm sediments. There is evidence showing that the organic enrichment of sediments influences the composition of SRB communities in sediments at marine fish farms. PMID:22791053

  5. Betanin reduces the accumulation and cross-links of collagen in high-fructose-fed rat heart through inhibiting non-enzymatic glycation.

    PubMed

    Han, Junyan; Tan, Chang; Wang, Yiheng; Yang, Shaobin; Tan, Dehong

    2015-02-01

    We attempted to determine whether betanin (from natural pigments) that has antioxidant properties would be protective against fructose-induced diabetic cardiac fibrosis in Sprague-Dawley rats. Fructose water solution (30%) was accessed freely, and betanin (25 and 100 mg/kg/d) was administered by intra-gastric gavage continuously for 60 d. Rats were sacrificed after overnight fast. The rat blood and left ventricle were collected. In vitro antiglycation assay in bovine serum albumin/fructose system was also performed. In rats treated only with fructose, levels of plasma markers: glucose, insulin, HOMA and glycated hemoglobin rised, left ventricle collagen accumulated and cross-linked, profibrotic factor-transforming growth factor (TGF)-β1 and connective tissue growth factor (CTGF) protein expression increased, and soluble collagen decreased, compared with those in normal rats, showing fructose induces diabetic cardiac fibrosis. Treatment with betanin antagonized the changes of these parameters, demonstrating the antifibrotic role of betanin in the selected diabetic models. In further mechanistic study, betanin decreased protein glycation indicated by the decreased levels of protein glycation reactive intermediate (methylglyoxal), advanced glycation end product (N(ε)-(carboxymethyl) lysine) and receptors for advanced glycation end products (AGEs), antagonized oxidative stress and nuclear factor-κB activation elicited by fructose feeding, suggesting inhibition of glycation, oxidative stress and nuclear factor-κB activation may be involved in the antifibrotic mechanisms. Betanin also showed anitglycative effect in BSA/fructose system, which supported that anitglycation was involved in betanin's protective roles in vivo. Taken together, the potential for using betanin as an auxillary therapy for diabetic cardiomyopathy deserves to be explored further. PMID:25559852

  6. Nitrogen-deprivation elevates lipid levels in Symbiodinium spp. by lipid droplet accumulation: morphological and compositional analyses.

    PubMed

    Jiang, Pei-Luen; Pasaribu, Buntora; Chen, Chii-Shiarng

    2014-01-01

    Stable cnidarian-dinoflagellate (genus Symbiodinium) endosymbioses depend on the regulation of nutrient transport between Symbiodinium populations and their hosts. It has been previously shown that the host cytosol is a nitrogen-deficient environment for the intracellular Symbiodinium and may act to limit growth rates of symbionts during the symbiotic association. This study aimed to investigate the cell proliferation, as well as ultrastructural and lipid compositional changes, in free-living Symbiodinium spp. (clade B) upon nitrogen (N)-deprivation. The cell proliferation of the N-deprived cells decreased significantly. Furthermore, staining with a fluorescent probe, boron dipyrromethane 493/503 (BODIPY 493/503), indicated that lipid contents progressively accumulated in the N-deprived cells. Lipid analyses further showed that both triacylglycerol (TAG) and cholesterol ester (CE) were drastically enriched, with polyunsaturated fatty acids (PUFA; i.e., docosahexaenoic acid, heneicosapentaenoic acid, and oleic acid) became more abundant. Ultrastructural examinations showed that the increase in concentration of these lipid species was due to the accumulation of lipid droplets (LDs), a cellular feature that have previously shown to be pivotal in the maintenance of intact endosymbioses. Integrity of these stable LDs was maintained via electronegative repulsion and steric hindrance possibly provided by their surface proteins. Proteomic analyses of these LDs identified proteins putatively involved in lipid metabolism, signaling, stress response and energy metabolism. These results suggest that LDs production may be an adaptive response that enables Symbiodinium to maintain sufficient cellular energy stores for survival under the N-deprived conditions in the host cytoplasm. PMID:24475285

  7. Analysis of intracellular reducing levels in human hepatocytes on three-dimensional focusing microchip.

    PubMed

    Xu, Chunxiu; Cai, Longfei

    2014-02-01

    A novel three-dimensional hydrodynamic focusing microfluidic device integrated with high-throughput cell sampling and detection of intracellular contents is presented. It has a pivotal role in maintaining the reducing environment in cells. Intracellular reducing species such as vitamin C and glutathione in normal and tumor cells were labeled by a newly synthesized 2,2,6,6-tetramethyl-piperidine-1-oxyl-based fluorescent probe. Hepatocytes are adherent cells, which are prone to attaching to the channel surface. To avoid the attachment of cells on the channel surface, a single channel microchip with three sheath-flow channels located on both sides of and below the sampling channel was developed. Hydrostatic pressure generated by emptying the sample waste reservoir was used as driving force of fluid on the microchip. Owing to the difference between the liquid levels of the reservoirs, the labeled cells were three-dimensional hydrodynamically focused and transported from the sample reservoir to the sample waste reservoir. Hydrostatic pressure takes advantage of its ease of generation on a microfluidic chip without any external pressure pump, which drives three sheath-flow streams to constrain a sample flow stream into a narrow stream to avoid blockage of the sampling channel by adhered cells. The intracellular reducing levels of HepG2 cells and L02 cells were detected by home-built laser-induced fluorescence detector. The analysis throughput achieved in this microfluidic system was about 59-68 cells/min. PMID:23297173

  8. Antagonism of P2Y₁₂ reduces physiological thromboxane levels.

    PubMed

    Bhavaraju, Kamala; Georgakis, Alexander; Jin, Jianguo; Gartner, Theodore Kent; Tomiyama, Yoshiaki; Nurden, Alan; Nurden, Paquita; Kunapuli, Satya P

    2010-01-01

    Antiplatelet therapy for the management of patients with cardiovascular risks often includes a combination therapy of aspirin and clopidogrel, acting through inhibition of thromboxane generation and blockade of G(i)-coupled P2Y₁₂ receptor, respectively. We hypothesized that ADP acting through P2Y₁₂ regulates physiological thromboxane levels. The serum thromboxane levels in mice (n = 3) dosed with clopidogrel and prasugrel were decreased by 83.1 ± 5.3% and 94.26 ± 1.75% respectively compared to untreated mice. Pre-treatment of human blood (n = 3) ex vivo with active metabolites of clopidogrel or prasugrel led to a reduction in thromboxane levels to 16.3 ± 3.2% and 4.9 ± 0.8% respectively, compared to untreated human serum. We also evaluated serum thromboxane levels in P2Y receptor null mice (n = 4). Whereas serum thromboxane levels in P2Y₁ null mice were similar to those in wild type littermates, those in the P2Y₁₂ null mice were inhibited by 83.15 ± 3.8%. Finally, in a pilot study, serum thromboxane levels were reduced by 76.05 ± 8.41% in healthy human volunteers (n = 6) upon dosing with clopidogrel, compared to the levels before dosing. In conclusion, P2Y₁₂ antagonism alone can decrease physiological thromboxane levels. Thus, this study could pave way the for newer/modified treatment regimens for the management of patients with thrombotic complications who are allergic or non-responsive to aspirin. PMID:21067313

  9. Observations on dietary aluminum level, time duration exposure to dietary aluminum, and the influence of specific dietary blocking agents on tissue aluminum accumulation in the rat

    SciTech Connect

    Kettleson, K.C.A.

    1986-01-01

    Two experiments were conducted to observe the association of dietary aluminum (Al) with tissue Al accumulation. Other objectives included: to determine if alginic acid (AA) and pectin (P) in the diet could inhibit Al accumulation in tissues, and to relate time of exposure of dietary Al to Al tissue accumulation. The first experiment was conducted with a test diet feeding period of 35 days in a factorial arrangement of treatments with 24 rats, six rats per treatment. The dietary treatments were: groups 0 and 1, no added dietary Al (Al < 20 ppm) with or without 5% AA; groups 2 and 3, 400 ppm additional dietary Al with or without 5% AA. Kidney tissue analyzed by neutron activation showed no significant Al accumulation, or influence of the blocking agent. The second experiment was conducted over two time intervals (phase I with 24 rats for 28 days, and phase II with 26 rats for 56 days) and was done with 7 different diets. The diets included a control (basal with no added Al or blocking agent), the basal with 425 or 640 ppm Al added, with 5% AA or 5% P added to each Al test level. The Al source for both experiments was aluminum dibasic acetate. Tissues collected and pooled for analyses by inductively coupled plasma atomic emission spectroscopy included bone, brain, and kidney. The addition of 425 ppm Al to the diets stimulated body weight gain by about 10% relative to the controls. The blocking agents suppressed Al-induced weight gain, although AA stimulated feed intake (P < 0.05). Trends in Al accumulation appeared to occur in bone and brain tissues associated with dietary Al; but independent of blocking agents and independent of time exposure to the dietary Al.

  10. Biota-sediment accumulation factor (BSAF), bioaccumulation factor (BAF), and contaminant levels in prey fish to indicate the extent of PAHs and OCPs contamination in eggs of waterbirds.

    PubMed

    Kwok, C K; Liang, Y; Leung, S Y; Wang, H; Dong, Y H; Young, L; Giesy, J P; Wong, M H

    2013-12-01

    Samples of pond sediment, fish, and shrimp were collected from the Ramsar site at Mai Po marshes, Hong Kong (south China), and samples of pond sediment, fish, and shrimp, as well as eggs of water birds (Chinese Pond Herons (Ardeola bacchus) and Little Egrets (Egretta garzetta)), were collected from two smaller wetland sites at Jiangsu Province (mid-China), between 2004 and 2007. Accumulation levels of polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in the biota were used to calculate biota-sediment accumulation factor (BSAF) and bioaccumulation factor (BAF). For fish and shrimp, BSAFs of OCPs (3.8-56) were greater than those of PAHs (0.12-6.3). BSAFs and BAFs of 11-79 and 4-34, respectively, were registered for OCPs in eggs of the birds and were greater than those for PAHs (0.11-1.5 and 0.02-1.3, respectively). Assuming that fish were the main prey of the birds, greater bioaccumulation of OCPs was detected for both bird species (BAFs =4.5-34), while accumulation of PAHs was only detected in Little Egret (BAF=1.3). A significant linear relationship (p<0.01) was observed between concentrations of OCPs in bird eggs and in the prey fish. The present study provides a new possibility of using OCP levels detected in prey fish to predict the extent of OCPs contamination in eggs of waterbirds including the endangered species, as a noninvasive method. PMID:23702571

  11. Global 5-Hydroxymethylcytosine Levels Are Profoundly Reduced in Multiple Genitourinary Malignancies

    PubMed Central

    Munari, Enrico; Chaux, Alcides; Vaghasia, Ajay M.; Taheri, Diana; Karram, Sarah; Bezerra, Stephania M.; Gonzalez Roibon, Nilda; Nelson, William G.; Yegnasubramanian, Srinivasan; Netto, George J.; Haffner, Michael C.

    2016-01-01

    Solid tumors are characterized by a plethora of epigenetic changes. In particular, patterns methylation of cytosines at the 5-position (5mC) in the context of CpGs are frequently altered in tumors. Recent evidence suggests that 5mC can get converted to 5-hydroxylmethylcytosine (5hmC) in an enzymatic process involving ten eleven translocation (TET) protein family members, and this process appears to be important in facilitating plasticity of cytosine methylation. Here we evaluated the global levels of 5hmC using a validated immunohistochemical staining method in a large series of clear cell renal cell carcinoma (n = 111), urothelial cell carcinoma (n = 55) and testicular germ cell tumors (n = 84) and matched adjacent benign tissues. Whereas tumor-adjacent benign tissues were mostly characterized by high levels of 5hmC, renal cell carcinoma and urothelial cell carcinoma showed dramatically reduced staining for 5hmC. 5hmC levels were low in both primary tumors and metastases of clear cell renal cell carcinoma and showed no association with disease outcomes. In normal testis, robust 5hmC staining was only observed in stroma and Sertoli cells. Seminoma showed greatly reduced 5hmC immunolabeling, whereas differentiated teratoma, embryonal and yolk sack tumors exhibited high 5hmC levels. The substantial tumor specific loss of 5hmC, particularly in clear cell renal cell carcinoma and urothelial cell carcinoma, suggests that alterations in pathways involved in establishing and maintaining 5hmC levels might be very common in cancer and could potentially be exploited for diagnosis and treatment. PMID:26785262

  12. CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice.

    PubMed

    Wolf, Risa M; Lei, Xia; Yang, Zhi-Chun; Nyandjo, Maeva; Tan, Stefanie Y; Wong, G William

    2016-03-01

    C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of-function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high-fat diet (HFD). Regardless of diet, no differences were observed in adiposity, food intake, metabolic rate, energy expenditure, or physical activity levels between wild-type (WT) and Ctrp3-knockout (KO) animals of either sex. Contrary to expectations, loss of CTRP3 in LFD- or HFD-fed male and female mice also had minimal or no impact on whole body glucose metabolism, insulin sensitivity, and fasting-induced hepatic gluconeogenesis. Unexpectedly, the liver sizes of HFD-fed Ctrp3-KO male mice were markedly reduced despite a modest increase in triglyceride content. Furthermore, liver expression of fat oxidation genes was upregulated in the Ctrp3-KO mice. Whereas the liver and adipose expression of profibrotic TGFβ1, as well as its serum levels, was suppressed in HFD-fed KO mice, circulating proinflammatory IL-6 levels were markedly increased; these changes, however, were insufficient to affect systemic metabolic outcome. We conclude that, although it is dispensable for physiological control of energy balance, CTRP3 plays a previously unsuspected role in modulating liver size and circulating cytokine levels in response to obesity. PMID:26670485

  13. Reduced alpha(2)-adrenergic sensitivity of subcutaneous abdominal adipocytes as a modulator of fasting and postprandial triglyceride levels in men.

    PubMed

    Imbeault, P; Couillard, C; Tremblay, A; Després, J P; Mauriège, P

    2000-09-01

    such as body weight, percent body fat, visceral and subcutaneous abdominal adipose tissue accumulation measured by CT, as well as subcutaneous abdominal fat cell alpha(2)-adrenoceptor sensitivity. Taken together, these results indicate that a reduced antilipolytic sensitivity of subcutaneous abdominal adipocytes to catecholamines may increase fasting TG levels, which in turn play a role in the etiology of an impaired postprandial TRL clearance in men. PMID:10974043

  14. ALA Inhibits ABA-induced Stomatal Closure via Reducing H2O2 and Ca(2+) Levels in Guard Cells.

    PubMed

    An, Yuyan; Liu, Longbo; Chen, Linghui; Wang, Liangju

    2016-01-01

    5-Aminolevulinic acid (ALA), a newly proved natural plant growth regulator, is well known to improve plant photosynthesis under both normal and stressful conditions. However, its underlying mechanism remains largely unknown. Stomatal closure is one of the major limiting factors for photosynthesis and abscisic acid (ABA) is the most important hormone in provoking stomatal closing. Here, we showed that ALA significantly inhibited ABA-induced stomatal closure using wild-type and ALA-overproducing transgenic Arabidopsis (YHem1). We found that ALA decreased ABA-induced H2O2 and cytosolic Ca(2+) accumulation in guard cells with stomatal bioassay, laser-scanning confocal microscopy and pharmacological methods. The inhibitory effect of ALA on ABA-induced stomatal closure was similar to that of AsA (an important reducing substrate for H2O2 removal), CAT (a H2O2-scavenging enzyme), DPI (an inhibitor of the H2O2-generating NADPH oxidase), EGTA (a Ca-chelating agent), and AlCl3 (an inhibitor of calcium channel). Furthermore, ALA inhibited exogenous H2O2- or Ca(2+)-induced stomatal closure. Taken together, we conclude that ALA inhibits ABA-induced stomatal closure via reducing H2O2, probably by scavenging, and Ca(2+) levels in guard cells. Moreover, the inhibitive effect of ALA on ABA-induced stomatal closure was further confirmed in the whole plant. Finally, we demonstrated that ALA inhibits stomatal closing, but significantly improves plant drought tolerance. Our results provide valuable information for the promotion of plant production and development of a sustainable low-carbon society. PMID:27148309

  15. ALA Inhibits ABA-induced Stomatal Closure via Reducing H2O2 and Ca2+ Levels in Guard Cells

    PubMed Central

    An, Yuyan; Liu, Longbo; Chen, Linghui; Wang, Liangju

    2016-01-01

    5-Aminolevulinic acid (ALA), a newly proved natural plant growth regulator, is well known to improve plant photosynthesis under both normal and stressful conditions. However, its underlying mechanism remains largely unknown. Stomatal closure is one of the major limiting factors for photosynthesis and abscisic acid (ABA) is the most important hormone in provoking stomatal closing. Here, we showed that ALA significantly inhibited ABA-induced stomatal closure using wild-type and ALA-overproducing transgenic Arabidopsis (YHem1). We found that ALA decreased ABA-induced H2O2 and cytosolic Ca2+ accumulation in guard cells with stomatal bioassay, laser-scanning confocal microscopy and pharmacological methods. The inhibitory effect of ALA on ABA-induced stomatal closure was similar to that of AsA (an important reducing substrate for H2O2 removal), CAT (a H2O2-scavenging enzyme), DPI (an inhibitor of the H2O2-generating NADPH oxidase), EGTA (a Ca-chelating agent), and AlCl3 (an inhibitor of calcium channel). Furthermore, ALA inhibited exogenous H2O2- or Ca2+-induced stomatal closure. Taken together, we conclude that ALA inhibits ABA-induced stomatal closure via reducing H2O2, probably by scavenging, and Ca2+ levels in guard cells. Moreover, the inhibitive effect of ALA on ABA-induced stomatal closure was further confirmed in the whole plant. Finally, we demonstrated that ALA inhibits stomatal closing, but significantly improves plant drought tolerance. Our results provide valuable information for the promotion of plant production and development of a sustainable low-carbon society. PMID:27148309

  16. Experimentally elevated levels of testosterone at independence reduce fitness in a territorial bird.

    PubMed

    Martínez-Padilla, J; Pérez-Rodríguez, L; Mougeot, F; Ludwig, S C; Redpath, S M

    2014-04-01

    Environmental conditions and individual strategies in early life may have a profound effect on fitness. A critical moment in the life of an organism occurs when an individual reaches independence and stops receiving benefits from its relatives. Understanding the consequences of individual strategies at the time of independence requires quantification of their fitness effects. We explored this period in the Red Grouse (Lagopus lagopus scoticus). In this system, testosterone and parasite (Trichostrongylus tenuis) levels are known to influence survival and reproduction, the two key components of individual fitness. We experimentally and simultaneously manipulated testosterone and parasites at three levels (high, intermediate, and control levels for both factors) in 195 young males in five populations using a factorial experimental design. We explored the effects of our treatments on fitness by monitoring reproduction and survival throughout the life of all males and estimating lambda(ind), a rate-sensitive index of fitness. Parasite challenges increased the number of worms with a time lag, as previously found. However, we did not find significant effects of parasite manipulations on fitness, possibly because parasite abundance did not increase to harmful levels. Our hormone manipulation was successful at increasing testosterone at three different levels. Such increases in hormone levels decreased overall fitness. This was caused by reduced offspring production in the first breeding attempt rather than by any effect of the treatment on bird survival. Our results highlight that investing in high testosterone levels at independence, a strategy that might enhance short-term recruitment probability in territorial species such as Red Grouse, has a fitness cost, and can influence the resolution of the trade-off between reproduction and survival later in life. PMID:24933821

  17. Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

    SciTech Connect

    Basavarajappa, Mallikarjuna S. Craig, Zelieann R. Hernandez-Ochoa, Isabel Paulose, Tessie Leslie, Traci C. Flaws, Jodi A.

    2011-06-15

    The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E{sub 2}) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E{sub 2} metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E{sub 2}, testosterone, androstenedione, and progesterone (P{sub 4}) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17{beta}-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17{alpha}-hydroxylase/17,20-lyase (Cyp17a1), 3{beta} hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels. - Highlights: > MXC inhibits steroidogenesis > MXC inhibits steroidogenic enzymes > MXC induces metabolic enzymes

  18. Hypoxia-inducible factor 1 mediates hypoxia-induced cardiomyocyte lipid accumulation by reducing the DNA binding activity of peroxisome proliferator-activated receptor {alpha}/retinoid X receptor

    SciTech Connect

    Belanger, Adam J.; Luo Zhengyu; Vincent, Karen A.; Akita, Geoffrey Y.; Cheng, Seng H.; Gregory, Richard J.; Jiang Canwen

    2007-12-21

    In response to cellular hypoxia, cardiomyocytes adapt to consume less oxygen by shifting ATP production from mitochondrial fatty acid {beta}-oxidation to glycolysis. The transcriptional activation of glucose transporters and glycolytic enzymes by hypoxia is mediated by hypoxia-inducible factor 1 (HIF-1). In this study, we examined whether HIF-1 was involved in the suppression of mitochondrial fatty acid {beta}-oxidation in hypoxic cardiomyocytes. We showed that either hypoxia or adenovirus-mediated expression of a constitutively stable hybrid form (HIF-1{alpha}/VP16) suppressed mitochondrial fatty acid metabolism, as indicated by an accumulation of intracellular neutral lipid. Both treatments also reduced the mRNA levels of muscle carnitine palmitoyltransferase I which catalyzes the rate-limiting step in the mitochondrial import of fatty acids for {beta}-oxidation. Furthermore, adenovirus-mediated expression of HIF-1{alpha}/VP16 in cardiomyocytes under normoxic conditions also mimicked the reduction in the DNA binding activity of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha})/retinoid X receptor (RXR), in the presence or absence of a PPAR{alpha} ligand. These results suggest that HIF-1 may be involved in hypoxia-induced suppression of fatty acid metabolism in cardiomyocytes by reducing the DNA binding activity of PPAR{alpha}/RXR.

  19. Glycine Betaine, Carnitine, and Choline Enhance Salinity Tolerance and Prevent the Accumulation of Sodium to a Level Inhibiting Growth of Tetragenococcus halophila

    PubMed Central

    Robert, Hervé; Le Marrec, Claire; Blanco, Carlos; Jebbar, Mohamed

    2000-01-01

    Natural-abundance 13C-nuclear magnetic resonance was used to probe the intracellular organic solute content of the moderately halophilic bacterium Tetragenococcus halophila. When grown in complex growth media supplemented or not with NaCl, T. halophila accumulates glycine betaine and carnitine. Unlike other moderate halophiles, T. halophila was not able to produce potent osmoprotectants (such as ectoines and glycine betaine) through de novo synthesis when cultured in defined medium under hyperosmotic constraint. Addition of 2 mM carnitine, glycine betaine, or choline to defined medium improved growth parameters, not only at high salinity (up to 2.5 M NaCl) but also in media lacking NaCl. These compounds were taken up when available in the surrounding medium. The transport activity occurred at low and high salinities and seems to be constitutive. Glycine betaine and carnitine were accumulated by T. halophila in an unmodified form, while exogenously provided choline led to an intracellular accumulation of glycine betaine. This is the first evidence of the existence of a choline-glycine betaine pathway in a lactic acid bacterium. An assay showed that the compatible solutes strikingly repressed the accumulation of glutamate and slightly increased the intracellular potassium level only at high salinity. Interestingly, osmoprotectant-treated cells were able to maintain the intracellular sodium concentration at a relatively constant level (200 to 300 nmol/mg [dry weight]), independent of the NaCl concentration of the medium. In contrast, in the absence of osmoprotectant, the intracellular sodium content increased sharply from 200 to 2,060 nmol/mg (dry weight) when the salinity of the medium was raised from 1 to 2 M. Indeed, the imported compatible solutes play an actual role in regulating the intracellular Na+ content and confer a much higher salt tolerance to T. halophila. PMID:10653711

  20. Improving patients' sleep: reducing light and noise levels on wards at night.

    PubMed

    Hewart, Carol; Fethney, Loveday

    2016-02-01

    There is much research concerning the psychological and physical effects of sleep deprivation on patients in healthcare systems, yet interrupted sleep on hospital wards at night remains a problem. Staff at Plymouth Hospitals NHS Trust, Devon, wanted to identify the factors that prevent patients from sleeping well at night. Two audits were carried out, between April and August 2015, to assess noise and light levels on wards at night, and to engage nurses in ways of reducing these. A number of recommendations were made based on the audit findings, many of which have been put into practice. PMID:26938911

  1. 1α,25-Dihydroxyvitamin D3 reduces cerebral amyloid-β accumulation and improves cognition in mouse models of Alzheimer's disease.

    PubMed

    Durk, Matthew R; Han, Kyung; Chow, Edwin C Y; Ahrens, Rosemary; Henderson, Jeffrey T; Fraser, Paul E; Pang, K Sandy

    2014-05-21

    We demonstrate a role of the vitamin D receptor (VDR) in reducing cerebral soluble and insoluble amyloid-β (Aβ) peptides. Short-term treatment of two human amyloid precursor protein-expressing models, Tg2576 and TgCRND8 mice, with 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], the endogenous active ligand of VDR, resulted in higher brain P-glycoprotein (P-gp) and lower soluble Aβ levels, effects negated with coadministration of elacridar, a P-gp inhibitor. Long-term treatment of TgCRND8 mice with 1,25(OH)2D3 during the period of plaque formation reduced soluble and insoluble plaque-associated Aβ, particularly in the hippocampus in which the VDR is abundant and P-gp induction is greatest after 1,25(OH)2D3 treatment, and this led to improved conditioned fear memory. In mice fed a vitamin D-deficient diet, lower cerebral P-gp expression was observed, but levels were restored on replenishment with VDR ligands. The composite data suggest that the VDR is an important therapeutic target in the prevention and treatment of Alzheimer's disease. PMID:24849345

  2. Phosphorus speciation by coupled HPLC-ICPMS: low level determination of reduced phosphorus in natural materials

    NASA Astrophysics Data System (ADS)

    Atlas, Zachary; Pasek, Matthew; Sampson, Jacqueline

    2015-04-01

    Phosphorus is a geologically important minor element in the Earth's crust commonly found as relatively insoluble apatite. This constraint causes phosphorus to be a key limiting nutrient in biologic processes. Despite this, phosphorus plays a direct role in the formation of DNA, RNA and other cellular materials. Recent works suggest that since reduced phosphorus is considerably more soluble than oxidized phosphorus that it was integrally involved in the development of life on the early Earth and may continue to play a role in biologic productivity to this day. This work examines a new method for quantification and identification of reduced phosphorus as well as applications to the speciation of organo-phosphates separated by coupled HPLC - ICP-MS. We show that reduced phosphorus species (P1+, P3+ and P5+) are cleanly separated in the HPLC and coupled with the ICPMS reaction cell, using oxygen as a reaction gas to effectively convert elemental P to P-O. Analysis at M/Z= 47 producing lower background and flatter baseline chromatography than analyses performed at M/Z = 31. Results suggest very low detection limits (0.05 μM) for P species analyzed as P-O. Additionally we show that this technique has potential to speciate at least 5 other forms of phosphorus compounds. We verified the efficacy of method on numerous materials including leached Archean rocks, suburban retention pond waters, blood and urine samples and most samples show small but detectible levels of reduced phosphorus and or organo-phaospates. This finding in nearly all substances analyzed supports the assumption that the redox processing of phosphorus has played a significant role throughout the history of the Earth and it's presence in the present environment is nearly ubiquitous with the reduced oxidation state phosphorus compounds, phosphite and hypophosphite, potentially acting as significant constituents in the anaerobic environment.

  3. Reducing greenhouse gas emissions, water use, and grain arsenic levels in rice systems.

    PubMed

    Linquist, Bruce A; Anders, Merle M; Adviento-Borbe, Maria Arlene A; Chaney, Rufus L; Nalley, L Lanier; da Rosa, Eliete F F; van Kessel, Chris

    2015-01-01

    Agriculture is faced with the challenge of providing healthy food for a growing population at minimal environmental cost. Rice (Oryza sativa), the staple crop for the largest number of people on earth, is grown under flooded soil conditions and uses more water and has higher greenhouse gas (GHG) emissions than most crops. The objective of this study was to test the hypothesis that alternate wetting and drying (AWD--flooding the soil and then allowing to dry down before being reflooded) water management practices will maintain grain yields and concurrently reduce water use, greenhouse gas emissions and arsenic (As) levels in rice. Various treatments ranging in frequency and duration of AWD practices were evaluated at three locations over 2 years. Relative to the flooded control treatment and depending on the AWD treatment, yields were reduced by <1-13%; water-use efficiency was improved by 18-63%, global warming potential (GWP of CH4 and N2 O emissions) reduced by 45-90%, and grain As concentrations reduced by up to 64%. In general, as the severity of AWD increased by allowing the soil to dry out more between flood events, yields declined while the other benefits increased. The reduction in GWP was mostly attributed to a reduction in CH4 emissions as changes in N2 O emissions were minimal among treatments. When AWD was practiced early in the growing season followed by flooding for remainder of season, similar yields as the flooded control were obtained but reduced water use (18%), GWP (45%) and yield-scaled GWP (45%); although grain As concentrations were similar or higher. This highlights that multiple environmental benefits can be realized without sacrificing yield but there may be trade-offs to consider. Importantly, adoption of these practices will require that they are economically attractive and can be adapted to field scales. PMID:25099317

  4. Rising sea levels will reduce extreme temperature variations in tide-dominated reef habitats

    PubMed Central

    Lowe, Ryan Joseph; Pivan, Xavier; Falter, James; Symonds, Graham; Gruber, Renee

    2016-01-01

    Temperatures within shallow reefs often differ substantially from those in the surrounding ocean; therefore, predicting future patterns of thermal stresses and bleaching at the scale of reefs depends on accurately predicting reef heat budgets. We present a new framework for quantifying how tidal and solar heating cycles interact with reef morphology to control diurnal temperature extremes within shallow, tidally forced reefs. Using data from northwestern Australia, we construct a heat budget model to investigate how frequency differences between the dominant lunar semidiurnal tide and diurnal solar cycle drive ~15-day modulations in diurnal temperature extremes. The model is extended to show how reefs with tidal amplitudes comparable to their depth, relative to mean sea level, tend to experience the largest temperature extremes globally. As a consequence, we reveal how even a modest sea level rise can substantially reduce temperature extremes within tide-dominated reefs, thereby partially offsetting the local effects of future ocean warming. PMID:27540589

  5. Rising sea levels will reduce extreme temperature variations in tide-dominated reef habitats.

    PubMed

    Lowe, Ryan Joseph; Pivan, Xavier; Falter, James; Symonds, Graham; Gruber, Renee

    2016-08-01

    Temperatures within shallow reefs often differ substantially from those in the surrounding ocean; therefore, predicting future patterns of thermal stresses and bleaching at the scale of reefs depends on accurately predicting reef heat budgets. We present a new framework for quantifying how tidal and solar heating cycles interact with reef morphology to control diurnal temperature extremes within shallow, tidally forced reefs. Using data from northwestern Australia, we construct a heat budget model to investigate how frequency differences between the dominant lunar semidiurnal tide and diurnal solar cycle drive ~15-day modulations in diurnal temperature extremes. The model is extended to show how reefs with tidal amplitudes comparable to their depth, relative to mean sea level, tend to experience the largest temperature extremes globally. As a consequence, we reveal how even a modest sea level rise can substantially reduce temperature extremes within tide-dominated reefs, thereby partially offsetting the local effects of future ocean warming. PMID:27540589

  6. Benthic invertebrate metals exposure, accumulation, and community-level effects downstream from a hard-rock mine site

    SciTech Connect

    Beltman, D.J.; Lipton, J.; Cacela, D.; Clements, W.H.

    1999-02-01

    This study quantitatively evaluated the relationships among As, Co, and Cu concentrations in exposure media (surface water, sediment, and aufwuchs), As, Co, and Cu concentrations in aquatic macroinvertebrates, and invertebrate community structure in a mine-affected stream. Concentrations of As, Co, and Cu were significantly elevated in both exposure media and invertebrate tissue downstream from the mine. Copper in invertebrates was significantly correlated only with Cu in aufwuchs, and Co in invertebrates was significantly correlated only with dissolved Co in water, suggesting different mechanisms of invertebrate accumulation for these two metals. The invertebrate community was severely affected downstream from the mine, with a loss of metals-sensitive species and reductions in both total biomass and number of species. Total abundance was not affected. Principal components analysis was performed on the invertebrate community data to develop a simplified description of community response to mine inputs. Based on this index, metal concentrations in invertebrates were poor predictors of community structure. Copper concentrations in water, combined with an estimate of invertebrate drift from clean tributaries, were statistically significant predictors of community structure.

  7. Reduced mRNA expression levels of MBD2 and MBD3 in gastric carcinogenesis.

    PubMed

    Pontes, Thaís Brilhante; Chen, Elizabeth Suchi; Gigek, Carolina Oliveira; Calcagno, Danielle Queiroz; Wisnieski, Fernanda; Leal, Mariana Ferreira; Demachki, Samia; Assumpção, Paulo Pimentel; Artigiani, Ricardo; Lourenço, Laércio Gomes; Burbano, Rommel Rodriguez; Arruda Cardoso Smith, Marília

    2014-04-01

    Aberrant methylation has been reported in several neoplasias, including gastric cancer. The methyl-CpG-binding domain (MBD) family proteins have been implicated in the chromatin remodeling process, leading to the modulation of gene expression. To evaluate the role of MBD2 and MBD3 in gastric carcinogenesis and the possible association with clinicopathological characteristics, we assessed the mRNA levels and promoter methylation patterns in gastric tissues. In this study, MBD2 and MBD3 mRNA levels were determined by RT-qPCR in 28 neoplastic and adjacent nonneoplastic and 27 gastritis and non-gastritis samples. The promoter methylation status was determined by bisulfite sequencing, and we found reduced MBD2 and MBD3 levels in the neoplastic samples compared with the other groups. Moreover, a strong correlation between the MBD2 and MBD3 expression levels was observed in each set of paired samples. Our data also showed that the neoplastic tissues exhibited higher MBD2 promoter methylation than the other groups. Interestingly, the non-gastritis group was the only one with positive methylation in the MBD3 promoter region. Furthermore, a weak correlation between gene expression and methylation was observed. Therefore, our data suggest that DNA methylation plays a minor role in the regulation of MBD2 and MBD3 expression, and the presence of methylation at CpGs that interact with transcription factor complexes might also be involved in the modulation of these genes. Moreover, reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis, and thus, further investigations about these genes should be conducted for a better understanding of the role of abnormal methylation involved in this neoplasia. PMID:24338710

  8. Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows

    PubMed Central

    Noyes, Pamela D.; Lema, Sean C.; Macaulay, Laura J.; Douglas, Nora K.; Stapleton, Heather M.

    2013-01-01

    Polybrominated diphenyl ether (PBDE) flame retardants have been shown to disrupt thyroid hormone regulation, neurodevelopment, and reproduction in some animals. However, effects of the most heavily used PBDE, decabromodiphenyl ether (BDE-209), on thyroid functioning remain unclear. This study examined low-dose effects of BDE-209 on thyroid hormone levels and signaling in fathead minnows. Adult males received dietary exposures of BDE-209 at a low dose (~3 ng/g bw-day) and high dose (~300 ng/g bw-day) for 28 days followed by a 14-day depuration to evaluate recovery. Compared to controls, fish exposed to the low dose for 28 days experienced a 53% and 46% decline in circulating total thyroxine (TT4) and 3,5,3'-triiodothyronine (TT3), respectively, while TT4 and TT3 deficits at the high dose were 59% and 62%. Brain deiodinase activity (T4-ORD) was reduced by ~65% at both doses. BDE-209 elevated the relative mRNA expression of genes encoding deiodinases, nuclear thyroid receptors, and membrane transporters in the brain and liver in patterns that varied with time and dose, likely in compensation to hypothyroidism. Declines in the gonadal-somatic index (GSI) and increased mortality were also measured. Effects at the low dose were consistent with the high dose, suggesting non-linear relationships between BDE-209 exposures and thyroid dysfunction. PMID:23899252

  9. The Associations Between Smoking Habits and Serum Triglyceride or Hemoglobin A1c Levels Differ According to Visceral Fat Accumulation

    PubMed Central

    Koda, Michiko; Kitamura, Itsuko; Okura, Tomohiro; Otsuka, Rei; Ando, Fujiko; Shimokata, Hiroshi

    2016-01-01

    Background Whether smokers and former smokers have worse lipid profiles or glucose levels than non-smokers remains unclear. Methods The subjects were 1152 Japanese males aged 42 to 81 years. The subjects were divided according to their smoking habits (nonsmokers, former smokers, and current smokers) and their visceral fat area (VFA) (<100 cm2 and ≥100 cm2). Results The serum triglyceride (TG) levels of 835 males were assessed. In the VFA ≥100 cm2 group, a significantly greater proportion of current smokers (47.3%) exhibited TG levels of ≥150 mg/dL compared with former smokers (36.4%) and non-smokers (18.8%). The difference in TG level distribution between former smokers and non-smokers was also significant. However, among the subjects with VFA of <100 cm2, the TG levels of the three smoking habit groups did not differ. The serum hemoglobin A1c (HbA1c) levels of 877 males were also assessed. In the VFA <100 cm2 group, significantly higher proportions of current smokers (17.9%) and former smokers (14.9%) demonstrated HbA1c levels of ≥5.6% compared with non-smokers (6.3%). In contrast, in the VFA ≥100 cm2 group, significantly fewer former smokers displayed HbA1c levels of ≥5.6% compared with non-smokers and current smokers. Furthermore, the interaction between smoking habits and VFA was associated with the subjects’ TG and HbA1c concentrations, and the associations of TG and HbA1c concentrations and smoking habits varied according to VFA. Conclusions Both smoking habits and VFA exhibited associations with TG and HbA1c concentrations. The associations between smoking habits and these parameters differed according to VFA. PMID:26616395

  10. Leveling coatings for reducing the atomic oxygen defect density in protected graphite fiber epoxy composites

    NASA Astrophysics Data System (ADS)

    Jaworske, D. A.; Degroh, Kim K.; Podojil, G.; McCollum, T.; Anzic, J.

    1992-11-01

    Pinholes or other defect sites in a protective oxide coating provide pathways for atomic oxygen in low Earth orbit to reach underlying material. One concept of enhancing the lifetime of materials in low Earth orbit is to apply a leveling coating to the material prior to applying any reflective and protective coatings. Using a surface tension leveling coating concept, a low viscosity epoxy was applied to the surface of several composite coupons. A protective layer of 1000 A of SiO2 was deposited on top of the leveling coating, and the coupons were exposed to an atomic oxygen environment in a plasma asher. Pinhole populations per unit area were estimated by counting the number of undercut sites observed by scanning electron microscopy. Defect density values of 180,000 defects/sq cm were reduced to about 1000 defects/sq cm as a result of the applied leveling coating. These improvements occur at a mass penalty of about 2.5 mg/sq cm.

  11. Probiotic treatment reduces appetite and glucose level in the zebrafish model

    PubMed Central

    Falcinelli, Silvia; Rodiles, Ana; Unniappan, Suraj; Picchietti, Simona; Gioacchini, Giorgia; Merrifield, Daniel Lee; Carnevali, Oliana

    2016-01-01

    The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation. PMID:26727958

  12. Probiotic treatment reduces appetite and glucose level in the zebrafish model.

    PubMed

    Falcinelli, Silvia; Rodiles, Ana; Unniappan, Suraj; Picchietti, Simona; Gioacchini, Giorgia; Merrifield, Daniel Lee; Carnevali, Oliana

    2016-01-01

    The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation. PMID:26727958

  13. Leveling coatings for reducing the atomic oxygen defect density in protected graphite fiber epoxy composites

    NASA Technical Reports Server (NTRS)

    Jaworske, D. A.; Degroh, K. K.; Podojil, G.; Mccollum, T.; Anzic, J.

    1992-01-01

    Pinholes or other defect sites in a protective oxide coating provide pathways for atomic oxygen in low Earth orbit to reach underlying material. One concept for enhancing the lifetime of materials in low Earth orbits is to apply a leveling coating to the material prior to applying any reflective and protective coatings. Using a surface tension leveling coating concept, a low viscosity epoxy was applied to the surface of several composite coupons. A protective layer of 1000 A of SiO2 was deposited on top of the leveling coating, and the coupons were exposed to an atomic oxygen environment in a plasma asher. Pinhole populations per unit area were estimated by counting the number of undercut sites observed by scanning electron microscopy. Defect density values of 180,000 defects/sq cm were reduced to about 1000 defects/sq cm as a result of the applied leveling coating. These improvements occur at a mass penalty of about 2.5 mg/sq cm.

  14. Leveling coatings for reducing the atomic oxygen defect density in protected graphite fiber epoxy composites

    NASA Technical Reports Server (NTRS)

    Jaworske, D. A.; Degroh, Kim K.; Podojil, G.; Mccollum, T.; Anzic, J.

    1992-01-01

    Pinholes or other defect sites in a protective oxide coating provide pathways for atomic oxygen in low Earth orbit to reach underlying material. One concept of enhancing the lifetime of materials in low Earth orbit is to apply a leveling coating to the material prior to applying any reflective and protective coatings. Using a surface tension leveling coating concept, a low viscosity epoxy was applied to the surface of several composite coupons. A protective layer of 1000 A of SiO2 was deposited on top of the leveling coating, and the coupons were exposed to an atomic oxygen environment in a plasma asher. Pinhole populations per unit area were estimated by counting the number of undercut sites observed by scanning electron microscopy. Defect density values of 180,000 defects/sq cm were reduced to about 1000 defects/sq cm as a result of the applied leveling coating. These improvements occur at a mass penalty of about 2.5 mg/sq cm.

  15. Sodium salicylate reduces the level of GABAB receptors in the rat's inferior colliculus.

    PubMed

    Butt, S; Ashraf, F; Porter, L A; Zhang, H

    2016-03-01

    Previous studies have indicated that sodium salicylate (SS) can cause hearing abnormalities through affecting the central auditory system. In order to understand central effects of the drug, we examined how a single intraperitoneal injection of the drug changed the level of subunits of the type-B γ-aminobutyric acid receptor (GABAB receptor) in the rat's inferior colliculus (IC). Immunohistochemical and western blotting experiments were conducted three hours following a drug injection, as previous studies indicated that a tinnitus-like behavior could be reliably induced in rats within this time period. Results revealed that both subunits of the receptor, GABABR1 and GABABR2, reduced their level over the entire area of the IC. Such a reduction was observed in both cell body and neuropil regions. In contrast, no changes were observed in other brain structures such as the cerebellum. Thus, a coincidence existed between a structure-specific reduction in the level of GABAB receptor subunits in the IC and the presence of a tinnitus-like behavior. This coincidence likely suggests that a reduction in the level of GABAB receptor subunits was involved in the generation of a tinnitus-like behavior and/or used by the nervous system to restore normal hearing following application of SS. PMID:26705739

  16. Sulforaphane reduces the alterations induced by quinolinic acid: modulation of glutathione levels.

    PubMed

    Santana-Martínez, R A; Galván-Arzáte, S; Hernández-Pando, R; Chánez-Cárdenas, M E; Avila-Chávez, E; López-Acosta, G; Pedraza-Chaverrí, J; Santamaría, A; Maldonado, P D

    2014-07-11

    Glutamate-induced excitotoxicity involves a state of acute oxidative stress, which is a crucial event during neuronal degeneration and is part of the physiopathology of neurodegenerative diseases. In this work, we evaluated the ability of sulforaphane (SULF), a natural dietary isothiocyanate, to induce the activation of transcription factor Nrf2 (a master regulator of redox state in the cell) in a model of striatal degeneration in rats infused with quinolinic acid (QUIN). Male Wistar rats received SULF (5mg/kg, i.p.) 24h and 5min before the intrastriatal infusion of QUIN. SULF increased the reduced glutathione (GSH) levels 4h after QUIN infusion, which was associated with its ability to increase the activity of glutathione reductase (GR), an antioxidant enzyme capable to regenerate GSH levels at 24h. Moreover, SULF treatment increased glutathione peroxidase (GPx) activity, while no changes were observed in γ-glutamyl cysteine ligase (GCL) activity. SULF treatment also prevented QUIN-induced oxidative stress (measured by oxidized proteins levels), the histological damage and the circling behavior. These results suggest that the protective effect of SULF could be related to its ability to preserve GSH levels and increase GPx and GR activities. PMID:24814729

  17. The awareness level and needs for education on reducing sugar consumption among mothers with preschool children

    PubMed Central

    Lee, Younhee

    2016-01-01

    BACKGROUND/OBJECTIVES The purpose of this study was to find out the level of knowledge on sugar-related nutrition among mothers with preschool children. SUBJECTS/METHODS The study conducted a survey on 350 mothers whose children attended daycare. The dietary lives of the children and the nutritional knowledge of the mothers on sugar were checked. In order to analyze results, SPSS 18.0 was used. ANOVA and t-test were also performed to analyze recognition and educational needs. RESULTS When the degree of nutritional knowledge was measured and analyzed, the results showed about 11 average points out of 15. The higher a group's nutritional knowledge, the better the dietary habits and activities were and the activities were more ccommon. The group with a low level of nutritional knowledge consumed more foods with high sugar content, but this difference was not statistically significant. Also the children from the group of mothers that provided nutritional education to their children were more likely to engage in better dietary habits and activities. CONCLUSIONS 66.5% respondents did not know about policies to reduce sugar consumption, but most indicated that education on reducing sugar consumption is needed. Therefore, a government-driven search for efficient methods to campaign and publicize sugar reduction is needed in order to continuously provide appropriate education. PMID:27087908

  18. Ultraviolet-ozone treatment reduces levels of disease-associated prion protein and prion infectivity

    USGS Publications Warehouse

    Johnson, C.J.; Gilbert, P.; McKenzie, D.; Pedersen, J.A.; Aiken, Judd M.

    2009-01-01

    Background. Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases caused by novel infectious agents referred to as prions. Prions appear to be composed primarily, if not exclusively, of a misfolded isoform of the cellular prion protein. TSE infectivity is remarkably stable and can resist many aggressive decontamination procedures, increasing human, livestock and wildlife exposure to TSEs. Findings. We tested the hypothesis that UV-ozone treatment reduces levels of the pathogenic prion protein and inactivates the infectious agent. We found that UV-ozone treatment decreased the carbon and prion protein content in infected brain homogenate to levels undetectable by dry-ashing carbon analysis or immunoblotting, respectively. After 8 weeks of ashing, UV-ozone treatment reduced the infectious titer of treated material by a factor of at least 105. A small amount of infectivity, however, persisted despite UV-ozone treatment. When bound to either montmorillonite clay or quartz surfaces, PrPTSE was still susceptible to degradation by UV-ozone. Conclusion. Our findings strongly suggest that UV-ozone treatment can degrade pathogenic prion protein and inactivate prions, even when the agent is associated with surfaces. Using larger UV-ozone doses or combining UV-ozone treatment with other decontaminant methods may allow the sterilization of TSE-contaminated materials. ?? 2009 Aiken et al; licensee BioMed Central Ltd.

  19. Itching, pain, and anxiety levels are reduced with massage therapy in burned adolescents.

    PubMed

    Parlak Gürol, Ayşe; Polat, Sevinç; Akçay, Müfide Nuran

    2010-01-01

    Burn can be among the most severe physical and psychologic traumas a person may face. Patients with burns commonly have severe itching and pain. Severe itching has also been associated with anxiety, sleep disturbance, and disruption of daily living activities. The addition of complementary treatments to standard care may lead to improved pain management and may offer a safer approach for reducing pain and procedural anxiety for patients with burns. The authors conducted an experimental study to examine whether the effects of massage therapy reduced burned adolescents' pain, itching, and anxiety levels. Sixty-three adolescents were enrolled in this study shortly after admission (mean days = 3 +/- 0.48) at a burn unit in a large university hospital from February 2008 to June 2009. The measures including the pain, itching, and state anxiety were collected on the first and last days of the 5-week study period. The participants had an average age of 14.07 +/- 1.78 years and came usually from the lower socioeconomic strata. The authors observed that massage therapy reduced all these measures from the first to the last day of this study (P < .001). In most cultures, massage treatments are used to alleviate a wide range of symptoms. Although health professionals agree on the use of nonpharmacologic method for patients with burns, these applications are not yet common. PMID:20453734

  20. Apolipoprotein AI levels are increased in part as a consequence of reduced catabolism in nephrotic rats.

    PubMed

    Kaysen, G A; Hoye, E; Jones, H

    1995-03-01

    Apolipoprotein AI (apo AI) synthesis, measured as the turnover of 125I-labeled apo AI-labeled high-density lipoprotein (HDL), was increased significantly in rats with Heymann nephritis (HN) vs. control Sprague-Dawley (SD) rats. However, fractional apo AI catabolic rate was also significantly less in HN vs. SD. We used 125I-apo AI tyramine cellobiose HDL, a marker retained at the catabolic site, to establish where apo AI catabolism decreased in six HN rats, seven rats with adriamycin (Adria)-induced nephrosis, and six control SD. Total renal apo AI catabolism, plus urinary losses, were the same in all three groups, despite significant urinary apo AI in HN and Adria rats. Apo AI catabolism was reduced in skin in both nephrotic groups, accounting for approximately 44% of reduced in apo AI catabolism. Thus a significant fraction of apo AI is catabolized in skin of normal male rats. Reduced apo AI catabolism in skin contributes to increased plasma levels in nephrotic rats. PMID:7900854

  1. A heuristic re-mapping algorithm reducing inter-level communication in SAMR applications.

    SciTech Connect

    Steensland, Johan; Ray, Jaideep

    2003-07-01

    This paper aims at decreasing execution time for large-scale structured adaptive mesh refinement (SAMR) applications by proposing a new heuristic re-mapping algorithm and experimentally showing its effectiveness in reducing inter-level communication. Tests were done for five different SAMR applications. The overall goal is to engineer a dynamically adaptive meta-partitioner capable of selecting and configuring the most appropriate partitioning strategy at run-time based on current system and application state. Such a metapartitioner can significantly reduce execution times for general SAMR applications. Computer simulations of physical phenomena are becoming increasingly popular as they constitute an important complement to real-life testing. In many cases, such simulations are based on solving partial differential equations by numerical methods. Adaptive methods are crucial to efficiently utilize computer resources such as memory and CPU. But even with adaption, the simulations are computationally demanding and yield huge data sets. Thus parallelization and the efficient partitioning of data become issues of utmost importance. Adaption causes the workload to change dynamically, calling for dynamic (re-) partitioning to maintain efficient resource utilization. The proposed heuristic algorithm reduced inter-level communication substantially. Since the complexity of the proposed algorithm is low, this decrease comes at a relatively low cost. As a consequence, we draw the conclusion that the proposed re-mapping algorithm would be useful to lower overall execution times for many large SAMR applications. Due to its usefulness and its parameterization, the proposed algorithm would constitute a natural and important component of the meta-partitioner.

  2. Temporal characterization of mercury accumulation at different trophic levels and implications for metal biomagnification along a coastal food web.

    PubMed

    Cardoso, P G; Pereira, E; Duarte, A C; Azeiteiro, U M

    2014-10-15

    The main goal of this study was to assess temporal mercury variations along an estuarine food web to evaluate the mercury contamination level of the system and the risks that humans are exposed to, due to mercury biomagnification. The highest mercury concentrations in the sediments and primary producers (macrophytes) were observed during winter sampling. Instead, the highest mercury concentrations in the water, suspended particulate matter as well as in the zooplanktonic and suprabenthic communities were observed during summer sampling. Evidences of mercury biomagnification along the food web were corroborated by the positive biomagnification factors, particularly for omnivorous macrobenthic species. Comparing the mercury levels at distinct components with several environmental quality criteria it suggests that sediments, water and edible species (e.g., bivalve Scrobicularia plana and the crustacean Carcinus maenas) presented higher mercury levels than the values accepted by legislation which represent a matter of concern for the environment and human health. PMID:25172612

  3. Attenuation of virulence in an apicomplexan hemoparasite results in reduced genome diversity at the population level

    PubMed Central

    2011-01-01

    Background Virulence acquisition and loss is a dynamic adaptation of pathogens to thrive in changing milieus. We investigated the mechanisms of virulence loss at the whole genome level using Babesia bovis as a model apicomplexan in which genetically related attenuated parasites can be reliably derived from virulent parental strains in the natural host. We expected virulence loss to be accompanied by consistent changes at the gene level, and that such changes would be shared among attenuated parasites of diverse geographic and genetic background. Results Surprisingly, while single nucleotide polymorphisms in 14 genes distinguished all attenuated parasites from their virulent parental strains, all non-synonymous changes resulted in no deleterious amino acid modification that could consistently be associated with attenuation (or virulence) in this hemoparasite. Interestingly, however, attenuation significantly reduced the overall population's genome diversity with 81% of base pairs shared among attenuated strains, compared to only 60% of base pairs common among virulent parental parasites. There were significantly fewer genes that were unique to their geographical origins among the attenuated parasites, resulting in a simplified population structure among the attenuated strains. Conclusions This simplified structure includes reduced diversity of the variant erythrocyte surface 1 (ves) multigene family repertoire among attenuated parasites when compared to virulent parental strains, possibly suggesting that overall variance in large protein families such as Variant Erythrocyte Surface Antigens has a critical role in expression of the virulence phenotype. In addition, the results suggest that virulence (or attenuation) mechanisms may not be shared among all populations of parasites at the gene level, but instead may reflect expansion or contraction of the population structure in response to shifting milieus. PMID:21838895

  4. Sesamol treatment reduces plasma cholesterol and triacylglycerol levels in mouse models of acute and chronic hyperlipidemia.

    PubMed

    Kumar, Nitesh; Mudgal, Jayesh; Parihar, Vipan K; Nayak, Pawan G; Kutty, N Gopalan; Rao, C Mallikarjuna

    2013-06-01

    The active constituents of Sesamum indicum, sesamin and sesamolin, have already been explored for hypolipidemic action. In this study we have explored the anti-dyslipidemic activity of another active component and metabolite of sesamolin (sesamol), by using acute models of hyperlipidemia viz., a fat tolerance test, a tyloxapol-induced hyperlipidemia model and a chronic model of hyperlipidemia viz., a high-fat diet-induced hyperlipidemia model in Swiss albino mice. Sesamol (100 and 200 mg/kg) significantly (P < 0.05) decreased triacylglycerol absorption in the fat tolerance test by showing a dose-dependent decrease in triacylglycerol levels. The hypolipidemic effect of sesamol at 200 mg/kg was equivalent to 10 mg/kg of orlistat. In the tyloxapol-induced hyperlipidemia model, Sesamol at 200 mg/kg reversed the elevated levels of cholesterol and triacylglycerol compared with the tyloxapol group at 12 and 24 h, which indicates its probable effect on cholesterol synthesis. Chronic hyperlipidemia in mice was produced by feeding a high-diet, a mixture of cholesterol (2 % w/w), cholic acid (1 % w/w) and coconut oil 30 % (v/w) with standard powdered standard animal chow (up to 100 g). Niacin (100 mg/kg) and sesamol (100 mg/kg) significantly (P < 0.05) reduced the elevated body weight compared with the high fat diet control group. Elevated levels of cholesterol and triacylglycerol were significantly (P < 0.05) reversed by the sesamol (50 and 100 mg/kg), implying that it might reduce the absorption and increase the excretion of cholesterol as well. PMID:23504268

  5. Increasing Level of Leisure Physical Activity Could Reduce the Risk of Hip Fracture in Older Women

    PubMed Central

    Rong, Ke; Liu, Xiao-yu; Wu, Xu-hua; Li, Xiao-liu; Xia, Qing-quan; Chen, Jiong; Yin, Xiao-fan

    2016-01-01

    Abstract We carried out the study to investigate and quantitatively assess the potential association between current level of physical activity and the risk of osteoporosis hip fracture in older women. Relevant publications before October 2015 were identified using the PubMed and Ovid searching tools. A dose–response meta-analysis was carried out to combine and analysis results. Fourteen prospective studies were included in the meta-analysis. A general analysis of 9 studies showed a significant inverse relationship between increasing level of physical activity and risk of hip fracture in older women [relative risk (RR) = 0.93, 95% confidence interval (95% CI): 0.91–0.96]. The result of a sensitivity analysis was consistent with the general analysis (RR = 0.94, 95% CI: 0.93–0.96). The association between increasing level of physical activity and risk of wrist fracture was not statistically significant in a general analysis of three studies (RR = 1.004, 95% CI: 0.98–1.03). A potential direct association between increasing level of physical activity and risk of wrist fracture was observed after removing 1 study with the greatest weight (RR = 1.01, 95% CI: 1.00–1.03). No significant publication bias was observed in our analysis. Our results show that increasing level of physical activity within an appropriate range may reduce the risk of hip fracture but not the risk of wrist fracture in older women. PMID:26986111

  6. Diagnostic accuracy at several reduced radiation dose levels for CT imaging in the diagnosis of appendicitis

    NASA Astrophysics Data System (ADS)

    Zhang, Di; Khatonabadi, Maryam; Kim, Hyun; Jude, Matilda; Zaragoza, Edward; Lee, Margaret; Patel, Maitraya; Poon, Cheryce; Douek, Michael; Andrews-Tang, Denise; Doepke, Laura; McNitt-Gray, Shawn; Cagnon, Chris; DeMarco, John; McNitt-Gray, Michael

    2012-03-01

    Purpose: While several studies have investigated the tradeoffs between radiation dose and image quality (noise) in CT imaging, the purpose of this study was to take this analysis a step further by investigating the tradeoffs between patient radiation dose (including organ dose) and diagnostic accuracy in diagnosis of appendicitis using CT. Methods: This study was IRB approved and utilized data from 20 patients who underwent clinical CT exams for indications of appendicitis. Medical record review established true diagnosis of appendicitis, with 10 positives and 10 negatives. A validated software tool used raw projection data from each scan to create simulated images at lower dose levels (70%, 50%, 30%, 20% of original). An observer study was performed with 6 radiologists reviewing each case at each dose level in random order over several sessions. Readers assessed image quality and provided confidence in their diagnosis of appendicitis, each on a 5 point scale. Liver doses at each case and each dose level were estimated using Monte Carlo simulation based methods. Results: Overall diagnostic accuracy varies across dose levels: 92%, 93%, 91%, 90% and 90% across the 100%, 70%, 50%, 30% and 20% dose levels respectively. And it is 93%, 95%, 88%, 90% and 90% across the 13.5-22mGy, 9.6-13.5mGy, 6.4-9.6mGy, 4-6.4mGy, and 2-4mGy liver dose ranges respectively. Only 4 out of 600 observations were rated "unacceptable" for image quality. Conclusion: The results from this pilot study indicate that the diagnostic accuracy does not change dramatically even at significantly reduced radiation dose.

  7. Annual Sea Level Variability Induced by Changes in Sea Ice Extent and Accumulation on Ice Sheets: An Assessment Based on Remotely Sensed Data

    NASA Technical Reports Server (NTRS)

    Zwally, H. J.; Giovinetto, M. B.

    1997-01-01

    Changes of mean annual net accumulation at the surface on the grounded ice sheets of East Antarctica, West Antarctica, and Greenland in response to variations in sea ice extent are estimated using grid-point values 100 km apart. The data bases are assembled principally by bilinear interpolation of remotely sensed brightness temperature (Nimbus-5 ESMR, Nimbus-7 SMMR), surface temperature (Nimbus-7 THIR), and surface elevation (ERS-1 radar altimeter). These data, complemented by field data where remotely sensed data are not available, are used in multivariate analyses in which mean annual accumulation (derived from firn emissivity) is the dependent variable; the independent variables are latitude, surface elevation, mean annual surface temperature, and mean annual distance to open ocean (as a source of energy and moisture). The last is the shortest distance measured between a grid point and the mean annual position of the 10% sea ice concentration boundary, and is used as an index of changes in sea ice extent as well as of mean concentration. Stepwise correlation analyses indicate that variations in sea ice extent of +/-50 km would lead to changes in accumulation inversely of +/-4% on East Antarctica, +/- 10% on West Antarctica, and +4% on Greenland. These results are compared with those obtained in a previous study using visually interpolated values from contoured compilations of field data; they substantiate the findings for the Antarctic ice sheets (+/-4% on East Antarctica, +/-9% in West Antarctica), and suggest a reduction by one half of the probable change of accumulation on Greenland (from +/-8%). The results also suggest a reduction of the combined contribution to sea level variability to +/- 0.19 mm/a (from +/- 0.22 mm/a).

  8. 5 CFR 630.301 - Annual leave accrual and accumulation-Senior Executive Service, Senior-Level, and Scientific and...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... system established under 5 U.S.C. chapter 43 and 5 CFR part 430, subparts B and C, or other applicable... subject to 5 U.S.C. 5383; or (2) Holds a senior-level (SL) or scientific or professional (ST) position... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Annual leave accrual and...

  9. 5 CFR 630.301 - Annual leave accrual and accumulation-Senior Executive Service, Senior-Level, and Scientific and...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... system established under 5 U.S.C. chapter 43 and 5 CFR part 430, subparts B and C, or other applicable... subject to 5 U.S.C. 5383; or (2) Holds a senior-level (SL) or scientific or professional (ST) position... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Annual leave accrual and...

  10. 5 CFR 630.301 - Annual leave accrual and accumulation-Senior Executive Service, Senior-Level, and Scientific and...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... system established under 5 U.S.C. chapter 43 and 5 CFR part 430, subparts B and C, or other applicable... subject to 5 U.S.C. 5383; or (2) Holds a senior-level (SL) or scientific or professional (ST) position... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Annual leave accrual and...

  11. 5 CFR 630.301 - Annual leave accrual and accumulation-Senior Executive Service, Senior-Level, and Scientific and...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... system established under 5 U.S.C. chapter 43 and 5 CFR part 430, subparts B and C, or other applicable... subject to 5 U.S.C. 5383; or (2) Holds a senior-level (SL) or scientific or professional (ST) position... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Annual leave accrual and...

  12. Arbuscular mycorrhiza increase artemisinin accumulation in Artemisia annua by higher expression of key biosynthesis genes via enhanced jasmonic acid levels.

    PubMed

    Mandal, Shantanu; Upadhyay, Shivangi; Wajid, Saima; Ram, Mauji; Jain, Dharam Chand; Singh, Ved Pal; Abdin, Malik Zainul; Kapoor, Rupam

    2015-07-01

    It is becoming increasingly evident that the formation of arbuscular mycorrhiza (AM) enhances secondary metabolite production in shoots. Despite mounting evidence, relatively little is known about the underlying mechanisms. This study suggests that increase in artemisinin concentration in Artemisia annua colonized by Rhizophagus intraradices is due to altered trichome density as well as transcriptional patterns that are mediated via enhanced jasmonic acid (JA) levels. Mycorrhizal (M) plants had higher JA levels in leaf tissue that may be due to induction of an allene oxidase synthase gene (AOS), encoding one of the key enzymes for JA production. Non-mycorrhizal (NM) plants were exogenously supplied with a range of methyl jasmonic acid concentrations. When leaves of NM and M plants with similar levels of endogenous JA were compared, these matched closely in terms of shoot trichome density, artemisinin concentration, and transcript profile of artemisinin biosynthesis genes. Mycorrhization increased artemisinin levels by increasing glandular trichome density and transcriptional activation of artemisinin biosynthesis genes. Transcriptional analysis of some rate-limiting enzymes of mevalonate and methyl erythritol phosphate (MEP) pathways revealed that AM increases isoprenoids by induction of the MEP pathway. A decline in artemisinin concentration in shoots of NM and M plants treated with ibuprofen (an inhibitor of JA biosynthesis) further confirmed the implication of JA in the mechanism of artemisinin production. PMID:25366131

  13. GLP-1 Receptor Stimulation Reduces Amyloid-β Peptide Accumulation and Cytotoxicity in Cellular and Animal Models of Alzheimer’s Disease

    PubMed Central

    Li, Yazhou; Duffy, Kara B.; Ottinger, Mary Ann; Ray, Balmiki; Bailey, Jason A.; Holloway, Harold W.; Tweedie, David; Perry, TracyAnn; Mattson, Mark P.; Kapogiannis, Dimitrios; Sambamurti, Kumar; Lahiri, Debomoy K.; Greiga, Nigel H.

    2010-01-01

    Type 2 (T2) diabetes mellitus (DM) has been associated with an increased incidence of neurodegenerative disorders, including Alzheimer’s disease (AD). Several pathological features are shared between diabetes and AD, including dysfunctional insulin signaling and a dysregulation of glucose metabolism. It has therefore been suggested that not only may the two conditions share specific molecular mechanisms but also that agents with proven efficacy in one may be useful against the other. Hence, the present study characterized the effects of a clinically approved long-acting analogue, exendin-4 (Ex-4), of the endogenous insulin releasing incretin, glucagon-like peptide-1 (GLP-1), on stress-induced toxicity in neuronal cultures and on amyloid-β protein (Aβ) and tau levels in triple transgenic AD (3xTg-AD) mice with and without streptozocin (STZ)-induced diabetes. Ex-4 ameliorated the toxicity of Aβ and oxidative challenge in primary neuronal cultures and human SH-SY5Y cells in a concentration-dependent manner. When 11 to 12.5 month old female 3xTg AD mice were challenged with STZ or saline, and thereafter treated with a continuous subcutaneous infusion of Ex-4 or vehicle, Ex-4 ameliorated the diabetic effects of STZ in 3xTg-AD mice, elevating plasma insulin and lowering both plasma glucose and hemoglobin A1c (HbA1c) levels. Furthermore, brain levels of Aβ protein precursor and Aβ, which were elevated in STZ 3xTg-AD mice, were significantly reduced in Ex-4 treated mice. Brain tau levels were unaffected following STZ challenge, but showed a trend toward elevation that was absent following Ex-4 treatment. Together, these results suggest a potential value of Ex-4 in AD, particularly when associated with T2DM or glucose intolerance. PMID:20308787

  14. 7-ketocholesterol accumulates in ocular tissues as a consequence of aging and is present in high levels in drusen

    PubMed Central

    Rodriguez, Ignacio R.; Clark, Mark E.; Lee, Jung Wha; Curcio, Christine A.

    2014-01-01

    We analyzed by LCMS lipid extracts of lens, retina (MNR) and RPE/Choroid (MPEC) from macaque monkeys 2–25 yr in age to determine their content of 7-ketocholesterol (7KCh) as function of age. In addition we also analyzed drusen capped with retinal pigment epithelium (RPE), RPE, and neural retina from human donors age 72–95 yr. The lowest 7KCh levels were found in monkey lens (<0.5 to 3.5 pmol 7KCh per nmol Ch), the second highest in MNR (1–15 pmol/nmol), and the highest in MPEC (1 to > 60 pmol/nmol). Despite individual variability all three tissues demonstrated a strong age-related increase. In older human donors 7KCh levels were significantly higher. The levels in human neural retina ranged from 8–20 pmol/nmol, similar to the oldest monkeys, but 7-KCh levels in RPE ranged from 200–17,000 pmol/nmol, and in RPE-capped drusen from 200–2,000 pmol/nmol, levels that would be lethal in most cultured cell systems. Most of the 7KCh is sequestered and not readily available to the surrounding tissue, based on published histochemical evidence that extracellular cholesterol (Ch) and cholesteryl fatty acid esters (CEs) are highly concentrated in Bruch’s membrane and drusen. However, adjacent tissues, especially RPE but also choriocapillaris endothelium, could be chronically inflamed and in peril of receiving a lethal exposure. Implications for initiation and progression of age-related macular degeneration are discussed. PMID:25261634

  15. Predicting preferred coring level to reduce toner scatter in electrophotographic printing

    NASA Astrophysics Data System (ADS)

    Park, Hyung Jun; Allebach, Jan P.

    2011-01-01

    The electrophotographic process depends on a complex interplay between electrostatically charged toner particles, the developer roller, and the organic photoconductor during development; and between the toner particles, the organic photoconductor, and the paper during transfer. The task of controlling the imaging process is made even more challenging by the fact that colorant planes are developed independently and in succession. At high colorant levels, toner particles for a given colorant plane may be strongly repelled by toner that has already been deposited for previously developed colorant planes. The result is scattering of toner away from the edges of thin lines and character strokes. In previous work, we have proposed a coring method to reduce the occurrence of the toner scatter, and conducted psychophysical experiments to determine the preferred level of coring as a function of line width and colorant level. In this paper, we apply the edge transition width (ETW) metric to physically measure the impact of toner scatter on the sharpness of edges of lines and character strokes. We consider ETW both with and without coring, and compare it to the results from our earlier psychophysical experiments.

  16. Low-level laser therapy (LLLT) reduces inflammatory infiltrate and enhances skeletal muscle repair: Histomorphometric parameters

    NASA Astrophysics Data System (ADS)

    Paiva-Oliveira, E. L.; Lima, N. C.; Silva, P. H.; Sousa, N. T. A.; Barbosa, F. S.; Orsini, M.; Silva, J. G.

    2012-09-01

    Low level laser therapy (LLLT) has been suggested as an effective therapeutics in inflammatory processes modulation and tissue repairing. However, there is a lack of studies that analyze the anti-inflammatory effects of the infrared lasers in muscular skeletal injury. The aim of this study was to investigate the effects of low-level laser therapy 904 nm in the repair process of skeletal muscle tissue. Swiss mice were submitted to cryoinjury and divided in test (LLLT-treated) and control groups. Histological sections were stained with hematoxylin-eosin to assess general morphology and inflammatory influx, and Picrossirus to quantify collagen fibers deposition. Our results showed significant reduction in inflammatory infiltrated in irradiated mice after 4 days of treatment compared to control ( p = 0.01). After 8 days, the irradiated group showed high levels at regenerating myofibers with significant statistically differences in relation at control group ( p < 0.01). Collagen deposition was significantly increased in the final stages of regeneration at test group, when compared with control group ( p = 0.05). Our data suggests that LLLT reduces the inflammatory response in the initial stages of injury and accelerates the process of muscular tissue repair.

  17. Rho-associated protein kinase 1 (ROCK1) is increased in Alzheimer's disease and ROCK1 depletion reduces amyloid-β levels in brain.

    PubMed

    Henderson, Benjamin W; Gentry, Erik G; Rush, Travis; Troncoso, Juan C; Thambisetty, Madhav; Montine, Thomas J; Herskowitz, Jeremy H

    2016-08-01

    Alzheimer's disease (AD) is the leading cause of dementia and mitigating amyloid-β (Aβ) levels may serve as a rational therapeutic avenue to slow AD progression. Pharmacologic inhibition of the Rho-associated protein kinases (ROCK1 and ROCK2) is proposed to curb Aβ levels, and mechanisms that underlie ROCK2's effects on Aβ production are defined. How ROCK1 affects Aβ generation remains a critical barrier. Here, we report that ROCK1 protein levels were elevated in mild cognitive impairment due to AD (MCI) and AD brains compared to controls. Aβ42 oligomers marginally increased ROCK1 and ROCK2 protein levels in neurons but strongly induced phosphorylation of Lim kinase 1 (LIMK1), suggesting that Aβ42 activates ROCKs. RNAi depletion of ROCK1 or ROCK2 suppressed endogenous Aβ40 production in neurons, and Aβ40 levels were reduced in brains of ROCK1 heterozygous knock-out mice compared to wild-type littermate controls. ROCK1 knockdown decreased amyloid precursor protein (APP), and treatment with bafilomycin accumulated APP levels in neurons depleted of ROCK1. These observations suggest that reduction of ROCK1 diminishes Aβ levels by enhancing APP protein degradation. Collectively, these findings support the hypothesis that both ROCK1 and ROCK2 are therapeutic targets to combat Aβ production in AD. Mitigating amyloid-β (Aβ) levels is a rational strategy for Alzheimer's disease (AD) treatment, however, therapeutic targets with clinically available drugs are lacking. We hypothesize that Aβ accumulation in mild cognitive impairment because of AD (MCI) and AD activates the RhoA/ROCK pathway which in turn fuels production of Aβ. Escalation of this cycle over the course of many years may contribute to the buildup of amyloid pathology in MCI and/or AD. PMID:27246255

  18. Lower levels of transgene silencing in roots is associated with reduced DNA methylation levels at non-symmetrical sites but not at symmetrical sites.

    PubMed

    Andika, Ida Bagus; Kondo, Hideki; Rahim, Muhammad Danial; Tamada, Tetsuo

    2006-02-01

    Transgene transcripts were recently shown to accumulate at higher levels in roots, relative to leaves, of silenced-transgenic Nicotiana benthamiana plants and to be inversely related with the accumulation of small interfering RNAs (siRNAs), suggesting that RNA silencing is less active in roots than in leaves (Andika et al., 2005. Mol. Plant-Microbe Interact. 18: 194). Here we show that the lower transgene RNA silencing activity in roots was associated with lower transgene methylation levels at non-symmetrical CpNpN context but not at symmetrical CpG or CpNpG context in three sets of transformant plants with different exogenous genes. In contrast, such a difference between roots and leaves was not observed for the Tnt1 retrotransposon: no Tnt1 transcript was detected in roots or in leaves of N. benthamiana, while equal levels of Tnt1-derived siRNA accumulation and Tnt1 methylation were found. From our data and previously reported information, we suggest that roots have less of an activity that acts at the step of generation of siRNAs. PMID:16514564

  19. Elevated Blood Lead Levels Are Associated with Reduced Risk of Malaria in Beninese Infants

    PubMed Central

    Moya-Alvarez, Violeta; Mireku, Michael Osei; Ayotte, Pierre; Cot, Michel; Bodeau-Livinec, Florence

    2016-01-01

    Introduction Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far. Materials and Methods Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed. Results At 12 months, the mean BLL of infants was 7.41 μg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 μg/dL. Lead poisoning, defined as BLL>10 μg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators. Conclusion Our study shows for the first time that BLL are negatively associated with malarial risk considering other risk factors. Malaria is one of the main causes of morbidity and mortality in infants under 5 years worldwide, and lead poisoning is the 6th most important contributor to the global burden of diseases measured in disability adjusted life years (DALYs) according to the

  20. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

    PubMed

    Isidori, A M; Caprio, M; Strollo, F; Moretti, C; Frajese, G; Isidori, A; Fabbri, A

    1999-10-01

    Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced

  1. Linked gene networks involved in nitrogen and carbon metabolism and levels of water-soluble carbohydrate accumulation in wheat stems.

    PubMed

    McIntyre, C Lynne; Casu, Rosanne E; Rattey, Allan; Dreccer, M Fernanda; Kam, Jason W; van Herwaarden, Anthony F; Shorter, Ray; Xue, Gang Ping

    2011-12-01

    High levels of water-soluble carbohydrates (WSC) provide an important source of stored assimilate for grain filling in wheat. To better understand the interaction between carbohydrate metabolism and other metabolic processes associated with the WSC trait, a genome-wide expression analysis was performed using eight field-grown lines from the high and low phenotypic tails of a wheat population segregating for WSC and the Affymetrix wheat genome array. The 259 differentially expressed probe sets could be assigned to 26 functional category bins, as defined using MapMan software. There were major differences in the categories to which the differentially expressed probe sets were assigned; for example, probe sets upregulated in high relative to low WSC lines were assigned to category bins such as amino acid metabolism, protein degradation and transport and to be involved in starch synthesis-related processes (carbohydrate metabolism bin), whereas downregulated probe sets were assigned to cell wall-related bins, amino acid synthesis and stress and were involved in sucrose breakdown. Using the set of differentially expressed genes as input, chemical-protein network analyses demonstrated a linkage between starch and N metabolism via pyridoxal phosphate. Twelve C and N metabolism-related genes were selected for analysis of their expression response to varying N and water treatments in the field in the four high and four low WSC progeny lines; the two nitrogen/amino acid metabolism genes demonstrated a consistent negative association between their level of expression and level of WSC. Our results suggest that the assimilation of nitrogen into amino acids is an important factor that influences the levels of WSC in the stems of field-grown wheat. PMID:21789636

  2. Effect of metal accumulation on metallothionein level and condition of the periwinkle Littorina littorea along the Scheldt estuary (the Netherlands).

    PubMed

    Van den Broeck, Heidi; De Wolf, Hans; Backeljau, Thierry; Blust, Ronny

    2010-05-01

    Metal (i.e. Ag, As, Ca, Cd, Co, Cu, Mn, Pb and Zn) and metallothionein (MT) concentrations in the soft tissue of Littorina littorea were measured along the heavily polluted Western Scheldt (WS) and relatively clean Eastern Scheldt (ES) estuary. Along the WS metal and MT levels in periwinkles reflected the known downstream decreasing pollution gradient. Surprisingly in ES animals As, Mn and Zn concentrations decreased from east to west reflecting past pollution. Compared to the WS metal concentrations of ES periwinkles were significantly lower and both estuaries were maximally discriminated from each other based on their Cd soft tissue concentration using a canonical discriminant analysis. Furthermore, no overall difference was found in MT levels among animals from both estuaries. Using previously obtained condition data (i.e. dry/wet weight ratio and lipid content) the relation between soft tissue metal concentration (i.e. Cd, Cu and Zn) and fitness indicators (i.e. MT and condition data) was examined using a canonical correlation analysis. Periwinkles with a high metal load (i.e. Cd and Zn) also had high MT levels but were in a relatively poor condition. PMID:19948373

  3. Postmenopausal vegetarians' low serum ferritin level may reduce the risk for metabolic syndrome.

    PubMed

    Kim, Mi-Hyun; Bae, Yun Jung

    2012-10-01

    The present study was conducted to compare the serum ferritin status between the postmenopausal vegetarians and non-vegetarians and to identify the relation of serum ferritin with metabolic syndrome (MetS) risk factors in postmenopausal women. The two study groups consisted of postmenopausal vegetarians (n=59) who maintained a vegetarian diet for over 20 years and age-matched non-vegetarian controls (n=48). Anthropometric measurements, dietary intakes, serum metabolic syndrome-related parameters, and serum ferritin level between the two groups were compared. The vegetarians exhibited significantly lower weight (p<0.01), body mass index (BMI) (p<0.001), percentage of body fat (p<0.001), waist circumference (p<0.01), SBP (p<0.001), DBP (p<0.001), and fasting glucose (p<0.05). According to the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III criteria for MetS applying Korean guidelines for waist circumference, the prevalence of MetS was lower in vegetarians (33.9 %) than in non-vegetarians (47.9 %). Vegetarians had significantly lower serum level of ferritin (p<0.01) than non-vegetarians. In the correlation analysis, serum ferritin was positively related to fasting glucose (r=0.264, p<0.01), triglycerides (r=0.232, p<0.05), and the NCEP score (r=0.214, p<0.05) and negatively related to high-density lipoprotein-cholesterol (r=-0.225, p<0.05) after adjusting for BMI, lifestyle, and dietary factors (animal protein, animal fat, and dietary fiber intake). In conclusion, postmenopausal vegetarians had lower MetS presence and a lower serum ferritin level compared to non-vegetarians. Furthermore, vegetarians' low serum ferritin level may reduce the risk of MetS in postmenopausal women. PMID:22528775

  4. U18666A Treatment Results in Cholesterol Accumulation, Reduced Na(+), K(+)-ATPase Activity, and Increased Oxidative Stress in Rat Cortical Astrocytes.

    PubMed

    Copetti-Santos, Daniela; Moraes, Vitoria; Weiler, Dácio Franco; de Mello, Alexandre Silva; Machado, Fernanda de Souza; Marinho, Jéssica Pereira; Siebert, Cassiana; Kolling, Janaina; Funchal, Cláudia; Wyse, Angela T S; Coelho, Janice Carneiro

    2015-10-01

    The objective of this study was to determine the effect of U18666A, an inhibitor of cholesterol synthesis and its intracellular transport, on oxidative stress parameters in cortical astrocytes cultured from Wistar rats (0-3 days old). The cultures were incubated with U18666A (0.25 µg/mL) for 48 h, conditions that are considered ideal to mimic Niemann-Pick type C disease. A variety of indicators of oxidative stress were measured. U18666A treatment increased cholesterol 2-fold in treated compared to control astrocytes. Oxidative stress was significantly elevated in treated cells as demonstrated by a 1.7-fold increase in thiobarbituric acid reactive substances, a 60% decrease is sulfhydral groups, and a 3.7-fold increase in carbonyl groups, indicative of increased lipid and protein oxidation following U18666A treatment. Consistent with these changes, both catalase and superoxide dismutase activities were significantly reduced nearly 50% in treated compared to control astrocytes. Collectively, these change resulted in a 50% reduction in Na(+), K(+)-ATPase specific activity following U18666A treatment, suggesting a significant alteration in its plasma membrane environment. Overall, these changes indicate that U18666A treatment results in increased cholesterol levels and an increased level of oxidative stress in cortical astrocytes, consistent with what is observed in Niemann-Pick type C disease. PMID:26344921

  5. Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration.

    PubMed

    Chiang, Huei-Hsin; Forsell, Charlotte; Lilius, Lena; Öijerstedt, Linn; Thordardottir, Steinunn; Shanmugarajan, Krishnan; Westerlund, Marie; Nennesmo, Inger; Thonberg, Håkan; Graff, Caroline

    2013-11-01

    Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disease with an age at onset generally below 65 years. Mutations in progranulin (GRN) have been reported to be able to cause FTLD through haploinsufficiency. We have sequenced GRN in 121 patients with FTLD and detected six different mutations in eight patients: p.Gly35Glufs*19, p.Asn118Phefs*4, p.Val200Glyfs*18, p.Tyr294*, p.Cys404* and p.Cys416Leufs*30. Serum was available for five of the mutations, where the serum-GRN levels were found to be >50% reduced compared with FTLD patients without GRN mutations. Moreover, the p.Cys416Leufs*30 mutation segregated in an affected family with different dementia diagnoses. The mutation frequency of GRN mutation was 6.6% in our FTLD cohort. PMID:23463024

  6. Selenite supplementation reduces arsenate uptake greater than phosphate but compromises the phosphate level and physiological performance in hydroponically grown Oryza sativa L.

    PubMed

    Kumar, Navin; Dubey, Arvind Kumar; Jaiswal, Praveen Kumar; Sahu, Nayan; Behera, Soumit Kumar; Tripathi, Rudra Deo; Mallick, Shekhar

    2016-01-01

    The present study evaluates the reduction of arsenate (As[V]) uptake in rice seedlings through individual and combined supplementation of phosphate (PO4(3-)) and selenite (Se[IV]) in a hydroponic condition. The toxic response in seedlings receiving As(V) manifested as inhibition in physiological parameters such as water use efficiency, stomatal conductance, photosynthetic assimilation rate, transpiration rate, photochemical quenching, and electron transport rate, along with growth. Arsenic accumulation significantly decreased with Se(IV) treatment (0.5 μg mL(-1), 1 μg mL(-1), and 2 μg mL(-1)) in a dose-dependent manner (20%, 35%, and 53%, respectively); however, it compromised the PO4(3-) level and physiological performance. The lower level of Se(IV), (0.5 μg mL(-1)), was relatively beneficial in terms of reduction in As accumulation than the higher level of Se(IV), (2 μg mL(-1)), which was rather toxic. Further, decrease in As uptake, replenished the level of PO4(3-) and physiological performance in seedlings treated with As+Se+P compared with those treated with As+Se. However, supplementation with only PO4(3-) (10 μg mL(-1) and 20 μg mL(-1)) along with As(V) was less effective in reducing As accumulation compared with As+Se. Seedlings receiving As+Se+P also exhibited lower thiobarbituric acid-reactive substances (TBARS) and electrical conductivity levels compared with both As+Se and As+P. Among all the treatments, the activity of antioxidant enzymes was highest in plants treated with As+Se+P. Hence, the higher antioxidant enzyme activity in As+Se+P along with lower levels of TBARS, H2 O2 , and As accumulation are attributed to the competitive reduction in As uptake in the presence of Se(IV) and PO4(3-). PMID:26189439

  7. High propionic acid fermentations and mineral accumulation in the cecum of rats adapted to different levels of inulin.

    PubMed

    Levrat, M A; Rémésy, C; Demigné, C

    1991-11-01

    The digestive and metabolic effects of inulin (from chicory) were studied in rats adapted to semipurified diets containing 0, 5, 10 or 20% inulin (wt/wt). Moderate levels of inulin (5-10%) did not significantly affect food intake or body weight gain. Dietary inulin resulted in considerably greater cecal fermentation and a significantly greater intraluminal concentration of propionate (peaking at 58.4 mmol/L). A lower concentration of acetate (42.6 mmol/L) was observed in rats fed 20% inulin. Lactic fermentations were observed in rats fed the 10 or 20% inulin diets. The cecal pool of volatile fatty acids tended to reach a plateau in rats fed diets containing more than 10% inulin (up to 600-700 mumol), but volatile fatty acid absorption was a slightly hyperbolic function of the dietary inulin level. Butyrate absorption was proportionally lower than that of propionate. Inulin-containing diets induced an enlargement of the cecal pool of calcium, phosphate and (to a lesser extent) magnesium. There was also an enhanced absorption of these divalent cations. The cecal pool of bile acids was greater in rats fed inulin, and this oligosaccharide displayed a slight hypocholesterolemic effect, even in rats fed the 5% inulin diet. However, plasma triglycerides were depressed only in rats fed the 20% inulin diet. In conclusion, inulin seems very effective in promoting propionic fermentation and in enhancing the calcium content of the large intestine. However, high levels of inulin (greater than 10%) may affect growth in rats and lead to acidic (pH 5.65) cecal fermentation. PMID:1941180

  8. Bacteriophages of wastewater foaming-associated filamentous Gordonia reduce host levels in raw activated sludge

    PubMed Central

    Liu, Mei; Gill, Jason J.; Young, Ry; Summer, Elizabeth J.

    2015-01-01

    Filamentous bacteria are a normal and necessary component of the activated sludge wastewater treatment process, but the overgrowth of filamentous bacteria results in foaming and bulking associated disruptions. Bacteriophages, or phages, were investigated for their potential to reduce the titer of foaming bacteria in a mixed-microbial activated sludge matrix. Foaming-associated filamentous bacteria were isolated from activated sludge of a commercial wastewater treatment plan and identified as Gordonia species by 16S rDNA sequencing. Four representative phages were isolated that target G. malaquae and two un-named Gordonia species isolates. Electron microscopy revealed the phages to be siphophages with long tails. Three of the phages - GordTnk2, Gmala1, and GordDuk1 - had very similar ~76 kb genomes, with >93% DNA identity. These genomes shared limited synteny with Rhodococcus equi phage ReqiDocB7 and Gordonia phage GTE7. In contrast, the genome of phage Gsput1 was smaller (43 kb) and was not similar enough to any known phage to be placed within an established phage type. Application of these four phages at MOIs of 5–15 significantly reduced Gordonia host levels in a wastewater sludge model by approximately 10-fold as compared to non-phage treated reactors. Phage control was observed for nine days after treatment. PMID:26349678

  9. Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated fatty acids in a transgenic oilseed crop.

    PubMed

    Ruiz-Lopez, Noemi; Haslam, Richard P; Napier, Johnathan A; Sayanova, Olga

    2014-01-01

    Omega-3 (also called n-3) long-chain polyunsaturated fatty acids (≥C20; LC-PUFAs) are of considerable interest, based on clear evidence of dietary health benefits and the concurrent decline of global sources (fish oils). Generating alternative transgenic plant sources of omega-3 LC-PUFAs, i.e. eicosapentaenoic acid (20:5 n-3, EPA) and docosahexaenoic acid (22:6 n-3, DHA) has previously proved problematic. Here we describe a set of heterologous genes capable of efficiently directing synthesis of these fatty acids in the seed oil of the crop Camelina sativa, while simultaneously avoiding accumulation of undesirable intermediate fatty acids. We describe two iterations: RRes_EPA in which seeds contain EPA levels of up to 31% (mean 24%), and RRes_DHA, in which seeds accumulate up to 12% EPA and 14% DHA (mean 11% EPA and 8% DHA). These omega-3 LC-PUFA levels are equivalent to those in fish oils, and represent a sustainable, terrestrial source of these fatty acids. We also describe the distribution of these non-native fatty acids within C. sativa seed lipids, and consider these data in the context of our current understanding of acyl exchange during seed oil synthesis. PMID:24308505

  10. Body Fat Accumulation in Zebrafish Is Induced by a Diet Rich in Fat and Reduced by Supplementation with Green Tea Extract

    PubMed Central

    Meguro, Shinichi; Hasumura, Takahiro; Hase, Tadashi

    2015-01-01

    Fat-rich diets not only induce obesity in humans but also make animals obese. Therefore, animals that accumulate body fat in response to a high-fat diet (especially rodents) are commonly used in obesity research. The effect of dietary fat on body fat accumulation is not fully understood in zebrafish, an excellent model of vertebrate lipid metabolism. Here, we explored the effects of dietary fat and green tea extract, which has anti-obesity properties, on body fat accumulation in zebrafish. Adult zebrafish were allocated to four diet groups and over 6 weeks were fed a high-fat diet containing basal diet plus two types of fat or a low-fat diet containing basal diet plus carbohydrate or protein. Another group of adult zebrafish was fed a high-fat diet with or without 5% green tea extract supplementation. Zebrafish fed the high-fat diets had nearly twice the body fat (visceral, subcutaneous, and total fat) volume and body fat volume ratio (body fat volume/body weight) of those fed low-fat diets. There were no differences in body fat accumulation between the two high-fat groups, nor were there any differences between the two low-fat groups. Adding green tea extract to the high-fat diet significantly suppressed body weight, body fat volume, and body fat volume ratio compared with the same diet lacking green tea extract. 3-Hydroxyacyl-coenzyme A dehydrogenase and citrate synthase activity in the liver and skeletal muscle were significantly higher in fish fed the diet supplemented with green tea extract than in those fed the unsupplemented diet. Our results suggest that a diet rich in fat, instead of protein or carbohydrate, induced body fat accumulation in zebrafish with mechanisms that might be similar to those in mammals. Consequently, zebrafish might serve as a good animal model for research into obesity induced by high-fat diets. PMID:25785691

  11. Forest fragmentation reduces parasitism via species loss at multiple trophic levels.

    PubMed

    Fenoglio, Maria Silvina; Srivastava, Diane; Valladares, Graciela; Cagnolo, Luciano; Salvo, Adriana

    2012-11-01

    Although there is accumulating evidence from artificially assembled communities that reductions of species diversity result in diminished ecosystem functioning, it is not yet clear how real-world changes in diversity affect the flow of energy between trophic levels in multi-trophic contexts. In central Argentina, forest fragmentation has led to species loss of plants, herbivore and parasitoid insects, decline in trophic processes (herbivory and parasitism), and food web contraction. Here we examine if and how loss of parasitoid species following fragmentation causes decreased parasitism rates, by analyzing food webs of leaf miners and parasitoids from 19 forest fragments of decreasing size. We asked three questions: Do reductions in parasitoid richness following fragmentation directly or indirectly affect parasitism rate? Are changes in community parasitism rate driven by changes in the parasitism rate of individual leaf miner species, or changes in leaf miner composition, or both? Which traits of species determine the effects of food web change on parasitism rates? We found that habitat loss initiated a bottom-up cascade of extinctions from plants to leaf miners to parasitoids, with reductions in parasitoid richness ultimately driving decreases in parasitism rates. This relationship between parasitoid richness and parasitism depended on changes in the relative abundance (but not occurrence) of leaf miners such that parasitoid-rich fragments were dominated by leaf miner species that supported high rates of parasitism. Surprisingly, we found that only a small subset of species in the food web could account for much of the increase in parasitism with parasitoid richness: lepidopteran miners that attained exceptionally high densities in some fragments and their largely specialist parasitoids. How specialized a parasitoid is, and the relative abundance of leaf miners, had important effects on the diversity-parasitism rate relationship, but not other leaf miner traits

  12. 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. PMID:24121737

  13. Reducing the likelihood of future human activities that could affect geologic high-level waste repositories

    SciTech Connect

    Not Available

    1984-05-01

    The disposal of radioactive wastes in deep geologic formations provides a means of isolating the waste from people until the radioactivity has decayed to safe levels. However, isolating people from the wastes is a different problem, since we do not know what the future condition of society will be. The Human Interference Task Force was convened by the US Department of Energy to determine whether reasonable means exist (or could be developed) to reduce the likelihood of future human unintentionally intruding on radioactive waste isolation systems. The task force concluded that significant reductions in the likelihood of human interference could be achieved, for perhaps thousands of years into the future, if appropriate steps are taken to communicate the existence of the repository. Consequently, for two years the task force directed most of its study toward the area of long-term communication. Methods are discussed for achieving long-term communication by using permanent markers and widely disseminated records, with various steps taken to provide multiple levels of protection against loss, destruction, and major language/societal changes. Also developed is the concept of a universal symbol to denote Caution - Biohazardous Waste Buried Here. If used for the thousands of non-radioactive biohazardous waste sites in this country alone, a symbol could transcend generations and language changes, thereby vastly improving the likelihood of successful isolation of all buried biohazardous wastes.

  14. Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells

    PubMed Central

    Han, Ihn; Jung, Ji Hoon; Lee, Eun-Ok; Zhu, Shudong; Chen, Chang-Yan; Kim, Sung-Hoon

    2010-01-01

    Background We previously reported the anti-angiogenic activity of paeonol isolated from Moutan Cortex. In the present study, we investigated the negative effect of paeonol oxime (PO, a paeonol derivative) on basic fibroblast growth factor (bFGF)-mediated angiogenesis in human umbilical vein endothelial cells (HUVECs) (including tumor angiogenesis) and pro-survival activity in HT-1080 fibrosarcoma cell line. Methodology/Principal Findings We showed that PO (IC50  = 17.3 µg/ml) significantly inhibited bFGF-induced cell proliferation, which was achieved with higher concentrations of paeonol (IC50 over 200 µg). The treatment with PO blocked bFGF-stimulated migration and in vitro capillary differentiation (tube formation) in a dose-dependent manner. Furthermore, PO was able to disrupt neovascularization in vivo. Interestingly, PO (25 µg/ml) decreased the cell viability of HT-1080 fibrosarcoma cells but not that of HUVECs. The treatment with PO at 12.5 µg/ml reduced the levels of phosphorylated AKT and VEGF expression (intracellular and extracelluar) in HT-1080 cells. Consistently, immunefluorescence imaging analysis revealed that PO treatment attenuated AKT phosphorylation in HT-1080 cells. Conclusions/Significance Taken together, these results suggest that PO inhibits bFGF-induced angiogenesis in HUVECs and decreased the levels of PI3K, phospho-AKT and VEGF in HT-1080 cells. PMID:20808805

  15. Highly charged swelling mica reduces free and extractable Cu levels in Cu-contaminated soils.

    PubMed

    Stuckey, Jason W; Neaman, Alexander; Ravella, Ramesh; Komarneni, Sridhar; Martínez, Carmen Enid

    2008-12-15

    Smelting of copper (Cu) results in the atmospheric deposition of Cu onto surrounding soils. Excess concentrations of Cu in soils can be absorbed by soil biota to toxic levels or leached into the groundwater, threatening the entire ecosystem. A means to restrict Cu mobility and uptake by plants is to remove it from the aqueous phase by applying an adsorptive material. A synthetic clay (highly charged swelling mica) was tested for its ability to decrease the levels of free and 0.1 M KNO3-extractable Cu in 15 surface soils from three different Cu mining areas in central Chile. The soils contained excessive total Cu levels (112-2790 mg Cu (kg soil)(-1)), while extractable Cu ranged from 0.3 to 22.9 mg Cu L(-1). The mica was applied to each soil at rates of 0.1%, 1%, and 2% (w/w). A 2% sodium-montmorillonite treatment and the nonamended soil served as controls. The order of treatment efficacy in reducing extractable Cu and free Cu2+ for low pH soils ( 1% mica > 2% montmorillonite > 0.1% mica. At 120 days, the 2% mica treatment maintained reductions of up to 93% in the free Cu2+ activity and up to 75% in the extractable Cu concentration upon acidification to the original soil pH value. In addition, Cu retention in mica-treated soils was more resistant to acidification than in lime-treated soils. This mica has promise for the remediation of acidic soils with metal contamination at the surface. PMID:19174892

  16. Automated concept-level information extraction to reduce the need for custom software and rules development

    PubMed Central

    Nguyen, Thien M; Goryachev, Sergey; Fiore, Louis D

    2011-01-01

    Objective Despite at least 40 years of promising empirical performance, very few clinical natural language processing (NLP) or information extraction systems currently contribute to medical science or care. The authors address this gap by reducing the need for custom software and rules development with a graphical user interface-driven, highly generalizable approach to concept-level retrieval. Materials and methods A ‘learn by example’ approach combines features derived from open-source NLP pipelines with open-source machine learning classifiers to automatically and iteratively evaluate top-performing configurations. The Fourth i2b2/VA Shared Task Challenge's concept extraction task provided the data sets and metrics used to evaluate performance. Results Top F-measure scores for each of the tasks were medical problems (0.83), treatments (0.82), and tests (0.83). Recall lagged precision in all experiments. Precision was near or above 0.90 in all tasks. Discussion With no customization for the tasks and less than 5 min of end-user time to configure and launch each experiment, the average F-measure was 0.83, one point behind the mean F-measure of the 22 entrants in the competition. Strong precision scores indicate the potential of applying the approach for more specific clinical information extraction tasks. There was not one best configuration, supporting an iterative approach to model creation. Conclusion Acceptable levels of performance can be achieved using fully automated and generalizable approaches to concept-level information extraction. The described implementation and related documentation is available for download. PMID:21697292

  17. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    PubMed Central

    Funamoto, Masafumi; Sunagawa, Yoichi; Katanasaka, Yasufumi; Miyazaki, Yusuke; Imaizumi, Atsushi; Kakeya, Hideaki; Yamakage, Hajime; Satoh-Asahara, Noriko; Komiyama, Maki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2016-01-01

    Purpose COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD. Patients and methods This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated. Results There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin® group compared with the placebo group. Conclusion Theracurmin® reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects. PMID:27616885

  18. Polyphenol-rich extract of Nelumbo nucifera leaves inhibits alcohol-induced steatohepatitis via reducing hepatic lipid accumulation and anti-inflammation in C57BL/6J mice.

    PubMed

    Tang, Chang-Chieh; Lin, Wea-Lung; Lee, Yi-Ju; Tang, Yu-Chi; Wang, Chau-Jong

    2014-04-01

    The present study was undertaken to evaluate the hepatoprotective effect mechanisms of Nelumbo nucifera leaves extract (NLE) in experimental alcoholic steatohepatitis animal models. We found that the NLE contained polyphenols (phenolic acids and flavonoids), and more than 70% of the main functional components in NLE could potentially provide benefits for alcoholic liver disease. The parameters of histopathology, immunohistochemistry, antioxidant defense, proinflammatory mediator and lipid synthesis-related proteins demonstrated the inhibitory effect of NLE on alcoholic steatohepatitis. Plasma and hepatic content analysis showed that NLE inhibited lipid accumulation by altering the levels of triglycerides (TG) and cholesterol (TC). Treatment with NLE increased the expression of the p-AMPK/AMPK ratio and PPAR-α. Furthermore, fatty acid oxidation and transport via carnitine palmitoyltransferase-1 (CPT1) and microsomal triglyceride transfer protein (MTP) were through the activation of the AMPK and PPAR-α signal. These results revealed that the polyphenol-rich component of NLE prevents alcoholic steatohepatitis by multiple pathways, including reduced lipid synthesis, enhanced fatty acid oxidation and transport responses, inhibited oxidative stress and facilitated anti-inflammation. Suggesting that NLE might be regarded as a beneficial food that has the potential to be developed as a natural agent for preventing alcoholic steatohepatitis. PMID:24513924

  19. Nobiletin, a citrus flavonoid, improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of Alzheimer's disease (3XTg-AD).

    PubMed

    Nakajima, Akira; Aoyama, Yuki; Shin, Eun-Joo; Nam, Yunsung; Kim, Hyoung-Chun; Nagai, Taku; Yokosuka, Akihito; Mimaki, Yoshihiro; Yokoi, Tsuyoshi; Ohizumi, Yasushi; Yamada, Kiyofumi

    2015-08-01

    Alzheimer's disease (AD), the most common form of dementia among the elderly, is characterized by the progressive decline of cognitive function. Increasing evidence indicates that the production and accumulation of amyloid β (Aβ), particularly soluble Aβ oligomers, is central to the pathogenesis of AD. Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, ameliorates learning and memory impairment in olfactory-bulbectomized mice, amyloid precursor protein transgenic mice, NMDA receptor antagonist-treated mice, and senescence-accelerated mouse prone 8. Here, we present evidence that this natural compound improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of AD (3XTg-AD) that progressively develops amyloid plaques, neurofibrillary tangles, and cognitive impairments. Treatment with nobiletin (30 mg/kg) for 3 months reversed the impairment of short-term memory and recognition memory in 3XTg-AD mice. Our ELISA analysis also showed that nobiletin reduced the levels of soluble Aβ1-40 in the brain of 3XTg-AD mice. Furthermore, nobiletin reduced ROS levels in the hippocampus of 3XTg-AD as well as wild-type mice. These results suggest that this natural compound has potential to become a novel drug for the treatment and prevention of AD. PMID:25913833

  20. Naphthoquinone-tyrptophan reduces neurotoxic Aβ*56 levels and improves cognition in Alzheimer's disease animal model.

    PubMed

    Scherzer-Attali, R; Farfara, D; Cooper, I; Levin, A; Ben-Romano, T; Trudler, D; Vientrov, M; Shaltiel-Karyo, R; Shalev, D E; Segev-Amzaleg, N; Gazit, E; Segal, D; Frenkel, D

    2012-06-01

    An increasing body of evidence indicates a role for oligomers of the amyloid-β peptide (Aβ) in the neurotoxicity of this peptide and the pathology of Alzheimer's disease (AD). Several neurotoxic oligomeric forms of Aβ have been noted ranging from the larger Amyloid β-Derived Diffusible Ligands (ADDLs) to smaller trimers and dimers of Aβ. More recently a dodecameric form of Aβ with a 56 kDa molecular weight, denoted Aβ*56, was shown to cause memory impairment in AD model mice. Here, we present for the first time a potential therapeutic strategy for AD that targets the early stages in the formation of neurotoxic Aβ*56 oligomers using a modified quinone-Tryptophan small molecule N-(3-chloro-1,4-dihydro-1,4-dioxo-2-naphthalenyl)-L-Tryptophan (Cl-NQTrp). Using NMR spectroscopy we show that this compound binds the aromatic recognition core of Aβ and prevents the formation of oligomers. We assessed the effect of Cl-NQTrp in vivo in transgenic flies expressing Aβ(1-42) in their nervous system. When these flies were fed with Cl-NQTrp a marked alleviation of their Aβ-engendered reduced life span and defective locomotion was observed. Finally, intraperitoneal injection of Cl-NQTrp into an aggressive AD mouse model reduced the level of the Aβ*56 species in their brain and reversed their cognitive defects. Further experiments should assess whether this is a direct effect of the drug in the brain or an indirect peripheral effect. This is the first demonstration that targeted reduction of Aβ*56 results in amelioration of AD symptoms. This second generation of tryptophan-modified naphthoquinones could therefore serve as potent disease modifying therapeutic for AD. PMID:22449754

  1. System level analysis of cacao seed ripening reveals a sequential interplay of primary and secondary metabolism leading to polyphenol accumulation and preparation of stress resistance.

    PubMed

    Wang, Lei; Nägele, Thomas; Doerfler, Hannes; Fragner, Lena; Chaturvedi, Palak; Nukarinen, Ella; Bellaire, Anke; Huber, Werner; Weiszmann, Jakob; Engelmeier, Doris; Ramsak, Ziva; Gruden, Kristina; Weckwerth, Wolfram

    2016-08-01

    Theobroma cacao and its popular product, chocolate, are attracting attention due to potential health benefits including antioxidative effects by polyphenols, anti-depressant effects by high serotonin levels, inhibition of platelet aggregation and prevention of obesity-dependent insulin resistance. The development of cacao seeds during fruit ripening is the most crucial process for the accumulation of these compounds. In this study, we analyzed the primary and the secondary metabolome as well as the proteome during Theobroma cacao cv. Forastero seed development by applying an integrative extraction protocol. The combination of multivariate statistics and mathematical modelling revealed a complex consecutive coordination of primary and secondary metabolism and corresponding pathways. Tricarboxylic acid (TCA) cycle and aromatic amino acid metabolism dominated during the early developmental stages (stages 1 and 2; cell division and expansion phase). This was accompanied with a significant shift of proteins from phenylpropanoid metabolism to flavonoid biosynthesis. At stage 3 (reserve accumulation phase), metabolism of sucrose switched from hydrolysis into raffinose synthesis. Lipids as well as proteins involved in lipid metabolism increased whereas amino acids and N-phenylpropenoyl amino acids decreased. Purine alkaloids, polyphenols, and raffinose as well as proteins involved in abiotic and biotic stress accumulated at stage 4 (maturation phase) endowing cacao seeds the characteristic astringent taste and resistance to stress. In summary, metabolic key points of cacao seed development comprise the sequential coordination of primary metabolites, phenylpropanoid, N-phenylpropenoyl amino acid, serotonin, lipid and polyphenol metabolism thereby covering the major compound classes involved in cacao aroma and health benefits. PMID:27136060

  2. The Role of Sea Level Rise and in Situ Carbonate Accumulation on the Morphodynamic Evolution of a Carbonate Tidal Channel. The Case of the Bahamas Islands.

    NASA Astrophysics Data System (ADS)

    Borhani, S.; Viparelli, E.; Imran, J.; Mahjabeen, N.; Abdo, K.; Kendall, C.; Rankey, E. C.

    2015-12-01

    We explore the problem of morphodynamic evolution of carbonate tidal channels, bounded seaward by the ocean and shoaling landward, as observed in coastal lagoons and estuaries. Governing model equations are the conservation of mass and momentum for the flow, and the conservation of sediment mass in the water column and in the bed deposit. We model carbonate accumulation in terms of a specified depth-dependent carbonate "production rate" based on modern rates of carbonate accumulation rate. We further assume that 1) there is no input of clastic sediments to the system, 2) cementation processes are slow when compared to carbonate accumulation, 3) there is an absence of particles in the silt/mud range, and 4) we treat the carbonate sediments as non-cohesive particles. Governing equations are integrated with finite volume for unsteady, two-dimensional, depth averaged shallow-water flow over arbitrary topography. This method is known to capture sharp fronts accurately. We use Roe's approximate Riemann solver for the computation of fluxes at the interfaces between one finite volume and the other. For second order accuracy we implement MUSCL (Monotone Upstream Scheme for Conservation Laws) and a predictor-corrector time stepping scheme. We validate the model at field scale by comparing the numerical results with field data collected in the Bahamas channels. The comparison is presented in terms of flow velocities, bed profiles and grain size distributions of the bed surface. Finally, we use the validated model to explore how different rates of sea level rise will affect the morphodynamic evolution of the tidal channels under different "production rate" scenarios, e.g. constant, depth dependent.

  3. The Sphingosine Kinase 2 Inhibitor ABC294640 Reduces the Growth of Prostate Cancer Cells and Results in Accumulation of Dihydroceramides In Vitro and In Vivo.

    PubMed

    Venant, Heather; Rahmaniyan, Mehrdad; Jones, E Ellen; Lu, Ping; Lilly, Michael B; Garrett-Mayer, Elizabeth; Drake, Richard R; Kraveka, Jacqueline M; Smith, Charles D; Voelkel-Johnson, Christina

    2015-12-01

    Despite recent advances in the development of novel therapies against castration-resistant prostate cancer, the advanced form of the disease remains a major treatment challenge. Aberrant sphingolipid signaling through sphingosine kinases and their product, sphingosine-1-phosphate, can promote proliferation, drug resistance, angiogenesis, and inflammation. The sphingosine kinase 2 inhibitor ABC294640 is undergoing clinical testing in cancer patients, and in this study we investigated the effects this first-in-class inhibitor in castration-resistant prostate cancer. In vitro, ABC294640 decreased prostate cancer cell viability as well as the expression of c-Myc and the androgen receptor, while lysosomal acidification increased. ABC294640 also induced a greater than 3-fold increase in dihydroceramides that inversely correlated with inhibition of dihydroceramide desaturase (DEGS) activity. Expression of sphingosine kinase 2 was dispensable for the ABC294640-mediated increase in dihydroceramides. In vivo, ABC294640 diminished the growth rate of TRAMP-C2 xenografts in syngeneic hosts and elevated dihydroceramides within tumors as visualized by MALDI imaging mass spectroscopy. The plasma of ABC294640-treated mice contained significantly higher levels of C16- and C24:1-ceramides (but not dihydro-C16-ceramide) compared with vehicle-treated mice. In summary, our results suggest that ABC294640 may reduce the proliferative capacity of castration-resistant prostate cancer cells through inhibition of both sphingosine kinase 2 and dihydroceramide desaturase, thereby providing a foundation for future exploration of this small-molecule inhibitor for the treatment of advanced disease. PMID:26494858

  4. Taurine reduces ammonia- and N-methyl-D-aspartate-induced accumulation of cyclic GMP and hydroxyl radicals in microdialysates of the rat striatum.

    PubMed

    Hilgier, Wojciech; Anderzhanova, Elmira; Oja, Simo S; Saransaari, Pirjo; Albrecht, Jan

    2003-05-01

    Acute ammonia neurotoxicity caused by intraperitoneal administration of ammonium salts is mediated by overactivation of N-methyl-D-aspartate (NMDA) receptors, with ensuing generation of free radicals and extracellular accumulation of cyclic GMP (cGMP) arising from stimulation of nitric oxide (NO) synthesis. In this study, infusion of ammonium chloride or NMDA into the striata of rats via microdialysis probes increased the contents of cyclic GMP and hydroxyl radicals in the microdialysates. Co-infusion of taurine virtually abolished both the ammonia- and NMDA-induced accumulation of cGMP. Taurine also attenuated accumulation of hydroxyl radicals evoked by either treatment. This result is the first evidence of a potential of taurine to attenuate the effects of NMDA receptor overactivation by ammonia in vivo and points to the inhibition of the NMDA receptor-mediated NO synthesis as a possible mechanism of its neuroprotective action. Taurine or its blood-brain barrier penetrating analogues may be applicable in treatment of ammonia-induced neurological deficits. PMID:12729839

  5. Sucrose Transporter AtSUC9 Mediated by a Low Sucrose Level is Involved in Arabidopsis Abiotic Stress Resistance by Regulating Sucrose Distribution and ABA Accumulation.

    PubMed

    Jia, Wanqiu; Zhang, Lijun; Wu, Di; Liu, Shan; Gong, Xue; Cui, Zhenhai; Cui, Na; Cao, Huiying; Rao, Longbing; Wang, Che

    2015-08-01

    Sucrose (Suc) transporters (SUCs or SUTs) are important regulators in plant growth and stress tolerance. However, the mechanism of SUCs in plant abiotic stress resistance remains to be dietermined. Here, we found that AtSUC9 expression was induced by abiotic stress, including salt, osmotic and cold stress conditions. Disruption of AtSUC9 led to sensitive responses to abiotic stress during seed germination and seedling growth. Further analyses indicated that the sensitivity phenotype of Atsuc9 mutants resulted from higher Suc content in shoots and lower Suc content in roots, as compared with that in wild-type (WT) plants. In addition, we found that the expression of AtSUC9 is induced in particular by low levels of exogenous and endogenous Suc, and deletion of AtSUC9 affected the expression of the low Suc level-responsive genes. AtSUC9 also showed an obvious response to treatments with low concentrations of exogenous Suc during seed germination, seedling growth and Suc distribution, and Atsuc9 mutants hardly grew in abiotic stress treatments without exogenous Suc. Moreover, our results illustrated not only that deletion of AtSUC9 blocks abiotic stress-inducible ABA accumulation but also that Atsuc9 mutants had a lower content of endogenous ABA in stress conditions than in normal conditions. Deletion of AtSUC9 also inhibited the expression of many ABA-inducible genes (SnRk2.2/3/6, ABF2/3/4, ABI1/3/4, RD29A, KIN1 and KIN2). These results indicate that AtSUC9 is induced in particular by low Suc levels then mediates the balance of Suc distribution and promotes ABA accumulation to enhance Arabidopsis abiotic stress resistance. PMID:26063392

  6. Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

    PubMed Central

    Wöhr, Markus; Roullet, Florence I.; Hung, Albert Y.; Sheng, Morgan; Crawley, Jacqueline N.

    2011-01-01

    Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1−/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1−/− mice as compared to wildtype Shank1+/+ littermate controls. Shank1−/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1−/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1−/− mice were unaffected, indicating a failure of Shank1−/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1−/− mice are consistent with a phenotype relevant to social communication deficits in autism. PMID:21695253

  7. The chromium accumulation and its physiological effects in juvenile rockfish, Sebastes schlegelii, exposed to different levels of dietary chromium (Cr(6+)) concentrations.

    PubMed

    Kim, Jun-Hwan; Kang, Ju-Chan

    2016-01-01

    Juvenile rockfish (mean length 13.7±1.7 cm, and mean weight 55.6±4.8 g) were exposed for 4 weeks with the different levels of dietary chromium (Cr(6+)) at 0, 30, 60, 120 and 240 mg/kg. The profile of chromium in the tissues of rockfish is dependent on the exposure periods and chromium concentration. After 4 weeks, the order of chromium accumulation in tissues was liver>kidney>spleen>intestine>gill>muscle. The dietary chromium exposure decreased the growth rate and hepatosomatic index of rockfish. The major hematological findings were significant decrease in the red blood cell (RBC) count, hematocrit (Ht) value, and hemoglobin (Hb) concentration exposed to ≥120 mg/kg chromium concentrations. The dietary chromium exposure (≥120 mg/kg) led to notable increase in glucose, cholesterol, glutamic oxalate transaminase (GOT), and glutamic pyruvate transaminase (GPT) in plasma, whereas there was no considerable change in calcium, magnesium, total protein, and alkaline phosphatase (ALP). The results indicated that the dietary chromium exposure to rockfish can induce significant chromium accumulation in the specific tissues, inhibition of growth, and hematological alterations. PMID:26705966

  8. Changing levels of heavy metal accumulation in birds at Tumacacori National Historic Park along the Upper Santa Cruz River Watershed in southern Arizona

    USGS Publications Warehouse

    Van Riper, Charles; Lester, Michael B.

    2016-01-01

    National Parks and other protected areas can be influenced by contamination from outside their boundaries. This is particularly true of smaller parks and those in riparian ecosystems, a habitat that in arid environments provides critical habitat for breeding, migratory, and wintering birds. Animals living in contaminated areas are susceptible to adverse health effects as a result of long-term exposure and bioaccumulation of heavy metals. We investigated the distribution and cascading extent of heavy metal accumulation in Song Sparrows (Melospiza melodia) at Tumacacori National Historic Park (TUMA) along the upper Santa Cruz River watershed in southern Arizona. This study had three goals: (1) quantify the concentrations and distributional patterns of heavy metals in blood and feathers of Song Sparrows at Tumacacori National Historic Park, (2) quantify hematocrit values, body conditions (that is, residual body mass), and immune conditions of Song Sparrows in the park (3) compare our findings with prior studies at the park to assess the extent of heavy metal accumulation in birds at downstream sites after the 2009 wastewater treatment plant upgrade, and (4) quantify concentrations and distributional patterns of heavy metals in blood and feathers of Song Sparrows among six study sites throughout the upper Santa Cruz River watershed. This study design would allow us to more accurately assess song sparrow condition and blood parameters among sites with differing potential sources of contamination exposure, and how each location could have contributed to heavy metal levels of birds in the park.

  9. Rapid Accumulation of Total Lipid in Rhizoclonium africanum Kutzing as Biodiesel Feedstock under Nutrient Limitations and the Associated Changes at Cellular Level

    PubMed Central

    Satpati, Gour Gopal; Kanjilal, Sanjit; Narayana Prasad, Rachapudi Badari; Pal, Ruma

    2015-01-01

    Increase of total lipid and the proportion of the favorable fatty acids in marine green filamentous macroalga Rhizoclonium africanum (Chlorophyceae) was studied under nitrate and phosphate limitations. These stresses were given by both eliminating and doubling the required amounts of nitrate and phosphate salts in the growth media. A significant twofold increase in total lipid (193.03 mg/g) was achieved in cells in absence of nitrate in the culture medium, followed by phosphate limitation (142.65 mg/g). The intracellular accumulation of neutral lipids was observed by fluorescence microscopy. The scanning electron microscopic study showed the major structural changes under nutrient starvation. Fourier transform infrared spectroscopy (FTIR) revealed the presence of ester (C-O-C stretching), ketone (C-C stretching), carboxylic acid (O-H bending), phosphine (P-H stretching), aromatic (C-H stretching and bending), and alcohol (O-H stretching and bending) groups in the treated cells indicating the high accumulation of lipid hydrocarbons in the treated cells. Elevated levels of fatty acids favorable for biodiesel production, that is, C16:0, C16:1, C18:1, and C20:1, were identified under nitrate- and phosphate-deficient conditions. This study shows that the manipulation of cultural conditions could affect the biosynthetic pathways leading to increased lipid production while increasing the proportion of fatty acids suitable for biodiesel production. PMID:26880924

  10. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

    PubMed Central

    Staszewski, Vincent; Reece, Sarah E.; O'Donnell, Aidan J.; Cunningham, Emma J. A.

    2012-01-01

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns. PMID:22357264

  11. Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors

    PubMed Central

    Austin, Adelaide; Jiga-Boy, Gabriela M.; Rea, Sara; Newstead, Simon A.; Roderick, Sian; Davis, Nick J.; Clement, R. Marc; Boy, Frédéric

    2016-01-01

    Negative emotional responses to the daily life stresses have cumulative effects which, in turn, impose wide-ranging negative constraints on emotional well being and neurocognitive performance (Kalueff and Nutt, 2007; Nadler et al., 2010; Charles et al., 2013). Crucial cognitive functions such as memory and problem solving, as well more short term emotional responses (e.g., anticipation of- and response to- monetary rewards or losses) are influenced by mood. The negative impact of these behavioral responses is felt at the individual level, but it also imposes major economic burden on modern healthcare systems. Although much research has been undertaken to understand the underlying mechanisms of depressed mood and design efficient treatment pathways, comparatively little was done to characterize mood modulations that remain within the boundaries of a healthy mental functioning. In one placebo-controlled experiment, we applied daily prefrontal transcranial Direct Current Stimulation (tDCS) at five points in time, and found reliable improvements on self-reported mood evaluation. Using a new team of experimenters, we replicated this finding in an independent double-blinded placebo-controlled experiment and showed that stimulation over a shorter period of time (3 days) is sufficient to create detectable mood improvements. Taken together, our data show that repeated bilateral prefrontal tDCS can reduce psychological distress in non-depressed individuals. PMID:26973591

  12. Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors.

    PubMed

    Austin, Adelaide; Jiga-Boy, Gabriela M; Rea, Sara; Newstead, Simon A; Roderick, Sian; Davis, Nick J; Clement, R Marc; Boy, Frédéric

    2016-01-01

    Negative emotional responses to the daily life stresses have cumulative effects which, in turn, impose wide-ranging negative constraints on emotional well being and neurocognitive performance (Kalueff and Nutt, 2007; Nadler et al., 2010; Charles et al., 2013). Crucial cognitive functions such as memory and problem solving, as well more short term emotional responses (e.g., anticipation of- and response to- monetary rewards or losses) are influenced by mood. The negative impact of these behavioral responses is felt at the individual level, but it also imposes major economic burden on modern healthcare systems. Although much research has been undertaken to understand the underlying mechanisms of depressed mood and design efficient treatment pathways, comparatively little was done to characterize mood modulations that remain within the boundaries of a healthy mental functioning. In one placebo-controlled experiment, we applied daily prefrontal transcranial Direct Current Stimulation (tDCS) at five points in time, and found reliable improvements on self-reported mood evaluation. Using a new team of experimenters, we replicated this finding in an independent double-blinded placebo-controlled experiment and showed that stimulation over a shorter period of time (3 days) is sufficient to create detectable mood improvements. Taken together, our data show that repeated bilateral prefrontal tDCS can reduce psychological distress in non-depressed individuals. PMID:26973591

  13. Chemical genoprotection: reducing biological damage to as low as reasonably achievable levels

    PubMed Central

    Alcaraz, M; Armero, D; Martínez-Beneyto, Y; Castillo, J; Benavente-García, O; Fernandez, H; Alcaraz-Saura, M; Canteras, M

    2011-01-01

    Objectives The aim of this study was to evaluate the antioxidant substances present in the human diet with an antimutagenic protective capacity against genotoxic damage induced by exposure to X-rays in an attempt to reduce biological damage to as low a level as reasonably possible. Methods Ten compounds were assessed using the lymphocyte cytokinesis-block micronucleus (MN) cytome test. The compounds studied were added to human blood at 25 μM 5 min before exposure to irradiation by 2 Gy of X-rays. Results The protective capacity of the antioxidant substances assessed was from highest to lowest according to the frequency of the MN generated by X-ray exposure: rosmarinic acid = carnosic acid = δ-tocopherol = l-acid ascorbic = apigenin = amifostine (P < 0.001) > green tea extract = diosmine = rutin = dimetylsulfoxide (P < 0.05) > irradiated control. The reduction in genotoxic damage with the radiation doses administered reached 58%, which represents a significant reduction in X-ray-induced chromosomal damage (P < 0.001). This degree of protection is greater than that obtained with amifostine, a radioprotective compound used in radiotherapy and which is characterised by its high toxicity. Conclusion Several antioxidant substances, common components of the human diet and lacking toxicity, offer protection from the biological harm induced by ionizing radiation. Administering these protective substances to patients before radiological exploration should be considered, even in the case of small radiation doses and regardless of the biological damage expected. PMID:21697157

  14. Developing Community-Level Policy and Practice to Reduce Traffic-Related Air Pollution Exposure

    PubMed Central

    Brugge, Doug; Patton, Allison P.; Bob, Alex; Reisner, Ellin; Lowe, Lydia; Bright, Oliver-John M.; Durant, John L.; Newman, Jim; Zamore, Wig

    2016-01-01

    The literature consistently shows associations of adverse cardiovascular and pulmonary outcomes with residential proximity to highways and major roadways. Air monitoring shows that traffic-related pollutants (TRAP) are elevated within 200–400 m of these roads. Community-level tactics for reducing exposure include the following: 1) HEPA filtration; 2) Appropriate air-intake locations; 3) Sound proofing, insulation and other features; 4) Land-use buffers; 5) Vegetation or wall barriers; 6) Street-side trees, hedges and vegetation; 7) Decking over highways; 8) Urban design including placement of buildings; 9) Garden and park locations; and 10) Active travel locations, including bicycling and walking paths. A multidisciplinary design charrette was held to test the feasibility of incorporating these tactics into near-highway housing and school developments that were in the planning stages. The resulting designs successfully utilized many of the protective tactics and also led to engagement with the designers and developers of the sites. There is a need to increase awareness of TRAP in terms of building design and urban planning. PMID:27413416

  15. Polyhydroxyalkanoate (PHA) storage within a mixed-culture biomass with simultaneous growth as a function of accumulation substrate nitrogen and phosphorus levels.

    PubMed

    Valentino, Francesco; Karabegovic, Lamija; Majone, Mauro; Morgan-Sagastume, Fernando; Werker, Alan

    2015-06-15

    PHA content was attributed to interpreted differences in the biomass initial physiological state and not due to changes in feedstock nutrient loading. We found that the accumulation process production rates for mixed cultures can be sustained long after the maximum PHA content of the biomass was reached. Within the specific context of the applied fed-batch feed-on-demand methods, active biomass growth was interpreted to have been largely restricted to the PHA-storing phenotypic fraction of the biomass. This study suggests practical prospects for mixed culture PHA production using a wide range of volatile fatty acid (VFA) rich feedstocks. Such VFA sources derived from residual industrial or municipal organic wastes often naturally contain associated nutrients ranging in levels from limitation to excess. PMID:25846983

  16. Rare Earth Ion Mediated Fluorescence Accumulation on a Single Microbead: An Ultrasensitive Strategy for the Detection of Protein Kinase Activity at the Single-Cell Level.

    PubMed

    Zhang, Xiaobo; Liu, Chenghui; Wang, Honghong; Wang, Hui; Li, Zhengping

    2015-12-01

    A single microbead-based fluorescence imaging (SBFI) strategy that enables detection of protein kinase activity from single cell lysates is reported. We systematically investigated the ability of various rare earth (RE) ions, immobilized on the microbead, for specific capturing of kinase-induced phosphopeptides, and Dy(3+) was found to be the most prominent one. Through the efficient concentration of kinase-induced fluorescent phosphopeptides on a Dy(3+) -functionalized single microbead, kinase activity can be detected and quantified by reading the fluorescence on the microbead with a confocal fluorescence microscope. Owing to the extremely specific recognition of Dy(3+) towards phosphopeptides and the highly-concentrated fluorescence accumulation on only one microbead, ultrahigh sensitivity has been achieved for the SBFI strategy which allows direct kinase analysis at the single-cell level. PMID:26482714

  17. Effect of apple pomace fiber and pork fat levels on quality characteristics of uncured, reduced-fat chicken sausages.

    PubMed

    Choi, Yun-Sang; Kim, Young-Boong; Hwang, Ko-Eun; Song, Dong-Heon; Ham, Youn-Kyung; Kim, Hyun-Wook; Sung, Jung-Min; Kim, Cheon-Jei

    2016-06-01

    The effects of reducing pork fat level from 30 to 25 and 20% by partially substituting pork fat with 1 and 2% apple pomace fiber were investigated based on the evaluation of physicochemical properties and textural properties of uncured, reduced-fat chicken sausages. Increased fat level resulted in decreased moisture content, cooking loss, total expressible fluid separation, fat separation, and yellowness of uncured, reduced-fat chicken sausages, whereas, an increase in fat content, caloric energy, pH, lightness, redness, hardness, cohesiveness, gumminess, and chewiness was observed. The results showed that uncured, reduced-fat chicken sausage samples with increased apple pomace fiber level had lower cooking loss, total expressible fluid separation, fat separation, pH, and redness. The results from this study show that inclusion of apple pomace fiber in the formulation will successfully reduce fat content in emulsion sausages, while improving quality characteristics relative to regular-fat (30%) control. PMID:27030694

  18. Reduced gene expression levels after chronic exposure to high concentrations of air pollutants.

    PubMed

    Rossner, Pavel; Tulupova, Elena; Rossnerova, Andrea; Libalova, Helena; Honkova, Katerina; Gmuender, Hans; Pastorkova, Anna; Svecova, Vlasta; Topinka, Jan; Sram, Radim J

    2015-10-01

    We analyzed the ability of particulate matter (PM) and chemicals adsorbed onto it to induce diverse gene expression profiles in subjects living in two regions of the Czech Republic differing in levels and sources of the air pollution. A total of 312 samples from polluted Ostrava region and 154 control samples from Prague were collected in winter 2009, summer 2009 and winter 2010. The highest concentrations of air pollutants were detected in winter 2010 when the subjects were exposed to: PM of aerodynamic diameter <2.5μm (PM2.5) (70 vs. 44.9μg/m(3)); benzo[a]pyrene (9.02 vs. 2.56ng/m(3)) and benzene (10.2 vs. 5.5μg/m(3)) in Ostrava and Prague, respectively. Global gene expression analysis of total RNA extracted from leukocytes was performed using Illumina Expression BeadChips microarrays. The expression of selected genes was verified by quantitative real-time PCR (qRT-PCR). Gene expression profiles differed by locations and seasons. Despite lower concentrations of air pollutants a higher number of differentially expressed genes and affected KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was found in subjects from Prague. In both locations immune response pathways were affected, in Prague also neurodegenerative diseases-related pathways. Over-representation of the latter pathways was associated with the exposure to PM2.5. The qRT-PCR analysis showed a significant decrease in expression of APEX, ATM, FAS, GSTM1, IL1B and RAD21 in subjects from Ostrava, in a comparison of winter 2010 and summer 2009. In Prague, an increase in gene expression was observed for GADD45A and PTGS2. In conclusion, high concentrations of pollutants in Ostrava were not associated with higher number of differentially expressed genes, affected KEGG pathways and expression levels of selected genes. This observation suggests that chronic exposure to air pollution may result in reduced gene expression response with possible negative health consequences. PMID:26298100

  19. An element in the bovine papillomavirus late 3' untranslated region reduces polyadenylated cytoplasmic RNA levels.

    PubMed

    Furth, P A; Baker, C C

    1991-11-01

    Expression of the two bovine papillomavirus type 1 (BPV-1) late genes, L1 and L2, coding for the two capsid proteins, is limited to terminally differentiated keratinocytes in bovine fibropapillomas. This pattern of expression is determined both by the activity of the late promoter and by the inhibition of late region expression in less well differentiated cells. Inhibition of L1 and L2 mRNA production in nonpermissive cells must occur since the late region potentially could be transcribed from early region promoters. Nuclear runoff analysis of the late region has demonstrated that up to 95% of transcripts which are initiated in the early region in nonpermissive cells terminate within the late region upstream of the late polyadenylation site (C. C. Baker and J. Noe, J. Virol. 63:3529-3534, 1989). However, very few of the primary transcripts which include the late polyadenylation site are processed into mRNA. In this study, we have used expression vectors to characterize an inhibitory element active in nonpermissive cells which is located in the late 3' untranslated region (3'UTR). While the late polyadenylation site is functional in these cells, a 53-bp element in the late 3'UTR reduces levels of polyadenylated cytoplasmic RNA. This element inhibited chloramphenicol acetyltransferase (CAT) expression 6- to 10-fold when cloned in the sense orientation into the 3'UTR of a CAT expression vector. No block to expression was seen when the fragment was cloned immediately downstream of the poly(A) site, in an intron upstream of the CAT coding sequence, or in an antisense orientation in the 3'UTR. When the same fragment was deleted from a BPV-1 L1 expression vector, a sixfold increase in mRNA levels was seen. Actinomycin D chase experiments using BPV-1 L1 expression vectors indicated that the element does not destabilize cytoplasmic polyadenylated RNA. Therefore, the element must act before the mature mRNA reaches the cytoplasm. The data presented are consistent with effects

  20. Ecological feedbacks can reduce population-level efficacy of wildlife fertility control

    USGS Publications Warehouse

    Ransom, Jason I.; Powers, Jenny G.; Hobbs, N. Thompson; Baker, Dan L.

    2014-01-01

    1. Anthropogenic stress on natural systems, particularly the fragmentation of landscapes and the extirpation of predators from food webs, has intensified the need to regulate abundance of wildlife populations with management. Controlling population growth using fertility control has been considered for almost four decades, but nearly all research has focused on understanding effects of fertility control agents on individual animals. Questions about the efficacy of fertility control as a way to control populations remain largely unanswered. 2. Collateral consequences of contraception can produce unexpected changes in birth rates, survival, immigration and emigration that may reduce the effectiveness of regulating animal abundance. The magnitude and frequency of such effects vary with species-specific social and reproductive systems, as well as connectivity of populations. Developing models that incorporate static demographic parameters from populations not controlled by contraception may bias predictions of fertility control efficacy. 3. Many population-level studies demonstrate that changes in survival and immigration induced by fertility control can compensate for the reduction in births caused by contraception. The most successful cases of regulating populations using fertility control come from applications of contraceptives to small, closed populations of gregarious and easily accessed species. 4. Fertility control can result in artificial selection pressures on the population and may lead to long-term unintentional genetic consequences. The magnitude of such selection is dependent on individual heritability and behavioural traits, as well as environmental variation. 5. Synthesis and applications. Understanding species' life-history strategies, biology, behavioural ecology and ecological context is critical to developing realistic expectations of regulating populations using fertility control. Before time, effort and funding are invested in wildlife

  1. Phytochemicals from Tradescantia albiflora Kunth Extracts Reduce Serum Uric Acid Levels in Oxonate-induced Rats

    PubMed Central

    Wang, Wen-Ling; Sheu, Shi-Yuan; Huang, Wen-Dar; Chuang, Ya-Ling; Tseng, Han-Chun; Hwang, Tzann-Shun; Fu, Yuan-Tsung; Kuo, Yueh-Hsiung; Yao, Chun-Hsu; Kuo, Tzong-Fu

    2016-01-01

    Background: Tradescantia albiflora (TA) Kunth (Commelinaceae) has been used for treating gout and hyperuricemia as folklore remedies in Taiwan. Therefore, it is worthwhile to study the effect of TA extracts on lowering uric acid activity. The hypouricemic effects of TA extracts on potassium oxonate (PO)-induced acute hyperuricemia were investigated for the first time. Materials and Methods: All treatments at the same volume (1 ml) were orally administered to the abdominal cavity of PO-induced hyperuricemic rats. One milliliter of TA extract in n-hexane (HE), ethyl acetate (EA), n-butanol (BuOH), and water fractions has 0.28, 0.21, 0.28, and 1.03 mg TA, respectively; and the plasma uric acid (PUA) level was measured for a consecutive 4 h after administration. Results: All four fractions' extracts derived from TA were observed to significantly reduce PUA compared with the PO group. The EA-soluble fraction (TA-EA) exhibited the best xanthine oxidase (XO) inhibitory activity. Following column chromatography, 12 phytochemicals were isolated and identified from the EA fraction. The IC50 values of isolated phytochemicals indicated that bracteanolide A (AR11) showed the remarkable XO inhibitory effect (IC50 value of 76.4 μg/ml). These findings showed that the in vivo hypouricemic effect in hyperuricemic rats was consistent with in vitro XO inhibitory activity, indicating that TA extracts and derived phytochemicals could be potential candidates as hypouricemic agents. SUMMARY Tradescantia albiflora extracts possess in vivo hypouricemic action in hyperuricemic ratsT. albiflora extracts exhibited strong inhibitory activity against xanthine oxidase (XO)Butenolide may play an important role in XO inhibitionThe extract bracteanolide A was demonstrated potent XO inhibitory activity in vitro. Abbreviations used: TA: Tradescantia albiflora, PO: potassium oxonate, HE: n-hexane, EA: ethyl acetate, BuOH: n-butanol, PUA: plasma uric acid, XO: xanthine oxidase, MeOH: methanol, IP

  2. Ecological feedbacks can reduce population-level efficacy of wildlife fertility control

    PubMed Central

    Ransom, Jason I; Powers, Jenny G; Thompson Hobbs, N; Baker, Dan L

    2014-01-01

    Anthropogenic stress on natural systems, particularly the fragmentation of landscapes and the extirpation of predators from food webs, has intensified the need to regulate abundance of wildlife populations with management. Controlling population growth using fertility control has been considered for almost four decades, but nearly all research has focused on understanding effects of fertility control agents on individual animals. Questions about the efficacy of fertility control as a way to control populations remain largely unanswered. Collateral consequences of contraception can produce unexpected changes in birth rates, survival, immigration and emigration that may reduce the effectiveness of regulating animal abundance. The magnitude and frequency of such effects vary with species-specific social and reproductive systems, as well as connectivity of populations. Developing models that incorporate static demographic parameters from populations not controlled by contraception may bias predictions of fertility control efficacy. Many population-level studies demonstrate that changes in survival and immigration induced by fertility control can compensate for the reduction in births caused by contraception. The most successful cases of regulating populations using fertility control come from applications of contraceptives to small, closed populations of gregarious and easily accessed species. Fertility control can result in artificial selection pressures on the population and may lead to long-term unintentional genetic consequences. The magnitude of such selection is dependent on individual heritability and behavioural traits, as well as environmental variation. Synthesis and applications. Understanding species' life-history strategies, biology, behavioural ecology and ecological context is critical to developing realistic expectations of regulating populations using fertility control. Before time, effort and funding are invested in wildlife contraception, managers

  3. Somatostatin reduces sup 3 H-thymidine incorporation and c-myc, but not thyroglobulin ribonucleic acid levels in human thyroid follicular cells in vitro

    SciTech Connect

    degli Uberti, E.C.; Hanau, S.; Rossi, R.; Piva, R.; Margutti, A.; Trasforini, G.; Pansini, G.; del Senno, L. )

    1991-06-01

    The action of somatostatin (SRIH) on {sup 3}H-thymidine (thy) incorporation and on c-myc and thyroglobulin RNA levels in a suspension of follicles from normal and goitrous human thyroid was examined. SRIH, at 10{sup {minus} 7} M concentration, inhibited basal thy incorporation (maximally by 4 h lasting for up 24 h), which effect was greater in goiter than in normal thyroid and was also detected in growing adherent epithelial cells. Moreover, in a follicle suspension SRIH prevented TSH-stimulated thy incorporation, both in normal and in goitrous thyroid. Basal expression of c-myc RNA was not affected by SRIH in either tissue, whereas the TSH-stimulated c-myc RNA level was significantly reduced in goiter. No effect of SRIH was observed on basal or TSH-stimulated thyroglobulin RNA levels. SRIH did not alter basal cAMP concentrations in normal or goitrous follicles, but it significantly reduced TSH-stimulated cAMP accumulation both in normal thyroid and in goiter. Overall, our data indicate a direct inhibitory action of SRIH on growth, but not on differentiation, of human thyroid, probably by a mechanism not entirely cAMP dependent.

  4. Arsenic accumulation in root and shoot vis-a-vis its effects on growth and level of phytochelatins in seedlings of Cicer arietinum L.

    PubMed

    Gupta, D K; Tripathi, R D; Mishra, S; Srivastava, S; Dwivedi, S; Rai, U N; Yang, X E; Huanji, H; Inouhe, M

    2008-05-01

    Arsenic (As) contamination of water and soil has become a subject of prime interest due to its direct effect on human health through drinking water and food. In present study two varieties (CSG-8962 and C-235) of chickpea, Cicer arietinum L., which is a major supplementary food in many parts of India and a valuable source of protein, has been selected to estimate the level of arsenate in root and shoot of five day old seedlings vis-à-vis effect of arsenate on seedling growth and induction of thiols including glutathione (GSH) and phytochelatins (PCs) and their homologues. Both varieties accumulated arsenate to similar levels and most of the metalloid was confined to roots, only about 2.5% was translocated to shoot. Plant growth was also not affected significantly in both the varieties. Arsenate exposure significantly induced the levels of thiols including PCs and homophytochelatins (hPCs). The induction of thiols was much higher in roots than shoots and was greater in var C-235 between the two tested ones. Thus, both varieties tolerated and detoxified arsenic through chelation with GSH, PCs and hPCs, primarily in roots, however var C-235 performed better PMID:18972678

  5. Accumulation of PrLeg, a Perilla legumin protein in potato tuber results in enhanced level of sulphur-containing amino acids.

    PubMed

    Goo, Young-Min; Kim, Tae-Won; Lee, Min-Kyung; Lee, Shin-Woo

    2013-09-01

    Potato is the fourth staple food in the world, following rice, wheat, and maize, whereas tubers contain high quality of starch, relatively high amounts of vitamin C and many other important substances. It also contains relatively good quality of protein (about 3 to 6% of the dried weight) and patatin, and 11S globulin is a major storage protein with high level of lysine. However, tuber protein contains relatively low amounts of sulphur-containing amino acids, which may result in low nutritional value. Recently, we cloned a gene encoding PrLeg polypeptide, a seed storage protein from Perilla, which contains relatively higher levels of sulphur-containing amino acids. We transformed PrLeg cDNA into a potato plant to over-express under the direction of the tuber-specific promoter, patatin. Most of the transgenic lines identified through PCR and RT-PCR analyses were able to accumulate high amount of prLeg transcript in their tuber tissue, while very little or no transcript that were detected in their leaf tissues. The level of methionine content was elevated up to three-fold compared to non-transgenic parental line, without any significant changes in other amino acids, suggesting that further research is required to get a deeper insight into their nutritional value. PMID:24161240

  6. [Effects of plant species combination and water body nutrient level on the biomass accumulation and allocation of three kinds functional plants].

    PubMed

    Sun, Li-Fang; Sun, Yi-Xiang; Zhou, Chang-Fang; An, Shu-Qing

    2009-10-01

    Four nutrient levels, i.e., 0.5 mg N x L(-1) and 0.1 mg P x L(-1) (I), 1.5 mg N x L(-1) and 0.3 mg P x L(-1) (II), 4.5 mg N x L(-1) and 0.9 mg P x L(-1) (III), and 13.5 mg N x L(-1) and 2.7 mg P x L(-1) (IV), were installed to study the effects of water body's nutrient level, plant species combination, and their interactions on the biomass accumulation and allocation of invasive floating species Eichhornia crassipes, native rooted leaf-floating species Jussiaea stipulacea, and submerged plant Vallisneria spiralis. The total, root, stem, and leaf biomass of E. crassipes and J. stipulacea, either in monoculture or in mixed-culture, increased with increasing water body's nutrient level, their total biomass in treatments III and IV being averagely 54.47% and 102.63% higher than that in treatments I and II, respectively. Under different plant species combination, the total, root, stem, and leaf biomass of V. spiralis showed a declining trend with the increase of nutrient level, and the total biomass of V. spiralis in treatments III and IV was averagely 45.88% lower than that in treatments I and II. The results of two-way ANOVA showed that water body's nutrient level had significant positive effects on the biomass of E. crassipes and J. stipulacea but negative effects on that of V. spiralis, and the effects of plant species combination varied with target plant species. PMID:20077692

  7. Resolvin D1 reduces ER stress-induced apoptosis and triglyceride accumulation through JNK pathway in HepG2 cells.

    PubMed

    Jung, Tae Woo; Hwang, Hwan-Jin; Hong, Ho Cheol; Choi, Hae Yoon; Yoo, Hye Jin; Baik, Sei Hyun; Choi, Kyung Mook

    2014-06-25

    Research has indicated that stress on the endoplasmic reticulum (ER) of a cell affects the pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Resolvins, a novel family derived from ω-3 polyunsaturated fatty acids, have anti-inflammatory and insulin sensitizing properties, and it has been suggested that they play a role in the amelioration of obesity-related metabolic dysfunctions. This study showed that pretreatment with resolvin D1 (RvD1) attenuated ER stress-induced apoptosis and also decreased caspase 3 activity in HepG2 cells. Furthermore, RvD1 significantly decreased tunicamycin-induced triglycerides accumulation as well as SREBP-1 expression. However, tunicamycin-induced ER stress markers were not significantly affected by RvD1 treatment. Moreover, RvD1 treatment did not affect the tunicamycin-induced expression of chaperones that assist protein folding in the ER. These results suggest that RvD1-conferred cellular protection may occur downstream of the ER stress. This was supported by the finding that RvD1 significantly inhibited tunicamycin-induced c-Jun N-terminal kinase (JNK) expression, although P38 and ERK1/2 phosphorylation were not affected. In addition, anisomycin, a JNK activator, increased caspase 3 activity and apoptosis as well as triglycerides accumulation and SREBP1 expression, and RvD1 treatment reversed these changes. In conclusion, RvD1 attenuated ER stress-induced hepatic steatosis and apoptosis via the JNK-mediated pathway. This study may provide insight into a novel underlying mechanism and a strategy for treating NAFLD. PMID:24784707

  8. Seasonal variation of Sarpa salpa fish toxicity, as related to phytoplankton consumption, accumulation of heavy metals, lipids peroxidation level in fish tissues and toxicity upon mice.

    PubMed

    Bellassoued, Khaled; Hamza, Asma; van Pelt, Jos; Elfeki, Abdelfatteh

    2013-02-01

    The aim of this work was to investigate for Sarpa salpa the seasonal trend in the food sources, heavy metals bioaccumulation and the oxidative stress in the organs. In addition, the toxicity was assessed by mouse bioassay of extract of the fish's organs collected in autumn, the peak of occurrence of hallucinatory syndrome. The toxicity was further studied for compounds present in epiphyte collected from the sea at the end of spring and in summer that are digested by the S. salpa in these seasons. We observed a higher lipid peroxydation in different tissues of S. salpa compared to the control fish Diplodus annularis. Furthermore, heavy metals accumulation in organs of these fish showed a significant variation between the two species (P < 0.05). The lethal dose (LD50%) determined for crude ciguatoxin (neurotoxins) extracts of viscera, liver, brain and muscle of S. salpa were as follows: 1.217, 2.195, 14.395, 18.645 g/kg mouse, respectively. We noticed a significant correlation (P < 0.05) between the total amount of toxic dinoflagellates and the level of TBARS in the liver, the brain and the muscle, this for all seasons and all sizes. Moreover, the cytotoxic effect observed for epiphytes extract confirms the transfer of toxins originating from toxic dinoflagellates, which live as epiphytes on P. oceanica leaves, to the fish by grazing. Our work indicates that, toxic phytoplanktons and heavy metals accumulation are responsible for the increase of oxidative stress in the organs of S. salpa. Hence, the edible part of S. salpa, especially the viscera and liver, can cause a threat to human health, and consumption should, for this reason, be dissuaded. PMID:22535366

  9. Metabolic engineering of oilseed crops to produce high levels of novel acetyl glyceride oils with reduced viscosity, freezing point and calorific value.

    PubMed

    Liu, Jinjie; Rice, Adam; McGlew, Kathleen; Shaw, Vincent; Park, Hyunwoo; Clemente, Tom; Pollard, Mike; Ohlrogge, John; Durrett, Timothy P

    2015-08-01

    Seed oils have proved recalcitrant to modification for the production of industrially useful lipids. Here, we demonstrate the successful metabolic engineering and subsequent field production of an oilseed crop with the highest accumulation of unusual oil achieved so far in transgenic plants. Previously, expression of the Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) gene in wild-type Arabidopsis seeds resulted in the accumulation of 45 mol% of unusual 3-acetyl-1,2-diacyl-sn-glycerols (acetyl-TAGs) in the seed oil (Durrett et al., 2010 PNAS 107:9464). Expression of EaDAcT in dgat1 mutants compromised in their ability to synthesize regular triacylglycerols increased acetyl-TAGs to 65 mol%. Camelina and soybean transformed with the EaDAcT gene accumulate acetyl-triacylglycerols (acetyl-TAGs) at up to 70 mol% of seed oil. A similar strategy of coexpression of EaDAcT together with RNAi suppression of DGAT1 increased acetyl-TAG levels to up to 85 mol% in field-grown transgenic Camelina. Additionally, total moles of triacylglycerol (TAG) per seed increased 20%. Analysis of the acetyl-TAG fraction revealed a twofold reduction in very long chain fatty acids (VLCFA), consistent with their displacement from the sn-3 position by acetate. Seed germination remained high, and seedlings were able to metabolize the stored acetyl-TAGs as rapidly as regular triacylglycerols. Viscosity, freezing point and caloric content of the Camelina acetyl-TAG oils were reduced, enabling use of this oil in several nonfood and food applications. PMID:25756355

  10. Oxidized and Reduced Nicotinamide Adenine Dinucleotide Phosphate Levels of Plants Hardened and Unhardened Against Chilling Injury

    PubMed Central

    Kuraishi, Susumu; Arai, Noriko; Ushijima, Tadahiro; Tazaki, Tadayoshi

    1968-01-01

    Pea plants (Pisum sativum L. var. Alaska) subjected to low temperature (5°) in the light acquired resistance against chilling injury. Unhardened plants maintained high NADP and low NADPH levels during illumination at 25° but hardened plants had low NADP and high NADPH levels in the light. When the unhardened plants were transferred to the dark room at 25°, their NADPH levels decreased immediately. On the other hand, hardened plants maintained a high NADPH level for a few hours even in the dark. PMID:16656757

  11. Increased neuronal PreP activity reducesaccumulation, attenuates neuroinflammation and improves mitochondrial and synaptic function in Alzheimer disease's mouse model.

    PubMed

    Fang, Du; Wang, Yongfu; Zhang, Zhihua; Du, Heng; Yan, Shiqiang; Sun, Qinru; Zhong, Changjia; Wu, Long; Vangavaragu, Jhansi Rani; Yan, Shijun; Hu, Gang; Guo, Lan; Rabinowitz, Molly; Glaser, Elzbieta; Arancio, Ottavio; Sosunov, Alexander A; McKhann, Guy M; Chen, John Xi; Yan, Shirley ShiDu

    2015-09-15

    Accumulation of amyloid-β (Aβ) in synaptic mitochondria is associated with mitochondrial and synaptic injury. The underlying mechanisms and strategies to eliminate Aβ and rescue mitochondrial and synaptic defects remain elusive. Presequence protease (PreP), a mitochondrial peptidasome, is a novel mitochondrial Aβ degrading enzyme. Here, we demonstrate for the first time that increased expression of active human PreP in cortical neurons attenuates Alzheimer disease's (AD)-like mitochondrial amyloid pathology and synaptic mitochondrial dysfunction, and suppresses mitochondrial oxidative stress. Notably, PreP-overexpressed AD mice show significant reduction in the production of proinflammatory mediators. Accordingly, increased neuronal PreP expression improves learning and memory and synaptic function in vivo AD mice, and alleviates Aβ-mediated reduction of long-term potentiation (LTP). Our results provide in vivo evidence that PreP may play an important role in maintaining mitochondrial integrity and function by clearance and degradation of mitochondrial Aβ along with the improvement in synaptic and behavioral function in AD mouse model. Thus, enhancing PreP activity/expression may be a new therapeutic avenue for treatment of AD. PMID:26123488

  12. Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages

    PubMed Central

    Lanuti, Mirko; Talamonti, Emanuela; Maccarrone, Mauro; Chiurchiù, Valerio

    2015-01-01

    The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer. However, its physiological role and underlying mechanism remain unclear. In the present work, we demonstrate for the first time its presence in human macrophages and its increased expression in ox-LDL-induced foam cells. In addition, pharmacological activation of GPR55 by its selective agonist O-1602 increased CD36- and SRB-I-mediated lipid accumulation and blocked cholesterol efflux by downregulating ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, as well as enhanced cytokine- and pro-metalloprotease-9 (pro-MMP-9)-induced proinflammatory responses in foam cells. Treatment with cannabidiol, a selective antagonist of GPR55, counteracted these pro-atherogenic and proinflammatory O-1602-mediated effects. Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases. PMID:25970609

  13. Nutrient Plasma Levels Achieved During Treatment that Reduces Noise-Induced Hearing Loss

    PubMed Central

    Le Prell, C. G.; Dolan, D. F.; Bennett, D. C.; Boxer, P. A.

    2011-01-01

    Hearing loss encompasses both temporary and permanent deficits. If temporary threshold shift (TTS) and permanent threshold shift (PTS) share common pathological mechanisms, then agents that reduce PTS should also reduce TTS. Several antioxidant agents have reduced PTS in rodent models; however, reductions in TTS have been inconsistent. This study first determined whether dietary antioxidants (beta-carotene, and vitamins C and E) delivered in combination with magnesium (Mg) reliably increase plasma concentrations of the active agents. Then, additional manipulations tested the hypothesis that these nutrients reduce acute TTS insult in the first 24 hours following loud sound, as well as longer lasting changes in hearing measured up to 7 days post-noise. Saline or nutrients were administered to guinea pigs prior to and after noise exposure. Sound-evoked electrophysiological responses were measured before noise, with tests repeated 1-hour post-noise, as well as 1-, 3-, 5-, and 7-days post-noise. All subjects showed significant functional recovery; subjects treated with nutrients recovered more rapidly, and had better hearing outcomes at early post-noise times as well as the final test time. Thus, this combination of nutrients, which produced significant increases in plasma concentrations of vitamins C and E and Mg, effectively reduced hearing loss at multiple post-noise times. These data suggest free radical formation contributes to TTS as well as PTS insults, and suggest a potential opportunity to prevent TTS in human populations. PMID:21708356

  14. Prolonged fasting and cortisol reduce myostatin mRNA levels in tilapia larvae; short-term fasting elevates.

    PubMed

    Rodgers, Buel D; Weber, Gregory M; Kelley, Kevin M; Levine, Michael A

    2003-05-01

    Myostatin negatively regulates muscle growth and development and has recently been characterized in several fishes. We measured fasting myostatin mRNA levels in adult tilapia skeletal muscle and in whole larvae. Although fasting reduced some growth indexes in adults, skeletal muscle myostatin mRNA levels were unaffected. By contrast, larval myostatin mRNA levels were sometimes elevated after a short-term fast and were consistently reduced with prolonged fasting. These effects were specific for myostatin, as mRNA levels of glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphatase were unchanged. Cortisol levels were elevated in fasted larvae with reduced myostatin mRNA, whereas in addition immersion of larvae in 1 ppm (2.8 microM) cortisol reduced myostatin mRNA in a time-dependent fashion. These results suggest that larval myostatin mRNA levels may initially rise but ultimately fall during a prolonged fast. The reduction is likely mediated by fasting-induced hypercortisolemia, indicating divergent evolutionary mechanisms of glucocorticoid regulation of myostatin mRNA, since these steroids upregulate myostatin gene expression in mammals. PMID:12676749

  15. The use of asparaginase to reduce acrylamide levels in cooked food.

    PubMed

    Xu, Fei; Oruna-Concha, Maria-Jose; Elmore, J Stephen

    2016-11-01

    Strategies proposed for reducing the formation of the suspected carcinogen acrylamide in cooked foods often rely on a reduction in the extent of the Maillard reaction, in which acrylamide is formed from the reaction between asparagine and reducing sugars. However, the Maillard reaction also provides desirable sensory attributes of cooked foods. Mitigation procedures that modify the Maillard reaction may negatively affect flavour and colour. The use of asparaginase to convert asparagine to aspartic acid may provide a means to reduce acrylamide formation, while maintaining sensory quality. This review collates research on the use of enzymes, asparaginase in particular, to mitigate acrylamide formation. Asparaginase is a powerful tool for the food industry and it is likely that its use will increase. However, the potential adverse effects of asparaginase treatment on sensory properties of cooked foods and the need to achieve sufficient enzyme-substrate contact remain areas for future research. PMID:27211635

  16. Astragaloside IV reduces the expression level of P-glycoprotein in multidrug-resistant human hepatic cancer cell lines

    PubMed Central

    WANG, PEI-PEI; XU, DU-JUAN; HUANG, CAN; WANG, WEI-PING; XU, WEN-KE

    2014-01-01

    Astragaloside is a saponin widely used in traditional Chinese medicine and has been reported to be a potent multidrug resistance (MDR) reversal agent. The present study investigated the role of astragaloside IV (ASIV) in the regulation of P-glycoprotein (P-gp, encoded by the mdr1 gene) and its effect on the reversal of MDR. The activity of ASIV was evaluated using human hepatic cancer cells Bel-7402 and the corresponding 5-fluorouracil (5-FU) resistant cells Bel-7402/FU. ASIV (0.08 mg/ml) potentiated the cytotoxicity of 5-FU which was demonstrated using the MTT assay on Bel-7402/FU cells. ASIV reduced the expression of P-gp as was revealed by immunocytochemistry. Accumulation and efflux studies with the P-gp substrate, rhodamine 123 (Rh123), demonstrated that ASIV inhibited P-gp-mediated drug efflux. Furthermore, it was demonstrated that ASIV enhanced the drug accumulation of 5-FU using a high performance liquid chromatography (HPLC) assay for drug resistant cells. Furthermore, ASIV may downregulate the expression of P-gp, which was examined using western blot analysis and polymerase chain reaction. In conclusion, the results of the present study indicated that ASIV reverses the drug resistance of Bel-7402/FU cells by downregulating the expression of mdr1. ASIV may represent a potent modulator of P-gp-mediated MDR in hepatic cancer therapy. PMID:24676670

  17. Astragaloside Ⅳ reduces the expression level of P-glycoprotein in multidrug-resistant human hepatic cancer cell lines.

    PubMed

    Wang, Pei-Pei; Xu, Du-Juan; Huang, Can; Wang, Wei-Ping; Xu, Wen-Ke

    2014-06-01

    Astragaloside is a saponin widely used in traditional Chinese medicine and has been reported to be a potent multidrug resistance (MDR) reversal agent. The present study investigated the role of astragaloside Ⅳ (ASIV) in the regulation of P-glycoprotein (P-gp, encoded by the mdr1 gene) and its effect on the reversal of MDR. The activity of ASIV was evaluated using human hepatic cancer cells Bel-7402 and the corresponding 5-fluorouracil (5-FU) resistant cells Bel-7402/FU. ASIV (0.08 mg/ml) potentiated the cytotoxicity of 5-FU which was demonstrated using the MTT assay on Bel-7402/FU cells. ASIV reduced the expression of P-gp as was revealed by immunocytochemistry. Accumulation and efflux studies with the P-gp substrate, rhodamine 123 (Rh123), demonstrated that ASIV inhibited P-gp-mediated drug efflux. Furthermore, it was demonstrated that ASⅣ enhanced the drug accumulation of 5-FU using a high performance liquid chromatography (HPLC) assay for drug resistant cells. Furthermore, ASIV may downregulate the expression of P-gp, which was examined using western blot analysis and polymerase chain reaction. In conclusion, the results of the present study indicated that ASIV reverses the drug resistance of Bel-7402/FU cells by downregulating the expression of mdr1. ASIV may represent a potent modulator of P-gp-mediated MDR in hepatic cancer therapy. PMID:24676670

  18. Low-cost household paint abatement to reduce children's blood lead levels

    SciTech Connect

    Taha, T.; Kanarek, M.S.; Schultz, B.D.; Murphy, A.

    1999-11-01

    The purpose was to examine the effectiveness of low-cost abatement on children's blood lead levels. Blood lead was analyzed before and after abatement in 37 homes of children under 7 years old with initial blood lead levels of 25--44 {micro}g/dL. Ninety-five percent of homes were built before 1950. Abatement methods used were wet-scraping and repainting deteriorated surfaces and wrapping window wells with aluminum or vinyl. A control group was retrospectively selected. Control children were under 7 years old, had initial blood lead levels of 25--44 {micro}g/dL and a follow-up level at least 28 days afterward, and did not have abatements performed in their homes between blood lead levels. After abatement, statistically significant declines occurred in the intervention children's blood lead levels. The mean decline was 22%, 1 to 6 months after treatment. After adjustment for seasonality and child's age, the mean decline was 6.0 {micro}g/dL, or 18%. The control children's blood levels did not decline significantly. There was a mean decline of 0.25 {micro}g/dL, or 0.39%. After adjustment for seasonality and age, the mean decline for control children was 1.6 {micro}g/dL, or 1.8%. Low-cost abatement and education are effective short-term interim controls.

  19. Stimulation of adenosine A2A receptors reduces intracellular cholesterol accumulation and rescues mitochondrial abnormalities in human neural cell models of Niemann-Pick C1.

    PubMed

    Ferrante, A; De Nuccio, C; Pepponi, R; Visentin, S; Martire, A; Bernardo, A; Minghetti, L; Popoli, P

    2016-04-01

    Niemann Pick C 1 (NPC1) disease is an incurable, devastating lysosomal-lipid storage disorder characterized by hepatosplenomegaly, progressive neurological impairment and early death. Current treatments are very limited and the research of new therapeutic targets is thus mandatory. We recently showed that the stimulation of adenosine A2A receptors (A2ARs) rescues the abnormal phenotype of fibroblasts from NPC1 patients suggesting that A2AR agonists could represent a therapeutic option for this disease. However, since all NPC1 patients develop severe neurological symptoms which can be ascribed to the complex pathology occurring in both neurons and oligodendrocytes, in the present paper we tested the effects of the A2AR agonist CGS21680 in human neuronal and oligodendroglial NPC1 cell lines (i.e. neuroblastoma SH-SY5Y and oligodendroglial MO3.13 transiently transfected with NPC1 small interfering RNA). The down-regulation of the NPC1 protein effectively resulted in intracellular cholesterol accumulation and altered mitochondrial membrane potential. Both effects were significantly attenuated by CGS21680 (500 nM). The protective effects of CGS were prevented by the selective A2AR antagonist ZM241385 (500 nM). The involvement of calcium modulation was demonstrated by the ability of Bapta-AM (5-7 μM) in reverting the effect of CGS. The A2A-dependent activity was prevented by the PKA-inhibitor KT5720, thus showing the involvement of the cAMP/PKA signaling. These findings provide a clear in vitro proof of concept that A2AR agonists are promising potential drugs for NPC disease. PMID:26631535

  20. Conjugation to Poly(amidoamine) Dendrimers and Pulmonary Delivery Reduce Cardiac Accumulation and Enhance Antitumor Activity of Doxorubicin in Lung Metastasis.

    PubMed

    Zhong, Qian; Bielski, Elizabeth R; Rodrigues, Leonan S; Brown, Matthew R; Reineke, Joshua J; da Rocha, Sandro R P

    2016-07-01

    Lung is one of the most common sites to which almost all other primary tumors metastasize. The major challenges in the chemotherapy of lung metastases include the low drug concentration found in the tumors and high systemic toxicity upon systemic administration. In this study, we combine local lung delivery and the use of nanocarrier-based systems for improving pharmacokinetics and biodistribution of the therapeutics to fight lung metastases. We investigate the impact of the conjugation of doxorubicin (DOX) to carboxyl-terminated poly(amidoamine) dendrimers (PAMAM) through a bond that allows for intracellular-triggered release, and the effect of pulmonary delivery of the dendrimer-DOX conjugate in decreasing tumor burden in a lung metastasis model. The results show a dramatic increase in efficacy of DOX treatment of the melanoma (B16-F10) lung metastasis mouse model upon pulmonary administration of the drug, as indicated by decreased tumor burden (lung weight) and increased survival rates of the animals (male C57BL/6) when compared to iv delivery. Conjugation of DOX further increased the therapeutic efficacy upon lung delivery as indicated by the smaller number of nodules observed in the lungs when compared to free DOX. These results are in agreement with the biodistribution characteristics of the DOX upon pulmonary delivery, which showed a longer lung accumulation/retention compared to iv administration. The distribution of DOX to the heart tissue is also significantly decreased upon pulmonary administration, and further decreased upon conjugation. The results show, therefore, that pulmonary administration of DOX combined to conjugation to PAMAM dendrimer through an intracellular labile bond is a potential strategy to enhance the therapeutic efficacy and decrease systemic toxicity of DOX. PMID:27253493

  1. L-Arginine supplementation 0.5% of diet during the last 90 days of gestation and 14 days postpartum reduced uterine fluid accumulation in the broodmare.

    PubMed

    Mesa, A M; Warren, L K; Sheehan, J M; Kelley, D E; Mortensen, C J

    2015-08-01

    L-Arginine is an essential amino acid in many species that has been shown to influence reproduction. However, in horses a dose of 1% L-arginine of total dietary intake impaired absorption of other amino acids, whereas a dose of 0.5% did not. The objectives of this experiment were to evaluate postpartum parameters on mares supplemented with 0.5% L-arginine through the last 90d of gestation and 14d postpartum. Sixteen light-horse mares were randomly divided in two groups: 8 mares supplemented with 0.5% L-arginine and 8 mares fed an isonitrogenous equivalent. Gestation length, days to uterine clearance and days to first ovulation were compared. Uterine body depth, diameter of uterine horns, and length of largest pocket of uterine fluid were recorded daily via transrectal ultrasound. Measurements of foal weight, height, and cannon bone circumference were recorded for 9 weeks. Arginine treatment had no effect on gestation length (P=0.58). Supplemented mares cleared fluid quicker postpartum (6.8±0.53d; P=0.026) compared to control (9.0±0.38d). Mares supplemented with L-arginine had smaller diameter of fluid present in the postpartum uterus (P≤0.05). Days to first postpartum ovulation were not affected by treatment nor any influence on uterine involution. Finally, treatment had no effect on any foal's measured parameters. L-Arginine supplementation fed at 0.5% of daily intake during the last 90d of gestation and early postpartum in mares decreased uterine fluid accumulation, yet did not appear to have any effect on any other parameters measured. PMID:26036908

  2. Molecular interactions between the specialist herbivore Manduca sexta (Lepidoptera, Sphingidae) and its natural host Nicotiana attenuata. IV. Insect-Induced ethylene reduces jasmonate-induced nicotine accumulation by regulating putrescine N-methyltransferase transcripts.

    PubMed

    Winz, R A; Baldwin, I T

    2001-04-01

    Attack by the specialist herbivore, Manduca sexta, on its native host Nicotiana attenuata Torr. ex Wats. produces a dramatic ethylene release, a jasmonate burst, and a suppression of the nicotine accumulation that results from careful simulations of the herbivore's damage. Methyl-jasmonate (MeJA) treatment induces nicotine biosynthesis. However, this induction can be suppressed by ethylene as pretreatment of plants with 1-methylcyclopropene (1-MCP), a competitive inhibitor of ethylene receptors, restores the full MeJA-induced nicotine response in herbivore attacked plants (J. Kahl, D.H. Siemens, R.J. Aerts, R. Gäbler, F. Kühnemann, C.A. Preston, I.T. Baldwin [2000] Planta 210: 336-342). To understand whether this herbivore-induced signal cross-talk occurs at the level of transcript accumulation, we cloned the putrescine methyltransferase genes (NaPMT1 and NaPMT2) of N. attenuata, which are thought to represent the rate limiting step in nicotine biosynthesis, and measured transcript accumulations by northern analysis after various jasmonate, 1-MCP, ethephon, and herbivory treatments. Transcripts of both root putrescine N-methyltransferase (PMT) genes and nicotine accumulation increased dramatically within 10 h of shoot MeJA treatment and immediately after root treatments. Root ethephon treatments suppressed this response, which could be reversed by 1-MCP pretreatment. Moreover, 1-MCP pretreatment dramatically amplified the transcript accumulation resulting from both wounding and M. sexta herbivory. We conclude that attack from this nicotine-tolerant specialist insect causes N. attenuata to produce ethylene, which directly suppresses the nitrogen-intensive biosynthesis of nicotine. PMID:11299398

  3. [Experience in reducing the levels of raticides during open area disinfestations].

    PubMed

    Turyshev, A G; Korneev, A G; Konstantinova, E L

    2009-01-01

    The experience in combining disinfestation and forestry engineering measures is described to achieve a long-term effect: in minimizing the number of murine rodents, which has considerably reduced the amount of poisoned baits placed into the environment when disinfestation is made in open areas. PMID:19802943

  4. Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis

    PubMed Central

    Bhatt, Dhaval P.; Houdek, Heidi M.; Watt, John A.; Rosenberger, Thad A.

    2013-01-01

    Acetate supplementation in rats increases plasma acetate and brain acetyl-CoA levels. Although acetate is used as a marker to study glial energy metabolism, the effect that acetate supplementation has on normal brain energy stores has not been quantified. To determine the effect(s) that an increase in acetyl-CoA levels has on brain energy metabolism, we measured brain nucleotide, phosphagen and glycogen levels, and quantified cardiolipin content and mitochondrial number in rats subjected to acetate supplementation. Acetate supplementation was induced with glyceryl triacetate (GTA) by oral gavage (6 g/Kg body weight). Rats used for biochemical analysis were euthanized using head-focused microwave irradiation at 2, and 4 hr following treatment to immediately stop metabolism. We found that acetate did not alter brain ATP, ADP, NAD, GTP levels, or the energy charge ratio [ECR, (ATP + ½ ADP) / (ATP + ADP + AMP)] when compared to controls. However, after 4 hr of treatment brain phosphocreatine levels were significantly elevated with a concomitant reduction in AMP levels with no change in glycogen levels. In parallel studies where rats were treated with GTA for 28 days, we found that acetate did not alter brain glycogen and mitochondrial biogenesis as determined by measuring brain cardiolipin content, the fatty acid composition of cardiolipin and using quantitative ultra-structural analysis to determine mitochondrial density/unit area of cytoplasm in hippocampal CA3 neurons. Collectively, these data suggest that an increase in brain acetyl-CoA levels by acetate supplementation does increase brain energy stores however it has no effect on brain glycogen and neuronal mitochondrial biogenesis. PMID:23321384

  5. Reducing the substrate dependent scanner leveling effect in low-k1 contact printing

    NASA Astrophysics Data System (ADS)

    Chang, C. S.; Tseng, C. F.; Huang, C. H.; Yang, Elvis; Yang, T. H.; Chen, K. C.

    2015-03-01

    As the scaling down of design rule for high-density memory device, the small depth of focus (DoF) budget may be deteriorated by focus leveling errors, which arises in unpredicted reflectivity from multilayer structures on the topographic wafer. The leveling sensors of ASML scanner use near infrared (NIR) range wavelength which can penetrate through most of films using in semiconductor fabrication such as photo-resist, bottom anti reflective coating (BARC) and dielectric materials. Consequently, the reflected light from underlying substructures would disturb leveling sensors from accurate leveling. The different pattern densities and layout characteristics between array and periphery of a memory chip are expected to result in different leveling signals. Furthermore, the process dependent variations between wafer central and edge areas are also considered to yield different leveling performances during wafer exposure. In this study, lower blind contact immunity was observed for peripheral contacts comparing to the array contacts especially around wafer edge region. In order to overcome this problem, a series of investigations have been carried out. The wafer edge leveling optimization through circuit dependent focus edge clearance (CDFEC) option doesn't get improvement. Air gauge improved process leveling (AGILE) function of ASML immersion scanner doesn't show improved result either. The ILD uniformity improvement and step height treatments around wafer edge such as edge exclusion of film deposition and bevel etching are also ineffective to mitigate the blind contact problem of peripheral patterns. Altering the etch hard-mask stack is finally found to be an effective approach to alleviate the issue. For instance, through either containing high temperature deposition advanced patterning film (APF) in the hard-mask or inserting higher opaque film such as amorphous Si in between the hard-mask stack.

  6. Depression-like behavior and reduced plasma testosterone levels in the senescence-accelerated mouse.

    PubMed

    Egashira, Nobuaki; Koushi, Emi; Okuno, Ryoko; Shirakawa, Atsunori; Mishima, Kenichi; Iwasaki, Katsunori; Oishi, Ryozo; Fujiwara, Michihiro

    2010-05-01

    During aging, levels of testosterone gradually decline in men and low levels of testosterone in aged men are accompanied by increased incidence of depressive disorders. The senescence-accelerated-prone mouse 10 (SAMP10) is well known as an animal model of aging. The purpose of this study was to investigate the motor function, anxiety levels, depression-related emotional responses, attentional function and plasma levels of testosterone and dehydroepiandrosterone (DHEA) in SAMP10. SAMP10 exhibited a significant prolongation of immobility time compared to that of the aged-matched control senescence-accelerated-resistant mouse 1 (SAMR1) in the tail suspension test for measuring depression. Moreover, significant low levels of plasma testosterone but not DHEA were found in SAMP10, and the testosterone levels were inversely correlated with the depression-like behavior. By contrast, we did not observe any significant differences between SAMP10 and SAMR1 in the open-field, rota-rod, elevated plus-maze, marble-burying behavior, or prepulse inhibition test. The results of the present study indicate that testosterone may play an important role in the depression-like behavior in SAMP10. PMID:20117148

  7. A national project to evaluate and reduce high sound pressure levels from music.

    PubMed

    Ryberg, Johanna Bengtsson

    2009-01-01

    The highest recommended sound pressure levels for leisure sounds (music) in Sweden are 100 dB LAeq and 115 dB LAFmax for adults, and 97 dB LAeq and 110 dB LAFmax where children under the age of 13 have access. For arrangements intended for children, levels should be consistently less than 90 dB LAeq. In 2005, a national project was carried out with the aim of improving environments with high sound pressure levels from music, such as concert halls, restaurants, and cinemas. The project covered both live and recorded music. Of Sweden's 290 municipalities, 134 took part in the project, and 93 of these carried out sound measurements. Four hundred and seventy one establishments were investigated, 24% of which exceeded the highest recommended sound pressure levels for leisure sounds in Sweden. Of festival and concert events, 42% exceeded the recommended levels. Those who visit music events/establishments thus run a relatively high risk of exposure to harmful sound levels. Continued supervision in this field is therefore crucial. PMID:19414933

  8. Overexpression of ACC gene from oleaginous yeast Lipomyces starkeyi enhanced the lipid accumulation in Saccharomyces cerevisiae with increased levels of glycerol 3-phosphate substrates.

    PubMed

    Wang, Jiancai; Xu, Ronghua; Wang, Ruling; Haque, Mohammad Enamul; Liu, Aizhong

    2016-06-01

    The conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase (ACC) is the rate-limiting step in fatty acid biosynthesis. In this study, a gene coding for ACC was isolated and characterized from an oleaginous yeast, Lipomyces starkeyi. Real-time quantitative PCR (qPCR) analysis of L. starkeyi acetyl-CoA carboxylase gene (LsACC1) showed that the expression levels were upregulated with the fast accumulation of lipids. The LsACC1 was co-overexpressed with the glycerol 3-phosphate dehydrogenase gene (GPD1), which regulates lipids biosynthesis by supplying another substrates glycerol 3-phosphate for storage lipid assembly, in the non-oleaginous yeast Saccharomyces cerevisiae. Further, the S. cerevisiae acetyl-CoA carboxylase (ScACC1) was transferred with GPD1 and its function was analyzed in comparison with LsACC1. The results showed that overexpressed LsACC1 and GPD1 resulted in a 63% increase in S. cerevisiae. This study gives new data in understanding of the molecular mechanisms underlying the regulation of fatty acids and lipid biosynthesis in yeasts. PMID:26865376

  9. PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: alirocumab.

    PubMed

    Dahagam, Chanukya; Goud, Aditya; Abdelqader, Abdelhai; Hendrani, Aditya; Feinstein, Matthew J; Qamar, Arman; Joshi, Parag H; Swiger, Kristopher J; Byrne, Kathleen; Quispe, Renato; Jones, Steven R; Blumenthal, Roger S; Martin, Seth S

    2016-03-01

    In this review, we examine alirocumab (Praluent(®)), a monoclonal antibody to PCSK9 and its role in reducing LDL-C levels. By comparing the results of various studies and trials we discuss the efficacy and safety of alirocumab. We aim to guide clinicians of the role of alirocumab in clinical practice. Overall, PCSK9 inhibitors are promising new agents in further reducing LDL-C levels in addition to diet and maximally tolerated statin therapy. Long-term outcome studies are currently ongoing and will further delineate the role of PCSK9 inhibitors. PMID:26911710

  10. Linalool is a PPARα ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome[S

    PubMed Central

    Jun, Hee-jin; Lee, Ji Hae; Kim, Jiyoung; Jia, Yaoyao; Kim, Kyoung Heon; Hwang, Kwang Yeon; Yun, Eun Ju; Do, Kyoung-Rok; Lee, Sung-Joon

    2014-01-01

    We investigated the hypotriglyceridemic mechanism of action of linalool, an aromatic monoterpene present in teas and fragrant herbs. Reporter gene and time-resolved fluorescence resonance energy transfer assays demonstrated that linalool is a direct ligand of PPARα. Linalool stimulation reduced cellular lipid accumulation regulating PPARα-responsive genes and significantly induced FA oxidation, and its effects were markedly attenuated by silencing PPARα expression. In mice, the oral administration of linalool for 3 weeks reduced plasma TG concentrations in Western-diet-fed C57BL/6J mice (31%, P < 0.05) and human apo E2 mice (50%, P < 0.05) and regulated hepatic PPARα target genes. However, no such effects were seen in PPARα-deficient mice. Transcriptome profiling revealed that linalool stimulation rewired global gene expression in lipid-loaded hepatocytes and that the effects of 1 mM linalool were comparable to those of 0.1 mM fenofibrate. Metabolomic analysis of the mouse plasma revealed that the global metabolite profiles were significantly distinguishable between linalool-fed mice and controls. Notably, the concentrations of saturated FAs were significantly reduced in linalool-fed mice. These findings suggest that the appropriate intake of a natural aromatic compound could exert beneficial metabolic effects by regulating a cellular nutrient sensor. PMID:24752549

  11. Linalool is a PPARα ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome.

    PubMed

    Jun, Hee-Jin; Lee, Ji Hae; Kim, Jiyoung; Jia, Yaoyao; Kim, Kyoung Heon; Hwang, Kwang Yeon; Yun, Eun Ju; Do, Kyoung-Rok; Lee, Sung-Joon

    2014-06-01

    We investigated the hypotriglyceridemic mechanism of action of linalool, an aromatic monoterpene present in teas and fragrant herbs. Reporter gene and time-resolved fluorescence resonance energy transfer assays demonstrated that linalool is a direct ligand of PPARα. Linalool stimulation reduced cellular lipid accumulation regulating PPARα-responsive genes and significantly induced FA oxidation, and its effects were markedly attenuated by silencing PPARα expression. In mice, the oral administration of linalool for 3 weeks reduced plasma TG concentrations in Western-diet-fed C57BL/6J mice (31%, P < 0.05) and human apo E2 mice (50%, P < 0.05) and regulated hepatic PPARα target genes. However, no such effects were seen in PPARα-deficient mice. Transcriptome profiling revealed that linalool stimulation rewired global gene expression in lipid-loaded hepatocytes and that the effects of 1 mM linalool were comparable to those of 0.1 mM fenofibrate. Metabolomic analysis of the mouse plasma revealed that the global metabolite profiles were significantly distinguishable between linalool-fed mice and controls. Notably, the concentrations of saturated FAs were significantly reduced in linalool-fed mice. These findings suggest that the appropriate intake of a natural aromatic compound could exert beneficial metabolic effects by regulating a cellular nutrient sensor. PMID:24752549

  12. Deferiprone reduces amyloid-β and tau phosphorylation levels but not reactive oxygen species generation in hippocampus of rabbits fed a cholesterol-enriched diet.

    PubMed

    Prasanthi, Jaya R P; Schrag, Matthew; Dasari, Bhanu; Marwarha, Gurdeep; Dickson, April; Kirsch, Wolff M; Ghribi, Othman

    2012-01-01

    Accumulation of amyloid-β (Aβ) peptide and the hyperphosphorylation of tau protein are major hallmarks of Alzheimer's disease (AD). The causes of AD are not well known but a number of environmental and dietary factors are suggested to increase the risk of developing AD. Additionally, altered metabolism of iron may have a role in the pathogenesis of AD. We have previously demonstrated that cholesterol-enriched diet causes AD-like pathology with iron deposition in rabbit brain. However, the extent to which chelation of iron protects against this pathology has not been determined. In this study, we administered the iron chelator deferiprone in drinking water to rabbits fed with a 2% cholesterol diet for 12 weeks. We found that deferiprone (both at 10 and 50 mg/kg/day) significantly decreased levels of Aβ40 and Aβ42 as well as BACE1, the enzyme that initiates cleavage of amyloid-β protein precursor to yield Aβ. Deferiprone also reduced the cholesterol diet-induced increase in phosphorylation of tau but failed to reduce reactive oxygen species generation. While deferiprone treatment was not associated with any change in brain iron levels, it was associated with a significant reduction in plasma iron and cholesterol levels. These results demonstrate that deferiprone confers important protection against hypercholesterolemia-induced AD pathology but the mechanism(s) may involve reduction in plasma iron and cholesterol levels rather than chelation of brain iron. We propose that adding an antioxidant therapy to deferiprone may be necessary to fully protect against cholesterol-enriched diet-induced AD-like pathology. PMID:22406440

  13. The application of high-pressure treatment in the reduction of salt levels in reduced-phosphate breakfast sausages.

    PubMed

    O'Flynn, Claire C; Cruz-Romero, Malco C; Troy, Declan; Mullen, Anne M; Kerry, Joe P

    2014-03-01

    This study investigated the effects of high pressure (HP) treatment of pork meat before manufacturing sausages with reduced salt levels and compared them to sausages manufactured with untreated meat (control sausages). A 2×5 factorial design was set up incorporating two pressure levels (0 or 150 MPa) and five salt levels (0.5, 1.0, 1.5, 2.0 and 2.5%). Most quality attributes were affected when salt levels were reduced below 1.5%. Fat loss (FL) was (P<0.05) affected by salt level; samples with <1.5% salt had the highest FL. HP treatment increased emulsion stability and reduced cook loss (CL) compared to control sausages. Increased CL was observed when salt was reduced below 2.0%. Salt reduction below 1.5% adversely affected colour, sensory and texture attributes. Independent of salt, HP treatment affected adversely juiciness and cohesiveness while adhesiveness was improved. Overall, there is potential to manufacture sausages maintaining organoleptic and functional properties traditionally associated with sausages using HP treated meat. PMID:24334049

  14. 4-Phenylbutyric acid reduces mutant-TGFBIp levels and ER stress through activation of ERAD pathway in corneal fibroblasts of granular corneal dystrophy type 2.

    PubMed

    Choi, Seung-Il; Lee, Eunhee; Jeong, Jang Bin; Akuzum, Begum; Maeng, Yong-Sun; Kim, Tae-Im; Kim, Eung Kweon

    2016-09-01

    Granular corneal dystrophy type 2 (GCD2) is caused by a point mutation (R124H) in the transforming growth factor β-induced (TGFBI) gene. In GCD2 corneal fibroblasts, secretion of the accumulated mutant TGFBI-encoded protein (TGFBIp) is delayed via the endoplasmic reticulum (ER)/Golgi-dependent secretory pathway. However, ER stress as the pathogenic mechanism underlying GCD2 has not been fully characterized. The aim of this study was to confirm whether ER stress is linked to GCD2 pathogenesis and whether the chemical chaperone, 4-phenylbutyric acid (4-PBA), could be exploited as a therapy for GCD2. We found that the ER chaperone binding immunoglobulin protein (BiP) and the protein disulfide isomerase (PDI) were elevated in GCD2. Western bolt analysis also showed a significant increase in both the protein levels and the phosphorylation of the key ER stress kinases, inositol-requiring enzyme 1α (IRE1α) and double stranded RNA activated protein kinase (PKR)-like ER kinase, as well as in levels of their downstream targets, X box-binding protein 1 (XBP1) and activating transcription factor 4, respectively, in GCD2 corneal fibroblasts. GCD2 cells were found to be more susceptible to ER stress-induced cell death than were wild-type corneal fibroblasts. Treatment with 4-PBA considerably reduced the levels of BiP, IRE1α, and XBP1 in GCD2 cells; notably, 4-PBA treatment significantly reduced the levels of TGFBIp without change in TGFBI mRNA levels. In addition, TGFBIp levels were significantly reduced under ER stress and this reduction was considerably suppressed by the ubiquitin proteasome inhibitor MG132, indicating TGFBIp degradation via the ER-associated degradation pathway. Treatment with 4-PBA not only protected against the GCD2 cell death induced by ER stress but also significantly suppressed the MG132-mediated increase in TGFBIp levels under ER stress. Together, these results suggest that ER stress might comprise an important factor in GCD2 pathophysiology and

  15. Hydrophobic carboxy-terminal residues dramatically reduce protein levels in the haloarchaeon Haloferax volcanii

    PubMed Central

    Reuter, Christopher J.; Uthandi, Sivakumar; Puentes, Jose A.; Maupin-Furlow, Julie A.

    2010-01-01

    Proteolysis is important not only to cell physiology but also to the successful development of biocatalysts. While a wide-variety of signals are known to trigger protein degradation in bacteria and eukaryotes, these mechanisms are poorly understood in archaea, known for their ability to withstand harsh conditions. Here we present a systematic study in which single C-terminal amino acid residues were added to a reporter protein and shown to influence its levels in an archaeal cell. All 20 amino acid residues were examined for their impact on protein levels, using the reporter protein soluble modified red-shifted GFP (smRS-GFP) expressed in the haloarchaeon Haloferax volcanii as a model system. Addition of hydrophobic residues, including Leu, Cys, Met, Phe, Ala, Tyr, Ile and Val, gave the most pronounced reduction in smRS-GFP levels compared with the addition of either neutral or charged hydrophilic residues. In contrast to the altered protein levels, the C-terminal alterations had no influence on smRS-GFP-specific transcript levels, thus revealing that the effect is post-transcriptional. PMID:19850616

  16. Persimmon fruit tannin-rich fiber reduces cholesterol levels in humans.

    PubMed

    Gato, Nobuki; Kadowaki, Akio; Hashimoto, Natsumi; Yokoyama, Shin-ichiro; Matsumoto, Kenji

    2013-01-01

    Bile acid-binding agents are known to lower blood cholesterol levels and have been clinically used for the treatment of hypercholesterolemia. We previously showed that tannin-rich fiber from young persimmon (Diospyros kaki) fruits had bile acid-binding properties. In this study, we performed a randomized, double-blind, placebo-controlled trial to investigate the hypocholesterolemic effects of tannin-rich fiber in humans. The subjects (n = 40, plasma total cholesterol levels 180-259 mg/dl) were divided into 3 groups and ingested cookie bars containing 0 g (placebo group, n = 14), 3 g (low-dose group, n = 13), or 5 g (high-dose group, n = 13) of tannin-rich fiber 3 times daily before meals for 12 weeks. Plasma total cholesterol levels decreased significantly in the low-dose (12 weeks, p < 0.005) and high-dose (6 weeks, p < 0.05; 12 weeks, p < 0.001) groups. In addition, plasma low-density lipoprotein cholesterol levels decreased significantly in the high-dose group (6 weeks, p < 0.05; 12 weeks, p < 0.001). These improvements were not accompanied by changes in plasma high-density lipoprotein cholesterol or plasma triglyceride levels. Our findings indicate that tannin-rich fiber from young persimmon fruits is a useful food material for treating hypercholesterolemia. PMID:23171573

  17. Use of cationic polymers to reduce pathogen levels during dairy manure separation.

    PubMed

    Liu, Zong; Carroll, Zachary S; Long, Sharon C; Gunasekaran, Sundaram; Runge, Troy

    2016-01-15

    Various separation technologies are used to deal with the enormous amounts of animal waste that large livestock operations generate. When the recycled waste stream is land applied, it is essential to lower the pathogen load to safeguard the health of livestock and humans. We investigated whether cationic polymers, used as a flocculent in the solid/liquid separation process, could reduce the pathogen indicator load in the animal waste stream. The effects of low charge density cationic polyacrylamide (CPAM) and high charge density cationic polydicyandiamide (PDCD) were investigated. Results demonstrated that CPAM was more effective than PDCD for manure coagulation and flocculation, while PDCD was more effective than CPAM in reducing the pathogen indicator loads. However, their combined use, CPAM followed by PDCD, resulted in both improved solids separation and pathogen indicator reduction. PMID:26513324

  18. Future development programs. [for defining the emission problem and developing hardware to reduce pollutant levels

    NASA Technical Reports Server (NTRS)

    Jedrziewski, S.

    1976-01-01

    The emission problem or source points were defined and new materials, hardware, or operational procedures were developed to exercise the trends defined by the data collected. The programs to reduce the emission output of aircraft powerplants were listed. Continued establishment of baseline emissions for various engine models, continued characterization of effect of production tolerances on emissions, carbureted engine development and flight tests, and cylinder cooling/fin design programs were several of the programs investigated.

  19. Could low dead-space syringes really reduce HIV transmission to low levels?

    PubMed

    Vickerman, P; Martin, N K; Hickman, M

    2013-01-01

    Studies published by Zule and colleagues have suggested that use of low dead-space syringes (LDSS) instead of high dead-space syringes (HDSS) by injecting drug users (IDUs) could dramatically reduce HIV transmission. However, evidence is limited because experiments have considered a small range of syringe types and have been unable to reliably estimate the efficacy of using LDSS for reducing HIV transmission. We critically appraise available evidence to determine whether using LDSS is likely to dramatically reduce HIV transmission. We systematically review the literature on the dead-space volume of syringes and estimate the factor difference in blood volume transferred from sharing LDSS or HDSS. Existing data on the relationship between host viral load and HIV transmission risk is used to evaluate the likely efficacy of using LDSS instead of HDSS. An HIV transmission model is used to make conservative impact projections for switching to using LDSS, and explore the implications of heterogeneity in IDU transmission risk and syringe preferences. Although highly variable, reviewed studies suggest that HDSS have on average 10 times the dead-space volume of LDSS and could result in 6/54/489 times more blood being transferred after 0/1/2 water rinses. Assuming a conservative 2-fold increase in HIV transmission risk per 10-fold increase in infected blood inoculum, HDSS use could be associated with a mean 1.7/3.6/6.5-fold increase in transmission risk compared to LDSS for 0/1/2 rinses. However, even for a low efficacy estimate, modelling suggests that partially transferring to LDSS use from using HDSS could dramatically reduce HIV prevalence (generally >33% if LDSS use is 50%), but impact will depend on IDU behavioural heterogeneity and syringe preference. Indirect evidence suggests that encouraging HDSS users to use LDSS could be a powerful HIV prevention strategy. There is an urgent need to evaluate the real life effectiveness of this strategy. PMID:23206493

  20. Feeding Jerusalem artichoke reduced skatole level and changed intestinal microbiota in the gut of entire male pigs.

    PubMed

    Vhile, S G; Kjos, N P; Sørum, H; Overland, M

    2012-05-01

    Different levels of dried Jerusalem artichoke were fed to entire male pigs 1 week before slaughter. The objective was to investigate the effect on skatole level in the hindgut and in adipose tissue, as well as the effect on microflora and short-chain fatty acids (SCFA) in the hindgut. Five experimental groups (n = 11) were given different dietary treatments 7 days before slaughtering: negative control (basal diet), positive control (basal diet + 9% chicory-inulin), basal diet + 4.1% Jerusalem artichoke, basal diet + 8.1% Jerusalem artichoke and basal diet + 12.2% Jerusalem artichoke. Samples from colon, rectum, faeces and adipose tissue were collected. Effect of dietary treatment on skatole, indole and androstenone levels in adipose tissue and on skatole, indole, pH, dry matter (DM), microbiota and SCFA in the hindgut was evaluated. Feeding increasing levels of Jerusalem artichoke to entire male pigs reduced skatole in digesta from colon and in faeces (linear, P < 0.01). There was also a tendency towards a decreased level of skatole in adipose tissue (linear, P = 0.06). Feeding Jerusalem artichoke decreased DM content in colon and faeces and pH in colon (linear, P < 0.01). Increasing levels of Jerusalem artichoke resulted in a reduced level of Clostridium perfringens in both colon and rectum (linear, P < 0.05) and a tendency towards decreased levels of enterobacteria in colon (linear, P = 0.05). Further, there was an increase in total amount of SCFA (linear, P < 0.05), acetic acid (linear, P < 0.05) and valerianic acid (linear, P < 0.01) in faeces. In conclusion, adding dried Jerusalem artichoke to diets for entire male pigs 1 week before slaughter resulted in a dose-dependent decrease in skatole levels in the hindgut and adipose tissue. The reduced skatole levels might be related to the decrease in C. perfringens and the increase in SCFA with subsequent reduction in pH. PMID:22558928

  1. Plumbagin reduces chronic lymphocytic leukemia cell survival by downregulation of Bcl-2 but upregulation of the Bax protein level.

    PubMed

    Fu, Chunling; Gong, Yanqing; Shi, Xuanxuan; Sun, Zengtian; Niu, Mingshan; Sang, Wei; Xu, Linyan; Zhu, Feng; Wang, Ying; Xu, Kailin

    2016-09-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis rates. The aberration of apoptosis-related genes in CLL cells results in defective apoptosis of CLL cells in response to traditional therapeutic medicine. Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a natural compound from Plumbago zeylinica, has been shown to exhibit pro-apoptotic activities in tumor cells. In the present study, we report that plumbagin effectively inhibited CLL cell viability with a lower dose compared to fludarabine, and inhibited cell proliferation in a dose-dependent manner. In addition, plumbagin promoted accumulation of MEC-1 cells in the S phase, and blocked cell cycle transition of HG3 cells from G0/G1 to S phase. Molecularly, plumbagin markedly induced CLL cell apoptosis through reduction of Bcl-2, but through an increase in the Bax protein level. These results suggest that plumbagin may be considered as a potential anticancer agent for CLL therapy. PMID:27461100

  2. INCREASING SAFETY AND REDUCING ENVIRONMENTAL DAMAGE RISK FROM AGING HIGH-LEVEL RADIOACTIVE WASTE TANKS

    EPA Science Inventory

    There exists a paramount need for improved understanding of the behavior of high-level nuclear waste containers and the impact on structural integrity in terms of leak tightness and mechanical stability. The current program, which at the time of this writing is in its early stage...

  3. The mathematical model reduces the effect of distance to the scatter images gray level

    NASA Astrophysics Data System (ADS)

    Sun, Li-na

    2013-09-01

    In x-ray scanning system, scatter images are obtained to provide information on material density. The forward and backward scatter is related to solid angle. Scatter is therefore dependent on the distance of the scanned object from the x-ray source. In the real world, an object may be placed anywhere on the conveyer belt, so the measured intensity will contain errors relative to the ideal intensity. This makes classification results less reliable. Extraction of characteristic values L associated with the density; need to know the gray levels of scatter images, so how to base on forward scatter and back scatter images to determine the scatter image gray level is first necessary to solve the problem. The author combined with the forward scatter and backscatter images,then established higher order gray-level mathematical model of scattering images, to eliminate the impact of distance on the scatter images, to obtain more accurate gray level of scatter image. Then compare the error use of LMS algorithm and the LS algorithm to solving mathematical model parameters, LS algorithm ultimately prove less error and experimental validation of the superiority of the LS algorithm.

  4. Phosphorothioate Oligonucleotides Reduce PrPSc Levels and Prion Infectivity in Cultured Cells

    PubMed Central

    Karpuj, Marcela V; Giles, Kurt; Gelibter-Niv, Sagit; Scott, Michael R; Lingappa, Vishwanath R; Szoka, Francis C; Peretz, David; Denetclaw, Wilfred; Prusiner, Stanley B

    2007-01-01

    Prions are composed solely of the disease-causing prion protein (PrPSc) that is formed from the cellular isoform PrPC by a posttranslational process. Here we report that short phosphorothioate DNA (PS-DNA) oligonucleotides diminished the levels of both PrPC and PrPSc in prion-infected neuroblastoma (ScN2a) cells. The effect of PS-DNA on PrP levels was independent of the nucleotide sequence. The effective concentration (EC50) of PS-DNA required to achieve half-maximal diminution of PrPSc was ~70 nM, whereas the EC50 of PS-DNA for PrPC was more than 50-fold greater. This finding indicated that diminished levels of PrPSc after exposure to PS-DNA are unlikely to be due to decreased PrPC levels. Bioassays in transgenic mice demonstrated a substantial diminution in the prion infectivity after ScN2a cells were exposed to PS-DNAs. Whether PS-DNA will be useful in the treatment of prion disease in people or livestock remains to be established. PMID:17592554

  5. A method for reducing the level of spurious signals in surface acoustic wave filters

    NASA Astrophysics Data System (ADS)

    Borodii, Iu. N.; Grankin, I. M.; Zapunnyi, A. P.; Kolomeiko, A. V.

    1986-03-01

    A method for reducing spurious signals in surface acoustic wave (SAW) filters is proposed whereby both bulk and reflected wave signals are attenuated by electrodes of special configuration providing synphase addition of the useful signal and nonsynphase addition of spurious signal components. The electrodes of the input and output converters are made with a common focus point and equal angular apertures. The shape of the electrodes of the focusing converters on anisotropic crystal surfaces is determined by the corresponding SAW group velocity curve. An implementation of the method proposed here is examined together with some test results.

  6. Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle.

    PubMed

    Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

    2015-01-01

    The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid content in skeletal muscle was measured. Genes and proteins of the AMPK signaling pathway were analyzed by real time RT-PCR and Western blot. Adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) and other genes involved in mitochondrial function and fat oxidation were analyzed by real time RT-PCR. Histological staining was also performed. JLD or pioglitazone administration ameliorated fasting plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), ALT, AST and non-esterified fatty acid (NEFA) (P < 0.05). Treatment with JLD or pioglitazone significantly reverted muscle lipid content (P < 0.05). JLD (1.5 g/kg) significantly increased plasma adiponectin concentration by 60.17% and increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in skeletal muscle (P < 0.05). JLD administration increased levels of ADIPOR1 and ADIPOR2 by 1.48 and 1.29 respectively. Levels of genes involved in mitochondrial function and fat oxidation were increased. This study provides the molecular mechanism by which JLD ameliorates HFD-induced insulin resistance in rats. PMID:26064395

  7. Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle

    PubMed Central

    Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

    2015-01-01

    The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid content in skeletal muscle was measured. Genes and proteins of the AMPK signaling pathway were analyzed by real time RT-PCR and Western blot. Adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) and other genes involved in mitochondrial function and fat oxidation were analyzed by real time RT-PCR. Histological staining was also performed. JLD or pioglitazone administration ameliorated fasting plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), ALT, AST and non-esterified fatty acid (NEFA) (P < 0.05). Treatment with JLD or pioglitazone significantly reverted muscle lipid content (P < 0.05). JLD (1.5 g/kg) significantly increased plasma adiponectin concentration by 60.17% and increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in skeletal muscle (P < 0.05). JLD administration increased levels of ADIPOR1 and ADIPOR2 by 1.48 and 1.29 respectively. Levels of genes involved in mitochondrial function and fat oxidation were increased. This study provides the molecular mechanism by which JLD ameliorates HFD-induced insulin resistance in rats. PMID:26064395

  8. Reduced Levels of Membrane-Bound Alkaline Phosphatase Are Common to Lepidopteran Strains Resistant to Cry Toxins from Bacillus thuringiensis

    PubMed Central

    Jurat-Fuentes, Juan Luis; Karumbaiah, Lohitash; Jakka, Siva Rama Krishna; Ning, Changming; Liu, Chenxi; Wu, Kongming; Jackson, Jerreme; Gould, Fred; Blanco, Carlos; Portilla, Maribel; Perera, Omaththage; Adang, Michael

    2011-01-01

    Development of insect resistance is one of the main concerns with the use of transgenic crops expressing Cry toxins from the bacterium Bacillus thuringiensis. Identification of biomarkers would assist in the development of sensitive DNA-based methods to monitor evolution of resistance to Bt toxins in natural populations. We report on the proteomic and genomic detection of reduced levels of midgut membrane-bound alkaline phosphatase (mALP) as a common feature in strains of Cry-resistant Heliothis virescens, Helicoverpa armigera and Spodoptera frugiperda when compared to susceptible larvae. Reduced levels of H. virescens mALP protein (HvmALP) were detected by two dimensional differential in-gel electrophoresis (2D-DIGE) analysis in Cry-resistant compared to susceptible larvae, further supported by alkaline phosphatase activity assays and Western blotting. Through quantitative real-time polymerase chain reaction (qRT-PCR) we demonstrate that the reduction in HvmALP protein levels in resistant larvae are the result of reduced transcript amounts. Similar reductions in ALP activity and mALP transcript levels were also detected for a Cry1Ac-resistant strain of H. armigera and field-derived strains of S. frugiperda resistant to Cry1Fa. Considering the unique resistance and cross-resistance phenotypes of the insect strains used in this work, our data suggest that reduced mALP expression should be targeted for development of effective biomarkers for resistance to Cry toxins in lepidopteran pests. PMID:21390253

  9. METHODS FOR CONDUCTING SNAIL (APLEXA HYPNORUM) EMBRYO THROUGH ADULT EXPOSURES: EFFECTS OF CADMIUM AND REDUCED PH LEVELS

    EPA Science Inventory

    Two separate embryo through adult exposures were conducted with cadmium and with reduced pH levels to validate various test methodologies and to determine the feasibility of testing and ease of handling the freshwater snail (Aplexa hypnorum) in a test system designed for fish bio...

  10. Increased plasma neopterin levels are associated with reduced endothelial function and arterial elasticity in hypertension.

    PubMed

    Zhang, Y-Y; Tong, X-Z; Xia, W-H; Xie, W-L; Yu, B-B; Zhang, B; Chen, L; Tao, J

    2016-07-01

    Inflammation has been shown to play a pivotal role in the pathogenesis and development of hypertensive vascular injury. Neopterin is a novel marker of immune activation produced mainly by activated macrophages. Few data are available to show the association between neopterin and vascular function in hypertension. The present study was designed to investigate the relationship between neopterin levels related to arterial stiffness and endothelial function in patients with hypertension, and their changes after blood pressure-lowering treatment. Twenty-four hypertensive patients and 30 age- and gender-matched healthy volunteers were recruited. Plasma neopterin levels were higher in hypertensive patients compared with their counterparts (log-neopterin: 0.77±0.18 versus 0.61±0.16, P=0.003). Increased neopterin levels were correlated with increased brachial-ankle pulse wave velocity (baPWV; control: r=0.659, P<0.001; hypertension: r=0.487, P=0.021), and inversely associated with impaired brachial flow-mediated dilation (FMD; control: r=-0.735, P<0.001; hypertension: r=-0.557, P=0.005). Fifteen hypertensives received 3 months of standard antihypertensive treatment. Three months later, their plasma neopterin levels decreased (log-neopterin: 0.63±0.17 versus 0.50±0.19, P=0.001), whereas arterial elasticity (baPWV: 1764±101 versus 1685±96 cm s(-1), P=0.272) and endothelial function (FMD: 5.92±1.43% versus 7.73±1.31%, P<0.05) were improved. The decline in neopterin levels was linearly correlated with baPWV decrease (r=0.800, P<0.001), FMD improvement (r=0.670, P=0.006) and blood pressure reduction (r=0.548, P=0.042). Our present study demonstrated for the first time that neopterin is closely correlated with vascular dysfunctions, and measurement of plasma neopterin levels might be used as a surrogate biomarker for the clinical evaluation of vascular damage and risk stratification of future atherosclerotic cardiovascular disease in patients with hypertension. PMID

  11. Exposure to Organic Solvents Used in Dry Cleaning Reduces Low and High Level Visual Function

    PubMed Central

    Jiménez Barbosa, Ingrid Astrid

    2015-01-01

    Purpose To investigate whether exposure to occupational levels of organic solvents in the dry cleaning industry is associated with neurotoxic symptoms and visual deficits in the perception of basic visual features such as luminance contrast and colour, higher level processing of global motion and form (Experiment 1), and cognitive function as measured in a visual search task (Experiment 2). Methods The Q16 neurotoxic questionnaire, a commonly used measure of neurotoxicity (by the World Health Organization), was administered to assess the neurotoxic status of a group of 33 dry cleaners exposed to occupational levels of organic solvents (OS) and 35 age-matched non dry-cleaners who had never worked in the dry cleaning industry. In Experiment 1, to assess visual function, contrast sensitivity, colour/hue discrimination (Munsell Hue 100 test), global motion and form thresholds were assessed using computerised psychophysical tests. Sensitivity to global motion or form structure was quantified by varying the pattern coherence of global dot motion (GDM) and Glass pattern (oriented dot pairs) respectively (i.e., the percentage of dots/dot pairs that contribute to the perception of global structure). In Experiment 2, a letter visual-search task was used to measure reaction times (as a function of the number of elements: 4, 8, 16, 32, 64 and 100) in both parallel and serial search conditions. Results Dry cleaners exposed to organic solvents had significantly higher scores on the Q16 compared to non dry-cleaners indicating that dry cleaners experienced more neurotoxic symptoms on average. The contrast sensitivity function for dry cleaners was significantly lower at all spatial frequencies relative to non dry-cleaners, which is consistent with previous studies. Poorer colour discrimination performance was also noted in dry cleaners than non dry-cleaners, particularly along the blue/yellow axis. In a new finding, we report that global form and motion thresholds for dry cleaners

  12. Regional growth management policies: Toward reducing global warming at state and local levels

    SciTech Connect

    Purdie, J.

    1995-09-01

    State and local governments in the United States are accepting mandates to coordinate legislated land use and growth management planning with vigorous environmental protection and resource conservation. These mandates, implemented or planned in states with populations totaling over 100 million, will directly impact growth patterns and ultimately affect the level of atmospheric gases and particulates generated within their borders. This paper addresses the issues of growth management and land use planning at the local, state and regional levels and identifies areas impacting global warming. A review of existing systems will be presented, and recommendations will be made to improve monitoring of growth management mechanisms and organizational structures with the goal of global atmospheric improvement. The issues discussed include urban sprawl, transportation, and growth patterns as managed by policies also designed to protect environments and provide for sustainable growth. Areas for improved coordination between jurisdictions to ease global warming will also be examined.

  13. G5, a Phage Single-Stranded DNA-Binding Protein, Fused with a Nuclear Localization Signal, Attenuates Symptoms and Reduces Begomovirus-Betasatellite Accumulation in Transgenic Plants.

    PubMed

    Rasool, Ghulam; Yousaf, Sumaira; Akram, Afzal; Mansoor, Shahid; Briddon, Rob W; Saeed, Muhammad

    2016-09-01

    Cotton leaf curl disease is caused by several monopartite begomoviruses and is the major threat to cotton production in the Indian subcontinent. The disease has been shown to be associated with four distinct species, including Cotton leaf curl Kokhran virus (CLCuKoV), and a specific betasatellite-Cotton leaf curl Multan betasatellite (CLCuMuB). Transgenic Nicotiana benthamiana plants were produced which constitutively express the Escherichia coli phage M13 encoded, sequence nonspecific single-stranded (ss) DNA-binding protein, G5 alone and fused with the maize opaque-2 nuclear localization signal (NLS), to evaluate resistance against CLCuKoV-CLCuMuB. Transgenic plants expressing only G5 performed poorly exhibiting symptoms of infection and high virus DNA levels upon inoculation with CLCuKoV and CLCuKoV with CLCuMuB. In contrast, plants transformed with G5 fused to the NLS developed mild symptoms and showed a reduction in virus and betasatellite DNA levels in comparison to nontransformed plants. The results show that G5 may be useful in developing broad-spectrum resistance against ssDNA viruses. PMID:27364491

  14. Effectiveness of flushing on reducing lead and copper levels in school drinking water.

    PubMed Central

    Murphy, E A

    1993-01-01

    Samples from drinking water fountains in 50 schools in New Jersey were collected at specific times during a typical school day and analyzed for lead, copper, pH, alkalinity, and hardness. First-draw lead and copper levels (medians 0.010 mg/l and 0.26 mg/l, respectively) decreased significantly after 10 min of flushing in the morning (medians 0.005 mg/l lead and 0.068 mg/l copper), but levels increased significantly by lunchtime (medians 0.007 mg/l lead and 0.12 mg/l copper) after normal use of fountains in the morning by students. Corrosive water, as defined by the aggressive index, contained significantly higher levels of lead and copper (medians 0.012 mg/l and 0.605 mg/l, respectively) than noncorrosive water (medians 0.005 mg/l and 0.03 mg/l, respectively). Images p240-a PMID:8404761

  15. by ligand exchange: utilizing energy level alignment for efficiently reducing carrier rec ombination

    NASA Astrophysics Data System (ADS)

    Wang, Xia; Kou, Dong-Xing; Zhou, Wen-Hui; Zhou, Zheng-Ji; Wu, Si-Xin; Cao, Xuan

    2014-05-01

    In this work, we employed a convenient one-step synthesis method for synthesizing Cu2ZnSnSe4 (CZTSe) nanocrystals (NCs) in an excess selenium environment. This excess selenium situation enhanced the reaction of metal acetylacetonates with selenium, resulting in the burst nucleation of NCs at relatively low temperatures. The phase morphology and surface and optoelectronic properties of NCs before and after ligand exchange were discussed in depth. It was found that pure tetragonal-phase structure CZTSe NCs with approximately 1.7-eV bandgap could be synthesized. The removal of large organic molecules on CZTSe NCs after ligand exchange by S2- decreased the resistivity. The bandgap of the films after ligand exchange by 550°C selenization was also decreased due to better crystallinity. For potential application in CZTSe solar cells, we constructed an energy level diagram to explain the mutual effect between the absorption layer and CdS layer. Using cyclic voltammetry (CV) measurement, we found that the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of CZTSe films shifted down after ligand exchange. After energy level alignment at the CdS/CZTSe interface, a type I band alignment structure was more conveniently formed after ligand exchange. This structure acted as the barrier against injection electrons from ZnO to the CZTSe layer, and recombination would subsequently be depressed.

  16. Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring.

    PubMed

    Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Christiansen, Sofie; Hass, Ulla

    2013-09-01

    Thyroid disrupting chemicals can potentially disrupt brain development. Two studies investigating the effect of the antibacterial compound triclosan on thyroxine (T₄) levels in rats are reported. In the first, Wistar rat dams were gavaged with 75, 150 or 300 mg triclosan/kg bw/day throughout gestation and lactation. Total T₄ serum levels were measured in dams and offspring, and all doses of triclosan significantly lowered T₄ in dams, but no significant effects on T₄ levels were seen in the offspring at the end of the lactation period. Since this lack of effect could be due to minimal exposure through maternal milk, a second study using direct per oral pup exposure from postnatal day 3-16 to 50 or 150 mg triclosan/kg bw/day was performed. This exposure pointed to significant T₄ reductions in 16 day old offspring in both dose groups. These results corroborate previous studies showing that in rats lactational transfer of triclosan seems limited. Since an optimal study design for testing potential developmental neurotoxicants in rats, should include exposure during both the pre- and postnatal periods of brain development, we suggest that in the case of triclosan, direct dosing of pups may be the best way to obtain that goal. PMID:23831729

  17. Optical Mass Gauging System for Measuring Liquid Levels in a Reduced Gravity Environment

    NASA Technical Reports Server (NTRS)

    Sullenberger, Ryan M.; Munoz, Wesley M.; Lyon, Matt P.; Vogel, Kenny; Yalin, Azer P.; Korman, Valentin; Polzin, Kurt A.

    2010-01-01

    A compact and rugged fiber-coupled liquid volume sensor designed for flight on a sounding rocket platform is presented. The sensor consists of a Mach-Zehnder interferometer capable of measuring the amount of liquid contained in a tank under any gravitational conditions, including a microgravity environment, by detecting small changes in the index of refraction of the gas contained within a sensing region. By monitoring changes in the interference fringe pattern as the system undergoes a small compression provided by a piston, the ullage volume of a tank can be directly measured allowing for a determination of the liquid volume. To demonstrate the technique, data are acquired using two tanks containing different volumes of liquid, which are representative of the levels of liquid in a tank at different time periods during a mission. The two tanks are independently exposed to the measurement apparatus, allowing for a determination of the liquid level in each. In a controlled, laboratory test of the unit, the system demonstrated a capability of measuring a liquid level in an individual tank of 10.53 mL with a 2% error. The overall random uncertainty for the flight system is higher than that one test, at +/- 1.5 mL.

  18. Low level laser therapy reduces oxidative stress in cortical neurons in vitro

    NASA Astrophysics Data System (ADS)

    Huang, Ying-Ying; Tedford, Clark E.; McCarthy, Thomas; Hamblin, Michael R.

    2012-03-01

    It is accepted that the mechanisms of low level laser therapy (LLLT) involves photons that are absorbed in the mitochondria of cells and lead to increase of mitochondrial metabolism resulting in more electron transport, increase of mitochondrial membrane potential, and more ATP production. Intracellular calcium changes are seen that correlate with mitochondrial stimulation. The situation with two other intermediates is more complex however: reactive oxygen species (ROS) and nitric oxide (NO). Evidence exists that low levels of ROS are produced by LLLT in normal cells that can be beneficial by (for instance) activating NF-kB. However high fluences of light can produce large amounts of ROS that can damage the cells. In oxidatively stressed cells the situation may be different. We exposed primary cultured cortical neurons to hydrogen peroxide (H2O2) or cobalt chloride (CoCl2) oxidative insults in the presence or absence of LLLT (810-nm laser at 0.3 or 3 J/cm2). Cell viability of cortical neurons was determined by lactate dehydrogenase assay. ROS in neurons was detected using an ROS probe, MitoRox with confocal microscopy. Results showed that LLLT dose-dependently reversed ROS production and protected cortical neurons against H2O2 or CoCl2 induced oxidative injury in cultured cortical neurons. Conclusion: LLLT can protect cortical neurons against oxidative stress by reversing the levels of ROS.

  19. Effectiveness of mandated oxygenated fuel usage to reduce carbon monoxide exhaust levels in Colorado

    SciTech Connect

    Cagle, G.A.

    1989-01-01

    An examination of Colorado Automobile Inspection and Readjustment (A.I.R.) two-speed exhaust emissions testing results was undertaken to evaluate changes in carbon monoxide exhaust levels due to the use of oxygenated fuels. Vehicles utilized within the study were separated according to their various emission control technologies: precatalyst (1938 to 1974), catalyst (1975 to 1980), and closed-loop (1981 to 1988). It was found that pre-catalyst and catalyst vehicles utilizing oxygenated fuels had significant reductions in carbon monoxide exhaust levels at 2,500 R.P.M. Results for closed-loop vehicles at 2,500 R.P.M. showed no significant reductions in carbon monoxide exhaust levels. Further examination of idle data for closed-loop vehicles indicated that a small percentage of these vehicles were considered gross-emitters based on the 1.5 percent cut-point set in Colorado. Results of the study indicated that the impact of oxygenated fuels, as well as the rationale for using such fuels as a carbon monoxide reduction strategy, may be difficult to justify as newer, more sophisticated light-duty vehicles comprise a larger proportion of the overall vehicle population in Colorado.

  20. Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer's disease

    PubMed Central

    Khermesh, Khen; D'Erchia, Anna Maria; Barak, Michal; Annese, Anita; Wachtel, Chaim; Levanon, Erez Y.; Picardi, Ernesto; Eisenberg, Eli

    2016-01-01

    Adenosine to inosine (A-to-I) RNA editing, catalyzed by the ADAR enzyme family, acts on dsRNA structures within pre-mRNA molecules. Editing of the coding part of the mRNA may lead to recoding, amino acid substitution in the resulting protein, possibly modifying its biochemical and biophysical properties. Altered RNA editing patterns have been observed in various neurological pathologies. Here, we present a comprehensive study of recoding by RNA editing in Alzheimer's disease (AD), the most common cause of irreversible dementia. We have used a targeted resequencing approach supplemented by a microfluidic-based high-throughput PCR coupled with next-generation sequencing to accurately quantify A-to-I RNA editing levels in a preselected set of target sites, mostly located within the coding sequence of synaptic genes. Overall, editing levels decreased in AD patients’ brain tissues, mainly in the hippocampus and to a lesser degree in the temporal and frontal lobes. Differential RNA editing levels were observed in 35 target sites within 22 genes. These results may shed light on a possible association between the neurodegenerative processes typical for AD and deficient RNA editing. PMID:26655226

  1. HLA reduces KIR expression level and frequency in a humanized mouse model1

    PubMed Central

    van Bergen, Jeroen; Thompson, Allan; Retière, Christelle; van Pel, Melissa; Salvatori, Daniela; Lemonnier, François; Raulet, David; Trowsdale, John; Koning, Frits

    2014-01-01

    Many human Natural Killer (NK) cells are prevented from killing autologous cells by virtue of inhibitory Killer cell Immunoglobulin-like Receptors (KIR) binding `self' HLA class I molecules. Individual NK cells stably express a selected set of KIR, but it is currently disputed whether the fraction of NK cells expressing a particular inhibitory KIR is influenced by the presence of the corresponding HLA ligand. This issue has been particularly hard to tackle in a statistically meaningful way due to the extreme polymorphism of the KIR and HLA loci, with widely varying affinities for individual KIR and HLA allele combinations. Here, we use a transgenic mouse model to investigate the effect of HLA on KIR repertoire and function. In this model system, a functional interaction between HLA-Cw3 and KIR2DL2 reduced both the surface expression of KIR2DL2 as well as the frequency of KIR2DL2+ cells. PMID:23390293

  2. Diet-induced obesity and acute hyperlipidemia reduce IkappaBalpha levels in rat skeletal muscle in a fiber-type dependent manner.

    PubMed

    Bhatt, Bankim A; Dube, John J; Dedousis, Nikolas; Reider, Jodie A; O'Doherty, Robert M

    2006-01-01

    Increased activity of proinflammatory/stress pathways has been implicated in the pathogenesis of insulin resistance in obesity. However, the effects of obesity on the activity of these pathways in skeletal muscle, the major insulin-sensitive tissue by mass, are poorly understood. Furthermore, the mechanisms that activate proinflammatory/stress pathways in obesity are unknown. The present study addressed the effects of diet-induced obesity (DIO; 6 wk of high-fat feeding) and acute (6-h) hyperlipidemia (HL) in rats on activity of IKK/IkappaB/NF-kappaB c-Jun NH(2)-terminal kinase, and p38 MAPK in three skeletal muscles differing in fiber type [superficial vastus (Vas; fast twitch-glycolytic), soleus (Sol; slow twitch-oxidative), and gastrocnemius (Gas; mixed)]. DIO decreased the levels of the IkappaBalpha in Vas (24 +/- 3%, P = 0.001, n = 8) but not in Sol or Gas compared with standard chow-fed controls. Similar to DIO, HL decreased IkappaBalpha levels in Vas (26 +/- 5%, P = 0.006, n = 6) and in Gas (15 +/- 4%, P = 0.01, n = 7) but not in Sol compared with saline-infused controls. Importantly, the fiber-type-dependent effects on IkappaBalpha levels could not be explained by differential accumulation of triglyceride in Sol and Vas. HL, but not DIO, decreased phospho-p38 MAPK levels in Vas (41 +/- 7% P = 0.004, n = 6) but not in Sol or Gas. Finally, skeletal muscle c-Jun NH(2)-terminal kinase activity was unchanged by DIO or HL. We conclude that diet-induced obesity and acute HL reduce IkappaBalpha levels in rat skeletal muscle in a fiber-type-dependent manner. PMID:16081881

  3. Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients

    PubMed Central

    Espino, Javier; Mediero, Matías; Lozano, Graciela M; Bejarano, Ignacio; Ortiz, Águeda; García, Juan F; Pariente, José A; Rodríguez, Ana B

    2009-01-01

    Background Asthenozoospermia is one of the most common findings present in infertile males characterized by reduced or absent sperm motility, but its aetiology remains unknown in most cases. In addition, calcium is one of the most important ions regulating sperm motility. In this study we have investigated the progesterone-evoked intracellular calcium signal in ejaculated spermatozoa from men with normospermia or asthenozoospermia. Methods Human ejaculates were obtained from healthy volunteers and asthenospermic men by masturbation after 4–5 days of abstinence. For determination of cytosolic free calcium concentration, spermatozoa were loaded with the fluorescent ratiometric calcium indicator Fura-2. Results Treatment of spermatozoa from normospermic men with 20 micromolar progesterone plus 1 micromolar thapsigargin in a calcium free medium induced a typical transient increase in cytosolic free calcium concentration due to calcium release from internal stores. Similar results were obtained when spermatozoa were stimulated with progesterone alone. Subsequent addition of calcium to the external medium evoked a sustained elevation in cytosolic free calcium concentration indicative of capacitative calcium entry. However, when progesterone plus thapsigargin were administered to spermatozoa from patients with asthenozoospermia, calcium signal and subsequent calcium entry was much smaller compared to normospermic patients. As expected, pretreatment of normospermic spermatozoa with both the anti-progesterone receptor c262 antibody and with progesterone receptor antagonist RU-38486 decreased the calcium release induced by progesterone. Treatment of spermatozoa with cytochalasin D or jasplakinolide decreased the calcium entry evoked by depletion of internal calcium stores in normospermic patients, whereas these treatments proved to be ineffective at modifying the calcium entry in patients with asthenozoospermia. Conclusion Our results suggest that spermatozoa from

  4. Higher levels of serum lycopene are associated with reduced mortality in individuals with metabolic syndrome.

    PubMed

    Han, Guang-Ming; Meza, Jane L; Soliman, Ghada A; Islam, K M Monirul; Watanabe-Galloway, Shinobu

    2016-05-01

    Metabolic syndrome increases the risk of mortality. Increased oxidative stress and inflammation may play an important role in the high mortality of individuals with metabolic syndrome. Previous studies have suggested that lycopene intake might be related to the reduced oxidative stress and decreased inflammation. Using data from the National Health and Nutrition Examination Survey, we examined the hypothesis that lycopene is associated with mortality among individuals with metabolic syndrome. A total of 2499 participants 20 years and older with metabolic syndrome were divided into 3 groups based on their serum concentration of lycopene using the tertile rank method. The National Health and Nutrition Examination Survey from years 2001 to 2006 was linked to the mortality file for mortality follow-up data through December 31, 2011, to determine the mortality rate and hazard ratios (HR) for the 3 serum lycopene concentration groups. The mean survival time was significantly higher in the group with the highest serum lycopene concentration (120.6 months; 95% confidence interval [CI], 118.8-122.3) and the medium group (116.3 months; 95% CI, 115.2-117.4), compared with the group with lowest serum lycopene concentration (107.4 months; 95% CI, 106.5-108.3). After adjusting for possible confounding factors, participants in the highest (HR, 0.61; P = .0113) and in the second highest (HR, 0.67; P = .0497) serum lycopene concentration groups showed significantly lower HRs of mortality when compared with participants in the lower serum lycopene concentration. The data suggest that higher serum lycopene concentration has a significant association with the reduced risk of mortality among individuals with metabolic syndrome. PMID:27101758

  5. Public acceptability of population-level interventions to reduce alcohol consumption: a discrete choice experiment.

    PubMed

    Pechey, Rachel; Burge, Peter; Mentzakis, Emmanouil; Suhrcke, Marc; Marteau, Theresa M

    2014-07-01

    Public acceptability influences policy action, but the most acceptable policies are not always the most effective. This discrete choice experiment provides a novel investigation of the acceptability of different interventions to reduce alcohol consumption and the effect of information on expected effectiveness, using a UK general population sample of 1202 adults. Policy options included high, medium and low intensity versions of: Minimum Unit Pricing (MUP) for alcohol; reducing numbers of alcohol retail outlets; and regulating alcohol advertising. Outcomes of interventions were predicted for: alcohol-related crimes; alcohol-related hospital admissions; and heavy drinkers. First, the models obtained were used to predict preferences if expected outcomes of interventions were not taken into account. In such models around half of participants or more were predicted to prefer the status quo over implementing outlet reductions or higher intensity MUP. Second, preferences were predicted when information on expected outcomes was considered, with most participants now choosing any given intervention over the status quo. Acceptability of MUP interventions increased by the greatest extent: from 43% to 63% preferring MUP of £1 to the status quo. Respondents' own drinking behaviour also influenced preferences, with around 90% of non-drinkers being predicted to choose all interventions over the status quo, and with more moderate than heavy drinkers favouring a given policy over the status quo. Importantly, the study findings suggest public acceptability of alcohol interventions is dependent on both the nature of the policy and its expected effectiveness. Policy-makers struggling to mobilise support for hitherto unpopular but promising policies should consider giving greater prominence to their expected outcomes. PMID:24858928

  6. Cyclic di-AMP homeostasis in bacillus subtilis: both lack and high level accumulation of the nucleotide are detrimental for cell growth.

    PubMed

    Mehne, Felix M P; Gunka, Katrin; Eilers, Hinnerk; Herzberg, Christina; Kaever, Volkhard; Stülke, Jörg

    2013-01-18

    The genome of the Gram-positive soil bacterium Bacillus subtilis encodes three potential diadenylate cyclases that may synthesize the signaling nucleotide cyclic di-AMP (c-di-AMP). These enzymes are expressed under different conditions in different cell compartments, and they localize to distinct positions in the cell. Here we demonstrate the diadenylate cyclase activity of the so far uncharacterized enzymes CdaA (previously known as YbbP) and CdaS (YojJ). Our work confirms that c-di-AMP is essential for the growth of B. subtilis and shows that an excess of the molecule is also harmful for the bacteria. Several lines of evidence suggest that the diadenylate cyclase CdaA is part of the conserved essential cda-glm module involved in cell wall metabolism. In contrast, the CdaS enzyme seems to provide c-di-AMP for spores. Accumulation of large amounts of c-di-AMP impairs the growth of B. subtilis and results in the formation of aberrant curly cells. This phenotype can be partially suppressed by elevated concentrations of magnesium. These observations suggest that c-di-AMP interferes with the peptidoglycan synthesis machinery. The activity of the diadenylate cyclases is controlled by distinct molecular mechanisms. CdaA is stimulated by a regulatory interaction with the CdaR (YbbR) protein. In contrast, the activity of CdaS seems to be intrinsically restricted, and a single amino acid substitution is sufficient to drastically increase the activity of the enzyme. Taken together, our results support the idea of an important role for c-di-AMP in B. subtilis and suggest that the levels of the nucleotide have to be tightly controlled. PMID:23192352

  7. High-level accumulation of recombinant miraculin protein in transgenic tomatoes expressing a synthetic miraculin gene with optimized codon usage terminated by the native miraculin terminator.

    PubMed

    Hiwasa-Tanase, Kyoko; Nyarubona, Mpanja; Hirai, Tadayoshi; Kato, Kazuhisa; Ichikawa, Takanari; Ezura, Hiroshi

    2011-01-01

    In our previous study, a transgenic tomato line that expressed the MIR gene under control of the cauliflower mosaic virus 35S promoter and the nopaline synthase terminator (tNOS) produced the taste-modifying protein miraculin (MIR). However, the concentration of MIR in the tomatoes was lower than that in the MIR gene's native miracle fruit. To increase MIR production, the native MIR terminator (tMIR) was used and a synthetic gene encoding MIR protein (sMIR) was designed to optimize its codon usage for tomato. Four different combinations of these genes and terminators (MIR-tNOS, MIR-tMIR, sMIR-tNOS and sMIR-tMIR) were constructed and used for transformation. The average MIR concentrations in MIR-tNOS, MIR-tMIR, sMIR-tNOS and sMIR-tMIR fruits were 131, 197, 128 and 287 μg/g fresh weight, respectively. The MIR concentrations using tMIR were higher than those using tNOS. The highest MIR accumulation was detected in sMIR-tMIR fruits. On the other hand, the MIR concentration was largely unaffected by sMIR-tNOS. The expression levels of both MIR and sMIR mRNAs terminated by tMIR tended to be higher than those terminated by tNOS. Read-through mRNA transcripts terminated by tNOS were much longer than those terminated by tMIR. These results suggest that tMIR enhances mRNA expression and permits the multiplier effect of optimized codon usage. PMID:21076835

  8. GUN1 Controls Accumulation of the Plastid Ribosomal Protein S1 at the Protein Level and Interacts with Proteins Involved in Plastid Protein Homeostasis.

    PubMed

    Tadini, Luca; Pesaresi, Paolo; Kleine, Tatjana; Rossi, Fabio; Guljamow, Arthur; Sommer, Frederik; Mühlhaus, Timo; Schroda, Michael; Masiero, Simona; Pribil, Mathias; Rothbart, Maxi; Hedtke, Boris; Grimm, Bernhard; Leister, Dario

    2016-03-01

    Developmental or metabolic changes in chloroplasts can have profound effects on the rest of the plant cell. Such intracellular responses are associated with signals that originate in chloroplasts and convey information on their physiological status to the nucleus, which leads to large-scale changes in gene expression (retrograde signaling). A screen designed to identify components of retrograde signaling resulted in the discovery of the so-called genomes uncoupled (gun) mutants. Genetic evidence suggests that the chloroplast protein GUN1 integrates signals derived from perturbations in plastid redox state, plastid gene expression, and tetrapyrrole biosynthesis (TPB) in Arabidopsis (Arabidopsis thaliana) seedlings, exerting biogenic control of chloroplast functions. However, the molecular mechanism by which GUN1 integrates retrograde signaling in the chloroplast is unclear. Here we show that GUN1 also operates in adult plants, contributing to operational control of chloroplasts. The gun1 mutation genetically interacts with mutations of genes for the chloroplast ribosomal proteins S1 (PRPS1) and L11. Analysis of gun1 prps1 lines indicates that GUN1 controls PRPS1 accumulation at the protein level. The GUN1 protein physically interacts with proteins involved in chloroplast protein homeostasis based on coimmunoprecipitation experiments. Furthermore, yeast two-hybrid and bimolecular fluorescence complementation experiments suggest that GUN1 might transiently interact with several TPB enzymes, including Mg-chelatase subunit D (CHLD) and two other TPB enzymes known to activate retrograde signaling. Moreover, the association of PRPS1 and CHLD with protein complexes is modulated by GUN1. These findings allow us to speculate that retrograde signaling might involve GUN1-dependent formation of protein complexes. PMID:26823545

  9. (Reduce uncertainty in projection of future sea-level change due to ice wastage)

    SciTech Connect

    Meier, M.F.

    1991-01-01

    Three basic goals were stated in the original proposal. These were: (1) develop an understanding of the heat and mass flow into subfreezing snow and firn, in order to model the evolution of the temperature distribution and the infiltration rates through the firn; (2) relate changes in climate, as given by general circulation model predictions, to changes in the surface mass and energy balances of glaciers; and (3) use the above results to analyze the effects of changed surface mass and energy balances on the flow of meltwater through snow and firn, and on the runoff from these glaciers, in a CO{sub 2}-affected climate. This final report summarizes our progress toward these goals. The primary product of this research program has been the communication of this progress in the form of publications in the scientific literature and presentations at scientific meetings. Our research activities in the past three years have provided a new basis for modeling of multiphase flow in subfreezing snow, new field data on the structural properties of arctic firn pertinent to hydrological modeling, and estimates of sea level change in response to changing patterns of runoff from the Greenland Ice Sheet. We conclude that forecasts of future sea level changes from all glacier runoff sources may be in error by amounts on the order of +8 cm over the next 150 years, due to the lag in generating runoff to the sea. Our specific research products include two distributed-parameter models of water flow through snow with melting and freezing, a theoretical model of wetting-front advance into subfreezing snow for inclusion in a future model, and a simple large-scale model of the response of Greenland runoff in a changing climate which provides estimates of the effect of melt water refreezing phenomena on sea level changes in response to a range of possible future climates.

  10. Reiki brief report: using Reiki to reduce stress levels in a nine-year-old child.

    PubMed

    Bukowski, Elaine L; Berardi, Diana

    2014-01-01

    A nine-year-old female with a history of perinatal stroke, seizures, and type-I diabetes was seen for six weeks of Reiki to determine the effects of Reiki on relaxation, and in turn, the prevention of future seizures. The secondary and tertiary aims were to determine the effects of Reiki on sleep patterns and the stress levels of the mother. There was a decrease in stress in both the child and the mother, as measured by a modified Perceived Stress Scale and a Perceived Stress Scale, respectively. There was no change in the child's overall sense of well-being, as measured by a global questionnaire. There was a positive change in sleep patterns on 33.3% of the nights during which the study occurred, as reported on a sleep log kept by the mother. The child and the Reiki Master (a Reiki practitioner who has completed all three levels of Reiki certification training and trains and certifies individuals in the practice of Reiki as well as provides Reiki to individuals) experienced warmth and tingling sensations on the same area of the child during the Reiki sessions. The child relaxed within the first five to seven minutes of each session as reported by the Reiki Master. There were no reports of seizures during this study. Reiki may be a useful adjunct for children with increased stress levels and sleep disturbances secondary to their medical condition. Further research is warranted to evaluate the use of Reiki in children, particularly with a large sample size, and to evaluate the long-term use of Reiki and its effects on adequate sleep. PMID:25037669

  11. Reduced Levels of Proteasome Products in a Mouse Striatal Cell Model of Huntington’s Disease

    PubMed Central

    Dasgupta, Sayani; Fishman, Michael A.; Mahallati, Hana; Castro, Leandro M.; Tashima, Alexandre K.; Ferro, Emer S.; Fricker, Lloyd D.

    2015-01-01

    Huntington’s disease is the result of a long polyglutamine tract in the gene encoding huntingtin protein, which in turn causes a large number of cellular changes and ultimately results in neurodegeneration of striatal neurons. Although many theories have been proposed, the precise mechanism by which the polyglutamine expansion causes cellular changes is not certain. Some evidence supports the hypothesis that the long polyglutamine tract inhibits the proteasome, a multiprotein complex involved in protein degradation. However, other studies report normal proteasome function in cells expressing long polyglutamine tracts. The controversy may be due to the methods used to examine proteasome activity in each of the previous studies. In the present study, we measured proteasome function by examining levels of endogenous peptides that are products of proteasome cleavage. Peptide levels were compared among mouse striatal cell lines expressing either 7 glutamines (STHdhQ7/Q7) or 111 glutamines in the huntingtin protein, either heterozygous (STHdhQ7/Q111) or homozygous (STHdhQ111/Q111). Both of the cell lines expressing huntingtin with 111 glutamines showed a large reduction in nearly all of the peptides detected in the cells, relative to levels of these peptides in cells homozygous for 7 glutamines. Treatment of STHdhQ7/Q7 cells with proteasome inhibitors epoxomicin or bortezomib also caused a large reduction in most of these peptides, suggesting that they are products of proteasome-mediated cleavage of cellular proteins. Taken together, these results support the hypothesis that proteasome function is impaired by the expression of huntingtin protein containing long polyglutamine tracts. PMID:26691307

  12. Reduced levels of skeletal muscle Na+K+ -ATPase in McArdle disease

    NASA Technical Reports Server (NTRS)

    Haller, R. G.; Clausen, T.; Vissing, J.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    We evaluated the hypothesis that impaired sarcolemmal function associated with exaggerated potassium release, impaired potassium uptake, or both may contribute to exertional fatigue and abnormal circulatory responses to exercise in McArdle disease (MD). The cellular mechanism of exertional fatigue and muscle injury in MD is unknown but likely involves impaired function of the ATPases that couple ATP hydrolysis to cellular work, including the muscle sodium potassium pump (Na+K+-ATPase). However, the concentration of muscle Na+K+ pumps in MD is not known, and no studies have related exercise increases in blood potassium concentrations to muscle Na+K+ pump levels. We measured muscle Na+K+ pumps (3H-ouabain binding) and plasma K+ in response to 20 minutes of cycle exercise in six patients with MD and in six sex-, age-, and weight-matched sedentary individuals. MD patients had lower levels of 3H-ouabain binding (231 +/- 18 pmol/g w.w., mean +/- SD, range, 210 to 251) than control subjects (317 +/- 37, range, 266 to 371, p < 0.0004), higher peak increases in plasma potassium in response to 45 +/- 7 W cycle exercise (MD, 1.00 +/- 0.15 mmol/L; control subjects, 0.48 +/- 0.09; p < 0.0001), and mean exercise heart rate responses to exercise that were 45 +/- 12 bpm greater than control subjects. Our results indicate that Na+K+ pump levels are low in MD patients compared with healthy subjects and identify a limitation of potassium reuptake that could result in sarcolemmal failure during peak rates of membrane activation and may promote exaggerated potassium-activated circulatory responses to submaximal exercise. The mechanism of the low Na+K+ pump concentrations in MD is unknown but may relate to deconditioning or to disruption of a close functional relationship between membrane ion transport and glycolysis.

  13. Increasing Safety and Reducing Environmental Damage Risk from Aging High-Level Radioactive Waste Tanks

    SciTech Connect

    Steffler, Eric D.; McClintock, Frank A.; Lloyd, W. Randolph; Rashid, Mark M.; Williamson, Richard L.

    2005-06-01

    Cracks of various shapes and sizes exist in large high-level waste (HLW) tanks at several DOE sites. There is justifiable concern that these cracks could grow to become unstable causing a substantial release of liquid contaminants to the environment. Accurate prediction of crack growth behavior in the tanks, especially during accident scenarios, is not possible with existing analysis methodologies. This research project responds to this problem by developing an improved ability to predict crack growth in material structure combinations that are ductile (Fig. 1). This new model not only addresses the problem for these tanks, but also has applicability to any crack in any ductile structure.

  14. Low Level Laser Therapy to Reduce Recurrent Oral Ulcers in Behçet's Disease

    PubMed Central

    Babu, D. B. Gandhi; Chavva, Sunanda; Waghray, Shefali

    2016-01-01

    Behçet's disease (BD) is a chronic, relapsing multisystemic vascular condition. Behçet's disease was described by Hulusi Behçet in 1937. This rare multisystem relapsing-remitting inflammatory disease is poorly understood but is thought to be an autoimmune inflammatory vasculitic process in a genetically predisposed population. Diagnosis of Behçet's disease is based on International Criteria of Behçet's Disease (ICBD). The present paper describes a case report of Behçet's syndrome where aphthous stomatitis was treated with low level laser therapy. PMID:27555969

  15. Low Level Laser Therapy to Reduce Recurrent Oral Ulcers in Behçet's Disease.

    PubMed

    Babu, D B Gandhi; Chavva, Sunanda; Waghray, Shefali; Allam, Neeharika Satya Jyothi; Kondaiah, Marella

    2016-01-01

    Behçet's disease (BD) is a chronic, relapsing multisystemic vascular condition. Behçet's disease was described by Hulusi Behçet in 1937. This rare multisystem relapsing-remitting inflammatory disease is poorly understood but is thought to be an autoimmune inflammatory vasculitic process in a genetically predisposed population. Diagnosis of Behçet's disease is based on International Criteria of Behçet's Disease (ICBD). The present paper describes a case report of Behçet's syndrome where aphthous stomatitis was treated with low level laser therapy. PMID:27555969

  16. Opportunities for State-Level Action to Reduce Firearm Violence: Proceeding From the Evidence

    PubMed Central

    Braga, Anthony A.

    2011-01-01

    Firearm violence remains an important problem, and a large body of evidence shows that guns used in crime follow generally predictable paths from manufacturer to criminal end user. Policy initiatives based on that evidence have been shown to be effective. A recently published study conducted by a leading policy organization presents new evidence and makes specific recommendations for action by state-level policymakers. Unfortunately, the study's analysis is overly simplified, and the recommendations are therefore misleading. We suggest alternatives that are evidence based. PMID:21778510

  17. Presence of the siderophores pyoverdine and pyochelin in the extracellular medium reduces toxic metal accumulation in Pseudomonas aeruginosa and increases bacterial metal tolerance.

    PubMed

    Braud, Armelle; Geoffroy, Valérie; Hoegy, Françoise; Mislin, Gaëtan L A; Schalk, Isabelle J

    2010-06-01

    In order to get access to iron, Pseudomonas aeruginosa strain PAO1 produces two major siderophores pyoverdine (PVD) and pyochelin (PCH). Both siderophores are able to chelate many other metals in addition to iron. However, despite this property, only iron is transported efficiently into the bacteria by the PVD and PCH uptake pathways. Growth studies with P. aeruginosa strains showed a lower sensitivity to toxic metals for the siderophore-producing strain than for the mutants unable to produce siderophores. Moreover, addition of PVD or PCH to the growth medium of a siderophore-deficient strain considerably reduced the toxicity of toxic metals present at concentrations of 100 µM in iron-limited and iron-supplemented growth conditions. Measurement by Inductively Coupled Plasma-Atomic Emission Spectrometry of the concentration of metals present in bacteria incubated with metals in the presence or absence of PVD or PCH indicated that both siderophores were able to sequester metals from the extracellular medium of the bacteria, decreasing metal diffusion into the bacteria. Pyoverdine was able to sequester Al(3+) , Co(2+) , Cu(2+) , Eu(3+) , Ni(2+) , Pb(2+) , Tb(3+) and Zn(2+) from the extracellular medium, and PCH, Al(3+) , Co(2+) , Cu(2+) , Ni(2+) , Pb(2+) and Zn(2+) . Moreover, the presence of 100 µM Cu(2+) and Ni(2+) increased PVD production by 290% and 380%, respectively, in a medium supplemented with iron. All these data suggest that PVD and PCH may contribute to P. aeruginosa resistance to heavy metals. PMID:23766115

  18. Arginine vasotocin reduces levels of cooperative behaviour in a cleaner fish.

    PubMed

    Cardoso, Sónia C; Paitio, José R; Oliveira, Rui F; Bshary, Redouan; Soares, Marta C

    2015-02-01

    Cooperation between unrelated individuals usually involves investments that often mean a decrease in immediate payoffs, but ensure future benefits. Here we investigated the potential role of the neuropeptides Arginine-vasotocin (AVT) and Isotocin (IT) as proximate agents affecting individuals' cooperative levels in the Indo-pacific bluestreak cleaner wrasse Labroides dimidiatus. Their 'client' reef fish partners only benefit from interacting if cleaners eat ectoparasites and refrain from gleaning preferred client mucus. Thus, cleaners must control their impulse to eat according to their preference, and eat less preferred items to maintain ongoing interactions and avoid clients' leaving or punishing. We found that solely the experimental transient higher dosage of AVT led to a decrease of cleaners' willingness to feed against their preference, while IT and AVT antagonists had no significant effects. The sole effect of AVT on cleaner's performance may imply a link between AVT's influence and a potential activation of a stress response. Our results confirm the importance of the AVT/AVP system as an agent affecting levels of cooperation, offering a potential mechanistic pathway for the reported flexible service quality that cleaners provide their clients. PMID:25449412

  19. Acrylamide in Caribbean foods - residual levels and their relation to reducing sugar and asparagine content.

    PubMed

    Bent, Grace-Anne; Maragh, Paul; Dasgupta, Tara

    2012-07-15

    The acrylamide levels in commercial and homemade Caribbean foods were determined by pre-derivatisation of acrylamide to 2-bromopropenamide and analysed by gas chromatography with mass spectrometric (GC/MS) detection. Over 100 Caribbean food samples were analysed for the presence of acrylamide. These samples include: biscuits, breakfast cereals, banana chips and home-prepared foods: breadfruit; Artocarpus altilis, banana fritters, and dumplings. The limit of detection (LOD) for the GC/MS method was found to be dependent on the type of column used for the GC/MS analysis. The DB-1701 and the DB-VRX columns gave LODs of 20 and 4 μg/kg, respectively. Acrylamide has not been found in raw foods or foods which have been cooked by boiling. Its content in all other foods had concentrations in the range, 65-3,640 μg/kg. The relationship between acrylamide levels and precursor concentration as well as the health implications of our findings are discussed. PMID:25683419

  20. Ethanol exposure affects gene expression in the embryonic organizer and reduces retinoic acid levels.

    PubMed

    Yelin, Ronit; Schyr, Racheli Ben-Haroush; Kot, Hadas; Zins, Sharon; Frumkin, Ayala; Pillemer, Graciela; Fainsod, Abraham

    2005-03-01

    Fetal Alcohol Spectrum Disorder (FASD) is a set of developmental malformations caused by alcohol consumption during pregnancy. Fetal Alcohol Syndrome (FAS), the strongest manifestation of FASD, results in short stature, microcephally and facial dysmorphogenesis including microphthalmia. Using Xenopus embryos as a model developmental system, we show that ethanol exposure recapitulates many aspects of FAS, including a shortened rostro-caudal axis, microcephally and microphthalmia. Temporal analysis revealed that Xenopus embryos are most sensitive to ethanol exposure between late blastula and early/mid gastrula stages. This window of sensitivity overlaps with the formation and early function of the embryonic organizer, Spemann's organizer. Molecular analysis revealed that ethanol exposure of embryos induces changes in the domains and levels of organizer-specific gene expression, identifying Spemann's organizer as an early target of ethanol. Ethanol also induces a defect in convergent extension movements that delays gastrulation movements and may affect the overall length. We show that mechanistically, ethanol is antagonistic to retinol (Vitamin A) and retinal conversion to retinoic acid, and that the organizer is active in retinoic acid signaling during early gastrulation. The model suggests that FASD is induced in part by an ethanol-dependent reduction in retinoic acid levels that are necessary for the normal function of Spemann's organizer. PMID:15708568

  1. The efficacy of low-level laser treatment in reducing pain and swelling after endodontic surgery: a systematic review

    NASA Astrophysics Data System (ADS)

    Moshari, Amirabbas; Vatanpour, Mehdi; Zakershahrak, Mehrsa

    2016-03-01

    Introduction: LLLT in oral cavity believed to reduce pain after endodontic surgery and wisdom tooth removal, to accelerate wound healing and to have an anti-inflammatory and regenerative effect. The aim of this systematic review therefore was to assess the proof available for the efficacy of low-level laser treatment in reducing pain and swelling after endodontic surgery. Methods: The PubMed service of the U.S. National Library of Medicine was searched with applicable search strategies. No language restriction was applied. The last electronic search was accomplished on August 31, 2015. All randomized clinical trials on the efficiency of low-level laser treatment in reducing pain and swelling after endodontic surgery was considered for the Meta-analysis. Quality consideration of the included randomized clinical trials was appraised according to CONSORT guidelines. Results: Only two randomized clinical trials were attained. These studies clarified that laser treatment could reduce pain and swelling, but the results were not significant. Conclusions: Low-level laser therapy can be advantageous for the reduction of postoperative pain but there is no strong confirmation for its efficiency. Its clinical utility and applicability relating to endodontic surgery, Along with the optimal energy dosage and the number of laser treatments needed after surgery, still, demand further research and experiment.

  2. Trypsin inhibitor from tamarindus indica L. seeds reduces weight gain and food consumption and increases plasmatic cholecystokinin levels

    PubMed Central

    do Nascimento Campos Ribeiro, Joycellane Alline; Serquiz, Alexandre Coellho; dos Santos Silva, Priscila Fabíola; Barbosa, Patrícia Batista Barra Medeiros; Sampaio, Tarcísio Bruno Montenegro; de Araújo, Raimundo Fernandes; de Oliveira, Adeliana Silva; Machado, Richele Janaina Araújo; Maciel, Bruna Leal Lima; Uchôa, Adriana Ferreira; dos Santos, Elizeu Antunes; de Araújo Morais, Ana Heloneida

    2015-01-01

    OBJECTIVES: Seeds are excellent sources of proteinase inhibitors, some of which may have satietogenic and slimming actions. We evaluated the effect of a trypsin inhibitor from Tamarindus indica L. seeds on weight gain, food consumption and cholecystokinin levels in Wistar rats. METHODS: A trypsin inhibitor from Tamarindus was isolated using ammonium sulfate (30–60%) following precipitation with acetone and was further isolated with Trypsin-Sepharose affinity chromatography. Analyses were conducted to assess the in vivo digestibility, food intake, body weight evolution and cholecystokinin levels in Wistar rats. Histological analyses of organs and biochemical analyses of sera were performed. RESULTS: The trypsin inhibitor from Tamarindus reduced food consumption, thereby reducing weight gain. The in vivo true digestibility was not significantly different between the control and Tamarindus trypsin inhibitor-treated groups. The trypsin inhibitor from Tamarindus did not cause alterations in biochemical parameters or liver, stomach, intestine or pancreas histology. Rats treated with the trypsin inhibitor showed significantly elevated cholecystokinin levels compared with animals receiving casein or water. CONCLUSION: The results indicate that the isolated trypsin inhibitor from Tamarindus reduces weight gain by reducing food consumption, an effect that may be mediated by increased cholecystokinin. Thus, the potential use of this trypsin inhibitor in obesity prevention and/or treatment should be evaluated. PMID:25789523

  3. Stigmasterol reduces plasma cholesterol levels and inhibits hepatic synthesis and intestinal absorption in the rat.

    PubMed

    Batta, Ashok K; Xu, Guorong; Honda, Akira; Miyazaki, Teruo; Salen, Gerald

    2006-03-01

    Plant sterols compete with cholesterol (cholest-5-en-3beta-ol) for intestinal absorption to limit absorption and lower plasma concentrations of cholesterol. Stigmasterol (24-ethyl-cholesta-5,22-dien-3beta-ol; Delta(22) derivative of sitosterol [24-ethyl-cholest-5-en-3beta-ol]), but not campesterol (24-methyl-cholest-5-en-3beta-ol) and sitosterol, is reported to inhibit cholesterol biosynthesis via inhibition of sterol Delta(24)-reductase in human Caco-2 and HL-60 cell lines. We studied the effect of feeding 0.5% stigmasterol on plasma and liver sterols and intestinal cholesterol and sitosterol absorption in 12 wild-type Kyoto (WKY) and 12 Wistar rats. After 3 weeks of feeding, cholesterol and sitosterol absorption was determined in 6 rats from each group by plasma dual-isotope ratio method. After 3 more weeks, plasma and hepatic sterols and hepatic enzyme activities were determined in all rats. After feeding stigmasterol, baseline plasma cholesterol was 1.3 times and plant sterols 3 times greater in WKY compared with Wistar rats. Stigmasterol feeding lowered plasma cholesterol by approximately 11%, whereas plasma campesterol and sitosterol levels were virtually unchanged in both rat strains, and stigmasterol constituted 3.2% of plasma sterols in WKY rats and 1% in Wistar rats. After 6 weeks of feeding, cholesterol and sitosterol absorption decreased 23% and 30%, respectively, in WKY, and 22% and 16%, respectively, in the Wistar rats as compared with untreated rats. The intestinal bacteria in both rat strains metabolized stigmasterol to mainly the 5beta-H stanol (>40%), with only small amounts of 5alpha-H derivative (approximately 1.5%), whereas the C-22 double bond was resistant to bacterial metabolism. Hepatic stigmasterol levels increased from 11 microg/g liver tissue to 104 mug/g in WKY rats and from 5 microg/g liver tissue to 21 microg/g in Wistar rats. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was suppressed 4-fold in the WKY and almost 1.8-fold

  4. Projected Near-Future Levels of Temperature and pCO2 Reduce Coral Fertilization Success

    PubMed Central

    Albright, Rebecca; Mason, Benjamin

    2013-01-01

    Increases in atmospheric carbon dioxide (pCO2) are projected to contribute to a 1.1–6.4°C rise in global average surface temperatures and a 0.14–0.35 reduction in the average pH of the global surface ocean by 2100. If realized, these changes are expected to have negative consequences for reef-building corals including increased frequency and severity of coral bleaching and reduced rates of calcification and reef accretion. Much less is known regarding the independent and combined effects of temperature and pCO2 on critical early life history processes such as fertilization. Here we show that increases in temperature (+3°C) and pCO2 (+400 µatm) projected for this century negatively impact fertilization success of a common Indo-Pacific coral species, Acropora tenuis. While maximum fertilization did not differ among treatments, the sperm concentration required to obtain 50% of maximum fertilization increased 6- to 8- fold with the addition of a single factor (temperature or CO2) and nearly 50- fold when both factors interact. Our results indicate that near-future changes in temperature and pCO2 narrow the range of sperm concentrations that are capable of yielding high fertilization success in A. tenuis. Increased sperm limitation, in conjunction with adult population decline, may have severe consequences for coral reproductive success. Impaired sexual reproduction will further challenge corals by inhibiting population recovery and adaptation potential. PMID:23457572

  5. Projected near-future levels of temperature and pCO2 reduce coral fertilization success.

    PubMed

    Albright, Rebecca; Mason, Benjamin

    2013-01-01

    Increases in atmospheric carbon dioxide (pCO2) are projected to contribute to a 1.1-6.4°C rise in global average surface temperatures and a 0.14-0.35 reduction in the average pH of the global surface ocean by 2100. If realized, these changes are expected to have negative consequences for reef-building corals including increased frequency and severity of coral bleaching and reduced rates of calcification and reef accretion. Much less is known regarding the independent and combined effects of temperature and pCO2 on critical early life history processes such as fertilization. Here we show that increases in temperature (+3°C) and pCO2 (+400 µatm) projected for this century negatively impact fertilization success of a common Indo-Pacific coral species, Acropora tenuis. While maximum fertilization did not differ among treatments, the sperm concentration required to obtain 50% of maximum fertilization increased 6- to 8- fold with the addition of a single factor (temperature or CO2) and nearly 50- fold when both factors interact. Our results indicate that near-future changes in temperature and pCO2 narrow the range of sperm concentrations that are capable of yielding high fertilization success in A. tenuis. Increased sperm limitation, in conjunction with adult population decline, may have severe consequences for coral reproductive success. Impaired sexual reproduction will further challenge corals by inhibiting population recovery and adaptation potential. PMID:23457572

  6. Salivary Cortisol Levels: The Importance of Clown Doctors to Reduce Stress

    PubMed Central

    Saliba, Flávia G.; Adiwardana, Natanael S.; Uehara, Eliane U.; Silvestre, Renata N.; Leite, Victor V.; Faleiros, Francisca T.V.; Padovani, Flávia H.P.; De Gobbi, Juliana I.F.

    2016-01-01

    This study was designed to correlate entertainment of clown-doctors (CD) activities on hospitalized children and aphysiological bio-marker. For this purpose we collected saliva samples and verified children satisfaction with these activities by using a visual analog scale (VAS). Children from 6 to 7 years-old, with diagnosis of any acute pathology, interned in the Pediatric Ward of the Botucatu Medical School Hospital (São Paulo, Brazil) were interviewed. Two groups were taken into consideration: lunchCD and dinnerCD. The following protocol was applied in each group (lunch and dinner): collection of the first saliva sample and presentation of VAS prior to CD activities, followed by collection of a second saliva sample and another VAS assessment after CD activities. The salivary cortisol was reduced in both groups comparing the first saliva sample. The satisfaction of the intervention was evident for lunchCD. The CD intervention is effective in decreasing an important physiological biomarker of stress factor, cortisol, in hospitalized children, been effective for the healing process. PMID:27114816

  7. Vitamins A, C, and E May Reduce Intestinal 210Po Levels after Ingestion.

    PubMed

    Kemp, Francis W; Portugal, Frank; Akudugu, John M; Neti, Prasad V S V; Ferraris, Ronaldo P; Howell, Roger W

    2016-07-01

    Damage to the gut mucosa is a probable contributory cause of death from ingested Po. Therefore, medical products are needed that can prevent, mitigate, and/or repair gastrointestinal (GI) damage caused by high-LET radiation emitted by Po. The present studies investigated the capacity of a diet highly enriched with vitamins A, C, and E (vitamin ACE) to protect against intestinal mucosal damage indicated by functional reductions in nutrient transport caused by orally ingested Po. Mice were gavaged with 0 or 18.5 kBq Po-citrate and fed a control or vitamin ACE-enriched diet (the latter beginning either 96 h before or immediately after gavage). Mouse intestines significantly retained Po on day 8 post-gavage. The concentration of Po in intestinal tissues was significantly (p<0.05) lower in all vitamin ACE groups compared to control. There were borderline significant Po-induced reductions in intestinal absorption of D-fructose. The combination of vitamins A, C, and E may reduce Po incorporation in the intestines when given before, or enhance decorporation when provided after, Po gavage. PMID:27218295

  8. Pro: Reducing salt intake at population level: is it really a public health priority?

    PubMed

    Cappuccio, Francesco P

    2016-09-01

    A reduction in salt intake reduces blood pressure, stroke and other cardiovascular events, including chronic kidney disease, by as much as 23% (i.e. 1.25 million deaths worldwide). It is effective in both genders, any age, ethnic group, and in high-, medium- and low-income countries. Population salt reduction programmes are both feasible and effective (preventive imperative). Salt reduction programmes are cost-saving in all settings (high-, middle- and low-income countries) (economic imperative). Public health policies are powerful, rapid, equitable and cost-saving (political imperative). The important shift in public health has not occurred without obstinate opposition from organizations concerned primarily with the profits deriving from population high salt intake and less with public health benefits. A key component of the denial strategy is misinformation (with 'pseudo' controversies). In general, poor science has been used to create uncertainty and to support inaction. This paper summarizes the evidence in favour of a global salt reduction strategy and analyses the peddling of well-worn myths behind the false controversies. PMID:27488355

  9. Salivary Cortisol Levels: The Importance of Clown Doctors to Reduce Stress.

    PubMed

    Saliba, Flávia G; Adiwardana, Natanael S; Uehara, Eliane U; Silvestre, Renata N; Leite, Victor V; Faleiros, Francisca T V; Padovani, Flávia H P; De Gobbi, Juliana I F

    2016-03-31

    This study was designed to correlate entertainment of clown-doctors (CD) activities on hospitalized children and aphysiological bio-marker. For this purpose we collected saliva samples and verified children satisfaction with these activities by using a visual analog scale (VAS). Children from 6 to 7 years-old, with diagnosis of any acute pathology, interned in the Pediatric Ward of the Botucatu Medical School Hospital (São Paulo, Brazil) were interviewed. Two groups were taken into consideration: lunchCD and dinnerCD. The following protocol was applied in each group (lunch and dinner): collection of the first saliva sample and presentation of VAS prior to CD activities, followed by collection of a second saliva sample and another VAS assessment after CD activities. The salivary cortisol was reduced in both groups comparing the first saliva sample. The satisfaction of the intervention was evident for lunchCD. The CD intervention is effective in decreasing an important physiological biomarker of stress factor, cortisol, in hospitalized children, been effective for the healing process. PMID:27114816

  10. Displacement Behaviour Is Associated with Reduced Stress Levels among Men but Not Women

    PubMed Central

    Mohiyeddini, Changiz; Bauer, Stephanie; Semple, Stuart

    2013-01-01

    Sex differences in the ability to cope with stress may contribute to the higher prevalence of stress-related disorders among women compared to men. We recently provided evidence that displacement behaviour - activities such as scratching and face touching - represents an important strategy for coping with stressful situations: in a healthy population of men, displacement behaviour during a social stress test attenuated the relationship between anxiety experienced prior to this test, and the subsequent self-reported experience of stress. Here, we extend this work to look at physiological and cognitive (in addition to self-reported) measures of stress, and study both men and women in order to investigate whether sex moderates the link between displacement behaviour and the response to stress. In a healthy study population, we quantified displacement behaviour, heart rate and cognitive performance during the Trier Social Stress Test, and used self-report questionnaires to assess the experience of stress afterwards. Men engaged in displacement behaviour about twice as often as women, and subsequently reported lower levels of stress. Bivariate correlations revealed that for men, higher rates of displacement behaviour were associated with decreased self-reported stress, fewer mistakes in the cognitive task and a trend towards lower heart rate; no relationships between displacement behaviour and stress measures were found for women. Moreover, moderation analyses revealed that high rates of displacement behaviour were associated with lower stress levels in men but not in women, and that high displacement behaviour rates were associated with poorer cognitive performance in women, but not men. These results point to an important sex difference in coping strategies, and highlight new avenues for research into sex biases in stress-related disorders. PMID:23457555

  11. Effects of carvedilol reduce conjunctivitis through changes in inflammation, NGF and VEGF levels in a rat model

    PubMed Central

    CHEN, YING; HONG, XIANFEI

    2016-01-01

    Carvedilol is a novel third generation β-blocker that acts as an antagonist of β and α adrenergic receptors, and is able to regulate various cell factors. In addition, it possesses antioxidant activity, is capable of reversing cardiac remodeling effects and has anti-arrhythmic effects. The present study aimed to investigate whether the effects of carvedilol were able to reduce conjunctivitis clinical scores. Initially, 24 Sprague Dawley (SD) rats were randomly divided into three equal groups as follows: Control group, model group and carvedilol group. The model and carvedilol group adult SD rats were injected with lipopolysaccharide (LPS) to induce conjunctivitis. In the carvedilol group, the eight SD rats with LPS-induced conjunctivitis also received 50 mg/kg/day of carvedilol for 4 weeks. Next, the effects carvedilol were assessed utilizing a system of clinical sign scores, and an enzyme-linked immunosorbent assay was used to determine the expression levels of interleukin-1β (IL-1β), IL-6, IL-8 and tumor necrosis factor-α (TNF-α). Finally, nuclear factor-κB (NF-κB), nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) were analyzed by western blotting. Carvedilol was observed to significantly reduce clinical sign scores in a dose-dependent manner (P<0.01), and reduce IL-1β, IL-6, IL-8 and TNF-α expression levels (P<0.01) in the LPS-induced rat model of conjunctivitis. Carvedilol was also able to significantly reduce the protein expression levels of NF-κB, and induce the protein expression levels of NGF and VEGF in the LPS-induced rat model of conjunctivitis (P<0.01). In conclusion, the effects of carvedilol may reduce conjunctivitis clinical scores through inflammation, NGF and VEGF in LPS-induced rat models. PMID:27168839

  12. Auxotrophic Mutations Reduce Tolerance of Saccharomyces cerevisiae to Very High Levels of Ethanol Stress

    PubMed Central

    Swinnen, Steve; Goovaerts, Annelies; Schaerlaekens, Kristien; Dumortier, Françoise; Verdyck, Pieter; Souvereyns, Kris; Van Zeebroeck, Griet; Foulquié-Moreno, María R.

    2015-01-01

    Very high ethanol tolerance is a distinctive trait of the yeast Saccharomyces cerevisiae with notable ecological and industrial importance. Although many genes have been shown to be required for moderate ethanol tolerance (i.e., 6 to 12%) in laboratory strains, little is known of the much higher ethanol tolerance (i.e., 16 to 20%) in natural and industrial strains. We have analyzed the genetic basis of very high ethanol tolerance in a Brazilian bioethanol production strain by genetic mapping with laboratory strains containing artificially inserted oligonucleotide markers. The first locus contained the ura3Δ0 mutation of the laboratory strain as the causative mutation. Analysis of other auxotrophies also revealed significant linkage for LYS2, LEU2, HIS3, and MET15. Tolerance to only very high ethanol concentrations was reduced by auxotrophies, while the effect was reversed at lower concentrations. Evaluation of other stress conditions showed that the link with auxotrophy is dependent on the type of stress and the type of auxotrophy. When the concentration of the auxotrophic nutrient is close to that limiting growth, more stress factors can inhibit growth of an auxotrophic strain. We show that very high ethanol concentrations inhibit the uptake of leucine more than that of uracil, but the 500-fold-lower uracil uptake activity may explain the strong linkage between uracil auxotrophy and ethanol sensitivity compared to leucine auxotrophy. Since very high concentrations of ethanol inhibit the uptake of auxotrophic nutrients, the active uptake of scarce nutrients may be a major limiting factor for growth under conditions of ethanol stress. PMID:26116212

  13. Enhanced fluorescence cyanide detection at physiologically lethal levels: reduced ICT-based signal transduction.

    PubMed

    Badugu, Ramachandram; Lakowicz, Joseph R; Geddes, Chris D

    2005-03-16

    Three water-soluble fluorescent probes have been specifically designed to determine free cyanide concentrations up to physiologically lethal levels, >20 microM. The probes have been designed in such a way as to afford many notable sensing features, which render them unique with regard to signal transduction, photophysical characteristics, and their application to physiological cyanide determination and safeguard. The probes are readily able to reversibly bind free aqueous cyanide with dissociation constants around 4 microM3. Subsequent cyanide binding modulates the intramolecular charge transfer within the probes, a change in the electronic properties within the probes, resulting in enhanced fluorescence optical signals as a function of increased solution cyanide concentration. The ground-state chelation with cyanide produces wavelength shifts, which also enable the probes to sense cyanide in both an excitation and emission ratiometric manner, in addition to enhanced fluorescence signaling. This has enabled a generic cyanide sensing platform to be realized that is not dependent on fluorescent probe concentration, probe photodegradation, or fluctuations in the intensity of any employed excitation sources, ideal for remote cyanide sensing applications. Further, the >600 nm fluorescence emission of the probes potentially allows for enhanced fluorescence ratiometric cyanide sensing in the optical window of tissues and blood, facilitating their use for the transdermal monitoring of cyanide for mammalian safeguard or postmortem in fire victims, both areas of active research. PMID:15755185

  14. Numerical method for reducing stress level in GaAs crystals

    NASA Astrophysics Data System (ADS)

    Dupret, F.; Nicodème, P.; Ryckmans, Y.

    1989-09-01

    We have developed a numerical method based on the finite element technique for calculating heat transfer in crystal growth furnaces. Our model is global, as it entirely relies upon external control parameters, such as the pulling rate and the power input, while internal heat exchange is calculated on the basis of geometrical and material properties of all constituents of the puller. Radiative exchanges within the furnace are calculated with the assumptions of an axisymmetric geometry and of diffuse-gray surfaces. The viewed and hidden parts of the bodies are taken into account. The influence of the meniscus at the tri-junction is also investigated. It is generally agreed that the presence of structural defects in the grown crystal is related to thermoelastic stresses generated during growth. A finite element prediction of these thermal stresses is coupled to the global heat transfer calculation. The aim of this paper is to show how the thermal stress level in the crystal can be decreased by modifying the thermal exchanges inside the furnace. We study the evolution of the temperature and stress fields during growth and research the optimal pulling rate to obtain a flat solid-liquid interface. Moreover we point out how the temperature gradients and the stress field in the crystal could be affected using a heat shield inside the crucible. Different configurations are studied. Performing quasi-steady simulations at different growth stages, we show that our global numerical model provides a powerful tool for the computer-aided design of crystal growth furnaces.

  15. Pharmacological modulation of GSAP reduces amyloid-β levels and tau phosphorylation in a mouse model of Alzheimer's disease with plaques and tangles.

    PubMed

    Chu, Jin; Lauretti, Elisabetta; Craige, Caryne P; Praticò, Domenico

    2014-01-01

    Accumulation of neurotoxic amyloid-β (Aβ) is a major hallmark of Alzheimer's disease (AD) pathology and an important player in its clinical manifestations. Formation of Aβ is controlled by the availability of an enzyme called γ-secretase. Despite its blockers being attractive therapeutic tools for lowering Aβ, this approach has failed because of their serious toxic side-effects. The discovery of the γ-secretase activating protein (GSAP), a co-factor for this protease which facilitates Aβ production without affecting other pathways responsible for the toxicity, is giving us the opportunity to develop a safer anti-Aβ therapy. In this study we have characterized the effect of Imatinib, an inhibitor of GSAP, in the 3×Tg mice, a mouse model of AD with plaques and tangles. Compared with controls, mice receiving the drug had a significant reduction in brain Aβ levels and deposition, but no changes in the steady state levels of AβPP, BACE-1, ADAM-10, or the four components of the γ-secretase complex. By contrast, Imatinib-treated animals had a significant increase in CTF-β and a significant reduction in GSAP expression levels. Additionally, we observed that tau phosphorylation was reduced at specific epitopes together with its insoluble fraction. In vitro studies confirmed that Imatinib prevents Aβ formation by modulating γ-secretase activity and GSAP levels. Our findings represent the first in vivo demonstration of the biological role that GSAP plays in the development of the AD-like neuropathologies. They establish this protein as a viable target for a safer anti-Aβ therapeutic approach in AD. PMID:24662099

  16. Low Circulating Levels of IGF-1 in Healthy Adults Are Associated With Reduced β-Cell Function, Increased Intramyocellular Lipid, and Enhanced Fat Utilization During Fasting

    PubMed Central

    Thankamony, Ajay; Capalbo, Donatella; Marcovecchio, M. Loredana; Sleigh, Alison; Jørgensen, Sine Wanda; Hill, Nathan R.; Mooslehner, Katrin; Yeo, Giles S. H.; Bluck, Les; Juul, Anders; Vaag, Allan; Dunger, David B.

    2015-01-01

    Context Low serum IGF-1 levels have been linked to increased risk for development of type 2 diabetes. However, the physiological role of IGF-1 in glucose metabolism is not well characterized. Objective Our objective was to explore glucose and lipid metabolism associated with variations in serum IGF-1 levels. Design, Setting and Participants IGF-1 levels were measured in healthy, nonobese male volunteers aged 18 to 50 years from a biobank (n = 275) to select 24 subjects (age 34.8 ± 8.9 years), 12 each in the lowest (low-IGF) and highest (high-IGF) quartiles of age-specific IGF-1 SD scores. Evaluations were undertaken after a 24-hour fast and included glucose and glycerol turnover rates using tracers, iv glucose tolerance test to estimate peripheral insulin sensitivity (IS) and acute insulin and C-peptide responses (indices of insulin secretion), magnetic resonance spectroscopy to measure intramyocellular lipids (IMCLs), calorimetry, and gene expression studies in a muscle biopsy. Main Outcome Measures Acute insulin and C-peptide responses, IS, and glucose and glycerol rate of appearance (Ra) were evaluated. Results Fasting insulin and C-peptide levels and glucose Ra were reduced (all P < .05) in low-IGF compared with high-IGF subjects, indicating increased hepatic IS. Acute insulin and C-peptide responses were lower (both P < .05), but similar peripheral IS resulted in reduced insulin secretion adjusted for IS in low-IGF subjects (P = 0.044). Low-IGF subjects had higher overnight levels of free fatty acids (P = .028) and β-hydroxybutyrate (P = .014), increased accumulation of IMCLs in tibialis anterior muscle (P = .008), and a tendency for elevated fat oxidation rates (P = .058); however, glycerol Ra values were similar. Gene expression of the fatty acid metabolism pathway (P = .0014) was upregulated, whereas the GLUT1 gene was downregulated (P = .005) in the skeletal muscle in low-IGF subjects. Conclusions These data suggest that serum IGF-1 levels could be an

  17. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats

    PubMed Central

    Bjørndal, Bodil; Ramsvik, Marie S.; Lindquist, Carine; Nordrehaug, Jan E.; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and γ-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and γ-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC’s content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis. PMID:26371012

  18. Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth

    PubMed Central

    Rogan, Mark P.; Reznikov, Leah R.; Pezzulo, Alejandro A.; Gansemer, Nicholas D.; Samuel, Melissa; Prather, Randall S.; Zabner, Joseph; Fredericks, Douglas C.; McCray, Paul B.; Welsh, Michael J.; Stoltz, David A.

    2010-01-01

    People with cystic fibrosis (CF) exhibit growth defects. That observation has been attributed, in part, to decreased insulin-like growth factor 1 (IGF1) levels, and the reduction has been blamed on malnutrition and pulmonary inflammation. However, patients with CF already have a reduced weight at birth, a manifestation not likely secondary to poor nutrition or inflammation. We found that, like humans, CF pigs were smaller than non-CF littermates and had lower IGF1 levels. To better understand the basis of IGF1 reduction, we studied newborn pigs and found low IGF1 levels within 12 h of birth. Moreover, humerus length and bone mineral content were decreased, consistent with less IGF1 activity in utero. These findings led us to test newborn humans with CF, and we found that they also had reduced IGF1 levels. Discovering lower IGF1 levels in newborn pigs and humans indicates that the decrease is not solely a consequence of malnutrition or pulmonary inflammation and that loss of cystic fibrosis transmembrane conductance regulator function has a more direct effect. Consistent with this hypothesis, we discovered reduced growth hormone release in organotypic pituitary slice cultures of newborn CF pigs. These findings may explain the long-standing observation that CF newborns are smaller than non-CF babies and why some patients with good clinical status fail to reach their growth potential. The results also suggest that measuring IGF1 levels might be of value as a biomarker to predict disease severity or the response to therapeutics. Finally, they raise the possibility that IGF1 supplementation beginning in infancy might be beneficial in CF. PMID:21059918

  19. Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth.

    PubMed

    Rogan, Mark P; Reznikov, Leah R; Pezzulo, Alejandro A; Gansemer, Nicholas D; Samuel, Melissa; Prather, Randall S; Zabner, Joseph; Fredericks, Douglas C; McCray, Paul B; Welsh, Michael J; Stoltz, David A

    2010-11-23

    People with cystic fibrosis (CF) exhibit growth defects. That observation has been attributed, in part, to decreased insulin-like growth factor 1 (IGF1) levels, and the reduction has been blamed on malnutrition and pulmonary inflammation. However, patients with CF already have a reduced weight at birth, a manifestation not likely secondary to poor nutrition or inflammation. We found that, like humans, CF pigs were smaller than non-CF littermates and had lower IGF1 levels. To better understand the basis of IGF1 reduction, we studied newborn pigs and found low IGF1 levels within 12 h of birth. Moreover, humerus length and bone mineral content were decreased, consistent with less IGF1 activity in utero. These findings led us to test newborn humans with CF, and we found that they also had reduced IGF1 levels. Discovering lower IGF1 levels in newborn pigs and humans indicates that the decrease is not solely a consequence of malnutrition or pulmonary inflammation and that loss of cystic fibrosis transmembrane conductance regulator function has a more direct effect. Consistent with this hypothesis, we discovered reduced growth hormone release in organotypic pituitary slice cultures of newborn CF pigs. These findings may explain the long-standing observation that CF newborns are smaller than non-CF babies and why some patients with good clinical status fail to reach their growth potential. The results also suggest that measuring IGF1 levels might be of value as a biomarker to predict disease severity or the response to therapeutics. Finally, they raise the possibility that IGF1 supplementation beginning in infancy might be beneficial in CF. PMID:21059918

  20. Clinical efficiency of low-level diode laser in reducing dentin hypersensitivity

    NASA Astrophysics Data System (ADS)

    Clavijo, E. M. A.; Clavijo, V. R. G.; Bandéca, M. C.; Nadalin, M. R.; Andrade, M. F.; Saad, J. R. C.; Pelegrine, A. A.

    2009-10-01

    Dentin hipersensitivity (DH) is a relatively common clinical condition, especially in periodontal patients after treatment. In this study it was evaluated 28 teeth who presented dentin hypersensitivity. The teeth were subjected to clinical and radiographic exams and were divided into groups following the treatment and the time of examination after application proposed: GI: PO 3% (Potassium Oxalate—group control)/Baseline; GII: PO 3%/3 days after first session; GIII: PO 3%/6 days; GIV: PO 3%/30 days; GV: PO 3%/60 days; GVI: PO 3%/90 days; GVII: Laser (Low_level diode laser with 110 mW/cm2)/Baseline; GVIII: Laser/7 days after first session; GIX: Laser/14 days; GX: Laser/30 days; GXI: Laser/60 days; and GXII: Laser/90 days. The groups I-VI, the teeth were subjected to 3 applications (GI-GIII) of desensitizing agent at regular intervals of seven days. The Groups VII-XI, each tooth was subjected to three applications (GVII-GIX) in three different points (mesial, meddle and distal surfaces) with an interval of 72 h. The time of application in each point was of 33 s and the patients from both groups were followed up to 90 days. The nonparametric test Friedman (α = 0.05) was applied and the test of Mann Whitney (α = 0.05) was used to compare the time of examination between groups. The application of Laser was effective 6 days after first session and to PO was 30 days. It was observed that both treatments were effective for the reduction of dentin hypersensitivity, however the laser presented better effectiveness.